MCC950, a NLRP3 inhibitor, ameliorates lipopolysaccharide-induced lung inflammation in mice.
Acute respiratory distress syndrome/chronic obstructive pulmonary disease (ARDS/COPD) is a diffuse inflammatory injury of the lung that is characterized by respiratory distress and vascular leakage and is caused by various factors. Although the treatment strategy for ARDS/COPD continues to be improved, it still lacks effective drugs. MCC950 is a potent and selective inhibitor ofthe nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) inflammasome. However, there have been no reports on the effects of MCC950 on lipopolysaccharide (LPS)-induced lung inflammation in mice. The objective of the present study was to evaluate the effects of MCC950 (given either intranasally or intraperitoneally) on inhibiting LPS-induced lung inflammation in mice. Acute lung inflammation was induced by intratracheal administration of LPS in ICR mice. The results showed that MCC950 at 50 mg/kg efficiently suppressed neutrophil lymphocytes (p < 0.001) and macrophage accumulation (p < 0.01) in bronchoalveolar lavage fluid (BALF) in LPS-instilled mice. In addition, hematoxylin and eosin (H&E) staining revealed that MCC950 at 50 mg/kg significantly inhibited pathological progress in the lung tissues (p < 0.01). Furthermore, treatment with MCC950 substantially reduced mRNA expression of IL-1β, IL-8, TGF-β1, and MMP-9 and also reduced protein levels of IL-1β, IL-18 and caspase-1 at 24 h after LPS instillation. The results of the present study indicate that MCC950 effectively inhibits LPS-induced lung inflammation in vivo, which can be considered for clinical translation.


Outcome of hypovascular hepatic nodules with positive uptake of gadoxetic acid in patients with cirrhosis.
To evaluate the longitudinal risk to patients with cirrhosis of hypervascular hepatocellular carcinoma (HCC) developing from hypovascular hepatic nodules that show positive uptake of gadoxetic acid (hyperintensity) on hepatocyte phase images. In 69 patients, we evaluated findings from serial follow-up examinations of 633 hepatic nodules that appeared hypovascular and hyperintense on initial gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) until the nodules demonstrated hypervascularity and were diagnosed as hypervascular HCC. Cox analyses were performed to identify risk factors for the development of hypervascular HCCs from the nodules. The median follow-up was 663 days (range, 110 to 1215 days). Hypervascular HCCs developed in six of the 633 nodules (0.9 %) in five of the 69 patients. The only independent risk factor, the nodule's initial maximum diameter of 10 mm or larger, demonstrated a hazard ratio of 1.25. The one-year risk of hypervascular HCC developing from a nodule was 0.44 %. The risk was significantly higher for nodules of larger diameter (1.31 %) than those smaller than 10 mm (0.10 %, p < 0.01). Hypervascular HCC rarely develops from hypovascular, hyperintense hepatic nodules. We observed low risk even for nodules of 10 mm and larger diameter at initial examination. • Hypervascularization was rare on follow-up examination of hypovascular, hyperintense nodules • The risk of hypervascularization in a nodule increased with large size • Hypovascular, hyperintense nodules require neither treatment nor more intense follow-up.


Genetic dissection of myopia: evidence for linkage of ocular axial length to chromosome 5q.
To estimate heritability and locate quantitative trait loci influencing axial length. Classic twin study of monozygotic and dizygotic twins reared together. Eight hundred ninety-three individuals from 460 families were recruited through the Twin Eye Study in Tasmania and the Brisbane Adolescent Twin Study (BATS) and had ocular axial length measured. Structural equation modeling on the entire sample was used to estimate genetic and environmental components of variation in axial length. Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 individuals from 142 BATS families. Ocular axial length. The heritability estimate for axial length, adjusted for age and sex, in the full sample was 0.81. The highest multipoint logarithm of the odds (LOD) score observed was 3.40 (genomewide P = 0.0004), on chromosome 5q (at 98 centimorgans [cM]). Additional regions with suggestive multipoint LOD scores were also identified on chromosome 6 (LOD scores, 2.13 at 76 cM and 2.05 at 83 cM), chromosome 10 (LOD score, 2.03 at 131 cM), and chromosome 14 (LOD score, 2.84 at 97 cM). Axial length, a major endophenotype for refractive error, is highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.


Environmental heme utilization by heme-auxotrophic bacteria.
Heme, an iron-containing porphyrin, is the prosthetic group for numerous key cellular enzymatic and regulatory processes. Many bacteria encode the biosynthetic enzymes needed for autonomous heme production. Remarkably, however, numerous other bacteria lack a complete heme biosynthesis pathway, yet encode heme-requiring functions. For such heme-auxotrophic bacteria (HAB), heme or porphyrins must be captured from the environment. Functional studies, aided by genomic analyses, provide insight into the HAB lifestyle, how they acquire and manage heme, and the uses of heme that make it worthwhile, and sometimes necessary, to capture this bioactive molecule.


Convergence of Plasma Metabolomics and Proteomics Analysis to Discover Signatures of High-Grade Serous Ovarian Cancer.
The 5-year survival rate in the early and late stages of ovarian cancer differs by 63%. In addition, a liquid biopsy is necessary because there are no symptoms in the early stage and tissue collection is difficult without using invasive methods. Therefore, there is a need for biomarkers to achieve this goal. In this study, we found blood-based metabolite or protein biomarker candidates for the diagnosis of ovarian cancer in the 20 clinical samples (10 ovarian cancer patients and 10 healthy control subjects). Plasma metabolites and proteins were measured and quantified using mass spectrometry in ovarian cancer patients and control groups. We identified the differential abundant biomolecules (34 metabolites and 197 proteins) and statistically integrated molecules of different dimensions to better understand ovarian cancer signal transduction and to identify novel biological mechanisms. In addition, the biomarker reliability was verified through comparison with existing research results. Integrated analysis of metabolome and proteome identified emerging properties difficult to grasp with the single omics approach, more reliably interpreted the cancer signaling pathway, and explored new drug targets. Especially, through this analysis, proteins (PPCS, PMP2, and TUBB) and metabolites (L-carnitine and PC-O (30:0)) related to the carnitine system involved in cancer plasticity were identified.


Validation of bacterial growth inhibition models based on molecular properties of organic acids.
Organic acids occur naturally in foods and have been used in many food products as preservatives because they inhibit the growth of most microorganisms. The acids commonly found in foods differ greatly in both their structure and inhibitory effects for different bacteria. A way to represent relationships between different acids was previously described in which principal components analysis (PCA) was applied to 11 physical and chemical properties of 17 organic acids, to arrive at principal properties. These were used for development of regression models that related the minimum inhibitory concentrations (MICs) of organic acids to their principal properties. Separate MIC models were constructed for six different bacteria. The objective of the present study was to test the predictive capabilities of the organism models using different organic acids from the ones used to construct the original models. MIC predictions were made for three acids for each of the six bacteria for which models were previously constructed. MIC determinations for these acids were then carried out and compared with the predictions; these were in good agreement, thus validating the models. The new data were combined with that obtained previously to produce similar, but slightly stronger models. These had R(2) values between 0.861 and 0.992.


On the stabilization of animal numbers. Problems of testing : I. Power estimates and estimation errors.
It is tried to remove some misunderstandings about the "regulation" of animal numbers by density-dependent processes. Staying between limits is called "stabilization", and only when this results from density-dependent processes it is considered "regulation". We discuss two tests that may be used to detect the existence of regulation: the parametric tests of Bulmer and a nonparametric "permutation" test. The powers of these tests are compared. The first test of Bulmer and the permutation test do not differ very much in power, but the second test of Bulmer has hardly any power and therefore cannot be used in cases where densities were only estimated. The arguments from which Bulmer's second test is derived are critically discussed and found not to be very convincing. We propose, rather than using Bulmer's second test, to correct the test statistic of his first test for estimation error, and present a possible solution for this. In a following paper this method will be applied to some long series of population counts of univoltine insects, for, a basic assumption of all regulation-tests is, that the sequence of population counts is a realization of a piece of first-order Markov chain. This highly restricts the usefulness of regulation-tests. Some other recent attempts to construct such tests are discussed within the present context.


A continuous cell line (KK-2) from a supratentorial primitive neuroectodermal tumor.
Tumor tissue located in the occipital lobe with hemorrhage was obtained from a 19-year-old patient. Histological examination indicated it to consist of undifferentiated small, round cells without neuronal or glial differentiation, and possibly to be a type of primitive neuroectodermal tumor. The tumor cells were cultured for 3 years and a continuous cell line (KK-2) was established. KK-2 was transplantable to nude mice. With immunocytochemistry, neuron-specific enolase, protein gene product 9.5, vimentin, TUJ1 (a monoclonal antibody specific for neuron-associated class III beta-tubulin isotype) and 6H7 (a monoclonal antibody to NCAM produced by us) were detected. None of the following could be found: glial fibrillary acidic protein, S-100 protein, neurofilament and synaptophysin, calcitonin gene-related peptide, gastrin releasing peptide corticotropin-releasing factor, substance P, somatostatin, chromogranin, aromatic L-amino acid decarboxylase and tyrosine hydroxylase. The original tumor and KK-2 cells obtained after 3 years of culture and transplants in nude mice displayed essentially the same ultrastructural and immunohistochemical characteristics. KK-2 cells showed no differentiation to mature neuronal, glial or ependymal cells. This cell line may possibly serve as a useful model for studying cellular differentiation of human neuroectodermal tumors and normal neuronal development.


The role of vitamin D in the metabolic homeostasis of diabetic bone.
Most studies across a variety of geographic locations suggest that vitamin D insufficiency is more common in individuals with type 1 diabetes (T1D) compared to the general population. In type 2 diabetes (T2D), while obesity is commonplace and lower vitamin D levels are present in obese adolescents and adults, the association between vitamin D insufficiency and T2D is less clear. Studies suggest that the relationship between T2D and vitamin D may be concurrently influenced by ethnicity, geography, BMI and age. None-the-less, diabetic osteopathy is a significant co-morbidity of both forms of diabetes, and is characterized by micro-architectural changes that decrease bone quality leading to an increased risk for bone fracture in both disorders. The question remains, however, to what degree vitamin D homeostasis contributes to or exacerbates skeletal pathology in diabetes. Proposed mechanisms for vitamin D deficiency in diabetes include: 1) genetic predisposition (T1D); 2) increased BMI (T2D); 3) concurrent albuminuria (T1D or T2D); or 4) exaggerated renal excretion of vitamin D metabolites or vitamin D binding protein (T1D, T2D, animal models). The specific effects of vitamin D treatment on diabetic osteoporosis have been examined in rodents, and demonstrate skeletal improvements even in the face of untreated diabetes. However, human clinical trial data examining whether vitamin D status can be directly related to or is predictive of bone quality and fracture risk in those with diabetes is still needed. Herein, we provide a review of the literature linking vitamin D, diabetes and skeletal health.


Evolution of Boldness and Exploratory Behavior in Giant Mice from Gough Island.
Island populations are hallmarks of extreme phenotypic evolution. Radical changes in resource availability and predation risk accompanying island colonization drive changes in behavior, which Darwin likened to tameness in domesticated animals. Although many examples of animal boldness are found on islands, the heritability of observed behaviors, a requirement for evolution, remains largely unknown. To fill this gap, we profiled anxiety and exploration in island and mainland inbred strains of house mice raised in a common laboratory environment. The island strain was descended from mice on Gough Island, the largest wild house mice on record. Experiments utilizing open environments across two ages showed that Gough Island mice are bolder and more exploratory, even when a shelter is provided. Concurrently, Gough Island mice retain an avoidance response to predator urine. F1 offspring from crosses between these two strains behave more similarly to the mainland strain for most traits, suggesting recessive mutations contributed to behavioral evolution on the island. Our results provide a rare example of novel, inherited behaviors in an island population and demonstrate that behavioral evolution can be specific to different forms of perceived danger. Our discoveries pave the way for a genetic understanding of how island populations evolve unusual behaviors.


Hyperuricaemia with deposition: latest evidence and therapeutic approach.
This article reviews recent evidence on urate deposition and the opportunity for a therapeutic approach. We reviewed Pubmed 2013-2015 literature using the search terms 'deposition' with 'hyperuricaemia', 'gout', 'ultrasonography', 'DECT' (dual-energy computed tomography), 'radiography', 'CT'(computed tomography), 'MRI' (magnetic resonance imaging), or 'cardiovascular', in addition to a digital bibliographic library compiled by the authors with 2072 papers on hyperuricaemia and gout. Relevant papers on the topic were selected. Recent evidence, mostly based on imaging studies, showed a continuum from hyperuricaemia to deposition and clinical manifestations. Chronic inflammation and structural damage may be present even in asymptomatic patients with crystal-proved deposition. The impact of early intervention in patients with asymptomatic deposition either on vascular outcomes or further structural joint damage has not been demonstrated yet. In conclusion, a worldwide definition of gout is still lacking, stages from hyperuricaemia to clinical gout not being definitively defined. Although there is increasing interest on the impact of early deposits on joint damage and cardiovascular outcomes, robust evidence is still lacking to fully support interventions.


Conjugated linoleic acid reduces hepatic steatosis and restores liver triacylglycerol secretion and the fatty acid profile during protein repletion in rats.
Protein depletion is associated with hepatic steatosis and decreased circulating triacylglycerol (TAG). Since conjugated linoleic acid (CLA) increases lean body mass, protects against muscle catabolism, and modulates lipid metabolism, the aim of this work was to investigate the effects of CLA with two different amounts of dietary fat on the regulation of plasma and hepatic TAG concentration, and its possible connections with changes in fatty acid (FA) profile in plasma, liver and adipose tissue and hepatic oxidative status during protein repletion. Rats were fed a low protein diet (14 days) and then a protein repletion diet (30 days), supplemented or not with CLA, containing 7% (w/w) or 20% (w/w) of fat. Hepatic TAG secretion and removal by muscle and adipose tissue lipoprotein lipase, FA profile and liver oxidative status were evaluated. Protein depletion affected hepatic TAG secretion and peripheral removal, decreasing plasma and increasing liver TAG concentration, whereas protein repletion with CLA improved these abnormalities independently of the amount of dietary fat by increasing hepatic TAG secretion. This prevention in the absence of CLA was not observed. CLA was incorporated in plasma and tissues (adipose > liver > plasma, and c9,t11-CLA > t10,c12-CLA), accompanied by alterations in FA composition, mainly in adipose tissue. The hepatic oxidative stress was overcome by protein repletion. CLA had a beneficial impact on TAG metabolism in protein repleted animals, preventing hepatic steatosis through higher hepatic TAG secretion.


Expression of human beta defensins (HBDs) 1, 2 and 3 in gingival crevicular fluid of patients affected by localized aggressive periodontitis.
To study the effect of nonsurgical periodontal therapy on the expression frequencies of human beta-defensin (HBD)-1, -2, and -3 in the gingival crevicular fluid (GCF) of patients affected by localized aggressive periodontitis. Twenty patients affected by localized aggressive periodontitis (age range, 20-35 years) and 20 healthy subjects (age range, 21-37 years) were examined with clinical periodontal parameters and radiographic examination with the long-cone parallel technique. All periodontitis patients underwent nonsurgical periodontal therapy combined with doxycycline treatment and a maintenance program (including brushing with regular toothpaste). GCF samples were collected from patients and healthy control subjects at baseline as well as 3 months after periodontal therapy for the patient group. In the patient group, the expression frequencies of HBD-1, -2, and -3 mRNA at baseline were 30%, 85%, and 35%, respectively, which changed after periodontal therapy to 80%, 45%, and 85%, respectively (all P < 0.001). In the healthy control subjects, the expression frequencies were 95%, 40%, and 95% for HBD-1, -2, and -3, respectively, which were different from those of diseased patients at baseline (all P < 0.001). The appropriate expression of HBD peptides in health and disease may contribute to the maintenance of periodontal homeostasis, possibly through its antimicrobial effects and the promotion of adaptive immune responses.


The importance of predation, substrate and spatial refugia in determining lotic insect distributions.
An experiment was conducted to evaluate the interaction between predation, substrate, and spatial refugia in the organization of a stream insect community (Reeds Creek, Pendleton Co., West Virginia). Patterns of insect colonization were compared between fish exclusion cages and open controls that allowed access to vertebrate predators. Each cage contained 4 different substrates that varied in the relative amount of spatial refugia. Fish had little influence on the diversity or abundance of any insect taxa, even when spatial refugia were limited. The only significant effect due to predation, was an increased diversity of large (>8 mm) invertebrates in the absence of predators. However, because these taxa were relatively rare, the overall role of fish predation on insect community structure was minimal.In contrast, substrate had a marked effect on insect colonization. Insects were always more abundant (number/basket) on loose substrates containing large numbers of interstitial spaces, compared to cement-embedded substrates with few refuges available. In addition, invertebrates were more abundant on loose gravel compared to loose cobbles. Howver, when substrate "preferencesrd were examined according to insect density (number/m2), loose cobbles were generally the preferred substrate. The present experiment rejects the hypothesis that patterns of substrate colonization can be explained as differential insect mortality by predators, due to varying amounts of refugia. Alternative mechanisms such as differing amounts of trapped detritus and substrate surface area may account for substrate "preference".


Interferon induction in human cell cultures by small molecular inducers (tilorone and acridines).
Attempts were made to stimulate interferon production in human cell cultures by two related acridin drugs, mepacrine and Acranil. Tilorone was included for comparison. In human embryo lung fibroblasts and in normal human leukocytes only tilorone stimulated some interferon production. All three drugs stimulated modest interferon production in two lymphoblastoid cell lines. All three drugs enhanced the Sendai virus-induced interferon production in lymphoblastoid cells.


On-line mapping system for the visualization of the electrical activation of the heart.
A simple but still versatile datalogging system based on a VCR (video cassette recorder) has been developed. The VCR allows mass storage of data originating from a maximum of 256 channels as used, for example, in the recording of the time-dependent potential distribution at the surface of the myocardium. Incorporated in the system is a display memory allowing on-line simultaneous visualization of the assessed recordings of 16 channels. On an interactive base display parameters (time-window, channel-selection) can be altered without loss of data. A link with a personal computer allows modification of system parameters and storage of data for off-line analysis of the recorded data. The high data rate to and from the VCR (4.3 MHz) fully utilizes the bandwidth available. A normal videotape can, therefore, contain up to 2 Gigabyte of data. Despite this, the use of the tapecounter and the decoding of the time-code inserted into the signal allows quick retrieval of the stored data without needing expensive equipment. The system described brings mass data logging within the reach of a vast number of laboratoria and cardiovascular centers.


Allelopathic interaction between a reef coelenterate and benthic algae.
We did in situ experiments to study the influence of a water-borne substance, exuded by the reef anthozoan Condylactis gigantea, on filamentous algae. Algal biomass accumulation on experimental glass slides was significantly inhibited by the exudate. Algal spores and diatoms were present in equal numbers on experimental and control slides, but the exudate inhibited germination of spores and was toxic to developing green, red and brown algae. The algal population on the control slides consisted of early colonizers as well as later successional species and reflected the natural population. The described allelochemic mechanism will be important in interference competition between the anemone and algae. Settling of larvae in supposedly space-limited systems such as reefs is facilitated when algaecovered surfaces are open to settlement.


Conformational mapping of a viral fusion peptide in structure-promoting solvents using circular dichroism and electrospray mass spectrometry.
The N-terminal domain of human immunodeficiency virus (HIV)-1 glycoprotein 41,000 (FP; residues 1-23; NH2-AVGIGALFLGFLGAAGSTMGARS-CONH2) is involved in the fusion and cytolytic processes underlying viral-cell infection. Here, we use circular dichroism (CD) spectroscopy, along with electrospray ionization (ESI) mass spectrometry and tandem (MS/MS) mass spectrometry during the course of hydrogen/deuterium exchange, to probe the local conformations of this synthetic peptide in two membrane mimics. Since amino acids that participate in defined secondary structure (i.e., alpha-helix or beta-sheet) exchange amido hydrogens more slowly than residues in random structures, deuterium exchange was combined with CD spectroscopy to map conformations to specific residues. For FP suspended in the highly structure-promoting solvent hexafluoroisopropanol (HFIP), CD spectra indicated high alpha-helix and disordered structures, whereas ESI and MS/MS mass spectrometry indicated that residues 5-15 were alpha-helical and 16-23 were disordered. For FP suspended in the less structure-promoting solvent trifluoroethanol (TFE), CD spectra showed lower alpha-helix, with ESI and MS/MS mass spectrometry indicating that only residues 9-15 participated in the alpha-helix. These results compare favorably with previous two-dimensional nuclear magnetic resonance studies on the same peptide.


Significance of acoustic field for the myocardial opacification by intravenous contrast echocardiography.
Myocardial opacification is not always homogeneous even in a normal heart. The aim of this study is to clarify why myocardial opacification is faint at the lateral side of the field or at the part far from the focus point. In canine study, videointensity of the opacification at septal and lateral walls of the short axis view was examined by using both electric and mechanical transducers. In in vitro study, acoustic pressure at several points away from the beam direction was measured using a hydrophone in a water tank. In particular, the effect of position of focus point was evaluated with an electronic transducer. In canine experiment, myocardial opacification of the lateral wall was faint with the electronic transducer, however the mechanical one obtained homogeneous opacification. In vitro, using the electronic type the acoustic pressure was low as the beam shifted, laterally, whereas it was almost uniform in the mechanical type. With the electronic type, moreover, the beam width at the near field was not sharp when the focus point was far, resulting in execessive acoustic pressure. To obtain homogeneous opacifiction, a homogeneous acoustic field is indispensable.


Acute myeloid leukemia after 10 years of azathioprine treatment for Crohn's disease.
Azathioprine, which is an immunosuppressive agent commonly used for chronic inflammatory bowel disease, may be associated with an increased risk of certain cancers such as hematologic malignancies. A 50-year-old man with a 27-year history of Crohn's disease had been under azathioprine treatment at a dose of 2.5 mg/kg/day (150 mg/day) since 2007, after ileocecal resection to avoid postoperative recurrences. Ten years later, the patient presented with a 3-week history of worsening general condition and fever. The physical examination revealed skin paleness and fever. The biological assessment showed pancytopenia. Hematological toxicity of azathioprine was suspected. The drug was immediately stopped. A bone marrow biopsy with immunophenotyping studies confirmed the diagnosis of acute myeloid leukemia. Chemotherapy was indicated but the patient passed away 2 weeks later. Azathioprine may be implicated in therapy-related acute myeloid leukemia. Close monitoring of its hematological toxicity, as well as patient education to adhere to this monitoring program, are crucial to detect this life-threatening complication.


Isolation of microRNAs that regulate seed dormancy and germination.
MicroRNAs (miRNAs) play an important role in gene regulation in many plant tissues and organs during various developmental stages. Previous studies have suggested the importance of gene regulation by miRNA in seeds. Characterizing the expression of miRNAs and their target genes in dormant and germinating seeds helps to gain a better understanding of the regulatory role of miRNAs during seed dormancy and germination. This can be achieved by implementing a simple miRNA extraction method using fractionation with isopropanol and Northern blot analysis using nonradioactive miRNA probes. Functional analysis of miRNA target genes potentially associated with seed dormancy and germination can be examined using mutant seeds in which specific miRNAs are deregulated by introducing silent mutations in the miRNA target sites of these genes.


Risk-induced hatching timing shows low heritability and evolves independently of spontaneous hatching in red-eyed treefrogs.
Plasticity in the timing of transitions between stages of complex life cycles allows organisms to adjust their growth and development to local environmental conditions. Genetic variation in such plasticity is common, but the evolution of context-dependent transition timing may be constrained by information reliability, lag-time and developmental constraints. We studied the genetic architecture of hatching plasticity in embryos of the red-eyed treefrog (Agalychnis callidryas) in response to simulated predator attacks using a series of paternal and maternal half-sibs from a captive breeding colony of wild-collected animals. We compared the developmental timing of induced early hatching across sibships and estimated cross-environment genetic correlations between induced and spontaneous hatching traits. Additive genetic variance for induced early hatching was very low, indicating a constraint on the short-term evolution of earlier hatching timing. This constraint is likely related to the maturation of the hatching mechanism. The most plastic genotypes produced the most extreme spontaneous hatching phenotypes, indicating that developmental range, per se, is not constrained. Cross-environment genetic correlation in hatching timing was negligible, so the evolution of spontaneous hatching in this species has not depended on the evolution of risk-induced hatching and vice versa.


Genetic analysis for drought resistance of rice at reproductive stage in field with different types of soil.
Drought resistance of rice is a complex trait and is mainly determined by mechanisms of drought avoidance and drought tolerance. The present study was conducted to characterize the genetic basis of drought resistance at reproductive stage in field by analyzing the QTLs for drought response index (DRI, normalized by potential yield and flowering time), relative yield, relative spikelet fertility, and four traits of plant water status and their relationships with root traits using a recombinant inbred population derived from a cross between an indica rice and upland rice. A total of 39 QTLs for these traits were detected with individual QTL explained 5.1-32.1% of phenotypic variation. Only two QTLs for plant water status were commonly detected in two environments, suggesting different mechanisms might exist in two types of soil conditions. DRI has no correlation with potential yield and flowering time under control, suggesting that it can be used as a good drought resistance index in field conditions. The co-location of QTLs for canopy temperature and delaying in flowering time suggested a usefulness of these two traits as indexes in drought resistance screening. Correlation and QTL congruence between root traits and putative drought tolerance traits revealed that drought avoidance (via thick and deep root traits) was the main genetic basis of drought resistance in sandy soil condition, while drought tolerance may play more role in the genetic basis of drought resistance in paddy soil condition. Therefore, both drought mechanisms and soil textures must be considered in the improvement of drought resistance at reproductive stage in rice.


Effect of chronic renal failure and methylprednisolone treatment on the uptake of labelled plasma cholesterol into the aorta of normocholesterolemic rabbits.
The effects of chronic renal failure (CRF) and corticosteroid treatment on the aortic uptake of labelled free and esterified cholesterol (FC and EC) were investigated in normocholesterolemic rabbits. Methylprednisolone, 0.4 mg/day, or placebo was administered for 14 weeks to rabbits with normal renal function and with CRF. Then [3H]- and [14C]cholesterol were administered intravenously and orally, respectively. The radioactivity levels of FC and EC in plasma were measured at regular intervals. After 48 h the accumulation of 3H and 14C radioactivity of FC and EC in the intima-media of the thoracic aorta was determined. An aortic uptake coefficient was calculated by dividing the tissue radioactivity (dpm/cm2/h) by the mean plasma radioactivity (dpm/ml). The mean uptake coefficient of EC in normal rabbits was 6 nl/cm2/h, the value for FC being 180 nl/cm2/h. In normal rabbits treated with methylprednisolone the uptake coefficients of both FC and EC were significantly decreased to about 50% of the values in normal rabbits receiving placebo. A similar significant decrease in the uptake coefficients was found in the CRF rabbits receiving placebo. No further decrease was observed in the CRF rabbits treated with methylprednisolone. The cholesterol content of the aortic intima-media was significantly decreased only in CRF rabbits on methylprednisolone treatment. The results do not indicate an acceleration of uremic arterial disease by steroid treatment in the rabbit.


Synthesis and controlling the morphology of CdS nanocrystals via hydrothermal microemulsions.
Wurtzite CdS nanocrystals were synthesized via a hydrothermal microemulsion method. With the preaddition of increasing amounts of dodecanethiol, the resulting crystals changed from nanorods to pyramidal particles with decreasing sizes. The control effect of dodecanethiol was attributed to the competition process during the crystal growth and the relevant change in the film flexibility of inverse micelles. The effects of water content, ion concentration, and hydrothermal temperature on the crystal morphologies and size distributions were also investigated.


Metagenomic ventures into outer sequence space.
Sequencing DNA or RNA directly from the environment often results in many sequencing reads that have no homologs in the database. These are referred to as "unknowns," and reflect the vast unexplored microbial sequence space of our biosphere, also known as "biological dark matter." However, unknowns also exist because metagenomic datasets are not optimally mined. There is a pressure on researchers to publish and move on, and the unknown sequences are often left for what they are, and conclusions drawn based on reads with annotated homologs. This can cause abundant and widespread genomes to be overlooked, such as the recently discovered human gut bacteriophage crAssphage. The unknowns may be enriched for bacteriophage sequences, the most abundant and genetically diverse component of the biosphere and of sequence space. However, it remains an open question, what is the actual size of biological sequence space? The de novo assembly of shotgun metagenomes is the most powerful tool to address this question.


Characterization of seven new related impurities and forced degradation products of tetracaine hydrochloride and proposal of degradation pathway by UHPLC-Q-TOF-MS.
A rapid and highly sensitive method was developed for separation and identification of the related impurities and degradation products in tetracaine hydrochloride by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The chromatographic separation was achieved on an Agilent Infinity Lab Poroshell 120 EC-C18 column (4.6 ×100 mm, 2.7 µm) using gradient elution with mobiles phase of A (10 mM ammonium acetate buffer containing 0.1% formic acid) and B (acetonitrile) at a flow rate of 1.0 mL/min. Forced degradation experiments were also performed under acidic, alkaline, thermal, photolytic, and oxidative stress conditions following ICH guidance. The result revealed that tetracaine hydrochloride is extremely sensitive to oxidation condition and highly sensitive to alkaline/acidic hydrolysis, and susceptible to light condition. In total, five related impurities and seven degradation products were successfully detected in the positive mode of electrospray ionization. The structures of all these impurities were characterized based on the high-resolution MS data and manufacture process, and the fragmentation pathways of tetracaine and these impurities were constructed and discussed. Seven of them have not been reported before, and two of them were specified impurities described in various pharmacopoeias. The fragmentation pathways and plausible mechanisms for the formation of these impurities were proposed.


Kinship ecology of competition: size hierarchies in kin and nonkin laboratory cohorts of tadpoles.
This study provides an experimental test of the ecological significance of kinship in competitive interactions among individuals. Tadpoles of the fire-bellied toad, Bombina variegata (Anura, Discoglossidae) reared in the laboratory in a high density of siblings grew better and developed faster than when they were reared with similar densities of nonrelatives. Kinship-based genotypic uniformity may therefore be advantageous: it can lead to faster and more uniform growth. In nature it may well be kin recognition that permits such advantage to be realised. The largest tadpoles from pure-sibship cohorts accounted, on average, for the smaller fraction of the cohort total biomass than the largest tadpoles reared with cohorts of nonrelatives, although they attained the same absolute weight and developmental stage. The smallest individuals from pure-sibship cohorts had a much larger absolute body weight than the smallest tadpoles from mixed-sibship cohorts, and were also much more advanced developmentally. The results could be an effect of an altruistic restraint in growth rate on the part of the largest tadpoles in sibling cohorts and certainly not of the smallest ones. However, the results could also be due to the altruism-independent facilitation of living conditions in pure-sibship groups, resulting solely from potential advantages of homogeneous water conditioning.


Flicker adaptation in the peripheral retina.
With strict fixation, a flickering light spot smaller than 3 deg presented to the peripheral retina will rapidly appear to lose contrast and stop flickering within 35 s, before fading away completely. The time required for this adaptation to occur decreases with: decreasing depth of modulation (97-9%); decreasing stimulus diameter (2 deg-7 min arc); increasing retinal eccentricity (20-50 deg); and increasing flicker frequency (1-7 Hz). Interestingly, the effect does not depend upon the regularity of the flickering stimulus, and it occurs twice as fast for stimuli presented to the temporal retina as for stimuli presented to the nasal retina. When changes in retinal eccentricity are compensated for by taking into account the cortical magnification factor, the time needed for perceived flicker to disappear remains constant at all eccentricities. With dichoptic stimulation interocular transfer is about 35%, suggesting a cortical contribution to flicker adaptation. The results indicate that the visual system adapts rather easily to peripheral flickering stimuli. Similarities as well as differences to motion adaptation are discussed.


Urinary Dialkyl Phosphate Concentrations and Lung Function Parameters in Adolescents and Adults: Results from the Canadian Health Measures Survey.
Epidemiological studies have reported associations between lung function parameters and organophosphate (OP) pesticide exposures in agricultural occupations, but to our knowledge associations have not been evaluated in general populations. We examined associations between OP metabolite dialkyl phosphates (DAPs) and lung function using data from the Canadian Health Measures Survey (CHMS) Cycle 1. Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC (FEF25%-75%) were measured for 4,446 CHMS participants. Urinary concentrations of six DAP metabolites (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP), smoking status, and other predictors of lung function were also measured in the CHMS-Cycle 1. Multiple linear regression analyses were used to examine the relationship between total DAP concentrations (ΣDAPs) and lung function in adolescents (12-19 years) and adults (20-79 years). In adults, estimates from multiple regression analyses suggested that a 1-unit increase on natural logarithmic scale (171% increase on the original scale) in the creatinine-corrected urinary concentration (nanomoles per gram creatinine) of ΣDAP was associated with a 32.6-mL (95% CI: -57.2, -8.1) reduction in FVC, 32.6-mL (95% CI: -59.0, -6.3) reduction in FEV1, 0.2% (95% CI: -0.6, 0.2) reduction in FEV1/FVC ratio, and 53.1-mL/sec (95% CI: -113.9, 7.7) reduction in FEF25%-75%. In adolescents, associations between ΣDAP and FEV1 were closer to the null and positive for FVC, whereas associations with FEV1/FVC and FEF25%-75% were negative, as in adults. However, none of the associations were significant in adolescents. The negative association between ΣDAP and lung function in adult participants suggests a detrimental effect of OP pesticides on lung function in the adult general population. Further studies using prospective designs are warranted to confirm the findings reported in this study. Ye M, Beach J, Martin JW, Senthilselvan A. 2016. Urinary dialkyl phosphate concentrations and lung function parameters in adolescents and adults: results from the Canadian Health Measures Survey. Environ Health Perspect 124:491-497; http://dx.doi.org/10.1289/ehp.1509745.


Revisiting the association between human leukocyte antigen and end-stage renal disease.
Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n = 497) and controls (n = 672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD, among which A*3_26 combination showed the highest strength of association (OR = 4.488, P≤ 0.05) with ESRD. Interestingly, the age of ESRD onset was not affected by HLA allele combinations at different loci. We also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. Our analysis showed that at least certain HLA alleles, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4, display a significant association with ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.


Comparison of efficiencies of selected sample extraction techniques for the analysis of selected antiretroviral drugs in human plasma using LC-MS.
Sample preparation in bio analytical chemistry poses a challenge because it can be compound dependent. We compared six sample extraction techniques i.e. QuEChERS (Q), liquid extraction (LE), protein precipitation (PPT), Q-PPT, Q-LE and LE-PPT for the extraction of antiretroviral drugs emtricitabine, tenofovir, efavirenz, lopinavir and rotinavir in human blood plasma. A multiple reaction monitoring liquid chromatography- tandem mass spectrometry method for the determination of the same antiretroviral drugs developed and validated in this laboratory was used. Comparisons were based on the efficiencies of extraction, the precisions and accuracies. Using United States Food and Drug Administration guidelines, analytical performance characteristics i.e. limits of detection, lower limits of quantification and upper limits of quantification were also compared. The percent mean recoveries ranged between 68.8 and 81.2% for single modes and 52.4-70.5% for mixed mode techniques. The precisions of all the extraction techniques were within the Using United States Food and Drug Administration guidelines acceptable range of <15% at all concentration levels for all analytes. Accuracy ranged between 8.73 and 65.94% for single mode techniques and between 21.73 and 51.59% for mixed mode techniques. The mixed modes gave slightly lower recoveries but Q-LE compared well with the single modes at slightly higher spike levels. Limits of detection for all the six sample preparation techniques fell below the clinically relevant therapeutic range of approximately 3-8ppm. Therefore all techniques can be employed for routine therapeutic drug monitoring studies.


Modification of thymo-dependent and thymo-independent antibody responses during non-specific acute inflammation.
An acute non-immunological inflammatory reaction, induced in mice by injecting intrapleurally a non-bacterial, non-antigenic and endotoxin-free irritant (40,000 molecular weight dextran or monoclinic dihydrated calcium pyrophosphate microcrystals), provoked an increase of antibody responses to thymus-dependent SRBC or thymus-independent TNP-LPS or DNP-Ficoll when the phlogistic stimulus was applied before immunisation. The increase in the number of IgM plaque-forming cells per spleen was obtained for different time intervals between the induction of the inflammatory stimulus and the antigen administration according to the type of irritant and the antigen used. However, no stimulation could be observed when this time interval was greater than three days. No stimulation of the antibody response to SRBC was observed when the irritant was applied one to three days after the antigen. The (stimulatory) effect could not be entirely related to a polyclonal activation as an augmentation in the production of antibody against non-cross-reactive antigen could only be seen four days after the onset of the inflammatory process, when the specific antibody response was not maximal. These observations indicate that an acute non-immunological inflammatory reaction lasting for 48 h can affect the immune reactivity of the host, even after the inflammatory process has disappeared.


What we know so far about postural balance training: An exploratory scoping review of nomenclature and related issues.
Different terms are used to refer to postural balance training, but the ontological debate involving the concepts to pursue nomenclature consensus is unusual. The goal of this study was to analyze how often the terms balance, neuromuscular, proprioceptive, functional and sensorimotor training/exercise are used in the literature, and to propose a conceptual critical appraisal to determine the most appropriate terminology to address postural balance exercises. A literature search was conducted in the Scopus electronic database. Eligibility criteria: papers with the selected expressions on the title or keywords, published in English, were included. The most used term was balance training (471 of 1105 included papers). Europe, followed by Asia and North America, had the highest number of publications. In the 21st century, the number of publications increased considerably. However, the terms have conceptual differences and controversies regarding its use. Despite a large variety of exercise types and divergences, balance training seems to be the most suitable term, given it refers to postural equilibrium exercises.


Correlation of CT scanning and pathologic features of ophthalmic Graves' disease.
Correlating the CT scan features of patients with orbital Graves' disease with histopathologic observations allows one to focus more specifically on the distinguishing features of this disease with future research implications. Both CT scanning and pathologic studies have shown clearly that the extraocular muscles are the primary focus of the disease. Swelling of the extraocular muscles generally occurs within their bellys with sparing of the tendons. This contrast with idiopathic inflammation of the muscles or myositis, which tends to involve the tendon as well. All of the associated findings in orbital Graves' disease probably flow from the enlarged volume of the extraocular muscles: proptosis, bowing of the medial lamina papyracea to accommodate the swollen belly of the medial rectus muscle, venous engorgement from stasis induced by direct compression of the orbital venous drainage, conjunctival and lid swelling, and lacrimal gland enlargement. Both radiographic and pathologic changes in the orbital fat are secondary and comparatively insignificant. While there appears to be no selective inflammation of the optic nerve meninges or the perineural connective tissues, enlargement of the extraocular muscle bellys where they converge at the crowded orbital apex brings about compression of the optic nerve, impairs its function, and causes visual decrease. Lymphocytic and plasmacytic infiltration along with edema within the endomysium of the extraocular muscles leads to the activation of fibroblasts with the production of acid mucopolysaccharides and progressive fibrosis. It is not known what attracts the lymphocytes to the extraocular muscles, why certain extraocular muscles are affected preferentially, why the disease may be asymmetrically unilateral, and whether a defect in T cell or B cell functions (or both) is immunologically at fault.


It is vital students are looked after safely.
Not all mentors have the skills proposed by the Nursing and Midwifery Council for newly qualified nurses, so who is going to look after students' safely?


Effect of denervation on adenine nucleotides in skeletal muscle from normal and dystrophic mice.
The effect of denervation on the adenine nucleotide content of fast- and slow-twitch skeletal muscle of the C57BL mouse was studied by high-performance liquid chromatography. From the adenine nucleotide content the energy charge, a measure of high-energy phosphate available to the cell, was calculated. The energy charge of the extensor digitorum longus muscle was significantly higher than that of the same muscle from dystrophic mice (C57BL/6J dy2j/dy2j) and on denervation decreased to the values found in the innervated muscle from dystrophic animals. Denervation of the muscle in dystrophic mice did not change the energy charge of that muscle. The energy charge of the soleus muscle from both normal and dystrophic mice was similar and did not change on denervation. It is proposed that in the dystrophic process a functional denervation of skeletal muscle occurs which preferentially affects fast-twitch muscle, leading to a reduction in the energy charge.


Local extracellular acidification caused by Ca2+-dependent exocytosis in PC12 cells.
Exocytosis of acidic synaptic vesicles may produce local extracellular acidification, but this effect has not been measured directly and its magnitude may depend on the geometry and pH-buffering capacity of both the vesicles and the extracellular space. Here we have used SNARF dye immobilized by conjugation to dextran to measure the release of protons from PC12 cells. The PC12 cells were stimulated by exposure to depolarizing K(+)-rich solution and activation was verified by fluorescence measurement of intracellular Ca(2+) and the release kinetics of GFP-labeled vesicles. Confocal imaging of the pH-dependent fluorescence from the immobile extracellular SNARF dye showed transient acidification around the cell bodies and neurites of activated PC12 cells. The local acidification was abolished when extracellular solution was devoid of Ca(2+) or strong pH-buffering was imposed with 10mM of HEPES. We conclude that the release of secretory vesicles induces local rises in proton concentrations that are co-released from synaptic vesicles with the primary neurotransmitter, and propose that the co-released protons may modulate the signaling in confined micro-domains of synapses.


Variations in the Organisms Causing Deep Surgical Site Infections in Fracture Patients at a Level I Trauma Center (2006-2015).
To quantify the current bacteriology of deep surgical site infections (SSIs) after fracture surgery at 1 institution and to compare those data with historical controls at the same institution, assessing variations in infecting organisms over the past decade. Retrospective review. Level I trauma center. Two hundred forty-three patients requiring surgical intervention for deep SSI between January 2011 and December 2015 were compared with 211 patients requiring surgical intervention for deep SSI between December 2006 and December 2010. None. Bacteria were categorized as Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus, Enterococcus, gram-negative rods (GNR), gram-positive rods, anaerobes, or negative cultures. The proportion of each bacterial type was determined and compared with previously published data from the same trauma center (December 2006 to December 2010). Patients most commonly had S. aureus infections (48%), followed by GNR (40%) and CoNS (19%). The proportion of CoNS species (26% vs. 12%, P < 0.01) in infected patients was significantly higher during the current study period compared with historical controls. The proportion of S. aureus species in infected patients was significantly less during the current study period (39% vs. 56%, P < 0.01). The reduction in the proportion of S. aureus species in infected patients was driven by a decrease in the proportion of methicillin-resistant S. aureus (MRSA) in the overall sample. Bacteriology of deep SSI of fractures has changed substantially over the past decade at our center, specifically the proportions of GNR, CoNS, and MRSA. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subchronic exposure to atrazine induces biochemical and histopathological changes in the gills of a Neotropical freshwater fish, Prochilodus lineatus.
The impact of acute (48 h) and subchronic (14 days) exposures to environmentally realistic atrazine concentrations (2, 10 and 25 μg L(-1)) were evaluated on the gills of Prochilodus lineatus by assessing the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), the levels of reduced glutathione (GSH) and lipid peroxide (LPO) as well as the histopathological damage. Acute and subchronic exposure to atrazine at 2 or 25 μg L(-1) did not change the activities of GST, SOD, CAT or GPx or the concentrations of GSH and LPO; however, subchronic exposure to 10 μg L(-1) increased the activity of GST, SOD and CAT and the LPO level. Histopathological indexes indicated normal gill function with scattered epithelial changes after acute and chronic exposure to 2 or 10 μg L(-1) of atrazine; however, fish chronically exposed to 25 μg L(-1) of atrazine, although had scattered lesions, the severity of lesions resulted in slightly to moderately gill damage. Acute exposure to atrazine decreased the type 3 MCs (containing acid mucosubstances with sulfate esters) in fish exposed to 2 or 10 μg L(-1) and increased the type 4 MCs (containing all types of mucosubstances) in fish exposed to 25 μg L(-1). Chronic exposure to atrazine reduced the type 3 MCs in fish exposed to 10 or 25 μg L(-1). The gills showed a low sensitivity to atrazine after acute exposure. However, the persistence of atrazine in water (subchronic exposure) promoted an increase of LPO levels in the gills and increased the frequency and severity of histopathological changes. The decreased density of type 3 MCs in fish exposed to atrazine suggests a mechanism to wash toxic substances away from the gill surface.


SnapShot: Tissue Clearing.
Tissue clearing has become an important tool for the investigation of biological systems in three dimensions. However, many pioneering techniques were based on serendipitous discoveries. Next-generation clearing methods have been (re)designed with a better understanding of the chemistry and physics required to equalize the refractive index throughout a sample which prevents the random bending of light that clouds biological tissues.


Mediastinal teratoma in a neonate.
A neonate with severe respiratory distress due to a benign mediastinal teratoma (MT) is reported. Despite early and easy surgical excision of the tumor, the child died due to poor cardiac function. Only ten cases of MT in neonates have been reported in the literature so far. While the tumor has been known to interfere with lung development in utero, postnatal myocardial dysfunction due to poor heart development has not been previously documented.


How Do Type of Preoperative P2Y12 Receptor Inhibitor and Withdrawal Time Affect Bleeding?
Despite recommendations for standardized preoperative waiting of at least 3, 5, and 7 days for ticagrelor, clopidogrel, and prasugrel, respectively, there is still substantial interinstitutional variation in preoperative discontinuation of dual antiplatelet therapy in patients needing coronary artery bypass grafting (CABG). In 299 patients undergoing CABG with or without valve intervention less than 7 days after last P2Y12 receptor inhibition, this study evaluated calculated red blood cell loss and Bleeding Academic Research Consortium type 4 (BARC-4) bleeding. A total of 83% of patients underwent CABG less than 48 hours after last drug intake. Calculated blood loss was lower in patients taking clopidogrel as compared with prasugrel or ticagrelor (1063 mL [690 to 1394 mL] vs 1351 mL [876 to 1829 mL] vs 1330 mL [994 to 1691 mL]; P < .001). Overall, 135 (45%) patients sustained BARC-4 bleeding; the incidence differed among the groups (P = .015) and was significantly higher in prasugrel-treated patients, as compared with clopidogrel-treated patients. In multivariable linear regression analysis, European System for Cardiac Operative Risk Evaluation II (EuroSCORE II), aspirin dose, cardiopulmonary bypass time, drug withdrawal time, and type of P2Y12 receptor inhibitor were significantly associated with red blood cell loss. Compared with 0 to 24 hours, a period of more than 48 hours of preoperative discontinuation substantially reduced calculated blood loss by 37% to 48% and BARC-4 bleeding by 58% to 71%, depending on the P2Y12 receptor inhibitor. Exposure to prasugrel and ticagrelor 24 hours or less before CABG increases both calculated blood loss and BARC-4 bleeding as compared with clopidogrel. Although discontinuation for longer than 48 hours substantially reduced calculated blood loss and BARC-4 bleeding across all P2Y12 receptor inhibitors, our single-center data further support strict adherence to the 2017 guidelines whenever justified by stable hemodynamics and nonjeopardized myocardium.


Deep Neck Space Infection: Study of 52 Cases.
Deep neck spaces are still common in developing countries like India, even though its less prevalent in developed nations. It can lead to serious complications like jugular vein thrombosis and dissemination of infection if not diagnosed early and intervened. This is a retrospective chart review of 52 patients from 2014 to 2017 in a tertiary care hospital. Only patients with infection deeper to the superficial fascia of neck were included. Submandibular space infection was the most common and precipitating factor being dental infection. Most common comorbid condition was diabetes mellitus. Klebsiella pneumoniae was the most common isolated organism and few patients had mixed culture with anaerobes. Injectable cephalosporin with metronidazole was the most effective antibiotic combination against such infections. Low threshold for early surgical intervention reduce hospital stay and enable quick recovery of patients. Usage of over the counter antibiotics masks the conditions and complicate diagnosis and treatment of this condition.


Magnetic resonance imaging measurement reproducibility for calf muscle and adipose tissue volume.
To describe a new semiautomated method for segmenting and measuring the volume of the muscle, bone, and adipose (subcutaneous and intermuscular) tissue in calf muscle compartments using magnetic resonance (MR) images and determine the intrarater and interrater reproducibility of the measures. Proton-density weighted MR images were acquired from the right calf of 21 subjects. Three raters segmented and measured the volumes of bones, adipose tissue, and five individual muscle compartments. Two raters repeated the segmentations. The intra- and interrater reproducibility of the measures (intraclass correlation coefficients; ICC) were determined using generalizability theory. All ICC values were greater than 0.96. The average standard error of the mean (SEM) of all measures was 1.21 cm(3) and none were greater than 2.3 cm(3) . Essentially all variation (≥97% for all measures) was due to subject differences, indicating low error in the measurements. The volumetric measurements for the bones, adipose tissue, and muscle in each of the compartments using MRI were highly reproducible. MRI can provide quantitative, reproducible volumetric measures of bone, adipose tissue, and individual muscle compartments in the calf. We believe these methods can be used to quantify specific muscle or adipose volumetric measures for other clinical or research purposes.


The effect of ICI 74,917 on asthma and bronchial provocation tests.
A study was made of the protective action of the anti-allergic drug ICI 74,917, a phenanthroline derivative, in specific allergen provocation tests and in combating clinical symptoms in thirteen asthmatic out-patients. It was found that ICI 74,917 was able to diminish allergen-induced bronchoconstriction significantly (P less than 0.01) during both the placebo period and during chronic treatment with ICI 74,917 for 4 weeks. The results obtained during these two periods did not differ significantly. There was not, however, any statistically significant difference in the symptom scores or PEF rates during the treatment with ICI 74,917 or placebo for 1 month. This may indicate that although ICI 74,197 is able to prevent bronchoconstriction in an allergen provocation test, it failed to improve asthma clinically. No signs of the phenomenon of tachyphylaxis were observed in the present study. The Student's t-test was used in the statistical analysis.


Active center differences between cathepsins L and B: the S1 binding region.
The substrate peptide bond cleaved by cathepsins B and L is determined not by the amino acid contributing the carboxyl group to this bond as in the case of serine proteases but rather by the presence of a neighboring amino acid with a large hydrophobic side chain. From a study of the inhibitory potency in a series, Cbz-Phe-X-CHN2, in which Phe promotes binding at S2 (terminology of [(1968) Biochem. Biophys. Res. Commun. 32, 898-902]) while the amino acid X probes S1, it is shown that this region of cathepsin L also has the ability to accommodate large hydrophobic side chains. In this respect cathepsin L differs from cathepsin B. Thus Cbz-Phe-Tyr(O-t-Bu)CHN2 inactivates cathepsin L with a rate 2.5 x 10(4) greater than that for cathepsin B.


Technical success rates and reliability of spin-echo echo-planar imaging (SE-EPI) MR elastography in patients with chronic liver disease or liver cirrhosis.
To determine the technical success rates of MR elastography (MRE) according to established gradient-recalled echo (GRE) and spin-echo echo-planar imaging (SE-EPI) sequences and to compare liver stiffness (LS) values between the sequences during expiratory and inspiratory phases in patients with chronic liver disease or liver cirrhosis. One hundred and eight patients who underwent MRE were included in this retrospective study. MRE was performed at 3 T based on both sequences during expiration as well as inspiration. Technical failure of MRE was determined if there was no pixel value with a confidence index higher than 95% and/or no apparent shear waves imaged. LS measurements were performed using free-drawing region of interest. To evaluate clinical factors related to the technical success rate of MRE, we assessed etiology of liver disease, ascites, body habitus, iron deposition, and liver morphology of patients. Statistical analysis was performed with the Wilcoxon test, Bland-Altman plot, independent t test, Mann-Whitney test, and McNemar test. The technical success rate of MRE in SE-EPI was significantly higher than that of GRE (98.1% vs. 80.7%, p < 0.0001). On the basis of univariate analysis, height, weight, and BMI were significantly associated with failure of MRE (p < 0.05). There was no significant difference in LS values between GRE and SE-EPI (2.82 kPa vs. 2.92 kPa (p > 0.05)). However, the LS values were significantly higher during inspiration than expiration with both GRE and SE-EPI (p < 0.0001). MRE in SE-EPI during expiratory breath-hold can be used as a reliable examination to evaluate liver fibrosis. • The technical success rate of MR elastography in spin-echo echo-planar imaging (SE-EPI) was significantly higher than that in gradient-recalled echo (GRE) during both the inspiratory and expiratory phases. • Liver stiffness values were significantly higher during inspiration than during expiration in both GRE and SE-EPI. • MR elastography in SE-EPI during expiratory breath-hold can be used as a reliable examination in patients with liver fibrosis.


Impact of Early Passive Exercise With Cycle Ergometer on Ventilator Interaction.
Early exercise has been recommended in critically ill patients, but its impact on subject-ventilator interaction is still unclear. Therefore, the aim of this study was to evaluate the occurrence of subject-ventilator asynchrony during passive exercise in mechanically ventilated subjects. This study included deeply sedated subjects who were under mechanical ventilation for < 72 h. Subjects were coupled to a cycle ergometer and maintained at rest for 5 min (baseline period). After this period, they started 20 min of passive exercise, followed by 10 min of rest (recovery period). The occurrence of asynchrony was monitored by the analysis of flow and airway pressure waveforms, registered throughout the protocol during the baseline, exercise, and recovery periods. Hemodynamic and respiratory parameters were registered at the end of each period. Finally, arterial blood gas analysis was performed twice, at the end of the baseline period and at the end of the recovery period. 8 subjects were enrolled (63.3 ± 16.7 y old, 50% male). The asynchrony index increased during exercise (median 32.1% [interquartile range (IQR) 18.6-47.6%]), compared to baseline (median 6.6% [IQR 3.9-10.4%]), returning to initial levels during the recovery period (median 2.7% [IQR 0-12.2%]). The most frequent types of asynchrony were ineffective triggering (index of 11.8% [IQR 1.2-22.5%] during exercise, compared to 2.0% [IQR 1.4-4.4%] at baseline), and insufficient flow (index of 11.7% [IQR 4.7-19.3%] during exercise, compared to 2.0% [IQR 1.1 to 3.3%] at baseline). There were no significant changes in the hemodynamic and respiratory variables. Early cycle ergometer passive exercise in deeply sedated subjects can worsen subject-ventilator interaction, due to ineffective triggering and insufficient flow. Adjustments in the ventilatory parameters may be necessary to avoid asynchrony during exercise.


Deep sternal wound infection - latissimus dorsi flap is a reliable option for reconstruction of the thoracic wall.
At present, data describing patients' long-term outcomes, quality of life, and survival after deep sternal wound infection are rarely available. The purpose of our study was to evaluate functional outcome and patient well-being after debridement and reconstruction of the sternal defect using a pedicled latissimus dorsi flap following deep sternal wound infection (DSWI). This retrospective analysis reviewed 106 cases of DSWI after open-heart surgery treated between May 1, 2012, and May 31, 2015. The parameters of interest were demographic and medical data, including comorbidity and mortality. Follow-up consisted of physical examination of the patients using a specific shoulder assessment, including strength tests and measurements of pulmonary function. The population consisted of 69 (65%) male and 37 (35%) female patients. Their average age at the time of plastic surgery was 69 years (range: 35-85). The 30-day mortality was 20% (n = 21); after one-year, mortality was 47% (n = 50), and at follow-up, it was 54% (n = 58). Heart surgery was elective in 45 cases (42%), urgent in 31 cases (29%) and for emergency reasons in 30 cases (28%). The preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE) averaged 16.3 (range: 0.88-76.76). On the dynamometer assessment, a value of 181 Newton (N) (±97) could be achieved on the donor side, in contrast to 205 N (±91) on the contralateral side. The inspiratory vital capacity of the lung was reduced to an average of 70.58% (range: 26-118), and the forced expiratory volume in 1 s was decreased to an average of 69.85% (range: 38.2-118). Given that only small adverse effects in shoulder function, strength, and pulmonary function were observed, the latissimus dorsi flap appears to be a safe and reliable option for the reconstruction of the sternal region after DSWI.


Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.
Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include decreasing the levels of DAergic markers in the striatum. We have determined that high-dose METH destabilizes microtubules in this pathway, which is manifested by decreased levels of acetylated (Acetyl) and detyrosinated (Detyr) α-tubulin (I). A microtubule stabilizing agent epothilone D protects striatal microtubules form the METH-induced loss of DAergic markers (II). These findings provide a new strategy for protection form METH - restoration of proper axonal transport.


The multidimensional nature of early prosocial behavior: a motivational perspective.
A majority of current work indicates that the different types of prosocial behavior in young children (helping, sharing, comforting) are not related to each other. Here, I review recent studies that examined the relations between prosocial actions as well as the antecedents and correlates of the particular domains of prosociality. I argue that in addition to different social-cognitive demands also different motivations are involved in early prosocial action, and that prosociality is thus a concept that encompasses-at least early in development-heterogeneous behaviors and motivations.


Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors.
Despite clinical intervention, glioblastoma (GBM) remains the deadliest brain tumor in adults. Its incurability is partly related to the establishment of drug resistance, both to standard and novel treatments. In fact, even though small kinase inhibitors have changed the standard clinical practice for several solid cancers, in GBM, they did not fulfill this promise. Drug resistance is thought to arise from the heterogeneity of GBM, which leads the development of several different mechanisms. A better understanding of the evolution and characteristics of drug resistance is of utmost importance to improve the current clinical practice. Therefore, the development of clinically relevant preclinical in vitro models which allow careful dissection of these processes is crucial to gain insights that can be translated to improved therapeutic approaches. In this review, we first discuss the heterogeneity of GBM, which is reflected in the development of several resistance mechanisms. In particular, we address the potential role of drug resistance mechanisms in the failure of small kinase inhibitors in clinical trials. Finally, we discuss strategies to overcome therapy resistance, particularly focusing on the importance of developing in vitro models, and the possible approaches that could be applied to the clinic to manage drug resistance.


National Survey to Assess Gender, Racial, and Ethnic Differences Among Radiology Residency Applicants Regarding Factors Impacting Program Selection.
Radiology has one of the lowest female representation rates in medicine and recruiting female residents is a challenge for some residency programs. There is limited understanding of gender differences among residency applicants during program selection. The study objective is to investigate which program factors were considered most important by radiology residency applicants and to assess for differences by gender, race and ethnicity. An anonymous survey was distributed electronically to diagnostic and interventional radiology residency programs in the US and Canada via the Association of Program Coordinators in Radiology (APCR). Residents were asked to evaluate the importance of 30 factors during evaluation of residency programs using a 5-point Likert scale (1 = not important, 5 = extremely important). 370 residents and 1 fellow completed the survey. Of the respondents, 269 were male (72.5%) and 101 were female (27.2%). The most important factors to respondents during program selection were program culture (4.42), geographic location (4.17), fellowship placement (4.14), and imaging and/or procedure volume (3.98). There was a significant difference between male and female respondents in the importance of program culture (p = 0.002), composition of current residents (p = 0.007), percentage of current female residents (p < 0.0001), program size (p = 0.047), call schedule (p = 0.025), percentage of female faculty (p < 0.0001), faculty ethnic and racial diversity (p < 0.0001), resident ethnic and racial diversity (p < 0.0001), which female respondents ranked more highly. Applicants consider many factors during residency program selection. Program culture, geographic location, fellowship placement and imaging and/or procedural volume were most important. There were significant differences by gender, race and ethnicity in importance of several factors.


A novel canine model of spinal cord ischemia with reproducible neurologic outcomes.
To develop a canine model of spinal cord ischemia (SCI) with highly reproducible neurologic outcomes. Spinal cord ischemia was induced by cross-clamping the proximal descending aorta. To produce substantial ischemia in the critical lumbar region, the proximal aortic blood pressure (PAP) was reduced to 80 mmHg by withdrawing blood into a reservoir connected to the left subclavian artery. We conducted an intraischemia spinal cord electrophysiologic study and a postischemia assessment of hindlimb motor function in six animals subjected to this procedure with an aortic occlusion time of 40 min, and in six animals subjected only to aortic occlusion for 60 min. All the animals subjected to this procedure exhibited a significant decrease in motor-evoked spinal cord potentials to transcranial electric stimulation (MEPs) during the acute ischemic phase, and they were paraplegic 48 h after ischemia. In contrast, two of the animals not subjected to PAP reduction showed complete functional recovery with intact MEP findings. This model is feasible for experimental SCI studies because it can reliably and easily reproduce substantial ischemia.


Sensory gating and psychosis vulnerability in cocaine-dependent individuals: preliminary data.
Factors increasing vulnerability of a cocaine user to develop psychotic symptoms are unknown. Deficits in sensory gating and attention, such as those occurring in idiopathic psychosis, might represent experimentally tractable factors contributing to vulnerability to cocaine-induced paranoia. Severity of cocaine-induced paranoid symptoms was assessed with the Cocaine Experience Questionnaire (CEQ) in 30 abstinent cocaine-dependent individuals. Sensory gating was assessed in a paired-click auditory evoked potential paradigm (S1 and S2) using the S2/S1 attenuation ratio of the P50 evoked response as the primary outcome measure. The Wender-Utah Rating Scale (WURS) for attention deficit was also administered. Subjects were divided into those with high CEQ scores (n = 10) and those with low CEQ scores (n = 20). The mean P50 ratios were significantly higher for the high CEQ subjects compared with the low CEQ group (F = 4.6, p <.04). The WURS did not correlate with the total CEQ but correlated with the CEQ Severity subscale, r =.432, p <.02. The data suggest that deficient P50 sensory gating and attention deficits may be associated with increased proneness to developing psychotic symptoms in the context of cocaine use. Further exploration of these factors seems warranted.


Demonstration of competition between endogenous dopamine and [11C]raclopride binding in in vitro brain slices using a dynamic autoradiography technique.
To elucidate the mechanism of in vivo binding competition between radioligand and endogenously released transmitter, we examined the influence of depolarization-induced dopamine (DA) release on [11C]raclopride-specific binding to D2 receptors in slices of living brain tissues using dynamic positron autoradiography. Rat brain slices were incubated in a chamber with [11C]raclopride in oxygenated medium at 34 degrees C for 150 min. Two-dimensional images of radioactivity in the slices were recorded on a storage phosphor screen and dynamic changes were measured. When the brain slices were exposed to the depolarization agents (25 mM K+, 50 mM K+, and 20 microM veratridine), the percentage inhibition of striatal [11C]raclopride-specific binding was 22 +/- 4%, 44 +/- 8% and 54 +/- 7% of the control, respectively. The percentage inhibition of [11C]raclopride-specific binding during each depolarization treatment agreed proportionally with the amount of DA released into the medium. However, preexposure of brain slices to the same depolarization treatment (50 mM K+) did not affect the [11C]raclopride-specific binding, suggesting that the reduction in receptor density and/or affinity was not involved in the decrease of [11C]raclopride-specific binding. [11C]Raclopride-specific binding decreased dose-dependently in the presence of exogenously added DA (range 0.005-3mM). The synaptic DA concentration during each depolarization treatment estimated using three different methods. These results suggest that the decrease of [11C]raclopride-specific binding to striatal slices following evoked DA release is due to competition between endogenous DA and raclopride. It is unlikely that changes in D(2) receptor density or in affinity of the receptors for raclopride are involved. These results provide supportive evidence for in vivo binding competition between radioligand and endogenous neurotransmitter.


Human chagas disease and migration in the context of globalization: some particular aspects.
Human Chagas disease originated in Latin America, being spread around the world in relation with multiple bioecological, sociocultural, and political factors. The process of the disease production and dispersion is discussed, emphasizing the human migration and correlated aspects, in the context of globalization. Positive and negative consequences concern the future of this trypanosomiasis, mainly in terms of the ecologic and sociopolitical characteristics of the endemic and nonendemic countries.


Comparative 16S rDNA metagenomics study of two samples of cassava peel heap from Nigeria and India.
The microbiology of many cassava products and the wastes generated during the processing have been reported; however, majority of these reports used culture-dependent methods. This has resulted in a dearth of information on the bacterial diversity of cassava peels and peel heaps. Large amounts of cassava peels generated during the processing of cassava root are usually discharged on land or water as wastes and are allowed to rot in the open, especially in some developing countries. Culture-independent methods such as PCR-based amplification and sequencing of 16S rRNA genes, among others have been used in recent times to study the diversity of microbes in different environmental samples. In this study, bacterial isolates were screened for cellulase and xylanase enzyme activities on minimal agar and genomic DNA was isolated from cassava peel samples; metagenomics was carried out using MiSeq 2 × 300 with primers specific for V3-V4 bacterial region. Samples collected from Nigeria (AAG) had more species compared with samples from India (JHA) with 793 and 525 observed OTUs (operational taxonomic units), respectively. Five bacterial isolates from cassava peel-heap samples obtained from Ogbomoso, Nigeria showed no ability to produce cellulase enzyme, seven isolates from the Nigeria samples and three from Jorhat samples were positive for xylanase production; the highest amylase activity was shown by isolate AG18 (10,055 U/mL), while the lowest was recorded for isolate JA2 (2333 U/mL) with a significant difference observed in the amylase activities of isolates (p ≤ 0.05). Comparing the most abundant taxonomy for each of the samples at different taxonomic levels, the most abundant for sample AAG were phylum Firmicutes (42.11%), class Bacilli (41.27%), order Lactobacillales (33.11%), family Acetobacteraceae (31.30%), genus Acetobacter (30.02%) and unclassified species of Acetobacter (29.88%), while sample JHA had Actinobacteria (47.47%) as the highest phylum and class, order Actinomycetales (47.47%), family Brevibacteriaceae (46.97%), genus Brevibacterium (46.97%) and unclassified species of Brevibacterium (46.89%). This study provides an insight into the vast diversity of the bacteria associated with cassava peel heaps and the ability of some of the bacteria to produce selected extracellular enzymes.


Management of inflamed sigmoid diverticulum inside an incarcerated right inguinal hernia: Case report of a rare discovery.
Incarcerated inguinal hernia is one of the most common emergencies in surgery. The diagnosis is usually made by physical examination, but the contents of the hernia sac may vary. We present a rare case of inflamed diverticulum of the sigmoid colon found within an incarcerated right inguinal hernia sac in a 77-year-old man. The inflamed diverticulum was resected, and the hernia was repaired with synthetic mesh. No postoperative complication occurred. No previous study has reported a similar approach. It is most unusual for an uncomplicated inflamed sigmoid colon diverticulum to be found in the hernia sac when performing acute repair of an incarcerated inguinal hernia. Resection of the diverticulum and subsequent repair of the hernia with synthetic mesh is an attractive alternative. Acute diverticulitis should always be considered in patients with an acute abdomen, this includes those with a painful hernia. Emergency surgery should not be delayed, and local resection of the inflamed diverticulum may be an option if no perforation is apparent, and the surrounding colon is unaffected.


Non-enzymatic amperometric detection of hydrogen peroxide in human blood serum samples using a modified silver nanowire electrode.
In this paper, we report a highly sensitive amperometric H2O2 sensor based on silver nanowires (AgNWs) modified screen printed carbon electrode. The AgNWs were synthesized using polyol method. The synthesized AgNWs were characterized by scanning electron microscopy, UV-vis spectroscopy and X-ray diffraction techniques. The average diameter and length of the synthesized AgNWs were found as 86±5 and 385nm, respectively. Under optimum conditions, the AgNWs modified electrode shows a stable amperometric response for H2O2 and was linear over the concentrations ranging from 0.3 to 704.8μM. The non-enzymatic sensor showed a high sensitivity of 662.6μAmM(-1)cm(-2) with a detection limit of 29nM. The response time of the sensor was found as 2s. Furthermore, the AgNWs modified electrode exhibited a good recovery of H2O2 (94.3%) in the human blood serum samples.


Application of lithium cationization tandem mass spectrometry for structural analysis of lignin model oligomers with β-β' and β-O-4' linkages.
Structural elucidation of lignin degradation products is a requirement for successfully developing lignin valorization technology. Most of mass spectrometry-based techniques have utilized negative ion mode mass spectrometry for structural elucidation of lignin-derived compounds. Unfortunately, simple deprotonation can lead to in-source fragmentation and may not be suitable for condensed lignin structures without acidic moieties. Herein, we present a lithium cationization methodology for mass spectrometry sequencing of advanced lignin oligomers having β-β' and β-O-4' bonding motifs. To do so, two advanced lignin oligomers were first synthesized through a step-by-step synthetic route, and then subjected to two different ESI mass spectrometry techniques in positive ion mode using lithium cations for ionization. An orbitrap mass spectrometer was used to obtain exact mass information, and higher-energy collisional dissociation (HCD) was used to sequence the lignin model oligomers. Based on the sequence-specific fragment ions, sequence rules were proposed. Multi-stage (MSn) collision-induced dissociation (CID) using an ion trap mass spectrometer provided data to investigate the origin of each fragment ion and to further confirm proposed fragmentation pathways. In addition to β-O-4' bond cleavage, the presented lithium cationization approach led to cleavage of β-β' bonds on the model oligomers in both ion trap and orbitrap mass spectrometry experiments. Additionally, MSn experiments were used to investigate possible lithium cationization sites on the model oligomers. Lithium cationization in positive ion mode mass spectrometry proved to be a robust tool for characterization and sequencing of advanced lignin oligomers with different bonding motifs.


Chronic fluoxetine treatment in socially-isolated rats modulates the prefrontal cortex synaptoproteome.
Exposure to chronic social isolation (CSIS) and synapse dysfunction have been implicated in the etiology of major depressive disorder (MDD). Fluoxetine (Flx) has been widely used to treat MDD, but its mechanisms of action remain elusive. We employed comparative synaptoproteomics to investigate the changes in the levels of proteins and molecular signaling pathways in prefrontal cortical samples of adult male Wistar rats exposed to CSIS, a rat model of depression, and CSIS rats treated with chronic Flx and controls, using liquid chromatography coupled to tandem mass spectrometry. Flx-treated control rats showed a decreased level of proteins involved in vesicle-mediated transport, and a predominantly increased level of exocytosis-associated proteins. CSIS significantly reduced the level of proteins involved in the ATP metabolic process, clathrin-dependent endocytosis, and proteolysis. Flx treatment in CSIS rats stimulated synaptic vesicle trafficking by increasing the regulation of exo/endocytosis-associated proteins, proteins involved in synaptic plasticity including neurogenesis, Cox5a, mitochondria-associated proteins involved in oxidative phosphorylation, and ion transport proteins (Slc8a2, Atp1b2). Flx treatment resulted in an increased synaptic vesicle dynamic, plasticity and mitochondrial functionality, and a suppression of CSIS-induced impairment of these processes. BIOLOGICAL SIGNIFICANCE: Identifying biomarkers of MDD and treatment response is the goal of many studies. Contemporary studies have shown that many molecular alterations associated with the pathophysiology of MDD reside within the synapse. As part of this research, a growing importance is the use of proteomics, as monitoring the changes in protein levels enables the identification of (possible) biochemical pathways and processes of importance for the development of depressive-like behavior and the efficacy of antidepressant treatments. We profiled proteomic changes representative of the development of CSIS-induced depressive-like behavior and the antidepressant effects of Flx. Our study has identified synaptosomal proteins and altered molecular pathways that may be potential markers of prefrontal cortical synaptic dysfunction associated with depressive-like behavior, and further clarified the mechanisms of depressive-like behavior and mode of action of Flx. Our findings indicate potential PFC synaptic targets for antidepressant treatment.


Surface properties of cells isolated from non-metastasizing and metastasizing hamster lymphosarcomas.
Present evidence suggests that the cell surface has an important role in metastasis. To examine this idea further, the surface properties of single cells isolated from the primary growths of a liver-metastasizing (ML) and a non-metastasizing (NML) lymphosarcoma were compared for adhesion to cell monolayers, cytopherometry, isoelectric focusing, adhesion to immobilized lectins and surface labelling with lactoperoxidase-catalysed radioiodination. It was found that the ML cells had increased adhesion to 3 out of 4 of the monolayers studies; a lower overall surface charge but greater peripheral concentrations of charge; and increased surface expression of the fucose moiety. No consistent difference between the two cell types was detected in the electrophoretic pattern of the labelled surface proteins. These findings are discussed in the light of present knowledge of the cell surface, and it is concluded that the significance of any of the observed changes in relation to metastasis has yet to be established.


IDEM: a Web application of case-based reasoning in histopathology.
Different software engineering and artificial intelligence methods can be used to design Internet retrieval of prototypical medical images. We used the case-based reasoning (CBR) approach to provide an 'intelligent' access to a collection of illustrated medical cases through the Internet. This paper presents a Web interface for the CBR system IDEM (image and diagnosis from examples in medicine) in the domain of breast pathology. Thanks to the definition of a similarity measure between the descriptions of cases we propose a flexible querying of the case-base and a quantitative browsing among cases through similarity links. The resemblance rates provided by the system argue for the quality and the relevancy of the retrieved data. The flexibility of the querying process is robust to missing information and could be adapted to a daily practice. The CBR approach is a promising method for a clinical relevant and an efficient retrieval of reference images and diagnosis clues through Internet.


Otolith formation in a mutant Medaka with a deficiency in gravity-sensing.
Mutant Medaka ha exhibit spontaneous mutation that is characterized by frequent inhibition or perturbation in the formation of utricular otoliths and/or semicircular canals. Three major features of otolith morphogenesis were observed in ha strain: 1) The initial appearance of otoliths was delayed, mispositioned, and malformed compared to normal embryos. 2) No utricular otoliths appeared on macula of any ha fry just after hatching. A symmetric state of otoliths was seen only when saccular otoliths were situated on macula in both inner ears. 3) In some fry, formation of utricular otoliths was observed in their later development. However, no new utricular otoliths appeared after fish were seventy or more days old after hatching. These observations show that otolith morphogenesis in ha is very different from that of wild-type. In this study, we classified adult ha into four different phenotypes using the existence or absence of utricular otoliths as our criteria. We concluded that dysfunction of utricular otoliths and semicircular canals cause a defect that affects the gravity-sensing abilities of medaka ha.


Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection.
The liquid biopsy has the potential to improve current clinical practice in oncology by providing real-time personalized information about a patient's disease status and response to treatment. In this study, we evaluated 161 peripheral blood (PB) samples that were collected around surgical resection from 47 metastatic colorectal cancer (mCRC) patients using the High-Definition Single Cell Assay (HDSCA) workflow. In conjunction with the standard circulating tumor cell (CTC) enumeration, cellular morphology and kinetics between time-points of collection were considered in the survival analysis. CTCs, CTC-Apoptotic, and CTC clusters were found to indicate poor survival with an increase in cell count from pre-resection to post-resection. This study demonstrates that CTC subcategorization based on morphological differences leads to nuanced results between the subtypes, emphasizing the heterogeneity within the CTC classification. Furthermore, we show that factoring in the time-point of each blood collection is critical, both for its static enumeration and for the change in cell populations between draws. By integrating morphology and time-based analysis alongside standard CTC enumeration, liquid biopsy platforms can provide greater insight into the pathophysiology of mCRC by highlighting the complexity of the disease across a patient's treatment.


Mould-ripened meat products: New selection scheme for non-toxigenicPenicillium spp.
Species belonging to the genusPenicillium are known to produce a variety of mycotoxins. The use of non-toxigenic isolates is therefore of a major concern when selecting strains for improving mould-ripened food products. For initial selection 249 different strains of the genusPenicillium originally isolated from food products have been used in this study. The isolates were grouped according to the pattern of their secondary metabolites by TLC methods. Mould ripened salamis were then produced to prove the technological suitability of the strains. The potency of selected strains to produce antibiotic, cytotoxic and mutagenic metabolites was proven by the use of bacterial test systems, the MTT (3-(4.5-dimethylthiazol-2yl)-2.5-diphenyltetrazoliumbromide) -cell culture bioassay and the AMES-test, respectively.A total of 13 isolates out of 249 strains tested were found to meet the demands on technological suitability and toxicological safety to the greatest extent and could thus be recommended for the use in the meat industry. The chemotaxonomic characterisation of the strains showed correlation with the technological suitability and offers a simple but useful first step in selecting appropriate strains. Moreover, the overall selection scheme presented in this study was found to be useful for screening out toxigenic species and to enhance food safety aspects.


High-pressure injection injury with river water.
A case of high pressure injection and laceration of the calf with river water is reported, the first such case appearing in the literature. As with high pressure injection of grease, paint, paint thinner, mineral spirits, diesel oil, gasoline, and turpentine, this injury is a surgical emergency. All patients must be admitted for surgical debridement, irrigation, parenteral antibiotics, and observation. River water, contaminated by sewage and industrial wastes, has great irritative and infective potential.


The effect of lattice spacing change on cross-bridge kinetics in chemically skinned rabbit psoas muscle fibers. I. Proportionality between the lattice spacing and the fiber width.
Chemically skinned rabbit psoas muscle fibers/bundles were osmotically compressed with a macromolecule dextran T-500 (0-16%, g/100 ml) at 20 degrees C, 200 mM ionic strength, and pH 7.0. The lattice spacing of psoas bundles was measured by equatorial x-ray diffraction studies during relaxation and after rigor induction, and the results were compared with the fiber width measurements by optical microscopy. The purpose of the present study is to determine whether fiber width is a reliable measure of the lattice spacing, and to determine the available spacing for myosin cross-bridges between the thick and thin filaments. We observed that both the lattice spacing and the fiber width decreased with an increase in the dextran concentration during relaxation or after rigor induction, and that the spacing and the fiber width were proportionately related. We further observed that, in the absence of dextran, the lattice spacing (and the fiber width) shrank on a relax-to-rigor transition, whereas in the presence of 16% dextran, the spacing expanded on a relax-to-rigor transition. The cross-over of these plots occurred at the 4-7% dextran concentration. During Ca activation, the fiber width shrank in the absence of dextran, and it slightly expanded in the presence of 14.4% dextran. The degree of expansion was not as large as in the relax-to-rigor transition, and the cross-over occurred at about 11% dextran concentration. We also carried out experiments with dextran T-40 and T-10 to determine the upper limit of the molecular weight that enters the lattice space. We found that the upper limit is about 20 kD.