Prevalence estimates of violence in the dating experiences of college women.
Young women are vulnerable to experiencing psychological, physical, and sexual violence and stalking through dating experiences. This study used a correlational design to report prevalence estimates of psychological, physical, and sexual violence and stalking that occur within the dating experiences of college women. This study also compared prevalence estimates of violence between African-American and White college women. A convenience sample of 863 (N = 863) women between 18 and 25 years of age from a private, historically African-American college in the south and a private, historically primarily White college in the mid-Atlantic completed the Abuse Assessment Screen, and a background data sheet. All participants had the option of completing a narrative note. Data analysis consisted of frequencies, and chi2. Almost half of the total sample 48% (n = 412) reported the experience of violence and of these, 39% (n = 160) reported more than one form of violence. Specific prevalence was as follows: psychological violence 22% (n = 190), stalking or harassment 31% (n = 266), physical violence 12% (n = 99), and all unwanted sexual activity 9% (n = 80). Prevalence estimates were consistent for African-American and White college students in all types of violence except in reporting threats of physical violence and threats plus actual physical violence. Study findings highlight the need for nurses to routinely screen and assess all young women for psychological, physical, and sexual violence and stalking Surveillance efforts will help identify victims and potential victims so that appropriate referrals for treatment and support can be made.


Solid-state transformations of ribavirin as a result of high-shear mechanical processing.
Ribavirin (C8H12N4O5; anti-viral agent) was crystallized as two unique, phase-pure polymorphs (R-I and R-II). Calorimetrically determined isobaric heat capacities and heat of transition data were utilized to determine the solid-state transition temperature (Ttr), confirming enantiotropism, while R-I was determined to be kinetically stable at ambient temperature. Unprocessed samples of the low Tm polymorph, R-II, did not convert into R-I when held isothermally well above Ttr for 7days. In contrast milled R-II completely transformed to R-I after 15min at the same storage conditions, indicating that defects sustained during processing reduced the energy barrier for transformation, allowing it to occur. R-II was subjected to both cryogenic milling and impact milling at ambient temperature for various durations. Cryomilling resulted in an in situ progressive reduction of crystallinity, with complete conversion to amorphous ribavirin after 2h. Limited molecular mobility attributable to the low milling temperature (Texp=-196°C) likely inhibited recrystallization, allowing the amorphous solid to persist. In contrast, continuous impact milling at ambient temperature resulted in complete in situ conversion from R-II to R-I after 3h. The data suggested rapid conversion to R-I from highly disordered regions during extended milling, facilitated by localized heat buildup that likely exceeded Tg and/or Ttr.


Impact of maternal HAART on the prevention of mother-to-child transmission of HIV: results of an 18-month follow-up study in Ouagadougou, Burkina Faso.
Mother-to-child transmission remains the main cause of global pediatric HIV infections, especially in sub-Saharan Africa. Many interventions based on single-dose antiretroviral therapy have been implemented to reduce the mother-to-child transmission of HIV. In resource-limited settings, highly active antiretroviral therapy (HAART) has only been recommended for HIV-infected pregnant women requiring treatment for their own health. Here, we assessed the efficacy over 18 months of maternal HAART versus peripartum short-course antiretroviral therapy (SCART) regimens for the prevention of mother-to-child transmission (PMTCT) of HIV. We conducted a retrospective cohort study of patients from two medical centers in Ouagadougou, Burkina Faso. The PMTCT files and registers from 1 January 2003 to 31 December 2006 were obtained from routine data collected at these sites. The main assessment criterion was the rate of HIV-1 positivity in children born to HIV-positive mothers as measured with HIV-1 rapid tests at 18 months. A total of 586 pregnant HIV-1-infected women in PMTCT programs were selected. Among these women, 260 were undergoing HAART and 326 received single-dose nevirapine (91.3%) or single-dose zidovudine (8.7%) at delivery. HIV-1 serological tests were performed on 454 children at 18 months old. The rate of HIV-1 vertical transmission was 0% (0/195) in the HAART group and 4.6% (12/259) in the single-dose monotherapy group (P<0.01). Eight infants in the HAART cohort and 30 in the SCART cohort were breastfed; three in the SCART group were HIV-positive. A total of 62 children died, 19 in the HAART group and 43 in the single-dose monotherapy group. Our study confirms that HAART for mothers effectively reduces the risk of infant HIV infection while preserving the breastfeeding option for mothers.


CEA in colonic adenocarcinomas and precancerous lesions. An immunohistochemical study with a novel monoclonal antibody.
Using a new anti-CEA (CB-CEA-1) murine monoclonal antibody, the expression of carcinoembryonic antigen (CEA) was studied in normal, premalignant and malignant human adult tissues with particular emphasis on colorectal mucosa. The CB-CEA-1 epitope was poorly expressed in normal adult tissues but was consistently found in colon cancers and adenomas in distinctive immunohistochemical patterns. Some apical staining was found with CB-CEA-1 in cells of normal colon mucosa whereas colon adenocarcinomas had a predominantly cytoplasmic staining pattern. Colonic adenomas presented a varied staining pattern. Some showed apical staining, others a CEA distribution pattern similar to that of adenocarcinomas, particularly those with a villous component. Our findings indicate a differential expression of CB-CEA-1 in adenoma cells in relation to their potential for malignant transformation. The possible usefulness of this Mab defined epitope for diagnostic and therapeutic purposes is indicated.


Gene expression analysis of Chironomus riparius in response to acute exposure to tire rubber microparticles and leachates.
Tire rubber microparticles (TRPs) entering aquatic ecosystems through stormwater runoffs is a significant challenge. TRPs are formed by the abrasion of tires with the road surface and include chemical additives that are an additional cause for concern. Currently, information on the molecular effects of TRPs, or especially its additives, in freshwater organisms is scarce. To address this problem, an array covering different cellular processes has been designed for the freshwater midge Chironomus riparius. Fourth-instar larvae were exposed to two concentrations of TRPs (1 mg L-1, 10 mg L-1) and tire rubber leachates (TRLs) (0,0125 %, 5 %) to evaluate the transcriptional activity by Real-Time PCR. To assess acute toxicity, larvae were exposed for 24 h and genes related to the endocrine system, stress response, DNA repair mechanisms, immune system, oxidative stress, and detoxification mechanisms were evaluated. The activity of the enzymes: glutathione S-transferase (GST) and catalase was also examined. The main pathway affected was the stress response showing overexpression of HSPs (HSC70.3, HSC70.4, HSC70.5, HSP60). Moreover, there was a reduction of the GSTd3 and catalase disrupting the antioxidant system. The upregulation of InR indicates a potential disturbance in the insulin pathway and ABCB6 activation only in TRPs exposure suggests its potential implication in their transport. However, most of these alterations are caused by TRLs, showing higher toxicity than TRPs. The results obtained in this work provide the first approach at the molecular and cellular levels to elucidate the impact of TRLs in freshwater organisms. To perform a realistic evaluation of the TR effects, additional research is required to assess the TR's long-term effects at the molecular level.


A walking robot called human: lessons to be learned from neural control of locomotion.
From what we know at present with respect to the neural control of walking, it can be concluded that an optimal biologically inspired robot could have the following features. The limbs should include several joints in which position changes can be obtained by actuators across the joints. The control of mono- and biarticular actuators should occur at least at three levels: one at direct control of the actuators (equivalent to motoneuron level), the second at indirect control acting at a level which controls whole limb movement (flexion or extension) and the third at a still higher level controlling the interlimb coordination. The limb level circuits should be able to produce alternating flexion and extension movements in the limb by means of coupled oscillator flexor and extensor parts which are mutually inhibitory. The interlimb control level should be able to command the various limb control centers. All three control levels should have some basic feedback circuits but the most essential one is needed at the limb control level and concerns the decision to either flex or extend a given limb. The decision to activate the extensor part of the limb oscillator has to be based on feedback signalling the onset of loading of the limb involved. This should be signalled by means of load sensors in the limb. The decision to activate the flexor part of the limb oscillator has to depend on various types of feedback. The most important requirement is that flexion should only occur when the limb concerned is no longer loaded above a given threshold. The rule for the initiation of limb flexion can be made more robust by adding the requirement that position at the base of the limb ("hip") should be within a normal end of stance phase range. Hence, human locomotion is thought to use a number of principles which simplify control, just as in other species such as the cat. It is suggested that cat and human locomotion are good models to learn from when designing efficient walking robots.


Physical activity and prenatal depression: going beyond statistical significance by assessing the impact of reliable and clinical significant change.
Previous literature supports exercise as a preventative agent for prenatal depression; however, treatment effects for women at risk for prenatal depression remain unexplored. The purpose of the study was to examine whether exercise can lower depressive symptoms among women who began pregnancy at risk for depression using both a statistical significance and reliable and clinically significant change criteria. This study is a secondary analysis of two randomized controlled trials that followed the same exercise protocol. Pregnant women were allocated to an exercise intervention group (IG) or control group (CG). All participants completed the Center for Epidemiological Depression (CES-D) scale at gestational week 9-16 and 36-38. Women with a baseline score ⩾16 were included. A clinically reliable cut-off was calculated as a 7-point change in scores from pre- to post-intervention. Thirty-six women in the IG and 25 women in the CG scored ⩾16 on the CES-D at baseline. At week 36-38 the IG had a statistically significant lower CES-D score (14.4 ± 8.6) than the CG (19.4 ± 11.1; p < 0.05). Twenty-two women in the IG (61%) had a clinically reliable decrease in their post-intervention score compared to eight women in the CG (32%; p < 0.05). Among the women who met the reliable change criteria, 18 (81%) in the IG and 7 (88%) in the CG had a score <16 post-intervention, with no difference between groups (p > 0.05). A structured exercise program might be a useful treatment option for women at risk for prenatal depression.


Daily Supplementation with 4000 IU Vitamin D3 for Three Years Does Not Modify Cardiovascular Risk Markers in Patients with Advanced Heart Failure: The Effect of Vitamin D on Mortality in Heart Failure Trial.
We aimed to investigate the effect of a moderately high vitamin D dose on lipid parameters and biochemical markers of vascular calcification (VC) in patients with established cardiovascular disease. We included in this pre-specified secondary analysis of a randomized controlled trial 161 patients with advanced heart failure and 25-hydroxyvitamin D (25OHD) concentrations < 75 nmol/L (vitamin D group: n = 80; placebo group: n = 81), who received a daily vitamin D3 supplement of 4,000 IU for 3 years. We assessed between-group differences of the lipid parameters total-cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides, and the VC markers fetuin-A and non-phosphorylated undercarboxylated matrix gla protein (MGP) at study termination, with adjustment for baseline values. Lipid parameters, the percentage of patients with dyslipoproteinemia, and VC markers did not differ significantly between groups at study termination (p values: 0.395-0.939). Likewise, vitamin D achieved no significant treatment effect on these markers in subgroup analyses in patients with 25OHD concentrations < 30 nmol/L, nonusers of lipid-lowering drugs, or diabetic patients (p values: 0.245-0.998). Our data indicate that vitamin D does not improve the lipid profile and does not influence the calcification inhibitors fetuin-A and non-phosphorylated undercarboxylated MGP in patients with advanced heart failure.


Brachial plexus palsy secondary to clavicular nonunion. Case report and literature survey.
Compression neurapraxias of the brachial plexus secondary to nonunion of the clavicle are extremely rare. These palsies routinely affect the medial cord, producing primarily ulnar nerve symptoms. The nonunions that cause them are almost exclusively hypertrophic and are usually in the middle third of the clavicle. These palsies result from the entrapment of the medial cord of the brachial plexus within the costoclavicular space of Berkheiser. Onset of symptoms is highly variable. Treatment recommendations are divided between partial clavicular excision and open reduction with internal fixation. Because this lesion requires operative intervention, it must be carefully distinguished from traction palsy of the plexus for which it is easily mistaken. This distinction requires a meticulous neurologic examination during the initial evaluation of the patient with an acute calvicular fracture.


[Reduction of the severity of affective disorders in patients with the first episode of schizophrenia using the method of bioacoustics correction].
Authors examined 17 adolescents, aged 15-17 years, during the manifestation of slow-progressive schizophrenia. The possibility of the correction of affective disorders, on the basis of involuntary self-regulation using bioacoustics correction (BAC), was studied. BAC method is based on on computed EEG transformation into acoustic signals. The use of BAC method led to the stable reduction of depression and anxiety and their corresponding clinical presentations. The positive changes in the patient's state were accompanied by the EEG reorganization. The decrease in the intensity of beta- and delta-index, the increase of the power of the alpha-rhythm and the decrease of the interhemispheric asymmetry were noted. It has been concluded, that the bioacoustics correction procedures promote the formation of new skills and behaviors by means of restructuring of conditioned reflexes and reshaping (redesigning) of time constraints in the central nervous system. BAC is recommended as an effective and physiologically adequate way of therapy in adolescent schizophrenic patients with anxiety-depressive syndromes.


A case of solitary median maxillary central incisor (SMMCI) syndrome with bilateral pyriform aperture stenosis and choanal atresia.
Solitary median maxillary central incisor syndrome is a rare disorder involving midline abnormalities. It may present with life threatening respiratory distress in the neonate secondary to nasal malformations. These include pyriform aperture stenosis and choanal atresia. We present the first reported case of simultaneous choanal atresia and pyriform aperture stenosis in a neonate with solitary median maxillary central incisor syndrome. The clinical presentation and the management of congenital pyriform aperture stenosis are discussed.


Clinical Effect of Rebound Hyperthermia After Cooling Postcardiac Arrest: A Meta-Analysis.
Rebound hyperthermia (RH) is frequently seen after completion of targeted temperature management (TTM) in comatose survivors of cardiac arrest. However, its clinical significance is not well understood. Previous studies analyzing the association of RH with clinical outcome have reported conflicting results. The purpose of this meta-analysis is to examine the impact of RH after completion of TTM in patients postcardiac arrest. We reviewed six studies that evaluated the incidence of RH (T > 38°C) with documentation of outcome based on the presence of hyperthermia. We reviewed all six articles and extracted the data for mortality and neurological outcome. A total of 729 patients were analyzed for neurological outcome and 950 patients were analyzed for mortality. RH was found to be associated with a significantly worse neurological outcome (odds ratio [OR] 1.55; 95% confidence interval [CI] 1.13-2.14). RH was not significantly associated with a higher mortality (OR 1.31; 95% CI 1.00-1.72). We also analyzed three studies totaling 206 patients for neurological outcomes and mortality that included patients with severe RH (T > 38.5°C). Severe RH was found to be associated with significantly worse neurological outcome (OR 1.92, 95% CI 1.28-1.90) and significantly worse mortality (OR 2.22, 95% CI 1.50-3.29). RH is common after completion of TTM in comatose patients because of cardiac arrest and is associated with poor neurological outcomes. The clinical impact of RH is likely proportional to the magnitude of RH.


High-Frequency Nanocapacitor Arrays: Concept, Recent Developments, and Outlook.
We have developed a measurement platform for performing high-frequency AC detection at nanoelectrodes. The system consists of 65 536 electrodes (diameter 180 nm) arranged in a sub-micrometer rectangular array. The electrodes are actuated at frequencies up to 50 MHz, and the resulting AC current response at each separately addressable electrode is measured in real time. These capabilities are made possible by fabricating the electrodes on a complementary metal-oxide-semiconductor (CMOS) chip together with the associated control and readout electronics, thus minimizing parasitic capacitance and maximizing the signal-to-noise ratio. This combination of features offers several advantages for a broad range of experiments. First, in contrast to alternative CMOS-based electrical systems based on field-effect detection, high-frequency operation is sensitive beyond the electrical double layer and can probe entities at a range of micrometers in electrolytes with high ionic strength such as water at physiological salt concentrations. Far from being limited to single- or few-channel recordings like conventional electrochemical impedance spectroscopy, the massively parallel design of the array permits electrically imaging micrometer-scale entities with each electrode serving as a separate pixel. This allows observation of complex kinetics in heterogeneous environments, for example, the motion of living cells on the surface of the array. This imaging aspect is further strengthened by the ability to distinguish between analyte species based on the sign and magnitude of their AC response. Finally, we show here that sensitivity down to the attofarad level combined with the small electrode size permits detection of individual 28 nm diameter particles as they land on the sensor surface. Interestingly, using finite-element methods, it is also possible to calculate accurately the full three-dimensional electric field and current distributions during operation at the level of the Poisson-Nernst-Planck formalism. This makes it possible to validate the interpretation of measurements and to optimize the design of future experiments. Indeed, the complex frequency and spatial dependence of the data suggests that experiments to date have only scratched the surface of the method's capabilities. Future iterations of the hardware will take advantage of the higher frequencies, higher electrode packing densities and smaller electrode sizes made available by continuing advances in CMOS manufacturing. Combined with targeted immobilization of targets at the electrodes, we anticipate that it will soon be possible to realize complex biosensors based on spatial- and time-resolved nanoscale impedance detection.


Population admixture, biological invasions and the balance between local adaptation and inbreeding depression.
When previously isolated populations meet and mix, the resulting admixed population can benefit from several genetic advantages, including increased genetic variation, the creation of novel genotypes and the masking of deleterious mutations. These admixture benefits are thought to play an important role in biological invasions. In contrast, populations in their native range often remain differentiated and frequently suffer from inbreeding depression owing to isolation. While the advantages of admixture are evident for introduced populations that experienced recent bottlenecks or that face novel selection pressures, it is less obvious why native range populations do not similarly benefit from admixture. Here we argue that a temporary loss of local adaptation in recent invaders fundamentally alters the fitness consequences of admixture. In native populations, selection against dilution of the locally adapted gene pool inhibits unconstrained admixture and reinforces population isolation, with some level of inbreeding depression as an expected consequence. We show that admixture is selected against despite significant inbreeding depression because the benefits of local adaptation are greater than the cost of inbreeding. In contrast, introduced populations that have not yet established a pattern of local adaptation can freely reap the benefits of admixture. There can be strong selection for admixture because it instantly lifts the inbreeding depression that had built up in isolated parental populations. Recent work in Silene suggests that reduced inbreeding depression associated with post-introduction admixture may contribute to enhanced fitness of invasive populations. We hypothesize that in locally adapted populations, the benefits of local adaptation are balanced against an inbreeding cost that could develop in part owing to the isolating effect of local adaptation itself. The inbreeding cost can be revealed in admixing populations during recent invasions.


Antioxidant activity in barley (Hordeum Vulgare L.) grains roasted in a microwave oven under conditions optimized using response surface methodology.
Microwave processing and cooking of foods is a recent development that is gaining momentum in household as well as large-scale food applications. Barley contains phenol compounds which possess antioxidant activity. In this study the microwave oven roasting condition was optimized to obtain grains with high antioxidant activity measured as the ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. Antioxidant activity of grains roasted under optimum conditions was assessed based on DPPH radical scavenging activity, reducing power and inhibition of oxidation in linoleic acid system. The optimum condition for obtaining roasted barley with high antioxidant activity (90.5% DPPH inhibition) was found to be at 600 W microwave power, 8.5 min roasting time, and 61.5 g or 2 layers of grains. The roasting condition influenced antioxidant activity both individually and interactively. Statistical analysis showed that the model was significant (P < 0.0001). The acetone extract had significantly high inhibition of lipid peroxidation and DPPH radical scavenging activity compared to the aqueous extract and alpha-tocopherol. The reducing power of acetone extracts was not significantly different from alpha-tocopherol. The acetone extract had twice the amount of phenol content compared to the aqueous extract indicating its high extraction efficiency. GC-MS analysis revealed the presence of phenol acids, amino phenols, and quinones. The aqueous extract did not contain 3,4-dihydroxybenzaldehyde and 4-hydroxycinnamic acid which are phenol compounds reported to contribute to antioxidant activity in barley grain.


Phaeovibrio sulfidiphilus gen. nov., sp. nov., phototrophic alphaproteobacteria isolated from brackish water.
Two strains (JA480(T) and JA481) of phototrophic alphaproteobacteria were isolated from sediment samples collected from brackish water near Nagapattinam, India. They were Gram-negative, vibrioid cells containing bacteriochlorophyll a and rhodopin as major photosynthetic pigments. Most cells of both strains were non-flagellated; 1 % of cells showed two monopolar flagella. Cells showed positive phototaxis. Both strains showed chimeric intracellular photosynthetic membranes, where both lamellar stacks and vesicles were present together in a single cell. The major fatty acids were C(18 : 1)ω7c and C(16 : 0) in both strains. The genomic G+C content was 67.2-68.8 mol% and the two strains were closely related (mean DNA-DNA hybridization >85 %). 16S rRNA gene sequence comparisons indicated that the isolates represent members of the Rhodospirillaceae within the class Alphaproteobacteria. According to the sequence comparison data, strain JA480(T) is positioned distinctly outside the group formed by the phototrophic genera Rhodospirillum, Rhodocista, Phaeospirillum, Rhodovibrio, Rhodospira and Roseospira, with only 80-92 % 16S rRNA gene sequence similarity. Distinct morphological, physiological and genotypic differences from previously described taxa support the classification of this isolate as a representative of a novel species in a new genus, for which the name Phaeovibrio sulfidiphilus gen. nov., sp. nov. is proposed. The type strain of Phaeovibrio sulfidiphilus is JA480(T) ( = KCTC 5825(T) = NBRC 106163(T) = DSM 23193(T)).


Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging.
Even with effective viral control, HIV-infected individuals are at a higher risk for morbidities associated with older age than the general population, and these serious non-AIDS events (SNAEs) track with plasma inflammatory and coagulation markers. The cell subsets driving inflammation in aviremic HIV infection are not yet elucidated. Also, whether ART-suppressed HIV infection causes premature induction of the inflammatory events found in uninfected elderly or if a novel inflammatory network ensues when HIV and older age co-exist is unclear. In this study we measured combinational expression of five inhibitory receptors (IRs) on seven immune cell subsets and 16 plasma markers from peripheral blood mononuclear cells (PBMC) and plasma samples, respectively, from a HIV and Aging cohort comprised of ART-suppressed HIV-infected and uninfected controls stratified by age (≤35 or ≥50 years old). For data analysis, multiple multivariate computational algorithms [cluster identification, characterization, and regression (CITRUS), partial least squares regression (PLSR), and partial least squares-discriminant analysis (PLS-DA)] were used to determine if immune parameter disparities can distinguish the subject groups and to investigate if there is a cross-impact of aviremic HIV and age on immune signatures. IR expression on gamma delta (γδ) T cells exclusively separated HIV+ subjects from controls in CITRUS analyses and secretion of inflammatory cytokines and cytotoxic mediators from γδ T cells tracked with TIGIT expression among HIV+ subjects. Also, plasma markers predicted the percentages of TIGIT+ γδ T cells in subjects with and without HIV in PSLR models, and a PLS-DA model of γδ T cell IR signatures and plasma markers significantly stratified all four of the subject groups (uninfected younger, uninfected older, HIV+ younger, and HIV+ older). These data implicate γδ T cells as an inflammatory driver in ART-suppressed HIV infection and provide evidence of distinct "inflamm-aging" processes with and without ART-suppressed HIV infection.


Nonlinear diffusion and thermo-electric coupling in a two-variable model of cardiac action potential.
This work reports the results of the theoretical investigation of nonlinear dynamics and spiral wave breakup in a generalized two-variable model of cardiac action potential accounting for thermo-electric coupling and diffusion nonlinearities. As customary in excitable media, the common Q10 and Moore factors are used to describe thermo-electric feedback in a 10° range. Motivated by the porous nature of the cardiac tissue, in this study we also propose a nonlinear Fickian flux formulated by Taylor expanding the voltage dependent diffusion coefficient up to quadratic terms. A fine tuning of the diffusive parameters is performed a priori to match the conduction velocity of the equivalent cable model. The resulting combined effects are then studied by numerically simulating different stimulation protocols on a one-dimensional cable. Model features are compared in terms of action potential morphology, restitution curves, frequency spectra, and spatio-temporal phase differences. Two-dimensional long-run simulations are finally performed to characterize spiral breakup during sustained fibrillation at different thermal states. Temperature and nonlinear diffusion effects are found to impact the repolarization phase of the action potential wave with non-monotone patterns and to increase the propensity of arrhythmogenesis.


Intramolecular Michael addition reaction for the synthesis of benzylbutyrolactones.
A convenient synthesis of benzyl-gamma-butyrolactone derivatives via intramolecular Michael addition reaction of nitro-substituted aryl allyl beta-ketocarboxylates is reported. The method features simple operation, mild reaction conditions and high efficiency.


In vivo three-dimensional EPR imaging of nitric oxide production from isosorbide dinitrate in mice.
Recently, in vivo electron paramagnetic resonance (EPR) spectroscopy and imaging have been widely used to investigate free radical distribution and metabolism in tissues, organs, and whole body of small animals. Endogenous nitric oxide (NO) is an attractive target of this method. In the present study, NO production from a nitrovasodilator, isosorbide dinitrate (ISDN), in live mice was investigated by in vivo EPR spectroscopy and imaging combined with the spin-trapping technique. A highly water-soluble Fe complex with N-(dithiocarboxy)sarcosine (DTCS) was used as an NO-trapping agent. Mice received [14N]-ISDN, and the Fe-DTCS complex subcutaneously exhibited the characteristic triplet EPR signal of the NO adduct [14NO-Fe(DTCS)2]2-. Using [15N]ISDN instead of [14N]ISDN, we were able to observe that the doublet EPR signal stemmed from the 15NO adduct, which directly demonstrated that NO was produced from ISDN. The three-dimensional EPR images of the upper abdomen of living mice showed that the NO adducts were distributed in the liver and the kidneys. This EPR image combined with the ex vivo EPR measurements of the blood suggested that NO production from ISDN occurred in the liver in this experimental condition.


Ethical funding for trustworthy AI: proposals to address the responsibilities of funders to ensure that projects adhere to trustworthy AI practice.
AI systems that demonstrate significant bias or lower than claimed accuracy, and resulting in individual and societal harms, continue to be reported. Such reports beg the question as to why such systems continue to be funded, developed and deployed despite the many published ethical AI principles. This paper focusses on the funding processes for AI research grants which we have identified as a gap in the current range of ethical AI solutions such as AI procurement guidelines, AI impact assessments and AI audit frameworks. We highlight the responsibilities of funding bodies to ensure investment is channelled towards trustworthy and safe AI systems and provides case studies as to how other ethical funding principles are managed. We offer a first sight of two proposals for funding bodies to consider regarding procedures they can employ. The first proposal is for the inclusion of a Trustworthy AI Statement' section in the grant application form and offers an example of the associated guidance. The second proposal outlines the wider management requirements of a funding body for the ethical review and monitoring of funded projects to ensure adherence to the proposed ethical strategies in the applicants Trustworthy AI Statement. The anticipated outcome for such proposals being employed would be to create a 'stop and think' section during the project planning and application procedure requiring applicants to implement the methods for the ethically aligned design of AI. In essence it asks funders to send the message "if you want the money, then build trustworthy AI!".


Baicalin inhibits the metastasis of highly aggressive breast cancer cells by reversing epithelial-to-mesenchymal transition by targeting β-catenin signaling.
Metastasis is the main cause of death in breast cancer patients, which is due partly to the lack of effective treatment. Baicalin, a flavonoid compound isolated from the roots of Scutellaria lateriflora Georgi (Huang Qin), has recently been confirmed as an effective agent for the treatment of a variety of cancers. Yet, the effects and underlying molecular mechanisms of baicalin in regards to the metastasis of breast cancer remain unclear. In the present study, we found that baicalin had the potential to suppress the migration and invasion of highly aggressive breast cancer cells in a dose-dependent manner but had no impact on the viability of these cancer cells. Additionally, baicalin reversed the epithelial-to-mesenchymal transition (EMT) process, as evaluated by EMT markers in breast cancer cell lines with a change from a mesenchymal feature to an epithelial type. At the same time, the expression of β-catenin mRNA and protein was dose-dependently downregulated by baicalin in highly invasive breast cancer cell lines, and overexpression of β-catenin by adenoviruses abolished these beneficial effects of baicalin in regards to the migration and invasion, and EMT of breast cancer cells. Furthermore, using a xenograft mouse model, baicalin markedly reduced liver and lung metastasis of breast cancer, inhibited expression of β-catenin, and degraded the EMT molecules vimentin and Slug in the orthotopic tumor tissues. Taken together, all these results indicate that baicalin effectively suppresses the metastasis of breast cancer by reversing EMT, which may be mediated by downregulation of β-catentin expression.


Mechanism for recognition of polyubiquitin chains: balancing affinity through interplay between multivalent binding and dynamics.
RAP80 plays a key role in signal transduction in the DNA damage response by recruiting proteins to DNA damage foci by binding K63-polyubiquitin chains with two tandem ubiquitin-interacting motifs (tUIM). It is generally recognized that the typically weak interaction between ubiquitin (Ub) and various recognition motifs is intensified by themes such as tandem recognition motifs and Ub polymerization to achieve biological relevance. However, it remains an intricate problem to develop a detailed molecular mechanism to describe the process that leads to amplification of the Ub signal. A battery of solution-state NMR methods and molecular dynamics simulations were used to demonstrate that RAP80-tUIM employs mono- and multivalent interactions with polyUb chains to achieve enhanced affinity in comparison to monoUb interactions for signal amplification. The enhanced affinity is balanced by unfavorable entropic effects that include partial quenching of rapid reorientation between individual UIM domains and individual Ub domains in the bound state. For the RAP80-tUIM-polyUb interaction, increases in affinity with increasing chain length are a result of increased numbers of mono- and multivalent binding sites in the longer polyUb chains. The mono- and multivalent interactions are characterized by intrinsically weak binding and fast off-rates; these weak interactions with fast kinetics may be an important factor underlying the transient nature of protein-protein interactions that comprise DNA damage foci.


Interaction of human cathepsin D with the inhibitor pepstatin.
1. Because of the proposed role of cathepsin D in a variety of biological and pathological processes, the characteristics of inhibition by the potentially useful agent, pepstatin, were determined. 2. The beta and gamma forms of human cathepsin D, separated by isoelectric focusing, have identical specific extinction coefficients and specific activity in the degradation of haemoglobin. 3. Cathepsin D showed tight binding of 1 mol of pepstatin per 43000 g of protein, indicating that titration with the inhibitor represents a useful method for determination of absolute concentrations of the enzyme. 4. The titration curves were used to determine apparent dissociation constants (KD) for the binding of pepstatin and pepstatin methyl ester at pH3.5; values of approx. 5 X 10(-10)M were obtained. 5. Pepstatinyl-[3H]glycine was synthesized and shown to have a KD similar to that of pepstatin. Gel-chromatographic experiments showed that the binding of pepstatin and its derivatives is strongly pH-dependent. 6. The effect of pH on the KD for pepstatinyl-glycine was determined by equilibrium dialysis. As the pH was raised from 5.0 to 6.4, KD rose from 5 X 10(-10)M to 2 X 10(-6)M. 7. The catalytic activity of cathepsin D declines essentially to zero on going from pH5.0 to pH7.0, and we suggest that the binding site for substrate and pepstatin is abolished by a conformational change in the enzyme molecule. 8. The data indicate that, in biological experiments near neutral pH, large molar excesses of pepstatin over cathepsin D will be required for efficient inhibition.


Parallel perceptual enhancement and hierarchic relevance evaluation in an audio-visual conjunction task.
Attention directs limited-capacity information processing resources to a subset of available perceptual representations. The mechanisms by which attention selects task-relevant representations for preferential processing are not fully known. Triesman and Gelade's [Triesman, A., Gelade, G., 1980. A feature integration theory of attention. Cognit. Psychol. 12, 97-136.] influential attention model posits that simple features are processed preattentively, in parallel, but that attention is required to serially conjoin multiple features into an object representation. Event-related potentials have provided evidence for this model showing parallel processing of perceptual features in the posterior Selection Negativity (SN) and serial, hierarchic processing of feature conjunctions in the Frontal Selection Positivity (FSP). Most prior studies have been done on conjunctions within one sensory modality while many real-world objects have multimodal features. It is not known if the same neural systems of posterior parallel processing of simple features and frontal serial processing of feature conjunctions seen within a sensory modality also operate on conjunctions between modalities. The current study used ERPs and simultaneously presented auditory and visual stimuli in three task conditions: Attend Auditory (auditory feature determines the target, visual features are irrelevant), Attend Visual (visual features relevant, auditory irrelevant), and Attend Conjunction (target defined by the co-occurrence of an auditory and a visual feature). In the Attend Conjunction condition when the auditory but not the visual feature was a target there was an SN over auditory cortex, when the visual but not auditory stimulus was a target there was an SN over visual cortex, and when both auditory and visual stimuli were targets (i.e. conjunction target) there were SNs over both auditory and visual cortex, indicating parallel processing of the simple features within each modality. In contrast, an FSP was present when either the visual only or both auditory and visual features were targets, but not when only the auditory stimulus was a target, indicating that the conjunction target determination was evaluated serially and hierarchically with visual information taking precedence. This indicates that the detection of a target defined by audio-visual conjunction is achieved via the same mechanism as within a single perceptual modality, through separate, parallel processing of the auditory and visual features and serial processing of the feature conjunction elements, rather than by evaluation of a fused multimodal percept.


Multiplexer displays two pressure signals on single oscilloscope channel.
High-fidelity pressure transducers may drift during long experiments. To correct for this drift, many investigators periodically rebalance the high-fidelity transducer, comparing the results from the high-fidelity transducer with those from a fluid-filled catheter connected to an external transducer. This procedure is subject to error because the high-fidelity and reference signals have to be displayed on different oscilloscope channels; thus these channels can drift differently, being subject to parallax and other problems. This procedure also requires two display channels, which are often in short supply during two display channels, which are often in short supply during complex experiments. We present a design for a multiplexer that will display two pressure signals on one oscilloscope channel, thereby solving these problems and saving one channel to display other information.


SARS-CoV-2 and Aspergillus section Fumigati coinfection in an immunocompetent patient treated with corticosteroids.
Patients with severe viral pneumonia are likely to receive high-dose immunomodulatory drugs to prevent clinical worsening. Aspergillus species have been described as frequent secondary pneumonia agents in severely ill influenza patients receiving steroids. COVID-19 patients admitted to Intensive Care Unit (ICU) are receiving steroids as part of their treatment and they share clinical characteristics with other patients with severe viral pneumonias. COVID-19 patients receiving steroids should be considered a putative risk group of invasive aspergillosis. We are reporting a SARS-CoV-2/Aspergillus section Fumigati coinfection in an elderly intubated patient with a history of pulmonary embolism treated with corticosteroids. The diagnosis was made following the ad hoc definitions described for patients admitted to ICU with severe influenza, including clinical criteria (fever for 3 days refractory to the appropriate antibiotic therapy, dyspnea, pleural friction rub, worsening of respiratory status despite antibiotic therapy and need of ventilator support), a radiological criterion (pulmonary infiltrate) and a mycological criterion (several positive galactomannan tests on serum with ratio ≥0.5). In addition, Aspergillus section Fumigati DNA was found in serum and blood samples. These tests were positive 4 weeks after the patient was admitted to the ICU. The patient received voriconazole and after two month in ICU his respiratory status improved; he was discharged after 6 weeks of antifungal treatment. Severely ill COVID-19 patients would be considered a new aspergillosis risk group. Galactomannan and Aspergillus DNA detection would be useful methods for Aspergillus infection diagnosis as they allow avoiding the biosafety issues related to these patients.


Copeptin and its potential role in diagnosis and prognosis of various diseases.
The need for faster diagnosis, more accurate prognostic assessment and treatment decisions in various diseases has lead to the investigations of new biomarkers. The hope is that this new biomarkers will enable early decision making in clinical practice. Arginine vasopressin (AVP) is one of the main hormones of the hypothalamic-pituitary-adrenal axis. Its main stimulus for secretion is hyperosmolarity, but AVP system is also stimulated by exposure of the body to endogenous stress. Reliable measurement of AVP concentration is difficult because it is subject to preanalytical and analytical errors. It is therefore not used in clinical practice. Copeptin, a 39-aminoacid glycopeptide, is a C-terminal part of the precursor pre-provasopressin (pre-proAVP). Activation of AVP system stimulates copeptin secretion into the circulation from the posterior pituitary gland in equimolar amounts with AVP. Therefore, copeptin directly reflects AVP concentration and can be used as surrogate biomarker of AVP secretion. Even mild to moderate stress situations contribute to release of copeptin. These reasons have lead to a handful of research on copeptin in various diseases. This review summarizes the current achievements in the research of copeptin as a diagnostic and prognostic marker and also discusses its association in different disease processes.


Allelic loss of chromosomal arm 8p in breast cancer progression.
Loss of heterozygosity (LOH) of chromosomal arm 8p has been reported to occur at high frequency for a number of common forms of human cancer, including breast cancer. The objectives of this study were to define the regions on this chromosomal arm that are likely to contain breast cancer tumor suppressor genes and to determine when loss of chromosomal arm 8p occurs during breast cancer progression. For mapping the tumor suppressor gene loci, we evaluated 60 cases of infiltrating ductal cancer for allelic loss using 14 microsatellite markers mapped to this chromosomal arm and found LOH of 8p in 36 (60%) of the tumors. Whereas most of these tumors had allelic loss at all informative markers, five tumors had partial loss of 8p affecting two nonoverlapping regions. LOH for all but one of the tumors with 8p loss involved the region between markers D8S560 and D8S518 at 8p21.3-p23.3, suggesting that this is the locus of a breast cancer tumor suppressor gene. We then studied LOH of 8p in 38 cases of ductal carcinoma in situ (DCIS) with multiple individually microdissected tumor foci evaluated for each case. LOH of 8p was found in 14 of the DCIS cases (36%), including 6 of 16 cases of low histological grade and 8 of 22 cases of intermediate or high histological grade. In four of these DCIS cases, 8p LOH was seen in some but not all of the multiple tumor foci examined. These data suggest that during the evolution of these tumors, LOH of 8p occurred after loss of other chromosomal arms that were lost in all tumor foci. Thus, LOH of 8p, particularly 8p21.3-p23, is a common genetic alteration in infiltrating and in situ breast cancer. Although 8p LOH is common even in low histological grade DCIS, this allelic loss often appears to be preceded by loss of other alleles in the evolution of breast cancer.


Auditory backward recognition masking in children with a specific language impairment and children with a specific reading disability.
The auditory backward recognition masking (ABRM) and intensity discrimination (ID) thresholds of children with a specific language impairment and poor reading (SLI-poor readers), children with an SLI and average reading (SLI-average readers), children with a specific reading disability and average spoken language skills (SRD-average language), and children with normal spoken and written language (controls) were estimated with "child-friendly" psychophysical tasks. The pattern of ABRM and ID scores suggests that a subset of children with concomitant oral language and reading impairments has poor ABRM thresholds, and that a subgroup of children with an SLI or SRD has poorer ID thresholds than controls. The latter result warns against using rapid auditory processing tasks that do not actively control for auditory discrimination ability. Further, some unusually poor ABRM scores and ID scores question the validity of extreme scores produced by children on psychophysical tasks. Finally, the poor oral language scores of many of the children who had impaired reading highlight the need to test the oral language skills of SRD samples to ascertain how homogeneous and specifically disabled they really are.


Identification of new mutations of the HFE, hepcidin, and transferrin receptor 2 genes by denaturing HPLC analysis of individuals with biochemical indications of iron overload.
Hereditary hemochromatosis is a recessive disorder characterized by iron accumulation in parenchymal cells, followed by organ damage and failure. The disorder is mainly attributable to the C282Y and H63D mutations in the HFE gene, but additional mutations in the HFE, transferrin receptor 2 (TfR2), and hepcidin genes have been reported. The copresence of mutations in different genes may explain the phenotypic heterogeneity of the disorder and its variable penetrance. We used denaturing HPLC (DHPLC) for rapid DNA scanning of the HFE (exons 2, 3, and 4), hepcidin, and TfR2 (exons 2, 4 and 6) genes in a cohort of 657 individuals with altered indicators of iron status. DHPLC identification of C282Y and H63D HFE alleles was in perfect agreement with the restriction endonuclease assay. Fourteen DNA samples were heterozygous for the HFE S65C mutation. In addition, we found novel mutations: two in HFE (R66C in exon 2 and R224G in exon 4), one in the hepcidin gene (G71D), and one in TfR2 (V22I), plus several intronic or silent substitutions. Six of the seven individuals with hepcidin or TfR2 coding mutations carried also HFE C282Y or S65C mutations. DHPLC is an efficient method for mutational screening for the genes involved in hereditary hemochromatosis and for the study of their copresence.


Impulsive action: emotional impulses and their control.
This paper presents a novel theoretical view on impulsive action, integrating thus far separate perspectives on non-reflective action, motivation, emotion regulation, and impulse control. We frame impulsive action in terms of directedness of the individual organism toward, away, or against other givens - toward future states and away from one's present state. First, appraisal of a perceived or thought-of event or object on occasion, rapidly and without premonition or conscious deliberation, triggers a motive to modify one's relation to that event or object. Situational specifics of the event as perceived and appraised motivate and guide selection of readiness for a particular kind of purposive action. Second, perception of complex situations can give rise to multiple appraisals, multiple motives, and multiple simultaneous changes in action readiness. Multiple states of action readiness may interact in generating action, by reinforcing or attenuating each other, thereby yielding impulse control. We show how emotion control can itself result from a motive state or state of action readiness. Our view links impulsive action mechanistically to states of action readiness, which is the central feature of what distinguishes one kind of emotion from another. It thus provides a novel theoretical perspective to the somewhat fragmented literature on impulsive action.


Comparative evaluation of various miniplate systems for the repair of mandibular corpus fractures.
Miniplates have been used during the last decade to facilitate stability between bony fragments in the maxillofacial region and are currently the preferred surgical method for the fixation of fractures and osteotomies. The aim of this study was to evaluate and compare the biomechanical behaviors of six different types of miniplates used to reconstruct mandibular body fractures: Group 1 (straight, 2 holes, 12.0 mm spacing), Group 2 (straight, 4 holes, 9.0 spacing), Group 3 (straight, 6 holes, 9.0 mm spacing), Group 4 (L-shaped, 4 holes, 9.0 mm spacing, right hand plate), Group 5 (Y-shaped, 5 holes, 12.0 mm spacing), and Group 6 (double Y-shaped, 6 holes, 9.0 mm spacing). Thirty bovine hemimandibles and a custom-made 3-point biomechanical test frame mounted on a Shimadzu universal test machine were used to evaluate the six different miniplate systems. Results revealed that Group 1 (straight, 2 holes, 12.0 mm spacing) and Group 4 (9.0 mm spacing, right hand plate) had the lowest biomechanical stability, whereas Group 6 (6 holes, 9.0 mm spacing) had the highest biomechanical stability. Group 6 also provided statistically greater resistance to displacement than Group 1 and Group 4.


Central Venous Catheters for Hemodialysis: How to Overcome the Problems.
The use of central venous dialysis catheters is increasing in clinical practice. These devices, although relatively easy to insert, do have problems. Catheter size limits the amount of dialysis that can be delivered. Central venous hemodialysis catheters minimize cardiopulmonary recirculation, but have increased potential for access recirculation compared to native or artificial arteriovenous (AV) fistulas and grafts. Developments in catheter design and optimal positioning have improved the amount of dialysis that can be delivered. Similarly, infection rates are improving with careful attention to peri-insertion care and the use of topical antiseptics and antibiotics. Although catheter thrombus remains a problem, the introduction of recombinant tissue plasminogen activator and mechanical dislodgement with an endoluminal brush have improved patency rates, but some patients may require long-term warfarin therapy.


Prevalence of dyslipidemias in the Middle East region: A systematic review & meta-analysis study.
Dyslipidemia is a known main risk factor for cardiovascular diseases, and it can be controlled to reduce the incidence of cardiovascular diseases. This meta-analysis aimed to estimate the prevalence of dyslipidemias in the Middle East. The relevant published articles between 2000 and 2021 that investigated the prevalence of dyslipidaemias in the Middle East were found through international data sources such as Medline, PubMed, and Google Scholar. The random-effects model was used to estimate the pooled prevalence with 95% confidence intervals. The pooled prevalence of dyslipidemias, hypertriglyceridemia, hypercholesterolemia, high levels of low-density lipoprotein cholesterol and low levels of high-density lipoprotein cholesterol in the Middle East were 54.08% (95% CI: 43.83-66.71), 32.51% (95% CI: 28.59-36.43), 29.44% (95% CI: 18.74-40.13), 32.09% (95% CI: 22.17-42.01), 44.71% (95% CI: 37.86-51.57), respectively. During the last two decades, an increasing trend in the prevalence of dyslipidemias was observed overall and in both sexes. Also, the age groups over 30 significantly had the highest prevalence of hypercholesterolemia, high levels of low-density lipoprotein cholesterol, and low levels of high-density lipoprotein cholesterol (p < 0.05). The increasing trend in the prevalence of dyslipidemias during the last two decades is an alarming and significant concern in the Middle East. Therefore, special measures are needed to deal with dyslipidemias as a health priority in the Middle East.


Comparing visual and objective skin assessment with pressure injury risk.
Contemporary approaches to pressure injury (PI) risk identification rely on the use of risk assessment tools and visual skin assessment. Objective biophysical measures that assess skin hydration, melanin, erythema and lipids have not been traditionally used in PI risk; however, these may prove useful as a risk assessment tool. The relationship between subjective visual assessments of skin condition, biophysical measures and PI risk warrants investigation. This study used a descriptive correlational design to examine the relationship between measures of skin hydration, colour (melanin and erythema) and lipids at PI-prone areas amongst geriatric persons (n = 38), obtained using biophysical skin measures and visual skin assessment. Twice daily measures of epidermal hydration, colour and lipids were assessed using the SD202 Skin Diagnostic (Courage + Khazaka GmBH, Cologne, Germany) over pressure-prone areas of the body of study participants over seven consecutive days. Concurrent visual assessment of skin hydration and colour was performed. Results obtained using the SD202 Skin Diagnostic were compared with results gathered from visual assessment and examined for their association with participants' PI risk based on scores of the Norton Risk Assessment Scale. While epidermal hydration and skin colour reading scores did not vary significantly over the data collection period, lipid readings could not be registered on any occasion. With the exception of skin dryness, skin parameters via both objective and subjective means had significant, positive correlations. Statistically significant correlations emerged between visual assessment of skin wetness at the sacrum (r = -0·441, P < 0·01) and ischia (r = -0·468, P < 0·01) and Norton Risk Assessment Scale scores. It was found that the objective assessment of epidermal hydration (skin wetness) was also significantly associated with PI risk at the sacrum (r = -0·528, P < 0·01), as well as the right ischia (r = -0·410, P < 0·05) and left ischia (r = -0·407, P < 0·05). Erythema, when assessed objectively, was significantly correlated with PI risk at the sacrum (r = -0·322, P < 0·05). Such findings indicating that the finer measures afforded by the SD202 Skin Diagnostic in the assessment of the subtle red hues displayed in erythematous skin may provide an additional advantage over traditional, clinician assessment.


Repair of extrahepatic biliary duct over T-tube.
To evaluate the result of surgical procedures adopted for repair of iatrogenic injuries of extrahepatic biliary tract over T-tube. An interventional study conducted at Surgical Unit 1 of Abbasi Shaheed Hospital, Karachi; and private hospitals in Karachi, from 1974 to 2004 (30 years). All the iatrogenic injuries of extrahepatic biliary tract during open cholecystectomies were recorded. The records included age and sex of patients, site and extent of injury, method of repair and post-operative complications, if any. All primary repairs were done over T-tube. For injuries at the confluence, the T-tube was converted into a Y-tube, and its short limbs were introduced into the lumen of right and left hepatic ducts. Follow up was done in the outpatient department weekly for a month after discharge, and then annually for maximum 5 years. A total number of 5,000 open cholecystectomies were performed during the study period. Eleven patients (0.22%) had intraoperative extrahepatic biliary tract injury: 6 out of 11 had injury of common bile duct (CBD), 2 had common hepatic duct (CHD) and 3 had injury at the confluence. One patient was lost to follow up after a year. One patient died of myocardial infarction after two years. Nine patients were clinically and biochemically well at five years follow up after primary repair of the injuries. Primary repair of extrahepatic duct injuries, situated at CBD, CHD or at the confluence, over the T-tubes is safe. In case of injury at the confluence the T-tube may be shaped like a Y-tube for secure anastomosis of all the three cut ends.


Weakened resilience of benthic microbial communities in the face of climate change.
Increased ocean temperature associated with climate change is especially intensified in coastal areas and its influence on microbial communities and biogeochemical cycling is poorly understood. In this study, we sampled a Baltic Sea bay that has undergone 50 years of warmer temperatures similar to RCP5-8.5 predictions due to cooling water release from a nuclear power plant. The system demonstrated reduced oxygen concentrations, decreased anaerobic electron acceptors, and higher rates of sulfate reduction. Chemical analyses, 16S rRNA gene amplicons, and RNA transcripts all supported sediment anaerobic reactions occurring closer to the sediment-water interface. This resulted in higher microbial diversities and raised sulfate reduction and methanogenesis transcripts, also supporting increased production of toxic sulfide and the greenhouse gas methane closer to the sediment surface, with possible release to oxygen deficient waters. RNA transcripts supported prolonged periods of cyanobacterial bloom that may result in increased climate change related coastal anoxia. Finally, while metatranscriptomics suggested increased energy production in the heated bay, a large number of stress transcripts indicated the communities had not adapted to the increased temperature and had weakened resilience. The results point to a potential feedback loop, whereby increased temperatures may amplify negative effects at the base of coastal biochemical cycling.


Risk factors among elderly for short term deaths related to high levels of air pollution.
Air pollution has been linked to increased rates of mortality, but little is known about individual characteristics related to the increase in risk. To examine short term effects of air pollution on daily mortality in elderly people in Bordeaux and compare characteristics of subjects > or =65 years old who died with levels of particulate air pollution. Daily mortality data from Bordeaux were used to determine the core model of mortality for the period 1988-97. The air pollution indicator was regressed on the core model of mortality, allowing control of the main effect modifiers and confounding factors of air pollution on the same day. The residual series of this regression model was classified from the lowest to the highest to determine "low level days" and "high level days". A sample of 1469 elderly people in a French cohort study were studied. From 1988 to 1997, 543 subjects died; 55 deaths were during days with low air pollution and 51 during days with high air pollution. Only gender differed significantly according to both types of days, with a proportion of women significantly higher in high air pollution days than men. After adjustment for smoking habits, the odds ratio was 5.2 for women. The risk of mortality between women and men was determined on days with "high air pollution levels" above the 50-90th centiles compared to below the 10th centile. No clear pattern was observed between days with low levels of air pollution and the different centiles of exposure.


Astroglial FMRP modulates synaptic signaling and behavior phenotypes in FXS mouse model.
Fragile X syndrome (FXS) is one of the most common inherited intellectual disability (ID) disorders, in which the loss of FMRP protein induces a range of cellular signaling changes primarily through excess protein synthesis. Although neuron-centered molecular and cellular events underlying FXS have been characterized, how different CNS cell types are involved in typical FXS synaptic signaling changes and behavioral phenotypes is largely unknown. Recent evidence suggests that selective loss of astroglial FMRP is able to dysregulate glutamate uptake, increase spine density, and impair motor-skill learning. Here we investigated the effect of astroglial FMRP on synaptic signaling and FXS-related behavioral and learning phenotypes in astroglial Fmr1 cKO and cON mice in which FMRP expression is selectively diminished or restored in astroglia. We found that selective loss of astroglial FMRP contributes to cortical hyperexcitability by enhancing NMDAR-mediated evoked but not spontaneous miniEPSCs and elongating cortical UP state duration. Selective loss of astroglial FMRP is also sufficient to increase locomotor hyperactivity, significantly diminish social novelty preference, and induce memory acquisition and extinction deficits in astroglial Fmr1 cKO mice. Importantly, re-expression of astroglial FMRP is able to significantly rescue the hyperactivity (evoked NMDAR response, UP state duration, and open field test) and social novelty preference in astroglial Fmr1 cON mice. These results demonstrate a profound role of astroglial FMRP in the evoked synaptic signaling, spontaneously occurring cortical UP states, and FXS-related behavioral and learning phenotypes and provide important new insights in the cell type consideration for the FMRP reactivation strategy.


Promoter Effects of Alkali Metal Cations on the Electrochemical Reduction of Carbon Dioxide.
The electrochemical reduction of CO2 is known to be influenced by the identity of the alkali metal cation in the electrolyte; however, a satisfactory explanation for this phenomenon has not been developed. Here we present the results of experimental and theoretical studies aimed at elucidating the effects of electrolyte cation size on the intrinsic activity and selectivity of metal catalysts for the reduction of CO2. Experiments were conducted under conditions where the influence of electrolyte polarization is minimal in order to show that cation size affects the intrinsic rates of formation of certain reaction products, most notably for HCOO-, C2H4, and C2H5OH over Cu(100)- and Cu(111)-oriented thin films, and for CO and HCOO- over polycrystalline Ag and Sn. Interpretation of the findings for CO2 reduction was informed by studies of the reduction of glyoxal and CO, key intermediates along the reaction pathway to final products. Density functional theory calculations show that the alkali metal cations influence the distribution of products formed as a consequence of electrostatic interactions between solvated cations present at the outer Helmholtz plane and adsorbed species having large dipole moments. The observed trends in activity with cation size are attributed to an increase in the concentration of cations at the outer Helmholtz plane with increasing cation size.


Elucidation of trophic interactions in an unusual single-cell nitrogen-fixing symbiosis using metabolic modeling.
Marine nitrogen-fixing microorganisms are an important source of fixed nitrogen in oceanic ecosystems. The colonial cyanobacterium Trichodesmium and diatom symbionts were thought to be the primary contributors to oceanic N2 fixation until the discovery of the unusual uncultivated symbiotic cyanobacterium UCYN-A (Candidatus Atelocyanobacterium thalassa). UCYN-A has atypical metabolic characteristics lacking the oxygen-evolving photosystem II, the tricarboxylic acid cycle, the carbon-fixation enzyme RuBisCo and de novo biosynthetic pathways for a number of amino acids and nucleotides. Therefore, it is obligately symbiotic with its single-celled haptophyte algal host. UCYN-A receives fixed carbon from its host and returns fixed nitrogen, but further insights into this symbiosis are precluded by both UCYN-A and its host being uncultured. In order to investigate how this syntrophy is coordinated, we reconstructed bottom-up genome-scale metabolic models of UCYN-A and its algal partner to explore possible trophic scenarios, focusing on nitrogen fixation and biomass synthesis. Since both partners are uncultivated and only the genome sequence of UCYN-A is available, we used the phylogenetically related Chrysochromulina tobin as a proxy for the host. Through the use of flux balance analysis (FBA), we determined the minimal set of metabolites and biochemical functions that must be shared between the two organisms to ensure viability and growth. We quantitatively investigated the metabolic characteristics that facilitate daytime N2 fixation in UCYN-A and possible oxygen-scavenging mechanisms needed to create an anaerobic environment to allow nitrogenase to function. This is the first application of an FBA framework to examine the tight metabolic coupling between uncultivated microbes in marine symbiotic communities and provides a roadmap for future efforts focusing on such specialized systems.


Estradiol 17 beta-hydroxysteroid dehydrogenase, a marker of breast cancer hormone dependency.
Intratumoral activity of the progesterone-dependent enzyme 17 beta-hydroxysteroid dehydrogenase (E2DH) was measured in 114 patients with breast cancer (33 pre- and 81 postmenopausal) before and/or after 8 days of a progestin treatment (lynestrenol, 10 mg/day). In 12 postmenopausal patients, the ability of E2DH to be stimulated by lynestrenol was compared to estradiol receptor (ER) and progesterone receptor (PR) levels. In premenopausal patients, E2DH was higher when tumors were excised in the luteal phase than when excised in the follicular phase. In postmenopausal patients, E2DH was higher after progestin treatment. However, E2DH stimulation by lynestrenol depended on receptor levels. It was most often markedly stimulated in ER-positive, PR-positive tumors. It remained low in ER-negative, PR-negative tumors. Intratumoral measurement of the progesterone-dependent enzyme E2DH in breast cancer after progestin treatment could therefore provide a fine and reliable index of the presence and functional character of PR and hormone dependency of the tumor.


Degradation of abnormal proteins in Escherichia coli. Differential proteolysis in vitro of E. coli alkaline phosphatase cyanogen-bromide-cleavage products.
Escherichia coli alkaline phosphatase has been purified and modified by either carboxymethylation or treatment with cyanogen bromide (CNBr). Only the CNBr-treated protein was degradable in an E. coli cell extract. Separation of the CNBr cleavage products by gel filtration in non-denaturing conditions gave rise to a number of oligomeric complexes, of which only those of molecular weight less than approximately 29000 were degradable in E. coli cell-free extracts. Carboxymethylation of the non-degradable complexes (greater than 29000 molecular weight) resulted in the formation of some complexes of less than 29000 molecular weight: such newly formed complexes were degradable by E. coli cell-free extracts. It is suggested that E. coli cell-free extracts may contain a protease/peptidase system which is active against peptide complexes below 29000 molecular weight, but inactive against peptide oligomers of greater molecular weight.


European survey on principles of prudent antibiotic prescribing teaching in undergraduate students.
We surveyed European medical schools regarding teaching of prudent antibiotic prescribing in the undergraduate curriculum. We performed a cross-sectional survey in 13 European countries (Belgium, Croatia, Denmark, France, Germany, Italy, Netherlands, Norway, Serbia, Slovenia, Spain, Switzerland, United Kingdom) in 2013. Proportional sampling was used, resulting in the selection of two to four medical schools per country. A standardized questionnaire based on literature review and validated by a panel of experts was sent to lecturers in infectious diseases, medical microbiology and clinical pharmacology. In-depth interviews were conducted with four lecturers. Thirty-five of 37 medical schools were included in the study. Prudent antibiotic use principles were taught in all but one medical school, but only four of 13 countries had a national programme. Interactive teaching formats were used less frequently than passive formats. The teaching was mandatory for 53% of the courses and started before clinical training in 71%. We observed wide variations in exposure of students to important principles of prudent antibiotic use among countries and within the same country. Some major principles were poorly covered (e.g. reassessment and duration of antibiotic therapy, communication skills). Whereas 77% of the respondents fully agreed that the teaching of these principles should be prioritized, lack of time, mainly due to rigid curriculum policies, was the main reported barrier to implementation. Given the study design, these are probably optimistic results. Teaching of prudent antibiotic prescribing principles should be improved. National and European programmes for development of specific learning outcomes or competencies are urgently needed.


Mechanism of absorption wavelength shifts in anion channelrhodopsin-1 mutants.
Using a quantum mechanical/molecular mechanical approach, we show the mechanisms of how the protein environment of Guillardia theta anion channelrhodopsin-1 (GtACR1) can shift the absorption wavelength. The calculated absorption wavelengths for GtACR1 mutants, M105A, C133A, and C237A are in agreement with experimentally measured wavelengths. Among 192 mutant structures investigated, mutations at Thr101, Cys133, Pro208, and Cys237 are likely to increase the absorption wavelength. In particular, T101A GtACR1 was expressed in HEK293T cells. The measured absorption wavelength is 10 nm higher than that of wild type, consistent with the calculated wavelength. (i) Removal of a polar residue from the Schiff base moiety, (ii) addition of a polar or acidic residue to the β-ionone ring moiety, and (iii) addition of a bulky residue to increase the planarity of the β-ionone and Schiff base moieties are the basis of increasing the absorption wavelength.


[Evolution of the methods of peritonization of the vermiform process stump in acute destructive appendicitis complicated by typhlitis].
A comparative assessment of effectiveness of various non-traditional and non-typical variants of appendectomy was made with using non-standard (non-classical) methods of treatment and peritonization of the vermiform stump developed by different authors for destructive forms of acute appendicitis complicated by inflammatory infiltration of the blind gut cupola and typhlitis. An analysis of results of using the proposed non-typical technical methods and techniques as well as an assessment of the authors' technique used in 43 patients suggests that the above variants of peritonization of the vermiform process stump should not be considered as competing. Each of the methods can be successfully used depending on the concrete clinical situations and for the corresponding indications as the most optimal method of choice or as an alternative of the classical variant of appendectomy in patients with acute destructive appendicitis complicated by inflammatory infiltration of the blind gut cupola and typhlitis.


Physical Separation of Enantiomeric Products by Compartmentalized Parallel Kinetic Resolution.
Accessing each enantiomer of a chiral molecule starting from a racemic mixture remains a daunting challenge in chemistry. Indeed, until now, only a few solutions exist to separate enantiomers of an equimolar mixture of a chiral precursor. In this study, we establish a new strategy to prepare simultaneously and physically separate both enantioenriched enantiomers of a molecule starting from a racemic substrate. This process combines two enantiomeric catalytic systems, working in parallel, and separation by an achiral membrane with selective permeability. This unprecedented system was successfully applied to the simultaneous preparation of both enantiomers of chiral 1,2-diols starting from racemic epoxides using Jacobsen's hydrolytic kinetic resolution (HKR) in parallel.


The association of self-reported awake bruxism and sleep bruxism with temporomandibular pain and dysfunction in adult patients with temporomandibular disorders.
To investigate the association of the severity of temporomandibular disorders (TMD) pain and dysfunction with the frequency of self-reported awake bruxism (AB), sleep bruxism (SB), and stress in an adult TMD-patient population. This cross-sectional study included 237 TMD patients based on the Diagnostic Criteria for TMD. Age, sex, frequency of self-reported AB and SB, and stress were included as independent variables. TMD pain and TMD dysfunction were included as dependent variables in regression analyses. Univariate and multivariable linear regression analyses were used to predict TMD pain and TMD dysfunction in two separate models. Finally, network analysis was performed to investigate the associations between all variables. In the univariate analyses, TMD pain was significantly associated with self-reported AB-frequent (unstandardized coefficient (B) = 3.196, 95%CI 1.198-5.195, p = 0.002). TMD dysfunction was significantly associated with AB-frequent (B = 2.208, 95%CI 0.177-4.238, p = 0.033) and SB-sometimes (B = 1.698, 95%CI 0.001-3.394, p = 0.050). In the multivariable analyses, TMD pain was significantly associated with TMD dysfunction (B = 0.370, p < 0.001), stress (B=0.102, p < 0.001). TMD dysfunction was significantly associated with TMD pain (B = 0.410, p < 0.001) only. Network analysis showed that TMD pain is a bridge factor between AB, stress, and TMD dysfunction. TMD pain is directly associated with AB, stress, and TMD dysfunction, while TMD dysfunction is only associated with TMD pain. Reducing pain may improve pain-related dysfunction, and the management of AB and stress may improve TMD pain and dysfunction, and vice versa.


Connecting Provider to home: A home-based social intervention program for older adults.
Patients with multiple medical conditions and complex social issues are at risk for high utilization and poor outcomes. The Connecting Provider to Home program deployed teams of a social worker and a community health worker (CHW) to support patients with social issues and access to primary care. Our objectives were to examine the impact of the program on utilization and satisfaction with care among older adults with complex social and medical issues. Retrospective quasi-experimental observational study with matched comparator group. Community-based program in Southern California. Four hundred twenty community dwelling adults. Community-based healthcare program delivered by a social worker and CHW team for older adults with complex medical and social needs. Acute hospitalization and emergency department (ED) visits in the 12 months preceding and following enrollment in the pilot program. A "difference-in-difference" analysis using a matched comparator group was conducted. Comparator group data of patients receiving usual care were obtained. Surveys were conducted to assess patient satisfaction and experiences with the program. The mean age of patients was 74 years, and the program demonstrated statistically significant reductions in acute hospitalizations and ED use compared with 700 comparator patients. Pre/post-acute hospitalizations and ED visits were reduced in the intervention group. The average per patient per year reduction in acute hospitalizations was -0.66, whereas the average per patient reduction in ED use was -0.57. Patients enrolled in the program reported high levels of satisfaction and rated the program favorably. A care model with a social worker and CHW can be linked to primary care to address patient social needs and potentially reduce utilization of healthcare services and enhance patient experiences with care.


Effect of Stimulus Polarity on Physiological Spread of Excitation in Cochlear Implants.
Contemporary cochlear implants (CIs) use cathodic-leading, symmetrical, biphasic current pulses, despite a growing body of evidence that suggests anodic-leading pulses may be more effective at stimulating the auditory system. However, since much of this research on humans has used pseudomonophasic pulses or biphasic pulses with unusually long interphase gaps, the effects of stimulus polarity are unclear for clinically relevant (i.e., symmetric biphasic) stimuli. The purpose of this study was to examine the effects of stimulus polarity on basic characteristics of physiological spread-of-excitation (SOE) measures obtained with the electrically evoked compound action potential (ECAP) in CI recipients using clinically relevant stimuli. Using a within-subjects (repeated measures) design, we examined the differences in mean amplitude, peak electrode location, area under the curve, and spatial separation between SOE curves obtained with anodic- and cathodic-leading symmetrical, biphasic pulses. Fifteen CI recipients (ages 13-77) participated in this study. All were users of Cochlear Ltd. devices. SOE functions were obtained using the standard forward-masking artifact reduction method. Probe electrodes were 5-18, and they were stimulated at an 8 (of 10) loudness rating ("loud"). Outcome measures (mean amplitude, peak electrode location, curve area, and spatial separation) for each polarity were compared within subjects. Anodic-leading current pulses produced ECAPs with larger average amplitudes, greater curve area, and less spatial separation between SOE patterns compared with that for cathodic-leading pulses. There was no effect of polarity on peak electrode location. These results indicate that for equal current levels, the anodic-leading polarity produces broader excitation patterns compared with cathodic-leading pulses, which reduces the spatial separation between functions. This result is likely due to preferential stimulation of the central axon. Further research is needed to determine whether SOE patterns obtained with anodic-leading pulses better predict pitch discrimination.


Sociocultural characteristics and responses to cancer education materials among African American women.
Culture has been linked to cancer-related beliefs and practices. The purpose of the present study was to examine the effects of culture on responses to cancer education materials. Religiosity, collectivism, racial pride, and time orientation were measured among 1,227 African American women. Analyses tested the hypothesis that women scoring higher and lower on each construct would differ in their liking, attention, attitude change, recall, and perceived relevance of tailored materials that did or did not frame cancer issues in a cultural context. Responses to culturally tailored materials were no different than responses to other materials, regardless of women's cultural characteristics. However, for all types of materials, women scoring high on religiosity or racial pride paid more attention to materials, liked them more, and found them more personally relevant than women low on these constructs (all ps<.005). Women scoring high on present time orientation paid less attention to materials than women low on this construct (P<.01). In this population of women, cultural characteristics appear to moderate responses to tailored health education materials.


Cytochemical labeling for fungal and host components in plant tissues inoculated with fungal wilt pathogens.
Antibodies to detect pectin in present investigations attached to distinct fibrils in vessel lumina. In carnation infected with an isolate of Fusarium oxysporum f.sp., labeling of pathogen cells also occurred; in a resistant cultivar (cv.), it was coincident with proximate pectin fibrils and linked to altered fungal walls, which was the opposite in the susceptible cv., indicating that hindrance of pathogen ability to degrade pectin may be related to resistance. Labeling of the fungus in culture was nil, except in media containing pectin, showing that pectin is not native to the pathogen. Labeling of fungal walls for cellulose in elm (inoculated with Ophiostoma novo-ulmi) and carnation also occurred, linked to adsorbed host wall components. The chitin probe often attached to dispersed matter, in vessel lumina, traceable to irregularly labeled fungal cells and host wall degradation products. With an anti-horseradish peroxidase probe, host and fungal walls were equally labeled, and with a glucosidase, differences of labeling between these walls were observed, depending on pH of the test solution. Fungal extracellular matter and filamentous structures, present in fungal walls, predominantly in another elm isolate (Phaeotheca dimorphospora), did not label with any of the probes used. However, in cultures of this fungus, extracellular material labeled, even at a distance from the colony margin, with an anti-fimbriae probe.


Development and assessment of the Korean Author Recognition Test.
This research reports the development and evaluation of a Korean Author Recognition Test (KART), designed as a measure of print exposure among young adults. Based on the original, English-language version of the Author Recognition Test (ART), the KART demonstrates significant relationships with offline measures of language ability, as well as online measures of word recognition. In particular, KART scores were related to participants' responses on the Comparative Reading Habits (CRH) checklist, suggesting that KART is a valid measure of print exposure. In addition, KART scores showed reliable correlations with offline measures of vocabulary knowledge and language comprehension. Finally, results from a lexical decision task showed that KART scores modulated the magnitude of the word familiarity effect, such that the effect was smaller for participants with higher KART scores The results suggest that the ART is a language-universal task that measures print exposure, which is useful for explaining individual differences in language comprehension abilities and word recognition processes.


Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as "spacer" elements.
We report 31 point mutations in the factor IX gene and explore the relationship between the level of evolutionary conservation of an amino acid and the probability of a mutation causing hemophilia B. From our total sample of 125 hemophiliacs and from those reported by others, we identify 95 independent missense mutations, 94 of which occur at amino acids that are evolutionarily conserved in the available mammalian factor IX sequences. The likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X, and protein C. Most of the possible missense mutations in generically conserved residues (i.e., those conserved in factor IX and in all the related proteases) should cause disease. In contrast, missense mutations in factor IX-specific residues (i.e., those conserved in human, cow, dog, and mouse factor IX but not in the related proteases) are sixfold less likely to cause disease. Missense mutations at nonconserved residues are 33-fold less likely to cause disease. At least three models are compatible with these observations. A comparison of sequence alignments from four and nine species of factor IX and an examination of the missense mutations occurring at CpG residues suggest a model in which most residues fall on opposite ends of a spectrum. In about 40% of residues, virtually any missense mutation in a minority of the residues will cause disease, while virtually no missense mutations will cause disease in most of the remaining residues. Thus, many of the residues in factor IX are spacers; that is, the main chains are presumably necessary to keep other amino acid interactions in register, but the nature of the side chain is unimportant.


[The potentials of gastric biopsy in the diagnosis of dysplasia and cancer of the stomach].
The paper is concerned with the clinico-morphological analysis of the state of the art in diagnosing dysplasia and cancer of the stomach using gastric biopsy in a nononcological department of a regional hospital. Within three years, 13,459 gastroscopies were performed, 31.7% of them involving a biopsy. Cancer of the stomach was diagnosed in 87 patients including incipient form--in 8 (9.2%). Degree II-III dysplasia and alterations suspicious of cancer were identified in 49 while degree I-II dysplasia--in 180 cases. It is emphasized that patients with dysplasia including degree I-II lesions be followed using morphologic, endoscopic and clinical procedures.


Superparamagnetic behaviour of metallic Co nanoparticles according to variable temperature magnetic resonance.
Investigating the size distributions of Co nanoparticle ensembles is an important problem, which has no straightforward solution. In this work, we use the combination of 59Co internal field nuclear magnetic resonance (59Co IF NMR) and ferromagnetic resonance (FMR) spectroscopies on a metallic Co nanoparticle sample with a narrow Co nanoparticle size distribution due to encapsulation within the inner channels of carbon nanotubes. High-resolution transmission electron microscopy (TEM) images showed that the nanoparticles can be represented as prolate spheroids, with the majority of particles having an aspect ratio between 1 and 2. This observation has increased the accuracy of superparamagnetic blocking size calculations from Néel relaxation model by introducing the actual volume of the ellipsoids taken from the image processing. 59Co IF NMR and FMR experiments conducted under different temperatures allowed us to observe the thermal blocking of superparamagnetic particles in full accordance with the TEM particle volume distribution. This proved that these magnetic resonance techniques can be used jointly for characterization of Co nanoparticles in the bulk of the sample.


Electroclinical features of epilepsy in patients with InvDup(15).
InvDup(15) syndrome is one of the most common chromosomal abnormalities associated with epilepsy. Here we review the seizure types described in InvDup(15) patients and the main electroclinical, therapeutic, and prognostic aspects of the syndrome. A literature search of PubMed, MEDLINE, and EMBASE was performed to identify papers examining InvDup(15) syndrome and epilepsy. About 65% of the InvDup(15) patients described in the literature had multiple seizure types with a predominance (40.4%) of tonic-clonic seizures. Age at seizure onset was before 10 years in more than half of them. Patients suffered from a variety of EEG abnormalities, generalized spike activity being the most frequent. Brain MRI was unremarkable in the majority of patients. Treatment was with several anticonvulsant drugs used as mono- or polytherapy. Valproic acid was the most common treatment against generalized seizures and was often effective, although drug resistance was a major concern in a large number of cases. Finally, more than 30% of the children suffered from infantile spasms, and status epilepticus was described in nearly 20% of patients, occasionally resulting in death. Seizures are very common in InvDup(15) patients, who suffer from a variety of seizure types. Information about EEG and brain MRI findings, seizure treatment, and prognosis is often poor. The overall prognosis is fair. Prospective studies of larger samples are needed, to gain further insights into the natural history of InvDup(15) syndrome.


RNA interference screen reveals an essential role of Nedd4-2 in dopamine transporter ubiquitination and endocytosis.
The function of the dopamine transporter (DAT) to terminate dopamine neurotransmission is regulated by endocytic trafficking of DAT. To elucidate the mechanisms of DAT endocytosis, we generated a fully functional mutant of the human DAT in which a hemagglutinin epitope (HA) was incorporated into the second extracellular loop. The endocytosis assay, based on the uptake of an HA antibody, was designed to study constitutive- and protein kinase C (PKC)-dependent internalization of HA-DAT expressed in non-neuronal cells and rat dopaminergic neurons. Large-scale RNA interference analysis of PKC-dependent endocytosis of HA-DAT revealed the essential and specific role of an E3 ubiquitin ligase, Nedd4-2 (neural precursor cell expressed, developmentally downregulated 4-2), as well as the involvement of adaptor proteins present in clathrin-coated pits, such as epsin, Eps15 (epidermal growth factor pathway substrate clone 15), and Eps15R (Eps15-related protein). Depletion of Nedd4-2 resulted in a dramatic reduction of PKC-dependent ubiquitination of DAT. Endogenous Nedd4-2, epsin, and Eps15 were coimmunoprecipitated with heterologously expressed human HA-DAT and endogenous DAT isolated from rat striatum. A new mechanistic model of DAT endocytosis is proposed whereby the PKC-induced ubiquitination of DAT mediated by Nedd4-2 leads to interaction of DAT with adaptor proteins in coated pits and acceleration of DAT endocytosis.


Mapping Neurotransmitter Identity in the Whole-Mount Drosophila Brain Using Multiplex High-Throughput Fluorescence in Situ Hybridization.
Identifying the neurotransmitters used by specific neurons is a critical step in understanding the function of neural circuits. However, methods for the consistent and efficient detection of neurotransmitter markers remain limited. Fluorescence in situ hybridization (FISH) enables direct labeling of type-specific mRNA in neurons. Recent advances in FISH allow this technique to be carried out in intact tissue samples such as whole-mount Drosophila melanogaster brains. Here, we present a FISH platform for high-throughput detection of eight common neurotransmitter phenotypes in Drosophila brains. We greatly increase FISH throughput by processing samples mounted on coverslips and optimizing fluorophore choice for each probe to facilitate multiplexing. As application examples, we demonstrate cases of neurotransmitter coexpression, reveal neurotransmitter phenotypes of specific cell types, and explore the onset of neurotransmitter expression in the developing optic lobe. Beyond neurotransmitter markers, our protocols can in principle be used for large-scale FISH detection of any mRNA in whole-mount fly brains.


Human dendritic cells respond to Porphyromonas gingivalis LPS by promoting a Th2 effector response in vitro.
Understanding how mucosal pathogens modulate the immune response may facilitate the development of vaccines for disparate human diseases. In the present study, human monocyte-derived DC (MDDC)were pulsed with LPS of the oral pathogen Porphyromonas gingivalis and Escherichia coli 25922 and analyzed for: (i) production of Th-biasing/inflammatory cytokines; (ii) maturation/costimulatory molecules; and (iii) induction of allogeneic CD4+ and naive CD45RA+ T cell proliferation and release of Th1 or Th2 cytokines. We show that E. coli LPS-pulsed MDDC released Th1-biasing cytokines - consisting of high levels of IL-12 p70, IFN-gamma-inducible protein 10 (IP-10) - but also TNF-alpha, IL-10, IL-6 and IL-1beta. In contrast, no IL-12 p70 or IP-10, and lower levels of TNF-alpha and IL-10 were induced by P. gingivalis LPS. These differences were sustained at LPS doses that yielded nearly equivalent maturation of MDDC; moreover the T cell response was consistent: E. coli LPS-pulsed MDDC induced higher T cell proliferation, and T cells released more IFN-gamma and IL-2, but less IL-5 than T cells co-cultured with P. gingivalis LPS pulsed-MDDC. IL-13 was secreted by naive CD45RA+CD45RO-CD4+ T cells in response to P. gingivalisLPS-pulsed MDDC. These results suggest that human MDDC can be polarized by LPS from the mucosal pathogen P. gingivalis to induce a Th2 effector response in vitro.


[The specific features of the hemostatic system and platelet metabolism in pregnant women with gestosis for the prediction of the clinical status of neonatal infants].
The specific features of the hemostatic system and platelet metabolism were studied in women, who were 32-38 weeks pregnant and had varying gestosis, in relation to the clinical status of neonatal infants. The pregnant women who had higher levels of fibrinogen and soluble fibrin-monomer complexes along with decreased platelet enzyme activity regard their neonates' status as having Apgar scores of 6 or less and requiring additional medical intervention.


Brief communication: prehistoric dentistry in the American southwest: a drilled canine from Sky Aerie, Colorado.
A prehistoric Native American mandible from a Fremont site (circa AD 1025) in Colorado has a conical pit in the worn occlusal surface of the lower right canine. Natural causes for this modification are ruled out by the presence of internal striae, a finding confirmed by experimental replication. The canine was artificially drilled before the individual's death and is associated with a periapical abscess. This is one of a very few examples of prehistoric dentistry in the world, and the first from the American Southwest.


[Significance of PCNA proliferating fraction for prognosis of ovarian carcinoma].
The prognostic value of the PCNA-proliferative fraction as compared to conventional clinical and histomorphological factors (FIGO-stage, tumour type, histological grading, lymph node status, size of residual tumour) was investigated in 81 ovarian cancer patients. Categorisation of PCNA-expression into tumours with low and high proliferative activity (< 20%/ > or = 20% according to laboratory standards) had the highest prognostic value. Categorisation on the basis of the median value (< or = 34%/> 34%) or classification of PCNA as a continuous variable did not prove advantageous. PCNA-proliferative fraction was significantly directly correlated with histological grading (p = 0.006). Tumours with a high PCNA expression had a greater frequency of macroscopically detectable residual tumours. In univariate survival analyses patients with highly proliferating tumours had a worse outcome than patients with tumour of low proliferation (PCNA </> or = 20%/20%, p = 0.012; PCNA < or = 34%/ > 34%, p = 0.08). The result was consistent in subgroup of FIGO III-tumours (p = 0.031, PCNA < 20%/> or = 20%), of FIGO l-tumours (p = 0.036, PCNA < 20%/> or = 20%), of carcinomas without post-operative residual tumour (p = 0.03 PCNA < 20%/> or = 20%) and also of FIGO III-tumour without residual tumours (p = 0.041 PCNA < 20%/> or = 20%). Multivariate survival analysis comprising all the patients revealed PCNA expression (< 20%/> or = 20%) as an independent prognostic factor second to the size of the residual tumour. In patients with FIGO III-tumours PCNA proves significant as an independent factor after the size of the residual tumour was removed from the model. Thus, PCNA provides additional information which may prove beneficial in determining prognostic estimates for ovarian cancer.