Least-squares finite-element lattice Boltzmann method.
A new numerical model of the lattice Boltzmann method utilizing least-squares finite element in space and Crank-Nicolson method in time is presented. The new method is able to solve problem domains that contain complex or irregular geometric boundaries by using finite-element method's geometric flexibility and numerical stability, while employing efficient and accurate least-squares optimization. For the pure advection equation on a uniform mesh, the proposed method provides for fourth-order accuracy in space and second-order accuracy in time, with unconditional stability in the time domain. Accurate numerical results are presented through two-dimensional incompressible Poiseuille flow and Couette flow.


Does the presence of anxiety affect the validity of a screening test for depression in the elderly?
Depression in the elderly is frequently detected by screening instruments and often accompanied by anxiety. We set out to study if anxiety will affect the ability to detect depression by a screening instrument. To validate the short Zung depression rating scale in Israeli elderly and to study the affect of anxiety on its validity. The short Zung was validated against a psychiatric evaluation, in a geriatric inpatient and outpatient service. The overall validity was determined, as well as for subgroups of sufferers and non-sufferers of anxiety. An urban geriatric service in Israel. 150 medical inpatients and outpatients, aged 70 years and older. Psychiatric evaluation of modified Anxiety Disorders Interview Schedule for DSM-IV as criterion standard for anxiety and depression and short Zung instrument for depression. By criterion validity, 60% suffered from depression. The overall validity of the short Zung was high (sensitivity 71.1%, specificity 88.3%, PPV 90.1%, NPV 67.1%). The validity for those not suffering from anxiety was good (sensitivity 71.1%, specificity 90.2%, PPV 84.4%, NPV 80.7%). In those with anxiety, sensitivity, specificity and PPV were high (71.2%, 77.8%, 94.9% respectively), although the specificity was less than in non-suffers. However major difference was in the NPV rate being much lower (31.8%). The short Zung, an easily administered instrument for detecting depression, is also valid in the Israeli elderly. However, anxiety limits the usefulness of this instrument in correctly ruling out depression. The clinician must be aware, therefore, that those suffering from anxiety may score negatively for depression on a screening instrument, such as the short Zung.


Cerebral flow pattern monitoring by transcranial Doppler during cardiopulmonary resuscitation.
We describe the transcranial Doppler pattern during a period of cardiopulmonary resuscitation in a patient undergoing a transcatheter off-pump aortic valve implantation. Transcranial Doppler of the middle cerebral artery flow was measured as a part of a separate ongoing study. The patient developed a cardiac arrest during deployment of the valve prosthesis. The incidental presence of the transcranial Doppler allowed us to assess middle cerebral artery flow during cardiopulmonary resuscitation in real time. An initial lack of a diastolic flow pattern seen with transcranial Doppler at the beginning of cardiopulmonary resuscitation led to volume loading and optimisation of the resuscitation technique. After increasing the depth of external cardiac massage, the cerebral flow pattern improved to produce sufficient diastolic flow. The transcranial Doppler provided additional information during cardiopulmonary resuscitation, which was helpful in clinical management. The use of transcranial Doppler may be helpful for other cardiac procedures where cerebral malperfusion may occur.


Solid-phase extraction cleanup for ivermectin in liver tissue.
Extraction of liver tissue with organic solvent produces coextractants with compounds of interest. The solid-phase extraction (SPE) cleanup of liver tissue developed for ivermectin removes nonpolar coextractants. Liver extract that has been reduced to dryness is reconstituted in 0.5 mL acetonitrile. The mixture is passed through 0.1 g C18 SPE column, and the eluate is collected. The column is eluted further with 2 mL acetonitrile. Combined eluates are derivatized with 1-methylimidazole and trifluoroacetic anhydride, and the ivermectin derivative is determined by liquid chromatography with fluorescence detection.


Does quantitative tibial ultrasound predict low bone mineral density defined by dual energy X-ray absorptiometry?
Efforts for the early detection of bone loss and subsequent fracture risk by quantitative ultrasound (QUS), which is a non-invasive, radiation free, and cheaper method, seem rational to reduce the management costs. We aimed in this study to assess the probable correlation of speed of sound (SOS) values obtained by QUS with bone mineral density (BMD) as measured by the gold standard method, dual energy X-ray absorptiometry (DEXA), and to investigate the diagnostic value of QUS to define low BMD. One hundred twenty-two postmenopausal women having prior standard DEXA measurements were included in the study. Spine and proximal femur (neck, trochanter and Ward's triangle) BMD were assessed in a standard protocol by DEXA. The middle point of the right tibia was chosen for SOS measurement by tibial QUS. The SOS values were observed to be significantly higher in the normal BMD (t score > -1) group at all measurement sites except for the lumbar region, when compared with the low BMD group (t score < -1). SOS was negatively correlated with age (r= -0.66) and month since menopause (r= -0.57). The sensitivity, specificity, and positive and negative predictive values for QUS t score to diagnose low BMD did not seem to be satisfactory at either of the measurement sites. Tibial SOS was correlated weakly with BMD values of femur and lumbar spine as measured by DEXA and its diagnostic value did not seem to be high for discriminating between normal and low BMD, at these sites.


Nondestructive Identification and Accurate Isolation of Single Cells through a Chip with Raman Optical Tweezers.
Raman optical tweezers (ROT) as a label-free technique plays an important role in single-cell study such as heterogeneity of tumor and microbial cells. Herein we designed a chip utilizing ROT to isolate a specific single cell. The chip was made from a polydimethylsiloxane (PDMS) slab and formed into a gourd-shaped reservoir with a connected channel on a cover glass. On the chip an individual cell could be isolated from a cell crowd and then extracted with ∼0.5 μL of phosphate-buffered saline (PBS) via pipet immediately after Raman spectral measurements of the same cell. As verification, we separated four different type of cells including BGC823 gastric cancer cells, erythrocytes, lymphocytes, and E. coli cells and quantifiably characterized the heterogeneity of the cancer cells, leukocyte subtype, and erythrocyte status, respectively. The average time of identifying and isolating a specific cell was 3 min. Cell morphology comparison and viability tests showed that the successful rate of single-cell isolation was about 90%. Thus, we believe our platform could further couple other single-cell techniques such as single-cell sequencing and become a multiperspective analytical approach at the level of a single cell.


Baseline dependent minimally important differences for clinical outcomes of pulmonary rehabilitation in people with COPD.
Minimally important differences (MIDs) for common outcomes of pulmonary rehabilitation are well documented for people with chronic obstructive pulmonary disease (COPD). It is not known whether MIDs differ based on COPD disease characteristics. This study aimed to estimate MIDs for clinical outcomes of pulmonary rehabilitation dependent upon baseline characteristics. A database containing 2791 people with COPD was split into derivation (n=2245; age 66±9 years; 50% males; FEV1 47±20% predicted) and comparator (n=546; age 66±9 years; 47% males; FEV1 46±21% predicted) cohorts. MIDs were estimated using 0.5 x SD (symmetrically distributed) or 0.5 x IQR (non-symmetrically distributed) for: 6-minute walk test (6MWT), constant work rate test (CWRT), COPD assessment test (CAT), St. George's respiratory questionnaire (SGRQ), hospital anxiety and depression scale (HADS), and fat-free mass index (FFMI). MIDs were estimated based on baseline outcome scores, lung function, modified medical research council (mMRC) grade and FFMI. MID estimates were comparable to previously reported values. MIDs for SGRQ domains (Symptom=8.7 points, Activity=7.1 points, Impact=8.1 points) and FFMI were produced (0.36kg/m2). There was greater variation of change in 6MWT, SGRQ-activity, SGRQ-impact, HADS and FFMI on which the MIDs were determined when categorising for baseline values (all, p<0.05). Greater variation of change in 6MWT on which the MIDs were determined was evident with COPD disease severity grouping (p<0.05). The magnitude of change in 6MWT, CAT, CWRT, SGRQ-activity, and FFMI with baseline mMRC score categorisation resulted in greater variation on which the MIDs were determined (all, p<0.05). Baseline stratification for FFMI resulted in greater variation of change in CWRT (p<0.001) and HADS-depression (p = 0.043) on which MIDs were determined. Findings suggest that baseline presentation should be considered for people with COPD when assessing the efficacy of pulmonary rehabilitation. However, clinical significance of the variation underpinning MIDs is yet to be determined.


Morphometric characteristics of neutrophils stimulated by adhesion and hypochlorite.
The aim of this work was to compare cell form, size and volume as well as the locomotor activity of polymorphonuclear leukocytes (PMNLs) stimulated by adhesion to glass and exposed to hypochlorous acid at non-toxic dose. After 20min of adhesion to a glass surface, volume, cell surface area and projection area of PMNLs were equaled to 143.1±21.4μm3, 288.8±28.8μm2 and 248.3±32.3μm2, respectively. Projection area of PMNLs exposed to NaOCl was noticeably enlarged as compared with control samples. The cell volume of 20min adherent cells exposed to NaOCl was enlarged in comparison with both control cells and 5min adhered exposed to NaOCl cells. NaOCl exposure induced a degranulation of PMNLs as measured by lysozyme release. Granules could be found both above the cell surface and on the substratum near the cell. The S/V ratio for PMNLs increased (from 1.52 to 2.02μm-1) with the increasing of cell activation time. But at NaOCl addition the reverse tendency was observed (from 2.10 to 1.87μm-1). In cells exposed to NaOCl the redistribution and decrease of concentration of F-actin took place. This observation supports the hypothesis that the priming of PMNLs with hypochlorous acid modifies cell motility and morphology and reflects also on other functions.


Dihydro pyrimidine dehydrogenase deficiency in patients treated with capecitabine based regimens: a tertiary care centre experience.
Dihydropyrimidine dehydrogenase (DPD) enzyme is the rate limiting step in the metabolism of capecitabine, and its deficiency leads to severe toxicities and rarely, death. A total of 506 patients were treated in the GI Medical Oncology unit of our institution with capecitabine containing regimens with a dose range of 1,250 to 2,000 mg/m(2)/day during the period from June 2013 to June 2015. Patients with grade (Gr) 3/4 toxicities requiring in-patient care (life threatening complications) were planned for DPD activity testing by peripheral blood PCR sequencing. Thirty-one patients developed Gr 3/4 toxicities during cycle 1 of capecitabine. This included mucositis in 24 (77%), diarrhea in 29 (94%), hand-foot syndrome (HFS) in 13 (42%) and myelosuppression in 5 (16%) patients. Twenty-two (81.4%) were found to be DPD deficient with 6 patients negative for DPD mutation. Three patients did not undergo the DPD analysis as advised. More than one mutation was seen in 11 patients. The relative frequencies of the mutations were IVS14+1G→A in 39%, with 13% having homozygosity, 85 T→C in 36%, 1627 A→G in 32%, 496 A→G in 18% and 2194 G→A in 18%, respectively. After dose reduction in cycle 2 in 17 patients of the DPD mutation positive cohort, statistically significant reduction in the toxicities was seen. Dose reduction in DPD deficient patients, reduces risk of life threatening complications significantly but not completely. Upfront screening for DPD deficiency in Indian patients should be evaluated further in view of potentially high homozygous DPD mutation prevalence.


Quantitation of fluoroquinolones in honey using tandem mass spectrometry (LC-MS/MS): nested validation with two mass spectrometers.
A number of drugs in the quinolone and fluoroquinolone families, approved for veterinary treatment of food animals by various countries, may be used to treat bee diseases and thereby contaminate honey. An LC-MS/MS method has been developed for the quantification of the quinolones: flumequine, nalidixic acid, oxolinic acid, and pipemidic acid; and the fluoroquinolones ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, norfloxacin, ofloxacin, orbifloxacin, marbofloxacin, sarafloxacin, and sparfloxacin. A method-matched calibration curve is used with several internal standards, i.e., ciprofloxacin-d8, Iomefloxacin, and cinoxacin, to correct for the various types of honey matrices: white, light, medium, and dark colors. Enoxacin is added as an external recovery standard. The LOD values range from 0.05 microg/kg (ofloxacin) to 0.4 microg/kg (flumequine). The compounds are verified by LC-MS/MS retention times and ion ratios. Method uncertainty was determined using two separate analytical systems. The method has successfully measured the presence of norfloxacin in several samples of honey imported into Canada.


Structure of water incorporated in amphoteric polymer thin films as revealed by FT-IR spectroscopy.
The structure and hydrogen bonding of water incorporated in a thin film of amphoteric terpolymers composed of various ratios of MA, DMAPMA, and BMA were analyzed using the band shapes of the O--H stretching in the IR spectra. At an early stage of sorption of water, the IR spectrum for the water incorporated in the film with comparative contents of MA and DMAPMA residues was similar to that for free water. This is consistent with the tendency for zwitterionic polymers, but is in contrast with the drastic change in the IR spectrum of water incorporated in non-ionic polymer films such as polyBMA. These results suggest a correlation between the mildness of the charge-balanced polymers to the structure of incorporated water and their blood compatibilities.


[An overview on biomarkers of arsenic-induced health hazardsan].
A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan area in China. Arsenic levels in urine, hair, and nail could be biomarkers for short-term internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis could be biomarkers for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine could be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic could include blood levels of reactive oxidants and antioxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Biomarkers of susceptibility to arsenic-induced health hazards could include genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions could be involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress.


Expression and regulation of mRNA coding for acidic and basic fibroblast growth factor and transforming growth factor alpha in cells derived from human skin.
We investigated the regulation of mRNAs coding for acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF alpha) in cultures of human neonatal foreskin fibroblasts, keratinocytes, and melanocytes. Each cell type was propagated in an optimized serum-free medium. In rapidly growing fibroblasts, the addition of fetal bovine serum caused a modest induction of aFGF message within 2 h in conjunction with a concomitant elevation of bFGF transcripts. In these same cells, TGF alpha mRNA could not be detected in any experimental condition. In contrast, keratinocytes rapidly growing in the presence of epidermal growth factor (EGF) contained transcripts for TGF alpha that increased substantially when these cells were treated with serum. This observation suggests that factors present in serum can elevate the levels of TGF alpha mRNA beyond the levels already present in keratinocyte cultures growing in the presence of EGF. These same keratinocyte cultures had low to undetectable levels of bFGF or aFGF message, and the levels of these mRNAs were not affected by serum treatment. Treatment of keratinocytes proliferating in the presence of EGF with TGF beta for 48 h caused expression of bFGF mRNA in four of six independent cell strains. TGF beta-enhanced expression of bFGF mRNA occurred as early as 12-24 h after TGF beta exposure. TGF beta did not enhance the expression of mRNA for aFGF or TGF alpha in keratinocytes. Melanocytes failed to express detectable levels of mRNA coding for any of these growth factors in the presence of absence of TGF beta or serum.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidural buprenorphine and bupivacaine in major gynaecological operations.
Eight patients underwent major gynaecological operations. Their post-operative analgesia was provided by epidural buprenorphine 0.15 mg and bupivacaine 0.5%. The efficacy and side-effects of this combination were assessed. All patients had satisfactory analgesia ranging in duration from 10 hours to greater than 36 hours after a single dose injection. No significant side-effect was noted.


Acute protection against exercise-induced bronchoconstriction by formoterol, salmeterol and terbutaline.
The onset of bronchoprotection as obtained by various beta2-agonists has not been examined in a comparitive study. In this study, the onset of bronchodilation and protection against exercise-induced bronchoconstriction in asthmatics after inhalation of the long-acting beta2-agonists formoterol and salmeterol and the short-acting beta2-agonist terbutaline were measured. Twenty-five subjects with asthma and a history of exercise-induced bronchoconstriction (mean baseline forced expiratory volume in one second (FEV1): 90% predicted; mean fall in FEV1 after exercise: 31% from baseline) were enrolled in this double-blind, double-dummy, placebo-controlled, randomized, four-period crossover study. Exercise challenges were performed on 12 days at either 5, 30, or 60 min after inhalation of a single dose of formoterol (12 microg Turbuhaler), salmeterol (50 microg Diskus), terbutaline (500 microg Turbuhaler) or placebo. Exercise-induced bronchoconstriction (maximum fall in FEV1 or area under the curve) did not differ significantly between terbutaline, formorerol and salmeterol either 5, 30, or 60 min after inhalation of the study medication. In contrast, the onset of bronchodilation was slower after salmeterol compared to terbutaline and formoterol (p<0.05, each), which both showed a similar time course. At all time points between 5 and 60 min, formoterol provided significantly greater bronchodilation than salmeterol (p<0.05). These data indicate that equipotent doses of the bronchodilators salmeterol, formoterol and terbutaline were similarly effective with respect to their short-term protective potency against exercise-induced bronchoconstriction, despite the fact that the time course of bronchodilation was significantly different between the three beta2-agonists.


Introduction to a special issue on military neuropsychology: Serving those who serve.
The military has a long history with neuropsychology and its precursors. From developing intelligence tests during World War I, to developing early capacity and personality assessments during World War II, to forward deploying for the evaluation and treatment of frequent concussive brain injuries during more recent conflicts, clinical neuropsychology has been at the forefront of military selection, healthcare and research. The objective of this special issue is to provide an overview of the latest clinical research relevant to military neuropsychology-some contributors address assessment and treatment issues that are relevant to current practice and others foretell the future of our field. We solicited papers from established researchers and issued a general call for papers for the special issue on military neuropsychology. Results: We received submissions from several authors, eleven of which are included in this issue. These submissions cover assessment and treatment issues, as well as healthcare utilization and return to duty issues. Two apparent themes are the importance of assessing, treating, and attending to comorbidities following traumatic brain injury (TBI) and future assessment techniques moving beyond traditional cognitive performance assessment. The issue highlights the importance of research in clinical neuropsychology to the practice and advancement of military neuropsychology.


Extraction and characterization of chickpea (Cicer arietinum) albumin and globulin.
Albumin and globulin fractions of 1 Desi and 2 Kabuli varieties of chickpeas (Cicer arietinum) were extracted with water and salt solutions (K(2)SO(4) and NaCl). The extractable yields and particularly the albumin-globulin ratio varied greatly with the extraction medium and chickpea variety. Depending on the procedure employed, albumin could be extracted as a major fraction of chickpea proteins. Higher levels of essential amino acids and sulfur containing amino acids were found in albumins than in globulins of all chickpeas investigated. The common structural characteristics of both Kabuli and Desi chickpea albumins and globulins were clearly identified by densitometric profiles of their sodium dodecyl sulfate polyacrylamide gel patterns. Albumins contained subunits with higher molecular weights than those of globulins. The in vitro digestibility of the chickpea proteins by papain, pepsin, chymotrypsin, and trypsin indicated that globulins were more susceptible to proteolytic hydrolysis.


Structure, photoluminescence and wettability properties of well arrayed ZnO nanowires grown by hydrothermal method.
Well aligned ZnO nanowire arrays with high crystal quality were grown on Si substrates at a low temperature (50 degrees C) by hydrothermal method using a pre-formed ZnO seed layer. ZnO seeds were prepared via radio-frequency magnetron sputtering onto Si substrates. The morphologies of the ZnO nanowire arrays were shown by field emission scanning electron microscopy. X-ray diffraction spectra showed that the full width at the half maximum of the (0002) peak of the nanowire arrays without any heat treatment was only 0.07 degrees, indicating very high crystal quality. Furthermore, the room-temperature photoluminescence spectra of the ZnO nanowire arrays exhibited excellent UV emission. The special micro/nano surface structure of the ZnO nanowire arrays can enhance the dewettability for surfaces modified via low surface energy materials such as long chain fluorinated organic compounds. The surface of the ZnO nanowire arrays is also found to be superhydrophobic with a contact angle of 165 degrees +/- 1 degrees, while the sliding angle is 3 degrees.


The effect of peritoneal dialysis with and without aprotinin on acute experimental pancreatitis in rats.
Acute pancreatitis was induced in 139 Wistar rats by injection of trypsin in the common bilio-pancreatic duct. Peritoneal dialysis was performed in 93 rats. In some of these rats, aprotinin (250,000 UI/L) was added to the lavage fluid. Macroscopically, we noted the amount of steatonecrosis, pulmonary congestion and pleural effusion produced. The pancreatic and pulmonary lesions were studied microscopically. The effect of peritoneal dialysis with and without aprotinin on the survival rate was evaluated. Survival curves were established for the different groups of rats i.e. the non-treated group and the two groups of dialysed rats (with and without aprotinin). Peritoneal dialysis reduces the amount of steatonecrosis and the incidence of pulmonary complications of trypsin-induced pancreatitis in rats, but does not influence the pancreatic lesions. Peritoneal dialysis significantly improves the early survival rate. Addition of aprotinin to the dialysis fluid reduces the total mortality rate.


Effect of theophylline on endogenous hydrogen sulfide production in patients with COPD.
Airway inflammation plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Endogenous hydrogen sulfide (H2S) is involved in the physiological and pathophysiological process in systemic inflammation and may be involved in the pathogenesis of airway inflammation and airflow obstruction in COPD. The non-selective phosphodiesterase inhibitor theophylline has bronchodilator/anti-inflammatory properties and is widely used in the treatment of airways diseases. It is not fully understood whether endogenous H2S mediates the mechanism of theophylline anti-inflammatory effect. The effect of short-term theophylline treatment on airway inflammation and endogenous H2S production was prospectively studied in thirty-seven patients with stable COPD. Patients were randomly divided into theophylline-treatment group (nineteen patients, orally given sustained theophylline tablets for 1 month, 0.2g, q 12h) and control group (eighteen patients, not given any theophylline). Symptom score, lung function, total and differential cell counts in sputum, serum H2S and nitric oxide (NOx) levels, sputum and serum IL-8 levels were measured at baseline and 1 month later. No significant difference was found in symptom scores, lung function and other investigated experimental parameters at baseline between treatment and control groups, and between baseline and a month follow-up in control patients. Symptom scores were significantly lowered only in the treated patients after treatment, compared with those before (P<0.01). The proportion of neutrophils in sputum was significantly decreased (P<0.05) while that of macrophages was markedly increased (P<0.01) in the treated patients after treatment, compared with that before. No significant change was found in serum H2S and NOx levels, serum and sputum IL-8 levels before and after experiment in treatment group. Serum H2S level correlated positively with percentage of predicted FEV1 (r=0.465, P=0.005), and with proportion of sputum macrophages (r=0.349, P=0.05), but negatively with proportion of sputum neutrophils (r=-0.351, P=0.049) in all patients at baseline. Short-term theophylline treatment improved symptoms and decreased sputum neutrophils in COPD, while serum H2S levels were not affected in our study population. Large samples will be needed to illustrate the effect of long-term theophylline treatment on inflammatory mediators and H2S generation in COPD.


Optical communication beyond orbital angular momentum.
Mode division multiplexing (MDM) is mooted as a technology to address future bandwidth issues, and has been successfully demonstrated in free space using spatial modes with orbital angular momentum (OAM). To further increase the data transmission rate, more degrees of freedom are required to form a densely packed mode space. Here we move beyond OAM and demonstrate multiplexing and demultiplexing using both the radial and azimuthal degrees of freedom. We achieve this with a holographic approach that allows over 100 modes to be encoded on a single hologram, across a wide wavelength range, in a wavelength independent manner. Our results offer a new tool that will prove useful in realizing higher bit rates for next generation optical networks.


Order-order and order-disorder transitions in thin films of an amphiphilic liquid crystalline diblock copolymer.
In this study, we quantitatively investigated the temperature-dependent phase transition behaviors of thin films of an interesting amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly(11-[4-(4-butylphenylazo)phenoxy]undecyl methacrylate) (p(EO)-b-p(MAAZ)) and the resulting morphological structures by using synchrotron grazing incidence X-ray scattering (GIXS) and differential scanning calorimetry. The quantitative GIXS analysis showed that the diblock copolymer in the homogeneous, isotropic melt state undergoes phase-separation near 190 degrees C and then forms a body-centered cubic (BCC) structure of spherical p(EO) domains in the p(MAAZ) matrix, at which point the p(EO) domains and the p(MAAZ) matrix are both in amorphous, liquid states. The BCC structure of spherical p(EO) domains is converted to a hexagonal cylinder structure near 120 degrees C, which is induced by the transformation of the isotropic phase of the p(MAAZ) matrix to the smectic A phase, which is composed of a laterally ordered structure of p(MAAZ) blocks with fully extended side groups. The resulting hexagonal cylinder structure is very stable below 120 degrees C. This microscopic hexagonal cylinder structure is retained as the smectic A phase of the p(MAAZ) matrix undergoes further transitions to smectic C near 104 degrees C and to a smectic X phase near 76 degrees C, while the amorphous, liquid phase of the p(EO) cylinders undergoes crystallization near -15 degrees C. These complicated temperature-dependent disorder-order and order-order phase transitions in the films were found to take place reversibly during the heating run. A face-centered orthorhombic structure of p(EO) domains was also found during the heating run and is an intermediate structure in the hexagonal cylinder structure to BCC structure transformation. We use these structural analysis results to propose molecular structure models at various temperatures for thin films of the diblock polymer.


Critical advances and future opportunities in upcycling commodity polymers.
The vast majority of commodity plastics do not degrade and therefore they permanently pollute the environment. At present, less than 20% of post-consumer plastic waste in developed countries is recycled, predominately for energy recovery or repurposing as lower-value materials by mechanical recycling. Chemical recycling offers an opportunity to revert plastics back to monomers for repolymerization to virgin materials without altering the properties of the material or the economic value of the polymer. For plastic waste that is either cost prohibitive or infeasible to mechanically or chemically recycle, the nascent field of chemical upcycling promises to use chemical or engineering approaches to place plastic waste at the beginning of a new value chain. Here state-of-the-art methods are highlighted for upcycling plastic waste into value-added performance materials, fine chemicals and specialty polymers. By identifying common conceptual approaches, we critically discuss how the advantages and challenges of each approach contribute to the goal of realizing a sustainable plastics economy.


Results and prognostic factors in the radical sinus operation for chronic sinusitis.
Radical surgical procedures of the maxillary sinus with or without involvement of the ethmoid, sphenoid and frontal sinuses were performed in 382 adult patients in the Department of Otorhinolaryngology. Tokai University Hospital in the 8-year period from 1984 to 1991. Of 382 patients, the postoperative symptomatology was studied in 189 patients by mcans of questionnaires. The postoperative results were finally analyzed in 63 patients whose subjective symptoms and objective findings were completely recorded. The follow-up period was over 3 months and subjective postoperative improvement was achieved in 83% and objective postoperative improvement in 75%; the overall improvement rate was 73%. In an analysis of results of the radical surgical operation, it appeared that poor results were closely related to the following factors: (1) maxillary sinus mucosa with cellular infiltration or edematous changes; (2) multiplicity of bacterial species including Gram-negative rods isolated from maxillary sinus secretion; (3) poor mucociliary clearance function; and (4) unsatisfactory postoperative treatment.


Communication: Fully coherent quantum state hopping.
In this paper, we describe a new and fully coherent stochastic surface hopping method for simulating mixed quantum-classical systems. We illustrate the approach on the simple but unforgiving problem of quantum evolution of a two-state quantum system in the limit of unperturbed pure state dynamics and for dissipative evolution in the presence of both stationary and nonstationary random environments. We formulate our approach in the Liouville representation and describe the density matrix elements by ensembles of trajectories. Population dynamics are represented by stochastic surface hops for trajectories representing diagonal density matrix elements. These are combined with an unconventional coherent stochastic hopping algorithm for trajectories representing off-diagonal quantum coherences. The latter generalizes the binary (0,1) "probability" of a trajectory to be associated with a given state to allow integers that can be negative or greater than unity in magnitude. Unlike existing surface hopping methods, the dynamics of the ensembles are fully entangled, correctly capturing the coherent and nonlocal structure of quantum mechanics.


[Prosthesis of patients after continuant frontal resection of the lower jaw].
The authors stress upon the various functional, physiological and cosmetic disorders in patients with frontal continuat resection of the lower jaw. Their experience in the treatment of eight patients with frontal resection reveals the advantages of the two-part prosthetic constructions, consisting of one fixed part blocking the teeth and one removable part replacing the defect. In all cases with big bone defects in the frontal region of the lower jaw the authors recommend removable partial denture with intracornal channel-shoulder-pin-attachement, being with high functional, medicobiological and aesthetic indices.


Methodology for fast development of digital solutions in integrated continuous downstream processing.
The methodology for production of biologics is going through a paradigm shift from batch-wise operation to continuous production. Lot of efforts are focused on integration, intensification, and continuous operation for decreased foot-print, material, equipment, and increased productivity and product quality. These integrated continuous processes with on-line analytics become complex processes, which requires automation, monitoring, and control of the operation, even unmanned or remote, which means bioprocesses with high level of automation or even autonomous capabilities. The development of these digital solutions becomes an important part of the process development and needs to be assessed early in the development chain. This work discusses a platform that allows fast development, advanced studies, and validation of digital solutions for integrated continuous downstream processes. It uses an open, flexible, and extendable real-time supervisory controller, called Orbit, developed in Python. Orbit makes it possible to communicate with a set of different physical setups and on the same time perform real-time execution. Integrated continuous processing often implies parallel operation of several setups and network of Orbit controllers makes it possible to synchronize complex process system. Data handling, storage, and analysis are important properties for handling heterogeneous and asynchronous data generated in complex downstream systems. Digital twin applications, such as advanced model-based and plant-wide monitoring and control, are exemplified using computational extensions in Orbit, exploiting data and models. Examples of novel digital solutions in integrated downstream processes are automatic operation parameter optimization, Kalman filter monitoring, and model-based batch-to-batch control.


Analysis of phosphatidylcholine oxidation products in human plasma using quadrupole time-of-flight mass spectrometry.
We report here an application of the previous method for the analysis of phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) oxidation products in human plasma using quadrupole time of flight (Q-TOF) mass spectrometry with electrospray ionization. We separated these products using an HPLC C8 column with a gradient of methanol and 10 mM aqueous ammonium acetate. Monohydroperoxides, epoxyhydroxy derivatives, oxo derivatives, and trihydroxides of palmitoyl-linoleoyl (C16:0/C18:2) PC and stearoyl-linoleoyl (C18:0/C18:2) PC were detected mainly as MH+ and [M+Na]+ ions in the plasma of alcoholic patients. Using standard synthetic PC-OH (C16:0/C18:2-OH), the lipid extract component was identified as (C16:0/C18:2-OH) PC based on the product ions of ESI-MS-MS. Using standard synthetic PCOOH (C16:0/C18:2-OOH) as a reference, the PCOOH concentration in plasma was quantified. Two oxidatively modified lysoPCs were also detected. This is the first report showing the presence of epoxyhydroxy derivatives, monohydroperoxides, oxo derivatives, and trihydroxides of (C16:0/C18:2) PC and (C18:0/C18:2) PC, and PC-OH (C16:0/C18:0-OH) in human plasma.


An evaluation of some assumptions underlying the articulation index.
The purposes of this investigation were to derive measurement and calculation procedures for the articulation index (AI) that were as precise and accurate as possible, and to evaluate the significance of the differences in assumptions made by early investigators. A nonsense syllable test specifically designed for this application was recorded. The implications of various assumptions utilized in different approaches to predicting speech sound identification were tested using 13 different conditions which differed with respect to filtering, level of interfering noise, or level of the speech signal. The listeners were three normal hearing individuals. A set of preferred assumptions was chosen based on a post hoc evaluation of the data. Predictions of speech sound identification were good, both for the average listener and for individual listeners.


Response assessment in locally advanced head and neck cancer based on RECIST and volume measurements using cone beam CT images.
The purpose of this work was to find potential trends in RECIST measurements and volume regressions obtained from weekly cone-beam computed tomography images and to evaluate their relationship to clinical outcomes in locally advanced head and neck cancer. We examined thirty head and neck cancer patients who underwent a pre-treatment planning CT and weekly cone-beam computed tomography (CBCT) during the 5-7 week treatment period. The gross tumor volume (GTV) and lymph nodes were manually contoured on the treatment planning CT. The regions of interest enclosed by delineated contours were converted to binary masks and warped to weekly CBCT images using the 3D deformation field obtained by deformable image registration. The RECIST diameters and volumes were measured from these warped masks. Different predictor variables based on these measurements were calculated and correlated with clinical outcomes, based on a clinical exam and a PET imaging study. We found that there was substantial regression of the gross tumor volume over the treatment course (average gross tumor volume regression of 25%). Among the gross tumor volume predicators, it was found that the early regression of gross tumor volume showed a marginal statistical significance (p = 0.045) with complete response and non-complete response treatment outcomes. RECIST diameter measurements during treatment varied very little and did not correlate with clinical outcomes. We concluded that regression of the gross tumor volume obtained from weekly CBCT images is a promising predictor of clinical outcomes for head and neck patients. A larger sample is needed to confirm its statistical significance.


[Relation between morphometric indicators in axons of myelinated peripheral nerve fibers and the age of experimental animals].
The authors observed the dependence of morphometric indicators of myelinated nerve fibers on the age of experimental animals. They performed a morphometric analysis of myelinated nerve fibers, namely nervous peroneus communis in male adult white rats of 17, 21, 25 and 31 weeks of age. They discovered that the values of individual morphometric indicators of axons of myelinated nerve fibers (axon perimeter, axon circular diameter, axon area, circular axon area) and their distribution vary in dependence on age of experimental animals. The authors emphasize that observation of experimental alterations of morphometric indicators of myelinated nerve fiber axons requires a comparison of findings in groups of animals with those in control groups of animals of the same age. (Tab. 2, Fig. 4, Ref. 28.)


Relationship between smoking and dental status in 35-, 50-, 65-, and 75-year-old individuals.
The aim of the present study was to examine the dental status and smoking habits in randomized samples of 35-, 50-, 65-, and 75-year-old subjects (n = 1093), recruited for a cross-sectional epidemiological study in the County of Värmland, Sweden. The following clinical variables were recorded by 4 well-calibrated dentists: number of edentuolous subjects, number of missing teeth, probing attachment level, furcation involvement, CPITN scores, DMF surfaces, plaque and stimulated salivary secretion rate (SSSR). In addition, the subjects reported in a questionnaire their tobacco habits, oral hygiene habits, dietary habits etc. The percentage of smokers in 35-, 50-, 65-, and 75-year-olds was 35%, 35%, 24% and 12%, respectively. In 75-year-olds, 41% of the smokers were edentulous compared to 35% of non-smokers. The difference in number of missing teeth between smokers and non-smokers was 0.6 (p=0.15), 1.5 (p=0.013), 3.5 (p=0.0007) and 5.8 (p=0.005) in the 4 age groups. Smokers had the largest mean probing attachment loss in all age groups. The differences between smokers and non-smokers in mean attachment level were 0.37 (p=0.001), 0.88 (p=0.001), 0.85 (p=0.001) and 1.33 mm (p=0.002) in the 35-, 50-, 65-, and 75-year-olds, respectively. Treatment need assessed by CPITN was in all age groups greatest among smokers. The number of intact tooth surfaces was fewer in 35-, 50-, and 75-year-old smokers than in non-smokers. The number of missing surfaces (MS) was higher in 50-, 65-, and 75-year-old smokers than in non-smokers. In addition, 35-year-old smokers exhibited a significantly larger number of decayed and filled tooth surfaces (DFS) than non-smokers. Male smokers had significantly higher SSSR than non-smoking males (p=0.012). Plaque index and oral hygiene were similar in smokers and non-smokers. Smokers reported a more frequent intake of sugar containing soft drinks (p=0.000) and snacks (p=0.003) than non-smokers. The opposite was reported for consumption of fruit (p=0.003). It was concluded that smoking is a significant risk indicator for tooth loss, probing attachment loss and dental caries.


[Bacterial infection in cirrhotic patient].
Bacterial infections at admission or during hospitalization are frequent complication of cirrhosis that occurs in about 30% of the cases. Furthermore they are responsible for 25% of deaths in this population. Evaluate the prevalence of bacterial infections in cirrhotic patients at a general hospital and determine its correlation with alcoholic etiology of liver disease; degree of hepatic dysfunction and upper gastrointestinal bleeding. Five hundred and forty one admissions were retrospectively evaluated in 426 cirrhotic patients at years 1992 to 2000. The mean age was 50.5 years (15-95), being 71.2% male. The alcoholic etiology of cirrhosis was 35.4%. The main outcome considered was discharge or death during admission. One hundred and thirty five episodes of bacterial infections (25%) were diagnosed. The most frequent are urinary tract infection (31.1%), spontaneous bacterial peritonitis (25.9%) and pneumonia (25.2%). The association between urinary tract infection and pneumonia occurred in 3.7% and erysipelas or cellulites in 11.1%. Bacteremia occurred in 2.9%. There was a correlation between bacterial infection and alcoholic etiology of liver disease, hepatic dysfunction and upper gastrointestinal bleeding. The mortality was higher in the infected patients (8.9%) and in those with a poor hepatic function. Bacterial infections are common complications in cirrhotic patients and are correlated with alcoholic etiology, Child Pugh classification and upper gastrointestinal bleeding. Furthermore, bacterial infections are correlated with poor prognosis.


A wireless charger powered the extracellular electron transfer for hydrogen recovery from organics.
Herein, a simple wireless charger which provided an alternative to conventional connection for delivering the electricity was employed to power the microbial electrolysis cell (MEC) for hydrogen recovery from organics. The coulombic efficiency of the wireless power transmission (WPT) was 75.37%, which was nearly similar to the average value of the conventional wired power transmission (CWPT) at the same experimental conditions (78.23%). The energy efficiency was 130.58%, it was clearly that the wireless charging (141.57%) slightly resulted in energy losing compared with conductive wire connection. The saving cost of WPT-driven MEC was a promising compensation to the energy loss according to the economic analysis of WPT, i.e., the WPT can be cost-beneficial once the distance between charger and reactor beyond a limited value. Overall, the feasibility of WPT suggests a straightforward way to construct large-scale MES with low cost and comparable performance.


Assessment of critical care nurses' knowledge of the pulmonary artery catheter. The Pulmonary Artery Catheter Study Group.
To assess the knowledge and understanding of the use of the pulmonary artery catheter and interpretation of data derived from it in a group of nurses attending the American Association of Critical Care Nurses' National Teaching Institute conference. A 37-question multiple choice examination that tested knowledge regarding the use of the pulmonary artery catheter was administered to a group of nurses, attending a national conference, who preregistered for a hemodynamics workshop. American Association of Critical Care Nurses' National Teaching Institute Conference, New Orleans, LA, May 1992. Two-hundred sixteen nurses completed the questionnaire. The mean test score was 16.5 +/- 5.7 (SD) (48.5%). Test scores were significantly associated with years of experience in critical care, critical care registered nurse certification, responsibility for repositioning and manipulating the catheter, frequency of use, and self-assessed adequacy of knowledge. A wide variation in the understanding of the use of the pulmonary artery catheter exists among nurses using this device in the care of seriously ill patients. The results indicate that current teaching practices regarding the pulmonary artery catheter need to be reevaluated and specific credentialing policies need to be considered.


Spreading of Pandemic Vibrio parahaemolyticus O3:K6 and Its Serovariants: A Re-analysis of Strains Isolated from Multiple Studies.
In China, V. parahaemolyticus has been a leading cause of foodborne outbreaks and bacterial infectious diarrhea since the 1990s, and most infections have been associated with the pandemic V. parahaemolyticus O3:K6 and its serovariants. However, a comprehensive overview of the sero-prevalence and genetic diversity of the pandemic V. parahaemolyticus clone in China is lacking. To compensate for this deficiency, pandemic isolates in both clinical and environmental Chinese samples collected from multiple studies were analyzed in this study. Surprisingly, as many as 27 clinical pandemic serovariants were identified and were widely distributed across nine coastal provinces and two inland provinces (Beijing and Sichuan). O3:K6, O4:K68, and O1:KUT represented the predominant clinical serovars. Only four environmental pandemic serovariants had previously been reported, and they were spread throughout Shanghai (O1:KUT, O3:K6), Jiangsu (O3:K6, O4:K48), Zhejiang (O3:K6), and Guangdong (O4:K9). Notably, 24 pandemic serovariants were detected within a short time frame (from 2006 to 2012). The pandemic isolates were divided into 15 sequence types (STs), 10 of which fell within clonal complex (CC) 3. Only three STs (ST3, ST192, and ST305) were identified in environmental isolates. Substantial serotypic diversity was mainly observed among isolates within pandemic ST3, which comprised 21 combinations of O/K antigens. The pandemic O3:K6 serotype showed a high level of sequence diversity, which was shared by eight different STs (ST3, ST227, ST431, ST435, ST487, ST489, ST526, and ST672). Antimicrobial susceptibility testing revealed that most isolates shared similar antibiotic susceptibility profiles. They were resistant to ampicillin but sensitive to most other drugs that were tested. In conclusion, the high levels of serotypic and genetic diversity of the pandemic clone suggest that the involved regions are becoming important reservoirs for the emergence of novel pandemic strains. We underscore the need for routine monitoring to prevent pandemic V. parahaemolyticus infection, which includes monitoring antimicrobial responses to avoid excessive misuse of antibiotics. Further investigations are also needed to delineate the specific mechanisms underlying the possible seroconversion of pandemic isolates.


Increased serum midkine levels during hemodialysis using heparin in chronic renal failure.
The heparin-binding growth factor midkine (MK) has been implicated in neuron growth, angiogenesis, and inflammation. In this study, to elucidate the involvement of MK in the development of pathologies associated with uremia, we examined the serum MK levels in patients receiving hemodialysis (HD) by a highly sensitive enzyme-linked immunoassay. Although no significant difference was found between control serum and serum before dialysis in HD patients, serum MK levels increased significantly at the early stage of HD sessions using heparin and gradually decreased after dialysis. In normal controls, intravenous administration of heparin induced a similar sudden increase of MK, but the subsequent decrease was also rapid. In an in vitro study, MK was released in time- and heparin-dose dependent manner from cultured vessels, but not from peripheral leukocytes. These results indicate that, in HD patients, MK is released mainly from endothelial cells immediately after administration of heparin during HD and disappears gradually from blood due to renal impairment. This phenomenon might affect some complications associated with HD.


Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions.
Telomeres are tandem arrays of repeated DNA sequences located at the ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase. Loss of telomeric DNA may play an important role in the development of human cancers. However, very little is known about the status of telomerase during human cervical cancer development. Telomerase activity was measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer patients and normal cervical tissues from 11 control individuals also were examined for the presence of telomerase activity. Twenty two of the 24 (91.7%) cervical cancer specimens and the single CIS tissue were strongly positive for telomerase activity. Relatively weak but distinctive telomerase activity also was detectable in one of four CIN-I (25%), two of eight CIN-II (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity was not found in the 24 corresponding nontumor cervical tissues from the same cervical cancer patients and the 11 normal cervical tissues from control individuals. The majority of cervical cancers contain strong telomerase activity. Significant proportions of noncancerous CIN tissues also contain telomerase activity, although weaker than that in cervical cancer. It seems that there is a progressive increase of telomerase activity in association with an increased degree of cervical malignancy. These results seem to suggest that the expression of telomerase may play a crucial role in cervical cancer carcinogenesis.


Family Mealtimes: A Systematic Umbrella Review of Characteristics, Correlates, Outcomes and Interventions.
Systematic reviews have examined the multitude of studies investigating family mealtimes and their importance to child/adolescent health and psychosocial outcomes, but the focus of each is limited to specific aspects of family meals (e.g., frequency) and/or specific outcomes (e.g., nutrition). Their findings require synthesis and so a systematic umbrella review was undertaken. Databases were searched to identify systematic reviews (with or without meta-analysis/meta-synthesis) addressing at least one of the following questions: what are the characteristics and/or correlates of family mealtimes; what outcomes are associated with family mealtimes; are interventions aimed at promoting family mealtimes effective? Forty-one eligible reviews were retrieved. Their findings demonstrate that families with children/adolescents typically eat together at least a few days each week. More frequent family meals are predicted by a more positive mealtime environment, more positive attitudes towards family meals, the presence of younger children, and families having more time. Greater family meal frequency protects children/adolescents against a poorer diet, obesity, risk behaviours, poorer mental health and wellbeing, and poorer academic outcomes. Findings from interventions seeking to promote family mealtimes are mixed. This umbrella review provides a comprehensive and integrated understanding of research into family mealtimes, establishing where evidence is sound and where further research is needed.


Serious, prolonged hypoglycaemia with glibenclamide in a patient with Mendenhall's syndrome.
Mendenhall's syndrome, characterized by familial insulin resistant diabetes, pineal hyperplasia and multiple somatic abnormalities, is associated with defects involving the alpha-subunit of the insulin receptor. The associated insulin-resistant diabetes is extremely difficult to treat; insulin is required in very large doses to control hyperglycaemia and oral hypoglycaemic agents are ineffective. We report a case of severe, prolonged hypoglycaemia that occurred in a 24-year-old patient with Mendenhall's syndrome following therapy with glibenclamide. He had glibenclamide 10 mg daily for 1 week following which he was admitted to hospital in hypoglycaemic coma with blood glucose levels < 1.0 mmol/l. This subject had undergone hypophysectomy at the age of 11 years. Prior to pituitary ablation, oral hypoglycaemic agents did not improve glycaemic control. Thus, previous hypophysectomy in this patient appears to have made it possible for glibenclamide to exert its hypoglycaemic effect. The occurrence of hypoglycaemia in this patient suggests alternative mechanisms for insulin action in conditions characterized by severe insulin resistance due to insulin receptor defects.


The Mechanism of miR-222 Targets Matrix Metalloproteinase 1 in Regulating Fibroblast Proliferation in Hypertrophic Scars.
This study aimed to investigate the value of miR-222 in hypertrophic scars (HS). Specific mechanisms were used to measure the level of miR-222, while MTT assay, flow cytometry, western blot and qRT-PCR were employed to detect the relative proteins after fibroblasts were transfected with the miR-222 mimic/inhibitor. The direct target of miR-222 was determined by Dual-Luciferase Reporter assay. Furthermore, qRT-PCR and western blot were employed to detect the matrix metalloproteinase 1 (MMP1) RNA/protein after fibroblasts were transfected with the miR-222 mimic/inhibitor. These results revealed that miR-222 was significantly upregulated in HS fibroblasts. The overexpression of miR-222 enhanced the HS fibroblast proliferation, increased the cell population in the S phase, inhibited the cell apoptosis, enhanced the expression levels of Col1A1, Col3A1 mRNA/protein, proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E1 and CDK1 and reduced the expression levels of cleaved caspase-3/9. However, the miR-222 suppression triggered opposite effects. Furthermore, miR-222 played a regulatory role in HS by negatively regulating its target gene MMP1 by binding with its 3'-untranslated region. The overexpression of MMP1 reduced the expression levels of PCNA and cyclin D1, but enhanced the expression levels of cleaved caspase-3. Therefore, MiR-222 and MMP1 have potential value for HS. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


The nucleic acids of some insect viruses.
Purine and pyrimidine bases have been estimated from the desoxyribonucleic acids of eleven insect viruses. Their proportions vary in the different species in a balanced way so that the molar ratios adenine:thymine and guanine:cytosine are constant and close to unity, whereas adenine + thymine:guanine + cytosine ranges from 0.71 to 1.87. This ratio is identical for some biologically dissimilar viruses, and no general parallelism is evident between DNA composition and biological relationship. Two different viruses from one host have distinct DNA's.


Effectiveness of a group resilience intervention for people with multiple sclerosis delivered via frontline services.
This study aims to evaluate the effectiveness of an Acceptance and Commitment Therapy-based group resilience intervention (The REsilience and Activities for every DaY program, READY) delivered to people with MS (PwMS) via frontline Italian services. This is a single-arm longitudinal study (with a nested qualitative study). READY is composed of seven weekly in-person sessions (2.5-h each) plus a booster session five weeks later. Data were collected immediately before the program, after the booster session, and at 3-months follow-up. Thirty-three READY groups (237 participants) were run by thirty-three trained psychologists. Participants improved in resilience (primary outcome), anxiety, depression, stress, health-related quality of life (HRQoL), and psychological flexibility and associated processes (acceptance, defusion, and values). Improvements on most outcomes occurred post-intervention and were maintained at a 3-month follow-up. No demographic or illness variables predicted these improvements. Psychological flexibility mediated improvements in resilience, anxiety, depression, stress, and HRQoL. Qualitative data confirmed READY feasibility and the positive psychological impacts on participants. Study findings support READY effectiveness with PwMS, its broad applicability in this population, and its delivery through frontline services.IMPLICATIONS FOR REHABILITATIONREADY for MS is a highly structured, brief manualized group intervention.It is effective in improving participants' psychological functioning (resilience, anxiety, depression, stress, HRQoL, psychological flexibility, and related ACT processes).Psychological flexibility mediated the improvements in resilience, anxiety, depression, stress, HRQoL.READY can be effectively delivered through frontline services for PwMS without limitation in terms of participants' demographic and illness characteristics.


The effect of a practical nutrition education programme on feeding skills of caregivers of children with cerebral palsy at Muhimbili National Hospital, in Tanzania.
Feeding children with cerebral palsy (CP) is challenging and can lead to poor health outcomes. Using a facility-based intervention, we assessed the effect of a practical nutrition programme on feeding skills in caregivers of children with CP attending a pediatric clinic in urban Tanzania. A randomized-controlled intervention study, involving 2-block stratified sample of under-5 CP children attending a specialized pediatric clinic at the Muhimbili National Hospital was done. One hundred ten moderate-to-severe, new and follow-up cases of children with CP were randomly allocated to the intervention (N = 63) and control groups (N = 47). A short nutrition education on feeding and positioning skills was provided to caregivers and occupational therapy sessions to CP children. Bivariate and multivariable logistic regression analyses of collected data were done. Statistical significance was assessed at p < .05. The intervention significantly improved feeding skills of caregiver in the select indicators assessed. More caregivers appropriately positioned the children (AOR = 5.29; 95% CI: 2.00-13.96), fed children slowly (AOR: 5.17, 95% CI: 1.99-13.44), and involved the child during the feeding process (AOR = 3.46; 95% CI: 1.42-8.44). During feeding, caregiver's reported being less stressed (AOR = 2.53, 95% CI: 1.04-6.13) and the child's mood was more likely to be reported as improved (AOR = 3.15, 95% CI: 1.33-7.474). Although changes were observed in oral motor feeding skills (AOR = 1.67; 95% CI: 0.72-3.91) and functional feeding skills (AOR = 2.28; 95% CI: 0.86-6.06), they did not reach statistical significance in the multivariable models. Strengthening nutrition education and services for caregivers of children with CP has great value in the care of children with special needs and may improve the health outcomes of children as well as reduce stress among parents/caregivers.


Relative Contribution of Seed Tuber- and Soilborne Inoculum to Potato Disease Development and Changes in the Population Genetic Structure of Rhizoctonia solani AG 3-PT under Field Conditions in South Africa.
Understanding the contribution of seed tuber- and soilborne inocula of Rhizoctonia solani AG 3-PT in causing potato disease epidemics is an important step in implementing effective management strategies for the pathogen. A 2-year study was conducted to evaluate the contribution of each source of inoculum using an integrative experimental approach combining field trials and molecular techniques. Two distinct sets of genetically marked isolates were used as seed tuberborne and soilborne inocula in a mark-release-recapture experiment. Disease assessments were done during tuber initiation and at tuber harvest. Both inoculum sources were found to be equally important in causing black scurf disease, whereas soilborne inocula appeared to be more important for root and stolon infection, and seedborne inocula contributed more to stem canker. However, seed tuber-transmitted genotypes accounted for 60% of the total recovered isolates when genotyped using three polymerase chain reaction restriction fragment length polymorphism markers. The changes in population structure of the experimental R. solani population over the course of the growing season and across two growing seasons were investigated using eight microsatellite markers. The populations at different sampling times were somewhat genetically differentiated, as indicated by Nei's gene diversity (0.24 to 0.27) and the fixation index (FST). The proportion of isolates with genotypes that differed from the inoculants ranged from 13 to 16% in 2013 and 2014, respectively, suggesting the possibility of emergence of new genotypes in the field. Because both soilborne and tuberborne inocula are critical, it is important to ensure the use of pathogen-free seed tubers to eliminate seed tuberborne inoculum and the introduction of new genotypes of R. solani for sustainable potato production in South Africa.


Selective targeting of MAPK family kinases JNK over p38 by rationally designed peptides as potential therapeutics for neurological disorders and epilepsy.
Human mitogen-activated protein kinase (MAPK) family members JNK and p38 are two homologous protein-serine/threonine kinases but play distinct roles in the pathological process of neurological disorders. Selective targeting of JNK over p38 has been established as a potential therapeutic approach to epilepsy and other nervous system diseases. Herein, we describe an integrated in vitro-in silico protocol to rationally design kinase-peptide interaction specificity based on crystal structure data. In the procedure, a simulated annealing (SA) iteration optimization strategy is described to improve peptide selectivity between the two kinases. The optimization accepts moderate compromise in peptide affinity to JNK in order to maximize the affinity difference between peptide interactions with JNK and p38. The structural basis, energetic properties and dynamic behavior of SA-improved peptides bound with the peptide-docking sites of JNK and p38 kinase domains are investigated in detail using atomistic molecular dynamics (MD) simulations and post binding free energy analysis. The theoretical findings and computational designs are then confirmed by fluorescence polarization assays. Using the integrated protocol we successfully obtain three decapeptide ligands, namely RLHPSMTDFL, RAKLPTSVDY and KPSRPWNLEI, that exhibit both potent affinity to JNK (K = 8.0, 5.4 and 12.1 μM, respectively) and high selectivity for JNK over p38 (K/K = 9.2, 17.9 and 6.3 fold, respectively). We also demonstrate that a JNK-over-p38 selective peptide should have a positively charged N-terminus, a polar central region and a negatively charged C-terminus, in which a number of hydrophobic residues distribute randomly along the peptide sequence. In particular, the residue positions 1, 6 and 9 play a crucial role in shaping peptide selectivity; the presence of, respectively, Arg, Thr and Asp at the three positions confers high specificity to kinase-peptide interactions.


5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.
Staphylococcus aureus (S. aureus) is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT), which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA), a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT) to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.


Metabolism of benzene in human liver microsomes: individual variations in relation to CYP2E1 expression.
In human liver microsomes the oxidations of benzene, chlorzoxazone, aniline, dimethylformamide, and 4-nitrophenol were significantly correlated with each other and with the level of cytochrome P450 (CYP) 2E1 estimated by immunoblotting. Moreover, benzene oxidation to water-soluble metabolites was suppressed by 0.1 mM diethyldithiocarbamate, supposedly a specific inhibitor of CYP2E1 at this level. None of these metabolic rates correlated with immunochemically determined levels of CYP1A2, 2C9, and 3A4 nor oxidation of 7-ethoxyresorufin, tolbutamide, and nifedipine. Benzene oxidation to water-soluble metabolites was characterized by typical Michaelis-Menten kinetics. The different benzene K(m) values seen in individual human microsomal samples were not correlated with the level or activity of CYP1A2, 2C9, 2E1, and 3A4 but could be due to CYP2E1 microheterogeneity. The lowest K(m) for benzene oxidation could be related to C/D and/or c1/c2 polymorphism of CYP2E1 gene. Covalent binding of benzene reactive metabolites to microsomal proteins was also correlated with the CYP2E1 metabolic rates and immunochemical levels. At high concentrations of benzene covalent binding was inversely related to benzene concentrations (as well as to formation of water-soluble metabolites) in agreement with the view that secondary metabolites, mainly benzoquinone, are responsible for the covalent binding.


Identification of novel genetic variants associated with short stature in a Baka Pygmies population.
Human growth is a complex trait determined by genetic factors in combination with external stimuli, including environment, nutrition and hormonal status. In the past, several genome-wide association studies (GWAS) have collectively identified hundreds of genetic variants having a putative effect on determining adult height in different worldwide populations. Theoretically, a valuable approach to better understand the mechanisms of complex traits as adult height is to study a population exhibiting extreme stature phenotypes, such as African Baka Pygmies. After phenotypic characterization, we sequenced the whole exomes of a cohort of Baka Pygmies and their non-Pygmies Bantu neighbors to highlight genetic variants associated with the reduced stature. Whole exome data analysis revealed 29 single nucleotide polymorphisms (SNPs) significantly associated with the reduced height in the Baka group. Among these variants, we focused on SNP rs7629425, located in the 5'-UTR of the Hyaluronidase-2 (HYAL2) gene. The frequency of the alternative allele was significantly increased compared to African and non-African populations. In vitro luciferase assay showed significant differences in transcription modulation by rs7629425 C/T alleles. In conclusion, our results suggested that the HYAL2 gene variants may play a role in the etiology of short stature in Baka Pygmies population.


Evaluation of the liver targeting and anti‑liver cancer activity of artesunate‑loaded and glycyrrhetinic acid‑coated nanoparticles.
Globally, liver cancer ranks among the most lethal cancers, with chemotherapy being one of its primary treatments. However, poor selectivity, systemic toxicity, a narrow treatment window, low response rate and multidrug resistance limit its clinical application. Liver-targeted nanoparticles (NPs) exhibit excellent targeted delivery ability and promising effectivity in treating liver cancer. The present study aimed to investigate the liver-targeting and anti-liver cancer effect of artesunate (ART)-loaded and glycyrrhetinic acid (GA)-decorated polyethylene glycol (PEG)-poly (lactic-co-glycolic acid) (PLGA) (ART/GA-PEG-PLGA) NPs. GA-coated NPs significantly increased hepatoma-targeted cellular uptake, with micropinocytosis and caveolae-mediated endocytosis as its chief internalization pathways. Moreover, ART/GA-PEG-PLGA NPs exhibited pro-apoptotic effects on HepG2 cells, mainly via the induction of a high level of reactive oxygen species, decline in mitochondrial membrane potential and induction of cell cycle arrest. Additionally, ART/GA-PEG-PLGA NPs induced internal apoptosis pathways by upregulating the activity of cleaved caspase-3/7 and expression of cleaved poly (ADP-Ribose)-polymerase and Phos-p38 mitogen-activated protein kinase in HepG2 cells. Furthermore, ART/GA-PEG-PLGA NPs exhibited higher liver accumulation and longer mean retention time, resulting in increased bioavailability. Finally, ART/GA-PEG-PLGA NPs promoted the liver-targeting distribution of ART, increased the retention time and promoted its antitumour effects in vivo. Therefore, ART/GA-PEG-PLGA NPs afforded excellent hepatoma-targeted delivery and anti-liver cancer efficacy, and thus, they may be a promising strategy for treating liver cancer.


Association of interleukin-18 gene polymorphism with susceptibility to visceral leishmaniasis in endemic area of Bihar, an Indian population.
Interleukin-18 (IL-18) is a cytokine that mediates Th1 response by inducing interferon-gamma (IFN-γ) production in T cells and natural killer cells. Genetic polymorphisms in the IL-18 gene have been found to be associated with its expression in cancer, tuberculosis, HBV infection, and various other diseases. Lower plasma level of IL-18 in visceral leishmaniasis (VL) patients might be associated with polymorphisms in the regulating or coding region of the gene. Three single nucleotide polymorphisms (SNPs), rs1946519 (-656 G/T) and rs187238 (-137 G/C) in the promoter region and rs549908 (+105 A/C) in the codon region, were genotyped in 204 parasitological confirmed VL patients and 267 controls with no past history of VL. For each locus, polymerase chain reaction (PCR) followed by restriction digestion was performed. IL-18 expression in peripheral blood mononuclear cells (PBMC) collected from VL patients and controls was measured by quantitative real-time RT-PCR. Distribution of G allele at position -656 (P < 0.0001) and double haplotypes GGC/GGA (P = 0.05) were found to be significantly associated with controls while genotypes TT (P < 0.0001) and single haplotypes TGA (P = 0.0002), with cases. The inheritance of G allele at the position -656 might be considered as a protective allele for VL.


Selection of effective cocrystals former for dissolution rate improvement of active pharmaceutical ingredients based on lipoaffinity index.
New theoretical screening procedure was proposed for appropriate selection of potential cocrystal formers possessing the ability of enhancing dissolution rates of drugs. The procedure relies on the training set comprising 102 positive and 17 negative cases of cocrystals found in the literature. Despite the fact that the only available data were of qualitative character, performed statistical analysis using binary classification allowed to formulate quantitative criterions. Among considered 3679 molecular descriptors the relative value of lipoaffinity index, expressed as the difference between values calculated for active compound and excipient, has been found as the most appropriate measure suited for discrimination of positive and negative cases. Assuming 5% precision, the applied classification criterion led to inclusion of 70% positive cases in the final prediction. Since lipoaffinity index is a molecular descriptor computed using only 2D information about a chemical structure, its estimation is straightforward and computationally inexpensive. The inclusion of an additional criterion quantifying the cocrystallization probability leads to the following conjunction criterions Hmix<-0.18 and ΔLA>3.61, allowing for identification of dissolution rate enhancers. The screening procedure was applied for finding the most promising coformers of such drugs as Iloperidone, Ritonavir, Carbamazepine and Enthenzamide.


Effective theory of Floquet topological transitions.
We develop a theory of topological transitions in a Floquet topological insulator, using graphene irradiated by circularly polarized light as a concrete realization. We demonstrate that a hallmark signature of such transitions in a static system, i.e., metallic bulk transport with conductivity of order e^{2}/h, is substantially suppressed at some Floquet topological transitions in the clean system. We determine the conditions for this suppression analytically and confirm our results in numerical simulations. Remarkably, introducing disorder dramatically enhances this transport by several orders of magnitude.


Acetohydroxyacid synthase, a novel target for improvement of L-lysine production by Corynebacterium glutamicum.
The influence of acetohydroxy acid synthase (AHAS) on L-lysine production by Corynebacterium glutamicum was investigated. An AHAS with a deleted C-terminal domain in the regulatory subunit IlvN was engineered by truncating the ilvN gene. Compared to the wild-type AHAS, the newly constructed enzyme showed altered kinetic properties, i.e., (i) an about twofold-lower K(m) for the substrate pyruvate and an about fourfold-lower V(max); (ii) a slightly increased K(m) for the substrate alpha-ketobutyrate with an about twofold-lower V(max); and (iii) insensitivity against the inhibitors L-valine, L-isoleucine, and L-leucine (10 mM each). Introduction of the modified AHAS into the L-lysine producers C. glutamicum DM1729 and DM1933 increased L-lysine formation by 43% (30 mM versus 21 mM) and 36% (51 mM versus 37 mM), respectively, suggesting that decreased AHAS activity is linked to increased L-lysine formation. Complete inactivation of the AHAS in C. glutamicum DM1729 and DM1933 by deletion of the ilvB gene, encoding the catalytic subunit of AHAS, led to L-valine, L-isoleucine, and L-leucine auxotrophy and to further-improved L-lysine production. In batch fermentations, C. glutamicum DM1729 Delta ilvB produced about 85% more L-lysine (70 mM versus 38 mM) and showed an 85%-higher substrate-specific product yield (0.180 versus 0.098 mol C/mol C) than C. glutamicum DM1729. Comparative transcriptome analysis of C. glutamicum DM1729 and C. glutamicum DM1729 Delta ilvB indicated transcriptional differences for about 50 genes, although not for those encoding enzymes involved in the L-lysine biosynthetic pathway.


Synthesis and in vitro evaluation of novel nortropane derivatives as potential radiotracers for muscarinic m(2) receptors.
Disturbances of the cerebral cholinergic neurotransmitter system are present in neurodegenerative disorders. SPECT or PET imaging, using radiotracers that selectively target muscarinic receptor subtypes, may be of value for in vivo evaluation of such conditions. 6β-acetoxynortropane, a potent muscarinic M(2) receptor agonist, has previously demonstrated nanomolar affinity and high selectivity for this receptor. Based on this compound we synthesized four nortropane derivatives that are potentially suitable for SPECT imaging of the M(2) receptor. 6β-acetoxynortropane and the novel derivatives were tested in vitro for affinity to the muscarinic M(1-3) receptors. The original 6β-acetoxynortropane displayed high affinity (K(i) = 70-90 nM) to M(2) receptors and showed good selectivity ratios to the M(1) (65-fold ratio) and the M(3) (70-fold ratio) receptors. All new derivatives showed reduced affinity to the M(2) subtype and loss of subtype selectivity. It is therefore concluded that the newly synthesized derivatives are not suitable for human SPECT imaging of M(2) receptors.


Diabetic nephropathy with interstitial nephritis presenting with a false-positive anti-GBM antibody.
A 56-year-old male with DM and HTN presented with flank pain and nausea. Review of systems was negative, physical examination was notable for mild hypovolemia and laboratory revealed BUN 51 mg/dl, creatinine (Cr) 5.1 mg/dl (baseline 1.5), Westergren ESR 122 mm/h, fractional excretion of sodium 0.2% and UA positive for blood and protein. Despite volume resuscitation the Cr continued to rise. Urine sediment analysis revealed granular casts, renal tubular epithelial cells and a negative Hansel's stain. Hemodialysis was initiated with Cr 13.7 mg/ dl for dyspnea and dysgeusia. Subsequent laboratory data revealed 2 separate positive anti-GBM antibody titers and prednisone therapy was initiated. Renal biopsy was performed for further diagnostic, therapeutic and prognostic information and demonstrated interstitial nephritis with linear IgG and albumin deposition consistent with diabetic nephropathy. Follow-up antibody titers were negative. prednisone was discontinued and Cr stabilized with conservative therapy. Anti-GBM antibody disease is characterized by circulating IgG antibodies directed against the glomerular basement membrane, specifically the alpha-3 (IV) collagen chain. Anti-GBM nephritis is a rapidly progressive, isolated glomerulonephritis in association with circulating anti-GBM antibodies. A positive immunofluorescence (IF) test is considered diagnostic in the appropriate clinical setting. Therapies include immunosuppressive agents to suppress new antibody production and plasmapheresis to eliminate circulating antibodies. Anti-GBM antibody is not rapidly cleared by steroid therapy and the recovery of renal function is rare if initiation Cr is greater than 7 mg/dl. This case demonstrates that the current ELISA for alpha-3 (IV) collagen is not pathognomonic for anti-GBM nephritis and that renal biopsy with IF for IgG and albumin may be indicated to prevent administration of potentially toxic treatment.


[Modified orbital decompression for severe thyroid associated ophthalmopathy].
To present a new technique for orbital decompression that minimizes surgical approaches while maximizing the removed areas of orbital walls and to evaluate the efficacy and safety of it for patients with severe thyroid associated ophthalmopathy (TAO). A retrospective review of 40 cases (66 eyes) with severe TAO undergoing the modified decompression between January 2009 and January 2011 was conducted. All patients were assigned to three groups, which were group CON: compressive optic neuropathy in 30 eyes, group MP: marked proptosis in 30 eyes, and group EK: exposure keratopathy in 6 eyes. The deep lateral, medial walls and orbital floor decompressions were underwent via an eyelid crease or a lateral sub-brow S-shape approach with a transcaruncular approach. Clinical outcomes were recorded including visual acuity, exophthalmometry, diplopia, clinical activity score (CAS) and CT scans before and 6 months after surgery. Intra- and postoperative complications were recorded. The postoperative visual acuity was improved in 17 eyes (56.7%, P < 0.05) of group CON. The mean proptosis reduction was (8.1 ± 2.7) mm (t = 11.73, P < 0.01) and (11.4 ± 3.1) mm (t = 15.52, P < 0.01) in group CON and group MP, respectively. The CAS was decreased in group CON (P < 0.01). Compared with preoperative records, the degree of diplopia was not significantly different in group CON (U = 131.0, P = 0.309) and group MP (U = 157.5, P = 0.881). Diplopia resolved in 7 cases (39%) of group CON, 5 cases (28%) of group MP. New-onset diplopia or its aggravation was recorded in 3 cases (17%) of group CON, 4 cases (22%) of group MP. The other postoperative improvement included recovered color vision, reduced intraocular pressure, and healing keratopathy. The important complications were intraoperative dural tears, new-onset diplopia and ocular inferior displacement. The modified orbital decompression offers wide exposure to the three orbital walls, marked proptosis reduction, and no apparent scar. It is efficacious and safety for the treatment of CON and inflammatory activity of TAO without serious complications, meanwhile, has little risk of induced diplopia.


5-Year trends in use of hallucinogens and other adjunct drugs among UK dance drug users.
To describe and assess trends in the use of hallucinogens and other adjunct drugs over a 5-year period. Repeated-measures cross-sectional survey. Annual magazine-based survey targeting people who use drugs in dance contexts. Lifetime use prevalence (ever used); age of first use; current use prevalence (any use within the last month), and extent of use within the last month (number of days used) for LSD, psilocybin, ketamine, GHB and nitrates. Prevalence increases for psilocybin, ketamine, GHB and nitrates use have been detected, with a sharp recent rise in current psilocybin use in 2002-2003 contrasting with more gradual and comprehensive evidence of increased ketamine use throughout the period 1999-2003. The declining prevalence of LSD use in general population surveys is replicated in this sentinel population study. The rise in prevalence of hallucinogen and other adjunct drugs identified among dance drug users may be mirrored by wider prevalence increases among young people with a consequent need to study these trends carefully and to develop effective interventions, where required.


[Decrease of the incidence of sepsis syndrome after early enteral nutrition of patients with severe burns].
The objective of this study was to evaluate the effect of early enteral nutrition on the incidence of the septic syndrome as well as its tolerance, in patients with severe burns. We retrospectively studied 64 patients older than 15 years of age, with a greater than 20% burned body surface area. They were divided into 2 groups as a function of the time elapsed between the beginning of Enteral Nutrition and the time of the burning: 23 patients were given Enteral Nutrition within 24 hours after the burn, and in 41 patients the enteral nutrition was started later than 24 hours after sustaining the thermal injury. Both groups were similar with respect to age, sex, percentage of 2nd and 3rd degree burns, incidence of inhalation, and deaths. All patients received the Enteral Nutrition through a nasogastric tube, with administration of a polymeric, hyperprotein and hypocaloric formula through a continuous infusion pump. In our study we saw a reduction of the incidence of the septic syndrome in the patients who received early enteral Nutrition (26%; 6 patients of a total of 23), with respect to those who did non receive early Enteral Nutrition (54%; 22 patients of a total of 41), with a statistical significance of p > 0.05. There were no differences between both groups with respect to the digestive tolerance to Enteral Nutrition. From our study we can deduce that early Enteral Nutrition reduces the incidence of septic complications, without this increasing the digestive intolerance to the same.


Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure.
Antiretroviral therapy (ART) has become more available throughout the developing world during the past 5 years. The World Health Organization recommends nonnucleoside reverse-transcriptase inhibitor-based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of human immunodeficiency virus (HIV)-1. There is no simple and efficient method to detect such mutations at the initiation of ART. One hundred eighty-one women who were participating in a clinical trial to prevent mother-to-child transmission and who started NVP-ART after they had received sdNVP or a placebo were included in the study. One hundred copies of each patient's HIV-1 DNA were tested for NVP-resistance point-mutations (K103N, Y181C, and G190A) with a sensitive oligonucleotide ligation assay that was able to detect mutants even at low concentrations (> or = 5% of the viral population). Virologic failure was defined as confirmed plasma HIV-1 RNA >50 copies/mL after 6 to 18 months of NVP-ART. At initiation of NVP-ART, resistance mutations were identified in 38 (26%) of 148 participants given sdNVP (K103N in 19 [13%], Y181C in 8 [5%], G190A in 28 [19%], and > or = 2 mutations in 15 [10%]), at a median 9.3 months after receipt of sdNVP. The risk of virologic failure was 0.62 (95% confidence interval [CI], 0.46-0.77) in women with > or = 1% resistance mutation, compared with a risk of 0.25 (95% CI, 0.17-0.35) in those without detectable resistance mutations (P < .001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load higher than the median at NVP-ART initiation. Access to simple and inexpensive assays to detect low concentrations of NVP-resistant HIV-1 DNA before the initiation of ART could help improve the outcome of first-line ART.


Local constraints in either the GluN1 or GluN2 subunit equally impair NMDA receptor pore opening.
The defining functional feature of N-methyl-d-aspartate (NMDA) receptors is activation gating, the energetic coupling of ligand binding into opening of the associated ion channel pore. NMDA receptors are obligate heterotetramers typically composed of glycine-binding GluN1 and glutamate-binding GluN2 subunits that gate in a concerted fashion, requiring all four ligands to bind for subsequent opening of the channel pore. In an individual subunit, the extracellular ligand-binding domain, composed of discontinuous polypeptide segments S1 and S2, and the transmembrane channel-forming domain, composed of M1-M4 segments, are connected by three linkers: S1-M1, M3-S2, and S2-M4. To study subunit-specific events during pore opening in NMDA receptors, we impaired activation gating via intrasubunit disulfide bonds connecting the M3-S2 and S2-M4 in either the GluN1 or GluN2A subunit, thereby interfering with the movement of the M3 segment, the major pore-lining and channel-gating element. NMDA receptors with gating impairments in either the GluN1 or GluN2A subunit were dramatically resistant to channel opening, but when they did open, they showed only a single-conductance level indistinguishable from wild type. Importantly, the late gating steps comprising pore opening to its main long-duration open state were equivalently affected regardless of which subunit was constrained. Thus, the NMDA receptor ion channel undergoes a pore-opening mechanism in which the intrasubunit conformational dynamics at the level of the ligand-binding/transmembrane domain (TMD) linkers are tightly coupled across the four subunits. Our results further indicate that conformational freedom of the linkers between the ligand-binding and TMDs is critical to the activation gating process.


Performance of modified first-stage French Vertical Flow Constructed Wetlands under extreme operational conditions.
Operation conditions considerably affect the removal efficiency of wastewater treatment systems, and yet we still lack data on how these systems function under extreme dilution rates and climatic conditions at high altitudes. Here, we applied two modified First-Stage French Vertical Flow Constructed Wetlands (FS-FVFCWs) for sewage treatment in Northern Tropical Andes. Specifically, within 18 months, we conducted a pilot-scale experiment at two hydraulic loading rates (HLRs) of 0.94 and 0.56 m d-1, representing 2.5 and 1.5 times the recommended design values, with two different feeding/resting periods to investigate the impact of HLRs and operational strategy on system performance. We found that chemical oxygen demand (COD) and total suspended solids (TSS) removal was satisfactory, with average values of 53 ± 18 and 69 ± 16%, respectively. Moreover, reducing HLRs resulted in higher removal efficiency for COD, from 46 ± 15 to 64 ± 15%, but had no impact on TSS removal, with 3 days of feeding and 6 days of resting. For an equal time of feeding and resting, COD and TSS removals were not affected by the modified HLR. These findings suggest that high HLRs can be applied to FS-FVFCW without compromising the system operation and obtaining satisfactory results, leading to opportunities to reduce areas and costs.


Morbidity and mortality of carotid endarterectomy under local anesthesia: a retrospective study.
It has been shown that carotid endarterectomy reduces the incidence of stroke in patients with symptomatic extracranial occlusive vascular disease in the absence of major perioperative complications such as stroke or death. We present a retrospective study of 106 carotid endarterectomies performed under local anesthesia in 100 patients in whom transient ischemic attack (TIA) or minor stroke had occurred. Nonfatal stroke occurred in 2%, and TIA occurred in 1%. There was no perioperative mortality. Our study suggests that, under local anesthesia, even high risk patients can be operated safely and the majority of carotid endarterectomies can be performed without the use of an indwelling shunt. Meticulous surgical technique is of great importance for achieving low perioperative complications.


[The depression ward--a review of the current status].
New therapeutic concepts are usually developed and realised step by step. Over the past years changes occurred mainly in two ways. There is a trend to reduce the size of the psychiatric hospital as such and/or to section off certain areas by introducing specialised units. From the experience with the so called "Affective Disorder Units" or "Mood Clinics" developed the concept of a Depression Unit, first introduced in Europe for research purposes at the Psychiatric University Hospital in Basle in 1968. In Germany the first Depression Unit was established at the PLK Weissenau in 1976. Similar units followed over the years at the PLK Reichenau, Weinsberg, the BKH Günzburg, the Landesklinik Nordschwarzwald Hirsau/Calw and the Rheinische Landesklinik Bedburg-Hau, other hospitals are planning them. Existing units are described in terms of their structural organisation, staffing situation and the service they provide. The concept of the Depression Unit according to criteria laid down agreed upon in the literature is summed up, and emotional atmosphere, structural organisation, activation, and individual therapeutic measures, discussed. Advantages are mentioned such as better understanding of patients, allowing them to let go and be cared for, aimed regression, the effects of being taken along, improved communication, and a way of dealing with suicidal thoughts and depressive behavior that reduces anxiety. Disadvantages such as the danger of spoiling patients or inducing a sense of resignation both in patients and staff are discussed.


Generalized Net Model of the Foreign Object Principle and its Network Physiology Interpretations.
The Foreign Object Principle has been introduced in a formalized form for first time. Proven as a suitable tool for modelling of parallel processes flowing in real time, the generalized nets have been used for an interpretation of the Foreign Object Principle. It is illustrated by some examples from network physiology.


Lipopolysaccharide Biosynthesis Genes of Yersinia pseudotuberculosis Promote Resistance to Antimicrobial Chemokines.
Antimicrobial chemokines (AMCs) are a recently described family of host defense peptides that play an important role in protecting a wide variety of organisms from bacterial infection. Very little is known about the bacterial targets of AMCs or factors that influence bacterial susceptibility to AMCs. In an effort to understand how bacterial pathogens resist killing by AMCs, we screened Yersinia pseudotuberculosis transposon mutants for those with increased binding to the AMCs CCL28 and CCL25. Mutants exhibiting increased binding to AMCs were subjected to AMC killing assays, which revealed their increased sensitivity to chemokine-mediated cell death. The majority of the mutants exhibiting increased binding to AMCs contained transposon insertions in genes related to lipopolysaccharide biosynthesis. A particularly strong effect on susceptibility to AMC mediated killing was observed by disruption of the hldD/waaF/waaC operon, necessary for ADP-L-glycero-D-manno-heptose synthesis and a complete lipopolysaccharide core oligosaccharide. Periodate oxidation of surface carbohydrates also enhanced AMC binding, whereas enzymatic removal of surface proteins significantly reduced binding. These results suggest that the structure of Y. pseudotuberculosis LPS greatly affects the antimicrobial activity of AMCs by shielding a protein ligand on the bacterial cell surface.


A randomised trial of cisplatin and vindesine versus supportive care only in advanced non-small cell lung cancer.
The value of chemotherapy in advanced non-small cell lung cancer (NSCLC) remains contentious. Because of this two separate but very similar trials were set up in Australia and Southampton (UK). Two hundred and one patients with stage IIIb or IV NSCLC were randomly assigned to cisplatin 120 mg m-2 on days 1 and 29 and vindesine 3 mg m-2 weekly x 6 or to no chemotherapy. Both groups were eligible to receive radiotherapy or other palliative treatment as required. Of 188 evaluable patients, 97 received chemotherapy and 91 were in the control arm. Response was assessed between days 42 and 49. Responders continued chemotherapy at the same doses though cisplatin being given 6 weekly x 4 and the vindesine 2 weekly x 12. The overall response rate to chemotherapy was 28%; there were no significant differences according to major prognostic criteria. Although the overall survival of the chemotherapy group (median 27 weeks) was longer than that of the no chemotherapy group (median 17 weeks) this was not statistically significant (log rank P = 0.33). For patients without dissemination (IIIb), median survival was 45 weeks in the chemotherapy arm and 26 weeks in the non-chemotherapy (log rank P = 0.075). Toxicity was universal and frequently severe: of 17 patients discontinuing chemotherapy after one cycle, 13 did so because of unacceptable toxicity. This chemotherapy cannot be recommended as routine treatment. Further phase III studies of chemotherapy in advanced NSCLC should continue to use a no chemotherapy control and should also attempt to measure quality of life, an issue not addressed effectively in this or other recent trials.