Do Demographic Increases in LGBT and Nonreligious Americans Increase Threat?
Building on previous research demonstrating that demographic growth of racial minorities increases realistic threat and prejudice among majority group members, we examined whether demographic increases of groups associated with symbolic threat (lesbian, gay, bisexual, and transgender [LGBT] and nonreligious groups) increased realistic threat, symbolic threat, and/or prejudice. In a single-paper meta-analysis across four studies, participants who read that LGBT groups were becoming more prevalent in the United States exhibited heightened perceptions of realistic threat and (especially) symbolic threat from these groups, which in turn predicted anti-LGBT prejudice. Two similar studies examining the growth of nonreligious groups demonstrated weaker effects. Implications for America's growing diversity and future directions for studying these effects are discussed.


DAG expression: high-throughput gene expression analysis of real-time PCR data using standard curves for relative quantification.
Real-time quantitative PCR (qPCR) is still the gold-standard technique for gene-expression quantification. Recent technological advances of this method allow for the high-throughput gene-expression analysis, without the limitations of sample space and reagent used. However, non-commercial and user-friendly software for the management and analysis of these data is not available. The recently developed commercial microarrays allow for the drawing of standard curves of multiple assays using the same n-fold diluted samples. Data Analysis Gene (DAG) Expression software has been developed to perform high-throughput gene-expression data analysis using standard curves for relative quantification and one or multiple reference genes for sample normalization. We discuss the application of DAG Expression in the analysis of data from an experiment performed with Fluidigm technology, in which 48 genes and 115 samples were measured. Furthermore, the quality of our analysis was tested and compared with other available methods. DAG Expression is a freely available software that permits the automated analysis and visualization of high-throughput qPCR. A detailed manual and a demo-experiment are provided within the DAG Expression software at http://www.dagexpression.com/dage.zip.


Effect of an orphan response regulator on Streptococcus mutans sucrose-dependent adherence and cariogenesis.
Streptococcus mutans is the principal acidogenic component of dental plaque that demineralizes tooth enamel, leading to dental decay. Cell-associated glucosyltransferases catalyze the sucrose-dependent synthesis of sticky glucan polymers that, together with glucan binding proteins, promote S. mutans adherence to teeth and cell aggregation. We generated an S. mutans Tn916 transposon mutant, GMS315, which is defective in sucrose-dependent adherence and significantly less cariogenic than the UA130 wild-type progenitor in germfree rats. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting, and N-terminal sequence analysis confirmed the absence of a 155-kDa glucosyltransferase S (Gtf-S) from GMS315 protein profiles. Mapping of the unique transposon insertion in GMS315 revealed disruption of a putative regulatory region located upstream of gcrR, a gene previously described by Sato et al. that shares significant amino acid identity with other bacterial response regulators (Y. Sato, Y. Yamamoto, and H. Kizaki, FEMS Microbiol. Lett. 186: 187-191, 2000). The gcrR regulator, which we call "tarC," does not align with any of the 13 proposed two-component signal transduction systems derived from in silico analysis of the S. mutans genome, but rather represents one of several orphan response regulators in the genome. The results of Northern hybridization and/or real-time reverse transcription-PCR experiments reveal increased expression of both Gtf-S and glucan binding protein C (GbpC) in a tarC knockout mutant (GMS900), thereby supporting the notion that TarC acts as a negative transcriptional regulator. In addition, we noted that GMS900 has altered biofilm architecture relative to the wild type and is hypocariogenic in germfree rats. Taken collectively, these findings support a role for signal transduction in S. mutans sucrose-dependent adherence and aggregation and implicate TarC as a potential target for controlling S. mutans-induced cariogenesis.


Behavioral evidence for memory replay of video episodes in the macaque.
Humans recall the past by replaying fragments of events temporally. Here, we demonstrate a similar effect in macaques. We trained six rhesus monkeys with a temporal-order judgement (TOJ) task and collected 5000 TOJ trials. In each trial, the monkeys watched a naturalistic video of about 10 s comprising two across-context clips, and after a 2 s delay, performed TOJ between two frames from the video. The data are suggestive of a non-linear, time-compressed forward memory replay mechanism in the macaque. In contrast with humans, such compression of replay is, however, not sophisticated enough to allow these monkeys to skip over irrelevant information by compressing the encoded video globally. We also reveal that the monkeys detect event contextual boundaries, and that such detection facilitates recall by increasing the rate of information accumulation. Demonstration of a time-compressed, forward replay-like pattern in the macaque provides insights into the evolution of episodic memory in our lineage.


Aneurysmal Bone Cyst of the Lateral Malleolus Treated with Intralesional Curettage and Masquelet Technique: A Case Report.
An aneurysmal bone cyst is a locally destructive lesion considered to be a pseudotumor arising from the bone. Although this benign-like lesion is generally considered rare, several approaches for treatment have been presented. We report a case involving a 15-year-old female diagnosed with aneurysmal bone cyst of the lateral malleolus. Applying the Masquelet technique enabled the treatment of the lesion without causing instability to the ankle joint and the prevention of recurrence through the application of polymethylmethacrylate. To our knowledge this is the first documented case in our region and possibly in the Philippines.


Transmural differences of lipofuscin pigment accumulation in the left ventricule of rat heart during growth and aging.
In view of the higher metabolic rate in subendocardial heart tissue, the rate of age-related lipofuscin pigment accumulation was explored in different regions of the left ventricle heart wall of Sprague-Dawley rats. Hearts were removed from 2-, 6-, 12- and 24-month-old rats, and lipofuscin pigment accumulation was assessed in the subepicardial and subendocardial layers, either by measuring extractable fluorescent material, or by direct visualization with fluorescence microscopy. Findings showed that the amount of extractable fluorescent material and the number, size and brightness of the fluorescent lipofuscin granules increased with age in all the myocardial tissue layers. The rate of accumulation of extractable fluorescent material was higher in subendocardial compared to subepicardial tissue. At the microscope, fluorescent granules exhibited a different morphological appearance in the subendocardial and subepicardial tissue of the two older age-groups. These data support the hypothesis that liposoluble age-pigment deposition is linked to the rate of local oxidative metabolism.


Iron homeostasis alteration in transgenic tobacco overexpressing ferritin.
Intracellular iron concentration requires tight control and is regulated both at the uptake and storage levels. Our knowledge of the role that the iron-storage protein ferritins play in plants is still very limited. Overexpression of this protein, either in the cytoplasm or the plastids of transgenic tobacco, was obtained by placing soybean ferritin cDNA cassettes under the control of the CAMV 35S promoter. The protein accumulated in 4- and 6-day-old seedlings and in leaves of 3-week-old plants but not in dry seeds or in 2-day-old seedlings, which is consistent with previous reports describing a post-transcriptional control of ferritin amounts during the germination process. Overaccumulated ferritin in leaves was correctly assembled as 24-mers. Transformants were more resistant to methylviologen toxicity, indicating that the transgenic ferritins were functional in vivo. Ferritin overaccumulation in transgenic tobacco leaves leads to an illegitimate iron sequestration. As a consequence, these transgenic plants behave as iron deficient and activate iron transport systems as revealed by an increase in root ferric reductase activity and in leaf iron content.


Using vignettes to understand heart failure self-care.
To explore hospitalised heart failure (HF) patients' self-care decisions. Heart failure self-care is integral to maintain and manage health, and may prevent unnecessary HF hospitalisations. Nevertheless, self-care remains challenging for patients, and using vignettes offer a new perspective to understand patient HF self-care decision-making. This qualitative descriptive analysis was conducted as part of a mixed methods study. We conducted semi-structured interviews (N = 20) to elicit patient decisions about self-care in responses to three vignettes, which varied in symptom severity. Content analysis was used to extract quotes describing participant responses. Participants were on average 60 years old, primarily male, African American, unemployed and highly symptomatic (NYHA Class III or IV). Overall, participants were able to identify when symptoms required a decision to seek urgent medical attention, but had difficulty identifying the appropriate decision to make in response to less acute symptoms such as swelling. Symptoms other than shortness of breath were challenging for patients to interpret and manage appropriately. Understanding how to apply HF knowledge to alleviate symptoms was also difficult. Vignettes may be a helpful tool to prompt patient-healthcare provider communication about self-care management and prompt discussions about appropriate self-care decisions in response to varying levels of symptom severity.


Dielectric approach to investigation of erythrocyte aggregation. II. Kinetics of erythrocyte aggregation-disaggregation in quiescent and flowing blood.
A method based on dielectric properties of dispersed systems was applied to investigate the kinetics of RBC aggregation and the break-up of the aggregates. Experimentally, this method consists of measuring the capacitance at a frequency in the beginning of the beta-dispersion. Two experimental protocols were used to investigate the aggregation process. In the first case, blood samples were fully dispersed and then the flow was decreased or stopped to promote RBC aggregation. It was found that the initial phases of RBC aggregation are not affected by the shear rate. This finding indicates that RBC aggregation is a slow coagulation process. In the second case, RBCs aggregated under flow conditions at different shear rates and after the capacitance reached plateau levels, the flow was ceased. The steady-state capacitance of the quiescent blood and the kinetics of RBC aggregation after stoppage of shearing depend on the prior shear rate. To clarify the reasons for this effect, the kinetics of the disaggregation process was studied. In these experiments, time courses of the capacitance were recorded under different flow conditions and then a higher shear stress was applied to break up RBC aggregates. It was found that the kinetics of the disaggregation process depend on both the prior and current shear stresses. Results obtained in this study and their analysis show that the kinetics of RBC aggregation in stasis consists of two consecutive phases: At the onset, red blood cells interact face-to-face to form linear aggregates and then, after an accumulation of an appropriate concentration of these aggregates, branched rouleaux are formed via reactions of ends of the linear rouleaux with sides of other rouleaux (face-to-side interactions). Branching points are broken by low shear stresses whereas dispersion of the linear rouleaux requires significantly higher energy.


NLRP3 Inflammasome Involvement in Heart, Liver, and Lung Diseases-A Lesson from Cytokine Storm Syndrome.
Inflammation and inflammasomes have been proposed as important regulators of the host-microorganism interaction, playing a key role in morbidity and mortality due to the coronavirus disease 2019 (COVID-19) in subjects with chronic conditions and compromised immune system. The inflammasome consists of a multiprotein complex that finely regulates the activation of caspase-1 and the production and secretion of potent pro-inflammatory cytokines such as IL-1β and IL-18. The pyrin containing NOD (nucleotide-binding oligomerization domain) like receptor (NLRP) is a family of intracellular receptors, sensing patterns associated to pathogens or danger signals and NLRP3 inflammasome is the most deeply analyzed for its involvement in the innate and adaptive immune system as well as its contribution to several autoinflammatory and autoimmune diseases. It is highly expressed in leukocytes and up-regulated in sentinel cells upon inflammatory stimuli. NLRP3 expression has also been reported in B and T lymphocytes, in epithelial cells of oral and genital mucosa, in specific parenchymal cells as cardiomyocytes, and keratinocytes, and chondrocytes. It is well known that a dysregulated activation of the inflammasome is involved in the pathogenesis of different disorders that share the common red line of inflammation in their pathogenetic fingerprint. Here, we review the potential roles of the NLRP3 inflammasome in cardiovascular events, liver damage, pulmonary diseases, and in that wide range of systemic inflammatory syndromes named as a cytokine storm.


A self-loading microfluidic device for determining the minimum inhibitory concentration of antibiotics.
This article describes a portable microfluidic technology for determining the minimum inhibitory concentration (MIC) of antibiotics against bacteria. The microfluidic platform consists of a set of chambers molded in poly(dimethylsiloxane) (PDMS) that are preloaded with antibiotic, dried, and reversibly sealed to a second layer of PDMS containing channels that connect the chambers. The assembled device is degassed via vacuum prior to its use, and the absorption of gas by PDMS provides the mechanism for actuating and metering the flow of fluid in the microfluidic channels and chambers. During the operation of the device, degas driven flow introduces a suspension of bacterial cells, dissolves the antibiotic, and isolates cells in individual chambers without cross contamination. The growth of bacteria in the chambers in the presence of a pH indicator produces a colorimetric change that can be detected visually using ambient light. Using this device we measured the MIC of vancomycin, tetracycline, and kanamycin against Enterococcus faecalis 1131, Proteus mirabilis HI4320, Klebsiella pneumoniae, and Escherichia coli MG1655 and report values that are comparable to standard liquid broth dilution measurements. The device provides a simple method for MIC determination of individual antibiotics against human pathogens that will have applications for clinical and point-of-care medicine. Importantly, this device is designed around simplicity: it requires a single pipetting step to introduce the sample, no additional components or external equipment for its operation, and provides a straightforward visual measurement of cell growth. As the device introduces a novel approach for filling and isolating dead-end microfluidic chambers that does not require valves and actuators, this technology should find applications in other portable assays and devices.


A first generation integrated map of the rainbow trout genome.
Rainbow trout (Oncorhynchus mykiss) are the most-widely cultivated cold freshwater fish in the world and an important model species for many research areas. Coupling great interest in this species as a research model with the need for genetic improvement of aquaculture production efficiency traits justifies the continued development of genomics research resources. Many quantitative trait loci (QTL) have been identified for production and life-history traits in rainbow trout. An integrated physical and genetic map is needed to facilitate fine mapping of QTL and the selection of positional candidate genes for incorporation in marker-assisted selection (MAS) programs for improving rainbow trout aquaculture production. The first generation integrated map of the rainbow trout genome is composed of 238 BAC contigs anchored to chromosomes of the genetic map. It covers more than 10% of the genome across segments from all 29 chromosomes. Anchoring of 203 contigs to chromosomes of the National Center for Cool and Cold Water Aquaculture (NCCCWA) genetic map was achieved through mapping of 288 genetic markers derived from BAC end sequences (BES), screening of the BAC library with previously mapped markers and matching of SNPs with BES reads. In addition, 35 contigs were anchored to linkage groups of the INRA (French National Institute of Agricultural Research) genetic map through markers that were not informative for linkage analysis in the NCCCWA mapping panel. The ratio of physical to genetic linkage distances varied substantially among chromosomes and BAC contigs with an average of 3,033 Kb/cM. The integrated map described here provides a framework for a robust composite genome map for rainbow trout. This resource is needed for genomic analyses in this research model and economically important species and will facilitate comparative genome mapping with other salmonids and with model fish species. This resource will also facilitate efforts to assemble a whole-genome reference sequence for rainbow trout.


Bimetallic Al-Sn clusters: mixing at the nanoscale.
Metals which are not miscible in the bulk solid phase can form clusters at the nanoscale, and a typical example is the Al-Sn system. We have investigated the reasons for the enhanced miscibility occurring at the nanoscale. Density functional calculations have been performed for small AlmSnn clusters at all compositions when the total number of atoms N = m + n is equal to or smaller than N = 6, and for selected compositions for N = 10 and N = 11. The cohesive energies show that the clusters are energetically stable with respect to the separated atoms. Also, after an AlmSnn cluster has formed, its separation into two pure clusters Alm and Snn is energetically forbidden. This justifies the observation that those clusters can form by condensation in gas phase experiments. The different miscibility criteria explored reveal a substantial dependence on the reference state. Between those miscibility criteria, a particularly valuable one consists in studying the substitution reactions in which an Al atom of the gas replaces a Sn atom of the AlmSnn cluster to produce Alm+1Snn-1, or a Sn atom replaces an Al atom to produce Alm-1Snn+1. The conclusion is that substitution reactions enriching the clusters in Sn and depleting the cluster in Al are favorable. However, AlSn10 is an exception to this general trend. This is a special cluster. It readily forms by replacing a Sn atom by an Al atom in Sn11. Also, AlSn10 forms easily by adding an Al atom to Sn10. The geometric structures of Sn11 and Sn10 easily reorganize to form AlSn10 accommodating the Al atom inside a Sn cage. The exceptionally stable character of AlSn10 justifies the identification of AlSn10 as a magic cluster with the highest population in the measured mass spectra of this family. Even if Al and Sn can form clusters, the degree of mixing of these two elements in the clusters is modest, and a tendency for segregation of Al and Sn atoms on different parts of the cluster is incipient.


[Treatment of progressive muscular dystrophy].
The paper summarizes experience in treating 306 patients with progressive muscular dystrophy during different phases of the disease. The treatment was made with due consideration for a disturbed protein metabolism, a decreased permeability of the membrane in muscular filaments, a normalization of the metabolic product supply from the blood, improvement of the blood flow and cardio-vascular and respiratory insufficiency. The treatment was carried out in the form of a continuous use in in- and out-patient conditions of a session of anabolic hormones, vascular dilatative drugs, anticholinesterase preparations, amino acids, vitamins, drugs facilitating the cardio-vascular and respiratory activity. Besides, the patients were treated by oxygenobarotherapy, muscular electrostimulation by currents of sound frequencies, remedial gymnastics, massage, hypdrotherapy, etc. The authors propose typical treatment complexes. A follow-up study of patients who received a full course of therapy during three years demonstrated its effectiveness which was expressed by the absence of clinical signs of progressiveness.


Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity.
In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity. A TRV ≥ 2.7 m/s and a 6-minute walk distance (6MWD) between 150 and 500 m were required for enrollment in this 16-week, double-blind, placebo-controlled sildenafil trial. After 74 of the screened subjects were randomized, the study was stopped early due to a higher percentage of subjects experiencing serious adverse events in the sildenafil arm (45% of sildenafil, 22% of placebo, P = .022). Subject hospitalization for pain was the predominant cause for this difference: 35% with sildenafil compared with 14% with placebo (P = .029). There was no evidence of a treatment effect on 6MWD (placebo-corrected effect -9 m; 95% confidence interval [95% CI] -56-38; P = .703), TRV (P = .503), or N-terminal pro-brain natriuretic peptide (P = .410). Sildenafil appeared to increase hospitalization rates for pain in patients with SCD. This study is registered at www.clinicaltrials.gov as NCT00492531.


Organ donation attitudes and general self-efficacy: exploratory views from a rural primary care setting.
Behavioral determinants can enable or hinder motivation towards registration and donorship and, subsequently, action or inertia towards organ donation. Nevertheless, there is limited information about the role of self-efficacy in relation to organ donation awareness and presumed consent among individuals and their families. The aim of this study was to explore knowledge, attitudes and general self-efficacy as behavioral determinants for organ donation among rural primary care attendants, in order to tailor awareness strategies for reversing inertia within an opt-out system. This was a prospective face-to-face survey during regularly scheduled appointments of 203 attendants at a rural primary care unit in northern Greece. Responses to a 12-item adapted 'Organ donation awareness' questionnaire measuring knowledge, attitudes and awareness were related to participants' General Self-Efficacy (GSE) Scale score. Hierarchical modelling of a multiple linear regression model was adopted with GSE score added. About one-third of respondents (34.0%) had discussed presumed consent with a partner, family member or friend. More than half (54.2%) were concerned that donated organs might be used without consent for other purposes, such as medical research. A total of 30% found organ donation unacceptable because of religious beliefs. Organ donation awareness was not influenced by respondents' specific characteristics, but was significantly related to the GSE score (standard β=0.155, p=0.033). Overall, organ donation perceptions among rural primary care recipients were determined by knowledge of the presumed consent procurement system, pre-conceptions, religious beliefs, altruism and GSE scores. The association of self-efficacy with raised awareness could potentially explain the gap between high intent to consent as a donor and subsequent lack of follow-up action. Further comparative research across behavioral determinants between rural/urban groups is needed in order to tailor awareness strategies suitable for an opt-out system.


A conserved mechanism for nitrile metabolism in bacteria and plants.
Pseudomonas fluorescens SBW25 is a plant growth-promoting bacterium that efficiently colonizes the leaf surfaces and rhizosphere of a range of plants. Previous studies have identified a putative plant-induced nitrilase gene (pinA) in P. fluorescens SBW25 that is expressed in the rhizosphere of sugar beet plants. Nitrilase enzymes have been characterised in plants, bacteria and fungi and are thought to be important in detoxification of nitriles, utilisation of nitrogen and synthesis of plant hormones. We reveal that pinA is a NIT4-type nitrilase that catalyses the hydrolysis of beta-cyano-L-alanine, a nitrile common in the plant environment and an intermediate in the cyanide detoxification pathway in plants. In plants cyanide is converted to beta-cyano-L-alanine, which is subsequently detoxified to aspartic acid and ammonia by NIT4. In P. fluorescens SBW25 pinA is induced in the presence of beta-cyano-L-alanine, and the beta-cyano-L-alanine precursors cyanide and cysteine. pinA allows P. fluorescens SBW25 to use beta-cyano-L-alanine as a nitrogen source and to tolerate toxic concentrations of this nitrile. In addition, pinA is shown to complement a NIT4 mutation in Arabidopsis thaliana, enabling plants to grow in concentrations of beta-cyano-L-alanine that would otherwise prove lethal. Interestingly, over-expression of pinA in wild-type A. thaliana not only resulted in increased growth in high concentrations of beta-cyano-L-alanine, but also resulted in increased root elongation in the absence of exogenous beta-cyano-L-alanine, demonstrating that beta-cyano-L-alanine nitrilase activity can have a significant effect on root physiology and root development.


Neuronal avalanches in neocortical circuits.
Networks of living neurons exhibit diverse patterns of activity, including oscillations, synchrony, and waves. Recent work in physics has shown yet another mode of activity in systems composed of many nonlinear units interacting locally. For example, avalanches, earthquakes, and forest fires all propagate in systems organized into a critical state in which event sizes show no characteristic scale and are described by power laws. We hypothesized that a similar mode of activity with complex emergent properties could exist in networks of cortical neurons. We investigated this issue in mature organotypic cultures and acute slices of rat cortex by recording spontaneous local field potentials continuously using a 60 channel multielectrode array. Here, we show that propagation of spontaneous activity in cortical networks is described by equations that govern avalanches. As predicted by theory for a critical branching process, the propagation obeys a power law with an exponent of -3/2 for event sizes, with a branching parameter close to the critical value of 1. Simulations show that a branching parameter at this value optimizes information transmission in feedforward networks, while preventing runaway network excitation. Our findings suggest that "neuronal avalanches" may be a generic property of cortical networks, and represent a mode of activity that differs profoundly from oscillatory, synchronized, or wave-like network states. In the critical state, the network may satisfy the competing demands of information transmission and network stability.


[Myocardial infarction in young mexicans associated to metabolic syndrome].
Acute coronary diseases are catastrophic, especially in young patients. To determine the risk of metabolic syndrome (MS) for premature acute myocardial infarction (AMI), combined with familial, behavioral, and nutritional factors in the northeast of Mexico. This is a case control study of patients less than 47 years of age with no personal history of angina, AMI, or cerebrovascular disease. Cases corresponded to patients with AMI (incident and primary cases; n = 55) and controls were blood donors located at the same hospital (n = 55). Behavioral, nutritional, and cardiometabolic risk factors were measured. Multivariate logistic regression was used for estimating odds ratios (OR) and 95% confidence intervals (95% CI). MS increased the risk for premature AMI (95% CI: 1.73-39.5) eightfold, followed by smoking (OR: 7.76; 95% CI: 1.27-47.3), family history of AMI or sudden death (OR: 11.0; 95% CI: 2.03-60.4), and sedentary lifestyle (OR: 2.26; 95% CI: 2.52-9.80), independent of potential confounders. The study highlights the magnitude of the risk of MS for AMI in Mexican young adults. The phenomenon of coronary diseases among young adults needs essential attention from the health sector.


Immediate breast reconstruction in two stages using anatomical tissue expansion.
Over the last four years, 43 modified radical mastectomies and 13 simple mastectomies were done for 56 patients with breast cancer followed by immediate reconstruction in two stages using anatomical tissue expansion. In 49 patients a permanent prosthesis was successfully implanted while three patients refused a further operation, and four required removal of the expander. Complications were seen in 21 cases, including infection (n = 4), Baker III-IV contractures (n = 5), radiodermitis with breast distorsion (n = 3), and seroma (n = 2). Four patients required removal of the expander, and no further attempts were made to reconstruct the breast. All 10 patients given radiotherapy developed some kind of complication. After a mean follow up of 2.5 years (range 6-48 months), the aesthetic result was rated 6.9 and patient satisfaction 7.8 on a 0-10 scale. We concluded that immediate breast reconstruction with anatomical tissue expansion gives predictable aesthetic results, which satisfied most patients. Although the complication rate is high, it does not exceed complication rates associated with mastectomy alone or delayed reconstruction. At present, only patients undergoing preoperative or postoperative radiotherapy and hesitant patients are not considered to be candidates for this procedure.


Observation of a temperature dependent anomaly in the UV translucency of milk useful for UV-C preservation techniques.
Milk fat globules and casein micelles are the dispersed particles of milk that are responsible for its typical white turbid appearance and usually make it difficult to treat with modern ultraviolet light (UV) preservation techniques. The translucency of milk depends largely on the refractive indices of the dispersed particles, which are directly affected by temperature changes, as incorporated triglycerides can crystallize, melt or transition into other polymorphs. These structural changes have a significant effect on the scattering properties and thus on the UV light propagation in milk, especially by milk fat globules. In this study, a temporary minimum in the optical density of milk was observed within UV wavelength at 14 °C when heating the milk from 6 to 40 °C. This anomaly is consistent with structural changes detected by a distinct endothermic peak at 14 °C using differential scanning calorimetry. Apparently, the optical density anomaly between 10 and 20 °C disappears when the polymorphic transition already has proceeded through previous isothermal equilibration. Thus, melting of equilibrated triglycerides may not affect the RI of milk fat globules at ca. 14 °C as much as melt-mediated polymorphic transitioning. An increased efficiency of UV-C preservation (254 nm) at the translucency optimum was demonstrated by temperature-dependent microbial inactivation experiments.


Impact of COVID-19 lockdown on the incidence and mortality of acute exacerbations of chronic obstructive pulmonary disease: national interrupted time series analyses for Scotland and Wales.
The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape. The pandemic's impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood. We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations. We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments. Using data from Public Health Scotland and the Secure Anonymised Information Linkage Databank in Wales, we accessed weekly counts of emergency hospital admissions and deaths due to COPD over the first 30 weeks of 2020 and compared these to the national averages over the preceding 5 years. For both Scotland and Wales, we undertook interrupted time-series analyses to model the impact of instigating lockdown on these outcomes. Using fixed-effect meta-analysis, we derived pooled estimates of the overall changes in trends across the two nations. Lockdown was associated with 48% pooled reduction in emergency admissions for COPD in both countries (incidence rate ratio, IRR 0.52, 95% CI 0.46 to 0.58), relative to the 5-year averages. There was no statistically significant change in deaths due to COPD (pooled IRR 1.08, 95% CI 0.87 to 1.33). In Wales, lockdown was associated with 39% reduction in primary care consultations for acute exacerbation of COPD (IRR 0.61, 95% CI 0.52 to 0.71) and 46% reduction in COPD-related emergency department attendances (IRR 0.54, 95% CI 0.36 to 0.81). The UK-wide lockdown was associated with the most substantial reductions in COPD exacerbations ever seen across Scotland and Wales, with no corresponding increase in COPD deaths. This may have resulted from reduced transmission of respiratory infections, reduced exposure to outdoor air pollution and/or improved COPD self-management.


Observations on the ultrastructure of the choanoflagellate Codosiga botrytis (Ehr.) Saville-Kent with special reference to the flagellar apparatus.
The ultrastructure of the choanoflagellate Codosiga botrytis is described with particular reference to the flagellar appendages, the flagellar rootlet system, the transition zone, the basal body and accessory centrioles, and the stalk. The controversial early reports of flagellar appendages in this species have been confirmed and they have been detected in 2 further species, Salpingoeca frequentissima and Monosiga sp. The appendages consist of a delicate bilateral vane 2 mum wide on either side of the axis, composed of extremely fine overlapping or interwoven fibrils. The flagellar root system consists of a large number of radiating microtubules associated with bands of electron-dense material near the basal body; striated roots are absent. The microtubules extend from several separate foci, those in any one group originating near a composite electron-dense band, and for a distance of 300 nm from the basal body they are separated by blocks of interstitial material. The flagellar basal body forms one of a diplosome pair of centrioles. The triplet microtubules of the accessory centriole are embedded in amorphous electron-dense material and the whole is enveloped in a sheath of similar appearance. The existence of a third centriole close to the diplosome pair is also reported. The relatively complex structure of the flagellar transitional zone is described. The stalk is composed of a core of circular lacunae, which may or may not contain finger-like protoplasmic extensions of the posterior end of the cell, surrounded by a continuation of the sheath material which encloses the remainder of the protoplast. In the stalk only there is a further closely sheathing layer about 15 nm thick which is regularly striated, the spacing of the striations in shadowcast material and sections being about 3 times that measured by negative staining. The structure of choanoflagellates differs widely from that of the algal class Chrysophyceae, the group in which they are included in some classifications, and from the remainder of the algae; they do not appear to have a place in either the algae or the plant kingdom. The structure of Codosiga botrytis is briefly compared with that of sponge choanocytes and collared cells in the Metazoa and some of the possible phylogenetic implications of this are indicated.


What is causing the reduced drug-placebo difference in recent schizophrenia clinical trials and what can be done about it?
On September 18, 2007, a collaborative session between the International Society for CNS Clinical Trials and Methodology and the International Society for CNS Drug Development was held in Brussels, Belgium. Both groups, with membership from industry, academia, and governmental and nongovernmental agencies, have been formed to address scientific, clinical, regulatory, and methodological challenges in the development of central nervous system therapeutic agents. The focus of this joint session was the apparent diminution of drug-placebo differences in recent multicenter trials of antipsychotic medications for schizophrenia. To characterize the nature of the problem, some presenters reported data from several recent trials that indicated higher rates of placebo response and lower rates of drug response (even to previously established, comparator drugs), when compared with earlier trials. As a means to identify the possible causes of the problem, discussions covered a range of methodological factors such as participant characteristics, trial designs, site characteristics, clinical setting (inpatient vs outpatient), inclusion/exclusion criteria, and diagnostic specificity. Finally, possible solutions were discussed, such as improving precision of participant selection criteria, improving assessment instruments and/or assessment methodology to increase reliability of outcome measures, innovative methods to encourage greater subject adherence and investigator involvement, improved rater training and accountability metrics at clinical sites to increase quality assurance, and advanced methods of pharmacokinetic/pharmacodynamic modeling to optimize dosing prior to initiating large phase 3 trials. The session closed with a roundtable discussion and recommendations for data sharing to further explore potential causes and viable solutions to be applied in future trials.


Effect of IL-18 binding protein on hepatic ischemia-reperfusion injury induced by infrarenal aortic occlusion.
Severe local and systemic tissue damage called ischemia/reperfusion (IR) injury occurs during the period of reperfusion. Free oxygen radicals and proinflammatory cytokines are responsible for reperfusion injury. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting. The present study aimed to investigate whether IL-18BP had a protective role in remote organ hepatic IR injury. Wistar-Albino rats were divided into three groups that contained seven rats. Group I (sham): Laparotomy and infrarenal abdominal aorta (AA) dissection were done but no clamping was done. Group II (I/R): The infrarenal AA was clamped by atraumatic microvascular clamp for 30 minutes and then was exposed to 90 minutes of reperfusion. Group III (IR + IL-18BP): 75 µg/kg of IL-18BP in 0.9% saline (1 mL) was administered 30 minutes before infrarenal AA dissection and clamping; 30 minutes of ischemia was applied and then was exposed to 90 minutes of reperfusion. Serum AST, ALT, and LDH levels were remarkably higher in IR group and returned to normal levels in treatment group. The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group. Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP. This study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.


Real-Time Monitoring of Bond Slip between GFRP Bar and Concrete Structure Using Piezoceramic Transducer-Enabled Active Sensing.
Glass fiber-reinforced polymers (GFRPs) have received increasing attention in recent years due to their overall performance of light weight, low cost and corrosion resistance, and they are increasingly used as reinforcement in concrete structures. However, GFRP material has low elastic modulus and linear elastic properties compared with steel bars, which introduces different bonding characteristics between bars and concrete. Therefore, a reliable monitoring method is urgently needed to detect the bond slip in GFRP-reinforced concrete structures. In this paper, a piezoceramic-based active sensing approach is proposed and developed to find the debonding between a GFRP bar and the concrete structure. In the proposed method, we utilize PZT (lead zirconate titanate) as two transducers. One acts as an actuator which is buried in the concrete structure, and the other acts as a sensor which is attached to the GFRP bar by taking advantage of machinability of the GRRP material. Both transducers are strategically placed to face each other across from the interface between the GFRP bar and the concrete. The actuator provokes a stress wave that travels through the interface. Meanwhile, the PZT patch that is attached to the GFRP bar is used to detect the propagating stress wave. The bonding condition determines how difficult it is for the stress wave traveling through the interface. The occurrence of a bond slip leads to cracks between the bar and the concrete, which dramatically reduces the energy carried by the stress wave through the interface. In this research, two specimens equipped with the PZT transducers are fabricated, and pull-out tests are conducted. To analyze the active sensing data, we use wavelet packet analysis to compute the energy transferred to the sensing PZT patch throughout the process of debonding. Experimental results illustrate that the proposed method can accurately capture the bond slip between the GFRP bar and the concrete.


The value of LH supplementation in young women with diminished ovarian reserve treated with GnRH Antagonist Protocol for ovarian hyperstimulation in ICSI-cycles.
To compare the success of two controlled ovarian hyperstimulation protocols; rFSH + hp-hMG with only rFSH in the GnRH antagonist protocol in diminished ovarian reserve under 35 years of age. Data from January 2015 to June 2019 were abstracted from the hospital records of IVF Clinic. The women younger than 35 years of age who were diagnosed as diminished ovarian reserve and underwent standard GnRH antagonist protocol were included. Patients in Group-1 underwent controlled ovarian stimulation with rFSH alone and Group-2 with rFSH in combination with hp-hMG. Patients in both groups were divided into three subgroups according to their antral follicle count at Day 3: < 4 (a), 4-6 (b), and 7-10 (c). Demographic features and IVF outcomes of the patients were extracted. Total number of retrieved oocytes, was higher in Group-1 than Group-2 (6.5 ± 2.1 vs 5.5 ± 2.3, respectively, p < 0.001). However, there were no significant differences between the two groups in terms of clinical pregnancy rate, implantation rate, miscarriage rate and live birth rate. Although the main study outcome parameters did not show significant difference between Group-1a and Group-2a, the number of mature oocytes (5 ± 2.8 vs 1.8 ± 1.2, respectively, p = 0.006) was higher in Group-1a. We observed no beneficial effect of LH supplementation during IVF for the treatment of women under 35 years old with diminished ovarian reserve in the first treatment cycle when compared with rFSH only in the antagonist protocols.


Robust computation with rhythmic spike patterns.
Information coding by precise timing of spikes can be faster and more energy efficient than traditional rate coding. However, spike-timing codes are often brittle, which has limited their use in theoretical neuroscience and computing applications. Here, we propose a type of attractor neural network in complex state space and show how it can be leveraged to construct spiking neural networks with robust computational properties through a phase-to-timing mapping. Building on Hebbian neural associative memories, like Hopfield networks, we first propose threshold phasor associative memory (TPAM) networks. Complex phasor patterns whose components can assume continuous-valued phase angles and binary magnitudes can be stored and retrieved as stable fixed points in the network dynamics. TPAM achieves high memory capacity when storing sparse phasor patterns, and we derive the energy function that governs its fixed-point attractor dynamics. Second, we construct 2 spiking neural networks to approximate the complex algebraic computations in TPAM, a reductionist model with resonate-and-fire neurons and a biologically plausible network of integrate-and-fire neurons with synaptic delays and recurrently connected inhibitory interneurons. The fixed points of TPAM correspond to stable periodic states of precisely timed spiking activity that are robust to perturbation. The link established between rhythmic firing patterns and complex attractor dynamics has implications for the interpretation of spike patterns seen in neuroscience and can serve as a framework for computation in emerging neuromorphic devices.


Bethanechol: Is it still being prescribed for bladder dysfunction in women?
Few medical treatment options exist for detrusor underactivity or urinary retention in women. Bethanechol, a cholinergic agonist, may improve detrusor contractility in these conditions; however, its clinical efficacy is limited. We sought to examine the patterns of Bethanechol use by physicians in an ambulatory care setting using a national database to determine if it is still prescribed for patients with bladder dysfunction. The National Ambulatory Medical Care Survey (NAMCS) database was queried for a sample of patient visits to office-based physicians from 2003-2013. Visits were included for women aged 18 years or older with diagnosed lower urinary tract symptoms (LUTS), neurogenic bladder, or urinary retention based on ICD-9-CM codes. Visits in which Bethanechol was prescribed were analysed with descriptive statistics. Sampling weights were adjusted for nonresponders to yield an unbiased national estimate of ambulatory care visits. Out of a weighted sample of 17 321 630 included patient visits, 132 281 (0.8%) visits included a prescription for Bethanechol. Patients prescribed Bethanechol had a mean age of 62.3 ± 2.1 and were predominantly Caucasian (67%) followed by African American (18%). The primary diagnosis associated with Bethanechol was atony of bladder (35%), urinary retention (20%), neurogenic bladder (18%), urinary incontinence (16%), and incomplete bladder emptying (10%). Visits were primarily for chronic conditions (63%). It was typically prescribed as a continued medication (79%) most often by urologists (92%) followed by internal medicine clinicians (8%). Bethanechol continues to be prescribed in elderly women primarily for detrusor atony, urinary retention, or incomplete bladder emptying.


Stigma Experiences, Mental Health, Perceived Parenting Competence, and Parent-Child Relationships Among Lesbian, Gay, and Heterosexual Adoptive Parents in the United States.
Adoptive parents often face stigma related to "non-traditional" family structures. Lesbian and gay (LG) adoptive parents often face additional stigmatization based on sexual identity, which in turn may negatively affect parents' mental health. Despite controversy about LG parenting, research demonstrates that family processes are more strongly associated with individual outcomes than family structure. Thus, family systems and minority stress theories provided our conceptual foundation in examining how adoptive LG parents' stigma experiences were associated with mental health, parenting competence, and parent-child relationships. Participating families (N = 106; n = 56 LG parent families) were originally recruited from five US domestic private infant adoption agencies and completed two waves of data collection (W1, W2; 91% retention) when children were preschool-age (M age = 3.01 years) and school-age (M age = 8.36 years), respectively. Data for the current study are largely drawn from W2. Via Qualtrics, parents completed assessments of mental health symptoms, adoption stigma, and perceived childcare competence. LG parents also reported on their experiences of homonegative microaggressions, and children responded to a measure about their relationships with parents. No significant differences emerged as a function of parental sexual orientation and gender except that lesbian mothers, heterosexual mothers, and gay fathers all reported higher parenting competence than heterosexual fathers. Although parents' mental health did not significantly predict parent-child relationship quality, parents' perceived competence and LG parents' current homonegative microaggression experiences did (e.g., greater competence, greater closeness; more microaggressions, lower closeness). Consistent with our conceptual framework, our results-derived from parent and child reports-demonstrate that although adoptive and LG parent families experience stigma, family processes (rather than structure) are most associated with individual outcomes. Researchers, policy makers, and practitioners should work together to employ identity-affirming practices to reduce stigma and support adoptive family functioning and well-being.


Fragmentation of gallstones by extracorporeal shock waves.
We treated nine patients with functioning gallbladders containing one to three symptomatic radiolucent stones not larger than 25 mm in diameter, as well as five patients with stones in the common bile duct that were not removable by endoscopic procedures, by means of extracorporeally generated shock waves during general anesthesia. The patients with gallbladder stones received adjuvant treatment with a combination of ursodeoxycholic acid and chenodeoxycholic acid. All gallbladder stones were disintegrated into sludge or fragments with diameters of no more than 8 mm. In six of the nine patients the fragments disappeared completely within 1 to 25 weeks. No adverse effects were detected during a follow-up period of 10 to 34 weeks, except transient biliary pain in two patients, with mild pancreatitis in one. In four of the five patients with common-bile-duct stones, shock-wave treatment permitted stone disintegration and successful endoscopic extraction or spontaneous passage of fragments. We conclude that gallstone disease may be treated successfully and without serious adverse effects by extracorporeally generated shock waves in selected patients.


Proximity ligation assays of protein and RNA interactions in the male-specific lethal complex on Drosophila melanogaster polytene chromosomes.
In Drosophila, the male-specific lethal (MSL) complex specifically targets the male X chromosome and participates in a twofold increase in expression output leading to functional dosage compensation. The complex includes five proteins and two non-coding RNAs (ncRNAs). A number of additional associated factors have also been identified. However, the components' roles and interactions have not been fully elucidated. The in situ proximity ligation assay (PLA) provides a sensitive means to determine whether proteins and other factors have bound to chromosomes in close proximity to each other, and thus may interact. Thus, we modified, tested, and applied the assay to probe interactions of MSL complex components on polytene chromosomes. We show that in situ PLA can detect and map both protein-protein and protein-ncRNA interactions on polytene chromosomes at high resolution. We further show that all five protein components of the MSL complex are in close proximity to each other, and the ncRNAs roX1 and roX2 bind the complex in close proximity to MLE. Our results also indicate that JIL1, a histone H3 Ser10 kinase enriched on the male X chromosome, interacts with MSL1 and MSL2, but not MSL3 of the MSL complex. In addition, we corroborate proposed interactions of the MSL complex with both CLAMP and TopoII.


Clearing and release of basement membrane proteins from substrates by metastatic tumor cell variants.
A variety of normal cells and tumor cell lines of differing metastatic potential were evaluated for their effect on various substrates consisting of purified preparations of the basement membrane-associated proteins fibronectin, laminin, and type IV collagen, which were labeled with tritium and/or rhodamine isothiocyanate. Different degrees of clearing or release of material from the substrate were observed, depending on the cell-protein combination. Normal fibroblasts as well as transformed cells and cells of low metastatic potential showed extensive clearing of surfaces coated with fibronectin, laminin, and type IV collagen. This clearing of protein began at sites of initial cell adhesion and was restricted to areas beneath and/or along the apparent paths of cell migration and beneath cellular processes. Covalent attachment of adhesion proteins to glass coverslips nearly eliminated clearing and release. Studies showed that a substantial amount of the fibronectin released from the substrate by HT-1080 fibrosarcoma cells is due to proteolysis. Release and clearing of substratum-attached protein is reduced by approximately 50% by antibodies specific for the protein on the substrate. Tumor cells with low metastatic potential were found to produce higher levels of clearing and release of protein adsorbed to the substrate than tumor cells with high metastatic potential. This was true for variants of the murine K-1735 melanoma and the UV-2237 fibrosarcoma with high and low metastatic capability on all three basement membrane-associated protein substrates. The differences in clearing and release between high and low metastatic cells were not due to differences in initial cell adhesion to the substrates but may be associated with differences in the affinity, type of cell-substrate interactions, proteases, or other variables.


Relative affinities of bovine brain 14 kDa galactose lectin binding to individual endogenous gangliosides.
Sugar-specific binding of bovine brain 14 kDa galactose-binding lectin (BBL) to individual endogenous gangliosides (GM1, GM2, GD1a, GD1b and GT1b) was studied using affinity electrophoresis of ganglioside-lectin mixture in polyacrylamide gel at pH 8.3. Unbound (free) lectin moved ahead while ganglioside-lectin complex moved very little. Sugar-specificity of binding was confirmed by reversal of the interaction by (i) presence of lactose along with the lectin and (ii) pretreatment of gangliosides with another galactose-binding lectin, Ricinus communis agglutinin. Stoichiometry of ganglioside-BBL interaction revealed that GT1b had the highest affinity for the lectin followed by GD1b and GM2, while GM1 and GD1a had the least affinity. Results indicated that a terminal sialic acid moiety covering a galactose moiety may at times enhance BBL recognition of the latter and that changes in ganglioside pattern is a possible modulator of lectin function in vivo.


Prescription Disposal Practices: A 2-Year Ecological Study of Drug Drop Box Donations in Appalachia.
We quantified controlled substance donations via permanent drug donation boxes over 2 years in a region with high prescription abuse, assessing medication characteristics, time between dispensing and donation, and weight of medications donated per capita. In partnership with Drug Enforcement Administration and local law enforcement, we analyzed permanent drug donation box collections in 8 Northeast Tennessee locations from June 2012 to April 2014. We recorded controlled substance dosage units along with the product dispensing date. We collected 4841 pounds of pharmaceutical waste, 4.9% (238.5 pounds) of which were controlled substances, totaling 106,464 controlled substance doses. Analysis of dispensing dates for controlled substances indicated a median of 34 months lapsed from dispensing to donation (range = 1-484 months). The mean controlled substance donation rate was 1.39 pounds per 1000 residents. Communities with fewer than 10,000 residents had a statistically higher controlled substance donation rate (P = .002) compared with communities with 10,000 or more residents. Permanent drug donation boxes can be an effective mechanism to remove controlled substances from community settings. Rural and urban community residents should be provided convenient and timely access to drug disposal options.


Exome sequencing reveals the likely involvement of SOX10 in uveal melanoma.
To identify the spectrum of somatic mutations in an Asian Indian patient with uveal melanoma (UM) without metastasis using exome sequencing. A 49-year-old man from India was diagnosed as having cilio-choroidal (uveal) melanoma (UM), without metastasis, in his right eye with the help of magnetic resonance imaging. This was later confirmed by histopathological evaluation. Two individuals from India with non-neoplastic blind eyes were recruited as controls. The affected eyes from the UM patient and the two control individuals were enucleated, and uveal tissues were collected. DNA was extracted from uveal tissue, and the matched blood sample from each of the three individuals was followed by exome sequencing. Statistical and bioinformatic analyses were done to identify somatic mutations and their putative associations with UM. Thirty-one somatic mutations (25 amino acid altering) in protein-coding (exonic) regions were detected in the UM patient. Of the amino acid-altering somatic mutations, 16 mutations were predicted to be candidate mutations relevant to UM. Somatic mutations, putatively causal for UM, were identified in GNAQ, SF3B1, and SOX10. Somatic mutations in GNAQ and SF3B1 genes were probable drivers of UM in the Indian patient; these were also reported earlier in some White patients. In addition, a frameshift deletion of 20 base pairs has been identified in SOX10 in the UM patient. Somatic mutations in SOX10, a transcription factor, which acts upstream of microphthalmia-associated transcription factor and synergizes with microphthalmia-associated transcription factor, was identified in some melanoma cell lines. The transcription factor SOX10 was found to have an essential role in melanocyte development and pigmentation. Our finding of the frameshift deletion (p.H387fs) in exon 4 of SOX10 in UM provides an important insight and complements earlier findings of mutations in GNAQ and SF3B1 on the genomic basis of UM.


Diffusion-weighted magnetic resonance imaging of the brain of neurologically normal dogs.
OBJECTIVE To acquire MRI diffusion data (apparent diffusion coefficient [ADC] and fractional anisotropy [FA] values, including separate measures for gray and white matter) at 3.0 T for multiple locations of the brain of neurologically normal dogs. 13 neurologically normal dogs recruited from a group of patients undergoing tibial plateau leveling osteotomy. MRI duration ranged from 20 to 30 minutes, including obtaining preliminary images to exclude pathological changes (T2-weighted fluid-attenuated inversion recovery transverse and dorsal images) and diffusion-weighted images. Globally, there were significant differences between mean values for gray and white matter in the cerebral lobes and cerebellum for ADC (range of means for gray matter, 0.8349 × 10-3 s/mm2 to 0.9273 × 10-3 s/mm2; range of means for white matter, 0.6897 × 10-3 s/mm2 to 0.7332 × 10-3 s/mm2) and FA (range of means for gray matter, 0.1978 to 0.2364; range of means for white matter, 0.5136 to 0.6144). These values also differed among cerebral lobes. In most areas, a positive correlation was detected between ADC values and patient age but not between FA values and patient age. Cerebral interlobar and cerebellar diffusion values differed significantly, especially in the gray matter. Information about diffusion values in neurologically normal dogs may be used to diagnose and monitor abnormalities and was the first step in determining the clinical use of diffusion imaging. This information provided an important starting point for the clinical application of diffusion imaging of the canine brain.


Regional Citrate Anticoagulation versus No Anticoagulation for CKRT in Patients with Liver Failure with Increased Bleeding Risk.
The opinions on the efficacy and safety of no anticoagulation versus regional citrate anticoagulation for continuous KRT (CKRT) were controversial in patients with severe liver failure with a higher bleeding risk. We performed a randomized controlled trial to assess no anticoagulation versus regional citrate anticoagulation for CKRT in these patients. Adult patients with liver failure with a higher bleeding risk who required CKRT were considered candidates. The included participants were randomized to receive regional citrate anticoagulation or no-anticoagulation CKRT. The primary end point was filter failure. Of the included participants, 44 and 45 were randomized to receive regional citrate anticoagulation and no-anticoagulation CKRT, respectively. The no-anticoagulation group had a significantly higher filter failure rate (25 [56%] versus 12 [27%], P = 0.003), which was confirmed by cumulative incidence function analysis and sensitive analysis including only the first CKRT sessions. In the cumulative incidence function analysis, the cumulative filter failure rates at 24, 48, and 72 hours of the no-anticoagulation and regional citrate anticoagulation groups were 31%, 58%, and 76% and 11%, 23%, and 35%, respectively. Participants in the regional citrate anticoagulation group had significantly higher incidences of Ca2+tot/Ca2+ion >2.5 (7% versus 57%, P < 0.001), hypocalcemia (51% versus 82%, P = 0.002), and severe hypocalcemia (13% versus 77%, P < 0.001). However, most (73%) of the increased Ca2+tot/Ca2+ion ratios were normalized after the upregulation of the calcium substitution rate. In the regional citrate anticoagulation group, there was no significant additional increase in the systemic citrate concentration after 6 hours. For patients with liver failure with a higher bleeding risk who required CKRT, regional citrate anticoagulation resulted in significantly longer filter lifespan than no anticoagulation. However, regional citrate anticoagulation in patients with liver failure was associated with a significantly higher risk of hypocalcemia, severe hypocalcemia, and Ca2+tot/Ca2+ion >2.5. RCA for CRRT in Liver Failure and High Risk Bleeding Patients, NCT03791190.


High-performance pyramid-SiNWs biosensor for NH3 gas detection.
NH3 is widely existed in the environment and is closely associated with various health issues. Additionally, detecting the small amounts of NH3 exhaled by patients with liver and kidney diseases offers potential opportunities for painless early disease diagnosis. Therefore, there is an urgent need for a convenient, rapid, and highly sensitive real-time NH3 monitoring method. This work presents a high-performance NH3 sensor based on olfactory receptor-derived peptides (ORPs) on a pyramid silicon nanowires (SiNWs) structure substrate. First, we successfully fabricated the pyramid-SiNWs structure on a silicon substrate using a chemical etching method. Subsequently, by dehydrative condensation reaction between the amino groups on APTES and the carboxyl groups of ORPs, ORPs were successfully immobilized onto the pyramid-SiNWs structure. This methodology allows the ORPs sensor on the pyramid-SiNWs substrate to detect NH3 as low as 1 ppb, which was the reported lowest limit of detection (LOD), with a higher response rate compared to ORPs sensors on flat SiNWs substrates. The sensors also exhibit good sensitivity and stability for NH3 gas detection. The results show the feasibility and potential applications of ORPs-pyramid-SiNWs structure sensors, in the fields of food safety, disease monitoring, and environmental protection, etc.


Bacterial pneumonia as a suprainfection in young adults with measles.
The aim of this study was to report the clinical and laboratory characteristics of bacterial pneumonia related to measles infection, and also to assess any correlation between severity and time of onset. Four hundred and twenty-four previously healthy young males (age 22+/-2.1 yrs) were hospitalized with typical symptoms and signs of measles. One hundred and twelve (26%) developed bacterial pneumonia on admission (n=41), during their hospital stay (n=20) or days after their discharge (n=51): groups A, B and C, respectively. Single lobar consolidation was the most common finding, accounting for 89% of cases. Pleural effusion was uncommon and associated in half of the cases with empyema. A microbiological diagnosis was made in 81 cases. Streptococcus pneumoniae (65 cases) and Klebsiella pneumoniae (9 cases) were the most commonly identified organisms. Patients from group C had significantly higher values of white blood cell count and erythrocyte sedimentation rate, and lower values of arterial oxygen tension (14+/-0.8 x 10(9) x L(-1), 88+/-4 mm and 6.3+/-0.4 kPa (47+/-3 mmHg), respectively) than the other two groups. There were no deaths during the hospitalization period. The mean duration of hospital stay was 13+/-2.4 days and was longer in the presence of K. pneumoniae infection (19+/-1.6 days). Six patients from group C were admitted to the intensive care unit. In conclusion, these data suggest that bacterial pneumonia associated with measles is not unusual in hospitalized adults, and it seems to be more severe when it occurs days after the onset of rash.


B cell receptor-independent stimuli trigger immunoglobulin (Ig) class switch recombination and production of IgG autoantibodies by anergic self-reactive B cells.
In both humans and animals, immunoglobulin (Ig)G autoantibodies are less frequent but more pathogenic than IgM autoantibodies, suggesting that controls over Ig isotype switching are required to reinforce B cell self-tolerance. We have used gene targeting to produce mice in which hen egg lysozyme (HEL)-specific B cells can switch to all Ig isotypes (SWHEL mice). When crossed with soluble HEL transgenic (Tg) mice, self-reactive SWHEL B cells became anergic. However, in contrast to anergic B cells from the original nonswitching anti-HEL x soluble HEL double Tg model, self-reactive SWHEL B cells also displayed an immature phenotype, reduced lifespan, and exclusion from the splenic follicle. These differences were not related to their ability to Ig class switch, but instead to competition with non-HEL-binding B cells generated by VH gene replacement in SWHEL mice. When activated in vitro with B cell receptor (BCR)-independent stimuli such as anti-CD40 monoclonal antibody plus interleukin 4 or lipopolysaccharide (LPS), anergic SWHEL double Tg B cells proliferated and produced IgG anti-HEL antibodies as efficiently as naive HEL-binding B cells from SWHEL Ig Tg mice. These results demonstrate that no intrinsic constraints to isotype switching exist in anergic self-reactive B cells. Instead, production of IgG autoantibodies is prevented by separate controls that reduce the likelihood of anergic B cells encountering BCR-independent stimuli. That bacteria-derived LPS could circumvent these controls may explain the well-known association between autoantibody-mediated diseases and episodes of systemic infection.


Prevalence of Cryptosporidium infection among livestock and humans in contact with livestock in Hamadan district, Iran, 2012.
Cryptosporidium is a protozoan parasite causes cryptosporidial diarrhea, which is typically a short-lasting benign infection, but can become severe and non-resolving in immunocompromised individuals. The aim of the present study was to determinate the prevalence of Cryptosporidium infection in livestock and humans that were in contact with livestock in Hamadan district, Iran. In this cross sectional study a total of 660 fecal specimens were collected; 228, 195 and 237 from humans, whom raising livestock, their calves and lambs/goats, respectively in spring 2012. Samples were concentrated by formalin-ether concentration technique and examined using cold modified Ziehl-Neelsen staining method. Two (0.87%) out of 228, 25 (12.8%) out of 195 and 6 (2.5%) out of 237 fecal samples of humans, calves and lambs/goats were positive for Cryptosporidium oocysts, respectively. There was no significant relationship between the infection to Cryptosporidium and demographic variables of humans. However, Cryptosporidium infection rate was higher in diarrheic calves (OR=3.81; 95% CI: 1.30, 11.21; P=0.010). Despite studies conducted in some regions of Iran that resulted in a relatively high rate of infection in humans in contact with livestock, our results showed low prevalence and low carrier status in the asymptomatic persons in Hamadan region. Because the infection in calves and lambs/goats was relatively high, these animals could be probable reservoir of infection for humans in this area.


Overall Essen's experience with the E-vita open hybrid stent graft system and evolution of the surgical technique.
The hybrid stent graft prosthesis E-vita open was designed and introduced by us in 2005 to avoid a two-stage surgical approach in the surgical treatment of complex thoracic aortic disease. Experience in ascending aortic and arch replacement with simultaneous stent grafting of the descending aorta was accumulated over the past 8 years. Facilitation of surgical technique by moving the distal suture line from Zone 3 into Zone 2 took place in 2009. We report our mid-term single-center experience comparing both surgical periods. Between January 2005 and July 2013 a total of 132 patients (mean age 59±11 years) underwent one stage surgery for acute (AAD, n=74), chronic aortic dissection (CAD, n=35) or an extensive thoracic aortic aneurysm (TAA, n=23). Patients were separated in two groups according to distal anastomosis level in Zone 2 (Z2, 41/132) and Zone 3 (Z3, 91/132). Outcome, ischemic and operative times as well as adverse events were monitored during follow up. Overall in-hospital mortality was 13% (17/132) without difference between the groups. However, Zone 2 anastomosis resulted in reduction of cardioplegic arrest (117±39 vs. 147±35 minutes; P<0.001), selective cerebral perfusion (52±15 vs. 68±18 minutes; P<0.001) and visceral ischemic time (51±19 vs. 72±23 minutes; P<0.001). The incidence of postoperative temporary hemodialysis decreased from 40% to 20% in Z2 (P=0.028), postoperative re-exploration rate from 15% to 2% (P=0.037). No difference was found in dissection with complete false lumen thrombosis in 83% (90/109) within 10 days, as well as in TAA, where 100% aneurysm exclusion was observed. Three-year survival, freedom from thoracoabdominal aortic surgery and endovascular repair was 93%, 88%, 88%, respectively. Overall 5-year survival was 76% in AAD, 85% in CAD and 79% in TAA patients. The dimension of surgery could be successfully reduced, indicated by significantly shortened ischemic times and postoperative complications. Durable one-stage repair of complex thoracic aortic disease could be achieved in the majority of cases with acceptable mortality. Distal reintervention is infrequent but associated with low risk when indicated.


Imaging in Suspected Renal Colic: Systematic Review of the Literature and Multispecialty Consensus.
Renal colic is common, and CT is frequently utilized when the diagnosis of kidney stones is suspected. CT is accurate but exposes patients to ionizing radiation and has not been shown to alter either interventional approaches or hospital admission rates. This multi-organizational transdisciplinary collaboration sought evidence-based, multispecialty consensus on optimal imaging across different clinical scenarios in patients with suspected renal colic in the acute setting. In conjunction with the American College of Emergency Physicians (ACEP) eQual network, we formed a nine-member panel with three physician representatives each from ACEP, the ACR, and the American Urology Association. A systematic literature review was used as the basis for a three-step modified Delphi process to seek consensus on optimal imaging in 29 specific clinical scenarios. From an initial search yielding 6,337 records, there were 232 relevant articles of acceptable evidence quality to guide the literature summary. At the completion of the Delphi process consensus, agreement was rated as perfect in 15 (52%), excellent in 8 (28%), good in 3 (10%), and moderate in 3 (10%) of the 29 scenarios. There were no scenarios where at least moderate consensus was not reached. CT was recommended in 7 scenarios (24%), with ultrasound in 9 (31%) and no further imaging needed in 12 (45%). Evidence and multispecialty consensus support ultrasound or no further imaging in specific clinical scenarios, with reduced-radiation dose CT to be employed when CT is needed in patients with suspected renal colic.


Uterine natural killer cell partnerships in early mouse decidua basalis.
The decidua basalis of developing mouse implantation sites is highly enriched in CD45+ leukocytes. In intact, syngeneically mated C57BL/6 decidua basalis examined at gestation day 8.5 by whole-mount in situ immunohistochemistry, leukocyte, but not trophoblast, conjugations were reported. Nothing is known regarding time course, frequency, composition, or importance of physiologic decidual CD45+ cell pairing. In this study, we confirmed the presence of anti-CD54+/anti-CD11a+ immune synapses in CD45+ decidual cell conjugates and characterized their cellular heterogeneity. Conjugated cell pairs were virtually absent before implantation (virgin and gestation days 3.5 and 4.5), were infrequent at gestation day 5.5, but involved 19% of all CD45+ cells by gestation day 8.5, then declined. By gestation day 8.5, almost all CD45+ cells coexpressed CD31, and 2 CD45+CD31+ cells composed most conjugates. Conjugation partners were defined for 2 nonoverlapping uterine natural killer cell subsets (Ly49C/I +/Dolichos biflorus agglutinin lectin- and Ly49C/I-/Dolichos biflorus agglutinin lectin+). Ly49C/I+ uterine natural killer cells were the major subset from before mating up to gestation day 6.5. At gestation day 5.5/6.5, uterine natural killer cell conjugates involving Ly49C/I + cells were more abundant. By gestation day 8.5/9.5, Dolichos biflorus agglutinin lectin+ uterine natural killer cells were the dominant subset with Dolichos biflorus agglutinin lectin+/Dolichos biflorus agglutinin lectin+ homologous conjugates and Dolichos biflorus agglutinin lectin+/Dolichos biflorus agglutinin lectin- heterologous conjugates dominating uterine natural killer cell pairings. At gestation day 6.5, both Ly49C/I+/CD45+ and Dolichos biflorus agglutinin lectin+/CD45+ heterologous conjugate pairs strongly engaged antigen-presenting cells (CD11c+, CD68+, or major histocompatibility complex class II+). By gestation day 8.5, dominant partners of Ly49C/I+/CD45+ and Dolichos biflorus agglutinin lectin+/CD45+ heterologous conjugates are T cells (CD8+ >CD4+). Heterologous conjugates that did not involve uterine natural killer cells occurred but did not suggest antigen presentation to T cells. These data identify gestation day 6.5-8.5 in the pregnant mouse as a critical window for leukocyte interactions that may establish immune regulation within implantation sites.


Sources of vitamin D and calcium in the diets of preschool children in the UK and the theoretical effect of food fortification.
Dietary intakes of vitamin D are very low in the UK. Dietary calcium is also necessary to promote bone health. The fortification of foods with vitamin D could be a safe and effective way of increasing intake. Diets of preschool children, 755 at 18 months and 3.5 years, from the Avon Longitudinal Study of Parents and Children were assessed using dietary records completed by parents. Energy, vitamin D and calcium intakes were calculated. Multinomial logistic regression was used to estimate the odds ratio for being in the highest/lowest quartile of intake. Intakes were recalculated to test different fortification regimes. Vitamin D intakes were low; all children were below the UK and US dietary recommendations. Calcium intakes decreased between the two ages as a result of reduced milk consumption. Children in the lowest quartile for vitamin D intake at 18 months were twice as likely to remain in that quartile at 3.5 years (odds ratio = 2.35; 95% confidence interval = 1.56-3.55). The majority of foods provide no vitamin D with fat spreads and milk as the main sources. The contribution from breakfast cereals increased, from 6% to 12%, as a result of the increased consumption of fortified cereals. Dairy foods provided the highest contribution to calcium at 18 months but were less important at 3.5 years. Theoretical intakes from different fortification regimens suggest that milk fortified at 2 μg 100 g(-1) vitamin D would provide most children with adequate but not excessive intakes. Dietary vitamin D intakes were very low and calcium intakes were mostly adequate. Fortification of milk with vitamin D could be a good way to boost intakes.


Induction of complete and incomplete chromosome aberrations by bleomycin in human lymphocytes.
Bleomycin (BLM) is a clastogenic compound, which due to the overdispersion in the cell distribution of induced dicentrics has been compared to the effect of high-LET radiation. Recently, it has been described that in fibroblast derived cell lines BLM induces incomplete chromosome elements more efficiently than any type of ionizing radiation. The objective of the present study was to evaluate in human lymphocytes the induction of dicentrics and incomplete chromosome elements by BLM. Peripheral blood samples have been treated with different concentrations of BLM. Two cytogenetic techniques were applied, fluorescence plus Giemsa (FPG) and FISH using pan-centromeric and pan-telomeric probes. The observed frequency of dicentric equivalents increases linearly with the BLM concentration, and for all BLM concentrations the distribution of dicentric equivalents was overdispersed. In the FISH study the ratio between total incomplete elements and multicentrics was 0.27. The overdispersion in the dicentric cell distribution, and the linear BLM-concentration dependence of dicentrics can be compared to the effect of high-LET radiation, on the contrary the ratio of incomplete elements and multicentrics is similar to the one induced by low-LET radiation (~0.40). The elevated proportion of interstitial deletions in relation to total acentric fragments, higher than any type of ionizing radiation could be a characteristic signature of the clastogenic effect of BLM.


In vivo gene transfer of PPAR gamma is insufficient to induce adipogenesis in skeletal muscle.
Skeletal muscle contains several progenitor/stem cells with myogenicity as well as adipogenicity such as satellite cells. Our previous study demonstrated that forced expression of PPAR gamma is sufficient to induce transdifferentiation of predetermined myoblasts in vitro. In the present study, we examined whether introduction of PPAR gamma gene could induce adipogenesis of satellite cells in vivo. A plasmid vector containing enhanced green fluorescent protein (EGFP) or PPAR gamma gene was introduced into rat tibialis anterior muscle by electroporation. Histological analyses revealed that electroporation induces degenerative/regenerative response in skeletal muscle, including activation of satellite cells. When EGFP gene was introduced, newly formed myotubes resulted from fusion of activated satellite cells, showed EGFP expression, indicating that electroporation could transfect satellite cells with exogenously introduced gene. Gene transfer of PPAR gamma resulted in an increase of PPAR gamma-positive mononucleated cells on day 3 after electroporation but failed to induce adipogenesis thereafter. These results suggested that, in addition to an expression of PPAR gamma, niches that support adipogenesis are required for satellite cells to enter adipogenesis in vivo.


A Ca2(+)-sensitive glycoprotein, GP90, associated with the cytoskeleton from brain and gizzard.
We describe here the expression during development, tissue distribution and molecular properties of GP90: a major concanavalin A (ConA)-binding glycoprotein present in the neuronal membrane skeleton from chicken brain. GP90 is co-isolated with, and has a similar developmental profile to contactin (previously called GP130). In whole brain, GP90 undergoes rapid synthesis between embryonic days 10 and 12. Unlike contactin, it is not restricted to nervous tissue and is quite abundant in gizzard, where there are two antigenically related proteins of 100K and 90K (K = 10(3) Mr). In both brain and gizzard GP90 and (GP100) are enriched in the membrane skeleton fraction. Trypsinization of live cells suggest that GP90 from gizzard is related to GP100 by the removal of a polypeptide chain. GP90 from both neurones and gizzard cells is protected from proteolysis by the presence of extracellular Ca2+. In the absence of Ca2+ a soluble fragment of approximately 70K can be released from the surface of cells indicating that a large fraction of GP90 is extracellular. Deglycosylation of GP90 from brain using endoglycosidase F demonstrates the presence of at least five carbohydrate chains and a polypeptide chain of approximately 80K. Immunofluorescence studies show that GP90 is exposed on the surface of cultured neurones, gizzard cells and most glial cells with the exception of Schwann cells. It is observed in clusters or patches even when cells are prefixed, suggesting this may be the normal distribution of GP90.


Heart rate and heart failure.
Resting heart rate has long been thought to be a risk factor in cardiovascular disease and a prognostic factor in heart failure. β-Blockers were originally used in heart failure for their heart rate control abilities. However, they also have negative inotropic effects contributing to their overall benefit. The role of isolated heart rate modification is unclear in left ventricular systolic dysfunction. Two recent studies looked at the heart rate-lowering effects of the If, or funny current inhibitor ivabradine and its potential role in heart failure therapy. At the doses chosen for the studies, ivabradine is presumed to have only effects on heart rate with no other cardiotropic effects. Thus, the cardiovascular outcome benefits are presumed to be secondary to heart rate modification. The two recent trials showed both heart rate and cardiovascular events to be significantly lower in the ivabradine-treated group of patients with left ventricular systolic dysfunction and initial heart rate at least 70 beats/min. However, neither of these trials proved causality. Hence, the link between heart rate and improved cardiovascular outcomes still remains muddled.


Paternal and maternal concerns for their very low-birth-weight infants transitioning from the NICU to home.
This study examines qualitatively the concerns and coping mechanisms of fathers and mothers of very low-birth-weight (VLBW; <1500 g) neonatal intensive care unit (NICU) infants as they transition to home from the NICU. In-depth, semistructured phone interviews were conducted with a sample of fathers and mothers of VLBW NICU infants in the Chicago area who had transitioned home, and parental concerns were examined during the transition to home. Phone interviews lasting 30 to 60 minutes were transcribed verbatim, and all interviews were coded using content and narrative analysis. Twenty-five parents (10 fathers, 15 mothers) of 16 VLBW infants who had an average gestational age of 29.5 weeks and an average NICU stay of 58.38 days completed the interview. Overriding concerns included pervasive uncertainty, lingering medical concerns, and partner-related adjustment concerns that differed by gender. A variety of resilient coping methods during this stressful transition are also described. Fathers and mothers of VLBW NICU graduates have evolving but often differing concerns as they transition from the NICU to home. Many of these concerns can be addressed with improved discharge information exchanges and anticipatory guidance. Supporting parents during this stressful and often difficult transition may lead to decreased family stress, improved care, and better infant outcomes.


A New Molecular Detection System for Canine Distemper Virus Based on a Double-Check Strategy.
Due to changing distemper issues worldwide and to inadequate results of an inter-laboratory study in Germany, it seems sensible to adapt and optimize the diagnostic methods for the detection of the canine distemper virus (CDV) to the new genetic diversity of virus strains. The goal of the project was the development, establishment and validation of two independent one-step reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) methods for the safe detection of CDV in domestic and wild animals. For this purpose, an existing CDV-RT-qPCR was decisively adapted and, in addition, a completely new system was developed. Both CDV-RT-qPCR systems are characterized by a very high, comparable analytical and diagnostic sensitivity and specificity and can be mutually combined with inhibition or extraction controls. The reduction in the master mix used allows for the parallel implementation of both CDV-RT-qPCR systems without significant cost increases. For validation of the new CDV-RT-qPCR duplex assays, a panel comprising 378 samples derived from Germany, several European countries and one African country were tested. A sensitivity of 98.9% and a specificity of 100% were computed for the new assays, thus being a reliable molecular diagnostic tool for the detection of CDV in domestic and wild animals.


Nutrition, infection and child growth in Papua New Guinea.
Growth patterns of populations in Papua New Guinea (PNG) have traditionally shown considerable variation, with the greatest difference lying between coastal and highland populations. While genetic differences in explaining these patterns cannot be excluded, the generally poor growth relative to western growth references is largely due to the complex interactive effects of undernutrition and infection. The effects of diet, nutrition and infection on the nutritional status of a child vary with age, the general disease ecology and the type and extent of exposure to it, patterns of infant and young child feeding, and types of food consumed. There are two possible ways in which the relationship between undernutrition and infection can begin; one in which poor nutritional status leads to impaired immunocompetence and reduced resistance to infection, and the other in which exposure to infectious disease can lead to a range of factors that reduce food intake, absorption of nutrients, or increase nutrient requirements. In PNG prior to, and at early stages of modernisation, primary malnutrition is likely to have been the usual initiating factor in the onset of growth faltering due to undernutrition-infection interactions. However, the possibility that infection may have been the initiating event in some societies cannot be excluded. This would have happened by way of early dietary supplementation of infants with foods of minor nutritional significance, which could have acted as a vehicle for the introduction of infectious disease to the child. With modernisation and adoption of primary health care principles, earlier supplementation of infant diet than was previously the case became common in PNG. This has lead to general improvements in growth and nutritional status. However, in populations where undernutrition is still common, infection has become more important than primary malnutrition as the initiator of growth faltering due to undernutrition-infection interactions.


Anchorage-independent growth-conferring factor production by rat mammary tumor cells.
Conditioned medium from cultures of 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor cells contain factors that resemble sarcoma growth factor and other transforming growth factors in biological activity but differ in their physical properties. The mammary tumor factors (MTF) are acid stable and heat and protease sensitive. They inhibit the binding of epidermal growth factor, but not insulin, to mouse embryonal carcinoma cells. MTF confers upon normal rat kidney and BALB/c-3T3 cells the ability to grow in soft agar. This effect is enhanced synergistically by high concentrations of fetal calf serum but not by epidermal growth factor. Anchorage-independent growth promotion, however, is not seen with normal mammary epithelial cells, although MTF is mitogenic for these cells as well as normal rat kidney cells, BALB/c-3T3 cells, and chick embryo fibroblasts in monolayer culture, MTF is not mitogenic for primary cultures of the tumor cells from which the factors are derived. Two major molecular weight species of MTF, eluting at Mr 6,000 and 65,000 to 70,000 on Bio-Gel P-100 columns, are present in acid-ethanol extracts of 7,12-dimethylbenz(a)anthracene- and nitrosomethylurea-induced rat mammary tumors. Transplantable tumors derived from primary 7,12-dimethylbenz(a)anthracene- or nitrosomethylurea-induced tumors have little or no MTF activity. These results demonstrate that different chemically induced rat mammary tumors contain transforming growth factor-like activities. Furthermore, it is possible that MTF is unnecessary for the maintenance of tumorigenicity, since some tumors contain no detectable MTF.


Evolutionary analysis of orthologous cDNA sequences from cultured and symbiotic dinoflagellate symbionts of reef-building corals (Dinophyceae: Symbiodinium).
Dinoflagellates are ubiquitous marine and freshwater protists. The endosymbiotic relationship between dinoflagellates of the genus Symbiodinium (also known as zooxanthellae) and corals forms the basis of coral reefs. We constructed and analyzed a cDNA library from a cultured Symbiodinium species clade A (CassKB8). The majority of annotated ESTs from the Symbiodinium sp. CassKB8 library cover metabolic genes. Most of those belong to either carbohydrate or energy metabolism. In addition, components of extracellular signal transduction pathways and genes that play a role in cell-cell communication were identified. In a subsequent analysis, we determined all orthologous cDNA sequences between this library (1,484 unique sequences) and a library from a Symbiodinium species clade C (C3) (3,336 unique sequences) that was isolated directly from its symbiotic host. A set of 115 orthologs were identified between Symbiodinium sp. CassKB8 and Symbiodinium sp. C3. These orthologs were subdivided into three groups that show different characteristics and functions: conserved across eukaryotes (CE), dinoflagellate-specific (DS) and Symbiodinium-specific (SS). Orthologs conserved across eukaryotes are mainly comprised of housekeeping genes, photosynthesis-related transcripts and metabolic proteins, whereas the function for most of the dinoflagellate-specific orthologs remains unknown. A dN/dS analysis identified the highest ratio in a Symbiodinium-specific ortholog and evidence for positive selection in a dinoflagellate-specific gene. Evolution of genes and pathways in different dinoflagellates seems to be affected by different lifestyles, and a symbiotic lifestyle may affect population structure and strength of selection. This study is the first evolutionary comparative analysis of orthologs from two coral dinoflagellate symbionts.


Public-private interactions in global food safety governance.
In response to an apparent decline in global food safety, numerous public and private regulatory initiatives have emerged to restore public confidence. This trend has been particularly marked by the growing influence of private regulators such as multinational food companies, supermarket chains and non-governmental organizations (NGOs), who employ private standards, certification protocols, third-party auditing, and transnational contracting practices. This paper explores how the structure and processes of private food safety governance interact with traditional public governance regimes, focusing on Global Good Agricultural Practices (GlobalGAP) as a primary example of the former. Due to the inefficiency and ineffectiveness of public regulation in the face of global problems, private governance in food safety has gradually replaced states' command-and-control regulation with more flexible, market-oriented mechanisms. The paper concludes by emphasizing the importance of constructive regime interaction instead of institutional boundary building to global food safety governance. Public and private ordering must each play a role as integral parts of a larger, dynamic and evolving governance complex.


Exposure to cigarette smoke induces overexpression of von Hippel-Lindau tumor suppressor in mouse skeletal muscle.
Cigarette smoke (CS) is a well-established risk factor in the development of chronic obstructive pulmonary disease (COPD). In contrast, the extent to which CS exposure contributes to the development of the systemic manifestations of COPD, such as skeletal muscle dysfunction and wasting, remains largely unknown. Decreased skeletal muscle capillarization has been previously reported in early stages of COPD and might play an important role in the development of COPD-associated skeletal muscle abnormalities. To investigate the effects of chronic CS exposure on skeletal muscle capillarization and exercise tolerance, a mouse model of CS exposure was used. The 129/SvJ mice were exposed to CS for 6 mo, and the expression of putative elements of the hypoxia-angiogenic signaling cascade as well as muscle capillarization were studied. Additionally, functional tests assessing exercise tolerance/endurance were performed in mice. Compared with controls, skeletal muscles from CS-exposed mice exhibited significantly enhanced expression of von Hippel-Lindau tumor suppressor (VHL), ubiquitin-conjugating enzyme E2D1 (UBE2D1), and prolyl hydroxylase-2 (PHD2). In contrast, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was reduced. Furthermore, reduced muscle fiber cross-sectional area, decreased skeletal muscle capillarization, and reduced exercise tolerance were also observed in CS-exposed animals. Taken together, the current results provide evidence linking chronic CS exposure and induction of VHL expression in skeletal muscles leading toward impaired hypoxia-angiogenesis signal transduction, reduced muscle fiber cross-sectional area, and decreased exercise tolerance.


Achiral Zeolites as Reaction Media for Chiral Photochemistry.
Obtaining enantiomerically-enriched photoproducts from achiral reactants has been a long-sought goal. The various methods developed to achieve chiral induction in photoproducts during the last fifty years still suffer from a lack of predictability, generality, and simplicity. With the current emphasis on green chemistry, obtaining enantiomerically enriched products via photochemistry is a likely viable alternative for the future. Of the various approaches developed during the last three decades, the one pioneered in the author's laboratory involved the use of commercially-available and inexpensive achiral zeolites as the media. This approach does not use any solvent for the reaction. Examples from these studies are highlighted in this article. Since no chiral zeolites were available, when the work was initiated in the author's laboratory, commercially-available zeolites X and Y were modified with chiral inductors so that the reaction space becomes chiral. The results obtained established the value of chirally-modified, commercial zeolites as media for achieving chiral induction in photochemical reactions. A recent report of the synthesis of a chiral zeolite is likely to stimulate zeolite-based chiral photochemistry in synthesizing enantiomerically-pure organic molecules. The availability of chiral zeolites in future is likely to energize research in this area. Our earlier observations on this topic, we believe, would be valuable for progress of the field. Keeping this in mind, I have summarized the work carried out in our laboratory on chiral photochemistry on chirally-modified zeolites. This review does not include examples where high chiral induction has been obtained via a strategy that examines molecules appended with chiral auxiliary within achiral and chirally-modified zeolites. The latter approach yields products with diastereomeric excess >80%.


Human lymphocyte subpopulations effect of epinephrine.
The effect of administration of 0-2 mg of epinephrine (Parke-Davis) on circulatory lymphocytes was investigated in fifteen normal subjects. Blood samples were taken prior to, 10 and 20 min after, subcutaneous injections. Thymus-derived (T) cells were assayed by sheep red blood cell rosettes, bone marrow-derived (B) cells by their complement receptors and immunofluorescent detection of Fc receptors plus surface immunoglobulins. Their percentages prior to injections were 72-2 +/- 1-4, 13-8 +/- 1-1, and 20-3 +/- 1-3. Ten minutes after injections, the absolute concentrations of these cells increased to 164 +/- 14%, 326 +/- 57%, and 272 +/- 45% respectively of the values prior to injection (averages +/- standard errors). Further, when cells with receptors for both sheep red blood cells and complement were assayed by simultaneous rosette technique, they increased from 2-5 +/- 0-4% to 10-5 +/- 1-3% of the lymphocytes. Such changes were also observed in three subjects who had undergone splenectomy more than 2 years previously, but not in four subjects receiving injections of saline instead of epinephrine.