A multi-country analysis on potential adaptive mechanisms to cold and heat in a changing climate.
Temporal variation of temperature-health associations depends on the combination of two pathways: pure adaptation to increasingly warmer temperatures due to climate change, and other attenuation mechanisms due to non-climate factors such as infrastructural changes and improved health care. Disentangling these pathways is critical for assessing climate change impacts and for planning public health and climate policies. We present evidence on this topic by assessing temporal trends in cold- and heat-attributable mortality risks in a multi-country investigation. Trends in country-specific attributable mortality fractions (AFs) for cold and heat (defined as below/above minimum mortality temperature, respectively) in 305 locations within 10 countries (1985-2012) were estimated using a two-stage time-series design with time-varying distributed lag non-linear models. To separate the contribution of pure adaptation to increasing temperatures and active changes in susceptibility (non-climate driven mechanisms) to heat and cold, we compared observed yearly-AFs with those predicted in two counterfactual scenarios: trends driven by either (1) changes in exposure-response function (assuming a constant temperature distribution), (2) or changes in temperature distribution (assuming constant exposure-response relationships). This comparison provides insights about the potential mechanisms and pace of adaptation in each population. Heat-related AFs decreased in all countries (ranging from 0.45-1.66% to 0.15-0.93%, in the first and last 5-year periods, respectively) except in Australia, Ireland and UK. Different patterns were found for cold (where AFs ranged from 5.57-15.43% to 2.16-8.91%), showing either decreasing (Brazil, Japan, Spain, Australia and Ireland), increasing (USA), or stable trends (Canada, South Korea and UK). Heat-AF trends were mostly driven by changes in exposure-response associations due to modified susceptibility to temperature, whereas no clear patterns were observed for cold. Our findings suggest a decrease in heat-mortality impacts over the past decades, well beyond those expected from a pure adaptation to changes in temperature due to the observed warming. This indicates that there is scope for the development of public health strategies to mitigate heat-related climate change impacts. In contrast, no clear conclusions were found for cold. Further investigations should focus on identification of factors defining these changes in susceptibility.


Are hydroxychloroquine and chloroquine effective in the treatment of SARS-COV-2 (COVID-19)?
Data sources The authors of this rapid review did not disclose which electronic databases were included in their literature search. The inclusion and exclusion criteria for the data sources are not reported in the manuscript.Study selection The authors included six studies on the effectiveness of hydroxychloroquine or chloroquine for the prevention and treatment of COVID-19 in humans. Studies comprised of two randomised controlled trials, two non-randomised trials both of which were non-blinded and open-label and one that was uncontrolled, a prospective cohort study and an interim report. The authors did not report details of any studies that were excluded.Data extraction and synthesis The data extraction methodology was not reported and it is unclear if the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed. Treatment regimens and the study outcomes were extracted where available and overall findings were presented in a table. There were no comparable outcome measures; therefore, results were deemed unsuitable to combine and no statistical analyses were carried out. A narrative synthesis of each study is presented.Results The results of the studies in this rapid review are difficult to quantify as each study had different outcome parameters. Due to the heterogeneity of the studies, results were not combined, and no statistical analysis was carried out. Narrative synthesis of each of the included studies identified important and significant limitations, precluding the studies from demonstrating a statistically significant difference in outcomes.Conclusions This review highlights the urgent need for more high quality evidence on the use of hydroxychloroquine and chloroquine in the prevention and treatment of COVID-19. The results of the studies included should be interpreted with caution due to the weak supporting data and numerous methodological limitations. The authors suggested that the studies be viewed as hypothesis-generating and should not be used in decision making around the recommendations and guidelines in the prevention and treatment of COVID-19. There are currently several ongoing randomised controlled trials looking at the effectiveness and efficacy of these drugs on COVID-19. It is hoped the outcome of these studies can help guide future recommendations and national guidelines.


Health Regulatory Focus, Selection Optimization and Compensation Strategy and Sports Practice: A Mediational Analysis.
This study aimed to investigate associations of health promotion and prevention regulatory foci with sports practice, and examined the Selection, Optimization and Compensation (SOC) process behind the positive relationship between health promotion focus and sports practice. A cross-sectional study was conducted with 513 French volunteer sports participants aged from 18 to 82. Participants completed an online self-report survey measuring health regulatory foci, SOC strategy, Amount of Sports Practice (ASP), health condition, and educational level. Path analysis main results (χ2 = 16.64; df = 5; p < .01; RMSEA = 0.067; CFI = 0.98; R2 = .24) demonstrated that ASP was positively related with health promotion focus (β = .13, p < .01), SOC strategy (β = .28, p < .001) and negatively related with health prevention focus (β = -.20, p < .001). SOC strategy was positively related with health promotion focus (β = .39, p < .001) and bootstrapping analyses revealed that this strategy partially mediated the positive relationship between health promotion focus and ASP, 95% CI [.13, .29]. Finally, additional analyses showed that it was specifically the elective selection, optimization and compensation sub-components of SOC strategy which played mediating roles in this link, [.13, .29] < 95% CI < [.13, .29]. For the first time in the literature, these results evidenced direct links between health regulatory foci and sports practice, and a mechanistic pathway between health promotion focus and sports practice. The theoretical and applied implications of these results for sports promotion are discussed.


Parasites as accumulation indicators of heavy metal pollution.
Parasites are attracting increasing interest from parasite ecologists as potential indicators of environmental quality because of the variety of ways in which they respond to anthropogenic pollution. However, until recently, little was known about the accumulation of toxins within parasites. Certain parasites, particularly intestinal acanthocephalans and cestodes of fish, can accumulate heavy metals at concentrations that are orders of magnitude higher than those in the host tissues or the environment. In this review, Bernd Sures, Roy Siddall and Horst Taraschewski discuss the recently described phenomenon of conspicuous metal accumulation by parasites and how this might be applied to environmental monitoring. They also suggest how environmental science and parasitology might profit from each other in the near future.


Rapid liquid chromatographic assay for the determination of acetaminophen in plasma after propacetamol administration: application to pharmacokinetic studies.
A simple method for the rapid estimation of acetaminophen in plasma is described here. p-Propionamidophenol was used as internal standard. The assay involved a single ethyl acetate extraction and liquid chromatographic analysis at a wavelength of 242 nm using a reversed-phase encapped column, with a mobile phase of acetonitrile and 0.005 M potassium dihydrogen phosphate adjusted at pH 3.00. The limit of quantitation of acetaminophen by this method was 0.05 microg ml(-1), only 0.1 ml of the plasma sample was required for the determination. The calibration graph was linear from 0.05 to 100 microg ml(-1). Intra and inter-day precision (CV) did not exceed 8.93%. Mean recoveries of 90.31% with a CV of 1.38% were obtained. Applicability of the method was demonstrated by a pharmacokinetic study in normal volunteers who received 2 mg propacetamol.


Aortic tissue properties in porcine models: A comparison of ex vivo mechanical test results after simulated aortic arch reconstructions.
Surgical interventions on the arterial wall can produce modifications to its tissue characteristics, and the addition of synthetic materials of different types can have implications on hemodynamics and blood vessel wall behavior. This work studies the midterm effects of end-to-end anastomosis (E/E), Gore-tex graft interposition (GGI) and Gore-tex patch graft aortoplasty (GPGA) in aortic arch reconstruction. The study comprised of two groups of healthy Danish sows. The sows in the first group (short term (ST)) weighed about 40 kg, underwent a surgical operation and were sacrificed on the same day. The sows in the second group (midterm (MT)) weighed 5-10 kg, underwent a surgical operation and were then allowed to grow to a weight of about 30-40 kg, before being sacrificed. One sow in each group was scheduled for E/E and one sow for GGI. One sow in ST and two sows in MT received GPGA. The overall average wall thickness was 1.93 mm. Relaxation constant values were significantly higher for ST (5.221 +/- 1.832 sec) than for MT (2.184 +/- 1.216 sec). GPGA showed a greater impact on relaxation than other procedures, enhancing the viscous character. The working-point Young's modulus (Epw ) was not significantly different in ST and MT. Circumferential samples had different Epw (0.419 +/- 0.77 MPa) from longitudinal samples (0.902 +/- 0.378 MPa). There also appeared to be a significant difference between samples cut longitudinally on the left and the right sides of the wall. The overall average Epw value was 0.6609 +/- 0.3641 MPa.


Form I Rubiscos from non-green algae are expressed abundantly but not assembled in tobacco chloroplasts.
Non-green algae have Rubiscos that are phylogenetically distinct from their counterparts in green algae and higher plants. Some non-green-algal Rubiscos are more specific for CO2, relative to O2, than higher-plant Rubiscos, sometimes coupled with lower Michaelis constants for CO2. If these Rubiscos could be substituted for the higher-plant enzyme, and if they functioned successfully in the higher-plant chloroplast and were regulated appropriately, they would improve the CO2 use and quantum efficiency of higher-plant photosynthesis. To assess the feasibility of expressing non-green algal Rubiscos in higher-plant chloroplasts, we inserted the rbcLS operons from the rhodophyte Galdieria sulphuraria and the diatom Phaeodactylum tricornutum into the inverted repeats of the plastid genome of tobacco, leaving the tobacco rbcL gene unaltered. Homoplasmic transformants were selected. The transgenes directed the synthesis of abundant amounts of transcripts and both subunits of the foreign Rubiscos. In some circumstances, leaves of the transformants with the P. tricornutum Rubisco contained as much foreign Rubisco protein as endogenous tobacco Rubisco (>30% of the soluble leaf protein). However, the subunits of the foreign Rubiscos were not properly folded and/or assembled. All the foreign large subunits and most of the foreign small subunits were recovered in the insoluble fractions of leaf extracts. Edman sequencing yielded the expected N-terminal sequences for the foreign small subunits but the N-termini of the foreign large subunits were blocked. Accumulation of large amounts of denatured foreign Rubisco in the leaves, particularly of the P. tricornutum transformants, caused a reduction in the amount of tobacco Rubisco present, with concomitant reductions in leaf CO2 assimilation and plant growth.


Hemocompatible curcumin-dextran micelles as pH sensitive pro-drugs for enhanced therapeutic efficacy in cancer cells.
Curcumin, a component in spice turmeric, is renowned to possess anti-cancer therapeutic potential. However, low aqueous solubility and instability of curcumin which subsequently affects its bioavailability pose as major impediments in its translation to clinical application. In this regard, we focused on conjugating hydrophobic curcumin to the hydrophilic backbone of dextran via succinic acid spacer to design a pro-drug. The structural confirmation of the conjugates was carried out using FTIR and (1)H NMR spectroscopy. Critical micelle measurement affirmed the micelle formation of the pro-drug in aqueous media. The size distribution and zeta potential of the curcumin-dextran (Cur-Dex) micelles were determined using dynamic light scattering technique. The micellar architecture bestowed curcumin negligible susceptibility to degradation under physiological conditions along with enhanced aqueous solubility. Biocompatibility of the micelles was proved by the blood component aggregation and plasma protein interaction studies. In vitro release studies demonstrated the pH sensitivity release of curcumin which is conducive to the tumour micro environment. Profound cytotoxic effects of Cur-Dex micelles in C6 glioma cells were observed from MTT and Live/Dead assay experiments. Moreover, enhanced cellular internalization of the Cur-Dex micelles compared to free curcumin in the cancer cells was revealed by fluorescence microscopy. Our study focuses on the feasibility of Cur-Dex micelles to be extrapolated as promising candidates for safe and efficient cancer therapy.


The Environmental Determinants of Diabetes in the Young (TEDDY) Study.
The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints.


Amide isosteres in structure-activity studies of antibacterial minor groove binders.
Antibacterial minor groove binders related to the natural product, distamycin, are development candidates for novel antibiotics. Alkenes have been found to be effective substitutes for the isosteric amide links in some positions and alkyl groups larger than methyl have been found to increase binding to DNA in both selectivity and affinity. However the impact of other isosteres such as diazenes and the position of an alkyl group with respect to DNA binding and antibacterial activity are not known. The effects of some systematic variations in the structure of polyamide minor groove binders are investigated. Isosteres of the amide link (alkenes and diazenes) are compared: it is shown that all three are competent for binding to DNA but that alkene links give the tightest binding and highest antibacterial activity; no significant antibacterial activity was found for compounds with a diazene link. Within a series of alkene linked compounds, the effect of branched N-alkyl substituents on binding to DNA and antibacterial activity is investigated: it was found that C3 and C4 branched chains are acceptable at the central pyrrole residue but that at the pyrrole ring adjacent to the basic tail group, a C4 branched chain was too large both for DNA binding and for antibacterial activity. The active branched alkyl chain compounds were found to be especially active against Mycobacterium aurum, a bacterium related to the causative agent of tuberculosis.


Potential commercial applications of microbial surfactants.
Surfactants are surface-active compounds capable of reducing surface and interfacial tension at the interfaces between liquids, solids and gases, thereby allowing them to mix or disperse readily as emulsions in water or other liquids. The enormous market demand for surfactants is currently met by numerous synthetic, mainly petroleum-based, chemical surfactants. These compounds are usually toxic to the environment and non-biodegradable. They may bio-accumulate and their production, processes and by-products can be environmentally hazardous. Tightening environmental regulations and increasing awareness for the need to protect the ecosystem have effectively resulted in an increasing interest in biosurfactants as possible alternatives to chemical surfactants. Biosurfactants are amphiphilic compounds of microbial origin with considerable potential in commercial applications within various industries. They have advantages over their chemical counterparts in biodegradability and effectiveness at extreme temperature or pH and in having lower toxicity. Biosurfactants are beginning to acquire a status as potential performance-effective molecules in various fields. At present biosurfactants are mainly used in studies on enhanced oil recovery and hydrocarbon bioremediation. The solubilization and emulsification of toxic chemicals by biosurfactants have also been reported. Biosurfactants also have potential applications in agriculture, cosmetics, pharmaceuticals, detergents, personal care products, food processing, textile manufacturing, laundry supplies, metal treatment and processing, pulp and paper processing and paint industries. Their uses and potential commercial applications in these fields are reviewed.


Harmonic publication and citation counting: sharing authorship credit equitably - not equally, geometrically or arithmetically.
Bibliometric counting methods need to be validated against perceived notions of authorship credit allocation, and standardized by rejecting methods with poor fit or questionable ethical implications. Harmonic counting meets these concerns by exhibiting a robust fit to previously published empirical data from medicine, psychology and chemistry, and by complying with three basic ethical criteria for the equitable sharing of authorship credit. Harmonic counting can also incorporate additional byline information about equal contribution, or the elevated status of a corresponding last author. By contrast, several previously proposed counting schemes from the bibliometric literature including arithmetic, geometric and fractional counting, do not fit the empirical data as well and do not consistently meet the ethical criteria. In conclusion, harmonic counting would seem to provide unrivalled accuracy, fairness and flexibility to the long overdue task of standardizing bibliometric allocation of publication and citation credit.


Graphle: Interactive exploration of large, dense graphs.
A wide variety of biological data can be modeled as network structures, including experimental results (e.g. protein-protein interactions), computational predictions (e.g. functional interaction networks), or curated structures (e.g. the Gene Ontology). While several tools exist for visualizing large graphs at a global level or small graphs in detail, previous systems have generally not allowed interactive analysis of dense networks containing thousands of vertices at a level of detail useful for biologists. Investigators often wish to explore specific portions of such networks from a detailed, gene-specific perspective, and balancing this requirement with the networks' large size, complex structure, and rich metadata is a substantial computational challenge. Graphle is an online interface to large collections of arbitrary undirected, weighted graphs, each possibly containing tens of thousands of vertices (e.g. genes) and hundreds of millions of edges (e.g. interactions). These are stored on a centralized server and accessed efficiently through an interactive Java applet. The Graphle applet allows a user to examine specific portions of a graph, retrieving the relevant neighborhood around a set of query vertices (genes). This neighborhood can then be refined and modified interactively, and the results can be saved either as publication-quality images or as raw data for further analysis. The Graphle web site currently includes several hundred biological networks representing predicted functional relationships from three heterogeneous data integration systems: S. cerevisiae data from bioPIXIE, E. coli data using MEFIT, and H. sapiens data from HEFalMp. Graphle serves as a search and visualization engine for biological networks, which can be managed locally (simplifying collaborative data sharing) and investigated remotely. The Graphle framework is freely downloadable and easily installed on new servers, allowing any lab to quickly set up a Graphle site from which their own biological network data can be shared online.


On the interfacial activation of Candida antarctica lipase A and B as compared with Humicola lanuginosa lipase.
The interfacial activation of Candida antarctica lipase A (CALA) and B (CALB) has been investigated and compared with that of Humicola lanuginosa lipase (HLL). CALB displayed no interfacial activation towards p-nitrophenyl butyrate (PNPB) when exceeding the solubility limit of the substrate. No activation was observed towards p-nitrophenyl acetate (PNPA) at the addition of sodium dodecyl sulfate (SDS) nor in the presence of a solid polystyrene surface. The catalytic action of CALB was very different from that of Humicola lanuginosa lipase, which showed a pronounced interfacial activation with the same substrates. The basis for the anomalous behaviour of CALB is proposed to be due to the absence of a lid that regulates the access to the active site. In contrast to CALB, CALA expressed interfacial activation, but the activation was not as prominent as for Humicola lanuginosa lipase (HLL). The structural basis for the activation of CALA is unknown.


Neurofeedback: A Comprehensive Review on System Design, Methodology and Clinical Applications.
Neurofeedback is a kind of biofeedback, which teaches self-control of brain functions to subjects by measuring brain waves and providing a feedback signal. Neurofeedback usually provides the audio and or video feedback. Positive or negative feedback is produced for desirable or undesirable brain activities, respectively. In this review, we provided clinical and technical information about the following issues: (1) Various neurofeedback treatment protocols i.e. alpha, beta, alpha/theta, delta, gamma, and theta; (2) Different EEG electrode placements i.e. standard recording channels in the frontal, temporal, central, and occipital lobes; (3) Electrode montages (unipolar, bipolar); (4) Types of neurofeedback i.e. frequency, power, slow cortical potential, functional magnetic resonance imaging, and so on; (5) Clinical applications of neurofeedback i.e. treatment of attention deficit hyperactivity disorder, anxiety, depression, epilepsy, insomnia, drug addiction, schizophrenia, learning disabilities, dyslexia and dyscalculia, autistic spectrum disorders and so on as well as other applications such as pain management, and the improvement of musical and athletic performance; and (6) Neurofeedback softwares. To date, many studies have been conducted on the neurofeedback therapy and its effectiveness on the treatment of many diseases. Neurofeedback, like other treatments, has its own pros and cons. Although it is a non-invasive procedure, its validity has been questioned in terms of conclusive scientific evidence. For example, it is expensive, time-consuming and its benefits are not long-lasting. Also, it might take months to show the desired improvements. Nevertheless, neurofeedback is known as a complementary and alternative treatment of many brain dysfunctions. However, current research does not support conclusive results about its efficacy.


Additional US or DBT after digital mammography: which one is the best combination?
Digital mammography (DM) is widespread used for the detection of breast cancer, but its sensitivity drops in dense breasts. It is well known that additional breast ultrasound (US) and digital breast tomosynthesis (DBT) increase the sensitivity of DM. However, to our knowledge, there are no articles comparing the role of both additional techniques. To assess the diagnostic performance of DM and the different combinations of DM + additional DBT and DM + additional US in an enriched sample of patients. Retrospective study in an enriched sample of 1042 patients. Out of them, 84 patients had histologically proven malignant lesions and 258 patients had benign lesions. Finally 700 patients with normal explorations or benign lesions without biopsy confirmation (but stable for at least 12 months) were included. All of them underwent DM, US, and DBT examinations that were retrospectively reviewed by one expert radiologist, blinded to the final diagnoses. The DBT examinations were performed using one single view with wide angle (50°). The reader categorized the cases as benign (BI-RADS 1 or 2) or malignant (BI-RADS 3-5) for DM and the different combination of techniques. The sensitivity (SE) and specificity (SP) were calculated with the PEPI software and the ROC curves of the different techniques and combinations were calculated by using the SPSS 15.0 software. The SE and SP of DM were 69.05% and 88.20%, respectively. Additional DBT significantly increased the AUC of DM as well as additional US or the combination DM + DBT + US (P < 0.05). However there were no significant differences between the AUC of DM + US and DM + DBT (P = 0.7). Additional US, DBT, or both, in combination with DM, significantly increased the AUC of DM. However, there were no significant differences between DM + DBT and DM + US.


Nasopharyngeal Pneumococcal Colonization Density Is Associated With Severe Pneumonia in Young Children in the Lao People's Democratic Republic.
No studies have explored the association between pneumococcal nasopharyngeal density and severe pneumonia using the World Health Organization (WHO) 2013 definition. In Lao People's Democratic Republic (Lao PDR), we determine the association between nasopharyngeal pneumococcal density and severe pneumonia in children. A prospective observational study was undertaken at Mahosot Hospital, Vientiane, from 2014 to mid-2018. Children <5 years admitted with acute respiratory infections (ARIs) were included. Clinical and demographic data were collected alongside nasopharyngeal swabs for pneumococcal quantification by lytA real-time quantitative polymerase chain reaction. Severe pneumonia was defined using the 2013 WHO definition. For pneumococcal carriers, a logistic regression model examined the association between pneumococcal density and severe pneumonia, after adjusting for potential confounders including demographic and household factors, 13-valent pneumococcal conjugate vaccine status, respiratory syncytial virus co-detection, and preadmission antibiotics. Of 1268 participants with ARI, 32.3% (n = 410) had severe pneumonia and 36.9% (n = 468) had pneumococcal carriage. For pneumococcal carriers, pneumococcal density was positively associated with severe pneumonia (adjusted odds ratio, 1.4 [95% confidence interval, 1.1-1.8]; P = .020). Among children with ARIs and pneumococcal carriage, pneumococcal carriage density was positively associated with severe pneumonia in Lao PDR. Further studies may determine if pneumococcal density is a useful marker for pneumococcal conjugate vaccine impact on childhood pneumonia.


Involvement of alpha-1 and alpha-2 adrenoceptors in the postlaparotomy intestinal motor disturbances in the rat.
The effects of phentolamine, yohimbine and prazosin on laparotomy induced intestinal motor disturbances were studied in anaesthetised fasted rats previously equipped with electrodes, chronically implanted on the duodenum and jejunum. During continuous recording of interdigestive myoelectric activity, laparotomy under thiopental anaesthesia (Nesdonal 40 mg/kg ip) induced a primary phase of total inhibition of spiking activity lasting 26.1 +/- 1.3 min (mean +/- SE) followed by a period of disorganised activity, the first propagated migrating myoelectric complex (MMC) occurring 71.4 +/- 7.9 min after laparotomy. Phentolamine (3 mg/kg), or yohimbine (1 mg/kg) given im before laparotomy decreased by 48 and 49%, respectively, the duration of postsurgical inhibition, with a normal MMC pattern occurring immediately after. In contrast, there was only a shortening of the postlaparotomy initial inhibition of spiking activity after im prazosin (100 micrograms/kg), with a late (50-60 min) recovery of the MMC pattern. These results suggest that the initial inhibition of intestinal motility induced by laparotomy may involve alpha-1 and alpha-2 adrenoceptors, while the disruption of the MMC pattern is mainly caused by the activation of alpha-2 receptors.


Bio-optical model describing the distribution of irradiance at the sea surface resulting from a point source embedded in the ocean.
A model of the optical properties of the ocean, providing the absorption and scattering coefficients of the medium as nonlinear functions of the concentration of pigments associated with phytoplankton and their immediate detrital material, is presented. Monte Carlo computations of the attenuation coefficient of downwelling irradiance K(d) for an ocean-atmosphere system illuminated by the sun at zenith, agree well with experimental data and demonstrate the validity of such a model for studying the influence of phytoplankton biomass on the propagation to the surface of light generated through bioluminescence. The radiative transfer equation for the irradiance at the sea surface resulting frow illumination by a point source embedded in the water is solved by Monte Carlo techniques. The solution technique is validated through comparison with an asymptotic analytic solution for isotropic scattering. The computations show that the irradiance distribution just beneath the surface as a function of R, the distance measured along the surface from a point vertically above the source, is described by two regimes: (1) a regime in which the irradiance is governed mostly by absorption and geometry with scattering playing a negligible role-the near field; (2) a regime in which the light field at the surface is very diffuse and the irradiance decays approximately exponentially in R and is a very weak function of the source depth-the diffusion regime. The near field is of primary interest because it contains most of the power reaching the sea surface. An analytical model of the irradiance distribution just beneath the surface as a function of R, the source depth, and the pigment concentration for the near field is presented. This model is based on the observation that at most scattering events the change in the photon's direction is slight, and therefore, scattering is rather ineffective in attenuating the irradiance. An analytic solution for the irradiance from the point source, then, is first carried out ignoring scattering altogether; however, recognizing that backscattering will attenuate the irradiance, the absorption coefficient is replaced by an effective attenuation coefficient k. This effective attenuation coefficient is determined by fitting the total power just beneath the surface determined from the Monte Carlo computations to the analytical model. The resulting k is closely related to K(d), and the Monte Carlo irradiance as a function of R and source depth in the near-field regime can be approximated with high accuracy using the model. These results indicate K(d) can be estimated at night by releasing a point source in the water, measuring the irradiance at the surface as it sinks, and fitting the measurements to the relationships developed here to determine k. The analytic model also enables estimation of the source depth and power from the irradiance distribution just beneath the surface.


Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop.
Cyclin-dependent kinase 7 (CDK7) is the catalytic subunit of the metazoan CDK-activating kinase (CAK), which activates CDKs, such as CDC2 and CDK2, through phosphorylation of a conserved threonine residue in the T loop. Full activation of CDK7 requires association with a positive regulatory subunit, cyclin H, and phosphorylation of a conserved threonine residue at position 170 in its own T loop. We show that threonine-170 of CDK7 is phosphorylated in vitro by its targets, CDC2 and CDK2, which also phosphorylate serine-164 in the CDK7 T loop, a site that perfectly matches their consensus phosphorylation site. In contrast, neither CDK4 nor CDK7 itself can phosphorylate the CDK7 T loop in vitro. The ability of CDC2 or CDK2 and CDK7 to phosphorylate each other but not themselves implies that each kinase can discriminate among closely related sequences and can recognize a substrate site that diverges from its usual preferred site. To understand the basis for this paradoxical substrate specificity, we constructed a chimeric CDK with the T loop of CDK7 grafted onto the body of CDK2. Surprisingly, the hybrid enzyme, CDK2-7, was efficiently activated in cyclin A-dependent fashion by CDK7 but not at all by CDK2. CDK2-7, moreover, phosphorylated wild-type CDK7 but not CDK2. Our results suggest that the primary amino acid sequence of the T loop plays only a minor role, if any, in determining the specificity of cyclin-dependent CAKs for their CDK substrates and that protein-protein interactions involving sequences outside the T loop can influence substrate specificity both positively and negatively.


A Comparison between School and Home Rating Scales and Reliability-Validity of the Scales-the Scales for Diagnosing Attention-Deficit/Hyperactivity Disorder.
The purpose of the present research is to compare the Turkish translations of school and home versions of the Scales for Diagnosing Attention-Deficit/Hyperactivity Disorder (SCALES) developed by Ryser and McConnell with respect to age and gender and to examine the correlation between the two scales. The research was conducted with 102 teachers and parents of 891 children aged between 5.0 and 14.11 years. 656 scale forms of parents returned to us were included in the study. The teachers filled in teacher information form, child information form, SCALES-School Rating Scale and the Turkish version of Conners' Teacher Rating Scale. The parents filled in family information form, child information form and SCALES-Home Rating Scale and the Turkish version of the Conners' Home Rating Scale. When SCALES-Home Rating Scale and SCALES-School Rating Scale scores of each age group were compared using t-test, it was observed that the difference in all sub-scale scores in the 5-9 age group was significant and it was also observed that in the 10-13 and 13+ age groups, the difference was significant only in the hyperactivity field. The correlation between SCALES-School Rating Scale and SCALES-Home Rating Scale was investigated. The correlation between sub-scales measuring the same abilities was found to be between 0.1 and 0.26. We assume that the Turkish version of the SCALES is a valid and reliable instrument for diagnosing ADHD. Since SCALES-Home Rating Scale scores were higher than SCALES-School Rating Scale scores and the correlation between the two scales was low, we assume that the objectivity of parents' ratings was limited. Future validity studies on diagnosed children are needed.


Simultaneous measurement of the refractive index and thickness of thin films by S-polarized reflectances.
We have developed an innovation of the polarized reflectances measurement technique for thickness and index (PRETTI) method, PRETTI-S, which is a simple and accurate technique to obtain the refractive index n and thickness d of a thin film by using S-polarized and P-polarized reflectances measured at oblique angles of incidence. In the PRETTI-S method, the n and d are determined by using only S-polarized reflectances. Therefore, the measurement and numerical procedure to extract the n and d are simpler than the conventional PRETTI method. As an example, measurement of a single-layer film (SiO(2)/Si) is carried out and excellent confirmation is obtained.


Profiles of observed infant anger predict preschool behavior problems: moderation by life stress.
Using both traditional composites and novel profiles of anger, we examined associations between infant anger and preschool behavior problems in a large, longitudinal data set (N = 966). We also tested the role of life stress as a moderator of the link between early anger and the development of behavior problems. Although traditional measures of anger were largely unrelated to later behavior problems, profiles of anger that dissociated typical from atypical development predicted behavior problems during preschool. Moreover, the relation between infant anger profiles and preschool behavior problems was moderated such that, when early life stress was low, infants with atypical profiles of early anger showed more preschool behavior problems than did infants with normative anger profiles. However, when early life stress was high, infants with atypical and normative profiles of infant anger did not differ in preschool behavior problems. We conclude that a discrete emotions approach including latent profile analysis is useful for elucidating biological and environmental developmental pathways to early problem behaviors.


Label-free quantitative mass spectrometry reveals novel pathways involved in LL-37 expression.
Antimicrobial peptides are important for a healthy host-microbe homeostasis. In infections characterized by low levels of the human cathelicidin, LL-37, induction of its expression increases clearance of pathogens. Our aim was to discover signaling pathways and compounds capable of affecting the expression of LL-37. We recently observed a synergistic induction of LL-37 expression by stimulating the colonic epithelial cell-line HT-29 with lactose and phenylbutyrate (PBA). Here, we studied regulatory circuits mediating this synergism in HT-29 cells stimulated with lactose (60 g/l) and PBA (2 mM) for 24 h by using mass spectrometry and pathway analyses. Selected pathways were evaluated for their involvement in LL-37 regulation in a CAMP gene-luciferase reporter system. Three pathways were examined in detail: thyroid hormone receptor and retinoid X receptor (TR/RXR) activation, eicosanoid signaling and steroid biosynthesis. Induced expression of LL-37 was observed upon stimulation with triiodothyronine (T3, 2.5 nM-1 µM for 3-30 h) and thyroxine (T4, 2.5-10 nM for 24 h). Furthermore, the synergism of lactose and PBA was reduced in cells coincubated with inhibitors of phospholipase A2, cyclooxygenase 2 or HMG-CoA reductase. Based on these results, we conclude that proteomics and pathway analyses are valuable tools for dissecting the regulatory networks involved in LL-37 expression.


Intra-abdominal abscess formation in mice: quantitative studies on bacteria and abscess-potentiating agents.
A model of intra-abdominal (IA) abscess formation has been developed in mice. Intraperitoneal (i.p.) injection of a mixture of a potentiating agent (autoclaved colonic and caecal contents (ACC), 0.2 mg dry wt/mouse or sterile bran, 1 mg dry wt/mouse), Escherichia coli (1 X 10(6) colony forming units (cfu)/mouse) and Bacteroides fragilis (5 X 10(8) cfu/mouse) induced abscesses in 98% of mice inoculated. The abscesses persisted for at least 4 weeks in 60% of inoculated animals, and for 10 weeks in 36%. From 1 to 5 abscesses per mouse were found. Abscess formation was quantified by weighing the dissected abscesses and by culturing bacteria from them. Histologically, the abscesses were characterized by a central region of polymorphonuclear leucocytes, often with a thin mononuclear phagocyte infiltrate surrounding it, and an outer wall of vascularized connective tissue. Fluorescent antibody studies demonstrated that antigens from both bacterial species were distributed throughout the abscess. At the concentrations used, neither ACC nor sterile bran induced formation in the absence of viable bacteria.


Mindfulness is positively related to socioeconomic job status and income and independently predicts mental distress in a long-term perspective: Danish validation studies of the Five-Factor Mindfulness Questionnaire.
The Five Factor Mindfulness Questionnaire (FFMQ) measures 5 factor-analytically derived mindfulness aspects (Observe, Describe, Non-Judgment, Non-Reactivity, and Acting with Awareness) and is commonly used as an indicator of mindfulness in population surveys and studies of mindfulness-based interventions (MBI). Outside MBI, FFMQ scores are hypothesized to reflect relatively stable human dispositions of importance to psychological health. However, the long-term test-retest reliability of FFMQ scores is virtually untested and it remains unknown whether FFMQ scores predict psychological health after controlling for standardized socioeconomic status classifications. First, we focused on psychometric validation of the FFMQ translated to Danish in a randomly invited healthy and nonmeditating adult community sample (N = 490). Confirmatory factor analyses primarily supported a four-factor construct excluding the Observe facet. The four-factor model showed adequate composite reliability, convergent validity and satisfactory-excellent internal consistency, Cronbach αs = .72-.91. Structural equation modeling revealed that FFMQ Total scores were positively related to income and socioeconomic status but independently predicted psychological distress and mental health scores, respectively, after controlling for age, gender, body mass index, socioeconomic job classification, stressful life events, and social desirability, β = -.24-.29, ps < .001. Second, FFMQ scores showed adequate short-term (two weeks) test-retest reliability among 99 healthy university students, Spearman's ρs ≥ .82. Finally, all FFMQ mean scores showed satisfactory test-retest reliability across a long-term (six months) interval (N = 407), intraclass correlation coefficients ≥.74. We recommend the Danish FFMQ for further use. The Observe facet should be interpreted with caution. Remaining FFMQ facet scores comprise an internally consistent four-dimensional construct reflecting long-term-reliable human dispositions of independent significance for predicting mental health. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL-2 inhibitor, in patients with non-Hodgkin lymphoma.
To examine the effect of a strong cytochrome P450 (CYP) 3A inhibitor, ketoconazole, on the pharmacokinetics, safety and tolerability of venetoclax. Twelve patients with non-Hodgkin lymphoma (NHL) were enrolled in this Phase 1, open-label, fixed-sequence study. Patients received a single 50 mg dose of venetoclax orally on Day 1 and Day 8, and a 400 mg once daily dose of ketoconazole on Days 5-11. Blood samples were collected predose and up to 96 h after each venetoclax dose on Day 1 and Day 8. Eleven patients had evaluable pharmacokinetic data and were therefore included in the statistical analyses. Compared to administration of a single 50 mg dose of venetoclax alone, ketoconazole increased the venetoclax mean maximum observed plasma concentration (Cmax ) and area under the plasma concentration-time curve from time 0 to infinity (AUC∞ ) by 2.3-fold (90% confidence interval [CI]: 2.0-2.7) and 6.4-fold (90% CI: 4.5-9.2; range: 2- to 12-fold), respectively. Coadministration of venetoclax with multiple doses of ketoconazole resulted in a significant increase of venetoclax exposures, strongly suggesting that CYP3A plays a major role in elimination of venetoclax in patients. These results suggest the need to avoid concomitant use with strong and moderate inhibitors or inducers of CYP3A during the venetoclax ramp-up phase in chronic lymphocytic leukaemia (CLL) patients. For patients who have completed the ramp-up phase, a modification in venetoclax dose for use with strong and moderate inhibitors or inducers of CYP3A is recommended.


Pain scores among emergency department (ED) patients: comparison by ED diagnosis.
Treatment for pain and pain-related conditions has been identified as the most common reason for Emergency Department (ED) visits. This study was undertaken to characterize the distribution of self-reported pain scores for common ED diagnoses. In this retrospective exploratory chart review, eligible participants included all adult ED patients age 18 years and over, with a self-reported triage pain score of 1 or higher during January-June 2011. Data were collected from ED electronic medical records. Among 1229 patients, the mean age was 44 years; 56% of patients were female, and 59% were white. The mean triage pain score for all patients was 7.1 (interquartile range 6-9). The most common reported diagnoses included: minor injuries (10%), abdominal pain (8%), and respiratory infections (8%). The diagnoses with the highest mean pain scores were: sickle cell crisis (mean pain score 8.7), back/neck/shoulder pain (8.5), and headache/migraine (8.3). Higher pain scores were significantly correlated with younger age (p<0.001) and number of ED visits (p<0.001). Demographic factors including female gender, African American race, and Medicaid insurance reported significantly higher pain scores (p<0.001). Patients with multiple ED visits in the recent 12 months reported significantly higher pain scores (p<0.001). ED patients report a wide variety of pain scores. Factors associated with higher pain scores included younger age, female gender, African American race, Medicaid insurance status, multiple ED visits in the past year, and ED diagnoses of sickle cell crisis, back/neck/shoulder pain, and headache.


Analysis and interrater reliability of pB-C2 using MRI and CT: data from the Park-Reeves Syringomyelia Research Consortium on behalf of the Pediatric Craniocervical Society.
OBJECTIVE The distance to the ventral dura, perpendicular to the basion to C2 line (pB-C2), is commonly employed as a measure describing the anatomy of the craniovertebral junction. However, both the reliability among observers and the clinical utility of this measurement in the context of Chiari malformation Type I (CM-I) have been incompletely determined. METHODS Data were reviewed from the first 600 patients enrolled in the Park-Reeves Syringomyelia Research Consortium with CM-I and syringomyelia. Thirty-one cases were identified in which both CT and MRI studies were available for review. Three pediatric neurosurgeons independently determined pB-C2 values using common imaging sequences: MRI (T1-weighted and T2-weighted with and without the inclusion of retro-odontoid soft tissue) and CT. Values were compared and intraclass correlations were calculated among imaging modalities and observers. RESULTS Intraclass correlation of pB-C2 demonstrated strong agreement between observers (intraclass correlation coefficient [ICC] range 0.72-0.76). Measurement using T2-weighted MRI with the inclusion of retro-odontoid soft tissue showed no significant difference with measurement using T1-weighted MRI. Measurements using CT or T2-weighted MRI without retro-odontoid soft tissue differed by 1.6 mm (4.69 and 3.09 mm, respectively, p < 0.05) and were significantly shorter than those using the other 2 sequences. Conclusions pB-C2 can be measured reliably by multiple observers in the context of pediatric CM-I with syringomeyelia. Measurement using T2-weighted MRI excluding retro-odontoid soft tissue closely approximates the value obtained using CT, which may allow for the less frequent use of CT in this patient population. Measurement using T2-weighted MRI including retro-odontoid soft tissue or using T1-weighted MRI yields a more complete assessment of the extent of ventral brainstem compression, but its association with clinical outcomes requires further study.


Collapsing factors in multitrait-multimethod models: examining consequences of a mismatch between measurement design and model.
Models of confirmatory factor analysis (CFA) are frequently applied to examine the convergent validity of scores obtained from multiple raters or methods in so-called multitrait-multimethod (MTMM) investigations. Many applications of CFA-MTMM and similarly structured models result in solutions in which at least one method (or specific) factor shows non-significant loading or variance estimates. Eid et al. (2008) distinguished between MTMM measurement designs with interchangeable (randomly selected) vs. structurally different (fixed) methods and showed that each type of measurement design implies specific CFA-MTMM measurement models. In the current study, we hypothesized that some of the problems that are commonly seen in applications of CFA-MTMM models may be due to a mismatch between the underlying measurement design and fitted models. Using simulations, we found that models with M method factors (where M is the total number of methods) and unconstrained loadings led to a higher proportion of solutions in which at least one method factor became empirically unstable when these models were fit to data generated from structurally different methods. The simulations also revealed that commonly used model goodness-of-fit criteria frequently failed to identify incorrectly specified CFA-MTMM models. We discuss implications of these findings for other complex CFA models in which similar issues occur, including nested (bifactor) and latent state-trait models.


Ferroelectric mesocrystalline BaTiO3/BaBi4Ti4O15 nanocomposite: formation mechanism, nanostructure, and anomalous ferroelectric response.
Ferroelectric mesocrystalline nanocomposites are promising materials for the enhancement of ferroelectricity via lattice strain engineering due to their high density of heteroepitaxial interfaces. In the present study, a ferroelectric mesocrystalline BaTiO3/BaBi4Ti4O15 (BT/BBT) nanocomposite was synthesized using the layered titanate H1.07Ti1.73O4via a facile two-step topochemical process. The BT/BBT nanocomposite is constructed from well-aligned BT and BBT nanocrystals oriented along the [110] and [11-1] crystal-axis directions, respectively. Lattice strain is introduced into the nanocomposite through the formation of a BT/BBT heteroepitaxial interface, which results in a greatly elevated Curie temperature for BBT in the range of 400 °C to 700 °C and an improved piezoelectric response with . In addition, the BT/BBT nanocomposite is stable up to a high temperature of 1100 °C; therefore, mesocrystalline ceramics can be fabricated as high-performance ferroelectric materials.


Stream cipher based on pseudorandom number generation with optical affine transformation.
We propose a new, to our knowledge, stream cipher technique for two-dimensional (2-D) image data that can be implemented by iterative optical transformation. The stream cipher uses a pseudorandom number generator (PRNG) to generate a pseudorandom bit sequence. The proposed method for the PRNG is composed of the iterative operation of 2-D affine transformation achieved by optical components and by modulo-n addition of the transformed images. We expect efficient execution of the method by optical parallel processing. We verify the performance of the proposed method in terms of security strength and clarify problems on optical implementation by the optical fractal synthesizer.


Divergence in genital morphology may contribute to mechanical reproductive isolation in a millipede.
Genitalia appear to evolve rapidly and divergently in taxa with internal fertilization. The current consensus is that intense directional sexual selection drives the rapid evolution of genitalia. Recent research on the millipede Antichiropus variabilis suggests that the male genitalia are currently experiencing stabilizing selection - a pattern of selection expected for lock-and-key structures that enforce mate recognition and reproductive isolation. Here, we investigate how divergence in genital morphology affects reproductive compatibility among isolated populations of A. variabilis. Females from a focal population were mated first to a male from their own population and, second, to a male from one of two populations with divergent genital morphology. We observed variation in mating behavior that might indicate the emergence of precopulatory reproductive barriers: males from one divergent population took significantly longer to recognize females and exhibited mechanical difficulty in genital insertion. Moreover, we observed very low paternity success for extra-population males who were successful in copulating. Our data suggest that divergence in genital shape may be contributing to reproductive isolation, and incipient speciation among isolated populations of A. variabilis.


Migratory behaviour predicts greater parasite diversity in ungulates.
Long-distance animal movements can increase exposure to diverse parasites, but can also reduce infection risk through escape from contaminated habitats or culling of infected individuals. These mechanisms have been demonstrated within and between populations in single-host/single-parasite interactions, but how long-distance movement behaviours shape parasite diversity and prevalence across host taxa is largely unknown. Using a comparative approach, we analyse the parasite communities of 93 migratory, nomadic and resident ungulate species. We find that migrants have higher parasite species richness than residents or nomads, even after considering other factors known to influence parasite diversity, such as body size and host geographical range area. Further analyses support a novel 'environmental tracking' hypothesis, whereby migration allows parasites to experience environments favourable to transmission year-round. In addition, the social aggregation and large group sizes that facilitate migration might increase infection risk for migrants. By contrast, we find little support for previously proposed hypotheses, including migratory escape and culling, in explaining the relationship between host movement and parasitism in mammals at this cross-species scale. Our findings, which support mechanistic links between long-distance movement and increased parasite richness at the species level, could help predict the effects of future environmental change on parasitism in migratory animals.


Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers-Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT.
The theranostic concept represents a paradigmatic example of personalized treatment. It is based on the use of radiolabeled compounds which can be applied for both diagnostic molecular imaging and subsequent treatment, using different radionuclides for labelling. Clinically relevant examples include somatostatin receptor (SSTR)-targeted imaging and therapy for the treatment of neuroendocrine tumors (NET), as well as prostate-specific membrane antigen (PSMA)-targeted imaging and therapy for the treatment of prostate cancer (PC). As such, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy using positron emission tomography (PET). While interpreting PSMA- or SSTR-targeted PET/computed tomography scans, the reader has to navigate certain pitfalls, including (I.) varying normal biodistribution between different PSMA- and SSTR-targeting PET radiotracers, (II.) varying radiotracer uptake in numerous kinds of both benign and malignant lesions, and (III.) resulting false-positive and false-negative findings. Thus, two novel reporting and data system (RADS) classifications for PSMA- and SSTR-targeted PET imaging (PSMA- and SSTR-RADS) have been recently introduced under the umbrella term molecular imaging reporting and data systems (MI-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied. Learning objectives of the present case-based review are as follows: (I.) the theranostic concept for the treatment of NET and PC will be briefly introduced, (II.) the most common pitfalls on PSMA- and SSTR-targeted PET/CT will be identified, (III.) the novel framework system for theranostic radiotracers (MI-RADS) will be explained, applied to complex clinical cases and recent studies in the field will be highlighted. Finally, current treatment strategies based on MI-RADS will be proposed, which will demonstrate how such a generalizable framework system truly paves the way for clinically meaningful molecular imaging-guided treatment of either PC or NET. Thus, beyond an introduction of MI-RADS, the present review aims to provide an update of recently published studies which have further validated the concept of structured reporting systems in the field of theranostics.


Investigation of the influence of training status on the relationship between the acute exercise and serum leptin levels in obese females.
Recent studies have concluded that an energy expenditure by an acute exercise session has no immediate effect on leptin levels while some showed a decline in leptin levels. The purpose of this study was to investigate any possible effects of training status of the subjects on acute exercise-leptin relationship in obese patients. Fourteen obese sedentary females were enrolled to the study and effects of acute incremental exercise on serum leptin levels were determined at rest and at maximal exercise performance. Then, they participated to a 12-weeks endurance aerobic training programme performed in the laboratory on a computer controlled cycle ergometer and their leptin levels were re-evaluated and the leptin-acute exercise relationships obtained under different training levels in the same group of subjects were compared. The body compositions were determined by bioelectrical impedance. Pre and post training blood samples were taken at rest and at the maximal exercise performance. Serum leptin levels were analysed in duplicate by RIA. Data were evaluated using, paired t and Pearson's tests. Leptin levels were not acutely affected by the incremental exercise either before (23.62+/-3.5 ng/ml and 22.62+/-3.6 ng/ml) or after (13.13+/-3.4 ng/ml and 13.82+/-3.6 ng/ml) endurance training. The marked decrease in leptin levels following training was closely correlated with fat mass loss R= 0.899 (P= 0.0001). This study indicates that an increase in energy expenditure by acute exercise has no significant acute effect on leptin level regardless of the training status of the subjects and decrease in leptin levels after a 12-weeks endurance aerobic training programme are closely associated with the fat mass loss.


Dopamine and memory: modulation of the persistence of memory for novel hippocampal NMDA receptor-dependent paired associates.
Three experiments investigated the role in memory processing of dopamine (DA) afferents to the hippocampus (HPC) that arise from the ventral tegmental area. One hypothesis is that D(1)/D(5) receptor activation in HPC is necessary for the encoding of novel, episodic-like information; the other is that DA activation ensures the greater temporal persistence of transient hippocampal memory traces. Rats (n = 35) were trained, in separate experiments using an episodic-like memory task, to learn six paired associates (PAs) in an "event arena" involving a repeated association between specific flavors of food and locations in space. After 6 weeks of training, rats had learned a "schema" such that two new paired associates could be acquired in a single trial in one session (episodic-like memory). We show that encoding of novel PAs is sensitive to intrahippocampal microinfusion of the NMDA antagonist d-AP-5. Experiment 1 established that intrahippocampal infusion of the D(1)/D(5) dopaminergic antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride] before encoding of new PAs caused impaired memory 24 h later but that SCH23390 had no effect on the later memory of previously established PAs. Experiment 2 established that SCH23390 modulated the persistence of new memories over time (30 min vs 24 h) rather than affecting initial encoding. Experiment 3 revealed that the impact of SCH23390 was not mediated by state dependence nor had an effect on memory retrieval. These findings support the second hypothesis and establish that persistent, long-term memory of rapid, hippocampal-mediated acquisition of new paired associates requires activation of D(1)/D(5) receptors in HPC at or around the time of encoding.


Factors associated with monozygosity in assisted reproductive technology pregnancies and the risk of recurrence using linked cycles.
To evaluate factors associated with monozygosity (MZ) (number of fetal heartbeats on early ultrasound greater than the number of embryos transferred) and the risk of recurrence in subsequent pregnancies using a national assisted reproduction database. Historical cohort study. Clinic-based data. 197,327 pregnancies (including 2,824 with evidence of MZ) from cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) between 2004 and 2010. None. Evidence of MZ, adjusted odds ratios and their 95% confidence intervals computed from logistic regression models. In the univariate analysis, the risk of MZ was increased with ovulation disorders, donor oocytes, gonadotropin-releasing hormone agonist (GnRH-a) suppression, assisted hatching (AZH), and day 5-6 transfer, and was decreased with higher follicle-stimulating hormone (FSH) doses (≥3,000 IU). In the multivariate analysis, the risk of MZ was increased with GnRH-a suppression, AZH, and decreased with intracytoplasmic sperm injection (ICSI) and higher FSH dose. The interaction showed that although MZ was more likely with day 5-6 embryos, AZH had a minimal nonsignificant effect, whereas in day 2-3 embryos, AZH had a substantial statistically significant effect. Only one woman had a recurrence of MZ in a subsequent assisted reproduction pregnancy, which is consistent with randomness. The risk of MZ was higher with fresh day 5-6 embryos, donor oocytes, GnRH-a suppression, lower FSH doses, and AZH (particularly with day 2-3 embryos).


The forkhead box M1 transcription factor contributes to the development and growth of mouse colorectal cancer.
In this study, we used Forkhead Box m1b (Foxm1b) transgenic mice and conditional Foxm1 knock-out mice to examine the role of Foxm1 in colon cancer development and proliferation. To induce mouse colorectal cancer, we used a single intraperitoneal injection of azoxymethane (AOM) followed by three 1-week cycles of 2.5% dextran sodium sulfate (DSS) water, each cycle separated by 2 weeks. For these colon tumor studies, we used either Rosa26-Foxm1b transgenic mice that ubiquitously expressed the human Foxm1b complementary DNA or mice in which the Foxm1 fl/fl targeted allele was deleted in colonic epithelial cells using the gut-specific Villin-Cre recombinase transgene (Villin-Cre). Colorectal tumor number and bromodeoxyuridine labeling were determined in Rosa26-Foxm1b mice, Villin-Cre Foxm1-/-, mice and wild-type mice after 12 weeks of AOM/DDS exposure. We also used Foxm1 small interfering RNA-depleted human DLD1 and mouse CT26 colon cancer cell lines to examine DNA replication and anchorage-independent growth. After 12 weeks of treatment with AOM/DSS, Rosa26 Foxm1b transgenic mice showed an increase in the number and size of colorectal tumors compared with wild-type mice. Likewise, a significant reduction in the development and growth of colorectal tumors was found in Villin-Cre Foxm1-/- mice compared with Foxm1 fl/fl mice after AOM/DSS treatment, which was associated with decreased expression of cyclin A2, cyclin B1, survivin, and T-cell factor 4 genes. Moreover, Foxm1-depleted colon cancer cell lines showed reduced DNA replication and anchorage-independent growth. These studies suggest that Foxm1 is critical for the proliferation and growth of colorectal cancer.


National-level differences in the adoption of environmental health technologies: a cross-border comparison from Benin and Togo.
Environmental health problems such as malaria, respiratory infections, diarrhoea and malnutrition pose very high burdens on the poor rural people in much of the tropics. Recent research on key interventions-the adoption and use of relatively cheap and effective environmental health technologies-has focused primarily on the influence of demand-side household-level drivers. Relatively few studies of the promotion and use of these technologies have considered the role of contextual factors such as governance, the enabling environment and national policies because of the challenges of cross-country comparisons. We exploit a natural experimental setting by comparing household adoption across the Benin-Togo national border that splits the Tamberma Valley in West Africa. Households across the border share the same culture, ethnicity, weather, physiographic features, livelihoods and infrastructure; however, they are located in countries at virtually opposite ends of the institutional spectrum of democratic elections, voice and accountability, effective governance and corruption. Binary choice models and rigorous non-parametric matching estimators confirm that households in Benin are more likely than households in Togo to plant soybeans, build improved cookstoves and purchase mosquito nets, ceteris paribus. Although we cannot identify the exact mechanism for the large and significant national-level differences in technology adoption, our findings suggest that contextual institutional factors can be more important than household characteristics for technology adoption.


Kingfisher feathers--colouration by pigments, spongy nanostructures and thin films.
The colours of the common kingfisher, Alcedo atthis, reside in the barbs of the three main types of feather: the orange breast feathers, the cyan back feathers and the blue tail feathers. Scanning electron microscopy showed that the orange barbs contain small pigment granules. The cyan and blue barbs contain spongy nanostructures with slightly different dimensions, causing different reflectance spectra. Imaging scatterometry showed that the pigmented barbs create a diffuse orange scattering and the spongy barb structures create iridescence. The extent of the angle-dependent light scattering increases with decreasing wavelength. All barbs have a cortical envelope with a thickness of a few micrometres. The reflectance spectra of the cortex of the barbs show oscillations when measured from small areas, but when measured from larger areas the spectra become wavelength independent. This can be directly understood with thin film modelling, assuming a somewhat variable cortex thickness. The cortex reflectance appears to be small but not negligible with respect to the pigmentary and structural barb reflectance.


Causes of fever in pregnant women with acute undifferentiated fever: a prospective multicentric study.
The etiologies of undifferentiated fever in pregnant women have not been studied thoroughly. Because of its non-specific presentation but severe prognosis, listeriosis is often suspected in this setting, but in most cases not confirmed. We studied the causes of undifferentiated fever in pregnant women who received preemptive listeriosis treatment. We conducted from November 1, 2011, to June 30, 2013, a prospective multicentric observational cohort study of pregnant women referred to obstetrical wards with undifferentiated fever and who received listeriosis preemptive treatment. Clinical and biological features, treatment, outcome, and final diagnosis were collected. We enrolled 103 febrile pregnant women. A cause was identified in 77/103 (75%): viral infection in 52/103 (50%, influenza in 21 (20%)), bacterial infection in 22 (21%, including 16 pyelonephritis (16%) and 3 pneumonias (3%)), and TORCH infection in 3 (3%, varicella, toxoplasmosis, and cytomegalovirus primo-infections, n=1, each). Viral infections collected during influenza outbreaks (December-March) accounted for 43/57 (75%) cases. Two fetal losses were reported in the context of febrile pneumonia. Final diagnoses required adapting medical care in 46/77 (60%) of cases, for bacterial, influenza, or TORCH infections. A large array of benign to potentially severe infections manifests as acute undifferentiated fever in pregnant women, requiring careful repeated evaluation.


Wide variations in blood product transfusion practices among providers who care for patients with acute leukemia in the United States.
Transfusion of blood products is a key component of the supportive management in patients with acute leukemia (AL). However high-quality trial evidence and clinical outcome data to support specific transfusion goals for blood products for patients with AL remain limited leading to diverse transfusion practices. The primary objective of this study was to determine the spectrum of transfusion patterns in a variety of care settings among providers who treat AL patients. A 31-question survey queried providers caring for AL patients about the existence of institutional guidelines for transfusion of blood products, transfusion triggers for hemoglobin (Hb), platelets (PLTs), and fibrinogen in various settings including inpatient and outpatient and before procedures. We analyzed 130 responses and identified divergent transfusion Hb goals in hospitalized and ambulatory patients, fibrinogen goals for cryoprecipitate transfusions, and variation in practice for use of certain PLTs and red blood cell products. The least variable transfusion patterns were reported for PLT goals in thrombocytopenia and in the setting of invasive procedures such as bone marrow biopsy and lumbar punctures. This survey confirmed wide variations in blood product transfusion practices across several clinical scenarios in patients with AL. The findings emphasized the need for large prospective randomized trials to develop standardized evidence-based guidelines for blood product transfusions in patients with AL with the goal of limiting unnecessary transfusions without compromising outcomes.


Synaptotagmin III isoform is compartmentalized in pancreatic beta-cells and has a functional role in exocytosis.
Synaptotagmin is involved in Ca2+-regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+-dependent secretory process. Previous studies of pancreatic beta-cells were unable to show presence of synaptotagmin I. We now present biochemical and immunohistochemical data showing that synaptotagmin III is present in pancreatic beta-cells as well as in the insulin-secreting cell line HIT-T15 and in rat insulinoma. By subcellular fractionation, we found synaptotagmin III in high-density fractions together with insulin and secretogranin I, indicating colocalization of synaptotagmin III and insulin in secretory granules. We could also show that blockade of synaptotagmin III by a specific antibody inhibited Ca2+-induced changes in beta-cell membrane capacitance, suggesting that synaptotagmin III is part of the functional protein complex regulating beta-cell exocytosis. The synaptotagmin III antibody did not affect the activity of the voltage-gated L-type Ca2+-channel. These findings are compatible with the view that synaptotagmin III, because of its distinct localization in the pancreatic beta-cell, functionally modulates insulin exocytosis. This indicates that synaptotagmin may have a general role in the regulation of exocytosis not only in neuronal cells but also in endocrine cells.


Continuous decrease of consanguineous marriages among Arabs in Israel.
To describe the trend in the rate of consanguineous marriages among the Israeli Arab population and to identify factors associated with this custom shift in recent years. The study was conducted between November 2009 and January 2010 in Family Health Centers. A questionnaire was presented to parents during routine visits to the center with their children. Information on 6,437 couples was collected. The rate of consanguineous marriages decreased from 35.8% among those married before 2000, to 28.2% among those married in 2000-2004, and to 24.0% among those married in 2005-2009 (P for trend <0.001). First cousin marriages were the most common type of consanguineous marriages in all the time periods. Consanguineous marriages were associated with consanguinity between the couples' parents (both husband and wife), a high consanguinity rate in the place of residence and younger age at marriage (wife). The rates of consanguineous marriages among Israeli Arabs are decreasing but still high. Because consanguineous marriages are widely acceptable, the role of public health professionals and primary care personnel is to provide comprehensive information about the potential genetic risks of consanguinity on offspring health and to increase the accessibility of premarital and preconception counseling services.


The bipolar kinesin, KLP61F, cross-links microtubules within interpolar microtubule bundles of Drosophila embryonic mitotic spindles.
Previous genetic and biochemical studies have led to the hypothesis that the essential mitotic bipolar kinesin, KLP61F, cross-links and slides microtubules (MTs) during spindle assembly and function. Here, we have tested this hypothesis by immunofluorescence and immunoelectron microscopy (immunoEM). We show that Drosophila embryonic spindles at metaphase and anaphase contain abundant bundles of MTs running between the spindle poles. These interpolar MT bundles are parallel near the poles and antiparallel in the midzone. We have observed that KLP61F motors, phosphorylated at a cdk1/cyclin B consensus domain within the BimC box (BCB), localize along the length of these interpolar MT bundles, being concentrated in the midzone region. Nonphosphorylated KLP61F motors, in contrast, are excluded from the spindle and display a cytoplasmic localization. Immunoelectron microscopy further suggested that phospho-KLP61F motors form cross-links between MTs within interpolar MT bundles. These bipolar KLP61F MT-MT cross-links should be capable of organizing parallel MTs into bundles within half spindles and sliding antiparallel MTs apart in the spindle midzone. Thus we propose that bipolar kinesin motors and MTs interact by a "sliding filament mechanism" during the formation and function of the mitotic spindle.


Blockade of acetylcholine receptors: a model of myasthenia gravis.
In order to block acetylcholine receptors of muscle, the alpha toxin of the Formosan cobra (Naja naja atra) was given intravenously to rats. Electrophysiological and pharmacological changes typical of myasthenia gravis were recorded, including decremental responses to repetitive stimuli, curare sensitivity, neostigmine reversal, and posttetanic phenomena. This model supports the concept that a reduction of available acetylcholine receptors may play an important role in myasthenia gravis.


Acroangiodermatitis (Pseudo-Kaposi sarcoma).
Acroangiodermatitis or Pseudo-Kaposi sarcoma is a rare angioproliferative entity, related to chronic venous insufficiency or certain other vascular anomalies. It is often associated with chronic venous insufficiency, arteriovenous malformation of the legs, chronic renal failure treated with dialysis, paralyzed legs and amputation stumps. We hereby describe a case of 45 year old female presenting with pitting pedal edema, multiple ulcers over bilateral lower limbs with irregular margins with erythema and hyperpigmentation of the surrounding skin. Color Doppler study of bilateral lower limbs was normal. Histopathological examination from one of the lesions showed hyperplastic epidermis, proliferation of capillaries in dermis, hemosiderin deposits and lymphocytic infiltrate. These features thus confirmed the diagnosis of Acroangiodermatitis.


Testosterone treatment in multiple sclerosis: a pilot study.
To study the effect of testosterone supplementation on men with multiple sclerosis (MS). Men are less susceptible to many autoimmune diseases, including MS. Possible causes for this include sex hormones and/or sex chromosome effects. Testosterone treatment ameliorates experimental allergic encephalomyelitis, an animal model of MS, but the effect of testosterone supplementation on men with MS is not known. Therefore, 10 men with relapsing-remitting MS were studied using a crossover design whereby each patient served as his own control. There was a 6-month pretreatment period followed by a 12-month period of daily treatment with 10 g of the gel containing 100 mg of testosterone. Clinical measures of disability and cognition (the Multiple Sclerosis Functional Composite and the 7/24 Spatial Recall Test) and monthly magnetic resonance imaging measures of enhancing lesion activity and whole brain volumes. One year of treatment with testosterone gel was associated with improvement in cognitive performance (P = .008) and a slowing of brain atrophy (P <.001). There was no significant effect of testosterone treatment on gadolinium-enhancing lesion numbers (P = .31) or volumes (P = .94). Lean body mass (muscle mass) was increased (P = .02). These exploratory findings suggest that testosterone treatment is safe and well tolerated and has potential neuroprotective effects in men with relapsing-remitting MS.


Cancer-preventive Properties of an Anthocyanin-enriched Sweet Potato in the APCMIN Mouse Model.
Anthocyanin-rich foods and preparations have been reported to reduce the risk of life-style related diseases, including cancer. The SL222 sweet potato, a purple-fleshed cultivar developed in New Zealand, accumulates high levels of anthocyanins in its storage root. We examined the chemopreventative properties of the SL222 sweet potato in the C57BL/6J-APC MIN/+ (APCMIN) mouse, a genetic model of colorectal cancer. APCMIN and C57BL/6J wild-type mice (n=160) were divided into four feeding groups consuming diets containing 10% SL222 sweet potato flesh, 10% SL222 sweet potato skin, or 0.12% ARE (Anthocyanin rich-extract prepared from SL222 sweet potato at a concentration equivalent to the flesh-supplemented diet) or a control diet (AIN-76A) for 18 weeks. At 120 days of age, the mice were anaesthetised, and blood samples were collected before the mice were sacrificed. The intestines were used for adenoma enumeration. The SL222 sweet potato-supplemented diets reduced the adenoma number in the APCMIN mice. These data have significant implications for the use of this sweet potato variant in protection against colorectal cancer.


Dorsal and ventral attention systems underlie social and symbolic cueing.
Eye gaze is a powerful cue for orienting attention in space. Studies examining whether gaze and symbolic cues recruit the same neural mechanisms have found mixed results. We tested whether there is a specialized attentional mechanism for social cues. We separately measured BOLD activity during orienting and reorienting attention following predictive gaze and symbolic cues. Results showed that gaze and symbolic cues exerted their influence through the same neural networks but also produced some differential modulations. Dorsal frontoparietal regions in left intraparietal sulcus (IPS) and bilateral MT(+)/lateral occipital cortex only showed orienting effects for symbolic cues, whereas right posterior IPS showed larger validity effects following gaze cues. Both exceptions may reflect the greater automaticity of gaze cues: Symbolic orienting may require more effort, while disengaging attention during reorienting may be more difficult following gaze cues. Face-selective regions, identified with a face localizer, showed selective activations for gaze cues reflecting sensory processing but no attentional modulations. Therefore, no evidence was found linking face-selective regions to a hypothetical, specialized mechanism for orienting attention to gaze cues. However, a functional connectivity analysis showed greater connectivity between face-selective regions and right posterior IPS, posterior STS, and inferior frontal gyrus during gaze cueing, consistent with proposals that face-selective regions may send gaze signals to parts of the dorsal and ventral frontoparietal attention networks. Finally, although the default-mode network is thought to be involved in social cognition, this role does not extend to gaze orienting as these regions were more deactivated following gaze cues and showed less functional connectivity with face-selective regions during gaze cues.


Homing of annexin-labeled stem cells to apoptotic cells.
Ischemic diseases are characterized by the presence of pro-apoptotic stimuli, which initiate a cascade of processes that lead to cell injury and death. Several molecules and events represent detectable indicators of the different stages of apoptosis. Among these indicators is phosphatidylserine (PS) translocation from the inner to the outer leaflet of the plasma membrane, which can be detected by annexinV (ANXA5) conjugation. This is a widely used in vivo and in vitro assay marking the early stages of apoptosis. We report here on an original method that employs PS-ANXA5 conjugation to target stem cells to apoptotic cells. Mesenchymal stem cells (MSCs) from GFP-positive transgenic rats were biotinylated on membrane surfaces with sulfosuccinimidyl-6-(biotinamido) hexanoate (sulfo-NHS-LC-biot) and then bound to avidin. The avidin-biotinylated MSCs were labeled with biotin conjugated ANXA5. Bovine aortic endothelial cells (BAE-1 cells) were exposed to UVC to induce caspasedependent apoptosis. Finally, we tested the ability of ANXA5-labeled MSCs to bind BAE-1 apoptotic cells: suspended ANXA5-labeled MSCs were seeded for 1 hour on a monolayer of UV-treated or control BAE-1 cells. After washing, the number of MSCs bound to BAE-1 cells was evaluated by confocal microscopy. Statistical analysis demonstrated a significant increase in the number of MSCs tagged to apoptotic BAE-1 cells. Therefore, stem cell ANXA5 tagging via biotin-avidin bridges could be a straightforward method of improving homing to apoptotic tissues.


The effect of body fat mass and fat free mass on migraine headache.
Obesity seems to be associated to migraine headache. Increase in body fat, especially in gluteofemoral region, elevates adiponectin and leptin secretion which in turn impair inflammatory processes that could be contributing to migraine risk. This study was designed to assess the relationship between body composition and risk of migraine for the first time. In this cross-sectional study, 1510 middle-aged women who were visited in a weight reduction clinic of university were recruited. Migraine was diagnosed with HIS criteria. Body composition parameters including total fat mass (FATM), total fat free mass (FFM), truncal fat mass (TFATM), and truncal fat free mass (TFFM) was assessed using bioelectric impedance. We further assessed cardiovascular risk factors and smoking as confounding factors. To determine the real association between different variables and risk of migraine, the associations were adjusted by multivariate logistic regression analysis. Elevation in fasting blood sugar, total cholesterol, LDL cholesterol, FFM, TFFM, and waist-to-hip ratio increased the risk of migraine. When the associations were adjusted for other factors, only the association between migraine and FFM remained statistically significant. Lower FFM increased the risk of migraine in overweight and obese individuals. In the other words, higher fat free mass could be a protective factor for migraine.


A Multi-Purpose Realistic Haze Benchmark With Quantifiable Haze Levels and Ground Truth.
Imagery collected from outdoor visual environments is often degraded due to the presence of dense smoke or haze. A key challenge for research in scene understanding in these degraded visual environments (DVE) is the lack of representative benchmark datasets. These datasets are required to evaluate state-of-the-art object recognition and other computer vision algorithms in degraded settings. In this paper, we address some of these limitations by introducing the first realistic haze image benchmark, from both aerial and ground view, with paired haze-free images, and in-situ haze density measurements. This dataset was produced in a controlled environment with professional smoke generating machines that covered the entire scene, and consists of images captured from the perspective of both an unmanned aerial vehicle (UAV) and an unmanned ground vehicle (UGV). We also evaluate a set of representative state-of-the-art dehazing approaches as well as object detectors on the dataset. The full dataset presented in this paper, including the ground truth object classification bounding boxes and haze density measurements, is provided for the community to evaluate their algorithms at: https://a2i2-archangel.vision. A subset of this dataset has been used for the "Object Detection in Haze" Track of CVPR UG2 2022 challenge at https://cvpr2022.ug2challenge.org/track1.html.


Adipose Organ Development and Remodeling.
During the last decades, research on adipose tissues has spread in parallel with the extension of obesity. Several observations converged on the idea that adipose tissues are organized in a large organ with endocrine and plastic properties. Two parenchymal components: white (WATs) and brown adipose tissues (BATs) are contained in subcutaneous and visceral compartments. Although both have endocrine properties, their function differs: WAT store lipids to allow intervals between meals, BAT burns lipids for thermogenesis. In spite of these opposite functions, they share the ability for reciprocal reversible transdifferentiation to tackle special physiologic needs. Thus, chronic need for thermogenesis induces browning and chronic positive energy balance induce whitening. Lineage tracing and data from explant studies strongly suggest other remodeling properties of this organ. During pregnancy and lactation breast WAT transdifferentiates into milk-secreting glands, composed by cells with abundant cytoplasmic lipids (pink adipocytes) and in the postlactation period pink adipocytes transdifferentiate back into WAT and BAT. The plastic properties of mature adipocytes are supported also by a liposecretion process in vitro where adult cell in culture transdifferentiate to differentiated fibroblast-like elements able to give rise to different phenotypes (rainbow adipocytes). In addition, the inflammasome system is activated in stressed adipocytes from obese adipose tissue. These adipocytes die and debris are reabsorbed by macrophages inducing a chronic low-grade inflammation, potentially contributing to insulin resistance and T2 diabetes. Thus, the plastic properties of this organ could open new therapeutic perspectives in the obesity-related metabolic disease and in breast pathologies. © 2018 American Physiological Society. Compr Physiol 8:1357-1431, 2018.


Increased mean platelet volume in patients with aortic stenosis.
Systemic thromboembolism is a serious complication in patients with aortic stenosis (AS). Previous studies have demonstrated that platelet activation occurs in patients with AS. The aim of this study was to assess the mean platelet volume (MPV), an indicator of platelet activation in patients with AS. The study group consisted of 43 patients with AS. An age-, gender-, and body mass index-matched control group consisted of 35 healthy volunteers. All patients and control participants underwent echocardiographic examination. We measured the serum MPV values in patients and control participants. Mean platelet volume was significantly higher among patients with AS when compared with the control group (8.7 ± 1.0 vs 7.9 ± 0.9 fL, respectively; P = .001). We have shown that MPV was significantly elevated in patients with AS compared to control participant.


Detection of a new microsporidium Perezia sp. in shrimps Penaeus monodon and P. indicus by histopathology, in situ hybridization and PCR.
Samples of microsporidia-infected shrimps exhibiting clinical signs of cotton shrimp disease were collected from Madagascar, Mozambique, and the Kingdom of Saudi Arabia from 2005 to 2014. The tails of the infected shrimps appeared opaque and whitish; subsequent histological examination revealed the presence of cytoplasmic inclusions and mature spores in tissues of the muscle, hepatopancreas, gills, heart, and lymphoid organ. PCR analysis targeting the small subunit rDNA (SSU rDNA) from infected samples resulted in the amplification of a 1.2 kbp SSU rDNA sequence fragment 94% identical to the corresponding region in the genome of the microsporidian Perezia nelsoni, which infects populations of Penaeus setiferus in the USA. Its SSU rDNA sequence was 100% identical among isolates from Madagascar and Saudi Arabia, indicating that shrimps from the Red Sea and Indian Ocean were infected with the same microsporidium, the novel Perezia sp. A 443 bp fragment of the SSU rDNA sequence was cloned, labeled with digoxigenin and subjected to an in situ hybridization assay with tissue sections of Perezia sp.-infected Penaeus monodon from Madagascar and Mozambique, and P. indicus from Saudi Arabia. The probe hybridized to the mature spores in the hepatopancreas and muscle from which the spores had been obtained for DNA isolation. This assay was specific, showing no reaction to another microsporidium, Enterocytozoon hepatopenaei (EHP), infecting the hepatopancreas of shrimp P. stylirostris cultured in SE Asian countries. We also developed an SSU rDNA-based PCR assay, specific for the novel Perezia sp. This PCR did not react to EHP, nor to genomic DNA of shrimp and other invertebrates.


The research agenda for general practice/family medicine and primary health care in Europe. Part 3. Results: person centred care, comprehensive and holistic approach.
The recently published 'Research Agenda for General Practice/Family Medicine and Primary Health Care in Europe' summarizes the evidence relating to the core competencies and characteristics of the Wonca Europe definition of GP/FM, and its implications for general practitioners/family doctors, researchers and policy makers. The European Journal of General Practice publishes a series of articles based on this document. In a first article, background, objectives, and methodology were discussed. In a second article, the results for the two core competencies 'primary care management' and 'community orientation' were presented. This article reflects on the three core competencies, which deal with person related aspects of GP/FM, i.e. 'person centred care', 'comprehensive approach' and 'holistic approach'. Though there is an important body of opinion papers and (non-systematic) reviews, all person related aspects remain poorly defined and researched. Validated instruments to measure these competencies are lacking. Concerning patient-centredness, most research examined patient and doctor preferences and experiences. Studies on comprehensiveness mostly focus on prevention/care of specific diseases. For all domains, there has been limited research conducted on its implications or outcomes.


Clinical Gaze in Risk-Factor Haze: Swedish GPs' Perceptions of Prescribing Cardiovascular Preventive Drugs.
Aims. To explore general practitioners' (GPs') descriptions of their thoughts and action when prescribing cardiovascular preventive drugs. Methods. Qualitative content analysis of transcribed group interviews with 14 participants from two primary health care centres in the southeast of Sweden. Results. GPs' prescribing of cardiovascular preventive drugs, from their own descriptions, involved "the patient as calculated" and "the inclination to prescribe," which were negotiated in the interaction with "the patient in front of me." In situations with high cardiovascular risk, the GPs reported a tendency to adopt a directive consultation style. In situations with low cardiovascular risk and great uncertainty about the net benefit of preventive drugs, the GPs described a preference for an informed patient choice. Conclusions. Our findings suggest that GPs mainly involve patients at low and uncertain risk of cardiovascular disease in treatment decisions, whereas patient involvement tends to decrease when GPs judge the cardiovascular risk as high. Our findings may serve as a memento for clinicians, and we suggest them to be considered in training in communication skills.


Recurrent gestational trophoblastic disease after hCG normalization following hydatidiform mole in The Netherlands.
To determine the risk for recurrent trophoblastic disease after spontaneous normalization of human chorionic gonadotropin (hCG) levels in patients with hydatidiform mole and to determine the risk for tumor relapse after apparent remission following chemotherapy in patients with low- and high-risk persistent trophoblastic disease. From 1994 until 2004, 355 patients with hydatidiform mole were registered at the Dutch Central Registry of Hydatidiform Mole and were monitored by sequential hCG assays in serum at the department of Chemical Endocrinology of the Radboud University Nijmegen Medical Centre. HCG regression curves were analyzed together with clinical information collected from the Hydatidiform Mole Database. Among the 355 registered hydatidiform mole patients, 265 patients attained spontaneous normalization following evacuation. Of the 265 patients, one patient (0.38%) subsequently required chemotherapeutic treatment for recurrent trophoblastic disease (95% confidence interval 0.0% to 2.1%). HCG levels did not decline to normal (<2.0 ng/ml) spontaneously in 90 patients; those patients were subsequently treated. Relapse rates were 8.1% (6/74) and 6.3% (1/16) for the low- and high-risk category respectively. Our analysis indicates that relapse risk in hydatidiform mole patients with spontaneous normalization is extremely low (one in 265 patients) after two normal hCG levels (<2.0 ng/ml) are achieved. Our results support the suggestion that two subsequent normal hCG levels may be sufficient to ensure sustained remission after hydatidiform mole evacuation. In contrary, in order to assure sustained remission, the relapse rates after chemotherapy in the current study emphasize the need for surveillance of trophoblastic tumor patients even after complete remission has apparently been achieved.


Functional study of the equine beta-casein and kappa-casein gene promoters.
Casein genes are expressed in a tissue-specific and highly coordinated manner. The main goals of casein gene promoter studies are to unravel cis- and trans-acting factors involved in the complex signalling pathway controlling milk production, and to explore the possibility of using these promoters for tissue-specific production of heterologous proteins in the mammary gland. Here we present a comparative study of the equine beta-casein and kappa-casein gene proximal promoters. In order to confirm the assumption that in the horse, as in other mammalian species, casein genes are organized in a cluster located on a single chromosome, we performed in situ hybridization of pro-metaphase chromosomes with two BAC clones containing different equine casein genes. Sequence analysis of the beta-casein and kappa-casein gene proximal promoters revealed binding sites for activators (STAT5, GRE, NF1, MAF) and repressors (YY1, PMF), characteristic for casein genes. The alignments of casein gene promoters revealed the highest sequence identity in the proximal promoter region between the equine and human beta-casein gene promoters. We directly compared the activity of equine beta-casein and kappa-casein gene promoters in vitro using bovine mammary gland cell line BME-UV1. In this system, the kappa-casein gene proximal promoter activated the reporter gene expression more efficiently than the beta-casein gene promoter of approximately the same length. The 810 bp of beta-casein promoter activated the reporter gene expression more efficiently than the long fragment (1920 bp) and the 1206 bp fragment of the same promoter, which included also 396 bp of 5' UTR.


Effect of social influence, environmental awareness, and safety affordance on actual use of 5G technologies among Chinese students.
5G technology continues to evolve, and its potential to revolutionize various aspects of society is becoming increasingly evident. However, the successful adoption and utilization of 5G technology depends on various factors, particularly among consumers expected to be early adopters and critical drivers of technological advancements. This study investigates the effect of social influence, environmental awareness, and safety affordance on Chinese university students' actual use of 5G (AU5G) technologies. It also analyzed the mediating role of trustworthiness and intention to use 5G (ITU5G) between them and the moderating role of facilitation conditions between trustworthiness and ITU5G. Data was collected from university students (n = 364) in Beijing and was examined employing the structural equation modelling (SEM) approach. The outcomes confirm that trustworthiness and ITU5G significantly mediate the relationship between social influence, environmental awareness, and safety affordance on AU5G technologies among Chinese students. Further, the supportive facilitation conditions strengthen the relationship between trustworthiness and ITU5G. These findings are backed by UTAUT2 models that support the technology acceptance and adoption among the users. The study outcomes can help policymakers design strategies to address potential barriers and encourage greater uptake of 5G services among university students.