Identification of 5-Fluoro ADB in Human Whole Blood in Four Death Cases.
Four deaths that seemed to have been caused by a designer drug occurred within a 3-week period in Sendai, Japan. In each case, the decedent possessed the same sachet, labeled "Heart Shot BLACK", which contained a dried plant material with an aromatic scent. It was revealed in our analysis that the product contained a synthetic cannabinoid receptor agonist, 5-fluoro ADB (methyl 2-[1-(5-fluoropentyl)-1H-indazole-3-carboxamide]-3,3-dimethylbutanoate, also known as 5-fluoro MDMB-PINACA), which is now classified as a restricted designer drug in Japan after it caused several casualties. For standard samples, the detection of 5-fluoro ADB in whole blood in the calibration range (0.04-4 ng/mL) was successful with recoveries of 94.6-98.1%, limits of detection of 6 pg/mL, and limits of quantification of 40 pg/mL. The intraday and interday precisions were 0.9-4.8% and 1.1-6.6%, respectively. The bias was -1.1 to 2.9%. We were able to confirm that 5-fluoro ADB was present in the blood of all four decedents at a concentration of 0.11-1.92 ng/mL. From the autopsy, toxicological findings, and circumstances surrounding the cases, it was considered that inhalation of 5-fluoro ADB could have contributed to the deaths. However, the extent to which 5-fluoro ADB contributed to the deaths remains unclear due to the current lack of toxicological information on the compound. In future research, the toxicity of 5-fluoro ADB in humans and the mechanism underlying this effect need to be elucidated.


Evaluating Indoor Air Chemical Diversity, Indoor-to-Outdoor Emissions, and Surface Reservoirs Using High-Resolution Mass Spectrometry.
Detailed offline speciation of gas- and particle-phase organic compounds was conducted using gas/liquid chromatography with traditional and high-resolution mass spectrometers in a hybrid targeted/nontargeted analysis. Observations were focused on an unoccupied home and were compared to two other indoor sites. Observed gas-phase organic compounds span the volatile to semivolatile range, while functionalized organic aerosols extend from intermediate volatility to ultra-low volatility, including a mix of oxygen, nitrogen, and sulfur-containing species. Total gas-phase abundances of hydrocarbon and oxygenated gas-phase complex mixtures were elevated indoors and strongly correlated in the unoccupied home. While gas-phase concentrations of individual compounds generally decreased slightly with greater ventilation, their elevated ratios relative to controlled emissions of tracer species suggest that the dilution of gas-phase concentrations increases off-gassing from surfaces and other indoor reservoirs, with volatility-dependent responses to dynamically changing environmental factors. Indoor-outdoor emissions of gas-phase intermediate-volatility/semivolatile organic hydrocarbons from the unoccupied home averaged 6-11 mg h-1, doubling with ventilation. While the largest single-compound emissions observed were furfural (61-275 mg h-1) and acetic acid, observations spanned a wide range of individual volatile chemical products (e.g., terpenoids, glycol ethers, phthalates, other oxygenates), highlighting the abundance of long-lived reservoirs resulting from prior indoor use or materials, and their gradual transport outdoors.


Long-term efficacy and tolerability of abdominal once-yearly histrelin acetate subcutaneous implants in patients with advanced prostate cancer.
Objectives. Long-term assessment of the efficacy and tolerability of subcutaneous abdominal histrelin acetate implants that have been inserted for more than two years. Materials and Methods. Retrospective data collected over a six-year period at a single center from charts of 113 patients who received the subcutaneous abdominal histrelin acetate implant. Results. Following insertion of the first implant, 92.1% and 91.8% of patients had a serum testosterone level of ≤30 ng/dL at 24 and 48 weeks, respectively. Serum testosterone levels remained at <30 ng/dL for 96% of patients at two years and for 100% of patients at 3, 4, and 5 years. The testosterone levels remained significantly less than baseline (P < 0.05). Six patients (5.3%) had androgen-independent progression when followed up on the long term, increasing the mean serum PSA at 3, 4, and 5 years to 35.0 µg/L (n = 22), 30.7 µg/L (n = 13), and 132.9 µg/L (n = 8), respectively. The mean serum PSA was significantly greater than baseline during these years (P < 0.05). Eight patients (7.1%) experienced minor, but not serious, adverse events from the histrelin acetate. Conclusion. Subcutaneous abdominal histrelin acetate implants are an effective long-term and well-tolerated administration method for treating patients with advanced prostate cancer.


Identification of the ral and rac1 gene products, low molecular mass GTP-binding proteins from human platelets.
Identification of the GTP-binding proteins from human platelet particulate fractions was attained by their purification via successive column chromatography steps followed by amino acid sequencing. To enhance the likelihood of identifying the GTP-binding proteins, two assays were employed to monitor GTP-binding activities: (i) guanosine 5'-(3-O-[35S]thio)triphosphate (GTP gamma S)-binding followed by rapid filtration and ii) [alpha-32P]GTP-binding following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting onto nitrocellulose membranes. The latter assay permitted the isolation of a 28-kDa GTP-binding protein that bound [alpha-32P]GTP prominently but was only poorly detected with the GTP gamma S-binding assay. The amino acid sequences of three peptide fragments derived from the 28-kDa protein were identical to regions of the amino acid sequence deduced from a simian ral cDNA with the exception of one conservative substitution (Asp147----Glu). A full length human ral cDNA was isolated from a placental cDNA library, and its deduced amino acid sequence, compared with simian ral, also contained the Asp----Glu substitution along with two other substitutions and an additional three NH2-terminal amino acids. In addition to the 28-kDa protein, two distinct 25-kDa GTP-binding proteins were purified from platelets. One of these proteins has been previously characterized as G25K, an abundant low molecular mass GTP-binding protein. Partial amino acid sequence obtained from the second unidentified 25-kDa protein indicates that it is the product of the rac1 gene; a member of a newly identified gene family which encode for low molecular mass GTP-binding proteins (Didsbury, J., Weber, R.F., Bokoch, G. M., Evans, T., and Snyderman, R. (1989) J. Biol. Chem. 264, 16378-16382). These results identify two new GTP-binding proteins in human platelets, ral, the major protein that binds [alpha-32P]GTP on nitrocellulose transfers, and rac1, a substrate for botulinum C3 ADP-ribosyltransferase.


Undernutrition and aging.
Diet restriction is a well-recognised method of slowing aging and prolonging life span in animals. However, previous studies of this have tended to start after weaning and the effects of prenatal or early postnatal diet restriction have rarely been considered. Here we summarise the existing literature, which suggests that reducing nutrition at this earlier stage of life has opposite effects, resulting in accelerated aging and a reduction in life span. These findings support emerging epidemiological evidence in man that poor nutrition in early life may programme accelerated aging and predispose to a variety of age-related diseases.


Bayesian estimation of diagnostic accuracy of a new bead-based antibody detection test to reveal Toxoplasma gondii infections in pig populations.
The success of a Toxoplasma gondii surveillance program in European pig production systems depends partly on the quality of the test to detect infection in the population. The test accuracy of a recently developed serological bead-based assay (BBA) was investigated earlier using sera from experimentally infected animals. In this study, the accuracy of the BBA was determined by the use of sera from animals from two field subpopulations. As no T. gondii infection information of these animals was available, test accuracy was determined through a Bayesian approach allowing for conditional dependency between BBA and an ELISA test. The priors for prevalence were based on available information from literature, whereas for specificity vague non-informative priors were used. Priors for sensitivity were based either on available information or specified as non-informative. Posterior estimates for BBA sensitivity and specificity were (mode) 0.855 (Bayesian 95% credibility interval (bCI) 0.702-0.960) and 0.913 (bCI 0.893-0.931), respectively. Comparing the results of BBA and ELISA, sensitivity was higher for the BBA while specificity was higher for ELISA. Alternative priors for the sensitivity affected posterior estimates for sensitivity of both BBA and ELISA, but not for specificity. Because the difference in prevalence between the two subpopulations is small, and the number of infected animals is small as well, the precision of the posterior estimates for sensitivity may be less accurate in comparison to the estimates for specificity. The estimated value for specificity of BBA is at least optimally defined for testing pigs from conventional and organic Dutch farms.


Neutralizing Antibodies in COVID-19 Patients and Vaccine Recipients after Two Doses of BNT162b2.
The evaluation of the neutralizing capacity of anti-SARS-CoV-2 antibodies is important because they represent real protective immunity. In this study we aimed to measure and compare the neutralizing antibodies (NAbs) in COVID-19 patients and in vaccinated individuals. One-hundred and fifty long-term samples from 75 COVID-19 patients were analyzed with a surrogate virus neutralization test (sVNT) and compared to six different SARS-CoV-2 serology assays. The agreement between the sVNT and pseudovirus VNT (pVNT) results was found to be excellent (i.e., 97.2%). The NAb response was also assessed in 90 individuals who had received the complete dose regimen of BNT162b2. In COVID-19 patients, a stronger response was observed in moderate-severe versus mild patients (p-value = 0.0006). A slow decay in NAbs was noted in samples for up to 300 days after diagnosis, especially in moderate-severe patients (r = -0.35, p-value = 0.03). In the vaccinated population, 83.3% of COVID-19-naive individuals had positive NAbs 14 days after the first dose and all were positive 7 days after the second dose, i.e., at day 28. In previously infected individuals, all were already positive for NAbs at day 14. At each time point, a stronger response was observed for previously infected individuals (p-value < 0.05). The NAb response remained stable for up to 56 days in all participants. Vaccinated participants had significantly higher NAb titers compared to COVID patients. In previously infected vaccine recipients, one dose might be sufficient to generate sufficient neutralizing antibodies.


Disease severity and therapy as predictors of cardiovascular risk in psoriasis: a population-based cohort study.
Previous studies suggest an increased risk of cardiovascular disease in psoriasis, but the relative contributions of traditional risk factors and markers of disease severity are unclear. We examined the effect of psoriasis disease characteristics on cardiovascular risk after adjusting for traditional cardiovascular risk factors. Study populations included (a) case-cohort sample of 771 patients nested within a population-based psoriasis incidence cohort, and (b) cohort of 1905 patients with incident and prevalent psoriasis patients. Both cohorts were followed-up to ascertain disease and treatment characteristics, traditional cardiovascular risk factors and cardiovascular outcomes. Cox proportional hazards regression models were used to identify predictors of cardiovascular outcomes. After adjusting for traditional risk factors, increasing number of psoriasis-affected body sites at disease onset (HR: 1.53 per additional site, 95% CI: 1.20, 1.95) was significantly associated with an increased risk of cardiovascular outcomes. Phototherapy (HR: 3.76, 95% CI: 2.45, 5.77) and systemic therapy (HR: 2.17, 95% CI: 1.50, 3.13) were associated with a higher risk of cardiovascular outcomes in univariate analyses, but these relatively strong associations disappeared after adjusting for cardiovascular risk factors. Increasing number of psoriasis-affected body sites may be a severity indicator in psoriasis and is associated with an increased cardiovascular risk. Due to low number of patients exposed to systemic therapy, this study had limited power to examine the effect of treatment on cardiovascular risk. Strong associations with phototherapy and systemic therapy suggest that the cardiovascular risk in psoriasis is confined to patients with severe disease.


Screw fixation of odontoid fractures and nonunions.
Surgical treatment of odontoid fractures has usually been carried out by C1-2 arthrodesis rather than by fracture fixation. An alternative treatment of compression screw fixation was used to treat selected acute odontoid fractures and nonunions. Ten patients were operated on. A variety of lag-screw types were used to compress and secure the fracture. Screw placement was considered excellent in five cases; in four, the screw tip protruded through the posterosuperior cortex of the dens by 1-3 mm. One patient died as a result of multiple injuries 2 days after surgery. In all other cases, including four cases of odontoid pseudarthroses, the fractures achieved solid union. It was concluded that screw fixation can be used for the successful treatment of selected odontoid fractures and nonunions.


The Invisible Classes in High Stakes Reproduction.
This essay argues that what separates poor mothers from their middle class counterparts are many factors — not simply couples' ability to plan, the power of their choices, and agency. For example, power, social clout, and access to health care (and health information) influence status and parenting. Historically, for white women choice has been about abortion; for many women of color, choice is about being able to be a mother. This essay begs the question whether real parallels can be drawn on questions of contraception, abortion, and ART simply by examining class and to what extent race and sexual orientation matter in research on parenting.


Divergence in nitrogenases of Azoarcus spp., Proteobacteria of the beta subclass.
Nitrogenase is a functionally constant protein catalyzing N2 reduction, which is found in many phylogenetic lineages of Archaea and Bacteria. A phylogenetic analysis of nif genes may provide insights into the evolution of the bacterial genomes. Moreover, it may be used to study diazotrophic communities, when classical isolation techniques may fail to detect all contributing populations. Among six species of the genus Azoarcus, diazotrophic Proteobacteria of the beta subclass, the deduced amino acid sequences of nifH genes of two species were unusually divergent from each other. Nitrogenases of the "authentic" Azoarcus branch formed a monophyletic unit with those of gamma Proteobacteria, thus being in accordance with 16S ribosomal DNA phylogeny. The nitrogenase proteins of the two aberrant strains clustered within the alpha proteobacterial clade with rhizobial nitrogenases. This relationship was supported by bootstrap values of 87 to 98% obtained by various distance and maximum parsimony methods. Phylogenetic distances of NifH proteins indicate a possible lateral gene transfer of nif genes to Azoarcus from a common donor of the alpha subclass at the time of species diversification or several more recent, independent transfers. Application of the phylogenetic analysis to DNA isolated from environmental samples demonstrated novel habitats for Azoarcus: in guts of termites and rice grown in Japan, nifH genes belonging to the authentic Azoarcus branch were detected. This is the first evidence suggesting the occurrence of Azoarcus spp. in a plant other than its originally described host, Kallar grass. Moreover, evidence for expression of nif genes inside grass roots was obtained by in situ hybridization studies with antisense nifH probes.


Experimental assessment of resolution improvement of a zoom-in PET.
We have proposed a zoom-in positron emission tomography (PET) system that incorporates a high-resolution detector into an existing PET scanner to obtain high-resolution images of a region of interest. Previously we have shown by computer simulations that the high-resolution detector can improve the overall system performance in terms of spatial resolution and lesion detectability. In this study, we assessed the resolution improvement in a real system by incorporating a high-resolution detector into our existing microPET II scanner. The high-resolution detector consists of a 14 × 28 array of 0.5 × 0.5 × 10 mm³ lutetium oxyorthosilicate scintillator elements and is placed near the center of the microPET II scanner. It is coupled to two 64-channel photomultiplier tubes (PMTs) via tapered optical fiber bundles. The PMT signals were read out by the electronics in the microPET II scanner. A 15 µCi Na-22 point source was positioned at various locations above the high-resolution detector. Images were reconstructed using the data measured by the microPET II scanner alone and the microPET II data combined with the high-resolution detector data. Profiles taken through the reconstructed point sources show substantial reduction in full-width-at-half-maximum along the direction parallel to the face of the high-resolution detector.


Serum nitric oxide levels in children with Wilson's disease.
It is known that the synthesis of nitric oxide (NO) is increased in cirrhosis. In humans, NO levels were investigated mostly in adult cirrhotics with portal hypertension. Because there is no study investigating NO status in childhood cirrhosis and because Wilson's disease (WD) has some specific properties due its copper overload with powerful prooxidant action, we aimed to determine serum NO levels in children with untreated WD and to investigate the probable relationship between NO level and both clinical presentation and the severity of the disease. Twenty children with newly diagnosed WD and sex and age matched 14 healthy children were included. Serum NO levels were determined by spectrophotometric method using Griess reaction. Serum NO level of children with WD and of healthy children were 156.8 +/- 28.2 and 135.6 +/- 21.17 micromol/l respectively (p = 0.024). Serum NO level was not different in respect with the clinical presentation, such as presence of ascites, neurological involvement, cholestasis or haemorrhagic diathesis. Severity of the disease did not influence the serum NO level. Serum NO levels of patients with low and normal ceruloplasmin levels were not different. It was demonstrated that serum NO level was higher in children with WD compared to healthy children. Because we could not find a correlation between raised NO and any clinical or biochemical findings in the present study, we concluded that NO could not be used as a prognostic or predicting factor in children with WD.


Birth outcome and risk of neonatal hypoglycaemia following in utero exposure to pivmecillinam: a population-based cohort study with 414 exposed pregnancies.
Concerns have been raised as to the safety of using pivaloyl-conjugated beta-lactam antibiotics during pregnancy as they cause carnitine depletion. Restrictions have been recommended in some Scandinavian countries as drug-induced carnitine depletion could constitute a risk to the developing foetus. One of these drugs, pivmecillinam, is widely used against urinary tract infections but few data exist concerning its safety in pregnancy. In a cohort study, we compared the prevalences of congenital abnormalities, pre-term delivery, low birth weight, low Apgar score and neonatal hypoglycaemia in the offspring of 414 women who had at least 1 prescription for pivmecillinam redeemed during pregnancy with those of the offspring of 7472 pregnant women for whom no drugs were prescribed during pregnancy. The prevalence of congenital abnormalities was 1.7% among 119 infants exposed in the first trimester and 3.7% among the reference group [odds ratio (OR) 0.46; 95% confidence interval (CI) 0.11-1.86]. We found no significantly increased risks in either pre-term delivery (OR 0.91, 95% CI 0.11-1.86), low birth weight (OR 0.57, 95%, CI 0.23-1.41), low Apgar score (OR 2.32, 95% CI 0.30-18.16) or hypoglycaemia (OR 0.73, 95% CI 0.18-3.00) that were induced by carnitine depletion. No significantly increased risk in adverse birth outcome was therefore found in women treated with pivmecillinam.


Preterm Gut Microbiome Depending on Feeding Type: Significance of Donor Human Milk.
Preterm microbial colonization is affected by gestational age, antibiotic treatment, type of birth, but also by type of feeding. Breast milk has been acknowledged as the gold standard for human nutrition. In preterm infants breast milk has been associated with improved growth and cognitive development and a reduced risk of necrotizing enterocolitis and late onset sepsis. In the absence of their mother's own milk (MOM), pasteurized donor human milk (DHM) could be the best available alternative due to its similarity to the former. However, little is known about the effect of DHM upon preterm microbiota and potential biological implications. Our objective was to determine the impact of DHM upon preterm gut microbiota admitted in a referral neonatal intensive care unit (NICU). A prospective observational cohort study in NICU of 69 neonates <32 weeks of gestation and with a birth weight ≤1,500 g was conducted. Neonates were classified in three groups according to feeding practices consisting in their MOM, DHM, or formula. Fecal samples were collected when full enteral feeding (defined as ≥150 cc/kg/day) was achieved. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Despite the higher variability, no differences in microbial diversity and richness were found, although feeding type significantly influenced the preterm microbiota composition and predictive functional profiles. Preterm infants fed MOM showed a significant greater presence of Bifidobacteriaceae and lower of Staphylococcaceae, Clostridiaceae, and Pasteurellaceae compared to preterm fed DHM. Formula fed microbial profile was different to those observed in preterm fed MOM. Remarkably, preterm infants fed DHM showed closer microbial profiles to preterm fed their MOM. Inferred metagenomic analyses showed higher presence of Bifidobacterium genus in mother's milk group was related to enrichment in the Glycan biosynthesis and metabolism pathway that was not identified in the DHM or in the formula fed groups. In conclusion, DHM favors an intestinal microbiome more similar to MOM than formula despite the differences between MOM and DHM. This may have potential beneficial long-term effects on intestinal functionality, immune system, and metabolic activities.


Protein localization with flexible DNA or RNA.
Localization of activity is ubiquitous in life, and also within sub-cellular compartments. Localization provides potential advantages as different proteins involved in the same cellular process may supplement each other on a fast timescale. It might also prevent proteins from being active in other regions of the cell. However localization is at odds with the spreading of unbound molecules by diffusion. We model the cost and gain for specific enzyme activity using localization strategies based on binding to sites of intermediate specificity. While such bindings in themselves decrease the activity of the protein on its target site, they may increase protein activity if stochastic motion allows the acting protein to touch both the intermediate binding site and the specific site simultaneously. We discuss this strategy in view of recent suggestions on long non-coding RNA as a facilitator of localized activity of chromatin modifiers.


The secret life of pronouns: flexibility in writing style and physical health.
Numerous disclosure studies have demonstrated that individuals randomly assigned to write about emotional topics evidence improved physical health compared with those who write about superficial topics. The writing samples from three previously published studies of 74 first-year students, 50 upper-division students, and 59 maximum-security prisoners were reanalyzed using Latent Semantic Analysis (LSA) to explore possible relationships of writing content and style to changes in frequency of physician visits following the disclosure intervention. LSA revealed that flexibility in the use of common words-particularly personal pronouns--when writing about traumatic memories was related to positive health outcomes. The findings point to the importance of the role of discussing the self and social relationships in writing and, at the same time, to the remarkable potential of techniques such as LSA.


The role of ubiquinone in the respiratory chain of Acetobacter xylinum.
1. Whole cells of Acetobacter xylinum were found to contain a quinone of the ubiquinone (coenzyme Q) group. The quinone was isolated from the cells and crystallized. It was identified by its physical, chemical and spectroscopic properties as a ubiquinone with 10 isoprene units (ubiquinone-10). No naphthaquinone was detected in the cells. 2. Cell-free extracts prepared by means of a French pressure cell were separated into three fractions by differential centrifugation. The ubiquinone was located predominantly in the particulate fraction sedimenting at 33000g, which also contained most of the NADH oxidase and malate oxidase activities. The concentration of ubiquinone-10 in extracts was similar to that of the flavoproteins and about three times the concentration of the individual cytochromes. 3. Aerobic incubations of crude extracts with either NADH or malate resulted in reduction of the endogenous ubiquinone-10 to steady-state concentrations of 55 and 40% of the total quinone respectively. In the presence of cyanide more than 95% of the endogenous ubiquinone-10 was reduced by either NADH or malate. 4. The initial rate of reduction of endogenous ubiquinone-10 by malate and the rate of ubiquinol oxidation, in A. xylinum extracts, were found to be compatible with the overall rate of malate oxidation with oxygen. 5. The effects of various respiratory inhibitors on the oxidation-reduction reactions of the endogenous quinone indicate that its position on the respiratory chain is between the malate flavoprotein dehydrogenase and the cytochrome chain.


Modeling the Maximum Spreading of Liquid Droplets Impacting Wetting and Nonwetting Surfaces.
Droplet impact has been imaged on different rigid, smooth, and rough substrates for three liquids with different viscosity and surface tension, with special attention to the lower impact velocity range. Of all studied parameters, only surface tension and viscosity, thus the liquid properties, clearly play a role in terms of the attained maximum spreading ratio of the impacting droplet. Surface roughness and type of surface (steel, aluminum, and parafilm) slightly affect the dynamic wettability and maximum spreading at low impact velocity. The dynamic contact angle at maximum spreading has been identified to properly characterize this dynamic spreading process, especially at low impact velocity where dynamic wetting plays an important role. The dynamic contact angle is found to be generally higher than the equilibrium contact angle, showing that statically wetting surfaces can become less wetting or even nonwetting under dynamic droplet impact. An improved energy balance model for maximum spreading ratio is proposed based on a correct analytical modeling of the time at maximum spreading, which determines the viscous dissipation. Experiments show that the time at maximum spreading decreases with impact velocity depending on the surface tension of the liquid, and a scaling with maximum spreading diameter and surface tension is proposed. A second improvement is based on the use of the dynamic contact angle at maximum spreading, instead of quasi-static contact angles, to describe the dynamic wetting process at low impact velocity. This improved model showed good agreement compared to experiments for the maximum spreading ratio versus impact velocity for different liquids, and a better prediction compared to other models in literature. In particular, scaling according to We(1/2) is found invalid for low velocities, since the curves bend over to higher maximum spreading ratios due to the dynamic wetting process.


RF peak power reduction in CAIPIRINHA excitation by interslice phase optimization.
The purpose of this work was to show that the overall peak power of RF pulses for CAIPIRINHA excitation can be substantially reduced by applying interslice phase relaxation. The optimal phases are scan dependent and can be quickly calculated by the proposed method. The multi-band RF pulse design is implemented as the minimization of a linear objective function with quadratic constraints. The interslice phase is considered to be a variable for optimization. In the case of a phase cycling scheme (CAIPIRINHA), the peak power is considered over all pulses. The computation time (about 1 s) is compatible with online RF pulse design. It is shown that the optimal interslice phases depend on the CAIPIRINHA scheme used and that RF peak power is reduced when the CAIPIRINHA phase cycling is taken into account in the optimization. The proposed method is extremely fast and results in RF pulses with low peak power for CAIPIRINHA excitation. The MATLAB implementation is given in the appendix; it allows for online determination of scan-dependent phase parameters. Furthermore, the method can be easily extended to pTx shimming systems in the context of multi-slice excitations, and this possibility is included in the software.


Destruction of cytochrome P 450 by secobarbital and other barbiturates containing allyl groups.
Administration of certain commonly used barbiturates containing allyl groups, such as secobarbital, allobarbital, or aprobarbital to rats treated chronically with a microsomal enzyme inducer causes a rapid destruction of the liver microsomal hemoprotein that serves as the terminal oxidase for drug metabolism. In contrast, barbiturates without an allyl group do not have this effect. The decrease in this hemoprotein, cytochrome P(450), by the barbiturates containing an allyl group could also be demonstrated in an in vitro liver microsomal system requiring reduced nicotinamide adenine dinucleotide phosphate. These results suggest that the barbiturates containing an allyl group are converted to a metabolite that leads to the destruction of cytochrome P(450).


Optimal evaluation time point for patch testing to predict skin irritation of commercial topical drugs.
To develop patch testing (PT) that better reflects the skin irritation resulting from repeated applications, we methodically classified PT results and examined correlations between these results with results from repeated application tests. A total of 115 commercial topical drugs were used for patch testing. In two groups of 30 healthy individuals with normal back skin, 55 or 60 commercial topical drugs were applied to the back for 24 h. Skin reactions were scored for each group at 2 and 24 h after patch removal. Based on time-dependent changes in skin reaction at each evaluation time, PT results were classified into six different types. For repeated application testing, a total of 17 products with different types of PT results were selected. A total of 104 healthy individuals divided into three groups (n = 22-52 each) received application of 6-7 test materials, differing for each group, for 3 weeks on both arms. Incidences of positive symptoms induced by repeated drug application excluding transient erythema showed a greater correlation with reaction levels at 24 h after patch removal than 2 h after patch removal. Many test materials that triggered a high incidence of positive symptoms after repeated application also exhibited erythema or greater reaction up to 24 h after patch removal. PT offers a useful test system for predicting skin irritation that develops after repeated application of topical drug. Moreover, assessment at 24 h after patch removal is suggested as the optimal evaluation time point to reflect the results of repeated application tests.


Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study).
The undercarboxylated form of the osteoblast-secreted protein osteocalcin has favorable effects on fat and glucose metabolism in mice. In human subjects, cross-sectional studies suggest a relevant association. We investigated whether changes in undercarboxylated osteocalcin (ucOC) during osteoporosis treatment are associated with changes in metabolic parameters. We measured ucOC in sera from a subset of osteoporotic postmenopausal women who were treated with PTH(1-84) or alendronate (n = 64 and n = 33, respectively) during the Parathyroid Hormone and Alendronate study. We measured serum adiponectin, leptin, and insulin and analyzed existing data on body weight, fat mass, and serum glucose concentration. Three-month changes in ucOC levels were evaluated as predictors of 12-month changes in indices of fat and glucose metabolism. ucOC levels increased with PTH(1-84) and decreased with alendronate administration (P ≤ 0.01 for both treatment groups). Three-month change in ucOC was inversely associated with 12-month changes in body weight (standardized β = -0.25, P = 0.04) and fat mass (β = -0.23, P = 0.06), after adjustment for the treatment group. Three-month change in ucOC was positively associated with a 12-month change in adiponectin (β = 0.30, P = 0.01), independent of change in fat mass. There were no interactions between treatment and change in ucOC on changes in weight, fat mass, or adiponectin. PTH(1-84) increases and alendronate decreases ucOC levels. Changes in ucOC induced by PTH(1-84) and alendronate are associated with changes in metabolic indices. These associations are consistent with observations from animal models and support a role for ucOC in the skeletal regulation of energy metabolism in humans.


Mechanisms for picrotoxin block of alpha2 homomeric glycine receptors.
It is well known that the convulsant alkaloid picrotoxin (PTX) can inhibit neuronal gamma-aminobutyric acid (GABA) and homomeric glycine receptors (GlyR). However, the mechanism for PTX block of alpha(2) homomeric GlyR is still unclear compared with that of alpha(1) homomeric GlyR, GABA(A), and GABA(C) receptors. Furthermore, PTX effects on GlyR kinetics have been poorly explored at the single-channel level. Hence, we used the patch-clamp technique in the outside-out configuration to investigate the mechanism of PTX suppression of currents carried by alpha(2) homomeric GlyRs stably transfected into Chinese hamster ovary cells. PTX inhibited the alpha(2) homomeric GlyR current elicited by glycine in a concentration-dependent and voltage-independent manner. Both competitive and noncompetitive mechanisms were observed. PTX decreased the mean open time of the GlyR channel in a concentration-dependent manner, suggesting that PTX can block channel openings and bind to the receptor in the open channel conformation. When PTX and glycine were co-applied, a small rebound current was observed during drug washout. Application of PTX during the deactivation phase of glycine-induced currents eliminated the rebound current and accelerated the deactivation time course in a concentration-dependent manner. PTX could not bind to the unbound conformation of GlyR, but could be trapped at its binding site when the channel closed during glycine dissociation. Based on these observations, we propose a kinetic Markov model in which PTX binds to the alpha(2) homomeric GlyR in both the open channel state and the fully liganded closed state. Our data suggest a new allosteric mechanism for PTX inhibition of wild-type homomeric alpha(2) GlyR.


Genome sequence of the deep-sea gamma-proteobacterium Idiomarina loihiensis reveals amino acid fermentation as a source of carbon and energy.
We report the complete genome sequence of the deep-sea gamma-proteobacterium, Idiomarina loihiensis, isolated recently from a hydrothermal vent at 1,300-m depth on the Loihi submarine volcano, Hawaii. The I. loihiensis genome comprises a single chromosome of 2,839,318 base pairs, encoding 2,640 proteins, four rRNA operons, and 56 tRNA genes. A comparison of I. loihiensis to the genomes of other gamma-proteobacteria reveals abundance of amino acid transport and degradation enzymes, but a loss of sugar transport systems and certain enzymes of sugar metabolism. This finding suggests that I. loihiensis relies primarily on amino acid catabolism, rather than on sugar fermentation, for carbon and energy. Enzymes for biosynthesis of purines, pyrimidines, the majority of amino acids, and coenzymes are encoded in the genome, but biosynthetic pathways for Leu, Ile, Val, Thr, and Met are incomplete. Auxotrophy for Val and Thr was confirmed by in vivo experiments. The I. loihiensis genome contains a cluster of 32 genes encoding enzymes for exopolysaccharide and capsular polysaccharide synthesis. It also encodes diverse peptidases, a variety of peptide and amino acid uptake systems, and versatile signal transduction machinery. We propose that the source of amino acids for I. loihiensis growth are the proteinaceous particles present in the deep sea hydrothermal vent waters. I. loihiensis would colonize these particles by using the secreted exopolysaccharide, digest these proteins, and metabolize the resulting peptides and amino acids. In summary, the I. loihiensis genome reveals an integrated mechanism of metabolic adaptation to the constantly changing deep-sea hydrothermal ecosystem.


Physical function and associations with diet and exercise: Results of a cross-sectional survey among elders with breast or prostate cancer.
BACKGROUND: Functional decline threatens independent living and is common among individuals diagnosed with cancer, especially those who are elderly. The purpose of this study was to explore whether dietary and exercise practices are associated with physical function status among older cancer survivors. METHODS: Mailed surveys were used to ascertain data on physical function, dietary fat, fruit and vegetable (F&V) consumption, and exercise among elderly diagnosed with early stage (I-II) breast (N = 286) or prostate cancer (N = 402) within the past 18 months. RESULTS: Sixty-one percent of respondents reported diets with <30% of energy from fat, 20.4% reported F&V intakes of 5+ daily servings, and 44.6% reported regular vigorous exercise. Significant, independent associations were found between physical functioning and reported dietary fat intake, F&V consumption, and exercise. A simultaneous multiple regression model controlled for age, race, gender, time since diagnosis and concurrent health behaviors yielded the following estimates: (1) 0.2 increase in the SF-36 physical function subscale (PFS) score with each reported 1% decrease in percent energy from fat (p < .0001); (2) 0.9 increase in the SF-36 PFS score for each reported serving of F&V/day (p = .0049); and (3) 15.4 increase in the SF-36 PFS score with a positive response for regular vigorous exercise (p < .0001). CONCLUSIONS: Results of this cross-sectional survey suggest that regular vigorous exercise and consumption of diets low in fat and rich in F&Vs are associated with higher levels of physical functioning among older cancer survivors. Interventions that promote healthful lifestyle change may deliver considerable benefit within this ever increasing and vulnerable population.


Children with encopresis: a study of treatment outcome.
A pediatric treatment program for encopresis was established in a large medical center. This consisted of counseling and education, initial bowel catharsis, a supportive maintenance program to potentiate optimum evacuation, retraining, and careful monitoring and follow-up. A group of 127 children received care for this problem. At the end of one year, outcome data were obtained on 110 patients. Of these, 51% had not had "accidents" for more than six months. Another 27% showed marked improvement and were having only rare episodes of incontinence. 14% of these children showed some improvement, but continued to have incontinence, while 8% showed no improvement whatsoever during the treatment year. These four outcome groups were compared with respect to a large number of demographic, developmental, psychosocial, and clinical variables.


Complement Receptor 2 Based Immunoassay Measuring Activation of the Complement System at C3-Level in Plasma Samples From Mice and Humans.
We aimed at establishing a sensitive and robust assay for estimation of systemic complement activation at complement component C3 level in mouse and human plasma samples. In order to capture the activation products iC3b and C3dg in a specific and physiological relevant manner we utilized a construct consisting of the iC3b/C3dg-binding site of human complement receptor 2 (CR2) attached to an Fc-part of mouse IgG. This construct binds C3dg and iC3b from both mice and humans. We purified the CR2-IgG construct from mouse B myeloma cell line supernatants, J558L-CR2-IgG, by protein G affinity chromatography. The CR2-IgG construct was used for capturing C3 fragments in microtiter wells and an anti-mouse or an anti-human-C3 antibody was used for detection of bound C3 fragments. Initially we tested the specificity of the assays with the use of purified C3 fragments. Further, with the use of the CR2-based assay, we measured an up to three-fold higher signal in activated mouse serum as compared to non-activated mouse serum, whereas activated serum from a C3 knock-out mouse gave no signal. We tested in vivo generated samples from a mouse experiment; complement activation was induced by injecting cobra venom factor or heat aggregated IgG into C57bl6 mice, followed by withdrawal of EDTA blood samples at different time points and measurement of iC3b/C3dg. We observed a clear time-dependent distinction in signals between samples with expected high and low complement activation. Furthermore, with the use of the assay for human C3 fragments, we observed that patients with systemic lupus erythematosus (SLE) (n = 144) had significantly higher iC3b/C3dg levels as compared to healthy individuals (n = 144) (p < 0.0001). We present two functional immunoassays, that are able to measure systemic levels of the C3-activation products iC3b and C3dg in mice and humans. To our knowledge, these are the first assays for complement activation that use a physiological relevant capture construct such as CR2. These assays will be a relevant tool when investigating mouse models and human diseases involving the complement system.


RORα suppresses breast tumor invasion by inducing SEMA3F expression.
Inactivation of tumor suppressors and inhibitory microenvironmental factors is necessary for breast cancer invasion; therefore, identifying those suppressors and factors is crucial not only to advancing our knowledge of breast cancer, but also to discovering potential therapeutic targets. By analyzing gene expression profiles of polarized and disorganized human mammary epithelial cells in a physiologically relevant three-dimensional (3D) culture system, we identified retinoid orphan nuclear receptor alpha (RORα) as a transcription regulator of semaphorin 3F (SEMA3F), a suppressive microenvironmental factor. We showed that expression of RORα was downregulated in human breast cancer tissue and cell lines, and that reduced mRNA levels of RORα and SEMA3F correlated with poor prognosis. Restoring RORα expression reprogrammed breast cancer cells to form noninvasiveness structures in 3D culture and inhibited tumor growth in nude mice, accompanied by enhanced SEMA3F expression. Inactivation of RORα in nonmalignant human mammary epithelial cells inhibited SEMA3F transcription and impaired polarized acinar morphogenesis. Using chromatin immunoprecipitation and luciferase reporter assays, we showed that transcription of SEMA3F is directly regulated by RORα. Knockdown of SEMA3F in RORα-expressing cancer cells rescued the aggressive 3D phenotypes and tumor invasion. These findings indicate that RORα is a potential tumor suppressor and inhibits tumor invasion by inducing suppressive cell microenvironment.


The galactolipase activity of Fusarium solani (phospho)lipase.
The purified (phospho)lipase of Fusarium solani (FSL), was known to be active on both triglycerides and phospholipids. This study aimed at assessing the potential of this enzyme in hydrolyzing galactolipids. FSL was found to hydrolyze at high rates of synthetic medium chains monogalactosyldiacylglycerol (4658±146U/mg on DiC8-MGDG) and digalactosyldiacylglycerol (3785±83U/mg on DiC8-DGDG) and natural long chain monogalactosyldiacylglycerol extracted from leek leaves (991±85U/mg). It is the microbial enzyme with the highest activity on galactolipids identified so far with a level of activity comparable to that of pancreatic lipase-related protein 2. FSL maximum activity on galactolipids was measured at pH8. The analysis of the hydrolysis product of natural MGDG from leek showed that FSL hydrolyzes preferentially the ester bond at the sn-1 position of galactolipids. To investigate the structure-activity relationships of FSL, a 3D model of this enzyme was built. In silico docking of medium chains MGDG and DGDG and phospholipid in the active site of FSL reveals structural solutions which are in concordance with in vitro tests.


Desulfurization Activated Phosphorothioate DNAzyme for the Detection of Thallium.
Thallium (Tl) is a highly toxic heavy metal situated between mercury and lead in the periodic table. While its neighbors have been thoroughly studied for DNA-based sensing, little is known about thallium detection. In this work, in vitro selection of RNA-cleaving DNAzymes is carried out using Tl(3+) as the target metal cofactor. Both normal DNA and phosphorothioate (PS)-modified DNA are tested for this purpose. While no Tl(3+)-dependent DNAzymes are obtained, a DNA oligonucleotide containing a single PS-modified RNA nucleotide is found to cleave by ∼7% by Tl(3+) at the RNA position. The remaining 93% are desulfurized. By hybridization of this PS-modified oligonucleotide with the Tm7 DNAzyme, the cleavage yield increases to ∼40% in the presence of Tl(3+) and Er(3+). Tm7 is an Er(3+)-dependent RNA-cleaving DNAzyme. It cleaves only the normal substrate but is completely inactive using the PS-modified substrate. Tl(3+) desulfurizes the PS substrate to the normal substrate to be cleaved by Tm7 and Er(3+). This system is engineered into a catalytic beacon for Tl(3+) with a detection limit of 1.5 nM, which is below its maximal contamination limit defined by the U.S. Environmental Protection Agency (10 nM).


Occupational electromagnetic field exposures associated with sleep quality: a cross-sectional study.
Exposure to electromagnetic field (EMF) emitted by mobile phone and other machineries concerns half the world's population and raises the problem of their impact on human health. The present study aims to explore the effects of electromagnetic field exposures on sleep quality and sleep duration among workers from electric power plant. A cross-sectional study was conducted in an electric power plant of Zhejiang Province, China. A total of 854 participants were included in the final analysis. The detailed information of participants was obtained by trained investigators using a structured questionnaire, which including socio-demographic characteristics, lifestyle variables, sleep variables and electromagnetic exposures. Physical examination and venous blood collection were also carried out for every study subject. After grouping daily occupational electromagnetic exposure into three categories, subjects with long daily exposure time had a significantly higher risk of poor sleep quality in comparison to those with short daily exposure time. The adjusted odds ratios were 1.68 (95%CI: 1.18, 2.39) and 1.57 (95%CI: 1.10, 2.24) across tertiles. Additionally, among the subjects with long-term occupational exposure, the longer daily occupational exposure time apparently increased the risk of poor sleep quality (OR (95%CI): 2.12 (1.23∼3.66) in the second tertile; 1.83 (1.07∼3.15) in the third tertile). There was no significant association of long-term occupational exposure duration, monthly electric fee or years of mobile-phone use with sleep quality or sleep duration. The findings showed that daily occupational EMF exposure was positively associated with poor sleep quality. It implies EMF exposure may damage human sleep quality rather than sleep duration.


Flavone deglycosylation increases their anti-inflammatory activity and absorption.
Flavones have reported anti-inflammatory activities, but the ability of flavone-rich foods to reduce inflammation is unclear. Here, we report the effect of flavone glycosylation in the regulation of inflammatory mediators in vitro and the absorption of dietary flavones in vivo. The anti-inflammatory activities of celery extracts, some rich in flavone aglycones and others rich in flavone glycosides, were tested on the inflammatory mediators tumor necrosis factor α (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lipopolysaccharide-stimulated macrophages. Pure flavone aglycones and aglycone-rich extracts effectively reduced TNF-α production and inhibited the transcriptional activity of NF-κB, while glycoside-rich extracts showed no significant effects. Deglycosylation of flavones increased cellular uptake and cytoplasmic localization as shown by high-performance liquid chromatography (HPLC) and microscopy using the flavonoid fluorescent dye diphenylboric acid 2-aminoethyl ester (DPBA). Celery diets with different glycoside or aglycone contents were formulated and absorption was evaluated in mice fed with 5 or 10% celery diets. Relative absorption in vivo was significantly higher in mice fed with aglycone-rich diets as determined by HPLC-MS/MS (where MS/MS is tandem mass spectrometry). These results demonstrate that deglycosylation increases absorption of dietary flavones in vivo and modulates inflammation by reducing TNF-α and NF-κB, suggesting the potential use of functional foods rich in flavones for the treatment and prevention of inflammatory diseases.


Using needs assessment surveys to understand priorities for pregnant and parenting community college students: Comparing US and foreign-born parents.
To better understand differing needs of US and foreign-born pregnant and/or parenting community college students. We conducted online survey with 608 students living in a rural Midwestern state who were pregnant and/or parenting, 15% of whom were born outside of the United States. We used chi-square tests to determine differences between US and foreign-born students. Results of our survey highlighted several areas in the following categories which are clear needs for this group of students: personal/mental health, child's health, basic needs (ie food insecurity), academic/professional development, and parenting supports. In many cases, foreign-born students reported significantly higher need than their US counterparts. Parenting and foreign-born students attend community colleges at higher rates than other four-year institutions and therefore these colleges need to understand how to best serve these populations. Conducting a needs assessment survey is an efficient way to collect information that allows administrators to tailor services that will help students succeed.


Advances in countercurrent chromatography for protein separations.
Countercurrent chromatography (CCC) is a preparative purification technique working with biphasic liquid systems. One phase of the liquid system is selected to be the mobile phase, the other phase is the stationary phase, held still by centrifugal fields. Aqueous two-phase systems (ATPS) have demonstrated their use in biological purifications. This article reviews protein separations done by CCC using ATPS. The two types of CCC 'columns'--hydrostatic and hydrodynamic instruments--are presented. All commercially available CCC equipments are listed. The hydrostatic CCC columns have an interesting potential to purify proteins working with ATPS aqueous liquid phases. The ATPS properties are briefly summarized, giving the polyethylene glycol 1000/dipotassium phosphate/water ternary mass phase diagram, along with the full chemical compositions of the two aqueous phases of important mixtures of this ATPS. Most published protein purifications were performed in academic laboratories. The highest throughput listed is 1.65 g/h of pure lyzozyme, obtained using a 5.5 l hydrostatic CCC column.


A Methodology for Remote Microwave Sterilization Applicable to the Coronavirus and Other Pathogens Using Retrodirective Antenna Arrays.
This paper describes an innovative remote surface sterilization approach applicable to the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The process is based on the application of a liquid film on the surface or object under sterilization (OUS). A beacon signal is used to self-steer the transmitted power from the designed retrodirective antenna array (RDA) towards the OUS using circularly polarized fields; then, the sterilization is completed by raising and maintaining the required temperature for a certain time. Results suggest that the process takes 5 minutes or less for an angular coverage range over 60 degrees whilst abiding by the relevant safety protocols. This paper also models the power incident onto the OUS, providing consistent results with full-wave simulations. A practical RDA system is developed using a 2 × 1 microstrip patch array operating at 2.5 GHz and tested through the positioning of a representative target surface. Measurements, developed by sampling the power transmitted by the heterodyne RDA, are reported for various distances and angles, operating in the near-field of the system. To further validate the methodology, an additional experiment investigating virus deactivation through microwave heating was also developed. Measurements have been performed with an open cavity microwave oven on the Coronavirus (strain 229E) and egg white protein in a cuvette. This demonstrates that the temperature increases of aqueous films up to 70 [Formula: see text]C by remote microwave-induced heat can denature proteins and deactivate viruses. Possible applications of the method include sterilization of ambulances, medical equipment, and internet of things (IoT) devices.


Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver.
Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology.


National Childhood Encephalopathy Study: an interim report.
Data from the first year of the National Childhood Encephalopathy Study were reviewed to see whether any relation was apparent between pertussis vaccination and brain disease. Three hundred and eighty-seven cases of encephalitis and other specified neurological conditions in which the children were admitted to hospital were reported, of which 267 satisfied the study criteria. Control children were matched for age with the index cases, and medical and immunisation histories were reviewed. Few of the index cases had been vaccinated within 28 days before admission to hospital, so that no close association between vaccination and brain disease existed in most cases. The number of children who had recently been immunised was too small for any statistically useful conclusion to be reached about the risk associated with pertussis vaccine. The study is continuing.


The Predictive Value of the Load Sharing Classification Concerning Sagittal Collapse and Posterior Instrumentation Failure: A Systematic Literature Review.
Systematic review. In 1994, the Load Sharing Classification (LSC) was introduced to aid the choice of surgical treatment of thoracolumbar spine fractures. Since that time this classification system has been commonly used in the field of spine surgery. However, current literature varies regarding its use and predictive value in relation to implant failure and sagittal collapse. The objective of this study is to assess the predictive value of the LSC concerning the need for anterior stabilization to prevent sagittal collapse and posterior instrumentation failure. An electronic search of PubMed, Medline, Embase, and the Cochrane Library was performed. Inclusion criteria were (1) cohort or clinical trial (2) including patients with thoracolumbar burst fractures (3) whose severity of the fractured vertebrae was assessed by the LSC. Five thousand eighty-two articles have been identified, of which 21 articles were included for this review. Twelve studies reported no correlation between the LSC and sagittal collapse or instrumentation failure in patients treated with short-segment posterior instrumentation (SSPI). Seven articles found no significant relation; 5 articles found no instrumentation failure at all. The remaining 9 articles experienced failure in patients with a high LSC or recommended a different surgical technique. Although the LSC was originally developed to predict the need for anterior stabilization in addition to SSPI, many studies show that SSPI only can be sufficient in treating thoracolumbar fractures regardless of the LSC. The LSC might have lost its value in predicting sagittal collapse and posterior instrumentation failure.


Structural characterization of crystalline ternary inclusion compounds at the air-water interface.
Crystalline ternary inclusion monolayers consisting of a two-dimensional hydrogen-bonded host network of guanidinium (G) ions and organosulfonate (S) amphiphiles, and biphenylalkane guests, can be generated at the air-water interface through synergistic structural enforcement by hydrogen bonding and host-guest packing. Surface pressure-area isotherms of the 4'-hexadecylbiphenyl-4-sulfonate (C16BPS) amphiphile in the presence of G, with or without guest, are characterized by lift-off molecular areas expected for the GS sheet based on single-crystal X-ray structures of homologous bulk crystals. Intercalation of biphenylalkane guests (4-C(n)()H(2)(n)()(+1)-C(6)H(4)-C(6)H(5), n = 1, 4, 6, 10, 16; denoted CnBP) between organosulfonate hydrophobes, which define pocketlike cavities in the GS monolayer host, afford ternary inclusion monolayers with a 1:1 host-guest stoichiometry. These inclusion monolayers are less compressible than the guest-free host, consistent with dense packing of the biphenylalkane moieties of the host and the biphenylalkane guests. The inclusion monolayers are distinguished from the amorphous guest-free host and from selected guanidinium-free mixed monolayers by structural characterization with grazing-angle incidence X-ray diffraction (GIXD). The GIXD data for the ternary (G)C16BPS:C16BP and (G)C16BPS:C6BP inclusion monolayers obtained upon compression are consistent with a rectangular unit cell. The dimensions of these unit cells and refinement of the GIXD data suggest a "rotated shifted ribbon" GS hydrogen-bonding motif similar to that observed in some bulk GS crystals, including (G)(ethylbiphenylsulfonate). GIXD reveals that (G)C16BPS:C16BP and (G)C16BPS:C6BP are more crystalline than the corresponding guanidinium-free mixed monolayers. The (G)C16BPS:C6BP inclusion monolayer is stable upon compression, even though the alkyl-alkyl host-guest interactions are reduced due to the shorter hexyl substituents of the guest, demonstrating an important reinforcing role for the hydrogen-bonded GS sheet. The structure of a C16BPS:tetracosane (C24) mixed monolayer is independent of G; the unit cell symmetry and dimensions suggest a structure governed by alkyl-alkane interactions that prohibit formation of a GS network. These results illustrate that the existence of ternary inclusion monolayers with an intact GS network requires guest molecules that are structurally homologous with the hydrophobes of the host, in this case biphenylalkanes. The observation of these inclusion compounds suggests an approach for introducing functional nonamphiphilic molecules to an air-water interface through inclusion in a well-defined host.


[Activity of the complement system in blood serum of dogs after treatment of acute necrotic pancreatitis with boiled pancreatic juice].
The investigations were conducted on 14 dogs. To assess the blood serum complement system, the erythrocyte lytic rate of a rabbit (RE) and a sheep (SE), the hemolytic capacity of the complement system against rabbit (RH) and sheep (SH) was measured. In acute necrotic pancreatitis, no changes in SE and SH were revealed either in the control and experimental animals. RH was decreased both in the control and experimental animals. Lower RE was found only in the controls untreated with boiled pancreatic juice. It can be suggested that in the controls the decrease in the parameter RE that characterized the activity of the complement system is associated with the emergence of complement inhibitors, which did not take place when the boiled juice was given. Preventing the complement inhibitors from forming, pancreatic juice is likely to be able to diminish the body's endogenous intoxication which is a cause of death in acute necrotic pancreatitis. This may be suggested by the higher survival of the animals and lower relative extent of pancreatic acinar tissue necrosis after boiled pancreatic juice treatment of acute necrotic pancreatitis.


Functional Characterization of the M36 Metalloprotease FgFly1 in Fusarium graminearum.
Fungalysin metallopeptidase (M36), a hydrolase, catalyzes the hydrolysis of alanine, glycine, etc. Normally, it is considered to play an important role in the progress of fungal infection. However, the function of fungalysin metallopeptidase (M36) in Fusarium graminearum has not been reported. In this study, we explored the biological functions of FgFly1, a fungalysin metallopeptidase (M36) of F. graminearum. We found that ΔFgFly1 did not affect the ability to produce DON toxin, although it inhibited spore germination during asexual reproduction and reduction in pathogenicity compared with PH-1. Therefore, we speculated that FgFly1 affects the pathogenicity of F.graminearum by affecting pathways related to wheat disease resistance. Target protein TaCAMTA (calmodulin-binding transcription activator) was selected by a yeast two-hybrid (Y2H) system. Then, the interaction between FgFly1 and TaCAMTA was verified by bimolecular fluorescent complimentary (BiFC) and luciferase complementation assay (LCA). Furthermore, compared with wild-type Arabidopsis thaliana, the morbidity level of ΔAtCAMTA was increased after infection with F.graminearum, and the expression level of NPR1 was significantly reduced. Based on the above results, we concluded that FgFly1 regulated F. graminearum pathogenicity by interacting with host cell CAMTA protein.


A microsatellite-based genetic linkage map of the waterflea, Daphnia pulex: On the prospect of crustacean genomics.
We describe the first genetic linkage map for Daphnia pulex using 185 microsatellite markers, including 115 new markers reported in this study. Our approach was to study the segregation of polymorphisms in 129 F2 progeny of one F1 hybrid obtained by crossing two genetically divergent lineages of Daphnia isolated from two Oregon populations. The map spanned 1206 Kosambi cM and had an average intermarker distance of 7 cM. Linkage groups ranged in size from 7 to 185 cM and contained 4 to 27 markers. The map revealed 12 linkage groups corresponding to the expected number of chromosomes and covers approximately 87% of the genome. Tests for random segregation of alleles at individual loci revealed that 21% of the markers showed significant transmission ratio distortion (primarily homozygote deficiency) likely due to markers being linked to deleterious recessive alleles. This map will become the anchor for the physical map of the Daphnia genome and will serve as a starting point for mapping single and quantitative trait loci affecting ecologically important phenotypes. By mapping 342 tentative orthologous gene pairs (Daphnia/Drosophila) into the Daphnia linkage map, we facilitate future comparative projects.


Mechanistically probing lipid-siRNA nanoparticle-associated toxicities identifies Jak inhibitors effective in mitigating multifaceted toxic responses.
A major hurdle for harnessing small interfering RNA (siRNA) for therapeutic application is an effective and safe delivery of siRNA to target tissues and cells via systemic administration. While lipid nanoparticles (LNPs) composed of a cationic lipid, poly-(ethylene glycol) lipid and cholesterol, are effective in delivering siRNA to hepatocytes via systemic administration, they may induce multi-faceted toxicities in a dose-dependent manner, independently of target silencing. To understand the underlying mechanism of toxicities, pharmacological probes including anti-inflammation drugs and specific inhibitors blocking different pathways of innate immunity were evaluated for their abilities to mitigate LNP-siRNA-induced toxicities in rodents. Three categories of rescue effects were observed: (i) pretreatment with a Janus kinase (Jak) inhibitor or dexamethasone abrogated LNP-siRNA-mediated lethality and toxicities including cytokine induction, organ impairments, thrombocytopenia and coagulopathy without affecting siRNA-mediated gene silencing; (ii) inhibitors of PI3K, mammalian target of rapamycin (mTOR), p38 and IκB kinase (IKK)1/2 exhibited a partial alleviative effect; (iii) FK506 and etoricoxib displayed no protection. Furthermore, knockout of Jak3, tumor necrosis factor receptors (Tnfr)p55/p75, interleukin 6 (IL-6) or interferon (IFN)-γ alone was insufficient to alleviate LNP-siRNA-associated toxicities in mice. These indicate that activation of innate immune response is a primary trigger of systemic toxicities and that multiple innate immune pathways and cytokines can mediate toxic responses. Jak inhibitors are effective in mitigating LNP-siRNA-induced toxicities.


Diversity and Bioactive Potential of Actinobacteria from Unexplored Regions of Western Ghats, India.
The search for novel bioactive metabolites continues to be of much importance around the world for pharmaceutical, agricultural, and industrial applications. Actinobacteria constitute one of the extremely interesting groups of microorganisms widely used as important biological contributors for a wide range of novel secondary metabolites. This study focused on the assessment of antimicrobial and antioxidant activity of crude extracts of actinobacterial strains. Western Ghats of India represents unique regions of biologically diverse areas called "hot spots". A total of 32 isolates were obtained from soil samples of different forest locations of Bisle Ghat and Virjapet situated in Western Ghats of Karnataka, India. The isolates were identified as species of Streptomyces, Nocardiopsis, and Nocardioides by cultural, morphological, and molecular studies. Based on preliminary screening, seven isolates were chosen for metabolites extraction and to determine antimicrobial activity qualitatively (disc diffusion method) and quantitatively (micro dilution method) and scavenging activity against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS(2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. Crude extracts of all seven isolates exhibited fairly strong antibacterial activity towards MRSA strains (MRSA ATCC 33591, MRSA ATCC NR-46071, and MRSA ATCC 46171) with MIC varying from 15.62 to 125 μg/mL, whereas showed less inhibition potential towards Gram-negative bacteria Salmonella typhi (ATCC 25241) and Escherichia coli (ATCC 11775) with MIC of 125-500 μg/mL. The isolates namely S1A, SS5, SCA35, and SCA 11 inhibited Fusarium moniliforme (MTCC 6576) to a maximum extent with MIC ranging from 62.5 to 250 μg/mL. Crude extract of SCA 11 and SCA 13 exhibited potent scavenging activities against DPPH and ABTS radicals. The results from this study suggest that actinobacterial strains of Western Ghats are an excellent source of natural antimicrobial and antioxidant compounds. Further research investigations on purification, recovery, and structural characterization of the active compounds are to be carried out.


Factors affecting disclosure of HIV-positive serostatus among people living with HIV/AIDS attending an antiretroviral therapy center of Eastern India.
HIV serostatus disclosure plays an important role in reducing the risk of HIV transmission. However, its negative effects may include rejection, assault, separation, divorce, stigma, and discrimination. This study was undertaken to find out the proportion of HIV-positive serostatus disclosure to any family member and different factors influencing disclosure among people living with HIV/AIDS (PLWHA). A cross-sectional study was conducted among all patients aged 18-49 years with confirmed HIV infection registered at the antiretroviral therapy center of a tertiary care hospital in eastern part of Uttar Pradesh, India, for the duration of 1 year, from July 2017 to June 2018. Most of the respondents were aged 30-49 years (79.9%), male (63.2%), married (85.4%), rural residents (60.4%), Hindu (96.5%), literate (84%), employed/driver (61.8%), and belonged to lower/lower middle class (62.6%). The rate of disclosure of HIV-positive status to any family member was quite high in this study (238/288 or 82.6%), among which 92.9% (221/238) to the spouse only. The number of sexual partners before disclosure, educational status, and socioeconomic status of the respondents were found to be independent predictors of disclosure of HIV-positive status to any family member (P < 0.05). This study indicates the need of giving more emphasis on creating awareness regarding the importance of HIV serostatus disclosure to any family member, especially to spouse, and encourage all PLWHA in the community to disclose their status. Effective strategies also need to be evolved that will target those not likely to disclose their status to anybody.


Coated pellets with delayed-release glucose for prevention of hypoglycemic episodes.
Patients tend to prevent hypoglycemia by excessive saccharide intake leading to poorer glycemic control with potentially fatal consequences. This problem could be resolved by means of pellets with glucose release delayed by 120-360 min as a compensation of the antidiabetic drug peak effect. No glucose is released before; hence there is no risk of hyperglycemia and secondary complications. The pellets contain glucose in combination with an osmotically active ingredient and are coated with an ethylcellulose dispersion, which forms an insoluble semipermeable membrane and ensures delayed release. The release of glucose was assessed using dissolution and high-performance liquid chromatography. Dissolution profiles indicated the possibility of achieving the requested lag time using a combination of adequate compositions and coating concentrations. Lag times of 60, 240 and 360 min were achieved. The sample containing carboxymethyl starch was found to be most suitable for the intent of this work.


A Domain-Oblivious Approach for Learning Concise Representations of Filtered Topological Spaces for Clustering.
Persistence diagrams have been widely used to quantify the underlying features of filtered topological spaces in data visualization. In many applications, computing distances between diagrams is essential; however, computing these distances has been challenging due to the computational cost. In this paper, we propose a persistence diagram hashing framework that learns a binary code representation of persistence diagrams, which allows for fast computation of distances. This framework is built upon a generative adversarial network (GAN) with a diagram distance loss function to steer the learning process. Instead of using standard representations, we hash diagrams into binary codes, which have natural advantages in large-scale tasks. The training of this model is domain-oblivious in that it can be computed purely from synthetic, randomly created diagrams. As a consequence, our proposed method is directly applicable to various datasets without the need for retraining the model. These binary codes, when compared using fast Hamming distance, better maintain topological similarity properties between datasets than other vectorized representations. To evaluate this method, we apply our framework to the problem of diagram clustering and we compare the quality and performance of our approach to the state-of-the-art. In addition, we show the scalability of our approach on a dataset with 10k persistence diagrams, which is not possible with current techniques. Moreover, our experimental results demonstrate that our method is significantly faster with the potential of less memory usage, while retaining comparable or better quality comparisons.


Relationship between HBV cccDNA expression in the human ovary and vertical transmission of HBV.
This study aimed to investigate the relationship between hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the ovary and vertical transmission of HBV. HBV DNA and HBV cccDNA were assayed in the ovaries of 33 pregnant women who were positive for HBV DNA. The HBVM (HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) level and the HBV DNA content in peripheral blood of infants were measured. The overall positive rate of HBV DNA and HBV cccDNA in samples was 51·52% (17/33). The intrauterine infection rate of the infants was 12·12% (4/33). When HBV DNA and HBV cccDNA were both positive, the intrauterine infection rate of infants was significantly higher than when they were both negative (P<0·05). Levels of HBV cccDNA and the rate of positive samples were significantly higher in mothers with infants with intrauterine infection than in those without (P<0·01 and P<0·05, respectively). HBV can infect the human ovary and may transmit to the filial generation via the ovum.


Genetic addiction: selfish gene's strategy for symbiosis in the genome.
The evolution and maintenance of the phenomenon of postsegregational host killing or genetic addiction are paradoxical. In this phenomenon, a gene complex, once established in a genome, programs death of a host cell that has eliminated it. The intact form of the gene complex would survive in other members of the host population. It is controversial as to why these genetic elements are maintained, due to the lethal effects of host killing, or perhaps some other properties are beneficial to the host. We analyzed their population dynamics by analytical methods and computer simulations. Genetic addiction turned out to be advantageous to the gene complex in the presence of a competitor genetic element. The advantage is, however, limited in a population without spatial structure, such as that in a well-mixed liquid culture. In contrast, in a structured habitat, such as the surface of a solid medium, the addiction gene complex can increase in frequency, irrespective of its initial density. Our demonstration that genomes can evolve through acquisition of addiction genes has implications for the general question of how a genome can evolve as a community of potentially selfish genes.


An evaluation of digital, split-site and traditional formats in conference poster sessions.
The paper reports an evaluation of digital, split-site and traditional poster presentations at the Association for Medical Education in Europe (AMEE) conference in September 2004. The programme included 300 posters in 19 sessions, viewed, potentially, by 1265 conference participants, in parallel with other events. The instrument was a questionnaire of 16 open- and closed-format questions applied opportunistically and gaining 250 complete responses. Qualitative and quantitative analysis suggested that no one format was preferred. Each had different strengths and weaknesses relating to seeing and hearing the presenter and viewing the poster. Opportunities for discussion were highly valued.


Minimally Invasive Tendon Release for Symptomatic Accessory Soleus Muscle in an Athlete: A Case Report.
The accessory soleus muscle can pose a diagnostic dilemma for exertional ankle pain, especially in athletes. Once diagnosed, the current treatment options require an extensile approach and can be associated with substantial risk and a slow recovery. We describe a minimally invasive, safe method that has proved successful in our practice.


Chiari malformation Type I and syrinx in children undergoing magnetic resonance imaging.
Chiari malformation Type I (CM-I) with an associated spinal syrinx is a common pediatric diagnosis. A better understanding of the relative age-related prevalence and MR imaging characteristics of these associated conditions may lead to improved treatment decisions. The authors performed a retrospective review of 14,116 consecutive individuals 18 years of age or younger who had undergone brain or cervical spine MR imaging at the University of Michigan between November 1997 and August 2008. In the patients with CM-I, demographic, clinical, and radiographic information was recorded. Five hundred nine children (3.6%) with CM-I were identified. Among these patients, 23% also had a spinal cord syrinx, and 86% of the syringes were found in the cervical spine. The MR imaging prevalence of CM-I with a syrinx was 1.2% in girls and 0.5% in boys (p < 0.0001). The severity of impaired CSF flow at the foramen magnum was associated with the amount of tonsillar herniation (p < 0.0001) and conformation of the tonsils (p < 0.0001). Patients with CM-I were treated surgically in 35% of cases; these patients exhibited more severe tonsillar herniation (p < 0.0001) and impaired CSF flow (p < 0.0001) as compared with those who did not undergo surgery. On imaging, 32% of all the patients with CM-I were considered symptomatic by the treating physician. Patients were more likely to be considered symptomatic if they were female, had a syrinx, displayed abnormal tonsillar pulsations, or had a greater amount of tonsillar herniation. In this study the authors describe the age-related prevalence and MR imaging characteristics of CM-I and its association with a syrinx and other abnormalities in a large group of children who underwent MR imaging for any indication. Syringes are more common in older children, in girls, and in patients with a greater degree of tonsillar descent and CSF flow impairment.


Osteocyte-viability-based simulations of trabecular bone loss and recovery in disuse and reloading.
Osteocyte apoptosis is known to trigger targeted bone resorption. In the present study, we developed an osteocyte-viability-based trabecular bone remodeling (OVBR) model. This novel remodeling model, combined with recent advanced simulation methods and analysis techniques, such as the element-by-element 3D finite element method and the ITS technique, was used to quantitatively study the dynamic evolution of bone mass and trabecular microstructure in response to various loading and unloading conditions. Different levels of unloading simulated the disuse condition of bed rest or microgravity in space. The amount of bone loss and microstructural deterioration correlated with the magnitude of unloading. The restoration of bone mass upon the reloading condition was achieved by thickening the remaining trabecular architecture, while the lost trabecular plates and rods could not be recovered by reloading. Compared to previous models, the predictions of bone resorption of the OVBR model are more consistent with physiological values reported from previous experiments. Whereas osteocytes suffer a lack of loading during disuse, they may suffer overloading during the reloading phase, which hampers recovery. The OVBR model is promising for quantitative studies of trabecular bone loss and microstructural deterioration of patients or astronauts during long-term bed rest or space flight and thereafter bone recovery.


A polarizing beam splitter using negative refraction of photonic crystals.
Light passing through a photonic crystal can undergo a negative or a positive refraction. The two refraction states can be functions of the contrast index, the incident angle and the slab thickness. By suitably using these properties it is possible to realize very simple and very efficient optical components to route the light. As an example we present a passive device acting as a polarizing beam splitter where TM polarization is refracted in positive direction whereas TE component is negatively refracted.


Connecting the solution chemistry of PbI2 and MAI: a cyclodextrin-based supramolecular approach to the formation of hybrid halide perovskites.
The evolution from solvated precursors to hybrid halide perovskite films dictates most of the photophysical and optoelectronic properties of the final polycrystalline material. Specifically, the complex equilibria and the importantly different solubilities of lead iodide (PbI2) and methylammonium iodide (MAI) induce inhomogeneous crystal growth, often leading to a defect dense film showing non-optimal optoelectronic properties and intrinsic instability. Here, we explore a supramolecular approach based on the use of cyclodextrins (CDs) to modify the underlying solution chemistry. The peculiar phenomenon demonstrated is a tunable complexation between different CDs and MA+ cations concurrent to an out of cage PbI2 intercalation, representing the first report of a connection between the solvation equilibria of the two perovskite precursors. The optimal conditions in terms of CD cavity size and polarity translate to a neat enhancement of PbI2 solubility in the reaction media, leading to an equilibration of the availability of the precursors in solution. The macroscopic result of this is an improved nucleation process, leading to a perovskite material with higher crystallinity, better optical properties and improved moisture resistance. Remarkably, the use of CDs presents a great potential for a wide range of device-related applications, as well as for the development of tailored composite materials.


[The efficacy of antibacterial treatment in chronic gastritis of Helicobacter etiology].
A study of 140 patients with chronic gastritis revealed Helicobacter pylori in the gastric antral mucosa in 100% and in the duodenum in 50%. There is a direct correlation between the presence and amount of Helicobacter pylori in the mucosa, lymphoplasmocytic infiltration, dystrophic changes of epithelium. Ampiox treatment proved beneficial both clinically and morphologically. After treatment Helicobacter pylori was absent in 65.7%, in the remaining cases it reduced by 5-10 times.


Prescribing Patterns of Sodium-Glucose Cotransporter-2 Inhibitors in Patients with CKD: A Cross-Sectional Registry Analysis.
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduce kidney disease progression and mortality in patients with chronic kidney disease (CKD), regardless of diabetes status. However, the prescribing patterns of these novel therapeutics in the CKD population in real-world settings remain largely unknown. This cross-sectional study included adults with stages 3-5 CKD included in the Mass General Brigham (MGB) CKD registry in March 2021. We described the adoption of SGLT-2i therapy and evaluated factors associated with SGLT-2i prescription using multivariable logistic regression models in the CKD population, with and without diabetes. A total of 72,240 patients with CKD met the inclusion criteria, 31,688 (44%) of whom were men and 61,265 (85%) White. A total of 22,653 (31%) patients were in the diabetic cohort, and 49,587 (69%) were in the nondiabetic cohort. SGLT-2i prescription was 6% in the diabetic cohort and 0.3% in the nondiabetic cohort. In multivariable analyses, younger Black men with a history of heart failure, use of cardiovascular medications, and at least one cardiologist visit in the previous year were associated with higher odds of SGLT-2i prescription in both diabetic and nondiabetic cohorts. Among patients with diabetes, advanced CKD stages were associated with lower odds of SGLT-2i prescription, whereas urine dipstick test and at least one subspecialist visit in the previous year were associated with higher odds of SGLT-2i prescription. In the nondiabetic cohort, CKD stage, urine dipstick test, and at least one nephrologist visit in the previous year were not significantly associated with SGLT-2i prescription. In this registry study, prescription of SGLT-2i was low in the CKD population, particularly among patients without diabetes.


A new combined parameter predicts re-treatment for coil-embolized aneurysms: a computational fluid dynamics multivariable analysis study.
Coil embolization is a minimally invasive method used to treat cerebral aneurysms. Although this endovascular treatment has a high success rate, aneurysmal re-treatment due to recanalization remains a major problem of this method. The purpose of this study was to determine a combined parameter that can be useful for predicting aneurysmal re-treatment due to recanalization. Patient-specific geometries were used to retrospectively analyze the blood flow for 26 re-treated and 74 non-retreated aneurysms. Post-operatively aneurysms were evaluated at 12-month follow-up. The hemodynamic differences between the re-treatment and non-retreatment aneurysms were analyzed before and after coil embolization using computation fluid dynamics. Basic fluid characteristics, rates of change, morphological factors of aneurysms and patient-specific clinical information were examined. Multivariable analysis and logistic regression analysis were performed to determine a combined parameter-re-treatment predictor (RP). Among examined hemodynamic, morphological, and clinical parameters, slight reduction of blood flow velocity rate in the aneurysm, slight increase of pressure rate at the aneurysmal neck and neck area, and hypertension were the main factors contributing to re-treatment. Notably, hemodynamic parameters between re-treatment and non-retreatment groups before embolization were similar: however, we observed significant differences between the groups in the post-embolization average velocity and the rate of reduction in this velocity in the aneurysmal dome. The combined parameter, RP, which takes into consideration hemodynamic, morphological, and clinical parameters, accurately predicts aneurysm re-treatment. Calculation of RP before embolization may be able to predict the aneurysms that will require re-treatment.


Childhood sleep duration and associated demographic characteristics in an English cohort.
To provide reference data on sleep duration throughout childhood and explore the demographic characteristics associated with sleep. Population-based prospective longitudinal birth-cohort study. South-West England, children born in 1991-1992 and followed since birth. Eleven thousand five hundred children with repeat measures of sleep from birth based on parent-reported questionnaires. Data on daytime and nighttime sleep duration and timings and night awakenings at 8 timepoints from age 6 months to 11 years. Total sleep duration steadily fell from 13 hours and 12 minutes during infancy to 9 hours and 49 minutes at 11 years of age. Compared with earlier studies, the younger children in this cohort slept for a shorter period. The variation in sleep duration was very wide: from 10 to 17 hours in early infancy, narrowing to 8.5 to 11 hours at 11 years. Half of the children at preschool age woke at least once during the night, but frequent waking (> 3 times) peaked in infancy (10% of all infants) and steadily declined in the preschool-aged years. Despite going to bed at the same time, girls slept consistently longer than boys (by 5-10 minutes). Children from low-income families went to bed later and woke up later, but there was little difference in total sleep duration. Children of younger mothers (< 21 years) slept longer, whereas children of older mothers (> 35 years) slept persistently less. Children in larger families tended to go to bed later, as did the minority group of non-White children in the cohort. Given the wide natural variation of sleep in the childhood population, any recommendations on optimal sleep duration at any age must take into account considerable individual variability.


Fluorescent affibody peptide penetration in glioma margin is superior to full antibody.
Fluorescence imaging has the potential to significantly improve neurosurgical resection of oncologic lesions through improved differentiation between normal and cancerous tissue at the tumor margins. In order to successfully mark glioma tissue a fluorescent tracer must have the ability to penetrate through the blood brain barrier (BBB) and provide delineation in the tumor periphery where heterogeneously intact BBB may exist. In this study it was hypothesized that, due to its smaller size, fluorescently labeled anti-EGFR Affibody protein (∼7 kDa) would provide a more clear delineation of the tumor margin than would fluorescently labeled cetuximab, a full antibody (∼150 kDa) to the epidermal growth factor receptor (EGFR). Cetuximab and anti-EGFR targeted Affibody were conjugated to two different fluorescent dyes (both emitting in the near-infrared) and injected intravenously into 6 athymic mice which were inoculated orthotopically with green fluorescent protein (GFP) expressing human U251 glioma cells. Each mouse was sacrificed at 1-h post injection, at which time brains were removed, snap frozen, sectioned and quantitatively analyzed for fluorescence distribution. Ex vivo analysis showed on average, nearly equal concentrations of cetuximab and Affibody within the tumor (on average Affibody made up 49±6% of injected protein), however, the cetuximab was more confined to the center of the tumor with Affibody showing significantly higher concentrations at the tumor periphery (on average Affibody made up 72±15% of injected protein in the outer 50 um of the tumor). Further ex vivo analysis of detection studies showed that the Affibody provided superior discrimination for differentiation of tumor from surrounding normal brain. The present study indicates that fluorescently labeled anti-EGFR Affibody can provide significantly better delineation of tumor margins than a fluorescently labeled anti-EGFR antibody and shows considerable potential for guiding margin detection during neurosurgery.


Feasibility of tobacco interventions in anesthesiology practices: a pilot study.
Abstinence from smoking can improve postoperative outcomes, and surgery is also an excellent opportunity for smokers to permanently quit. One strategy for perioperative tobacco interventions is that anesthesiologists Ask, Advise, and Refer (AAR) -- Ask their patients about tobacco use, Advise them to abstain, and Refer them to resources such as telephone quit-lines. This pilot project determined the feasibility and acceptability of the AAR strategy in anesthesiology practices. An educational program, including presentations, written materials, and Web-based resources, was developed and disseminated to 14 U.S. anesthesiology practices, representing both academic and private practices, who agreed to implement the AAR strategy as a part of their routine clinical practice. Three months after implementation, a survey was administered to those members of these practices who were instructed in the AAR strategy. There were 97 respondents (75% response rate). Since the pilot project began, 91%, 79%, and 58% of respondents reported that they frequently or almost always asked, advised, and referred their patients who smoke, respectively. The majority of respondents (56%) agreed that they were responsible for helping patients get the help they need to quit smoking. Most (74%) also agreed that they planned to incorporate the AAR strategy into their routine practice. These results suggest that the AAR strategy is potentially feasible and well-accepted in anesthesiology clinical practice. Further work will be needed to define whether these practices and attitudes can be sustained and whether they are ultimately effective in modifying perioperative smoking behavior in surgical patients.


Steady-state pharmacokinetics of plasma tenofovir alafenamide (TAF), tenofovir (TFV) and emtricitabine (FTC), and intracellular TFV-diphosphate and FTC-triphosphate in HIV-1 infected old Japanese patients treated with bictegravir/FTC/TAF.
Emtricitabine (FTC) plus tenofovir alafenamide (TAF) has demonstrated efficacy and safety for pre-exposure prophylaxis (PrEP) to prevent HIV-1 infection. We measured the plasma PK of FTC, tenofovir (TFV), and TAF in a steady-state pharmacokinetic (PK) study of bictegravir/FTC/TAF in HIV-1-infected patients. Furthermore, validated liquid chromatography-tandem mass spectrometry was used to measure intracellular TFV-diphosphate (DP) and FTC-triphosphate (TP), the active metabolites of TFV and FTC, respectively. Plasma and dried blood spot samples were collected from 10 male patients aged ≥ 50 years at various time intervals: 0 (trough), 1, 2, 3, 4, 6, 8, 12, and 24 h after drug administration. The mean ± standard deviation of plasma PK parameters were as follows: The maximum concentrations of TAF, TFV, and FTC were 104.0 ± 72.5, 27.9 ± 5.2, and 3,976.0 ± 683.6 ng/mL, respectively. Additionally, their terminal elimination half-lives were 0.6 ± 0.5, 31.6 ± 10.4, and 6.9 ± 1.4 h, respectively. These results were consistent with previously reported data. The intracellular levels of TFV-DP and FTC-TP varied widely among individuals; however, they remained stable over 24 h in each individual at approximately 1,000-1,500 and 2,000-3,000 fmol/punch, respectively, indicating that plasma concentrations did not affect the intracellular concentrations of their active metabolites. These results demonstrated that measuring intracellular TFV-DP and FTC-TP could be useful for monitoring adherence to PrEP in clients on this regimen.


[A simple method of determination of antigenic determinants in proteins with known primary structure].
A simple and rapid method is proposed for the localization of antigenic determinants in proteins of known primary structure exemplified by human myoglobin. The polypeptide chain of myoglobin was cleaved with BrCN (at Met residues) or with bromosuccinimide (at Trp and Tyr residues) under conditions which on average gave less than one scission per myoglobin molecule. The "single-hit" cleavage products were separated by gel electrophoresis and transferred to nitrocellulose by electroblotting. The peptides containing intact antigenic determinants were vizualized by immuno-peroxidase staining with four monoclonal anti-myoglobin antibodies. Comparison of the lengths of the immuno-reactive peptides with the known positions of methionine, tryptophan and tyrosine residues suggested that the four monoclonal antibodies were bound by myoglobin over the region Trp-14 to Met-55. As compared with other methods of localization, the method proposed is much faster and takes much lesser amount of protein.


Testing the Strain Theory of Suicide - The Moderating Role of Social Support.
Background: According to the strain theory of suicide, strains, resulting from conflicting and competing pressures in an individual's life, are hypothesized to precede suicide. But social support is an important factor that can mitigate strains and lessen their input in suicidal behavior. Aims: This study was designed to assess the moderating role of social support in the relation between strain and suicidality. Methods: A sample of 1,051 employees were recruited in Beijing, the capital of China, through an online survey. Moderation analysis was performed using SPSS PROCESS Macro. Social support was measured with the Multidimensional Scale of Perceived Social Support, and strains were assessed with the Psychological Strains Scale. Results: Psychological strains are a good predictor of suicidality, and social support, a basic need for each human being, moderates and decreases the effects of psychological strains on suicidality. Limitations: The cross-sectional survey limited the extent to which conclusions about causal relationships can be drawn. Furthermore, the results may not be generalized to the whole of China because of its diversity. Conclusion: Social support has a tendency to mitigate the effects of psychological strains on suicidality.