[The development of a latex antigenic diagnostic agent for the serological determination of tuberculous infection].
Using two tuberculoproteins, phosphatide and polysaccharide antigens obtained from culture filtrate of pathogenic and vaccinal strains of Mycobacterium of human and bull types and standard monodispersed particles of latex modified by different chemical groups, the technology of creation of latex antigenic preparations for serologic express diagnosis of tuberculosis was elaborated. This method is based on the reaction of latex agglutination. Latex diagnostic preparation possesses sufficiently high serologic activity and specificity. The spectrum of microbacterial antigens allows one to characterize the status of immunity of patients with different forms of tuberculosis and to determine the degree of the process activity.


Cis-acting elements essential for light regulation of the nuclear gene encoding the A subunit of chloroplast glyceraldehyde 3-phosphate dehydrogenase in Arabidopsis thaliana.
We report the characterization of cis-acting elements involved in light regulation of the nuclear gene (GapA) that encodes the A subunit of glyceraldehyde 3-phosphate dehydrogenase in Arabidopsis thaliana. Our previous deletion analyses indicate that the -277 to -195 upstream region of GapA is essential for light induction of the beta-glucuronidase reporter gene in transgenic tobacco (Nicotiana tabacum) plants. This region contains three direct repeats with the consensus sequence 5'-CAAATGAA(A/G)A-3' (Gap boxes). Our results show that 2-bp substitutions of the last four nucleotides (AA or GA) of the Gap boxes by CC abolish light induction of the beta-glucuronidase reporter gene in vivo and affect binding of the Gap box binding factor in vitro. We have also identified an additional cis-acting element, AE (Activation Element) box, that is involved in regulation of GapA. A combination of a Gap box trimer and an AE box dimer can confer light responsiveness of the cauliflower mosaic virus 35S promoter containing the -92 to +6 upstream sequence, whereas oligomers of Gap boxes or AE boxes alone cannot confer light responsiveness on the same promoter. These results suggest that Gap boxes and AE boxes function together as the light-responsive element of GapA.


A gap between policy and practice: a case study on maternal mortality reports, kerman, iran.
Maternal mortality, a preventable tragedy, is an indicator of development, poverty and democracy. Therefore, prevention of maternal deaths is one of the main goals in many countries. Iran is one of the developing countries which aim to reduce maternal mortality through introduction of a new policy at national level. This study aimed to explore the extent to which this policy is practiced at peripheral levels. The data were collected through interviews with relevant people, observation, and review of the documents. The results showed that there is a gap between policy and practice which can be explained by inadequate training programs, inadequate collaboration, lack of guidelines and instigation of a specific investigation into maternal deaths. This study suggests a number of considerations such as an initiative to collaborate, developing a guideline and presenting training programs before such policies are launched.


Iodinated radiographic contrast media: comparison of low-osmolar with conventional ionic agents [corrected].
A large number of reports on radiographic contrast media have appeared over the past year. The majority of these compared various properties of the new, nonionic low-osmolar agents with those of conventional ionic contrast media, including types and rates of adverse reactions, nephrotoxicity, anticoagulant effects, degree of subcutaneous injury resulting from extravasation, and gastrointestinal tolerance. In this review, recent developments in each of these areas are discussed. Although, in general, the newer agents are safer and better tolerated than ionic contrast media, their greatly increased cost prevents them from completely replacing these media. In this time of increasingly cost-conscious health care, even expert opinion concerning indications for nonionic low-osmolar contrast media use (also summarized here) is widely divided.


Pneumococcal Vaccination and Pneumonia Associated With Pleural Effusion in a Pediatric Population.
The aim was to assess the effect of the nonsystematic pneumococcal conjugate vaccine (PCV) on incidence of pneumonia associated with parapneumonic pleural effusion (PPE) in vaccinated and unvaccinated children. Cases were patients <15 years of age who had been diagnosed with pneumonia associated with PPE in a tertiary hospital in Navarra (Spain) between 1995 and 2014. The population <15 years of age and covered by the public health service was used as reference. The vaccination status of the cases and population was obtained from computerized medical records. Logistic regression analyses included vaccination status, age group and time periods: prevaccine (1995-2001) and vaccination with PCV7 (2002-2010) and PCV13 (2011-2014). A total of 321 cases of PPE were included. The risk of PPE increased between the prevaccine and PCV7 period (adjusted odds ratio [OR], 3.34; 95% confidence interval [CI]: 2.37-4.71), while vaccination with PCV7 was found to be an independent risk factor (OR, 1.44; 95% CI: 1.09-1.89) in the same analysis. In the PCV13 period, the risk of PPE returned to the prevaccination incidence level among children vaccinated with PCV13 (OR, 1.07; 95% CI: 0.56-2.04), while unvaccinated children (OR, 1.69; 95% CI: 0.96-2.98) and overall those vaccinated with PCV7 (OR, 3.64; 95% CI: 2.15-6.17) maintained an increased risk of PPE. The nonsystematic introduction of PCV7 was followed by an increased incidence of PPE. The subsequent introduction of PCV13 was associated with a return to the incidence level in the prevaccine period, mainly in children vaccinated with PCV13.


Emotion regulation predicts change of perceived health in patients with rheumatoid arthritis.
To examine whether emotion regulation predicts change of perceived health in patients with rheumatoid arthritis (RA). Sixty six patients (44 female, 22 male; mean (SD) age 57.7 (11.6) years) participated in a prospective study. Hierarchical regression analysis was used to predict change of perceived health between study entry and follow up (1(1/2) years later) from the emotion regulation styles ambiguity, control, orientation, and expression at study entry. Valuing and intensely experiencing emotions (emotional orientation) predicted a decrease of positive affect. Difficulty recognising and expressing emotions (ambiguity) predicted an increase of perceived disease activity. Emotion regulation showed no associations with change of negative affect and social and physical functioning. Two styles of emotion regulation were shown to have a significant though modest role in the prediction of perceived health change in patients with RA. This suggests that the monitoring of emotion regulation may help to identify patients who are at risk for a reduction of perceived health. If our findings were confirmed by experimental research, improving emotion regulation skills might favourably affect perceived health.


Non-steady peristaltic propulsion with exponential variable viscosity: a study of transport through the digestive system.
A theoretical study is presented for transient peristaltic flow of an incompressible fluid with variable viscosity in a finite length cylindrical tube as a simulation of transport in physiological vessels and biomimetic peristaltic pumps. The current axisymmetric analysis is qualitatively similar to two-dimensional analysis but exhibits quantitative variations. The current analysis is motivated towards further elucidating the physiological migration of gastric suspensions (food bolus) in the human digestive system. It also applies to variable viscosity industrial fluid (waste) peristaltic pumping systems. First, an axisymmetric model is analysed in the limit of large wavelength ([Formula: see text]) and low Reynolds number ([Formula: see text]) for axial velocity, radial velocity, pressure, hydromechanical efficiency and stream function in terms of radial vibration of the wall ([Formula: see text]), amplitude of the wave ([Formula: see text]), averaged flow rate ([Formula: see text]) and variable viscosity ([Formula: see text]). Subsequently, the peristaltic flow of a fluid with an exponential viscosity model is examined, which is based on the analytical solutions for pressure, wall shear stress, hydromechanical efficiency and streamline patterns in the finite length tube. The results are found to correlate well with earlier studies using a constant viscosity formulation. This study reveals some important features in the flow characteristics including the observation that pressure as well as both number and size of lower trapped bolus increases. Furthermore, the study indicates that hydromechanical efficiency reduces with increasing magnitude of viscosity parameter.


Epidemiological Risk Factors for Animal Influenza A Viruses Overcoming Species Barriers.
Drivers and risk factors for Influenza A virus transmission across species barriers are poorly understood, despite the ever present threat to human and animal health potentially on a pandemic scale. Here we review the published evidence for epidemiological risk factors associated with influenza viruses transmitting between animal species and from animals to humans. A total of 39 papers were found with evidence of epidemiological risk factors for influenza virus transmission from animals to humans; 18 of which had some statistical measure associated with the transmission of a virus. Circumstantial or observational evidence of risk factors for transmission between animal species was found in 21 papers, including proximity to infected animals, ingestion of infected material and potential association with a species known to carry influenza virus. Only three publications were found which presented a statistical measure of an epidemiological risk factor for the transmission of influenza between animal species. This review has identified a significant gap in knowledge regarding epidemiological risk factors for the transmission of influenza viruses between animal species.


Biological phosphorus removal with nitrite as election acceptor.
Biological phosphorus removal was studied in a sequencing batch reactor (SBR). The results showed that nitrite could be used as electron acceptor in denitrifying phosphorus removal. Feed mode of nitrite had significant influence on denitrifying phosphorus removal. Anoxic phosphorus assimilation rate could reach 10.44 mgP/gSS.h and the percentage of anoxic phosphorus assimilation amount was more than 97% with continuous feed mode. Granular sludge with denitrifying phosphorus removal activity was found in the SBR. The effects of different operational conditions, such as COD loading, settling time, HRT etc., on the formation of granules were also studied.


Integrated technological and management solutions for wastewater treatment and efficient agricultural reuse in Egypt, Morocco, and Tunisia.
Mediterranean-African countries (MACs) face a major water crisis. The annual renewable water resources are close to the 500 m3 /capita threshold of absolute water scarcity, and water withdrawals exceed total renewable water resources by 30%. Such a low water availability curbs economic development in agriculture, which accounts for 86% of freshwater consumption. The analysis of the current situation of wastewater treatment, irrigation, and water management in MACs and of the research projects targeted to these countries indicates the need for 1) an enhanced capacity to analyze water stress, 2) the development of water management strategies capable of including wastewater reuse, and 3) development of locally adapted water treatment and irrigation technologies. This analysis shaped the MADFORWATER project (www.madforwater.eu), whose goal is to develop a set of integrated technological and management solutions to enhance wastewater treatment, wastewater reuse for irrigation, and water efficiency in agriculture in Egypt, Morocco, and Tunisia. MADFORWATER develops and adapts technologies for the production of irrigation-quality water from drainage canals and municipal, agro-industrial, and industrial wastewaters and technologies for water efficiency and reuse in agriculture, initially validated at laboratory scale, to 3 hydrological basins in the selected MACs. Selected technologies will be further adapted and validated in 4 demonstration plants of integrated wastewater treatment and reuse. Integrated strategies for wastewater treatment and reuse targeted to the selected basins are developed, and guidelines for the development of integrated water management strategies in other basins of the 3 target MACs will be produced. The social and technical suitability of the developed technologies and nontechnological tools in relation to the local context is evaluated with the participation of MAC stakeholders and partners. Guidelines on economic instruments and policies for the effective implementation of the proposed water management solutions in the target MACs will be developed. Integr Environ Assess Manag 2018;14:447-462. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).


Aggregation, dissolution, and stability of quantum dots in marine environments: importance of extracellular polymeric substances.
There is an increasing concern that a considerable fraction of engineered nanoparticles (ENs), including quantum dots (QDs), will eventually find their way into the marine environment and have negative impacts on plankton. As ENs enter the ocean, they will encounter extracellular polymeric substances (EPS) from microbial sources before directly interacting with plankton cells. In this study, EPS harvested from four phytoplankton species, Amphora sp., Dunaliella tertiolecta, Phaeocystis globosa, and Thalassiosira pseudonana, were examined for potential interactions with CdSe nonfunctionalized and functionalized (carboxyl- and amine-) QDs in artificial seawater. Our results show that EPS do not reduce the solubility of QDs but rather decrease their stability. The degradation rate of QDs was positively correlated to the protein composition of EPS (defined by the ratio of protein/carbohydrate). Two approaches showed significant inhibition to the degradation of carboxyl-functionalized QDs: (1) the presence of an antioxidant, such as N-acetyl cysteine, and (2) absence of light. Owing to the complexity in evaluating integrated effects of QDs intrinsic properties and the external environmental factors that control the stability of QDs, conclusions must be based on a careful consideration of all these factors when attempting to evaluate the bioavailability of QDs and other ENs in the marine environments.


5-HT(7)-like receptors mediate serotonergic modulation of photo-responsiveness of the medulla bilateral neurons in the cricket, Gryllus bimaculatus.
Serotonin (5-HT) suppresses the photo-responsiveness of medulla bilateral neurons (MBNs) that are involved in the coupling mechanism of the bilaterally paired optic lobe circadian pacemakers in the cricket, Gryllus bimaculatus. We found that forskolin, a highly specific activator of adenylate cyclase, mimicked the effects of serotonin on the MBNs. This fact suggests the involvement of cyclic 3', 5'-adenosine monophosphate (cAMP) in mediating the action of serotonin. We therefore tested the effects of various 5-HT receptor agonists and antagonists that are coupled to adenylate cyclase to specify the receptor involved. Application of 8-OH-DPAT that has affinity for both 5-HT(1A) and 5-HT(7) receptors suppressed the photo-responsiveness, like forskolin. The inhibitory effect of 8-OH-DPAT was effectively blocked by clozapine, a high affinity 5-HT(7) receptor antagonists with a very low affinity for 5-HT(2). Ketanserin, a selective 5-HT(2) antagonist, and NAN-190, a 5-HT(1A) antagonist, did not block it. These results suggest that serotonergic suppression of the photo-responsiveness of the MBNs is mediated by 5-HT(7)-like receptor subtypes.


Asynchrony of taxonomic, functional and phylogenetic diversity in birds.
We assessed the temporal trends of taxonomic, functional and phylogenetic diversities in the French avifauna over the last two decades. Additionally, we investigated whether and how this multifaceted approach to biodiversity dynamics can reveal an increasing similarity of local assemblages in terms of species, traits and/or lineages. France. We analysed a large-scale dataset that recorded annual changes in the abundance of 116 breeding birds in France between 1989 and 2012. We decomposed and analysed the spatio-temporal dynamics of taxonomic, phylogenetic and functional diversities and each of their α-, β- and γ-components. We also calculated the trend in the mean specialization of bird communities to track the relative success of specialist versus generalist species within communities during the same period. We found large variation within and among the temporal trends of each biodiversity facet. On average, we found a marked increase in species and phylogenetic diversity over the period considered, but no particular trend was found for functional diversity. Conversely, changes in β-diversities for the three facets were characterized by independent and nonlinear trends. We also found a general increase in the local occurrence and abundance of generalist species within local communities. These results highlight a relative asynchrony of the different biodiversity facets occurring at large spatial scales. We show why a multifaceted approach to biodiversity dynamics is needed to better describe and understand changes in community composition in macroecology and conservation biogeography.


Lobe-specific lineages of carcinogenesis in the transgenic adenocarcinoma of mouse prostate and their responses to chemopreventive selenium.
The transgenic adenocarcinoma of mouse prostate (TRAMP) model is by far the most practical transgenic model for preclinical prostate cancer chemoprevention studies. It is critical to characterize the prostate lobe-specificity of lesion lineages to consolidate the advantages of this model and minimize its limitations for chemoprevention studies. We dissected dorsolateral (DLP), ventral (VP), and anterior prostate (AP) lobes, and macroscopic tumors from 90 male C57BL/6J TRAMP mice at 22-24 weeks of age (WOA) and analyzed lesions by histological, biochemical and proteomic approaches. To determine whether methylseleninic acid (MSeA) led to a deletion of initiated cells, we gave oral MSeA to TRAMP mice from 5 to 23 WOA or from 5 to 15 WOA and analyzed lesions at 23 WOA. All tumors (n = 18) were T-antigen(+), synaptophysin (SYP)(+), androgen-receptor(-), and E-cadherin(-) poorly differentiated neuroendocrine carcinomas (NE-Ca). They were traceable most frequently to VP (66.7%) and rarely to DLP (11.1%) and AP (5.6%) with an estimated life-time incidence of 1 out of 3 mice. In DLP, epithelial lesions ranged from mild-to-severe atypical hyperplasia, with T-antigen(+), SYP(-), androgen-receptor(+), and E-cadherin(+). Proteomic profiling revealed many molecular differences between VP and DLP. In MSeA experiment, 6 out of 19 (31.5%) mice developed NE-Ca in the control group, only 2 in each MSeA group of 17-18 mice (11.1-11.8%) bore a detectable NE-Ca. The C57BL/6J TRAMP mouse represents at least two lineages of prostate carcinogenesis. Chemoprevention studies should incorporate this knowledge for efficacy assessment and molecular target validations.


Further Limitations of Synthetic Fungicide Use and Expansion of Organic Agriculture in Europe Will Increase the Environmental and Health Risks of Chemical Crop Protection Caused by Copper-Containing Fungicides.
Copper-containing fungicides have been used in agriculture since 1885. The divalent copper ion is a nonbiodegradable multisite inhibitor that has a strictly protective, nonsystemic effect on plants. Copper-containing plant protection products currently approved in Germany contain copper oxychloride, copper hydroxide, and tribasic copper sulfate. Copper is primarily used to control oomycete pathogens in grapevine, hop, potato, and fungal diseases in fruit production. In the environment, copper is highly persistent and toxic to nontarget organisms. The latter applies for terrestric and aquatic organisms such as earthworms, insects, birds, fish, Daphnia, and algae. Hence, copper fungicides are currently classified in the European Union as candidates for substitution. Pertinently, copper also exhibits significant mammalian toxicity (median lethal dose oral = 300-2500 mg/kg body wt in rats). To date, organic production still profoundly relies on the use of copper fungicides. Attempts to reduce doses of copper applications and the search for copper substitutes have not been successful. Copper compounds compared with modern synthetic fungicides with similar areas of use display significantly higher risks for honey bees (3- to 20-fold), beneficial insects (6- to 2000-fold), birds (2- to 13-fold), and mammals (up to 17-fold). These data contradict current views that crop protection in organic farming is associated with lower environmental or health risks. Further limitations in the range and use of modern single-site fungicides may force conventional production to fill the gaps with copper fungicides to counteract fungicide resistance. In contrast to the European Union Green Deal goals, the intended expansion of organic farming in Europe would further enhance the use of copper fungicides and hence increase the overall risks of chemical crop protection in Europe. Environ Toxicol Chem 2023;00:1-12. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route.
A murine model based on infection by the respiratory route has been used to study the pathogenesis of recombinant vaccinia viruses. The neurovirulent Western Reserve (WR) strain and the Wyeth smallpox vaccine strain were used as vectors. Recombinant viruses were constructed by insertion of the Epstein-Barr virus membrane glycoprotein 340 gene into the thymidine kinase (TK) gene of each vaccinia virus. Intranasal inoculation of DBA/2 mice with 10(6) pock-forming units (pk.f.u.) of the WR strain was lethal but mice survived similar infection with the WR recombinant virus. Each virus was recovered from lung, blood and brain but, unlike wild-type virus, the recombinant virus was subsequently cleared. No deaths occurred after similar infection with the Wyeth strain or the Wyeth recombinant virus. There was limited growth of the Wyeth strain in the respiratory tract, low levels of virus in the blood and only sporadic recovery in brain extracts. The Wyeth recombinant virus was cleared rapidly with little viraemia or detectable infection of the central nervous system. No phenotypic character determined in vitro could be related consistently to the virulence of wild-type and recombinant viruses. Although the lethal character of the WR strain was affected by its TK+ phenotype, mice survived infection by intranasal inoculation with 10(6) pk.f.u. of WR TK+ recombinant viruses which either expressed the human interleukin 2 gene or had a deficient vaccinia virus growth factor gene.


[Surgical treatment of malignant liver tumors].
One hundred and nineteen patients were operated upon, 89--for primary cancer of the liver, 30--for cancer metastases. Radical operations for primary cancer of the liver were performed in 5 of 89 patients, and in 8 of 30 patients with metastatic involvement of the liver. In radical operations for malignant hepatic neoplasms frequently there would arise the necessity of a temporary exclusion of the organ from the portal and caval circulation.


Supplementation of okra seed oil ameliorates ethanol-induced liver injury and modulates gut microbiota dysbiosis in mice.
This aim of this study is to assess the possible effects of dietary okra seed oil (OSO) consumption on attenuation of alcohol-induced liver damage and gut microbiota dysbiosis, and associated mechanisms in mice. Mice were orally administered alcohol alone or in combination with OSO at 400 and 800 mg per kg bw for 8 weeks. OSO caused a strong inhibition of abnormal weight loss and liver fat accumulation in alcohol-administered mice. Malonaldehyde production was also effectively antagonized, and glutathione peroxidase and superoxide dismutase activities were elevated by OSO treatment in ethanol-based mice (p < 0.05). Concentrations of hepatic TNF-α, IL-1 and IL-6 were decreased after OSO treatment when compared with alcohol-treated mice, respectively (p < 0.05). As revealed by 16S rDNA gene sequence analysis, OSO notably reduced the Proteobacteria proportion and enhanced the Bacteroidetes population of alcohol-treated mice, and a significant reduction in Clostridium XlVa and Staphylococcus was observed, revealing that OSO attenuated the alcohol-induced gut dysbiosis. OSO also attenuated lipid metabolic disorder by modulating metabolism of serum free fatty acids in ethanol-based mice, but had no significant difference in cecum total short-chain fatty acids among the tested mice. Amelioration of these parameters and liver injury via H&E staining examination demonstrated that OSO consumption could effectively protect against liver damage and maintain intestinal eubiosis in mice.


Interrelations between effective population size and other pedigree tools for the management of conserved populations.
Genetic parameters widely used to monitor genetic variation in conservation programmes, such as effective number of founders, founder genome equivalents and effective population size, are interrelated in terms of coancestries and variances of contributions from ancestors to descendants. A new parameter, the effective number of non-founders, is introduced to describe the relation between effective number of founders and founder genome equivalents. Practical recommendations for the maintenance of genetic variation in small captive populations are discussed. To maintain genetic diversity, minimum coancestry among individuals should be sought. This minimizes the variances of contributions from ancestors to descendants in all previous generations. The method of choice of parents and the system of mating should be independent of each other because a clear-cut recommendation cannot be given on the latter.


Built Environments to Support Rehabilitation for People With Stroke From the Hospital to the Home (B-Sure): Protocol for a Mixed Method Participatory Co-Design Study.
A global trend is to move rehabilitation closer to people's neighborhoods and homes. Still, little attention has been given to how the built environment outside the hospital setting might impact rehabilitation and recovery for stroke survivors. The overarching objective of this project is to develop conceptual models of built environments that support stroke rehabilitation and recovery outside the hospital setting. Specifically, the project will explore factors and characteristics of the built environment that support people with stroke and their families and identify innovative built environments that can be designed for local health care. The project will examine facilitators and obstacles for implementing built environmental solutions and evaluate the potential benefits, feasibility, and acceptability. The project uses a mixed methods design approach with 3 phases. In phase 1, factors and characteristics of the built environment for rehabilitation will be identified. Based on the results from phase 1, phase 2 will involve co-designing prototypes of environments to support the rehabilitation process for people with stroke. Finally, the prototypes will be evaluated in phase 3. Qualitative and quantitative methods will include a literature review, a concept mapping (CM) study, stakeholder interviews, prototype development, and testing. The project will use multidimensional scaling, hierarchical cluster analysis, descriptive statistics for quantitative data, and content analysis for qualitative data. Location analysis will rely on the location-allocation model for network problems, and the rule-based analysis will be based on geographic information systems data. As of the submission of this protocol, ethical approval for the CM study and the interview study has been obtained. Data collection is planned to start in September 2023 and the workshops later in the same year. The scoping review is ongoing from January 2023. The CM study is ongoing and will be finalized in the spring of 2024. We expect to finish the data analysis in the second half of 2024. The project is a 3-year project and will continue until December 2025. We aim to determine how new environments could better support a person's control over their day, environment, goals, and ultimately control over their recovery and rehabilitation activities. This "taking charge" approach would have the greatest chance of transferring the care closer to the patient's home. By co-designing with multiple stakeholders, we aim to create solutions with the potential for rapid implementation. The project's outcomes may target other people with frail health after a hospital stay or older persons in Sweden and anywhere else. The impact and social benefits include collaboration between important stakeholders to explore how new environments can support the transition to local health care, co-design, and test of new conceptual models of environments that can promote health and well-being for people post stroke. DERR1-10.2196/52489.


Exposing the small protein load of bacterial life.
The ever-growing repertoire of genomic techniques continues to expand our understanding of the true diversity and richness of prokaryotic genomes. Riboproteogenomics laid the foundation for dynamic studies of previously overlooked genomic elements. Most strikingly, bacterial genomes were revealed to harbor robust repertoires of small open reading frames (sORFs) encoding a diverse and broadly expressed range of small proteins, or sORF-encoded polypeptides (SEPs). In recent years, continuous efforts led to great improvements in the annotation and characterization of such proteins, yet many challenges remain to fully comprehend the pervasive nature of small proteins and their impact on bacterial biology. In this work, we review the recent developments in the dynamic field of bacterial genome reannotation, catalog the important biological roles carried out by small proteins and identify challenges obstructing the way to full understanding of these elusive proteins.


Echocardiographic parameters and all-cause mortality: the Rotterdam Study.
Even when heart failure has not yet become clinically manifest, preclinical ventricular dysfunction may be present, and therapeutic interventions introduced at this time may reduce morbidity and mortality. However, data on the predictive value of echocardiographic characteristics in the general population remain relatively scarce. The Rotterdam Study is a population-based cohort study in men and women aged >or=55 years. Participants with prevalent heart failure, myocardial infarction and atrial fibrillation and flutter at the time of echocardiography were excluded. Structural, systolic and diastolic parameters were assessed using two-dimensional, M-mode and Doppler echocardiography. Echocardiograms were available in 4425 participants. During a mean follow-up of 3.0 years, 226 participants died. Increased left ventricular mass was an independent risk factor for all-cause mortality, particularly in men (hazard ratio per standard deviation of natural log transformed left ventricular mass, 1.20 (95% CI, 1.01-1.43)). Fractional shortening and left ventricular systolic function did not show a clear association with mortality. E/A ratio <0.75 was an independent risk factor in men (age-adjusted hazard ratio 1.82 (95% CI 1.23-2.69)). This was further reflected by diastolic function: impaired relaxation was a risk factor in men, but not in women. Structural and diastolic echocardiographic parameters are associated with all-cause mortality in an asymptomatic population. However, the evidence is still inadequate to support the usefulness of echocardiography for screening to identify asymptomatic individuals with preclinical ventricular dysfunction.


Multiple recurrent mutations at four human Y-chromosomal single nucleotide polymorphism sites in a 37 bp sequence tract on the ARSDP1 pseudogene.
The male-specific region of the human Y chromosome (MSY) is passed down clonally from father to son and mutation is the single driving force for Y-chromosomal diversification. The geographical distribution of MSY variation is non-random. Therefore, Y-chromosomal single nucleotide polymorphisms (Y-SNPs) are of forensic interest, as they can be utilized, e.g. for deducing the bio-geographical origin of biological evidence. This extra information can complement short tandem repeat data in criminal investigations. For forensic applications, however, any targeted marker has to be unequivocally interpretable. Here, we report findings for 17 samples from a population study comprising specimens from ∼3700 men living in Tyrol (Austria), indicating apparent homoplasic mutations at four Y-SNP loci on haplogroup R-M412/L51/S167, R-U152/S28, and L-M20 Y chromosomes. The affected Y-SNPs P41, P37, L202, and L203 mapped to a 37bp region on Yq11.21. Observing in multiple phylogenetic contexts up to four homoplasic mutations within such a short sequence tract is unlikely to result from a series of independent parallel mutations. Hence, we rather propose X-to-Y gene conversion as a more likely scenario. Practical implications arising from markers exhibiting paralogues on the Y chromosome or sites with a high propensity to recurrent mutation for database searches are addressed.


Diminishing significance of HLA matching in kidney transplantation.
To determine trends in the significance of HLA matching and other risk factors in kidney transplantation, we analyzed data on graft survival in a consecutive sample of 33 443 transplant recipients who received deceased donor kidneys from December 1994 to December 1998 with a mean follow-up time of 2.2 years. HLA matching and other risk factors (peak panel reactive antibody, donor age, sex and cause of death, cold ischemia time, donor and recipient body size) were examined. Mean likelihood ratios of models, fit with and without each variable of interest, were calculated by generating bootstrapped samples from each single year cohort. Pooled censored and uncensored graft survival rates were 90.6% and 89.9% at 1 year, 85.8% and 84.5% at 2 years, and 80.7% and 78.6% at 3 years. HLA matching declined in significance while other factors retained similar levels of statistical significance over the four yearly cohorts. With evolving clinical practice, including the provision of safer and more potent immunosuppressive therapy, the significance of HLA matching has diminished. Non-immunologic factors continue to impede more marked improvements in long-term graft survival. Recognizing these trends, organ allocation algorithms may need to be revised.


The function and three-dimensional structure of a thromboxane A2/cysteinyl leukotriene-binding protein from the saliva of a mosquito vector of the malaria parasite.
The highly expressed D7 protein family of mosquito saliva has previously been shown to act as an anti-inflammatory mediator by binding host biogenic amines and cysteinyl leukotrienes (CysLTs). In this study we demonstrate that AnSt-D7L1, a two-domain member of this group from Anopheles stephensi, retains the CysLT binding function seen in the homolog AeD7 from Aedes aegypti but has lost the ability to bind biogenic amines. Unlike any previously characterized members of the D7 family, AnSt-D7L1 has acquired the important function of binding thromboxane A(2) (TXA(2)) and its analogs with high affinity. When administered to tissue preparations, AnSt-D7L1 abrogated Leukotriene C(4) (LTC(4))-induced contraction of guinea pig ileum and contraction of rat aorta by the TXA(2) analog U46619. The protein also inhibited platelet aggregation induced by both collagen and U46619 when administered to stirred platelets. The crystal structure of AnSt-D7L1 contains two OBP-like domains and has a structure similar to AeD7. In AnSt-D7L1, the binding pocket of the C-terminal domain has been rearranged relative to AeD7, making the protein unable to bind biogenic amines. Structures of the ligand complexes show that CysLTs and TXA(2) analogs both bind in the same hydrophobic pocket of the N-terminal domain. The TXA(2) analog U46619 is stabilized by hydrogen bonding interactions of the ω-5 hydroxyl group with the phenolic hydroxyl group of Tyr 52. LTC(4) and occupies a very similar position to LTE(4) in the previously determined structure of its complex with AeD7. As yet, it is not known what, if any, new function has been acquired by the rearranged C-terminal domain. This article presents, to our knowledge, the first structural characterization of a protein from mosquito saliva that inhibits collagen mediated platelet activation.


Isothermal microcalorimetry improves accuracy and time to bacterial detection of periprosthetic joint infection after total joint arthroplasty.
Isothermal microcalorimetry (IMC) was evaluated compared to conventional cultures to determine the clinical performance for diagnosing periprosthetic joint infection (PJI) of hip/knee replacements. We prospectively collected three to five deep tissue samples per patient from 152 patients undergoing conversion or revision hip/knee arthroplasty from July 2020 to November 2022. Cultures and IMC for each sample were compared for concordance, median time to detection (TTD), and diagnostic performance based on 2013 Musculoskeletal Infection Society criteria. Secondary analyses involved patients on antibiotics at sampling. The 152 total patients had 592 tissue samples (mean 3.9 ± 0.3) with sample concordance between cultures and IMC of 90%. IMC demonstrated a sensitivity of 83%, specificity of 100%, negative predictive value (NPV) of 89%, and positive predictive value (PPV) of 100% for PJI. Cultures resulted in 69% sensitivity, 100% specificity, 81% NPV, and 100% PPV. The accuracy of IMC was 93% compared to 87% for cultures (P < 0.001). The median TTD of PJI by cultures was 51 (21-410) hours compared to 10 (0.5-148) hours for IMC (P < 0.001). For 39 patients on chronic antibiotics, sensitivity in PJI detection was 93%, specificity 100%, NPV 85%, and PPV 100% by IMC compared to 79% sensitivity, 100% specificity, 65% NPV, and 100% PPV for cultures. The accuracy was 95% for IMC compared to 85% for cultures (P < 0.001) with median TTD of 12 (0.5-127) hours compared to 52 (21-174) hours (P < 0.001). Utilizing IMC for PJI detection improves TTD by nearly 2 days while improving diagnostic accuracy compared to cultures, particularly in patients on chronic antibiotics.


Clinical experience with venlafaxine in the treatment of hot flushes in women with a history of breast cancer.
To obtain practical experience with venlafaxine for hot flushes in breast cancer patients and incorporate this in a treatment protocol. Twenty-two women with a history of breast cancer (mean age 49.2 years, range 35-65) were referred for consideration of treatment with venlafaxine for hot flushes. Patients received extensive information on treatment with venlafaxine and were advised to self-monitor the frequency of their hot flushes. Eight women did not start venlafaxine because they had no postmenopausal complaints, were lost to follow-up, had too low a frequency of hot flushes, or refused treatment. Eventually 14 women started venlafaxine. Two of them did not tolerate venlafaxine, four reported some effect but stopped because of side effects, two women had no effect whatsoever. Six women observed a clear ( > 50%) reduction in their hot flush frequency that was maintained at a median follow-up of 13 months. The group of patients referred for treatment was more heterogeneous and more patients dropped out because of side effects than expected. Extensive patient education, patient selection and evaluation of the treatment effect (by self-monitoring of hot flush frequency) are mandatory to avoid useless (continuation of) treatment and to prepare patients for side effects. Under these conditions, a substantial minority of patients benefit from venlafaxine.


Pharmacologic actions of Ro 24-5913, a novel antagonist of leukotriene D4.
Ro 24-5913, (E)-4-[3-[2-(4-cyclobutyl-2- thiazolyl)ethenyl]phenylamino]-2,2-diethyl-4-oxobutanoic acid, has been identified as a chemically unique, potent and selective LTD4 antagonist. In vitro, Ro 24-5913 competes with [3H]LTD4 for its binding site on guinea pig lung membranes with an IC50 of 6.4 +/- 2.2 nM. In isolated guinea pig tracheal smooth muscle, Ro 24-5913 produces concentration-dependent rightward shifts of LTD4-induced contraction curves (pA2 value of 9.6 +/- 0.2). The slope of the Schild plot is not significantly different from 1, indicating that the antagonism is of a competitive nature. In the human bronchus, Ro 24-5913 is an effective antagonist of LTD4-induced contractions (pKB of 9.3 +/- 0.1). In vivo, Ro 24-5913 dose-dependently inhibits LTD4-induced bronchoconstriction in guinea pigs by the i.v. (ID50 0.13 mg/kg), oral (ID50 0.12 mg/kg) and aerosol (IC50 0.008%) routes of administration. This in vivo activity is specific as evidenced by the inability of Ro 24-5913 to inhibit bronchoconstriction induced by LTB4, PAF or histamine. In comparison with other LTD4 antagonists evaluated in this guinea pig model, Ro 24-5913 is markedly superior in terms of oral potency, bioavailability and oral duration of action. Ro 24-5913 also blocks allergic bronchospasm mediated by endogenously generated leukotrienes in guinea pigs; the potency and duration of action is nearly equivalent to that seen as an antagonist of bronchoconstrictions produced by exogenous LTD4. In summary, Ro 24-5913 is representative of a novel chemical class of LTD4 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)


Quality improvement in hospitals' surgery-related processes: A systematic review.
Background: There is a growing global movement toward quality and safety in healthcare and quality improvement (QI) in general surgery. The fundamentals of QI begin with an understanding of the underlying theoretical framework. This study aims to provide an overview of the existing QI models and frameworks for general surgery. Methods: In this systematic review, published literature from January 2007 until September 2018 were retrieved from PubMed, Scopus, Web of Science and Embase databases, and Google Scholar using the MeSH terms related to QI and surgery. In total, 25 fulltext articles were finally included, and data extraction was based on research objectives. Results: Nine models were identified for QI in general surgery. These models were categorized into two main groups: (i) conceptual models or frameworks designed for QI in industry and applied in surgery, and (ii) those designed specifically for QI in surgery. Identified QI models were more used for improving postoperative processes and pre-hospital trauma care, identifying causes of prolonged periods of stay and lowering LOS index, improving surgical antimicrobial prophylaxis and antibiotics administrating during surgery process, reducing and controlling infections, reducing complications, reducing mortality and morbidity, reducing waiting times and start time delays, reducing variability and improving surgical clinic experience, reducing costs, improving operating room efficiency by removing processes that add no value, and lowering per-capita costs. Conclusion: According to the findings of this study, there are different models and frameworks with different aspects and dimensions for QI in surgery, which is recommended to use either of these models alone or with each other for specific circumstances. The use of these models in surgery is increasing, and it is recommended that these models could be used according to their functions in cases such as reducing the unnecessary use of resources, increasing the satisfaction of patients and their families with health care and improving the efficiency, safety and quality of healthcare in the surgical departments.


The Impact of Child Behaviour Problems on Maternal Employment: A Longitudinal Cohort Study.
This prospective population-based study examined associations between children's behaviour problems and maternal employment. Information on children's behaviour problems at 3 years from 22,115 mothers employed before pregnancy and participating in the Norwegian Mother and Child Cohort Study were linked to national register data on employment and relevant social background factors, mothers' self-reported susceptibility to anxiety/depression and mother-reports of day-care attendance and fathers' income. Mothers reporting their child to have severe (>2 SD) internalizing or severe combined behaviour problems (5 %) had excess risk of leaving paid employment irrespective of other important characteristics generally associated with maternal employment (RR 1.24-1.31). The attributable risk percent ranged from 30.3 % (internalizing problems) to 32.4 % (combined problems). Externalizing behaviour problems were not uniquely associated with mothers leaving employment.


Identification of candidate genes involved in early iron deficiency chlorosis signaling in soybean (Glycine max) roots and leaves.
Iron is an essential micronutrient for all living things, required in plants for photosynthesis, respiration and metabolism. A lack of bioavailable iron in soil leads to iron deficiency chlorosis (IDC), causing a reduction in photosynthesis and interveinal yellowing of leaves. Soybeans (Glycine max (L.) Merr.) grown in high pH soils often suffer from IDC, resulting in substantial yield losses. Iron efficient soybean cultivars maintain photosynthesis and have higher yields under IDC-promoting conditions than inefficient cultivars. To capture signaling between roots and leaves and identify genes acting early in the iron efficient cultivar Clark, we conducted a RNA-Seq study at one and six hours after replacing iron sufficient hydroponic media (100 μM iron(III) nitrate nonahydrate) with iron deficient media (50 μM iron(III) nitrate nonahydrate). At one hour of iron stress, few genes were differentially expressed in leaves but many were already changing expression in roots. By six hours, more genes were differentially expressed in the leaves, and a massive shift was observed in the direction of gene expression in both roots and leaves. Further, there was little overlap in differentially expressed genes identified in each tissue and time point. Genes involved in hormone signaling, regulation of DNA replication and iron uptake utilization are key aspects of the early iron-efficiency response. We observed dynamic gene expression differences between roots and leaves, suggesting the involvement of many transcription factors in eliciting rapid changes in gene expression. In roots, genes involved iron uptake and development of Casparian strips were induced one hour after iron stress. In leaves, genes involved in DNA replication and sugar signaling responded to iron deficiency. The differentially expressed genes (DEGs) and signaling components identified here represent new targets for soybean improvement.


Marfanoid features in a child with combined methylmalonic aciduria and homocystinuria (CblC type).
Cobalamin is an essential cofactor for two mammalian enzymes: methionine synthase and methylmalonyl-CoA mutase. Patients with the cobalamin C (CblC) defect have combined methylmalonic aciduria and homocystinuria. Recently, the gene responsible for the CblC type, MMACHC, was identified, which enables molecular diagnostics. In this study, we describe two siblings, a 16-year-old girl and her 11-year-old brother, of a consanguineous family who presented with a very distinct clinical manifestation. The girl presented at the age of 13 years with macrocytic anaemia, cognitive regression and Marfanoid features such as increased arm-span, arachnodactyly, joint hyperlaxity and scoliosis. Her brother presented at the age of 10 months with developmental delay and behavioural abnormalities. Biochemical analysis showed severely increased homocysteine and methylmalonic acid levels in plasma of both siblings. In addition, plasma cysteine levels were decreased in the girl but not in her brother. The diagnosis of CblC defect was confirmed by genomic sequencing of the coding exons of the MMACHC gene. Two heterozygous mutations were identified in both siblings; the common c.271dupA p.Arg91LysfsX14 and a novel mutation, c.1A > G p.Met1?. Therapy consisting of folic acid, vitamin B6, l-carnitine and intramuscular vitamin B12 resulted in a clear improvement of biochemical parameters and, importantly, resulted in amelioration of the Marfanoid features in the girl. These data might suggest that low cysteine levels account for the Marfanoid features observed in the girl and indicate that the CblC type of combined methylmalonic aciduria and homocystinuria should be considered in the differential diagnosis of patients with Marfanoid features.


Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats.
Because of their potential therapeutic effects, N-methyl-D-aspartate (NMDA) receptor antagonists have been investigated for clinical use. Unfortunately, many channel-blocking antagonists have been associated with the production of side effects, including motor impairment and phencyclidine (PCP)-like subjective effects. This study investigated the relationship between NMDA receptor channel blockade and production of PCP-like side effects by evaluating a variety of NMDA channel blockers with different binding characteristics for the production of PCP-like discriminative stimulus effects. The NMDA channel blockers were tested in rats trained to discriminate 2 mg/kg PCP, i.p., from saline using a standard two-lever drug discrimination procedure with responding under a fixed ratio (FR) 32 schedule of food reinforcement. The high-affinity channel blockers PD 138289, PD 137889 and FR 115427, produced full, dose-dependent substitution for PCP. Of the moderate-affinity channel blockers, MRZ 2/579 fully substituted for PCP while 1-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline, 8-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline and alaproclate produced partial substitution. Drugs with the lowest affinity for the channel site and/or higher affinity for non-NMDA CNS sites, antazoline, idazoxan, 1-phenyl-1,2,3,4-tetrahydroisoquinoline, alpha-benzyl- N-methylphenethylamine and orphenadrine, failed to substitute for PCP. The results demonstrate that the cellular actions of the individual channel-blocking NMDA antagonists, in particular affinity for the channel site and NMDA receptor specificity, are important determinants of their discriminative stimulus effects. While higher affinity channel blockers show a correlation between affinity and PCP-like discriminative stimulus effects, behavioral disruption through action at non-NMDA receptors probably prevents achieving sufficient concentrations of the lower affinity compounds at NMDA receptors to produce PCP-like discriminative stimulus effects.


Is modeling of biological wastewater treatment a mature technology?
Based on three case studies it is demonstrated that the application of mathematical models in biological wastewater treatment has not yet reached its full potential. Model structure uncertainty and correlation of uncertain parameter values make up the first case. The combination of biokinetic and hydraulic models relates to the second case. The evolution of a full scale plant over its life expectancy is the frame for the third case. This paper was initially presented as a discussion starter and thus is raising questions rather than providing answers.


Application of HBx-induced anti-URGs as early warning biomarker of cirrhosis and HCC.
Hepatitis B virus (HBV) carriers are at high risk for the development of hepatocellular carcinoma (HCC), but there are no reliable markers that will identify such high-risk patients. HBV up-regulates the expression of selected genes (URGs) in the liver during chronic infection. These aberrantly expressed proteins trigger corresponding antibodies (anti-URGs) that appear prior to the detection of HCC. This study was undertaken to see if the anti-URGs could be used as early warning biomarker of HBV-induced liver cirrhosis and HCC. A cross sectional study using a total of 625 serum samples from HBV infected and uninfected controls were tested for the anti-URGs using specific ELISAs. The number and specificity of anti-URGs correlated with the severity of liver disease Anti-URGs were predominantly present among patients with HBV-associated HCC (55.2%) and cirrhosis (60.7%), and at a lower frequency among patients with chronic hepatitis (35.8%), and at still lower frequencies in most asymptomatic carriers (12.3%) with normal ALT, among patients with chronic hepatitis C (38.5%) and blood donors (0.9%). These anti-URGs were rarely detected in sera from those with tumors other than HCC, except among HBV infected patients with cholangioicarcinoma and in some patients with drug induced hepatitis. 3 or more anti-URGs could precede the diagnosis of cirrhosis or HCC 11.8 months on average, and HBV hepatitis patients with 3 or more anti-URGs have much higher risk (5/20 vs 0/30) to develop cirrhosis and HCC than those patients with less anti-URGs. As the early warning biomarker, 3 or more anti-URGs were served as the threshold to separate the cirrhosis and HCC from others with a moderate sensitivity (58.3%) and specificity (80.0%), which was better than other biomarkers (AFP, AFP-L3, GPC3 and GP73) and would improve up to 70.3% when combined with another biomarker. The results of this clinical validation study suggest that the anti-URGs might have diagnostic/prognostic utility among patients at high risk for the development of cirrhosis and HCC.


Indirect (herd) protection, following pneumococcal conjugated vaccines introduction: A systematic review of the literature.
Pneumococcal diseases are major causes of morbidity among adults, especially those over 50years of age. While pneumococcal conjugated vaccines (PCV's) impact on pneumococcal disease rates among children is well established, the extent of its impact on adult pneumococcal related illness remains unclear. The aim of this systematic literature review was to describe the impact of PCV introduction to childhood national immunization programs worldwide on PCV-naive adult population. A systematic literature search was performed using the PubMed database. The search was limited to articles written in English and published between January 2000 and February 2016. Studies evaluating pneumococcal disease rates in individuals over 5years of age were included. Independent extraction of articles was performed by the two authors. Search terms included: Pneumococcal conjugated vaccine, herd, indirect, adults, and pneumonia. Forty-nine articles meeting the selection criteria were identified, 39 regarding invasive pneumococcal disease (IPD, one on meningitis only), 8 regarding pneumonia, and 2 on both IPD and pneumonia. The majority of reports were from the US, UK and Canada. Considerable variability in the data sources, quality and completeness was observed. While most studies reported either statistically significant reduction or insignificant changes in IPD and pneumonia disease rates in adults following PCV nationwide implementation, few studies reported statistically significant increase in pneumococcal disease rates, these were mainly from countries with low PCV coverage rates and/or inadequate surveillance. Invasive pneumococcal diseases and pneumonia rates among the adult population decreased in most countries following PCV introduction into the NIP. This indirect effect on older population seems to be dependent on PCV coverage rates and time from PCV nationwide implementation. Adults >65years old seem to benefit the most from PCV introduction.


Evidence for two calcium-dependent potassium conductances in lizard motor nerve terminals.
Action potentials and afterpotentials were recorded with a microelectrode inserted into lizard motor axons within a few millimeters of their motor terminals. In the presence of 1 mM 4-aminopyridine (4-AP), the duration of the action potential recorded near motor terminals was Ca-sensitive: repolarization was more rapid when bath [Ca] was elevated, and became slower when bath [Ca] was removed or when 0.1-1 mM Mn was added. Repolarization was also slowed following addition of 3-10 nM charybdotoxin or 100-300 microM tetraethylammonium (TEA) to the bath, and following intra-axonal injection of the Ca buffer BAPTA. These results, in agreement with published extracellular recordings, indicate that the motor nerve terminal membrane contains rapidly activating, Ca-activated K channels. When these (and other) K channels were blocked by 10 mM TEA, the action potential recorded near motor terminals was followed by Ca-dependent depolarizing afterpotentials, followed in turn by a slow hyperpolarizing afterpotential (h.a.p.) that lasted several seconds. This slow h.a.p. was also Ca-sensitive: it became larger with increasing bath [Ca] and was abolished by removal of bath [Ca] and by addition of 1 mM Mn. Intra-axonal injection of BAPTA reduced the amplitude of the slow h.a.p., and prolonged injections promoted repetitive discharge. The slow h.a.p. following single action potentials was observed in 100 microM ouabain and in K-free solutions and thus is pharmacologically distinct from the hyperpolarization that follows tetanic stimulation. The slow h.a.p. was selectively inhibited by 100 nM apamin, but persisted in 100 nM charybdotoxin. This afterpotential was enhanced by 0.1-1 mM 4-AP and by the dihydropyridine Bay K 8644 (0.1-1 microM). These results suggest that the slow h.a.p. in lizard motor nerve terminals is mediated by Ca-activated K channels that can be activated near the resting potential and are pharmacologically distinct from the Ca-activated K channels that contribute to action potential repolarization. The slow h.a.p. was enhanced by 0.1-1 mM caffeine and inhibited by 100 microM procaine, raising the possibility that this afterpotential may be activated not only by Ca entering via the plasma membrane, but also by Ca released from intra-terminal stores.


Calcineurin/NFAT signaling pathway mediates titanium particle‑induced inflammation and osteoclast formation by inhibiting RANKL and M‑CSF in vitro.
Wear particles serve a central role in periprosthetic osteolysis, which leads to the aseptic loosening of prostheses. In the present study a lentiviral vector was constructed to silence macrophage colony stimulating factor (M‑CSF) and receptor activator of nuclear factor κ‑B ligand (RANKL) genes, which synergistically inhibit osteoclast formation and differentiation. To confirm the role of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in osteolysis, we transduced murine macrophage/monocyte RAW264.7 cells with M‑CSF‑short hairpin (sh)RNA‑RANKL‑shRNA. Tumor necrosis factor‑α (TNF‑α) protein levels were evaluated using enzyme‑linked immunosorbent assay. Transduced RAW264.7 cells were cultured in Transwell chambers in the presence of 0.1 mg/ml titanium particles to investigate the capacity of TNF‑α inhibition to reduce wear debris‑induced inflammation. RANKL, M‑CSF, TNF‑α, interleukin (IL)‑1β, IL‑6 and NFATc1 mRNA levels were also assessed by reverse transcription‑quantitative polymerase chain reaction. Osteoclastogenesis was measured by tartrate‑resistant acid phosphatase (TRAP) mRNA quantification. Lentiviral‑mediated double gene inhibition is known to be able to completely inhibit inflammatory osteolysis, simultaneously decreasing the number of NFATc1‑ and TRAP‑positive cells. The present study confirmed that the combined silencing of M‑CSF and RANKL genes can inhibit the osteolysis induced by the wear particles around the prosthesis. The calcineurin/NFAT pathway serves a role in the prevention of prosthesis loosening.


Liposomal Cu-64 labeling method using bifunctional chelators: poly(ethylene glycol) spacer and chelator effects.
Two bifunctional Cu-64 chelators (BFCs), (6-(6-(3-(2-pyridyldithio)propionamido)hexanamido)benzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (TETA-PDP) and 4-(2-(2-pyridyldithioethyl)ethanamido)-11-carboxymethyl-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane (CB-TE2A-PDEA), were synthesized and conjugated to long-circulating liposomes (LCLs) via attachment to a maleimide lipid. An in vitro stability assay of (64)Cu-TETA, (64)Cu-TETA-PEG2k, and (64)Cu-CB-TE2A-PEG2k liposomes showed that more than 86% of the radioactivity remains associated with the liposomal fraction after 48 h of incubation with mouse serum. The in vivo time activity curves (TAC) for the three liposomal formulations showed that approximately 50% of the radioactivity cleared from the blood pool in 16-18 h. As expected, the in vivo biodistribution and TAC data obtained at 48 h demonstrate that the clearance of radioactivity from the liver slows with the incorporation of a poly(ethylene glycol)-2k (PEG2k) brush. Our data suggest that (64)Cu-TETA and (64)Cu-CB-TE2A are similarly stable in the blood pool and accumulation of radioactivity in the liver and spleen is not related to the stability of Cu-64 chelator complex; however, clearance of Cu-64 from the liver and spleen are faster when injected as (64)Cu-TETA-chelated liposomes rather than (64)Cu-CB-TE2A-chelated liposomes.


An end-to-end Deep Hybrid Autoencoder based method for single-cell RNA-Seq data analysis.
Single-cell RNA sequencing technology provides powerful support for researchers to understand the complex mechanisms of cells at the single-cell level. Due to the high sparsity, technical noise, and computational complexity of single-cell transcriptome data, the existing data analysis methods are unable to effectively extract the fine-grained characteristics of scRNA-seq data, resulting in inaccurately analyze the heterogeneity of the individual cell from a great quantity of cell mixtures. To address these shortcomings, we proposed an end-to-end analysis method called dhaSCA, which integrates the Graph convolutional neural network (GCN) feature learning and downstream tasks such as classification and imputation into a unified deep learning manner. dhaSCA uses hybrid GCN-MLP deep autoencoder and to capture structural information between cells, and learn the low dimensional cell representation. It also introduces downstream tasks as constraints to guide the model to learn more accurate cell features. We conducted various experiments to evaluate the performance of dhaSCA based on eight real RNA-Seq datasets, including classification, imputation, clustering, and visualization. The results show that dhaSCA outperforms other state-of-the-art methods in these downstream tasks. Therefore, dhaSCA is able to obtain a richer representation of cells, and provides strong support for efficient analysis of single-cell data. Our method dhaSCA is freely available at https://github.com/NingYu-Lab/dhaSCA.


A prospective study of human polyomavirus infection in pregnancy.
Urine samples from 1,235 pregnant women were examined by light microscopy for cytologic evidence of virus infection. Smears of urine sediment from 40 women (3.2%) were observed to contain inclusion-bearing cells; polyomavirus infection was confirmed by virologic methods in 24 (60%). A polyomavirus was isolated from 12 women. Five isolates were identified as JC virus and one as BK virus. Another isolate designated AS virus appeared to be unique. Serologic studies on the 40 women were consistent with a high frequency of reactivation of JC virus, and virus excretion was related to gestation. The evidence suggests that selective excretion of JC virus may occur in pregnancy. Among 390 pregnant women without inclusion-bearing cells in their urine, 78 (20%) had a high or rising titer of serum antibody to JC or BK virus or both, a result suggesting virus reactivation, but virus excretion was not detected. In contrast to other reports, no evidence was found for transmission of BK virus to the fetus.


Two types of ON direction-selective ganglion cells in rabbit retina.
Direction-selective ganglion cells (DSGCs) respond with robust spiking to image motion in a particular direction. Previously, two main types of DSGCs have been described in rabbit retina: the ON-OFF DSGCs respond to both increases and decreases in illumination, whereas the ON DSGCs respond only to increases in illumination. In this study, we show that there are two distinct types of ON DSGCs, which can be separated by differences in their receptive-field properties, dendritic morphology and tracer-coupling pattern. While both types show robust direction-selectivity, one type responds to increases in illumination with sustained firing, whereas the other responds with relatively transient firing. The two types of ON DSGCs also have distinct dendritic morphologies: the sustained cells give rise to shorter and more numerous terminal dendrites, which are distributed throughout the dendritic field forming a space-filling lattice. In addition, the transient ON DSGCs, but not the sustained ON DSGCs, show tracer-coupling to a mosaic of amacrine cells when filled with Neurobiotin. Both types of ON DSGCs have been encountered in previous studies but were not recognized as distinct types. We propose that the two types also differ in their central projections, with only the sustained cells projecting to the medial terminal nucleus (MTN) of the accessory optic system (AOS).


Copolymers of poly(3-thiopheneacetic acid) with poly(3-hexylthiophene) as hole-transporting material for interfacially engineered perovskite solar cell by modulating band positions for higher efficiency.
In order to tune the band positions of the hole-transporting material (HTM) in an interfacially engineered perovskite solar cell (PSC), random copolymers of poly(3-thiopheneacetic acid) and poly(3-hexylthiophene) (P3TAA-co-P3HT) with different compositions were produced by oxidative polymerization. The copolymers were characterized using 1H NMR, FTIR, and UV-vis spectroscopy and gel permeation chromatography. Here, ZnO nanoparticles were used as the electron-transporting material (ETM) and methylammonium lead iodide (MAPbI3) perovskite was used as the light-absorbing material to form an FTO/ZnO/MAPbI3/copolymer/Ag device, of which the power conversion efficiency (PCE) was found to be dependent on the copolymer composition and reached a maximum (∼10%) at a P3TAA content of 43 mol% in the copolymer (P3). The band gaps of the copolymers as determined from UV-vis spectroscopy and cyclic voltammetry exhibit a staggered-gap hetero-interface configuration in which the HOMO and LUMO of P3 closely match those of MAPbI3 and give rise to the maximum PCE. Time-resolved photoluminescence spectra of MAPbI3/HTM samples indicate that charge transfer across the perovskite/copolymer interface was faster with a reduced recombination rate for a P3 sample. The electrochemical impedance spectra (EIS) of the PSCs exhibit Nyquist plots with two semicircles, which correspond to an equivalent circuit consisting of two parallel R-C and R-CPE circuits connected in series. Analysis of the data indicates that the effective electron lifetime was longest for the P3 copolymer, which indicates that the charge recombination was lower than that in the components and other copolymers. The copolymers exhibited an intermediate stability with respect to their components, and amongst the copolymers P3 exhibited the highest stability.


Comparative genomics of the mimicry switch in Papilio dardanus.
The African Mocker Swallowtail, Papilio dardanus, is a textbook example in evolutionary genetics. Classical breeding experiments have shown that wing pattern variation in this polymorphic Batesian mimic is determined by the polyallelic H locus that controls a set of distinct mimetic phenotypes. Using bacterial artificial chromosome (BAC) sequencing, recombination analyses and comparative genomics, we show that H co-segregates with an interval of less than 500 kb that is collinear with two other Lepidoptera genomes and contains 24 genes, including the transcription factor genes engrailed (en) and invected (inv). H is located in a region of conserved gene order, which argues against any role for genomic translocations in the evolution of a hypothesized multi-gene mimicry locus. Natural populations of P. dardanus show significant associations of specific morphs with single nucleotide polymorphisms (SNPs), centred on en. In addition, SNP variation in the H region reveals evidence of non-neutral molecular evolution in the en gene alone. We find evidence for a duplication potentially driving physical constraints on recombination in the lamborni morph. Absence of perfect linkage disequilibrium between different genes in the other morphs suggests that H is limited to nucleotide positions in the regulatory and coding regions of en. Our results therefore support the hypothesis that a single gene underlies wing pattern variation in P. dardanus.


Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions.
Notch signaling has been shown to play a pivotal role in inducing T lineage commitment. However, T cell progenitors are known to retain other lineage potential long after the first point at which Notch signaling is required. Thus, additional requirements for Notch signals and the timing of these events relative to intrathymic differentiation remain unknown. Here, we address this issue by culturing subsets of CD4 CD8 double negative (DN) thymocytes on control stromal cells or stromal cells expressing Delta-like 1 (Dll1). All DN subsets were found to require Notch signals to differentiate into CD4+ CD8+ T cells. Using clonal analyses, we show that CD44+ CD25+ (DN2) cells, which appeared committed to the T cell lineage when cultured on Dll1-expressing stromal cells, nonetheless gave rise to natural killer cells with a progenitor frequency similar to that of CD44+ CD25- (DN1) thymocytes when Notch signaling was absent. These data, together with the observation that Dll1 is expressed on stromal cells throughout the thymic cortex, indicates that Notch receptor-ligand interactions are necessary for induction and maintenance of T cell lineage specification at both the DN1 and DN2 stages of T cell development, suggesting that the Notch-induced repression of the B cell fate is temporally separate from Notch-induced commitment to the T lineage.


Drosophila blood cells.
Drosophila blood cells or haemocytes belong to three lineages: plasmatocytes, crystal cells and lamellocytes. There is no equivalent of a lymphoid lineage in insects which have no adaptive immunity. Haematopoiesis is under the control of a number of transcription factors and signalling pathways (such as GATA factors, JAK/STAT or Notch pathways) most of which have homologues which participate in the control of mammalian haematopoiesis. Drosophila plasmatocytes are professional phagocytes reminiscent of the cells from the mammalian monocyte/macrophage lineage. Several receptors responsible for recognition of microorganisms or apoptotic corpses have been identified, which include a Scavenger Receptor, a CD36 homologue and a peptidoglycan recognition protein. Crystal cells contain the enzymes necessary for humoral melanization that accompanies a number of immune reactions. The production of melanin generates, as by-products, cytotoxic free radicals that are believed to participate in the killing of pathogens. Finally, lamellocytes represent a cell type that specifically differentiates after parasitism of Drosophila larvae and forms a capsule around the invader. Encapsulation together with melanization eventually kill the parasite within the capsule.


Psychotherapists' practices in keeping a session 'on-track' in the face of clients' 'off-track' talk.
Based on an inspection of sessions with intellectually impaired and non-impaired clients, five conversational practices are identified by which a cognitive behaviour psychotherapist may keep the session 'on-track' in the face of possible deviation. Close inspection of audio- and video-recordings reveals a gradient of therapist responses. They range between minimal receipt of what the client has said, even when this would otherwise have warranted expansion, all the way to explicit active topic shift which is more directive. The operation of these topic-management practices is explained using Conversation Analysis, and their therapeutic utility and possible dangers are outlined. The article ends with a brief sketch of the tension between an 'outsider's' Conversation-Analysis perspective on the organization of therapy talk, and a therapist's, 'insider's' view of the meanings and intentions of what participants say.


Ethnic differences in patterns and correlates of age of initiation in a population of Air Force recruits.
Early age of initiation is a significant risk factor for long-term dependent smoking and may also relate to other unhealthy behaviors. The current study assessed age of initiation in relationship to smoking dependence and motivation to quit, physical activity, dietary intake, body mass index (BMI), attitude toward illegal drug use, binge drinking, seat belt use, and smoking status at follow-up. Subjects were 7995 Air Force recruits who reported smoking regularly up to Basic Military Training. Euro-Americans initiated smoking more than a year earlier on average (15.5 years) than did African-Americans (16.8 years), with Hispanic-Americans (16.0 years) between these two groups. No gender differences were found for age of initiation for any ethnic group. Early age of initiation in Euro-Americans was associated with greater dependence on tobacco, reduced motivation to quit, less likelihood of quitting in the next 12 months, and a number of other health risk factors including lower self-reported physical activity, greater intake of high-fat foods, more favorable attitudes toward illegal drugs, increased likelihood of binge drinking, and less reported use of seat belts. Relationships between early age of initiation and other unhealthy behaviors were less consistent for African-Americans and for neither African-Americans nor Hispanics did age of initiation predict smoking status at 1-year follow-up.


A basic macroeconomic agent-based model for analyzing monetary regime shifts.
In macroeconomics, an emerging discussion of alternative monetary systems addresses the dimensions of systemic risk in advanced financial systems. Monetary regime changes with the aim of achieving a more sustainable financial system have already been discussed in several European parliaments and were the subject of a referendum in Switzerland. However, their effectiveness and efficacy concerning macro-financial stability are not well-known. This paper defines the economic requirements for modeling the current monetary system and introduces the corresponding macroeconomic agent-based model (MABM) in a continuous-time stochastic agent-based simulation environment with a provenance model. This MABM aims to present a starting point for exploring and analyzing monetary reforms. In this context, the monetary system affects the lending potential of banks and might impact the dynamics of financial crises. MABMs are predestined to replicate emergent financial crisis dynamics, analyze institutional changes within a financial system, and thus measure macro-financial stability. The used simulation environment makes the model more accessible and facilitates exploring the impact of different hypotheses and mechanisms in a less complex way. Moreover, the model replicates a wide range of stylized economic facts, which validates it as an analysis tool to implement and compare monetary regime shifts.


An inadequate dose of ribavirin is related to virological relapse by chronic hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin.
The aim of this large-scale analysis was to assess the effect of 48-week pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) therapy on virological relapse by patients infected with hepatitis C virus (HCV) genotype 1. The relationship between virological relapse and the dose of PEG-IFNα-2b and RBV was investigated in 619 patients who had once cleared HCV RNA during PEG-IFNα-2b and RBV treatment for 48 weeks. The overall virological relapse rate was 34.1% (211 of 619). The relapse rate was 59.5% (22 of 37) for patients who received <6 mg/kg/day of RBV, even if a sufficient dose of PEG-IFNα-2b (≥1.5 μg/kg/day) was received. In contrast, the relapse rate was 28.1% (16 of 57) for patients who received ≥12 mg/kg/day of RBV, irrespective of the PEG-IFNα-2b dose. The relapse rates were significantly increased with the reduction of the RBV dose for both PEG-IFNα-2b doses of ≥1.2 and <1.2 μg/kg/week (P < 0.0001 and P = 0.0006, respectively). Moreover, the relapse rate was 41.2% (35 of 85) for patients with an early virological response (EVR) who received <6 mg/kg/day of RBV. The relapse rates were significantly increased with the reduction of the RBV dose in both those patients with an EVR and those with a late virological response (P = 0.0006 and P = 0.0088, respectively). To summarize, for HCV genotype 1 patients treated with PEG-IFNα-2b and RBV, the virological relapse of HCV was RBV dose-dependent, irrespective of the dose of PEG-IFNα or the effect of early viral kinetics.


Role of Age and Acculturation in Diet Quality Among Mexican Americans - Findings From the National Health and Nutrition Examination Survey, 1999-2012.
Age and acculturation may play a role in diet quality among Mexican Americans. This study examined diet quality in Mexican Americans by age and whether acculturation influences diet quality across different age groups, using data from the National Health and Nutrition Examination Survey (NHANES). Diet quality, measured by the Healthy Eating Index 2010, improved with age except in categories of dairy, sodium, and refined grains. More acculturation was associated with lower scores in overall diet quality and categories of vegetables, fruits, and sodium and empty calories across almost all ages, but higher scores in grain categories, especially in younger groups. A diet rich in fruits and vegetables but low in fat and sodium should be promoted among more acculturated Mexican Americans, and whole-grain foods should be promoted among young but less acculturated Mexican Americans.


[Effects of surgical ovariectomy on dopamine receptors of the heart and brain].
In female rat experiment menopause was induced by surgical ovariectomy. It is shown that false ovariectomy decreases affinity and density of dopamine receptors in the heart and brain. Surgical ovariectomy contributes to an increase in the affinity of the heart dopamine receptors as well as affinity and density of the brain dopamine receptors. Changes in density and affinity of dopamine receptors in the heart and brain of rats after surgical ovariectomy evidence for involvement of dopaminergic system in pathogenesis of menopausal syndrome.


Serum Ferritin, Weight Gain, Disruptive Behavior, and Extrapyramidal Symptoms in Risperidone-Treated Youth.
Iron deficiency disrupts dopaminergic signaling in rodents, resulting in cognitive deficits that may be reversed with psychostimulants. In humans, iron deficiency with or without anemia has similarly been found to cause neuropsychological and behavioral impairments. However, the clinical effects of low body iron stores in antipsychotic-treated children have not been examined. Medically healthy, 5- to 17-year-old boys treated with risperidone for at least 1 year were enrolled between February 2009 and November 2013 in a multiphase study, examining the skeletal effects of calcium and vitamin D supplementation in risperidone-induced hyperprolactinemia. Anthropometric measures were collected and medical and pharmacy records were reviewed to obtain treatment history. Psychiatric diagnoses were based on clinical interviews, structured interviews, rating scales, and a review of their medical records. Extrapyramidal symptoms were assessed, and a food frequency questionnaire was completed in a subsample. Laboratory tests, including ferritin concentration (a marker of body iron status), were obtained upon study entry. A total of 114 participants (mean age: 11.0 ± 2.6 years) were included, the vast majority (>90%) having attention-deficit/hyperactivity disorder and/or disruptive behavior disorder. They had taken risperidone for an average 3.1 ± 2.0 years. Their serum ferritin concentration was 37.3 ± 25.6 μg/L with 21% of the sample having a level <20 μg/L, despite appropriate daily dietary iron intake. Ferritin concentration was inversely associated with weight gain following risperidone treatment onset but was not significantly associated with prolactin. After adjusting for the weight-adjusted dose of psychostimulants and risperidone and the daily dose of selective serotonin reuptake inhibitors, ferritin was inversely associated with the severity of disruptive behavior and positively associated (albeit marginally) with prosocial behavior. No association was found between ferritin concentration and extrapyramidal symptoms. Body iron stores are inversely related to risperidone-induced weight gain, even after extended treatment and despite adequate iron intake. Low iron stores are associated with poorer treatment response. Future research should examine iron absorption during antipsychotic treatment and whether repleting iron stores would facilitate clinical response.


Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study.
Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0-5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.


Effects of oral epigallocatechin gallate supplementation on the minimal erythema dose and UV-induced skin damage.
Excessive exposure to UV radiation causes acute adverse effects like sunburn and photosensitivity reactions and is involved in the induction and development of skin cancer. It has been reported that antioxidants have photoprotective effects against solar UV radiation. We investigated the effect of oral epigallocatechin gallate (EGCG), a powerful antioxidant in green tea, on the minimal erythema dose (MED) and UV-induced skin damage. Female HWY/Slc hairless rats were fed the normal diet supplemented with 1,500 ppm EGCG for 8 weeks; then, the MED was determined and visual scores and transepidermal water loss were assessed to evaluate the severity of UV-induced skin damage. At week 8 of the study, the use of dietary EGCG significantly increased MED. UV-radiation-induced sunburn severity and alterations in epidermal barrier function were also attenuated by the supplementation of EGCG. Regular intake of EGCG strengthens the skin's tolerance by increasing MED and thus prevents UV-induced perturbation of epidermal barrier function and skin damage. These results suggest that EGCG is a potent candidate for systemic photoprotection.


[Localisation of brain function, 125 years after the thesis of Aletta Jacobs, the first Dutch female physician].
Aletta H. Jacobs was the first female physician in the Netherlands. In 1879, she defended her thesis which addressed the subject of localising brain functions. In it she described three neurological patients using systematic conventions highly resembling those in use today. Moreover, she discussed whether or not functions were regionally represented. Her discussion concluded in favour of localisation. These days, the concept of distributed networks goes beyond simple topographical representation. This is illustrated in the cerebral organisation of vision. It is possible to discern visual centres that are specialised in processing specific qualities such as colour or visual motion. An additional feature of such segregated processing streams is the presence of underlying connections to specific brain areas at a distance. Functioning as a node in multiple networks, one single brain region may potentially be involved in multiple functions. This depends on the interactions with other regions and on the actual dominance of information processing within such networks.


Phenotypic and evolutionary consequences of social behaviours: interactions among individuals affect direct genetic effects.
Traditional quantitative genetics assumes that an individual's phenotype is determined by both genetic and environmental factors. For many animals, part of the environment is social and provided by parents and other interacting partners. When expression of genes in social partners affects trait expression in a focal individual, indirect genetic effects occur. In this study, we explore the effects of indirect genetic effects on the magnitude and range of phenotypic values in a focal individual in a multi-member model analyzing three possible classes of interactions between individuals. We show that social interactions may not only cause indirect genetic effects but can also modify direct genetic effects. Furthermore, we demonstrate that both direct and indirect genetic effects substantially alter the range of phenotypic values, particularly when a focal trait can influence its own expression via interactions with traits in other individuals. We derive a function predicting the relative importance of direct versus indirect genetic effects. Our model reveals that both direct and indirect genetic effects can depend to a large extent on both group size and interaction strength, altering group mean phenotype and variance. This may lead to scenarios where between group variation is much higher than within group variation despite similar underlying genetic properties, potentially affecting the level of selection. Our analysis highlights key properties of indirect genetic effects with important consequences for trait evolution, the level of selection and potentially speciation.


Transcranial Direct Current Stimulation Does Not Counteract Cognitive Fatigue, but Induces Sleepiness and an Inter-Hemispheric Shift in Brain Oxygenation.
Sustained cognitive demands may result in cognitive fatigue (CF), eventually leading to decreased behavioral performance and compromised brain resources. In the present study, we tested the hypothesis that transcranial direct current stimulation (tDCS) would counteract the behavioral and neurophysiological effects of CF. Twenty young healthy participants were tested in a within-subject counterbalanced order across two different days. Anodal tDCS (real vs. sham) was applied over the left prefrontal cortex. In the real tDCS condition, a current of 1.5 mA was delivered for 25 min. Cortical oxygenation changes were measured using functional Near Infrared Spectroscopy (fNIRS) on the frontal cortices. CF was triggered using the TloadDback task, a sustained working memory paradigm that allows tailoring task demands according to each individual's maximal cognitive capacity. Sustained cognitive load-related effects were assessed using pre- versus post-task subjective fatigue and sleepiness scales, evolution of performance accuracy within the task, indirect markers of dopaminergic activity (eye blinks), and cortical oxygenation changes (fNIRS) both during the task and pre- and post-task resting state periods. Results consistently disclosed significant CF-related effects on performance. Transcranial DCS was not effective to counteract the behavioral effects of CF. In the control (sham tDCS) condition, cerebral oxygen exchange (COE) levels significantly increased in the right hemisphere during the resting state immediately after the induction of CF, suggesting a depletion of brain resources. In contrast, tDCS combined with CF induction significantly shifted interhemispheric oxygenation balance during the post-training resting state. Additionally, increased self-reported sleepiness was associated with brain activity in the stimulated hemisphere after recovery from CF during the tDCS condition only, which might reflect a negative middle-term effect of tDCS application.


One problem, many solutions: simple statistical approaches help unravel the complexity of the immune system in an ecological context.
The immune system is a complex collection of interrelated and overlapping solutions to the problem of disease. To deal with this complexity, researchers have devised multiple ways to measure immune function and to analyze the resulting data. In this way both organisms and researchers employ many tactics to solve a complex problem. One challenge facing ecological immunologists is the question of how these many dimensions of immune function can be synthesized to facilitate meaningful interpretations and conclusions. We tackle this challenge by employing and comparing several statistical methods, which we used to test assumptions about how multiple aspects of immune function are related at different organizational levels. We analyzed three distinct datasets that characterized 1) species, 2) subspecies, and 3) among- and within-individual level differences in the relationships among multiple immune indices. Specifically, we used common principal components analysis (CPCA) and two simpler approaches, pair-wise correlations and correlation circles. We also provide a simple example of how these techniques could be used to analyze data from multiple studies. Our findings lead to several general conclusions. First, relationships among indices of immune function may be consistent among some organizational groups (e.g. months over the annual cycle) but not others (e.g. species); therefore any assumption of consistency requires testing before further analyses. Second, simple statistical techniques used in conjunction with more complex multivariate methods give a clearer and more robust picture of immune function than using complex statistics alone. Moreover, these simpler approaches have potential for analyzing comparable data from multiple studies, especially as the field of ecological immunology moves towards greater methodological standardization.


A new time-domain narrowband velocity estimation technique for Doppler ultrasound flow imaging. II. Comparative performance assessment.
For pt.I see ibid., vol.45, no.4, pp.939-54 (1998). The statistical performance of the new 2-D narrowband time-domain root-MUSIC blood velocity estimator described previously is evaluated using both simulated and flow phantom wideband (50% fractional bandwidth) ultrasonic data. Comparisons are made with the standard 1-D Kasai estimator and two other wideband strategies: the time domain correlator and the wideband point maximum likelihood estimator. A special case of the root-MUSIC, the "spatial" Kasai, is also considered. Simulation and flow phantom results indicate that the root-MUSIC blood velocity estimator displays a superior ability to reconstruct spatial blood velocity information under a wide range of operating conditions. The root-MUSIC mode velocity estimator can be extended to effectively remove the clutter component from the sample volume data. A bimodal velocity estimator is formed by processing the signal subspace spanned by the eigenvectors corresponding to the two largest eigenvalues of the Doppler correlation matrix. To test this scheme, in vivo common carotid flow complex Doppler data was obtained from a commercially available color flow imaging system. Velocity estimates were made using a reduced form of this data corresponding to higher frame rates. The extended root-MUSIC approach was found to produce superior results when compared to both 1- and 2-D Kasai-type estimators that used initialized clutter filters. The results obtained using simulated, flow phantom, and in vivo data suggest that increased sensitivity as well as effective clutter suppression can be achieved using the root-MUSIC technique, and this may be particularly important for wideband high frame rate imaging applications.


Oral health status of patients seeking emergency dental care in Transkei.
The oral health status of a rural Black population seeking dental treatment was determined at three separate locations in Transkei. Of the patients who presented for treatment 92 per cent were suffering from acute or chronic pain. The main reason for seeking care was pain resulting from dental caries (84 per cent). Inadequate oral hygiene practice was uniformly evident in all the patients at the three locations, as well as within all the age groups. The pattern of gingival bleeding was also comparable by age and location and its distribution closely parallelled the oral debris scores. The mean DMFT for the total population (n = 290) was 5,7 (s.d. 6,1); and 17,0 per cent were caries-free. Caries was more widespread and severe in the patients at the military base in Port St Johns where the mean DMFT of 10,6 differed greatly from the mean DMFT scores of patients at Port St. Johns (3,6) and Elliotdale (4,5). Untreated dental decay accounted for a large percentage of the DMFT at all three sites but in the military group, the untreated decay component, (60,4 per cent of the DMFT), was the highest. With the stratification of the data by age, the average DMFT (8,4), was highest in the 31-50 age group.


Co-cultivation of antifungal Lactobacillus plantarum MiLAB 393 and Aspergillus nidulans, evaluation of effects on fungal growth and protein expression.
The fungal inhibitory effects of strain Lactobacillus plantarum MiLAB 393, producing broad-spectrum antifungal compounds, were evaluated. A co-cultivation method was set up to monitor effects on fungal growth and protein expression of growing Aspergillus nidulans with L. plantarum MiLAB 393. The effects of inhibitory metabolites produced by L. plantarum MiLAB 393, cyclo(l-Phe-l-Pro), lactic acid and 3-phenyllactic acid, were also investigated by addition of pure compounds to the growth medium of A. nidulans. The co-cultivation strongly affected the morphology of the fungal mycelium and decreased the biomass to 36% of control. Co-cultivation with Lactobacillus coryniformis MiLAB 123 gave only marginal morphological changes and minor biomass reduction, suggesting specific effects of L. plantarum MiLAB 393. The amount of several A. nidulans-proteins was increased during co-cultivation and by all of the inhibiting substances. This study shows that the growth of A. nidulans is inhibited during co-cultivation with L. plantarum MiLAB 393 and that the expression of fungal proteins is altered.