[Synthesis of several analogues of antifungal steroid alkaloids].
In order to search for new type antifungal drugs, seven analogues of antifungal alkaloids were synthesized, each through a reaction sequence of ten or eleven steps, using the commercially available steroid, 3 beta-acetoxy-5, 16-pregnadiene-20-one as the starting material. The preliminary antifungal tests in vitro showed that compounds 3a-c, and 5 were more effective than fluoconazole. Nineteen new compounds were synthesized in this work.


Sources of intraspecific variation in the isotopic niche of a semi-aquatic predator in a human-modified landscape.
Intraspecific variation modulates patterns of resource use by species, potentially affecting the structure and stability of food webs. In human-modified landscapes, habitat disturbance modifies trophic interactions and intraspecific niche variation, impacting population persistence. Here, we investigated the relationship of sex, ontogeny, and habitat factors with the trophic niche of Caiman crocodilus in an agricultural landscape. We evaluated temporal variation in the trophic niche parameters using carbon and nitrogen stable isotope analysis from different body tissues. We found that caimans exploit the same carbon and nitrogen pools through time, with low isotopic variability between seasons, partly due to the slow isotope turnover rates of tissues in crocodilians. Conversely, the trophic niche of caimans varied across habitats, but with no evidence of a difference between natural and anthropogenic habitats. It apparently results from the influence of habitat suitability, connectivity, and caiman movements during the foraging. Our findings highlight the broader niches of juvenile caimans relative to adults, possibly in response of territorialism and opportunistic foraging strategy. Although using similar resources, females had a larger niche than males, probably associated with foraging strategies during nesting. Considering the sex and body size categories, caimans occupied distinct isotopic regions in some habitats, indicating apparent niche segregation. Ontogenetic trophic shifts in the isotopes (δ13C and δ15N) depended on sex, leading to resource partitioning that can potentially reduce intraspecific competition. Decision-makers and stakeholders should consider the trophic dynamics of sex and body size groups for the sustainable management and conservation of caiman populations, which implies in the maintenance of wetland habitats and landscape heterogeneity in the Formoso River floodplain.


Hazardous drinking and HIV sexual risk behaviors among injection drug users in developing and transitional countries.
Studies in North America and Western Europe have reported an association between hazardous drinking and HIV sexual risk behaviors among injection drug users (IDUs). However, we lack such studies from developing and transitional countries, where different cultural norms and contexts of drinking may change this association. We used a multi-site study using standard survey instruments and methods to examine whether hazardous drinking is associated with HIV sexual risk behaviors (defined as unprotected sex and having multiple sex partners) among IDUs in 12 cities across different developing and transitional countries. Data were collected from May 1999 to November 2003. In individual site analyses, hazardous drinking was associated with increased HIV risk behaviors in 10 cities. Mixed effects models of the multi-site data, also, showed an association of hazardous drinking and HIV sexual risk behaviors. These findings in the context of the high prevalence of drinking in many sites point to the importance of addressing alcohol use in HIV education and prevention policy for IDUs.


Diagnosing anorexia based on partial least squares, back propagation neural network, and support vector machines.
Support vector machine (SVM), as a novel type of learning machine, for the first time, was used to develop a predictive model for early diagnosis of anorexia. It was based on the concentration of six elements (Zn, Fe, Mg, Cu, Ca, and Mn) and the age extracted from 90 cases. Compared with the results obtained from two other classifiers, partial least squares (PLS) and back-propagation neural network (BPNN), the SVM method exhibited the best whole performance. The accuracies for the test set by PLS, BPNN, and SVM methods were 52%, 65%, and 87%, respectively. Moreover, the models we proposed could also provide some insight into what factors were related to anorexia.


An efficient polymer molecular sieve for membrane gas separations.
Microporous polymers of extreme rigidity are required for gas-separation membranes that combine high permeability with selectivity. We report a shape-persistent ladder polymer consisting of benzene rings fused together by inflexible bridged bicyclic units. The polymer's contorted shape ensures both microporosity-with an internal surface area greater than 1000 square meters per gram-and solubility so that it is readily cast from solution into robust films. These films demonstrate exceptional performance as molecular sieves with high gas permeabilities and good selectivities for smaller gas molecules, such as hydrogen and oxygen, over larger molecules, such as nitrogen and methane. Hence, this polymer has excellent potential for making membranes suitable for large-scale gas separations of commercial and environmental relevance.


The association between drinking water turbidity and gastrointestinal illness: a systematic review.
Studies suggest that routine variations in public drinking water turbidity may be associated with endemic gastrointestinal illness. We systematically reviewed the literature on this topic. We searched databases and websites for relevant studies in industrialized countries. Studies investigating the association between temporal variations in drinking water turbidity and incidence of acute gastrointestinal illness were assessed for quality. We reviewed good quality studies for evidence of an association between increased turbidity and gastrointestinal illness. We found six relevant good quality studies. Of five studies investigating effluent water turbidity, two found no association. Two studies from Philadelphia reported increased paediatric and elderly hospital use on specific days after increased turbidity. A fifth study reported more telephone health service calls on specific days after peak turbidity. There were differences between studies affecting their comparability, including baseline turbidity and adjustment for seasonal confounders. It is likely that an association between turbidity and GI illness exists in some settings or over a certain range of turbidity. A pooled analysis of available data using standard methods would facilitate interpretation.


Kinetics of deamination of cytosine nucleosides with etherified sugar hydroxyls.
The kinetics of deamination of derivatives of the therapeutically important 1-beta-D-arabinofuranosylcytosine with etherified (methylated) sugar hydroxyls has provided additional direct evidence for involvement of the 2'-hydroxyl in intramolecular catalysed deamination. In the case of 1-beta-D-lyxofuranosylcytosine, the kinetics of deamination of its 2'-O-methyl and 3'-O-methyl derivatives pointed to similar involvement of the "up" 2'-OH in intramolecular catalysed deamination. Participation by the 3'-OH, which is also in the "up" position, was excluded. A qualitative correlation was shown to exist between the electron density distributions on C(4) and C(6) of the cytosine rings in cytosine, 1-methylcytosine and cytidine, and their relative susceptibilities to deamination.


Organic thin film transistor using a photo-curable organic/inorganic hybrid material as a gate dielectric.
A polyhedral oligomeric silsesquioxane derivative (POSS-OXT) containing photo-curable 4-membered cyclic oxetane functional groups was used as a gate dielectric of organic field effect transistor. The POSS-OXT was cross-linked and completely solidified by UV irradiation in the presence of a selected photo acid generator, and pinhole free uniform thin film was obtained. We fabricated a metal/insulator/metal device of Au/POSS-OXT (300 nm)/Au with area of 0.7 mm2 and the measured leakage current and capacitance of the device to evaluate the insulating properties of the POSS-OXT thin film. The maximum current was about 0.25 nA when 40 V was applied to the device. The observed values of the capacitance per unit area and dissipation factor were 11.4 nF/cm2 and 0.025, respectively. We fabricated an organic thin film transistor with pentacene as the active semiconductor and the photo-cross-linked POSS-OXT as an insulator. A field effect carrier mobility of 0.03 cm2/VN s was obtained with the device.


Polymorphism of angiotensin-converting enzyme (rs4340) and diabetic nephropathy in Caucasians with type 2 diabetes mellitus.
Diabetic nephropathy (DN) is the leading cause of endstage renal disease (ESRD) in developed countries. Several environmental and genetic factors predict the development and progression of DN. The renin-angiotensin system was demonstrated to be involved in the development of DN. We evaluated the association between rs4340 of the angiotensin-converting enzyme (ACE) gene and DN in Caucasians with type 2 diabetes mellitus (T2DM) in 276 Slovenian patients with T2DM who had DN, and 375 patients without clinical signs of DN. Genetic analysis was performed with either standard polymerase chain reaction (PCR) (for rs4340). Results were analyzed using the χ2 test and multivariate logistic regression analyses. We found no association between rs4340 and DN. Cystatin C was significantly higher in the DN+ group (p <0.001) than in the DN group. Cystatin C was a better marker for the estimation of renal function than estimated glomerular filtration rate (eGFR) according to the modification diet in renal disease (MDRD) equation mL/ min. We concluded that there was no association between the rs4340 of the ACE gene and DN in Caucasian patients who have T2DM.


Electrochemical transformations catalyzed by cytochrome P450s and peroxidases.
Cytochrome P450s (Cyt P450s) and peroxidases are enzymes featuring iron heme cofactors that have wide applicability as biocatalysts in chemical syntheses. Cyt P450s are a family of monooxygenases that oxidize fatty acids, steroids, and xenobiotics, synthesize hormones, and convert drugs and other chemicals to metabolites. Peroxidases are involved in breaking down hydrogen peroxide and can oxidize organic compounds during this process. Both heme-containing enzymes utilize active FeIVO intermediates to oxidize reactants. By incorporating these enzymes in stable thin films on electrodes, Cyt P450s and peroxidases can accept electrons from an electrode, albeit by different mechanisms, and catalyze organic transformations in a feasible and cost-effective way. This is an advantageous approach, often called bioelectrocatalysis, compared to their biological pathways in solution that require expensive biochemical reductants such as NADPH or additional enzymes to recycle NADPH for Cyt P450s. Bioelectrocatalysis also serves as an ex situ platform to investigate metabolism of drugs and bio-relevant chemicals. In this paper we review biocatalytic electrochemical reactions using Cyt P450s including C-H activation, S-oxidation, epoxidation, N-hydroxylation, and oxidative N-, and O-dealkylation; as well as reactions catalyzed by peroxidases including synthetically important oxidations of organic compounds. Design aspects of these bioelectrocatalytic reactions are presented and discussed, including enzyme film formation on electrodes, temperature, pH, solvents, and activation of the enzymes. Finally, we discuss challenges and future perspective of these two important bioelectrocatalytic systems.


Morbidity of Brown Recluse spider bites. Clinical picture, treatment and prognosis.
A retrospective review was made of 35 cases of Brown Recluse spider bites treated during a period of 21 years. The most common location of the bite was on the lower limbs, particularly the thigh. The main systemic manifestations were fever, malaise and maculopapular rash, but there were no cases of hemolysis, coagulopathy, or of renal or neurologic involvement. Signs indicating a poor prognosis appeared to be lymphangitis, generalized maculopapular rash and location of the bite on the thigh or abdomen. Most cases were treated effectively by rest, elevation of the affected part of the body, local cleansing, and prophylactic antibiotics. On the basis of this experience it was concluded that only when lesions show a necrotic area measuring 2 to 3 cm should patients be treated with systemic corticosteroids. In most such cases, administration of corticosteroids for 14-21 days proved sufficient to avoid the need for surgery. Only 5 cases required surgical intervention.


IP3 Receptor-Mediated Calcium Signaling and Its Role in Autophagy in Cancer.
Calcium ions (Ca2+) play a complex role in orchestrating diverse cellular processes, including cell death and survival. To trigger signaling cascades, intracellular Ca2+ is shuffled between the cytoplasm and the major Ca2+ stores, the endoplasmic reticulum (ER), the mitochondria, and the lysosomes. A key role in the control of Ca2+ signals is attributed to the inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), the main Ca2+-release channels in the ER. IP3Rs can transfer Ca2+ to the mitochondria, thereby not only stimulating core metabolic pathways but also increasing apoptosis sensitivity and inhibiting basal autophagy. On the other hand, IP3-induced Ca2+ release enhances autophagy flux by providing cytosolic Ca2+ required to execute autophagy upon various cellular stresses, including nutrient starvation, chemical mechanistic target of rapamycin inhibition, or drug treatment. Similarly, IP3Rs are able to amplify Ca2+ signals from the lysosomes and, therefore, impact autophagic flux in response to lysosomal channels activation. Furthermore, indirect modulation of Ca2+ release through IP3Rs may also be achieved by controlling the sarco/endoplasmic reticulum Ca2+ ATPases Ca2+ pumps of the ER. Considering the complex role of autophagy in cancer development and progression as well as in response to anticancer therapies, it becomes clear that it is important to fully understand the role of the IP3R and its cellular context in this disease. In cancer cells addicted to ER-mitochondrial Ca2+ fueling, IP3R inhibition leads to cancer cell death via mechanisms involving enhanced autophagy or mitotic catastrophe. Moreover, IP3Rs are the targets of several oncogenes and tumor suppressors and the functional loss of these genes, as occurring in many cancer types, can result in modified Ca2+ transport to the mitochondria and in modulation of the level of autophagic flux. Similarly, IP3R-mediated upregulation of autophagy can protect some cancer cells against natural killer cells-induced killing. The involvement of IP3Rs in the regulation of both autophagy and apoptosis, therefore, directly impact cancer cell biology and contribute to the molecular basis of tumor pathology.


Development of a loop-mediated isothermal amplification coupled lateral flow dipstick targeting erm(41) for detection of Mycobacterium abscessus and Mycobacterium massiliense.
Mycobacterium abscessus (M. abscessus) and Mycobacterium massiliense (M. massiliense) are major pathogens that cause post-surgical wound infection and chronic pulmonary disease. Although they are closely related subspecies of M. abscessus complex, their infections are associated with different drug-resistance and cure rate. In the present study, a loop-mediated isothermal amplification (LAMP) coupled with lateral flow dipstick (LFD) method was developed to simultaneous detect M. abscessus and M. massiliense, via specific erm(41) gene. The amplification was carried out at 65 °C for only 60 min, and the results could be visualized on a lateral flow strip. Positive results only occurred in M. abscessus and M. massiliense, no cross-reaction with other mycobacterial species was observed. Therefore, the cost-effective MABC (M. abscessus complex)-LAMP-LFD method developed here was able to correct the diagnose of M. abscessus and M. massiliense infection in a short time. Thus, this method could be used to guide clinicians in treatment of M. abscessus group infections.


The benefits of grouping as a main driver of social evolution in a halictine bee.
Over the past decade, the cause of sociality has been much debated. Inclusive fitness [br in Hamilton's rule (br - c > 0)] has been criticized but is still useful in the organization of a framework by elucidating mechanisms through which br (benefit × relatedness) becomes larger than c (cost). The bee Lasioglossum baleicum is suitable for investigation of this issue because of the sympatric occurrence of both social and solitary nesting in its populations. We show that a large part (approximately 92%) of the inclusive fitness of a eusocial worker can be attributed to the benefits of grouping. A 1.5-fold relatedness asymmetry benefit in singly mated haplo-diploids explains a small part (approximately 8.5%) of the observed inclusive fitness. Sociality enables this species to conduct foraging and nest defense simultaneously, which is not the case in solitary nests. Our results indicate that this benefit of grouping is the main source of the increased inclusive fitness of eusocial workers.


Induction of fecal cholesterol excretion is not effective for the treatment of hyperbilirubinemia in Gunn rats.
Unconjugated hyperbilirubinemia, a feature of neonatal jaundice or Crigler-Najjar syndrome, can lead to neurotoxicity and even death. We previously demonstrated that unconjugated bilirubin (UCB) can be eliminated via transintestinal excretion in Gunn rats, a model of unconjugated hyperbilirubinemia, and that this is stimulated by enhancing fecal fatty acid excretion. Since transintestinal excretion also occurs for cholesterol (TICE), we hypothesized that increasing fecal cholesterol excretion and/or TICE could also enhance fecal UCB disposal and subsequently lower plasma UCB concentrations. To determine whether increasing fecal cholesterol excretion could ameliorate unconjugated hyperbilirubinemia, we treated hyperbilirubinemic Gunn rats with ezetimibe (EZE), an intestinal cholesterol absorption inhibitor, and/or a liver X receptor (LXR) and farnesoid X receptor (FXR) agonist (T0901317 (T09) and obeticholic acid (OCA), respectively), known to stimulate TICE. We found that EZE treatment alone or in combination with T09 or OCA increased fecal cholesterol disposal but did not lower plasma UCB levels. These findings do not support a link between the regulation of transintestinal excretion of cholesterol and bilirubin. Furthermore, induction of fecal cholesterol excretion is not a potential therapy for unconjugated hyperbilirubinemia. Increasing fecal cholesterol excretion is not effective to treat unconjugated hyperbilirubinemia. This is the first time a potential relation between transintestinal excretion of cholesterol and unconjugated bilirubin is investigated. Transintestinal excretion of cholesterol and unconjugated bilirubin do not seem to be quantitatively linked. Unlike intestinal fatty acids, cholesterol cannot "capture" unconjugated bilirubin to increase its excretion. These results add to our understanding of ways to improve and factors regulating unconjugated bilirubin disposal in hyperbilirubinemic conditions.


Effect of Physician IT Use on Practice Performance.
The role of information technology (IT) remains important within the medical community. However, little is known about the extent to which practicing physicians improve practice performance by having and utilizing IT at the national level. The present study, analyzing a national physician survey (n = 4,720), seeks to explore associations of IT availability and utilization with practice performance at the national level. The multivariate regression analysis results suggest that patient information IT functionality upholds physician advantages in annual income but prescription drug IT functionality was reversely linked to annual income. We also found a negative association of patient information IT functionality with patient visit volume. Our study results revealed mixed findings. Not all IT functionalities would offer benefits to practicing physicians. Our data suggest that patient information IT functionality can moderate cost concerns related to IT investment among providers.


Clusters of amniotic fluid cells and their associated early neuroepithelial markers in experimental myelomeningocele: Correlation with astrogliosis.
Myelomeningocele (MMC) is the most common and severe disabling type of spina bifida resulting in the exposure of vulnerable spinal cord to the hostile intrauterine environment. In this study, we sought to examine the cellular content of fetal amniotic fluid (AF) in MMC and explore a correlation between these cells and pathological development of MMC. MMC was induced in fetal rats by exposing pregnant mothers to all-trans retinoic acid and AF samples were collected before term. Cells were isolated from AF samples and morphologically and phenotypically characterized in short-term cultures. In addition, the spinal cord injury in MMC fetuses was assessed by immunohistochemical examination of astrogliosis. We identified a population of cells from the AF of MMC fetuses (MMC-AF) that formed adherent clusters of tightly packed cells, which were absent from the AF of normal control fetuses (norm-AF). MMC-AF clusters contained cells co-expressing adherens junction associated proteins (ZO-1), N-cadherin and F-actin at sites of cell-cell contacts. In addition, they expressed markers of early neuroepithelial cells such as SOX-1 and Pax-6 along with other stem/progenitor cell markers such as SOX-2 and nestin. Subpopulations of cells in MMC-AF clusters also expressed more advanced differentiation markers such as doublecortin and GFAP. We found that the appearance of cluster forming cells in cultures from MMC-AF correlated with activation of astrogliosis associated with the spinal cord injury in MMC fetuses. In summary, we identified a neuroepithelial cell population in the AF of MMC fetuses that formed adherent clusters in culture and we characterized cellular markers of these cells. Our data suggests that the phase of the disease is a crucial factor in the emergence of these cells into the AF and that these cells may provide a new and important platform for studying the progression of MMC and development of improved strategies for the repair and diagnosis of MMC prenatally.


Suppression of BRCA1 sensitizes cells to proteasome inhibitors.
BRCA1 is a multifunctional protein best known for its role in DNA repair and association with breast and ovarian cancers. To uncover novel biologically significant molecular functions of BRCA1, we tested a panel of 198 approved and experimental drugs to inhibit growth of MDA-MB-231 breast cancer cells depleted for BRCA1 by siRNA. 26S proteasome inhibitors bortezomib and carfilzomib emerged as a new class of selective BRCA1-targeting agents. The effect was confirmed in HeLa and U2OS cancer cell lines using two independent siRNAs, and in mouse embryonic stem (ES) cells with inducible deletion of Brca1. Bortezomib treatment did not cause any increase in nuclear foci containing phosphorylated histone H2AX, and knockdown of BRCA2 did not entail sensitivity to bortezomib, suggesting that the DNA repair function of BRCA1 may not be directly involved. We found that a toxic effect of bortezomib on BRCA1-depleted cells is mostly due to deregulated cell cycle checkpoints mediated by RB1-E2F pathway and 53BP1. Similar to BRCA1, depletion of RB1 also conferred sensitivity to bortezomib, whereas suppression of E2F1 or 53BP1 together with BRCA1 reduced induction of apoptosis after bortezomib treatment. A gene expression microarray study identified additional genes activated by bortezomib treatment only in the context of inactivation of BRCA1 including a critical involvement of the ERN1-mediated unfolded protein response. Our data indicate that BRCA1 has a novel molecular function affecting cell cycle checkpoints in a manner dependent on the 26S proteasome activity.


Strong Binding of C-Glycosylic1,2-Thiodisaccharides to Galectin-3─Enthalpy-Driven Affinity Enhancement by Water-Mediated Hydrogen Bonds.
Galectin-3 is involved in multiple pathways of many diseases, including cancer, fibrosis, and diabetes, and it is a validated pharmaceutical target for the development of novel therapeutic agents to address unmet medical needs. Novel 1,2-thiodisaccharides with a C-glycosylic functionality were synthesized by the photoinitiated thiol-ene click reaction of O-peracylated 1-C-substituted glycals and 1-thio-glycopyranoses. Subsequent global deprotection yielded test compounds, which were studied for their binding to human galectin-3 by fluorescence polarization and isothermal titration calorimetry to show low micromolar Kd values. The best inhibitor displayed a Kd value of 8.0 μM. An analysis of the thermodynamic binding parameters revealed that the binding Gibbs free energy (ΔG) of the new inhibitors was dominated by enthalpy (ΔH). The binding mode of the four most efficient 1,2-thiodisaccharides was also studied by X-ray crystallography that uncovered the unique role of water-mediated hydrogen bonds in conferring enthalpy-driven affinity enhancement for the new inhibitors. This 1,2-thiodisaccharide-type scaffold represents a new lead for galectin-3 inhibitor discovery and offers several possibilities for further development.


Effects on health, performance, and tissue residues of the ionophore antibiotic salinomycin in finishing broilers (21 to 38 d).
A study was conducted to evaluate the effects of feeding salinomycin at the recommended prophylactic level, and at 2 and 3 times this level, to finishing male broilers (d 21 to 38). Four treatment groups were given the experimental diets containing 0, 60, 120, or 180 parts per million (ppm) salinomycin from d 21 to 38. Performance, relative organ weights, selected serum enzymes, and salinomycin residues in liver, muscle, and serum were determined. Salinomycin supplementation had no effect on body weight, feed intake, or feed conversion, and caused no overt signs of toxicity. After a week of being fed the salinomycin diets, the serum activity of aspartate aminotransferase was significantly increased in chickens fed 180 ppm compared with controls. These birds also showed microscopic lesions in breast and thigh muscles, but not in cardiac muscle. Salinomycin residues were not detected by high-performance liquid chromatography coupled to tandem mass spectrometry in liver or muscle samples from the birds fed 0, 60, or 120 ppm salinomycin. However, chickens fed 180 ppm salinomycin had detectable levels in liver and muscle above the maximum residue level of 5 μg/kg established by the European Union. All birds fed salinomycin had salinomycin in their sera with levels ranging from N.D. (not detected) in the controls to 24.4 ± 7.9, 61.4 ± 18.9, and 94.5 ± 9.1 μg/L for salinomycin dietary levels of 60, 120, and 180 ppm, respectively. Serum salinomycin concentration was linearly related with salinomycin content in feed (y = 0.584x - 10, r2 = 0.999). The results showed that even at 3 times the prophylactic level, salinomycin does not induce clinical toxicosis or mortality. No salinomycin residues were found in edible tissues at the recommended dietary level or at 2 times this level. However, salinomycin was detected in serum regardless of the dietary level. A simple method for salinomycin determination in serum is described which can be used as a marker of exposure and/or to predict levels in the diet.


Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil.
In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with different predominant virus strains. We performed a time trend study to evaluated excess of mortality for pneumonia and influenza, respiratory disease, and all-causes in southern region of Brazil, from 2002 to 2015. After considering other models, we opted for Serfling regression. Excess of death rates per 100,000 inhabitants were analyzed in specific age groups (24-59, 60-69, 70-79, ≥80 years) and by year of occurrence. Mortality information were taken from Brazilian Mortality Information System and etiological data were accessed in Sentinel Virological Surveillance database, getting the weekly positivity of the immunofluorescence tests for influenza A (H1N1, H3N2), and B. In southern Brazil, there is an evident seasonal pattern of all death outcomes among different age groups in the dry and cold season (April-September). The highest excess mortality rates occurs among older, particularly in years of circulation of influenza AH3N2, especially among people ≥80 years, in 2003 and 2007-years of great severity of influenza activity. After 2009, with the introduction of the pandemic influenza AH1N1, we observed a lower impact on the mortality of the elderly compared to <60 years. A cross reactivity antibody response from past exposure probably provided protection against disease in the elderly. Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. The reduced immune response to infection, and to vaccination, and presence of comorbidities recommend a special attention to this age group in Brazil. Besides medical assistance, the timeliness of vaccine campaigns, its composition, and etiological surveillance of respiratory diseases are some of the preventive and public health measures.


Respecting the autonomy of chronic mentally ill women in decisions about contraception.
Treatment of women patients with chronic mental illness who are at risk of unwanted pregnancies presents ethical challenges to the clinician who wishes to respect the patient's autonomy while also helping her avert the potential adverse consequences of unwanted pregnancy. The clinician who simply allows the patient to continue at risk or coerces her into using contraception may not have adequately considered the variable nature of the patient's autonomy. The authors suggest that the clinician should assess and treat conditions underlying the patient's variable impairment of autonomy to maximize her ability to participate in family planning decisions. Case examples are used to illustrate assessment of patients' decision-making capacity, development of family planning approaches that respect patients' autonomy, and use of a newly available contraceptive implant.


Nerve regeneration in cornea after penetrating keratoplasty in rabbit, with special reference to relationship between regenerating nerves and basal laminae.
The pattern of nerve regeneration in the grafted rabbit cornea was investigated by electron microscopy. Grafted corneas were excised 2, 7, 14 and 28 days after grafting, and processed for observation by conventional electron microscopy. In the normal, unoperated cornea Schwann cell basal laminae are, unlike those of ordinary peripheral nerves, discontinuous and fragmentary on the fibers coursing through the corneal stroma. In the early stage of regeneration, while numbers of regenerating axons extended through the Schwann cell columns of regenerating axons extended through the Schwann cell columns in the grafts, many other regenerating axons elongated as single fibers through the corneal stroma outside the Schwann cell columns. These single naked axons were later enveloped by Schwann cell cytoplasm, contributing to the overall dense irregular pattern of regenerated nerves in the grafted cornea. It was thought that the regenerating axons can extend throughout the stroma without the guidance of basal lamina tubes, making the corneal stroma a favorable environment for nerve regeneration.


One-year follow-up of bag-in-the-lens intraocular lens implantation in 60 eyes.
To report the feasibility and clinical results of implanting a bag-in-the-lens intraocular lens (IOL) designed to prevent posterior capsule opacification after cataract surgery. Departments of Ophthalmology, University of Antwerp, Antwerp, Belgium, and University of Munich, Munich, Germany. This prospective study comprised 63 eyes (55 patients; 7 children, 48 adults) scheduled for cataract surgery and bag-in-the-lens IOL implantation. A posterior curvilinear capsulorhexis the same size as the anterior capsulorhexis was created for IOL insertion. After surgery, lens epithelial cell (LEC) proliferation was documented every 6 months with a minimum follow-up of 12 months. Sixty of 63 eyes (95%) had implantation of the bag-in-the-lens IOL. Conversion to a conventional IOL was necessary in 2 cases. In 1 eye, postoperative luxation of the IOL into the vitreous occurred as a result of an oversized anterior and posterior capsulorhexis. Three eyes had early postoperative iris incarceration in the lens groove that required surgery. No LEC proliferation on the optic occurred during a mean follow-up of 22.7 months (range 12 to 64 months); LEC proliferation was confined to the peripheral capsular bag. Lens epithelial cell proliferation was mild and confined to the periphery of the capsular bag during follow-up, and the bag-in-the-lens IOL optic remained clear.


Association of Grb7 with phosphoinositides and its role in the regulation of cell migration.
Grb7 is the prototype of a family of adaptor molecules that also include Grb10 and Grb14 that share a conserved molecular architecture including Src homology 2 (SH2) and pleckstrin homology (PH) domains. Grb7 has been implicated as a downstream mediator of integrin-FAK signal pathways in the regulation of cell migration, although the molecular mechanisms are still not well understood. In this paper, we investigated the potential role and mechanisms of PH domain in Grb7 in the regulation of cell migration. We found that the PH domain mediated Grb7 binding to phospholipids both in vitro and in intact cells. Furthermore, both Grb7 and its PH domain preferentially interacted with phosphatidylinositol phosphates showing strongest affinity to the D3- and D5-phosphoinositides. The PH domain interaction with phosphoinositides was shown to play a role in the stimulation of cell migration by Grb7. It was also shown to be necessary for Grb7 phosphorylation by FAK, although it was not required for Grb7 interaction with FAK or recruitment to the focal contacts. Last, we found that PI 3-kinase activity played a role in both Grb7 association with phosphoinositides and its stimulation of cell migration. In addition, both FAK binding to PI 3-kinase via its autophosphorylated Tyr(397) and integrin-mediated cell adhesion increased Grb7 association with phosphoinositides. Together, these results identified the Grb7 PH domain interaction with phosphoinositides and suggested a potential mechanism by which several signaling molecules including Grb7, FAK, and PI 3-kinase and their interactions cooperate to mediate signal transduction pathways in integrin-mediated cell migration.


Papillary carcinoma of the thyroid gland seen as lateral neck cyst.
The clinical, roentgenographic, histologic, and cytologic features of four cases of papillary carcinoma of the thyroid gland seen as lateral neck cysts are discussed. Carcinoma of the thyroid gland characteristically is a solid tumor and appears as a firm, painless, and otherwise asymptomatic mass in the anterior paramedial part of the neck. A nontender fluctuant lateral neck mass commonly implies a benign lesion. The diagnostic procedures used (namely, fine-needle aspiration and ultrasound and thyroid scans) may belie the nature of the lateral neck lesion. Examination of the tissue is necessary to confirm the diagnosis.


Combined Mek inhibition and Pparg activation Eradicates Muscle Invasive Bladder cancer in a Mouse Model of BBN-induced Carcinogenesis.
Bladder cancers (BCs) can be divided into 2 major subgroups displaying distinct clinical behaviors and mutational profiles: basal/squamous (BASQ) tumors that tend to be muscle invasive, and luminal/papillary (LP) tumors that are exophytic and tend to be non-invasive. Pparg is a likely driver of LP BC and has been suggested to act as a tumor suppressor in BASQ tumors, where it is likely suppressed by MEK-dependent phosphorylation. Here we tested the effects of rosiglitazone, a Pparg agonist, in a mouse model of BBN-induced muscle invasive BC. Rosiglitazone activated Pparg signaling in suprabasal epithelial layers of tumors but not in basal-most layers containing highly proliferative invasive cells, reducing proliferation but not affecting tumor survival. Addition of trametinib, a MEK inhibitor, induced Pparg signaling throughout all tumor layers, and eradicated 91% of tumors within 7-days of treatment. The 2-drug combination also activated a luminal differentiation program, reversing squamous metaplasia in the urothelium of tumor-bearing mice. Paired ATAC-RNA-seq analysis revealed that tumor apoptosis was most likely linked to down-regulation of Bcl-2 and other pro-survival genes, while the shift from BASQ to luminal differentiation was associated with activation of the retinoic acid pathway and upregulation of Kdm6a, a lysine demethylase that facilitates retinoid-signaling. Our data suggest that rosiglitazone, trametinib, and retinoids, which are all FDA approved, may be clinically active in BASQ tumors in patients. That muscle invasive tumors are populated by basal and suprabasal cell types with different responsiveness to PPARG agonists will be an important consideration when designing new treatments.


Proteolysis associated with a deficit of peripheral energy fuel substrates in septic man.
Sixteen seriously septic patients were studied to determine whether proteolysis occurred to satisfy a deficit of peripheral fuel, as suggested by out previous experimental observations. Concentrations of glucose, lactate, free fatty acids,and alanine were measured in blood samples from the femoral artery and vein to determine extraction (+) and release (-) by the leg. Simultaneously, cardiac index (CI) was determined by thermal dilution, so that an estimate of uptake or production of fuel substrates could be made from the proportional relationship of cardiac index to peripheral blood flow. Due to the antilipolytic effect of elevated levels of insulin (42 +/- 4 muM per milliliter) in those patients with elevated cardiac indices (4.38 +/- 0.33 L. per square meter per minute), free fatty acid uptake (-0.59 +/- 0.021 mM.) was reduced. In low-flow septic shock (CI, 1.66 +/- .41 L. per square meter per minute), the majority of glucose taken up by the limb was converted to lactate (arterial lactate, 3.14 +/- 0.7 mM.; deltaA-V 0.68 +/- 0.17). Free fatty acid uptake also was impaired in low-flow sepsis. As opposed to fasting, arterial levels and uptake of ketone bodies were insignificant in sepsis. These findings suggest that there is a deficit of peripheral fuel with respect to glucose and fat. That protein is oxidized to fill this deficit is substantiated by the increased alanine release (-0.13 +/- 0.01, -0.33 +/- 0.12 mM.) in the high-flow and low-flow septic groups, respectively, whereas alanine production was three- and fourfold greater than that observed in fasting patients. Enhanced release of alanine reflects the magnitude of oxidation of branched-chain amino acids and accounts for the high rates of gluconeogenesis and proteolysis observed in sepsis.


Chemical and biological agent incident response and decision process for civilian and public sector facilities.
In the event of a terrorist attack or catastrophic release involving potential chemical and/or biological warfare agents, decisionmakers will need to make timely and informed choices about whether, or how, to respond. The objective of this article is to provide a decision framework to specify initial and follow-up actions, including possible decontamination, and to address long-term health and environmental issues. This decision framework consists of four phases, beginning with the identification of an incident and ending with verification that cleanup and remediation criteria have been met. The flowchart takes into account both differences and similarities among potential agents or toxins at key points in the decision-making process. Risk evaluation and communication of information to the public must be done throughout the process to ensure a successful effort.


Iterative Reconstructions in Reduced-Dose CT: Which Type Ensures Diagnostic Image Quality in Young Oncology Patients?
To compare adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) algorithms for reduced-dose computed tomography (CT). Forty-four young oncology patients (mean age 30 ± 9 years) were included. After routine thoraco-abdominal CT (dose 100%, average CTDIvol 9.1 ± 2.4 mGy, range 4.4-16.9 mGy), follow-up CT was acquired at 50% (average CTDIvol 4.5 ± 1.2 mGy, range 2.2-8.4 mGy) in 29 patients additionally at 20% dose (average CTDIvol 1.9 ± 0.5 mGy, range 0.9-3.4 mGy). Each reduced-dose CT was reconstructed using both ASIR and MBIR. Four radiologists (two juniors and two seniors) blinded to dose and technique read each set of CT images regarding objective and subjective image qualities (high- or low-contrast structures), subjective noise or pixilated appearance, diagnostic confidence, and lesion detection. At all dose levels, objective image noise was significantly lower with MBIR than with ASIR (P < 0.001). The subjective image quality for low-contrast structures was significantly higher with MBIR than with ASIR (P < 0.001). Reduced-dose abdominal CT images of patients with higher body mass index (BMI) were read with significantly higher diagnostic confidence than images of slimmer patients (P < 0.001) and had higher subjective image quality, regardless of technique. Although MBIR images appeared significantly more pixilated than ASIR images, they were read with higher diagnostic confidence, especially by juniors (P < 0.001). Reduced-dose CT during the follow-up of young oncology patients should be reconstructed with MBIR to ensure diagnostic quality. Elevated body mass index does not hamper the quality of reduced-dose CT.


Ectopic expression of retinoic acid receptors and change of myocardial structure in the offspring heart with vitamin A deficiency.
Vitamin A is a key micronutrient required during crucial stages of embryonic development and vitamin A deficiency (VAD) results in embryonic heart malformation. The pleiotropic functions of vitamin A are mediated by specific nuclear receptors: the retinoic acid receptors (RARα, -β, and -γ) and the retinoic X receptors (RXRα, -β, and -γ). The action of nuclear receptors has been implicated in controlling of cell proliferation, differentiation and apoptosis, and the expressions of these receptor genes are regulated by retinoic acid levels during the early stages of embryonic development. GATA-4 is one of the earliest transcription factors expressed in developing cardiac cells. However, the functional links of specific nuclear receptors to heart development in VAD embryos are not clearly understood. In our study, weaning female Sprague-Dawley rats were fed a modified diet containing different concentrations of vitamin A according to the American Institute of Nutrition 93 Growth Purified Diet. After 10-wk feeding, the female rats were mated with normal male rats, and a portion of them were transferred to a diet with enough added vitamin A for the pregnancy cycle. The embryo hearts were dissected out at embryonic day 13.5 (E13.5) to study the expression of RARs, RXRs and GATA-4. The embryo hearts from E18.5 were for observation of ultrastructural changes. In comparison to vitamin A supplemented groups, the embryo hearts from vitamin A insufficient groups exhibited ultrastructural changes and significantly lower expression of GATA-4, RARα, and -γ, and higher expression of RXRα and -β. Our findings suggest that the down-regulation of RARs and the up-regulation of RXRs resulted from VAD affected GATA-4 gene expression, which resulted in ultrastructural changes in embryo hearts due to maternal insufficiency of vitamin A during pregnancy.


[Evaluation of needs in early post-stroke rehabilitation in Poland].
According to European Stroke Initiative (EUSI) recommendations every stroke patient should undergo rehabilitation. We aimed to evaluate the needs of comprehensive stroke in-patient rehabilitation in Poland. We designed and distributed a questionnaire evaluating rehabilitation departments in Poland, where stroke patients undergo early rehabilitation. Comprehensive rehabilitation was defined as: kinesitherapy (minimum 60 minutes/day), speech therapy (minimum 30 minutes 5 days a week), rehabilitation of other cognitive impairments and group kinesitherapy. We separated rehabilitation departments where comprehensive post-stroke rehabilitation is conducted, and calculated the number of beds in these departments only for stroke patients. We estimated the number of acute stroke patients in Poland. We evaluated the number of patients requiring in-patient rehabilitation based on results from the 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, where all stroke patients who need in-patient rehabilitation have such a possibility. We estimated the number of beds required in rehabilitation departments for stroke patients in Poland. We obtained responses from 115 out of 172 (66.9%) rehabilitation departments. Comprehensive post-stroke rehabilitation is conducted in 11 departments. 159 beds in these departments are for stroke patients. From 64,896 acute stroke patients 9,927 will need in-patient rehabilitation. We need 604 more beds in rehabilitation departments for stroke patients in Poland. Only 10% of rehabilitation departments could provide comprehensive stroke rehabilitation in Poland. At present, the number of beds in rehabilitation departments for stroke patients covers about 20.8% of actual needs. An increased number of rehabilitation beds for stroke patients could result in a decreased number of disabled post-stroke patients.


Aldosterone: good guy or bad guy in cerebrovascular disease?
Stroke is a leading cause of disability in the Western world, yet the choices for therapeutic intervention are few. The complex role played by aldosterone in the pathogenesis of stroke is beginning to emerge. Chronic mineralocorticoid receptor (MR) blockade reduces the incidence of hemorrhagic strokes and the severity of damage caused by ischemic strokes. This appears to be a vascular phenomenon because MR blockade increases vessel lumen diameter, which presumably increases blood flow and perfusion of the tissue to reduce ischemic damage. However, the vascular protection afforded by MR antagonism is at odds with the results seen within the brain, where MR activation is required for neuronal survival. Both of these divergent effects have possible therapeutic implications for stroke.


Optimizing Direct Membrane and Direct Skin Feeding Assays for Plasmodium falciparum Transmission-Blocking Vaccine Trials in Bancoumana, Mali.
Malaria transmission-blocking vaccines (TBV) have been evaluated in field trials in Mali since 2013. However, the assays currently used to measure serum antibody TB activity (TBA) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. Herein, we report a study conducted in Bancoumana village, Mali, where we identify and optimize the parameters that contribute to successful mosquito feeding outcomes in both direct skin feeds (DSFs) and direct membrane feeding assays (DMFA). These parameters include: 1) mosquito age, 2) duration of mosquito starvation prior to feeding, 3) membrane selection for DMFA, 4) anatomical location of DSF feeding (arm, calf, and ankle), and 5) time of day for DSF (dawn or dusk). We found that younger mosquitoes were significantly associated with higher feeding, survival, and infection rates. Longer starvation times were positively, but not significantly, associated with higher infection rates, but were negatively associated with feeding and survival. Membrane type and body location did not affect infection outcome significantly. Although dusk was found to be associated with higher infection rates, this may be confounded by the time from positive blood smear. Based on these findings, we make specific recommendations for optimal feeding parameters in the different assay types to maximize the chance of detecting parasite transmission in a standardized manner.


Characterization of a collagenous cementum-derived attachment protein.
We report further characterization of a cementum-derived protein that promotes the adhesion and spreading of periodontal cells. The cementum attachment protein (CAP) was extracted from bovine cementum, separated by diethylamino ethyl (DEAE)-cellulose chromatography, and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and C18 reverse phase high performance liquid chromatography. The purified preparation contained a single protein band migrating with M(r) 56,000. It did not cross-react with polyclonal antibodies to osteopontin, vitronectin, or other attachment proteins. The attachment activity was resistant to chondroitinase ABC digestion. An internal amino acid sequence of six peptides was determined by microsequencing, and the peptide sequences were not present in other attachment proteins described in cementum. Four sequences contained Gly-X-Y repeats typical of collagen helix. One 17 amino acid peptide had 82% homology with a type XII collagen domain. However, bovine type XII collagen did not promote fibroblast attachment. Although another 19-amino-acid-long peptide had 95% homology to bovine alpha 1 [I], two other peptides were only 74% and 68% homologous, and the CAP was not recognized by anti-type I collagen antibody. The attachment activity of CAP was susceptible to bacterial collagenase. The CAP did not cross-react with antibodies to type V, XII, and XIV collagens. These data and our previous immunostaining data indicate that the CAP is not related to other collagens or attachment proteins and that it is a collagenous attachment protein localized in cementum.


Intravenous Remifentanil Analgaesia for an Obstetric Patient with Type I Neurofibromatosis and a Factor V Leiden Mutation.
Type I neurofibromatosis is characterised by altered skin pigmentation and the growth of benign tumours, particularly along the peripheral nerves and central nervous system. We report a 36-year-old primigravida woman in labour who was admitted to the obstetric suite of the Hospital Sant Joan de Déu, Barcelona, Spain, in 2007 with hypothyroidism, type I neurofibromatosis and a factor V Leiden mutation. Due to a lack of cranial and spinal imaging data, an epidural was not indicated; instead, continuous intravenous remifentanil analgaesia was administered. The remifentanil infusion was self-titrated by the patient using a visual analogue scale, with the dosage ranging from 0.01 to 0.25 μg/kg/minute. Due to rotational dystocia, Kjelland-type forceps were used during the delivery. After birth, the infant was found to have Apgar scores of 9 and 10, with no maternal or neonatal adverse effects observed. Although still controversial, remifentanil may be a successful alternative for analgaesia in similar cases; however, the specific risks and benefits for each patient should be considered prior to administration.


Management of penetrating juxtahepatic inferior vena cava injuries under total vascular occlusion.
Juxtahepatic inferior vena cava injuries are often lethal. Various operative strategies have been used to improve outcome, but the mortality rate reported in the literature is 80 percent or more. The atriocaval shunt has been advocated for isolation of bleeding retrohepatic vena cava, but recent reports suggest that mortality might be even higher in patients selected for shunting, perhaps owing to ongoing hemorrhage because of indecision and delay prior to insertion, or to technical difficulty with insertion. A series of patients with juxtahepatic inferior vena cava injuries treated successfully with total vascular isolation and occlusion were studied. Consecutive series of 10 patients with penetrating injuries to the juxtahepatic inferior vena cava were treated at an urban, university-affiliated Level I trauma center. A rapid and direct approach was used along with isolation techniques similar to those used in liver transplantation and elective resection for neoplasm. As resuscitation continued, repair of the inferior vena cava was accomplished in a bloodless field, created by manual compression of the liver, wide exposure, portal inflow occlusion, and proximal and distal control of the inferior vena cava. Aggressive fluid resuscitation and transient aortic cross-clamping controlled resulting systemic hypotension. Mean injury severity score was 26 and mean penetrating abdominal trauma index score was 28. After exposure, three patients had tangential injuries controlled by undersewing a partially occluding clamp. Subdiaphragmatic aortic cross-clamping was performed if total occlusion of the inferior vena cava reduced systolic blood pressure to 60 mm Hg, which was necessary in the remaining seven patients. Nine patients survived surgery, and seven of nine survived to hospital discharge. One postoperative death was a result of multiple organ dysfunction syndrome, and the other of necrotizing bacterial pneumonia. Total vascular occlusion with selective use of aortic cross-clamping yielded 70 percent survival in an injury that historically has been associated with survival of 20 percent or less. Minimization of visceral ischemia is accomplished by occluding the aorta only after complete isolation of the inferior vena cava.


Hospitalization Outcomes of Cleft Lip Repair in Neonates Across the United States.
Cleft lip repair surgeries in neonates have shown to be effective and safe, resulting in less scarring and excellent aesthetic outcomes. However, existing studies are based on single-center experiences with limited numbers of patients and surgeons. Complication rates and hospital outcomes of neonatal lip repair have not yet been established at the national level. The objective of this study was to examine the association between age at cleft lip repair and hospital outcomes. Retrospective analysis of hospital discharge database. Nationwide Inpatient Sample for years 2004 through 2010. Patients under 12 months of age diagnosed with cleft lip with or without cleft palate. Surgical repair for cleft lip. Occurrence of complications. There were 10 132 cleft lip repair procedures in 2004-2010 in the United States. Mean age was 144 days with 2.1 days of hospital stay and $22 037 charges. Less than 2% were performed in neonates (0-28 days). The overall complication rate was 2.1%. Compared to 2-4 months, cleft lip procedures in neonates were associated with longer length of stay ( P = .001) and hospital charges ( P = .03). Cleft lip repair among neonates were 15 times more likely to develop complications ( P = .0004) even after adjusting for confounding factors. Cleft lip repair in neonates is associated with significantly higher complication rates as well as longer length of stay and more hospital charges. Purported benefits of neonatal cleft lip repair may not outweigh significant safety issues and hospitalization outcomes.


Resection of a plasma cell granuloma combining a conventional posterolateral left-sided thoracotomy with a minimally invasive valve approach.
Plasma cell granuloma (PCG) is a rare benign tumor that is difficult to differentiate from malignancy. Depending on the location of the PCG, surgical management can be challenging. We describe a patient with a PCG involving the left lower lobe extending into the left atrium, that was resected en bloc using a conventional posterolateral thoracotomy combined with a surgical approach predominantly used for minimally invasive mitral valve surgery. This case illustrates how it is possible to utilize a technique used for cardiac surgery for tumors of pulmonary origin involving the heart.


Live Wait Times.
People in North Wales who need treatment for an injury can now obtain up-to-the minute information on waiting times at the region's minor injuries units and emergency departments.


Caution, "normal" BMI: health risks associated with potentially masked individual underweight-EPMA Position Paper 2021.
An increasing interest in a healthy lifestyle raises questions about optimal body weight. Evidently, it should be clearly discriminated between the standardised "normal" body weight and individually optimal weight. To this end, the basic principle of personalised medicine "one size does not fit all" has to be applied. Contextually, "normal" but e.g. borderline body mass index might be optimal for one person but apparently suboptimal for another one strongly depending on the individual genetic predisposition, geographic origin, cultural and nutritional habits and relevant lifestyle parameters-all included into comprehensive individual patient profile. Even if only slightly deviant, both overweight and underweight are acknowledged risk factors for a shifted metabolism which, if being not optimised, may strongly contribute to the development and progression of severe pathologies. Development of innovative screening programmes is essential to promote population health by application of health risks assessment, individualised patient profiling and multi-parametric analysis, further used for cost-effective targeted prevention and treatments tailored to the person. The following healthcare areas are considered to be potentially strongly benefiting from the above proposed measures: suboptimal health conditions, sports medicine, stress overload and associated complications, planned pregnancies, periodontal health and dentistry, sleep medicine, eye health and disorders, inflammatory disorders, healing and pain management, metabolic disorders, cardiovascular disease, cancers, psychiatric and neurologic disorders, stroke of known and unknown aetiology, improved individual and population outcomes under pandemic conditions such as COVID-19. In a long-term way, a significantly improved healthcare economy is one of benefits of the proposed paradigm shift from reactive to Predictive, Preventive and Personalised Medicine (PPPM/3PM). A tight collaboration between all stakeholders including scientific community, healthcare givers, patient organisations, policy-makers and educators is essential for the smooth implementation of 3PM concepts in daily practice.


[The evaluation of Mexican biomedical journals: a description of the 2005 process for the Artemisa index].
The production of scientific health publications is ever increasing and it is therefore essential to evaluate their quality as well as their repercussion and visibility in the scientific community, so that they can be included and indexed in the various national and international databases. The Information Center for Public Health Decisions (CENIDSP) at the National Public Health Institute (INSP) has produced since 1992 a CD ROM under the name Artemisa (articles on health information published in Mexico). In 2005 it included the full version of 56 journals which were rigorously evaluated and met the selection and evaluation criteria for inclusion. Describe the selection criteria and the evaluation process followed in 2005 to choose the biomedical journals included in Artemisa. It consists of a description of the universe of journals to be included according to the guidelines established and of the first stage of the evaluation (journal and article format). Based on the results, journals were selected for the second stage, which consisted of evaluating the content of the articles randomly selected. Twenty-one journals were included in the first stage, 19 of which were selected for the second stage. A total of 274 articles were selected for peer review by the Mexican Health Journals Evaluation System (SERM@S), with the participation of 64 evaluators. The final result of the second stage was satisfactory to all of them. The evaluation of biomedical journals conducted by CENIDSP has led to maintaining a quality standard of the biomedical publications in Mexico.


Control of Photoisomerization of an Azoazacryptand by Anion Binding and Cucurbit[8]uril Encapsulation in an Aqueous Solution.
Control of isomerization of a receptor bearing multiple light-switchable subunits in a confined space is critical for the design of synthetic molecular machines. Toward this goal, a new azacryptand containing three azobenzene subunits has been developed, and its photoisomerization in an aqueous solution has been studied depending on anion coordination and recognition by a larger host-cucurbit[8]uril (CB[8]). The cryptand in its hexaprotonated form shows considerable affinity for fluoride and perchlorate, which in turn affects the isomer distribution of the receptor under UV-light irradiation, stabilizing the isomers of the cryptand with Z-configurations. CB[8] was found to be able to encapsulate the isomers of the cryptand by forming a Matryoshka-type complex. The irradiation of a 10:1 CB[8]-cryptand mixture has led to a selective conversion of the cryptand to the E,E,Z isomer inside CB[8]. It has been demonstrated that the addition of fluoride to the resulted complex induces the release of the cryptand as a major E,E,E isomer, while other studied anions were ineffective in this reaction. To our knowledge, this work presents a first example of a host-controlled photoisomerization of an anion receptor bearing multiple switching azobenzenes that model the function of naturally occurring chaperones.


Safety of cesarean myomectomy in women with single anterior wall and lower uterine segment myomas.
Cesarean myomectomy (CM) is a safe procedure in selected cases. Nevertheless, literature lacks clear guidelines on patient selection. We aimed to evaluate CM safety in patients with single anterior wall and lower uterine segment (LUS) myomas. The authors selected pregnants at term, scheduled for CSs, with single anterior wall or LUS myomas. All their clinical, demographic, obstetric, and surgical parameters were recorded. Thirty-six women had a CM (study group), and 17 had a CS without myoma removal (control group). No significant differences were detected in the socio-demographic and clinical findings between the groups. The average size of myomas in the study and control group (p = .873), was 55.44 mm and 47.25 mm, respectively. The average surgery duration was 62.5 min in the study and 53.82 in the control group (p = .058). Intraoperative hemorrhage was more frequent in the study group (p = .045). Nevertheless, neither the number nor the volume of intraoperative transfusions was significantly different. None of the major CM complications were recorded, and the duration of hospitalization was similar in both groups. CM in patients with single anterior wall and LUS myomas does not cause increased perioperative morbidity, and, therefore, can be considered safe in such cases.


[Value of N-terminal pro-B-type natriuretic peptide on long-term outcome of patients with hypertrophic cardiomyopathy].
Objective: To determine the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the long-term outcome of patients with hypertrophic cardiomyopathy (HCM) . Methods: NT-proBNP was measured in 831 consecutive patients with HCM at Fuwai Hospital from October 2009 to December 2013 and patients were followed up clinically for (53.3±15.4) months. Patients were divided into 3 groups according to NT-proBNP values: NT-proBNP<860 pmol/L (n=276) , 860 pmol/L≤NT-proBNP≤1 905 pmol/L (n=278) , NT-proBNP>1 905 pmol/L (n=277) . The related baseline data, laboratory examination and echocardiographic results were compared among groups. The primary endpoints of this study were all-cause mortality and cardiac transplantation. Cox proportional hazards model was used to estimate hazard ratio (HR) . Kaplan-Meier analysis was used to evaluate the survival status of patients among the 3 groups. Results: During a median follow-up of (53.3±15.4) months, all-cause mortality or cardiac transplantation occurred in 37 patients (4.5%) , event rate was 1.4% (4/276) , 4.0% (11/278) and 7.9% (22/277) in patients with NT-proBNP<860 pmol/L, 860 pmol/L≤NT-proBNP≤1 905 pmol/L and NT-proBNP>1 905 pmol/L, respectively. Multivariable Cox regression analysis identified that age (HR 1.066, 95%CI 1.027-1.107) and NT-proBNP (HR 1.026, 95% CI 1.010-1.042) were independent predictors of all-cause mortality or cardiac transplantation. Among the 3 groups, the survival rate of the NT-proBNP<860 pmol/L group was the highest,and that of the NT-proBNP>1 905 pmol/L group was the lowest (P<0.01) . Conclusions: The level of NT-proBNP provides clinically relevant information for long-term adverse events risk stratification in patients with HCM.


Differential nucleolar staining affinity with a modified Papanicolaou staining procedure.
A modified Papanicolaou staining procedure using diluted Harris' hematoxylin with potassium alum is described. Nucleolar staining varies from blue to bright red. This technique has been applied to mammary tumor cell lines in vitro under several conditions of hormonal stimulation known to induce protein synthesis and cell differentiation. Blue nucleoli are observed in control resting cells, while bright red nucleoli are seen after hormonal stimulation.


Rationale for caries inhibition of debonded glass ionomer sealants: an in vitro study.
This study's purpose was to test the hypothesis that, after glass ionomer (GI) sealant debonding, remaining GI in the deepest parts of fissures and/or the inhibition of enamel demineralization after artificial caries challenge imparts the residual cariostatic property observed in clinical studies. Fuji IX GI sealant was placed on one tooth from 14 matched pairs of noncarious extracted human permanent molars and premolars; the other tooth was the control. Sealed teeth underwent thermocycling (4,000 cycles), and the sealant was manually debonded. The amount of remaining sealant in the fissures was determined using a stereomicroscope. All teeth were placed in lactic acid gel (pH 5.0) at 37 degrees Celsius for three weeks to simulate caries formation. The extent of demineralization was determined using the serial micro-hardness method on the cross-sectioned specimens at 0.5 mm from the depth of the central fissure. All teeth had GI retained in the fissures at a microscopic level. Enamel demineralization adjacent to the remaining GI was not significantly different from the control (t test; P=.88). The residual cariostatic property of glass ionomer sealant is most likely due to a physical barrier of remaining GI in the fissures rather than a chemical effect on demineralization inhibition.


Genetic evidence for a recent divergence and subsequent gene flow between Spanish and Eastern imperial eagles.
Dating of population divergence is critical in understanding speciation and in evaluating the evolutionary significance of genetic lineages, upon which identification of conservation and management units should be based. In this study we used a multilocus approach and the Isolation-Migration model based on coalescence theory to estimate the time of divergence of the Spanish and Eastern imperial eagle sister species. This model enables estimation of population sizes at split, and inference of gene flow after divergence. Our results indicate that divergence may have occurred during the Holocene or the late Pleistocene, much more recently than previously suspected. They also suggest a large population reduction at split, with an estimated effective population size several times smaller for the western population than for the eastern population. Asymmetrical gene flow after divergence, from the Eastern imperial eagle to the Spanish imperial eagle, was detected for the nuclear genome but not the mitochondrial genome. Male-mediated gene flow after divergence may explain this result, and the previously reported lower mitochondrial diversity but similar nuclear diversity in Spanish imperial eagles compared to the Eastern species. Spanish and Eastern imperial eagles split from a common ancestor much more recently than previously thought, and asymmetrical gene flow occurred after divergence. Revision of the phylogenetic proximity of both species is warranted, with implications for conservation.


Treatment of angioma serpiginosum using a pulsed tunable dye laser.
Angioma serpiginosum (AS) is a rare vascular naevoid disorder due to ectatic dilation of capillaries in the papillary dermis. The condition is found almost exclusively in females who have grouped erythematous punctate lesions usually on the lower limbs or buttocks, which may be unsightly. We report five patients with AS treated using a Candela SPLT1 pulsed tunable dye laser. All patients had a good to excellent response. The lesion resolved in one patient, virtually resolved in two and is considerably improved in a further patient in whom treatment is continuing. In one patient, the angiomatous lesion improved but the patient developed hyperpigmentation at the treatment site and the treatment has been temporarily suspended. The results suggest that treatment using the pulsed dye laser is very effective for AS and, in most patients, produces an excellent cosmetic result.


Malaria in a rural area of Sierra Leone. III. Vector ecology and disease transmission.
Studies were undertaken on the role of Anopheles gambiae and An. funestus in the transmission of malaria in four villages in a high-rainfall, forested area in the Bo district of southern Sierra Leone. Anopheles gambiae s.s., identified chromosomally as the Forest form, was the most important vector, with a mean annual sporozoite rate, based on ELISA, of 7.4%. Anopheles funestus, which was found in considerably lower numbers, was mainly a dry season vector, with an annual sporozoite rate of 11.4%. Despite these relatively high sporozoite rates, vector populations were at a low level, with approximate mean densities of only 1.0 An. gambiae and 0.1 An. funestus resting females per house room, and average biting rates of just 1.1 and 0.1 bites/person/night by these two species, respectively. In the rainy season, biting rates peaked at 9.5 An. gambiae bites/person/night and 1.0 An. funestus bites/person/night. Annual sporozoite inoculation rates by An. gambiae and An. funestus were 0.088 and 0.007 infective bites/person/night, respectively. ELISA showed that both species were highly anthropophagic. Exit-trap collections and outdoors searches showed that An. gambiae exhibited a considerable degree of exophily. Light traps inside houses caught nine anopheline species, whereas pyrethrum spray collections in houses caught only An. gambiae, An. funestus and An. hancocki.


Molecular mechanisms of plaque instability.
Coronary artery thrombosis superimposed on a disrupted atherosclerotic plaque initiates abrupt arterial occlusion and is the proximate event responsible for 60-80% cases of acute coronary syndromes. This article provides a concise update on the evolving concepts in the pathophysiology of plaque rupture and thrombosis. Over the past several years, the critical role of plaque composition rather than plaque size or stenosis severity, in plaque rupture and thrombosis have been recognized. The necrotic lipid core and plaque inflammation appear to be key factors. Extracellular matrix loss in the fibrous cap, a prelude to rupture, is attributed to matrix degrading enzymes as well as to death of matrix synthesizing smooth muscle cells; inflammation appears to play a critical role in both these processes. Inflammatory cell derived tissue factor is a key contributor to plaque thrombogenicity. Inflammation has also been implicated in plaque neovascularity, intraplaque hemorrhage and plaque expansion. Recent observations have also highlighted the important modulatory role of immune system in atherosclerosis and plaque composition. Improved understanding of mechanisms causing plaque instability should provide novel insights into prevention of athero-thrombotic cardiovascular events.


Decomposition analysis of energy-related carbon emissions from the transportation sector in Beijing.
In the process of rapid development and urbanization in Beijing, identifying the potential factors of carbon emissions in the transportation sector is an important prerequisite to controlling carbon emissions. Based on the expanded Kaya identity, we built a multivariate generalized Fisher index (GFI) decomposition model to measure the influence of the energy structure, energy intensity, output value of per unit traffic turnover, transportation intensity, economic growth and population size on carbon emissions from 1995 to 2012 in the transportation sector of Beijing. Compared to most methods used in previous studies, the GFI model possesses the advantage of eliminating decomposition residuals, which enables it to display better decomposition characteristics (Ang et al., 2004). The results show: (i) The primary positive drivers of carbon emissions in the transportation sector include the economic growth, energy intensity and population size. The cumulative contribution of economic growth to transportation carbon emissions reaches 334.5%. (ii) The negative drivers are the transportation intensity and energy structure, while the transportation intensity is the main factor that restrains transportation carbon emissions. The energy structure displays a certain inhibition effect, but its inhibition is not obvious. (iii) The contribution rate of the output value of per unit traffic turnover on transportation carbon emissions appears as a flat "M". To suppress the growth of carbon emissions in transportation further, the government of Beijing should take the measures of promoting the development of new energy vehicles, limiting private vehicles' increase and promoting public transportation, evacuating non-core functions of Beijing and continuingly controlling population size.


Right atrial myxoma associated with an atrial septal defect by real-time three-dimensional echocardiography.
A 40-year-old woman presented with a 1 month history of shortness of breath and easy fatigability. Two-dimensional echocardiography and real-time three-dimensional echocardiography (RT3DE) showed a large right atrial mass protruding into the right ventricle and an atrial septal defect (ASD). Successful excision of the mass, which proved to be a myxoma, and closure of the ASD completely relieved her symptoms. To our knowledge, this is the first report of RT3DE in a patient with right atrial myxoma associated with an ASD.


[Informational causality of the effect of drug signal].
Application of the inflammation theory in pharmacology leads to discuss the causality of the drug signal effect and compare the properties of informational causality with substantial and energetic causalities. This provides particular insight concerning drug efficacy.


Mammalian Target of Rapamycin (mTOR) and the Proteasome Attenuates IL-1β Expression in Primary Mouse Cardiac Fibroblasts.
Background: IL-1β is a highly potent pro-inflammatory cytokine and its secretion is tightly regulated. Inactive pro-IL-1β is transcribed in response to innate immune receptors activating NFκB. If tissue damage occurs, danger signals released from necrotic cells, such as ATP, can activate NLRP3-inflammasomes (multiprotein complexes consisting of NLRP3, ASC, and active caspase-1) which cleaves and activates pro-IL-1β. NLRP3 activation also depends on NEK7 and mitochondrial ROS-production. Thus, IL-1β secretion may be regulated at the level of each involved component. We have previously shown that NLRP3-dependent IL-1β release can be induced in cardiac fibroblasts by pro-inflammatory stimuli. However, anti-inflammatory mechanisms targeting IL-1β release in cardiac cells have not been investigated. mTOR is a key regulator of protein metabolism, including autophagy and proteasome activity. In this study we explored whether autophagy or proteasomal degradation are regulators of NLRP3 inflammasome activation and IL-1β release from cardiac fibroblasts. Methods and Results: Serum starvation selectively reduced LPS/ATP-induced IL-1β secretion from cardiac fibroblasts. However, no other inflammasome components, nor mitochondrial mass, were affected. The mTOR inhibitor rapamycin restored pro-IL-1β protein levels as well as LPS/ATP-induced IL-1β release from serum starved cells. However, neither serum starvation nor rapamycin induced autophagy in cardiac fibroblasts. Conversely, chloroquine and bafilomycin A (inhibitors of autophagy) and betulinic acid (a proteasome activator) effectively reduced LPS-induced pro-IL-1β protein levels. Key findings were reinvestigated in human monocyte-derived macrophages. Conclusion: In cardiac fibroblasts, mTOR inhibition selectively favors pro-IL-1β synthesis while proteasomal degradation and not autophagy is the major catabolic anti-inflammatory mechanism for degradation of this cytokine.


A systems approach to purchasing and implementing new technology.
There are many risks associated with purchasing and implementing new technology. The challenge is to reduce these risks to gain maximum benefit from the new technology purchased. In the high-cost world of healthcare, there is little room for wasting time and money related to technology implementation. If the workflow of the current system is not adequately understood before purchasing and implementing a new technology, that technology may mask underlying problems and/or create new ones. The purpose of this article is to present a framework for analyzing the current process or system, identifying the strengths and the areas in need of improvement. A thorough understanding of the problems with the current system and the barriers to change is necessary to ensure the selection of the "right" technology and promote its implementation.


[Hantavirus infection: a "new" exotic zoonosis among us].
Hantavirus disease is a recently recognized zoonosis. The main vectors are infected but healthy wild rodents or laboratory rats. Transmission to man occurs via inhalation of aerosolised excretions. Kidneys or lungs are the target organs during the disease, but a systemic affection with multi-organ involvement is possible, and can be fatal. To date, at least 16 different serotypes of hantavirus have been characterized, 8 of them being of clinical importance. Each serotype has its own rodent vector and its own geographical spread. In Europe, the red bank vole (Clethrionomys glareolus) is the main rodent vector carrying the Puumala serotype which is the etiologic agent of a viral affection known as nephropathia epidemica (NE). Belgium witnessed in 1993 its most important NE outbreak with more than 60 cases in the southern part of the region between Sambre and Meuse, Chimay being the main focus.


Very late transcatheter heart valve thrombosis.
We describe a case of very late transcatheter heart valve (THV) thrombosis of a first-generation SAPIEN prosthesis (Edwards Lifesciences, Irvine, CA) implanted in a 64-year-old woman with severe symptomatic aortic stenosis. More than 54 mo after implantation, she presented with severe symptomatic prosthesis dysfunction (stenosis) which was successfully treated with oral anticoagulation. To our knowledge, this is the tardiest case of THV thrombosis ever reported. This case should increase clinical awareness for THV thrombosis even beyond the first two-year period following implantation.


Two-compartment method for determination of the oxygen transfer rate with electrochemical sensors based on sulfite oxidation.
The dissolved oxygen concentration is a crucial parameter in aerobic bioprocesses due to the low solubility of oxygen in water. The present study describes a new method for determining the oxygen transfer rate (OTR) in shaken-culture systems based on the sodium sulfite method in combination with an electrochemical oxygen sensor. The method replaces the laborious titration of the remaining sulfite by an on-line detection of the end point of the reaction. This method is a two-step procedure that can be applied in arbitrary flasks that do not allow the insertion of electrodes. The method does not therefore depend on the type of vessel in which the OTR is detected. The concept is demonstrated by determination of the OTR for standard baffled 1-L shake flasks and for opaque Ultra Yield™ flasks. Under typical shaking conditions, k(L) a values in the standard baffled flasks reached values up to 220 h(-1) , whereas the k(L) a values of the Ultra Yield flasks were significantly higher (up to 422 h(-1) ).


Advanced Na-NiCl2 Battery Using Nickel-Coated Graphite with Core-Shell Microarchitecture.
Stationary electric energy storage devices (rechargeable batteries) have gained increasing prominence due to great market needs, such as smoothing the fluctuation of renewable energy resources and supporting the reliability of the electric grid. With regard to raw materials availability, sodium-based batteries are better positioned than lithium batteries due to the abundant resource of sodium in Earth's crust. However, the sodium-nickel chloride (Na-NiCl2) battery, one of the most attractive stationary battery technologies, is hindered from further market penetration by its high material cost (Ni cost) and fast material degradation at its high operating temperature. Here, we demonstrate the design of a core-shell microarchitecture, nickel-coated graphite, with a graphite core to maintain electrochemically active surface area and structural integrity of the electron percolation pathway while using 40% less Ni than conventional Na-NiCl2 batteries. An initial energy density of 133 Wh/kg (at ∼C/4) and energy efficiency of 94% are achieved at an intermediate temperature of 190 °C.


Inversion technique for IR heterodyne sounding of stratospheric constituents from space platforms.
The techniques which have been employed for inversion of IR heterodyne measurements for remote sounding of stratospheric trace constituents usually rely on either geometric effects based on limb-scan observations (i.e., onion peel techniques) or spectral effects by using weighting functions corresponding to different frequencies of an IR spectral line. An experimental approach and inversion technique are discussed which optimize the retrieval of concentration profiles by combining the geometric and the spectral effects in an IR heterodyne receiver. The results of inversions of some synthetic ClO spectral lines corresponding to solar occultation limb scans of the stratosphere are presented, indicating considerable improvement in the accuracy of the retrieved profiles. The effects of noise on the accuracy of retrievals are discussed for realistic situations.


RIS-PACS, patient safety, and clinical risk management.
Clinical risk management is the basis of safety procedures also in radiological workflows. In the literature, it has been documented that the incidence of reconciled radiological studies ranges between 0.2 and 0.5 % of stored studies, a non-negligible value if we consider the high number of diagnostic tests performed. In radiology, "non-compliance" or, more generally, data to be reconciled means any circumstance in which wrong information is recorded in RIS and/or PACS, which requires processing to amend or correct images, reports or other information in order to attribute them to the right patient/episode. Non-compliance corrections account for almost 50 % of the medical system administrator's (SA) workload. This paper describes how the Reggio Emilia Province Diagnostic Imaging and Laboratory Medicine Department manages risk in clinical radiology, in compliance with Regional indications on RIS-PACS safety. A dedicated RIS webpage has been developed in order to manage reconciliation requests. Native integration with PACS makes information about ongoing reconciliations available to anyone who consults the images. In 2013, non-compliances reported by radiology staff ranged between 0.25 and 0.35 % of studies sent to the PACS. More than 50 % of non-compliances can be related to high clinical risk, which requires implementation of efficient and effective rapid mechanisms of action-reaction inside and outside the radiology department. The RIS-integrated module has been the starting point for managing and monitoring errors, allowing improvement initiatives to guarantee and optimise workflow. Request and event traceability have allowed us to define personalised training programmes, designed to minimise procedural and/or systematic errors. To protect the availability and consistency of information produced by radiology units, it is necessary to provide integrated and effective mechanisms for reconciliation management. The integrated tool described in this paper is now widely used (not only by our centre): radiographers and radiologists can indicate non-compliances in an efficient and effective manner, informing all the operators involved with just a click of the mouse. Similar functionality should be implemented in the next generation of RIS-PACS in order to maintain the highest possible safety level for patients and workers.


Human coronaviruses are uncommon in patients with gastrointestinal illness.
Coronaviruses infect numerous animal species causing a variety of illnesses including respiratory, neurologic and enteric disease. Human coronaviruses (HCoV) are mainly associated with respiratory tract disease but have been implicated in enteric disease. To investigate the frequency of coronaviruses in stool samples from children and adults with gastrointestinal illness by RT-PCR. Clinical samples submitted for infectious diarrhea testing were collected from December 2007 through March 2008. RNA extraction and RT-PCR was performed for stools negative for Clostridium difficile using primer sets against HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. Clinical data from samples positive for coronaviruses were reviewed and recorded. Samples from 479 patients were collected including 151 pediatric (< or = 18 years), and 328 adults (>18 years). Of these samples, 4 patients (1.3%, 2 adult; 2 pediatric) screened positive for the presence of a coronavirus. All detected coronaviruses were identified as HCoV-HKU1. No stools screened positive for either HCoV-229E, HCoV-NL63 or HCoV-OC43. All HCoV-HKU1 positive samples occurred between mid-January to mid-February. Clinical manifestations from HCoV-HKU1 positive patients included diarrhea, emesis and respiratory complaints. Three (75%) patients were admitted to the hospital with a median length of stay of 6 days. Coronaviruses as a group are not commonly identified in stool samples of patients presenting with gastrointestinal illness. HCoV-HKU1 can be identified in stool samples from children and adults with gastrointestinal disease, with most individuals having respiratory findings as well. No stool samples screened positive for HCoV-NL63, HCoV-229E, or HCoV-OC43.


Effect of two erosive protocols using acidic beverages on the shear bond strength of orthodontic brackets to bovine enamel.
To assess the short-term effect of two in vitro erosive challenge protocols on the bond strength of metal orthodontic brackets on bovine enamel. Sixty bovine incisors were selected and randomly divided into six groups: AS7 (artificial saliva - 7 days, Control Group); CC7 (Coca-Cola™ - 7 days); LJ7 (lime juice - 7 days); AS30 (artificial saliva - 30 days, Control Group); CC30 (Coca-Cola™ - 30 days); LJ30 (lime juice - 30 days). Microhardness testing was performed prior to the erosive challenge to verify the standardization of samples. Immersion was performed 4x/day for five minutes, for either 7 or 30 days. After immersions were concluded, the brackets were bonded and shear bond strength was assessed after 48 hours. The Adhesive Remnant Index (ARI) was also assessed. Data were analyzed by two-way ANOVA, followed by Tukey's post-hoc and Student's t test for paired samples, and the Kruskal-Wallis non-parametric test (α = 5%). The mean and standard deviation of microhardness testing of total samples were 281.89 ± 44.51 KHN. There was no statistically significant difference in shear bond strength for the time factor (7 or 30 days; F5.54= 0.105; p = 0.901). However, there was a statistically significant difference for the solution factor (F5.54= 6.671; p = 0.003). These differences occurred among solutions of Saliva x Coca-Cola™ (p = 0.003) and Coca-Cola™ x Lime Juice (p = 0.029). The assessment of the Adhesive Remnant Index showed no significant difference between groups. The immersion time used in the erosion protocols did not affect the bond strength of brackets to teeth. Coca-Cola™ induced significantly higher shear bond strength values than lime juice and artificial saliva. However, the short term effects of 7/30 days in this in vitro study may not be extrapolated for in vivo ones. Clinical studies should be conducted, substantiating the laboratory results.


Magnetic anisotropy and slow magnetic relaxation processes of cobalt(ii)-pseudohalide complexes.
Three mononuclear six-coordinate Co(ii)-pseudohalide complexes [Co(L)X2] with two N-donor pseudohalido coligands occupying the cis-positions (X = NCS- (1), NCSe- (2) or N(CN)2- (3)), and a five-coordinate complex [Co(L)(NCO)][B(C6H5)4] (4) [L = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane (12-TMC)] have been prepared and structurally characterized. Easy-plane magnetic anisotropy for 1-3 and easy-axis anisotropy for 4 were revealed via the analyses of the direct-current magnetic data, high-frequency and -field EPR (HFEPR) spectra and ab initio theoretical calculations. They display slow magnetic relaxations under an external applied dc field. Typically, two slow relaxation processes were found in 1 and 2 while only one relaxation process occurs in 3 and 4. The Raman-like mechanism is found to be dominant in the studied temperature range in 1. For 2-4, the Raman process is dominant in the low temperature region, while the Orbach mechanism dominates in the high temperature range.


Bacterial microbiota compositions of naturally fermented milk are shaped by both geographic origin and sample type.
Naturally fermented dairy products contain a rich microbial biodiversity. This study aimed to provide an overview on the bacterial microbiota biodiversity of 85 samples, previously collected across a wide region of China, Mongolia, and Russia. Data from these 85 samples, including 55 yogurts, 18 naturally fermented yak milks, 6 koumisses, and 6 cheeses, were retrieved and collectively analyzed. The most prevalent phyla shared across samples were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria, which together accounted for 99% of bacterial sequences. The predominant genera were Lactobacillus, Lactococcus, Streptococcus, Acetobacter, Acinetobacter, Leuconostoc, and Macrococcus, which together corresponded to 96.63% of bacterial sequences. Further multivariate statistical analyses revealed significant differences in the microbiota structure across sample geographic origin and type. First, on the principal coordinate score plot, samples representing the 3 main sample collection regions (Russia, Xinjiang, and Tibet) were mostly located respectively in the upper left, lower right, and lower left quadrants, although slight overlapping occurred. In contrast, samples from the minor sampling areas (Inner Mongolia, Mongolia, Gansu, and Sichuan) were predominantly distributed in the lower left quadrant. These results suggest a possible association between sample geographical origin and microbiota composition. Second, bacterial microbiota structure was stratified by sample type. In particular, the microbiota of cheese was largely distinct from the other sample types due to its high abundances of Lactococcus and Streptococcus. The fermented yak milk microbiota was most like that of the yogurts. Koumiss samples had the lowest microbial diversity and richness. In conclusion, both geographic origin and sample type shape the microbial diversity of naturally fermented milk.


Recent rising temperatures drive younger and southern Korean pine growth decline.
The Earth has experienced an unequivocal warming, with the warmest period of the past 150 years occurring in the last three decades. Korean pine (Pinus koraiensis), a key tree species in northeast Asia, is predicted to be particularly vulnerable to climate change. Here, we use dendrochronological methods to test whether the observed growth decline of Korean pine in northeast China is related to climate warming and whether climate-growth responses varied with age. A total of 628 cores from 401 trees across 16 sites were sampled over the entire distribution area of Korean pine in China. Samples were divided into three age classes: younger (50-130 years), middle (131-210 years), and older trees (>210 years), and measured by the ring-width index and basal area increment (BAI). Results showed a significant decline in BAI in most sites coinciding with an increase of temperature in the growing season and a decrease in precipitation since the 1980s. Meanwhile, we found that temperature-induced growth decline was significantly related to tree age. The BAI of younger trees decreased significantly and sharply (0.44 cm2 year-1, P < 0.0001), while old trees either decreased slightly or stabilized (0.04 cm2 year-1, P = 0.33). Tree growth in the southernmost locations was more likely to decline, what was most likely a result of forest-stand age. The age-related growth decline induced by climate warming might be explained by tree species traits, differences in growth rates between age classes and their relation to stress, changes in root system, competition/stand structure or physiological mechanisms. Our results might also predict that early stand process-thinning is exacerbated by warming and drying. This research informs that the age effect of growth response to rising temperature should be considered in forest management under climate change, and particularly models of future carbon cycle patterns and forest dynamics.


Neuropilin-1 expression characterizes T follicular helper (Tfh) cells activated during B cell differentiation in human secondary lymphoid organs.
T follicular helper (Tfh) cells play an essential role in the development of antigen-specific B cell immunity. Tfh cells regulate the differentiation and survival of activated B cells outside and inside germinal centers (GC) of secondary lymphoid organs. They act through cognate contacts with antigen-presenting B cells, but there is no current marker to specifically identify those Tfh cells which productively interact with B cells. Here we show that neuropilin 1 (Nrp1), a cell surface receptor, is selectively expressed by a subset of Tfh cells in human secondary lymphoid organs. Nrp1 expression on Tfh cells correlates with B cell differentiation in vivo and in vitro, is transient, and can be induced upon co-culture with autologous memory B cells in a cell contact-dependent manner. Comparative analysis of ex vivo Nrp1(+) and Nrp1(-) Tfh cells reveals gene expression modulation during activation. Finally, Nrp1 is expressed by malignant Tfh-like cells in a severe case of angioimmunoblastic T-cell lymphoma (AITL) associated with elevated terminal B cell differentiation. Thus, Nrp1 is a specific marker of Tfh cells cognate activation in humans, which may prove useful as a prognostic factor and a therapeutic target in neoplastic diseases associated with Tfh cells activity.


Social Categories Alone Are Insufficient to Elicit an In-Group Advantage in Perceptions of Within-Person Variability.
Within-person variability affects identity perception of other-race faces more than own-race faces; when participants sort images into piles representing different identities, they sort photographs of two other-race identities into more piles than two own-race identities. These results have been interpreted in terms of perceptual expertise, such that lack of experience with other-race faces leads to reduced ability to extract identity-relevant information across images. However, an alternative explanation is that sociocognitive factors (e.g., cognitive disregard for out-group faces) lead to differences in the number of perceived identities. Here, we examined whether social factors alone elicit an in-group advantage in perceptions of within-person variability. Caucasian participants sorted 40 photographs of two unfamiliar Caucasian identities (20 photographs/model) into piles based on the number of identities they believed were present. Half of the participants were told that the images were of students attending their university (in-group), whereas half were told that the images were of students attending a rival university (out-group). Participants sorted the photographs into a comparable number of identities for in- and out-group faces. This lack of an in-group advantage suggests that sociocognitive factors alone cannot account for differences in the number of perceived identities across faces from two categories.