Dimer formation in nicotinamide and picolinamide in the gas and condensed phases probed by infrared spectroscopy.
Aggregation of nicotinamide (3-pyridine-carboxamide; NA) and picolinamide (2-pyridine-carboxamide; PA) has been investigated by matrix-isolation, supersonic jet and neat solid state infrared spectroscopy, complemented by DFT(B3LYP)/6-311++G(d,p) calculations. For both compounds, the most stable dimeric structure was shown to be the centrosymmetric dimer where two monomers in their most stable forms establish two NHO[double bond, length as m-dash]C hydrogen bonds. The most stable structures of monomers of NA and PA were characterized in detail experimentally by matrix-isolation spectroscopy and theoretically (at both the DFT(B3LYP)/6-311++G(d,p) and MP2/6-311++G(d,p) levels). For nicotinamide, two conformers were found in the matrices, with ca. 80% of the total population adopting the E form. The monomers and dimers of PA and NA were also investigated by infrared spectroscopy of the studied compounds seeded in supersonic jet expansions. These studies revealed that the constraints on the vibrational dynamics in the PA dimer are different from those in the NA dimer. In the PA dimer, the vibrational energy flow out of the N-H stretching mode was shown to be accelerated substantially by the presence of a secondary intramolecular hydrogen bond. In the glassy state of both compounds, the centrosymmetric dimer seems to be the prevalent structure. In the neat crystalline state (KBr pellet), picolinamide keeps this type of dimeric structure as the constituting unit, whereas nicotinamide molecules assume a different arrangement where one of the NHO[double bond, length as m-dash]C bonds is replaced by an NH...N(ring) bond. The different crystallograpic structures which were formed by the compounds are reflected in the vibrational spectra of the solids. These observations are correlated with the molecular properties of NA and PA, in particular with the greater conformational mobility of NA compared with PA. This is ascribable to the absence in the NA molecule of the intramolecular NH...N((ring)) interaction, which exists in PA.


Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells.
Imatinib mesylate (Gleevec) is effective therapy against Philadelphia chromosome-positive leukemia, but resistance develops in all phases of the disease. Bcr/Abl point mutations and other alterations reduce the kinase inhibitory activity of imatinib mesylate; thus, agents that target Bcr/Abl through unique mechanisms may be needed. Here we describe the activity of WP1130, a small molecule that specifically and rapidly down-regulates both wild-type and mutant Bcr/Abl protein without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML) cells. Loss of Bcr/Abl protein correlated with the onset of apoptosis and reduced phosphorylation of Bcr/Abl substrates. WP1130 did not affect Hsp90/Hsp70 ratios within the cells and did not require the participation of the proteasomal pathway for loss of Bcr/Abl protein. WP1130 was more effective in reducing leukemic versus normal hematopoietic colony formation and strongly inhibited colony formation of cells derived from patients with T315I mutant Bcr/Abl-expressing CML in blast crisis. WP1130 suppressed the growth of K562 heterotransplanted tumors as well as both wild-type Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. Collectively, our results demonstrate that WP1130 reduces wild-type and T315I mutant Bcr/Abl protein levels in CML cells through a unique mechanism and may be useful in treating CML.


Approach to cervicogenic dizziness: a comprehensive review of its aetiopathology and management.
Though there is abundant literature on cervicogenic dizziness with at least half a dozen of review articles, the condition remains to be enigmatic for clinicians dealing with the dizzy patients. However, most of these studies have studied the cervicogenic dizziness in general without separating the constitute conditions. Since the aetiopathological mechanism of dizziness varies between these cervicogenic causes, one cannot rely on the universal conclusions of these studies unless the constitute conditions of cervicogenic dizziness are separated and contrasted against each other. This narrative review of recent literature revisits the pathophysiology and the management guidelines of various conditions causing the cervicogenic dizziness, with an objective to formulate a practical algorithm that could be of clinical utility. The structured discussion on each of the causes of the cervicogenic dizziness not only enhances the readers' understanding of the topic in depth but also enables further research by identifying the potential areas of interest and the missing links. Certain peculiar features of each condition have been discussed with an emphasis on the recent experimental and clinical studies. A simple aetiopathological classification and a sensible management algorithm have been proposed by the author, to enable the identification of the most appropriate underlying cause for the cervicogenic dizziness in any given case. However, further clinical studies are required to validate this algorithm. So far, no single clinical study, either epidemiological or interventional, has incorporated and isolated all the constitute conditions of cervicogenic dizziness. There is a need for such studies in the future to validate either the reliability of a clinical test or the efficacy of an intervention in cervicogenic dizziness.


[Epidemiologic situation of viral hepatitis type A in Campania: perspectives of prevention and control of infections at the local level].
In the Region Campania (South Italy) the Hepatitis A infection reveals to be very present, despite of worldwide decreasing trend. Particularly Naples has a high incidence pathology as compared with other regional districts: the propose of this work is analysing the reasons by analysis of small but representative sample of this pathology. Health District of ASL Napoli 1 Center provides us with the notifications of this disease. The cases disease are attributable to consumption of contaminated shellfish purchased from mainly non-authorized dealers present on all city territory. A properly educational, of the population, increased repression control of dealers, careful monitoring of illegal dumping, can reduce the incidence of EVA in city live Naples.


Mistaken identity: misclassification of TPMT phenotype following blood transfusion.
Azathioprine (AZA) is an effective treatment for inflammatory bowel disease. The measurement of thiopurine methyltransferase (TPMT) activity levels helps to identify the one in 300 patients who are at risk of profound myelosuppression with standard doses of AZA. Thus, it is important that the measurement of TPMT activity is accurate. We report a case of misclassification of TPMT phenotype caused by prior blood transfusion. The patient appeared to have an intermediate level of TPMT enzyme activity as measured after the blood transfusion. However, following severe myelosuppression soon after starting AZA, her genotype was determined, which showed that she was homozygous for low TPMT activity. This report reviews some of the limitations in determining both the phenotype and the genotype of TPMT, especially following recent blood transfusion. The dilemma of whether or not to wait for the TPMT activity result before starting AZA is also discussed.


A head-to-head comparison: "clean-void" bag versus catheter urinalysis in the diagnosis of urinary tract infection in young children.
To compare the validity of the urinalysis on clean-voided bag versus catheter urine specimens using the catheter culture as the "gold" standard. This is a cross-sectional study of 303 nontoilet-trained children under age 3 years at risk for urinary tract infection (UTI) who presented to a children's hospital emergency department. Paired bag and catheter specimens were obtained from each child and sent for dipstick and microscopic urinalysis. Sensitivity and specificity were compared using McNemar's chi2 test for paired specimens and the ordinary chi2 test for unpaired comparisons. The bag dipstick was more sensitive than the catheter dipstick for the entire study sample: 0.85 (95% confidence interval [CI]=0.78 to 0.93) versus 0.71 (95% CI=0.61 to 0.81), respectively. Both bag and catheter dipstick sensitivities were lower in infants < or =90 days old (0.69 [95% CI=0.44 to 0.94] and 0.46 [95% CI=0.19 to 0.73], respectively) than in infants >90 days old (0.88 [95% CI=0.81 to 0.96] and 0.75 [95% CI=0.65 to 0.86], respectively). Specificity was consistently lower for the bag specimens than for the catheter specimens: 0.62 (95% CI=0.56 to 0.69) versus 0.97 (95% CI=0.95 to 0.99), respectively. Urine collection methods alter the diagnostic validity of urinalysis. These differences have important implications for the diagnostic and therapeutic management of children with suspected UTI.


Protein-RNA interactions: structural characteristics and hotspot amino acids.
Structural information about protein-RNA complexes supports the understanding of crucial recognition processes in the cell, and it can allow the development of high affinity ligands to interfere with these processes. In this respect, the identification of amino acid hotspots is particularly important. In contrast to protein-protein interactions, in silico approaches for protein-RNA interactions lag behind in their development. Herein, we report an analysis of available protein-RNA structures. We assembled a data set of 322 crystal and NMR structures and analyzed them regarding interface properties. In addition, we describe a computational alanine-scanning approach which provides interaction scores for interface amino acids, allowing the identification of potential hotspots in protein-RNA interfaces. We have made the computational approach available as an online tool, which allows interaction scores to be calculated for any structure of a protein-RNA complex by uploading atomic coordinates to the PRI HotScore web server (https://pri-hotscore.labs.vu.nl).


A repertoire of cationic and anionic conductances at the plasma membrane of Medicago truncatula root hairs.
Root hairs, as lateral extensions of epidermal cells, provide large absorptive surfaces to the root and are major actors in plant hydromineral nutrition. In contact with the soil they also constitute a site of interactions between the plant and rhizospheric microorganisms. In legumes, initiation of symbiotic interactions with N2 -fixing rhizobia is often triggered at the root hair cell membrane in response to nodulation factors secreted by rhizobia, and involves early signaling events with changes in H+ , Ca2+ , K+ and Cl- fluxes inducing transient depolarization of the cell membrane. Here, we aimed to build a functional repertoire of the major root hair conductances to cations and anions in the sequenced legume model Medicago truncatula. Five root hair conductances were characterized through patch-clamp experiments on enzymatically recovered root hair protoplasts. These conductances displayed varying properties of voltage dependence, kinetics and ion selectivity. They consisted of hyperpolarization- and depolarization-activated conductances for K+ , cations or Cl- . Among these, one weakly outwardly rectifying cationic conductance and one hyperpolarization-activated slowly inactivating anionic conductance were not known as active in root hairs. All five conductances were detected in apical regions of young growing root hairs using membrane spheroplasts obtained by laser-assisted cell-wall microdissection. Combined with recent root hair transcriptomes of M. truncatula, this functional repertoire of conductances is expected to help the identification of candidate genes for reverse genetics studies to investigate the possible role of each conductance in root hair growth and interaction with the biotic and abiotic environment.


Non-anatomical implantation of supra-aortic branches for customizing the standard form of Thoraflex™ hybrid prosthesis to a patient's anatomical requirements.
Frozen elephant trunk technique represents a valuable therapeutic option for patients with extensive pathology of thoracic aorta. Thoraflex™ hybrid prosthesis (Vascutek, Terumo, Inchinnan, UK) is one of the commercially available devices in which a stent graft is combined with branched vascular tube mimicking the aortic arch anatomy. Owing to the sewing collar between the stented and unstented portions, this hybrid prosthesis offers a valuable addition to the surgical armamentarium for patients with huge thoracic aorta aneurysms, in whom the aortic diameter exceeds the diameter of available stent grafts. However, the standard factory form of the quadrifurcated arch prosthesis does not always fit to the patient's anatomy and demands a deviation from the anatomical anastomosing of the branches with the respective supra-aortic arteries. A technique of non-anatomical implantation of supra-aortic arteries for customizing the standard form of the Thoraflex prosthesis is described, which facilitates the surgery without limiting the functionality of this hybrid prosthesis.


Longitudinal changes in IQ among fragile X females: a preliminary multicenter analysis.
Longitudinal declines in IQ among fragile X [fra(X)] males have been reported previously by several investigators. Remarkably little is known about longitudinal changes in IQ scores among fra(X) females. Previously, one cross-sectional study showed a significant negative correlation between age and IQ scores. However, a recent investigation of girls with fra(X) syndrome noted longitudinal increases in IQ scores in 8 of 11 individuals. Therefore, the purpose of this preliminary multicenter study was to determine: (1) the characteristics of longitudinal changes in IQ among fra(X) females; and (2) whether these changes were comparable to those which have been observed among fra(X) males. IQ test and retest scores for 11 fra(X) females were obtained from 3 centers: Greenwood, South Carolina; Ibaraki, Japan; and Leuven, Belgium. To ensure high reliability, only test-retest scores from the Wechsler and Stanford-Binet tests were used. Age of subjects at initial testing ranged from 5 to 35 years. Mean intertest interval was 4.5 years. In contrast to a report of longitudinal increases, we found 9/11 (82%) subjects demonstrated decreases in IQ scores. Mean decline was 9 points. Females over 18 years of age showed little or no change in IQ scores. Decreases in scores appeared to be related to initial IQ score. Females in the earlier longitudinal report were higher functioning than those in our study, which may account for the observed difference in direction of change; or, change in IQ score may be related to size of the fra(X) mutation.(ABSTRACT TRUNCATED AT 250 WORDS)


(+)-Dehydrofukinone modulates membrane potential and delays seizure onset by GABAa receptor-mediated mechanism in mice.
(+)-Dehydrofukinone (DHF), isolated from Nectandra grandiflora (Lauraceae) essential oil, induces sedation and anesthesia by modulation of GABAa receptors. However, no study has addressed whether DHF modulates other cellular events involved in the control of cellular excitability, such as seizure behavior. Therefore, the aim of the present study was to investigate the effect of DHF on cellular excitability and seizure behavior in mice. For this purpose, we used isolated nerve terminals (synaptosomes) to examine the effect of DHF on the plasma membrane potential, the involvement of GABAa receptors and the downstream activation of Ca2+ mobilization. Finally, we performed an in vivo assay in order to verify whether DHF could impact on seizures induced by pentylenetetrazole (PTZ) in mice. The results showed that DHF induced a GABA-dependent sustained hyperpolarization, sensitive to flumazenil and absent in low-[Cl-] medium. Additionally, (1-100μM) DHF decreased KCl-evoked calcium mobilization over time in a concentration-dependent manner and this effect was prevented by flumazenil. DHF increased the latency to myoclonic jerks (10mg/kg), delayed the onset of generalized tonic-clonic seizures (10, 30 and 100mg/kg), and these effects were also blocked by the pretreatment with flumazenil. Our data indicate that DHF has anticonvulsant properties and the molecular target underlying this effect is likely to be the facilitation of GABAergic neuronal inhibition. The present study highlights the therapeutic potential of the natural compound DHF as a suppressor of neuronal excitability.


Patterns of Migraine Disease in Otolaryngology: A CHEER Network Study.
Objective To evaluate the prevalence of migraine disease in an otolaryngologic cohort and migraine-related otologic and sinonasal symptoms in this population. Study Design Cross-sectional study utilizing the CHEER (Creating Healthcare Excellence through Education and Research) network for recruitment. Setting Patients were recruited in a cross-sectional and pragmatic manner in 14 CHEER sites between June 2015 and March 2017 (9 academic, 5 community based). Subjects and Methods Patients were included if they were aged ≥18 years and seen for any concern that was not head and neck cancer. Patients with any history of brain abnormality or headaches that began within 2 weeks of a medical illness, trauma, or head injury were excluded. Patients were screened for migraine with a validated instrument. If they screened positive on the Migraine Assessment Tool (MAT+), the subjects also filled out validated and custom questionnaires for sinonasal, otologic, and migraine-specific symptoms. Results Of 1458 patients screened, 235 (16.1%) screened positive for migraine (MAT+), which is higher than general population (13%, P < .001). The MAT+ group was significantly younger (47.2 vs 55.6 years of age, P < .001) and predominantly women (80.0% vs 55.9%, P < .001). The MAT+ cohort commonly reported ear- and sinus-related symptoms, such as tinnitus (70.5%), ear pressure (61.9%), balance problems (82%), facial pressure (85%), and rhinorrhea (49.9%). There were significantly higher levels of sinus burden with higher levels of dizziness handicap, Jonckheere-Terpstra test = 11,573.00, z = 7.471, P < .001. Conclusion Migraine disease has a higher prevalence in an otolaryngologic cohort than in the general population, presenting with a high rate of sinonasal and otologic symptoms that may be due to or exacerbated by migraines.


Suicidal behaviour in children and adolescents. Part 2: treatment and prevention.
To systematically review the treatment of suicidal behaviour in children and adolescents. After discussing the principles of treatment, we review the literature regarding adequate assessment, hospital-based services and their alternatives, and follow-up. Treatment modalities (including psychotherapy) and preventive strategies (including school-based interventions, gatekeeper and primary practitioner training, and treatment of psychiatric disorders) are considered in the light of existing evidence. The assessment of youth at risk for suicide should include attention to well-established risk factors, but prediction of risk remains difficult. Treatment of suicidal children and adolescents should be evidence-based and may include psychotherapy and psychopharmacology. Effective methods of prevention are emerging, but more research is needed.


The pharmacokinetics and pharmacodynamics of meropenem in the cerebrospinal fluid of neurosurgical patients.
This study examined the pharmacokinetics and pharmacodynamics of meropenem in cerebrospinal fluid (CSF). Meropenem (0.5 g every 8 h) was administered by 0.5-h infusion to six neurosurgical patients. Lumbar CSF and venous blood samples were obtained at 0.5-16 h after the start of the first infusion. Drug concentrations in the CSF and plasma were analyzed pharmacokinetically and used for a Monte Carlo simulation with the minimum inhibitory concentration (MIC) data of clinical isolates in Japan. Meropenem penetrated into the CSF with the area under the drug concentration-time curve ratio of 0.10 +/- 0.03 (mean +/- SD) and the repeated infusions caused the drug concentration in the CSF to accumulate slightly. Against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli isolates, 0.5 g q8h achieved a >90% probability of pharmacodynamic target (50% of the time above MIC) attainment, and 1 g q8h was needed for a >90% probability of target (100% of the time above MIC) attainment. However, against Pseudomonas aeruginosa, 2 g q8h achieved a lower probability of target attainment. These results should help us to better elucidate the pharmacokinetics of meropenem in the cerebrospinal space while also helping us to choose the appropriate drug dosages for the management of bacterial meningitis.


Sclerosing Sialadenitis Is Associated With Salivary Gland Hypofunction and a Unique Gene Expression Profile in Sjögren's Syndrome.
To develop a novel method to quantify the amount of fibrosis in the salivary gland and to investigate the relationship between fibrosis and specific symptoms associated with Sjögren's syndrome (SS) using this method. Paraffin-embedded labial salivary gland (LSG) slides from 20 female SS patients and their clinical and LSG pathology data were obtained from the Sjögren's International Collaborative Clinical Alliance. Relative interstitial fibrosis area (RIFA) in Masson's trichrome-stained LSG sections was quantified from digitally scanned slides and used for correlation analysis. Gene expression levels were assessed by microarray analysis. Core promoter accessibility for RIFA-correlated genes was determined using DNase I hypersensitive sites sequencing analysis. RIFA was significantly correlated with unstimulated whole saliva flow rate in SS patients. Sixteen genes were significantly and positively correlated with RIFA. In a separate analysis, a group of differentially expressed genes was identified by comparing severe and moderate fibrosis groups. This combined set of genes was distinct from differentially expressed genes identified in lung epithelium from idiopathic pulmonary fibrosis patients compared with controls. Single-cell RNA sequencing analysis of salivary glands suggested most of the RIFA-correlated genes are expressed by fibroblasts in the gland and are in a permissive chromatin state. RIFA quantification is a novel method for assessing interstitial fibrosis and the impact of fibrosis on SS symptoms. Loss of gland function may be associated with salivary gland fibrosis, which is likely to be driven by a unique set of genes that are mainly expressed by fibroblasts.


Cognitive behavioral therapy (CBT) for preventing Alzheimer's disease.
This review provides the rationale for implementing cognitive behavioral therapy (CBT) for the prevention of Alzheimer's disease (AD). There are known risk factors associated with the development of AD, some of which may be ameliorated with CBT. We posit that treating the risk factors of inactivity, poor diet, hyposmia and anosmia, sleep disorders and lack of regularly engaged challenging cognitive activity will modify the physiology of the brain sufficiently to avoid the accumulation of excess proteins, including amyloid beta, causal events in the development of AD. Further, the successful treatment of the listed risk factors is well within our technology to do so and, even further, it is cost effective. Also, there is considerable scientific literature to support the proposition that, if implemented by well-established practices, CBT will be effective and will be engaged by those of retirement age. That is, we present a biologically informed CBT for the prevention of the development of AD, i.e., an aspect of applied behavioral neuroscience.


Posttransplantation function of hearts preserved with fluorochemical emulsion.
This study was designed to determine whether the novel perfluoroperhydrophenanthrene-egg yolk phospholipid emulsion, APE-LM, was an effective oxygen carrier for long-term hypothermic heart preservation. We postulated that hearts preserved with APE-LM would be well oxygenated during 24-hour preservation and that reperfusion of such hearts with blood would not produce functional or metabolic evidence of myocardial ischemia. Four groups of rabbit hearts were studied (n = 7 per group): fresh controls: nonpreserved, nontransplanted hearts; surgical controls: fresh hearts transplanted heterotopically for 75 minutes before explant and study for 4 hours as isolated working hearts perfused at 37 degrees C; crystalloid-preserved: hearts preserved with crystalloid medium, followed by transplantation and isolated heart perfusion; APE-LM-preserved: hearts treated as those in the crystalloid-preserved group, but preservation was with medium containing APE-LM emulsion (10 ml/dl). Preservation was with continuous coronary perfusion at 18 mm Hg pressure, 12 degrees C, and oxygen tension 838 +/- 11 mm Hg. During preservation, APE-LM hearts had significantly higher pyruvate consumption, and correspondingly higher oxygen consumption, than that of crystalloid hearts. No significant differences were found among fresh controls, surgical controls, and APE-LM-preserved hearts with respect to contractile or output function, oxygen consumption and efficiency indexes, or lactate production during in vitro perfusion. Left ventricular peak systolic pressure and peak rate of pressure development were significantly lower for crystalloid-preserved hearts than for fresh and surgical controls. Left ventricular end-diastolic pressure of crystalloid-preserved hearts was higher than that of the other three groups. The data indicate that rabbit hearts in this model were well preserved with APE-LM and that this emulsion produced better recovery of function than did crystalloid preservation, possibly as a consequence of the high oxygen delivery by the fluorocarbon during preservation.


Blood flow velocity waveforms in large maternal and uterine vessels throughout pregnancy and postpartum: a longitudinal study using Duplex sonography.
Blood flow velocity waveforms in large maternal and uterine vessels were measured longitudinally from 16 weeks gestation onwards until 12 weeks postpartum in 21 singleton pregnancies by duplex sonography. In the maternal carotid artery, time average mean velocity (TAVmean) did not show significant changes. In both the femoral artery and vein, however, significant changes were observed. In the femoral artery, TAVmean and systolic maximum velocities decreased with advancing gestation. In the femoral vein, TAVmean remained constant throughout pregnancy and was lower than postpartum. The resistance index in the uterine arteries decreased with advancing gestation and increased after delivery. Among many factors contributing to femoral arterial blood flow velocity changes in pregnancy, we suggest that a major one is the increase in uterine blood flow. Reduction in venous femoral blood flow velocity and increase in the femoral vein diameter might be associated with the common occurrence of venous disorders in pregnancy.


Ligand dependent self-assembly of hydroxido-bridged dicopper units templated by sodium ion.
Crown-ether like interaction of two neutral [Cu2(μ-OH)(μ-L(1))] (H3L(1) = 2-(2'-hydroxyphenyl)-1,3-bis[4-(2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine) fragments, around a central Na(+) cation as self-assembly template, led to the formation of [Na{Cu2(μ-OH)(μ-L(1))}2]ClO4 (1). Di-tert-butyl group substituted H3L(2) {2-(3,5-di-tert-butyl-2-hydroxyphenyl)-1,3-bis[4-(3,5-di-tert-butyl-2-hydroxyphenyl)-3-azabut-3-enyl]-1,3-imidazolidine} conversely yields only [Cu2(μ-OH)(μ-L(2))]·1.5H2O (2), by discarding aggregation around the Na(+) ion. The crown-ether type aggregate 1 exhibits ferromagnetic interactions within the double oxido-phenoxido [Cu2] fragments and weak antiferromagnetic interactions are mediated by the ONa(+)O bridges. Complex 2 registers only weak antiferromagnetic interactions within the oxido-phenoxido bridged [Cu2] entity. UV-visible and emission titration spectroscopy establish the interaction of cationic complex 1 with calf thymus DNA in Tris buffer and it cleaves supercoiled pBR322 DNA from in situ generated ROS.


Evidence for a multigenic system controlling methyl-beta-carboline-3-carboxylate (beta-CCM)-induced seizures.
beta-CCM is a beta-carboline known to have properties opposite to those of benzodiazepines. Our approach was to analyze, in mice, the genetic mechanisms involved in beta-CCM-induced myoclonic seizures using recombinant congenic strains and F1 hybrids issued from these strains. Our aim was to define the extent of the multigenic character of beta-CCM-induced myoclonic seizures, while also evaluating the distribution of the strength of the genes implicated in this trait. The results show that the control of reactivity to beta-CCM is multigenic with notable epistatic involvement.


Direct-acting antiviral agents improved nephrotic syndrome associated with refractory pleural effusion and ascites caused by hepatitis C virus-related nephropathy: a case report.
A 74-year-old man with hepatitis C virus (HCV)-related cirrhosis was admitted because of dyspnea. Laboratory investigations revealed severe proteinuria (4.0g/day), low serum albumin level, and cryoglobulinemia. Computed tomography showed massive pleural effusion and ascites. Because these effusions were leaky and the hepatic reserve was relatively intact, we thought these were mainly caused by nephrotic syndrome. Renal biopsy revealed membranoproliferative glomerulonephritis with mesangial proliferation and excessive matrix deposition. Based on these histopathological findings and the presence of cryoglobulinemia, a diagnosis of HCV-related nephropathy was performed. Therefore, antiviral therapy was initiated with direct-acting antiviral (DAA) agents (daclatasvir+asunaprevir). Serum HCV-RNA level was observed to be negative at week 8, which was followed by an alleviation of proteinuria and a gradual decrease in the pleural effusion and ascites. HCV-related nephropathy should be considered in the differential diagnosis of patients with chronic hepatitis C and refractory ascites. DAA agents are effective in the treatment of these patients.


Body Pose Estimation Integrated With Notational Analysis: A New Approach to Analyze Penalty Kicks Strategy in Elite Football.
Body orientation of football players has proven to be an informative resource related to successful penalty kicks. OpenPose is one of the most popular open-source pose estimation technologies. This study aims: (i) to verify whether OpenPose can detect relevant body orientation angles from video data of penalty kicks in elite football and (ii) to investigate the relationship between these body angles and observable behaviors analyzed via an observational system for penalty kick analysis in football (OSPAF) with the penalty taker and goalkeeper strategy. A total of 34 penalty videos, with standardized viewing angle, from the main European leagues (2017-2020) were analyzed. Relevant body orientation variables were selected for penalty kicks analysis and were extracted from video data through OpenPose technique. The OSPAF, previously validated by experts, was used. The mean confidence score of OpenPose measures was 0.80 ± 0.14. OpenPose Retest reliability values was 0.976 ± 0.03. Logistic regressions were performed to investigate the relationship between OpenPose investigated variables (penalty taker: shoulder, hips, and nonkicking foot orientation; goalkeeper: right and left foot, anticipation), observable behaviors (OSPAF variables), and the strategy (penalty taker: goalkeeper dependent or independent; goalkeeper: shooter dependent or independent) in penalty kicks. The selected body orientation angle (goalkeeper anticipation) measured through OpenPose correlated significantly with the goalkeeper strategy. The prediction model of the goalkeeper's strategy had its accuracy increased to 97% when the variable goalkeeper anticipation was included [ χ ( 35 ) 2 = 49.648, p < 0.001]. Lower degrees of goalkeeper anticipation, the goalkeeper tactical action (awaiting), and run up speed (slow) were associated with a kicker-dependent strategy. Regarding the penalty taker, the selected body angles measured through OpenPose did not associate significantly with the shooter strategy. Body orientation analysis by using OpenPose has shown sufficient reliability and provides practical applications for analyzing the strategies adopted by goalkeepers in penalty kicks in elite football.


Biochemical bone markers, bone mineral content, and bone mineral density in rats with experimental nephrotic syndrome.
The human nephrotic syndrome (NS) is accompanied by important alterations of mineral and bone metabolism. The purpose of the present study was to examine bone metabolism in rats with experimental NS and normal creatinine clearance, and to evaluate the reversibility of this alteration. NS was induced by three injections of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g body weight, respectively). The biochemical markers of bone formation (osteocalcin and alkaline phosphatase) and bone resorption (hydroxyproline and pyridinoline), bone mineral content (BMC), and bone mineral density (BMD), determined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7, 14, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study. Hypoproteinemia was seen on days 7, 28, 42, and 56, returning to control values on days 84 and 112. In serum, osteocalcin (OC) concentration increased (p < 0.001), and alkaline phosphatase (ALP) decreased (p = 0.002). In urine, hydroxyproline increased (p < 0.001), but urinary pyridinoline was not different from the control group throughout the study. Increased serum parathyroid hormone concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were found from day 7. During the intense proteinuria, bone resorption predominates and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephrotic rats showed low BMC and BMD compared to control group (p < 0.001). At the end of the study, when proteinuria persisted but total serum protein returned to control values, the biochemical bone markers, BMC, and BMD returned to normal. In conclusion, PAN-nephrotic rats had reversible bone alterations that were related to the magnitude of proteinuria and the concentration of total serum protein.


Community-based amoxicillin treatment for fast breathing pneumonia in young infants 7-59 days old: a cluster randomised trial in rural Bangladesh, Ethiopia, India and Malawi.
Young infants 7-59 days old with fast breathing pneumonia presented to a primary level health facility receive a 7-day course of amoxicillin as per the WHO guideline. However, community-level health workers (CLHW) are not allowed to treat these infants. This trial evaluated the community level treatment of non-hypoxaemic young infants with fast breathing pneumonia by CLHWs. This cluster-randomised, open-label, non-inferiority trial was conducted in rural areas of Bangladesh, Ethiopia, India and Malawi. We randomly allocated clusters (first-level health facility) 1:1, stratified by the population size, to an intervention group (enhanced community case management) or control group (standard community case management). Infants aged 7-59 days with a respiratory rate of ≥60 breaths/min and oxygen saturation (SpO2) ≥90% were enrolled. In the intervention clusters, these infants were treated with a 7-day course of oral amoxicillin (according to WHO weight bands) and were regularly followed up by CLHWs. In the control clusters, CLHWs continued the standard management (assess and refer after pre-referral antibiotic dose) and followed up according to the national programme guideline. The primary outcome of treatment failure was assessed in both groups by independent outcome assessors on days 6 and 14 after enrolment. Secondary outcomes (accuracy and impact of pulse oximetry) were also assessed. Between September 2016 and December 2018, we enrolled 2334 infants (1168 in intervention and 1166 in control clusters) from 208 clusters (104 intervention and 104 control). Of 2334, 22 infants with fast breathing were excluded from analysis, leaving 2312 (1155 in intervention clusters and 1157 in control clusters) for intention-to-treat analysis. The proportion of treatment failure was 5.4% (63/1155) in intervention and 6.3% (73/1157) in the control clusters, including two deaths (0.2%) in each group. The adjusted risk difference for treatment failure between the two groups was -1.0% (95% CI -3.0% to 1.1%). The secondary outcome showed that CLHWs in the intervention clusters performed all recommended steps of pulse oximetry assessment in 94% (1050/1115) of enrolled patients. The 7-day amoxicillin treatment for 7-59 days old non-hypoxaemic infants with fast breathing pneumonia by CLHWs was non-inferior to the currently recommended referral strategy. CTRI/2017/02/007761 and ACTRN12617000857303.


Dosing-time dependent testicular toxicity of everolimus in mice.
The circadian timing system controls many biological functions in mammals including drug metabolism and detoxification, cell cycle events, and thus may affect pharmacokinetics, target organ toxicity and efficacy of medicines. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is effective against several cancers. The aim of this study was to investigate dosing-time dependent testicular toxicity of subacute everolimus administration in mice. C57BL/6 J male mice were synchronized with Light-Dark (12h:12 h) cycle, with Light-onset at Zeitgeber Time (ZT)-0. Everolimus (5 mg/kg/day) was administered orally to mice at ZT1rest-span or ZT13activity-span for 4 weeks. Body weight loss, clinical signs, changes in testicular weights, testis histology, spermatogenesis and proliferative activity of germinal epithelium of seminiferous tubules were examined. Steady-state everolimus concentrations in testes were determined with validated HPLC method. Everolimus toxicity was less severe following dosing at ZT13 compared to ZT1, as shown with least body weight loss (p<0.001), least reductions in testes weights (p<0.001) and least histopathological findings. Everolimus-induced histological changes on testes included vacuolisation and atrophy of germinal epithelium, and loss of germinal cell attachment. The severity of everolimus-induced histological toxicity on testes was significantly more evident in mice treated at ZT1 than ZT13 (p<0.001). Spermatogenic cell population significantly decreased when everolimus administered at ZT1 compared to ZT13 (p<0.001). Proliferative activity of germinal epithelium was significantly decreased due to treatment at ZT1 compared to ZT13 (p<0.001). Everolimus concentrations in testes indicated a pronounced circadian variation, which was greater in mice treated at ZT1 compared to ZT13 (p<0.05). Our study revealed dosing-time dependent testicular toxicity of everolimus in mice, which was greater in severity when everolimus administered at early rest-span (daytime-ZT1) than early activity-span (nighttime-ZT13). These findings support the concept of everolimus chronotherapy for minimizing reproductive toxicity and increasing the tolerability of everolimus, as a clinical advantage.


Current changes in smoking attitudes and behaviours among adolescents in Wales, 1986-1992.
This paper presents data on recent trends in adolescent smoking in Wales. The data are drawn from four large-scale surveys conducted across the Principality in 1986, 1988, 1990 and 1992. The results show that there has been some success in delaying early experimentation with smoking, as well as some improvement in the attitudes of smokers towards their habit. Against this, there has been little change in smoking prevalence amongst both boys and girls, and cigarettes remained widely available for purchase by the under-16s. The implications of these findings for further action on smoking and the young are discussed.


Health-related quality of life in overweight and obese youths: results of a multicenter study.
We examined treatment-seeking overweight and obese youths to better understand the gender, age, and treatment modality differences in generic and disease-specific health-related quality of life (HRQOL). This multicenter study included 1,916 patients (mean = 12.6 years; 57% females; mean zBMI = 2.4) who started treatment for overweight and obesity in 48 treatment facilities between July 2005 and October 2006. The facilities offered either inpatient treatment or outpatient programs. Prior to treatment, all participants completed the generic KIDSCREEN-27 HRQOL-questionnaire, the self-perception subscale of the generic KIDSCREEN-52 and the disease-specific obesity module of the KINDLR.The patients' HRQOL was compared to the KIDSCREEN reference sample from the general population by one-way analyses of variance, adjusting for age, gender, and socioeconomic status. Independent t-tests were conducted to compare disease-specific HRQOL scores between patients by gender and age group. Significant mean differences in HRQOL between inpatients and outpatients were explored by one-way analyses of variance, adjusting for age, gender, and zBMI. Effect sizes 'd' were calculated employing the estimated marginal means and the pooled standard deviation (m(treatment) - m(norm)/SD(pooled)). The patients' HRQOL scores were impaired relative to German norms, with effect sizes up to d = 1.12. The pattern of impairment was similar in boys and girls as well as in children and adolescents. In each of the analyses, at least three of six KIDSCREEN subscales were affected. Regardless of gender and age group, the highest impairments were found in self-perception and physical well-being. Because of the strong decrease in HRQOL in the general population during adolescence, compared to age-specific norms, adolescents were less impaired than were children. However, overweight and obese adolescents (especially females) reported the lowest absolute HRQOL scores. HRQOL varied with the intensity of treatment. Inpatients had significantly lower scores than did outpatients, even after adjusting for age, gender and zBMI. The results suggest the presence of differences in HRQOL with regard to gender, age, and treatment modality in treatment-seeking overweight and obese youths. Research and clinical practice must consider the particular impairments of inpatients as well as the impairments of (especially female) adolescents.


Behavioral dimensions of adjustment in persons with chronic pain: pain-related anxiety and acceptance.
Through empirical methods we now characterize patients with chronic pain as either dysfunctional, interpersonally distressed, or adaptive copers. Studying factors that differentiate these groups may reveal the behavioral processes that determine adjustment to pain. Subjects for this study were 190 patients referred for treatment of chronic pain. They were classified as dysfunctional (n = 41), interpersonally distressed (n = 28) or adaptive copers (n = 59) based on the Multidimensional Pain Inventory (Kerns, R.D., Turk, D.C. and Rudy, T.E., The West Haven-Yale Multidimensional Pain Inventory (WHYMPI), Pain, 23 (1985) 345-356) and compared on measures of pain-related anxiety and pain acceptance. Our analyses showed that the dysfunctional group reported greater pain-related anxiety and less acceptance of pain than the other groups. Additional analyses, statistically controlling for pain severity and depression, showed that the patient subtypes continued to differ on pain-related anxiety and acceptance. Discriminant function analyses including pain-related anxiety and acceptance correctly classified 72.5% of dysfunctional and 90.9% of adaptive copers. Again, anxiety and acceptance contributed uniquely to classification independent of depression and pain intensity. Pain-related anxiety and acceptance of pain appear to be unique behavioral dimensions of adjustment to chronic pain. Decreasing anxiety and increasing acceptance may 'move' patients with chronic pain from the dysfunctional to the adaptive coper category.


Cellulose-Derived Supercapacitors from the Carbonisation of Filter Paper.
Advanced carbon materials are important for the next-generation of energy storage apparatus, such as electrochemical capacitors. Here, the physical and electrochemical properties of carbonised filter paper (FP) were investigated. FP is comprised of pure cellulose and is a standardised material. After carbonisation at temperatures ranging from 600 to 1700 °C, FP was contaminant-free, containing only carbon and some oxygenated species, and its primary fibre structure was retained (diameter ≈20-40 μm). The observed enhancement in conductivity of the carbonised FP was correlated with the carbonisation temperature. Electrochemical capacitance in the range of ≈1.8-117 F g(-1) was achieved, with FP carbonised at 1500 °C showing the best performance. This high capacitance was stable with >87 % retained after 3000 charge-discharge cycles. These results show that carbonised FP, without the addition of composite materials, exhibits good supercapacitance performance, which competes well with existing electrodes made of carbon-based materials. Furthermore, given the lower cost and renewable source, cellulose-based materials are the more eco-friendly option for energy storage applications.


Synthesis of thick mesoporous gamma-alumina films, loading of Pt nanoparticles, and use of the composite film as a reusable catalyst.
Nanocrystalline mesoporous gamma-Al2O3 film of high thickness has been developed and characterized. The films were prepared on ordinary glass substrates by a single dip-coating method using boehmite (AlOOH) sols derived from aluminum tri-sec-butoxide in presence of cetyltrimethylammonium bromide (CTAB) as structure-directing agent. The dried films were heat-treated at 500 degrees C in air to remove the organics and strengthen the network. The GIXRD of the heat-treated (500 degrees C) film shows a broad peak in the low-angle region supporting the formation of worm-hole-like disordered mesostructures. The high-angle GIXRD, FTIR, and TEM of the films confirm the formation of gamma-Al2O3. N2 adsorption-desorption analyses showed that the heat-treated (500 degrees C) film has a BET surface area of 171 m(2) g(-1) with a pore volume of 0.188 cm(3) g(-1) and mean pore diameter 4.3 nm. Pt nanoparticles (NPs) (approximately 2.7 mol % with respect to the equivalent AlO(1.5)) were generated inside the mesopores of the heat-treated films simply by soaking H2PtCl6 solutions into it, and followed by thermal decomposition at 500 degrees C. The surface area and pore volume of the Pt-incorporated film have been reduced to 101 m(2) g(-1) and 0.119 cm(3) g(-1) respectively, confirming the inclusion of Pt NPs inside the pores. FESEM and TEM studies revealed uniform distribution of Pt NPs (2-8.5 nm; average diameter 4.9 nm) in the films. Catalytic properties of the Pt-incorporated films were investigated in two model (one inorganic and other organic) systems: reduction of hexacyanoferrate(III) ions by thiosulfate to ferrocyanide, and p-nitrophenol to p-aminophenol. In both the cases, the catalyst showed excellent activities, and the reduction reactions followed smoothly, showing isosbestic points in the UV-visible spectra. The catalyst films can be separated easily after the reactions and reused several times.


Predictive power of abnormal electroencephalogram for post-cerebral infarction depression.
Electroencephalography is a sensitive indicator for measuring brain condition, and can reflect early changes in brain function and severity of cerebral ischemia. However, it is not yet known whether electroencephalography can predict development of post-cerebral infarction depression. A total of 321 patients with ischemic stroke underwent electroencephalography and Hamilton Depression Rating Scale assessment to analyze the relationship between electroencephalography and post-cerebral infarction depression. Our results show that electroencephalograms of ischemic stroke patients with depression exhibit low-amplitude alpha activity and slow theta activity. In contrast, electroencephalograms of ischemic stroke patients without depression show fast beta activity and slow delta activity. These findings confirm that low-amplitude alpha activity and slow theta activity can be considered as independent predictors for post-cerebral infarction depression.


Distinct and non-cross-reactive epitopes are recognized on B16 melanoma by LAK cells and anti-B16 monoclonal antibodies.
Two rat anti-B16 melanoma monoclonal antibodies (MoAb), designated IB16-6 and IB16-8, recognize an epitope expressed with high density on the surface of B16 parental cells and B16-F1, F10, F10FLR, and BL6 sublines. The purpose of this study was to define by means of cytolytic and clonogenic assays whether these MoAbs reacted with the same or distinct determinants as those recognized on B16 targets by lymphokine-activated killer (LAK) cells. Using 125I-labeled antibody and Scatchard analysis, the affinity constant (KA) of IB16-6 was determined to range from 5.6 to 9.4 x 10(8) liter/M and the number of receptor sites per B16 cell was 4.8 x 10(4) to 2.5 x 10(5). The effects of anti-B16 MoAb on LAK activity were determined by either preincubating 51Cr-labeled B16 target cells with varying concentrations of MoAb, followed by the cytolytic assay, or exposing unlabeled B16 cells to MoAb, and then carrying out a 10-day clonogenic assay. Over a wide range of antibody concentrations, IB16-6 and IB16-8 had minimal effects on LAK activity, and even at MoAb concentrations up to 1 mg there were no changes in target cell sensitivity or colony-forming ability. Enzymatic treatment of B16 melanoma cells with either trypsin or pronase completely removed the epitope recognized by MoAb IB16-6 but did not alter B16 sensitivity to LAK cells. These observations indicate that the LAK recognition unit was distinct from the epitope reactive with MoAb IB16-6 and that the B16 determinant(s) recognized by LAK cells is resistant to proteolytic enzymes. The molecular structure of each of these remains to be determined.


Anatomical location and number of metastatic lymph nodes for prognosis of non-small cell lung cancer.
The nodal classification of lung cancer is determined by the anatomical location of metastatic lymph nodes (mLNs). However, prognosis can be heterogeneous at the same nodal stage, and the current classification system requires improvement. Therefore, we investigated the correlation between the number of mLNs and prognosis in patients with non-small cell lung cancer. Using a multicenter database in Japan, we retrospectively reviewed the records of patients who underwent complete resection for lung cancer between 2010 and 2016. Kaplan-Meier curves were used to determine recurrence-free and overall survival. Multivariate analyses were performed using the Cox proportional hazards model. We included 1,567 patients in this study. We could show a statistically significant difference in recurrence-free survival between pN2 patients with 1 mLN and pN2 patients with ≥2 mLNs (P=0.016). Patients with a combination of pN1 (≥4 mLNs) plus pN2 (1 mLN) had a poorer prognosis than pN1 patients (1-3 mLNs) (P=0.061) and a better prognosis than pN2 patients (≥2 mLNs) patients (P=0.007). Multivariate analysis showed that the number of mLNs was independently associated with cancer recurrence in patients with pN1 and pN2 disease (P=0.034 and 0.018, respectively). Nodal classification that combines anatomical location and the number of mLNs may predict prognosis more accurately than the current classification system. Our study provides the concept that supports the subdivision of nodal classification in the upcoming revision of the tumor, node, and metastasis staging system.


Phase diagrams for model heteronuclear dimers confined in narrow slitlike pores.
Monte Carlo simulation is used to study the phase behavior of a model of heteronuclear dimers on a lattice. The calculations are carried out for two- and three-dimensional bulk systems and for dimers confined in slitlike pores of different widths and for different segment-wall interactions. The calculations recover a rich variety of phase behaviors that includes transitions between gaslike and liquidlike phases, the latter being ordered or disordered. The topology of the obtained diagrams depends on the energy of interactions between segments forming a dimer, on the segment-wall interaction, and on the pore width.


Evaluation of a multidimensional assessment procedure for preschool children.
The Pediatric Examination of Educational Readiness was administered to 386 preschool children to determine whether the predictive value of this instrument could be enhanced by the inclusion of systematic measures of processing efficiency, selective attention, behavioral adaptation, and neuromaturation. Findings on these dimensions, as well as the traditional developmental attainment measure, were consistent with McCarthy cognitive scores. Concerns regarding developmental attainment, processing efficiency, and selective attention were more common in children later found to have weak kindergarten mastery skills. Data analysis revealed minimal redundancy and specific additive effects in this multidimensional assessment. It is concluded that such instruments can contribute to a broader, more integrated diagnostic procedure for behavioral and developmental problems.


Microalbuminuria: prevalence in hypertensives and diabetics.
Microalbuminuria is the mild elevation of urinary albumin excretion and reflects the progression of clinical nephropathy and cardiovascular disease and mortality risks of diabetic and hypertensive patients. The aim of this study was to determine the prevalence of and risk factors for microalbuminuria amongst Turkish people who had diabetes and/or hypertension and were older than 35 years of age. In this cross-sectional study, from a pool of 7708 people over 35 years of age living in the Park Health Centre Area of Ankara, Turkey, we randomly selected 550 out of 926 hypertensive and/or diabetic patients. The area is also the research district of Ankara University Medical Faculty's Public Health Department. The results of 493 of those examined for microalbuminuria are represented in the study. An immunospecific dipstick Micral Test II was used for microalbuminuria screening and Medi-test urinary strip for macroalbuminuria. Additionally, blood pressure levels were recorded, fasting blood glucose levels were measured by Glucotrend and questionnaire forms were filled out. Chi square and logistic regression analyses were used for statistical analyses. In the study population, 439 patients were hypertensive, 194 patients were diabetic and of these, 140 were both hypertensive and diabetic. Overall prevalence of microalbuminuria was 19.1% and macroalbuminuria was 4.4% in the study group. Microalbuminuria prevalence was 18.9% in the hypertensive group and 21.7% in the diabetic group. In the hypertensive group, diastolic pressure level, male sex and type of accommodation, in the diabetic group, duration of diabetes, fasting blood glucose levels and type of accommodation were all influential factors for microalbuminuria according to the results of the multiple logistic regression analyses. Our study shows a high prevalence of microalbuminuria in both hypertensive and diabetic patients, males being at Special risk. Lowering of diastolic blood pressure and amelioration of living Standards should be the first goal of treatment according to our results.


[Complications in catheterization of the subclavian vein].
The authors of the article inform about the complications of the infraclavicular subclavian vein catheterization, enclosing some practical cases. They suggest the applicable steps that should be taken in case of the death due to the catheterization not only for pathologists but also for the regular clinical staff.


Pyogenic and amebic liver abscesses.
Pyogenic and amebic liver abscesses are the two most common hepatic abscesses. Amebic abscesses are more common in areas where Entamoeba histolytica is endemic, whereas pyogenic abscesses are more common in developed countries. Pyogenic abscess severity is dependent on the bacterial source and the underlying condition of the patient. Amebic liver abscess is more prevalent in individuals with suppressed cell-mediated immunity, men, and younger people. The right lobe of the liver is the most likely site of infection in both types of hepatic abscess. Patients usually present with a combination of fever, right-upper-quadrant abdominal pain, and hepatomegaly. Jaundice is more common in the pyogenic abscess. The diagnosis is often delayed and is usually made through a combination of radiologic imaging and microbiologic, serologic, and percutaneous techniques. Treatment involves antibiotics along with percutaneous drainage or surgery.


A case report of salivary duct carcinoma.
We present a 65-year-old man with an enlarged mass in the right parotid gland. A fine-needle aspiration cytology suspected Warthin's tumor. The ill-defined margin of the tumor in diagnostic imaging and unexpected clinical course of the occurrence of facial nerve paralysis suggested malignant neoplasm. The patient was treated with surgical resection of the primary site and neck following radiation therapy. Pathologic diagnosis was a salivary duct carcinoma. Difficulty in early diagnosis of this tumor may result in local extension, early metastasis to regional lymph nodes and distant sites, and death.


Dynamic features of a heme delivery system for cytochrome C maturation.
In Escherichia coli, heme is delivered to cytochrome c in a process involving eight proteins encoded by the ccmABCDEFGH operon. Heme is transferred to the periplasmic heme chaperone CcmE by CcmC and from there to apocytochrome c. The role of CcmC was investigated by random as well as site-directed mutagenesis. Important amino acids were all located in periplasmic domains of the CcmC protein that has six membrane-spanning helices. Besides the tryptophan-rich motif and two conserved histidines, new residues were identified as functionally important. Mutants G111S and H184Y had a clear defect in CcmC-CcmE interaction, did not transfer heme to CcmE, and lacked c-type cytochromes. Conversely, mutants D47N, R55P, and S176Y were affected neither in interaction with nor in delivery of heme to CcmE but produced less than 10% c-type cytochromes. A strain carrying a CcmCE fusion had a similar phenotype, suggesting that CcmC is important not only for heme transfer to CcmE but also for its delivery to cytochrome c. Co-immunoprecipitation of CcmC with CcmF was not detectable although CcmE co-precipitated individually with CcmC and CcmF. This contradicts the idea of CcmCEF supercomplex formation. Our results favor a model that predicts CcmE to shuttle between CcmC and CcmF for heme delivery.


Extraction of spatial information for low-bandwidth telerehabilitation applications.
Telemedicine applications, based on two-dimensional (2D) video conferencing technology, have been around for the past 15 to 20 yr. They have been demonstrated to be acceptable for face-to-face consultations and useful for visual examination of wounds and abrasions. However, certain telerehabilitation assessments need the use of spatial information in order to accurately assess the patient's condition and sending three-dimensional video data over low-bandwidth networks is extremely challenging. This article proposes an innovative way of extracting the key spatial information from the patient's movement during telerehabilitation assessment based on 2D video and then presenting the extracted data by using graph plots alongside the video to help physicians in assessments with minimum burden on existing video data transfer. Some common rehabilitation scenarios are chosen for illustrations, and experiments are conducted based on skeletal tracking and color detection algorithms using the Microsoft Kinect sensor. Extracted data are analyzed in detail and their usability discussed.


Vasodilator Effects of Elcatonin, a Synthetic Eel Calcitonin, on Retinal Blood Vessels in Rats.
The aim of this study was to examine the effects of elcatonin, a synthetic derivative of eel calcitonin, on rat retinal blood vessels, and to determine how diabetes affects the retinal vascular responses. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring the diameter of retinal blood vessels contained in the digital images. Both systemic blood pressure and heart rate were continuously recorded. Elcatonin increased the diameter of retinal blood vessels but decreased mean blood pressure in a dose-dependent manner, whereas it had no significant effect on heart rate. A diminished retinal vasodilator response and significant pressor response to elcatonin were observed in rats injected intravenously with N(G)-nitro-L-arginine methyl ester, a nitric oxide (NO) synthase inhibitor. Intravitreal injection of indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ22536, an adenylyl cyclase inhibitor, markedly attenuated the vasodilator effects of elcatonin on retinal blood vessels. The retinal vasodilator responses to elcatonin were unaffected 2 weeks after the induction of diabetes by a combination of streptozotocin treatment and D-glucose feeding. These results suggest that elcatonin dilates rat retinal blood vessels via NO- and COX-dependent mechanisms and that the adenylyl cyclase-adenosine 3',5'-cyclic monophosphate system plays a major role in the vasodilator mechanisms. The retinal vasodilatory effects of elcatonin seem to be preserved at early stages of diabetes.


Reducing the trigger dose of recombinant hCG in high-responder patients attending an assisted reproductive technology program: an observational study.
Decreasing the dose of human chorionic gonadotropin (hCG) used to trigger final oocyte maturation in assisted reproductive technology programs is regarded as a useful intervention in the prevention of ovarian hyperstimulation syndrome, but the minimal effective dose has not been yet identified. In this study, the capacity of a reduced dose of recombinant hCG (r-hCG) to provide adequate oocyte maturation was tested for the first time. Thirty-five high-responder patients received a dose of 125 µg (half of the standard dose) of r-hCG for triggering final oocyte maturation. The number of oocytes retrieved per patient and the proportion of mature oocytes were evaluated. As a result, a mean number of 14 oocytes were retrieved, of which 85% were found to be mature (MII). There was only one patient developing a moderate form of ovarian hyperstimulation syndrome and not requiring hospitalization. It is suggested that r-hCG at 125 µg can be effective in triggering final oocyte maturation in high-responder patients. Additional properly powered and controlled studies are needed to support this contention.


Endoribonuclease type II toxin-antitoxin systems: functional or selfish?
Most bacterial genomes have multiple type II toxin-antitoxin systems (TAs) that encode two proteins which are referred to as a toxin and an antitoxin. Toxins inhibit a cellular process, while the interaction of the antitoxin with the toxin attenuates the toxin's activity. Endoribonuclease-encoding TAs cleave RNA in a sequence-dependent fashion, resulting in translational inhibition. To account for their prevalence and retention by bacterial genomes, TAs are credited with clinically significant phenomena, such as bacterial programmed cell death, persistence, biofilms and anti-addiction to plasmids. However, the programmed cell death and persistence hypotheses have been challenged because of conceptual, methodological and/or strain issues. In an alternative view, chromosomal TAs seem to be retained by virtue of addiction at two levels: via a poison-antidote combination (TA proteins) and via transcriptional reprogramming of the downstream core gene (due to integration). Any perturbation in the chromosomal TA operons could cause fitness loss due to polar effects on the downstream genes and hence be detrimental under natural conditions. The endoribonucleases encoding chromosomal TAs are most likely selfish DNA as they are retained by bacterial genomes, even though TAs do not confer a direct advantage via the TA proteins. TAs are likely used by various replicons as 'genetic arms' that allow the maintenance of themselves and associated genetic elements. TAs seem to be the 'selfish arms' that make the best use of the 'arms race' between bacterial genomes and plasmids.


Urinary tract infections in cats. Prevalence of comorbidities and bacterial species, and determination of antimicrobial susceptibility to commonly used antimicrobial agents.
To investigate the prevalence of comorbidities (CM) in cats with urinary tract infections (UTIs), as well as the prevalence of bacterial species in cats with different CM and their antimicrobial susceptibility to the commonly used antibacterial agents doxycycline, trimethoprim-sulfamethoxazole (TMS), amoxicillin-clavulanic acid (AMC), cephalothin, and enrofloxacin. A retrospective analysis of cats with positive urine cultures in the years 2003 to 2009 was performed. Cats were assigned to one of four groups: cats with systemic comorbidities (sCM), cats with indwelling urinary catheters (iUC), cats with local comorbidities (lCM), or cats without CM. To evaluate the potential effectivity of the antibiotics the antibacterial impact factors were calculated. A total of 194 cats with 219 isolates were included in the study. In 78.4% (152/194) of cats, a CM was identified; 49.5% had a sCM and 28.9% (56/194) had an iUC or a lCM. Cats with sCM were significantly older than cats in all other groups, and the proportion of female animals was higher in cats with sCM than in cats with iUC or lCM. More than half of the cats with sCM did not show clinical signs of lower urinary tract disease. The most commonly isolated bacteria species were Escherichia (E.) coli, Streptococcus spp., Staphylococcus spp., and Enterococcus spp. with a significantly higher proportion of E. coli isolates in cats with sCM and significantly higher proportions of Streptococcus and Staphylococcus spp. isolates in cats with iUC and other lCM. According to the antimicrobial impact factors bacterial isolates in cats with any CM were most likely susceptible to AMC and TMS. Isolates from cats with iUC and lCM had a lower likelihood to be susceptible to the tested antimicrobials than cats with sCM and cats without CM. Relevant comorbidities for bacterial urinary tract infection were identified in the majority of cats in the present study. Cats with sCM often do not show clinical signs of lower urinary tract disease. AMC and TMS were the antimicrobial agents with the highest antimicrobial impact factor in this population of cats.


[Influenza virus vaccines].
Influenza, despite the wide availability of vaccines, is still the one infectious disease with the highest mortality. In official statistics many thousands of influenza deaths are ascribed to other diseases (respiratory, heart, circulatory diseases) which, in reality, are triggered by influenza virus. Influenza virus appears in ever changing and new antigenic forms against which there is little or no immunity. Past failures in the battle against the disease may have been due to poor vaccines and limited vaccination strategies: vaccination of narrowly limited populations with vaccines that often are only poorly antigenic; frequent changing from one vaccine strain to another and the inherent problem of inadequate vaccine supplies for timely wide-scale public health campaigns; and the unjustified expectation that influenza virus vaccines will afford protection against non-influenza virus-induced influenza-like disease. Potent whole virus influenza vaccines should be given a chance in broad-scale vaccination programs designed to interrupt the spread of the virus and provide an immunological base against future virus variants.


Assessment of dynamic cerebral autoregulation and cerebral carbon dioxide reactivity during normothermic cardiopulmonary bypass.
Despite increased risk of neurological complications after cardiac surgery, monitoring of cerebral hemodynamics during cardiopulmonary bypass (CPB) is still not a common practice. Therefore, a technique to evaluate dynamic cerebral autoregulation and cerebral carbon dioxide reactivity (CO2R) during normothermic nonpulsatile CPB is presented. The technique uses continuous recording of invasive arterial blood pressure, middle cerebral artery blood flow velocity, absolute cerebral tissue oxygenation, in-line arterial carbon dioxide levels, and pump flow measurement in 37 adult male patients undergoing elective CPB. Cerebral autoregulation is estimated by transfer function analysis and the autoregulation index, based on the response to blood pressure variation induced by cyclic 6/min changes of indexed pump flow from 2.0 to 2.4 up to 2.8 L/min/m(2). CO2R was calculated from recordings of both cerebral blood flow velocity and cerebral tissue oxygenation. Cerebral autoregulation and CO2R were estimated at hypocapnia, normocapnia, and hypercapnia. CO2R was preserved during CPB, but significantly lower for hypocapnia compared with hypercapnia (p < 0.01). Conversely, cerebral autoregulation parameters such as gain, phase, and autoregulation index were significantly higher (p < 0.01) during hypocapnia compared with both normocapnia and hypercapnia. Assessing cerebral autoregulation and CO2R during CPB, by cyclic alteration of pump flow, showed an impaired cerebral autoregulation during hypercapnia.


Facial growth and morphology of cleft lip and/or palate patients after corrective surgery according to P.I.S.A. technique.
Cleft lip and/or palate patients (CLP) undergo corrective surgery that can affect facial growth. The aim of this study was to analyze facial growth and maxillary development of CLP subjects after surgery according to P.I.S.A. technique (Peri osteoplasty Improves Symmetry and Aesthetic). Cephalometric tracings of 55 patients were performed, thirty-three of which belonged to the test group, while the lasting twenty subjects were part of the control group. The test group was formed by cleft lip and/or palate patients after surgical repair according to P.I.S.A. technique. The control group included patients unaffected by this malformation, with an Angle's first class, selected from the Michigan Growth Study sample. Facial growth and upper maxilla development analysis was carried out by comparing the data obtained from the cephalometric traces of cleft patients who performed an early surgery, with the values of the same parameters measured in non-cleft subjects, providing the normal values. The results of this study showed, in the test group, a maxillary and mandibular bi-retrusion, a more negative facial convexity, the absence of a marked discrepancy in the skeletal relationships, a slight tendency towards hyper-divergence. .


Hepatocellular carcinoma presenting extrahepatic obstructive jaundice due to bile duct invasion--clinicopathological study of two cases.
Two rare cases of autopsy and surgery presenting extrahepatic biliary obstruction due to intrabile-duct growth of hepatocellular carcinoma were reported. Clinically obstructive jaundice was predominant in comparison with the other symptoms in both cases. In one autopsy case, hepatocellular carcinoma developed in the right lobe of the cirrhotic liver (posthepatitic). It involved the secondary branch of the right hepatic duct and grew into the common hepatic duct. In the other case of surgical operation, hepatocellular carcinoma, which developed in the posterior portion of the right lobe of the cirrhotic liver (posthepatitic), destroyed the posterior wall of the bifurcation of the bilateral hepatic duct and obstructed the common hepatic duct due to the intraductal cancer growth. From the site of the bile duct invasion or permeation by the tumor, two cases were classified into the peripheral (the former case) and proximal (the latter case) types, respectively. Furthermore, as far as obstructive jaundice is clinically concerned, the possibility should be kept in mind that hepatocellular carcinoma may proliferate into the large bile ducts, apart from that of cholangiocarcinoma or cholelithiasis.


Fe/Mn Bimetal-Doped ZIF-8-Coated Luminescent Nanoparticles with Up/Downconversion Dual-Mode Emission for Tumor Self-Enhanced NIR-II Imaging and Catalytic Therapy.
ZIF-8, as an important photoresponsive metal-organic framework (MOF), holds great promise in the field of cancer theranostics owing to its versatile physiochemical properties. However, its photocatalytic anticancer application is still restricted because of the wide bandgap and specific response to ultraviolet light. Herein, we developed lanthanide-doped nanoparticles (LDNPs) coated with Fe/Mn bimetal-doped ZIF-8 (LDNPs@Fe/Mn-ZIF-8) for second near-infrared (NIR-II) imaging-guided synergistic photodynamic/chemodynamic therapy (PDT/CDT). The LDNPs were synthesized by encapsulating an optimal Yb3+/Ce3+-doped active shell on the NaErF4:Tm core to achieve dual-mode red upconversion (UC) and NIR-II downconversion (DC) emission upon NIR laser irradiation. At the optimal doping concentration, the UC and DC NIR-II emission intensities of LDNPs were increased 30.2- and 13.2-fold above those of core nanoparticles, which endowed LDNPs@Fe/Mn-ZIF-8 with an outstanding capability to carry out UC-mediated PDT and NIR-II optical imaging. In addition, the dual doping of Fe2+/Mn2+ markedly decreased the bandgap of the ZIF-8 photosensitizer from 5.1 to 1.7 eV, expanding the excitation threshold of ZIF-8 to the visible light region (∼650 nm), which enabled Fe/Mn-ZIF-8 to be efficiently excited by UC photons to achieve photocatalytic-driven PDT. Furthermore, Fe2+/Mn2+ ions could be responsively released in the tumor microenvironment through degradation of Fe/Mn-ZIF-8, thereby producing hydroxyl radicals (·OH) by Fenton/Fenton-like reactions to realize CDT. Meanwhile, the degradation of Fe/Mn-ZIF-8 endowed the nanosystems with tumor self-enhanced NIR-II imaging function, providing precise guidance for CDT/PDT.


Impact of once- and twice-daily dosing regimens on adherence and overall safety.
Low-frequency dosing regimens are the best options for long-term HAART with regard to convenience, adherence, and efficacy. In a drive to simplify HIV treatment, once-daily dosing has been advocated as more effective than twice-daily dosing at maintaining adherence and, therefore, controlling viral load. However, there are only a limited number of systematic studies comparing the safety and efficacy of such regimens. This review presents an overview of reduced-frequency dosing regimens from recent HAART trials and critically examines the factors related to adherence and therapeutic efficacy. Clinical data to guide individual treatment decisions are limited, and therapy--whether a once-daily, twice-daily, or other dosing schedule--should be selected based on individual patient needs.


Hepatitis C virus diversification in Argentina: comparative analysis between the large city of Buenos Aires and the small rural town of O'Brien.
The estimated prevalence of HCV infection in Argentina is around 2%. However, higher rates of infection have been described in population studies of small urban and rural communities. The aim of this work was to compare the origin and diversification of HCV-1b in samples from two different epidemiological scenarios: Buenos Aires, a large cosmopolitan city, and O'Brien, a small rural town with a high prevalence of HCV infection. The E1/E2 and NS5B regions of the viral genome from 83 patients infected with HCV-1b were sequenced. Phylogenetic analysis and Bayesian Coalescent methods were used to study the origin and diversification of HCV-1b in both patient populations. Samples from Buenos Aires showed a polyphyletic behavior with a tMRCA around 1887-1900 and a time of spread of infection approximately 60 years ago. In contrast, samples from ÓBrien showed a monophyletic behavior with a tMRCA around 1950-1960 and a time of spread of infection more recent than in Buenos Aires, around 20-30 years ago. Phylogenetic and coalescence analysis revealed a different behavior in the epidemiological histories of Buenos Aires and ÓBrien. HCV infection in Buenos Aires shows a polyphyletic behavior and an exponential growth in two phases, whereas that in O'Brien shows a monophyletic cluster and an exponential growth in one single step with a more recent tMRCA. The polyphyletic origin and the probability of encountering susceptible individuals in a large cosmopolitan city like Buenos Aires are in agreement with a longer period of expansion. In contrast, in less populated areas such as O'Brien, the chances of HCV transmission are strongly restricted. Furthermore, the monophyletic character and the most recent time of emergence suggest that different HCV-1b ancestors (variants) that were in expansion in Buenos Aires had the opportunity to colonize and expand in O'Brien.


Leader RNA of Rinderpest virus binds specifically with cellular La protein: a possible role in virus replication.
Rinderpest virus (RPV) is an important member of the Morbillivirus genus in the family Paramyxoviridae and employs a similar strategy for transcription and replication of its genome as that of other negative sense RNA viruses. Cellular proteins have earlier been shown to stimulate viral RNA synthesis by isolated nucleocapsids from purified virus or from virus-infected cells. In the present work, we show that plus sense leader RNA of RPV, transcribed from 3' end of genomic RNA, specifically interacts with cellular La protein employing gel mobility shift assay as well as UV cross-linking of leader RNA with La protein. The leader RNA synthesized in virus-infected cells was shown to interact with La protein by immunoprecipitation of leader RNA bound to La protein and detecting the leader RNA in the immunoprecipitate by Northern hybridization with labeled antisense leader RNA. Employing a minireplicon system, we demonstrate that transiently expressed La protein enhances the replication/transcription of the RPV minigenome in cells. Sub-cellular immunolocalization shows that La protein is redistributed from nucleus to the cytoplasm upon infection. Our results strongly suggest that La protein may be involved in regulation of Rinderpest virus replication.


Identification of adenovirus neutralizing antigens using capsid chimeric viruses.
Human adenoviruses (HAdV) 3 and 7 can cause acute respiratory disease epidemics and outbreaks. Identification of neutralizing epitopes is vital for surveillance and vaccine development. In this study, we generated the recombinant capsid-chimeric human adenoviruses rAd3E-Fk7, containing the Ad3E backbone and the HAdV-7 fiber knob, and rAd3E-H7Fk7, which contain an Ad3E backbone but HAdV-7 hexon and fiber knob. In vitro neutralization tests with these chimeric adenoviruses using both mouse and human antisera indicated that hexon and fiber knob are the major targets recognized by neutralizing antibodies against HAdV-3 or HAdV-7, and other capsid proteins including the penton base and fiber shaft may not contribute to neutralizing antibody responses. In conclusion, both hexon and fiber knob structures in HAdV-3 and HAdV-7 may be the proteins which induce neutralizing antibody responses and thus may be important for adenovirus vaccine and drug development.


Levels of neutralizing antibodies against resident farm strain or vaccine strain are not indicators of protection against PRRSV-1 vertical transmission under farm conditions.
Vertical transmission is key for the maintenance of porcine reproductive and respiratory syndrome virus (PRRSV) infection. In vaccinated farms, vertical transmission can still occur despite sows having some level of immunity because of repeated vaccination or contact with the wild-type virus. The present study aimed to correlate the age of sows and the amplitude of neutralizing antibodies (Nab) (heterologous neutralization) with PRRSV-1 vertical transmission (VT). For this purpose, umbilical cords of 1,554 newborns (corresponding to 250 litters) were tested for PRRSV by RT-PCR in two PRRSV-unstable vaccinated farms. In parallel, the sows were bled after farrowing and the levels of antibodies were determined by ELISA and by the viral neutralization test against the vaccine virus, the virus circulating in the farm, and other unrelated contemporary PRRSV-1 strains. The relationship between the parity and the probability of delivering infected piglets and the presence of broadly Nabs examined. The proportion of VT events in the two examined farms ranged from 18.9% to 23.0%. Young sows (parity 1-2) were 1.7 times more likely to have VT than older sows (p < 0.05). Despite higher ELISA S/P antibody ratios in younger sows (p < 0.05), NAb against the resident farm strain were at a similar level between sows delivering infected and healthy piglets regardless of age, mostly with low titers (2-3 log2). The titers of NAb against the vaccine virus were also low, and no correlations with VT were observed. When a panel of another 4 strains (1 isolated in the 1990s, and 3 contemporary strains) were used for the neutralization test, most sow sera were not capable of neutralizing the contemporary strains. Titers of NAb could not be correlated with the occurrence of PRRSV VT. The amplitude of NAb present in most vaccinated sows is limited with a considerable proportion unresponsive regarding NAb production.


Chandra enables study of x-ray jets.
The exquisite angular resolution of the Chandra x-ray telescope has enabled the detection and study of resolved x-ray jets in a wide variety of astronomical systems. Chandra has detected extended jets in our galaxy from protostars, symbiotic binaries, neutron star pulsars, black hole binaries, extragalactic jets in radio sources, and quasars. The x-ray data play an essential role in deducing the emission mechanism of the jets, in revealing the interaction of jets with the intergalactic or intracluster media, and in studying the energy generation budget of black holes.


Depressive Features in Individuals with First Episode Psychosis: Psychopathological and Treatment Considerations from A 2-Year Follow-Up Study.
Comorbid depression is quite common in early psychosis and specifically related to suicidal behavior and poor long-term outcomes. However, Depressive Symptoms (DS) are often neglected in both research and treatment, especially at the psychosis onset. The goals of this investigation were: (a) to longitudinally explore DS levels in patients with First Episode Psychosis (FEP) during 24 months of follow-up, and (b) to investigate the associations of DS with psychopathology and intervention components of an "Early Intervention in Psychosis" (EIP) program across the follow-up period. The Global Assessment of Functioning (GAF) and the Positive And Negative Syndrome Scale (PANSS) were completed by 266 FEP subjects. A linear regression analysis with DS as the dependent parameter and psychopathological and treatment characteristics as independent variables was performed (both at baseline and across the follow-up period). DS had enduring associations with PANSS "Positive Symptoms" and "Negative Symptoms" subscores. During the investigation, FEP subjects significantly improved their DS severity levels. This was related to the number of individual psychotherapy meetings supplied within the EIP protocol, as well as to a higher antidepressant dose and a lower antipsychotic dose prescribed during the follow-up. DS are quite prominent in FEP, even at the recruitment time in EIP services. Nevertheless, DS severity tends to diminish overtime, especially with the provision of specialized EIP treatments.


Arsenic trioxide overcomes rapamycin-induced feedback activation of AKT and ERK signaling to enhance the anti-tumor effects in breast cancer.
Inhibitors of the mammalian target of rapamycin (mTORi) have clinical activity; however, the benefits of mTOR inhibition by rapamycin and rapamycin-derivatives (rapalogs) may be limited by a feedback mechanism that results in AKT activation. Increased AKT activity resulting from mTOR inhibition can be a result of increased signaling via the mTOR complex, TORC2. Previously, we published that arsenic trioxide (ATO) inhibits AKT activity and in some cases, decreases AKT protein expression. Therefore, we propose that combining ATO and rapamycin may circumvent the AKT feedback loop and increase the anti-tumor effects. Using a panel of breast cancer cell lines, we find that ATO, at clinically-achievable doses, can enhance the inhibitory activity of the mTORi temsirolimus. In all cell lines, temsirolimus treatment resulted in AKT activation, which was decreased by concomitant ATO treatment only in those cell lines where ATO enhanced growth inhibition. Treatment with rapalog also results in activated ERK signaling, which is decreased with ATO co-treatment in all cell lines tested. We next tested the toxicity and efficacy of rapamycin plus ATO combination therapy in a MDA-MB-468 breast cancer xenograft model. The drug combination was well-tolerated, and rapamycin did not increase ATO-induced liver enzyme levels. In addition, combination of these drugs was significantly more effective at inhibiting tumor growth compared to individual drug treatments, which corresponded with diminished phospho-Akt and phospho-ERK levels when compared with rapamycin-treated tumors. Therefore, we propose that combining ATO and mTORi may overcome the feedback loop by decreasing activation of the MAPK and AKT signaling pathways.


Return to work following ileostomy.
The experiences of 1033 members of the 51 English divisions of the Ileostomy Association of Great Britain and Ireland have been analysed in respect of their return to work after construction of an ileostomy. Although there was a fall in the number of patients returning to work after operation this was often for reasons unrelated to surgery. The majority of those returning to work resumed work with the same employer and usually in the same post. Fifty-nine (5.7 per cent) patients began work for the first time after operation, including 33 (3.2 per cent) who were previously inactive although of working age. Analysis of occupational class shows that, although a number of patients initially resumed work within a lower class, once established in employment successful career advancement was possible. Problems in the gaining or resumption of employment were reported by 56 (5.4 per cent) patients. In 22 (2.1 per cent) patients, almost all approaching or above retirement age, successful surgery resulted in a decision not to return to employment. An ileostomy is no barrier to successful return to work in nearly all occupations, and is accomplished by the majority of patients without major difficulty.


Exogenous succinic acid mediates responses of Larix olgensis A. Henry to cadmium stress.
Trace metal contamination of soil is an increasing problem. Organic acid application can restore trace metal elements such as cadmium (Cd) in contaminated soil. Changbai larch (Larix olgensis A. Henry) is an economically important forestry species in northeast China; however, growth is inhibited by severe Cd contamination. We investigated the effects of different concentrations of exogenous succinic acid (SA) on Cd tolerance and physiological and morphological toxicity in L. olgensis seedlings. Seedlings were planted in pots containing Cd-contaminated or uncontaminated Haplic Cambisol. Seedlings in Cd-contaminated soil were treated daily with SA solution at 0, 0.04, 0.2, 1.0, and 2.0 mmol kg-1 of soil for 10, 20 or 30 days. Cd treatment induced seedling damage and significantly increased the relative conductivity and malondialdehyde content of the leaves, inhibiting soluble protein and proline contents, superoxide dismutase and peroxidase activity, chlorophyl fluorescence and pigment content. Decreases in the length, surface area, volume of roots and leaves, and specific root length were also observed. Effects increased in control plants with time. SA treatment also reduced the Cd content of the fine roots and leaves and Mg, K, and Ca contents. Moreover, plant growth was significantly promoted and damage was reversed, especially at 5.0 and 10.0 mmol L-1 SA for 30 days. SA therefore alleviated Cd-induced injury, improving tolerance to Cd stress. SA application combined with afforestation could therefore help restore Cd-contaminated soil in northeast China. Further studies aimed at determining the detoxification mechanism of L. olgensis seedlings are now required.


Resetting the problem of cell death following muscle-derived cell transplantation: detection, dynamics and mechanisms.
We conducted a study in mice to reevaluate and clarify many aspects of the early survival of muscle cells following transplantation. Male mouse muscle cells (primary-cultures and T-antigen-immortalized clones) labeled with [14C]thymidine and beta-galactosidase were injected into female muscles. Each label was detected in the muscles after different time periods. TUNEL, alizarin red, and immunodetection of active caspase-3 were done in muscle sections. The donor cell labels disappeared from the muscles following donor cell death, but this was not instantaneous and even if the donor cells were killed before transplantation, the first 6 hours were not enough to clear [14C]thymidine and Y chromosome. Using the cell pellet before injection as the 100% baseline for cells injected to evaluate cell death can lead to misinterpretations: the Y-chromosome band was 5-fold stronger than that of a muscle injected with cells, irrespective of whether the cells were previously killed or not. There was no evidence of an immediate massive donor cell death. Necrosis (detected by alizarin red) and apoptosis (detected by active caspase-3) were present among the donor myoblasts following transplantation. Necrosis seemed to be the most important mechanism during the first hours. T-antigen immortalized cells died earlier and more massively than primary-cultured cells, but the surviving cells proliferated more. Indeed, they seemed to exhibit more apoptosis and they triggered a more rapid CD8+ cell infiltration. As a result of our findings, many concepts concerning the early donor cell death following myoblast transplantation must be reconsidered.


[Characteristics of nitrogen cycling in farm systems in a small watershed of Three Gorges Reservoir Area, China].
In China, the agricultural activities are often carried out by single family, and the balance of nitrogen in every farm may have great effect on agricultural production and environment. A farm survey was carried out on the amounts of chemical fertilizers consumed, the amounts of food and feed purchased, and the livestock manures used in Zhangjiachong watershed of Three Gorges Reservoir Area for each farmer. According to the characteristics of nitrogen flow, farms in this watershed could be divided into 5 types: breeding specialized farms, orange-growing farms, tea-growing farms, vegetable-growing farms and traditional farms. Differences in environmental nitrogen load were observed among the five farm types in the following order: breeding specialized farms > vegetable-growing farms > orange-growing farms > tea-growing farms approximately = traditional farms, being (363 +/- 129), (355 +/- 127), (345 +/- 107), (152 +/- 60) and (151 +/- 73) kg x (hm2 x a)(-1) respectively by nitrogen. Nitrogen cycle for different farm fields showed that field surplus nitrogen ranged from (102 +/- 68) to (303 +/- 134) kg x (hm2 x a)(-1) among different farms. Among the five farm types, the field surplus nitrogen followed the order of vegetable-growing farms > citrus-growing farms > tea-growing farms > breeding specialized farms approximately = traditional farms, being (303 +/- 134), (262 +/- 100), (111 +/- 46), (102 +/- 68) and (103 +/- 67) kg x (hm2 x a)(-1). The nitrogen from farm life activities accounted for 28% of the total N load, while the field surplus nitrogen was 72%. It was estimated that field nitrogen consumption was the predominated nitrogen pollution source in the watershed. However, the farmer's daily life pollution should not to be neglected. Breeding specialized farms, vegetable-growing farms and orange-growing farms were the high potential pollution sources for the water environment in the watershed, and the major attention should be paid to these types of farms. Field survey on farm nitrogen cycle is of significance in evaluating the nitrogen flows in the agro-ecosystems and revealing the characteristics of nitrogen cycling in the region.


Review of the three-field techniques in breast cancer radiotherapy.
Breast cancer is often treated with radiotherapy (RT), with two opposing tangential fields. When indicated, supraclavicular lymph nodes have to be irradiated, and a third anterior field is applied. The junction region has the potential to be over or underdosed. To overcome this problem, many techniques have been proposed. A literature review of 3 Dimensional Conformal RT (3D CRT) and older 3-field techniques was carried out. Intensity Modulated RT (IMRT) techniques are also briefly discussed. Techniques are categorized, few characteristic examples are presented and a comparison is attempted. Three-field techniques can be divided in monoisocentric and two-isocentric. Two-isocentric techniques can be further divided in full field and half field techniques. Monoisocentric techniques show certain great advantages over two-isocentric techniques. However, they are not always applicable and they require extra caution as they are characterized by high dose gradient in the junction region. IMRT has been proved to give better dosimetric results. Three-field matching is a complicated procedure, with potential of over or undredosage in the junction region. Many techniques have been proposed, each with advantages and disadvantages. Among them, monoisocentric techniques, when carefully applied, are the ideal choice, provided IMRT facility is not available. Otherwise, a two-isocentric half beam technique is recommended.


Plutonic xenoliths from Martinique, Lesser Antilles: evidence for open system processes and reactive melt flow in island arc crust.
The Lesser Antilles Volcanic Arc is remarkable for the abundance and variety of erupted plutonic xenoliths. These samples provide a window into the deeper crust and record a more protracted crystallisation history than is observed from lavas alone. We present a detailed petrological and in situ geochemical study of xenoliths from Martinique in order to establish their petrogenesis, pre-eruptive storage conditions and their contribution to construction of the sub-volcanic arc crust. The lavas from Martinique are controlled by crystal-liquid differentiation. Amphibole is rarely present in the erupted lavas, but it is a very common component in plutonic xenoliths, allowing us to directly test the involvement of amphibole in the petrogenesis of arc magmas. The plutonic xenoliths provide both textural and geochemical evidence of open system processes and crystal 'cargos'. All xenoliths are plagioclase-bearing, with variable proportions of olivine, spinel, clinopyroxene, orthopyroxene and amphibole, commonly with interstitial melt. In Martinique, the sequence of crystallisation varies in sample type and differs from other islands of the Lesser Antilles arc. The compositional offset between plagioclase (~An90) and olivine (~Fo75), suggests crystallisation under high water contents and low pressures from an already fractionated liquid. Texturally, amphibole is either equant (crystallising early in the sequence) or interstitial (crystallising late). Interstitial amphibole is enriched in Ba and LREE compared with early crystallised amphibole and does not follow typical fractionation trends. Modelling of melt compositions indicates that a water-rich, plagioclase-undersaturated reactive melt or fluid percolated through a crystal mush, accompanied by the breakdown of clinopyroxene, and the crystallisation of amphibole. Geothermobarometry estimates and comparisons with experimental studies imply the majority of xenoliths formed in the mid-crust. Martinique cumulate xenoliths are inferred to represent crystal mushes within an open system, through which melt can both percolate and be generated.


Gastric pneumatosis in infancy.
Gastric pneumatosis (gas in the wall of the stomach) is an uncommon but characteristic plain-film radiographic sign. In infancy it is associated either with gastric outlet obstruction, usually hypertrophic pyloric stenosis, or necrotizing gastroenterocolitis. Differential diagnosis is mainly based on associated clinical findings, as exemplified by the 2 cases reported here. Both infants had isolated gastric pneumatosis as the principal radiographic finding. Correct diagnosis was greatly aided by recognition of this x-ray sign so that appropriate therapy was started without delay.


Thermodynamic Acidity Studies of 6,6'-Dihydroxy-2,2'-bipyridine: A Combined Experimental and Computational Approach.
The organic ligand 6,6'-dihydroxy-2,2'-bipyridine (6,6'-dhbp) is frequently used to bind transition metals in order to form catalysts for many organic and inorganic transformations. 6,6'-dhbp exists in two tautomeric forms, the pyridinol tautomer and the amide (lactam) tautomer with each tautomer having two rotational conformers: cis or trans. Only the cis-pyridinol tautomer has the proper configuration to bind transition metals. The pendant OH (or O- groups when deprotonated) in 6,6'-dhbp typically do not bind the metal when forming the metal catalyst but can facilitate the proton transfer steps in the catalysis process. Electronic structure calculations were used to predict the stability of all possible isomers (including conformers and protonation states) in the gas phase and aqueous solution. These results have been compared to experimental data including UV-vis and NMR spectra as a function of pH. The pKa values for the 6,6'-dhbp ligand in the -2 to +2 structures were predicted, and these ligands show different behavior in the gas phase versus in aqueous solution.