Using a surrogate contact pair to evaluate polyethylene wear in prosthetic knee joints.
With recent improvements to the properties of ultra-high molecular weight polyethylene (UHMWPE) used in joint replacements, prosthetic knee and hip longevity may extend beyond two decades. However, it is difficult and costly to replicate such a long in vivo lifetime using clinically relevant in vitro wear testing approaches such as walking gait joint simulators. We advance a wear test intermediate in complexity between pin-on-disk and knee joint simulator tests. The test uses a surrogate contact pair, consisting of a surrogate femoral and tibial specimen that replicate the contact mechanics of any full-scale knee condyle contact pair. The method is implemented in a standard multi-directional pin-on-disk wear test machine, and we demonstrate its application via a two-million-cycle wear test of three different UHMWPE formulations. Further, we demonstrate the use of digital photography and image processing to accurately quantify fatigue damage based on the reduced transmission of light through a damage area in a UHMWPE specimen. The surrogate contact pairs replicate the knee condyle contact areas within -3% to +12%. The gravimetric wear test results reflect the dose of crosslinking radiation applied to the UHMWPE: 35 kGy yielded a wear rate of 7.4 mg/Mcycles, 55 kGy yielded 1.0 mg/Mcycles, and 75 kGy (applied to a 0.1% vitamin E stabilized UHMWPE) yielded 1.5 mg/Mcycles. A precursor to spalling fatigue is observed and precisely measured in the radiation-sterilized (35 kGy) and aged UHMWPE specimen. The presented techniques can be used to evaluate the high-cycle fatigue performance of arbitrary knee condyle contact pairs under design-specific contact stresses, using existing wear test machines. This makes the techniques more economical and well-suited to standardized comparative testing.


An overview of the transfer of radionuclides to farm animals and potential countermeasures of relevance to Fukushima releases.
Initial information since the releases of radioactive materials from the Fukushima Daiichi nuclear power plant, in Japan, shows that some animal food products are contaminated with 131I (mostly milk) and, to a lesser extent with 134Cs and 137Cs. Current knowledge on the transfer of these radioisotopes to animal products and available relevant countermeasures and management options to reduce radiation doses to humans are summarized. Much of this knowledge was obtained during the years of global fallout from atmospheric nuclear weapons tests and the response to the Chernobyl accident, in Ukraine in 1986.


Characteristics of brain glucose metabolism and metabolic connectivity in noise-induced hearing loss.
The purpose of this study was to evaluate the differences in cerebral glucose metabolism and metabolic connectivity between noise-induced hearing loss (NIHL) subjects and normal subjects. Eighty-nine subjects who needed close observation for NIHL or were diagnosed with NIHL and 89 normal subjects were enrolled. After pre-processing of positron emission tomography images including co-registration, spatial normalization, and smoothing, a two-sample t-test was conducted to compare cerebral glucose metabolism between the two groups. To evaluate metabolic connectivity between two groups, BRAPH-BRain Analysis using graPH theory, a software package to perform graph theory analysis of the brain connectome was used. NIHL subjects showed hypometabolism compared to normal subjects in both insulae (x - 38, y - 18, z 4; × 42, y - 12, z 4) and right superior temporal gyrus (× 44, y 16, z - 20). No brain regions showed hypermetabolism in the NIHL subjects. In metabolic connectivity analysis, NIHL subjects showed decreased average strength, global efficiency, local efficiency, and mean clustering coefficient when compared with normal subjects. Decreased glucose metabolism and metabolic connectivity in NIHL subject might reflect decreased auditory function. It might be characteristic of sensorineural hearing loss.


Cloning and sequence analysis of the Chlamydia trachomatis spc ribosomal protein gene cluster.
We identified and sequenced a segment of Chlamydia trachomatis chromosomal DNA that shows homology to the Escherichia coli spc and distal region of the S10 ribosomal protein (r-protein) operons. Its sequence revealed a high degree of nucleotide and operon context conservation with the E. coli r-protein genes. The C. trachomatis spec operon contains the r-protein genes for L14, L24, L5, S8, L6, L18, S5, L15, and Sec Y along with the genes for r-proteins L16, L29, and S17 of the S10 operon. The two operons are separated by a 16-bp intragenic region which contains no transcription signals. However, a putative promoter for the transcription of the spc operon was found 162 nucleotides upstream of the CtrL14e start site; it revealed significant homology to the E. coli consensus promoter sequences. Interestingly, our results indicate the absence of any structure resembling an EcoS8 regulatory target site on C. trachomatis spc mRNA in spite of significant amino acid identity between E. coli and C. trachomatis r-proteins. Also, the intrinsic aminoglycoside resistance in C. trachomatis is unlikely to be mediated by CtrL6e since E. coli expressing CtrL6e remained susceptible to gentamicin (MIC less than 0.5 micrograms/ml).


Comparative Analysis of Gut Microbiota of Culex restuans (Diptera: Culicidae) Females From Different Parents.
The potential for gut microbiota to impede or enhance pathogen transmission is well-documented but the factors that shape this microbiota in mosquito vectors are poorly understood. We characterized and compared the gut microbiota of adult females of Culex restuans (Theobald; Diptera: Culicidae) from different parents. Cx. restuans larvae from nine field-collected egg rafts were reared on a common diet and gut microbiota of newly emerged adult females characterized by MiSeq sequencing of the V4 hypervariable region of the 16S rRNA gene. Bacterial diversity and evenness in individuals from one egg raft were significantly lower compared to those of three of the other eight egg rafts. The gut microbiota of adult females reared from seven of the nine egg rafts clustered together suggesting that individuals from most egg rafts had similar profiles of gut microbiota. These findings suggest that the microbiota of adult females from the same parents do not differ appreciably from the microbiota of adult females from different parents. However, additional studies using mosquitoes separated by geographic distances greater than those studied here and estimating the genetic distances between populations from different egg rafts are needed to provide further insights into the influence of host genetics on gut microbiota. Also worthwhile are studies evaluating how individuals from different egg rafts and harboring different gut microbiota compare in relation to vector competence for different pathogens.


A step-by-step guide to ileoanal J-pouch MRI interpretation.
Multidisciplinary management of patients with an ileoanal pouch requires dedicated imaging to identify structural problems of the pouch associated with dysfunction. The purpose of this study is to provide a framework for interpretation of magnetic resonance imaging (MRI) scan of the ileoanal pouch to enable surgeons and radiologists to work cohesively, optimise diagnosis and ultimately improve patient care. We propose a protocol for structured MRI assessment of the ileal pouch, aiming to provide surgeons a systematic report of the anatomy, its variations and pouch complications. This guide consists of studying the characteristics of the bowel, mesentery and anal canal. The presented checklist is designed to systematically interpret and identify abnormalities of the ileoanal pouch on MRI. It focuses on the characteristics of the bowel (encompassing pre-pouch ileum, pouch and rectal cuff), mesentery and anal canal. The different elements of the checklist are presented in the associated supplementary video. A combination of clinical assessment, endoscopic evaluations and imaging is fundamental to achieving accurate diagnosis of ileoanal pouch surgery complications and pouch dysfunction.


The genetic pattern of population threat and loss: a case study of butterflies.
Recent decreases in biodiversity in Europe are commonly thought to be due to land use and climate change. However, the genetic diversity of populations is also seen as one essential factor for their fitness. Genetic diversity in species across the continent of Europe has been recognized as being in part a consequence of ice age isolation in southern refugia and postglacial colonization northwards, and these phylogeographical patterns may themselves affect the adaptability of populations. Recent work on butterfly species with different refugia, colonization paths and genetic structures allows this idea to be examined. The 'chalk-hill blue' pattern is one of decreasing genetic diversity from south to north, whereas the 'woodland ringlet' pattern shows greater genetic diversity in eastern than in western lineages. Comparison of population demographic trends in species with these biogeographical patterns reveals higher rates of decrease with lower genetic diversity. This indicates reduced adaptability due to genetic impoverishment as a result of glacial and postglacial range changes. Analysis of phylogeographical pattern may be a useful guide to interpreting demographic trends and in conservation planning.


Robust production of human neural cells by establishing neuroepithelial-like stem cells from peripheral blood mononuclear cell-derived feeder-free iPSCs under xeno-free conditions.
Neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) are expected to be a valuable cell source for cell therapies that target central nervous system disorders. For clinical applications, NS/PCs should be induced and maintained under clinical grade conditions, which are challenging to achieve. In the present study, we established a procedure to obtain xeno-free long-term self-renewing neuroepithelial-like stem cells (xf-lt-NES cells) from feeder-free hiPSCs using a newly developed xeno-free medium, StemFit(®)AS200. xf-lt-NES cells were cultured for long periods in StemFit(®)AS200 while retaining normal karyotypes, NS/PC marker expression and differentiation capacity for neuronal and glial differentiation in vitro and in vivo. Furthermore, the cells were cryopreserved using a defined serum-free freezing reagent, which demonstrated the feasibility of this xeno-free culture system for large-scale lt-NES cell production and cell banking. Taken together, our system represents a promising approach for the manufacture of clinically relevant products for cell therapy using NS/PCs.


[ULTRASOUND DIAGNOSIS OF PARASITIC INVASION OF THE GALLBLADDER].
Migration of ascaris from the lumen of the small intestine to the biliary system was previously thought to be very rare pathology and the diagnosis had not be without specific examination methods. At the present time widespread active ultrasonic technologies in the emergency surgical service can became more accessible to show worm in a gall bladder and ducts. The paper presents two cases of gallbladder ascariasis, identified by ultrasound.


Calycosin promotes angiogenesis involving estrogen receptor and mitogen-activated protein kinase (MAPK) signaling pathway in zebrafish and HUVEC.
Angiogenesis plays an important role in a wide range of physiological processes, and many diseases are associated with the dysregulation of angiogenesis. Radix Astragali is a Chinese medicinal herb commonly used for treating cardiovascular disorders and has been shown to possess angiogenic effect in previous studies but its active constituent and underlying mechanism remain unclear. The present study investigates the angiogenic effects of calycosin, a major isoflavonoid isolated from Radix Astragali, in vitro and in vivo. Tg(fli1:EGFP) and Tg(fli1:nEGFP) transgenic zebrafish embryos were treated with different concentrations of calycosin (10, 30, 100 microM) from 72 hpf to 96 hpf prior morphological observation and angiogenesis phenotypes assessment. Zebrafish embryos were exposed to calycosin (10, 100 microM) from 72 hpf to 78 hpf before gene-expression analysis. The effects of VEGFR tyrosine kinase inhibitor on calycosin-induced angiogenesis were studied using 72 hpf Tg(fli1:EGFP) and Tg(fli1:nEGFP) zebrafish embryos. The pro-angiogenic effects of calycosin were compared with raloxifene and tamoxifen in 72 hpf Tg(fli1:EGFP) zebrafish embryos. The binding affinities of calycosin to estrogen receptors (ERs) were evaluated by cell-free and cell-based estrogen receptor binding assays. Human umbilical vein endothelial cell cultures (HUVEC) were pretreated with different concentrations of calycosin (3, 10, 30, 100 microM) for 48 h then tested for cell viability and tube formation. The role of MAPK signaling in calycosin-induced angiogenesis was evaluated using western blotting. Calycosin was shown to induce angiogenesis in human umbilical vein endothelial cell cultures (HUVEC) in vitro and zebrafish embryos in vivo via the up-regulation of vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 mRNA expression. It was demonstrated that calycosin acted similar to other selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, by displaying selective potency and affinity to estrogen receptors ERalpha and ERbeta. Our results further indicated that calycosin promotes angiogenesis via activation of MAPK with the involvement of ERK1/2 and ER. Together, this study revealed, for the first time, that calycosin acts as a selective estrogen receptor modulator (SERM) to promote angiogenesis, at least in part through VEGF-VEGFR2 and MAPK signaling pathways.


Postural & striatal deformities in Parkinson`s disease: Are these rare?
Parkinson`s disease (PD) is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS) and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.


Various high-order modes in vertical-cavity surface-emitting lasers with equilateral triangular lateral confinement.
Large-aperture vertical-cavity surface-emitting lasers with an equilateral triangular lateral confinement are fabricated to investigate the formation of high-order resonant modes. The experimental lasing patterns are composed of the superscar mode, honeycomb eigenstate, and chaotic mode. Experimental results confirm the theoretical predictions that tiny symmetry breaking can cause the high-order modes to reveal miscellaneous states of integrable and chaotic systems.


Treatment of intermediate stage hepatocellular carcinoma: a review of intrahepatic doxorubicin drug-delivery systems.
The biopharmaceutical properties of doxorubicin delivered via two drug-delivery systems (DDSs) for the palliative treatment of unresectable hepatocellular carcinoma were reviewed with relation to the associated liver and tumor (patho)physiology. These two DDSs, doxorubicin emulsified with Lipiodol(®) and doxorubicin loaded into DC Bead(®) are different regarding tumor delivery, release rate, local bioavailability, if and how they can be given repeatedly, biodegradability, length of embolization and safety profile. There have been few direct head-to-head comparisons of these DDSs, and in-depth investigations into their in vitro and in vivo performance is warranted.


Interlaboratory survey of enzyme analyses. I. Preliminary.
Enzyme survey specimens were prepared by spiking portions of a normal serum pool with creatinine, urea, and five enzymes (lactate dehydrogenase, creatine phosphokinase, alkaline phosphatase, and aspartate and alanine aminotransferases), and preparing admixtures of the spiked pools with the original serum. This admixture technic established linear interspecimen relationships that could be confirmed by analyses for creatinine and urea nitrogen. Both ethylene glycol-stabilized liquid serum specimens and lyophilized specimens were prepared as sets of six to eight samples having six concentrations of each enzyme. The sets were distributed on five occasions to about ten laboratories that were widely separated geographically, and the specimens were analyzed by a variety of methods, by various instrumental systems, and in different reaction conditions, and results were reported in diverse units. This report describes how the analytic data obtained through the use of these specimens that were specifically designed for survey purposes can be analyzed statistically to provide meaningful assessments of laboratory performance in enzyme analyses.


Early life socioeconomic status and late life risk of Alzheimer's disease.
The authors examined the relation of early life socioeconomic status to incident Alzheimer's disease (AD), level of cognition and rate of cognitive decline in old age. For up to 10 years, 859 older Catholic clergy members without dementia at baseline completed annual clinical evaluations as part of the Religious Orders Study. The evaluations included clinical classification of AD and detailed cognitive testing. At baseline, indicators of early life household socioeconomic level (e.g., parental education) and the county of birth were ascertained. Socioeconomic features of the birth county (e.g., literacy rate) were estimated with data from the 1920 US Census. Composite measures of early life household and community socioeconomic level were developed. In analyses that controlled for age, sex and education, higher household and community socioeconomic levels in early life were associated with higher level of cognition in late life but not with risk of AD or rate of cognitive decline. The results suggest that early life socioeconomic level is related to level of cognition in late life but not to rate of cognitive decline or risk of AD.


High levels of grass pollen inside European dairy farms: a role for the allergy-protective effects of environment?
There is evidence of an allergy protective effect in children raised on farm. It has been assumed that microbial exposure may confer this protection. However in farm, little attention has been given to the pollen level and to concomitant microbiological exposure, and indoor pollen concentrations have never been precisely quantified. The kinetics of pollen in dairy farms have been studied in a pilot study (n = 9), and exposure in a sub-sample of the ongoing European birth cohort PASTURE (n = 106). Measurements of viable microorganisms and pollen were performed in air samples. To identify factors that modulate the pollen concentration multivariate regression analyses were run. Indoor pollen (95% of Poaceae fragments and grains) were significantly higher in winter than in summer (P = 0.001) and ranged between 858 to 11 265 counts/m(3) during feeding in winter, thus exceeding typical outdoor levels during the pollen season. Geometric mean in French farms was significantly higher than in German and Swiss farms (7 534, 992 and 1 079 count/m(3), respectively). The presence of a ventilation system and loose housing systems significantly reduced indoor pollen levels. This pollen concentration rise after feeding was accompanied by an increase in fungal and actinomycetal levels, whereas the concentration of bacteria was not associated with feeding. Farmers and their children who attend cowsheds during the feeding sessions are exposed perennially to high pollen concentrations. It might be speculated that the combined permanent exposure to microbes from livestock and grass pollen may initiate tolerance in children living on a farm.


Complete genome sequence of an M1 strain of Streptococcus pyogenes.
The 1,852,442-bp sequence of an M1 strain of Streptococcus pyogenes, a Gram-positive pathogen, has been determined and contains 1,752 predicted protein-encoding genes. Approximately one-third of these genes have no identifiable function, with the remainder falling into previously characterized categories of known microbial function. Consistent with the observation that S. pyogenes is responsible for a wider variety of human disease than any other bacterial species, more than 40 putative virulence-associated genes have been identified. Additional genes have been identified that encode proteins likely associated with microbial "molecular mimicry" of host characteristics and involved in rheumatic fever or acute glomerulonephritis. The complete or partial sequence of four different bacteriophage genomes is also present, with each containing genes for one or more previously undiscovered superantigen-like proteins. These prophage-associated genes encode at least six potential virulence factors, emphasizing the importance of bacteriophages in horizontal gene transfer and a possible mechanism for generating new strains with increased pathogenic potential.


Poorly conserved ORFs in the genome of the archaea Halobacterium sp. NRC-1 correspond to expressed proteins.
A large fraction of open reading frames (ORFs) identified as 'hypothetical' proteins correspond to either 'conserved hypothetical' proteins, representing sequences homologous to ORFs of unknown function from other organisms, or to hypothetical proteins lacking any significant sequence similarity to other ORFs in the databases. Elucidating the functions and three-dimensional structures of such orphan ORFs, termed ORFans or poorly conserved ORFs (PCOs), is essential for understanding biodiversity. However, it has been claimed that many ORFans may not encode for expressed proteins. A genome-wide experimental study of 'paralogous PCOs' in the halophilic archaea Halobacterium sp. NRC-1 was conducted. Paralogous PCOs are ORFs with at least one homolog in the same organism, but with no clear homologs in other organisms. The results reveal that mRNA is synthesized for a majority of the Halobacterium sp. NRC-1 paralogous PCO families, including those comprising relatively short proteins, strongly suggesting that these Halobacterium sp. NRC-1 paralogous PCOs correspond to true, expressed proteins. Hence, further computational and experimental studies aimed at characterizing PCOs in this and other organisms are merited. Such efforts could shed light on PCOs' functions and origins, thereby serving to elucidate the vast diversity observed in the genetic material.


Adsorption of colloidal proteins in ion-exchange chromatography under consideration of charge regulation.
Mechanistic modeling of protein adsorption has gained increasing importance in the development of ion-exchange (IEX) chromatography processes. The most common adsorption models use a stoichiometric representation of the adsorption process based on the law of mass action. Despite the importance of these models in model-based development, the stoichiometric representation of the adsorption process is not accurate for the description of long-range electrostatic interactions in IEX chromatography, limiting the application and mechanistic extension of these models. In this work an adsorption model is introduced describing the non-stoichiometric electrostatic interaction in IEX chromatography based on the linear Poisson-Boltzmann equation and a simplified colloidal representation of the protein. In contrast to most recent non-stoichiometric models, the introduced model accounts for charge regulation during the adsorption process. Its capability of describing the adsorption equilibrium is demonstrated by simulating partitioning coefficients of multiple proteins on different adsorber systems as a function of ionic strength and pH. Despite model simplifications the physical meaning and predictive value of the model could be preserved. By transferring model parameters of a monoclonal antibody (mAb) from one adsorber system to another, it could be demonstrated that protein parameters are theoretically not only valid on a specific adsorber system but freely transferable to other adsorbers. The predictive value of the mechanistic model on the new adsorber system was highlighted by predicting the elution behavior of charge variants of the mAb.


[Cardiac implantable devices and physiotherapy practices interaction: myth or real?].
Several reports of negative interactions between physiotherapy practices and cardiac rhythm devices (CRDs) have been described in the literature. In spite of this, there is very little evidence to suggest the extent to which it is safe to use physiotherapy practices in this patient population. Here we summarize the documented interactions between physiotherapy and CRDs, discuss the current standard of practice for treating CRD patients, and outline the main considerations that exist from the arrhythmia service perspective in terms of patient and device factors. Finally, we advocate for a stronger cooperation between physiotherapists and the electrophysiology service team in order to safely and effectively deliver optimal physiotherapy care to CRD patients.


Pharmacological modification of eye growth in normally reared and visually deprived chicks.
Regular injections of the gliotoxins D-alpha-aminoadipic acid and L-alpha-aminoadipic acid were made into the vitreous chamber of the eyes of newly-hatched chicks reared either in a normal visual environment or under conditions of monocular occlusion. Striking differences in the growth rates of the eyes from the different groups were observed. Injection of D-alpha-aminoadipic acid, which causes the Müller glial cells to swell and diminishes the retinal OFF-response, resulted in a marked increase in the rate of axial growth of the eye compared with normal eyes. However, injection of D-alpha-aminoadipic acid into occluded eyes caused a lesser growth rate than was observed in occluded control eyes. By contrast, injection of L-alpha-aminoadipic acid, which also causes severe glial swelling and abolishes the retinal ON-response, caused reduced eye growth in non-occluded eyes. However, injection of L-alpha-aminoadipic acid into occluded eyes caused eye growth in excess of that recorded in the occluded controls. We concluded that the different growth rates observed is more likely a result of the disruption of the neural ON and OFF mechanisms than of the indisposition of the Müller cells.


Effects of high-salt diet on CYP450-4A omega-hydroxylase expression and active tone in mesenteric resistance arteries.
This study investigated the role of changes in the expression of the cytochrome P-450 4A (CYP450-4A) enzymes that produce 20-hydroxyeicosatetraenoic acid (20-HETE) in modulating the responses of rat mesenteric resistance arteries to norepinephrine (NE) and reduced Po(2) after short-term (3-day) changes in dietary salt intake. The CYP450-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR in arteries obtained from rats fed a high-salt (HS, 4% NaCl) diet, whereas only the CYP450-4A3 isoform was detected in vessels from rats fed a low-salt (LS, 0.4% NaCl) diet. Expression of the 51-kDa CYP450-4A protein was significantly increased by a HS diet. Inhibiting 20-HETE synthesis with 30 muM N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE in arteries obtained from rats fed either a LS or HS diet, but NE sensitivity after DDMS treatment was significantly lower in vessels from rats on a HS diet. DDMS treatment also restored the vasodilator response to reduced Po(2) that was impaired in arteries from rats on a HS diet. These findings suggest that 1) a HS diet increases the expression of CYP450-4A enzymes in the mesenteric vasculature, 2) 20-HETE contributes to the vasoconstrictor response to NE in mesenteric resistance arteries, 3) the contribution of 20-HETE to the vasoconstrictor response to NE is greater in rats fed a HS diet than in rats fed a LS diet, and 4) upregulation of the production of 20-HETE contributes to the impaired dilation of mesenteric resistance arteries in response to hypoxia in rats fed a HS diet.


Factor Analysis of Negative Symptom Items in the Structured Interview for Prodromal Syndromes.
Negative symptoms occur early in the clinical high risk (CHR) state and indicate increased risk of conversion to psychotic disorder and poor functional outcome. However, while the negative symptom domain has shown to be parsimoniously explained by a 2-factor construct in schizophrenia, there has yet to be an established factor structure of negative symptoms in CHR. 214 individuals meeting the Structured Interview for Psychosis-Risk Syndromes (SIPS) criteria for CHR were recruited through 3 active research programs in the United States. Exploratory Factor Analysis was conducted on the 6 negative symptom items of the SIPS, and factors were evaluated with respect to functional outcome and depression. Factor analysis indicated a 2-factor hierarchical model with 2 negative symptom dimensions reflecting volition (Occupational Functioning and Avolition) and emotion (Expression of Emotion, Experience of Emotion and Social Anhedonia). Linear Regression showed that the emotion factor was associated with poor social function, and the volition factor was associated with poor role function and depression. Similar to factor solutions identified in adults diagnosed with psychotic disorders, results indicated that the SIPS negative symptom subscale is not a unidimensional construct. Rather, the SIPS negative subscale has 2 distinct factors that have different associations with clinical outcome and should be interpreted independently. Results have significant relevance for informing the valid assessment and conceptual interpretation of early clinical phenomenology in the psychosis prodrome.


Cancer of prostate metastatic to the skin diagnosed by immunoperoxidase staining.
The authors present a case in which the diagnosis of prostate cancer metastatic to the skin was made by skin biopsy with immunoperoxidase stains for prostatic specific antigen and prostatic acid phosphatase. These are tests that should be performed when the location of the primary malignancy is not otherwise evident.


Patient-reported outcomes with subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: the PATH study.
Chronic inflammatory demyelinating polyneuropathy (CIDP) causes weakness which adversely impacts function and quality of life (QOL). CIDP often requires long-term management with intravenous or subcutaneous immunoglobulin. The Polyneuropathy and Treatment with Hizentra® (PATH) study showed that subcutaneous immunoglobulin (SCIG) was efficacious in CIDP maintenance. Here, patient-reported outcomes in patients on SCIG are assessed. Subjects stabilized on intravenous immunoglobulin were randomly allocated to receive weekly 0.2 or 0.4 g/kg bodyweight of 20% SCIG (IgPro20) or placebo. Overall QOL/health status was assessed using the EuroQoL 5-Dimension (EQ-5D) health profile and visual analog scale, treatment satisfaction was assessed with the Treatment Satisfaction Questionnaire for Medicine (TSQM) and work-related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI-GH). The EQ-5D health profile was assessed in terms of the percentage of subjects maintained or improved at week 25 of SCIG therapy on each of the EQ-5D domains versus baseline after intravenous immunoglobulin stabilization. TSQM and WPAI-GH were assessed by median score changes from baseline to week 25. In total, 172 subjects were randomized to placebo (n = 57), 0.2 g/kg IgPro20 (n = 57) and 0.4 g/kg IgPro20 (n = 58). Significantly higher proportions of IgPro20-treated subjects improved/maintained their health status on the EQ-5D usual activities dimension, and in additional dimensions (mobility and pain/discomfort) in sensitivity analyses. TSQM and WPAI-GH scores were more stable with IgPro20 treatment compared with placebo. IgPro20 maintained or improved QOL in most subjects with CIDP, consistent with the PATH study findings that both IgPro20 doses were efficacious in maintaining CIDP.


Long-term incidence of cancer after index treatment for symptomatic peripheral arterial disease - a health insurance claims data analysis.
Background: Cancer as a concomitant condition in symptomatic peripheral arterial disease (PAD) patients could have an impact on further therapy and the long-term prognosis of these patients. Aim of this study was to investigate whether there is an increased incidence of cancer in PAD patients and to quantify the corresponding effect size. Materials and methods: Between January 1st, 2008 and December 31st, 2017, we analysed health insurance claims data from Germany's second-largest insurance fund, BARMER. Symptomatic PAD patients suffering from intermittent claudication (IC) or chronic limb-threatening ischaemia (CLTI) were stratified by gender at index treatment. PAD patients were then followed until an incident cancer diagnosis was recorded. To adjust for age and gender, standardized incidence ratios (SIR) were computed using the 2012 German standard population as reference. Results: 96,528 PAD patients (47% female, 44% IC, mean age 72 years) were included in the current study. When compared to the overall population, female and male PAD patients have a significantly increased risk of incident cancer of the lung (SIR 3.5 vs. 2.6), bladder (SIR 3.2 vs. 4.0), pancreas (SIR 1.4 vs. 1.6), and colon (SIR 1.3 vs. 1.3). During ten years of follow-up, some 7% of males and 4% of females developed lung cancer. For bladder, colon and pancreas cancer, the cumulative hazards were 1% vs. 3.2%, 2.2% vs. 2.8%, and 0.7% vs. 0.9%, respectively. Conclusions: Patients suffering from symptomatic PAD face a markedly higher risk for incident cancer in the long-term follow-up. The cancer risk increased continuously for certain types and PAD was strongly associated with cancer of the lung, bladder, pancreas, and colon. Taking these results into account, PAD patients could benefit from secondary and tertiary screening. These results also emphasize the impact of common risk factors such as tobacco smoke as target for health prevention.


Antiplatelet agents for preventing and treating pre-eclampsia.
Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a platelet-derived vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, and low dose aspirin in particular, might prevent or delay the development of pre-eclampsia. To assess the effectiveness and safety of antiplatelet agents when given to women at risk of developing pre-eclampsia, and to those with established pre-eclampsia. This review drew on the search strategy developed for the Pregnancy and Childbirth Group as a whole. The Cochrane Controlled Trials Register was also searched, The Cochrane Library 1999 Issue 1, Embase was searched from 1994-1999 and hand searches were performed of the congress proceedings of the International and European Societies for the Study of Hypertension in Pregnancy. All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent during pregnancy. Quasi random study designs were excluded. Participants were pregnant women considered to be at risk of developing pre-eclampsia, and those with pre-eclampsia before delivery. Women treated postpartum were excluded. Interventions were any comparisons of an antiplatelet agent (such as low dose aspirin or dipyridamole) with either placebo or no antiplatelet agent. Assessment of trials for inclusion in the review and extraction of data was performed independently and unblinded by two reviewers. Data were entered into the Review Manager software and double checked. Forty two trials involving over 32,000 women were included in this review, with 30,563 women in the prevention trials. There is a 15% reduction in the risk of pre-eclampsia associated with the use of antiplatelet agents [32 trials with 29,331 women; relative risk (RR) 0.85, 95% confidence interval (0.78, 0.92); Number needed to treat (NNT) 89, (59, 167)]. This reduction is regardless of risk status at trial entry or whether a placebo was used, and irrespective of the dose of asprin or gestation at randomisation. Twenty three trials (28,268 women) reported preterm delivery. There is a small (8%) reduction in the risk of delivery before 37 completed weeks [RR 0.92, (0.88, 0.97); NNT 72 (44, 200)]. Baby deaths were reported in 30 trials (30,093 women). Overall there is a 14% reduction in baby deaths in the antiplatelet group [RR 0.86, (0. 75, 0.98); NNT 250 (125, >10000)]. Small for gestational age babies were reported in 25 trials (20,349 women), with no overall difference between the groups, RR 0.92, (0.84, 1.01). There were no significant differences between treatment and control groups in any other measures of outcome. Five trials compared antiplatelet agents with placebo or no antiplatelet agent for the treatment of pre-eclampsia. There are insufficient data for any firm conclusions about the possible effects of these agents when used for treatment of pre-eclampsia. Antiplatelet agents, in this review largely low dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment should be started, and at what dose.


Polymorphonuclear leukocyte activation by a synthetic muramyl dipeptide analog.
N alpha-(N-Acetylmuramyl-L-alanyl-D-isoglutaminyl)-N epsilon -stearoyl-L-lysine, a synthetic derivative of muramyl dipeptide, stimulated the chemotactic mobility, phagocytic activity, and superoxide anion (O2-) productivity of peritoneal polymorphonuclear cells in mice. The chemotactic mobility of both cells preincubated with the adjuvant in vitro and those derived from the mice previously treated with the adjuvant was significantly enhanced. The phagocytic activity of cells preincubated in vitro with the adjuvant was also enhanced transiently, and that of the cells derived from the mice treated subcutaneously with the adjuvant 24 h before intraperitoneal inoculation with Escherichia coli was significantly greater than that of cells from the mice given phosphate-buffered saline instead of the adjuvant. The release of O2- from the cells derived from the adjuvant-treated mice was also greater than that from the cells of untreated control mice. However, the exposure of the cells derived from untreated mice to the adjuvant in vitro did not stimulate O2- generation by the cells.


Uterine adenomyomas excluding atypical polypoid adenomyomas and adenomyomas of endocervical type: a clinicopathologic study of 30 cases of an underemphasized lesion that may cause diagnostic problems with brief consideration of adenomyomas of other female genital tract sites.
We report 30 uterine tumors composed of an admixture of endometrioid glands, endometrioid stroma, and smooth muscle that lacked the characteristic features of atypical polypoid adenomyoma. The patients ranged from 26 to 64 (median 47) years of age. The usual presenting symptom was abnormal vaginal bleeding, which was "massive" in two patients. Six patients were treated by polypectomy only, with hysterectomy performed in the remainder. Twenty-seven adenomyomas were in the corpus (22 submucosal, two mural, and three subserosal) and three in the cervix. The subserosal and submucosal examples were polypoid. The tumors were 0.3 to 17 cm in greatest dimension, and firm with cystic areas often present on sectioning. Focal hemorrhage was described in five cases. On microscopic examination, the tumors were composed of glands and cysts lined by endometrial-type epithelium separated by endometrial stroma and smooth muscle, with smooth muscle predominating. Minor foci of tubal-type epithelium (14 cases), mucinous endocervical-type epithelium (2 cases), and squamous epithelium (1 case) were present. The smooth muscle component was cellular in three cases and contained occasional bizarre nuclei in three cases. The epithelial cells were uniformly bland. No mitotic activity was observed in the epithelial or mesenchymal elements in 20 cases. In the remainder, up to 5 mitotic figures/10 high-power fields were observed in the epithelium (3 cases), the stroma and smooth muscle (3 cases), or both compartments (4 cases). Follow-up in 14 cases revealed no recurrence or extrauterine spread in any case. A diagnosis of adenocarcinoma or adenosarcoma was entertained by the submitting pathologist in five of 14 consultation cases. Adenomyomas are unusual benign uterine tumors that can be misdiagnosed, in part, because the lesion has not often received attention in the literature. The most realistic considerations in the differential diagnosis are atypical polypoid adenomyoma and adenosarcoma. The former, by definition, has epithelial atypia and the latter a malignant (usually low grade) stromal component with typically absent or inconspicuous smooth muscle. Distinction of adenomyoma from adenosarcoma may have significant therapeutic implications, particularly in young women.


Computed tomography of the parapharyngeal space.
The parapharyngeal space is a potential anatomic space of appreciable clinical importance which, because of its location deep within the neck, has historically been difficult to evaluate by physical examination and conventional imaging methods. Computed tomography has provided an important and accurate means of noninvasively defining both the anatomy and pathology of this area. This discussion will initially pertain to the normal anatomy and anatomical relationships of the parapharyngeal space. Traditional methods of imaging will be briefly reviewed but emphasis will be on CT and the most appropriate means of utilization of CT. The more important pathology will be included in order to illustrate the advantages of current imaging techniques.


Clinical, pathological and genetic features of follicular lymphoma grade 3A: a joint analysis of the German low-grade and high-grade lymphoma study groups GLSG and DSHNHL.
Histologically, follicular lymphoma (FL) grades 1, 2 and 3A are composed of two distinct cell types, centroblasts and centrocytes. FL grade 3B is composed only of centroblasts and has been shown to differ in immunophenotype and genetics from FL that contain centrocytes. We aimed to understand the pathogenetic and clinical relation between FL grade 3A to FL grade 1/2 on the one hand and FL grade 3B on the other hand. Trial patients with long-term follow-up and diagnosis of FL grade 3 were selected and samples underwent a second central pathological review using a multiple-observer approach to assess grading. Interobserver variability for diagnosing FL grade 3 was high. FL grade 3A frequently harbored areas of FL grade 1/2 within the same tissue specimen. FL grade 3B rarely coexisted with grade 1/2 or 3A, suggesting divergent pathogenesis. There was no statistically significant difference in outcome between 47 cases of FL grade 3A and 14 cases of grade 3B. Compared with grade 1/2 FL, both groups showed longer progression-free survival without late events, especially after immunochemotherapy; this outcome difference was retained after adjustment for clinical prognostic factors. The subgroup of FL grade 3A with an additional FL grade 1/2 component or a translocation t(14;18) showed a poorer outcome. In contrast, the FL grade 3A lacking t(14;18) and of localized stage resembled the pediatric type of FL and showed a very good outcome. FL3 with MYC breaks showed a poor outcome. The results suggest that first-line immunochemotherapy might allow long-lasting remissions in a subgroup of FL grade 3A similar to diffuse large B-cell lymphoma. Within FL3A, prognostic subgroups can be identified by analyzing for coexisting FL1/2 and MYC breaks.


β1 integrin is critical for the maintenance of antigen-specific CD4 T cells in the bone marrow but not long-term immunological memory.
The long-term maintenance of memory CD4 T cells promotes protective immunity against future pathogen reinfection. As a site rich in survival cytokines, the bone marrow is proposed to be a critical niche for the survival of memory CD4 T cells. We demonstrate that endogenous, polyclonal Ag-specific CD4 T cells rapidly enter and are recovered long-term from the bone marrow following i.v. infection with Listeria monocytogenes. β(1) integrin-deficient CD4 T cells also populate the bone marrow early following an infection, but their numbers in this site rapidly decline. This decline was not caused by increased death of T cells lacking β(1) integrin but rather by reduced retention in the bone marrow after the primary immune response. The loss of memory CD4 T cells from the bone marrow does not lead to a loss of the predominant source of memory CD4 T cells in the spleen or the ability to mount a memory response. Thus, β(1) integrin-dependent maintenance of memory CD4 T cells in the bone marrow is not required for long-term CD4 T cell memory.


Bone marrow biopsy findings in angioimmunoblastic lymphadenopathy.
Bone marrow biopsies from 13 cases of lymph-node-biopsy-proven angioimmunoblastic lymphadenopathy (AILD) were studied. Eight cases (62%) showed a characteristic 'granulomatoid' lymphoreticular infiltrate composed of a mixture of lymphocytes, epithelioid histiocytes, immunoblasts, plasma cells and eosinophils in varying proportions. Proliferation of blood vessels, although much less prominent than that described in lymph nodes, and a marked degree of reticulin fibrosis were also noted. The pattern of involvement was mainly focal and rarely diffuse. The foci were either single or multiple, and were distributed throughout the marrow but were only rarely paratrabecular. The associated haematopoietic marrow findings were nonspecific regardless of degree of bone marrow involvement. The histopathology of involved bone marrows in angioimmunoblastic lymphadenopathy is such that in some cases it should strongly suggest the diagnosis even in the absence of a prior definitive lymph node biopsy. Differentiating features from other disorders that might be confused with AILD are discussed. Survival rate was adversely affected by bone marrow involvement.


Agenesis of the trachea: report of a case and review of the literature.
Immediately after birth, a full-term infant was noted to be in severe respiratory distress and died approximately five hours later, despite resuscitative efforts. Postmortem examination revealed agenesis of the trachea with a 1-mm fistula joining the esophagus and the main stem bronchi at the carina. The right kidney, ureter, Fallopian tube, and cornu of the uterus were also absent. The 25 previously reported cases of agenesis of the trachea are summarized, with special emphasis on associated abnormalities.


Correlation of echocardiographic wall stress and left ventricular pressure and function in aortic stenosis.
Previous studies have suggested that left ventricular pressure (P) can be predicted in patients with aortic stenosis by the equation P = 235 h/r, where 235 is a constant peak wall stress (sigma), h is end-systolic wall thickness, and r is end-systolic dimension/2; h and r are measured by M-mode echocardiography. In 73 patients with aortic stenosis (valve area less than 0.7 cm2), measured and predicted left ventricular pressure correlated poorly (r = 0.17). The measured wall stress in our patients varied from 120 to 250 mm Hg in patients with normal left ventricular function and from 250 to 550 mm Hg in patients with abnormal function. The correlation between sigma and h was only fair (r = 0.53), because many patients had inappropriate left ventricular hypertrophy. There was a statistically significant correlation between ejection fraction and sigma (r = 0.62) and between ejection fraction and end-systolic dimension (r = -0.70), but there was considerable scatter of ejection fractions for any given end-systolic dimension. We conclude that sigma is not constant in aortic stenosis, and the use of a constant sigma to predict left ventricular pressure is unreliable; inappropriate left ventricular hypertrophy may explain why sigma is not constant. M-mode echocardiography is not reliable in assessing the severity of aortic stenosis in adults; such assessment requires precise measurements of pressure gradients and flow by cardiac catheterization.


Machine learning algorithms for a novel cuproptosis-related gene signature of diagnostic and immune infiltration in endometriosis.
Endometriosis (EMT) is an aggressive disease of the reproductive system, also called "benign cancer". However, effective treatments for EMT are still lacking in clinical practice. Interestingly, immune infiltration is significantly involved in EMT pathogenesis. Currently, no studies have shown the involvement of cuproptosis-related genes (CRGs) in regulating immune infiltration in EMT. This study identified three CRGs such as GLS, NFE2L2, and PDHA1, associated with EMT using machine learning algorithms. These three CRGs were upregulated in the endometrium of patients with moderate/severe EMT and downregulated in patients with infertility. Single sample genomic enrichment analysis (ssGSEA) revealed that these CRGs were closely correlated with autoimmune diseases such as systemic lupus erythematosus. Furthermore, these CRGs were correlated with immune cells such as eosinophils, natural killer cells, and macrophages. Therefore, profiling patients based on these genes aid in a more accurate diagnosis of EMT progression. The mRNA and protein expression levels of GLS, NFE2L2 and PDHA1 were validated by qRT-PCR and WB studies in EMT samples. These findings provide a new idea for the pathology and treatment of endometriosis, suggesting that CRGs such as GLS, NFE2L2 and PDHA1 may play a key role in the occurrence and development of endometriosis.


Real-time insight into nanostructure evolution during the rapid formation of ultra-thin gold layers on polymers.
Ultra-thin metal layers on polymer thin films attract tremendous research interest for advanced flexible optoelectronic applications, including organic photovoltaics, light emitting diodes and sensors. To realize the large-scale production of such metal-polymer hybrid materials, high rate sputter deposition is of particular interest. Here, we witness the birth of a metal-polymer hybrid material by quantifying in situ with unprecedented time-resolution of 0.5 ms the temporal evolution of interfacial morphology during the rapid formation of ultra-thin gold layers on thin polystyrene films. We monitor average non-equilibrium cluster geometries, transient interface morphologies and the effective near-surface gold diffusion. At 1 s sputter deposition, the polymer matrix has already been enriched with 1% gold and an intermixing layer has formed with a depth of over 3.5 nm. Furthermore, we experimentally observe unexpected changes in aspect ratios of ultra-small gold clusters growing in the vicinity of polymer chains. For the first time, this approach enables four-dimensional insights at atomic scales during the gold growth under non-equilibrium conditions.


Nurses' and Physicians' Perceptions of Indwelling Urinary Catheter Practices and Culture in Their Institutions.
Indwelling urinary catheters (IUCs) are commonly used devices in acute care that may lead to catheter-associated urinary tract infections or noninfectious complications. Responsibilities for IUC are usually shared between nurses and physicians, and a common mental model among the two professional groups is thus essential for a successful reduction in catheter use. The aim of this study was to determine variation in the perceptions of current practices and culture regarding IUC use between these two groups. Nurses and physicians (N = 1579) from seven Swiss hospitals completed a written survey on safe IUC use in their institution. The survey assessed participant's perceptions of current practices and culture in their institution, and their perceived responsibilities related to IUC care. t tests and logistic regression were used to examine differences in responses between physicians and nurses. Nurses and physicians each have their own tasks but also share responsibilities for catheter placement, care, and removal. Overall, nurses were more positive than physicians about current practices and culture regarding IUC use within their institution (mean scale scores = 5.4 for nurses versus 5.1 for physicians, P < 0.001). Perceptions of the two professional groups diverged most strongly on practices to avoid unnecessary placement of IUCs, the presence of shared values and attitudes in support of restrictive catheter use, and the other group's leadership commitment. Indwelling urinary catheter management is a strong interprofessional domain and a shared responsibility. It is crucial that measures to raise awareness and to communicate new standards target both nurses and physicians and are discussed in interprofessional formats.


Altering the nucleophile specificity of a protein-tyrosine phosphatase-catalyzed reaction. Probing the function of the invariant glutamine residues.
Protein-tyrosine phosphatases (PTPases) catalysis involves a cysteinyl phosphate intermediate, in which the phosphoryl group cannot be transferred to nucleophiles other than water. The dual specificity phosphatases and the low molecular weight phosphatases utilize the same chemical mechanism for catalysis and contain the same (H/V)C(X)5R(S/T) signature motif present in PTPases. Interestingly, the latter two groups of phosphatases do catalyze phosphoryl transfers to alcohols in addition to water. Unique to the PTPase family are two invariant Gln residues which are located at the active site. Mutations at Gln-446 (and to a much smaller extent Gln-450) to Ala, Asn, or Met (but not Glu) residues disrupt a bifurcated hydrogen bond between the side chain of Gln-446 and the nucleophilic water and confer phosphotransferase activity to the Yersinia PTPase. Thus, the conserved Gln-446 residue is responsible for maintaining PTPases' strict hydrolytic activity and for preventing the PTPases from acting as kinases to phosphorylate undesirable substrates. This explains why phosphoryl transfer from the phosphoenzyme intermediate in PTPases can only occur to water and not to other nucleophilic acceptors. Detailed kinetic analyses also suggest roles for Gln-446 and Gln-450 in PTPase catalysis. Although Gln-446 is not essential for the phosphoenzyme formation step, it plays an important role during the hydrolysis of the intermediate by sequestering and positioning the nucleophilic water in the active site for an in-line attack on the phosphorus atom of the cysteinyl phosphate intermediate. Gln-450 interacts through a bound water molecule with the phosphoryl moiety and may play a role for the precise alignment of active site residues, which are important for substrate binding and transition state stabilization for both of the chemical steps.


Association of Interferon Lambda 3 and 4 Gene SNPs and Their Expression with COVID-19 Disease Severity: A Cross-Sectional Study.
Expression and certain SNPs of interferon lambda 3 and 4 (IFNL3 and 4) have been associated with variable outcomes in COVID-19 patients in different regions, suggesting population-specific differences in the disease outcome. This study examined the association of INFL3 and INFL4 SNPs (rs12979860 and rs368234815, respectively) and nasopharyngeal expression with COVID-19 disease severity in Pakistani patients. For this study, 117 retrospectively collected nasopharyngeal swab samples were used from individuals with mild and severe COVID-19 disease. qPCR assays were used to determine the viral loads and mRNA expression of IFNL3 and 4 through the Ct and delta Ct methods, respectively. Due to funding limitations, only one SNP each in INFL3 and INFL4 (found to be most significant through literature search) was analyzed using tetra-arm PCR and RFLP-PCR strategies, respectively. The Mann-Whitney U-test was applied to evaluate the statistical differences in the expression of IFNL3/4 genes in the mild and severe groups, while for SNPs, a Chi-square test was employed. A multivariate Cox regression test was performed to assess the relationship of different variables with COVID-19 severity. Comparative analysis of SNPs between mild and severe groups showed only the difference in SNP of the IFNL4 gene to be statistically significant (p = 0.001). Similarly, nasopharyngeal expression of IFNL3 and IFNL4 genes, respectively, was found to be 3.48-fold less and 3.48-fold higher in the severe group as compared to the mild group. Multivariate analysis revealed SNP in the IFNL4 gene and age to have a significant association with COVID-19 severity. Despite the small sample size, IFNL4 gene SNP and patient age were associated with COVID-19 severity. Age, IFNL3/IFNL4 mRNA expression in the nasopharyngeal milieu, and the presence of SNP in the IFNL4 (rs368234815) gene in COVID-19 patients may be biomarkers for infection severity and help improve SARS-CoV-2 infection management.


High-resolution microwave spectroscopic and ab initio studies of propanoic acid and its hydrates.
High-resolution microwave spectra of the propanoic acid monomer (PPA) and two of its hydrates, the PPA-(H2O) and the PPA-(H2O)2, were recorded using a pulsed nozzle Fourier transform microwave spectrometer. The rotational and centrifugal distortion constants of these species were determined. Agreements between the experimental and ab initio results of these constants, and of the planar moment of inertia, the dipole moments, and the orientation of the PPA relative to the H2O confirm the geometry of the hydrates, i.e. H2O binds to the carboxylic group of PPA and forms hydrogen-bonded ring complexes. The equilibrium constant and the change of entropy and enthalpy for the formation of PPA-(H2O) were also derived, based on the calculation of partition functions, to evaluate the abundance of this monohydrate in the troposphere.


Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring.
To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1 (rs2031920, rs3813867) polymorphisms involved in caffeine metabolism. In 90 pregnant women who gave birth to 98 preterm neonates, self-informed caffeine ingestion rate was 97%, laboratory confirmed rate was 93 %. Theobromine was the predominant metabolite found. Consumption of acetaminophen correlated significantly with changes in caffeine metabolism (acetaminophen R2 = 0.637, p = 0.01) due to activation of CYP2E1 alternate pathways. The main caffeine source was cola soft drinks. Environmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.


Effects of freezing on thermoluminescence in various plant species.
The aim of this study was to monitor the effect of sudden frost on the photosynthetic electron transport chain in the leaves of various plant species using the thermoluminescence (TL) technique. A short period of freezing caused a decrease in the afterglow (AG) band in young maize leaves, with a slight upshift in the maximum temperature. The B band induced by far-red (FR) illumination started to decrease at a significantly lower temperature. The flash-induced B band also showed a substantial decrease in intensity after short preliminary freezing. In contrast to other species, for which there was always a well-detectable TL signal even after relatively drastic freezing, there was no TL signal at all in geranium below a threshold temperature. The behavior of the FR-induced TL curve in cucumber plants was a mixture of that found in wheat or pea, on the one hand, and maize, on the other: the AG band gradually decreased with decreasing temperature and finally totally disappeared, as in maize. The FR-induced B band showed an upshift after freezing. These results suggest that AG is a normal component of TL bands induced not only by FR, but also by single turnover flash.


Outcomes of Concurrent Breast and Gynecologic Risk Reduction Surgery.
Women considering risk reduction surgery after a diagnosis of breast/ovarian cancer and/or inherited cancer gene mutation face difficult decisions. The safety of combined breast and gynecologic surgery has not been well studied; therefore, we evaluated the outcomes for patients who have undergone coordinated multispecialty surgery. We conducted a retrospective review of patients undergoing simultaneous breast and gynecologic surgery for newly or previously diagnosed breast cancer and/or an inherited cancer gene mutation during the same anesthetic at a single institution from 1999 to 2013. Seventy-three patients with a mean age of 50 years (range 27-88) were identified. Most patients had newly diagnosed breast cancer or ductal carcinoma in situ (62 %) and 28 patients (38 %) had an identified BRCA mutation. Almost all gynecologic procedures were for risk reduction or benign gynecologic conditions (97 %). Mastectomy was performed in 39 patients (53 %), the majority of whom (79 %) underwent immediate reconstruction. The most common gynecologic procedure involved bilateral salpingo-oophorectomy, which was performed alone in 18 patients (25 %) and combined with hysterectomy in 40 patients (55 %). A total of 32 patients (44 %) developed postoperative complications, most of which were minor and did not require surgical intervention or hospitalization. Two of the 19 patients who underwent implant reconstruction (11 %; 3 % of the entire cohort) had major infectious complications requiring explantation. Combined breast and gynecologic procedures for a breast cancer diagnosis and/or risk reduction in patients can be accomplished with acceptable morbidity. Concurrent operations, including reconstruction, can be offered to patients without negatively impacting their outcome.


A novel intestinal anastomotic device in a porcine model.
The purpose of this study was to evaluate a novel, intraluminally deployed anastomotic device (AD). A survival study was conducted in 18 farm pigs. One early subject was excluded and replaced due to premature expiration. Six animals were placed in 1 of 3 cohorts, with euthanasia and AD explantation planned at 2, 4, and 6 weeks. A distal small intestinal side-side [functional end-end] anastomosis using the AD was performed via midline laparotomy. Fluoroscopy with double-contrast dilute barium and burst pressure measurements were performed in 4 animals in each group. Two animals in each cohort underwent fluoroscopy without contrast and resection for histology. Mucosal healing, inflammation, anastomotic alignment of the muscularis propria, and fibrosis were graded on a 4-point scale. All animals survived to the date of planned euthanasia except the excluded subject, who expired from causes unrelated to the device. Normal weight gain was seen in all. Sixteen of 18 devices sloughed prior to extraction without evidence of injury or obstruction during the survival period or at necropsy. Filling pressures of >200 mm Hg were reached; no leakage was seen. Mucosal healing and continuity were graded good to excellent at 2 weeks and excellent at 4 and 6 weeks. Inflammation improved with time, with moderate change at 2 weeks and mild at 6 weeks. Anastomotic fibrosis was mild at 2 weeks, mild to minimal at 4 weeks, and minimal at 6 weeks. The anastomotic alignment was 100 per cent except in 1 animal at 2 weeks with >50 per cent but <100 per cent alignment. The AD resulted in a stable, functional anastomosis without narrowing. All tested anastomoses withstood supraphysiologic insufflation pressures without evidence of disruption. The applicability of this novel device will be explored for use in other gastrointestinal and biliary anastomoses using minimally invasive deployment techniques.


Suicide attempts in schizophrenia: the role of command auditory hallucinations for suicide.
We examined the presence of command auditory hallucinations for suicide (CAHS) in a sample of individuals with schizophrenia or schizoaffective disorder. We examined the relationship between CAHS and demographic and clinical variables. We also investigated the relationship between CAHS and suicide attempts. 100 individuals with DSM-IV schizophrenia or schizoaffective disorder hospitalized on an inpatient research unit participated. Information was gathered using the Diagnostic Interview for Genetic Studies and the Harkavy Asnis Suicide Scale. Data were gathered from 1995 to 2001. CAHS were frequent in this sample (22%), as were suicide attempts (33%). Eight percent of the entire sample (36% of those who experienced CAHS) made at least 1 suicide attempt in response to the hallucinations. The presence of CAHS was not related to demographic or clinical measures assessed. The frequency of CAHS was not statistically different for suicide attempters (30%) and nonattempters (18%). However, 80% (8/10) of attempters with CAHS reported at least 1 attempt in response to CAHS. Three of 6 repeat attempters who made at least 1 suicide attempt in response to CAHS also made other attempts that were not in response to CAHS. The presence of CAHS was not associated with a history of depression or substance abuse/dependence. The presence of CAHS does not directly predict suicide attempts. However, individuals who are already at risk for suicidal behavior (e.g., past attempters) may be at increased risk for a suicide attempt when experiencing CAHS.


Occurrence of parent-reported food hypersensitivities and food allergies among children aged 1-4 yr.
Food allergies (FAs) and hypersensitivities (FHSs) have rarely been studied in large unselected child populations. This population-based cross-sectional survey estimated the occurrence of FHS as perceived by parents and that of FA diagnosed by a physician among children aged 1-4 yr in south-eastern Finland. Before the scheduled annual follow-up visit to the local child health clinic, the parents of children who were born between 1 April, 2001 and 31 March, 2005, and living in the Province of South Karelia (data from Finnish Population Register) were mailed a questionnaire containing items on the child's background, physician-diagnosed FAs and FHSs perceived by the parents. The questionnaires were returned during the visit. Three thousand three hundred and eight (69%) out of the 4779 questionnaires were returned. The lifetime prevalence of physician-diagnosed FAs was 9%. In an additional 21%, FHSs were perceived by the parents only. In a further 19% at least one food item had been eliminated from the diet without any perception of symptoms, this proportion having a downward trend by age. Physician-diagnosed FAs were more common in boys than in girls. Cow's milk was the most commonly reported cause of food-associated symptoms (13% of all children). One-third of the children aged 1-4 yr suffered from food-associated symptoms, and in an additional fifth at least one food item had been eliminated from their diet, implying that every other child had possibly been subjected to some form of elimination diet.


Effect of tadalafil on male lower urinary tract symptoms: an integrated analysis of storage and voiding international prostate symptom subscores from four randomised controlled trials.
The international prostate symptom score (IPSS) evaluates lower urinary tract symptoms (LUTS) in men with suspected benign prostatic hyperplasia (BPH); the total score does not differentiate between storage and voiding and is unevenly weighted (four questions [57%] on voiding, three questions [43%] on storage). To evaluate the relative contributions of storage and voiding IPSS subscores to total IPSS at baseline and in response to treatment with tadalafil. Integrated analysis of data from four placebo-controlled, 12-wk studies of tadalafil (5mg once daily) in 1499 men with LUTS/BPH. Relationships between total IPSS and the storage and voiding subscores were assessed using graphical exploration and linear regression modelling. Linear modelling was performed for the baseline and endpoint and for changes in subscores. The optimal storage subscore to total IPSS (S:T) ratio for IPSS improvement was identified using nonparametric regression and gradient-descent optimisation. The contribution of storage and voiding subscores at baseline and endpoint was 38.8% and 61.2%, and 39.2% and 60.7%, respectively. This intuitive 40:60 storage-to-voiding ratio was similar at baseline and endpoint by treatment group and for changes in subscores, but spanned the entire range for individuals. Changes in total IPSS were greatest for a storage subscore percentage contribution to total IPSS of 42.7%. There was no statistical association between S:T ratio (≥ 40% vs < 40%) at baseline and response to tadalafil. The main limitation was the use of unvalidated storage and voiding IPSS subscores. A constant S:T ratio of 4:10 was observed at baseline and endpoint. The greatest effect on total IPSS was noted for an S:T percentage contribution of 42.7%. Tadalafil efficacy was unaffected by the level of storage dysfunction at baseline. This analysis shows that for men with BPH, improvements during treatment with tadalafil apply to both storage and voiding symptoms at a constant ratio. The extent of storage dysfunction before treatment did not affect the response to treatment.


Genotoxicity of metal ions: chemical insights.
The purpose of this review is to provide a reader with a brief account of current results and views in the area of genotoxicity of metal ions, with a special attention to underlying chemical mechanisms. The text is divided into six sections. Following a general introduction in Section 1, Section 2 describes main molecular mechanisms of formation of genotoxic lesions: hydrolysis, alkylation, and radical reactions of nucleobases and the phosphosugar DNA backbone. The basics of cellular repair of DNA lesions are also shortly presented. This section serves as a background source for Sections 3, 4, and 5. Section 3 covers the main mechanisms of metal ion genotoxicity, followed by Section 4, which describes genotoxicity of individual metals; i.e., of the confirmed carcinogens As, Be, Cd, Cr, and Ni, as well as of the suspected carcinogens Co, Cu, Fe, Pb, Pt, and 238U (also known as depleted uranium). The genotoxicity of exposures to metal mixtures is also discussed. Section 5 provides a critical overview of methodologies used for studying mutagenicity and carcinogenicity of metals; the final Section 6 summarizes the current state and future perspectives of research in genotoxic mechanisms of metal ions.


Plasma catecholamines and cardiovascular responses during converting enzyme inhibition in normotensive and hypertensive man.
The hemodynamic and plasma catecholamine responses to isometric exercise and head up tilt were investigated in normotensive and hypertensive subjects during normal and low sodium intake and before and during the administration of the converting enzyme inhibitors teprotide or captopril. Although teprotide and captopril decreased significantly the mean arterial pressure during both sodium intakes the normal pattern of hemodynamic response to hand grip and head up tilt was preserved. Moreover changes of plasma catecholamines during hand grip and head up tilt were not affected either by teprotide or captopril. When following the administration of teprotide or captopril fainting occurred either in the seated position or during head up tilt it was associated not only with a decrease in arterial pressure but also with a concurrent reduction in cardiac output and/or hypovolemia. It is concluded that converting enzyme inhibition does not impair significantly the cardiovascular responses which are mediated via the sympathetic nervous system either in normotensive or in hypertensive subjects.


Income and fertility: the elusive relationship.
This paper uses longitudinal data for 1962-1977 to examine the relationship of husband's income to 1962 expected fertility to final parity, and to the discrepancy between initial expectations and final parity, separately for four groups of women who in 1962 either had just given birth to a first, second, or fourth child or had just been married. Although economic reasons frequently were cited in 1977 for downward revisions in family size goals, husband's income was not positively related to fertility in three of the four parity groups. For the merged sample, excluding women with unwanted births, husband's income showed a small positive relationship to completed fertility.


[Clinico-epidemiologic aspects of myasthenia in the Georgian SSR].
A study of 161 myasthenic patients (91 women, 70 men) living in Georgia has shown that the incidence of myasthenia (M) in this republic is 3.2 per 100,000. A generalized form of M with bulbar disorders occurred most frequently (45.3%). A later onset of the disease (from 46-50 years of age) was observed in males. In women three peaks of disease onset could be determined (from 16 to 20, from 26 to 30 and 41 to 45 years of age). It is suggested that the process of urbanization of the population and urban living conditions (a high intensity of psychoemotional loads, environmental pollution, etc.) affect the development of the disease. Among signs that can be helpful in doubtful cases, the author cites the origin of the patient from places with a low relief, a comparatively dry climate, elevated mineralization of underground water and also coincidence of the time of their appearance with the "age peaks" characteristic of myasthenia patients in Georgia.


[Determining an appropriate scheme for "Quitline" in Japan].
"Quitline" is a telephone helpline that advises smokers who are contemplating quitting. Many countries, including East Asian countries, have been conducting nationwide quitline services; however, this has not been conducted in Japan. The aim of this study was to characterize quitline services abroad and review their efficacy in helping smokers quit, in order to determine an appropriate scheme for Japan. We investigated the present condition of quitline in Australia, New Zealand, Korea, Hong Kong, Singapore, Taiwan, Thailand, the United States, and the United Kingdom, focusing on its modalities. Subsequently, we searched "Medline"and "Cochrane Database of Systematic Review"using free text terms of "hotlines"and "smoking cessation"to review the efficacy of the modalities used by the quitline services. Relevant articles from the reference lists were also identified. In Asia Pacific countries, various tools were used by the quitline services, including a quit booklet, website, mobile phone service, and e-mail. Some of these countries conducted proactive counseling by a quitline counselor. There have been several meta-analyses and randomized-control trials showing the efficacy of individually tailored materials in quitline services. To introduce an effective quitline service in Japan, it is desirable to provide individually tailored materials. In addition, as Japanese smokers can easily access smoking cessation advice in hospitals, health check-up settings, and pharmacies, quitline services should be connected with this infrastructure. To introduce an effective nationwide quitline service in Japan, it is necessary to provide various individually tailored materials that complement the smoking cessation infrastructure.


Facilitation of penicillin haptenation to serum proteins.
Traditionally, penicillin binding to serum proteins was believed to be a passive chemical process; however, it appears to be facilitated by serum factors. The objectives of this in vitro investigation were to examine facilitated penicillin haptenation, to study the kinetics of haptenation, and to determine the nature of haptenation-facilitating factors. The model involved addition of [3H]benzylpenicillin to serum or albumin solutions (at pH 7.3 to 7.4) and incubation at 37 degrees C for up to 72 h. The extent of penicillin binding to proteins in serum was found to be four- to fivefold higher than with solutions having comparable concentrations of purified albumin, total protein, or total immunoglobulin. Ultrafiltration of serum reduced penicillin binding to serum proteins substantially. An ultrafiltrable haptenation-facilitating factor(s) was found to be less than 0.5 kDa but was not calcium or magnesium. Finally, the extent of penicillin binding was related to albumin purity, as binding substantially increased with albumin purity. These findings suggest that there is a factor(s) in serum that facilitates covalent binding of penicillin to serum proteins. The factor(s) can be removed and then restored to increase penicillin binding to albumin. It appears that at least one component of the facilitation factor is less than 0.5 kDa, which suggests that it is not a peptide and that it is some simple serum component other than calcium or magnesium.


Small businesses and the Affordable Care Act of 2010.
The Patient Protection and Affordable Care Act (ACA) includes several short- and long-term provisions designed to help small businesses pay for and maintain health insurance for their workers, and to allow workers without employer coverage to gain access to affordable, comprehensive health insurance. Provisions include a small business tax credit to offset premium costs for firms that offer coverage starting this taxable year, establishment of state-based insurance exchanges that promise to lower administrative costs and pool risk more broadly, and creation of new market rules and an essential benefit standard to protect small firms and their workers. Analysis shows that up to 16.6 million workers are in firms that would be eligible for the tax credit in 2010 to 2013. Over the next 10 years, small businesses and organizations could receive an estimated $40 billion in federal support through the premium credit program.


Exacerbation of the 2013-2016 Pan-Caribbean Drought by Anthropogenic Warming.
The Caribbean islands are expected to see more frequent and severe droughts from reduced precipitation and increased evaporative demand due to anthropogenic climate change. Between 2013 and 2016, the Caribbean experienced a widespread drought due in part to El Niño in 2015-2016, but it is unknown whether its severity was exacerbated by anthropogenic warming. This work examines the role of recent warming on this drought, using a recently developed high-resolution self-calibrating Palmer Drought Severity Index data set. The resulting analysis suggest that anthropogenic warming accounted for ~15-17% of the drought's severity and ~7% of its spatial extent. These findings strongly suggest that climate model projected anthropogenic drying in the Caribbean is already underway, with major implications for the more than 43 million people currently living in this region.


Persistent high self-focus after failure and low self-focus after success: the depressive self-focusing style.
Two studies were conducted to assess the spontaneous self-focusing tendencies of depressed and nondepressed individuals after success and failure. Based on a self-regulatory perseveration theory of depression, it was expected that depressed individuals would be especially high in self-focus after failure and low in self-focus after success. The results of Experiment 1 suggested that immediately after an outcome, both depressed and nondepressed individuals are more self-focused after failure than after success. This finding led us to hypothesize that differences between depressed and nondepressed individuals in self-focus following success and failure emerge over time. Specifically, immediately following an outcome, both types of individuals self-focus more after failure because of self-regulatory concerns. However, over time, depressed individuals persist in higher levels of self-focus after failure than after success, whereas nondepressed individuals shift to the opposite, more hedonically beneficial pattern. The results of Experiment 2 provided clear support for these hypotheses. Theoretical implications of these results were discussed.


FDG-PET in Cotard syndrome before and after treatment: can functional brain imaging support a two-factor hypothesis of nihilistic delusions?
Introduction: Cotard syndrome is a neuropsychiatric entity recognised by the presence of nihilistic delusions. Although different models have been proposed for the development of monothematic delusions, including Cotard syndrome, functional neuroanatomical models are lacking.Methods: A case report of a 19-year old male with autoimmune encephalitis and Cotard syndrome, in whom Positron Emission Tomography (18F-FDG-PET) scans were performed before and after successful treatment with electroconvulsive therapy (ECT), is presented. Literature review on brain imaging is provided to discuss a functional neuroanatomical model of Cotard syndrome, in accordance with the two-factor theory of delusions.Results: The patient's 18F-FDG-PET showed marked insular and prefrontal metabolic abnormalities. Except for insular hypometabolism, metabolic abnormalities improved after ECT. Previously reported structural neuroimaging studies in Cotard syndrome showed a predominance of right hemisphere lesions, in which frontal lobes were more frequently involved, followed by parietal and temporal lesions. Functional neuroimaging studies reported abnormalities in frontoparietal circuits as well as midline structures included in the "default mode network".Conclusions: Abnormalities in the functioning of the insular cortex and the prefrontal cortex could be related to the development of nihilistic delusions when a two-factor theory of delusions is considered.


A statistical approach for inferring the 3D structure of the genome.
Recent technological advances allow the measurement, in a single Hi-C experiment, of the frequencies of physical contacts among pairs of genomic loci at a genome-wide scale. The next challenge is to infer, from the resulting DNA-DNA contact maps, accurate 3D models of how chromosomes fold and fit into the nucleus. Many existing inference methods rely on multidimensional scaling (MDS), in which the pairwise distances of the inferred model are optimized to resemble pairwise distances derived directly from the contact counts. These approaches, however, often optimize a heuristic objective function and require strong assumptions about the biophysics of DNA to transform interaction frequencies to spatial distance, and thereby may lead to incorrect structure reconstruction. We propose a novel approach to infer a consensus 3D structure of a genome from Hi-C data. The method incorporates a statistical model of the contact counts, assuming that the counts between two loci follow a Poisson distribution whose intensity decreases with the physical distances between the loci. The method can automatically adjust the transfer function relating the spatial distance to the Poisson intensity and infer a genome structure that best explains the observed data. We compare two variants of our Poisson method, with or without optimization of the transfer function, to four different MDS-based algorithms-two metric MDS methods using different stress functions, a non-metric version of MDS and ChromSDE, a recently described, advanced MDS method-on a wide range of simulated datasets. We demonstrate that the Poisson models reconstruct better structures than all MDS-based methods, particularly at low coverage and high resolution, and we highlight the importance of optimizing the transfer function. On publicly available Hi-C data from mouse embryonic stem cells, we show that the Poisson methods lead to more reproducible structures than MDS-based methods when we use data generated using different restriction enzymes, and when we reconstruct structures at different resolutions. A Python implementation of the proposed method is available at http://cbio.ensmp.fr/pastis.


Length of Stay per Total Body Surface Area Burn Relative to Mechanism: A Pediatric Injury Quality Improvement Collaborative Study.
Studies on length of stay (LOS) per total body surface area (TBSA) burn in pediatric patients are often limited to single institutions and are grouped in ranges of TBSA burn which lacks specific detail to counsel patients and families. A LOS to TBSA burn ratio of 1 has been widely accepted but not validated with multi-institution data. The objective of this study is to describe the current relationship of LOS per TBSA burn and LOS per TBSA burn relative to burn mechanism with the use of multi-institutional data. Data from the Pediatric Injury Quality Improvement Collaborative (PIQIC) were obtained for patients across five pediatric burn centers from July 2018 to September 2020. LOS per TBSA burn ratios were calculated. Descriptive statistics and generalized linear regression which modeled characteristics associated with LOS per TBSA ratio are described. Among the 1267 pediatric burn patients, the most common mechanism was scald (64%), followed by contact (17%) and flame (13%). The average LOS/TBSA burn ratio across all cases was 1.2 (SD = 2.1). In adjusted models, scald burns and chemical burns had similar LOS/TBSA burn ratios of 0.8 and 0.9, respectively, whereas all other burns had a significantly higher LOS/TBSA burn ratio (p<0.0001). LOS/TBSA burn ratios were similar across races, although Hispanics had a slightly higher ratio at 1.4 days. These data establish a multi-institution LOS per TBSA ratio across PIQIC centers and demonstrate a significant variation in the LOS per TBSA burn relative to the burn mechanism sustained.


Clinical management of infections caused by Enterobacteriaceae that express extended-spectrum β-lactamase and AmpC enzymes.
The production of β-lactamase is the principal mechanism by which gram-negative bacteria resist the action of β-lactam antibiotics. In recent decades, there has been an alarming explosion in the diversity, global dissemination, host range, and spectrum of activity of β-lactamases. This has been most clearly reflected by the marked increase in infections caused by bacteria that express extended-spectrum β-lactamases (ESBLs). Some bacterial species possess chromosomally encoded broad-spectrum cephalosporinases (AmpC) that may be expressed at high level by mutational loss of regulatory genes and are intrinsic in some common Enterobacteriaceae, such as Enterobacter spp. Recently, high-level AmpC production has also been seen in new species such as Escherichia coli via plasmid acquisition. ESBL and AmpC producers present challenges to susceptibility testing and the selection of appropriate antimicrobial therapy. This review describes the current global epidemiology of ESBL producers, examines reported risk factors for infections caused by gram-negative bacteria that express ESBL or AmpC enzymes, and discusses the options for antimicrobial therapy, including "re-discovered" older antibiotics and novel agents in development.


Controlled release of simvastatin from biomimetic β-TCP drug delivery system.
Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin.


Green Stimulus in a Post-pandemic Recovery: the Role of Skills for a Resilient Recovery.
As nations struggle to restart their economy after COVID-19 lockdowns, calls to include green investments in a pandemic-related stimulus are growing. Yet little research provides evidence of the effectiveness of a green stimulus. We begin by summarizing recent research on the effectiveness of the green portion of the 2009 American Recovery and Reinvestment Act on employment growth. Green investments are most effective in communities whose workers have the appropriate "green" skills. We then provide new evidence on the skills requirements of both green and brown occupations, as well as from occupations at risk of job losses due to COVID-19, to illustrate which workers are most likely to benefit from a pandemic-related green stimulus. We find similarities between some energy sector workers and green jobs, but a poor match between green jobs and occupations at risk due to COVID-19. Finally, we provide suggestive evidence on the potential for job training programs to help ease the transition to a green economy.


[Features of the innervation of fascia and their microcirculatory bed in the rat].
By means of silver impregnation, methylene blue staining and using glyoxylic acid, the neural apparatus of the muscle fasciae in the shoulder girdle and back and their microcirculatory bed have been revealed in laboratory white rats. An uneven concentration of neuronal terminals makes the base of neurotissue interactions of the muscle fasciae of the shoulder girdle and the back of the rats. Only a small part of microvessels possesses neural elements. The fasciae and their microvessels are innervated both by sensitive and sympathetic neural fibers and their endings; they differ from each other morphologically and histochemically. The rat fasciae are useful objects for vital observations for behaviour both of the vascular nerves and the avascular areas.


X-ray crystallography and NMR reveal complementary views of structure and dynamics.
X-ray crystallography and nuclear magnetic resonance spectroscopy are not competing techniques, but rather they complement each other. Taken together they can provide an atomic detail picture of macromolecular structure and dynamics which can be used to obtain an understanding of life processes at the molecular level.


The androgenic regulation of prostate proteins with a high affinity for deoxyribonucleic acid. Evidence for a prostate deoxyribonucleic acid-unwinding protein.
1. When testosterone is injected into castrated rats in vivo, a significant increase in the incorporation of [35S]methionine into prostate proteins may be detected under conditions in vitro. 2. Studies based on DNA-cellulose chromatography show that the synthesis of prostate proteins with a high affinity for DNA is particularly enhanced by androgenic stimulation. 3. These changes in protein synthesis are negated when the anti-androgen, cyproterone acetate, is administered concomitantly with testosterone in vivo. 4. Two assays were developed for measuring the strand separation of prostate DNA; first, the retention of 3H-labelled native DNA on nitrocellulose membranes, and second, the activation of native DNA as a template for 9S prostate DNA polymerase. On the basis of these criteria, DNA-unwinding activity is present in the prostate gland and it is regulated by androgens in a steroid-and tissue-specific manner. 5. The results are discussed in the context of the mechanism of action of androgens, particularly since the changes provoked in DNA-unwinding activity by androgens precede the onset of DNA replication and mitosis.


Mindfulness-based stress reduction triggers a long-term shift toward more positive appraisals of emotional ambiguity.
Reducing negative impacts of stress, for example through mindfulness training, benefits physical and psychological well-being and is becoming ever more crucial owing to large-scale societal uncertainties (e.g., COVID-19). Whereas extensive research has focused on mindfulness-related reductions in self-reported negativity, essentially no research has targeted task-based behavioral outcomes throughout long-term mindfulness trainings. Responses to emotionally ambiguous signals (e.g., surprised expressions), which might be appraised as either positive or negative, provide a nuanced assessment of one's emotional bias across diverse contexts, offering unique leverage for assessing the effects of mindfulness. Here, we compared the effects of short- and long-term training via Mindfulness-Based Stress Reduction on ratings of faces with a relatively clear (angry, happy) and ambiguous (surprised) valence. Ratings became more positive for ambiguity from the start (Week 1) to end of training (Week 8; p < .001), but there were no short-term effects (from a single class session). This shift toward positivity continued through an additional 8-week follow-up (Week 16; p < .001). Notably, posttraining valence bias (Week 8) was uniquely predicted by the nonreactivity facet of mindfulness (p = .01). Together, mindfulness promotes a relatively long-lasting shift toward positivity bias, which is uniquely supported by reduced emotional reactivity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Evaluation and improvement of LAMP assays for detection of Escherichia coli serogroups O26, O45, O103, O111, O121, O145, and O157.
Escherichia coli serogroups O26, O45, O103, O111, O121, O145, and O157 are the causative agents of human diseases, and LAMP assays have been developed for detection of the seven leading STEC serogroups. To evaluate existing LAMP assays for detection of the seven STEC serogroups, if necessary, to improve these assays and to promote their practical application. Pure DNA extract from 23 strains reserved in our lab was used to evaluate the existing LAMP assays. The existing LAMP assays were modified via adding 1% tetramethylene sulfoxide and 5% dimethyl sulfoxide as well as optimizing reaction temperature. The detection limit of the modified LAMP assays was 0.1-1 pg per reaction, equivalent to 25-250 cfu per reaction, the non-specific amplification can completely be eliminated with optimal amplifying temperature, and the modified LAMP assays can specifically and sensitivly amplify targeted O serogroup-specific gene (wzx or wzy) of any concerned Escherichia coli serogroup as commercial kit Isothermal Master Mix did. In conclusion, the LAMP assays were highly susceptible to non-specific amplification caused by primer dimers, and these modified methods were free of non-specific amplification and can rapidly and reliably detect the seven major Shiga toxin-producing E. coli serogroups.


Verb-noun double dissociation in aphasic lexical impairments: the role of word frequency and imageability.
Neurolinguistic studies have provided important evidence regarding the organization of lexical representations and the structure of underlying conceptual knowledge; in particular, it has been shown that the retrieval of verbs and nouns can be damaged selectively. Dissociated lexical damage is proof of an independent mental organization of lexical representations and/or of the underlying processes. The aim of the present study is to estimate the rate of dissociated impairments for nouns and verbs on a large sample of mild to moderate aphasic patients and to investigate the mechanisms underlying such phenomena. In addition, the authors wished to verify to what degree the impairment for nouns and verbs is related to a specific type of language disorder. A confrontation naming task for verbs and nouns was administered to 58 aphasic patients. The major lexical (word frequency and age of acquisition) and semantic variables (familiarity and imageability of the underlying concept) were considered for each noun and verb used in the task. Verbs were distinguished by major functional classes (transitive, intransitive, and ergative verbs). The data collected from this task were analyzed twice: (i) as a group study comparison of major aphasic subgroups and (ii) as a multiple single case study to evaluate the differences on the naming of verbs and nouns and the effect of the lexical semantic variables on each individual patient. The results confirm the existence of dissociated naming impairments of verbs and nouns. Selective impairment of verbs is more frequent (34%) than that of nouns (10%). In many cases, the dissociated pattern of naming impairment disappeared when the effect of the concomitant variables (word frequency and imageability) was removed, but in approximately one-fifth of the cases the noun or verb superiority was preserved. Noun superiority emerged in five of six agrammatic patients. Both the naming of verbs (n = 9) or of nouns (n = 6) could be impaired selectively in fluent aphasic patients. The results lend support to the hypothesis of an independent mental organization of nouns and verbs, but a substantial effect of imageability and word frequency suggests an interaction of the naming impairment with underlying lexical and semantic aspects.