Real-time polymerase chain reaction in the diagnosis of acute postoperative endophthalmitis.
To evaluate the efficacy of quantitative real-time polymerase chain reaction (qPCR) in the diagnosis of postoperative bacterial endophthalmitis among patients who underwent cataract surgery at a tertiary care center. Prospective experimental study. This was a single-center study of 64 eyes of 64 patients presenting with clinical signs and symptoms of endophthalmitis within 1 year of cataract surgery. Patients with glaucoma filtering or cornea surgery in the past year, postoperative trauma, fungal endophthalmitis, or preoperative inflammatory conditions were excluded. Vitreous samples were obtained during vitreous tap or vitrectomy and sent for both culture and qPCR with sequencing. Vitreous samples obtained from 50 patients undergoing vitrectomy for noninflammatory indications served as controls. The main outcome measures were the sensitivity of qPCR compared to culture and concordance of results of pathogen identification with sequencing vs phenotypic speciation. qPCR detected 16s bacterial DNA in 37 patients (66%), compared to 19 (34%) with traditional culture. Only 1 patient had a positive result by culture (Nocardia species) but negative result by qPCR. For the 18 samples positive by both qPCR and culture, there was a 100% concordance in pathogen identification between sequencing and phenotypic speciation. In cases of suspected bacterial endophthalmitis, qPCR offers an improved diagnostic yield and may be a useful adjunct to traditional culture. Further large-scale clinical studies are needed to elucidate the full clinical utility of qPCR.


Investigation of nanoscale failure behaviour of cortical bone under stress by AFM.
The contribution of nanostructures of bone to the macroscale mechanical properties has received much attention, but most of nano-toughening mechanisms have remained in the theoretical stage or at static experimental observation. Our study shows that the medullary surface of the bovine femur provides a smooth natural surface ideal for observing nanostructures in bone. Mechanical loading is applied using an in situ mechanical device and the nanomechanical behaviours of the specimens are in situ recorded and imaged using an atomic force microscope (AFM). By the in situ observation of nanomechanical behaviours under stress, the existing nano-toughening mechanisms, such as fibril slippage and fibril bridging, are confirmed. Before the micro failure stage, mineralized collagen fibrils are strained with the increase of stress, followed by pre-separation (or slippage) due to stress concentration, resulting in cracked nanoscale interfaces. When micro-failure occurs (i.e. crack initiation), the nano-bridging mechanism contributes to resisting the formation of nanometre crack interface, the propagation of crack tip and the failure of crack bridging. Our study provides direct evidence for the connection between bridging-type mechanisms at different scale, which are composed of the corresponding bone structures at each level. Through the in situ observation of the microscopic failure in bone, some visual information are offered on the interaction between nanomechanical behaviours and nanostructures.


A phylotranscriptomic dataset of angiosperm species under cold stress.
Angiosperms are one of the most diverse and abundant plant groups that are widely distributed on Earth, from tropical to temperate and polar zones. The wide distribution of angiosperms may be attributed to the evolution of sophisticated mechanisms of environmental adaptability, including cold tolerance. Since the development of high-throughput sequencing, transcriptome has been widely utilized to gain insights into the molecular mechanisms of plants in response to cold stress. However, previous studies generally focused on single or two species, and comparative transcriptome analyses for multispecies responding to cold stress were limited. In this study, we selected 11 representative angiosperm species, performed phylotranscriptome experiments at four time points before and after cold stress, and presented a profile of cold-induced transcriptome changes in angiosperms. Our multispecies cold-responsive RNA-seq datasets provide valuable references for exploring conserved and evolutionary mechanisms of angiosperms in adaptation to cold stress.


Eye movement control during reading: II. Frequency of refixating a word.
An analysis of over 40,000 eye fixations made by college students during reading indicates that the frequency of immediately refixating a word following an initial eye fixation on it varies with the location of that fixation. The refixation frequency is lowest near the center of the word, positively accelerating with distance from the center. The data are well fit by a parabolic function. Assuming that refixation frequency is related to the frequency of successful word identification, the observed curvilinear relation results naturally from models that postulate a linear decrease in visual information with retinal eccentricity. A single letter difference in fixation location in a word can make a sizeable difference in the likelihood of refixating that word. The effects of word length and cultural frequency on the frequency of refixating are also examined.


Evaluation: methods and strategy for evaluation--Arizona.
In this report, the author describes a relatively new but novel approach for program evaluation currently underway in Arizona. The author notes the crucial importance of local initiatives in tobacco control buoyed by evaluations integrally connected with day-to-day programs and led by local staff.


Standards of neurologic-neurosurgical early rehabilitation--a concept of the study group neurological-neurosurgical early rehabilitation.
Neurological neurosurgical early rehabilitation (NNER) is a new important therapeutic link within the spectrum of neurorehabilitation. This concept was formulated by expert opinion of the German Task Force on NNER to define both the structural and process quality of rehabilitation in patients who sustained brain damage with sensory motor, cognitive, and neurobehavioural impairment. NNER is focused on improving higher nervous functions, preventing or treating secondary and tertiary complications and thus to recuse disabilities. This concept is based on interdisciplinary teamwork and needs multidisciplinary cooperation with all specialists involved. The progress of recovery can be measured with the aid of the Coma Remission Scale.


Sequence data mining in search of hookworm (Necator americanus) microRNAs.
The new world hookworm, Necator americanus is a soil-transmitted nematode responsible for Necatoriasis (a type of helminthiasis) in hosts such as humans, dogs, and cats. N. americanus genome and transcriptome has been sequenced and a draft assembly analysis has been published highlighting protein coding genes and possible drug target proteins. Hookworm microRNA identification, annotations and their public release is yet to be attempted. The same is evident from lack of hookworm miRNA information in related popular public nucleotide sequence repositories such as miRBase, GenBank, WormBase etc. Therefore, in the present study we addressed these issues using EST and assembled transcript sequence information of hookworm. Using computational approaches, we identified three miRNAs precursor sequences and their mature forms. We also identified their potential targets from hookworm ESTs and transcripts, and from human transcriptome. Overall, the results indicate presence of nematode specific miRNA homologs in N. americanus and shades light on their putative targets in worm itself and the human host.


Synthetic hydrogel microspheres as substrata for cell adhesion and growth.
Cross-linked poly(methyl methacrylate) (PMMA) microspheres were subjected to alkaline hydrolysis to obtain hydrophilic microspheres having carboxyl residues distributed throughout the matrix. These microspheres were found to support the growth of human skin fibroblasts and human heart and lung cells. Further, fibroblasts grown on them were found to be comparable with those grown on the commercial tissue culture plate with respect to [14C]amino acid uptake and incorporation into proteins. The hydrolyzed PMMA microspheres may find application as a microcarrier for cell culture.


Levels of the hemoglobin adduct N-(2,3-Dihydroxypropyl)-valine in cord and maternal blood: Prenatal transfer of glycidol in the ENVIRONAGE birth cohort.
Glycidol, a probable human carcinogen, is a reactive chemical released in the gastrointestinal tract from glycidyl fatty acid esters, which are heat-induced dietary contaminants. To investigate the prenatal transfer of glycidol, a specific hemoglobin adduct was measured as a biomarker for internal glycidol exposure in paired cord and maternal blood samples. In 100 mother-newborn pairs from the Belgian ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort, we studied the correlation between levels of the glycidol-derived hemoglobin adduct N-(2,3-dihydroxypropyl)-valine (2,3-diHOPr-Val) in paired cord and maternal blood samples. The adduct levels were determined after cleavage with a modified Edman degradation by using ultra-high performance liquid chromatography-tandem mass spectrometry and an isotope-labeled reference standard. 2,3-DiHOPr-Val was detectable in all 100 maternal blood samples and in 96 cord blood samples (LOD =0.5 pmol 2,3-diHOPr-Val/g hemoglobin), with medians of 5.4 (range: 2.3-29.2) and 1.6 (range: LOD - 8.9) pmol/g hemoglobin), respectively. In blood samples of mothers who smoked during pregnancy and in the cord blood samples of their newborns (n = 6), the median 2,3-diHOPr-Val levels were 16.7 (range: 6.4-29.2) and 6.2 (range: LOD - 8.6) pmol/g hemoglobin, respectively. The median ratio of 2,3-diHOPr-Val levels of cord to maternal blood was 0.35 (range: 0.19-1.14) (n = 49). The Spearman correlation coefficient between 2,3-diHOPr-Val levels in cord and maternal blood samples was 0.63 (p < 0.001) among all mother-newborn pairs and 0.59 (p < 0.001) among mother-newborn pairs of non-smoking mothers. Maternal data confirm widespread exposure to glycidol, also in non-smokers. Neonatal levels indicate prenatal exposure to glycidol, due to an obviously relatively unhindered passive transfer through the placental barrier. Possible health effects of fetal (and postnatal) glycidol exposure in children may be addressed in epidemiological studies.


Road to sexual maturity: Behavioral event schedule from eclosion to first mating in each sex of Drosophila melanogaster.
Animals achieve their first mating through the process of sexual maturation. This study examined the precise and detailed timing of a series of behavioral events, including wing expansion, first feeding, first excretion, and courtship, during sexual maturation from eclosion to first mating in D. melanogaster. We found that the time of first mating is genetically invariant and is not affected by light/dark cycle or food intake after eclosion. We also found sexual dimorphism in locomotor activity after eclosion, with females increasing locomotor activity earlier than males. In addition, we found a time rapidly changing from extremely low to high sexual activity in males post eclosion (named "drastic male courtship arousal" or DMCA). These behavioral traits leading up to the first mating could serve as clear indicators of sexual maturation and establish precisely timed developmental landmarks to explore further the mechanisms underlying the integration of behavioral and physiological sexual maturation.


Event-triggered data-driven control of discrete-time nonlinear systems with unknown disturbance.
This paper is dedicated to event-triggered data-driven control of nonlinear systems with unknown disturbance via model free iterative learning approach. An extended state observer is employed to reconstruct the disturbance in system output. An event-triggered model free iterative learning control strategy is constructed by system input, system output and the reconstructed disturbance. Sufficient conditions are proposed to make the resultant tracking error system be uniform ultimate bounded. Simulation examples are provided to validate the effectiveness of the proposed scheme.


Elevated serum CA 19-9 levels in patients with pulmonary nontuberculous mycobacterial disease.
Increased serum CA 19-9 levels in patients with nonmalignant diseases have been investigated in previous reports. This study evaluates the clinical significance of serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease and pulmonary tuberculosis. The median CA 19-9 level was higher in patients with pulmonary nontuberculous mycobacterial disease than in patients with pulmonary tuberculosis (pulmonary nontuberculous mycobacterial disease: 13.80, tuberculosis: 5.85, p<0.001). A multivariate logistic regression analysis performed in this study showed that Mycobacterium abscessus (OR 9.97, 95% CI: 1.58, 62.80; p=0.014) and active phase of pulmonary nontuberculous mycobacterial disease (OR 12.18, 95% CI: 1.07, 138.36, p=0.044) were found to be risk factors for serum CA 19-9 elevation in pulmonary nontuberculous mycobacterial disease. The serum CA 19-9 levels showed a tendency to decrease during successful treatment of pulmonary nontuberculous mycobacterial disease but not in pulmonary tuberculosis. These findings suggest that CA 19-9 may be a useful marker for monitoring therapeutic responses in pulmonary nontuberculous mycobacterial disease, although it is not pulmonary nontuberculous mycobacterial disease-specific marker.


Chitin-graft-poly(2-methyl-2-oxazoline) enhanced solubility and activity of catalase in organic solvent.
Catalase from bovine liver was lyophilized from an aqueous solution containing chitin-graft-poly(2-methyl-2-oxazoline) (3), which was synthesized by the reaction of 52% deacetylated chitin (1) with living poly(2-methyl-2-oxazoline) (2). The rate of consumption of H2O2 in chloroform catalyzed by the lyophilized catalase with 3 was enhanced more than 10 times that by catalase without 3. The dispersibility and solubility of lyophilized catalase with 3 in chloroform were improved in comparison with catalase itself.


Clinical effectiveness of oral antiviral agents in older patients with COVID-19 based on real-world data.
Several randomized controlled trials and real-world cohort studies have demonstrated the efficacies of nirmatrelvir plus ritonavir (NMV-r) and molnupiravir (MOV) in at-risk patients with COVID-19; however, the effectiveness of antisevere acute respiratory syndrome-coronavirus 2 treatments on older patients (≥65 years) remains unclear. This retrospective cohort study aimed to assess the clinical effectiveness of the oral antiviral agents, MOV and NMV-r, in older patients (≥65 years) infected with severe acute respiratory syndrome-coronavirus 2. Nonhospitalized older patients with COVID-19 between January 1, 2022, and December 31, 2022, were recruited from the TriNetX Research Network. Propensity score matching (PSM) was used to match patients who received either NMV-r or MOV treatment with those who did not receive any oral antiviral agents. Hazard ratios (HRs) for composite all-cause hospitalization or death during the 30-day follow-up period were calculated. PSM revealed two cohorts with 28 824 patients each having balanced baseline characteristics. The antiviral group was associated with significantly lower risk of the primary composite outcome of all-cause hospitalization or death than the control group (241 vs. 801; HR, 0.307; 95% confidence interval (CI), 0.27-0.36) during the follow-up period. For the secondary outcome, the antiviral group had a significantly lower risk of all-cause hospitalization (288 vs. 725; HR, 0.322; 95% CI, 0.28-0.37) and mortality (16 vs. 94; HR, 0.176; 95% CI, 0.10-0.30) than the control group. Moreover, the reduced risk of all-cause hospitalization or death remained consistent in patients receiving NMV-r (HR, 0.279; 95% CI, 0.24-0.33) and MOV (HR, 0.279; 95% CI, 0.21-0.38). Our results revealed that NMV-r and MOV decreased the all-cause hospitalization and death rates among older patients with COVID-19, supporting the use of antivirals in this vulnerable population.


Probability matching and strategy availability.
Findings from two experiments indicate that probability matching in sequential choice arises from an asymmetry in strategy availability: The matching strategy comes readily to mind, whereas a superior alternative strategy, maximizing, does not. First, compared with the minority who spontaneously engage in maximizing, the majority of participants endorse maximizing as superior to matching in a direct comparison when both strategies are described. Second, when the maximizing strategy is brought to their attention, more participants subsequently engage in maximizing. Third, matchers are more likely than maximizers to base decisions in other tasks on their initial intuitions, suggesting that they are more inclined to use a choice strategy that comes to mind quickly. These results indicate that a substantial subset of probability matchers are victims of "underthinking" rather than "overthinking": They fail to engage in sufficient deliberation to generate a superior alternative to the matching strategy that comes so readily to mind.


Clinical, Radiological, and Demographic Details of Benign External Hydrocephalus: A Population-Based Study.
Benign external hydrocephalus has an incidence of about 0.4 per 1000 live births. It affects infants and is characterized by an increasing head circumference and typical neuroimaging findings. Previously published studies on benign external hydrocephalus often contain groups of few and selected patients. This is a follow-up of a recently published article reporting the incidence of benign external hydrocephalus. This retrospective and population-based study covers two large health regions in Norway, over a 10-year period (1994 to 2003). Infants with increasing head circumference, combined with typical radiological findings of enlarged subarachnoid spaces, were included. Information about head circumference development, neuroimaging findings, and birth delivery methods, as well as demographic details, was retrieved from the hospital medical records. A total of 176 children with benign external hydrocephalus were included, 86.4% being boys. At birth, the head circumference was close to normal. Mean age for when the head circumference reached abnormal values, i.e., crossing two percentiles or reaching the 97.5 percentile, was 3.4 months; none was older than seven months. Around four of five children had dilated lateral ventricles in addition to enlarged subarachnoid spaces. The neuroimaging findings tended to normalize after age 12 months. About half of the patients ended up with head circumferences at or above the 97.5 percentile. Most infants with benign external hydrocephalus are born with a normal head circumference that increases too fast and reaches abnormally high values before age six months. This age and gender distribution is very similar to that described for infant subdural hemorrhage.


Human beta and delta globin messenger RNAs turn over at different rates.
We have tested the hypothesis of Winslow & Ingram (1966) that the steady-state levels of human beta and delta globin proteins are determined, in part, by the stabilities of their respective messenger RNAs. Nucleated bone marrow cells were cultured under different RNA "chase" conditions, and samples were harvested at intervals thereafter. The quantities of beta and delta globin mRNA sequences in total RNA from these cells were measured by solution hybridization with specific 32P-labeled DNA probes. The average half-lives of beta and delta globin mRNAs are 16.5 and 4.5 hours, respectively. Both mRNAs are polyadenylated. The rapid turnover of delta globin mRNA accounts, at least in part, for the low level of delta globin mRNA in non-nucleated peripheral blood reticulocytes. The possibility that the rate of mRNA decay is determined by nucleotide sequence signals located in the 3' untranslated region is discussed.


Early follow-up of patients with the Medtronic Intact porcine valve. A new cardiac bioprosthesis.
A new-generation porcine valve fixed in glutaraldehyde at zero pressure and mounted on an acetal copolymer flexible stent was inserted in 97 patients between August 1983 and October 1986. The mean age of the patients was 51 years (range 10 to 76) and eight were under the age of 20 years. There were 57 mitral, 33 aortic, and 10 tricuspid valve replacements. Concomitant coronary artery bypass grafting was performed in 9% of patients, 40% underwent multiple valve operations, and in 40% the procedure was a reoperation. Mean follow-up was 26 months (range 12 to 49) and was 99% complete. There were no examples of primary tissue failure, and only to reoperations have been undertaken for infective endocarditis alone. The early mortality rate was 8.2% and the late mortality rate, 12.1%. Four late deaths were valve related (two caused by infective endocarditis and two by embolism). The actuarial 3-year survival rate was 70%, freedom from infective endocarditis 879%, freedom from embolism 87%, freedom from reoperation 90%, and freedom from valve-related complications 77%. All but three surviving patients were in New York Heart Association class I or II. Doppler echocardiography, performed in 62 of 76 survivors, showed thin and mobile leaflets in all patients and trivial or mild regurgitation in four (6%). The mean gradient across the Medtronic Intact valves (Medtronic Blood Systems Inc., Minneapolis, Minn.) in the aortic position was 17 +/- 5.2 mm Hg, in the mitral position 3.8 +/- 1.33 mm Hg, and in the tricuspid position 4.1 +/- 1.14 mm Hg. We conclude that early results with the Intact valve are encouraging.


Reservoir optimized plunger lift technology reduces hydrocarbon emissions from aging gas wells.
Gas well liquification is a problematic process whereby liquids collect in the wellbore and near wellbore reservoir resulting in production impedance in aging gas wells. Removal of these liquids is traditionally performed through human operated blowdown events; however, this practice results in the release of hydrocarbon emissions into the atmosphere. The removal process, called 'deliquification', can also be accomplished through the utilization of various plunger lift technologies. These allow the extraction of retained fluids from the wellbore and near-wellbore reservoir; however, these technologies vary greatly with respect to automation, intelligence, and efficacy. Here we examined the rates of production loss and the frequency of emission events in mature natural gas wells equipped with various automated plunger lift technologies. Overall, 'intelligent' plunger lift systems that base their optimization on reservoir and wellbore conditions, as opposed to standardized or scheduled operations, performed the best exhibiting a 0.13% loss of production gas to atmospheric emissions compared to a 1.37% loss of production observed from wells without a plunger lift system. Additionally, wells equipped with a next generation reservoir optimized plunger lift demonstrated a reduced rate of production decline compared to those wells without a plunger lift technology (-0.066%/day and -0.242%/day, respectively). These data have widespread implications for the operational and environmental management of a consistently increasing count of aging natural gas production wells.


A General Method for Multimetallic Platinum Alloy Nanowires as Highly Active and Stable Oxygen Reduction Catalysts.
An unconventional class of high-performance Pt alloy multimetallic nanowires (NWs) is produced by a general method. The obtained PtNi NWs exhibit amazingly specific and mass oxygen reduction reaction (ORR) activities with improvement factors of 51.1 and 34.6 over commercial Pt/C catalysts, respectively, and are also stable in ORR conditions, making them among the most efficient electrocatalysts for ORR.


Intranasal vaccination with H5, H7 and H9 hemagglutinins co-localized in a virus-like particle protects ferrets from multiple avian influenza viruses.
Avian influenza H5, H7 and H9 viruses top the World Health Organization's (WHO) list of subtypes with the greatest pandemic potential. Here we describe a recombinant virus-like particle (VLP) that co-localizes hemagglutinin (HA) proteins derived from H5N1, H7N2, and H9N2 viruses as an experimental vaccine against these viruses. A baculovirus vector was configured to co-express the H5, H7, and H9 genes from A/Viet Nam/1203/2004 (H5N1), A/New York/107/2003 (H7N2) and A/Hong Kong/33982/2009 (H9N2) viruses, respectively, as well as neuraminidase (NA) and matrix (M1) genes from A/Puerto Rico/8/1934 (H1N1) virus. Co-expression of these genes in Sf9 cells resulted in production of triple-subtype VLPs containing HA molecules derived from the three influenza viruses. The triple-subtype VLPs exhibited hemagglutination and neuraminidase activities and morphologically resembled influenza virions. Intranasal vaccination of ferrets with the VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with H5N1, H7N2, and H9N2 viruses.


Viscous property and osteogenesis induction of hydroxyapatite thermal decomposition product mixed with gelatin implanted into rabbit femurs.
The viscosity of hydroxyapatite thermal decomposition product mixed with gelatin (HATDP-G) and the osteogenesis induced by this mixture were investigated. To determine the viscosity of HATDP-G, we measured the average diameter of a slumped mass of HATDP-G (0.5 ml) according to the American Dental Association Specification No. 8, with some modifications, and compared it with that of an equal mass of HATDP and of polymethylmethacrylate (PMMA) bone cement. The mean diameter of 10 samples each of HATDP-G, HATDP, and PMMA bone cement was 26.8+/-0.9 mm, 19.6+/-0.2 mm and 29.2+/-0.3 mm, respectively, 2 min after the mixing procedure. HATDP-G was injected into the bone marrow of the right femurs of 25 rabbits. As the control, gelatin with saline solution was injected into the left femurs. New bone formation was observed in all 20 femurs from three weeks after injection. No new bone formation was observed in the control femurs. The affinity index, a parameter of osteogenesis, was 19.8+/-6.1%, 27.5+/-2.6%, 52.9+/-9.5%, and 76.3+/-1.9% at 3, 6, 12 and 24 weeks after the injection, respectively. Significant increases in the affinity index were found between weeks 6 and 12, and weeks 12 and 24 (p < 0.05). Our findings indicated that HATDP-G might be successfully used as a bioactive bone cement.


A case report of three children with secondary hypertension caused by Liddle syndrome.
Liddle syndrome is a monogenetic cause of early-onset hypertension that is associated with hypokalemia and metabolic alkalosis that is inherited in an autosomal dominant fashion with variable penetrance. We present a case report of three children seen at a tertiary children's hospital with varying severity of hypertension and electrolyte disturbances, who had genetic testing performed due to strong family history of hypertension. They were each subsequently found with the same genetic mutation of SCNN1B consistent with Liddle syndrome and started on epithelial sodium channel inhibitors with improvement in their blood pressure. Due to its variable penetrance, Liddle syndrome can have varying severity of blood pressure and electrolyte disturbances. Prompt recognition of Liddle syndrome is important to prevent cardiovascular complications from uncontrolled hypertension.


Collision tumor: a peripheral neuroepithelioma and a transitional-cell carcinoma occurring simultaneously in the renal pelvis.
We report a unique case of a collision tumor of the kidney composed of a peripheral neuroepithelioma (PNE) and a transitional cell carcinoma (TCC) that occurred in a 67-year-old man with a long history of superficial TCC of both the bladder and bilateral upper urinary tracts. The PNE was composed of hyperchromatic, small, round cells, arranged in clusters and poorly cohesive sheets. Immunohistochemical studies revealed the small cells to be strongly positive for O13 (ie, a MIC2 gene product stain [CD99]) and vimentin. Electron microscopic examination found numerous interdigitating cell processes, multiple poorly formed cell-cell junctions, and dense-core granules. The latter were most conspicuous at the tips of the cell precesses. The PNE cells were clearly negative for cytokeratin, and they showed no transitional or intermediate features that would suggest evolution of the PNE from the adjacent TCC. The proximity of these two tumors appears to be serendipitous; thus, it can be considered a true collision tumor of the kidney.


Inhibitors of elastase and cathepsin G in Chédiak-Higashi (beige) neutrophils.
Previous studies have established that mature neutrophils from the peritoneal cavity, blood, and bone marrow of beige (Chédiak-Higashi syndrome) mice essentially lack activities of two lysosomal proteinases: elastase and cathepsin G. There are, however, significant levels of each enzyme in early neutrophil precursors in bone marrow. In the present experiments, it was found that the addition of extracts from mature beige neutrophils to extracts of normal neutrophils or to purified human neutrophil elastase and cathepsin G resulted in a significant inhibition of elastase and cathepsin G G activities. 125I-Labeled human neutrophil elastase formed high molecular mass complexes at 64 and 52 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis when added to beige neutrophil extracts. The molecular masses of the inhibitor-125I-elastase complexes suggested that the molecular masses of the inhibitors are approximately 36 and 24 kDa, respectively. These results were confirmed by gel filtration on Superose 12 under nondenaturing conditions. Cathepsin G was inhibited only by the 36-kDa component. The inhibitors formed a covalent complex with the active sites of elastase and cathepsin G. No inhibitory activity was present in mature neutrophil extracts of genetically normal mice or in extracts of bone marrow of beige mice. These results thus represent an unusual example of an enzyme deficiency state caused by the presence of excess inhibitors. Inactivation of neutrophil elastase and cathepsin G in mature circulating and tissue neutrophils may contribute to the increased susceptibility of Chédiak-Higashi patients to infection.


Analysis of a monofluorinated analogue of amphetamine in brain tissue using gas chromatography with electron-capture detection.
1. Difficulties encountered in the analysis of the monofluorinated amphetamine, 2-amino-3-fluoro-1-phenylpropane (AFP), are discussed. 2. A novel assay procedure and its application to the analysis of AFP in the rat brain are described. The procedure involves pentafluorobenzoylation of AFP under aqueous conditions and quantitation by a gas chromatography equipped with a capillary column and an electron-capture detector.


Pharma APMs: Can the Industry Learn To Play Well With Others?
The alternative payment model (APM) is a nontraditional financial arrangement that rewards health care providers who deliver cost-effective, high-quality care. Now we are facing the possibility that pharmaceutical manufacturers and insurers will embrace APMs as a payment mechanism in some situations.


Transcriptome sequencing and flavonoid metabolism analysis in the leaves of three different cultivars of Acer truncatum.
Young and mature leaves of three Acer truncatum varieties with different leaf colors were examined. Transcriptome sequencing and flavonoid metabolism were used to analyze the differential gene expression associated with different leaf colors and growth stages and the relationships between gene expression and flavonoid and anthocyanin contents to improve ornamental value and develop flavonoid-rich A. truncatum. Kyoto Encyclopedia of Genes and Genomes database annotation of differentially expressed genes indicated that the following genes were related to flavonoid synthesis: phenylpropanoid biosynthesis genes (PAL, C4H, 4CL and CHS), flavonoid biosynthesis genes (E18.104.22.168, CHI, FLS, F3'5'H and ANR), anthocyanin biosynthesis genes (ANS, DFR, HCT, BZ1, GT1, and UGT79B1), isoflavonoid biosynthesis genes (HIDH and CYP81E17), and their transcriptional regulator (MYB). A total of 234 types of flavonoids were detected. The types and contents of anthocyanins in the red-leaf varieties 'Hong Jingling' and 'Caidie Fanfei' were significantly higher than those in the green leaf cultivar 'Lv Baoshi', especially morning glory 3-O-glucoside, delphinidin 3-O-glucoside, and pelargonium-3-O-glucoside, which were not detected in 'Lv Baoshi'. Combined omics analysis showed that downregulated expression of C4H, CHS and F3'5'H and upregulated expression of FLS reduced the supply of raw materials for anthocyanin synthesis, and downstream ANR upregulation converted anthocyanins to procyanidins, increasing the total flavonoid content. F3'5'H expression was downregulated in the leaves of each variety with development, resulting in the accumulation of catechins and the gradual greening of the leaves. F3'5'H was significantly depleted in the young leaves of 'Hong Jingling' and 'Caidie Fanfei' compared with the young leaves of 'Lv Baoshi', while ANS and BZ1 were enriched significantly. It is concluded that F3'5'H, BZ1, and ANS are the key genes needed for breeding red A. truncatum and that ANR is the key gene needed for breeding varieties with a high flavonoids contens. These results may facilitate genetic modification or selection for further improvement of the ornamental qualities and flavonoid content of A. truncatum.


Severe intrauterine adhesions after life-threatening event caused by Epstein-Barr virus-associated atraumatic spleen laceration: Case report.
This is the first known case report of severe intrauterine adhesion (IUA) following a life-threatening event caused by an Epstein-Barr virus-associated atraumatic spleen laceration. A 22-year-old nulligravid female suffered from infectious mononucleosis for approximately 1 month. Sudden severe hypovolemic shock with massive hemoperitoneum appeared and hemostasis was completely achieved by a splenectomy for an atraumatic spleen laceration, although that was followed by multiorgan failure and abdominal compartment syndrome. Complete recovery without any neurological sequelae was achieved by intensive treatment. A postoperative pathological evaluation revealed Epstein-Barr virus-associated splenomegaly. The patient was referred to our department because of secondary amenorrhea for approximately 5 months since the last menstruation, which occurred just prior to the event. Laboratory blood test results demonstrated normal thyroid and ovarian functions. Hysterofiberscopy revealed complete obstruction at the end of the cervical canal, indicating secondary uterine amenorrhea caused by severe IUA. Hysteroscopic adhesiolysis with a rigid hysteroscope reached the opening of the uterine cavity and menstruation was restored.


Social policies and change in education-related disparities in mortality in Japan, 2000-2010.
Persistent socioeconomic disparity in mortality is a widely observed phenomenon despite improvements in the economic standard of living and the prevailing universal healthcare coverage policy. In this study, we selected Japan as a case in which public universal coverage has maintained horizontal equity in healthcare access while demographic and economic challenges have affected the life chances of vulnerable subpopulations over the past decade. We assessed the changing trends in the education-related disparity in mortality over a decade across demographic subpopulations for different causes of death, with the goal of generating social policy lessons to contribute to closing the mortality gap. Using a deterministic data merge between nationwide census and death records, we estimated age- and sex-specific mortality rates for 14 causes and their education-related gradients with absolute and relative indices of inequality in 2000 and 2010 via Poisson regression. Estimation parameters were standardized to the age structure of the sub-population of high school graduates in 2000 as the reference. The results demonstrated that the relative gaps in all-cause mortality persisted despite a decrease in the average mortality rate over the study period. The absolute gaps in mortality increased for preventable causes of death associated with lifestyle behavior choices. The average mortality worsened among socioeconomically vulnerable populations such as youth and women, who were left behind in the existing social/economic policy. External causes of death such as suicide and traffic accidents showed decreasing absolute gaps in a subpopulation targeted by universal social and labor policy measures. These change patterns indicate that, compared with a high-risk approach, a universal policy approach to dealing with societal and fundamental causes of health inequality seems more effective in reducing the education-related mortality gap in both absolute and relative terms.


Surprisingly complex community discovered in the mid-Devonian fossil forest at Gilboa.
The origin of trees by the mid-Devonian epoch (398-385 million years ago) signals a major change in terrestrial ecosystems with potential long-term consequences including increased weathering, drop in atmospheric CO(2), modified climate, changes in sedimentation patterns and mass extinction. However, little is known about the ecology of early forests or how changes in early terrestrial ecosystems influenced global processes. One of the most famous palaeontological records for this time is the 'oldest fossil forest' at Riverside Quarry, Gilboa, New York, USA, discovered in the 1920s. Hundreds of large Eospermatopteris sandstone casts, now thought to represent the bases of standing cladoxylopsid trees, were recovered from a horizon that was originally interpreted as a muddy swamp. After quarry operations ceased, relatively minor outcrops of similar fossils at nearby localities have provided limited opportunities to evaluate this pervasive view using modern methods. In 2010, removal of the quarry backfill enabled reappraisal of the palaeoecology of this important site. Here we describe a 1,200 m(2) map showing numerous Eospermatopteris root systems in life position within a mixed-age stand of trees. Unexpectedly, large woody rhizomes with adventitious roots and aerial branch systems identified as aneurophytalean progymnosperms run between, and probably climb into, Eospermatopteris trees. We describe the overall habit for these surprisingly large aneurophytaleans, the earliest fossil group having wood produced by a bifacial vascular cambium. The site also provides evidence for arborescence within lycopsids, extending the North American range for trees in this ecologically critical group. The rooting horizon is a dark grey sandy mudstone showing limited root penetration. Although clearly belonging to a wetland coastal plain environment, the forest was probably limited in duration and subject to periodic disturbance. These observations provide fundamental clarification of the palaeoecology of this mixed-group early forest, with important implications for interpreting coeval assemblage data worldwide.


Mangrove leaves: An undeniably important sink of MPs from tidal water and air.
Capturing microplastics (MPs) were one of the important characteristics for terrestrial plant. Whereas, role of mangrove leaves in capturing MPs from tidal water and air were still largely unexplored. Here, we detected the spatial distribution of MPs at both submerged (0.10-0.49 n/cm2) and non-submerged mangrove leaves (0.09-0.24 n/cm2) in the Beibu Gulf. Abundance of MPs on submerged mangrove leaves was significantly higher than that on non-submerged mangrove leaves in landward and middle zone (*p < 0.05). Almost no difference existed in the abundances of MPs detected on leaves of different mangrove species. Abundance of MPs on submerged mangrove leaves increased following the sequences of seaward zone (0.11 n/cm2) < middle zone (0.21 n/cm2) < landward zone (0.36 n/cm2). PE MPs with uncoloured/fiber characteristics dominated the MPs both on the non-submerged and submerged mangrove leaves. Furthermore, contribution of tidal water was significantly greater than that of atmospheric deposition on MPs retention on submerged mangrove leaves. Results of this work highlight the importance of tidal water and air in the spatial distribution of MPs at mangrove leaves, and the globally MPs gross reserves at mangrove leaves cannot be ignored in evaluating the MPs sink in mangrove wetland.


Interaction of a new fluorescent probe with DNA and its use in determination of DNA.
In this paper we reported a metal complex 1-Zn (2,5-di-[2-(3,5-bis(2-pyridylmethyl)amine-4-hydroxy-phenyl)-ethylene]-pyrazine-Zn) as a fluorescent probe sensing DNA. The result of the competitive experiment of the probe with ethidium bromide (EB) to bind DNA, absorption spectral change and polarization change in the presence and absence of DNA revealed that interaction between the probe and DNA was via intercalation. Ionic strength experiment showed the existence of electrostatic interaction as well. Scatchard plots also confirmed the combined binding modes. The fluorescence enhancement of the probe was ascribed to highly hydrophobic environment when it bound the macromolecules such as DNA, RNA or denatured DNA. The binding constant between the probe and DNA was estimated as 3.13 x 10(7) mol(-1) L. The emission intensity increase was proportional to the concentration of DNA. Based on this, the probe was used to determine the concentration of calf thymus DNA (ct-DNA). The corresponding linear response ranged from 2.50 x 10(-7) to 4.75 x 10(-6) mol L(-1), and detection limit was 1.93 x 10(-8) mol L(-1) for ct-DNA.


Synthesis of a sialic acid dimer derivative, 2'alpha-O-benzyl Neu5Ac-alph-(2-->5)Neu5Gc.
The preparation of a disaccharide 2, Neu5Ac-alpha-(2-->5)Neu5Gc having a alpha-benzyl protecting group at the reducing end, by the coupling of the easily accessible building units 4 and 5 is described. Subsequent deprotection of the coupling adduct led to the isolation of the target compound 2 in high yield.


Alteration of natural (37)Ar activity concentration in the subsurface by gas transport and water infiltration.
High (37)Ar activity concentration in soil gas is proposed as a key evidence for the detection of underground nuclear explosion by the Comprehensive Nuclear Test-Ban Treaty. However, such a detection is challenged by the natural background of (37)Ar in the subsurface, mainly due to Ca activation by cosmic rays. A better understanding and improved capability to predict (37)Ar activity concentration in the subsurface and its spatial and temporal variability is thus required. A numerical model integrating (37)Ar production and transport in the subsurface is developed, including variable soil water content and water infiltration at the surface. A parameterized equation for (37)Ar production in the first 15 m below the surface is studied, taking into account the major production reactions and the moderation effect of soil water content. Using sensitivity analysis and uncertainty quantification, a realistic and comprehensive probability distribution of natural (37)Ar activity concentrations in soil gas is proposed, including the effects of water infiltration. Site location and soil composition are identified as the parameters allowing for a most effective reduction of the possible range of (37)Ar activity concentrations. The influence of soil water content on (37)Ar production is shown to be negligible to first order, while (37)Ar activity concentration in soil gas and its temporal variability appear to be strongly influenced by transient water infiltration events. These results will be used as a basis for practical CTBTO concepts of operation during an OSI.


Femoral nerve blockade as a preemptive anesthetic in patients undergoing anterior cruciate ligament reconstruction: a prospective, randomized, double-blinded, placebo-controlled study.
Femoral nerve blockade has been purported to be an effective regional anesthetic in patients undergoing various procedures to lower extremities. Femoral nerve blockade will provide improved postoperative pain control over a local anesthetic in the knee joint alone in patients undergoing endoscopic patellar tendon anterior cruciate ligament reconstruction. Randomized, controlled trial; Level of evidence, 1. Fifty-six adult patients undergoing an endoscopic patellar tendon anterior cruciate ligament reconstruction under general anesthesia were prospectively randomized to receive either a bupivacaine femoral nerve blockade (block) or a saline placebo injection (control). Both groups received local bupivacaine injection and intravenous ketorolac at wound closure. Outcomes included postoperative pain measured on a validated visual analog scale at postoperative intervals for 72 hours, intraoperative and postoperative narcotic consumption, admission rates, hospital charges, patient satisfaction, and complications related to the femoral nerve block. There were 31 block patients and 25 control patients. No significant differences between groups for postoperative pain scores, intraoperative or postoperative narcotic consumption, readiness for discharge, duration of hospitalization, admission rates, hospital charges, or patient satisfaction were observed. There were no complications related to the femoral nerve block. A preemptive femoral nerve blockade, although safe, does not provide significant clinical benefit in this patient population to justify its routine use.


Parametric effect of biomass partial hydropyrolysis process in a downer reactor to co-produce high-quality tar and syngas.
Fast partial hydropyrolysis of biomass was carried out at the level with hydrogen concentration of 0% to 30% and temperatures ranging from 700 to 900 °C by using a downer pyrolyzer. A theoretical parametric effect on yields and properties of the hydropyrolysis products were clarified. It was found that the volatile matter evolved during pyrolysis was substantially increased in the presence of hydrogen. The yields of CH4, C2H6 and light tar increased with increasing elevated H2 ratio, CH4 showed an especially large yield increase. The produced methane mainly comes from the reactions of hydropyrolysis of biomass and secondary hydrogenation of tar. Moreover, the presence of alkali and alkaline earth metals matters was significant catalyzes on both reactions. The CH4 yield increased with elevating the operating temperature and optimal sweeping-gas flow rate is 150 mL/min. These results will be strengthening regulation of feedstocks-operating-products in the practical Biomass Fast Partial Hydropyrolysis technology.


Impact of stereochemistry on the biological activity of novel oleandomycin derivatives.
A set of 8-methylene-, 8-methyl-, and 8-methyl-9-dihydro-oleandomycin derivatives having different combinations of stereochemistries at positions C-8 and/or C-9 have been prepared in a chemoselective and stereoselective manner and tested in vitro for antibacterial activity and inhibition of IL-6 production. Configurations of the stereocenters at C-8 and C-9 were determined using 2D NMR techniques. We have shown that change of stereochemistry at these positions can exert a major influence on antibacterial activity as well as IL-6 inhibition, providing novel macrolide derivatives with diminished antibacterial and potent anti-inflammatory activity. In addition, the anti-inflammatory activity observed in vitro was confirmed in an in vivo model of lipopolysaccharide-induced inflammation.


Prevalence of Rickettsiales (Anaplasma phagocytophilum and Rickettsia spp.) in hard ticks (Ixodes ricinus) in the city of Hamburg, Germany.
To narrow the gap of missing knowledge on Rickettsia spp. and Anaplasma phagocytophilum infections in ticks in northwestern Germany and, at the same time, to provide first prevalence data on these pathogens in the city of Hamburg, a total of 1,400 questing Ixodes ricinus ticks were collected at ten different public green areas from April until October 2011. Ticks were examined using probe-based quantitative real-time PCR. A percentage of 3.6% (51/1,400) ticks were tested positive for A. phagocytophilum infections divided into 2.1% (3/141) adults [1.7% (1/60) females and 2.5% (2/81) males] and 3.8% (48/1,259) nymphs. The percentage of infected ticks per sampling site varied statistically significantly from 0.7% (1/140) to 12.1% (17/140), whereas between sampling months, no statistically significant differences were observed (2.0-6.5%, 4-13/140). The overall Rickettsia spp. infection rate was 52.5% (735/1,400). In adult ticks, Rickettsia spp. infection rate was 56% (79/141) divided into 61.7% (37/60) infected females and 51.9% (42/81) infected males. Nymphs showed an infection rate of 52.1% (656/1,259). In contrast to A. phagocytophilum infections, no statistically significant differences in Rickettsia spp. infection rates among sampling sites (44.3-63.6%, 62-89/140) were observed, whereas seasonal variations were obvious: the percentage of Rickettsia-positive ticks was significantly lower in April (36.5%, 73/200) and May (29.5%, 59/200) compared to the summer and fall months (55.0-64.5%, 110-129/200). Rickettsia species differentiation via real-time pyrosequencing revealed Rickettsia helvetica as the only occurring species. Co-infections with both Rickettsia spp. and A. phagocytophilum were detected in 2.0% (28/1,400) of the ticks. The present study revealed that in the city of Hamburg, the tick infection rate with A. phagocytophilum is comparable with other German data, whereas the Rickettsia spp. infection rate of 52.5% is by far the highest prevalence detected in Germany so far. As the city of Hamburg has 1.8 million inhabitants and attracts millions of tourists every year, the potential health risk should not be underestimated.


Clinical utility of reticulocyte haemoglobin in the assessment of iron deficiency and iron deficiency anaemia in the paediatric population.
Reticulocyte haemoglobin (Ret-He) is a useful marker in the assessment of iron stores in adult and paediatric patients. It is currently not utilised in Pathology Queensland. The objective of this study is to verify Ret-He in our Pathology Queensland laboratory and assess the clinical utility in the assessment of iron deficiency (ID) and iron deficiency anaemia (IDA) in paediatric patients. Samples from patients aged <18 years sent to the Pathology Queensland laboratory that had paired full blood count and iron studies were included in this study. A minimum of 120 samples were required for verification of testing requirements and a minimum of 30 samples per age range were required for confirmation of published age-related reference intervals. Published Ret-He reference intervals were confirmed for stated age ranges in normal (non-ID) patients. Ret-He below the reference range for age demonstrated a good correlation with ID and IDA. Ret-He is a useful marker in the assessment of ID and IDA in a paediatric population. It is not affected by acute or chronic inflammation. Ret-He is sensitive and specific (86% and 92%) for the diagnosis of ID.


A grease for domain walls motion in HfO2-based ferroelectrics.
A large coercive fieldECof HfO2based ferroelectric devices poses critical performance issues in their applications as ferroelectric memories and ferroelectric field effect transistors. A new design to reduceECby fabricating nanolaminate Hf0.5Zr0.5O2/ZrO2(HZZ) thin films is used, followed by an ensuing annealing process at a comparatively high temperature 700 °C. High-resolution electron microscopy imaging detects tetragonal-like domain walls between orthorhombic polar regions. These walls decrease the potential barrier of polarization reversal in HfO2based films compared to the conventional domain walls with a single non-polar spacer, causing about a 40% decrease inEC. Capacitance versus electric field measurements on HZZ thin film uncovered a substantial increase of dielectric permittivity near theECcompared to the conventional Hf0.5Zr0.5O2thin film, justifying the higher mobility of domain walls in the developed HZZ film. The tetragonal-like regions served as grease easing the movement of the domain wall and reducingEC.


Motivational interviewing and problem solving treatment to reduce type 2 diabetes and cardiovascular disease risk in real life: a randomized controlled trial.
Intensive lifestyle interventions in well-controlled settings are effective in lowering the risk of chronic diseases such as type 2 diabetes (T2DM) and cardiovascular diseases (CVD), but there are still no effective lifestyle interventions for everyday practice. In the Hoorn Prevention Study we aimed to assess the effectiveness of a primary care based lifestyle intervention to reduce the estimated risk of developing T2DM and for CVD mortality, and to motivate changes in lifestyle behaviors. The Hoorn Prevention Study is a parallel group randomized controlled trial, implemented in the region of West-Friesland, the Netherlands. 622 adults with ≥10% estimated risk of T2DM and/or CVD mortality were randomly assigned and monitored over a period of 12 months. The intervention group (n=314) received a theory-based lifestyle intervention based on an innovative combination of motivational interviewing and problem solving treatment, provided by trained practice nurses in 12 general practices. The control group (n=308) received existing health brochures. Primary outcomes was the estimated diabetes risk according to the formula of the Atherosclerosis Risk In Communities (ARIC) Study, and the estimated risk for CVD mortality according to the Systematic COronary Risk Evaluation (SCORE) formula. Secondary outcomes included lifestyle behavior (diet, physical activity and smoking). The research assistants, the principal investigator and the general practitioners were blinded to group assignment. Linear and logistic regression analysis was applied to examine the between-group differences in each outcome measure, adjusted for baseline values. 536 (86.2%) of the 622 participants (age 43.5 years) completed the 6-month follow-up, and 502 (81.2%) completed the 12-month follow-up. The mean baseline T2DM risk was 18.9% (SD 8.2) and the mean CVD mortality risk was 3.8% (SD 3.0). The intervention group participated in a median of 2 sessions. Intention-to-treat analyses showed no significant differences in outcomes between the two groups at 6 or 12-months follow-up. The lifestyle intervention was not more effective than health brochures in reducing risk scores for T2DM and CVD or improving lifestyle behavior in an at-risk population. Current Controlled Trials: ISRCTN59358434.


Pregnancy interruption after second trimester diagnosis of fetal structural anomalies: the New Jersey Fetal Abnormalities Registry.
The purpose of this study was to identify factors that predict a decision to interrupt a pregnancy in which there are fetal anomalies in the second trimester. The New Jersey Fetal Abnormalities Registry prospectively recruits and collects information on pregnancies (> or = 15 weeks of gestation) from New Jersey residents in whom a fetal structural anomaly has been suspected by maternal-fetal medicine specialists. Enrolled pregnancies that have major fetal structural abnormalities identified from 15 to 23 weeks of gestation were included. Outcomes were classified as either elective interruption or a natural pregnancy course, which might include a spontaneous fetal death or live birth. Predictors of elective interruption of pregnancy were examined with univariable and multivariable logistic regression analyses. Of the 97 cases, 33% of the women (n = 32) interrupted the pregnancy. Significant variables in the regression model that were associated with a decision to interrupt a pregnancy were earlier identification of fetal anomalies (19.0 +/- 2 weeks of gestation vs 20.5 +/- 2 weeks of gestation; P = .003), the presence of multiple anomalies (78% [25/32] vs 52% [33/63]; P = .01], and a presumption of lethality (56% [18/32] vs 14% [9/65]; P = .0001). These variables corresponded to an odds ratio for pregnancy interruption of 4.2 (95% CI, 1.0, 17.0) for multiple anomalies, 0.8 (95% CI, 0.7, 1.0) for each week of advancing gestational age, and 36.1 (95% CI, 2.9, 450.7) for presumed lethal abnormalities. Early diagnosis, the identification of multiple abnormalities, and an assessment of likely lethality of fetal anomalies are important factors for the optimization of parental autonomy in deciding pregnancy management.


Zinc, cadmium, and hypertension in parturient women.
Zinc deficiency and cadmium toxicity have both been implicated in hypertension during pregnancy. The goals of this study were twofold: first, to assess the different zinc indices (plasma, red blood cell zinc, heat-labile alkaline phosphatase, and placental zinc) in normotensive and hypertensive parturients to determine whether they are altered in the different types of hypertension that occur during pregnancy; second, to assess whole-blood cadmium and placental cadmium with regard to hypertension and zinc status. Patients were diagnosed as having chronic hypertension or preeclamptic toxemia and were then further divided into groups on the basis of smoking status. Each patient was matched with a normal control subject based on age, parity, and smoking status. Forty-three hypertensive patients and their matched control subjects were studied. No differences were found in the various zinc indices between chronic hypertensive parturients and normal control subjects. However, in parturients with preeclamptic toxemia, the plasma zinc level was 19% lower than in control subjects (p less than 0.02); these patients had the lowest plasma zinc level of the three groups. Placental zinc was also 12% lower in patients with preeclamptic toxemia than in control subjects (p less than 0.04). Whole-blood cadmium and placental cadmium levels did not differ between control subjects or hypertensive patients. However, a significant positive correlation was found between whole-blood cadmium and plasma zinc levels in preeclamptic toxemia (r = 0.53; p less than 0.05). The results support a marginal zinc deficiency in parturients with preeclamptic toxemia but not in those with chronic hypertension. The role of cadmium in the cause of preeclamptic toxemia remains unclear.


HPLC-MS-Method for A-Trichothecenes.
Gaschromatography with electron capture detection belongs to the most important methods for analysing the A-trichothecenes T-2 toxin, HT-2 toxin and diacetoxyscirpenol. The need of a derivatisation for these mycotoxins prior detection is the main disadvantage of this method. In this paper a sensitive high performance liquid chromatography method to analyse the A-trichothecenes in grain is described. The clean up was performed with multifunctional columns (MycoSep(TM), Romer Labs, Inc., MO). The detection limits of these methods are 3.5 μg/kg for T-2 toxin, 6.1 μg/kg for HT-2 toxin and 4.1 μg/kg for diacetoxyscirpenol. Limits of quantification were 12.7 μg/kg for T-2, 21.9 μg/kg for HT-2 and 14.8 μg/kg for DAS, respectively recovery rates were about 100% for each compound.


Growth hormone (GH) deficiency in patients with beta-thalassemia major and the efficacy of recombinant GH treatment.
Patients with beta-thalassemia major still suffer growth retardation. After excluding patients with cortisol deficiency, hypothyroidism, hypogonadism, delayed puberty, malnutrition, severe congestive heart failure, and severely impaired liver function, 29 patients were enrolled in this study. Fifteen (52%) patients exhibited growth retardation and underwent two growth hormone (GH) provocation tests. Eight (53%) of the 15 patients had GH deficiency and were subsequently treated with subcutaneous recombinant human GH (Genotropin, Pharmacia Corporation, Sweden). Growth velocity increased from the pretreatment rate of 3.1+/-0.4 cm/year to 7.1+/-1.6 cm/yr (p<0.001) after 1 year and to 6.8+/-1.3 cm/year (p<0.001) after 2 years. Patients with growth retardation had lower insulin like growth factor-1 (p=0.001) and insulin like growth factor binding protein-3 (p=0.003) levels than those without growth retardation. In patients with beta-thalassemia major, growth retardation is a common complication and GH deficiency plays an important role. Thalassemic patients with GH deficiency can safely increase their growth velocity with recombinant human GH for 2 years; however, the effect on final height still needs to be determined.


GENOMEPOP: a program to simulate genomes in populations.
There are several situations in population biology research where simulating DNA sequences is useful. Simulation of biological populations under different evolutionary genetic models can be undertaken using backward or forward strategies. Backward simulations, also called coalescent-based simulations, are computationally efficient. The reason is that they are based on the history of lineages with surviving offspring in the current population. On the contrary, forward simulations are less efficient because the entire population is simulated from past to present. However, the coalescent framework imposes some limitations that forward simulation does not. Hence, there is an increasing interest in forward population genetic simulation and efficient new tools have been developed recently. Software tools that allow efficient simulation of large DNA fragments under complex evolutionary models will be very helpful when trying to better understand the trace left on the DNA by the different interacting evolutionary forces. Here I will introduce GenomePop, a forward simulation program that fulfills the above requirements. The use of the program is demonstrated by studying the impact of intracodon recombination on global and site-specific dN/dS estimation. I have developed algorithms and written software to efficiently simulate, forward in time, different Markovian nucleotide or codon models of DNA mutation. Such models can be combined with recombination, at inter and intra codon levels, fitness-based selection and complex demographic scenarios. GenomePop has many interesting characteristics for simulating SNPs or DNA sequences under complex evolutionary and demographic models. These features make it unique with respect to other simulation tools. Namely, the possibility of forward simulation under General Time Reversible (GTR) mutation or GTRxMG94 codon models with intra-codon recombination, arbitrary, user-defined, migration patterns, diploid or haploid models, constant or variable population sizes, etc. It also allows simulation of fitness-based selection under different distributions of mutational effects. Under the 2-allele model it allows the simulation of recombination hot-spots, the definition of different frequencies in different populations, etc. GenomePop can also manage large DNA fragments. In addition, it has a scaling option to save computation time when simulating large sequences and population sizes under complex demographic and evolutionary situations. These and many other features are detailed in its web page [1].


Epidemiological survey in a day care center following toddler sudden death due to human metapneumovirus infection.
We report the sudden death of a 33-month-old child owing to acute respiratory distress syndrome due to human metapneumovirus (hMPV) infection. Of 30 children attending the same day care centre, 26% and 59% had hMPV and multiple infections, respectively; three of six children with pneumonia had a diagnosis of hMPV. hMPV infection is common in childhood viral co-infections but it can cause sudden death.


Protective effect of chorionic gonadotropin on DMBA-induced mammary carcinogenesis.
The effect of the placental hormone chorionic gonadotropin (hCG) on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumours was studied in young virgin Sprague-Dawley rats. This hormone when administered at a dose of 100 IU day-1 does not induce toxic effects, measured as alterations in body weight or weight of endocrine organs, and has a reversible effect on oestrous cycle. The lack of toxicity and the fact that hCG treatment terminated prior to administration of the chemical carcinogen DMBA protects the mammary gland from malignant transformation, led us to test the effect of hCG treatment on DMBA-initiated mammary tumours. Fifty day-old virgin Sprague-Dawley rats received intragastrically 8 mg DMBA per 100 g body weight and were divided into two groups: group I animals were treated with DMBA only and group II received DMBA at age 50 and in addition, a daily intraperitoneal injection of 100 IU hCG for days 21-81 post carcinogen administration. Tumorigenic response was evaluated by biweekly palpation of all animals and by complete autopsy 24 weeks after DMBA treatment. Group I animals developed an incidence of 100% of both tumours and adenocarcinomas. Group II animals developed a significantly lower incidence of tumours and adenocarcinomas, 51.5% and 45.5% respectively. In both groups lesions developed more frequently in thoracic than in abdominal mammary glands. It is postulated that hCG treatment, probably through stimulation of ovarian oestrogen and progesterone synthesis, induces differentiation of mammary epithelium that although affected by the carcinogen can still be rescued from malignant transformation.


A New Wide Bandgap Donor Polymer for Efficient Nonfullerene Organic Solar Cells with a Large Open-Circuit Voltage.
Significant progress has been made in nonfullerene small molecule acceptors (NF-SMAs) that leads to a consistent increase of power conversion efficiency (PCE) of nonfullerene organic solar cells (NF-OSCs). To achieve better compatibility with high-performance NF-SMAs, the direction of molecular design for donor polymers is toward wide bandgap (WBG), tailored properties, and preferentially ecofriendly processability for device fabrication. Here, a weak acceptor unit, methyl 2,5-dibromo-4-fluorothiophene-3-carboxylate (FE-T), is synthesized and copolymerized with benzo[1,2-b:4,5-b']dithiophene (BDT) to afford a series of nonhalogenated solvent processable WBG polymers P1-P3 with a distinct side chain on FE-T. The incorporation of FE-T leads to polymers with a deep highest occupied molecular orbital (HOMO) level of -5.60-5.70 eV, a complementary absorption to NF-SMAs, and a planar molecular conformation. When combined with the narrow bandgap acceptor ITIC-Th, the solar cell based on P1 with the shortest methyl chain on FE-T achieves a PCE of 11.39% with a large V oc of 1.01 V and a J sc of 17.89 mA cm-2. Moreover, a PCE of 12.11% is attained for ternary cells based on WBG P1, narrow bandgap PTB7-Th, and acceptor IEICO-4F. These results demonstrate that the new FE-T is a highly promising acceptor unit to construct WBG polymers for efficient NF-OSCs.


Sibutramine effect on metabolic control of obese patients with type 2 diabetes mellitus treated with pioglitazone.
Thiazolidinediones are supposed to be the pharmacologic agents that more physiologically fight the insulin resistance, but a possible adverse effect may be a weight increase. The aim of the study was to test the efficacy and tolerability of sibutramine on the metabolic effect of pioglitazone in obese patients with type 2 diabetes mellitus. All enrolled patients were required to have been diagnosed as being diabetic for at least 6 months and did not have glycemic control with diet and oral hypoglycemic agents such as sulfonylureas or metformin, both to the maximum tolerated dose. After a run-in period in which the eligible patients took a fixed dose of pioglitazone (30 mg/d), the patients were randomized to receive also sibutramine (10 mg/d) or placebo for 6 months. We assessed body mass index, hemoglobin A(1c) (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), lipid profile, lipoprotein parameters, and lipoprotein (a) at baseline and after 3 and 6 months. No body mass index change was observed after 3 and 6 months in the pioglitazone + placebo (pp) group. Significant decrease was present in the pioglitazone + sibutramine (ps) group after 3 (P < .05) and 6 months (P < .01) compared with the baseline values, and this variation was significant (P < .05) between groups. A significant HbA(1c) decrease was observed after 3 (P < .05) and 6 months (P < .01) in both groups with respect to the baseline values. There was no difference in HbA(1c) value between the 2 groups. No FPG, PPG, FPI, PPI, and homeostasis model assessment index change was observed at 3 months, whereas a significant decrease was present after 6 months (P < .05), in both groups with respect to the baseline values. There was no difference in FPG, PPG, FPI, PPI, and homeostasis model assessment index value between the pp and ps groups. No significant low-density lipoprotein cholesterol change was observed at 3 months, whereas a significant decrease was present after 6 months (P < .05), in both groups with respect to the baseline values. There was no difference in low-density lipoprotein cholesterol value between the pp and ps groups. No triglyceride variation was present at 3 and 6 months in the pp group and at 3 months in the ps group, whereas a significant decrease was observed at 6 months (P < .05) in the ps group with respect to the baseline values. There was no difference in triglyceride value between both groups. No high-density lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein B, and lipoprotein (a) changes were present in both groups with respect to the baseline values. Sibutramine appears to be a tolerable and efficacious drug when added to pioglitazone for the global management of obese diabetic patients.


Immunohistochemical localization of calmodulin in mouse brain.
Calmodulin is a well-known calcium-binding protein which is ubiquitous in the plant and animal kingdoms and regulates many cellular processes. In this paper, the distribution of calmodulin in mouse brain was studied immunohistochemically using specific anti-calmodulin IgG which was raised in the rabbit by immunization with native calmodulin. Immunoreactive staining was observed in the cells in almost all areas of the brain, but its intensity varied. Some areas were stained heavily even in the presence of high concentration of NaCl. These differed from those stained immunohistochemically with antibody against other calcium-binding proteins, parvalbumin or vitamin D-dependent calcium-binding protein.


Food Processing, According to the Nova Classification System, and Dietary Intake of US Infants and Toddlers.
High intake of ultra-processed foods (UPFs) is associated with increased risk of chronic disease; thus, it is important to understand how UPFs influence diet quality early in life. We describe complementary foods and beverages (CFBs) according to the Nova Classification System of Food Processing for infants and toddlers in the United States and estimate how Nova groups and subgroups contribute to energy and select nutrients and food groups. We used day 1 24-h recall from infants and toddlers aged 6-23 mo from the cross-sectional, nationally representative 2013-18 National Health and Nutrition Examination Survey (n = 1140). We estimated contributions of Nova groups and subgroups to energy and select nutrients and food groups consumed as CFBs (excluding human milk and formula) using the population ratio with weighted survey commands in SAS. For infants and toddlers in the United States, 42 ± 0.9% (mean ± standard error of the mean) of energy intake from CFBs came from unprocessed/minimally processed foods (U/MPFs) and 45 ± 0.8% from UPFs. U/MPFs contributed most to nutrient intakes (except iron, zinc, and sodium); ≥20% of all selected nutrients was from UPFs. UPFs contributed most to iron (75 ± 1.0%) and zinc (48 ± 1.3%); breakfast cereals were the top source. Most fruit, vegetables, and dairy were from U/MPFs. More than 80% of total grains, whole grains, refined grains, and added sugars were UPFs. U/MPFs support healthy dietary intake of infants and toddlers in the United States, whereas UPFs contribute meaningfully to nutrients and food groups to be encouraged (iron, zinc, and whole grains), as well as some that should be limited (added sugars and sodium). More research is needed to better understand the utility and sensitivities of using Nova for providing dietary guidance for infants and toddlers in the United States.


Successful pregnancy in a patient with severe 11-beta-hydroxylase deficiency and novel mutations in CYP11B1 gene.
11 beta-Hydroxylase deficiency is a rare form of congenital adrenal hyperplasia, resulting in virilization, glucocorticoid deficiency and hypertension. There have been no previous reports in the literature of a successful pregnancy in a severely affected female. We report the first successful pregnancy resulting in a live birth for a female with 11 beta-hydroxylase deficiency and outline management issues from preconception to successful birth. We also report 2 novel mutations in the CYP11B1 gene leading to 11 beta-hydroxylase deficiency.


Head-impulse testing in Fabry disease--vestibular function in male and female patients.
To study the prevalence of peripheral vestibular deficit in male and female patients with Fabry disease and to assess the effect of enzyme replacement therapy (ERT) on peripheral vestibular function using quantitative head-impulse testing. Using dual search-coils the vestibulo-ocular reflex during rapid rotational head thrusts to both sides was recorded in 21 patients (13 male, 8 female) with Fabry disease prior to ERT initiation. ERT consisted of infusions of gene-activated human alpha-galactosidase A (agalsidase alfa; Replagal) every 2 weeks at doses of 0.2 mg/kg. Eight patients were tested again approximately 6 and 12 months after the initiation of ERT. At baseline examination, 15 of the patients with Fabry disease (71%; 11 males, 4 females) showed reduced peripheral vestibular function. The deficit was unilateral in nine patients (3 females) and bilateral in six patients (1 female). The severity of the vestibular deficit was not significantly different between male and female patients. After 12 months of ERT, the average vestibular deficit on the weaker side tended to improve; however, the change was not significant (p = 0.10). Fabry disease affects peripheral vestibular function in both male and female patients. Females seem to be affected less frequently than males, but, on average, vestibular deficits are not different between the two groups. To confirm or reject the tendency for vestibular improvement during ERT, more patients need to be tested and longer follow-up periods are required.


Pre-service teacher's self-perception of digital literacy: The case of Israel.
Teachers provide society with literacy needs. They instruct students to acquire the essential skills and competencies required for a successful social integration. Thus, the need to identify digital readiness in teachers. The purpose of this study is to assess the level of digital literacies and digital readiness of students majoring in education. The research method includes a questionnaire comprising 54 items. The sample consists of 1265 students. The results show that more than half of the participants report an overall high level of literacy in all areas. Their sense of readiness for teamwork and their ethical readiness is high. Nonetheless, a low sense of readiness is found in a first and advanced order of readiness. The practical implications of these findings are crucial, as they can assist faculty and educational policymakers identify the strengths and weaknesses of students' digital literacies.


Health care in pregnancy during the COVID-19 pandemic and pregnancy outcomes in six low- and-middle-income countries: Evidence from a prospective, observational registry of the Global Network for Women's and Children's Health.
To assess, on a population basis, the medical care for pregnant women in specific geographic regions of six countries before and during the first year of the coronavirus disease 2019 (COVID-19) pandemic in relationship to pregnancy outcomes. Prospective, population-based study. Communities in Kenya, Zambia, the Democratic Republic of the Congo, Pakistan, India and Guatemala. Pregnant women enrolled in the Global Network for Women's and Children's Health's Maternal and Newborn Health Registry. Pregnancy/delivery care services and pregnancy outcomes in the pre-COVID-19 time-period (March 2019-February 2020) were compared with the COVID-19 time-period (March 2020-February 2021). Stillbirth, neonatal mortality, preterm birth, low birthweight and maternal mortality. Across all sites, a small but statistically significant increase in home births occurred between the pre-COVID-19 and COVID-19 periods (18.9% versus 20.3%, adjusted relative risk [aRR] 1.12, 95% CI 1.05-1.19). A small but significant decrease in the mean number of antenatal care visits (from 4.1 to 4.0, p = <0.0001) was seen during the COVID-19 period. Of outcomes evaluated, overall, a small but significant decrease in low-birthweight infants in the COVID-19 period occurred (15.7% versus 14.6%, aRR 0.94, 95% CI 0.89-0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites. Small but significant increases in home births and decreases in the antenatal care services were observed during the initial COVID-19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birthweight, or preterm birth rates during the COVID-19 period compared with the previous year. Further research should help to elucidate the relationship between access to and use of pregnancy-related medical services and birth outcomes over an extended period.


Surface and transmission ultrastructural characteristics of desquamative interstitial pneumonitis.
A prospective study of eight patients with desquamative interstitial pneumonitis was performed, correlating surface ultrastructure as elucidated by scanning electron microscopy, transmission electron microscopy, viral cultures of fresh sterile lung tissue obtained at thoracotomy, and immunomicroscopy. The hypothesis that environmental pollutants may act as sensitizing agents to induce macrophage migration was pursued using high resolution elemental analysis to obtain a profile of the inorganic content of phagolysosomes in the free alveolar cell population. Four surface ultrastructural changes were observed: mild alveolar septal thickening, an apparent decrease in the number of pores of Kohn, alteration of the predominant alveolar lining population from membranous to granular pneumonocytes, and prominent intra-alveolar collections of cells with broad based ruffled projections and pseudopodia representing a macrophage population. Transmission electron microscopy corroborated these observations. Individual pneumonocyte degeneration manifested as cytoplasmic dissolution, mitochondrial swelling, chromatin disruption, and loss of lamellar bodies and endoplasmic reticulum was identified; occasionally degenerating granular pneumonocytes were displaced into the alveolar space by a supraseptal bulla containing fibrin and extracellular fluid. Viruses were not identified by ultrastructural or tissue culture techniques. High resolution elemental analysis of individual phagolysosome contents failed to reveal the presence of heavy metals or other inorganic compounds. Immune complexes were not identified by immunofluorescence microscopy. However, alveolar transeptal macrophage migration was observed by transmission electron microscopy. These observations suggest that desquamative interstitial pneumonitis represents a disease in which cellular, rather than humoral, immune processes predominate. Other nonspecific cellular immune responses under the influence of various lymphokines may be responsible for the observed morphologic alterations.


Contribution of toxic nephropathies to end-stage renal failure in Europe: a report from the EDTA-ERA registry.
In countries which reported to the registry of the European Dialysis and Transplant Association (EDTA)-European Renal Association, 2.4% of 147 092 treated patients were recognized as having analgesic nephropathy (AN) as the cause of end-stage renal failure (ESRF) on 31 December 1986. A small number of patients had other specific drug nephropathies, but these do not yet make an important contribution to ESRF treatment programmes. It is possible that more patients have ESRF due to AN, and evidence from studies of age distribution, the demography of urothelial malignancies, a special study of diagnostic criteria, data on sales of analgesics, and a study of regional areas of high incidence lend some support to that view. Changes in prescription and self-medication practices over the last 20 years have almost eradicated analgesic nephropathy from the U.K. and Sweden, two countries in which there was previously a high frequency of ESRF due to AN. In other countries where action has been taken more recently, cases are still reported fairly frequently, and this seems likely to continue for several years to come.


Amino acid sequence of photosystem I subunit IV from the cyanobacterium Synechocystis PCC 6803.
We describe here the complete amino acid sequence of photosystem I subunit IV from Synechocystis 6803. The molecular mass of 8.0 kDa is lower than in higher plants and Chlamydomonas, due to the lack of a characteristic, proline-rich, N-terminal sequence. The remaining sequence exhibits a good conservation, with a hydrophilic and strongly basic N-terminal head followed by two hydrophobic domains. There is no possibility of classical membrane-spanning alpha helices. This component is likely to be one of the most stroma accessible subunits of photosystem I.


Surgical and percutaneous management of carotid artery stenosis.
Stroke is one of the leading causes of morbidity and mortality in the United States. Approximately 700,000 Americans suffer from a stroke per year and 270,000 of these patients will die as a result of their stroke. The etiology of cerebrovascular events can be attributed to carotid artery disease in 20-30% of cases. Carotid endarterectomy has been shown to be beneficial in selected patients with symptomatic and asymptomatic carotid artery stenosis. Percutaneous treatment of carotid disease appears to be effective when performed with distal protection by an experienced operator. This review presents the clinical trial data regarding surgical and percutaneous management of carotid disease.


How Compatible Are Immune Checkpoint Inhibitors and Thermal Ablation for Liver Metastases?
Cancer immunotherapy, which reactivates the weakened immune cells of cancer patients, has achieved great success, and several immune checkpoint inhibitors (ICIs) are now available in clinical practice. Despite promising clinical outcomes, favorable responses are only observed in a fraction of patients, and resistance mechanisms, including the absence of tumor antigens, have been reported. Thermal ablation involves the induction of irreversible damage to cancer cells by localized heat and may result in the release of tumor antigens. The combination of immunotherapy and thermal ablation is an emerging therapeutic option with enhanced efficacy. Since thermal ablation-induced inflammation and increases in tumor antigens have been suggested to promote the cancer-immunity cycle, the combination of immuno-oncology (IO) therapy and thermal ablation may be mutually beneficial. In preclinical and clinical studies, the combination of ICI and thermal ablation significantly inhibited tumor growth, and synergistic antitumor effects appeared to prolong the survival of patients with secondary liver cancer. However, evidence for the efficacy of ICI monotherapy combined with thermal ablation is currently insufficient. Therefore, the clinical feasibility of immune response activation by ICI monotherapy combined with thermal ablation may be limited, and thermal ablation may be more compatible with dual ICIs (the IO-IO combination) to induce strong immune responses.


A review: Pharmacology and pharmacokinetics of Schisandrin A.
Schisandrin A (SA) is a bioactive lignan isolated from the traditional Chinese medicine Fructus schisandrae chinensis. In recent years, it has attracted extensive attention because of its multiple pharmacological activities. This review is the first to provide an overview of SA-related pharmacological effects and pharmacokinetic characteristics. The results showed that SA had many pharmacological effects, such as antiinflammation, anticancer, hepatoprotection, antioxidation, neuroprotection, antidiabetes mellitus, and musculoskeletal protection. Among them, NF-κB, Nrf2, MAPK, NLRP3, PI3K/AKT, Wnt, miRNA, P-gp, CYP450, PXR, and other signal transduction pathways are involved. Pharmacokinetic studies showed that SA had good pharmacokinetic characteristics, but these were affected by other factors, such as drugs or hepatic fibrosis. Thus, SA has a variety of pharmacological effects and good pharmacokinetic characteristics, which is worthy of further research and development in the future.


Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role in brain, retinal, and renal development.
Joubert syndrome and related diseases (JSRD) are cerebello-oculo-renal syndromes with phenotypes including cerebellar hypoplasia, retinal dystrophy, and nephronophthisis (a cystic kidney disease). Mutations in AHI1 are the most common genetic cause of JSRD, with developmental hindbrain anomalies and retinal degeneration being prominent features. We demonstrate that Ahi1, a WD40 domain-containing protein, is highly conserved throughout evolution and its expression associates with ciliated organisms. In zebrafish ahi1 morphants, the phenotypic spectrum of JSRD is modeled, with embryos showing brain, eye, and ear abnormalities, together with renal cysts and cloacal dilatation. Following ahi1 knockdown in zebrafish, we demonstrate loss of cilia at Kupffer's vesicle and subsequently defects in cardiac left-right asymmetry. Finally, using siRNA in renal epithelial cells we demonstrate a role for Ahi1 in both ciliogenesis and cell-cell junction formation. These data support a role for Ahi1 in epithelial cell organization and ciliary formation and explain the ciliopathy phenotype of AHI1 mutations in man.


Significant accumulations of cathepsin B and prolylendopeptidase in inflammatory focus of delayed-type hypersensitivity induced by Mycobacterium tuberculosis in mice.
To clarify what kinds of proteinases are secreted into the foci of allergic-inflammation involving delayed-type hypersensitivity reaction, we examined the characteristic releases of various proteinases into the foci of Mycobacterium tuberculosis (M. tuber.)-induced delayed-type allergic-inflammation in mice. The significant activities of cathepsin B and prolylendopeptidase were observed in the washing-fluids of subcutaneous inflammatory foci of M. tuber.-induced delayed-type allergic-inflammation, but not M. tuber.-induced acute-inflammation. The SDS-resistant complex of cathepsin B and a protein substrate with apparent molecular mass of 74 kDa was observed by Western blot analysis. On the other hand, no significant accumulations of other proteinases, such as matrix metalloproteinases, cathepsin D, and serine proteinases, were determined. CA-074, a specific inhibitor of cathepsin B, suppressed both swelling and cathepsin B activity in the footpad having M. tuber.-induced delayed-type allergic-inflammation in vivo. These results suggest that cathepsin B may play an important role in the formation of M. tuber.-induced delayed-type allergic-inflammation.


To charge or not to charge: mechanistic insights into neuropathy-associated tRNA synthetase mutations.
Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes responsible for the first step of protein translation--attaching amino acids to cognate tRNA molecules. Interestingly, ARS gene mutations have been implicated in tissue-specific human diseases, including inherited peripheral neuropathies. To date, five loci encoding an ARS have been implicated in peripheral neuropathy, and alleles at each locus show loss-of-function characteristics. The majority of the phenotypes are autosomal dominant, and each of the implicated enzymes acts as an oligomer, indicating that a dominant-negative effect should be considered. On the basis of current data, impaired tRNA charging is likely to be a central component of ARS-related neuropathy. Future efforts should focus on testing this notion and developing strategies for restoring ARS function in the peripheral nerve.


Risk of Revictimization of Intimate Partner Violence: The Role of Attachment, Anger and Violent Behavior of the Victim.
Victims of intimate partner violence (IPV) are known to be at high risk for revictimization. Yet, to date, the mechanisms explaining the link between victimization and revictimization of IPV have not been extensively studied. In the present prospective study involving 74 female help-seeking victims of IPV, we investigated victim-related psychological mechanisms that may underlie this link. With this study, we aim to contribute to the development of theory addressing these psychological mechanisms and their role in explaining risk for IPV revictimization. Hypotheses regarding possibly relevant psychological mechanisms were derived from two conflicting approaches to IPV: the gender perspective, and the mutual IPV perspective. Results lend further support to the mutual IPV perspective, since our final prediction model indicates that victim-perpetrated IPV is an important risk factor for physical and psychological IPV revictimization. An avoidant attachment style shows to be a strong predictor as well, in particular for victims with high and average anger levels. Findings provide clear indications for risk assessment and treatment of IPV victims, and moreover offer opportunities to empower these victims in order to prevent future violence.


The relationship between depressive symptoms, illness perceptions and quality of life in ankylosing spondylitis in comparison to rheumatoid arthritis.
Anxiety and depressive symptoms as well as cognitive variables are important in determining outcome in rheumatic diseases. We aimed to compare psychological distress symptoms and illness perceptions in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) and to test whether their associations with health-related quality of life (HRQoL) were similar in these rheumatologic disorders. In 55 AS and 199 RA patients, we administered the Patient Health Questionnaire (PHQ-9), the Symptom Check-List and the Brief-Illness Perception Questionnaire to assess psychological variables and the World Health Organization Quality of Life Instrument, Short Form to assess HRQoL. We used hierarchical regression analyses to determine the associations between psychological variables and HRQoL after adjusting for demographic variables and disease parameters. The prevalence of clinically significant depressive symptoms (PHQ-9 ≥ 10) was 14.8 % in AS and 25.1 % in RA patients, but adjustment for demographics rendered these differences in depressive symptoms' severity non-significant. Psychological distress levels and HRQoL were similar in both disorders. Illness concern (b = -0.37) was the only significant independent correlate of physical HRQoL in AS. In RA, depression (b = -0.25), illness concern (b = -0.14) and worries about the consequences of the disease (b = -0.31) were the independent correlates of physical HRQoL. These findings suggest that cognitive variables are important correlates of HRQoL in AS, whereas in RA depressive symptoms and illness perceptions equally contribute to HRQoL. Our data encourage the design of psychotherapeutic trials targeting disease-related cognitions in AS in an attempt to improve patient's physical HRQoL.


Perforin and granzyme A release as novel tool to measure NK cell activation in chickens.
Natural killer (NK) cells are cytotoxic lymphocytes that are present in the circulation but also in many organs including spleen and gut, where they play an important role in the defense against infections. Interaction of NK cells with target cells leads to degranulation, which results in the release of perforin and granzymes in the direct vicinity of the target cell. Chicken NK cells have many characteristics similar to their mammalian counterparts and based on similarities with studies on human NK cells, surface expression of CD107 was always presumed to correlate with granule release. However, proof of this degranulation or in fact the actual presence of perforin (PFN) and granzyme A (GrA) in chicken NK cells and their release upon activation is lacking. Therefore, the purpose of the present study was to determine the presence of perforin and granzyme A in primary chicken NK cells and to measure their release upon degranulation, as an additional tool to study the function of chicken NK cells. Using human specific antibodies against PFN and GrA in fluorescent and confocal microscopy resulted in staining in chicken NK cells. The presence of PFN and GrA was also confirmed by Western blot analyses and its gene expression by PCR. Stimulation of NK cells with the pectin SPE6 followed by flow cytometry resulted in reduced levels of intracellular PFN and GrA, suggesting release of PFN and GrA. Expression of PFN and GrA reversely correlated with increased surface expression of the lysosomal marker CD107. Finally it was shown that the supernatant of activated NK cells, containing the NK cell granule content including PFN and GrA, was able to kill Escherichia coli. This study correlates PFN and GrA release to activation of chicken NK cells and establishes an additional tool to study activity of cytotoxic lymphocytes in chickens.


Variations in nuchal muscle tonus following paradoxical sleep deprivation in the rabbit.
Although tonic inhibition of nuchal or facial musculature is considered an intrinsic component of paradoxical sleep (PS) in mammals, this inhibition is either absent or greatly attenuated in the rabbit. To further explore the characteristics of this phenomenon in this species, variations in quantified nuchal muscle activity were examined before, during and following 24 h of PS deprivation. It was postulated that if the substrate for PS-associated tonic electromyogram (EMG) inhibition is present, this procedure--which is known to affect both tonic and phasic components of PS--might enhance such inhibition. For these investigations chronically implanted rabbits (electroencephalographic, eye movement and nuchal muscle placements) were recorded continuously for 5 consecutive days (two day baseline, one day deprivation, two day recovery). Muscle activity was quantified by resetting integration techniques and comparisons made of activity levels before, during and after PS episodes across conditions. The deprivation procedure significantly reduced the amount of PS relative to baseline values, and a significant PS increase (rebound) occurred during postdeprivation recordings. Across-condition EMG-related effects included the corroboration of previous reports of an absence of nuchal atonia during PS, a significant diurnal variation in EMG activity--with greater activity occurring during the dark portion of the light-dark cycle, and enhanced activity immediately following PS episodes relative to either pre-PS or PS levels. Deprivation-related changes in quantified EMG activity included a pre-PS decrease during both the last 12 h of deprivation and the initial 12 h of recovery sleep, and an enhancement of EMG activity during PS.(ABSTRACT TRUNCATED AT 250 WORDS)


PreView: a Randomized Trial of a Multi-site Intervention in Diverse Primary Care to Increase Rates of Age-Appropriate Cancer Screening.
Women aged 50-70 should receive breast, cervical (until age 65), and colorectal cancer (CRC) screening; men aged 50-70 should receive CRC screening and should discuss prostate cancer screening (PSA). PreView, an interactive, individually tailored Video Doctor Plus Provider Alert Intervention, adresses all cancers for which average risk 50-70-year-old individuals are due for screening or screening discussion. We conducted a randomized controlled trial in 6 clinical sites. Participants were randomized to PreView or a video about healthy lifestyle. Intervention group participants completed PreView before their appointment and their clinicians received a "Provider Alert." Primary outcomes were receipt of mammography, Pap tests (with or without HPV testing), CRC screening (FIT in last year or colonoscopy in last 10 years), and PSA screening discussion. Additional outcomes included breast, cervical, and CRC screening discussion. A total of 508 individuals participated, 257 in the control group and 251 in the intervention group. Screening rates were relatively high at baseline. Compared with baseline screening rates, there was no significant increase in mammography or Pap smear screening, and a nonsignificant increase (18% vs 12%) in CRC screening. Intervention participants reported a higher rate of PSA discussion than did control participants (58% vs 36%: P < 0.01). Similar increases were seen in discussions about mammography, cervical cancer, and CRC screening. In clinics with relatively high overall screening rates at baseline, PreView did not result in significant increases in breast, cervical, or CRC screening. PreView led to an increase in PSA screening discussion. Clinician-patient discussion of all cancer screenings significantly increased, suggesting that interventions like PreView may be most useful when discussion of the pros and cons of screening is recommended and/or with patients reluctant to undergo screening. Future research should investigate PreView's impact on those who are hesitant or reluctant to undergo screening. ClinicalTrials.gov: NCT02264782.