Identification of the major phosphorylation sites of the Raf-1 kinase.
Treatment of cells with various growth factors and mitogens results in the rapid hyperphosphorylation and activation of the Raf-1 kinase. To determine if phosphorylation events affect Raf-1 activity, we have initiated experiments to identify the phosphorylation sites of Raf-1. In this report, we find that Ser43, Ser259, and Ser621 are the major sites of Raf-1 which are phosphorylated in mammalian cells and in Sf9 insect cells infected with a recombinant baculovirus encoding human Raf-1. Mutant Raf-1 proteins lacking kinase activity are also phosphorylated on these sites in vivo, indicating that these phosphorylation events are not a consequence of autophosphorylation. Furthermore, we find that Thr268 is the predominant Raf-1 residue phosphorylated in in vitro autokinase assays. In addition, we have examined the biochemical activity of baculovirus-expressed Raf-1 proteins containing mutations at these phosphorylation sites. In in vitro protein kinase assays Ser259 mutant proteins were 2-fold more active than wild-type Raf-1 and Ser621 mutant proteins were inactive as kinases. Analysis of the residues surrounding Ser259 and Ser621 indicates that RSXSXP may be a consensus sequence for the kinase responsible for phosphorylation of Raf-1 at these sites. Interestingly, these RSXSXP sequences are completely conserved throughout evolution in all Raf family members.


Tissue angiotensin-converting-enzyme (ACE) deficiency leads to a reduction in oxidative stress and in atherosclerosis: studies in ACE-knockout mice type 2.
Background- Angiotensin II, produced by angiotensin-converting-enzyme (ACE), enhances oxidative stress and atherogenesis. In this study, we analyzed whether tissue ACE deficiency in ACE-knockout mice type-2 would affect their oxidative status. Moreover, by crossbreeding the ACE-knockout mice with atherosclerotic apolipoprotein E (apo E)-deficient (E0) mice, we questioned whether tissue ACE deficiency affects atherogenesis. ACE-deficient mice type-2 (ACE+/-) exhibited reduced serum lipid peroxidation compared with ACE+/+ mice. Peritoneal macrophages from ACE+/- mice demonstrated lower oxidative status, as exhibited by decreases of 47%, 33% 56%, and 51%, in their lipid peroxides, superoxide release, dichlorofluorescein fluorescence, and LDL oxidation, respectively, compared with ACE+/+ mice. ACE+/- mice crossbred with E0 mice, resulting in atherosclerotic mice heterozygous for ACE (ACE+/-/E0 mice), exhibited reduced lipid peroxidation, increased paraoxonase activity, and lower macrophage LDL oxidation compared with E0 and ACE+/+/E0 mice. ACE+/-/E0 mice also exhibited reduced NADPH-induced aortic superoxide ion production by 52% and a reduction of 43% in their atherosclerotic lesion size compared with E0 mice. Finally, 2 animals genotyped as homozygous-knockout for both ACE and APOE genes (ACE-/-/E0), exhibited a striking reduction of 86% in their atherosclerotic lesion area compared with E0 mice. Reduction of tissue ACE with the ACE-knockout mouse type-2 model inhibited oxidative stress and atherogenesis.


Tracking Air Pollution in China: Near Real-Time PM2.5 Retrievals from Multisource Data Fusion.
Air pollution has altered the Earth's radiation balance, disturbed the ecosystem, and increased human morbidity and mortality. Accordingly, a full-coverage high-resolution air pollutant data set with timely updates and historical long-term records is essential to support both research and environmental management. Here, for the first time, we develop a near real-time air pollutant database known as Tracking Air Pollution in China (TAP, http://tapdata.org.cn/) that combines information from multiple data sources, including ground observations, satellite aerosol optical depth (AOD), operational chemical transport model simulations, and other ancillary data such as meteorological fields, land use data, population, and elevation. Daily full-coverage PM2.5 data at a spatial resolution of 10 km is our first near real-time product. The TAP PM2.5 is estimated based on a two-stage machine learning model coupled with the synthetic minority oversampling technique and a tree-based gap-filling method. Our model has an averaged out-of-bag cross-validation R2 of 0.83 for different years, which is comparable to those of other studies, but improves its performance at high pollution levels and fills the gaps in missing AOD on daily scale. The full coverage and near real-time updates of the daily PM2.5 data allow us to track the day-to-day variations in PM2.5 concentrations over China in a timely manner. The long-term records of PM2.5 data since 2000 will also support policy assessments and health impact studies. The TAP PM2.5 data are publicly available through our website for sharing with the research and policy communities.


Mismatch Repair of DNA Replication Errors Contributes to Microevolution in the Pathogenic Fungus Cryptococcus neoformans.
The ability to adapt to a changing environment provides a selective advantage to microorganisms. In the case of many pathogens, a large change in their environment occurs when they move from a natural setting to a setting within a human host and then during the course of disease development to various locations within that host. Two clinical isolates of the human fungal pathogen Cryptococcus neoformans were identified from a collection of environmental and clinical strains that exhibited a mutator phenotype, which is a phenotype which provides the ability to change rapidly due to the accumulation of DNA mutations at high frequency. Whole-genome analysis of these strains revealed mutations in MSH2 of the mismatch repair pathway, and complementation confirmed that these mutations are responsible for the mutator phenotype. Comparison of mutation frequencies in deletion strains of eight mismatch repair pathway genes in C. neoformans showed that the loss of three of them, MSH2, MLH1, and PMS1, results in an increase in mutation rates. Increased mutation rates enable rapid microevolution to occur in these strains, generating phenotypic variations in traits associated with the ability to grow in vivo, in addition to allowing rapid generation of resistance to antifungal agents. Mutation of PMS1 reduced virulence, whereas mutation of MSH2 or MLH1 had no effect on the level of virulence. These findings thus support the hypothesis that this pathogenic fungus can take advantage of a mutator phenotype in order to cause disease but that it can do so only in specific pathways that lead to a mutator trait without a significant tradeoff in fitness.IMPORTANCE Fungi account for a large number of infections that are extremely difficult to treat; superficial fungal infections affect approximately 1.7 billion (25%) of the general population worldwide, and systemic fungal diseases result in an unacceptably high mortality rate. How fungi adapt to their hosts is not fully understood. This research investigated the role of changes to DNA sequences in adaption to the host environment and the ability to cause disease in Cryptococcus neoformans, one of the world's most common and most deadly fungal pathogens. The study results showed that microevolutionary rates are enhanced in either clinical isolates or in gene deletion strains with msh2 mutations. This gene has similar functions in regulating the rapid emergence of antifungal drug resistance in a distant fungal relative of C. neoformans, the pathogen Candida glabrata Thus, microevolution resulting from enhanced mutation rates may be a common contributor to fungal pathogenesis.


OPN induces FoxM1 expression and localization through ERK 1/2, AKT, and p38 signaling pathway in HEC-1A cells.
Mammalian embryo implantation is an extremely complex process and requires endometrial receptivity. In order to establish this receptivity, sequential proliferation and differentiation during the menstrual cycle is necessary. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion and progression. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. Osteopontin (OPN), an adhesion molecule, has been studied extensively in reproduction. In this study, we observed the expression and distribution of FoxM1 during the proliferative-phase and secretory-phase human endometrium and the pre-implantation mouse uterus firstly. Then we observed the relationship between OPN and FoxM1. Our results showed that FoxM1 was mainly distributed in glandular epithelium. OPN increased the expression of FoxM1 in the human uterine epithelial cell line HEC-1A cells in a time- and concentration-dependent manner. OPN regulates FoxM1 to influence HEC-1A cell proliferation through extracellular regulated protein kinases (ERK 1/2), protein kinase B (PKB, AKT), and the p38 mitogen activated protein kinases (p38MAPK, p38) signaling pathway. Inhibition of ERK 1/2, AKT and p38 suppressed OPN-induced FoxM1 expression and location. Our data indicate that FoxM1 might be regulated by OPN to influence endometrial proliferation to establish endometrial receptivity.


Efficacy and safety of 3-day azithromycin versus 5-day moxifloxacin for the treatment of acute bacterial exacerbations of chronic bronchitis.
Antibiotic therapy is of clinical benefit in certain patients with acute exacerbations of chronic bronchitis (AECB). In this randomised, investigator-blinded, multicentre trial, azithromycin (500mg once a day (qd) for 3 days) was compared with moxifloxacin (400mg qd for 5 days) for the treatment of outpatients with AECB (forced expiratory volume in 1s (FEV(1)) >35%). Of 342 patients randomised to either treatment, 169 received azithromycin and 173 received moxifloxacin. The mean age in the azithromycin and moxifloxacin groups was 56.4 years and 55.5 years, respectively. In the intent-to-treat analysis, clinical success rates for azithromycin and moxifloxacin were comparable at Days 10-12 (90% versus 90%, respectively) and Days 22-26 (81% versus 82%, respectively). Among patients who were culture-positive at baseline for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Haemophilus parainfluenzae, clinical efficacy for azithromycin versus moxifloxacin at Days 10-12 was 93% versus 84%, respectively, and at Days 22-26 it was 89% versus 73%, respectively. The incidence of at least one treatment-related adverse event (AE) in the azithromycin and moxifloxacin groups was 18.3% and 19.1%, respectively. The most common AEs were diarrhoea, nausea, abdominal pain and vaginitis. Most treatment-related AEs were of mild or moderate severity, with no serious treatment-related AEs. One subject in the moxifloxacin group discontinued treatment owing to a treatment-related AE (precordial pain and dry throat). Compliance with both regimens was >90%. Three-day azithromycin and 5-day moxifloxacin demonstrate comparable efficacy and safety for the treatment of AECB in outpatients.


Donor's age and replicative senescence favour the in-vitro mineralization potential of human fibroblasts.
Aberrant mineralization of soft connective tissues (ectopic calcification) may occur as a frequent age-related complication. Still, it remains unclear the role of mesenchymal cell donor's age and of replicative senescence on ectopic calcification. Therefore, the ability of cells to deposit in-vitro hydroxyapatite crystals and the expression of progressive ankylosis protein homolog (ANKH), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), tissue non specific alkaline phosphatase (TNAP) and osteopontin (OPN) have been evaluated in human dermal fibroblasts derived from neonatal (nHDF) and adult (aHDF) donors (ex-vivo ageing model) or at low and high cumulative population doublings (CPD) up to replicative senescence (in-vitro ageing model). This study demonstrates that: 1) replicative senescence favours hydroxyapatite formation in cultured fibroblasts; 2) donor's age acts as a major modulator of the mineralizing potential of HDF, since nHDF are less prone than aHDF to induce calcification; 3) donor's age and replicative senescence play in concert synergistically increasing the calcification process; 4) the ANKH+ENPP1/TNAP ratio, being crucial for pyrophosphate/inorganic phosphate balance, is greatly influenced by donor's age, as well as by replicative senescence, and regulates mineral deposition; 5) OPN is only modulated by replicative senescence.


Case report: Remote monitoring using Spectrum Medical Live Vue allows improved response time and improved quality of care for patients on cardiopulmonary support.
Clinician rounding on bedside extracorporeal membrane oxygenation (ECMO) is a common coverage practice at many centers across the USA. Occasionally, clinical issues or concerns may go unnoticed for a considerable period of time during the intervals of clinician rounds. We report a case utilizing the LiveVue (Spectrum Medical, Fort Mill, SC) remote monitoring for care of a patient on ECMO. A patient was placed on veno-arterial (VA) ECMO in our intensive care unit, using a Rotaflow centrifugal pump and a Quadrox D polymethylpentene (PMP) fiber oxygenator (both Maquet, Fairfield, NJ). Following ECMO initiation and stabilization, a two-hour rounding schedule was established for the covering perfusionist. On day two, shortly after the perfusionist had rounded, the ECMO flow began fluctuating between 0.1 and 2.1 L/min. A compliance alert (i.e. red flashing notification) was recognized by the perfusion team on a large screen monitor installed in the perfusion pump room. Immediate response from the perfusion team identified venous inflow obstruction due to cannula malposition. The pump revolutions per minute (rpm) and, thus, the resulting flow were temporarily reduced to prevent vessel intimal damage and the surgical team was summoned to reposition the venous cannula. Later in that ECMO run, a steady rise in pre-oxygenator pressure was noted by the perfusionist. This increasingly concerning event was able to be trended and monitored with the LiveVue from a remote location. After a few hours, a compliance alert was noticed again on the LiveVue screen in the pump room. The pre-oxygenator pressure increased by 150 mmHg and the circuit flow decreased by half. Again, the perfusionist response was immediate and an oxygenator change-out ensued. Once more, a potentially dangerous clinical scenario was avoided with continuous critical parameter remote monitoring using the LiveVue system.


Identification of quantitative trait loci conferring blast resistance in Bodao, a japonica rice landrace.
Bodao, a japonica landrace from the Taihu Lake region of China, is highly resistant to most Chinese isolates of Magnaporthe oryzea, a form of rice blast. To effectively dissect the influence of genetics on this blast resistance, a population of 155 recombinant inbred lines (F2:8) derived from a cross of Bodao x Suyunuo was inoculated with 12 blast isolates. Using a quantitative trait locus (QTL) mapping approach, 13 QTL on chromosomes 1, 2, 9, 11, and 12 were detected from Bodao. Five QTL, including qtl11-1-1, qtl11-3-7, qtl11-4-9, qtl12-1-1, and qtl12-2-3, have not been previously reported. The qtl11-3-7 and qtl11-4-9 may be the two main effective QTL and resistant to 7 and 9 isolates, respectively. The results of the present study will be valuable for the fine mapping and cloning of these two new resistance genes.


Dimensions of Caregiver Burden between Compound and Noncompound Caregivers of Adults with Autism.
The expanding population of adults with autism spectrum disorder (ASD) will increase the number of aging parents who often assume the role of primary caregivers. Among aging caregivers of adults with ASD, compound caregiving (caring for additional family members) has become an increasingly common scenario. However, limited research has examined the burden of compound caregivers and little is known about the specific dimensions of burden among this population. The present study aims to compare differences between compound 1, compound 2, and noncompound caregivers on specific dimensions of caregiver burden associated with adult children with ASD. Using a cross-sectional design, data were collected from 320 caregivers aged 50 and older through a web-based survey. Four dimensions of burden (time dependence, developmental, emotional, and financial) were compared using MANOVA. Compound 1 and noncompound caregivers experienced lower levels of time dependence burden than compound 2 caregivers. In terms of developmental burden, the social life of compound 2 caregivers was more affected by caregiving compared to noncompound caregivers. The findings have practice implications for identifying caregivers' multiple responsibilities and the multi-faceted impact of caregiving, and prioritizing interventions for compound caregivers and its subpopulations to reduce their time and developmental burden.


Bivalirudin Attenuates Thrombin-Induced Endothelial Hyperpermeability via S1P/S1PR2 Category: Original Articles.
Aims: To explore the role of the Sphingosine 1-Phosphate (S1P)/Receptor2 (S1PR2) pathway in thrombin-induced hyperpermeability (TIP) and to test whether bivalirudin can reverse TIP via the S1P-S1PRs pathway. Methods and Results: Using western blot, we demonstrated that Human umbilical vein endothelial cells (HUVECs) that were cultured with 2 U/ml thrombin showed significantly increased S1PR2 expression while S1PR1and three kept unchanged. Such increment was attenuated by JTE-013 pretreatment and by presence of bivalirudin. Exposure of 2 U/ml of thrombin brought a higher level of S1P both intracellularly and extracellularly within the HUVECs by using ELISA detecting. Thrombin induced S1P and S1PR2 increment was restored by usage of PF543 and bivalirudin. Bivalirudin alone did not influenced the level of S1P and S1PR1,2, and S1PR3 compare to control group. As a surrogate of cytoskeleton morphology, phalloidin staining and immunofluorescence imaging were used. Blurry cell edges and intercellular vacuoles or spaces were observed along thrombin-exposed HUVECs. Presence of JTE-013 and bivalirudin attenuated such thrombin-induced permeability morphological change and presence of heparin failed to show the protective effect. Transwell chamber assay and probe assay were used to measure and compare endothelial permeability in vitro. An increased TIP was observed in HUVECs cultured with thrombin, and coculture with bivalirudin, but not heparin, alleviated this increase. JTE-013 treatment yielded to similar TIP alleviating effect. In vivo, an Evans blue assay was used to test subcutaneous and organ microvascular permeability after the treatment of saline only, thrombin + saline, thrombin + bivalirudin, thrombin + heparin or thrombin + JTE-013. Increased subcutaneous and organ tissue permeability after thrombin treatment was observed in thrombin + saline and thrombin + heparin groups while treatment of bivalirudin and JTE-013 absent this effect. Conclusion: S1P/S1PR2 mediates TIP by impairing vascular endothelial barrier function. Unlike heparin, bivalirudin effectively blocked TIP by inhibiting the thrombin-induced S1P increment and S1PR2 expression, suggesting the novel endothelial protective effect of bivalirudin under pathological procoagulant circumstance.


Oxygen surface exchange kinetics of Ba0.5Sr0.5Co0.8Fe0.2O3-δ.
The mechanism of oxygen exchange between the gas phase and Ba0.5Sr0.5Co0.8Fe0.2O3-δ oxide was evaluated by considering the inhomogeneity of the oxide surface. The applicability of existing models for the analysis of the oxygen exchange mechanism was considered. A new model with a dissociation step was suggested. The rate-determining steps of the oxygen exchange process were revealed under different experimental conditions. The change in the rate-determining step occurred at 600-650 °C. The probable cause was considered taking into account the parameter of nonequivalency of adsorption centers. A relationship between the oxygen isotope redistribution rates and the rates of the elementary steps in a "gas phase-solid oxide" system was revealed.


Physicians' views on pay-for-performance as a reimbursement model: a quantitative study among Dutch surgical physicians.
To assess the views, knowledge, and experience of Dutch physicians with regard to the general objectives and values of the pay-for-performance (P4P) system, as the Dutch healthcare industry might find it useful, in terms of governance, to explore this approach further. A quantitative cross-sectional survey study was conducted among 48 physicians in surgical specialties in the Netherlands between May 2014 and July 2014. The survey questionnaire was designed to gather information regarding the intensity of feelings, on a 7-point Likert scale, toward statements that address the P4P system. Confidence intervals were calculated using the bootstrap technique with 1000 iterations. Physicians see a positive value in P4P for their organizations rather than for personal attainment (mean = 5.00; 95% CI = 4.62-5.39), even though they feared that P4P might put financial pressure on them (mean = 5.03; 95% CI = 4.50-5.54). They strongly share the view that other colleagues will resist adopting P4P as a business model (mean = 5.74; 95% CI = 5.43-6.04). Respondents stated that they would not leave their current jobs if P4P were to be incorporated in their organization. Physicians see value in P4P for their organizations, and consider that P4P could provide an incentive for improving medical outcomes. There seems to be potential for the P4P system in the Netherlands as participants expressed positive support for its values. There is an intersection of interests between the value of P4P and the physicians' aim of achieving quality outcomes; however, further studies would be needed to investigate perceptions about specific design features in a larger sample. In addition, prior to implementing P4P, broad education about the system should be provided in order to counteract pre-conceptions and prevent resistance.


The Mae On Project: using acupuncture for symptom relief and improved quality of life for people living with HIV and AIDS in rural Thailand.
Acupuncture in combination with antiretroviral therapies is a potentially useful treatment for HIV-related symptom relief in resource-poor settings. Traditional Chinese medicine has a long history of being used to enhance immune function. In the setting of HIV, Chinese traditional medicine allows for symptom treatment without adding extra medications to a complex drug regime. This paper provides details of a project at Mae On Hospital in rural northern Thailand where allopathic/conventional treatments are used in tandem with acupuncture. A preliminary evaluation of the project suggests that an integrated approach to symptom relief is viewed positively by respondents receiving acupuncture, though further studies are required to confirm the association between acupuncture and symptom relief. The project also demonstrates the feasibility of developing a cost-effective acupuncture programme using local healthcare staff.


Metastable states and space-time phase transitions in a spin-glass model.
We study large deviations of the dynamical activity in the random orthogonal model. This is a fully connected spin-glass model with one-step replica symmetry-breaking behavior, consistent with the random first-order transition scenario for structural glasses. We show that this model displays dynamical (space-time) phase transitions between active and inactive phases, as demonstrated by singularities in large deviation functions. We argue that such transitions are generic in systems with long-lived metastable states.


Invasive meningococcal disease in Scotland, 1994 to 1999, with emphasis on group B meningococcal disease.
A review was carried out on 774 invasive meningococcal isolates reported to the active meningococcal surveillance system in Scotland from 1994 to 1999. This showed that serogroups B (51.7%) and C (39.2%) caused the majority of disease. The six common PorB proteins (4, 1, 15, 2B, 12, and 21) and PorA proteins (serosubtypes) (P1.4, P1.15, P1.9, P1.14, P1.7, and P1.16) accounted for 50 and 51% of all group B isolates, respectively, during the study period.


The influence of green tea extract as the steeping solution on nutritional and microbial characteristics of germinated wheat.
This study examined the effect of green tea extract at 10 (GWG1%) and 50 (GWG5%) g/L as the steeping solution on the chemical, nutritional, and microbial quality of wheat grain during 14 days of germination. Fat, dry matter, and ash contents in the control was higher than GWG treatments due to the faster growth of control germs. Moisture, phenolic compounds, thiamin, niacin, and tocopherols decreased, whereas, fat, dry matter, carbohydrate, protein, crude fiber, ash, folic acid, Ca, Mg, Fe, Mn, and Zn increased significantly in all samples during germination. GWG5% showed the highest values in total phenols, vitamins, minerals, and carbohydrate, followed by GWG1% and then the control. No significant differences in protein and crude fiber content were detected among treatments. GWG decreased the growth of total bacterial, yeast, and mold in germinated seeds. Overall, GWG improved the microbial and nutritional quality of wheat germ during 14 days of germination.


Cerebrospinal fluid markers for Alzheimer's disease in a cognitively healthy cohort of young and old adults.
Low amyloid β42 (Aβ42) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer's disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. To study the effect of age on CSF Aβ42, total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. CSF Aβ42 levels of 81 subjects (27% female, 53 ± 15.3 years, range: 21-88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele ɛ4 carriers and noncarriers. The median levels of all markers were significantly different between young (<65 years) and old (≥65 years) subjects (Aβ42: P = .03; tau: P = .02; p-tau: P = .002; tau/Aβ42: P = .004; p-tau/Aβ42: P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/Aβ42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Aβ42 concentrations. In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Aβ42 low levels represent a preclinical AD biomarker.


Normalized regional brain atrophy measurements in multiple sclerosis.
There is still a controversy regarding the best regional brain atrophy measurements in multiple sclerosis (MS) studies. The aim of this study was to establish whether, in a cross-sectional study, the normalized measurements of regional brain atrophy correlate better with the MRI-defined regional brain lesions than the absolute measurements of regional brain atrophy. We assessed 45 patients with clinically definite relapsing-remitting (RR) MS (median disease duration 12 years), and measured T1-lesion load (LL) and T2-LL of frontal lobes and pons, using a reproducible semi-automated technique. The regional brain parenchymal volume (RBPV) of frontal lobes and pons was obtained by use of a computerized interactive program, which incorporates semi-automated and automated segmentation processes. A normalized measurement, the regional brain parenchymal fraction (RBPF), was calculated as the ratio of RBPV to the total volume of the parenchyma and the cerebrospinal fluid (CSF) in the frontal lobes and in the region of the pons. The total regional brain volume fraction (TRBVF) was obtained after we had corrected for the total volume of the parenchyma and the CSF in the frontal lobes and in the region of the pons for the total intracranial volume. The mean coefficient of variation (CV) for RBPF of the pons was 1% for intra-observer reproducibility and 1.4% for inter-observer reproducibility. Generally, the normalized measurements of regional brain atrophy correlated with regional brain volumes and disability better than did the absolute measurements. RBPF and TRBVF correlated with T2-LL of the pons (r=-0.37, P=0.011, and r= -0.40, P=0.0005 respectively) and with T1-LL of the pons (r=-0.27, P=0.046, and r=-0.31, P=0.04, respectively), whereas RBPV did not (r=-0.18, P = NS). T1-LL of the frontal lobes was related to RBPF (r=-0.32, P=0.033) and TRBVF (r=-0.29, P=0.05), but not to RBPV (R=-0.27, P= NS). There was only a trend of correlation between T2-LL of the frontal lobes and RBPF (r=-0.27, P=0.06) and TRBVF (r=-0.28, P=0.057), and no correlation with RBPV (r=-0.23, P= NS). The magnitude of correlation between the expanded disability status scale (EDSS) and pontine and frontal lobe RBPF and TRBVF was more than twice as high as the correlation between EDSS and RBPV of the same regions. These data suggest that normalized regional brain atrophy measurements are preferable to absolute regional measurements in cross-sectional studies.


Metabolic and energetic aspects of the growth response of Streptococcus rattus to environmental acidification in anaerobic continuous culture.
Streptococcus rattus, a serotype b strain of mutans streptococci, was grown in an anaerobic glucose-limited chemostat. The molar growth yield of glucose [Yglucose, g dry wt (mol glucose)-1] together with the maximum growth yields (Ymax) and maintenance coefficients for glucose utilization and calculated ATP generation were estimated as a function of pH. When the pH was lowered from 7.0 to 5.0, Yglucose decreased, with a concomitant gradual change in the composition of the end product from a mixture of formate, acetate and ethanol to one mostly of lactate. Whereas the Ymax for glucose decreased without any change in the Ymax for ATP on acidification, both of the maintenance coefficients markedly increased. Kinetic and immunochemical examinations indicated the presence of an F1F0-type proton-translocating ATPase in the membrane fraction prepared from bacterial cells grown under acidic conditions; no detectable level of the enzyme was found in cells grown at neutral pH. However, when incubated with glucose under non-growing conditions, these acid-adapted and unadapted cells showed an insignificant difference in the ability to maintain the intracellular pH alkaline relative to the acidic environments. These results suggest that the organism responds and adapts to environmental acidification by sacrificing some energy cost in terms of both the efficiency of glucose utilization to generate ATP and the extra maintenance required to continue biomass production as efficiently as under neutral pH.


Sex-Specific Postoperative Outcomes of Primary Total Hip Replacements: The Performance of Total Hip Replacement Procedures Leads to Worse Outcomes in Men.
The demand for primary total hip arthroplasty (THA) is expected to increase significantly in the coming years, and women are expected to account for the greatest proportion of this increased demand. The purpose of this study was to determine, using a national database, the effect of sex on 90-day outcomes in primary THA patients while matching for confounding variables. Specifically, we evaluated: (1) in-hospital lengths of stay; (2) 90-day readmission rates; (3) 90-day medical complications; (4) and total global 90-day episode-of-care (EOC) costs in men and women. Using the 100% Medicare Standard Analytical Files (SAF), a query from January 1, 2005 to March 31, 2014 from a nationwide database was performed to analyze patients who received a primary THA. The series was divided into two cohorts: men (n=436,737) and women (n=436,737). Male and female patients were matched according to age and Elixhauser-Comorbidity Index (ECI). Uni- and multi-variable regression analyses were performed to analyze the effects of sex on in-hospital lengths of stay, 90-day readmission rates, 90-day medical complications, and total global 90-day EOC costs. Men had greater overall 90-day medical complications compared to women following primary THA (1.28 vs. 1.19%, p<0.001). Men were found to have higher rates of acute kidney failure (0.12 vs 0.05%, p<0.0001), acute pancreatitis (0.02 vs. 0.01%, p<0.0001), cerebrovascular accidents (0.03 vs. 0.01%, p<0.0001), deep vein thromboses (0.06 vs. 0.04%, p<0.0001), and myocardial infarctions (0.02 vs. 0.01%, p<0.0001). Women were found to have higher rates of acute post-hemorrhagic anemiae (0.31 vs. 0.30%, p<0.001) and urinary tract infections (UTI; 0.40 vs. 0.28%, p<0.0001) compared to men. Men had shorter in-hospital lengths of stay (LOS) (3.42 vs. 3.54 days, p<0.001) but greater 90-day readmission rates (7.67 vs. 6.39% p<0.0001). Both cohorts had similar total global 90-day EOC costs ($14,869.85 ± $12,333.50 vs. $14,957.34 ± $10,915.61, p=0.36). Men undergoing THA have a greater number of overall 90-day medical complications and readmission rates while women have higher incidence of UTI, post-hemorrhagic anemia, and longer LOS. Understanding sex-based differences in complication rates and outcomes can help surgeons with preoperative counseling and targeted preoperative optimization.


Tumor suppressor microRNA-34a inhibits cell migration and invasion by targeting MMP-2/MMP-9/FNDC3B in esophageal squamous cell carcinoma.
MicroRNAs (miRNAs) are a large family of small, non-coding RNAs that play a pivotal role in tumorigenesis. miR‑34a, which is a member of the miR-34 family, is a downstream target of p53. Increasing evidence shows that miR-34a dysregulation may contribute to tumor development and progression in numerous cancers, including esophageal squamous cell carcinoma (ESCC). However, the mechanism of miR-34a in the regulation of ESCC cells need to be further elucidated because of the complex regulative network of miRNAs. The miR-34a expression in ESCC samples has been confirmed using quantitative reverse transcription polymerase chain reaction. The effects of miR-34a on cell migration and invasion were examined in ESCC cell lines using wound healing and Transwell assays, respectively. The effects of miR-34a on matrix metalloproteinase (MMP)-2 and -9 and fibronectin type III domain containing 3B (FNDC3B) expression levels were detected by luciferase reporter assays and western blot analysis. Quantitative polymerase chain reaction revealed that the miR‑34a expression is significantly downregulated in the ESCC tissues compared to that in the adjacent normal tissues. miR-34a overexpression was significantly suppressed migration and invasion in the ESCC cells and simultaneously inhibited the MMP-2, MMP-9 and FNDC3B expression levels by targeting the coding and 3'-untranslated regions, respectively. The findings indicated that microRNA‑34a suppresses cell migration and invasion by targeting MMP-2, MMP-9, and FNDC3B in ESCC.


[Laser Doppler flowmetry in vital bone transplantation. Experimental and clinical results].
Laser Doppler Flowmetry allows the measurement of the blood flow rate of different types of tissue. Rib on a muscle pedicle was compared with rib on a vascular pedicle in an animal experiment. The morphological results were compared with the LDF-results. During eleven clinical transfers of iliac crest bone grafts and one osteocutaneous scapular flap the blood flow values were measured intraoperatively before and after the transplantation. Postoperative monitoring was possible for 48 hours with the endoscopic probe and a screw implant. The blood flow of vascularized bone transplants is excellent and even rises post-operatively in some cases.


A rare adult cause of dizziness.
A 55-year-old man was seen with progressively worsening dizziness over 10 months. The initial assessment with unremarkable laboratory and imaging studies suggested a peripheral vestibular disorder. He was then lost to follow-up but later was seen with worsening ataxia. Additional imaging studies showed subtle parenchymal lesions in the posterior fossa. The differential diagnoses included nutritional deficiencies, autoimmune disorders, systemic malignancies, and intracranial tumors. The final diagnosis was confirmed by a biopsy.


Positive expression of basic transcription factor 3 predicts poor survival of colorectal cancer patients: possible mechanisms involved.
Basic transcription factor 3 (BTF3) is associated with the development of several cancers. The aim of our study was to elucidate the role of BTF3 in colorectal cancer (CRC) tissues. CRC tissues or their paired adjacent noncancerous (ANCT) tissues were obtained from 90 patients who underwent operations in our hospital from November 2011 to December 2016, and then we implemented a gene microarray assay for detecting significant changes in gene expression and confirmed expression in tissues using immunohistochemistry and real-time PCR. We transfected or injected the silencing BTF3 (BTF3-siRNA) plasmid into cells and nude mice, and measured the tumorigenicity of CRC cells with flow cytometry and studied the expression level of BTF3 downstream genes (MAD2L2, MCM3 and PLK1) in CRC cells. BTF3 expression level was not only significantly higher in CRC tissue than in ANCT tissue (2.61 ± 0.07 vs 1.90 ± 0.03, P < 0.001) but BTF3-siRNA decreased tumor formation in a nude mice model. Furthermore, based on the data of gene microarray analysis, MAD2L2, MCM3 and PLK1 were detected as the downstream target genes of BTF3 and their expressions were positive related with BTF3 expression. Also, through transfecting BTF3-siRNA into HCT116 cells, we found that BTF3-siRNA could decrease cell viability and induced cell apoptosis and blocking the cell cycle. In conclusion, BTF3 is positively related to CRC and BTF3-siRNA attenuated the tumorigenicity of colorectal cancer cells via MAD2L2, MCM3 and PLK1 activity reduction.


Omentum and reverse turnover latissimus dorsi musculocutaneous flap for the treatment of cerebrospinal fluid fistula.
Conventional procedures can usually prevent cerebrospinal fluid (CSF) leakages, but they may not work for complicated cases. In this case presentation, we demonstrated the effectiveness of combined omental and latissimus dorsi musculocutaneous flaps for management of difficult CSF fistula. A reverse turnover latissimus dorsi musculocutaneous flap and omental flap were transferred for reconstruction of the posterior wound and CSF leakage. The omental flap component was used for CSF absorption, and the latissimus dorsi muscle component was used for obliteration of the dead space, covering of the exposed bone, and tension-free closure of the wound. The wound healed dramatically, with no observed severe donor site morbidity. The patient has been followed for 30 months with no evidence of CSF leakage and no pseudomeningocele formation, which was confirmed by magnetic resonance imaging (MRI). Although this is a case presentation, we can say that the combination of the omental and musculocutaneous flaps allow effective treatment and prevention of CSF fistulas in selected high-risk patients and provide durable coverage of complex spinal wounds.


Curative-Intent Surgery for Pancreatic Tumors: A Review of Procedures From the Brazilian National Health System.
In Brazil, a country with major health access disparities, resource limitations make management of pancreatic cancer (PC) challenging. This study evaluated curative-intent surgery for PC in the Brazilian public health care system. We collected data for PC surgical procedures with curative intent in Brazil's public health care system (DATASUS) and from the demographic database. Costs, lengths of stay, number of perioperative deaths, and PC deaths were analyzed for each state and then associated with population, gross domestic product (GDP) per capita, and number of procedures. A total of 37,142 patients died as a result of PC in Brazil between 2008 and 2012. The number of deaths (per 100,000 person-years) was highest in the south and southeast regions. Mortality from PC had a positive association with the number of procedures and GDP per capita. Between January 2008 and July 2014, 3,386 procedures were performed, the majority (51.2%) in the southeast region. Four hundred ninety-three patients died, which translates to an inpatient mortality rate of 14.6%. The northern states had the highest perioperative mortality (mean, 25%). The number of procedures per 100,000 residents was higher in the southeast and south. Overall, cost tended to increase as the number of procedures or population increased. For fixed GDP per capita and population, cost tended to increase as the number of procedures increased, whereas for a fixed number of procedures and GDP per capita, cost tended to decrease as population increased. The mean length of hospital stay was 16.9 days, which was higher than in major international centers. This study is the first to our knowledge to evaluate regional disparities in PC care in Brazil. Perioperative mortality was high in the public health care system. Regionalized policies that improve care are needed.


Fasa University Medical School: a novel experience in medical education.
In early 1970`s a combination of a shortage and misdistribution of health services and growing public dissatisfaction about the health care available, along with increasing expectations, has put great strain on the mind of the staff of the Department of Medicine Shiraz University School of Medicine. The purpose of this report is to give an account of what was originally planned and what has happened since the start of Fasa Medical School in April 1978. This is a case report about an experience in medical education in Iran. At the time, two major problems were facing our country. The first was gross mal-distribution of these healthcare facilities, which were mostly concentrated in Tehran and big cities of Iran, and the second problem was continuous exodus of Iranian Medical graduates to the Western countries. The main idea of creating Fasa Medical School was to create a system in which primary care in small villages are provided by VHW with the middle level health workers of "Behdar Roustaee" to be supported by local physicians who reside in small towns. For Fasa Medical School, education was emphasized on community based, student centered, and problem based medical education located in the community and based on teamwork and cooperation.


An economic analysis of the benefits of sterilizing medical instruments in low-temperature systems instead of steam.
Hydrogen peroxide-based, low-temperature sterilization has been shown to do less damage to medical instruments than steam autoclaves. However, low-temperature systems are more expensive to run. Higher costs need to be balanced against savings from reduced repair costs to determine value for money when choosing how to sterilize certain instruments, which are able to be reprocessed in either system. This analysis examines the economic effects of using low-temperature sterilization systems to reprocess rigid and semi-rigid endoscopes, which are sensitive to heat and moisture, but still able to be sterilized using steam. It examines the changes to costs and frequency of repairs expected over 10 years, resulting from a choice to sterilize these instruments in a low-temperature system instead of steam. Overall, the results showed that increased sterilization costs are outweighed by the savings associated with less frequent repairs. Over a 10-year period, in large health care facilities, the probability of achieving an internal rate of return of at least 6% is 0.81. Our model shows it is likely to be a good decision for large health care facilities to invest in low-temperature sterilization systems.


Gestational diabetes mellitus and its complications.
Gestational diabetes mellitus (GDM) is a new epidemic among Australian women, especially those with Asian backgrounds. The 1998 Australia National Diabetes Strategy and Implementation Plan recognises GDM as an independent glucose metabolic disorder affecting sub-groups of Australians. Gestational diabetes mellitus is an Australian national diabetes priority area, along with insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). This paper reviews the many issues relating to GDM that continue to be debated by researchers and clinical service providers. These issues include the diagnosis of GDM, the effect of GDM on fetal outcomes, the long-term health effects on the offspring of GDM mothers, the effect of GDM on maternal outcomes and the long-term health effects on women with a history of GDM.


Ethical practices and beliefs of psychopathology researchers.
Ethical guidelines are vague concerning how situations should be handled when researchers encounter participants in preexisting psychological distress. Ethical issues of beneficence, autonomy, and the nature of informed consent may arise in these situations. This study investigated the ethical practices and beliefs of 84 psychopathology researchers when confronting research participants in distress. Results indicated that psychopathology researchers in general engaged in diverse ethical practices in providing debriefing, treatment referrals, and providing for distressed participants. Characteristics of the designated studies and of the researchers accounted for significant differences in ethical practices. In addition, the type of psychopathology being assessed accounted for significant differences in ethical practices and beliefs. Guidelines are offered to aid researchers who encounter participants in preexisting distress.


Measurement of secondary products during oxidation reactions of terpenes and ozone based on the PTR-MS analysis: effects of coexistent carbonyl compounds.
Continuous measurements using proton transfer reaction mass spectrometry (PTR-MS) can be used to describe the production processes of secondary products during ozone induced oxidation of terpenes. Terpenes are emitted from woody building materials, and ozone is generated from ozone air purifiers and copy machines in indoor environments. Carbonyl compounds (CCs) are emitted by human activities such as smoking and drinking alcohol. Moreover, CCs are generated during ozone oxidation of terpenes. Therefore, coexistent CCs should affect the ozone oxidation. This study has focused on the measurement of secondary products during the ozone oxidation of terpenes based on the use of PTR-MS analysis and effects of coexistent CCs on oxidized products. Experiments were performed in a fluoroplastic bag containing α-pinene or limonene as terpenes, ozone and acetaldehyde or formaldehyde as coexistent CCs adjusted to predetermined concentrations. Continuous measurements by PTR-MS were conducted after mixing of terpenes, ozone and CCs, and time changes of volatile organic compounds (VOCs) concentrations were monitored. Results showed that, high-molecular weight intermediates disappeared gradually with elapsed time, though the production of high-molecular weight intermediates was observed at the beginning. This phenomenon suggested that the ozone oxidation of terpenes generated ultrafine particles. Coexistent CCs affected the ozone oxidation of α-pinene more than limonene.


Comparison of multiple genotyping methods for the identification of the cancer predisposing founder mutation p.R337H in TP53.
Germline mutations in the TP53 gene are associated with Li-Fraumeni and Li-Fraumeni-Like Syndromes, characterized by increased predisposition to early-onset cancers. In Brazil, the prevalence of the TP53-p.R337H germline mutation is exceedingly high in the general population and in cancer-affected patients, probably as result of a founder effect. Several genotyping methods are used for the molecular diagnosis of LFS/LFL, however Sanger sequencing is still considered the gold standard. We compared performance, cost and turnaround time of Sanger sequencing, PCR-RFLP, TaqMan-PCR and HRM in the p.R337H genotyping. The performance was determined by analysis of 95 genomic DNA samples and results were 100% concordant for all methods. Sequencing was the most expensive method followed by TaqMan-PCR, PCR-RFLP and HRM. The overall cost of HRM increased with the prevalence of positive samples, since confirmatory sequencing must be performed when a sample shows an abnormal melting profile, but remained lower than all other methods when the mutation prevalence was less than 2.5%. Sequencing had the highest throughput and the longest turnaround time, while TaqMan-PCR showed the lowest turnaround and hands-on times. All methodologies studied are suitable for the detection of p.R337H and the choice will depend on the application and clinical scenario.


Isolation and structural characterization of a non-diketopiperazine phytotoxin from a potato pathogenic Streptomyces strain.
Two Streptomyces spp. strains responsible for potato common scab infections in Uruguay which do not produce diketopiperazines were identified through whole-genome sequencing, and the virulence factor produced by one of them was isolated and characterized. Phylogenetic analysis showed that both pathogenic strains can be identified as S. niveiscabiei, and the structure of the phytotoxin was elucidated as that of the polyketide desmethylmensacarcin using MS and NMR methods. The metabolite is produced in yields of ∼200 mg/L of culture media, induces deep necrotic lesions on potato tubers, stuns root and shoot growth in radish seedlings, and is comparatively more aggressive than thaxtomin A. This is the first time that desmethylmensacarcin, a member of a class of compounds known for their antitumor and antibiotic activity, is associated with phytotoxicity. More importantly, it represents the discovery of a new virulence factor related to potato common scab, an economically-important disease affecting potato production worldwide.


Hereditary diffuse gastric cancer: One family's story.
Hereditary diffuse gastric cancer (HDGC) is an inherited form of gastric cancer that carries a poor prognosis. Most HDGCs are caused by an autosomal dominant genetic mutation in the CDH1 gene, which carries a 70%-80% lifetime risk of gastric cancer. Given its submucosal origin, endoscopic surveillance is an unreliable means of early detection, and prophylactic gastrectomy is recommended for CDH1 positive individuals older than age 20 years. We describe the case of a male with recurrent gastric cancer who was diagnosed with HDGC secondary to the CDH1 mutation, and we also describe the patient's pedigree and outcomes of recommended genetic testing.


Effects of Qing Qiao Capsule in the treatment of chronic secretory otitis media and the levels of serum inflammatory factors.
To explore the effects of Qing Qiao Capsule in the treatment of chronic secretory otitis media and the levels of serum inflammatory factors, a total of 50 chronic secretory otitis media patients in the control group were subjected to caefaclor capsule, while the total of 50 cases in the observation group were treated with Qing Qiao Capsule. The traditional Chinese medicine (TCM) syndrome scores, therapeutic effects, and the levels of inflammatory factors were evaluated. After treatment, the scores of deafness, hearing loss, dizziness, soreness and weakness of the waist and knees, and fever is hens in palms and soles were significantly decreased in both groups (all P value <0.05). However, each score in the observation group was markedly less than that of the control group (all P value <0.05). Moreover, the C-reactive protein (CRP), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) levels measured after treatment were significantly lowered than those before treatment (all P value <0.05). Also, the levels of CRP, PCT and TNF-α in the observation group were obviously less than that of the control group (all P value <0.05). And the total therapeutic efficacy of the observation group was significantly higher than that of the control group (P<0.05). But no significant difference was observed in the rates of adverse reactions between both groups (P>0.05). Application of Qing Qiao Capsule in the treatment of chronic secretory otitis media yields better results, lowers TCM syndrome scores, and alleviates the body's inflammatory response, which is a safe drug in clinical use.


Defeating Urinary Incontinence with Exercise Training: Results of a Pilot Study in Frail Older Women.
To determine whether combining behavioral urinary incontinence (UI) treatments with physical activity improves UI in frail older women. Single-blind, two-arm pilot randomized controlled trial. Senior apartments. Frail women (mean age 84.9 ± 6.4) without dementia (n = 42). Twelve-week program of customized behavioral UI treatments: 150 minutes of weekly walking and twice weekly strength training classes. UI was measured using 3-day bladder diaries, the International Consultation on Incontinence Questionnaire (ICIQ), and UI global improvement questions. Toileting skills were measured using the Performance Oriented Timed Toileting Instrument (POTTI) and the Minnesota Toileting Skills Questionnaire (MTSQ). Physical function was measured using the Short Physical Performance Battery. UI-related quality of life was measured using the Incontinence Impact Questionnaire and Urogenital Distress Inventory. The treatment group reported a 50% reduction in daily leaks using bladder diaries, and the control group reported no change (P = .04). Although there were no group differences in total ICIQ scores (P = .66), the treatment group reported significantly greater improvement on the ICIQ item for urine leakage (P = .01). More than 81% of the treatment group and 36% of the control group reported improvement in UI (χ2 = 4.84, P = .01), with mean estimated percentage improvement of 65.3 ± 32.0 versus 34.1 ± 41.3 (P = .03). Although the difference was not statistically significant, treatment group participants improved their toileting skills, whereas those of the control group declined (P = .42 POTTI, P = .11 MTSQ). Balance (P = .33) and gait (P = .24) improved more in the treatment group, whereas chair stands improved more in the control group (P = .14). UI may be improved in frail older women by combining behavioral strategies for UI with physical activity, but larger trails are needed to determine whether these findings can be replicated and sustained.


Development of Silafluofen-Based Termiticides in Japan and Thailand.
With the advancement from natural pyrethrins to synthetic pyrethroids, their applications have expanded from household insecticides for indoor use against sanitary pests to outdoor use for agriculture, forestry, animal health, termite control, and many other pest situations. However, high fish toxicity and development of pyrethroid resistance in some pests have been cited as common shortcomings of pyrethroids. To overcome these pyrethroid problems such as high fish toxicity, Katsuda and fellow scientists invented silafluofen by introducing a silicone atom into the pyrethroidal chemical structure in 1984. In addition to the high insecticidal activity and low mammalian toxicity, this compound features low fish toxicity, chemical stability under sunlight, in the soil and under alkaline environments. These features make silafluofen unique among pyrethroids. In Japan, silafluofen has been used as an agricultural insecticide for 15 years since 1995 for various plants, especially useful for paddy rice protection because of its low fish toxicity. Over the last 20 years, silafluofen-based termiticides including emulsifiable concentrate (EC) and oil formulations have been widely used in Japan for soil treatment and timber treatments. Additional silafluofen product lines include anti-termitic plastic sheets which are laid under buildings. In this paper, literature on the development of silafluofen and its use in Japan are reviewed. On the other hand, in Thailand, we proceeded with development works of silafluofen-based termiticides from 2005 by starting laboratory efficacy tests and field efficacy tests in Phuket. Both laboratory and field tests showed good efficacy as a soil termiticide, suggesting that the material will perform well for commercial use in high biological hazard environments such as Thailand and can be used in environments close to water where fish toxicity might be a concern with other pyrethroids.


Epidemiology and Outcomes of Status Epilepticus.
Status epilepticus (SE) is a neurological and medical emergency, defined as a condition resulting either from the failure of the mechanisms responsible of seizure self-limitation or from the initiation of mechanisms which lead to atypically prolonged seizures. Further than death, SE can have long-term consequences, including neuronal injury, depending on the type, cause and duration of seizures with severe associated disabilities. In Europe, SE shows an incidence rate ranging about 9 to 40/100,000/y. In adults, mortality of patients with SE is ~30%, and even higher (up to 40%) in refractory status epilepticus. To date, etiology, duration, presence of comorbidity, level of consciousness, semiology and age are the main clinical predictors of SE outcome.


Experimental research into the potential therapeutic effect of GYY4137 on Ovariectomy-induced osteoporosis.
Evidence has shown that endogenous H2S plays an important role in the physiological and pathophysiological processes of many organs. The study aimed to explore whether exogenous H2S has a potential therapeutic effect on a rat ovariectomy-induced model of osteoporosis. The OVX osteoporosis model was established in female Sprague-Dawley rats by full bilateral ovariectomy. The rats were randomly divided into four groups, with the two experimental groups receiving an intraperitoneal injection of GYY4137 or sodium alendronate. The level of H2S in the plasma was determined and common laboratory indicators to diagnose osteoporosis, such as alkaline phosphatase (ALP) activity and the levels of osteocalcin (OCN), calcitonin, parathyroid hormone and leptin were measured. The bone mineral density (BMD) of the 4th and 5th lumbar vertebrae was measured using dual-energy X-ray absorptiometry. The maximum stress of femoral fracture was obtained through a three-point bending test of the femur. The OVX osteoporosis model was successfully established. GYY4137 was injected to increase the level of H2S in the plasma in one group, designated OVX-GYY during the observation period (p < 0.05). At 12 weeks, the BMD value of the fourth lumbar vertebra in the OVX-GYY group had increased (p < 0.05). The BMD femur value in the OVX-vehicle group had decreased (p < 0.05). Bilateral ovariectomy leads to biochemical disorders related to bone metabolism and hormone levels in rat plasma (all p < 0.05). Ovariectomy also reduced blood calcium, blood phosphate and calcitonin, and increased parathyroid hormone and leptin. The opposite results were obtained for the groups with alendronate sodium or GYY4137 treatment (all p < 0.05). Through the slow release of H2S, GYY4137 did an excellent job of simulating endogenous neuroendocrine gaseous signaling molecules. Exogenous H2S had a regulatory effect on osteoporosis in ovariectomized rats, showing potential value for the treatment of human postmenopausal osteoporosis.


Identification of new proteins in follicular fluid of mature human follicles.
Proteins present in human follicular fluid (HFF) have been poorly characterized to date. The purpose of our study was to analyse the protein content and identify new proteins originating from fluid of mature human follicles. A total of six females from infertile couples referred for in vitro fertilization (IVF) were stimulated and 44 follicular fluid samples from mature follicles yielding an oocyte were collected 34-36 h after human chorionic gonadotropin administration. HFF samples were processed for high-resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Comparative analysis of the 2-D gels revealed up to 600 spots, of which four were selected because of variations in their expression level. Using direct sequencing procedures (Edman degradation) or matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS), these four spots were identified as three new proteins: thioredoxin peroxydase 1 (TDPX1), transthyretin (TTR) and retinol-binding protein (RBP). The proteins identified here may emerge as potential candidates for specific functions during folliculogenesis and may prove useful as biomedical markers for follicle and/or oocyte maturation.


Differences in editing at homologous sites in messenger RNAs from angiosperm mitochondria.
Recent work has shown that amino acid sequence comparisons can be used to infer sites of C-to-U RNA editing in plant mitochondrial mRNAs (1). In order to test such predictions further and to search for conserved mRNA structural motifs that might provide insight into the mechanism of recognition of editing sites, the complete sequences of the cytochrome c oxidase subunit II (COXII) mRNAs of wheat, maize and pea were determined by reverse transcriptase sequencing. The results affirm the high reliability of editing predictions based on amino acid sequence alignments, and prompt us to make the further inference that COXI (cytochrome oxidase subunit I) mRNA is extensively edited in dicotyledonous plants but not in monocotyledons. In plant COXII mRNAs, additional non-predicted editing occurs such that the resulting derived amino acid sequences are more similar to those of non-plants than is indicated by the respective plant COXII DNA sequences. A number of homologous sites show differences in editing among species, and certain positions show partial editing within a species. Despite some deviation from expected nucleotide frequencies in the vicinity of editing sites, no extensive conserved primary or secondary structural motifs are apparent. The relevance of these data to the mechanism of RNA editing in plant mitochondria is discussed.


Minilaparotomy in the management of benign gynecologic disease.
Considering the enormous advantages of minimally invasive surgery, attempts to explore less invasive trans-abdominal incisions could represent an alternative to laparoscopic gynecologic surgery. The aim of this study was to assess the feasibility and clinical outcome of minilaparotomy in a large series of patients. In this retrospective study we describe our 6-year experience on 252 patients undergoing surgery by minilaparotomy for benign adnexal or uterine disease. Surgical treatments included total abdominal hysterectomy, myomectomy, mono or bilateral salpingo-oophorectomy and adnexal surgery. The mean population age and BMI were 39.2 years (+/-13.2 S.D.) and 23.6 (+/-3.31 S.D.), respectively. The mean operative time was 75.4 min (+/-31.8) and the estimated blood loss was never significant except in two cases (0.8%). The mean duration of ileus was 1.58 days (+/-0.6 S.D.) and the mean days until discharge were 3.06 (+/-1.14 S.D.), with a significantly lower duration of recovery in the group of simple adnexal surgery with respect to the others (p = 0.0001). No severe early post-operative morbidity was observed. The current report describes minilaparotomy as a feasible surgical approach in benign gynecological diseases. The operative time is quite similar or shorter than reported for laparoscopy, laparotomy and vaginal surgery. The estimated blood loss is not significant as well as the duration of the ileus and discharge. Moreover, a prospective randomised study, already ongoing in our department, will better answer the question of whether minilaparotomy could be an alternative to laparoscopic and vaginal surgery.


Behavioral decision-making of the government, farmer-specialized cooperatives, and farmers regarding the quality and safety of agricultural products.
The quality and safety of agricultural products is very important for farmers' professional cooperatives. This study incorporates the government, farmers' professional cooperatives and farmers into the evolutionary game model to explore the game relationship and evolutionary path of decision-making among the three parties related to the quality and safety of agricultural products. Through the dynamic analysis of decision-making replication, the analysis of strategy evolution stability and the verification of numerical simulation experiments, it is shown that the decision-making behavior of the government, farmers' professional cooperatives and farmers under the conditions of agricultural product quality and safety is the result of the game between three stakeholders; the government, farmers' professional cooperatives and farmers The evolution process of the decision-making behavior to the ideal state is affected by many factors, and the value ranges of different factors have different effects on the convergence speed of the three stakeholders to the ideal state; when certain conditions are met, the government, farmers' professional cooperatives and farmers' three The decision-making behavior of each stakeholder can evolve into an ideal state, and effective government supervision can promote the cooperatives to manage the green production of farmers, and then effectively encourage farmers to take the initiative in green production. In order to provide useful suggestions for the government to make safety supervision decisions, to effectively manage cooperatives, and to stimulate active green production behaviors by farmers.


Caries prevalence in northwest Michigan migrant children.
The purpose of this study was to describe the prevalence of dental caries in a sample of Hispanic-American migrant workers' children and compare the results with an earlier Northwest Michigan migrant study to assess if migrant children have benefited from the global caries decline. A non-probability convenience sample of migrant farm worker children was obtained from migrant schools in Northwest Michigan during the summer of 1999. Field dental equipment was used to examine caries, fluorosis, and urgent dental needs by 1 examiner. Statistical analysis was performed using SAS software with the student t-test used to test for differences between the samples. Intra-examiner reliability was high for caries at the surface level (kappa = 0.94). The sample consisted of 211 children with 95% ranging in ages from 5 to 13. Mean caries levels were as follows: DMFT = 1.1 (SD 1.6); DMFS = 1.6 (SD 2.5); dft = 3.0 (SD 2.9); dfs = 6.3 (SD 6.7) Fifty percent of children with at least 1 permanent tooth (189) were caries free, with 17% (34) having DMFT values greater than or equal to 3. The large number of caries-free children displayed a skewed distribution of caries where a small proportion of the population harbored the majority of the disease. A statistically significant decrease in caries was evident in permanent teeth (P = .0001) between 1999 and 1982 samples, but no change was realized in primary teeth (P = .7). Results indicated that the caries decline has extended to this long-neglected migrant group, but only in the permanent dentition. Caries remained moderate to high in the primary dentition and the caries burden was carried by a relatively small segment of the population. Dental treatment programs should be expanded to include preschool children who appear to be at the highest risk for caries.


Comparison of Standard Catheters Versus Radial Artery-Specific Catheter in Patients Who Underwent Coronary Angiography Through Transradial Access.
In this prospective, randomized controlled study, we aim to compare the performance outcomes of standard catheters with the radial artery-specific catheter. Over the past decade, transradial cardiac catheterization has gained widespread popularity because of its low complication rates compared with transfemoral access. Operators have the choice of using either standard catheters (used for both transfemoral and transradial approach, with need for separate catheter use for either right or left coronary artery engagement) or a dedicated radial artery catheter, which is specifically designed to engage both coronary arteries through radial artery access. A total of 110 consecutive patients who underwent coronary angiography at our institution from March 2015 to April 2015 were prospectively randomized to either radial artery-specific Tiger catheter (5Fr; Terumo Interventional Systems, Somerset, New Jersey) versus standard Judkins left and right catheters (5Fr R4, L4; Cordis Corporation, Miami, Florida). The end points of the study included fluoroscopy time, dose-area product, contrast volume used, and total procedure time for the coronary angiography. A total of 57 patients (52%) were randomized to radial artery-specific catheter and 53 (48%) to the standard catheter. Tiger catheter was associated with significantly lower fluoroscopy time (184 ± 91 vs 238 ± 131 seconds, p = 0.015), which was statistically significant. Other outcome measures such as dose-area product (2,882.4 ± 1,471.2 vs 3,524.6 ± 2,111.7 Gy·cm(2), p = 0.07), total contrast volume (48.1 ± 16.1 vs 53.4 ± 18.5 ml, p = 0.114), and total procedure time (337 ± 382 vs 434 ± 137 seconds, p = 0.085) were also lower in single-catheter group, but it did not reach statistical significance. A total of 8 patients (14%) were crossed over from radial-specific catheter arm to standard catheter arm because of substandard image quality and difficulty in coronary engagement. Six patients had to be switched to femoral access (3 in each group) secondary to radial artery spasm. In conclusion, the radial artery-specific catheter was shown to have significantly lower fluoroscopy times but higher failure rates compared with the standard catheters.


Allergic contact dermatitis: patch testing results at Mount Sinai Medical Center.
Patch testing is an important diagnostic tool commonly used to identify allergens responsible for allergic contact dermatitis, especially in cases where the diagnosis is not clearly apparent. The authors report the patch test results from 2004-2008 and compare the results with the North American Contact Dermatitis Group and Mayo Clinic. Four hundred thirty-four patients with suspected allergic contact dermatitis underwent standardized patch testing with a tray consisting of 50 allergens at Mount Sinai Medical Center. Two hundred ninety patients (66.8%) had positive reactions to at least one allergen. The most frequent contact allergens included nickel sulfate (13%), fragrance mix (9.6%), propylene glycol (7.8%), neomycin sulfate (6.6%), thimerosal (6.4%), bacitracin (6.2%), and sodium gold thiosulfate (5.8%).


Reversible escape from a well across a barrier by diffusion in one dimension.
Escape by diffusion in one dimension from a parabolic well across a parabolic barrier is investigated for a range of barrier heights. The probability of occupation of the well decays at long times inversely with the square root of time due to repeated return to the well after excursion in the outer space. The amplitude of the long-time tail increases as the barrier gets lower. The time dependence of the occupation probability can be described by a phenomenological rate equation with memory term and with a source term describing the rate of return from the outer space. For moderately high barrier the rate coefficient deviates from the Kramers expression.


Absence of correlation between oral contraceptive usage and cardiovascular mortality.
Oral contraceptive (OC) usage and cardiovascular mortality rates for all women (and men) of reproductive age, but specifically for those aged 35-44 years, were examined in the United Kingdom. These data show: OC-usage increased from 14.1 million packs in 1968, to 45.1 million in 1976, decreasing to 37.1 million in 1980. Ischaemic heart disease (IHD) mortality rates for the years 1968-1980 for women of reproductive age of 15-34 years were stable: for those aged 35-44 years the rates fell gradually by 19%. Mortality rates for all types of cerebrovascular disease (CVD) for 1969-1978 remained stable for women of 15-34 years, but for women of 35-44 years rates for subarachnoid haemorrhage and cerebral haemorrhage (the two largest groups) declined by 11% and 34% respectively. The absence of a positive correlation between OC usage and cardiovascular mortality rates is difficult to explain if OCs are the cause of fatalities, as claimed by some epidemiological studies. Possible counteracting variables--such as decreased ascertainment or decreased usage by women of 35-44 years, or decreased relative risk over the time period--which might account for this paradoxical result, were examined but discarded as being unlikely. Evidence from other data--e.g. the similarity of male and female mortality rates for each group, the increased mortality rates for women of 45-54 years (who do not take OCs), and the similarity of mortality rates in women in years when OC-usage was widely different--all suggest that a counteracting variable does not exist. The data on cardiovascular mortality rates in the UK, showing an absence of positive correlation with OC-usage, are thus opposed to the conclusions of epidemiological studies claiming an increased risk of cardiovascular mortality due to OCs, and specifically contradict the claim that such increased risk is found in 35-44 year-old OC-users.


Emergency serum and urine HCG analyses with the 'Tandem ICON' procedure.
A comparison between new urine and serum enzyme immunoassay techniques and existing serum radioimmunoassay techniques for the detection of HCG in the diagnosis of ectopic and early intrauterine pregnancy was undertaken. Urine HCG estimations by enzyme immunoassay were not found to be adequate for the exclusion of ectopic pregnancy due to a false negative rate of 12.5% (2 of 16 patients). Serum HCG estimations by enzyme immunoassay were found to compare favourably with radioimmunoassay techniques in the detection of HCG in both ectopic and early intrauterine pregnancy.


Delivery of Morpholino Antisense Oligonucleotides to a Developing Ovine Conceptus via Luminal Injection into a Ligated Uterine Horn.
In vivo delivery of morpholino antisense oligonucleotides (MAO) directly into the uterine lumen of a peri-implantation period pregnant sheep is an effective technique for evaluation of gene products for conceptus development. The highly phagocytic conceptus is undergoing rapid morphological change, thereby the available MAO are readily consumed and delivered to developing cells. Here, we describe the method for preparation and surgical delivery of MAO-Endo-Porter complex to developing ovine conceptus on day 8 postmating. Also outlined are methods for posttreatment sample recovery on day 16 postmating.


Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling.
It is well established that developmental exposure of sevoflurane (an inhalational anesthetic) is capable of inducing neuronal apoptosis and subsequent learning and memory disorders. Synaptic NMDA receptors activity plays an essential role in cell survival, while the extra-synaptic NMDA receptors activation is usually associated with cell death. However, whether synaptic or extra-synaptic NMDA receptors mediate developmental sevoflurane neurotoxicity is largely unknown. Here, we show that developmental sevoflurane treatment decreased NR2A, but increased NR2B subunit expression both in vitro and in vivo. Sevoflurane-induced neuronal apoptosis was attenuated by synaptic NMDA receptors activation or low dose of exogenous NMDA in vitro. Interestingly, these effects could be abolished by NR2A inhibitor PEAQX, but not NR2B inhibitor Ifenprodil in vitro. In contrast, activation of extra-synaptic NMDA receptors alone had no effects on sevoflurane neurotoxicity. In the scenario of extra-synaptic NMDA receptors stimulation, however, sevoflurane-induced neuronal apoptosis could be prevented by addition of Ifenprodil, but not by PEAQX in vitro. In addition, sevoflurane neurotoxicity could also be rescued by memantine, an uncompetitive antagonist for preferential blockade of extra-synaptic NMDA receptors both in vitro and in vivo. Furthermore, we found that developmental sevoflurane-induced phospho-ERK1/2 inhibition was restored by synaptic NMDA receptor activation (in vitro), low dose of NMDA (in vitro) or memantine (in vivo). And the neuroprotective role of synaptic NMDA activity was able to be reversed by MEK1/2 inhibitor U0126 in vitro. Finally, administration of memantine or NMDA significantly improved spatial learning and memory dysfunctions induced by developmental sevoflurane exposure without influence on locomotor activity. These results indicated that activation of synaptic NR2A-containing NMDA receptors, or inhibition of extra-synaptic NR2B-containing NMDA receptors contributed to the relief of sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling may be involved in this process.


Effects of 3-Methylgibberellin Analogs on Gibberellin 3β-Hydroxylases and Plant Growth.
Six 3-methylgibberellin analogs were synthesized, and their effects on the GA 3β-hydroxylases from immature seeds of Phaseolus vulgaris and Cucurbita maxima, and/or on the growth of dwarf rice (Oryza sativa L. cv. Tan-ginbozu) and cucumber (Cucumis sativus L. cv. Spacemaster) were investigated. 3-Methyl-GA5 and 2, 3-didehydro-3-methyl-GA9· inhibited the conversion of [2, 3-(3)H2]GA9 to [2-(3)H]GA4 by GA 3β-hydroxylases from both P. vulgaris and C. maxima at 3 μM and higher. Their C/D-ring-rearranged isomers, 2, 3-didehydro-3-methyl-DGC and 16-deoxo-2, 3-didehydro-3-methyl-DGC, inhibited 3β-hydroxylation by the enzyme from P. vulgaris threefold more strongly than the non-C/D-ring-rearranged compounds, but exhibited no effect on 3β-hydroxylation by the enzyme from C. maxima. In a dwarf rice seedling assay, 3-methyl-GA5 and 2, 3-didehydro-3-methyl-GA9 promoted shoot elongation at doses of 300 ng/plant and higher, and 3α-methyl-GA1 and 3α-methyl-GA4 at doses of 30 ng/plant and higher. In contrast 2, 3-didehydro-3-methyl-DGC inhibited shoot growth to half that of the control at a dose of 300 ng/plant, and 16-deoxo-2, 3-didehydro-3-methyl-DGC showed no effect on growth. In a cucumber seedling assay, 3α-methyl-GA4 promoted hypocotyl elongation at doses of 300 ng/plant and higher. The other C-3 methyl compounds showed no effect on the hypocotyl elongation of cucumber seedlings.


Metal-oxide-junction, triple point cathodes in a relativistic magnetron.
Triple point, defined as the junction of metal, dielectric, and vacuum, is the location where electron emission is favored in the presence of a sufficiently strong electric field. To exploit triple point emission, metal-oxide-junction (MOJ) cathodes consisting of dielectric "islands" over stainless steel substrates have been fabricated. The two dielectrics used are hafnium oxide (HfO(x)) for its high dielectric constant and magnesium oxide (MgO) for its high secondary electron emission coefficient. The coatings are deposited by ablation-plasma-ion lithography using a KrF laser (0-600 mJ at 248 nm) and fluence ranging from 3 to 40 J/cm(2). Composition and morphology of deposited films are analyzed by scanning electron microscopy coupled with x-ray energy dispersive spectroscopy, as well as x-ray diffraction. Cathodes are tested on the Michigan Electron Long-Beam Accelerator with a relativistic magnetron, at parameters V=-300 kV, I=1-15 kA, and pulse lengths of 0.3-0.5 micros. Six variations of the MOJ cathode are tested, and are compared against five baseline cases. It is found that particulate formed during the ablation process improves the electron emission properties of the cathodes by forming additional triple points. Due to extensive electron back bombardment during magnetron operation, secondary electron emission also may play a significant role. Cathodes exhibit increases in current densities of up to 80 A/cm(2), and up to 15% improvement in current start up time, as compared to polished stainless steel cathodes.


Statistical dissection of genetic pathways involved in prostate carcinogenesis.
Molecular markers that could stratify prostate cancer patients according to risk of disease progression would allow a significant improvement in the management of this clinically heterogeneous disease. In the present study, we analyzed the genetic profile of a consecutive series of 51 clinically confined prostate carcinomas and 27 benign prostatic hyperplasias using comparative genomic hybridization (CGH). We then added our findings to the existing literature data in order to perform a meta-analysis on a total of 294 prostate cancers with detailed CGH and clinicopathological information, using multivariate statistical methods that included principal component, hierarchical clustering, time of occurrence, and regression analyses. Whereas several genomic imbalances were shared by organ-confined, locally invasive, and metastatic prostate cancers, 6q and 10q losses and 7q and 8q gains were significantly more frequent in patients with extra-prostatic disease. Regression analysis indicated that 8q gain and 13q loss were the best predictors of locally invasive disease, whereas 8q gain and 6q and 10q losses were associated with metastatic disease. We propose a genetic pathway of prostate carcinogenesis with two distinct initiating events, namely, 8p and 13q losses. These primary imbalances are then preferentially followed by 8q gain and 6q, 16q, and 18q losses, which in turn are followed by a set of late events that make recurrent and metastatic prostate cancers genetically more complex. We conclude that significant differences exist in the genetic profile of organ-confined, locally invasive, and advanced prostate cancer and that genetic features may carry prognostic information independently of Gleason grade.


Efficacy and safety of the third-generation chloroethylnitrosourea fotemustine for the treatment of chemorefractory T-cell lymphomas.
Patients with recurring T-cell non-Hodgkin lymphoma (T-NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T-NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third-generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m(2) every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end-stage T-NHL. Formal studies with this agent are warranted in T-cell malignancies.


[Euthanasia: what the pharmacist should know].
It is not unusual for a pharmacist to get a prescription to deliver a "kit for euthanasia", without further explanation. However, such a kit is not available. Which products and materials are necessary to perform euthanasia? What are the conditions to which the prescription and delivery has to comply? This article summarizes what you need to know.


Design and Formulation of Optimized Microemulsions for Dermal Delivery of Resveratrol.
The objective of this study was to formulate optimal formulations of microemulsions (MEs) and evaluate their feasibility for delivery of resveratrol into human skin ex vivo. Oil-in-water MEs were formulated using surfactant (S) PEG-8 caprylic/capric glycerides and cosurfactant (CoS) polyglyceryl-6-isostearate. Ethyl oleate was used as an oily phase. MEs were formulated using 5 : 1, 6 : 1, and 7 : 1 surfactant and cosurfactant (S : CoS) weight ratios. Pseudoternary phase diagrams were constructed and optimal compositions of MEs were obtained using Design Expert software. Mean droplet size for optimized ME formulations was determined to be 68.54 ± 1.18 nm, 66.08 ± 0.16 nm, and 66.66 ± 0.56 nm for systems with S : CoS weight ratios 5 : 1, 6 : 1, and 7 : 1, respectively. Resveratrol loading resulted in mean droplet size increase. The distribution of droplet size between fractions changed during storage of formulated MEs. Results demonstrated the increase of number of droplets and relative surface area when S : CoS weight ratios were 6 : 1 and 7 : 1 and the decrease when S : CoS weight ratio was 5 : 1. The highest penetration of resveratrol into the skin ex vivo was determined from ME with S : CoS weight ratio 5 : 1. It was demonstrated that all MEs were similar in their ability to deliver resveratrol into the skin ex vivo.


Achieving an Accurate Surface Profile of a Photonic Crystal for Near-Unity Solar Absorption in a Super Thin-Film Architecture.
In this work, a teepee-like photonic crystal (PC) structure on crystalline silicon (c-Si) is experimentally demonstrated, which fulfills two critical criteria in solar energy harvesting by (i) its Gaussian-type gradient-index profile for excellent antireflection and (ii) near-orthogonal energy flow and vortex-like field concentration via the parallel-to-interface refraction effect inside the structure for enhanced light trapping. For the PC structure on 500-μm-thick c-Si, the average reflection is only ∼0.7% for λ = 400-1000 nm. For the same structure on a much thinner c-Si ( t = 10 μm), the absorption is near unity (A ∼ 99%) for visible wavelengths, while the absorption in the weakly absorbing range (λ ∼ 1000 nm) is significantly increased to 79%, comparing to only 6% absorption for a 10-μm-thick planar c-Si. In addition, the average absorption (∼94.7%) of the PC structure on 10 μm c-Si for λ = 400-1000 nm is only ∼3.8% less than the average absorption (∼98.5%) of the PC structure on 500 μm c-Si, while the equivalent silicon solid content is reduced by 50 times. Furthermore, the angular dependence measurements show that the high absorption is sustained over a wide angle range (θinc = 0-60°) for teepee-like PC structure on both 500 and 10-μm-thick c-Si.


Proteome-Wide Response of Dormant Caryopses of the Weed, Avena fatua, After Colonization by a Seed-Decay Isolate of Fusarium avenaceum.
Promoting seed decay is an ecological approach to reducing weed persistence in the soil seedbank. Previous work demonstrated that Fusarium avenaceum F.a.1 decays dormant Avena fatua (wild oat) caryopses and induces several defense enzyme activities in vitro. The objectives of this study were to obtain a global perspective of proteins expressed after F.a.1-caryopsis colonization by conducting proteomic evaluations on (i) leachates, soluble extrinsic (seed-surface) proteins released upon washing caryopses in buffer and (ii) proteins extracted from whole caryopses; interactions with aluminum (Al) were also evaluated in the latter study because soil acidification and associated metal toxicity are growing problems. Of the 119 leachate proteins classified as defense/stress, 80 were induced or repressed. Defense/stress proteins were far more abundant in A. fatua (35%) than in F.a.1 (12%). Avena defense/stress proteins were also the most highly regulated category, with 30% induced and 35% repressed by F.a.1. Antifungal proteins represented 36% of Avena defense proteins and were the most highly regulated, with 36% induced and 37% repressed by F.a.1. These results implicate selective regulation of Avena defense proteins by F.a.1. Fusarium proteins were also highly abundant in the leachates, with 10% related to pathogenicity, 45% of which were associated with host cell wall degradation. In whole caryopsis extracts, fungal colonization generally resulted in induction of a similar set of Avena proteins in the presence and absence of Al. Results advance the hypothesis that seed decay pathogens elicit intricate and dynamic biochemical responses in dormant seeds.


Population and formal genetics of the human C81(alpha-gamma) polymorphism.
One hundred and ninety-six unrelated healthy individuals and 30 families with 75 offspring have been studied for the C81(alpha-gamma) polymorphism. The following allele frequencies were calculated: C81*A = 0.5536; C81*B = 0.4286; C81*A1 = 0.0178. Observed and expected phenotype frequencies were in a good agreement according to the Hardy Weinberg law. No exceptions from the mode of inheritance were found. In family W the segregation of the rare allele C81*A1 could be followed. Comparing the results of this study with previous data from Boston and Oslo, a combined technology including C8-dependent lysis and C8 structural variation is suggested for future investigations.


A Retrospective Cohort Study of Birth Outcomes in Neonates Exposed to Naltrexone in Utero: A Comparison with Methadone-, Buprenorphine- and Non-opioid-Exposed Neonates.
Naltrexone may provide a suitable alternative to methadone and buprenorphine in the treatment of pregnant opioid-dependent women; however, little is known about its effects on neonatal morbidity and mortality. The aim was to evaluate the health of neonates exposed to naltrexone in utero, and compare it with outcomes in neonates exposed to methadone or buprenorphine and a non-exposed control group. Sequential cohorts of Western Australian (WA) opioid-dependent women treated with implant naltrexone, oral methadone or sublingual buprenorphine were identified via records from a drug and alcohol clinic (Subiaco, WA) for naltrexone and state prescribing records for methadone and buprenorphine. A control cohort of non-opioid-dependent women was obtained from the WA electoral roll. Identifying information and treatment records for these women were linked against the Midwife Notification System records to identify exposed offspring born between 2001 and 2011. Birth characteristics, congenital anomalies and perinatal mortality for all neonates were extracted from state records. The birth characteristics of naltrexone-exposed neonates (n = 68) were superior to methadone-exposed neonates (n = 199) in terms of birth size (birth weight, head circumference and length), hospital length of stay (5.5 vs. 11.3 days), and rates of neonatal abstinence syndrome (NAS) (7.5 vs. 51.5%). Naltrexone-exposed neonates were generally not significantly different to buprenorphine-exposed neonates (n = 124), with the exception of significantly lower rates of NAS (7.5 vs. 41.8%) and shorter hospital length of stay (5.5 vs. 8.0 days) in naltrexone-exposed neonates. Compared with the control group of neonates (n = 569), naltrexone-exposed neonates were not significantly different in terms of overall rates of congenital anomalies, stillbirths and neonatal mortality; however, they were significantly smaller (3137.1 vs. 3378.0 g), spent more time in hospital following birth (5.5 vs. 4.3 days) and had higher rates of NAS (7.5 vs. 0.2%). Exposure of neonates to prenatal methadone was associated with a high incidence of neonatal mortality (2.0 vs. 0.2 per 100 live births) and congenital anomalies (10.6 vs. 4.4 per 100 births) compared with the control group. Rates of neonatal mortality and congenital abnormalities in buprenorphine-exposed neonates were not significantly different to the control group. The use of implant naltrexone during pregnancy was not associated with higher rates of negative birth outcomes compared with methadone- and buprenorphine-exposed neonates. Significantly, naltrexone and buprenorphine were not associated with the high rates of neonatal mortality or congenital anomalies seen in methadone-exposed neonates.


Seroprevalence of anti-Leptospira antibodies in equines and associated workers-Isolation of Leptospira interrogans serogroup Canicola from equine urine.
To investigate seroprevalence of anti-Leptospira antibodies in equines and associated workers in Uruguay, 891 equine and 150 human sera were drawn; 212 equine urine samples were also taken for culture. Environmental conditions and equine raising or managing practices were recorded in all 72 visited establishments; epidemiological information was obtained from each worker. Microscopic agglutination technique (MAT) was performed with 10 Leptospira strains for equines and 18 for human sera, that were also studied with IgM indirect immunofluorescence (IgM-IIF). Equine titres ≥100 were considered positive, and human sera titres ≥200 suggested probable recent or past infection. Urines were cultured in Ellinghausen-McCullough-Johnson-Harris (EMJH) media; local identification of one obtained isolate with lipL32 PCR, Multiple Locus Variable number tandem repeat Analysis and partial rrs gene sequencing, were completed at Institut Pasteur, Paris. Estimated reactivity was 61.3% for equines, which was higher than the studied bovine national levels (21%) and mainly observed with Icterohaemorrhagiae serogroup (40.3%), Sejroe, Canicola, Pomona or Ballum. Aged animals from slaughterhouses and cattle farms were the most frequently positive. Multiple regression analysis confirmed a significant association between seropositivity and equine age. Only one positive culture could be fully studied, and confirmed to be Leptospira interrogans serogroup Canicola; it was added to the MAT antigen panel and revealed fairly frequent reaction with equine and human sera. Three workers (2%) showed titres = 200 with Icterohaemorrhagiae or Canicola serogroups, without recent clinical manifestations. Their attended equines reacted with the same serogroups, suggesting common source infections or infection transmitted by equines. Three other humans yielded titres = 100, and none of the 150 showed an IgM-IIF-positive result. Equines seem not to be an important origin of regional human leptospirosis, except perhaps during acute animal infection. More culture work is required to study intensity and lapses of leptospiruria, as well as to further identify circulating strains.


The novel cognitive flexibility in aphasia therapy (CFAT): A combined treatment of aphasia and executive functions to improve communicative success.
Over and above language deficits, persons with aphasia can present with impairments in executive functions, including deficits in cognitive flexibility. Cognitive flexibility constitutes the ability to update behaviour quickly and flexibly in a changing environment. Its deficits can restrict communicative ability, e. g. the ability to change a topic. To date, these deficits have been neglected in aphasia therapy, even though their consideration regarding language treatment may be beneficial for the persons affected. The present study aimed to evaluate whether aphasia therapy including cognitive flexibility leads to more improvement than conventional aphasia therapy. A pilot group study with ten patients was conducted. The patients received both the novel Cognitive Flexibility in Aphasia Therapy (CFAT) and conventional aphasia therapy in a cross-over design. Each therapy method was delivered for 20 sessions within two weeks. An assessment battery was applied five times, including language skills, communicative ability and verbal/nonverbal cognitive flexibility. Patients profited from CFAT regarding language skills, communicative ability and verbal cognitive flexibility. Furthermore, compared to conventional therapy, CFAT was more effective for verbal cognitive flexibility. This pilot study indicates that CFAT offers a novel opportunity to directly train cognitive flexibility in communicative settings and complements conventional therapy for optimal patient outcome.


Aromatic sulfonate anion-induced pseudorotaxanes: environmentally benign synthesis, selectivity, and structural characterization.
Anion-induced molecular threading is an emerging strategy for generating mechanically interlocked molecular architectures. Herein, we report the preparation of two pseudorotaxane structures generated from aromatic sulfonate anions and a tetraimidazolium-containing macrocycle in organic media, as well as under environmentally benign aqueous conditions.


The Effect of Position on PaCO2 and PETCO2 in Patients Undergoing Cervical Spine Surgery in Supine and Prone Position.
As per American Society of Anesthesiologists guidelines, continuous monitoring of end tidal carbon dioxide (PETCO2) is recommended as standard II basics of anesthetic monitoring especially to ensure adequate ventilation during all anesthetics. Continuous monitoring of PETCO2 can also be used as a guide to maintain the partial pressure of carbon dioxide in arterial blood (PaCO2) to desired level during the surgery. To study the effect of position on PaCO2 and PETCO2 during cervical spine surgery in prone position. Following institutional ethical committee approval and written informed consent, a prospective study was conducted in 40 patients of 18 to 60 years and of American Society of Anesthesiologists I and II scheduled for cervical spine surgery in prone position. In operating room, the patient is connected to standard monitoring and intravenous access was secured. A 20 G arterial cannula was placed. General anesthesia administered and oral endotracheal intubation done. Baseline values of systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, temperature, SpO2, Ppeak, Pmean, and Pplateau were measured in supine position. For each patient the capnometer was calibrated before use. The P(a-ET)CO2 was calculated in supine position (S1). The PaCO2 and ETCO2 were measured after prone positioning P1, at each subsequent hour (P2, P3, P4), and on completion of the procedure in supine position (S2). The mean values were used for further analysis. The PETCO2 and PaCO2 decreased significantly in cervical spine surgery patients with change of position from supine to prone with no significant change in arterial to end tidal CO2 gradient (P(a-ET)CO2). PETCO2 can be used as a reliable guide to estimate PaCO2 during cervical spine procedures in prone position.