Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS.
Astroglia play active and diverse roles in modulating neuronal/synaptic functions in the CNS. How these astroglial functions are regulated, especially by neuronal signals, remains largely unknown. Exosomes, a major type of extracellular vesicles (EVs) that originate from endosomal intraluminal vesicles (ILVs), have emerged as a new intercellular communication process. By generating cell-type-specific ILVs/exosome reporter (CD63-GFPf/f) mice and immuno-EM/confocal image analysis, we found that neuronal CD63-GFP+ ILVs are primarily localized in soma and dendrites, but not in axonal terminals in vitro and in vivo. Secreted neuronal exosomes contain a subset of microRNAs (miRs) that is distinct from the miR profile of neurons. These miRs, especially the neuron-specific miR-124-3p, are potentially internalized into astrocytes. MiR-124-3p further up-regulates the predominant glutamate transporter GLT1 by suppressing GLT1-inhibiting miRs. Our findings suggest a previously undescribed neuronal exosomal miR-mediated genetic regulation of astrocyte functions, potentially opening a new frontier in understanding CNS intercellular communication.


Second virial coefficient at the critical point in a fluid of colloidal spheres plus depletants.
Vliegenthart-Lekkerkerker (VL) criterion B2 = -6vc for second virial coefficient B2 at the critical (colloidal) gas-liquid point is considered for a mixture of spheres with volume vc plus depletants. For the onset of fluid-phase instability, the VL criterion holds for a wide range of shapes of direct attractive forces between hard-core spheres (Vliegenthart, G. A.; Lekkerkerker, H. N. W. J. Chem. Phys. 2000, 112, 5364). In the case of long-ranged attractions imposed indirectly via depletants, it is found that the VL relation fails. Instead, B2/vc at the critical point depends strongly on the sphere/depletant size ratio. By making the hard spheres sticky, we find that B2 moves gradually toward the VL criterion upon increasing the stickiness.


Brain Network Changes in Fatigued Drivers: A Longitudinal Study in a Real-World Environment Based on the Effective Connectivity Analysis and Actigraphy Data.
The analysis of neurophysiological changes during driving can clarify the mechanisms of fatigue, considered an important cause of vehicle accidents. The fluctuations in alertness can be investigated as changes in the brain network connections, reflected in the direction and magnitude of the information transferred. Those changes are induced not only by the time on task but also by the quality of sleep. In an unprecedented 5-month longitudinal study, daily sampling actigraphy and EEG data were collected during a sustained-attention driving task within a near-real-world environment. Using a performance index associated with the subjects' reaction times and a predictive score related to the sleep quality, we identify fatigue levels in drivers and investigate the shifts in their effective connectivity in different frequency bands, through the analysis of the dynamical coupling between brain areas. Study results support the hypothesis that combining EEG, behavioral and actigraphy data can reveal new features of the decline in alertness. In addition, the use of directed measures such as the Convergent Cross Mapping can contribute to the development of fatigue countermeasure devices.


Panfibrinonecrotic colitis in a dog treated by subtotal colectomy.
A dog with signs of small intestinal disease developed signs of severe large intestinal disease after being treated with multiple agents. Endoscopy and biopsy revealed total destruction of the colonic mucosa, which necessitated total parenteral nutrition plus subtotal colectomy. It was hypothesized that the multiple prior treatments led to an overgrowth of toxigenic or cytotoxic bacteria, which caused this colonic mucosal destruction.


Relationship of pre-S encoded antigens in liver and clinical manifestations of chronic hepatitis B infection.
Pre-S1 and pre-S2 encoded antigens of hepatitis B virus were localized in liver tissue using monoclonal antibodies. They were found to be exclusively expressed in the cytoplasm of liver cells. Cell bound pre-S1 encoded protein was often detected in patients with chronic liver disease and viremia. Only a small number of the HBsAg positive cells also contained pre-S1 antigen. There was no correlation with nuclear HBcAg. Livers of non-viremic HBsAg carriers contained many HBsAg expressing liver cells, that were frequently also positive for pre-S2 encoded protein but contained no detectable pre-S1 encoded protein at all. It remains open whether cell bound pre-S2 containing proteins of middle size have a significance for pathogenesis, as they are present in individuals with chronic liver disease as well as in healthy HBsAG carriers, and may be associated with both increased and normal liver enzymes. Cell bound pre-S1 antigen with viremia may, however, be involved in the maintenance of viremia and liver disease.


circRNA_0046367 Prevents Hepatoxicity of Lipid Peroxidation: An Inhibitory Role against Hepatic Steatosis.
Hepatic steatosis reflects the miRNA-related pathological disorder with triglyceride accumulation and lipid peroxidation, which leads to nonalcoholic steatohepatitis, liver fibrosis/cirrhosis, and even hepatocellular carcinoma. Circular RNA (circRNA)/miRNA interaction reveals a novel layer of epigenetic regulation, yet the miRNA-targeting circRNA remains uncertain in hepatic steatosis. Here, we uncover circRNA_0046367 to be endogenous modulator of miR-34a that underlies hepatic steatosis. In contrast to its expression loss during the hepatocellular steatosis in vivo and in vitro, circRNA_0046367 normalization abolished miR-34a's inhibitory effect on peroxisome proliferator-activated receptor α (PPARα) via blocking the miRNA/mRNA interaction with miRNA response elements (MREs). PPARα restoration led to the transcriptional activation of genes associated with lipid metabolism, including carnitine palmitoyltransferase 2 (CPT2) and acyl-CoA binding domain containing 3 (ACBD3), and then resulted in the steatosis resolution. Hepatotoxicity of steatosis-related lipid peroxidation, being characterized by mitochondrial dysfunction, growth arrest, and apoptosis, is resultantly prevented after the circRNA_0046367 administration. These findings indicate a circRNA_0046367/miR-34a/PPARα regulatory system underlying hepatic steatosis. Normalized expression of circRNA_0046367 may ameliorate the lipoxidative stress on the basis of steatosis attenuation. circRNA_0046367, therefore, is suggested to be potential approach to the therapy of lipid peroxidative damage.


Convergence of ventrolateral medullary and aortic baroreceptor inputs in nucleus of the solitary tract.
Experiments were done in alpha-chloralose anesthetized rats to investigate the effect of stimulating the intermediate region of the ventrolateral medulla (VLM) on the response of single units in nucleus of the solitary tract (NTS) that altered their rate of discharge during aortic baroreceptor stimulation. Of 178 units recorded within NTS, 65 responded orthodromically to VLM stimulation. An additional 16 units were activated antidromically by VLM stimulation. The interaction between the aortic depressor nerve and VLM orthodromic inputs was investigated in 38 units that received converging inputs from VLM and the aortic depressor nerve. A conditioning stimulus applied to VLM, regardless of whether the NTS unit was excited by (n = 13) or did not respond to (n = 9) VLM stimulation, decreased the excitatory response of the unit to aortic depressor nerve stimulation. These data suggest that VLM neurons are involved in the modulation of aortic baroreceptor afferent information at the level of the NTS and that this interaction of inputs in NTS may involve both postsynaptic and presynaptic mechanisms.


DJ-1 cleavage by matrix metalloproteinase 3 mediates oxidative stress-induced dopaminergic cell death.
Oxidative stress is commonly implicated in aging and neurodegenerative conditions such as Parkinson's disease (PD). Mutations in DJ-1 are associated with autosomal recessive early-onset PD. We investigated whether DJ-1 can be degraded in oxidative-stressed dopaminergic neuronal cells, leading to loss of its protective role against oxidative stress. We have shown previously and herein that the active form of matrix metalloproteinase-3 (MMP3) was accumulated in dopamine-producing CATH.a cells in the presence of MPP(+). We show that catalytically active MMP3 cleaved DJ-1, and impaired its antioxidant function. In CATH.a cells, both monomeric and dimeric forms of DJ-1 were diminished in the presence of MPP(+), and this was reversed by MMP3 knockdown or inhibition. While DJ-1 expression was decreased in the substantia nigra of mice administered with MPTP, its degradation was largely attenuated in MMP3 knockout mice. The AKT-signaling pathway, thought to mediate the effect of DJ-1 on cell survival, was also altered. MPP(+) caused decrease in both phospho-Thr308 and phospho-Ser473 forms of AKT, and this was restored by NNGH. Our data suggest that DJ-1 is fragmented by the intracellular MMP3 in response to cell stress, abolishing the protective role of DJ-1 against oxidative damage, and this contributes to the pathogenesis of PD.


A Confirmatory Method Based on HPLC-MS/MS for the Detection and Quantification of Residue of Tetracyclines in Nonmedicated Feed.
The Commission Regulation 574/2011/EC set up maximum levels of coccidiostats and histomonostats in nonmedicated feed as a consequence of carry-over during manufacturing. Carry-over takes place from medicated to nonmedicated feed during feed production. Similar contamination could also occur for other pharmaceuticals such as tetracyclines, a group of antibiotics commonly employed in food production animal. The objective of this work is to present a simple and fast method for the simultaneous detection of four tetracyclines (chlortetracycline, doxycycline, oxytetracycline, and tetracycline) in nontarget feed at a μg/kg level. Validation of the method was performed according to the guideline included in the Commission Decision 2002/657/EC for official method. The validated method was successfully applied to 50 feed samples collected from different milk farms and 25 samples obtained from feed manufacturers. While oxytetracycline was the tetracycline most frequently detected, chlortetracycline was the analyte measured at the highest concentration 15.14 mg/Kg. From 75 nonmedicated feed analysed 15% resulted to be positive for the presence of one tetracycline.


The Association between Tea Consumption and Nasopharyngeal Cancer: A Systematic Review and Meta-Analysis
Heated debates have been on-going about tea consumption and the incidence of cancer, especially in head and neck cancer types. This study aimed to review the association between tea consumption habits and nasopharyngeal cancer (NPC). Methods: This review was carried out in accordance with the PRISMA-P protocol. Literature search for journal articles that published studies on the relationship between tea consumption and NPC was performed via databases, such as Elsevier, PubMed, Science Direct, Springer Link, Google, and Google Scholar, for 10 years from 2008 to 2018. Relevant studies were obtained by applying the pre-determined keywords, such as nasopharyngeal cancer, tea consumption and NPC, risk factors of NPC and benefits of tea consumption. Results: A total of 126 articles was retrieved. These articles were subjected to eligibility assessment. Six articles remained after applying the inclusion criteria. Results suggest that habitual tea consumption reduces NPC. Tea consumption significantly reduces NPC with all the studies having a p-value ≤0.05. Meta-analysis showed statistical association between tea consumption and NPC risk with OR=0.865 at 95% CI (0.806-0.929). Conclusion: This study suggests that habitual tea consumption could be associated with prevention of NPC development. Additional studies are needed to further understand the molecular role of bioactive compound and potential health benefit of tea consumption in NPC prevention.


Metabolic syndrome and idiopathic sudden sensori-neural hearing loss.
The purpose of this study was to evaluate the association between the presence of Metabolic Syndrome (MetS) and idiopathic sudden sensorineural hearing loss (ISSHL) and the impact of MetS on recovery of patients with ISSHL. 39 Patients with ISSHL and 44 controls were enrolled in this study. Demographic, clinical characteristics and hearing recovery were evaluated. MetS was defined according to the diagnostic criteria of International Diabetes Federation (IDF) consensus definition. Patients affected by ISSHL presented a body mass index (BMI), waist circumference, waist hip ratio (WHR), fasting glucose and blood pressure significantly higher compared to controls. Considering patients with central obesity, 5 controls and 15 ISSHL patients met the criteria of MetS. According to Siegel criteria, a complete or partial recovery was observed in 60% of patients with MetS and in 91,66% of patients without MetS. MetS was associated with ISSHL and this association negatively influenced the hearing recovery of these patients.


Lithoseopsis Mockford (Psocodea: Troctomorpha: Amphientomidae): a new species and first record for South America.
A species of Lithoseopsis Mockford, from the Brazilian state of Pará, is described and illustrated. It is the first species of Lithoseopsis recorded in Brazil, and the first of that genus known in South America. It differs from all the other species in the genus in details of the forewing pigmentation and spermapore sclerite. A map with the distribution of the Lithoseopsis species is included and two species groups of Lithoseopsis are diagnosed.


Associations of health inequality factors with physical activity and sedentary behaviors in Korean cancer survivors.
Although physical activity (PA) benefits cancer survivors physically and psychosocially, health inequality may limit these benefits in a subset of cancer survivors, and its association with PA in cancer survivors has not been investigated. Therefore, the purpose of this study is to explore PA levels with regard to health inequality factors (i.e., demographic and socioeconomic profiles) in Korean cancer survivors using the Korean National Health and Nutrition Examination Survey (KNHANES). Data of 900 cancer survivors from the KNHANES in 2014-2017 were used. ANCOVA was used to determine differences in PA and sedentary behavior by healthy inequality factors. Logistic regression was used to estimate the associations of the health inequality factors with meeting the aerobic PA guidelines. Higher PA was reported in participants who were male (p = 0.004), younger (p = 0.006), and with higher education (p = 0.003). In adjusted logistic regression models, females were 37% less likely to meet the guideline compared to males (p = 0.045). Participants who were ≥ 70 years were 78% less likely to meet the guideline compared to < 50 years (p < 0.001). Compared to participants who graduated from college/university, participants who graduated from high-, middle-, or elementary-school were 50% (p = 0.005), 53% (p = 0.023), and 71% (p < 0.001) less likely to meet the guideline, respectively. Lower PA was prevalent in cancer survivors who were female, older, and less educated. Systematic efforts to promote PA are required for targeted cancer subgroups.


Dental anxiety and temperament in 15-year olds.
The aim of the present study was to analyze the prevalence of dental anxiety and its association with temperament, sociodemographic factors and previous painful and unpleasant experiences of dental care among 15-year old individuals. The sample included 263 randomly selected 15-year old individuals living in the municipality of Jönköping, Sweden. The school, parental and adolescent consent was acquired. Three self-reported questionnaires were used, one included items of sociodemography, while the others dealt with dental anxiety assessed by the Dental Fear Survey (DFS) and temperament assessed by an adapted version of The EAS Temperament Survey for Children modified for adults, the EASI temperament survey. The results showed that 6.5% of the adolescents were classified as dentally anxious and with girls proportionally more fearful than boys. The three temperaments activity, impulsivity and emotionality were significantly correlated with dental anxiety. A hierarchical multiple linear regression analysis showed that pain at the last dental appointment or previous pain experiences during dental care treatment were the strongest predictors regarding dental anxiety in 15-year olds. The temperament dimensions activity and impulsivity were also significantly predictive of dental anxiety. Although some of the temperament dimensions are correlated with dental anxiety, which may emphasize an important finding with regard to personality, this study showed that previous pain experiences during dental care treatment is a strong predictor for high dental anxiety in 15-year olds.


Bloodstream infections with rapidly growing nontuberculous mycobacteria.
Bloodstream infections (BSI) with rapidly growing mycobacteria (RGM) resulted in recent nosocomial outbreaks predominantly in immunocompromised patients. A little is known about the clinical implications of RGM BSI with different species. We conducted a multicenter retrospective cohort study of patients with RGM BSI from November 2011 to December 2020. Demographic data, clinical presentation, laboratory and radiographic findings and microbiological characteristics were used to tabulate descriptive statistics. We performed a comparative analysis of patients with BSI due to Mycobacterium abscessus complex (MABC) vs. other RGM. We identified 32 patients with positive blood cultures for RGM, 4/32 (12.5%) were considered to have unclear significance. The most common source for RGM BSI was intravascular catheters (14/28, 50%). Compared to other sources, patients with catheter-related bloodstream infection (CRBSI) received a shorter course of antimicrobial therapy (median [IQR]: one month [0.37-2.25] vs. six months [2-12]), (P = 0.01). The most common species isolated were MABC (12/28, 42.9%), followed by Mycobacterium fortuitum group (6/28, 21.4%) and Mycobacterium chelonae (6/28, 21.4%). Compared to other RGM, MABC BSI was more likely to be secondary to skin and soft tissue infection, associated with longer hospital stay (P = 0.04) and higher death rates despite a higher number of antimicrobial agents used for empirical and directed therapy per patient. MABC BSI is associated with an overall more resistant profile, longer hospital stay, and higher death rate despite a more aggressive therapy approach.


Quantitative Proteomic Analysis of Human Seminal Plasma from Normozoospermic and Asthenozoospermic Individuals.
Seminal plasma is a complex mixture of secretions from various glands in the male genital tract. Compared to sperm cells, it contains important proteins that are both directly and indirectly associated with sperm motility. Here, we constructed quantitative proteomes of human seminal plasma from three normozoospermic and asthenozoospermic individuals. A total of 524 proteins were identified, and 366 of them were found to be quantified in all six samples. We first investigated the absolute expression features of these proteins and found that the variations of protein identification among different samples and other published datasets were mainly due to some lowly expressed proteins. By integration of various proteomic datasets and bioinformatics databases, we comprehensively annotated the biological functions, physiological originations, and disease associations of these proteins. We found that our dataset could benefit the studies of both male infertility and other male diseases. Finally, based on the relative expression values determined by chemical labeling, we identified a total of 29 differentially expressed proteins, which could be used as candidate targets for studying the molecular bases of sperm motility or developing precise diagnostic biomarkers of asthenozoospermia. We further successfully verified the expression trends of four representative proteins by Western blotting. Compared to a previous dataset based on label-free quantification, our results showed that most of the important proteins could be identified in the sample collected only once for each individual, providing the bases for personalized examination of seminal plasma proteins in clinic.


Partially active HIV-1 Vif alleles facilitate viral escape from specific antiretrovirals.
The HIV-1 Vif protein counteracts the antiviral activity of the cytidine deaminases APOBEC3G and APOBEC3F. Natural variation in Vif may result in reduced efficacy against APOBEC3 proteins and in increased HIV-1 diversity. We speculated that this mechanism could facilitate viral escape from certain antiretroviral drugs. We analyzed the protease, reverse transcriptase and Vif sequences of viruses from plasma obtained from 92 HIV-1-infected individuals failing antiretroviral treatment and 65 antiretroviral-naive patients. Mutation K22H in Vif was more frequent in patients failing to antiretroviral compared to antiretroviral-naive patients. In-vitro experiments showed that mutant K22H failed to completely neutralize APOBEC3G. Upon infection of MT-2 cells, most of the K22H proviral clones encoded increased numbers of G-to-A mutations. Among these mutations, the lamivudine drug-resistance-associated mutation M184I in reverse transcriptase was detected in 25% of clones in the absence of any lamivudine exposure. In our population, among pretreated patients, 72% of K22H viruses versus 42% in WT K22 viruses harbored at least two drug-resistance-associated mutations in a GA/GG dinucleotide context. More specifically, K22H viruses harbored significantly more G16E and M36I in protease than in those isolated from pretreated patients harboring WT K22 viruses. This study provides evidence that patients experiencing virological failure frequently harbor Vif point mutants (i.e. K22H). Such Vif alleles lose their ability to counteract APOBEC3 proteins, leading to an increase of G-to-A viral mutations that can facilitate the emergence of some antiretroviral resistance mutations.


A Review About Lycopene-Induced Nuclear Hormone Receptor Signalling in Inflammation and Lipid Metabolism via still Unknown Endogenous Apo-10´-Lycopenoids.
Lycopene is the red pigment in tomatoes and tomato products and is an important dietary carotenoid found in the human organism. Lycopene-isomers, oxidative lycopene metabolites and apo-lycopenoids are found in the food matrix. Lycopene intake derived from tomato consumption is associated with alteration of lipid metabolism and a lower incidence of cardiovascular diseases (CVD). Lycopene is mainly described as a potent antioxidant but novel studies are shifting towards its metabolites and their capacity to mediate nuclear receptor signalling. Di-/tetra-hydro-derivatives of apo-10´-lycopenoic acid and apo-15´-lycopenoic acids are potential novel endogenous mammalian lycopene metabolites which may act as ligands for nuclear hormone mediated activation and signalling. In this review, we postulate that complex lycopene metabolism results in various lycopene metabolites which have the ability to mediate transactivation of various nuclear hormone receptors like RARs, RXRs and PPARs. A new mechanistic explanation of how tomato consumption could positively modulate inflammation and lipid metabolism is discussed.


Developing and implementing new safe practices: voluntary adoption through statewide collaboratives.
Disseminating new safe practices has proved challenging. In a statewide initiative we developed a framework for (1) selecting two safe practices, (2) developing operational details of implementation, (3) enlisting hospitals to participate, and (4) facilitating implementation. Potential topics were selected by a multistep process to identify candidate practices, review the evidence for efficacy and feasibility, and then select them on the basis of importance, efficacy, feasibility, and impact. A multi-stakeholder advisory group representing all constituencies selected two practices: reconciling medications (RM) and communicating critical test results (CTR). Operational details and strategies for implementation were then developed for each practice using a consensus process of discipline stakeholders led by content experts. Hospital CEOs were solicited to participate by the Massachusetts Hospital Association which made the project a "flagship" initiative. A collaborative model was used to facilitate implementation, following the IHI Model for Improvement. In addition to providing exposure to content and method experts, we gave teams a "toolkit" containing recommendations, a change package, and implementation strategies. Each collaborative met four times over an 18 month period. Results were assessed using the IHI team assessment scale and surveys of teams and hospital leaders. Hospital participation rate was high with 88% of hospitals participating in one or both collaboratives. Partial implementation of the practices was achieved by 50% of RM teams and 65% of CTR teams. Full implementation was achieved by 20% of teams for each. Major factors leading to hospital participation included the intrinsic appeal of the practices, access to experts, and the availability of implementation strategies. Team success was correlated with active engagement of a senior administrator, engagement of physicians, increased use of PDSA cycles, and attendance at collaborative meetings. The prior development of subpractices, recommendations and implementation strategies was essential for the hospital teams. These should be well worked out before hospitals are required to implement any guideline.


The influence of the neuropeptide galanin on the contractility and the effective refractory period of guinea-pig heart papillary muscle under normoxic and hypoxic conditions.
The aim of this study was to discover the effects of galanin, a neuropeptide comprising 29 amino acids capable of activating inward-rectifier K+ channels (IK1) in cardiomyocytes, on the force of contraction (Fc), velocity of contraction (+dF/dt), velocity of relaxation (-dF/dt) and effective refractory period (ERP) of guinea-pig heart. The influence of galanin on the time-course of hypoxia-induced disturbances in contractility and ERP was also examined. Experiments were performed on the isolated right ventricle papillary muscle of guinea-pig heart. In the concentration range 0.001-0.01 microM, galanin had no significant effect on the measured parameters. At 0.03 and 0.1 microM, galanin exerted a positive inotropic action and prolonged ERP. Further increasing the concentration led to a negative inotropic action and significant shortening of ERP. Although simulated hypoxia induced a significant drop in Fc, +dF/dt and -dF/dt, and a significant shortening of ERP, recovery of all the measured parameters was complete after 10 min reperfusion. In the presence of 0.03 and 0.1 microM galanin the effect of hypoxia on the contractility of papillary muscle was more profound and reperfusion did not result in complete recovery. In contrast, addition of 1 microM galanin to the hypoxic solution significantly protected the muscle and recovery of the tissues during reperfusion was rapid and complete (in 5 min). One can conclude that galanin at lower concentrations induced a positive inotropic action and a prolongation of ERP, but increased the sensitivity of heart muscle to hypoxia. At higher concentrations however, galanin exerted a negative inotropic action but protected the muscle against hypoxia-induced disturbances in contractility.


Gemcitabine and platinum pathway pharmacogenetics in Asian breast cancer patients.
Gemcitabine/carboplatin is efficacious in breast cancer but results in significant hematologic toxicities. We employed a multi-gene approach to identify variants to predict its toxicities. Twenty-six gemcitabine and platinum-based DNA repair pathway polymorphisms were correlated with gemcitabine pharmacokinetics, hematologic toxicities, response and survival in 41 Asian breast cancer patients receiving gemcitabine/carboplatin. The combined effects of solute carrier family (SLC)28A1+1528C>T and thymidylate synthetase (TYMS)+1494del6 significantly influenced hematologic toxicities: 89% of patients who possessed either SLC28A1+1528TT or TYMS+1494ins6/ins6 (n=9) developed grade 4 thrombocytopenia, versus 14% with neither genotype (n=29; p<0.001). In concordance, all patients who possessed either genotype developed grade 3/4 neutropenia, compared to 38% with neither genotype (p=0.001). None of the other genetic variants analyzed correlated with drug pharmacokinetics and pharmacodynamics. Approximately one-quarter of our Asian cohort carried SLC28A1+1528TT or TYMS+1494ins6/ins6, which are associated with increased myelotoxicity from gemcitabine/carboplatin. This has potential utility in treatment selection and genotype-based dosing strategies.


Molecular Fingerprint of Amphioxus Frontal Eye Illuminates the Evolution of Homologous Cell Types in the Chordate Retina.
The evolution of the vertebrate eye remains so far unresolved. Amphioxus frontal eye pigment cells and photoreceptors were proposed to be homologous to vertebrate photoreceptors and retinal pigmented epithelium, based on ultrastructural morphology and gene expression analysis in B. floridae. Here, we present comparative molecular data using two additional amphioxus species, a closely related B. lanceolatum, and the most divergent A. lucayanum. Taking advantage of a unique set of specific antibodies we characterized photoreceptors and putative interneurons of the frontal eye and investigated its neuronal circuitry. Our results corroborate generally conserved molecular fingerprint among cephalochordate species. Furthermore, we performed pharmacological perturbations and found that the Notch signaling pathway, a key regulator of retina development in vertebrates, is required for correct ratios among frontal eye cell types. In summary, our study provides a valuable insight into cell-type relationships in chordate visual organs and strengthens the previously proposed homology between amphioxus frontal eye and vertebrate eyes.


Biomechanical evaluation of wrist motor tendons after fractures of the distal radius.
We conducted a biomechanical study of changes in parameters of wrist motor tendons in fractures of the distal radius in 7 cadaveric extremities. Extra-articular distal radius fractures were simulated by distal radius osteotomy and fracture angulation was maintained by external fixators. Eight positions of the distal radius fractures were studied: dorsal angulation of 10 degrees, 20 degrees, 30 degrees, and 40 degrees and radial angulation of 5 degrees, 10 degrees, 15 degrees, and 20 degrees. Dorsal and radial angulation of the fractures were measured with respect to the shaft of the radius. Excursions of 5 principal wrist motor tendons extensor carpi radialis longus, extensor carpi radialis brevis, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris were recorded simultaneously with wrist joint angulation using a computer-assisted recording system. Data were collected from intact wrists and from wrists with fractures at each of 8 positions of angulation during wrist flexion and extension and radical and ulnar deviation. Moment arm of the wrist motor tendons was derived from tendon excursion and joint angulation. The results demonstrated that excursions and moment arms of principal wrist motor tendons are significantly affected by dorsal and radial angulation of distal radius fractures. Amplitude of changes in moment arms increased as the deformities became more severe. Statistical analysis revealed that dorsal angulation of 10 degrees or more significantly affected moment arms of all the prime wrist motors. Dorsal angulation of 30 degrees or 40 degrees changed the moment arms greatly. Radial angulation of 5 degrees did not affect moment arms of the tendons and angulation over 10 degrees had a statistically significant effect on the tendons. We conclude that deformities of distal radius fractures have a significant influence on the biomechanics of the wrist motors.


New dimension in the schlieren technique: flow field analysis using color.
The various techniques for introducing color into a schlieren system were explored, and all of them were found to have drawbacks such that the added dimension of color in a schlieren has never been utilized for extensive quantitative measurements. An entirely new technique using a diffraction grating to produce the color has been introduced as a modification of the conventional schlieren system. It provides solutions to the problems of sensitivity, range of measurement deflection and undesirable effects of diffraction which have limited the usefulness of color systems in the past. Methods for analyzing a conventional schlieren have been modified for the analysis of a color schlieren result. Surface pressures and flow field analysis for some simple two-dimensional airfoil shapes have been obtained by these color techniques developed here, and the results compare very well with theoretical pressure calculations.


Dietary approach to hypertension based on low glycaemic index and principles of DASH (Dietary Approaches to Stop Hypertension): a randomised trial in a primary care service.
Hypertension is one of the leading causes of morbidity and mortality in Brazil. Diet may play an important role in reducing blood pressure (BP), as has been shown for diets high in fruits, vegetables and low-fat dairy products and low in salt (Dietary Approaches to Stop Hypertension (DASH)-Na). A low-glycaemic index Brazilian diet combined with the principles of the DASH-Na diet was evaluated in a randomised study of 206 individuals who were followed for 6 months. In the control group (CG), counselling was based on standard care and mainly focused on salt intake reduction. An intention-to-treat analysis showed that, after 6 months, systolic BP was reduced by 14·4 mmHg and diastolic BP by 9·7 mmHg in the experimental group (EG), compared with 6·7 and 4·6 mmHg, respectively, in the CG. After adjusting for body weight, BP at baseline and age, these changes were 12·1 and 7·9 mmHg, respectively. Urinary Na excretion was also reduced by 43·4 mEq/24 h in the EG. Food intake was modified accordingly during the intervention with an increase in the consumption of vegetables (2·97-5·85 frequency of consumption measured in three non-consecutive days), fruits (4·09-7·18), beans (1·94-3·13) and fish (1·80-2·74) by the EG. The present study showed the feasibility of a Brazilian dietary approach to treating hypertension by reducing urinary Na excretion and BP, changes that may have a great impact on public health and promote the benefits of controlling hypertension.


Microstructure and gas-sensing property of the ordered mesoporous Co3O4.
We report the microstructure, gas-sensing properties of the ordered mesoporous Co3O4 prepared by modified KIT-6 template method. Highly ordered mesoporous nanostructures of the as-prepared products have been characterized by X-ray diffraction (XRD), extended X-ray absorption fine structure (EXAFS), high-resolution transmission electron microscopy (HRTEM) and N2 adsorption/desorption analysis. We find that the ordered mesoporous Co3O4 enables a significant improvement of sensor response and selectivity to ethanol, which demonstrates the potential use of the ordered mesoporous Co3O4 as alcohol gas-sensing material. Through the analysis of microstructure including HRTEM and N2 adsorption/desorption, the sensing properties for the ordered mesoporous Co3O4 can be attributed qualitatively to its large specific surface area and porous morphology. Moreover, the results of EXAFS illustrate that the disorder degree and unsaturated bond of the ordered mesoporous Co3O4 increase, which agree well with the results observed in gas sensors. This makes the nanostructured ordered mesoporous Co3O4 a promising sensor material for detecting the alcohol gas.


A qualitative study on safety perception among healthcare workers of a tertiary academic care center during the SARS-CoV-2 pandemic.
Protecting healthcare workers (HCWs) from exposure to SARS-CoV-2 during patient care is central to managing the current pandemic. Higher levels of trust in personal protective equipment (PPE) and infection prevention and control (IPC) strategies have been previously related to lower levels of emotional exhaustion, yet little is known on how to achieve such a perception of safety. We thus sought to identify institutional actions, strategies and policies related to HCWs' safety perception during the early phase of the pandemic at a tertiary care center in Switzerland by interviewing HCWs from different clinics, professions, and positions. For this qualitative study, 36 face-to-face semi-structured interviews were performed. Interviews were based on a guide that addressed the perception of institutional strategies and policies during the first phase of the pandemic in March 2020. The participants included doctors (n = 19) and nurses (n = 17) in senior and non-senior positions from eight clinics in the University Hospital Basel, Switzerland, all involved in patient care. All interviews were audio-recorded and transcribed verbatim. Data were analyzed using qualitative content analysis and organized using MAXQDA (VERBI Software GmbH, Berlin). Five recurring themes were identified to affect HCWs' perception of their safety during the SARS-CoV-2 pandemic: (1) transparency and clarity of information, (2) communication on the availability of PPE (with the provision of information alone increasing the feeling of safety even if supplies of PPE were reported as low), (3) uniformity and consistency of guidelines, (4) digital resources to support face-to-face teaching (although personal information transfer is still being considered superior in terms of strengthening safety perception) and (5) support and appreciation for the work performed. This study identifies institutional policies and actions influencing HCWs' safety perception during the first wave of the COVID-19 pandemic, the most important of which is the factor of transparent communication. This knowledge reveals potential areas of action critical to improving preparedness and management in hospitals faced with an infectious disease threat.


[The binding of exogenous DNA pRK31acZ by rabbit spermatozoa, its transfer to oocytes and expression in preimplantation embryos].
It was shown that 35.3% ejaculated rabbit spermatozoa washed from seminal plasma are capable of interacting with heterogeneous DNA. The major part (85.2%) of bound DNA was located in the post-acrosomal part of the sperm head. After incubation with plasmid pRK31acZ the spermatozoa transferred it in the oocytes during in vivo fertilization, as shown by expression of reporter gene lacZ in 19.3% of preimplantation embryos. Additional treatment of the mobile spermatozoa with DMSO and heat shock raised the efficiency of exogenous DNA incorporation in the spermatozoa, as expressed in the percentage of embryos containing bacterial beta-galactosidase (61.7%). It is proposed to use the capture of heterogeneous DNA by the spermatozoa and its transfer in the oocytes for production of transgenic animals and in studies of regulation of gene expression at the early stages of embryogenesis.


The C-terminal C1 cassette of the N -methyl-D-aspartate receptor 1 subunit contains a bi-partite nuclear localization sequence.
The N -methyl-D-aspartate receptor (NMDAR) is a multimeric transmembrane protein composed of at least two subunits. One subunit, NR1, is derived from a single gene and can be subdivided into three regions: the N-terminal extracellular domain, the transmembrane regions, and the C-terminal intracellular domain. The N-terminal domain is responsible for Mg2+ metal ion binding and channel activity, while the transmembrane domains are important for ion channel formation. The intracellular C-terminal domain is involved in regulating receptor activity and subcellular localization. Our recent experiments indicated that the intracellular C-terminal domain, when expressed independently, localizes almost exclusively in the nucleus. An examination of the amino acid sequence reveals the presence of a putative nuclear localization sequence (NLS) in the C1 cassette of the NR1 intracellular C-terminus. Using an expression vector designed to test whether a putative NLS sequence is a valid, functional NLS, we have demonstrated that a bi-partite NLS does in fact exist within the NR1-1 C-terminus. Computer algorithms identified a putative helix-loop-helix motif that spanned the C0C1 cassettes of the C-terminus. These data suggest that the NR1 subunit may represent another member of a family of transmembrane proteins that undergo intramembrane proteolysis, releasing a cytosolic peptide that is actively translocated to the nucleus leading to alterations in gene regulation.


Analysis of the functional domains of Arcanobacterium pyogenes pyolysin using monoclonal antibodies.
Pyolysin (PLO), secreted by Arcanobacterium pyogenes, is a novel member of the thiol-activated cytolysin (TACY) family of bacterial toxins. Four monoclonal antibodies (mAbs) to PLO were prepared for the analysis of functional domains of this toxin. Two (mAbs S and H) of these markedly inhibited the hemolytic activity of PLO, but the inhibiting activity of the other two antibodies (mAbs C and G) was weaker. Subsequently, nine truncated PLOs were derived from recombinant Escherichia coli by various deletions from the N-terminus. Strong hemolytic activity was recognized in truncates of PLO following the deletion of 30 or 55 amino acids, but not in the truncate with deletion of 74 residues. Truncated PLOs were used in immunoblotting experiments to locate the epitopes for the mAbs. The epitope for mAbs C and G lies within the undecapeptide region (amino acids 487-505) of the C-terminus of PLO, which seems to be the binding site to erythrocytes. In contrast, the epitopes for mAbs S and H, which showed strong neutralizing activity, were found to lie in the N-terminal regions of the PLO ranging from 55 to 73 and 123 to 166 amino acids, respectively. From these results, it seems that the N-terminal region of PLO, in particular, the region of amino acids 55-74 is important for hemolytic activity.


An unattended device for high-voltage sampling and passive measurement of thoron decay products.
An integrating measurement device for the concentration of airborne thoron decay products was designed and calibrated. It is suitable for unattended use over up to several months also in inhabited dwellings. The device consists of a hemispheric capacitor with a wire mesh as the outer electrode on ground potential and the sampling substrates as the inner electrode on +7.0 kV. Negatively charged and neutral thoron decay products are accelerated to and deposited on the sampling substrates. As sampling substrates, CR39 solid-state nuclear track detectors are used in order to record the alpha decay of the sampled decay products. Nuclide discrimination is achieved by covering the detectors with aluminum foil of different thickness, which are penetrated only by alpha particles with sufficient energy. Devices of this type were calibrated against working level monitors in a thoron experimental house. The sensitivity was measured as 9.2 tracks per Bq/m(3) × d of thoron decay products. The devices were used over 8 weeks in several houses built of earthen material in southern Germany, where equilibrium equivalent concentrations of 1.4-9.9 Bq/m(3) of thoron decay products were measured.


Analysis of the color alteration and radiopacity promoted by bismuth oxide in calcium silicate cement.
The aim of the study was to determine if the increase in radiopacity provided by bismuth oxide is related to the color alteration of calcium silicate-based cement. Calcium silicate cement (CSC) was mixed with 0%, 15%, 20%, 30% and 50% of bismuth oxide (BO), determined by weight. Mineral trioxide aggregate (MTA) was the control group. The radiopacity test was performed according to ISO 6876/2001. The color was evaluated using the CIE system. The assessments were performed after 24 hours, 7 and 30 days of setting time, using a spectrophotometer to obtain the ΔE, Δa, Δb and ΔL values. The statistical analyses were performed using the Kruskal-Wallis/Dunn and ANOVA/Tukey tests (p<0.05). The cements in which bismuth oxide was added showed radiopacity corresponding to the ISO recommendations (>3 mm equivalent of Al). The MTA group was statistically similar to the CSC/30% BO group (p>0.05). In regard to color, the increase of bismuth oxide resulted in a decrease in the ΔE value of the calcium silicate cement. The CSC group presented statistically higher ΔE values than the CSC/50% BO group (p<0.05). The comparison between 24 hours and 7 days showed higher ΔE for the MTA group, with statistical differences for the CSC/15% BO and CSC/50% BO groups (p<0.05). After 30 days, CSC showed statistically higher ΔE values than CSC/30% BO and CSC/50% BO (p<0.05). In conclusion, the increase in radiopacity provided by bismuth oxide has no relation to the color alteration of calcium silicate-based cements.


Feasibility of an electronic stethoscope system for monitoring neonatal bowel sounds.
Bowel dysfunction remains a major problem in neonates. Traditional auscultation of bowel sounds as a diagnostic aid in neonatal gastrointestinal complications is limited by skill and inability to document and reassess. Consequently, we built a unique prototype to investigate the feasibility of an electronic monitoring system for continuous assessment of bowel sounds. We attained approval by the Institutional Review Boards for the investigational study to test our system. The system incorporated a prototype stethoscope head with a built-in microphone connected to a digital recorder. Recordings made over extended periods were evaluated for quality. We also considered the acoustic environment of the hospital, where the stethoscope was used. The stethoscope head was attached to the abdomen with a hydrogel patch designed especially for this purpose. We used the system to obtain recordings from eight healthy, full-term babies. A scoring system was used to determine loudness, clarity, and ease of recognition comparing it to the traditional stethoscope. The recording duration was initially two hours and was increased to a maximum of eight hours. Median duration of attachment was three hours (3.75, 2.68). Based on the scoring, the bowel sound recording was perceived to be as loud and clear in sound reproduction as a traditional stethoscope. We determined that room noise and other noises were significant forms of interference in the recordings, which at times prevented analysis. However, no sound quality drift was noted in the recordings and no patient discomfort was noted. Minimal erythema was observed over the fixation site which subsided within one hour. We demonstrated the long-term recording of infant bowel sounds. Our contributions included a prototype stethoscope head, which was affixed using a specially designed hydrogel adhesive patch. Such a recording can be reviewed and reassessed, which is new technology and an improvement over current practice. The use of this system should also, theoretically, reduce risk of infection. Based on our research we concluded that while automatic assessment of bowel sounds is feasible over an extended period, there will be times when analysis is not possible. One limitation is noise interference. Our larger goals include producing a meaningful vital sign to characterize bowel sounds that can be produced in real-time, as well as providing automatic control for patient feeding pumps.


Demography and Life Histories of Sympatric Patas Monkeys, Erythrocebus patas, and Vervets, Cercopithecus aethiops, in Laikipia, Kenya.
Mortality patterns are thought to be strong selective forces on life history traits, with high adult mortality and low immature mortality favoring early and rapid reproduction. Patas monkeys (Erythrocebus patas) have the highest potential rates of population increase for their body size of any haplorhine primate because they reproduce both earlier and more often. We report here 10 yr of comparative demographic data on a population of patas monkeys and a sympatric population of vervet monkeys (Cercopithecus aethiops), a closely related species differing in aspects of social system, ecology, and life history. The data reveal that 1) adult female patas monkeys have significantly higher mortality than adult female vervets; 2) infant mortality in patas monkeys is relatively low compared to the norm for mammals because it is not significantly different from that of adult female patas monkeys; and 3) infant mortality is significantly higher than adult female mortality in vervets. For both species, much of the mortality could be attributed to predation. An epidemic illness was also a major contributor to the mortality of adult female patas monkeys whereas chronic exposure to pathogens in a cold and damp microenvironment may have contributed to the mortality of infant vervets. Both populations experienced large fluctuations during the study period. Our results support the prediction from demographic models of life history evolution that high adult mortality relative to immature mortality selects for early maturation.


The cystic fibrosis delta F508 mutation in the French population.
French families (n = 129) with at least one cystic fibrosis (CF) affected child and 44 unrelated subjects from the general population were tested for the presence of the delta F508 mutation by the polymerase chain reaction. The delta F508/CF mutation ratio (CF: uncharacterised CF mutations) was tested in the CF families with and without meconium ileus. The association between delta F508 and CF mutations and restriction fragment length polymorphism haplotypes (XV2c and KM19) has been estimated; these data suggest that the CF chromosomes include a panel of independent and probably different mutations.


CLASP promotes microtubule rescue by recruiting tubulin dimers to the microtubule.
Spatial regulation of microtubule (MT) dynamics contributes to cell polarity and cell division. MT rescue, in which a MT stops shrinking and reinitiates growth, is the least understood aspect of MT dynamics. Cytoplasmic Linker Associated Proteins (CLASPs) are a conserved class of MT-associated proteins that contribute to MT stabilization and rescue in vivo. We show here that the Schizosaccharomyces pombe CLASP, Cls1p, is a homodimer that binds an alphabeta-tubulin heterodimer through conserved TOG-like domains. In vitro, CLASP increases MT rescue frequency, decreases MT catastrophe frequency, and moderately decreases MT disassembly rate. CLASP binds stably to the MT lattice, recruits tubulin, and locally promotes rescues. Mutations in the CLASP TOG domains demonstrate that tubulin binding is critical for its rescue activity. We propose a mechanism for rescue in which CLASP-tubulin dimer complexes bind along the MT lattice and reverse MT depolymerization with their bound tubulin dimer.


Transformative, interdisciplinary and intercultural learning for developing HEI students' sustainability-oriented competences: a case study.
The literature has produced relevant theoretical insights into pedagogical frameworks, tools and competences that would be best suited to teach sustainability at higher education (HE). This article contributes to such a discussion using a course on sustainability developed by us as a case study. Two research questions are tackled in this article: (1) How to empower students to address urban sustainability challenges through the inclusion of transformative, interdisciplinary and intercultural learning into the current HE system? (2) Which pedagogical tools can be used to develop students' sustainability-oriented competences? To address the research questions, the case study consists of two parts. First, by reflecting on the course design, this article aims to shed light on the benefits and challenges of transformative pedagogy and of an interdisciplinary and intercultural framework. Second, by analyzing students' learning diaries (N = 36) using thematic analysis, this article offers insights into some of the students' learning process, allowing us to assess the strengths and weaknesses of the course design as well as draw implications to improve and renew courses on sustainability in HE. The findings from the learning diaries indicate the students' thirst for formal knowledge on sustainability, which they connected to their professional development and yearning for action. The learning diaries also suggest students' increasing awareness of sustainability as a systemic and structural issue during the course, which aligns with the transformative learning framework used. Finally, this study emphasizes the need for structural support to meaningfully integrate sustainability in HE curricula and teaching practices.


Otomycosis: an experimental evaluation of six antimycotic agents.
One hundred-and eight-six fungi were isolated from one hundred-and-eighty cases clinically diagnosed as otomycosis. They comprise 59 species of 26 genera of moulds, and 2 genera of yeasts. This large variety of mould isolates provided ample material for in vitro experiments, to evaluate the anti-fungal activity of six antimycotic substances found in the preparations currently used for the treatment of otomycosis. The antifungal activity of clotrimazole and tolnaftate in vitro was evident. For over 94 per cent of the 59 fungus species tested, the MIC was less than 0.1 micrograms/ml, and for 6 per cent it was between 0.4 and 1 microgram/ml. Concerning the other 4 antimycotic substances (iodochlorhydroxyquin, fluonilid, natamycine and polymyxin B sulphate) the MIC ranged from greater than 100 micrograms/ml to 1 microgram/ml for the majority of tested fungi. The clinical observations were mostly in accordance with these findings.


Geriatric primary care: a European perspective, Part I.
Europe is considered the parent of geriatric medicine, which was first recognized as a specialty in the United Kingdom. For the benefit of U.S. primary care physicians, GERIATRICS Editor-in Chief Robert N. Butler, MD, convened a panel of leading European geriatricians in Lausanne, Switzerland, for a discussion of the successes and problems they are encountering in providing medical care to the aging world population. In this first installment, the panelists describe the healthcare services available to the elderly, particularly in the United Kingdom and Switzerland. A physician who is a regional adviser for the World Health Organization adds the perspective of other European nations.


Effects of polylactic acid microcapsules containing prostaglandin E2 on the survival rates of grade II coma galactosamine induced fulminant hepatic failure rats.
Prostaglandin E2 was successfully incorporated into low molecular weight polylactic acid microcapsules. The size distribution of the microcapsules ranges from 20 to 50 micron. The microcapsules released drug continuously up to three days in vitro. The galactosamine induced fulminant hepatic failure rats model was used. 36 hours after the injection of galactosamine, those rats in grade II coma were chosen and pairs were matched for comparable degree of coma. Then each of the pair was randomly selected as control or treated. Each rat in the treated group received an intraperitoneal injection of PGE2 microcapsules containing 0.55 mg of PGE2. The control received blank PLA microcapsules only. The survival rate of the treated group was 40% compared to 10% in the control group. There was a significant (P less than 0.05) increase in the survival rate in the treated group.


Factors affecting the level of kanamycin resistance in transformed sunflower cells.
A 230 base pair DNA segment containing the sequences 5' to the 700 to 750 nucleotide (nt) transcript 7' (ORF 3; RF Barker, KB Idler, DV Thompson, JD Kemp 1983 Plant Mol Biol 2: 335-350) of the octopine tumor inducing plasmid pTiA6 has been isolated. This region has (a) 180 base pairs of DNA upstream of the TATA box, (b) the start of RNA synthesis, and (c) the entire 5' untranslated region of the gene. We have fused this presumed promoter fragment to the neomycin phosphotransferase II (NPTII) gene from Tn5 in a plant expression cassette. After recombination into a tumor inducing plasmid delivery plasmid, this cassette confers selectable kanamycin resistance to transformed sunflower cells. Removal of the out-of-frame ATG in the 5' leader sequence of the NPTII gene by two different modifications increased both the levels of NPTII enzyme activity and the ID(50) for kanamycin in the tumor cells. The promoter region of the transcript 7 gene gives levels of kanamycin resistance equivalent to the nopaline synthase promoter and octopine synthase promoter when used in the same constructions and assayed in the same tissues.


Water in Rechargeable Multivalent-Ion Batteries: An Electrochemical Pandora's Box.
Multivalent-ion batteries built on water-based electrolytes represent energy storage at suitable price points, competitive performance, and enhanced safety. However, to comply with modern energy-density requirements, the battery must be reversible within an operating voltage window greater than 1.23 V or the electrochemical stability limits of free water. Taking advantage of its powerful solvation and catalytic activities, adding water to electrolyte preparations can unlock a wider gamut of liquid mixtures compared with strictly nonaqueous systems. However, a point-by-point sweep of all potential formulations is arduous and ineffective without some form of systematic rationalization. The present Review consolidates recent progress, pitfalls, limits, and insights critical to expediting aqueous electrolyte designs to boost multivalent-ion battery outputs.


US prevalence of upper gastrointestinal symptoms: a systematic literature review.
To quantify the prevalence of dyspeptic and gastroesophageal symptoms and peptic ulcer disease (PUD) in the United States and to identify factors affecting their prevalence. Systematic search of MEDLINE and Web of Science through November 2010. We identified studies of US patients and evaluated a general (not disease-specific) adult sample that reported the prevalence of 1 or more upper gastrointestinal (GI) outcomes of interest, including dyspeptic symptoms, gastroesophageal symptoms, dyspeptic and/or gastroesophageal symptoms, or PUD. Proportions of individuals in each study reporting each symptom were pooled to derive separate prevalence estimates. Qualitative synthesis of data depicting multivariate relationships between covariates and upper GI outcomes was undertaken. A total of 36 citations representing 24 studies were included: 9 studies reporting dyspeptic symptoms (n = 14,181), 14 reporting gastroesophageal symptoms (n = 58,701), 5 reporting dyspeptic and/or gastroesophageal symptoms (n = 103,175), and 7 reporting PUD prevalence (n = 269,299). The pooled prevalences of dyspeptic, gastroesophageal, and dyspeptic and/or gastroesophageal symptoms were 16.3% (95% confidence interval [CI] 9.1%-25.1%), 24.2% (95% CI 18.2%-30.5%), and 35.2% (95% CI 14.9%-58.9%). The pooled prevalence for studies asking for shorter-term PUD recall was 3.3% (95% CI 2.2%-4.6%), with lifetime PUD prevalence estimated at 13.8% (95% CI 10.7%-17.0%). The influence of covariates evaluated as part of multivariate analyses was often inconsistent. It appears that upper GI symptoms and disorders are common in US inhabitants. We identified patient- and study-level factors that should be considered when assessing upper GI symptom prevalence and conducting future research.


Autism spectrum disorder and paediatric dentistry: A narrative overview of intervention strategy and introduction of an innovative technological intervention method.
When treating patients with Autism Spectrum Disorder (ASD) the doctor-patient relationship can be very challenging. The dentist is often forced to work under general anaesthesia or conscious sedation. Children with ASD are patients with an increased risk of caries due to poor oral hygiene, a cariogenic diet and the use of xerostomal drugs. In this work therapeutic strategies used to treat this kind of patients are evaluated and a new method to treat children with ASD is presented in order to increase awareness about this condition in the dental field. The Atlas Center (a non-profit organisation in Peurgia, Italy) has developed a software, called paINTeraction, that allows these special children to immerse themselves in a virtual reality with the help of an operator. Through this system the child can explore the dental office (and all its sounds and noises) before the real dental visit, thus connecting to the dental professional, achieving greater compliance and reducing anxiety. paINTeraction, with the use of digital technology tools, may be particularly well suited to introduce patients to the therapeutic environment, particularly in the dental setting.


Cannabinoid receptor-inactive N-acylethanolamines and other fatty acid amides: metabolism and function.
Although it is now generally accepted that long-chain N-acylethanolamines and their precursors, N-acylethanolamine phospholipids, exist as trace constituents in virtually all vertebrate cells and tissues, their possible biological functions are just emerging. While anandamide (N-arachidonoylethanolamine) has received much attention due to its ability to bind to and activate cannabinoid receptors, the saturated and monounsaturated N-acylethanolamines, which usually represent the vast majority, are cannabinoid receptor-inactive but appear to interact with endocannabinoids and to have other signaling functions as well. Also, primary fatty acid amides, including the amide of oleic acid, which acts as a sleep-inducing agent, do not interact with cannabinoid receptors but are catabolically related to endocannabinoids. Here we review published information on the occurrence, metabolism, and possible signaling functions of the cannabinoid receptor-inactive N-acylethanolamines and primary fatty acid amides.


Diagnosis and treatment of sleep disordered breathing in hospitalized cardiac patients: a reduction in 30-day hospital readmission rates.
Sleep disordered breathing (SDB) is associated with significant cardiovascular sequelae and positive airway pressure (PAP) has been shown to improve heart failure and prevent the recurrence of atrial fibrillation in cardiac patients with sleep apnea. Patients who are hospitalized with cardiac conditions frequently have witnessed symptoms of SDB but often do not have a diagnosis of sleep apnea. We implemented a clinical paradigm to perform unattended sleep studies and initiate treatment with PAP in hospitalized cardiac patients with symptoms consistent with SDB. We hypothesized that PAP adherence in cardiac patients with SDB would reduce readmission rates 30 days after discharge. 106 consecutive cardiac patients hospitalized for heart failure, arrhythmias, and myocardial infarction and who reported symptoms of SDB were evaluated. Patients underwent a type III portable sleep study and those patients diagnosed with sleep apnea were started on PAP. Demographic data, SDB type, PAP adherence, and data regarding 30-day hospital readmission/ED visits were collected. Of 106 patients, 104 had conclusive diagnostic studies using portable monitoring systems. Seventy-eight percent of patients (81/104) had SDB (AHI ≥ 5 events/h). Eighty percent (65/81) had predominantly obstructive sleep apnea, and 20% (16/81) had predominantly central sleep apnea. None of 19 patients (0%) with adequate PAP adherence, 6 of 20 (30%) with partial PAP use, and 5 of 17 (29%) of patients who did not use PAP were readmitted to the hospital or visited the emergency department (ED) for a cardiac issue within 30 days from discharge (p = 0.025). Performing diagnostic unattended sleep studies and initiating PAP treatment in hospitalized cardiac patients was feasible and provided important clinical information. Our data indicate that hospital readmission and ED visits 30 days after discharge were significantly lower in patients with cardiac disease and SDB who adhered to PAP treatment than those who were not adherent. A commentary on this article appears in this issue on page 1067.


Meiotic behavior as a selection tool in silage corn breeding.
In breeding programs, commercial hybrids are frequently used as a source of inbred lines to obtain new hybrids. Considering that maize production is dependent on viable gametes, the selection of populations to obtain inbred lines with high meiotic stability could contribute to the formation of new silage corn hybrids adapted to specific region. We evaluated the meiotic stability of five commercial hybrids of silage corn used in southern Brazil with conventional squashing methods. All of them showed meiotic abnormalities. Some abnormalities, such as abnormal chromosome segregation and absence of cytokinesis, occurred in all the genotypes, while others, including cytomixis and abnormal spindle orientation, were found only in some genotypes. The hybrid SG6010 had the lowest mean frequency of abnormal cells (21.27%); the highest frequency was found in the hybrid P30K64 (44.43%). However, the frequency of abnormal meiotic products was much lower in most genotypes, ranging from 7.63% in the hybrid CD304 to 43.86% in Garra. Taking into account the percentage of abnormal meiotic products and, hence, meiotic stability, only the hybrids CD304, P30K64, SG6010, and P30F53 are recommended to be retained in the breeding program to obtain inbred lines to create new hybrids.


Endoscopic Ultrasound-Guided Biliary Drainage Using a Fully Covered Metallic Stent after Failed Endoscopic Retrograde Cholangiopancreatography.
Background and Study Aims. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) is an alternative treatment for biliary obstruction after failed endoscopic retrograde cholangiopancreatography (ERCP). In this study, we present the outcomes of inpatients with obstructive jaundice treated with EUS-BD using a fully covered metallic stent after failed ERCP. Patients and Methods. A total of 21 patients with biliary obstruction due to malignant tumors and prior unsuccessful ERCP underwent EUS via an intra- or extrahepatic approach with fully covered metallic stent between March 2014 and October 2015. A single endoscopist performed all procedures. Results. Seven patients underwent hepatogastrostomy (HGS) and 14 underwent choledochoduodenostomy (CDS). The technical and clinical success rates were both 100%. There was no difference in efficacy between HGS and CDS. Adverse events occurred in three patients, including two in the HGS group (1 bile leakage and 1 sepsis) and one in the CDS group (sepsis). Four patients died as a result of their primary tumors during a median follow-up period of 13 months (range: 3-21 months). No patient presented with stent migration. Conclusion. EUS-BD using a fully covered metallic stent appears to be a safe and effective method for the treatment of obstructive jaundice.


Five-year retrospective review of the extended SMAS: critical landmarks and technical refinements.
The beneficial effects of SMAS flap manipulation have been clearly demonstrated for the neck and jowls; however, safe limits of subplatysmal dissection in the neck have not been established, and recommendations vary widely. Sixty patients undergoing rhytidectomy with an extended SMAS flap were retrospectively reviewed over a 5-year period. Five critical landmarks for extended SMAS flap dissection were marked preoperatively and confirmed intraoperatively. Skin flaps were mobilized and redraped independently. All patients were available for follow-up at an average of 8.3 months postoperatively (range 5-23 months). There were no clinically apparent facial or great auricular nerve injuries or pixy-ear deformities. Wound complication rates were acceptably low and included hematoma (3%), retroauricular epidermolysis (5%), and temporal scalp alopecia (1.6%). Extended SMAS flap dissection allows safe, predictable, and durable correction of the neck and jowls. The degree of mobilization proposed in this study allows anchoring points of the SMAS flap to be removed from potentially visible and palpable areas on the face to the temporal fascia superiorly and the mastoid fascia posteriorly. The study also represents a departure from more conventional facelifting techniques that advocate dissection of a mesomandibularis.


Prospective Studies on the Risk of Rheumatoid Arthritis: The European Risk RA Registry.
The accumulation of risk for the development of rheumatoid arthritis (RA) is regarded as a continuum that may start with interacting environmental and genetic factors, proceed with the initiation of autoimmunity, and result in the formation of autoantibodies such as anti-citrullinated peptide antibodies (ACPA). In parallel, at-risk individuals may be asymptomatic or experience joint pain (arthralgia) that is itself non-specific or clinically suspicious for evolving RA, even in the absence of overt arthritis. Optimal strategies for the management of people at-risk of RA, both for symptom control and to delay or prevent progression to classifiable disease, remain poorly understood. To help address this, groups of stakeholders from academia, clinical rheumatology, industry and patient research partners have collaborated to advance understanding, define and study different phases of the at-risk state. In this current report we describe different European initiatives in the field and the successful effort to build a European Registry of at-risk people to facilitate observational and interventional research. We outline similarities and differences between cohorts of at-risk individuals at institutions spanning several countries, and how to best combine them within the new database. Over the past 2 years, besides building the technical infrastructure, we have agreed on a core set of variables that all partners should strive to collect for harmonization purposes. We emphasize to address this process from different angles and touch on the biologic, epidemiologic, analytic, and regulatory aspects of collaborative studies within a meta-database of people at-risk of RA.


Visible-light-induced cascade dearomatization cyclization between alkynes and indole-derived bromides: a facile strategy to synthesize spiroindolenines.
A visible-light-initiated intermolecular dearomatization cyclization cascade reaction between alkynes and indole-derived bromides has been explored. This transformation exhibits a wide substrate scope and significant functional group tolerance, providing an efficient way to access a variety of spiroindolenines under mild conditions.


Relationship between epoetin alfa dose and mortality: findings from a marginal structural model.
Observational studies relating epoetin alfa (EPO) dose and mortality frequently use analytic methods that do not control time-dependent confounding by indication (CBI). The relationship between EPO dose and 1-year mortality, adjusting for the effects of time-dependent CBI, was examined using a marginal structural model. This retrospective cohort study included 27,791 hemodialysis patients between July 2000 and June 2002. Patients were grouped at successive 2-wk intervals into a zero-dose category or four nonzero-dose categories. Ordinal regression was used to calculate inverse probability of treatment weights of patients receiving their own dose level given their covariate and treatment history. Three treatment models with an increasing number of treatment predictors were evaluated to assess the effect of model specification. A small number of excessively large patient weights were truncated. Relative hazards for higher-dose groups compared with the lowest nonzero-dose group varied by treatment model specification and by level of weight truncation. Results differed appreciably between the simplest treatment model, which incorporated only hemoglobin and EPO dosing history with 2% weight truncation (hazard ratio: 1.51; 95% confidence interval: 1.09, 1.89 for highest-dose patients), and the most comprehensive treatment model with 1% weight truncation (hazard ratio: 0.98; 95% confidence interval: 0.76, 1.74). There is appreciable CBI at higher EPO doses, and EPO dose was not associated with increased mortality in marginal structural model analyses that more completely addressed this confounding.


Hyaluronidase-2 overexpression accelerates intracerebral but not subcutaneous tumor formation of murine astrocytoma cells.
Gliomas are highly invasive, invariably fatal intracerebral tumors. It seems that receptors for hyaluronan are required for the invasive process. Hyaluronan is a major component of the extracellular matrix in the brain, and all of the gliomas express CD44, the principal receptor for hyaluronan. To investigate the role of lysosomal hyaluronidases on tumor invasion we overexpressed hyaluronidase-2 (HYAL2) in murine astrocytoma cells. We found that high expression of HYAL2 accelerated intracerebral tumor growth dramatically, whereas the same cells formed s.c. tumors within the same time as the parental cells. The brain tumors were highly vascularized and more invasive than the control tumors. It seems that the interactions of the HYAL2-expressing tumor cells with the hyaluronan-containing extracellular matrix in the brain mediate these effects, whereas the same cells in a s.c. environment, which lacks the high hyaluronan level, behave like the parental cells.


Factor H and factor H-related protein 1 bind to human neutrophils via complement receptor 3, mediate attachment to Candida albicans, and enhance neutrophil antimicrobial activity.
The host complement system plays an important role in protection against infections. Several human-pathogenic microbes were shown to acquire host complement regulators, such as factor H (CFH), that downregulate complement activation at the microbial surface and protect the pathogens from the opsonic and lytic effects of complement. Because CFH can also bind to host cells, we addressed the role of CFH and CFH-related proteins as adhesion ligands in host-pathogen interactions. We show that the CFH family proteins CFH, CFH-like protein 1 (CFHL1), CFH-related protein (CFHR) 1, and CFHR4 long isoform bind to human neutrophil granulocytes and to the opportunistic human-pathogenic yeast Candida albicans. Two major binding sites, one within the N-terminus and one in the C-terminus of CFH, were found to mediate binding to neutrophils. Complement receptor 3 (CD11b/CD18; alpha(M)beta2 integrin) was identified as the major cellular receptor on neutrophils for CFH, CFHL1, and CFHR1, but not for CFHR4 long isoform. CFH and CFHR1 supported cell migration. Furthermore, CFH, CFHL1, and CFHR1 increased attachment of neutrophils to C. albicans. Adhesion of neutrophils to plasma-opsonized yeasts was reduced when CFH binding was inhibited by specific Abs or when using CFH-depleted plasma. Yeast-bound CFH and CFHR1 enhanced the generation of reactive oxygen species and the release of the antimicrobial protein lactoferrin by human neutrophils, and resulted in a more efficient killing of the pathogen. Thus, CFH and CFHR1, when bound on the surface of C. albicans, enhance antimicrobial activity of human neutrophils.


[Activity of selected antioxidant enzymes examination in people with colorectal cancer].
Colorectal cancer is a serious medical problem. According to one hypothesis of carcinogenesis, tumour creation process begins and develops when the balance between the production of reactive oxygen species (ROS) and their disactivation by the antioxidant protective barrier of the organism is disturbed. THE AIM OF THE STUDY was, following this theory, to examine the plasma concentration of the dietary minerals with antioxidant properties. The research material was the blood of 8 people, taken to vacuum test tubes with an anticoagulant - 4 ml of sodium heparin. The activity of catalase was marked following Beers method, while the activity of superoxide dismutase according to H.P. Misra and J. Fridovich method. The results show that the copper complex added, i.e. dichlorine(3,4,5-trimethyl-N1 - pyrazol-1yl) Cu(II) from derivatives of azoles, has a large impact on the activity of selected enzymes. After adding it, their activity increased by ca 67% in comparison with the control group. It proves the efficacy of this compound. The results prove the free radicals theory of carcinogenesis. They also confirm the part which the antioxidant protective barrier plays in the defense against ROS and their carcinogenic consequences.


Short-term lab assessments and microcolonies are insufficient for the risk assessment of insecticides for bees.
Risk assessment studies addressing effects of agrochemicals on bumblebees frequently use microcolonies. These are queenless colonies consisting of workers only in which typically one worker will lay unfertilized male-destined eggs. In the first tier of risk assessment for bees, short-term laboratory experiments (e.g. microcolonies) are used, the results of which will determine whether higher tier (semi-)field experiments are needed. To evaluate the suitability of microcolonies for risk assessment, a direct comparison between different assessment methods for the neonicotinoid pesticides acetamiprid and thiacloprid was made: microcolonies and queenright colonies under short-term laboratory conditions, queenright colonies under long-term laboratory conditions, and queenright colonies under field conditions. Here, we demonstrate that results from microcolonies contradict results from queenright colonies. While thiacloprid negatively impacted gyne production in queenright colonies, it had a positive effect on microcolony size. By contrast, thiacloprid had no significant effect on fitness parameters of queenright colonies under short-term laboratory conditions when mostly workers are produced. These results thus highlight both the need for long term assessments, allowing evaluation of gyne production, and the risk of reaching erroneous conclusions when using microcolonies. The negative effect of thiacloprid on colony fitness was confirmed under field conditions, where thiacloprid affected the production of reproductives, colony weight gain, worker weight, and foraging behaviour. For acetamiprid, a negative trend on colony fitness could only be shown in a field setup. Therefore, field-realistic setups, which allow colonies to forage freely, are most appropriate to assess sublethal effects of pesticides affecting behaviour and learning.


Chemical ecology of animal and human pathogen vectors in a changing global climate.
Infectious diseases affecting livestock and human health that involve vector-borne pathogens are a global problem, unrestricted by borders or boundaries, which may be exacerbated by changing global climate. Thus, the availability of effective tools for control of pathogen vectors is of the utmost importance. The aim of this article is to review, selectively, current knowledge of the chemical ecology of pathogen vectors that affect livestock and human health in the developed and developing world, based on key note lectures presented in a symposium on "The Chemical Ecology of Disease Vectors" at the 25th Annual ISCE meeting in Neuchatel, Switzerland. The focus is on the deployment of semiochemicals for monitoring and control strategies, and discusses briefly future directions that such research should proceed along, bearing in mind the environmental challenges associated with climate change that we will face during the 21st century.


Cucurbit[7]uril host-guest complexes of cholines and phosphonium cholines in aqueous solution.
The neutral host cucurbit[7]uril forms very stable complexes with a series of cationic cholines (R(3)NCH(2)CH(2)OR'(+)) and their phosphonium analogues (R(3)PCH(2)CH(2)OR'(+)) (R(3) = Me(3), Et(3), or Me(2)Bz, or R(3)N = quinuclidinium, and R' = H, COCH(3), CO(CH(2))(2)CH(3), or PO(3)H), and (+/-)-carnitine, in aqueous solution. The complexation behaviour has been investigated using (1)H and (31)P NMR spectroscopies, and ESI mass spectrometry. The complexation-induced chemical shift changes of the guests clearly indicate the effects of replacing the N(CH(3))(3)(+) end group by P(CH(3))(3)(+), and changing the nature of R on the position of the guest with respect to the CB[7] cavity and its polar portal-lining carbonyl groups. This study demonstrates that molecular recognition of cholines in aqueous solution is achievable with a neutral host without the need for aromatic walls for cation-pi interactions.


DNA Damage Clustering after Ionizing Radiation and Consequences in the Processing of Chromatin Breaks.
Charged-particle radiotherapy (CPRT) utilizing low and high linear energy transfer (low-/high-LET) ionizing radiation (IR) is a promising cancer treatment modality having unique physical energy deposition properties. CPRT enables focused delivery of a desired dose to the tumor, thus achieving a better tumor control and reduced normal tissue toxicity. It increases the overall radiation tolerance and the chances of survival for the patient. Further improvements in CPRT are expected from a better understanding of the mechanisms governing the biological effects of IR and their dependence on LET. There is increasing evidence that high-LET IR induces more complex and even clustered DNA double-strand breaks (DSBs) that are extremely consequential to cellular homeostasis, and which represent a considerable threat to genomic integrity. However, from the perspective of cancer management, the same DSB characteristics underpin the expected therapeutic benefit and are central to the rationale guiding current efforts for increased implementation of heavy ions (HI) in radiotherapy. Here, we review the specific cellular DNA damage responses (DDR) elicited by high-LET IR and compare them to those of low-LET IR. We emphasize differences in the forms of DSBs induced and their impact on DDR. Moreover, we analyze how the distinct initial forms of DSBs modulate the interplay between DSB repair pathways through the activation of DNA end resection. We postulate that at complex DSBs and DSB clusters, increased DNA end resection orchestrates an increased engagement of resection-dependent repair pathways. Furthermore, we summarize evidence that after exposure to high-LET IR, error-prone processes outcompete high fidelity homologous recombination (HR) through mechanisms that remain to be elucidated. Finally, we review the high-LET dependence of specific DDR-related post-translational modifications and the induction of apoptosis in cancer cells. We believe that in-depth characterization of the biological effects that are specific to high-LET IR will help to establish predictive and prognostic signatures for use in future individualized therapeutic strategies, and will enhance the prospects for the development of effective countermeasures for improved radiation protection during space travel.


Second cancers after testicular cancer diagnosed after 1980 in Sweden.
Testicular cancer treatment has become standardized in the 1980s involving radiotherapy preferentially for seminoma and chemotherapy for nonseminoma. The late effects of these therapeutic practices have not been properly evaluated because of the relatively short time since their application. We conducted a study among 5533 survivors of testicular cancer on the basis of Swedish Family-Cancer Database for which the cancer data were retrieved from the nationwide Cancer Registry. Standardized incidence ratios (SIRs) of second cancer were calculated by comparing with the rates of the first cancers. The follow-up was started in 1980 and carried on through 2006. A total of 370 second cancers (6.7% of all patients) were recorded, more in seminoma than in nonseminoma patients. Second testicular cancer showed an SIR of 29 after seminoma and an SIR of 13 after nonseminoma. A total of 10 discordant sites were increased after seminoma compared with seven sites after nonseminoma. Gastrointestinal tract cancers occurred mainly after seminoma and bladder cancers (SIR 8.6 when diagnosis before age 30) occurred after nonseminoma. Of the selective affected second tumors, it will be important to confirm the association of bladder cancer with nonseminoma treatment.


Autopsy case of MV2K-type sporadic Creutzfeldt-Jakob disease with spongiform changes of the cerebral cortex.
Comprehensive analysis is required for the accurate diagnosis of MV2-type sporadic Creutzfeldt-Jakob disease (sCJD) because it shows a wide clinicopathological spectrum. Here, we describe the clinical findings and neuropathologic observations of an autopsy-confirmed MV2K-type sCJD case with extensive spongiform changes of the cerebral cortex. In the early disease stages, the patient exhibited gait disturbance with ataxia and gradually showed cognitive dysfunction. Diffusion-weighted magnetic resonance images revealed hyperintense regions in the cerebral cortex, basal ganglia, and particularly in the thalamus. Prion protein (PrP) gene analysis revealed no mutations, and polymorphic codon 129 exhibited methionine and valine heterozygosity. During the course of the disease, a startle reaction was observed, whereas myoclonus was not observed. Electroencephalography showed no periodic sharp wave complexes. The patient died at age 61 years with 13 months total disease duration and did not reach the akinetic mutism state. Pathologic investigation revealed extensive fine vacuole-type spongiform change in the cerebral cortex, and the appearance of vacuolation tended to be more pronounced in the deeper layers. Numerous kuru plaques were observed in the cerebellum. PrP immunostaining revealed extensive diffuse synaptic-type PrP deposition in the cerebral cortex, and the finding was prominent in the deeper layer with perineuronal-type PrP deposition. In the limbic system, basal ganglia, and thalamus, mixed small plaque-type PrP with synaptic-type PrP deposition was observed. In the cerebellar cortex, diffuse synaptic-type PrP depositions were observed with numerous strongly immunopositive plaques. Western blot analysis of examined brain samples revealed mixed type 2 PrPSc (scrapie type) and intermediate-type PrPSc .


Characterization and molecular cloning of a putative binding protein for heparin-binding growth factors.
A novel Mr 17,000 heparin-binding protein was purified from culture medium conditioned by A431 human epidermoid carcinoma cells. This protein, designated HBp17, was found to bind the heparin-binding peptide growth factors HBGF-1 and HBGF-2 in a noncovalent, reversible manner. In addition HBp17 was found to inhibit the biological activities of both HBGF-1 and HBGF-2. Both the binding and inactivation of HBGF-1 and HBGF-2 by HBp17 were abolished by heparin. Full-length 1163-base pair HBp17 cDNA was cloned and sequenced by using the polymerase chain reaction technique. The deduced primary structure of HBp17 consisted of 234 amino acids including each of five partial peptide sequences obtained from proteolytic fragments of purified HBp17. The encoded protein included a 33-residue N-terminal signal sequence for secretion and a single potential N-linked glycosylation site. No homology with any known protein was found for the deduced primary structure of HBp17. The expression of HBp17 mRNA was found to occur preferentially in normal human keratinocytes and in squamous cell carcinomas. This pattern of HBp17 gene expression suggests that this binding protein for HBGFs 1 and 2 has a physiological role in squamous epithelia.


There is no item vs. I wish there were an item: Implicit negation causes false recall just as well as explicit negation.
When talking about absence, we may express it in a negative statement (using explicit negation e.g. I was not) or in a positive statement (using implicit negation e.g. I wished I were). Previous research has shown that explicitly negated statements may cause false recall-negated items may paradoxically be remembered as present. The current study compares false recall caused by implicit and explicit negation. Participants listened to a recording in which some objects were mentioned as present, some as absent, and some not mentioned at all. The absence of objects was expressed using explicit or implicit negation. Participants' recall of the recording was measured either five minutes or one week after exposure to the recording. Results indicate that implicit and explicit negation lead to a nearly identical false recall of negated items. However, items not mentioned in the recording (i.e. neither mentioned nor negated) were more often recognized as present by participants exposed to implicit, rather than explicit negation. We postulate that false recall of negated items could be explained by participants remembering the item itself, but forgetting the context in which it was present (an affirmative or a negative statement), hence objects would be recalled as present just because they were spoken of.


An event-related potential investigation of spatial attention orientation in children trained with mental abacus calculation.
The objective of this study was to investigate the effects of long-term mental abacus calculation training (MACT) on children's spatial attention orientation. Fifteen children with intensive MACT (MACT group) and 15 children without MACT (non-MACT group) were selected. The two groups of children were matched in age, sex, handedness, and academic grade. The participants were tested with a Posner spatial cueing task while their neural activities were recorded with a 32-channel electroencephalogram system. The participants' behavior scores (reaction time and accuracy) as well as early components of event-related potential (ERP) during the tests were statistically analyzed. The behavioral scores showed no significant difference between the two groups of children, although the MACT group tended to have a shorter reaction time. The early ERP components showed that under valid cueing condition, the MACT group had significantly higher P1 amplitude [F(1, 28)=5.06, P<0.05, effective size=0.72] and lower N1 amplitude [F(1, 28)=6.05, P<0.05, effective size=0.82] in the occipital region compared with the non-MACT group. In the centrofrontal brain region, the MACT group had lower N1 amplitude [F(1, 28)=4.89, P<0.05, effect size=0.70] and longer N1 latency [F(1, 28)=6.26, P<0.05, effect size=0.80] than the non-MACT group. In particular, the MACT group also showed a higher centrofrontal P2 amplitude in the right hemisphere [F(1, 28)=4.82, P<0.05, effect size 0.81] compared with the left hemisphere and the middle location. MACT enhances the children's spatial attention orientation, which can be detected in the early components of ERP.


Monocytic Myeloid-Derived Suppressor Cells Inhibit Myofibroblastic Differentiation in Mesenchymal Stem Cells Through IL-15 Secretion.
Background: Accumulating evidence indicates that mesenchymal stem cells (MSCs) are precursors of myofibroblasts, which play a vital role in renal fibrosis. The close interaction between MSCs and other immune cells regulates the development of multiple fibrosis-related diseases. However, the effect of myeloid-derived suppressor cells (MDSCs) on MSCs remains unexplored. Here, we investigated the effect of MDSCs on the myofibroblastic differentiation of MSCs. Methods: MSCs were induced to undergo myofibroblastic differentiation with transforming growth factor beta 1 (TGF-β1). M-MDSCs and G-MDSCs were sorted by flow cytometry. Supernatants derived from MDSCs were administered to cultured bone marrow MSCs (BM-MSCs) undergoing TGF-β1-induced myofibroblastic differentiation. Myofibroblastic differentiation was evaluated by immunostaining. The expression of fibrosis-related genes was determined by quantitative PCR and western blot analysis. In vitro, M-MDSC supernatant or M-MDSC supernatant with interleukin (IL)-15 mAbs was administered following unilateral renal ischemia-reperfusion injury (IRI) to observe the myofibroblast differentiation of renal resident MSCs (RRMSCs) in a murine model. Results: Myofibroblastic differentiation of MSCs was hindered when the cells were treated with MDSC-derived supernatants, especially that from M-MDSCs. The inhibitory effect of M-MDSC supernatant on the myofibroblastic differentiation of MSCs was partially mediated by IL-15-Ras-Erk1/2-Smad2/3 signaling. Treatment with M-MDSC supernatant ameliorated renal fibrosis and myofibroblastic differentiation in RRMSCs through IL-15. Additionally, M-MDSC supernatant increased M-MDSC infiltration in the kidney in a mouse IRI model. M-MDSC supernatant downregulated the adhesion and migration marker CD44 on the cell membrane of MSCs via IL-15. Conclusion: M-MDSC-derived supernatant inhibited the TGF-β1-induced myofibroblastic differentiation of MSCs through IL-15. Our findings shed new light on the effect of MDSCs on myofibroblastic differentiation and adhesion of MSCs, which might provide a new perspective in the development of treatment strategies for renal fibrosis.


"Biologic width"and crestal bone remodeling with sintered porous-surfaced dental implants: a study in dogs.
The aim of this study was to obtain histometric measurements of bone and peri-implant mucosal tissue contact with implants of 2 sintered porous-surfaced designs. The "short-collar" design had a collar height (smooth coronal region) of 0.75 mm, while the "long-collar" model had a smooth coronal region of 1.8 mm. Implants (2 per side) were placed in healed mandibular extraction sites of 4 beagle dogs using a submerged technique. After 4 weeks of healing, they were uncovered and used to support fixed partial dentures for a 9-month period. After sacrifice, specimens were retrieved and nondemineralized sections were examined histometrically to determine the most coronal bone-to-implant contact (first BIC) using the microgap as a reference and standard mucosal parameters of "biologic width." Significant (P = .001) differences in first BIC were found between designs (1.97 mm for long-collar versus 1.16 mm for short-collar implants) for posteriorly located implants but not for anteriorly located ones (1.21 mm versus 1.38 mm; P = .40). If crestal bone loss involved sintered surface, fibrous connective tissue ingrowth was observed to replace lost bone. No significant differences in peri-implant mucosal measurements (total peri-implant mucosal thickness; length of the epithelial component of this mucosa, and thickness of the connective tissue component) were detected between implant designs. Results suggest that "biologic width" accommodation drives initial crestal bone loss with sintered porous-surfaced implants. Histometric data obtained for bone contact showed no significant differences between the long- and short-collar implant designs.


Difference between ultramicroelectrodes and microelectrodes: influence of natural convection.
Natural convection in macroscopically immobile solutions may still alter electrochemical experiments performed with electrodes of micrometric dimensions. A model accounting for the influence of natural convection allowed delineating conditions under which it interferes with mass transport. Several electrochemical behaviors may be observed according to the time scale of the experiment, electrode dimensions, and intensity of natural convection. The range of parameters in which ultramicroelectrodes behave under a true diffusional steady state was identified. Mapping of concentration profiles was performed experimentally by scanning electrochemical microscopy in the vicinity of microelectrodes of various radii. The results validated remarkably the predictions of the model, evidencing in particular the alteration of the diffusional steady state by natural convection.


Characterizing Thermal Mixing Dynamic Nuclear Polarization via Cross-Talk between Spin Reservoirs.
Dynamic nuclear polarization (DNP) embraces a family of methods to increase signal intensities in nuclear magnetic resonance (NMR) spectroscopy. Despite extensive theoretical work that allows one to distinguish at least five distinct mechanisms, it remains challenging to determine the relative weights of the processes that are responsible for DNP in state-of-the-art experiments operating with stable organic radicals like nitroxides at high magnetic fields and low temperatures. Specifically, determining experimental conditions where DNP involves thermal mixing, which denotes a spontaneous heat exchange between different spin reservoirs, remains challenging. We propose an experimental approach to ascertain the prevalence of the thermal mixing regime by monitoring characteristic signature properties of the time evolution of the hyperpolarization. We find that thermal mixing is the dominant DNP mechanism at high nitroxide radical concentrations, while a mixture of different mechanisms prevails at lower concentrations.


Pharmacokinetics of nebivolol in the rat: low oral absorption, loss in the gut and systemic stereoselectivity.
Nebivolol is a third-generation β1-adrenoceptor blocker with β3 agonistic properties (AR). It has a low oral bioavailability that is speculated to be due to its hepatic first-pass metabolism. Inflammation is known to suppress the clearance of drugs with efficient hepatic metabolism. However, inflammation does not influence nebivolol clearance. Therefore, we looked into the mechanism involved in the drug's low bioavailability and stereoselectivity. Single 1 mg/kg i.v. or intraperitoneal (i.p.) or 2 mg/kg oral doses were administered to male Sprague-Dawley rats and the plasma nebivolol concentration was measured using chiral and achiral assays. The passage of nebivolol enantiomers through the gut was also measured using everted rat sacs. The serum protein binding of the enantiomers was studied in vitro using the ultrafiltration method. Plasma nebivolol concentrations were significantly lower after p.o., but not after i.p., compared with i.v. doses suggesting the gut as the site of pre-systemic loss. Approximately 50% of the enantiomers were lost during 90 min incubation in the presence of gut. Only 0.1% of the added drug crossed the gut wall with no evidence of stereoselectivity. Thus stereoselectivity in the pharmacokinetics of nebivolol (+ > -) is likely at the level of plasma protein binding. The low nebivolol bioavailability is due to its loss in the gut as well as its limited permeability through the intestinal wall.