Full-Dimensional Quantum Dynamics of SiO in Collision with H2.
We report the first full-dimensional potential energy surface (PES) and quantum mechanical close-coupling calculations for scattering of SiO due to H2. The full-dimensional interaction potential surface was computed using the explicitly correlated coupled-cluster (CCSD(T)-F12b) method and fitted using an invariant polynomial approach. Pure rotational quenching cross sections from initial states v1 = 0, j1 = 1-5 of SiO in collision with H2 are calculated for collision energies between 1.0 and 5000 cm-1. State-to-state rotational rate coefficients are calculated at temperatures between 5 and 1000 K. The rotational rate coefficients of SiO with para-H2 (p-H2) are compared with previous approximate results which were obtained using SiO-He PESs or scaled from SiO-He rate coefficients. Rovibrational state-to-state and total quenching cross sections and rate coefficients for initially excited SiO (v1 = 1, j1 = 0 and 1) in collisions with p-H2 (v2 = 0, j2 = 0) and ortho-H2 (o-H2) (v2 = 0, j2 = 1) are also obtained. The application of the current collisional rate coefficients to astrophysics is briefly discussed.


Herpesviruses and AIDS.
It is well recognized clinically that herpesviruses can cause disease in AIDS patients once human immunodeficiency virus (HIV) has precipitated marked immunosuppression. However, in addition to this opportunistic relationship, there is evidence to suggest that herpesviruses could increase the pathogenicity of HIV by acting as cofactors. Experiments in vitro have shown that several herpesviruses can activate HIV gene expression or alter the cellular tropism of HIV through a variety of mechanisms (antigen presentation, cytokine release, pseudotype formation, CD4 cell surface upregulation, Fc receptor formation, transactivation). Studies of human autopsy material have shown that some herpesviruses (particularly cytomegalovirus, human herpes virus 6 and herpes simplex virus) are found frequently in AIDS patients. If such herpesviruses act as cofactors in vivo, then their inhibition by aciclovir could explain why a survival benefit has been reported from the use of this drug in two double-blind, placebo-controlled randomized trials.


Visualization of polydnavirus sequences in a parasitoid wasp chromosome.
Polydnaviruses, obligatorily associated with endoparasitoid wasps, are unique in that their segmented genome is composed of multiple double-stranded DNA circles. We present here the first cytological evidence that virus segments are integrated in the wasp genome, obtained by using in situ hybridization of virus probes with viral sequences in the chromosomes of a wasp from the braconid family of hymenopterans.


Rich at risk: socio-economic drivers of COVID-19 pandemic spread.
COVID-19, the novel coronavirus affecting the most part of worldwide countries since early 2020, is fast increasing its prevalence around the world, representing a significant emergency for the population and the health systems at large. While proper treatments are being developed, in-depth studies concerning its way of diffusion are necessary, in order to understand how the virus is actually spreading, through the investigation on some socio-economic indicators for the various countries in the world, retrieved through open-access data publicly available. The correlation analysis displayed significant relationships between COVID-19 incidence with several of such indicators, including the Gross Domestic Product per capita and the number of flights per capita, whereas mortality is mainly related to the main age of the population. All such data displayed an interesting mean to understand the way the virus has diffused worldwide, possibly representing the basis for future preventive measures to effectively challenge a new COVID-19 pandemic wave, but also other, similar pandemics.


Hypertension in the elderly: conventional wisdom revisited.
Elevated systolic and/or diastolic blood pressure in the elderly is a problem the extent of which may be somewhat overstated. In those elderly with definite hypertension, pathophysiology may differ from that of younger counterparts. The contribution of elevated plasma renin activity to hypertension and to the choice of therapy also appears to be exaggerated. The risks of ignoring hypertension in the elderly are similar to those in younger patients, and therefore excessively elevated blood pressure should no longer be considered a normal consequence of aging. Notably, elevated systolic pressure is a better predictor of future adverse occurrences than is elevated diastolic pressure. Unfortunately, there is no well defined therapeutic regimen to manage isolated systolic hypertension. Conservative reduction of elevated systolic and diastolic pressures may nevertheless be accomplished safely and effectively. Individualization of therapy is recommended based primarily on concomitant disease(s). Thus no single agent or combination of agents is preferable in all elderly hypertensive patients. Aggressive use of non-pharmacologic therapy preferably precedes judicious of antihypertensive medication. Aggressive blood pressure reduction with potent drugs is not recommended.


Relapsing polychondritis with different types of ocular inflammations.
We were presented with two cases of relapsing polychondritis (RP) associated with different types of ocular inflammation. The first case was a 35-year-old man who had bilateral hyperemic conjunctiva and ocular pain, and was referred to Chiba University Hospital with a diagnosis of episcleritis refractory. He was treated with dexamethasone eye drops. He developed tinnitus, deafness in both ears, and left auriculitis. A left auricular biopsy showed an infiltration of lymphocytes surrounding the cartilage. He was diagnosed with RP and treated with 30 mg/day oral prednisolone. After tapering the prednisolone, the scleritis in both eyes improved. The second case was a 71-year-old man who was deaf in both ears and had bilateral scleritis. At the first visit to our hospital, his left eyelid and right auricula were reddish and swollen, and he reported some pain. He was treated with intravenous antibiotics, and the left orbital cellulitis quickly improved. However, he developed right scleritis and left gonitis. Magnetic resonance imaging showed bilateral posterior scleritis and right auricular perichondritis. Auricular biopsy showed an infiltration of lymphocytes into the periauricular tissue. He was diagnosed with RP, and 40 mg/day oral prednisolone was given and his symptoms improved. Although RP is rare, it is a life-threatening disease. Thus, ophthalmologists should consider RP in patients with both ocular and auricular inflammation.


Hydrothermal synthesis of ionic liquid [Bmim]OH-modified TiO2 nanoparticles with enhanced photocatalytic activity under visible light.
TiO(2) nanocomposites modified with the ionic liquid [Bmim]OH are synthesized by a hydrothermal procedure. X-ray diffraction, Zeta-potential measurement, TEM, thermogravimetric analysis, photoluminescence, UV/Vis, FTIR, and X-ray photoelectron spectroscopy are used to characterize the TiO(2) nanocomposites. The TiO(2) nanocomposites consist of pure anatase particles of about 10 nm. The modification of [Bmim]OH on the surface of the TiO(2) particles extends the TiO(2) absorption edge to the visible-light region. The electrochemical redox potentials indicated that the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of [Bmim]OH match well with the valence band (VB) and conduction band (CB) of the TiO(2) semiconductor. [Bmim]OH-modified TiO(2) is much more active than pristine TiO(2) under visible-light irradiation in the photocatalytic degradation of methylene blue in aqueous solution. [Bmim]OH is chemically bonded to the surface Ti-OH of TiO(2) particles rather than adsorbed on the surface. A possible mechanism for the photocatalysis is proposed.


GENETIC BASIS OF INBREEDING DEPRESSION IN ARABIS PETRAEA.
Inbreeding depression may be caused by (partially) recessive or overdominant gene action. The relative evolutionary importance of these two modes has been debated; the former mode is emphasized in the "dominance hypothesis," the latter in the "overdominance hypothesis." We analyzed the genetic basis of inbreeding depression in the self-incompatible herb Arabis petraea (L.) Lam.: In the selfed progeny of twelve parental plants, we studied the proportion of chlorophyll-deficient seedlings, the genotypic distributions of marker genes, and associations of marker genotypes with viability and quantitative traits. Early components of fitness were examined by scoring seed size, germination time, and early growth rate and by observing the proportion of chlorophyll-deficient seedlings. Later components of fitness, flowering, and root and aboveground biomass were also measured. Marker genotypes of young seedlings were scored for 11 enzyme loci and three microsatellite markers. We found a high proportion (about 70%) of families with chlorophyll-deficient seedlings, indicating a high mutational load. We found six significant deviations from 1:2:1 ratio at marker loci of 60 tests in seedlings, with three of these significant at the experimentwide level. Deviations from the expected ratio were assumed to be due to linked viability loci. A graphical and a Bayesian method were used to distinguish between the overdominance and dominance hypotheses. Most of the deviant segregation ratios suggested overdominance instead of recessivity of the deleterious allele. Neither the early (seed size, germination time, or early growth trait) nor the late quantitative traits (flowering, and root and aboveground biomass) showed significant linkage to markers at the experimentwide level. Presence of significant associations between markers and early viability, but lack thereof for quantitative traits expressed late, suggests either that there may be relatively low inbreeding depression in later life stages or that individual quantitative trait loci may have smaller effects than loci contributing to early viability.


All-cause and circulatory disease-related hospitalization, by generation status: Evidence from linked data.
Immigrants tend to have better health than the Canadian-born. However, the "healthy immigrant" effect diminishes over time and varies by source country. This study examines whether lower hospitalization rates persist from the first (G1) to the second generation (G2) of immigrants, compared with other Canadians (G3+). All-cause and circulatory disease-related hospitalization rates were examined by generation, with special attention to people of Chinese and South Asian descent. Data from the 2006 Census-hospitalization linkage database (which excludes Quebec) were analysed using logistic regression. Age-standardized all-cause (excluding pregnancy) and circulatory disease-related hospitalization rates were derived for the urban population aged 30 or older for the 2006/2007 to 2008/2009 fiscal years. Over the generations, immigrants' all-cause and circulatory disease-related hospitalization rates converged with those of the Canadian population overall. Compared with G3+, the age-adjusted odds of all-cause hospitalization among men were 0.49 (CI = 0.48-0.51) for recent G1 immigrants, 0.78 (CI = 0.77-0.79) for long-term G1 immigrants, and 0.95 (CI = 0.94-0.97) for G2. Adjustments for socioeconomic status reduced the difference, especially between G2 and G3+. For South Asians, rates converged for circulatory disease, notably among men. Hospitalization rates for people of Chinese descent rose across generations, but remained significantly below rates for G3+. The lower circulatory disease-related hospitalization risk experienced by G1 is maintained in G2 among people of Chinese descent, but not among South Asians.


Impact of gas injection on the apparent viscosity and viscoelastic property of waste activated sewage sludge.
Gas injection is known to play a major role on the particle size of the sludge, the oxygen transfer rate, as well as the mixing efficiency of membrane bioreactors and aeration basins in the waste water treatment plants. The rheological characteristics of sludge are closely related to the particle size of the sludge floc. However, particle size of sludge floc depends partly on the shear induced in the sludge and partly on physico-chemical nature of the sludge. The objective of this work is to determine the impact of gas injection on both the apparent viscosity and viscoelastic property of sludge. The apparent viscosity of sludge was investigated by two methods: in-situ and after sparging. Viscosity curves obtained by in-situ measurement showed that the apparent viscosity decreases significantly from 4000 Pa s to 10 Pa s at low shear rate range (below 10 s-1) with an increase in gas flow rate (0.5LPM to 3LPM); however the after sparging flow curve analysis showed that the reduction in apparent viscosity throughout the shear rate range is negligible to be displayed. Torque and displacement data at low shear rate range revealed that the obtained lower apparent viscosity in the in-situ method is not the material characteristics, but the slippage effect due to a preferred location of the bubbles close to the bob, causing an inconsistent decrease of torque and increase of displacement at low shear rate range. In linear viscoelastic regime, the elastic and viscous modulus of sludge was reduced by 33% & 25%, respectively, due to gas injection because of induced shear. The amount of induced shear measured through two different tests (creep and time sweep) were the same. The impact of this induced shear on sludge structure was also verified by microscopic images.


Bridging From the Picker Hospital Survey to the CAHPS Hospital Survey.
Illustrate an accessible method of bridging data from earlier surveys to the CAHPS Hospital Survey to support hospitals' internal quality improvement efforts. Survey of patients with more than 300,000 annual hospitalizations in a large urban hospital. STUDY DESIGN AND DATA: Six pairs of parallel items from the CAHPS and Picker Hospital Surveys were administered to the same 734 patients. We assessed item comparability and applied bridging adjustments to convert old items to predicted scores on the new CAHPS items. Differences in wording, response options, and cut points for "problem scores" yielded large differences in problem score rates between the Picker and CAHPS Hospital Surveys, requiring bridging formulas. Tetrachoric correlations for 5 of 6 pairs indicated high correspondence (r = 0.71-0.97, P < 0.001) in the underlying constructs assessed by the 2 surveys, validating the use of bridging. Bridged scores contain less information per observation than directly measured new scores, but with sufficient sample sizes they can be used to detect trends across the transition. Hospitals can use the methodology described here to trend their scores from a previous survey to the CAHPS Hospital Survey with sufficient precision to support ongoing quality improvement efforts. Hospitals should administer an instrument containing pairs of old and new items to enough patients to yield at least 625 completes to measure bridging parameters precisely. Where correspondence is high, old items can and should be replaced by CAHPS items. Important old items with weaker associations with new items may be retained.


[Expression of recombinant plasmid of HIV-1 gp120 and IFN-gamma in E. coli and its immunoregulatory effect].
To investigate the regulating effect of interferon-gamma (IFN-gamma) gene on the immune response induced by human immunodeficiency virus (HIV) gp120 in mice. The recombinant prokaryotic plasmid pet44b with HIV-1gp120 N and pet44b with HIV-1gp120 N linking IFN-gamma were constructed and expressed in E. coli BL21 (DE3) through IPTG. The purified proteins gp120 N and gp120 N/IFN-gamma were used in the following experiments: mice were injected with PBS i. s as control group 1, injected i. s with gp120 N as control group 2, and injected i. s with gp120 N/IFN-gamma as experiment group. The serum samples and spleen cells were collected 2 weeks after completion of immune program.T cells enlargement stimulated by gp120, CTL test and the detection of Th1 cytokines (SKs) IL-2, IFN-gamma and Th2 CKs IL-4, IL-10 were performed. SDS-PAGE and Western blot confirmed that gp120 N and gp120 N/IFN-gamma fusion proteins were successfully expressed. The immune experiments showed that the enlargement of specific T lymphocytes, the response of CTL and the expression of Th1 type CKs IL-2 and IL-gamma against gp120 were significantly different among the three groups (P < 0.05). And the response of gp120 N/IFN-gamma group was stronger than that of gp120 N group, the latter was stronger than that of PBS group (P < 0.05). The differences in expression of Th2 type CKs IL-4 and IL-10 were not significant among the three groups (P >0.05). The cell specific immune responses of BALB/c mice to HIV-1CNgp120 antigen can be enhanced when HIV-1CNgp120 gene and IFN-gamma gene are used in coordination.


Exercise-induced modifications in cardiorespiratory parameters of hypertensive patients treated with calcium antagonists.
The effects of calcium antagonists in reducing blood pressure at rest and during exercise were examined in patients with mild-to-moderate essential hypertension. The haemodynamic effects of calcium antagonists were evaluated at rest and during exercise. We also examined 10 patients with mild-to-moderate essential hypertension taking lacidipine, a new dihydropyridine calcium antagonist (4 mg once a day, at 0700 h). Compared with placebo, lacidipine induced significant mean reductions in 24-h blood pressure (P less than 0.001 for systolic blood pressure; P less than 0.002 for diastolic blood pressure). After 24 h, the blood pressure reductions were still significant (P less than 0.02 for systolic blood pressure; P less than 0.04 for diastolic blood pressure). The heart rate did not change. During dynamic exercise, blood pressure at maximal effort was reduced (P less than 0.01 for systolic and diastolic blood pressure) and the external workload reached at the anaerobic threshold was significantly increased (P less than 0.001), but not at maximum effort. Ventilation and tidal volume were similar at both the anaerobic threshold and peak exercise, while oxygen uptake and carbon dioxide production were increased at the anaerobic threshold (P less than 0.02 for carbon dioxide production) but were similar at peak exercise.


Inhibition of human bronchial kallikrein in asthma.
Human bronchial kallikrein (HBK) is the major kinin-generating enzyme in the airways of asthmatic subjects. We examined the in vitro inhibition of HBK and its in vivo regulation in asthma. HBK kininogenase activity was measured by cleavage of radiolabeled purified high molecular weight kininogen (HMWK) (125I HMWK). Functional inhibition of the enzyme was present after co-incubation with either normal human plasma (NHP) or preparations of alpha-1-proteinase inhibitor (alpha 1-PI). Stable HBK inhibitor complex was detected at 92 K by immunoblotting employing anti-HUK as a probe. Anti alpha 1-PI probes did not demonstrate the 92 K complex under identical conditions, raising the possibility of an additional co-purifying protein involved in HBK binding. alpha 1-PI antigenic and activity levels were measured in asthmatic bronchoalveolar lavage (BAL) fluid. In only a single sample of the six examined was alpha 1-PI activity detected. In two of the remaining five samples, low levels of alpha 1-PI antigen were present which were functionally inactive. In the BAL fluid containing alpha 1-PI activity, progressive functional inhibition of kininogenase activity correlating with HBK inhibitor complex formation occurred during BAL fluid incubation. In contrast, BAL fluid lacking alpha 1-PI activity failed to show progressive kininogenase inhibition or complex formation under identical conditions. In all experiments, the time course of HBK inhibitor interaction was markedly prolonged, requiring 150-min co-incubation with either NHP or the alpha 1-PI preparation for greater than 80% inhibition of function and near maximal complex formation. The slow rate of inhibition of HBK may allow for its continued activity and kinin generation in the airways of asthmatic subjects.


Lipoblastoma in children: an analysis of 5 cases.
Lipoblastoma is a very rare benign tumour that is caused by embryonal fat. The present five cases of lipoblastoma operated on during the years 1996-2005. The localization of the lipoblastomas in our series were very unusual. A six-monthold girl with giant mediastinal lipoblastoma; a two-year old boy with very rare lipoblastoma of the kidney; a three-year old boy with mesenterial lipoblastoma; a seven-year old boy with mesenterial lipoblastoma; and an eight-week old girl with perineal localization. Histological diagnosis can be difficult. The basic differential diagnosis is to be made between lipoblastoma, myxoid, and round cell liposarcoma. In our sample group of patients all lipoblastomas were successfully and completely removed and we did not see any recurrence of the tumours. In only one case was more radical surgery needed. One patient with mesenterial lipoblastoma had to undergo a 30 cm long resection of the small intestine.


[Long-term survival of patients operated on for carcinoma of the lung (author's transl)].
The long-term fate of patients treated surgically for carcinoma of the lung is not well known. In a careful review of the literature the authors found only nine papers with a postoperative followup of at least 10 years; the mean survival was 16,3% of patients so treated. Factors making for a good long-term prognosis include small initial tumor size, absence of mediastinal lymph node invasion, a favorable histologica type, and the type of surgery performed (partial exeresis). Translated into TNM code, this means that the best candidates for prolonged survival are patients with lung carcinoma of the squamous cell type, stage I, treated by limited lung exeresis.


Calibration and validation of a MCC/IMS prototype for exhaled propofol online measurement.
Propofol is a commonly used intravenous general anesthetic. Multi-capillary column (MCC) coupled Ion-mobility spectrometry (IMS) can be used to quantify exhaled propofol, and thus estimate plasma drug concentration. Here, we present results of the calibration and analytical validation of a MCC/IMS pre-market prototype for propofol quantification in exhaled air. Calibration with a reference gas generator yielded an R2≥0.99 with a linear array for the calibration curve from 0 to 20 ppbv. The limit of quantification was 0.3 ppbv and the limit of detection was 0.1 ppbv. The device is able to distinguish concentration differences >0.5 ppbv for the concentration range between 2 and 4 ppbv and >0.9 ppbv for the range between 28 and 30 ppbv. The imprecision at 20 ppbv is 11.3% whereas it is 3.5% at a concentration of 40 ppbv. The carry-over duration is 3min. The MCC/IMS we tested provided online quantification of gaseous propofol over the clinically relevant range at measurement frequencies of one measurement each minute.


Anti-inflammatory and antinociceptive effects, and safety toxicological profile of a new paracetamol analog, LQFM291.
In the scope of a research program with the goal of developing treatments for inflammatory diseases, the pharmacological evaluation of LQFM291, designed by molecular hybridization from butylated hydroxytoluene and paracetamol, was described. The antioxidant profile of LQFM291 was evaluated by electrochemical measurement. Also, acute or repeated treatments with equimolar doses to paracetamol were used to evaluate the antinociceptive and/or anti-inflammatory activities of LQFM291 in animal models. The toxicologic potential of LQFM291 was also evaluated and compared to paracetamol through biochemical and histopathological analysis after the repeated treatment schedule. As a result of the acute treatment, paracetamol showed a similar antinociceptive effect in formalin test compared to LQFM291. Whereas, after the repeated treatment, when carrageenan-induced hyperalgesia and edema tests were performed, paracetamol showed a delayed antinociceptive and anti-inflammatory effect compared to LQFM291. Furthermore, as other advantages the LQFM291 showed a high redox capacity, a gastroprotective activity and a safety pharmacological profile without any liver or kidney damage. These effects can be related to the prevention of oxidative stress by reduction of protein and lipid peroxidation in gastric tissue, maintenance of glutathione levels in hepatic homogenate, and a systemic reduction of pro-inflammatory cytokine levels, which may characterize the LQFM291 as a more viable and effective alternative to relief pain and inflammatory signs in patients with chronic disorders.


Rapid, time-division multiplexed, direct absorption- and wavelength modulation-spectroscopy.
We present a tunable diode laser spectrometer with a novel, rapid time multiplexed direct absorption- and wavelength modulation-spectroscopy operation mode. The new technique allows enhancing the precision and dynamic range of a tunable diode laser absorption spectrometer without sacrificing accuracy. The spectroscopic technique combines the benefits of absolute concentration measurements using calibration-free direct tunable diode laser absorption spectroscopy (dTDLAS) with the enhanced noise rejection of wavelength modulation spectroscopy (WMS). In this work we demonstrate for the first time a 125 Hz time division multiplexed (TDM-dTDLAS-WMS) spectroscopic scheme by alternating the modulation of a DFB-laser between a triangle-ramp (dTDLAS) and an additional 20 kHz sinusoidal modulation (WMS). The absolute concentration measurement via the dTDLAS-technique allows one to simultaneously calibrate the normalized 2f/1f-signal of the WMS-technique. A dTDLAS/WMS-spectrometer at 1.37 µm for H2O detection was built for experimental validation of the multiplexing scheme over a concentration range from 50 to 3000 ppmV (0.1 MPa, 293 K). A precision of 190 ppbV was achieved with an absorption length of 12.7 cm and an averaging time of two seconds. Our results show a five-fold improvement in precision over the entire concentration range and a significantly decreased averaging time of the spectrometer.


Rotavirus gastroenteritis hospitalisations following introduction of vaccination, Canberra.
To determine the effect of rotavirus vaccination on rotavirus hospitalisations in children under 5 years of age at The Canberra Hospital, Australian Capital Territory. Rotavirus hospitalisations in children under 5 years of age at the Canberra Hospital were identified through a retrospective clinical audit of electronic medical hospitalisations in the pre-vaccine (2004-2006) and post-vaccine (2008-2012) periods. Records and confirmation with rotavirus pathology results were compared using MS Excel and Stata. Laboratory confirmed rotavirus infections resulted in 289 children being admitted to the Canberra Hospital between January 2004 and December 2012. Hospitalisation for rotavirus gastroenteritis decreased by 76% in the 5 years following vaccine introduction compared with pre-vaccine periods. Seasonal patterns of hospitalisation were prominent in pre-vaccine periods but were attenuated post-vaccine. The greatest decreases in hospitalisation between pre- and post-vaccine periods were observed in the 12-23 (80%) and 24-35 (88%) month age categories. Decreases in hospitalisation were reported for patients unlikely to have received vaccine cover at that time, indicating an indirect protective effect of rotavirus vaccine. This study reports significant reductions in rotavirus hospitalisation of children under 5 years of age at The Canberra Hospital following vaccine introduction, mid-2007. These findings support rotavirus vaccination as an effective measure to reduce hospitalisation in children under 5 years of age.


How Are You Feeling? Interpretation of Emotions through Facial Expressions of People Wearing Different Personal Protective Equipment: An Observational Study.
(1) Background: The perception of others' emotions based on non-verbal cues, such as facial expressions, is fundamental for interpersonal communication and mutual support. Using personal protection equipment (PPE) in a work environment during the SAR-CoV-2 pandemic challenged health professionals' ability to recognise emotions and expressions while wearing PPE. The working hypothesis of this study was that the increased limitation of facial visibility, due to the use of a personal protective device, would interfere with the perception of basic emotions in the participants. (2) Methods: Through a cross-sectional descriptive study, the present research aimed to analyse the identification of four basic emotions (happiness; sadness; fear/surprise; and disgust/anger) through three types of PPE (FFP2 respirator, protective overall and powered air-purifying respirator (PAPR)), by using 32 photographs. The study was conducted using volunteer participants who met the inclusion criteria (individuals older than 13 without cognitive limitations). Participants had to recognise the emotions of actors in photographs that were randomly displayed in an online form. (3) Results: In general, the 690 participants better recognised happiness and fear, independently of the PPE utilised. Women could better identify different emotions, along with university graduates and young and middle-aged adults. Emotional identification was at its worst when the participants wore protective overalls (5.42 ± 1.22), followed by the PAPR (5.83 ± 1.38); the best scores were obtained using the FFP2 masks (6.57 ± 1.20). Sadness was the least recognised emotion, regardless of age. (4) Conclusions: The personal protective devices interfere in the recognition of emotions, with the protective overalls having the greatest impact, and the FFP2 mask the least. The emotions that were best recognised were happiness and fear/surprise, while the least recognised emotion was sadness. Women were better at identifying emotions, as well as participants with higher education, and young and middle-aged adults.


Nutritional awareness of pregnant women and the underlying influencing factors.
Nutritional awareness is described as having knowledge or understanding of nutrition. It is often related to the ability of an individual to make an accurate estimate of their food intake, which involves comparing their actual nutritional behavior with the recommended food consumption. Nutritional awareness of women during the various phases of pregnancy may vary significantly across countries due to cultural and lifestyle differences. There has been extensive research on nutritional awareness of pregnant women in selected countries or regions; however, relatively few studies have explored it during different stages of pregnancy. To fill this gap, this article reviews the existing literature and draws together insights into the following areas: changes in nutritional awareness during various phases of pregnancy, nutritional awareness of pregnant women and its underlying factors in various nations, and the research methods used to study nutritional awareness of pregnant women.


Autophagy and Exosome Coordinately Enhance Macrophage M1 Polarization and Recruitment in Influenza A Virus Infection.
Influenza A virus infection results in viral pneumonia, which is often accompanied by the infiltration and recruitment of macrophages, overactivation of inflammatory responses, and obvious cell autophagy and exosome production. However, little is known about the roles of autophagy and exosome production in these inflammatory responses. In this study, multiple methods, such as flow cytometry, real-time quantitative reverse transcription-polymerase chain reaction, immune-fluorescence technology, and western blot, were applied to explore the possible effects of autophagy and exosome production by H1N1-infected host cells. It was observed that a high number of polarized macrophages (CD11b+/F4/80+/CD86+) were recruited to the lung tissues of infected mice, which could be mimicked by tracking the movement of macrophages to H1N1-infected cells in vitro (transwell assays). Furthermore, there was some coordinated upregulation of M1 polarization signs (iNOS/Arg-1 bias) as well as autophagy (LC3) and exosome (CD63) biomarkers in the infected macrophages and epithelial cells. Moreover, exosomes extracted from the supernatant of virus-infected cells were shown to promote the recruitment and polarization of more peritoneal macrophages than the normal group. The fluorescence colocalization of LC3-CD63 and the inhibition of autophagy and exosome signaling pathway further revealed that H1N1 infection seemed to sequentially activate the M1 polarization and recruitment of macrophages via autophagy-exosome dependent pathway. Autophagy and exosome production coordinately enhance the M1 polarization and recruitment of macrophages in influenza virus infection, which also provides potential therapeutic targets.


Simultaneous determination of multiple active components in rat plasma using ultra-fast liquid chromatography with tandem mass spectrometry and application to a comparative pharmacokinetic study after oral administration of Suan-Zao-Ren decoction and Suan-Zao-Ren granule.
Suan-Zao-Ren decoction has been used to treat insomnia for many years. In this work, a rapid and sensitive ultra-fast liquid chromatography with tandem mass spectrometry method was first developed and fully validated for the simultaneous quantification of seven main active components, spinosin, mangiferin, neomangiferin, ferulic acid, liquiritin, isoliquiritin, and liquiritin apioside in rat plasma. The method was also successfully applied to compare the pharmacokinetics of these active ingredients after oral administration of Suan-Zao-Ren decoction and Suan-Zao-Ren granule. The separation was achieved on a Venusil MP C18 column and the detection was conducted by the multiple reaction monitoring mode using negative ion mode. Each calibration curve had good linearity over a wide concentration range. The precision of intra- and interday were all within 15%, and the extraction recoveries at different analyte concentrations were all above 82.0%. The established method was successfully applied to compare the pharmacokinetic profiles of the analytes between Suan-Zao-Ren decoction and Suan-Zao-Ren granule groups. The results indicated that all the analytes had similar mean concentration-time curves trend between two groups. No significant differences were observed in pharmacokinetic parameters of mangiferin, while the others had significant differences.


Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.
Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.


Fenofibrate therapy in carnitine palmitoyl transferase type 2 deficiency.
Bezafibrate therapy has been shown to improve beta-oxidation of fatty acids and to reduce episodes of rhabdomyolysis in patients with carnitine palmitoyltransferase type-2 (CPT2) deficiency. We report the efficacy of fenofibrate in a patient with CPT2 deficiency, in whom beta-oxidation was improved but an episode of rhabdomyolysis nevertheless occurred. This suggests additional methods to avoid rhabdomyolysis in patients with CPT2 deficiency should accompany fibrate therapy, including avoidance of muscular overexertion, dehydration, and heat exposure.


Standard Approaches to the Acetabulum Part 1: Kocher-Langenbeck Approach.
Historically, standard approaches for surgical treatment of displaced acetabular fractures were the KocherLangenbeck approach, the ilioinguinal approach and the extended iliofemoral approach (12). Presently, several modifications of these approaches are accepted alternatives, especially anterior modifications based on the intrapelvic approach described by Hirvensalo (8). Single access approaches allowing visualization of one acetabular column are the posterior Kocher-Langenbeck approach and the anterior ilioinguinal approach (12) and the use of a single approach is favoured (9, 24). For more complex situations, in the 80s and 90s extended approaches (extended iliofemoral approach according to Letournel (12), its modification to Reinert (19) (Baltimore approach), and the Triradiate approach according to Mears (14)) were introduced. These approaches are presently rarely choosen due to the extensive soft tissue dissection and higher complication rates (28). Alternatively, the combination of an anterior and posterior standard approach was recommended (7, 21, 22) having the disadvantage of longer operating time and blood loss and showed no superior results compared to a single approach. The meta-analysis by Giannoudis et al. stated that 48,7% of patients were treated using the Kocher-Langenbeck approach, followed by 21,9% ilioinguinal approaches and 12,4% extended approaches (6). More recent data from the years 2005-2007, showed that anterior approaches are now predominantly used according to a higher number of acetabular fractures with anterior column involvement. Overall, more than 40% of all patients with acetabular fractures are still approached via the Kocher-Langenbeck approach (18). Therefore, the Kocher-Langenbeck approach is still a "working horse" in approaching displaced acetabular fractures. The Kocher-Langenbeck approach consists of two parts. In 1874 von Langenbeck described a longitudinal incision starting from above the greater sciatic notch to the greater trochanter, dissecting the gluteal muscles for treating hip joint infections (11). Theodor Kocher in 1911 described a curved incision starting from the posterior-inferior corner of the greater trochanter, running across the postero-superior tip of the greater trochanter passing oblique in line with the fibres of the gluteus maximus muscle in direction to the posterior superior iliac spine (10). The aim of the present analysis is the detailed anatomi - cal analysis of this standard approach, focusing on fracture indication, positioning of the patient, exposure, dissection, reduction techniques of special fracture types, approach modifications/extensions, complications and approach-specific results.


Spatial and Temporal Distribution of Mutations Conferring QoI and SDHI Resistance in Alternaria solani Across the United States.
The application of succinate dehydrogenase inhibiting (SDHI) and quinone outside inhibiting (QoI) fungicide chemistries is a primary tactic in the management of early blight of potato, caused by Alternaria solani. Resistance to QoIs in A. solani has been attributed to the F129L mutation, while resistance to SDHIs is conferred by five different known point mutations on three AsSdh genes. In total, 1,323 isolates were collected from 2013 through 2015 across 11 states to determine spatial and temporal frequency distribution of these mutations. A real-time polymerase chain reaction (PCR) was used to detect the presence of the F129L mutation. Molecular detection of SDHI-resistant isolates was performed using SDH multiplex PCR specific for point mutations in AsSdhB, AsSdhC, or AsSdhD genes and mismatch amplification analysis PCR detecting the point mutations in AsSdhB. Previous work in our research group determined that substitutions of histidine for tyrosine (H278Y) or arginine (H278R) at codon 278 on the AsSdhB gene were the most prevalent mutations, detected in 46 and 21% of A. solani isolates, respectively, collected in 2011 to 2012, and uniformly distributed among six sampled states. In contrast, the substitution of histidine for arginine (H134R) at codon 134 in the AsSdhC gene was the most prevalent mutation in 2013 through 2015, identified in 36% of isolates, compared with 7.5% of isolates recovered in 2011 to 2012. Substitutions of histidine for arginine (H133R) at codon 133 and aspartic acid for glutamic acid (D123E) at codon 123 in the AsSdhD gene were detected in 16 and 12%, respectively, in the A. solani population by 2015 and were recovered across a wide range of states, compared with 15 and 1.5% of isolates collected in 2011 to 2012, respectively. Overall, SDHI- and QoI-resistant isolates were detected at high frequencies across all years, with evidence of significant spatial variability. Future research will investigate whether these results are due to differences in parasitic fitness.


A TEST OF THE SEQUENTIAL ASSESSMENT GAME: FIGHTING IN THE BOWL AND DOILY SPIDER FRONTINELLA PYRAMITELA.
Male bowl and doily spiders (Frontinella pyramitela: Linyphiidae) engage in dangerous fights over access to females. Relatively smaller individuals are more at risk of fatal injury than their larger opponents. Males assess relative fighting ability during contests: smaller individuals tend to give up quickly. Fights occur between a male with information about the value of the contested female (number of fertilizable eggs) and an intruding male with less information. In this paper, a sequential assessment game (a game theory model of fighting behavior) is adapted to male combat in the bowl and doily spider to attempt a quantitative test. The model makes predictions about fight duration, probability of winning, and the occurrence of fatalities as a function of resource value and size asymmetry. Comparison with empirical data from staged contests yields a generally good quantitative agreement with the predictions. A few deviations are also noted.


Metastatic Progression of Prostate Cancer Is Mediated by Autonomous Binding of Galectin-4-O-Glycan to Cancer Cells.
Metastatic prostate cancer continues to pose a difficult therapeutic challenge. Prostate cancer progression is associated with aberrant O-glycosylation of cancer cell surface receptors, but the functional impact of such events is uncertain. Here we report spontaneous metastasis of human prostate cancer xenografts that express high levels of galectin-4 along with genetic signatures of EGFR-HER2 signaling and O-glycosylation. Galectin-4 expression in clinical specimens of prostate cancer correlated with poor patient survival. Galectin-4 binding to multiple receptor tyrosine kinases stimulated their autophosphorylation, activated expression of pERK, pAkt, fibronectin, and Twist1, and lowered expression of E-cadherin, thereby facilitating epithelial-mesenchymal transition, invasion, and metastasis. In vivo investigations established that galectin-4 expression enabled prostate cancer cells to repopulate tumors in orthotopic and heterotopic tissues. Notably, these effects of galectin-4 relied upon O-glycosylation mediated by C1GALT1, a galactosyltransferase implicated in other cancers. Parallel changes in galectin-4 and O-glycosylation triggered aberrant receptor signaling and more aggressive invasive character in prostate cancer cells, which through better survival in the circulation also contributed to the bulk cell progeny of distal tumors. Our findings establish galectin-4 and C1GALT1-mediated glycosylation in a signaling axis that is activated during prostate cancer progression, with implications for therapeutic targeting of advanced metastatic disease. Cancer Res; 76(19); 5756-67. ©2016 AACR.


Vegetarian diet and mental disorders: results from a representative community survey.
The present study investigated associations between vegetarian diet and mental disorders. Participants were drawn from the representative sample of the German Health Interview and Examination Survey and its Mental Health Supplement (GHS-MHS). Completely vegetarian (N = 54) and predominantly vegetarian (N = 190) participants were compared with non-vegetarian participants (N = 3872) and with a non-vegetarian socio-demographically matched subsample (N = 242). Vegetarians displayed elevated prevalence rates for depressive disorders, anxiety disorders and somatoform disorders. Due to the matching procedure, the findings cannot be explained by socio-demographic characteristics of vegetarians (e.g. higher rates of females, predominant residency in urban areas, high proportion of singles). The analysis of the respective ages at adoption of a vegetarian diet and onset of a mental disorder showed that the adoption of the vegetarian diet tends to follow the onset of mental disorders. Vegetarian diet is associated with an elevated risk of mental disorders. However, there was no evidence for a causal role of vegetarian diet in the etiology of mental disorders.


INFLUENCE OF GLAUCOMA ON DIABETES-INDUCED CHANGES IN THE ANTERIOR OCULAR SEGMENT.
To monitor the influence of glaucoma on the changes caused by diabetes in the anterior ocular segment. Prospective, comparative clinical study, which included the patients with glaucoma and diabetes assessed at the Iaşi "Sf. Spiridon" Hospital, "Euro Medi Center" Clinic and "Oftaprof" Clinic. The study included a number of 142 patients, divided into two groups: 67 patients with glaucoma and diabetes (study group) and 75 patients with diabetes mellitus (control group). Upon enrollment the patients were subjected to a complete assessment of their ophthalmologic and metabolic status. Monitored aspects: prevalence of lens changes, extent of ocular surface disease and identification of the changes in corneal biomechanical parameters in the patients with glaucoma and diabetes. In both monitored groups, the cortical lens changes prevailed, both at the beginning and at the end of the study, with no statistically significant differences between groups (p>0.05). The risk of developing lens changes reaches 50% in the patients who have had diabetes for 20 years. In the patients in the study group, tear secretion was significantly lower at the end of the study (Schirmer's test values 11.61 vs. 10.67 mm, p=0.045). Tear film instability was present in 37.3% of the patients. Corneal hysteresis (CH) and comeal resistance factor were significantly reduced in the group with glaucoma and diabetes, as compared to the group with diabetes (p=0.001). There is significant ocular surface disease in the patients with glaucoma and diabetes, as compared to those with diabetes alone. Glaucoma and the number of antiglaucoma drugs are associated with a significant reduction in tear secretion. The association of glaucoma resulted in the reduction in CH and corneal resistance factor in the patients with glaucoma and diabetes as compared to the healthy ones.


Lifestyle Modifications for Migraine Management.
Migraine is a disabling disease that inflicts a heavy burden on individuals who suffer from it. Significant advances are being made in understanding the pathophysiology and treatment of the disease. The role of lifestyle modifications has become increasingly predominant. We reviewed the current and available data on the role of a healthy lifestyle in the management of migraine. Physical activity, management of obesity, a healthy diet, and a better lifestyle, such as adequate sleep and avoidance of drug abuse, significantly contribute to reducing the frequency and severity of attacks. It is important to consider these factors in the overall management strategies for migraine sufferers.


Encountering unexpected difficult airway: relationship with the intubation difficulty scale.
An unexpected difficult intubation can be very challenging and if it is not managed properly, it may expose the encountered patient to significant risks. The intubation difficulty scale (IDS) has been used as a validated method to evaluate a global degree of intubation difficulty. The aims of this study were to evaluate the prevalence and characteristics of unexpected difficult intubation using the IDS. We retrospectively reviewed 951 patients undergoing elective surgery in a single medical center. Patients expected to have a difficult intubation or who had history of difficult intubation were excluded. Each patient was assessed by the IDS scoring system with seven variables. Total prevalence of difficult intubation and the contributing individual factors were further analyzed. For the 951 patients, the difficult intubation cases presenting IDS > 5 was 5.8% of total cases (n = 55). The prevalence of Cormack-Lehane Grade 3 or 4 was 16.2% (n = 154). Most of the difficult intubation cases were managed by simple additional maneuvers and techniques such as stylet application, additional lifting force and laryngeal pressure. Unexpected difficult airway was present in 5.8% of patients and most was managed effectively. Among the components of IDS, the Cormack-Lehane grade was most sensitive for predicting difficult intubation.


An extended validation of the ScottCare 320 ambulatory blood pressure monitor: recommendations for clinical application.
The purpose of this study was to validate the ScottCare 320 ambulatory blood pressure monitor (ABPM) using both group-level and individual-level validation procedures. The group-level validation followed a modified protocol of the European Hypertension Society's validation protocol. The individual-level validation was conducted to ensure that the monitor is valid from both a research and clinical perspective. Participants (n=41) had three simultaneous blood pressure (BP) measurements taken by a trained listener using a mercury column sphygmomanometer and the ScottCare ABPM, which was used to validate the monitor at the group-level and the first half of the individual-level validation (i.e. the difference between the ABPM and auscultatory means for each participant <5 mmHg). The second half of the individual-level validation occurred by examining participants' responses on diary questionnaires taken immediately following the BP measurements (i.e. can extreme or deviant BP values be explained by situational factors). At the group level, the ABPM passed the criteria laid out by the European Hypertension Society. At the individual level, the difference between the auscultatory and ABPM means was less than 5 mmHg for both systolic and diastolic BP for 36 participants on the initial attempt, and the remaining five on the second attempt. Furthermore, the deviant values were largely attributed to explainable causes, mainly movement. The ScottCare ABPM is a highly accurate monitor that can be considered valid at both the group and the individual level, and thus appropriate for both clinical and research use.


Neurotrophins protect cultured cerebellar granule neurons against the early phase of cell death by a two-component mechanism.
Cerebellar granule neurons cultured with serum develop a mature neuronal phenotype, including stimulus-coupled release of glutamate, and depend on elevated potassium for survival. We find that cells cultured with serum undergo two phases of cell death. By 6 d in vitro, 30-50% of the cells present are dead; after this time the remaining cells die. Elevated potassium prevents only this later phase of death, whereas neurotrophins protect these cells against the early phase of death. Factors that bind p75(NTR) or TNF-R, members of the same receptor family, exhibit voltage-sensitive calcium channel-dependent protection, whereas ligands of expressed Trk receptors show additional calcium channel-independent protection. The cells express TrkB protein and show elevated c-Fos and c-Jun levels in response to BDNF. No TrkA is detected, although p75(NTR) protein is expressed and NGF induces depolarization-dependent elevation of c-Jun levels. In the presence of the protein kinase C inhibitor bisindolylmaleimide, BDNF-induced survival promotion is reduced partially, whereas NGF-induced death is unmasked. Basal survival mechanisms are insensitive to inhibition of PK-C or PI-3 kinase. We conclude that BDNF promotes survival in part via its TrkB receptor, whereas there is an additional pathway promoting survival and elevating c-Jun evoked by both NGF and BDNF via a non-Trk receptor.


Management of Intestinal Failure: The High-Output Enterostomy and Enterocutaneous Fistula.
This article provides an overview of the pathophysiology, causes, investigations, and management of high-output enterostomy and enterocutaneous fistula. High-output stoma and enterocutaneous fistula can result in intestinal failure and this is often fatal if not managed properly. The management involves reducing fluid losses, providing nutrients with fluids, and treating the underlying cause and sepsis. A multidisciplinary approach is required for successful management of patients with high-output enterostomy and enterocutaneous fistula.


Simultaneous determination of scutellarin and tetrahydropalmatine of Deng-yan granule in rat plasma by UFLC-MS/MS and its application to a pharmacokinetic study.
Deng-yan granule, consisting of Herba Erigerontis Breviscapi, Rhizoma Corydalis Yanhusuo and Radix Astragali Mongolici, is a widely used Traditional Chinese Medicine preparation for treatment of coronary heart disease. Scutellarin and tetrahydropalmatine are main active constituents in Herba Erigerontis Breviscapi and Rhizoma Corydalis Yanhusuo, and have been used as marker components for quality control of Deng-yan preparations. In order to make good and rational use of Deng-yan granule in the future, a rapid, sensitive and high throughput ultra-fast liquid chromatography with tandem mass spectrometry (UFLC-MS/MS) method was developed for the simultaneous determination of scutellarin and tetrahydropalmatine in rat plasma using rutin as internal standard (IS). The plasma samples were extracted by liquid-liquid extraction with ethyl acetate after acidification and separated on a Shim-pack XR-ODS C18 column (75mm×3.0mm, 2.2μm) with a mobile phase consisting of methanol-0.1% formic acid water (50:50, v/v) at a flow rate of 0.4mL/min. Mass spectrometric detection was conducted on an API 3200 QTRAP mass spectrometry equipped with electrospray ionization source in positive ionization mode. Quantification was performed using multiple reaction monitoring (MRM) by monitoring the fragmentation of m/z 463.2→287.1 for scutellarin, m/z 356.1→192.1 for tetrahydropalmatine and m/z 611.2→303.2 for IS, respectively. The linear range was 10-5000ng/mL for both scutellarin and tetrahydropalmatine with lower limit of quantitation (LLOQ) of 10ng/mL. The intra- and inter-day precisions were below 12.2% for scutellarin and below 9.7% for tetrahydropalmatine in terms of relative standard deviation (RSD), and the accuracy was within ±9.1% for scutellarin and within ±11.2% for tetrahydropalmatine in terms of relative error (RE). Extraction recovery, matrix effect and stability were satisfactory in rat plasma. The validated method was successfully applied to a pharmacokinetic study of scutellarin and tetrahydropalmatine after oral administration of Deng-yan granule to rats.


Identification of the immune checkpoint signature of multiple myeloma using mass cytometry-based single-cell analysis.
New targets or strategies are needed to increase the success of immune checkpoint-based immunotherapy for multiple myeloma (MM). However, immune checkpoint signals in MM microenvironment have not been fully elucidated. Here, we aimed to have a broad overview of the different immune subsets and their immune checkpoint status, within the MM microenvironment, and to provide novel immunotherapeutic targets to treat MM patients. We performed immune checkpoint profiling of bone marrow (BM) samples from MM patients and healthy controls using mass cytometry. With high-dimensional single-cell analysis of 30 immune proteins containing 10 pairs of immune checkpoint axes in 0.55 million of BM cells, an immune landscape of MM was mapped. We identified an abnormality of immune cell composition by demonstrating a significant increase in activated CD4 T, CD8 T, CD8+ natural killer T-like and NK cells in MM BM. Our data suggest a correlation between MM cells and immune checkpoint phenotypes and expand the view of MM immune signatures. Specifically, several critical immune checkpoints, such as programmed cell death 1 (PD-1)/PD ligand 2, galectin-9/T-cell immunoglobulin mucin-3, and inducible T-cell costimulator (ICOS)/ICOS ligand, on both MM and immune effector cells and a number of activated PD-1+ CD8 T cells lacking CD28 were distinguished in MM patients. A clear interaction between MM cells and the surrounding immune cells was established, leading to immune checkpoint dysregulation. The analysis of the immune landscape enhances our understanding of the MM immunological milieu and proposes novel targets for improving immune checkpoint blockade-based MM immunotherapy.


Assessing the information management requirements for behavioral health providers.
Behavioral health agencies will soon implement automated information-management systems to support their administrative, financial, and clinical care functions. Assessing current information-management capabilities and delineating future needs are prerequisite to recommending a specific information technology solution. Quantifying the discrepancy between current information-management capabilities and future requirements highlights the areas of greatest unmet need for information management. Selecting an information system that addresses the most critical areas of unmet need is a prudent purchase decision. This article describes the results of a process to assess the information-management requirements for agencies that were considering implementation of an integrated behavioral health information-management system. The assessment revealed that these agencies already employed automated systems to manage most financial functions and many administrative functions. Few agencies, however, utilized automated systems to manage clinical care functions. Selection of a behavioral health electronic medical record (EMR) effectively addressed clinical care information-management needs without duplicating existing financial and administrative management functions. Also, the EMR included features that addressed some administrative functions for which a discrepancy between current capabilities and future needs was found. Selecting an EMR instead of an integrated behavioral health information system was associated with a significant reduction in information system acquisition costs.


NSCLC: An Update of Driver Mutations, Their Role in Pathogenesis and Clinical Significance.
Lung cancer is the most common malignancy in the US and causes the most cancer-related deaths. Non-small-cell lung carcinoma (NSCLC) accounts for the majority of cases. NSCLC historically was considered one entity, reflected by platinum-based therapy as the standard of care; however, with the discovery of EGFR mutations and ALK rearrangements, the landscape of treatment has become more personalized reflecting genomic heterogeneity. The molecular basis for tumor genesis was recognized and became a new method of classification. The availability of tumor sequencing and testing for these mutations is also becoming more accessible outside of major academic institutions. Targeted therapies offer alternatives to dangerous cytotoxic chemotherapy with equal or better efficacy. With these changes, driver mutations will play an increasing role in the diagnosis and treatment of NSCLC. In this review we will examine the characteristics of several NSCLC driver mutations and gene rearrangements and emerging data on therapies directed against them.


Systemic Lupus Erythematosus is Not Necessarily a Contraindication to Adjuvant Breast Radiation Therapy.
A 41-year-old woman presented with pT4dN1aM0, right-sided, inflammatory breast cancer. She had a co-morbid diagnosis of systemic lupus erythematosus (SLE) at the age of 20 and was found to have significant kidney involvement (lupus-associated nephritis) at the age of 28. She went on to receive six cycles of neoadjuvant chemotherapy consisting of fluorouracil, epirubicin, cyclophosphamide, and docetaxcel (FEC-D) after which she had radiographically stable disease. She then had definitive treatment with bilateral mastectomy. Pathology showed a 4-cm residual invasive ductal carcinoma in the right breast and three residual metastatic lymph nodes in the right axilla. After extensive discussions with the patient, which included counseling on the potential increased risk of radiation-induced side effects, she received 50.4 Gy in 28 fractions of adjuvant radiotherapy (RT) to the chest wall and regional lymphatics including the internal mammary chains (IMCs). To minimize the risk of pulmonary toxicity, RT field arrangement consisted of a field-in-field modulated supraclavicular anterior/posterior parallel pair matched to shallow, photon tangent pair with 0.5 cm bolus to the lateral aspect of the chest wall and two matched direct anterior electron fields of 9 MeV with 1 cm bolus and 12 MeV with 0.5 cm bolus medially to cover the remaining residual chest wall and IMCs. This was immediately followed by a boost of 7.5 Gy in three fractions delivered via a photon tangent pair with 1 cm bolus to an area 6 cm superior and inferior to the surgical scar. Total treatment time was 50 days. The patient tolerated the therapy well but she developed grade three acute dermatitis. There were no pulmonary, shoulder joint movement, or brachial plexus side effects. This case is unusual in that SLE is generally considered a contraindication for elective RT. However, given her high risk for breast cancer recurrence, RT was offered with additional caution to minimize lung dose. Having completed the treatment, the side effects experienced were no greater than what would be expected in someone who did not have a diagnosis of SLE.


Somatic mitochondrial DNA mutations in Chinese patients with osteosarcoma.
Somatic mutations in mitochondrial DNA (mtDNA) have been long proposed to drive the pathogenesis and progression of human malignancies. Previous investigations have revealed a high frequency of somatic mutations in the D-loop control region of mtDNA in osteosarcoma. However, little is known with regard to whether or not somatic mutations also occur in the coding regions of mtDNA in osteosarcoma. To test this possibility, in the present study we screened somatic mutations over the full-length mitochondrial genome of 31 osteosarcoma tumour tissue samples, and corresponding peripheral blood samples from the same cohort of patients. We detected a sum of 11 somatic mutations in the mtDNA coding regions in our series. Nine of them were missense or frameshift mutations that have the potential to hamper mitochondrial respiratory function. In combination with our earlier observations on the D-loop fragment, 71.0% (22/31) of patients with osteosarcoma carried at least one somatic mtDNA mutation, and a total of 40 somatic mutations were identified. Amongst them, 29 (72.5%) were located in the D-loop region, two (5%) were in the sequences of the tRNA genes, two (5%) were in the mitochondrial ATP synthase subunit 6 gene and seven (17.5%) occurred in genes encoding components of the mitochondrial respiratory complexes. In addition, somatic mtDNA mutation was not closely associated with the clinicopathological characteristics of osteosarcoma. Together, these findings suggest that somatic mutations are highly prevalent events in both coding and non-coding regions of mtDNA in osteosarcoma. Some missense and frameshift mutations are putatively harmful to proper mitochondrial activity and might play vital roles in osteosarcoma carcinogenesis.


Further evidence for the spread of attention during contour grouping: a reply to Crundall, Dewhurst, and Underwood (2008).
In a contour-grouping task, subjects decide whether contour elements belong to the same or different curves. Houtkamp, Spekreijse, and Roelfsema (2003) demonstrated that object-based attention spreads gradually over contour elements that have to be grouped in perception. Crundall, Dewhurst, and Underwood (2008) challenged this spreading-attention model and suggested that attention in the contour-grouping task is not object based but rather has the shape of a zoom lens that moves along the relevant curve. To distinguish between object-based and spatial attention, they changed the stimulus and measured the impact on performance. Subjects were not able to correct for changes at the start of the relevant curve toward the end of the trial. They suggested that attention did not stay at the beginning of the curve, in accordance with a moving zoom lens model. Here, we examine the task of Crundall et al. and find that subjects perceive the changes but fail to correct their response. By measuring change detection directly, we find that performance is much better for the start of the relevant curve than for an irrelevant curve, at all times. Our findings do not support the zoom lens model but provide further support for the spreading attention model.


Lysyl Oxidase-like Protein LOXL2 Promotes Lung Metastasis of Breast Cancer.
The lysyl oxidase-like protein LOXL2 has been suggested to contribute to tumor progression and metastasis, but in vivo evidence has been lacking. Here we provide functional evidence that LOXL2 is a key driver of breast cancer metastasis in two conditional transgenic mouse models of PyMT-induced breast cancer. LOXL2 ablation in mammary tumor cells dramatically decreased lung metastasis, whereas LOXL2 overexpression promoted metastatic tumor growth. LOXL2 depletion or overexpression in tumor cells does not affect extracellular matrix stiffness or organization in primary and metastatic tumors, implying a function for LOXL2 independent of its conventional role in extracellular matrix remodeling. In support of this likelihood, cellular and molecular analyses revealed an association of LOXL2 action with elevated levels of the EMT regulatory transcription factor Snail1 and expression of several cytokines that promote premetastatic niche formation. Taken together, our findings established a pathophysiologic role and new function for LOXL2 in breast cancer metastasis. Cancer Res; 77(21); 5846-59. ©2017 AACR.


A narrative review and expert recommendations on the assessment of the clinical manifestations, follow-up, and management of post-OLT patients with ATTRv amyloidosis.
Orthotopic liver transplantation (OLT) was the first treatment able to modify the natural course of hereditary transthyretin (ATTRv) amyloidosis, which is a rare and fatal disorder caused by the accumulation of misfolded transthyretin (TTR) variants in different organs and tissues and which leads to a progressive and multisystem dysfunction. Because the liver is the main source of TTR, OLT dramatically reduces the production of the pathogenic TTR variant, which should prevent amyloid formation and halt disease progression. However, amyloidosis progression may occur after OLT due to wild-type TTR deposition, especially in the nerves and heart. In this review, we discuss the disease features influencing OLT outcomes and the clinical manifestations of ATTRv amyloidosis progression post-OLT to improve our understanding of disease worsening after OLT and optimize the follow-up and clinical management of these patients. By conducting a literature review on the PubMed database, we identified patient characteristics that have been associated with worse post-OLT outcomes, including late-onset V50M and non-V50M variants, age >40 years, long disease duration, advanced neuropathy and autonomic dysfunction, and malnutrition. Regarding post-OLT mortality, deaths occurring within the first year after OLT were mainly associated with fatal graft complications and infectious diseases, whereas cardiovascular-related deaths usually occurred later. Considering the diverse clinical manifestations of ATTRv amyloidosis progression post-OLT, including worsening neuropathy and/or cardiomyopathy, autonomic dysfunction, and oculoleptomeningeal involvement, we present advice on the most relevant tests for assessing disease progression post-OLT. Finally, we discuss the use of new therapies based on TTR stabilizers and TTR mRNA silencers for the treatment of ATTRv amyloidosis patients post-OLT.


Proof of concept demonstration of optimal composite MRI endpoints for clinical trials.
Atrophy measures derived from structural MRI are promising outcome measures for early phase clinical trials, especially for rare diseases such as primary progressive aphasia (PPA), where the small available subject pool limits our ability to perform meaningfully powered trials with traditional cognitive and functional outcome measures. We investigated a composite atrophy index in 26 PPA participants with longitudinal MRIs separated by two years. Rogalski et al. [Neurology 2014;83:1184-1191] previously demonstrated that atrophy of the left perisylvian temporal cortex (PSTC) is a highly sensitive measure of disease progression in this population and a promising endpoint for clinical trials. Using methods described by Ard et al. [Pharmaceutical Statistics 2015;14:418-426], we constructed a composite atrophy index composed of a weighted sum of volumetric measures of 10 regions of interest within the left perisylvian cortex using weights that maximize signal-to-noise and minimize sample size required of trials using the resulting score. Sample size required to detect a fixed percentage slowing in atrophy in a two-year clinical trial with equal allocation of subjects across arms and 90% power was calculated for the PSTC and optimal composite surrogate biomarker endpoints. The optimal composite endpoint required 38% fewer subjects to detect the same percent slowing in atrophy than required by the left PSTC endpoint. Optimal composites can increase the power of clinical trials and increase the probability that smaller trials are informative, an observation especially relevant for PPA, but also for related neurodegenerative disorders including Alzheimer's disease.


Fundamental reaction pathway and free energy profile for inhibition of proteasome by Epoxomicin.
First-principles quantum mechanical/molecular mechanical free energy calculations have been performed to provide the first detailed computational study on the possible mechanisms for reaction of proteasome with a representative peptide inhibitor, Epoxomicin (EPX). The calculated results reveal that the most favorable reaction pathway consists of five steps. The first is a proton transfer process, activating Thr1-O(γ) directly by Thr1-N(z) to form a zwitterionic intermediate. The next step is nucleophilic attack on the carbonyl carbon of EPX by the negatively charged Thr1-O(γ) atom, followed by a proton transfer from Thr1-N(z) to the carbonyl oxygen of EPX (third step). Then, Thr1-N(z) attacks on the carbon of the epoxide group of EPX, accompanied by the epoxide ring-opening (S(N)2 nucleophilic substitution) such that a zwitterionic morpholino ring is formed between residue Thr1 and EPX. Finally, the product of morpholino ring is generated via another proton transfer. Noteworthy, Thr1-O(γ) can be activated directly by Thr1-N(z) to form the zwitterionic intermediate (with a free energy barrier of only 9.9 kcal/mol), and water cannot assist the rate-determining step, which is remarkably different from the previous perception that a water molecule should mediate the activation process. The fourth reaction step has the highest free energy barrier (23.6 kcal/mol) which is reasonably close to the activation free energy (∼21-22 kcal/mol) derived from experimental kinetic data. The obtained novel mechanistic insights should be valuable for not only future rational design of more efficient proteasome inhibitors but also understanding the general reaction mechanism of proteasome with a peptide or protein.


Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1.
Neutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge. This study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env). Four groups of rabbits received a DNA vaccine expressing the V1V2 domain of the CRF01_AE A244 strain on a trimeric 2J9C scaffold (V1V2-2J9C) along with a protein vaccine consisting of an uncleaved prefusion-optimized A244 Env trimer with V3 truncation (UFO-BG.ΔV3) or a V1V2-2J9C protein and their respective immune complexes (ICs). These IC vaccines were made using 2158, a V1V2-specific monoclonal Ab (mAb), which binds the V2i epitope in the underbelly region of V1V2 while allosterically promoting the binding of broadly neutralizing mAb PG9 to its V2 apex epitope in vitro. Rabbit groups immunized with the DNA vaccine and uncomplexed or complexed UFO-BG.ΔV3 proteins (DNA/UFO-UC or IC) displayed similar profiles of Env- and V1V2-binding Abs but differed from the rabbits receiving the DNA vaccine and uncomplexed or complexed V1V2-2J9C proteins (DNA/V1V2-UC or IC), which generated more cross-reactive V1V2 Abs without detectable binding to gp120 or gp140 Env. Notably, the DNA/UFO-UC vaccine elicited neutralizing Abs against some heterologous tier 1 and tier 2 viruses from different clades, albeit at low titers and only in a fraction of animals, whereas the DNA/V1V2-UC or IC vaccines did not. In comparison with the DNA/UFO-UC group, the DNA/UFO-IC group showed a trend of higher neutralization against TH023.6 and a greater potency of V1V2-specific Ab-dependent cellular phagocytosis (ADCP) but failed to neutralize heterologous viruses. These data demonstrate the capacity of V1V2-2J9C-encoding DNA vaccine in combination with UFO-BG.ΔV3, but not V1V2-2J9C, protein vaccines, to elicit homologous and heterologous neutralizing activities in rabbits. The elicitation of neutralizing and ADCP activities was modulated by delivery of UFO-BG.ΔV3 complexed with V2i mAb 2158.


A Broadband Photodetector Based on PbS Quantum Dots and Graphene with High Responsivity and Detectivity.
A high-efficiency photodetector consisting of colloidal PbS quantum dots (QDs) and single-layer graphene was prepared in this research. In the early stage, PbS QDs were synthesized and characterized, and the results showed that the product conformed with the characteristics of high-quality PbS QDs. Afterwards, the photodetector was derived through steps, including the photolithography and etching of indium tin oxide (ITO) electrodes and the graphene active region, as well as the spin coating and ligand substitution of the PbS QDs. After application testing, the photodetector, which was prepared in this research, exhibited outstanding properties. Under visible and near-infrared light, the highest responsivities were up to 202 A/W and 183 mA/W, respectively, and the highest detectivities were up to 2.24 × 1011 Jones and 2.47 × 108 Jones, respectively, with light densities of 0.56 mW/cm2 and 1.22 W/cm2, respectively. In addition to these results, the response of the device and the rise and fall times for the on/off illumination cycles showed its superior performance, and the fastest response times were approximately 0.03 s and 1.0 s for the rise and fall times, respectively. All the results illustrated that the photodetector based on PbS and graphene, which was prepared in this research, possesses the potential to be applied in reality.


Effect of inorganic, synthetic and naturally occurring chelating agents on Fe(II) mediated advanced oxidation of chlorophenols.
This study examines the feasibility and application of Advanced Oxidation Technologies (AOTs) for the treatment of chlorophenols that are included in US EPA priority pollutant list. A novel class of sulfate/hydroxyl radical-based homogeneous AOTs (Fe(II)/PS, Fe(II)/PMS, Fe(II)/H2O2) was successfully tested for the degradation of series of chlorophenols (4-CP, 2,4-CP, 2,4,6-CP, 2,3,4,5-CP). The major objective of the present study was to evaluate the effectiveness of three representative chelating agents (citrate, ethylenediaminedisuccinate (EDDS), and pyrophosphate) on Fe(II)-mediated activation of three common peroxide (peroxymonosulfate (PMS), persulfate (PS), and hydrogen peroxide (H2O2)) at neutral pH conditions. Short term (4 h) and long term (7 days) experiments were conducted to evaluate the kinetics and longevity of different oxidative systems for 4-chlorophenol degradation. Results showed that each of the iron-chelating agent couple was superior in activating a particular oxidant and consequently for 4-CP degradation. In case of Fe(II)/PMS system, the inorganic chelating agent pyrophosphate showed effective activation of PMS whereas very fast dissociation of PMS was recorded in the case of EDDS without any apparent 4-CP degradation. In Fe(II)/H2O2 system, EDDS was proven to be the most effective whereas pyrophosphate showed negligible activation of H2O2. Fe(II)/Citrate system showed moderate activation of all three oxidants. PMS was found to be the most universal oxidant, which was activated by all three iron-chelating agent systems and Fe(II)/Citrate was the most universal chelating agent system, which was able to activate all three oxidants to a certain extent.


Clinical Study of the Lateral Supramalleolar Flap in the Soft Tissue Reconstruction around the Ankle Region.
Objective The purpose of this study is to present the efficiency of the lateral supramalleolar flap which is a very useful and yet underutilized in the soft tissue reconstruction of the regions extending from the distal leg, ankle, and foot. Methods Over a period of 3 years, 20 flaps were used in the reconstruction of soft tissue defects in the region extending from the distal leg, ankle, and foot. The location of the defects, the etiology, possible alternative flaps, outcome, and the complications were studied and presented. Results The follow-up period of the cases was from 1 month to 18 months after surgery. Seventeen flaps survived and three were lost. All the three lost flaps were those used over the tendocalcaneal region. The lost flaps were later replaced with split skin graft after the wound was debrided and was later covered with granulation tissue. Conclusion The lateral supramalleolar flap is a very useful flap in the regional soft tissue reconstruction around the ankle except in the tendocalcaneal region.


Content Validity Testing of the Maternal Fetal Triage Index.
To describe the development and content validity testing of the Maternal Fetal Triage Index (MFTI), a standardized tool for obstetric triage. Online survey. Participants included 15 registered nurses, 15 certified nurse-midwives, and 15 physicians from across the United States who provided maternity care. A convenience sample of experienced clinicians was used as content validators for the MFTI. An item content validity index (I-CVI) was computed for the tool's items and a scale content validity index (S-CVI) was computed for the tool's scale based on the responses submitted via the online survey. Two rounds of content validation occurred. In the first round of testing, a total of 12 of 61 items in the MFTI did not meet the I-CVI threshold of greater than 0.78 because of disagreement about clinical condition (75%) or priority level placement (25%). In the second round of testing, all but 3 of the 69 content items in the revised version of the MFTI had I-CVI thresholds greater than 0.78. These 3 items were related to vital sign values. The overall S-CVI score calculated for Round 2 only was 0.95, which was greater than the threshold of 0.90. The results of the content validity testing of multidisciplinary validators suggest that the MFTI is a valid tool for use in obstetric triage and evaluation settings.


Visuospatial short-term memory and dorsal visual gray matter volume.
Visual short-term memory (VSTM) is an important cognitive capacity that varies across the healthy adult population and is affected in several neurodevelopmental disorders. It has been suggested that neuroanatomy places limits on this capacity through a map architecture that creates competition for cortical space. This suggestion has been supported by the finding that primary visual (V1) gray matter volume (GMV) is positively associated with VSTM capacity. However, evidence from neurodevelopmental disorders suggests that the dorsal visual stream is more broadly vulnerable and atypical volumes of other map-containing regions may therefore play a role. For example, Turner syndrome is associated with concomitantly reduced volume of the right intraparietal sulcus (IPS) and deficits in VSTM. As posterior IPS regions (IPS0-2) contain topographic maps, together this suggests that posterior IPS volumes may also associate with VSTM. In this study, we assessed VSTM using two tasks, as well as a composite score, and used voxel-based morphometry of T1-weighted magnetic resonance images to assess GMV in V1 and right IPS0-2 in 32 healthy young adults (16 female). For comparison with previous work, we also assessed associations between VSTM and voxel-wise GMV on a whole-brain basis. We found that total brain volume (TBV) significantly correlated with VSTM, and that correlations between VSTM and regional GMV were substantially reduced in strength when controlling for TBV. In our whole-brain analysis, we found that VSTM was associated with GMV of clusters centered around the right putamen and left Rolandic operculum, though only when TBV was not controlled for. Our results suggest that VSTM ability is unlikely to be accounted for by the volume of an individual cortical region, and may instead rely on distributed structural properties.


Genetically stable infectious Schmallenberg virus persists in foetal envelopes of pregnant ewes.
Schmallenberg virus (SBV) is a recently emerged vector-borne virus, inducing congenital defects in bovines, ovines and caprines. Here we have shown that infectious SBV is capable of persisting until the moment of birth in the foetal envelopes of ewes infected with SBV-infectious serum at day 45 (1/5 positive) and 60 (4/6 positive) of gestation. This persistence of at least 100 days is a new aspect of the SBV pathogenesis that could help to explain how SBV overwinters the cold season in temperate climate zones. Furthermore, sequencing of the M segment shows that the persisting virus in the foetal envelopes is genetically stable since only a few mutations compared to the inoculum were found. This supports the hypothesis that persisting virus could start the infection of new hosts. Finally, neutralization tests showed that infectious SBV present in the foetal envelopes at birth can be neutralized by the humoral immunity present in the infected ewes.


Molecular and cytogenetic studies of the Prader-Willi syndrome.
Twenty-seven subjects with the Prader-Willi syndrome (PWS) were studied. Sixteen (59%) had a cytogenetic deletion involving chromosome 15q11-13. Nine were non-deletional and two patients had structural rearrangements of chromosome 15: 47,XY, + del(15)(pter----q12), var(15)(p11) and 45,XX,t(14q15q). At the DNA level, a greater proportion of patients (74%) showed loss of one chromosome 15q11-13 allele using a combination of densitometry and RFLP analysis. Deletion sizes were variable with 13 of 20 detectable both cytogenetically and with probe pML34 (D15S9). The remaining seven had microdeletions at the pML34 locus. Heterogeneity was further seen in three subjects who had cytogenetic deletions but normal DNA studies. In one patient there was evidence of a duplication at the pML34 locus. A new molecular rearrangement was identified with probe p3.21 (D15S10) in two patients and their mothers. Fifteen family studies were performed. In all 10 families where there was a molecular deletion, this was shown to have arisen de novo. DNA mapping confirmed that the paternal 15q allele was lost in three patients with PWS.


The Direct Actions of GABA, 2'-Methoxy-6-Methylflavone and General Anaesthetics at β3γ2L GABAA Receptors: Evidence for Receptors with Different Subunit Stoichiometries.
2'-Methoxy-6-methylflavone (2'MeO6MF) is an anxiolytic flavonoid which has been shown to display GABAA receptor (GABAAR) β2/3-subunit selectivity, a pharmacological profile similar to that of the general anaesthetic etomidate. Electrophysiological studies suggest that the full agonist action of 2'MeO6MF at α2β3γ2L GABAARs may mediate the flavonoid's in vivo effects. However, we found variations in the relative efficacy of 2'MeO6MF (2'MeO6MF-elicited current responses normalised to the maximal GABA response) at α2β3γ2L GABAARs due to the presence of mixed receptor populations. To understand which receptor subpopulation(s) underlie the variations observed, we conducted a systematic investigation of 2'MeO6MF activity at all receptor combinations that could theoretically form (α2, β3, γ2L, α2β3, α2γ2L, β3γ2L and α2β3γ2L) in Xenopus oocytes using the two-electrode voltage clamp technique. We found that 2'MeO6MF activated non-α-containing β3γ2L receptors. In an attempt to establish the optimal conditions to express a uniform population of these receptors, we found that varying the relative amounts of β3:γ2L subunit mRNAs resulted in differences in the level of constitutive activity, the GABA concentration-response relationships, and the relative efficacy of 2'MeO6MF activation. Like 2'MeO6MF, general anaesthetics such as etomidate and propofol also showed distinct levels of relative efficacy across different injection ratios. Based on these results, we infer that β3γ2L receptors may form with different subunit stoichiometries, resulting in the complex pharmacology observed across different injection ratios. Moreover, the discovery that GABA and etomidate have direct actions at the α-lacking β3γ2L receptors raises questions about the structural requirements for their respective binding sites at GABAARs.


Estimation and comparison of the contents of blood group B antigens in selected human tissues by microphotometric quantification of Griffonia simplicifolia agglutinin I-B4 staining with or without prior alpha-galactosidase digestion.
Griffonia simplicifolia agglutinin I-B4 (GSAI-B4) has broader specificity for B antigen variants and can recognize the antigens in a wide variety of human tissues. Thus, the concentration range of GSAI-B4 required for staining and the susceptibility of staining to alpha-galactosidase digestion is presumed to correlate well with the density of B antigens in tissue sections. By microphotometric quantification of staining intensity at different concentrations of GSAI-B4 with or without alpha-galactosidase digestion, concentration of B antigens in selected tissues was evaluated and compared. Based on the present results and the previous ones of direct measurement of galactose of B antigens in sublingual glands and red blood cells (Ito et al., 1993), the order of concentration of B antigens in tissues examined was estimated as follows; mucous cells of sublingual glands from German nonsecretors < red blood cells and vascular endothelial cells (= 2.7 x 10(-3) nmole/cm2), thyroid papillary carcinomas and Hassall's corpuscles from nonsecretors < mucous cells of sublingual gland from Japanese nonsecretors < pancreatic acinar cells from both secretor and nonsecretors, Hassall's corpuscles and kidney collecting tubules form secretors < mucous cells of sublingual gland from secretors (> 8.5-11.7 nmole/cm2) and mucous cells of Brunner's gland from nonsecretors < mucous cells of Brunner's gland from secretors. From the above estimation, it is apparent that the expression of B antigen in Brunner's gland is partly dependent on the secretor status of individuals and that Japanese nonsecretors secrete substantial amounts of B antigens from sublingual gland while German nonsecretors do not. The present results also revealed an unexpected staining behavior of GSAI-B4 in some tissues, i.e. in mucous cells of sublingual glands and collecting tubules of kidney from secretors, staining intensity was markedly depressed at higher concentration of the lectin and this depression was recovered by prior alpha-galactosidase digestion. In addition, the present method was successfully applied for the estimation of the content of B antigens neo-expressed in thyroid papillary carcinomas, showing that the content of B antigen had a similar level to that of red blood cells and vascular endothelial cells.


Evidence for four different polymerization sites involved in human fibrin formation.
The mechanism of association and the organization of human fibrin were studied by using affinity chromatography. Insolubilized fibrinogen, fibrin monomer, and crosslinked fibrin were used to localize the binding sites on fibrinogen and fibrin derivatives. Four different polymerization sites have been distinguished. A binding site ("a"), available without thrombin action, is present on the fibrinogen fragment D domain. The complementary ("A") is inoperative in fibrinogen and requires thrombin for activation; it is located on the fibrinogen NH2-terminal domain. A third polymerization site ("b") appears to be formed by the alignment of the fragment D domains on two fibrin monomer molecules upon polymerization; this site functions without thrombin mediation and the alignment is stabilized by the Factor XIIIa-catalyzed crosslink bonds. The "b" site is complementary to another thrombin-activated site ("B") on the fibrinogen NH2-terminal domain. The two thrombin activable sites, "A" and "B", are distinguishable, although they are located in the same fibrinogen domain.


Frequent loss of heterozygosity at the MCC locus on chromosome 5q21-22 in sporadic colorectal carcinomas.
Recent studies have identified a gene on chromosome 5q, designated MCC (mutated in colorectal cancers), as a candidate for the putative colorectal tumor suppressor gene that is located at 5q21. We examined loss of heterozygosity (LOH) at the MCC locus and its vicinity in sporadic colorectal carcinomas, using 12 RFLP (restriction fragment length polymorphism) markers. One clone, L5.71, had been used to identify the MCC gene; all 12 markers also had tight linkage to the gene responsible for adenomatous polyposis coli. All 40 cases studied were informative with at least one marker, and 22 of them (55%) showed LOH at one or more loci. LOH in the tumors was more frequent in the immediate vicinity of L5.71 than in distant parts of the chromosome, and a common region of deletion was detected between markers L5.62 and 15A6. In one case, alleles were retained at L5.71 and at loci proximal to L5.71, but alleles were lost at loci distal to L5.71. In another case, both alleles were retained at L5.71 but alleles were lost at loci proximal and distal to L5.71. These results support the conclusion that a tumor suppressor gene for colorectal carcinoma is located within or around locus L5.71.


[Mitochondrial DNA diversity in prehispanic bone remains on the eastern Colombian Andes].
DNA extracted from ancient human bones allows to analyze the genetic makeup of pre-Columbian populations and to determine the dynamics that gave rise to the diversity of contemporary populations. To determine the genetic diversity of skeletal remains associated with the Templo del Sol (Sun Temple) and their relationship with other contemporary and ancient communities of America. We analyzed 13 individuals belonging to the pre-Columbian Muisca Period (IX-XVI centuries AD) from the vicinities of the Templo del Sol (Sun Temple) (Sogamoso, Boyacá) in the eastern Colombian Andes. Mitochondrial DNA was amplified and RFLPs were performed in order to type the four traditional Amerindian haplogroups (A, B, C and D). In addition, autosomal markers including amelogenin and Y-chromosome STRs were amplified. Among the observed mitochondrial lineages, haplogroup A was the most frequent, followed by haplogroups B and C; no evidence of haplogroup D was found. The genetic variation analysis indicated a similar diversity of pre-ColumbianMuiscas to that of contemporary populations belonging to the Chibcha linguistic family from Colombia and Central America. Molecular sexing was accomplished and it was compared to osteological data. With only one exception, anthropological and molecular data were consistent. Our results contribute new genetic elements supporting the hypothesis of Central American origin of the Chibcha groups of the Cundiboyacense plateau, and allowed sex typing and kinship evaluations.


Studies of serum protein complexes with nickel using crossed immunoelectrophoresis.
Crossed immunoelectrophoresis of human serum spiked with nickel in the range 0.85-24 mmol Ni/L was used to study nickel-protein complexes. These high concentrations, which are far higher than the physiological level (approximately 7.8 nmol/L), were used to saturate both high and low affinity binding sites. Addition of increasing amounts of nickel resulted in dose-dependent changes of the electrophoretic patterns of prealbumin, alpha-1-lipoprotein, alpha-1-antitrypsin and alpha-2-macroglobulin. Radioactive 63Ni was used for crossed immunoelectrophoresis autoradiography experiments for further identification of nickel-protein complexes. When a 63Ni pulse of 740 kBq/application was used, many human serum proteins were labeled. When using a 63Ni pulse of 185 kBq/application only albumin and alpha-1-antitrypsin were visualized clearly. The binding of large amounts of nickel to albumin, visualized by autoradiography, may reflect the high abundance of albumin in human serum as compared to other serum proteins. Addition of nickel to serum proteins resulted in liquid phase precipitation of serum proteins, and rocket immunoelectrophoresis was used to demonstrate that IgG in particular is precipitated. This precipitation of serum proteins may disturb the elution profile when chromatographic techniques are used to analyze nickel-protein complexes. Consequently, immunoelectrophoretic methods may also be attractive alternatives to column chromatographic techniques. The present study demonstrated that, besides the nickel-binding of albumin and alpha-2-macroglobulin, several other serum proteins have nickel-binding affinity.


Outcome of adult horses with botulism treated at a veterinary hospital: 92 cases (1989-2013).
There are no studies evaluating a large population of adult horses treated for botulism. Reported survival rates in outbreak situations are low; however, many horses in outbreaks do not receive treatment. That adult horses treated at a veterinary hospital would have improved survival compared to outbreak situations. Additional aims included identification of predictors of nonsurvival. All horses greater than 6 months of age with a final diagnosis of botulism admitted to a veterinary teaching hospital between 1989 and 2013 were included. Retrospective study. Historical, admission, and hospitalization data were retrieved from medical records and associations between variables and nonsurvival were identified using logistic regression. Two multivariable models were developed pertaining to (1) information available at admission and (2) clinical findings during hospitalization. Ninety-two records met inclusion criteria. Retained variables for the two models indicated that higher rectal temperature (OR, 1.94; CI, 1.19-3.17) and dysphagia (OR, 4.04; CI, 1.01-16.17) observed at admission increased the odds of survival, as did treatment with antitoxin (OR, 121.30; CI, 9.94-1,480.65). Horses with abnormal respiratory effort or inability to stand had decreased odds of survival. Overall survival was 48% but was significantly higher (67%, P = .011) for horses that arrived standing, and even higher (95%, P < .001) for horses that remained able to stand throughout hospitalization. Complications occurred in 62% of horses but were not associated with nonsurvival. Horses that lose the ability to stand have a poor chance of survival. Complications are common in treated horses but do not reduce survival.


The Incidence of and Factors Associated with Vitamin D Deficiency in Newly Diagnosed Children with Cancer.
This retrospective chart review study aimed to assess vitamin D status and identify risk factors associated with vitamin D deficiency and bone parameters in children with cancer at admission. The data of 86 (50 males and 36 females) patients between April 2013 and June 2015 were analyzed. Calcium, phosphorus, alkaline phosphatase (ALP), 25(OH)D, age, gender, diagnostic category, body mass index, duration of complaints, and season of blood sampling were recorded. Median age was 7.17 years (range 0.31-17.40) in 29 hematological malignancy and 57 solid tumor patients. According to cut-off level of 20 ng/ml, 63% of children with cancer had vitamin D deficiency at diagnosis with a median 25(OH)D of 16.75 ng/ml. The mean vitamin D value of children >10 years was significantly low in comparison to that observed in younger children [11.83, 95% confidence interval (CI) = = 8.85-14.81 ng/ml vs. 19.81, 95% CI = = 17.02-22.60 ng/ml]. Vitamin D measurement between November and May was a risk factor for vitamin D deficiency (P < 0.05). The frequency of hypocalcemia and hypophosphatemia was not different between two groups of vitamin D. Further longitudinal studies are needed to investigate whether monitoring vitamin D status and supplementation in children with cancer might prevent future complications related to vitamin D deficiency.