Sex and race differences in fat distribution among Asian, African-American, and Caucasian prepubertal children.
Sexual dimorphism in fat distribution is thought to emerge during puberty. Truncal or android body fat distribution is characteristic of adult males but is also recognized as a human cardiovascular risk factor. Race differences in truncal fat are clearly evident in adults and have been described in prepubertal children but not between Asians and other race groups. The aim of this study in African-American, Asian, and Caucasian prepubertal children was to evaluate sex differences and race differences in body fat distribution. Analysis of covariance was used to explore fat distribution in 358 prepubertal children (176 girls and 182 boys; 143 Asians, 95 African-Americans, and 120 Caucasians), measured by skinfold thickness and dual-energy x-ray absorptiometry (DXA) in a cross-sectional study. Extremity and gynoid fat masses were evaluated after adjustment for trunk or android fat, respectively, and for covariates including age, weight, height, and interactions. In Asian children, sex differences were present in models for gynoid fat by DXA only (P < 0.001), with girls having greater gynoid fat than boys. In African-American and Caucasian children, sex differences were present in models for extremity and gynoid fat masses, measured by both methods. Among girls, Asians had generally lower adjusted extremity and gynoid fat than Caucasians and African-Americans. Among boys, Asians had lower adjusted extremity fat by DXA than Caucasians (P < 0.01) but greater gynoid fat by skinfolds than African-Americans (P < 0.01). This study of prepubertal children demonstrates that: 1) sex differences in body fat distribution are present in prepubertal children but that the specific characteristics for Asians differ from African-Americans and Caucasians, and 2) differences in body fat distribution in Asian children, compared with African-Americans and Caucasians, are present but vary by sex. This comparison of African-American, Asian, and Caucasian prepubertal children suggests phenotypic differences. Additional studies are needed to explore the metabolic and health risk implications of these findings.


Inhibition of GSK 3β activity is associated with excessive EZH2 expression and enhanced tumour invasion in nasopharyngeal carcinoma.
Enhancer of zeste homolog 2 (EZH2) has been shown to contribute to tumour development and/or progression. However, the signalling pathway underlying the regulation of EZH2 in nasopharyngeal carcinoma (NPC) remains unclear. Since EZH2 contains the putative Glycogen synthase kinase 3 beta (GSK3β) phosphorylation motif ADHWDSKNVSCKNC (591) and may act as a possible substrate of GSK-3β, it is possible that inactivation of GSK3β may lead to excessive EZH2 expression in NPC. We first examined the expression of EZH2 and phosphorylated GSK3β (p-GSK3β) by immunohistochemical staining in NPC samples. Then, we evaluated the interaction of GSK3β and EZH2 using immunoprecipitation and immune blot. Moreover, we determined the effect of inhibition of GSK3β activity on EZH2 expression and tumor invasiveness in NPC cell lines in vitro. Finally, we evaluated the invasive properties of NPC cells after knocking down EZH2 expression with EZH2 siRNA. We found that expression of EZH2 correlated with phosphorylated GSK3β (p-GSK3β) at Ser 9 (an inactivated form of GSK3β) in human nasopharyngeal carcinoma (NPC) samples. We also provided evidence that GSK3β is able to interact with EZH2 using immunoprecipitation and immune blot. Furthermore, we found that inhibition of GSK3β activity can lead to upregulation of EZH2 in NPC cell lines in vitro, with enhanced local invasiveness. By knocking down EZH2 expression with EZH2 siRNA, we found that these invasive properties were EZH2 dependent. Our findings indicate that GSK3β inactivation may account for EZH2 overexpression and subsequent tumour progression, and this mechanism might be a potential target for NPC therapy.


Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities.
The SV40 enhancer contains three genetically defined elements, called A, B and C, that can functionally compensate for one another. By using short, synthetic DNA oligonucleotides, we show that each of these elements can act autonomously as an enhancer when present as multiple tandem copies. Analysis of a progressive series of B element oligomers shows a single element is ineffective as an enhancer and that the activity of two or more elements increases with copy number. Assay in five different cell lines of two separate enhancers containing six tandem copies of either the B or C element shows that these elements possess different cell-specific activities. Parallel oligomer enhancer constructs containing closely spaced double point mutations display no enhancer activity in any of the cell lines tested, indicating that these elements represent single units of enhancer function. These elements contain either a 'core' or 'octamer' consensus sequence but these consensus sequences alone are not sufficient for enhancer activity. The different cell-specific activities of the B and C elements are consistent with functional interactions with different trans-acting factors. We discuss how tandem duplication of such dissimilar elements, as in the wild-type SV40 72-bp repeats, can serve to expand the conditions under which an enhancer can function.


Lightness perception in simple images: testing the anchoring rules.
One approach toward understanding how vision computes surface lightness is to first determine what principles govern lightness in simple stimuli and then test whether these hold for more complex stimuli. Gilchrist (2006) proposed that in the simplest images that produce the experience of a surface (two surfaces differing in luminance that fill the entire visual field) lightness can be predicted based on two anchoring rules: the highest luminance rule and the area rule, plus a scale normalization. To test whether these anchoring rules hold when critical features of the stimuli are varied, we probed lightness in simple stimuli, painted onto the inside of hemispheric domes viewed under diffuse lighting. We find that although the highest luminance surface appears nearly white across a large variation in illumination (as predicted by the highest luminance rule), its lightness tends to increase as its luminance increases. This effect is small relative to the size of the overall luminance change. Further, we find that when the darker region fills more than half of the visual field, it appears to lighten with further increases in area but only if it is a single surface. Splitting the dark region into smaller sectors that cover an equal cumulative area diminishes or eliminates the area effect.


Protective effect of coenzyme Q10 in simvastatin and gemfibrozil induced rhabdomyolysis in rats.
Administration of simvastatin (80 mg/kg, po. evening dose) and gemfibrozil (600 mg/kg, po twice) for 30 days produced significant decrease in the level of reduced glutathione, superoxide dismutase, catalase and increase in the level of lipid peroxidation and various serum parameters (creatine phosphokinase, lactate dehydrogenase, serum glutamate oxaloacetate transaminase, creatinine, urea and blood urea nitrogen). This suggested involvement of oxidative stress in rhabdomyolysis. Increase in the level of reduced glutathione, superoxide dismutase, catalase and decrease in the level of lipid peroxidation and serum parameters after administration of antioxidant CoQ10 (10 mg/kg.ip) proved the protective effect of CoQ10 in rhabdomyolysis.


Fluorescence Sensing of Circulating Diagnostic Biomarkers Using Molecular Probes and Nanoparticles.
The interplay of photonics, nanotechnology, and biochemistry has significantly improved the identification and characterization of multiple types of biomarkers by optical biosensors. Great achievements in fluorescence-based technologies have been realized, for example, by the advancement of multiplexing techniques or the introduction of nanoparticles to biochemical and clinical research. This review presents a concise overview of recent advances in fluorescence sensing techniques for the detection of circulating disease biomarkers. Detection principles of representative approaches, including fluorescence detection using molecular fluorophores, quantum dots, and metallic and silica nanoparticles, are explained and illustrated by pertinent examples from the recent literature. Advanced detection technologies and material development play a major role in modern biosensing and consistently provide significant improvements toward robust, sensitive, and versatile platforms for early detection of circulating diagnostic biomarkers.


Developmental testis-specific regulation of mRNA levels and mRNA translational efficiencies for TATA-binding protein mRNA isoforms.
Early spermatids contain roughly 1000-fold more TATA-binding protein (TBP) mRNA than do somatic cells. The appearance of TBP-overexpressing spermatids in the developing testis is accompanied by a large increase in whole-organ levels of total RNA and of poly(A)+ RNA per cell. Whereas somatic cells initiate transcription of TBP mRNA at a single promoter/first exon (exon 1C), in adult testis, two additional major promoter/first exons (1D and 1E) are used. We have examined the expression of the somatic and testis-specific TBP mRNA isoforms during rodent testis development. In juvenile testes TBP mRNAs containing either exon 1C or exon 1D, but none containing exon 1E, are detected. At 21 days of age, all TBP mRNA isoforms begin to overaccumulate. The onset of TBP mRNA overaccumulation is marked first by an increase in levels of polysomal TBP mRNA, and later by accumulation of mRNP-associated TBP mRNA. In adult testes, only 30% of the total TBP mRNA is engaged by polysomes; the remainder is sequestered as mRNP particles. All of the TBP mRNA isoforms in adults exist both as free mRNP particles and as polysomes; however, the fraction in polysomes varies from 60% (exon 1C) to 10% (exon 1E). This suggests that sequences within the first exons alter the probability that the mRNA will either assemble into polysomes or into translationally inactive mRNP particles.


Revised Kubelka-Munk theory. III. A general theory of light propagation in scattering and absorptive media.
A generally applicable theoretical model describing light propagating through turbid media is proposed. The theory is a generalization of the revised Kubelka-Munk theory, extending its applicability to accommodate a wider range of absorption influences. A general expression for a factor taking into account the effect of scattering on the total photon path traversed in a turbid medium is derived. The extended model is applied to systems of ink-dyed paper sheets-mixtures of wood fibers with dyes-which represent examples of systems that have thus far eluded the original Kubelka-Munk model. The results of simulations of the spectral dependence of Kubelka-Munk coefficients of absorption and scattering show that they compare very well with those derived from experimental results.


Measures of the brain functional network that correlate with Alzheimer's neuropsychological test scores: An fMRI and graph analysis study.
Neural degeneration in Alzheimer's disease (AD) leads to structural topology deformation that in turn changes brain functionality. The main aim of the present study is to find the brain's functional connectivity network (FCN) correlates of Alzheimer's psychological test scores. To this end, the brain's FCN is extracted from the resting state functional magnetic resonance images (rs-fMRI) of healthy controls and patients with AD and represented as a graph. Then, network measures are calculated from the graphs. The correlations between the brain network measures and five AD psychological assessment test scores are evaluated. The results show positive correlation between the Mini-Mental State Examination (MMSE) and nodal strength in the left insula and negative correlation between the Clinical Dementia Rating (CDR) score and local efficiency of left olfactory cortex and also eigenvector centrality of left supramarginal cortex. The Neuropsychiatric Inventory Questionnaire (NPI-Q) also seems to be correlated with network measures of the left superior parietal gyrus. Moreover, notable decreased continuity are spotted in the limbic system. These measures can be used to provide an objective tool for AD diagnosis.


Distribution and change of collagen types I and III and elastin in developing leg muscle in rat.
The distribution of collagen types I and III and elastin in the developing leg muscles were studied by immunohistochemistry in rat. From 0-day to 8-weeks old, the size of the gastrocnemius and plantaris muscles increased. The muscle connective tissue developed in the order of epimysium, perimysium and finally endomysium. The epimysium contained a considerable amount of collagen types I and III and some elastin in the neonates. These components in the epimysium remained almost unchanged in their distribution during development. The perimysium had little collagen type I and III or elastin at 0 day. Collagen type I and elastin slightly increased around 2 and 1 week, respectively, and returned to the previous levels. Collagen type III, however, increased and became abundant after 1 week. In the endomysium, the amounts of collagen type I and elastin were slight during postnatal growth, while collagen type III gradually increased after 2 weeks. The intramuscular tendons consistently showed intense reactivity for collagen type I and weak staining for elastin, whereas the staining for collagen type III decreased after 1 week and was finally restricted to the surface of intramuscular tendons. This study clearly demonstrated that the distribution of collagens, but not of elastin, significantly changed during development. The increase in collagen type III in the perimysium and endomysium, and its decrease in the intramuscular tendons probably reflect functional demands imposed on these connective tissues, i.e., shear forces in the former two and tensile loading in the latter.


Changes in distribution and microstructure of bauxite residue aggregates following amendments addition.
Bauxite residue is a highly alkaline byproduct which is routinely discarded at residue disposal areas. Improving soil formation process to revegetate the special degraded lands is a promising strategy for sustainable management of the refining industry. A laboratory incubation experiment was used to evaluate the effects of gypsum and vermicompost on stable aggregate formation of bauxite residue. Aggregate size distribution was quantified by fractal theory, whilst residue microstructure was determined by scanning electron microscopy and synchrotron-based X-ray micro-computed tomography. Amendments addition increased the content of macro-aggregates (>250 μm) and enhanced aggregate stability of bauxite residue. Following gypsum and vermicompost addition, fractal dimension decreased from 2.84 to 2.77, which indicated a more homogeneous distribution of aggregate particles. Images from scanning electron microscopy and three-dimensional microstructure demonstrated that amendments stimulate the formation of improved structure in residue aggregates. Pore parameters including porosity, pore throat surface area, path length, and path tortuosity increased under amendment additions. Changes in aggregate size distribution and microstructure of bauxite residue indicated that additions of gypsum and vermicompost were beneficial to physical condition of bauxite residue which may enhance the ease of vegetation.


The effectiveness and experience of self-management following acute coronary syndrome: A review of the literature.
To evaluate the effectiveness of interventions used to support self-management, and to explore patients' experiences after acute coronary syndrome in relation to self-management. Scoping review. Keyword search of CINAHL Plus, Medline, the Cochrane Library, and PsycINFO databases for studies conducted with adult population and published in English between 1993 and 2014. From title and abstract review, duplicated articles and obviously irrelevant studies were removed. The full texts of the remaining articles were assessed against the selection criteria. Studies were included if they were original research on: (1) effectiveness of self-management interventions among individuals following acute coronary syndrome; or (2) patients' experience of self-managing recovery from acute coronary syndrome. 44 articles (19 quantitative and 25 qualitative) were included. Most studies were conducted in western countries and quantitative studies were UK centric. Self-management interventions tended to be complex and include several components, including education and counselling, goal setting and problem solving skills which were mainly professional-led rather than patient-led. The review demonstrated variation in the effectiveness of self-management interventions in main outcomes assessed - anxiety and depression, quality of life and health behavioural outcomes. For most participants in the qualitative studies, acute coronary syndrome was unexpected and the recovery trajectory was a complex process. Experiences of making adjustment and adopting lifestyle changes following acute coronary syndrome were influenced by subjective life experiences and individual, sociocultural and environmental contexts. Participants' misunderstandings, misconceptions and confusion about disease processes and management were another influential factor. They emphasised a need for ongoing input and continued support from health professionals in their self-management of rehabilitation and recovery, particularly during the initial recovery period following hospital discharge. Evidence of the effectiveness of self-management interventions among people with acute coronary syndrome remains inconclusive. Findings from the patients' experiences in relation to self-management following acute coronary syndrome provided important insights into what problems patients might have encountered during self-managing recovery and what support they might need, which can be used to inform the development of self-management interventions. Theoretical or conceptual frameworks have been minimally employed in these studies and should be incorporated in future development and evaluation of self-management interventions as a way of ensuring clarity and consistency related to how interventions are conceptualised, operationalised and empirically studied. Further research is needed to evaluate self-management interventions among people following acute coronary syndrome for sustained effect and within different health care contexts.


KappaM-conotoxin RIIIK, structural and functional novelty in a K+ channel antagonist.
Venomous organisms have evolved a variety of structurally diverse peptide neurotoxins that target ion channels. Despite the lack of any obvious structural homology, unrelated toxins that interact with voltage-activated K(+) channels share a dyad motif composed of a lysine and a hydrophobic amino acid residue, usually a phenylalanine or a tyrosine. kappaM-Conotoxin RIIIK (kappaM-RIIIK), recently characterized from the cone snail Conus radiatus, blocks Shaker and TSha1 K(+) channels. The functional and structural study presented here reveals that kappaM-conotoxin RIIIK blocks voltage-activated K(+) channels with a novel pharmacophore that does not comprise a dyad motif. Despite the quite different amino acid sequence and no overlap in the pharmacological activity, we found that the NMR solution structure of kappaM-RIIIK in the C-terminal half is highly similar to that of mu-conotoxin GIIIA, a specific blocker of the skeletal muscle Na(+) channel Na(v)1.4. Alanine substitutions of all non-cysteine residues indicated that four amino acids of kappaM-RIIIK (Leu1, Arg10, Lys18, and Arg19) are key determinants for interaction with K(+) channels. Following the hypothesis that Leu1, the major hydrophobic amino acid determinant for binding, serves as the hydrophobic partner of a dyad motif, we investigated the effect of several mutations of Leu1 on the biological function of kappaM-RIIIK. Surprisingly, both the structural and mutational analysis suggested that, uniquely among well-characterized K(+) channel-targeted toxins, kappaM-RIIIK blocks voltage-gated K(+) channels with a pharmacophore that is not organized around a lysine-hydrophobic amino acid dyad motif.


Development of granulomas and vascular fibrocellular proliferation in the lungs of pigs receiving long-term lipid-based parenteral nutrition.
The lungs of pigs receiving long-term total parenteral nutrition (TPN) have been studied. A total of 20 pigs were tentatively infused with TPN through central venous catheters for 7 weeks. To secure adequate nutrition and gastrointestinal absorbance of nutrients, an additional full oral diet was given to eight of these animals. Fifteen control animals received Ringer solution through central venous catheters in addition to the oral diet. All animals infused with TPN for 7 weeks developed lung granulomas, a finding not observed in control animals. No lung granulomas were seen in three TPN animals sacrificed after 3 to 5 weeks owing to illness. All TPN animals also developed tissue reactions suggesting long-standing lung vascular inflammation. Similar vascular changes were seen in seven control animals that had bacterial infection or endotoxemia. The total amount of neutral fat in lung homogenate tended to increase in animals given TPN, and the linoleic acid content was significantly increased. In conclusion, long-term TPN caused lung granulomas in pigs. Vascular damage seemed to be accelerated by bacterial infection as well as by the TPN. The tissue reactions presumably involved long-term activation of monocytes/macrophages.


An enhanced bioluminescence-based Annexin V probe for apoptosis detection in vitro and in vivo.
The process of controlled cellular death known as apoptosis has an important central role not only in normal homeostatic maintenance of tissues, but also in numerous diseases such as cancer, neurodegenerative, autoimmune, and cardiovascular diseases. As a result, new technologies with the capability to selectively detect apoptotic cells represent a central focus of research for the study of these conditions. We have developed a new biosensor for the detection of apoptotic cells, incorporating the targeted selectivity for apoptotic cells from Annexin V with the sensitivity of bioluminescence signal generation from a serum-stable mutant of Renilla luciferase (RLuc8). Our data presents a complete characterization of the structural and biochemical properties of this new Annexin-Renilla fusion protein (ArFP) construct, as well as a validation of its ability to detect apoptosis in vitro. Moreover, this work represents the first report of a bioluminescent Annexin V apoptosis sensor utilized in vivo. With this new construct, we examine apoptosis within disease-relevant animal models of surgery-induced ischemia/reperfusion, corneal injury, and retinal cell death as a model of age-related macular degeneration. In each of these experiments, we demonstrate successful application of the ArFP construct for detection and bioluminescence imaging of apoptosis within each disease or treatment model. ArFP represents an important new tool in the continuously growing kit of technologies for apoptosis detection, and our results from both in vitro and in vivo experiments suggest a diverse range of potential clinically relevant applications including cancer therapeutic screening and efficacy analysis, atherosclerosis and cardiovascular disease detection, and the monitoring of any number of other conditions in which apoptosis has a central role.


Cardioselective beta-blockers for chronic obstructive pulmonary disease.
Beta-blocker therapy has a proven mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with chronic obstructive pulmonary disease (COPD). To assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. A comprehensive search of the Cochrane Airways Group Specialised Register (derived from systematic searches of CENTRAL, MEDLINE, EMBASE and CINAHL) was carried out to identify randomised blinded controlled trials from 1966 to May 2005. We did not exclude trials on the basis of language. Randomised, blinded, controlled trials of single dose or longer duration that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 second (FEV1) or symptoms in patients with COPD. Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Two interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. Eleven studies of single-dose treatment and 9 of treatment for longer durations, ranging from 2 days to 12 weeks, met selection criteria. Cardioselective beta-blockers, given as a single dose or for longer duration, produced no change in FEV1 or respiratory symptoms compared to placebo, and did not affect the FEV1 treatment response to beta2-agonists. A subgroup analysis revealed no change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component. Cardioselective beta-blockers, given to patients with COPD in the identified studies did not produce adverse respiratory effects. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should not be routinely withheld from patients with COPD.


Impacts of cannabinoid receptor ligands on nicotine- and chronic mild stress-induced cognitive and depression-like effects in mice.
Taking into account the rather frequent concomitance of nicotine abuse and stress, we aimed to research memory- and depression-related effects of nicotine administration in combination with chronic mild unpredictable stress (CMUS) in mice and an involvement of the endocannabinoid system through CB1 and CB2 receptors. Mice were submitted to the CMUS for 4 weeks. Effects on depression-like behaviors and cognition, exerted by a combined administration of CB1, i.e., Oleamide (2.5, 5.0 mg/kg), AM 251 (0.1, 0.25 mg/kg) and CB2, i.e., JWH 133 (0.5, 2.0 mg/kg), AM 630 (0.25, 2.0 mg/kg) receptor ligands and nicotine (0.05, 0.1, 0.2 and 0.5 mg/kg), were then studied in stressed and unstressed mice by the forced swimming test and the passive avoidance paradigm, respectively. The results revealed that the CMUS-exposed mice exhibited depression-like behaviors and memory disturbances, while both effects were alleviated by nicotine. CB1 receptor ligands decreased antidepressive and cognitive (the latter for CB1 receptor antagonist only) effects of subchronic nicotine administration in stressed mice. CB1 and CB2 receptor antagonists exerted themselves some procognitive effects in those mice. Regarding the unstressed mice, CB1 and CB2 receptor ligands reversed the antidepressive effects of subchronic nicotine administration, while nicotine, in an ineffective dose, co-administered with CB2 receptor ligands, improved cognition. We confirmed the role of the two main subtypes of cannabinoid receptors, termed CB1 and CB2, on stress- and nicotine-related behavioral changes in mice. Our study has contributed to the understanding of the mechanisms involved in stress- and nicotine-induced disorders, such as anhedonia and memory disturbances.


planck-->0 and classical-quantum correspondence in the kicked Harper model.
We investigate classical-quantum correspondence for the kicked Harper model for extremely small values of the Planck constant (planck). In the asymmetric case a pure quantum state shows a clear signature of classical diffusive as well as superdiffusive transitions asymptotically independent of planck. However, for the symmetric case, the planck independent behavior occurs only for the renormalized parameter (-)K=K/(2planck) with intriguing features such as a sharp transition from integrable to nonintegrable transport at (-)K=pi/2, a series of transitions at multiples of pi, and the periodicity of the transmission probability. We suggest that even as planck-->0, the quantum dynamics is influenced by cantori and additional features emerge in their absence.


Social Cognition in Children with High-Functioning Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Associations with Executive Functions.
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders characterized by social impairments. The first objective of this study was to analyze social cognition deficits of children with ADHD, high-functioning ASD (HFASD), and typical development (TD) in their performance on explicit and applied measures of theory of mind (ToM). The second objective was to investigate the relationships between executive functions and social cognition in HFASD and ADHD. One hundred and twenty-six 7- to 11-year old children, 52 with HFASD, 35 with ADHD, and 39 with TD, performed the NEPSY-II social perception subtests. Parents estimated their children's ToM skills using the Theory of Mind Inventory (ToMI). Teacher-reported data from the Behavior Rating Inventory of Executive Function (BRIEF) were also obtained. The HFASD and ADHD groups showed worse performance on the verbal ToM task than the TD group, and only the performance of the HFASD group was significantly lower than the TD group on the contextual ToM task. Parents also estimated that the HFASD group had more difficulties on the applied ToM than the ADHD and TD groups. Furthermore, there is a different executive function-theory of mind link in the HFASD and ADHD groups: behavioral regulation processes such as inhibition and emotional control are more associated with social cognition in children with ADHD, whereas metacognitive processes such as initiation and planning have a strong association with social cognition in children with HFASD. These findings have implications for understanding social perception deficits in neurodevelopmental disorders, highlighting the need for early intervention.


Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy: a PROVE IT-TIMI 22 substudy.
This study sought to evaluate the safety and efficacy of achieving very low calculated low-density lipoprotein (LDL) levels with intensive statin therapy. Intensive statin therapy reduces clinical events occurring after acute coronary syndrome (ACS) and may result in LDL levels markedly lower than guideline levels. Prior epidemiologic and preclinical studies raise concerns about the safety of very low cholesterol levels. The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study compared intensive therapy (atorvastatin, 80 mg) and moderate therapy (pravastatin, 40 mg) in patients after ACS. Patients treated with atorvastatin were divided by four-month LDL values into groups: >100, >80 to 100 (reference-range-meeting guidelines), >60 to 80, >40 to 60, and <40 mg/dl. Baseline, clinical, and safety data were compared among groups achieving guideline recommendation levels or lower. Among 1,825 patients with four-month LDL, 91% were at goal (<100 mg/dl). The distribution was >80 to 100 mg/dl (14%), >60 to 80 mg/dl (31%), >40 to 60 mg/dl (34%), and <40 mg/dl (11%). Those with lower LDL levels were more often male, older, and diabetic, and had lower baseline LDL levels. They had prior statin therapy and fewer prior myocardial infarctions (MI). There were no significant differences in safety parameters, including muscle, liver, or retinal abnormalities, intracranial hemorrhage, or death, in the very low LDL groups. The <40 mg/dl and 40 to 60 mg/dl groups had fewer major cardiac events (death, MI, stroke, recurrent ischemia, revascularization). Compared with patients treated with an accepted LDL goal (80 to 100 mg/dl), there was no adverse effect on safety with lower achieved LDL levels, and apparent improved clinical efficacy. These data identify no intrinsic safety concern of achieving low LDL and, therefore, a strategy of intensive treatment need not be altered in patients achieving very low LDL levels.


Bound for the moment generating function from the detailed fluctuation theorem.
A famous consequence of the detailed fluctuation theorem (FT), p(Σ)/p(-Σ)=exp(Σ), is the integral FT 〈exp(-Σ)〉=1 for a random variable Σ and a distribution p(Σ). When Σ represents the entropy production in thermodynamics, the main outcome of the integral FT is the second law, 〈Σ〉≥0. However, a full description of the fluctuations of Σ might require knowledge of the moment generating function (MGF), G(α):=〈exp(αΣ)〉. In the context of the detailed FT, we show the MGF is lower bounded in the form G(α)≥B(α,〈Σ〉) for a given mean 〈Σ〉. As applications, we verify that the bound is satisfied for the entropy produced in the heat exchange problem between two reservoirs mediated by a weakly coupled bosonic mode and a qubit swap engine.


Leveraging homologous recombination repair deficiency in sarcoma.
Personalised oncology is at the forefront of cancer research. The goal of personalised oncology is to selectively kill cancer cells while minimising side effects on normal tissue. This can be achieved by identifying and targeting cancer vulnerabilities that distinguish it from normal cells. Many cancers are deficient in high-fidelity DNA repair pathways that maintain genomic stability, such as homologous recombination (HR). Such cancers are highly sensitive to targeted therapies that induce DNA damage or inhibit DNA repair pathways. A notable example and a poster child of personalised oncology are PARP1/2 inhibitors (PARPi) that selectively kill HR-deficient (HRD) cancer cells by preventing repair of DNA gaps or single-strand breaks (SSBs) (Slade, 2020). Inhibitors of cell cycle checkpoints such as CHK1 and WEE1 can also eliminate HRD cancers by pushing cancer cells through the cell cycle despite unrepaired DNA damage and causing death by mitotic catastrophe (Groelly et al, 2022). PARPi have been approved for the treatment of ovarian, breast, pancreatic, and prostate cancer but other cancer types with an HRD signature (HRDness) may also respond to PARPi treatment. Planas-Paz et al (2023) now show that many sarcomas show HRDness and respond to PARP1/2 and WEE1 inhibitors, thus offering a new personalised oncology approach for this treatment-refractory cancer.


Titrimetric determination of ascorbic acid using chloranil.
Ascorbic acid is oxidized and quantitatively titrated with chloranil (2,3,5,6-tetrachloro-1,4-benzoquinone) in the presence of hexamethylenetetramine in acetone-water; the end point is determined visually by the appearance of a golden yellow color. Colored solutions are assayed by setting the initial absorbance at 451 nm to zero or the minimum, titrating with chloranil solution, and measuring absorbance after each increment of titrant. A plot of the volume of chloranil added against the absorbance gives a straight line with the volume intercept as the end point. Interference by the thiol group of cysteine, glutathione, etc., is avoided by masking with acrylamide; interference by iron(II) is masked with ammonium thiocyanate and sodium potassium tartrate. Hydrogen sulfite and thiourea (which do not interfere) are added as antioxidants during extraction of ascorbic acid from drugs and fruits.


A Comparison of Postoperative Outcomes in Immediate Versus Delayed Reconstruction After Mastectomy.
The objective of this study was to evaluate the frequency of various postoperative complications in patients undergoing either immediate or delayed breast reconstruction after mastectomy for malignancy. The ACS-NSQIP 2005-2012 database was queried for patients who underwent mastectomy for the treatment of breast malignancy. These mastectomy cases were then stratified, generating "mastectomy alone" and "mastectomy with immediate reconstruction" cohorts. Database analysis also identified "delayed-reconstruction" oncologic patients. All patients undergoing reconstruction were then stratified into the tissue expander/implant or flap-based reconstruction group. The frequency of postoperative complications was assessed. A multiplicative risk model was used to calculate the probability of postoperative complications after undergoing a mastectomy alone, followed by reconstruction on a different date. These values were compared with the frequency of postoperative complications in the "mastectomy with immediate reconstruction" cohort, and 1-sample binomial tests were performed to determine statistical significance. A total of 49,450 cases that underwent either mastectomy alone (n = 30,226), mastectomy with immediately tissue expander/implant reconstruction (n = 13,513), mastectomy with immediate flap reconstruction (n = 2854), delayed tissue expander/implant reconstruction (n = 2047), or delayed flap reconstruction (n = 810) were identified. When compared with a delayed reconstructive model, immediate reconstruction after mastectomy was associated with increased flap or tissue expander/implant failure. However, delayed reconstructive modalities were associated with increased postoperative medical and surgical complications. Finally, in flap-based reconstruction, the incidence of return to the operating room was higher in delayed reconstruction than in immediate reconstruction. Awareness of complications associated with each reconstructive modality will allow both surgeons and patients to effectively decide upon reconstructive options.


Transferred humoral immunity in chickens to Mycoplasma gallisepticum.
Progeny chicks of Mycoplasma gallisepticum (MG)-infected and MG-free white leghorns were used to evaluate the protective effects of maternal antibodies against aerosol challenge with the virulent R strain of MG at 3, 7, or 14 days of age. Interference by maternal antibodies with day-1 vaccination with the F strain of MG was also studied. In another trial, 8, 4, or 2 ml of high- or low-titered antiserum was given to 20-day-old commercial white leghorn chicks. Protection was measured in terms of air-sac lesions post-challenge with the R strain of MG as above. Maternal antibody in the chicks conferred very little protection against challenge and did not interfere with day-1 vaccination with the F strain of MG. Low-titered antibody gave no protection against growth of MG in the tracheas, but the high-titered MG antiserum did confer some protection against airsacculitis. This protection might be due to growth-inhibition antibody in the transferred serum.


Estimate of male urethritis incidences in France between 2007 and 2017 with a specific focus on Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis infections.
In a context of increasing use of Nucleic Acid Amplification Test, diagnoses of Neisseria gonorrhoeae and Chlamydia trachomatis infections among men increased in Europe and USA since 2007. We aimed to describe trends in the incidence of male urethritis in France between 2007 and 2017. We analysed male urethritis clinical cases reported by the French GPs' Sentinelles network. GPs reported 1944 cases of male urethritis during the study period. The estimated annual incidence rates in men aged 15 years and older remained stable between 226 cases per 100,000 seen in 2007 and 196 in 2017 (P value = 0.9). A third-generation cephalosporin with macrolide or tetracycline was prescribed in 17.5% of cases in 2009 (27/154) and 32.4% in 2017 (47/145) (P value = 0.0327). The incidence rates for adult male urethritis diagnosed in primary care have remained stable since 2007 in France in contrast with the increasing trend of Neisseria gonorrhoeae and Chlamydia trachomatis infections based on microbiological surveillance. Using stable clinical definition for male urethritis seems essential to follow correctly epidemiological dynamic.


Anatomical survival and visual prognosis of Boston type I keratoprosthesis in challenging cases.
To describe the outcome of patients with Boston type 1 keratoprosthesis, with regard to anatomical and visual success. Retrospective case series of patients who underwent Boston type I keratoprosthesis surgery at the Centro de Oftalmología Barraquer in Barcelona and at the University Eye Clinic in Salzburg between May 2006 and December 2011. Sixty-seven eyes were included. Anatomical success, visual acuity, and complication rate were evaluated and correlated with the initial diagnosis. The mean age of patients was 54 years; 62 % were male and 38 % were female. Eleven patients underwent Type I Boston Kpro implantation as a primary procedure, while the other 52 patients had previous graft failure. The most frequent diagnoses were autoimmune diseases (16 eyes), severe chemical or thermal burn (12 eyes), leukoma post-infectious keratitis (seven eyes) and bullous keratopathy (six eyes). The mean follow-up time was 26 months. Retention of the prosthesis was achieved in 95 % at 1 year and 78 % at 4.5 years. Two eyes suffered extrusion of the KPro, six underwent successful exchange of the prosthesis either due to infection, necrosis or extrusion, three KPro's had to be explantated, and two eyes ended up in enucleation due to panophthalmitis. The outcome of the autoimmune cases was similar to the group with "other diagnoses" and better than those with chemical/thermal burn. The most frequent complication was development of a retroprosthetic membrane in 21 eyes (34 %). Visual acuity (LogMAR) in the chemical/thermal burn group was 2.30 preoperatively, 0.69 at 1 year, 0.52 at 2 years and 0.39 at 3 years; in the autoimmune group visual acuity was 2.3 preoperatively, 0.65 at 1 year, 0.15 at 2 years, and 1.5 at 3 years. Boston type 1 keratoprosthesis is a viable option for patients with repeated graft failure, even for those with challenging diagnoses such as ocular burns and autoimmune syndromes.


Occupational exposure to particles and incidence of acute myocardial infarction and other ischaemic heart disease.
Ambient particulate air pollution has been linked to cardiovascular disease. Occupational particle exposure levels may be several times higher than ambient levels but has been less studied. The authors investigated the association between occupational exposure to particles and the incidence of ischaemic heart disease (IHD). The cohort included all manual workers in the Swedish national census of 1980 with information on demographic data and occupation. Information on hospital admissions for acute myocardial infarction or other IHDs and cause of death were obtained from nation-wide registers. A job-exposure matrix for exposure to small (<1 μm) and large (>1 μm) particles was developed. HRs were calculated with Cox regression with adjustment for sex, age, socioeconomic group and urban/rural residential area. Exposure to small particles was associated with an increased HR for acute myocardial infarction of 1.12 (95% CI 1.09 to 1.15), and HR for exposure to large particles was 1.14 (95% CI 1.10 to 1.18). The association was somewhat stronger for workers exposed to small particles for more than 5 years, 1.21 (95% CI 1.11 to 1.31), but no trend with exposure intensity was found. The risk associated with exposure to small particles was higher among women than among men, 1.30 (95% CI 1.12 to 1.51) and 1.10 (95% CI 1.07 to 1.14), respectively. Findings were essentially similar for other IHDs. This explorative study gives some support to the hypothesis that occupational exposure to particles increases the risk of acute myocardial infarction and other IHD. The findings must be interpreted cautiously due to lack of smoking data.


Weight Loss Outcomes With Telemedicine During COVID-19.
Amidst the COVID-19 pandemic, telemedicine was rapidly implemented to maintain patient care during quarantine. However, there is little data on how this transition may have impacted weight loss outcomes and interventions among patients with overweight or obesity. This was a retrospective observational study of adults who established care for medically managed obesity at the Weill Cornell Comprehensive Weight Control Center during September-November 2019 and May-July 2020 and who completed 6 months of follow-up. Weight loss outcomes and weight management interventions were explored and stratified by patient-provider interaction: in-person visits only, in-person and video visits, and video visits only. Of 499 charts eligible for review, 245 (49%) returned for their 6-month follow-up visit and were included for analysis. Of 245 patients, 69 had in-person visits only ("in-person"), 85 started in-person and later switched to video visits ("hybrid"), and 91 had video visits only ("video"). All cohorts were predominantly white and female. Median ages were 56, 49, and 49 years; baseline median weights were 98.9, 96.8, and 93.0 kg; and baseline median BMIs were 35.3, 34.4, and 34.0 kg/m2 for in-person, hybrid, and video cohorts, respectively. The median percent weight changes over 6 months were not significantly different among cohorts: -4.3% [-8.5, -1.5] in the in-person cohort, -5.6% [-8.7, -2.2] in the hybrid group, and -5.8% [-9.7, -2.4] in the video cohort. The percent of patients who achieved ≥5% weight loss were also similar: 46.4%, 55.3%, and 59.3%, respectively. The median number of visits in the video cohort was more than in the in-person or hybrid groups (5 vs. 4). Median number of anti-obesity medications (AOMs) prescribed was similar among groups. The most common AOMs were metformin (all cohorts) followed by semaglutide 1.0 mg (in-person and video) or topiramate (hybrid). Patients on anti-obesity medications who were followed for 6 months via video or video plus in-person visits (hybrid) experienced clinically significant weight loss. Median number of AOMs were similar among groups, and the most common AOMs were metformin, semaglutide 1.0 mg, and topiramate. More investigation is required to compare telemedicine models with in-person care.


Total Syntheses of the Reported Structures of Curcusones I and J through Tandem Gold Catalysis.
Total syntheses of the reported structures of the rhamnofolane diterpene natural products curcusones I and J in racemic form were achieved. The synthetic strategy features a novel tandem gold-catalyzed furan formation and furan-allene [4+3] cycloaddition to build the 5,7-fused ring system with an oxa-bridge in one step, and a stereoselective exo-Diels-Alder reaction to form the 6-membered ring. The newly developed tandem gold catalysis is quite general and can be scaled up. Our syntheses suggest that structural revisions of curcusones I and J are needed.


Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.
Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy-related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required.


[Research advances of the role of inflammatory responses in ARDS].
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an inflammatory lung injury induced by a variety of factors, and these diseases are associated with high rates of mortality due to the lack of effective treatments. Based on the latest research in ALI/ARDS, it is widely accepted that generalized inflammatory responses play a critical role in initiating and developing process of ALI/ARDS. We make a brief review on the immune-pathogenesis and the signaling pathways of ALI/ARDS from the perspective of inflammation, thereby helping develop novel therapeutic strategy for treatment of patients with ALI/ARDS.


Coupling between Grand cycles and Events in Earth's climate during the past 115 million years.
Geological sediment archives document a rich periodic series of astronomically driven climate, but record also abrupt, severe climatic changes called events, the multi-Myr boundary conditions of which have generally been ascribed to acyclic processes from Earth's interior dynamics. These events have rarely been considered together within extended time series for potential correlation with long-term (multi-million year, Myr) cycling. Here I show a coupling between events and multi-Myr cycles in a temperature and ice-volume climatic proxy of the geological past 115 Myr. I use Cenozoic through middle Cretaceous climatic variations, as recorded in benthic foraminifera δ18O, to highlight prominent ~9 and ~36 Myr cyclicities. These cyclicities were previously attributed either to astronomical or tectonic variations. In particular, I point out that most of the well-known events during the past 115 Myr geological interval occur during extremes in the ~9 and ~36 Myr cycling. One exception is the early Cenozoic hyperthermal events including the salient Paleocene-Eocene Thermal Maximum (~56 Ma), which do not match extremes in long-period cyclicities, but to inflection point of these cycles. Specific focus on climatic events, as inferred from δ18O proxy, suggest that some "events", marked by gradual trends within the ~9 and ~36 Myr cycle extremes, would principally be paced by long-term cycling, while "events", recorded as abrupt δ18O changes nearby cycle extremes, would be rather induced by acyclic processes. The connection between cyclic and acyclic processes, as triggers or feedbacks, is very likely. Such link between cycling and events in Earth's past climate provides insight into celestial dynamics governing perturbations in Earth's surface systems, but also the potential connection between external and Earth's interior processes.


Synthesis and electrochemical properties of LiFePO4/carbon nanocomposites in polyol medium.
LiFePO4/Carbon nanocomposites with varying amounts of carbon were synthesized using polyol process without any further heating as a post step. The X-ray diffraction patterns of all samples were indexed on the basis of orthorhombic olivine-type structure. The field emission-TEM images of composites with the amount of 3 approximately 15 wt% carbon showed the average sizes of 45 approximately 80 nm with nanorod shape surrounded by carbon. The initial discharge curves of LiFePO4/Carbon show 166, 157, 142, and 119 mAh/g capacities at a current density of 0.1 mA/cm2 in the voltage range of 2.5-4.2 V, respectively, without capacity fading and excellent cycle retentions during the 20 cycles. Especially, the sample of amount of 3 wt% carbon shows the excellent high rate performances at 15 and 30 C rates with high capacity retention compared with previously reported results of high temperature processed results, due to the existence of conductive agents such as carbon which suppresses particle growth and exhibits improved electronic conductivity and lithium ion diffusivity, simultaneously.


[In situ arterial allografting for aortoiliac infection].
From January 2009 to January 2013, we treated 83 patients for aortoiliac infection by resection of all infected material and in situ revascularization with an arterial allograft. Thirteen patients (15.7 %) died during the first month or before discharge. Perioperative mortality was associated with the presence of a visceral fistula: five deaths (27.8%) occurred among the 18 patients with a visceral fistula, and8 (12.3 %) among the 65 without a visceral fistula (p = 0.11). These results confirm those of our previous studies regarding the severity of aortoiliac infection, especially in patients with a visceral fistula, and endorse our in situ allografting strategy.


GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement.
Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responds to the primary regulatory sex steroid hormone, estradiol (E2), are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons and whether this changes with aging and/or E2 treatment. We used immunofluorescence double-labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2-year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double-labeled. Additionally, many GPER-labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust co-localization of GPER in GnRH in a clinically relevant model, and they support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates.


Paramagnetically induced residual dipolar couplings for solution structure determination of lanthanide binding proteins.
Lanthanides may substitute calcium in calcium-binding proteins, such as, for instance, EF-hand proteins. Paramagnetic lanthanides are capable of orienting the protein in high magnetic fields to an extent similar to that obtained by using orienting devices, and each lanthanide orients according to its magnetic susceptibility tensor. Here, Ce(3+), Tb(3+), Dy(3+), Ho(3+), Er(3+), Tm(3+), Yb(3+) in the C-terminal site of calbindin D(9k) have been investigated. Such systems provide (1)H-(15)N residual dipolar couplings (rdc) which can be used for solution structure determinations. Within the frame of optimizing the use of residual dipolar couplings for efficient solution structure determination, it is proposed here to use a number of lanthanides (e.g., >2) to obtain the orientations of the internuclear vectors with respect to an arbitrary reference system. This is facilitated by the independent knowledge of the magnetic susceptibility anisotropy tensor of each metal, obtained from the analysis of the pseudocontact shifts. A further module of the program PARAMAGNETIC-DYANA, called RDCDYANA-ANGLES, is developed to efficiently incorporate such rdc-derived orientations, instead of the rdc themselves, as constraints in the solution structure calculation. This strategy is absolutely general and can be extended to any other pair of dipole-dipole coupled nuclei. The effect of mobility is also assessed. In principle, information on the mobility can be obtained with a number of lanthanide ions >5, or by combining a smaller number of lanthanide ions with a few orienting devices.


Practical considerations in the treatment of the HIV-infected patient.
The HIV-infected patient presents a special challenge to the dentist because of the concerns relative to the diagnosis and management of their oral problems. Concerns about the patient's medical history, medications, and compromising health status, however, make the HIV-positive patient no more special than any other patient with these concerns. These principles of concern apply to all patients; infection control in the dental office no longer relates to any particular group of patients but to all who seek care and all who provide it. Through continuing education, dentists should become more comfortable in accepting HIV-positive patients in their offices, and through actually providing necessary dental treatment to all individuals, they should no longer consider the HIV-positive patient as special. Dentists need to maintain close contact with the infected patient's physician, however, to ensure maximum appropriate care and minimize any risk to the patient's general health as a result of dental treatment.


An unusual case of knee monoarthritis.
A 61-year-old woman, a known case of diabetic nephropathy on chronic ambulatory peritoneal dialysis, presented with acute onset severe pain in the right knee, of 7 days duration. She had red hot and tender knee and was unable to bear weight. The lower half of the right thigh was swollen and tender. Right knee synovial fluid revealed 130 cells/microL (all lymphocytes). The fluid was negative for crystals and bacterial cultures. Three week later she returned with worsening of her symptoms despite receiving non-steroidal anti-inflammatory drugs and intra-articular glucocorticoid. Magnetic resonance imaging of the right thigh showed heterogeneously hyperintense right vastus medialis muscle on T2-weighted image, suggestive of diabetic muscle infarction. Therapy with analgesics and physiotherapy led to recovery in pain and thigh swelling. Diabetic muscle necrosis is a rare complication of diabetes mellitus and may present with abrupt onset of pain and loss of function of the involved extremity, mimicking septic/reactive arthritis or pyomyositis. A high index of suspicion may avoid delay in diagnosis.


Rapid detection of Escherichia coli by using antibody-conjugated silver nanoshells.
Silver shells of 20 nm thickness have been deposited on silica particles of 200 nm diameter with narrow size distribution. Silver nanoshells dispersed in water exhibit a strong surface plasmon resonance band at 443 nm. This band was found to be very sensitive to rabbit immunoglobulin G antibodies, which were anchored on the nanoshells. These in turn could be utilized to detect the presence of small (approximately 5) to large numbers (approximately 10(9)) of Escherichia coli in water. The protocol presented here proves to be a specific, rapid, reliable, and inexpensive method to detect E. coli.


Assessment of Prognostic Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Patients with Pulmonary Embolism.
Acute pulmonary embolism is a serious medical condition that has a substantial global impact. Inflammation plays a role in the pathophysiology and prognosis of acute pulmonary embolism (APE). The aim of the present study was to investigate the prognostic value of admission parameters for complete blood count (CBC) in APE. A total of 203 patients who were hospitalized with diagnosed APE were retrospectively enrolled in the study. Clinical data, PESI scores, admission CBC parameters, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were all recorded. The clinical outcomes of study subjects were determined by the reported patient 30-day mortality and long-term mortality. During a median follow-up period of 20 months [interquantile range 17], 34 subjects in the study population (17%) died. NLR and PLR levels were significantly higher in patients who died within the 30 days (n = 14) [9.9 (5.5) vs. 4.5 (4.1), p = 0.01 and 280 (74) vs. 135 (75), p = 0.01, respectively] and during the long-term follow-up (n = 20) [8.4 (2.9) vs. 4.1 (3.8), p = 0.01 and 153 (117) vs. 133 (73), p = 0.03, respectively] when compared to the patients that survived. In Cox regression analysis, age, systolic blood pressure, systolic pulmonary arterial pressure, PESI scores (HR 1.02 95%CI 1.01-1.04, p = 0.01), elevated levels of NLR (HR 1.13 95%CI 1.04-1.23, p = 0.01) and PLR (HR 1.002 95%CI 1.001-1.004, p = 0.01) were independently correlated with total mortality. Admission NLR and PLR may have prognostic value in patients with APE.


The therapeutic response of three human tumor lines maintained in immune-suppressed mice.
Studies were made of the growth and therapeutic response of three lines of human tumor serially transplanted in immune-suppressed mice. They included a well-differentiated colonic carcinoma (HX 13), a poorly differentiated colonic carcinoma (HX 18), and undifferentiated small-cell carcinoma of the bronchus (HX 29). Their histological appearance and growth rates were stable, with volume-doubling times ranging from 6 to 12 days. Studies by the technique of labeled mitoses showed that the growth kinetics of the three tumor lines were very similar, with median intermitotic times in the range of 26 to 35 hr. An analysis of the incidence of single and double takes revealed evidence for variation in susceptibility among the recipient mice. One tumor (HX 18) was transplantable with single-cell suspensions but 10(5) cells were required for 50 percent takes. The response of the tumors to a range of chemotherapeutic agents was studied. There was evidence that drugs that are known to be effective in the treatment of patients did well, in particular 5-fluorouracil against the colonic tumors and cyclophosphamide against the bronchial carcinoma. Long-term regressions induced by cyclophosphamide in the bronchial carcinoma may reflect assistance from host defense mechanisms.


Are intravenous amino acid solutions unbalanced?
It is clear that amino acid-based nutritional support beneficially affects nitrogen balance. Less clear is the optimal composition of amino acids for nutritional support of the catabolic patient. We have addressed the optimal composition and proportions of amino acids for support of the critically ill, catabolic patient. We discuss the concept of conditionally indispensable amino acids and review the requirements for histidine, serine, arginine, taurine, cysteine, tyrosine, and glutamine. The use of dipeptides for parenteral support of critically ill patients is reviewed and proposed changes in amino acid content for the catabolic patient are advanced.


Long-term effects from bacterial meningitis in childhood and adolescence on postural control.
Bacterial meningitis in childhood is associated with cognitive deficiencies, sensorimotor impairments and motor dysfunction later in life. However, the long-term effects on postural control is largely unknown, e.g., whether meningitis subjects as adults fully can utilize visual information and adaptation to enhance stability. Thirty-six subjects (20 women, mean age 19.3 years) treated in childhood or adolescence for bacterial meningitis, and 25 controls (13 women, mean age 25.1 years) performed posturography with eyes open and closed under unperturbed and perturbed standing. The meningitis subjects were screened for subjective vertigo symptoms using a questionnaire, clinically tested with headshake and head thrust test, as well as their hearing was evaluated. Meningitis subjects were significantly more unstable than controls during unperturbed (p≤0.014) and perturbed standing, though while perturbed only with eyes open in anteroposterior direction (p = 0.034) whereas in lateral direction both with eyes open and closed (p<0.001). Meningitis subjects had poorer adaption ability to balance perturbations especially with eyes open, and they frequently reported symptoms of unsteadiness (88% of the subjects) and dizziness (81%), which was found significantly correlated to objectively decreased stability. Out of the 36 subjects only 3 had unilateral hearing impairment. Hence, survivors of childhood bacterial meningitis may suffer long-term disorders affecting postural control, and would greatly benefit if these common late effects became generally known so treatments can be developed and applied.


Estrogen receptor alpha gene polymorphisms are associated with the angiographic extent of coronary artery disease.
Sequence variants in the estrogen receptor alpha gene (ESR1) may alter the atheroprotective effects of estrogens, and be associated with the severity of coronary artery disease (CAD). This study seeks to investigate the association between the ESR1 haplotype created by the c.454-397 T>C and c.454-351 A>G polymorphisms, the length of the (TA)n repeats, and the angiographic extent of CAD. Consecutive subjects with age younger than or equal to 55 yr who had undergone coronary angiography between November 2003 and January 2004 were included in the study. The study was conducted in a referral center. One hundred five subjects with age younger than or equal to 55 yr (87 males, 18 females) participated in the study. The angiographic extent of CAD was graded by number of: 1) major coronary vessels with more than 50% narrowing (NMCV); 2) narrowed major coronary vessels and/or their second-order branch (NCV); and 3) coronary segments with any narrowing (NN). Analysis of covariance was used to test the effect of haplotype and (TA)n length on the angiographic extent of CAD with gender and number of CAD risk factors (hyperlipidemia, diabetes, hypertension, obesity, smoking, and family history of CAD) as covariates. The ESR1 haplotype c.454-397C and c.454-351G was associated with NCV and NN (P = 0.008 and 0.02, respectively). Carriers of two copies of haplotype C-G had a higher number of NCV compared with subjects with one or no copies combined (3.5 +/- 2.2 vs. 2.3 +/- 1.9, P = 0.012, respectively). A longer (TA)n repeat was associated with NCV (P = 0.04). The ESR1 c.454-397C and c.454-351G haplotype and longer (TA)n repeats are associated with the extent of CAD in young subjects, independent of the known CAD risk factors.


A de Bruijn graph approach to the quantification of closely-related genomes in a microbial community.
The wide applications of next-generation sequencing (NGS) technologies in metagenomics have raised many computational challenges. One of the essential problems in metagenomics is to estimate the taxonomic composition of a microbial community, which can be approached by mapping shotgun reads acquired from the community to previously characterized microbial genomes followed by quantity profiling of these species based on the number of mapped reads. This procedure, however, is not as trivial as it appears at first glance. A shotgun metagenomic dataset often contains DNA sequences from many closely-related microbial species (e.g., within the same genus) or strains (e.g., within the same species), thus it is often difficult to determine which species/strain a specific read is sampled from when it can be mapped to a common region shared by multiple genomes at high similarity. Furthermore, high genomic variations are observed among individual genomes within the same species, which are difficult to be differentiated from the inter-species variations during reads mapping. To address these issues, a commonly used approach is to quantify taxonomic distribution only at the genus level, based on the reads mapped to all species belonging to the same genus; alternatively, reads are mapped to a set of representative genomes, each selected to represent a different genus. Here, we introduce a novel approach to the quantity estimation of closely-related species within the same genus by mapping the reads to their genomes represented by a de Bruijn graph, in which the common genomic regions among them are collapsed. Using simulated and real metagenomic datasets, we show the de Bruijn graph approach has several advantages over existing methods, including (1) it avoids redundant mapping of shotgun reads to multiple copies of the common regions in different genomes, and (2) it leads to more accurate quantification for the closely-related species (and even for strains within the same species).


Retina regeneration in zebrafish.
Unlike mammals, zebrafish are able to regenerate a damaged retina. Key to this regenerative response are Müller glia that respond to retinal injury by undergoing a reprogramming event that allows them to divide and generate a retinal progenitor that is multipotent and responsible for regenerating all major retinal neuron types. The fish and mammalian retina are composed of similar cell types with conserved function. Because of this it is anticipated that studies of retina regeneration in fish may suggest strategies for stimulating Müller glia reprogramming and retina regeneration in mammals. In this review we describe recent advances and future directions in retina regeneration research using zebrafish as a model system.


Meta-analysis of short-term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis.
To determine whether short-term, oral low dose prednisolone (< or = 15 mg daily) is superior to placebo and non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis. Meta-analysis of randomised trials of oral corticosteroids compared with placebo or a non-steroidal anti-inflammatory drug. Trials conducted anywhere in the world. Patients with rheumatoid arthritis. Joint tenderness, pain, and grip strength. Outcomes measured on different scales were combined by using the standardised effect size (difference in effect divided by SD of the measurements). Ten studies were included in the meta-analysis. Prednisolone had a marked effect over placebo on joint tenderness (standardised effect size 1.31; 95% confidence interval 0.78 to 1.83), pain (1.75; 0.87 to 2.64), and grip strength (0.41; 0.13 to 0.69). Measured in the original units the differences were 12 (6 to 18) tender joints and 22 mm Hg (5 mm Hg to 40 mm Hg) for grip strength. Prednisolone also had a greater effect than non-steroidal anti-inflammatory drugs on joint tenderness (0.63; 0.11 to 1.16) and pain (1.25; 0.26 to 2.24), whereas the difference in grip strength was not significant (0.31; -0.02 to 0.64). Measured in the original units the differences were 9 (5 to 12) tender joints and 12 mm Hg (-6 mm Hg to 31 mm Hg). The risk of adverse effects during moderate and long term use seemed acceptable. Prednisolone in low doses (< or = 15 mg daily) may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means.


Enzymatic synthesis of alpha-arbutin by alpha-anomer-selective glucosylation of hydroquinone using lyophilized cells of Xanthomonas campestris WU-9701.
Alpha-arbutin, a useful cosmetic ingredient, was selectively synthesized by alpha-anomer-selective glucosylation of hydroquinone with maltose as a glucosyl donor using lyophilized cells of Xanthomonas campestris WU-9701 as a biocatalyst. When 45 mM hydroquinone and 120 mg of lyophilized cells showing 11 nkat of alpha-glucosyl transfer activity were shaken in 2 ml of 10 mM H3BO3NaOHKCl buffer (pH 7.5) containing 1.2 M maltose at 40 degrees C, only one form of hydroquinone glucoside was selectively obtained as a product and identified as hydroquinone 1-O-alpha-D-glucopyranoside (alpha-arbutin) by 13C-NMR, 1H-NMR and two-dimensional HMBC analysis. Although hydroquinone has two phenolic -OH groups at the para position in its structure, only one -OH group, but not both -OHs, was glucosylated and no other glucosylated products such as maltotriose were detected in the reaction mixture. The reaction at 40 degrees C for 36 h under optimum conditions yielded 42 mM alpha-arbutin, and the maximum molar conversion yield based on the amount of hydroquinone supplied reached 93%.


Cancer Cell Imaging Using in Situ Generated Gold Nanoclusters.
In situ generated fluorescent gold nanoclusters (Au-NCs) are used for bio-imaging of three human cancer cells, namely, lung (A549), breast (MCF7), and colon (HCT116), by confocal microscopy. The amount of Au-NCs in non-cancer cells (WI38 and MCF10A) is 20-40 times less than those in the corresponding cancer cells. The presence of a larger amount of glutathione (GSH) capped Au-NCs in the cancer cell is ascribed to a higher glutathione level in cancer cells. The Au-NCs exhibit fluorescence maxima at 490-530 nm inside the cancer cells. The fluorescence maxima and matrix-assisted laser desorption ionization (MALDI) mass spectrometry suggest that the fluorescent Au-NCs consist of GSH capped clusters with a core structure (Au8-13). Time-resolved confocal microscopy indicates a nanosecond (1-3 ns) lifetime of the Au-NCs inside the cells. This rules out the formation of aggregated Au-thiolate complexes, which typically exhibit microsecond (≈1000 ns) lifetimes. Fluorescence correlation spectroscopy (FCS) in live cells indicates that the size of the Au-NCs is ≈1-2 nm. For in situ generation, we used a conjugate consisting of a room-temperature ionic liquid (RTIL, [pmim][Br]) and HAuCl4. Cytotoxicity studies indicate that the conjugate, [pmim][AuCl4], is non-toxic for both cancer and non-cancer cells.


Treatment with potentially hepatotoxic drugs and the risk of hepatocellular carcinoma: results of a european case - control study.
Some toxicological data and case reports have suggested that patients taking potentially hepatotoxic drugs may have an increased risk of benign and malignant liver tumours. Pharmacoepidemiological studies on this issue are sparse, most of them focusing on the association between hepatocellular carcinoma (HCC) and the use of oral contraceptives (OC). The objectives of our study were to examine the risk of HCC in patients taking the drugs mentioned in these case reports and toxicological studies. We used data from an international case - control study which had investigated the risk of HCC in women taking OC including 317 cases of HCC and 1060 frequency age-matched hospital controls. We investigated the risk for oral antidiabetic and immunosuppressive drugs, methyldopa, nitrofurantoin and clofibrate using unconditional logistic regression analysis. The analysis was adjusted for age, hepatitis B, hepatitis C, alcohol abuse and other risk factors of HCC. The adjusted odds ratios for ever-use of the investigated drugs varied between 0.67 and 1.64, none of them being statistically significant. There was equally no significantly increased risk for long-term use of these drugs. Altogether there is no evidence for an increased risk of HCC in patients taking the drugs investigated, however, the relatively small statistical power for certain drugs with a low exposure prevalence has to be taken into account. Copyright (c) 2000 John Wiley & Sons, Ltd.


3D automatic quantification applied to optically sectioned images to improve microscopy analysis.
New fluorescence microscopy techniques, such as confocal or digital deconvolution microscopy, allow to easily obtain three-dimensional (3D) information from specimens. However, there are few 3D quantification tools that allow extracting information of these volumes. Therefore, the amount of information acquired by these techniques is difficult to manipulate and analyze manually. The present study describes a model-based method, which for the first time shows 3D visualization and quantification of fluorescent apoptotic body signals, from optical serial sections of porcine hepatocyte spheroids correlating them to their morphological structures. The method consists on an algorithm that counts apoptotic bodies in a spheroid structure and extracts information from them, such as their centroids in cartesian and radial coordinates, relative to the spheroid centre, and their integrated intensity. 3D visualization of the extracted information, allowed us to quantify the distribution of apoptotic bodies in three different zones of the spheroid.


Performing a lung disability evaluation: how, when, and why?
The objective of this review is to present a case-based clinical discussion on this topic. The article represents part of the proceedings of the Occupational and Environmental Lung Disease conference held by the American College of Chest Physicians at Toronto, Ontario, Canada, in 2013, and is based upon a nonsystematic review of the current literature by the author. Although the American Medical Association Guides to the Evaluation of Permanent Impairment is the mainstay for evaluating respiratory impairment, many other impairment schemata are currently available in the United States. Impairment evaluation for a case with chronic respiratory disease and a separate case with asthma is discussed. Pulmonary function tests are the cornerstone for evaluating respiratory impairment. Impairment values differ between various impairment schemata. Impairment evaluation for asthma may be particularly difficult.


Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells.
Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds and releases. HIV-1 viral particles incorporate a number of host proteins to facilitate or inhibit HIV-1 replication. Here we identify a new host protein, coiled-coil domain containing protein 8 (CCDC8), in HIV-1 particles. Incorporation of CCDC8 into virions is dependent on the interaction between CCDC8 and Gag matrix region. Exogenous overexpression of CCDC8 can strongly inhibit HIV-1 production, up to ~30 fold. CCDC8 is a membrane-associated protein. The interaction between exogenously expressed CCDC8 and Gag on the plasma membrane changes the assembly of Gag, and redirects it into intracellular sites, or causes Gag endocytosis. CCDC8, along with cytoskeleton protein obscuring-like1 (Obsl1) and E3 ligase Cul7, induces Gag polyubiquitination and degradation. Thus we identify a new host protein and a new pathway for HIV-1 Gag polyubiquitination and degradation. This pathway presents potential therapeutic strategies against HIV infection.


Peritoneal Dialysis Penetration and Peritonitis Rate at a Single Centre during Last Decade.
Peritoneal dialysis (PD) has been intensively offered at our centre to patients (pts) with end-stage renal disease (ESRD) from 2000, and the number of PD pts was noticed to raise. We aimed to analyse the PD population from the aspect of penetration and peritonitis rate during eleven years. Cumulative number of new RRT pts was 378 during the study period. We found high PD penetration rate: 53% (range 32-72%). The rate of peritonitis was as high as 9.8 during first study years, but it has declined progressively last year being 29.1 by September 2010 and 21.7 by December 2010. Most cases of peritonitis were due to gram-positive pathogens. We have demonstrated steady high single-centre PD penetration rate and improvement of management of patients during last decade probably because of the result of better pts education and a continued dedication of the staff.


Nitrogen regulation of fungal secondary metabolism in fungi.
Fungi occupy diverse environments where they are constantly challenged by stressors such as extreme pH, temperature, UV exposure, and nutrient deprivation. Nitrogen is an essential requirement for growth, and the ability to metabolize a wide variety of nitrogen sources enables fungi to colonize different environmental niches and survive nutrient limitations. Favored nitrogen sources, particularly ammonium and glutamine, are used preferentially, while the expression of genes required for the use of various secondary nitrogen sources is subject to a regulatory mechanism called nitrogen metabolite repression. Studies on gene regulation in response to nitrogen availability were carried out first in Saccharomyces cerevisiae, Aspergillus nidulans, and Neurospora crassa. These studies revealed that fungi respond to changes in nitrogen availability with physiological and morphological alterations and activation of differentiation processes. In all fungal species studied, the major GATA transcription factor AreA and its co-repressor Nmr are central players of the nitrogen regulatory network. In addition to growth and development, the quality and quantity of nitrogen also affects the formation of a broad range of secondary metabolites (SMs). Recent studies, mainly on species of the genus Fusarium, revealed that AreA does not only regulate a large set of nitrogen catabolic genes, but can also be involved in regulating production of SMs. Furthermore, several other regulators, e.g., a second GATA transcription factor, AreB, that was proposed to negatively control nitrogen catabolic genes by competing with AreA for binding to GATA elements, was shown to act as activator of some nitrogen-repressed as well as nitrogen-induced SM gene clusters. This review highlights our latest understanding of canonical (AreA-dependent) and non-canonical nitrogen regulation mechanisms by which fungi may regulate biosynthesis of certain SMs in response to nitrogen availability.


Familial testicular cancer: interest in genetic testing among high-risk family members.
This study is part of an ongoing National Cancer Institute multidisciplinary, etiologically-focused, cross-sectional study of Familial Testicular Cancer (FTC). The current report targets interest in clinical genetic testing for susceptibility to FTC. Demographics, knowledge, health beliefs, and psychological and social factors were evaluated as covariates related to interest in genetic testing. The majority (66%) of 229 participants (64 affected men, 66 unaffected men, and 99 women) from 47 multiple-case FTC families expressed interest in having a genetic test within 6 months, should such a test become available. Interest was similar among the three subgroups mentioned above. Worries about insurance discrimination based on genetic test results were associated with a significantly lower interest in testing. Alternatively, participants were more likely to be interested in genetic testing if they were younger and had higher levels of family support, a physician's recommendation supporting testing, cancer distress, and a need for information to inform the health care of their children. This study reveals social and relationship factors that FTC survivors and their relatives considered important when contemplating the use of new genetic technologies. This is the first study describing hypothetical interest in genetic testing for familial testicular cancer.


[Rehabilitation patients after fractures of upper limb].
Rehabilitation after fractures of upper limb is very complicated and should be coordinated with orthopedic procedures. A choice of method and schema is depended on general health status of patient and used orthopedic treatment. This process should start immediately after surgeon's intervention. An aim of rehabilitation is improvement of range movement, straight of muscles and acceleration of callus formation. It is very important to restore proprioception in a region of trauma. An intensity and velocity of rehabilitation is the greatest after extra bone consolidation and the slowest after conservative tutor management.


Faculty Development for Metro New York City Postdoctoral Dental Program Directors: Delphi Assessment and Program Response.
Faculty development for dental academicians is essential to cultivate a continuous faculty workforce, retain existing faculty members, enhance their teaching skill sets, and remain responsive to changing program requirements and curricular reforms. To maximize the utility of dental faculty development, it is important to systematically assess and address faculty members' perceived training needs. The aims of this study were to determine priority topics among one group of postdoctoral program directors and to translate those topics into faculty development programs as part of Columbia University's Health Resources and Services Administration (HRSA)-sponsored faculty training program for primary care educators. The study was conducted in 2013-16. A Delphi consensus technique was implemented with three sequential surveys of 26 New York City metropolitan area general, pediatric, and public health dentistry residency program directors. On the first survey, the five respondents (19% response rate) identified 31 topics. On the second survey, 17 respondents (response rate 65%) rated the 15 most important topics. In the third and final round, 19 respondents (73% response rate) ranked teaching research methods and teaching literature reviews as the topics of greatest interest. Overall, the responses highlighted needs for faculty development on teaching research methods, motivating trainees, trainee evaluation, and clinical care assessment. Based on these results, a series of six Faculty Forums was developed and implemented for dental educators in the metropolitan area, starting with the topic of teaching research methods. The process flow used for assessing training needs and developing and evaluating training can be applied to a variety of populations of educators.


Mechanisms of hormone resistance: lessons from insulin-resistant patients.
Hormones are secreted by endocrine glands and transported to the target cell at which the hormone acts. The hormone binds to its receptor, thereby eliciting various biological responses within the target cell. Examples of disease mechanisms that function at the different stages in the development of the insulin receptor, and result in insulin resistance, are discussed in this review. Antibodies to insulin can impair delivery of the hormone to the target cell, and can desensitize that target cell to insulin action. In recent years, several genetic diseases have been identified that result from mutations in the genes encoding the relevant receptors. Studies of syndromes of insulin resistance provide illustrations of the multiple types of defects in receptor function that can generally cause hormone resistance (12, 13). For example, mutations in the receptor can decrease the number of receptors on the cell surface by inhibiting receptor biosynthesis, impairing receptor transport to the cell surface, or accelerating the rate of receptor degradation. Alternatively, mutations have been identified that decrease the affinity of insulin binding or inhibit receptor tyrosine kinase activity. In recent years, there has been considerable progress toward elucidating post-receptor mechanisms in the biochemical pathways of hormone action. At present, there are a limited number of examples of mutations in genes encoding proteins that function in this part of the pathway, but it seems likely that additional examples will be discovered in the future. It is likely that these insights into biochemical mechanisms of disease will ultimately lead to an improvement in our ability to treat human disease.


Rectal bioavailability of bacampicillin hydrochloride in man as determined by reversed-phase liquid chromatography.
The relative bioavailability of bacampicillin hydrochloride, a pro-drug of ampicillin, was compared after rectal and oral administration. Bacampicillin was administered rectally as a microenema . The oral formulation was an aqueous microcapsule suspension. They were given as single doses of 400 mg to 12 healthy volunteers after overnight fasting using a randomized cross-over design. Ampicillin and bacampicillin were determined in plasma and blood, respectively, using HPLC. Bacampicillin was rapidly absorbed from the rectum but to a much smaller degree compared to the oral dose. The median t-max was 0.5 and 0.75 h after the rectal and oral doses, respectively. The mean (SD) Cp-max was 1.2 (0.33) mg/l after rectal and 4.8 (0.98) mg/l after oral administration, respectively. Blood concentrations of bacampicillin were extremely low or undetectable with no indication of differences between the two modes of administration. The 95% confidence limits for the relative bioavailability of the microenema were 22.4-39.2 and 22.5-40.4% based on area under the plasma concentration time curve and urinary recovery, respectively. The rectal dose was followed by distress, diarrhea or pain, in 7 subjects. There were no adverse reactions after the oral dose. Bacampicillin was unaffected by beta-lactamases produced by intestinal bacteria.


Inhibition of Methotrexate Uptake via Organic Anion Transporters OAT1 and OAT3 by Glucuronides of Nonsteroidal Anti-inflammatory Drugs.
Combination therapy of non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate (MTX) sometimes triggers adverse effects, such as liver injury, renal failure, gastrointestinal disorders, and myelosuppression, owing to the reduction of MTX clearance. Previous reports have suggested that NSAIDs inhibit renal MTX uptake via organic anion transporters (OATs) and reduced folate transporter (RFC)-1 and efflux via multidrug resistance-associated proteins (MRPs). Recently, our laboratory found inhibitory effects of NSAIDs-glucuronide (NSAIDs-Glu), a major metabolite of NSAIDs, on MRP-mediated MTX transport as a new site of interaction between MTX and NSAIDs. However, it remains unclear that whether NSAIDs-Glu inhibit renal uptake of MTX. Therefore, the present study aimed to evaluate inhibitory effects of several NSAIDs-Glu (diclofenac, R- and S-ibuprofen, R- and S-flurbiprofen, and R- and S-naproxen) on human OAT1 and OAT3-mediated MTX transport. In this study, [3H]MTX uptake was observed by using human OAT1 and OAT3-overexpressing HEK293 cells in the presence or absence of NSAIDs-Glu. All examined NSAIDs-Glu exhibited concentration-dependent inhibitory effects on MTX uptake via OAT1 and OAT3. Our results indicated that NSAIDs-Glu are more potent (5- to 15-fold) inhibitors of OAT3 than OAT1. Moreover, stereoselective inhibitory effects of NSAIDs-Glu on OATs-mediated MTX uptake were not observed, unlike on MRPs-mediated transport. These findings suggest that inhibition of OAT1 and OAT3-mediated renal uptake of MTX by plasma NSAIDs-Glu may be one of the competitive sites underlying complex drug interaction between MTX and NSAIDs.


Auditory feedback affects the long-range correlation of isochronous serial interval production: support for a closed-loop or memory model of timing.
Long-range dependence is a characteristic property of successively produced time intervals, such as in un-paced or continuation tapping. We hypothesise in the present paper that serial dependence in such tasks could be related to a closed-loop regulation process, in which the current interval is determined by preceding ones. As a consequence, the quality of sensory feedback is likely to affect serial dependence. An experiment with human participants shows that diminished sensory information tends to increase the Hurst exponent for short inter-onset intervals and tends to decrease it for long intervals. A simulation shows that a simple auto-regressive model, whose order depends on the ratio between the inter-onset interval and an assumed temporal integration span, is able to account for most of our empirical results, including the duration specificity of long-range correlation.


The correlation between acromion-axillary nerve distance and upper arm length; a cadaveric study.
Deltoid splitting is one of common and useful approaches in proximal humerus surgery. The disadvantage of this approach is high risk of axillary nerve injury. Nowadays, there is no consensus in the proper mean of the individual's axillary nerve location. The present study aim to determine the correlation between the axillary nerve and the upper arm length that may create equations to calculate the nerve location. Seventy shoulders were measured the distance from lateral acromial edge to axillary nerve and compared with upper arm length in three positions of the shoulder (adduction 30°, abduction 45° and 90°). The authors used distance of lateral acromial edge to lateral epicondyle and tip ofgreater tuberosity to lateral epicondyle as the upper arm length. The average distance ofshoulder adduction 30°, abduction 45° and90° were 57.9, 57.1 and 52.9 mm, respectively. All of three positions showed linear correlation to upper arm length from both of reference sites. From acromion edge reference, where "Y" is axillary nerve distance in mm and "x" is upper arm length in cm, the relation were Y= 2.3x-10, Y= 2x-2 and Y= 2x-7with the accuracy rate were 88.57%, 85.71% and 81.43%, respectively. From greater tuberosity reference, the relations were Y = 2.54x-14, Y = 2x and Y = 2.3x-12 with the accuracy rates 87.14%, 80% and 84.29%, respectively. There is linear correlation between distance from the lateral acromial edge to axillary nerve and the upper arm length. The authors can predict the danger zone in the location of the anterior upper branch of the axillary nerve. However, further clinical study may helpful to prove the equations. Level ofevidence: Basic science anatomy study.


Dexamethasone minimizes the risk of cranial nerve injury during CEA.
The incidence of cranial and cervical nerve injury during carotid endarterectomy (CEA) ranges from less than 7.6% to more than 50%. Lesions are mainly due to surgical maneuvers such as traction, compression, tissue electrocoagulation, clamping, and extensive dissections. The use of dexamethasone (DEX) and its beneficial effects in spinal cord injuries have already been described. We investigated whether DEX could also be beneficial to minimize the incidence of cranial and cervical nerve injury during CEA. To evaluate whether dexamethasone is able to reduce the incidence of cranial nerve injuries. From March 1999 through April 2006, 1126 patients undergoing CEA because of high-grade carotid stenosis were enrolled and randomized by predetermined randomization tables into two groups. The first group, "A", included 586 patients that all received an intravenous administration of dexamethasone following a therapeutic scheme. The second group, "B", included 540 control subjects that received the standard pre- and postoperative therapy. All patients were submitted to a deep cervical plexus block, eversion carotid endarterectomy, and selective shunting. Three days after the operation, an independent neurologist and otorhinolaryngologist evaluated the presence of cranial nerve deficits. All patients (group A and group B) showing nerve injuries continued the treatment (8 mg of dexamethasone once in the morning) for 7 days and were re-evaluated after 2 weeks, 30 days, and every 3 months for 1 year. Recovery time took from 2 weeks to 12 months, with a mean time of 3.6 months. The chi(2) test was used to compare the two groups and to check for statistical significance. The incidence of cranial nerve dysfunction was higher in group B and the statistical analysis showed a significant effect of dexamethasone in preventing the neurological damage (P = .0081). The incidence of temporary lesions was lower in group A and the chi(2) test yielded a P value of .006. No statistically significant differences were found when comparing the effect of dexamethasone in men and women. In addition, dexamethasone had no statistically significant effect on the incidence of permanent cranial nerve injuries. Finally, no adverse effect related to the administration of dexamethasone was observed. Perioperative administration of dexamethasone is effective in minimizing the incidence of temporary cranial nerve injuries during CEA.


The use of existing low-cost technologies to enhance the medical record documentation using a summary patient record [SPR].
The Institute of Medicine has described the Electronic Medical Record [EMR] as an essential technology for health care that improves patient safety and the quality of care when compared to traditional paper-based records. [1,2,3] Despite major financial expenditures on health information technology related to EMRs in developed countries such as North America, Britain and Australia, success rates for successful implementations have been low. One specific domain of information management relates to the communication of health care between those involved in the care process. Summarization of patient histories is a core component of EMR systems and assists in the communication of health care. This paper demonstrates how the utilization of simple technologies, can lead to the successful implementation of the Summary Patient Record [SPR] component of an EMR system.


Investigations on silicon/amorphous-carbon and silicon/nanocrystalline palladium/ amorphous-carbon interfaces.
Our previous work revealed that significant enhancement in sp3-carbon content of amorphous carbon films could be achieved when grown on nanocrystalline palladium interlayer as compared to those grown on bare silicon substrates. To find out why, the nature of interface formed in both the cases has been investigated using Electron Probe Micro Analysis (EPMA) technique. It has been found that a reactive interface in the form of silicon carbide and/silicon oxy-carbide is formed at the interface of silicon/amorphous-carbon films, while palladium remains primarily in its native form at the interface of nanocrystalline palladium/amorphous-carbon films. However, there can be traces of dissolved oxygen within the metallic layer as well. The study has been corroborated further from X-ray photoelectron spectroscopic studies.


Specificity and crossreactivity of immune serum and hybridoma antibodies to various species of avian coccidia.
The species-specificity and crossreactivity of serum antibodies (Ab) from birds immunized specifically with six different species of coccidia and of 24 hybridoma antibodies (Ab) developed against four species of chicken and two species of turkey coccidia were determined by use of the indirect immunofluorescent antibody (IFA) test on air-dried sporozoites. With few exceptions, the immune chicken sera were found to crossreact with all species of coccidia tested. Seven of the hybridoma Ab were species-specific, while the other 17 Ab demonstrated varying degrees of crossreactivity. Similar types of IFA patterns were seen with both the species-specific and crossreactive hybridoma Ab. Some of the crossreactive hybridoma Ab produced one type of IFA pattern with the sporozoites against which they were originally raised and different patterns with other species of sporozoites. The development of the hybridoma Ab has made it possible to identify the species of coccidia found in mixed infections and check the purity of laboratory strains.