Hepatobiliary transport kinetics of the conjugated bile acid tracer 11C-CSar quantified in healthy humans and patients by positron emission tomography.
Hepatobiliary secretion of bile acids is an important liver function. Here, we quantified the hepatic transport kinetics of conjugated bile acids using the bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) and positron emission tomography (PET). Nine healthy participants and eight patients with varying degrees of cholestasis were examined with 11C-CSar PET and measurement of arterial and hepatic venous blood concentrations of 11C-CSar. Results are presented as median (range). The hepatic intrinsic clearance was 1.50 (1.20-1.76) ml blood/min/ml liver tissue in healthy participants and 0.46 (0.13-0.91) in patients. In healthy participants, the rate constant for secretion of 11C-CSar from hepatocytes to bile was 0.36 (0.30-0.62)min-1, 20 times higher than the rate constant for backflux from hepatocytes to blood (0.02, 0.005-0.07min-1). In the patients, rate constant for transport from hepatocyte to bile was reduced to 0.12 (0.006-0.27)min-1, 2.3times higher than the rate constant for backflux to blood (0.05, 0.04-0.09). The increased backflux did not fully normalize exposure of the hepatocyte to bile acids as mean hepatocyte residence time of 11C-CSar was 2.5 (1.6-3.1)min in healthy participants and 6.4 (3.1-23.7)min in patients. The rate constant for transport of 11C-CSar from intrahepatic to extrahepatic bile was 0.057 (0.023-0.11)min-1 in healthy participants and only slightly reduced in patients 0.039 (0.017-0.066). This first in vivo quantification of individual steps involved in the hepatobiliary secretion of a conjugated bile acid in humans provided new insight into cholestatic disease. Positron emission tomography (PET) using the radiolabelled bile acid (11C-CSar) enabled quantification of the individual steps of the hepatic transport of bile acids from blood to bile in man. Cholestasis reduced uptake and secretion and increased backflux to blood. These findings improve our understanding of cholestatic liver diseases and may support therapeutic decisions. The trial is registered at ClinicalTrials.gov (NCT01879735).


Analysis of gene expression and proteomic profiles of clonal genotypes from Theobroma cacao subjected to soil flooding.
Soil flooding causes changes in gene transcription, synthesis and degradation of proteins and cell metabolism. The main objective of this study was to understand the biological events of Theobroma cacao during soil flooding-induced stress, using the analyses of gene expression and activity of key enzymes involved in fermentation, as well as the identification of differentially expressed proteins by mass spectrometry in two contrasting genotypes for flooding tolerance (tolerant - TSA-792 and susceptible - TSH-774). Soil anoxia caused by flooding has led to changes in the expression pattern of genes associated with the biosynthesis of alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC) and lactate dehydrogenase (LDH) in leaves and roots of the two evaluated genotypes. Significant differences were observed between the enzyme activities of the two genotypes. Leaves and roots of the TSA-792 genotype showed higher ADH activity as compared to the TSH-774 genotype, whereas the activities of PDC and LDH have varied over the 96 h of soil flooding, being higher for TSA-792 genotype, at the initial stage, and TSH-774 genotype, at the final stage. Some of the identified proteins are those typical of the anaerobic metabolism-involved in glycolysis and alcoholic fermentation-and different proteins associated with photosynthesis, protein metabolism and oxidative stress. The ability to maintain glycolysis and induce fermentation was observed to play an important role in anoxia tolerance in cacao and may also serve to distinguish tolerant and susceptible genotypes in relation to this stressor.


Laquinimod, a once-daily oral drug in development for the treatment of relapsing-remitting multiple sclerosis.
Laquinimod is a novel, small, orally administered medication that has demonstrated efficacy in the treatment of multiple sclerosis, a chronic inflammatory demyelinating disease of the CNS. In preclinical testing, laquinimod inhibited the development of both acute and chronic paralysis in the multiple sclerosis model, experimental autoimmune encephalomyelitis. Furthermore, laquinimod reduced inflammation, demyelination and axonal damage in experimental autoimmune encephalomyelitis in mice treated at disease induction or at clinical disease onset. Recent findings from the clinical trials indicate that laquinimod has significant effects in reducing relapse rate and has more pronounced effects in reducing sustained disability progression as well as brain atrophy, with a good safety profile. In conclusion, preclinical studies show that laquinimod's unique mechanisms of action, including its immunomodulatory and CNS-protective effects, translate into clinical benefits in relapsing-remitting multiple sclerosis patients.


Discovery and Survey of a New Mandarivirus Associated with Leaf Yellow Mottle Disease of Citrus in Pakistan.
During biological indexing for viruses in citrus trees, in a collection of Symons sweet orange (SSO) (Citrus sinensis L. Osbeck) graft inoculated with bark tissues of citrus trees from the Punjab Province in Pakistan, several SSO trees exhibited leaf symptoms of vein yellowing and mottle. High-throughput sequencing by Illumina of RNA preparation depleted of ribosomal RNAs from one symptomatic tree, followed by BLAST analyses, allowed identification of a novel virus, tentatively named citrus yellow mottle-associated virus (CiYMaV). Genome features of CiYMaV are typical of members of the genus Mandarivirus (family Alphaflexiviridae). Virus particles with elongated flexuous shape and size resembling those of mandariviruses were observed by transmission electron microscopy. The proteins encoded by CiYMaV share high sequence identity, conserved motifs, and phylogenetic relationships with the corresponding proteins encoded by Indian citrus ringspot virus (ICRSV) and citrus yellow vein clearing virus (CYVCV), the two current members of the genus Mandarivirus. Although CYVCV is the virus most closely related to CiYMaV, the two viruses can be serologically and biologically discriminated from each other. A reverse-transcription PCR method designed to specifically detect CiYMaV revealed high prevalence (62%) of this virus in 120 citrus trees from the Punjab Province, Pakistan, where the novel virus was found mainly in mixed infection with CYVCV and citrus tristeza virus. However, a preliminary survey on samples from 200 citrus trees from the Yunnan Province, China failed to detect CiYMaV in this region, suggesting that the molecular, serological, and biological data provided here are timely and can help to prevent the spread of this virus in citrus-producing countries.


Intrathecal IgG Synthesis and Persistent Inflammation Are Associated with White Matter Lesions in HIV-negative Patients with Cryptococcal Meningoencephalitis.
Objective Cryptococcal meningoencephalitis (CM) causes significant morbidity and mortality in human immunodeficiency virus (HIV)-negative and HIV-positive populations. White matter lesions (WMLs) have been reported in both populations of CM patients; however, the mechanisms underlying WML formation remain unknown. We herein report the relationship between the intrathecal immune response and the development of WMLs in HIV-negative patients with CM. Methods Eleven consecutive HIV-negative patients with CM who presented at one of three emergency hospitals in Japan from April 2001 to March 2018 were enrolled. For all patients, we retrospectively assessed the relationships between clinical and laboratory information and the presence of WMLs. Results At presentation, 6 patients had WMLs on magnetic resonance imaging (MRI). The cerebrospinal fluid immunoglobulin G (CSF IgG) index was significantly higher in the patients with WMLs than in those without WMLs (mean, 1.34 vs. 0.70, p=0.017). The time from the symptom onset to initial neuroimaging was also significantly longer in the patients with WMLs than in those without WMLs (median, 31.5 vs. 7.0 days; p=0.008). The clinical outcome was comparable among the patients with and without WMLs. Conclusion In HIV-negative patients with CM, a persistent, aberrant immune response to Cryptococcus, such as intrathecal IgG synthesis, may induce WML formation.


Stereospecific antagonism by d-butaclamol of dopamine-induced relaxation of the isolated rabbit mesenteric artery.
We characterized the properties of vascular dopamine receptors on isolated rabbit mesenteric arteries preincubated with phenoxybenzamine (10(-5) M) and contracted with prostaglandin F2 alpha (PGF2 alpha). The dose-response curve for dopamine-induced relaxation was shifted to the right by the dopamine receptor antagonist d-butaclamol (10(-7)--3 X 10(-6) M) in a concentration-dependent manner. The pA2 value for d-butaclamol was calculated as 6.77. In contrast, even a very high concentration (3 X 10(-6) M) of l-butaclamol had no effect, indicating that vascular dopamine receptors require stereospecificity of antagonists. In the same preparation the mechanism of relaxation by 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN; 3 X 10(-7)--10(-4) M) and bromocriptine (10(-6)--3 X 10(-4) M) was found to be dopaminomimetic, since only the dopamine receptor antagonists droperidol (10(-5) M) and metoclopramide (5 X 10(-5) M) could inhibit relaxations, whereas the beta-adrenoceptor antagonists pindolol (10(-7) M) and propranolol (10(-6) M) were without effect. It is concluded that receptors specific for dopamine exist on the rabbit mesenteric artery, which may tentatively be classified as belonging to the D1-type.


Molecular organization of Gram-negative peptidoglycan.
The stress-bearing component of the bacterial cell wall--a multi-gigadalton bag-like molecule called the sacculus--is synthesized from peptidoglycan. Whereas the chemical composition and the 3-dimensional structure of the peptidoglycan subunit (in at least one conformation) are known, the architecture of the assembled sacculus is not. Four decades' worth of biochemical and electron microscopy experiments have resulted in two leading 3-D peptidoglycan models: "Layered" and "Scaffold", in which the glycan strands are parallel and perpendicular to the cell surface, respectively. Here we resolved the basic architecture of purified, frozen-hydrated sacculi through electron cryotomography. In the Gram-negative sacculus, a single layer of glycans lie parallel to the cell surface, roughly perpendicular to the long axis of the cell, encircling the cell in a disorganized hoop-like fashion.


Electroconvulsive seizures protect against methamphetamine-induced inhibition of neurogenesis in the rat hippocampus.
Following methamphetamine consumption and during abstinence many behavioral consequences emerge (i.e., cognitive deficits, ongoing episodes of psychosis, depression, severe cravings, brain neurotoxicity), which are likely linked to propensity to relapse. In this line of thought, we recently showed that binge methamphetamine administration enhanced negative affect and voluntary drug consumption in rats, while it induced persistent neurotoxic effects (i.e., impaired hippocampal neurogenesis), effects that emerged long after drug removal. To date, no pharmacological strategies have been proven to be effective for the treatment of methamphetamine toxicity. A few studies have evaluated the impact of combining methamphetamine pretreatment with electroconvulsive seizures (ECS) post-treatment, an alternative non-pharmacological option used in psychiatry for resistant depression that offers a safe and really potent therapeutic response. Against this background, the present study aimed at testing whether repeated ECS treatment could ameliorate some of the long-term neurotoxicity effects induced by adolescent methamphetamine exposure in rats and emerging after drug removal. At the behavioral level, the main results showed that methamphetamine administration did not alter negative affect immediate during adolescence or later on in adulthood. Interestingly, repeated ECS improved the negative impact of methamphetamine administration on reducing hippocampal neurogenesis, demonstrating that ECS can attenuate certain degree of methamphetamine-induced neurotoxicity in rats, and suggesting ECS as a good therapeutical candidate that deserves further studies.


Supportive, aversive, ambivalent, and indifferent partner evaluations in midlife and young-old adulthood.
Age group differences in self-reported supportive, aversive, ambivalent, and indifferent partner relations were examined in a large sample of midlife (aged 40-44 at baseline, n = 1,719) and older (aged 60-64 at baseline, n = 1,675) married and partnered adults assessed on two occasions 4 years apart. Older adults, particularly older men, were more likely to rate their relationship as supportive and less likely to rate their relationship as aversive relative to midlife adults. Midlife adults were more likely to provide ambivalent or indifferent assessments (as opposed to supportive assessments) of their relationship relative to older adults. Results are discussed in the context of possible developmental changes in interpersonal and intimate relations occurring in middle and older adulthood.


Neuroplasticity. Key to recovery after central nervous system injury.
After an injury to the central nervous system, physical and cognitive impairments and disabilities often abate. These gains may be partly mediated by mechanisms that allow reorganizing of the structure and function within gray and white matter. The potential to enhance neurologic recovery by manipulating the brain and spinal cord must now be considered in clinical practice. Today's rehabilitation routines may not encourage maximum recovery. Indeed, some commonly used physical and pharmacologic methods could inhibit the restoration of motor activities such as walking. On the other hand, therapies that use our expanding knowledge of neuroplasticity could lead to better results for patients.


SnoN upregulation ameliorates renal fibrosis in diabetic nephropathy.
Progressive reduction of SnoN is associated with gradual elevation of TGF-β1 during diabetic nephropathy progression, suggesting SnoN to be a possible mediator of TGF-β1 signaling, with potential therapeutic benefits against TGF- β1 -induced renal fibrosis. To characterize SnoN for its role in renal fibrosis, we assessed SnoN expression patterns in response to high glucose stress, and evaluated the effects of upregulating SnoN on renal fibrosis. High glucose stress induced significantly elevated SnoN, TGF-β1, and Arkadia transcription; however, significantly reduced SnoN protein levels were observed under these conditions. Upregulating the SnoN protein was achieved by Arkadia knockdown, which resulted in inhibited high glucose-induced epithelial-mesenchymal transition (EMT) in renal tubular cells, the onset phase of renal fibrosis. Alternatively, EMT was suppressed by dominantly expressed exogenous SnoN without interfering with TGF-β1. Overall, renal SnoN upregulation ameliorates renal fibrosis by relieving high glucose-induced EMT; these findings support a translational approach targeting SnoN for the treatment of diabetic nephropathy.


Lamin A/C Maintains Exocrine Pancreas Homeostasis by Regulating Stability of RB and Activity of E2F.
Lamins have important roles in nuclear structure and cell signaling. Several diseases are associated with mutations in the lamin A/C gene (LMNA in humans). Patients with familial partial lipodystrophy caused by LMNA mutations develop pancreatitis, but lamin function in the pancreas and how these mutations affect pancreatic regulation are unknown. We generated mice with inducible exocrine pancreas-specific disruption of Lmna and showed that LMNA is lost from most exocrine pancreas cells. LMNA-knockout pancreata develop endoplasmic reticulum stress with loss of acinar cell markers, increased autophagy, apoptosis, and cell proliferation, compared to CreERT2- mice (littermate controls). Disruption of Lmna led to a phenotype that resembled chronic pancreatitis, with increased Sirius Red staining and α-smooth muscle actin in male LMNA-knockout mice compared to littermate males, but not in female mice. LMNA-knockout pancreata have reduced levels of RB and activation of E2F, based on increased expression of E2F target genes. Therefore, lamins maintain pancreatic homeostasis by regulating RB stability and E2F activity.


Coming home from war.
Many American military personnel who served in the Iraq and Afghanistan wars will need long-term management of war-related conditions. There is pressing need for expertise in veterans' care outside of the Military Health System (MHS) and Department of Veterans Affairs (VA), as many will seek care elsewhere: Veterans receive free MHS care only while on active duty; enhanced eligibility for VA healthcare ends 5 years after military discharge; many veterans eligible for VA healthcare use non-VA services instead; and the Affordable Care Act will expand Medicaid coverage for uninsured veterans. Families of veterans also may need care for conditions related to war service. Most medical schools lack veteran-focused curricula beyond VA clerkships, which often do not provide specific training on service-related conditions. The VA, Department of Defense (DoD), veterans groups, and medical professional organizations should partner to develop technical competencies in veteran and family health care for clinicians at all career stages, and cultural competencies to ensure contextually appropriate care. National and state licensing boards should assess these competencies formally. Partnerships between VA, DoD, and the community for care delivery can improve transitions and the quality of veterans' post-deployment care.


Cognitive functioning in school-aged children with vertically acquired HIV infection being treated with highly active antiretroviral therapy (HAART).
In today's era of highly active antiretroviral therapy (HAART), few children with HIV-1 infection experience severe central nervous system (CNS) manifestations indicative of encephalopathy. However, little is known about the neurocognitive strengths and weaknesses of HIV-infected children treated with HAART. This cross-sectional study is the first to systematically investigate the relation between cognitive functioning and medical markers in HIV-infected children and adolescents treated with HAART with varying levels of computed tomography (CT) brain scan abnormalities. The Wechsler Intelligence Scale for Children-Third Edition was administered to 41 vertically infected children (mean age = 11.2 years) treated with HAART for at least 1 year. Other procedures at the time of testing included CT brain scans and collection of CD4 cell counts and plasma HIV1 RNA PCR. Although global cognitive functioning among participants was in the Average range, children with minimal to moderate CT brain scan abnormalities scored significantly lower than children with normal scans on composite measures of cognitive functioning and five specific subtests, especially tasks involving executive functions. Furthermore, children with worse immune status (CD4+ counts < or = 500) scored lower on subtests measuring processing speed. Viral load was unrelated to cognitive test scores. Thus, children with HIV being treated with HAART remain at risk for developing CNS disease. Findings emphasize the importance of conducting neuropsychological assessments in this population, particularly for children with cortical atrophy and absolute CD4+ cell counts < or = 500.


[Prevention of stress hemorrhage in an internal medicine intensive care station: sucralfate versus ranitidine].
Stress ulcer bleeding is a serious complication of critical illness and is associated with increased morbidity and mortality. For the prophylaxis of stress ulcers, antacids, H2-blockers, or sucralfate are prescribed. While H2-blockers inhibit the secretion of gastric acid, sucralfate appears to provide protection without reducing levels of gastric acid. Inhibition of acid secretion increases gastric pH, allowing bacterial overgrowth of the stomach by Gram negative bacteria, which colonize the pharynx and trachea and increase the risk of nosocomial pneumonia. For this reason, H2 blockers appear disadvantageous, though they offer adequate prophylaxis for stress ulcer bleeding. As it does not increase gastric pH, sucralfate provides adequate protection against Gram negative gastric overgrowth, however its prophylactic efficacy is not generally accepted. Therefore, we compared the H2-blocker ranitidine to sucralfate in the prophylactic treatment of stress ulcer bleeding and studied the incidence of positive bacteriological findings in the blood and bronchial secretions of the two groups. In a randomized study, 84 patients undergoing general intensive care received either ranitidine (6 x 50 to 6 x 100 mg daily i.v.) or sucralfate (6 x 1 g via gastric tube or per os). Both groups were comparable with respect to age, underlying disorders, and factors predisposing to the development of stress ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)


Implications of Combined Exposure to Household Air Pollution and HIV on Neurocognition in Children.
Air pollution exposure and HIV infection can each cause neurocognitive insult in children. The purpose of this study was to test whether children with combined high air pollution exposure and perinatal HIV infection have even greater risk of neurocognitive impairment. This was a cross-sectional study of HIV-uninfected unexposed (HUU) and HIV-infected children and their caregivers in Nairobi, Kenya. We used a detailed neuropsychological battery to evaluate neurocognitive functioning in several domains. We measured caregiver 24-h personal CO exposure as a proxy for child CO exposure and child urinary 1-hydroxypyrene (1-OHP), a biomarker for exposure to polycyclic aromatic hydrocarbons (PAHs). Median 24-h caregiver CO exposure was 6.1 and 3.7 ppm for 45 HIV-infected (mean age 6.6 years) and 49 HUU (mean age 6.7 years), respectively; 48.5% of HIV-infected and 38.6% of HUU had caregiver 24-h CO levels exceeding the WHO recommended level. Median 1-OHP exposure was 0.6 and 0.7 µmol/mol creatinine among HIV-infected and HUU children, respectively. HIV-infected children with high urinary 1-OHP (exceeding 0.68 µmol/mol creatinine) had significantly lower global cognition (p = 0.04), delayed memory (p = 0.01), and attention scores (p = 0.003). Among HUU children, urinary 1-OHP and caregiver 24-h caregiver CO were not significantly associated with neurocognitive function. Our findings suggest that combined chronic exposure to air pollutants and perinatal HIV infection may be associated with poorer neurocognitive outcomes. High prevalence of air pollution exposure highlights the need to reduce these exposures.


Incomplete and noisy network data as a percolation process.
We discuss the ramifications of noisy and incomplete observations of network data on the existence of a giant connected component (GCC). The existence of a GCC in a random graph can be described in terms of a percolation process, and building on general results for classes of random graphs with specified degree distributions we derive percolation thresholds above which GCCs exist. We show that sampling and noise can have a profound effect on the perceived existence of a GCC and find that both processes can destroy it. We also show that the absence of a GCC puts a theoretical upper bound on the false-positive rate and relate our percolation analysis to experimental protein-protein interaction data.


StatSensor-i point-of-care creatinine analyzer may identify patients at high-risk of contrast-induced nephropathy.
The current study assessed the accuracy of the StatSensor-i (STA) point-of-care creatinine analyzer prior to and following adjustment (offset correction) by linear regression scatter plots produced by the reference samples from patients and volunteers for detecting high risk of contrast-induced nephropathy in patients with an estimated glomerular filtration rate <45 ml/min/1.73 m2. Blood samples were obtained from 233 consecutive outpatients scheduled for contrast-enhanced CT studies. Of the 233 patients, 123 patient samples were evaluated prior to adjustment and the other 110 following adjustment. Serum creatinine levels and estimated glomerular filtration rate were measured using the analyzer and compared with the values returned by laboratory tests. Analysis was with the paired t-test, the Pearson correlation coefficient and Bland-Altman plotting. The sensitivity, specificity, positive and negative predictive values (PPV, NPV), and accuracy for detecting patients with an estimated glomerular filtration rate <45 ml/min/1.73 m2 were subsequently calculated. Mean serum creatinine levels measured with the analyzer were significantly higher than those returned by laboratory tests before (P<0.0001) and after adjustment (P<0.01). Following adjustment, the difference in serum creatinine values obtained with the STA analyzer and by laboratory methods did not exceed 0.3 mg/dl. Prior to adjustment, 9.7% of the samples were overdiagnosed as having an estimated glomerular filtration rate of <45 ml/min/1.73 m2; following adjustment, the overdiagnosis rate was 2.7%. The sensitivity, specificity, PPV, NPV and accuracy were 100, 89, 50, 100 and 90.2% before and 100, 96.3, 33.3, 100 and 96.4% after adjustment, respectively. With the adjusted point-of-care creatinine analyzer, estimated glomerular filtration rate may be reliably evaluated in the radiology suite.


[The development of therapeutics targeting oxidative stress in prostate cancer].
Oxidative stress is caused by increased reactive-oxygen species (ROS) due to augmented ROS production and impaired anti-oxidative capacity. Recently, oxidative stress has been revealed to promote castration resistance via androgen receptor(AR)-dependent pathway such as AR overexpression, AR cofactor, and AR post-translational modification as well as AR-independent pathway, leading to the emergence of castration-resistant prostate cancer (CRPC). Therefore, antioxidants therapy using natural and chemical ROS scavengers and inhibitors of ROS production seems to be a promising therapy for CRPC as well as preventing castration resistance. However, at present, the application to therapeutics is limited. Therefore, further research on oxidative stress in prostate cancer, as well as on the development for clinical application would be needed.


Cystine metabolism in human fibroblasts. Comparison of normal, cystinotic, and gamma-glutamylcysteine synethetase-deficient cells.
Incubation of normal human skin fibroblasts or fibroblasts derived from patients with erythrocyte deficiency of gamma-glutamylcysteine synthetase (gamma-glutamylcysteine synthetase-deficient) in culture medium containing L-[35S]cystine resulted in incorporation of radioactivity into protein, cysteine, and glutathione, gamma-Glutamylcysteine synthetase-deficient fibroblasts synthesized glutathione from [35S]cystine at 30% the rate of normal cells and contained 30% the normal amount of glutathione. Cystinotic fibroblasts incorporated [35S]cystine into the large intracellular cystine pool not found in normal or gamma-glutamylcysteine synthetase-deficient cells and also appeared to synthesize glutathione more slowly than normal cells. However, the radioactivity recovered as cystine was reduced greatly and the rate of [35S]cystine incorporation into glutathione increased if cystinotic cells were first depleted of their intracellular cystine pool before incubation in [35S]cystine. This suggests that the apparent reduced rate of glutathione synthesis observed in untreated cystinotic cells was a secondary effect caused by dilution of the [35S]cystine by the large pool of nonradioactive cystine. Cystinotic cells depleted of cystine by treatment with mercaptoethylamine reaccumulate 30 to 50% of their initial cystine in 24 hours in the absence of extracellular cystine. Both normal and cystinotic cells lose more than 90% of their intracellular glutathione in 24 hours in cystine-free medium. Both cell types can reutilize cysteine from glutathione for protein synthesis.


Head shape evolution in monitor lizards (Varanus): interactions between extreme size disparity, phylogeny and ecology.
Characterizing patterns of observed current variation, and testing hypotheses concerning the potential drivers of this variation, is fundamental to understanding how morphology evolves. Phylogenetic history, size and ecology are all central components driving the evolution of morphological variation, but only recently have methods become available to tease these aspects apart for particular body structures. Extant monitor lizards (Varanus) have radiated into an incredible range of habitats and display the largest body size range of any terrestrial vertebrate genus. Although their body morphology remains remarkably conservative, they have obvious head shape variation. We use two-dimensional geometric morphometric techniques to characterize the patterns of dorsal head shape variation in 36 species (375 specimens) of varanid, and test how this variation relates to size, phylogenetic history and ecology as represented by habitat. Interspecific head shape disparity is strongly allometric. Once size effects are removed, principal component analysis shows that most shape variation relates to changes in the snout and head width. Size-corrected head shape variation has strong phylogenetic signal at a broad level, but habitat use is predictive of shape disparity within phylogenetic lineages. Size often explains shape disparity among organisms; however, the ability to separate size and shape variation using geometric morphometrics has enabled the identification of phylogenetic history and habitat as additional key factors contributing to the evolution of head shape disparity among varanid lizards.


A novel algorithm for reducing false arrhythmia alarms in intensive care units.
Alarm fatigue in intensive care units (ICU) is one of the top healthcare issues in the US. False alarms in ICU will decrease the quality of care and staff response time over the alarms. Normally, false alarm will cause desensitization of the clinical staff which leads to warnings and misleading, if the triggered alarm is true. In this study, we have proposed a multi-model ensemble approach to reduce the false alarm rate in monitoring systems. We have used 750 patient records from PhysioNet database. At First arrhythmia based features from electrocardiogram (ECG), arterial blood pressure (ABP) and photoplethysmogram (PPG) features were extracted from the records. Next, the dataset has been separated into two subsets on the basis of available features information. The first dataset (DS1) is the combination of ECG physiological, ABP and PPG features. Their correlation coefficient and p-values criteria have been applied for relevant alarm-wise feature-set selection, and random forest classifier was used for model development and validation. The threshold based approach was used on second dataset (DS2) which is the combination of arrhythmia, ABP and PPG features. The developed ensemble model is able to achieve sensitivity 83.33-100 % (average 95.56 %) being true alarms and suppress false alarms rate 66.67-89% (average 77.25%). The predictability of classifier shows the advantage to deal with unbalanced set of information, therefore overall model performance has reached to 83.96% accuracy.


Regional management of liver metastases. I.
This is the first of a two part series. In this issue, Part I presents the natural history of liver metastasis and various proposed staging systems. Indications for surgical resection, which remains the treatment of choice are reviewed. For the majority of patients with unresectable metastases of the liver, various regional treatment approaches seem to give higher response rates than systemic chemotherapy. Technical aspects and therapeutic results of infusion chemotherapy via the hepatic artery and ligation of hepatic artery alone are considered. The totally implantable pump represents and advance in long-term infusion chemotherapy.


Exogenous GnRH induces ovulation in seasonally anoestrous lactating goats (Capra hircus).
A specific sheep LH radioimmunoassay was validated for the measurement of goat LH, and used to monitor luteal-phase LH episodes and the preavulatory LH surge in progestagen sponge-synchronized cycling goats. No luteal-phase LH episodes were detected during 12 h of frequent (15-min) blood sampling in 2 goats. A preovulatory LH surge was recorded in 5/5 goats, with a mean amplitude of 45.4 +/- 7.2 ng/ml and a mean time of onset of 38.4 +/- 1.2 h after removal of a progestagen-impregnated sponge. In anoestrous goats, single i.v. injections of 1000 and 2000 ng GnRH induced LH episodes with a mean amplitude of 2.04 +/- 0.11 and 3.67 +/- 0.06 ng/ml respectively, but injections of 250 or 500 ng did not consistently elevate LH concentrations. Progestagen-primed, seasonally anoestrous lactating goats were treated with repeated injections of 1500 ng GnRH (every 2 h for 52 or 78 h) in May 1985 or 1986. All 10 had kidded in March of the same year, and were consequently at peak lactation at the time of GnRH treatment. A preovulatory LH surge was detected in 9 goats with a mean time of onset of 59.5 +/- 2.9 h (1985) or 39.6 +/- 3.3 h (1986) after vaginal sponge removal. All animals displayed oestrus and ovulated, and 9 of the goats were mated: in 5 of these animals pregnancies were successfully carried to term. The results show episodic LH release in response to GnRH and indicate that ovulation can be induced in seasonally anoestrous goats, even at peak lactation, and normal pregnancies may result.


Psychological distress and adherence to the medical regimen among adolescent renal transplant recipients.
This longitudinal pilot study of adolescent renal transplant recipients (a) describes the prevalence of psychological distress, (b) describes the prevalence of nonadherence, and (c) explores the association between the recipient's psychological distress and his/her subsequent medical adherence. Twenty-two adolescents, aged 13-18 years, completed two interviews that were separated by approximately 12 months. Psychological distress was assessed in three domains: symptoms of depression, anxiety, and anger. Adherence was assessed in three domains: medication taking, blood work, and clinic attendance. At the initial interview, 36.4% had symptoms of depression, 36.4% endorsed anxiety, and 18.2% endorsed excessive state anger. Non-adherence rates were 13.6% for medication, 22.7% for blood work, and 50% for missed clinic. At the second interview, nonadherence with medication remained the same and the other domains decreased. Our small pilot sample, however, limited our ability to detect statistically significant changes over time. Predictive analyses demonstrated that adolescents with excessive anger were at greater risk for subsequently missing medications than adolescents without excessive anger. These findings suggest that while symptoms of depression and anxiety are observed among some adolescents with renal transplants, only anger is associated with elevated risk for nonadherence with medication.


Metastatic lobular carcinoma of breast mimics primary cervix carcinoma: two case reports and a review of the literature.
Invasive lobular carcinoma (ILC) of the breast exhibits unusual clinicopathological, radiological, histological, and metastatic patterns. We present here two cases of ILC of the breast that presented with an unusual pattern of metastasis involving the uterus. Our first patient presented to her primary gynaecologist with profuse vaginal bleeding and underwent total abdominal hysterectomy and bilateral salpingo-oophrectomy. She had fibroadenoma excised from her left breast four years previously. Histopathology revealed lobular carcinoma diffusely infiltrating uterus, cervix, and bilateral ovaries. Retrospective examination of the left breast showed induration along the previous fibroadenoma excision scar. A biopsy from the scar suggested lobular carcinoma. Our second patient presented with a hard indurated cervix mass that mimicked primary cervix carcinoma. She had ILC of the right breast four years previously for which she underwent mastectomy followed by adjuvant chemotherapy and radiotherapy. She was on tamoxifen. Further evaluation at presentation with imaging showed extensive intra-abdominal disease involving peritoneum with moderate ascites, adnexal masses, and confluent para-aortic nodal mass. A cervix biopsy confirmed metastasis from lobular carcinoma. Metastatic involvement of the genital tract should be considered in women with a history of breast cancer who present with abnormal vaginal bleeding, suspicious pelvic examination, or radiological findings. We suggest such patient be vigorously screened with biopsy even if the patient is disease-free for several years. It is crucial to differentiate the metastasis from primary carcinoma of the genital tract as there are vast differences in the management of each.


[Clinical analysis of lymphangioleiomyomatosis].
To improve the diagnosis and treatment of lymphangioleiomyomatosis (LAM). The clinical data of four cases of lymphangioleiomyomatosis diagnosed in our hospital were analyzed and corresponding literature was reviewed. Lymphangioleiomyomatosis, a rare disorder of unknown cause that occured almost exclusively in women of child bearing ages, was characterized microscopically by atypical smooth muscle proliferation. It could occur as a sporadic diseases or as a part of tuberous sclerosis complex (TSC). LAM was associated with progressive dyspnea, recurrent spontaneous pneumothoraces, chylous effusions, and hamartomas. Clinicians should be familiar with the characteristics of LAM so that diagnosis and treatment can be made earlier to improve the prognosis.


Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas.
Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening. The objective of the study was to assess mutation-specific clinical and biochemical characteristics of SDHB-related PGL. The study design was retrospective descriptive. PATIENTS included 29 patients (16 males) with SDHB-related abdominal or thoracic PGL. There was no intervention. Clinical presentations, plasma and urine concentrations of catecholamines and O-methylated metabolites, and genotype-phenotype correlations were measured. Mean +/- sd age at diagnosis was 33.7 +/- 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of patients and was the sole symptom in 14%. Seventy-six percent had hypertension, and 90% lacked a family history of PGL. All primary tumors but one originated from extraadrenal locations. Mean +/- sd tumor size was 7.8 +/- 3.7 cm. In this referral-based study, 28% presented with metastatic disease and all but one eventually developed metastases after 2.7 +/- 4.1 yr. Ten percent had additional head and neck PGLs. The biochemical phenotype was consistent with hypersecretion of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels, consistent with biochemically silent PGL. No obvious genotype-phenotype correlations were identified. SDHB-related PGL often presents as apparently sporadic PGL with symptoms related to tumor mass effect rather than to catecholamine excess. The predominant biochemical phenotype consists of hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are biochemically silent. The clinical expression of these tumors cannot be predicted by the genotype.


Atmospheric pressure matrix-assisted laser desorption/ionization in transmission geometry.
In both atmospheric pressure matrix-assisted laser desorption/ionization (AP MALDI) and vacuum MALDI, the laser typically illuminates the analyte on the front side of an opaque surface (reflection geometry). Another configuration consisting of laser illumination through the sample backside (transmission geometry) has been used in conventional MALDI; however, its use and the number of reports in the literature are limited. The viability of transmission geometry with AP MALDI is demonstrated here. Such a geometry is simple to implement, eliminates the restriction for a metallic sample holder, and allows for the potential analysis of samples on their native transparent surfaces, e.g., cells or tissue sections on slides.


Supraventricular Tachycardia as the Initial Presentation of New-Onset Lupus: A Case Report.
Systemic lupus erythematosus (SLE) is a chronic, autoimmune, multisystem disorder that can sometimes be life-threatening. The presentation varies widely given the wide range of clinical and serological manifestations coupled with the disease's ability to affect any organ. Prognosis depends on the organ systems involved, as well as the severity of the involvement. This case involves a 17-year-old with initial presentation of supraventricular tachycardia subsequently found to have pancreatitis, myocarditis, and nephritis secondary to a new diagnosis of SLE. Systemic lupus erythematosus can involve virtually any organ system, which leads to the variable nature of presentation, as was the case for our patient and his presentation being supraventricular tachycardia from underlying myocarditis secondary to SLE. Lupus myocarditis is rare, but when present often indicates severe systemic illness. The echocardiogram will often show global hypokinesis without evidence of coronary artery disease. This was the case with our patient. His echocardiogram demonstrated new-onset systolic left-sided heart failure due to nonischemic cardiomyopathy with an ejection fraction of 25%. Unfortunately for our patient, he had several poor prognostic factors on his initial presentation prior to any treatment being started, including renal disease, male, age (17 years), low socioeconomic status, African American race, and high disease activity. Systemic lupus erythematosus is the great mimicker and can present in a variety of ways. Given its ability to involve virtually any organ system, it is important to consider it on the differential diagnoses, especially in patients with a strong family history.


France: genetics education for non-genetics health care providers.
This paper explores the treatment of medical genetics in undergraduate medical education, specialists' training and continuing medical education (CME) for general practitioners, specialists, nurses and midwives. We conducted a qualitative survey of websites, published or unpublished documents, telephone interviews and mailed questionnaires. Genetics is a medical specialty in France, and the small number of university professors in genetics are in charge of the genetic component of medical training of all future practitioners. The study was complicated by the ongoing waves of reforms in the French health and educational systems and by the autonomy of the faculties. Specialist training and CME in genetics is heterogeneous and not organised as a priority. Specialist education and CME in genetics of non-geneticist health care providers needs to be adapted to the fast ongoing developments of this field of knowledge.


Quinoline-based tetradendate nitrogen ligands stabilize the bis(micro-oxo) dinuclear manganese(iii,iii) core.
Quinoline-based, tetradentate nitrogen ligands, N,N'-bis(2-quinolylmethyl)-N,N'-dialkyl-1,2-ethanediamine (alkyl = methyl, bqdmen; ethyl, bqdeen; isopropyl, bqdpen), have been investigated as the supporting ligands for the formation of bis(micro-oxo) dinuclear manganese complexes. Bis(micro-oxo)Mn(2)(iii,iii) complexes and were obtained for bqdmen and bqdeen, respectively, as evidenced by X-ray crystallography, whereas bqdpen did not afford any manganese complexes due to its steric bulk. Complexes and exhibit highly positive Mn(2)(iii,iii)/Mn(2)(iii,iv) and Mn(2)(iii,iv)/Mn(2)(iv,iv) redox couples relative to the corresponding pyridine-ligated (micro-O)(2)Mn(2)(iii,iii) complexes.


Anomalous Biceps Femoris Tendon Insertion Leading to a Snapping Knee in a Young Male.
Snapping biceps femoris tendon is an uncommon problem that can be caused by various anatomical aberrations around the knee joint. There are several case reports in the literature describing some of these anatomical variations and their treatment. We present a case of unilateral snapping biceps femoris tendon due to a previously unreported anatomical variation, our technique for successful surgical treatment, and a review of the literature.


Local Heating Test for Detection of Microcirculation Abnormalities in Patients with Diabetes-Related Foot Complications.
In this study, authors used a wavelet analysis of skin temperature (WAST) to assess the mechanisms of microvascular tone regulation during the local heating test in patients with diabetic foot syndrome (DFS). The participants included control subjects and 36 hospitalized patients with DFS between 52 and 79 years old (68 ± 8 years old). They were distributed among 5 groups: 15 control subjects, 8 patients with DFS who did not develop ulcerative or necrotic disorders, 10 patients who developed the neuroischemic form of DFS complicated by foot ulceration, 12 patients with DFS complicated by toe necrosis, and 6 patients with DFS and foot gangrene. A comparison among the groups was made using a nonparametric Mann-Whitney U test. Spearman correlation coefficients were used to assess the relationship between WAST results, aortoarteriography, and ultrasonic dopplerography data. In control subjects, a local increase in temperature (up to 42° C) causes a more than 3-fold increase in the amplitude of foot skin temperature oscillations. In patients with DFS, the response to the local heating test was much weaker. High correlations of WAST results to arterial patency of the lower extremities and the state of the vascular walls were established. The WAST technique may have considerable value in evaluating the progression of DFS and the effectiveness of therapeutic interventions. The low cost of an individual test makes the WAST technique suitable for routine use in most healthcare facilities.


The Bovine Hepatic Cell Line BFH12 as a Possible Model for Hepatosteatosis in Dairy Cows.
Hepatosteatosis is a common metabolic disorder of dairy cows, especially during early lactation. Currently, there are a few models of bovine hepatic steatosis available, including primary hepatocytes, liver slices, and animal models. Studies that elucidate the influence of single fatty acids on lipid classes, fatty acid pattern, gene expression, and phenotypic changes are still limited. Hence, we investigated the suitability of the fetal bovine hepatocyte-derived cell line BFH12 as a model for hepatosteatosis. To create a steatotic environment, we treated BFH12 with stearic acid, palmitic acid, or oleic acid in non-toxic doses. Thin-layer chromatography and gas chromatography were used to analyze lipid classes and fatty acid pattern, and qPCR was used to quantify gene expression of relevant target genes. Lipid droplets were visualized with confocal laser scanning microscopy and evaluated for number and size. Treatment with oleic acid increased triglycerides, as well as lipid droplet count per cell and upregulated carnitine palmitoyl transferase 1, which correlates with findings of in vivo models. Oleic acid was largely incorporated into triglycerides, phospholipids, and non-esterified fatty acids. Stearic acid was found mainly in non-esterified fatty acids and triglycerides, whereas palmitic acid was mainly desaturated to palmitoleic acid. All three fatty acids downregulated stearyl-CoA-desaturase 1. In conclusion, BFH12 can acquire a steatotic phenotype by incorporating and accumulating fatty acids. Oleic acid is particularly suitable to produce hepatosteatosis. Therefore, BFH12 may be a useful in vitro model to study bovine hepatosteatosis and its underlying molecular mechanisms.


Remote post-mortem radiology reporting in disaster victim identification: experience gained in the 2017 Grenfell Tower disaster.
On 14 June 2017 at 00:54 h, the worst residential fire since the conclusion of the Second World War broke out in Flat 16, 4th floor of the 24-storey residential Grenfell Tower Block of flats, North Kensington, West London, UK. Seventy-one adults and children died, including one stillbirth. All victims of the Grenfell Tower disaster who died at the scene underwent post-mortem computed tomography (PMCT) imaging using a mortuary-sited mobile computed tomography scanner. For the first time, to the authors' knowledge, the disaster victim identification (DVI) radiology reporting was undertaken remote to the mortuary scanning. Over an 11-week period, 119 scans were undertaken on 16 days, with up to 18 scans a day. These were delivered to a remote reporting centre at Leicester on 13 days with between 2 and 20 scans arriving each day. Using a disaster-specific process pathway, a team of 4 reporters, with 3 support staff members, trialled a prototype INTERPOL DVI radiology reporting form and produced full radiology reports and supporting image datasets such that they were able to provide 96% of prototype DVI forms, 99% of image datasets and 86% of preliminary reports to the DVI teams in London within one working day of image receipt. This paper describes the first use of remote radiology reporting for DVI and exemplifies how remote PMCT reporting can be used to support a DVI process of this scale.


[Medicine and society. Schools of thought in the health field].
The article considers the answers given by different schools of thought to the fundamental questions about the degree of autonomy of medicine and the kind of articulation between medicine and society as a whole and in its "parts." The answers vary with the thinking in the different social sciences and the philosophic schools associated with them. The author divides his presentation in two broad chapters: The first covers schools of thought in the health field, and attempts to delineate the philosophical foundations underlying the principal current schools of thought in this field, without attempting a history of the philosophical schools or analyzing each of them in detail. Thus, two idealist currents are studied which have exerted great influence in the health field--neopositivism and neo-Kantianism--and marxism as the materialist school, which recognizes the primary of matter, nature, and objective reality, and views consciousness as a property of matter. The second chapter considers the theoretical contest now going on among the schools of thought discussed in the first chapter, which try to explain the relationship between medicine and the social structure; the effectiveness of medical action, and the social determinants of disease. Prior to the seventies, the author says, the dominant view of the autonomy of medicine, its effectiveness, the potential for social change of the medical institutions, and the benefits to health of economic development, was endorsed by the predominance of positivism among these schools of medical thought. The view that medicine was broadly autonomous and at the same level with other subsystems such as the economic, the political and the educational subsystems, assumed the possibility of changing society by an effort begun through any of these "sectors." The enormous growth of productive forces that took place in the developed capitalist countries during the fifties, and even more during the sixties, collided at the end of the latter decade with the existing social production relations, which checked the progress of the production forces and generated a series of challenges in civil society to the aims of economic development and the achievements of science in relation to the inequality of the distribution of wealth. In the health sector, this was a time of criticism of the positivist view and of pointing out the negative effects of medicalization, highlighting the ideological and self-perpetuating character of medical institutions, and proposals for the demedicalization of society.(ABSTRACT TRUNCATED AT 400 WORDS)


Identifying drug-target interactions based on graph convolutional network and deep neural network.
Identification of new drug-target interactions (DTIs) is an important but a time-consuming and costly step in drug discovery. In recent years, to mitigate these drawbacks, researchers have sought to identify DTIs using computational approaches. However, most existing methods construct drug networks and target networks separately, and then predict novel DTIs based on known associations between the drugs and targets without accounting for associations between drug-protein pairs (DPPs). To incorporate the associations between DPPs into DTI modeling, we built a DPP network based on multiple drugs and proteins in which DPPs are the nodes and the associations between DPPs are the edges of the network. We then propose a novel learning-based framework, 'graph convolutional network (GCN)-DTI', for DTI identification. The model first uses a graph convolutional network to learn the features for each DPP. Second, using the feature representation as an input, it uses a deep neural network to predict the final label. The results of our analysis show that the proposed framework outperforms some state-of-the-art approaches by a large margin.


Hyperoxia Improves Repeated-Sprint Ability and the Associated Training Load in Athletes.
This study investigated the impact of hyperoxic gas breathing (HYP) on repeated-sprint ability (RSA) and on the associated training load (TL). Thirteen team- and racquet-sport athletes performed 6-s all-out sprints with 24-s recovery until exhaustion (power decrement ≥ 15% for two consecutive sprints) under normoxic (NOR: FIO2 0.21) and hyperoxic (HYP: FIO2 0.40) conditions in a randomized, single-blind and crossover design. The following variables were recorded throughout the tests: mechanical indices, arterial O2 saturation (SpO2), oxygenation of the vastus lateralis muscle with near-infrared spectroscopy, and electromyographic activity of the vastus lateralis, rectus femoris, and gastrocnemius lateralis muscles. Session TL (work × rate of perceived exertion) and neuromuscular efficiency (work/EMG [Electromyography]) were calculated. Compared with NOR, HYP increased SpO2 (2.7 ± 0.8%, Cohen's effect size ES 0.55), the number of sprints (14.5 ± 8.6%, ES 0.28), the total mechanical work (13.6 ± 6.8%, ES 0.30), and the session TL (19.4 ± 7.0%, ES 0.33). Concomitantly, HYP increased the amplitude of muscle oxygenation changes during sprints (25.2 ± 11.7%, ES 0.36) and recovery periods (26.1 ± 11.4%, ES 0.37), as well as muscle recruitment (9.9 ± 12.1%, ES 0.74), and neuromuscular efficiency (6.9 ± 9.0%, ES 0.24). It was concluded that breathing a hyperoxic mixture enriched to 40% O2 improves the total work performed and the associated training load during an open-loop RSA session in trained athletes. This ergogenic impact may be mediated by metabolic and neuromuscular alterations.


Vascular inflammation stratified by C-reactive protein and low-density lipoprotein cholesterol levels: analysis with 18F-FDG PET.
We examined the severity of vascular inflammation in healthy individuals without hyperlipidemia but with elevated high-sensitivity C-reactive protein (hsCRP) using 18F-FDG PET, which is a promising imaging technique for the assessment of vascular inflammation within atherosclerotic plaques. Vascular inflammation in the carotid arterial wall, represented as the target-to-background ratio (TBR), was measured using 18F-FDG PET in 120 healthy subjects without a history of cardiovascular diseases. Subjects with high hsCRP (≥2 mg/L) and low low-density lipoprotein cholesterol (LDL-C) (<130 mg/dL) levels had a significantly higher maximum TBR than did those with low hsCRP (<2 mg/L) and low LDL-C levels (<130 mg/dL) or low hsCRP (<2 mg/L) and high LDL-C levels (≥130 mg/dL) (1.29±0.13, 1.12±0.10, and 1.16±0.05, respectively), even though there were no significant differences in the carotid intima-media thickness. The maximum TBR values had the strongest positive correlation with hsCRP level among the various cardiovascular risk factors (r=0.68, P<0.01). However, other emerging inflammatory markers such as lipoprotein-associated phospholipase A(2) or monocyte chemoattractant protein-1 were not coherently associated with TBR values. Multiple stepwise regression analyses showed that hsCRP and diastolic blood pressure were independent decisive factors for maximum TBR, whereas age, diastolic blood pressure, and LDL-C were factors that determined the maximum intima-media thickness. Vascular inflammation measured using 18F-FDG PET was increased in healthy individuals without hyperlipidemia but with elevated hsCRP.


Association between metabolic syndrome and osteoporosis: a meta-analysis.
Metabolic syndrome (MetS) consists of several independent clinically recognisable features that have their own independent effects on bone metabolism, and even a single disease could have apparently contradictory effects on bone metabolism. This meta-analysis aimed to detect a relationship between MetS and osteoporosis. The PubMed, Embase, and Cochrane library databases were searched for relevant studies published before April 1, 2013. On June 22, 2013, the databases were searched again for additional studies. Studies clearly reporting a comparison of bone mineral density (BMD) in subjects with or without MetS were selected for our analysis. From these results, we analysed the crude BMD and the BMD adjusted for all covariates (age, weight, height, alcohol intake, cigarette smoking and exercise). Weighted mean differences were calculated using a random-effects model. Nine studies were included in this meta-analysis. No significant differences were found when analysing the crude lumbar spine BMD and the femoral neck BMD. However, the MetS (-) group showed a significantly higher BMD when all covariates were adjusted for femoral neck BMD (0.02, p=0.0002) and lumbar spine BMD (0.01, p=0.007). Subgroup analysis suggested a negative effect of MetS on BMD in men but not in women. These findings suggest that MetS is a risk factor for developing osteoporosis in men.


Life-time and current suicide-ideation in Australian secondary school students: Socio-demographic, health and psychological predictors.
This study involved a multi-level analysis of factors related to self-reported suicidality (both current and life-time) in adolescents A sample of 2552 students aged 14-16 years answered questions relating to demographics, social and familial functioning, psychological well-being and suicidality. Suicidality, defined as being at least some element of reported suicide ideation, Behaviourally, suicidality was also more likely if students smoked, drank alcohol without adult supervision or if they took illicit drugs was more likely in girls, and in those with poorer social, family and psychological functioning. Behaviourally, suicidality was also more likely if students smoked, drank alcohol or took illicit drugs. Multi-level modelling showed that negative affect, substance use and the presence of romantic relationships were most strongly associated with suicidality. Both current and life-time measures of suicidality showed similar results. Both models suggested that the presence of substance use in teenagers is a potentially useful indicator of elevated suicide risk and that many of the social problems commonly associated with suicidality are likely to be mediated by negative affective states. The study had several limitations. First, it was cross-sectional so it was not possible to examine how variables measured at one time predicted subsequent suicidality. Second, the present analyses were based on a single measure of suicidality that did not differentiate between ideation and attempts. Thus, the analyses did not indicate the severity of the suicidality: whether it involved ideation or actual attempts. Adolescent girls and adolescents with poor social and family functioning and those who engage in substance use are at risk of suicidal ideation (a known precursor of suicide attempts). School counsellors and teachers need to be aware of the risks.


Deployment-based lifetime optimization model for homogeneous Wireless Sensor Network under retransmission.
Sensor-deployment-based lifetime optimization is one of the most effective methods used to prolong the lifetime of Wireless Sensor Network (WSN) by reducing the distance-sensitive energy consumption. In this paper, data retransmission, a major consumption factor that is usually neglected in the previous work, is considered. For a homogeneous WSN, monitoring a circular target area with a centered base station, a sensor deployment model based on regular hexagonal grids is analyzed. To maximize the WSN lifetime, optimization models for both uniform and non-uniform deployment schemes are proposed by constraining on coverage, connectivity and success transmission rate. Based on the data transmission analysis in a data gathering cycle, the WSN lifetime in the model can be obtained through quantifying the energy consumption at each sensor location. The results of case studies show that it is meaningful to consider data retransmission in the lifetime optimization. In particular, our investigations indicate that, with the same lifetime requirement, the number of sensors needed in a non-uniform topology is much less than that in a uniform one. Finally, compared with a random scheme, simulation results further verify the advantage of our deployment model.


The sensitivity and specifity of DR-70 immunoassay as a tumor marker for non-small cell lung cancer.
Lung cancer is the most important causes of the cancer related mortality. Patients with lung cancer are usually diagnosed at advanced or locally advanced stage, for this reason early diagnosis of lung cancer is very important. For early detection of lung cancer some methods are emphasized such as low-dose computed tomography or tumor biomarkers. In this study we aimed to evaluate DR-70 sensitivity and specificity as a tumor marker in detection of non-small cell lung cancers. Between May 2013 and April 2014, the serum samples from 88 non lung cancer patients, 86 patients with chronic obstructive pulmonary disesase were obtained. Blood samples from each participant were analyzed for DR-70 level. Totally 174 patients were enrolled to the study (152 male, 22 female). Histopathologically 47(53.4%) patients were diagnosed with squamous cell lung cancer, 34 (38.6%) with adenocarcinoma, and 7 (8%) with non-small cell lung cancer. The mean serum DR-70 levels in lung cancer patients (2.43 ± 1.82 µg/mL) was significantly higher compared to the 86 non-cancerous subjects (1.15 ± 0.70 µg/mL) (p< 0.01). DR-70 exhibited clinical sensitivity and specificity of 54.5 and 83.7%, respectively, at an optimal cut off at 1.98 µg/mL. It could be said that the risk of the presence of the disease is 6.171 times higher in the cases where DR-70 level is 1.98 µg/mL and higher. DR-70, a marker used to measure fibrin degradation products, generated by all major cancers, may helps to find high risk lung cancer patients.


Modulation of intracellular calcium levels inhibits secretion of collagenase 1 by migrating keratinocytes.
Calcium concentration influences keratinocyte differentiation, and, following injury, keratinocytes move through an environment of changing calcium levels. Because these migrating cells in wounds invariably express collagenase 1, we assessed if modulation of calcium levels regulates collagenase 1 production by primary human keratinocytes. Accurately reflecting the confined spatial pattern of enzyme production seen in vivo, collagenase 1 mRNA was expressed only by keratinocytes migrating from foci of differentiated cells. Treatment with calcium ionophores A23187 or thapsigargin markedly inhibited the basal and phorbol 12-myristate 13-acetate-(PMA) stimulated accumulation of keratinocyte collagenase 1 in the medium but did not affect collagenase 1 production by control or PMA-treated fibroblasts. A23187-mediated inhibition of collagenase 1 protein was not associated with a decrease in mRNA levels but rather was controlled by a selective and reversible block of enzyme secretion. This block in secretion was likely not due to altered protein folding as the proenzyme within A23187-treated cells remained capable of autolytic activation upon treatment with p-aminophenylmercuric acetate. In contrast, 92-kDa gelatinase mRNA and secreted protein levels were coordinately reduced by A23187. Keratin 14 expression, a basal keratinocyte marker, was reduced with PMA treatment, but A23187 did not affect keratin 14 expression. In human wounds, both basal and suprabasal keratinocytes at the migrating front of epidermis stained for keratin 14, but only the basal cells expressed collagenase 1. These data suggest that collagenase 1 production is not necessarily linked with expression of basal cell markers and that modulation of intracellular calcium levels can block secretion of collagenase 1 by keratinocytes which have moved away from the stratum basalis and from their natural substrate.


Molecular clock evidence for survival of Antarctic cyanobacteria (Oscillatoriales, Phormidium autumnale) from Paleozoic times.
Cyanobacteria are well adapted to freezing and desiccation; they have been proposed as possible survivors of comprehensive Antarctic glaciations. Filamentous types from the order Oscillatoriales, especially the species Phormidium autumnale Kützing ex Gomont 1892, have widely diverse morphotypes that dominate in Antarctic aquatic microbial mats, seepages, and wet soils. Currently little is known about the dispersion of cyanobacteria in Antarctica and of their population history. We tested the hypothesis that cyanobacteria survived Antarctic glaciations directly on site after the Gondwana breakup by using the relaxed and strict molecular clock in the analysis of the 16S rRNA gene. We estimated that the biogeographic history of Antarctic cyanobacteria belonging to P. autumnale lineages has ancient origins. The oldest go further back in time than the breakup of Gondwana and originated somewhere on the supercontinent between 442 and 297 Ma. Enhanced speciation rate was found around the time of the opening of the Drake Passage (c. 31-45 Ma) with beginning of glaciations (c. 43 Ma). Our results, based primarily on the strains collected in maritime Antarctica, mostly around James Ross Island, support the hypothesis that long-term survival took place in glacial refuges. The high morphological diversification of P. autumnale suggested the coevolution of lineages and formation of complex associations with different morphologies, resulting in a specific endemic Antarctic cyanobacterial flora.


Interactions between the juvenile Batten disease gene, CLN3, and the Notch and JNK signalling pathways.
Mutations in the gene CLN3 are responsible for the neurodegenerative disorder juvenile neuronal ceroid lipofuscinosis or Batten disease. CLN3 encodes a multi-spanning and hydrophobic transmembrane protein whose function is unclear. As a consequence, the cell biology that underlies the pathology of the disease is not well understood. We have developed a genetic gain-of-function system in Drosophila to identify functional pathways and interactions for CLN3. We have identified previously unknown interactions between CLN3 and the Notch and Jun N-terminal kinase signalling pathways and have uncovered a potential role for the RNA splicing and localization machinery in regulating CLN3 function.


A high throughput screening system for predicting chemically-induced reproductive organ deformities.
There is a great need for alternative testing methods for reproductive toxicants that are practical, fast, cost-effective and easy to interpret. Previously we followed a pragmatic approach using readily available tests, which was successful in predicting reproductive toxicity of chemicals [13]. This initial battery still contained apical tests and is fairly complex and low in its throughput. The current study aimed to simplify this screening battery using a mechanistic approach and a panel of high throughput CALUX reporter gene assays. A mechanistic approach was taken to validate this high throughput test battery. To this end it was challenged with two preselected sets of chemicals addressing two major apical effect classes relevant in reproductive toxicity. We found selectivity in this battery in that 82% of the compounds inducing reproductive organ deformities were predicted correctly, while for compounds inducing neural tube defects this was the case in 47% only. This is consistent with the mechanisms of toxicity covered in the battery. The most informative assays in the battery were ERalpha CALUX to measure estrogenicity and the AR-anti CALUX assay to measure androgen receptor antagonism.


Pharmacotherapy for stress urinary incontinence.
The purpose of this review article is to highlight new pharmacotherapies on the horizon for the treatment of stress urinary incontinence. Although behavioral and surgical therapies are currently the mainstay of treatment for this condition, we are hopeful that pharmacotherapy will one day take center stage of the various treatment options. Currently, there are no medications approved by the US Food and Drug Administration for the treatment of stress urinary incontinence. However, exciting clinical data are becoming available about an oral medication for the treatment of stress urinary incontinence that appears to be clinically safe and efficacious. In addition to discussing medications currently under development, this article also discusses pharmacologic targets that could be suitable future targets to treat stress urinary incontinence.


Highly compact circulators in square-lattice photonic crystal waveguides.
We propose, demonstrate and investigate highly compact circulators with ultra-low insertion loss in square-lattice- square-rod-photonic-crystal waveguides. Only a single magneto- optical square rod is required to be inserted into the cross center of waveguides, making the structure very compact and ultra efficient. The square rods around the center defect rod are replaced by several right-angled-triangle rods, reducing the insertion loss further and promoting the isolations as well. By choosing a linear-dispersion region and considering the mode patterns in the square magneto-optical rod, the operating mechanism of the circulator is analyzed. By applying the finite-element method together with the Nelder-Mead optimization method, an extremely low insertion loss of 0.02 dB for the transmitted wave and ultra high isolation of 46 dB∼48 dB for the isolated port are obtained. The idea presented can be applied to build circulators in different wavebands, e.g., microwave or Tera-Hertz.


COMBO-FISH enables high precision localization microscopy as a prerequisite for nanostructure analysis of genome loci.
With the completeness of genome databases, it has become possible to develop a novel FISH (Fluorescence in Situ Hybridization) technique called COMBO-FISH (COMBinatorial Oligo FISH). In contrast to other FISH techniques, COMBO-FISH makes use of a bioinformatics approach for probe set design. By means of computer genome database searching, several oligonucleotide stretches of typical lengths of 15-30 nucleotides are selected in such a way that all uniquely colocalize at the given genome target. The probes applied here were Peptide Nucleic Acids (PNAs)-synthetic DNA analogues with a neutral backbone-which were synthesized under high purity conditions. For a probe repetitively highlighted in centromere 9, PNAs labeled with different dyes were tested, among which Alexa 488(®) showed reversible photobleaching (blinking between dark and bright state) a prerequisite for the application of SPDM (Spectral Precision Distance/Position Determination Microscopy) a novel technique of high resolution fluorescence localization microscopy. Although COMBO-FISH labeled cell nuclei under SPDM conditions sometimes revealed fluorescent background, the specific locus was clearly discriminated by the signal intensity and the resulting localization accuracy in the range of 10-20 nm for a detected oligonucleotide stretch. The results indicate that COMBO-FISH probes with blinking dyes are well suited for SPDM, which will open new perspectives on molecular nanostructural analysis of the genome.


The cellular basis for resistance to induction of tolerance in BXSB SLE male mice.
The autoimmune BXSB male mouse early in life displays a resistance to tolerance induction that is common with the other autoimmune strains (MRL/1, NZB x W, and NZB) whereas its female counterpart, which in early life is immunologically normal, is easily tolerized. The cellular basis for the BXSB male's resistance to tolerance induction with DHGG was investigated by using adoptive male-female cell transfer systems. We found that irradiated female recipients of male T-depleted bone marrow cells, plus either male or female thymus cells, resisted tolerance induction, had hyperactive splenic Ig-secreting cells, and developed early glomerulonephritis. Recipients of male thymic cells plus T-depleted female bone marrow cells could be tolerized, did not have enhanced Ig secretion, and did not develop glomerulonephritis. Furthermore, donor male T-depleted bone marrow cells--but not male thymic, female thymic, or female bone marrow cells--resisted induction of tolerance before their transfer to produce lymphoid chimeras.


A pilot study using preoperative cerebral tissue oxygen saturation to stratify cardiovascular risk in major non-cardiac surgery.
This prospective pilot study evaluated whether low preoperative cerebral tissue oxygen saturation is associated with unfavourable outcomes after major elective non-cardiac surgery. Eighty-one patients over 60 years of age, American Society of Anesthesiologists physical status 3 or 4, were recruited. Resting cerebral tissue oxygen saturation was recorded on room air, and after oxygen supplementation, using cerebral oximetry. The primary outcome was 30-day major adverse event of combined mortality or severe morbidity, and the secondary outcome was 30-day new disability. Eleven patients (13.6%) suffered a major adverse event, and 28 patients (34.6%) experienced new disability. Room air cerebral tissue oxygen saturation was significantly different between patients who had a major adverse event, 67% (95% confidence interval [CI] 65-70) versus unaffected, 71% (95% CI 70-72; P=0.04). No statistical difference was found between patients for new disability (range 70%-74%; P=0.73). Room air cerebral tissue oxygen saturation was significantly associated with major adverse events (odds ratio 1.36 (95% CI 1.03-1.79), P=0.03). Saturation levels ≤68% carried a positive likelihood ratio of 2.2 for death or severe morbidity, P=0.04. A definitive trial is required to confirm if cerebral oximetry can be used to stratify the cardiovascular risk of patients presenting for non-cardiac surgery.


The bilateral effect of theophylline on immune response mechanisms.
The effect of sodium-8-chlorotheophyllinate (S8CT) on transplantation immunity and on PHA-reactivity of thymocytes in transformation experiments was studied. S8CT rather stimulated first graft reaction whereas 'second set' reaction is clearly inhibited. Analogous experiments with the adoptive transfer of transplantation immunity showed comparable results. Thymocytes of S8CT treated and once grafted mice had no significant effect compared with cells from non-treated animals. In contrast, an inhibition was seen if thymocytes of twice grafted and S8CT treated mice were taken. The PHA-P reactivity of thymocytes was clearly enhanced if cell donors were grafted once and treated with S8CT. Here again, the PHA-P reactivity was inhibited if the cell donors were grafted twice and treated during second transplantation. Comparable results were obtained, when instead of transplantation animals were injected with PHA.


Structural inhibition and reactivation of Escherichia coli septation by elements of the SOS and TER pathways.
The inhibition of cell division caused by induction of the SOS pathway in Escherichia coli structurally blocks septation, as deduced from two sets of results. Potential septation sites active at the time of SOS induction became inactivated, while those initiated during the following doubling time were active. Penicillin resistance increased in wild-type UV light-irradiated cells, a behavior similar to that observed in mutants in which structural blocks were introduced by inactivation of FtsA. Potential septation sites that have been structurally blocked by either the SOS division inhibitor, furazlocillin inhibition of PBP3, or inactivation of a TER pathway component, FtsA3, could be reactivated one doubling time after removal of the inhibitory agent in the presence of an active lon gene product. Reactivation of potential septation sites blocked by the presence of an inactivated FtsA3 was significantly lower when the lon protease was not active, suggesting that Lon plays a role in the removal of inactivated TER pathway products from the blocked potential septation sites.


Acute otitis media in infants less than three months of age: clinical presentation, etiology and concomitant diseases.
Acute otitis media (AOM) in the neonatal period can be difficult to diagnose. This infection can be isolated and localized, or it may be associated with serious bacterial infections or other illnesses. The objectives of this study were to determine the clinical presentation, etiology, susceptibility pattern, and frequency of bacteremia, meningitis and other serious bacterial infections associated with the first episode of AOM in young infants. From July 2002 to August 2004, infants less than 12 weeks of age with confirmed AOM underwent tympanocentesis with culture of the middle ear fluid. Sepsis work-up was performed in all infants, and they were admitted to the pediatric department. Parenteral antibiotic therapy with a combination of ampicillin and gentamicin was initiated. Sixty-eight infants were diagnosed with AOM. The median age was 43+/-17 days, 17 infants (25%) were less than 4 weeks of age. Fever was present in 45 (66%) of the patients. Meningitis or bacteremia was not diagnosed in any of the cases. Concomitant urinary tract infection was diagnosed in six (8.8%) cases and broncholitis in seven (10.4%). Forty-seven bacterial pathogens were isolated from the middle-ear fluid. Streptococcus pneumoniae was the leading pathogen with 18 isolates (38%), followed by non-typable Haemophilus influenzae with nine (19%). Fourteen of the S. pneumoniae (78%) isolates were susceptible to penicillin and the other four (22%) were intermediately resistant. Three (33%) of the nine H. influenzae isolates were beta-lactamase producers. In our study, AOM in infants less than 3 months of age is a localized infection and it is not associated with severe bacterial infections. S. pneumoniae and H. influenzae are the leading pathogens. In our region, most of S. pneumoniae strains are still susceptible to penicillin. Although only small number of patients were under 4 weeks of age, the results of the present study raise the question of whether the current policy of a full sepsis work-up in neonates with AOM is relevant.


Cobalt-catalyzed enantioselective directed C-H alkylation of indole with styrenes.
A cobalt-chiral phosphoramidite catalyst promotes enantioselective imine-directed C2-alkylation of Boc-protected indoles with styrenes. The reaction affords 1,1-diarylethane products in moderate to good yields with good enantioselectivities under mild conditions. A deuterium-labeling experiment suggests that the enantioselectivity is controlled by both the styrene insertion and the C-C reductive elimination steps.


Current status of adverse event profile of tacrolimus in patients with solid organ transplantation from a pharmacovigilance study.
The calcineurin inhibitor tacrolimus has been widely used to prevent allograft rejection after transplantation. The purpose of this study was to clarify the adverse events associated with tacrolimus in solid organ transplantation using a spontaneous reporting system database. We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio (ROR) and 95% confidence interval (CI) for each adverse event were calculated. The database comprised 26,620 reports associated with tacrolimus, of which 2,014, 1,988, and 725 reports involved heart, kidney, and liver transplantation, respectively. Infectious disorder was commonly detected in these transplant patients. There was a significant association between tacrolimus use and colon cancer in patients undergoing heart transplantation (ROR: 3.33, 95% CI: 2.18 - 5.08), but not kidney or liver transplantation. Tacrolimus use in those undergoing kidney transplantation is strongly associated with bronchitis (ROR, 8.95; 95% CI, 6.34 - 12.6). A signal for seizure was detected in liver transplant patients with tacrolimus (ROR, 4.12; 95% CI, 1.77 - 9.59). It was suggested that there is a diversity in the strength of the association between tacrolimus and adverse events in patients receiving heart, kidney, and liver transplantation. Our results may provide useful information for treatment with tacrolimus, although further research with more data is needed to clarify this.


Materno-fetal cardiovascular complications in Turner syndrome after oocyte donation: insufficient prepregnancy screening and pregnancy follow-up are associated with poor outcome.
Recombinant human GH treatment and oocyte donation (OD) have improved the quality of life in women with Turner syndrome (TS). However, life expectancy is reduced, mainly due to cardiovascular complications. Pregnancy may itself increase that risk and be associated with hazardous materno-fetal outcome. The objective of this study was to evaluate the materno-fetal outcome of ongoing pregnancies beyond 20 wk of gestation obtained by OD in TS. This was a multicenter retrospective study including all assisted reproductive technology centers affiliated with the French Study Group for Oocyte Donation. Among 93 patients, only 37.6% were prescreened with echocardiography or thoracic magnetic resonance imaging. Maternal outcome was dominated by 37.8% of pregnancy-associated hypertensive disorders including preeclampsia in 54.8% and severe eclampsia in four patients. Prematurity occurred in 38.3% and was correlated with pregnancy-associated hypertensive disorder (P = 0.01). The frequency of in utero growth retardation was 27.5%. One fetal demise was linked to eclampsia. Two patients died from aortic rupture after cesarean section in a context of aortic root dilatation. Only 40% of pregnancies were associated with an absolutely normal materno-fetal outcome. OD pregnancies in TS who have not been managed following recent specific recommendations were at high risk for maternal death by aortic dissection and for preeclampsia and its complications (fetal distress and in utero growth retardation). These recommendations include previous echocardiography, thoracic magnetic resonance imaging, and overnight blood pressure monitoring associated with a tight follow-up during pregnancy. Until future assessment of these recent recommendations, pregnancies obtained in TS after OD must be still considered as very high-risk pregnancies.


FRAXA locus in fragile X diagnosis: family studies, prenatal diagnosis, and diagnosis of sporadic cases of mental retardation.
Three hundred eighty-seven individuals from 32 Finnish fragile X families were studied, using the probe StB12.3 [Oberlé et al., 1991: Science 252:1097-1102] for the FRAXA locus, to reveal length variations in the FMR-1 gene. As expected, the affected individuals (with few exceptions) showed a full mutation; a few affected individuals with a premutation only were found. Seventy percent of the females with a full mutation were affected. The size of the mutation remained unchanged in 6, increased in 73, and decreased in 6 female meioses. In male meioses the size was unchanged in 15 cases, increased in 2 cases, and decreased in 1 case. Prenatal diagnosis was performed in 20 cases. In 7 of these the mutation was inherited by the fetus. Four hundred sixty-four mentally retarded patients were referred to us for FRAXA analysis. In 5% of these the fragile X mutation was found. In addition to the clear cut negative or positive results there were 6 cases in which an increase of 50-80 bp was detected. These findings may represent either large normal alleles or small premutations suggesting a possible tissue mosaicism which could explain the retardation of the patients.


Managing alarm systems for quality and safety in the hospital setting.
To provide an overview of documented studies and initiatives that demonstrate efforts to manage and improve alarm systems for quality in healthcare by human, organisational and technical factors. A literature review, a grey literature review, interviews and a review of alarm-related standards (IEC 60601-1-8, IEC 62366-1:2015 and ANSI/Advancement of Medical Instrumentation HE 75:2009/2013) were conducted. Qualitative analysis was conducted to identify common themes of improvement elements in the literature and grey literature reviews, interviews and the review of alarm-related standards. 21 articles and 7 publications on alarm quality improvement work were included in the literature and grey literature reviews, in which 10 themes of improvement elements were identified. The 10 themes were categorised into human factors (alarm training and education, multidisciplinary teamwork, alarm safety culture), organisational factors (alarm protocols and standard procedures, alarm assessment and evaluation, alarm inventory and prioritisation, and sharing and learning) and technical factors (machine learning, alarm configuration and alarm design). 26 clinicians were interviewed. 9 of the 10 themes were identified from the interview responses. The review of the standards identified 3 of the 10 themes. The study findings are also presented in a step-by-step guide to optimise implementation of the improvement elements for healthcare organisations. Improving alarm safety can be achieved by incorporating human, organisational and technical factors in an integrated approach. There is still a gap between alarm-related standards and how the standards are translated into practice, especially in a clinical environment that uses multiple alarming medical devices from different manufacturers. Standardisation across devices and manufacturers and the use of machine learning in improving alarm safety should be discussed in future collaboration between alarm manufacturers, end users and regulators.


Fabrication of self-supported patterns of aligned beta-FeOOH nanowires by a low-temperature solution reaction.
Self-supported patterns of oriented alignment of beta-FeOOH nanowires are fabricated through a simple solution reaction from the complex [Fe(phen)(3)](2+) at 60 degrees C. The alignment of nanowires with a diameter of 40 nm and length of 6 mum is relatively uniform. HRTEM studies show that the growing direction of beta-FeOOH nanowires is perpendicular to the orientation plane of self-formed beta-FeOOH flake-like substrates. In the reaction and crystal growth process, the precursor [Fe(phen)(3)](2+) is undoubtedly vital to the formation of nanowire alignment. In detail, the formation of aligned nanowires is thought to be realized by controlling two competing reactions. Electrochemical and UV-visible measurements suggest that the product might have potential applications in lithium batteries and semiconductor electronics. This synthetic process is simple, mild, clean, reproducible, and free of any template; it provides a novel pathway for the low-temperature growth of nanowires and their simultaneous oriented alignment.


Acute inflammation occurring in gastric aberrant pancreas followed up by endoscopic ultrasonography.
We describe a case of gastric aberrant pancreas with acute pancreatitis followed up with subsequent endoscopic ultrasound. A 20-year-old woman known to have aberrant pancreas in the stomach was admitted to our hospital because of severe epigastralgia. Laboratory tests showed slight C reactive protein elevation without hyperamylasemia. Esophagogastroduodenoscopy revealed a swollen submucosal lesion (SML) to a greater degree compared with the previous findings. Subsequent endoscopic ultrasonography (EUS) revealed a swollen lesion of 35 mm in diameter. The internal echo-pattern was more hypoechoic than in the previous EUS. The border between the fourth layer (muscularis propria) and the SML was unclear. The anechoic lumen in the mass, considered as the ductal lumen, was dilated. Based on these results, we diagnosed the patient as having acute inflammation, resembling pancreatitis, in the aberrant pancreas.


In situ atomic-scale imaging of phase boundary migration in FePO(4) microparticles during electrochemical lithiation.
The electrochemical lithiation of FePO4 particles is investigated by in situ high-resolution transmission electron microscopy (HRTEM), and the anisotropic lithiation mechanism is directly observed. For the first time and in contrast to the previous post mortem HRTEM observations, a sharp (010) phase boundary between LiFePO4 and FePO4 is observed, which migrates along the [010] direction during lithiation.


Identification and sequence analysis of the soxB gene essential for sulfur oxidation of Paracoccus denitrificans GB17.
The coding region for lithotrophic sulfur oxidation (Sox) in Paracoccus denitrificans GB17 was identified by isolation of a transposon Tn5-mob mutant with a Sox- phenotype (strain TP19). The corresponding wild-type region was cloned previously (G. Mittenhuber, K. Sonomoto, M. Egert, and C. G. Friedrich, J. Bacteriol. 173:7340-7344, 1991). Sequence analysis of a 2.5-kb subclone that complemented strain TP19 revealed that Tn5-mob was inserted into a coding region for a 553-amino-acid polypeptide named SoxB. This polypeptide had an M(r) of 60.573, including a possible signal peptide. The function of the SoxB protein of P. denitrificans GB17 appeared to be identical to that of enzyme B of the thiosulfate-oxidizing enzyme system of Thiobacillus versutus. The amino acid compositions of the two proteins were identical, and the amino acid sequences of three internal peptides of enzyme B as determined by Edman degradation were identical to corresponding sequences of the deduced SoxB protein of P. denitrificans GB17.


Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs).
4-Thio-substituted phenethylamines (2C-T drugs) are potent psychedelics with poorly defined pharmacological properties. Because of their psychedelic effects, 2C-T drugs are sometimes sold as new psychoactive substances (NPSs). The aim of the present study was to characterize the monoamine receptor and transporter interaction profiles of a series of 2C-T drugs. We determined the binding affinities of 2C-T drugs at monoamine receptors and transporters in human cells that were transfected with the respective receptors or transporters. We also investigated the functional activation of serotonergic 5-hydroxytryptamine 2A (5-HT2A) and 5-HT2B receptors, activation of human trace amine-associated receptor 1 (TAAR1), and inhibition of monoamine uptake transporters. 2C-T drugs had high affinity for 5-HT2A and 5-HT2C receptors (1-54 nM and 40-350 nM, respectively). With activation potencies of 1-53 nM and 44-370 nM, the drugs were potent 5-HT2A receptor and 5-HT2B receptor, respectively, partial agonists. An exception to this were the benzylthiophenethylamines, which did not potently activate the 5-HT2B receptor (EC50 > 3000 nM). Furthermore, the compounds bound to serotonergic 5-HT1A and adrenergic receptors. The compounds had high affinity for the rat TAAR1 (5-68 nM) and interacted with the mouse but not human TAAR1. The 2C-T drugs did not potently interact with monoamine transporters (Ki > 4000 nM). The receptor binding profile of 2C-T drugs predicts psychedelic effects that are mediated by potent 5-HT2 receptor interactions. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'


Extramedullary fixation implants and external fixators for extracapsular hip fractures in adults.
Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Randomised or quasi-randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results.Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates.The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration.One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants.Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures.Two trials of 676 participants compared the Medoff plate with three different screw-plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer-term outcomes.Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra-operative problems with the PCCP, some of which precluded its use.Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable.There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions.


Oncocytic cyst of the larynx: a rare finding.
A 75-year-old woman presented with an 18-month history of severe, slowly worsening dysphonia. She was a smoker and known to have multiple benign cystic thyroid lesions. She reported no associated symptoms and other medical and social history was unremarkable. Fibreoptic nasendoscopy revealed a right-sided supraglottic cyst appearing to arise from the right false vocal cord. Further bedside examination was unremarkable. She underwent microlaryngoscopy and biopsy which showed a cyst originating from the right anterior ventricle, successfully removed without rupture using cold steel. Formal histopathology revealed a 14×10×7 mm unilocular, completely excised cyst lined by oncocytic epithelium and composed of columnar cells with darkly stained nuclei and abundant granular, eosinophilic cytoplasm. Three weeks postoperatively the patient's voice had returned to normal. To date, 11 months postoperatively, there is no evidence of recurrence, and she will continue long-term follow-up.


Imaging features of primary breast sarcoma: A case report.
Primary breast sarcoma (PBS) is a rare group of non-epithelial tumours arising from connective tissue of the breast. We report the case of a 55-year-old female who presented with rapidly increasing mass in the left breast. The mammogram showed a large high density mass occupying the whole of the left breast, while Doppler ultrasound showed a mass of increased vascularity. Diagnosis was confirmed by histopathology of ultrasound-guided biopsy. Although there are no pathognomonic imaging features of PBS, presence of a solitary large mass showing rapid growth, with circumscribed or indistinct margins without axillary lymph node involvement should raise the suspicion of sarcoma and prompt biopsy to ensure early diagnosis and treatment; particularly considering the aggressive nature of these sarcomas.