Trends of presentation and clinical outcome of treated renal angiomyolipoma.
The purpose of this study is to set guidelines for the management of renal angiomyolipoma (AML), clinical prognosis according to tumor size, in association with tuberous sclerosis complex (TSC), multiplicity, radiographic finding, and treatment modality. Between March 1998 and October 2008, 129 out of 254 patients with AML who underwent surgical intervention or angioembolization were enrolled. Diagnosis of AML was determined by the presence of a low attenuated component on CT imaging or by pathological confirmation. Indications of treatment were intractable pain, hematuria, suspicion of malignancy, large tumor size, spontaneous rupture, and radiographically equivocal tumors in which a differential diagnosis was needed to rule out malignancy. Parameters including age, sex, tumor size, multiplicity, radiographic characteristics, association with TSC, and treatment modality were reviewed. Age at presentation was 50.6 years and mean tumor size was 3.5 cm. Presentation symptoms were flank pain, hematuria, spontaneous rupture, and fatigue. 97 (75.2%) patients were incidentally discovered. 100 (77.5%) were females. 68 (52.7%) underwent nephron-sparing surgery (NSS), 35 (27.1%) radical nephrectomy, and 26 (20.2%) angioembolization. TSC was accompanied in 12 (9.3%) patients. No patient developed renal function impairment during the mean follow-up period of 64.8 months. Patients with TSC presented at a younger age, along with larger, bilateral, and multiple lesions. Significant differences in clinical manifestations and treatment outcomes were noted in respect to tumor characteristics, association with TSC, and treatment modality. Considering the benign nature of AML, these parameters ought to be considered when deciding upon active surveillance or prophylactic intervention.


ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients.
As culture-based methods for the diagnosis of invasive fungal diseases (IFD) in leukemia and hematopoietic SCT patients have limited performance, non-culture methods are increasingly being used. The third European Conference on Infections in Leukemia (ECIL-3) meeting aimed at establishing evidence-based recommendations for the use of biological tests in adult patients, based on the grading system of the Infectious Diseases Society of America. The following biomarkers were investigated as screening tests: galactomannan (GM) for invasive aspergillosis (IA); β-glucan (BG) for invasive candidiasis (IC) and IA; Cryptococcus Ag for cryptococcosis; mannan (Mn) Ag/anti-mannan (A-Mn) Ab for IC, and PCR for IA. Testing for GM, Cryptococcus Ag and BG are included in the revised EORTC/MSG (European Organization for Research and Treatment of Cancer/Mycoses Study Group) consensus definitions for IFD. Strong evidence supports the use of GM in serum (A II), and Cryptococcus Ag in serum and cerebrospinal fluid (CSF) (A II). Evidence is moderate for BG detection in serum (B II), and the combined Mn/A-Mn testing in serum for hepatosplenic candidiasis (B III) and candidemia (C II). No recommendations were formulated for the use of PCR owing to a lack of standardization and clinical validation. Clinical utility of these markers for the early management of IFD should be further assessed in prospective randomized interventional studies.


Three-dimensional evaluation of social smile symmetry.
To evaluate the social smile symmetry using three-dimensional (3D) stereophotogrammetric images. The study was conducted with 3D facial images of 30 individuals (age range 13-25 years). The rest position was considered as the reference image and the social smile image was aligned on this image using the best-fit alignment method. The spatial differences between the same points established on both images using 3D analyses were determined for right and left points in X, Y, and Z planes. The highest difference related to spatial distance in right and left points was -0.56 mm (95% confidence interval [CI], -1.19, 0.06 mm) between right and left commissure (Com) points. The difference was not significant, and the Bland-Altman upper and lower limits were -3.85 mm and 2.71 mm, respectively. The highest difference for the transversal plane was found in Com points, similarly to the spatial distance (mean: 0.50 mm, 95% CI, -2.62, 1.02 mm). The differences between the changes in the left and right points in the Y and Z plane were not significant (P > .05). The social smile was observed to show asymmetry in varying amounts in the different directions. Asymmetry increases in some cases, specifically for the corners of the mouth.


The use of antimicrobial-impregnated fabrics in health services: an integrative review.
to analyze evidence concerning the feasibility of antimicrobial-impregnated fabrics in preventing and controlling microbial transmission in health services. an integrative review using the following databases: MEDLINE (via PubMed), Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and Latin American and Caribbean Health Sciences Literature (LILACS), regardless of language and date of publication. Seven studies were included in the analysis to verify the types of fabrics and substances used to impregnate the fabrics, applicability in health services, and decrease in microbial load. silver nanoparticles and copper oxide are the main antimicrobial substances used to impregnate the fabrics. The patients' use of these fabrics, such as in bed and bath linens and clothing, was more effective in reducing antimicrobial load than in health workers' uniforms. the use of these antimicrobial-impregnated textiles, especially by patients, is a viable alternative to prevent and control microbial transmission in health services. Implementing these fabrics in health workers' uniforms requires further studies, however, to verify its effectiveness in decreasing microbial load in clinical practice.


Decreasing photobleaching by silver nanoparticles on metal surfaces: application to muscle myofibrils.
Recently it has become possible to study single protein molecules in a cell. However, such experiments are plagued by rapid photobleaching. We recently showed that the interaction of fluorophores with localized surface plasmon polaritons (LSPs) induced in the metallic nanoparticles led to a substantial reduction of photobleaching. We now investigate whether the photobleaching could be further reduced when the excited fluorophore interacts with the LSP excited in the metallic nanoparticles resident on mirrored surface. As an example we use myofibrils, subcellular structures within skeletal muscle. We compare nanoparticle-enhanced fluorescence of myofibrils in the presence and in the absence of a mirrored surface. The proximity of the mirrored surface led to enhancement of fluorescence and to a decrease in fluorescent lifetime, much greater than that observed in the presence of nanoparticles alone. We think that the effect is caused by the near-field interactions between fluorophores and LSP, and between fluorophores and propagating surface plasmons (PSPs) produced in the metallic surface by the nanoparticles. Photobleaching is decreased because fluorescence enhancement enables illumination with a weaker laser beam and because the decrease in fluorescence lifetime minimizes the probability of oxygen attack during the time a molecule is in the exited state.


Nietzsche's aesthetic critique of Darwin.
Despite his position as one of the first philosophers to write in the "post-Darwinian" world, the critique of Darwin by Friedrich Nietzsche is often ignored for a host of unsatisfactory reasons. I argue that Nietzsche's critique of Darwin is important to the study of both Nietzsche's and Darwin's impact on philosophy. Further, I show that the central claims of Nietzsche's critique have been broadly misunderstood. I then present a new reading of Nietzsche's core criticism of Darwin. An important part of Nietzsche's response can best be understood as an aesthetic critique of Darwin, reacting to what he saw as Darwin having drained life of an essential component of objective aesthetic value. For Nietzsche, Darwin's theory is false because it is too intellectual, because it searches for rules, regulations, and uniformity in a realm where none of these are to be found - and, moreover, where they should not be found. Such a reading goes furthest toward making Nietzsche's criticism substantive and relevant. Finally, I attempt to relate this novel explanation of Nietzsche's critique to topics in contemporary philosophy of biology, particularly work on the evolutionary explanation of culture.


Visualizing circuits and systems using transgenic reporters of neural activity.
Genetically encoded sensors of neural activity enable visualization of circuit-level function in the central nervous system. Although our understanding of the molecular events that regulate neuronal firing, synaptic function, and plasticity has expanded rapidly over the past 15 years, an appreciation for how cellular changes are functionally integrated at the circuit level has lagged. A new generation of tools that employ fluorescent sensors of neural activity promises unique opportunities to bridge the gap between cellular level and system level analysis. This review will focus on genetically encoded sensors. A primary advantage of these indicators is that they can be nonselectively introduced to large populations of cells using either transgenic-mediated or viral-mediated approaches. This ability removes the nontrivial obstacles of how to get chemical indicators into cells of interest, a problem that has dogged investigators who have been interested in mapping neural function in the intact CNS. Five different types of approaches and their relative utility will be reviewed here: first, reporters of immediate-early gene (IEG) activation using promoters such as c-fos and arc; second, voltage-based sensors, such as GFP-coupled Na+ and K+ channels; third, Cl*-based sensors; fourth, Ca2+-based sensors, such as Camgaroo and the troponin-based TN-L15; and fifth, pH-based sensors, which have been particularly useful for examining synaptic activity of highly convergent afferents in sensory systems in vivo. Particular attention will be paid to reporters of IEG expression, because these tools employ the built-in threshold function that occurs with activation of gene expression, provoking new experimental questions by expanding the timescale of analysis for circuit-level and system-level functional mapping.


Causes of preventable drug-related hospital admissions: a qualitative study.
To explore the causes of preventable drug-related admissions (PDRAs) to hospital. Qualitative case studies using semi-structured interviews and medical record review; data analysed using a framework derived from Reason's model of organisational accidents and cascade analysis. 62 participants, including 18 patients, 8 informal carers, 17 general practitioners, 12 community pharmacists, 3 practice nurses and 4 other members of healthcare staff, involved in events leading up to the patients' hospital admissions. Nottingham, UK. PDRAs are associated with problems at multiple stages in the medication use process, including prescribing, dispensing, administration, monitoring and help seeking. The main causes of these problems are communication failures (between patients and healthcare professionals and different groups of healthcare professionals) and knowledge gaps (about drugs and patients' medical and medication histories). The causes of PDRAs are similar irrespective of whether the hospital admission is associated with a prescribing, monitoring or patient adherence problem. The causes of PDRAs are multifaceted and complex. Technical solutions to PDRAs will need to take account of this complexity and are unlikely to be sufficient on their own. Interventions targeting the human causes of PDRAs are also necessary--for example, improving methods of communication.


A Gratuitous Grace: The Influence of Religious Set and Intent on the Psychedelic Experience.
Psychedelic drugs, or entheogens, have been used for religious purposes among various cultures for thousands of years. Recently, these substances have caught the attention of Westerners for many reasons, including their propensity to induce mystical experiences. This study examined the relationship between religion and having mystical experiences. A total of 119 participants were drawn from psychedelic-related websites and asked to complete an anonymous online questionnaire containing items regarding history of psychedelic use, set and setting for psychedelic use, and a measure for mystical experiences. A majority of respondents were White males who displayed at least some level of post-secondary education. The findings indicated that respondents who used psychedelics for specifically religious purposes, as well as those who identified with a religion, were more likely to score higher on the Mysticism Scale than those who did not.


Validity of the oxygen uptake efficiency slope in children with cystic fibrosis and mild-to-moderate airflow obstruction.
The oxygen uptake efficiency slope (OUES) has been proposed as an 'effort-independent' measure of cardiopulmonary exercise capacity, which could be used as an alternative measurement for peak oxygen uptake (VO(2peak)) in populations unable or unwilling to perform maximal exercise. The aim of the current study was to investigate the validity of the OUES in children with cystic fibrosis (CF). Exercise data of 22 children with CF and mild to moderate airflow obstruction were analyzed and compared with exercise data of 22 healthy children. The OUES was calculated using data up to three different relative exercise intensities, namely 50%, 75%, and 100% of the total exercise duration, and normalized for body surface area (BSA). Only the OUES/BSA using the first 50% of the total exercise duration was significantly different between the groups. OUES/BSA values determined at different exercise intensities differed significantly within patients with CF and correlated only moderately with VO(2peak) and the ventilatory threshold. The OUES is not a valid submaximal measure of cardiopulmonary exercise capacity in children with mild to moderate CF, due to its limited distinguishing properties, its nonlinearity throughout progressive exercise, and its moderate correlation with VO(2peak) and the ventilatory threshold.


Survey of the genomic landscape surrounding the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant Amaranthus palmeri from geographically distant populations in the USA.
Glyphosate resistance in Amaranthus palmeri, one of the most prevalent herbicide-resistant weeds in the USA, is attributable to amplification and increased expression of the gene encoding the target site of glyphosate, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS). The EPSPS gene and the surrounding 287 kilobases (kb) of amplified sequence are unique to glyphosate-resistant plants and termed the EPSPS cassette. It has only been sequenced in one A. palmeri population from Mississippi. This research compares EPSPS cassettes in seven resistant and five sensitive populations from geographically distant locations within the USA, including Mississippi, Arizona, Kansas, Maryland, Delaware and Georgia. Polymerase chain reaction (PCR) products from 40 primer pairs specific to the cassette were similar in size and sequence in resistant populations. Several primer pairs failed to generate PCR products in sensitive populations. Regions of the cassette sequenced in the resistant populations were found to be nearly identical to those from Mississippi. Gene expression analysis showed that both EPSPS and another gene in the cassette, a reverse transcriptase, were elevated in all resistant populations tested relative to the sensitive populations. EPSPS cassettes from distant resistant populations were nearly homologous. Considering the complexity of the cassette, and the degree of similarity among some cassette sequences, the results are consistent with the hypothesis that glyphosate resistance probably evolved once and then rapidly spread across the USA. © 2017 Society of Chemical Industry.


Association between brain similarity to severe mental illnesses and comorbid cerebral, physical, and cognitive impairments.
Severe mental illnesses (SMIs) are often associated with compromised brain health, physical comorbidities, and cognitive deficits, but it is incompletely understood whether these comorbidities are intrinsic to SMI pathophysiology or secondary to having SMIs. We tested the hypothesis that cerebral, cardiometabolic, and cognitive impairments commonly observed in SMIs can be observed in non-psychiatric individuals with SMI-like brain patterns of deviation as seen on magnetic resonance imaging. 22,883 participants free of common neuropsychiatric conditions from the UK Biobank (age = 63.4 ± 7.5 years, range = 45-82 years, 50.9% female) were split into discovery and replication samples. The regional vulnerability index (RVI) was used to quantify each participant's respective brain similarity to meta-analytical patterns of schizophrenia spectrum disorder, bipolar disorder, and major depressive disorder in gray matter thickness, subcortical gray matter volume, and white matter integrity. Cluster analysis revealed five clusters with distinct RVI profiles. Compared with a cluster with no RVI elevation, a cluster with RVI elevation across all SMIs and brain structures showed significantly higher volume of white matter hyperintensities (Cohen's d = 0.59, pFDR < 10-16), poorer cardiovascular (Cohen's d = 0.30, pFDR < 10-16) and metabolic (Cohen's d = 0.12, pFDR = 1.3 × 10-4) health, and slower speed of information processing (|Cohen's d| = 0.11-0.17, pFDR = 1.6 × 10-3-4.6 × 10-8). This cluster also had significantly higher level of C-reactive protein and alcohol use (Cohen's d = 0.11 and 0.28, pFDR = 4.1 × 10-3 and 1.1 × 10-11). Three other clusters with respective RVI elevation in gray matter thickness, subcortical gray matter volume, and white matter integrity showed intermediate level of white matter hyperintensities, cardiometabolic health, and alcohol use. Our results suggest that cerebral, physical, and cognitive impairments in SMIs may be partly intrinsic via shared pathophysiological pathways with SMI-related brain anatomical changes.


Chemical genetics approach to restoring p27Kip1 reveals novel compounds with antiproliferative activity in prostate cancer cells.
The cyclin-dependent kinase (CDK) inhibitor p27(Kip)¹ is downregulated in a majority of human cancers due to ectopic proteolysis by the ubiquitin-proteasome pathway. The expression of p27 is subject to multiple mechanisms of control involving several transcription factors, kinase pathways and at least three different ubiquitin ligases (SCF(SKP)², KPC, Pirh2), which regulate p27 transcription, translation, protein stability and subcellular localization. Using a chemical genetics approach, we have asked whether this control network can be modulated by small molecules such that p27 protein expression is restored in cancer cells. We developed a cell-based assay for measuring the levels of endogenous nuclear p27 in a high throughput screening format employing LNCaP prostate cancer cells engineered to overexpress SKP2. The assay platform was optimized to Z' factors of 0.48 - 0.6 and piloted by screening a total of 7368 chemical compounds. During the course of this work, we discovered two small molecules of previously unknown biological activity, SMIP001 and SMIP004, which increase the nuclear level of p27 at low micromolar concentrations. SMIPs (small molecule inhibitors of p27 depletion) also upregulate p21(Cip)¹, inhibit cellular CDK2 activity, induce G1 delay, inhibit colony formation in soft agar and exhibit preferential cytotoxicity in LNCaP cells relative to normal human fibroblasts. Unlike SMIP001, SMIP004 was found to downregulate SKP2 and to stabilize p27, although neither SMIP is a proteasome inhibitor. Whereas the screening endpoint - nuclear p27 - was robustly modulated by the compounds, SMIP-mediated cell cycle arrest and apoptosis were not strictly dependent on p27 and p21 - a finding that is explained by parallel inhibitory effects of SMIPs on positive cell cycle regulators, including cyclins E and A, and CDK4. Our data provide proof-of-principle that the screening platform we developed, using endogenous nuclear p27 as an endpoint, presents an effective means of identifying bioactive molecules with cancer selective antiproliferative activity. This approach, when applied to larger and more diverse sets of compounds with refined drug-like properties, bears the potential of revealing both unknown cellular pathways globally impinging on p27 and novel leads for chemotherapeutics targeting a prominent molecular defect of human cancers.


Perceptual-cognitive universals as reflections of the world.
The universality, invariance, and elegance of principles governing the universe may be reflected in principles of the minds that have evolved in that universe--provided that the mental principles are formulated with respect to the abstract spaces appropriate for the representation of biologically significant objects and their properties. (1) Positions and motions of objects conserve their shapes in the geometrically fullest and simplest way when represented as points and connecting geodesic paths in the six-dimensional manifold jointly determined by the Euclidean group of three-dimensional space and the symmetry group of each object. (2) Colors of objects attain constancy when represented as points in a three-dimensional vector space in which each variation in natural illumination is canceled by application of its inverse from the three-dimensional linear group of terrestrial transformations of the invariant solar source. (3) Kinds of objects support optimal generalization and categorization when represented, in an evolutionarily-shaped space of possible objects, as connected regions with associated weights determined by Bayesian revision of maximum-entropy priors.


Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist treatment.
Entorhinal cortex lesioning (ECL) causes an extensive deafferentation of the hippocampus that is classically followed by a compensatory reinnervation, where apolipoprotein E, the main extracellular lipid-carrier in the CNS, has been shown to play a crucial role by shuttling cholesterol to reconstructing neurons terminals. Hence, we investigated whether the ATP-binding cassette (ABC) transporters -A1 and -G1, known to regulate cellular cholesterol efflux and lipidation of the apolipoprotein E-containing lipoprotein complex are actively involved in this context of brain׳s plastic response to neurodegeneration and deafferentation. We assessed ABCA1 and ABCG1 mRNA and protein levels throughout the degenerative phase and the reinnervation process and evaluated the associated cholinergic sprouting following ECL in the adult mouse brain. We subsequently tested the effect of the pharmacological activation of the nuclear receptor LXR, prior to versus after ECL, on hippocampal ABCA1 and G1 expression and on reinnervation. ECL induced a time-dependent up-regulation of ABCA1, but not G1, that coincided with a significant increase in acetylcholine esterase (AChE) activity in the ipsilateral hippocampus. Pre-ECL, but not post-ECL i.p. treatment with the LXR agonist TO901317 also led to a significant increase solely in hippocampal ABCA1 expression, paralleled by increases in both AchE and synaptophysin protein levels in the deafferented hippocampus. Thus, ABCA1 and -G1 are differentially regulated in the lesioned brain and upon treatment with an LXR agonist. Further, TO901317-induced up-regulation of ABCA1 appears to be more beneficial in a prevention (pre-lesion) than rescue (post-lesion) treatment; both findings support a central role for ABC transporters in brain plasticity.


Seroepidemiology of Toxoplasma gondii infection among two mountain aboriginal populations and Southeast Asian laborers in Taiwan.
A seroepidemiological survey of Toxoplasma gondii infection among Atayal and Paiwan mountain aborigines and Southeast Asian laborers in Taiwan was assessed from February 1998 to July 2000 using a latex agglutination test. To determine risk factors for T. gondii infection among Taiwan aborigines, the consumption of raw meat and valley water were given particular attention in a self-administered questionnaire. The overall seroprevalence of T. gondii infection was 19.4% for Atayal, 26.7% for Paiwan, 42.9% for Indonesian, 14.7% for Thai, and 11.3% for Filipinos. No significant gender difference in seroprevalence was found among Atayals, Paiwans, Indonesians, and Filipinos (P > 0.05). In the Thai group, however, males had a higher seroprevalence than females (P < 0.001). Results of the multiple logistic regression analysis indicate a higher odds ratios (OR) with age in both aboriginal groups. In contrast, the OR was lower among older Indonesians and Thais. Those Atayals and Paiwans with a history of eating raw meat seemed more susceptible to T. gondii infection than those who had never consumed raw meat. Ethnically, a significant difference in seroprevalence was observed between Indonesians and Paiwans, Atayals, Thais, and Filipinos (P < 0.001).


Gestational weight gain and obesity, adiposity and body size in African-American and Dominican children in the Bronx and Northern Manhattan.
Gestational weight gain (GWG) is potentially modifiable and is associated with infant size and body composition; however, long-term effects on childhood obesity have not been reported among multi-ethnic urban populations. We examined the association between GWG and child anthropometric measures and body composition at 7 years [waist circumference (WC), body mass index z-score (BMIZ), obesity (BMIZ ≥95%ile) and bioelectrical impedance analysis estimates of percentage body fat (%fat)] in African-American and Dominican dyads (n = 323) in the Columbia Center for Children's Environmental Health prospective birth cohort study from 1998 to 2013. Linear and logistic regression evaluated associations between excessive GWG [>Institute of Medicine (IOM) 2009 guidelines] and outcomes, adjusting for pre-pregnancy BMI and covariates. Pre-pregnancy BMI (mean ± standard deviation, all such values) and total GWG were 25.8 ± 6.2 kg m(-2) (45% overweight/obese) and 16.4 ± 7.9 kg (64% > IOM guidelines), respectively. Excessive GWG was associated with higher BMIZ {0.44 [95% confidence interval (CI): 0.2, 0.7], P < 0.001}, WC [β: 2.9 cm (95% CI: 1.1, 4.6), P = 0.002], %fat at 7 years [β: 2.2% (95% CI: 1.0, 3.5), P = 0.001)] and obesity [odds ratio: 2.93 (95% CI: 1.5, 5.8), P = 0.002]. Pre-pregnancy BMI was positively associated with child size, adiposity and obesity (all P < 0.05). Excessive GWG was highly prevalent and was associated with child obesity, greater percentage body fat and abdominal adiposity. Strategies to support healthy GWG are warranted to promote healthy growth and prevent childhood obesity.


Early brain vulnerability in Wolfram syndrome.
Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development.


A comparative study to evaluate the efficacy of lycopene and curcumin in oral submucous fibrosis patients: A randomized clinical trial.
: Oral submucous fibrosis (OSMF) is a most prevalent potentially malignant disorder associated with betel quid chewing frequently observed in the Indian population. The present study conducted is much of a keen interest because there is much new information, both in the press and the medical literature, about the benefits of fresh fruits and vegetables and antioxidants (such as lycopene and curcumin) for both prevention and treatment of diseases. As clinicians, we often prescribe medications with significant adverse effects, and certainly, if armed with evidence to support using such antioxidants as safer therapeutic alternatives for treatment of OSMF. The aim of the study was to compare and evaluate the efficacy of lycopene and curcumin given orally in clinically diagnosed OSMF patients. Sixty patients were divided randomly into two groups Group A and Group B. After fulfilling the eligibility criteria, sixty patients were randomly allotted based on fishbowl method into thirty each. This technique eliminated the selection bias arising in the study. Group A individuals were treated with 4 mg of lycopene and Group B individuals were given 300 mg of curcumin thrice daily for 3 months. Both the groups were assessed in terms of mouth opening and burning sensation. The statistical analysis was done using SPSS Version 16.0 statistical Analysis Software. In Group A, the initial burning sensation was 65.83 ± 3.98%, and in Group B, it was 62.33 ± 5.22% (visual analog scale). After 3 months, there was complete cessation of burning sensation in both the groups. Burning sensation between the groups was statistically nonsignificant (P > 0.05). In Group A, mean mouth opening at baseline (1st visit) observed was 3.17 ± 0.08 cm which improved to 3.52 ± 0.07 cm after 3 months of the treatment period. In Group B, mean mouth opening at baseline (1st visit) observed was 3.32 ± 0.07 cm which improved to 3.52 ± 0.08 cm after 3 months of the treatment period. On comparing intergroup, the difference was statistically nonsignificant (P > 0.05). However, on comparing intergroup, average percent change in mean mouth opening from 1st visit to subsequent time intervals across the time period was found to be statistically significant (P < 0.05). Group A showed 11.1 ± 1.0% improvement in mean mouth opening and Group B showed 6.2 ± 0.4% improvement in the mean mouth opening from the 1st visit till the posttreatment period. The change in the mean mouth opening from 1st visit till posttreatment in Group A was 0.35 ± 0.14, and in Group B, it was 0.20 ± 0.09. Lycopene showed better results than curcumin in improving mouth opening; both the drugs were equally effective in decreasing burning sensation in OSMF patients.


Inhibitory engrams in perception and memory.
Nervous systems use excitatory cell assemblies to encode and represent sensory percepts. Similarly, synaptically connected cell assemblies or "engrams" are thought to represent memories of past experience. Multiple lines of recent evidence indicate that brain systems create and use inhibitory replicas of excitatory representations for important cognitive functions. Such matched "inhibitory engrams" can form through homeostatic potentiation of inhibition onto postsynaptic cells that show increased levels of excitation. Inhibitory engrams can reduce behavioral responses to familiar stimuli, thereby resulting in behavioral habituation. In addition, by preventing inappropriate activation of excitatory memory engrams, inhibitory engrams can make memories quiescent, stored in a latent form that is available for context-relevant activation. In neural networks with balanced excitatory and inhibitory engrams, the release of innate responses and recall of associative memories can occur through focused disinhibition. Understanding mechanisms that regulate the formation and expression of inhibitory engrams in vivo may help not only to explain key features of cognition but also to provide insight into transdiagnostic traits associated with psychiatric conditions such as autism, schizophrenia, and posttraumatic stress disorder.


Effects of a combination of plant bioactive lipid compounds and biotin compared with monensin on body condition, energy metabolism and milk performance in transition dairy cows.
The aim of this study was to test whether a combination of plant bioactive lipid compounds (also termed 'essential oils') and biotin (PBLC+B) could decrease the mobilization of body reserves and ketosis incidence in postpartum dairy cows. We compared non-supplemented control (CON) cows with cows receiving monensin (MON) as a controlled-release capsule at d -21, and with cows receiving PBLC+B from day (d) -21 before calving until calving (Phase 1) and further until d 37 after calving (Phase 2), followed by PBLC+B discontinuation from d 38 to d 58 (Phase 3). The PBLC+B cows had higher body weight and higher back fat thickness than CON cows and lesser body weight change than MON and CON cows in Phase 3. Body condition score was not different among groups. Milk protein concentration tended to be higher on the first herd test day in PBLC+B vs. CON cows. Milk fat concentration tended to be highest in PBLC+B cows throughout Phases 2 and 3, with significantly higher values in PBLC+B vs. MON cows on the second herd test day. Yields of energy-corrected milk were higher in PBLC+B vs. CON and MON cows in Phase 2 and higher in PBLC+B and MON cows vs. CON cows in Phase 3. The incidence of subclinical ketosis was 83%, 61% and 50% in CON, PBLC+B and MON cows, respectively, with lower mean β-hydroxybutyrate values in MON than in PBLC+B cows in Phase 1 prepartum. The serum triglyceride concentration was higher in PBLC+B vs. CON cows on d 37. No differences were observed in serum glucose, urea, non-esterified fatty acids, cholesterol and bilirubin concentrations. Aspartate transaminase and γ-glutamyltranspeptidase but not glutamate dehydrogenase activities tended to be highest in MON and lowest in PBLC+B in Phase 2. We conclude that PBLC+B prevent body weight loss after parturition and are associated with similar ketosis incidence and partly higher yields of energy-corrected milk compared to MON supplementation of dairy cows.


Segregation and overlap of callosal and association neurons in frontal and parietal cortices of primates: a spectral and coherency analysis.
The spatial relations between selected classes of association and callosal neurons were studied in the frontal and parietal lobes of the macaque monkey using retrogradely transported fluorescent dyes. Fast blue and nuclear yellow were injected in the left frontal (areas 4 and 6) and right posterior parietal (area 5) cortices, respectively. These injections led to the retrograde labeling, in the right frontal cortex, of callosal neurons projecting homotopically and association neurons projecting to ipsilateral area 5; in the left superior parietal lobule, of callosal neurons projecting to contralateral area 5 and association neurons projecting to the ipsilateral frontal lobe. In both frontal and parietal cortices, callosal and association neurons were located in layers III and V-VI; a few neurons were also found in layer II. The contribution of layers V-VI to the callosum was significantly higher in areas 4 and 6 than in area 5. Only a small number of neurons (less than 1%) were double labeled. Spectral analyses were used to characterize the spatial periodicities of the distributions of callosal and association neurons. In areas 4, 6, and 5, both association and callosal spectra were dominated by a strong elevation in the range of low spatial frequencies, corresponding to periodicities in cell density with a peak-to-peak distance of about 8 mm. This indicated an arrangement of these corticocortical cells in the form of bands. The latter displayed various shapes and orientations and were composed of more discrete assemblies of cell clusters of about 400-1000 microns width. Their presence was revealed in the power spectra by a small elevation in the range of high spatial frequencies. The coherency analysis assessed the degree of linear relationships for each spatial frequency, and therefore the degree of similarity, between callosal and association cell distributions, together with their phase relations. Little coherency was found in areas 4 and 6 between bands of callosal and association neurons, which suggests that the 2 cell populations are differently and independently distributed in the tangential domain, with no simple phase relations. The overall mean coherency was higher in area 5 than in the frontal cortex: callosal and association bands were more similar in shape, with more extensive zones of overlap. These data indicate that callosal and association neurons share common principles of spatial organization despite the great regional variability of their interrelations in the tangential cortical domain.(ABSTRACT TRUNCATED AT 400 WORDS)


Atrial fibrillation and stroke prevention with warfarin in the long-term care setting.
While the benefits of warfarin sodium therapy for stroke prevention in patients with atrial fibrillation (AF) have been extensively documented, generalizing clinical trial results to the majority of elderly persons with AF, especially to those who reside in the long-term care setting, remains challenging. To determine the prevalence of AF in the institutionalized elderly population and the proportion receiving anticoagulation therapy with warfarin: to identify the clinical and functional characteristics of institutionalized elderly persons with AF that are associated with the use of warfarin; and to assess the quality of prescribing and monitoring of warfarin therapy in institutionalized elderly persons with AF. This study involved 30 long-term care facilities (total No. of beds, 6437) located in New England, Quebec, and Ontario. The proportion of patients with AF who were receiving treatment with warfarin was determined. The association between clinical and functional characteristics and the use of warfarin was examined with crude and multivariable-adjusted analyses. For study subjects with at least 2 weeks of warfarin therapy during the 12-month period preceding the date of medical record abstraction, we assessed the quality of warfarin prescribing based on all international normalized ratio or prothrombin time ratio values during this period. An electrocardiogram indicating AF was present in the records of 413 of 5500 long-term care residents (7.5%); 32% of such patients were being treated with warfarin. Only a history of stroke was found to be positively associated with the use of warfarin in this setting. Patients with a diagnosis of dementia and those in the oldest age group (> or = 85 years) were less likely to receive warfarin therapy. Warfarin was commonly prescribed to patients with a history of bleeding, substantial comorbidity and functional impairment, a history of falls, or concomitant potentiating drug therapy. Patients were maintained above or below the recommended therapeutic range 60% of the time. Atrial fibrillation is common in patients residing in long-term care facilities, but its management with warfarin is highly variable. A more systematic approach to decision making regarding the use of warfarin for stroke prevention in these patients is required. Among patients receiving warfarin, the quality of anticoagulation care warrants improvement.


Topography of N-CAM structural and functional determinants. II. Placement of monoclonal antibody epitopes.
The accompanying report (Watanabe, M., A. L. Frelinger III, and U. Rutishauser, 1986, J. Cell Biol., 103:1721-1727) describes a set of monoclonal antibodies (mAbs) directed against N-CAM epitopes representing the known major structural and functional domains of the molecule. In this study, we have generated and separated a variety of peptide fragments from N-CAM, and then used their size and reactivity with each antibody to position the antigenic sites along the peptide chain. This epitope map, together with the biological properties of the antibodies and previous studies on N-CAM, have been used to construct a topographical model for the molecule in the cell membrane.


The Effectiveness of Attention Bias Modification with and without Trans Cranial Direct Current Stimulation in Chronic Low Back Pain.
Objective: The present study aimed to compare the effect of ABM (attention bias modification) with and without tDCS (transcranial direct current stimulation) on attention bias, pain intensity, and disability due to pain and pain-related psychological consequences, such as depression, anxiety, and stress. Method : Using convenience sampling, 60 individuals who met the criteria for chronic low back pain (LBP) were selected and randomly assigned in to 2 experimental groups and 2 control and sham-tDCS groups. The experimental ABM group received 5 sessions of the dot-probe task, while the second experimental group received 5 sessions of dot-probe task combined with tDCS. Results: The findings indicated that ABM and ABM+tDCS could reduce attention bias and pain-related psychological consequences significantly, compared to the control and sham groups. Also, attention bias and pain outcomes (depression, anxiety, disability due to pain and pain intensity) remained in ABM+tDCS group than in ABM group in a 1-month follow-up. Conclusion: It was found that tDCS + ABM had no additional effects at the end of intervention, but led to more long-lasting effects in 1-month follow-up. Randomized clinical trial registry number: IRCT20171107037306N1.


High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability.
The EPH/EFN family of receptor tyrosine kinases regulates cell adhesion and migration and has an important role in controlling cell positioning in the normal intestinal epithelium. Inactivation of EPHB2 has recently been shown to accelerate tumorigenesis in the colon and rectum, and we have previously demonstrated frequent frameshift mutations (41%) in an A9 coding microsatellite repeat in exon 17 of EPHB2 in colorectal tumors with microsatellite instability (MSI). In this study, we extended these analyses to extracolonic MSI cancers, and found frameshift EPHB2 mutations in 39% (25/64) of gastric tumors and 14% (8/56) of endometrial tumors. Regression analysis of these EPHB2 mutation data on the basis of our previously proposed statistical model identified EPHB2 as a selective target of frameshift mutations in MSI gastric cancers but not in MSI endometrial carcinomas. These results suggest a functional role for EPHB2 in gastric tumor progression, and emphasize the differences between the tumorigenic processes in MSI gastrointestinal and endometrial cancer.


In vitro sodium fluoride exposure decreases torsional and bending strength and increases ductility of mouse femora.
Fluoride exposure in vivo can reduce the material strength of bone, an effect that has been attributed to a change in mineral structure. An in vitro model of fluoride exposure offers the potential to study directly the effects of fluoride on bone mineral. Previous investigators have reported that soaking bones in sodium fluoride in vitro reduces bone strength. However, long soaking times and the absence of physiological buffering ions from their treatment solutions may have caused mineral dissolution that contributed to the decrease in bone strength. Our objectives were to further characterize the effects of in vitro fluoride exposure on bone mechanical properties and to determine if the changes reported in previous studies of bovine cortical bone would be observed for whole rodent bones. We soaked 60 mouse femora in sodium fluoride solutions, with and without physiological buffering ions, and evaluated their torsional and bending properties. Fluoride soaked bones had a 30-fold increase in fluoride content and a 23% increase in water content compared to controls. These changes were associated with average reductions in ultimate load of 45%, reductions in rigidity of 70%, and increases in deformation to failure of 80%. The effect of fluoride was similar for bones treated in buffered and non-buffered solutions, and was observed in both torsion and bending. Our findings confirm those of previous studies and highlight the strong effect that in vitro fluoride exposure has on bone mechanical properties. The in vitro model of fluoride exposure offers a tool to further study the effects of ion substitution in bone.


Effects of deception in social networks.
Honesty plays a crucial role in any situation where organisms exchange information or resources. Dishonesty can thus be expected to have damaging effects on social coherence if agents cannot trust the information or goods they receive. However, a distinction is often drawn between prosocial lies ('white' lies) and antisocial lying (i.e. deception for personal gain), with the former being considered much less destructive than the latter. We use an agent-based model to show that antisocial lying causes social networks to become increasingly fragmented. Antisocial dishonesty thus places strong constraints on the size and cohesion of social communities, providing a major hurdle that organisms have to overcome (e.g. by evolving counter-deception strategies) in order to evolve large, socially cohesive communities. In contrast, white lies can prove to be beneficial in smoothing the flow of interactions and facilitating a larger, more integrated network. Our results demonstrate that these group-level effects can arise as emergent properties of interactions at the dyadic level. The balance between prosocial and antisocial lies may set constraints on the structure of social networks, and hence the shape of society as a whole.


GABA and responses to GABA in the stomatogastric ganglion of the crab Cancer borealis.
The multifunctional neural circuits in the crustacean stomatogastric ganglion (STG) are influenced by many small-molecule transmitters and neuropeptides that are co-localized in identified projection neurons to the STG. We describe the pattern of gamma-aminobutyric acid (GABA) immunoreactivity in the stomatogastric nervous system of the crab Cancer borealis and demonstrate biochemically the presence of authentic GABA in C. borealis. No STG somata show GABA immunoreactivity but, within the stomatogastric nervous system, GABA immunoreactivity co-localizes with several neuropeptides in two identified projection neurons, the modulatory proctolin neuron (MPN) and modulatory commissural neuron 1 (MCN1). To determine which actions of these neurons are evoked by GABA, it is necessary to determine the physiological actions of GABA on STG neurons. We therefore characterized the response of each type of STG neuron to focally applied GABA. All STG neurons responded to GABA. In some neurons, GABA evoked a picrotoxin-sensitive depolarizing, excitatory response with a reversal potential of approximately -40 mV. This response was also activated by muscimol. In many STG neurons, GABA evoked inhibitory responses with both K(+)- and Cl(-)-dependent components. Muscimol and beta-guanidinopropionic acid weakly activated the inhibitory responses, but many other drugs, including bicuculline and phaclofen, that act on vertebrate GABA receptors were not effective. In summary, GABA is found in projection neurons to the crab STG and can evoke both excitatory and inhibitory actions on STG neurons.


Effects of pre-exercise ingestion of carbohydrate on glycaemic and insulinaemic responses during subsequent exercise at differing intensities.
The development of rebound hypoglycaemia has been reported after pre-exercise carbohydrate (CHO) ingestion in some studies but not in others. Differences in the experimental design and factors such as the exercise intensity are likely to be responsible for the discrepancies between these studies. Exercise intensity might be a crucial factor since it affects both insulinaemia and glucose uptake. Therefore the aim of the present study was to compare the glycaemic and insulinaemic responses to exercise at different intensities after ingestion of a standardized pre-exercise CHO load. Eight moderately trained subjects consumed 75 g of glucose 45 min prior to 20 min of exercise at 40%, 65% or 80% maximal power output. Blood samples were collected before glucose ingestion, at 15 min intervals at rest and 5 min intervals during exercise. During exercise, measurements of heart rate and breath-by-breath analysis of expired gas were performed continuously. The trials were performed at [mean (SEM)] 55 (1), 77 (1) and 90 (1) percentages maximal oxygen uptake. At the onset of exercise, plasma glucose concentration returned to pre-ingestion levels, while the insulin concentration was more than three times higher than at rest [on average 57 (7) compared to 16 (1) microU.ml(-1)]. During exercise, plasma glucose concentrations decreased during the first 5 min of exercise and then stabilized in all trials at concentrations that would not be considered to be hypoglycaemic. There were no significant differences in glucose or insulin concentrations between the three trials during exercise. These data suggest that the glycaemic response to ingestion of 75 g of CHO 45 min pre-exercise is similar during exercise of different intensities.


Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance.
The mechanisms by which the enteroinsular axis influences beta-cell function have not been investigated in detail. We performed oral and isoglycemic intravenous (IV) glucose administration in subjects with normal (NGT; n = 11) or impaired glucose tolerance (IGT; n = 10), using C-peptide deconvolution to calculate insulin secretion rates and mathematical modeling to quantitate beta-cell function. The incretin effect was taken to be the ratio of oral to IV responses. In NGT, incretin-mediated insulin release [oral glucose tolerance test (OGTT)/IV ratio = 1.59 +/- 0.18, P = 0.004] amounted to 18 +/- 2 nmol/m(2) (32 +/- 4% of oral response), and its time course matched that of total insulin secretion. The beta-cell glucose sensitivity (OGTT/IV ratio = 1.52 +/- 0.26, P = 0.02), rate sensitivity (response to glucose rate of change, OGTT/IV ratio = 2.22 +/- 0.37, P = 0.06), and glucose-independent potentiation were markedly higher with oral than IV glucose. In IGT, beta-cell glucose sensitivity (75 +/- 14 vs. 156 +/- 28 pmol.min(-1).m(-2).mM(-1) of NGT, P = 0.01) and potentiation were impaired on the OGTT. The incretin effect was not significantly different from NGT in terms of plasma glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide responses, total insulin secretion, and enhancement of beta-cell glucose sensitivity (OGTT/IV ratio = 1.73 +/- 0.24, P = NS vs. NGT). However, the time courses of incretin-mediated insulin secretion and potentiation were altered, with a predominance of glucose-induced vs. incretin-mediated stimulation. We conclude that, under physiological circumstances, incretin-mediated stimulation of insulin secretion results from an enhancement of all dynamic aspects of beta-cell function, particularly beta-cell glucose sensitivity. In IGT, beta-cell function is inherently impaired, whereas the incretin effect is only partially affected.


Does BDNF Val66Met Polymorphism Confer Risk for Posttraumatic Stress Disorder?
Evidence has indicated that BDNF (brain-derived neurotrophic factor) Val66Met genetic variant could be linked to the development of posttraumatic stress disorder (PTSD). However, clinical observations studying the BDNF polymorphism and the risk of PTSD yielded contradictory results. In this meta-analysis we evaluated the association between BDNF Val66Met and PTSD risk. Systematic searches in online databases retrieved 6 relevant publications. Different inherited models were utilized to perform the pooled analysis. Subgroup analyses and sensitive analyses based on Hardy-Weinberg equilibrium (HWE) test results were also carried out. Our study did not found a significant overall effect of BDNF Val66Met on the susceptibility to PTSD under various genetic models. In contrast, subgroup analyses suggested that the stress status of the control group, but not ethnicity, may influence the relationship of BDNF Val66Met with PTSD risk. After the exclusion of a study that was not in HWE, our conclusions remained unchanged during the influence analyses. This meta-analysis suggested no genetic association of BDNF Val66Met with vulnerability to PTSD. Further research studies are warranted to clarify the impact of BDNF variants on the occurrence of PTSD.


New treatments of hepatorenal syndrome.
Hepatorenal syndrome (HRS) is a common complication of advanced cirrhosis, characterized by renal failure and major abnormalities in the systemic circulatory function. Renal failure is caused by intense vasoconstriction of the renal circulation. The syndrome is probably the final consequence of an extreme underfilling of the arterial circulation, secondary to vasodilatation in the splanchninc vascular bed and a decrease in cardiac output due to central hypovolemia. The diagnosis of HRS is based on the exclusion of other causes of renal failure. The survival of patients with HRS is very short, particularly when there is rapidly progressive renal failure (type-1 HRS). Liver transplantation is the best therapeutic option but its applicability is low. During the past few years effective treatment for HRS, such as vasoconstrictor drugs (vasopressin analogues, proportional variant-adrenergic agonists) associated with intravenous albumin infusion and transjugular intrahepatic portosystemic shunts (TIPS), have been introduced. They improve circulatory function, normalize serum creatinine, and may improve survival. Sequential treatment with vasoconstrictors plus albumin and TIPS is an attractive therapeutic possibility. Plasma volume expansion with albumin at infection diagnosis in patients with spontaneous bacterial peritonitis and the administration of pentoxiphilline in patients with severe alcoholic hepatitis significantly reduce the development of type-1 HRS.


Predicting Residence Time and Drug Unbinding Pathway through Scaled Molecular Dynamics.
Computational approaches currently assist medicinal chemistry through the entire drug discovery pipeline. However, while several computational tools and strategies are available to predict binding affinity, predicting the drug-target binding kinetics is still a matter of ongoing research. Here, we challenge scaled molecular dynamics simulations to assess the off-rates for a series of structurally diverse inhibitors of the heat shock protein 90 (Hsp90) covering 3 orders of magnitude in their experimental residence times. The derived computational predictions are in overall good agreement with experimental data. Aside from the estimation of exit times, unbinding pathways were assessed through dimensionality reduction techniques. The data analysis framework proposed in this work could lead to better understanding of the mechanistic aspects related to the observed kinetic behavior.


Human gender differences in the perception of conspecific alarm chemosensory cues.
It has previously been established that, in threatening situations, animals use alarm pheromones to communicate danger. There is emerging evidence of analogous chemosensory "stress" cues in humans. For this study, we collected alarm and exercise sweat from "donors," extracted it, pooled it and presented it to 16 unrelated "detector" subjects undergoing fMRI. The fMRI protocol consisted of four stimulus runs, with each combination of stimulus condition and donor gender represented four times. Because olfactory stimuli do not follow the canonical hemodynamic response, we used a model-free approach. We performed minimal preprocessing and worked directly with block-average time series and step-function estimates. We found that, while male stress sweat produced a comparably strong emotional response in both detector genders, female stress sweat produced a markedly stronger arousal in female than in male detectors. Our statistical tests pinpointed this gender-specificity to the right amygdala (strongest in the superficial nuclei). When comparing the olfactory bulb responses to the corresponding stimuli, we found no significant differences between male and female detectors. These imaging results complement existing behavioral evidence, by identifying whether gender differences in response to alarm chemosignals are initiated at the perceptual versus emotional level. Since we found no significant differences in the olfactory bulb (primary processing site for chemosensory signals in mammals), we infer that the specificity in responding to female fear is likely based on processing meaning, rather than strength, of chemosensory cues from each gender.


Chronic administration of the soluble, nonbacterial fraction of kefir attenuates lipid deposition in LDLr-/- mice.
Kefir is obtained by the action of acidic bacteria and yeasts that exist in symbiotic association in kefir grains. Recently, this fermented milk drink has been recommended for the treatment of several clinical conditions, such as inflammatory, gastrointestinal, or cardiovascular-related diseases, or a combination of these diseases. However, its effects on atherosclerosis are not yet clear. The aim of this study was to prove that chronic treatment with a soluble, nonbacterial fraction of kefir could reduce the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr-/-) mice. LDLr-/- mice were divided into four groups as follows: RESULTS: The soluble, nonbacterial fraction of kefir reduced lipid deposition (P < 0.05) independent of hypercholesterolemia. Moreover, kefir was capable of diminishing the circulating proinflammatory intereukin (IL)-6 level and the ratio of tumor necrosis factor-α to IL-10 (50% and 42%, P < 0.05, respectively) and augmenting the antiinflammatory IL-10 level by approximately 74% (P < 0.05). Chronic treatment with a soluble nonbacterial fraction of kefir was able to decrease the lipid deposition in LDLr-/- hypercholesteremic mice, at least in part through modifying the circulating cytokine profile. The beneficial effects of kefir provide new perspectives for its use as an adjuvant in the prevention of atherosclerosis.


The role of depression, anxiety, fatigue, and fibromyalgia on the evaluation of the remission status in patients with rheumatoid arthritis.
To investigate the effect of depression, anxiety, fatigue, and fibromyalgia (FM) on the remission status in patients with rheumatoid arthritis (RA), defined according to the 28-joint count Disease Activity Score (DAS28)-erythrocyte sedimentation rate (ESR) and the Boolean-based new American College of Rheumatology/European League Against Rheumatism remission criteria. The subjects were patients with RA who participated in a hospital-based observational cohort. Patients who met the DAS28-ESR remission criteria at their latest visit were invited to participate in our study. The patient groups fulfilling or not fulfilling the Boolean remission criteria were identified and compared with each other with regard to the presence of depression, anxiety, fatigue (0-50), and FM. The relationship between psychosocial factors and Simplified Disease Activity Index (SDAI) remission, which is the index-based definition of remission in RA, was also investigated. A total of 87 out of 428 patients (20%) with RA met the DAS28-ESR remission criteria and 32 (37%) of these also met the Boolean remission criteria, while 55 (63%) did not. Forty patients were also in SDAI remission. In the Boolean remission group, 2 patients had depression and 2 had anxiety (p = 0.004). In the Boolean nonremission group, 19 patients had depression and 13 had anxiety (p = 0.04). Continuous scales of anxiety (3.34 ± 3.76 vs 5.83 ± 4.70, p = 0.012) and depression (2.18 ± 2.75 vs 4.63 ± 4.10, p = 0.001) were also lower in the Boolean remission group in comparison with the nonremission group. Though FM syndrome was detected in only 1 patient of the Boolean remission group and in 7 patients of the Boolean nonremission group (p = 0.249), patients' polysymptomatic distress scores of FM in the Boolean remission group were significantly lower than those of the nonremission group (3.12 ± 3.25 vs 6.27 ± 5.19, p = 0.001). The mean fatigue scores were 9.5 ± 10.6 in the Boolean remission group and 16.8 ± 12.8 in the Boolean nonremission group (p = 0.006). In multivariate analysis, patient's global assessment (PtGA) and depression were found as the independent discriminators of Boolean-based definition. Similar relationships were also observed between psychosocial factors and SDAI remission. In patients with RA who do not fulfill the Boolean remission criteria, to avoid overtreatment, assessment of anxiety, fatigue, FM, and especially depression must be considered if PtGA scores and disease activity variables are significantly different.


Clinical and nutritional outcomes in children with idiopathic superior mesenteric artery syndrome.
There are no available data for outcomes in children's idiopathic superior mesenteric artery syndrome (SMAS) strictly treated conservatively. The aim of the study was to evaluate clinical and nutritional outcome in children with idiopathic SMAS. A 1-year prospective observation study of effects of treatment and outcome was performed in 27 children (8 boys, 19 girls) with idiopathic SMAS who underwent an upper gastrointestinal (UGI) series, ultrasound measurement of the aortomesenteric angle, treatment, clinical assessment, growth evaluation, and regular clinical visits for more than 12 months. Mean age of the patients was 11.77 +/- 2.15 years. The major clinical complaints were postprandial pain or fullness (88.9%), vomiting (55.6%), and early satiety (51.9%). Eight patients (29.6%) had weight loss. The UGI series revealed typical features of SMAS. The aortomesenteric angle on ultrasound was 10 degrees to 19 degrees. The height of most patients (92.6%) was above the 10th percentile, whereas 15 (55.6%) patients weighed below the 10th percentile. Six patients underwent surgical intervention (3 for obstruction and 3 for persistent anorexia with weight loss), and their clinical symptoms and weight status improved steadily during the follow-up months. Among the 21 patients not subject to surgical intervention, 11 (52.4%) experienced a reduction of symptoms >50% after 3 months of treatment, and weight-for-age percentile increased significantly after 6 months of treatment. Overall, a significant increase in the weight-for-age status was seen in the patients with surgical treatment or with medication only after 6 and 12 months of treatment. An aortomesenteric angle <20 degrees is a constant phenomenon in children with idiopathic SMAS. A duodenojejunostomy can effectively relieve the obstructive symptoms, such as anorexia, and improve nutritional status, whereas long-term medical treatment may aid in relieving the clinical symptoms, promoting appetite, and improving nutritional status in pediatric patients with idiopathic SMAS.


Fibroblast growth factor-21 potentiates glucose transport in skeletal muscle fibers.
Fibroblast growth factor 21 (FGF21) is a pleiotropic peptide hormone that is considered a myokine playing a role in a variety of endocrine functions, including regulation of glucose transport and lipid metabolism. Although FGF21 has been associated with glucose metabolism in skeletal muscle cells, its cellular mechanism in adult skeletal muscle fibers glucose uptake is poorly understood. In the present study, we found that FGF21 induced a dose-response effect, increasing glucose uptake in skeletal muscle fibers from flexor digitorum brevis muscle of mice, evaluated using the fluorescent glucose analog 2-NBDG (300 µM) in single living fibers. This effect was prevented by the use of either Cytochalasin B (5 µM) or Indinavir (100 µM), both antagonists of GLUT4 activity. The use of PI3K inhibitors such as Wortmannin (100 nM) and LY294002 (50 µM) completely prevented the FGF21-dependent glucose uptake. In fibers electroporated with the construct encoding GLUT4myc-eGFP chimera and stimulated with FGF21 (100 ng/mL), a strong sarcolemmal GLUT4 label was detected. This effect promoted by FGF21 was demonstrated to be dependent on atypical PKC-ζ, by using selective PKC inhibitors. FGF21 at low concentrations potentiated the effect of insulin on glucose uptake but at high concentrations, completely inhibited the uptake in the presence of insulin. These results suggest that FGF21 regulates glucose uptake by a mechanism mediated by GLUT4 and dependent on atypical PKC-ζ- in skeletal muscle.


Correlative light- and electron microscopy with chemical tags.
Correlative microscopy incorporates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Several approaches exist for correlative microscopy, most of which have used the green fluorescent protein (GFP) as the label for light microscopy. Here we use chemical tagging and synthetic fluorophores instead, in order to achieve protein-specific labeling, and to perform multicolor imaging. We show that synthetic fluorophores preserve their post-embedding fluorescence in the presence of uranyl acetate. Post-embedding fluorescence is of such quality that the specimen can be prepared with identical protocols for scanning electron microscopy (SEM) and transmission electron microscopy (TEM); this is particularly valuable when singular or otherwise difficult samples are examined. We show that synthetic fluorophores give bright, well-resolved signals in super-resolution light microscopy, enabling us to superimpose light microscopic images with a precision of up to 25 nm in the x-y plane on electron micrographs. To exemplify the preservation quality of our new method we visualize the molecular arrangement of cadherins in adherens junctions of mouse epithelial cells.


Recovery of citrus triploid hybrids by embryo rescue and flow cytometry from 2x x 2x sexual hybridisation and its application to extensive breeding programs.
Seedlessness is one of the most important characteristics for mandarins for the fresh-fruit market and mandarin triploid hybrids have this trait. Citrus triploid plants can be recovered by 2x x 2x sexual hybridisations as a consequence of the formation of unreduced gametes at low frequency. Triploid embryos are found in small seeds that do not germinate under greenhouse conditions. Extensive breeding programs based on this type of hybridisation require very effective methodologies for embryo rescue and ploidy evaluation. In this work, we describe an effective methodology to recover triploid hybrids from 2x x 2x hybridisations based on in vitro embryo rescue and ploidy level determination by means of flow cytometry. The influence of parents and environmental conditions on obtaining triploid hybrids has been analysed. The strongest effect was associated with the genotype of the female parent while a strong interaction was found between the male parent genotype and environmental conditions. The effect of the female parent genotype on the length of the juvenile phase was also demonstrated by observing a large number of progenies over the last 10 years. The methodology described here has enabled us to obtain over 4,000 triploid hybrids so far, of which 13 have been protected in the European Union and two are being extensively planted by citrus growers to establish new commercial plots. These triploid hybrids have been analysed with simple sequence repeats markers to differentiate all the new triploid varieties and their parents, and thus molecular identification will help defend plant breeders' rights.


Platelets from Asthmatic Individuals Show Less Reliance on Glycolysis.
Asthma, a chronic inflammatory airway disease, is typified by high levels of TH2-cytokines and excessive generation of reactive nitrogen and oxygen species, which contribute to bronchial epithelial injury and airway remodeling. While immune function plays a major role in the pathogenesis of the disease, accumulating evidence suggests that altered cellular metabolism is a key determinant in the predisposition and disease progression of asthma. Further, several studies demonstrate altered mitochondrial function in asthmatic airways and suggest that these changes may be systemic. However, it is unknown whether systemic metabolic changes can be detected in circulating cells in asthmatic patients. Platelets are easily accessible blood cells that are known to propagate airway inflammation in asthma. Here we perform a bioenergetic screen of platelets from asthmatic and healthy individuals and demonstrate that asthmatic platelets show a decreased reliance on glycolytic processes and have increased tricarboxylic acid cycle activity. These data demonstrate a systemic alteration in asthma and are consistent with prior reports suggesting that oxidative phosphorylation is more efficient asthmatic individuals. The implications for this potential metabolic shift will be discussed in the context of increased oxidative stress and hypoxic adaptation of asthmatic patients. Further, these data suggest that platelets are potentially a good model for the monitoring of bioenergetic changes in asthma.


Reelin signals through apolipoprotein E receptor 2 and Cdc42 to increase growth cone motility and filopodia formation.
Lipoprotein receptor signaling regulates the positioning and differentiation of postmitotic neurons during development and modulates neuronal plasticity in the mature brain. Depending on the contextual situation, the lipoprotein receptor ligand Reelin can have opposing effects on cortical neurons. We show that Reelin increases growth cone motility and filopodia formation, and identify the underlying signaling cascade. Reelin activates the Rho GTPase Cdc42, known for its role in neuronal morphogenesis and directed migration, in an apolipoprotein E receptor 2-, Disabled-1-, and phosphatidylinositol 3-kinase-dependent manner. We demonstrate that neuronal vesicle trafficking, a Cdc42-controlled process, is increased after Reelin treatment and further provide evidence that the peptidergic VIP/PACAP38 system and Reelin can functionally interact to promote axonal branching. In conclusion, Reelin-induced activation of Cdc42 contributes to the regulation of the cytoskeleton of individual responsive neurons and converges with other signaling cascades to orchestrate Rho GTPase activity and promote neuronal development. Our data link the observation that defects in Rho GTPases and Reelin signaling are responsible for developmental defects leading to neurological and psychiatric disorders.


Evidence-based sex-related outcomes after radical nephroureterectomy for upper tract urothelial carcinoma: results of large multicenter study.
To assess the sex differences in the clinical and pathologic characteristics of upper tract urothelial carcinoma (UTUC) and to determine the effect on prognosis after radical nephroureterectomy (RNU) in a large multicenter series. The records of 1363 patients who had undergone RNU were reviewed from the UTUC Collaboration database. The median follow-up was 47 months (range 0-250). The pathologic slides were re-evaluated by genitourinary pathologists unaware of the original findings from the slides and the clinical outcomes. The endpoints were freedom from tumor recurrence and disease-specific survival. The male-to-female ratio was 2.1:1. The women were older than the men at diagnosis (70 +/- 11 vs 68 +/- 11 years; P < .001). No significant sex-related differences were found in the presence of symptoms at presentation (P = .70), pathologic stage (P = .98), tumor grade (P = .28), tumor architecture (P = .27), presence of lymphovascular invasion (P = .42), presence of concomitant carcinoma in situ (P = .08), or the presence of lymph node metastases (P = .24). Recurrence developed in 379 patients (28%), and 313 patients (23%) died of their disease. Sex was not associated with disease recurrence (P = .07) or disease-specific survival (P = .13). An adjustment for the effects of the pathologic features did not change the lack of association of sex with the clinical outcomes. To our knowledge, this is the largest series analyzing the effect of sex on the outcomes after RNU. No difference was found in the clinicopathologic features or prognosis between women and men treated with RNU for UTUC. The results of this large, international series show that RNU provides durable local control and disease-specific survival for both men and women with UTUC.


Gyrification and neural connectivity in schizophrenia.
There is emerging evidence for a connection between the surface morphology of the brain and its underlying connectivity. The foundation for this relationship is thought to be established during brain development through the shaping influences of tension exerted by viscoelastic nerve fibers. The tension-based morphogenesis results in compact wiring that enhances efficient neural processing. Individuals with schizophrenia present with multiple symptoms that can include impaired thought, action, perception, and cognition. The global nature of these symptoms has led researchers to explore a more global disruption of neuronal connectivity as a theory to explain the vast array of clinical and cognitive symptoms in schizophrenia. If cerebral function and form are linked through the organization of neural connectivity, then a disruption in neural connectivity may also alter the surface morphology of the brain. This paper reviews developmental theories of gyrification and the potential interaction between gyrification and neuronal connectivity. Studies of gyrification abnormalities in children, adolescents, and adults with schizophrenia demonstrate a relationship between disrupted function and altered morphology in the surface patterns of the cerebral cortex. This altered form may provide helpful clues in understanding the neurobiological abnormalities associated with schizophrenia.


Prognostic value of left atrial volume index in patents with first acute myocardial infarction.
We evaluated the usefulness of left atrial volume index (LAVI) and the degree of changes in LAVI (delta LAVI) during hospitalization for the prediction of prognosis after acute myocardial infarction (AMI). We investigated 205 consecutive patients with first AMI. They underwent echocardiography on admission as well as at discharge. Delta LAVI was calculated by subtracting the value on admission from that at discharge. The primary endpoints were major cardiac events (MACE): cardiac death due to heart failure and heart failure hospitalization. During a mean follow-up of 26 months, MACE occurred in 29 patients. Patients were divided into two groups according to the optimal cut-off values of LAVI (32.0 mL/m(2)) at discharge and delta LAVI (2.5 mL/m(2)) derived from receiver operating characteristic curves, respectively; Group I: LAVI ≤ 32.0 mL/m(2), Group II: LAVI > 32.0 mL/m(2) and Group A: delta LAVI ≤ 2.5 mL/m(2), Group B: delta LAVI > 2.5 mL/m(2). In comparisons of two groups, respectively, the incidence of MACE between the groups showed significant differences [Group I (3.8%) vs. Group II (32.0%): P < 0.001, log-rank, Group A (7.4%) vs. Group B (20.0%): P = 0.0079, log-rank]. In multivariate analysis, LAVI at discharge [risk ratio (RR): 1.077, 95% CI: 1.035-1.124, P = 0.0002] and delta LAVI (RR: 1.056, 95% CI: 1.012-1.108, P = 0.0109) were significant. LAVI > 32.0 mL/m(2) at discharge (sensitivity: 93%, specificity: 69%) and delta LAVI > 2.5 mL/m(2) (sensitivity: 79%, specificity: 50%) were predictors of MACE. LAVI at discharge and delta LAVI would be useful predictors for MACE after first AMI.


Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution.
HIV-related enhancement of gut microbial translocation is associated with progression of hepatic fibrosis. Although hepatic macrophages (Kupffer cells) clear most microbial translocation products and can be infected by HIV, their fate in HIV progression has not been carefully investigated. We studied Kupffer cell density (KCD) in 76 HIV-hepatitis C virus coinfected patients investigated at various stages of liver disease and CD4(+) lymphocyte depletion (and restoration). KCD averaged 23 cells per high-powered field (range 4.4-52.2) and was highest in portal and periportal regions as compared with centrilobular regions (P < 0.001). No differences were detected in KCD by age, liver fibrosis stage, or hepatic inflammatory score. Compared with individuals without apparent HIV-related immunosuppression, however, KCD was substantially lower in persons with lower peripheral blood CD4(+) lymphocyte counts (P = 0.027) and lowest among those with deepest CD4(+) lymphocyte nadir (P = 0.006). After the initial liver biopsy, eight patients began antiretroviral therapy and had immune restoration (> or = 2-fold increase in peripheral CD4(+) lymphocyte count) and a second histologic evaluation with a median of 36.8 months later (range 28.1-58.4 months); KCD increased in all (P = 0.007). Given the central role of Kupffer cells in controlling microbial translocation, these data suggest Kupffer cell loss needs to be considered in the pathogenesis of liver fibrosis in HIV-hepatitis C virus coinfected persons. The abundance of portal and periportal Kupffer cells is suggestive of their contribution to fibrosis in periportal regions in chronic viral hepatitis.


Association of daily coffee and tea consumption and metabolic syndrome: results from the Polish arm of the HAPIEE study.
The aim of this study was to evaluate whether daily consumption of coffee and tea was associated with components and prevalence of metabolic syndrome (MetS) in the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe cohort study. A cross-sectional population-based survey including 8,821 adults (51.4% female) was conducted in Krakow, Poland. Coffee and tea consumption was evaluated using food frequency questionnaires. MetS was defined according to the International Diabetes Federation definition. Linear and logistic regression models were performed to estimate odds ratios and confidence intervals. Among high coffee and tea consumers (3 or more cups/day), high prevalence of female gender, young age, medium-high educational and occupational level, high total energy intake, and smoking habit were found. High coffee drinkers had lower BMI, waist circumference, systolic and diastolic blood pressure, triglycerides, and higher HDL cholesterol than those drinking less than 1 cup/day. In contrast, high tea consumers had lower BMI, waist circumference, but not diastolic blood pressure, which was higher than low drinkers. After adjusting for potential confounding factors, both higher coffee and tea consumption were negatively associated with MetS (OR 0.75, 95% CI 0.66, 0.86 and OR 0.79, 95% CI 0.67, 0.92, respectively). Among specific components of MetS, high coffee consumption was negatively associated with waist circumference, hypertension, and triglycerides, whereas tea consumption with central obesity and fasting plasma glucose in women, but not in men. Coffee and tea consumption was negatively associated with MetS and some of its components.


A mathematical model of umbilical venous pulsation.
Pulsations in the fetal heart propagate through the precordial vein and the ductus venosus but are normally not transmitted into the umbilical vein. Pulsations in the umbilical vein do occur, however, in early pregnancy and in pathological conditions. Such transmission into the umbilical vein is poorly understood. In this paper we hypothesize that the mechanical properties and the dimensions of the vessels do influence the umbilical venous pulsations, in addition to the magnitude of the pressure and flow waves generated in the fetal atria. To support this hypothesis we established a mathematical model of the umbilical vein/ductus venosus bifurcation. The umbilical vein was modeled as a compliant reservoir and the umbilical vein pressure was assumed to be equal to the stagnation pressure at the ductus venosus inlet. We calculated the index of pulsation of the umbilical vein pressure ((max-min)/mean), the reflection and transmission factors at the ductus venosus inlet, numerically and with estimates. Typical dimensions in the physiological range for the human fetus were used, while stiffness parameters were taken from fetal sheep. We found that wave transmission and reflection in the umbilical vein ductus venosus bifurcation depend on the impedance ratio between the umbilical vein and the ductus venosus, as well as the ratio of the mean velocity and the pulse wave velocity in the ductus venosus. Accordingly, the pulsations initiated by the fetal heart are transmitted upstream and may arrive in the umbilical vein with amplitudes depending on the impedance ratio and the ratio between the mean velocity and the pulse wave velocity in the ductus venosus.


Follow-up of children diagnosed with pervasive developmental disorders: stability and change during the preschool years.
Forty-one children with pervasive developmental disorders (PDDs) receiving eclectic services were assessed twice during their preschool years. Measures were compared over time for the whole group and for diagnostic subgroups: Childhood autism (CA group) and Other PDDs group. The mean intelligence quotient/developmental quotient (IQ/DQ) of the whole group was stable (P = 0.209) and scores on the Childhood Autism Rating Scale (CARS) decreased (P = 0.001). At time 2, the CA group was more impaired than the other PDDs group: autistic symptoms were more severe (P = 0.01), adaptive behavior scores were lower (P = 0.014), and a trend for lower IQ/DQs (P = 0.06). Children in this study seemed to fare better than reported in previous follow-up studies on children with autism.


Adrenocortical function in hospitalised patients with active pulmonary tuberculosis receiving a rifampicin-based regimen -- a pilot study.
To assess whether adrenocortical function was compromised in patients with active tuberculosis (TB) during the first 5 days of therapy with either a rifampicin-based or ciprofloxacin-based regimen. Patients were randomised into two groups of 10 each. Adrenocortical function was compared in both groups by the measurement of biochemical indices, electrolytes, osmolality and pituitary-adrenocortical hormones. Adrenal reserve was assessed by intravenous 250 mug adrenocorticotropin hormone (ACTH) stimulation tests. Department of Medicine, Johannesburg Hospital. Twenty hospitalised patients who were diagnosed with TB. Respiratory rate, pulse rate and blood pressure were recorded, and urinary sodium and osmolality were measured. Serum ACTH, cortisol, dehydroepiandrosterone- sulphate (DHEA-S) and aldosterone were assayed. None of the patients demonstrated biochemical evidence of overt adrenal insufficiency. There were no significant differences between the two groups before or during therapy for any biochemical indices, electrolytes, hormones or calculated osmolality. Mean basal cortisol concentrations were substantially elevated and DHEA-S levels were consistently subnormal, resulting in a high cortisol/ DHEA-S ratio. In the ciprofloxacin group, cortisol responses to ACTH stimulation on day 1 were not significantly lower than on day 5. In the rifampicin group, cortisol concentrations decreased at each time point on day 5 compared with day 1 (p = 0.001). However, a significantly higher mean incremental rise from the basal cortisol concentration was measured on day 5 at 60 minutes (p = 0.04). In the entire cohort of 20 patients, 40% demonstrated an incremental cortisol rise of < 250 nmol/l after ACTH stimulation on day 1. Rifampicin did not additionally impair adrenocortical function during the initial period of therapy. The high cortisol/DHEA-S ratio might be of clinical relevance.


Donor human milk in preterm infant feeding: evidence and recommendations.
In preterm infants, feeding with human milk (HM) is a very effective intervention for the prevention of infections and necrotizing enterocolitis (NEC), and for potentially improved neurocognitive and cardiovascular outcomes in the long-term. Hospitals and physicians are advised to recommend HM for preterm and other high-risk infants either by direct breastfeeding and/or using the mother's own expressed milk. Donor HM is the preferred feeding when the mother's own milk is not available in sufficient quantity. While in some countries donor HM has been considered an effective tool in the delivery of health care to infants, skepticism regarding its nutritional and immunological quality has limited its distribution in other countries. The purpose of this paper is to summarize the clinical benefits of donor HM in preterm infants, and to discuss common concerns limiting its distribution as standard care. Clinically, the use of donor HM has been shown to prevent NEC, reduce feeding intolerance and improve long-term outcomes in premature infants. Common concerns, such as slow growth and loss of important biological components of donor HM due to storage and pasteurization, should not be a reason for denial of donor milk. Optimization of banking procedures and of HM fortification is available and should be applied. Banked donor milk should be promoted as standard component of health care for premature infants.


[A prospective cohort study on the influence of high doses of herbs for clearing heat and resolving stasis on survival rates in patients with hepatitis B-related acute-on-chronic liver failure].
Hepatitis B-related acute-on-chronic liver failure (ACLF) is a severe clinical syndrome characterized by jaundice, coagulopathy, ascites and hepatic encephalopathy and with a high mortality rate of 65% to 93%. It involves significant ethical issues when a randomized, double-blinded, placebo-controlled clinical study is conducted to such a serious disease. Therefore, a prospective cohort study design was utilized to explore a new treatment modality of applying integrated traditional Chinese and Western medicine. To evaluate the efficacy, safety and recent survival rates of high-dose herbs with the function of clearing heat and resolving stasis, named Qingre Huayu, in patients with hepatitis B-related ACLF with heat toxin stagnation syndrome. A matched, prospective cohort study was conducted. Participants who met the inclusion criteria were recruited from the Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. Patients were assigned to either an integrated medicine group or a Western medicine group according to their own preference and received either a regime of classic Western medical treatment (control group) or a regime of classic Western medical treatment plus Qingre Huayu herbs (treatment group). The regimes were conducted for 12 weeks. Survival rates of non-liver transplantation patients were evaluated after 12-week treatment. The levels of total bilirubin (TBiL), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and prothrombin activity (PTA) were detected at baseline and weeks 4, 8 and 12. Scores of traditional Chinese medicine (TCM) syndrome and complications were evaluated at baseline and study completion. Adverse events were recorded. All patients were followed up to the deadline for this study. There were 21 cases (31.8%) who died in the treatment group (n=66) and 19 cases (59.4%) in the control group (n=32). Significant difference (X(2)=6.775, P<0.01) was found in comparing the survival and death rates between the two groups by X(2) test. At 12 weeks, mean survival time of the two groups was 69.9 and 47.2 d respectively; cumulative survival rate of patients in the treatment group was higher than that of patients in the control group (P<0.01). Levels of TBiL, ALT, AST, ALB and PTA at weeks 4, 8 and 12 in the treatment group were superior to those in the control group with statistical significance (P<0.01 or P<0.05). In comparison of the TCM syndrome scores at week 12, the average score of the TCM syndrome of the treatment group (n=45) was 7.52±2.41, lower than 18.34±4.36 of the control group (n=13), and the difference was significant (t=8.784, P<0.01). Complication incidences after 12 weeks of treatment were statistically different between the treatment group (n=45) and the control group (n=13) by X(2) test (P<0.05 or P<0.01). Incidence rates of ascites, infection and hepatic encephalopathy accounted for 22.22%(10/45) and 69.23% (9/13), 8.89% (4/45) and 53.85% (7/13), and 11.11% (5/45) and 46.15% (6/13) in the two groups respectively. The incidence rates of adverse events in the treatment group and the control group were 0.00% and 12.50% respectively and the difference was statistically significant (X(2)=5.705, P<0.05). No drug-related adverse events were found in blood, urine and stool routine tests, renal function test and electrocardiography. High doses of Qingre Huayu herbs can significantly improve liver function and coagulation function, reduce complications, and reduce mortality in patients with hepatitis B-related ACLF.


Benefit of home blood pressure measurement after a finding of high blood pressure at a community screening.
Many hypertensive individuals are not under medical management. We studied whether incorporating home blood pressure measurement and subsequent tailored advice into the primary care system improved hypertension management among untreated hypertensive individuals (screening systolic blood pressure >or= 140 mmHg or diastolic blood pressure >or= 90 mmHg and not taking antihypertensive medication) diagnosed during a community screening. All residents aged 30 years or older in one district were asked to measure their blood pressure at home for 30 days, then received tailored advice (intervention area). Four of five Japanese districts served as a control. A self-administered questionnaire monitored the awareness and treatment of hypertension. Eighty-eight per cent (106/120) of untreated hypertensive individuals in the intervention area measured home blood pressure. Of men and women meeting the criteria for untreated hypertension at a community screening in 2003, 97 intervention and 390 control individuals were rescreened in 2004. Among the untreated 2003 screening hypertensive individuals with home hypertension (home systolic blood pressure >or= 135 mmHg or diastolic blood pressure >or= 85 mmHg), the proportion not starting antihypertensive medication was 56%, and the proportion taking 'no action against hypertension' was 41%. These proportions were lower than in the control group (76%, 60%), yielding odds ratios (95% confidence interval) of 0.38 (0.21-0.68) and 0.42 (0.24-0.75), respectively. Incorporating home blood pressure measurement coupled with tailored advice into the primary care system has the potential to reduce the risk of untreated hypertension.


Ultrahigh mobility and giant magnetoresistance in the Dirac semimetal Cd3As2.
Dirac and Weyl semimetals are 3D analogues of graphene in which crystalline symmetry protects the nodes against gap formation. Na3Bi and Cd3As2 were predicted to be Dirac semimetals, and recently confirmed to be so by photoemission experiments. Several novel transport properties in a magnetic field have been proposed for Dirac semimetals. Here, we report a property of Cd3As2 that was unpredicted, namely a remarkable protection mechanism that strongly suppresses backscattering in zero magnetic field. In single crystals, the protection results in ultrahigh mobility, 9 × 10(6) cm(2) V(-1) s(-1) at 5 K. Suppression of backscattering results in a transport lifetime 10(4) times longer than the quantum lifetime. The lifting of this protection by the applied magnetic field leads to a very large magnetoresistance. We discuss how this may relate to changes to the Fermi surface induced by the applied magnetic field.


Clinico-pathologic characteristics and treatment outcomes in children with neuroblastoma at the Kenyatta National Hospital, Nairobi.
To determine clinical-pathologic characteristics, treatment modalities and treatment outcomes of children diagnosed with neuroblastoma. Cross-sectional descriptive study based on secondary data from patient records. Records department of Kenyatta National Hospital (KNH), a tertiary teaching and referral hospital based in Nairobi. Children aged 15 years and below, admitted with the diagnosis of neuroblastoma, between January 1997 and December 2005. Presenting clinical features, diagnostic modalities including laboratory and imaging data, treatment modalities, response to treatment and patient survival. Twenty six patients were eligible for the study; 13 males and 13 females giving a M:F ratio of 1:1. The age range was 5 days to 12 years, with a median age of five years. Abdominal swelling (53.8%), inability to walk due to bone pains, (50%), and cranial or periorbital swelling, (38.5%) were the commonest presenting features. Diagnosis of neuroblastoma was based on tissue biopsy in 50% (95% CI 40.6-79.8%) of the patients, and on fine needle aspiration cytology of mass or bone marrow in the rest. Bone marrow involvement was present in 16, (75%). Anaemia, was common with 72.7% patients having a haemoglobin (HB) <8 g/dl at presentation. Immunohistochemistry and cytological grading were done in two, (8%), patients. Urinary vanilly 1 mandelic acid (VMA), screening was positive in 50% (95% CI 29.9%-70.1%). The most frequently involved organs were abdomen (88.9%), and skeleton, (84.6%). Majority of patients, (92.3%), presented with advanced stage IV disease. Three patients died before commencement of treatment. All treated patients (100%), received cytotoxic therapy. Only two patients (8.6%) had surgery as part of treatment while one, (4.3%) was treated with radiotherapy. The initial treatment regimen was similar for all the patients. Although most patients had a complete initial response to treatment, early relapse, treatment failure, death or loss to follow up of patients with progressive disease were common. Overall survival (OS) at one year and two years were 19.2% (95% CI 6.6-39.4%) and 7.7% (95% CI 0.9%-25.1%) respectively. Only one patient was alive, (also free of disease), five years after diagnosis. Although other clinical-pathologic findings of the patients were similar to those reported elsewhere, virtually all study patients presented with advanced stage IV disease, which would be associated with poor prognosis irrespective of quality of care. Priority must therefore be on ensuring early diagnosis and referral of patients with neuroblastoma before any other interventions can be expected to positively impact on outcome. The limited role of surgery and radiotherapy observed over the study period may be attributed to late presentation of the patients. Pathologic evaluation of important information could have been availed at minimal extra cost. To be at par with current internationally accepted treatment approaches that have been associated with improved survival, there is need to base choice of regimens for individual patients on clinical and readily accessible pathologic markers.


Costs and benefits of nitrogen for Europe and implications for mitigation.
Cost-benefit analysis can be used to provide guidance for emerging policy priorities in reducing nitrogen (N) pollution. This paper provides a critical and comprehensive assessment of costs and benefits of the various flows of N on human health, ecosystems and climate stability in order to identify major options for mitigation. The social cost of impacts of N in the EU27 in 2008 was estimated between €75-485 billion per year. A cost share of around 60% is related to emissions to air. The share of total impacts on human health is about 45% and may reflect the higher willingness to pay for human health than for ecosystems or climate stability. Air pollution by nitrogen also generates social benefits for climate by present cooling effects of N containing aerosol and C-sequestration driven by N deposition, amounting to an estimated net benefit of about €5 billion/yr. The economic benefit of N in primary agricultural production ranges between €20-80 billion/yr and is lower than the annual cost of pollution by agricultural N which is in the range of €35-230 billion/yr. Internalizing these environmental costs would lower the optimum annual N-fertilization rate in Northwestern Europe by about 50 kg/ha. Acknowledging the large uncertainties and conceptual issues of our cost-benefit estimates, the results support the priority for further reduction of NH3 and NOx emissions from transport and agriculture beyond commitments recently agreed in revision of the Gothenburg Protocol.