Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin.
The presence of activated platelets and platelet-leukocyte aggregates in the circulation accompanies major surgical procedures and occurs in several chronic diseases. Recent findings that activated platelets contribute to the inflammatory disease atherosclerosis made us address the question whether activated platelets stimulate normal healthy endothelium. Infusion of activated platelets into young mice led to the formation of transient platelet-leukocyte aggregates and resulted in a several-fold systemic increase in leukocyte rolling 2 to 4 hours after infusion. Rolling returned to baseline levels 7 hours after infusion. Infusion of activated P-selectin-/- platelets did not induce leukocyte rolling, indicating that platelet P-selectin was involved in the endothelial activation. The endothelial activation did not require platelet CD40L. Leukocyte rolling was mediated solely by the interaction of endothelial P-selectin and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1). Endothelial P-selectin is stored with von Willebrand factor (VWF) in Weibel-Palade bodies. The release of Weibel-Palade bodies on infusion of activated platelets was indicated by both elevation of plasma VWF levels and by an increase in the in vivo staining of endothelial P-selectin. We conclude that the presence of activated platelets in circulation promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and P-selectin-mediated leukocyte rolling.


Atypical Perinuclear Anti-Neutrophil Cytoplasmic Antibodies in Ocular Inflammatory Diseases.
Purpose: To characterize the clinical features of patients with ocular inflammatory diseases (OID) who tested positive for atypical perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA). Methods: Retrospective case series of patients with OID seen at the Massachusetts Eye Research and Surgery Institute (MERSI) from April 2014 to April 2016. Results: 813 patients were tested for ANCA with 34 patients (4%) being positive for atypical P-ANCA. Among those with positive atypical P-ANCA, the most frequent diagnoses were anterior uveitis in 62% (n = 21) followed by scleritis in 20% (n = 7). Only one patient had an episode of recurrent disease flare-up. All but one patient, who had concomitant C-ANCA seropositivity and granulomatosis with polyangiitis, had a favorable disease course with controlled inflammation using topical and/or systemic immunomodulatory therapy. Conclusion: In contrast to typical C-ANCA and P-ANCA, atypical P-ANCA seropositivity was not associated with severe vasculitis or poor prognosis in patients with the OID.


Increased subgenual cingulate cortex volume in pediatric bipolar disorder associated with mood stabilizer exposure.
The subgenual cingulate (SGC) cortex has been implicated in the pathophysiology of mood disorders. We sought to study morphometric characteristics of the SGC in pediatric subjects with familial bipolar disorder (BD) compared with healthy controls. Twenty children and adolescents with BD (mean age = 14.6 years, 4 females) and 20 healthy age-, gender-, and intelligence quotient-matched controls underwent high-resolution anatomical magnetic resonance imaging. Patients were primarily euthymic and most were taking medications. SGC cortex volumes were determined by manual tracings from a reliable rater, blinded to diagnosis. Analyses of covariance were performed with total cerebral gray matter and age as covariates. No differences were found in SGC volumes between BD subjects and healthy controls. Further analysis revealed that BD subjects with past mood stabilizer exposure had significantly increased SGC volumes compared with BD subjects without mood stabilizer exposure, and compared with controls. The increase was driven by larger bilateral posterior SGC volumes. Youth with familial BD do not appear to have abnormalities in SGC volume. Mood stabilizer exposure, however, may be correlated with increases in SGC volume.


Oxygen-ozone autohemotherapy in breast cancer patients suffering from fatigue and musculoskeletal pain upon aromatase inhibitors treatment: a case-series study.
In patients with breast cancer and positive hormone receptors, aromatase inhibitors are effective in reducing the risk of recurrences and are active in progressing the disease in this setting. On the other hand, fatigue and painful musculoskeletal side effects can significantly reduce treatment compliance. With no further treatment options to control these symptoms, non-pharmaceutical interventions, such as oxygen-ozone therapy, may play a role in managing rheumatologic symptomatology inasmuch. We have previously reported evidence on the effectiveness of oxygen-ozone in the treatment of pain and fatigue in chronic fatigue syndrome and fibromyalgia patients and in oncological patients as well. In this study, we reported 6 cases of patients (mean age 64 yrs, all Caucasian females) with breast cancer upon treatment with anastrozole (Arimidex®), suffering from musculoskeletal pain, weakness and fatigue, and therefore treated with oxygen-ozone major autohemotherapy according to the Italian Scientific Society of Oxygen Ozone Therapy (SIOOT) protocol. Pain was measured with a 10-item Numerical Rating Scale (NRS) and fatigue with a 7-item Fatigue Scoring Scale (FSS). A reduction of at least 66% of pain (from 9.43 ±0.54 SD to 2.36 ±1.32 SD, p<0.001) and 66.26% of fatigue were obtained for all the cases. Pain and fatigue disappeared within one month from ozone therapy, and a healthy painless state lasted for many months following the oxygen-ozone therapy. The oxygen-ozone therapy is a sound opportunity for breast cancer patients to reduce anti-aromatase-induced pain, fatigue, and musculoskeletal symptoms.


Inhibition of erythrocyte Ca2+-ATPase by activated oxygen through thiol- and lipid-dependent mechanisms.
We have studied erythrocyte Ca2+-ATPase as a model target for elucidating effects of activated oxygen on the erythrocyte membrane. Either intracellular or extracellular generation of activated oxygen causes parallel decrements in Ca2+-ATPase activity and cytoplasmic GSH, oxidation of membrane protein thiols, and lipid peroxidation. Subsequent incubation with either dithiothreitol or glucose allows only partial recovery of Ca2+-ATPase, indicating both reversible and irreversible components which are modeled herein using diamide and t-butyl hydroperoxide. The reversible component reflects thiol oxidation, and its recovery depends upon GSH restoration. The irreversible component is largely due to lipid peroxidation, which appears to act through mechanisms involving neither malondialdehyde nor secondary thiol oxidation. However, some portion of the irreversible component could also reflect oxidation of thiols which are inaccessible for reduction by GSH, since we demonstrate existence of different classes of thiols relevant to Ca2+-ATPase activity. Activated oxygen has an exaggerated effect on Ca2+-ATPase of GSH-depleted cells. Sickle erythrocytes treated with dithiothreitol show a heterogeneous response of Ca2+-ATPase activity. These findings are potentially relevant to oxidant-induced hemolysis. They also may be pertinent to oxidative alteration of functional or structural membrane components in general, since many components share with Ca2+-ATPase both free thiols and close proximity to unsaturated lipid.


Association Between Discrimination Stress and Suicidality in Preadolescent Children.
Youth suicide rates in the United States have been increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality; hence there is a need to study stressors that have a disproportionate impact on Black youths. We aimed to disentangle the unique contribution of racial/ethnic discrimination from other adversities associated with childhood suicidal ideation and attempts (suicidality). We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, which included a large, diverse sample of US children (N = 11,235, mean age 10.9 years, 20.2% Black), assessed for multiple environmental adversities including discrimination. Multivariate regression models tested the association of self-reported racial/ethnic discrimination with suicidality, covarying for multiple confounders including other discrimination types (toward non-US-born individuals, sexual orientation-based, and weight-based). Matched analyses contrasted effects of racial/ethnic discrimination and racial identity on suicidality. Black youths reported more discrimination and higher suicidality rates than non-Black youths. High racial/ethnic discrimination was positively and significantly associated with suicidality, adjusting for other discrimination types (odds ratio = 2.6, 95% CI = 2.1-3.2). Findings remained significant after adjusting for multiple suicidality risk factors. Once experienced, racial/ethnic discrimination was similarly associated with suicidality in White, Black, and Hispanic youths. Matched analyses revealed that racial/ethnic discrimination was associated with suicidality (relative risk = 2.7, 95% CI = 2-3.5), whereas Black race was not (relative risk = 0.9, 95% CI = 0.7-1.2). Racial/ethnic discrimination is disproportionately experienced by Black children, and is associated with preadolescent suicidality, over and above other adversities. Findings highlight the need to address discrimination as part of suicide prevention strategies. Cross-sectional design hampers causal inferences.


Detection and characterization of low abundance glycopeptides via higher-energy C-trap dissociation and orbitrap mass analysis.
Broad-scale mass spectrometric analyses of glycopeptides are constrained by the considerable complexity inherent to glycoproteomics, and techniques are still being actively developed to address the associated analytical difficulties. Here we apply Orbitrap mass analysis and higher-energy C-trap dissociation (HCD) to facilitate detailed insights into the compositions and heterogeneity of complex mixtures of low abundance glycopeptides. By generating diagnostic oxonium product ions at mass measurement errors of <5 ppm, highly selective glycopeptide precursor ion detections are made at sub-fmol limits of detection: analyses of proteolytic digests of a hen egg glycoprotein mixture detect 88 previously uncharacterized glycopeptides from 666 precursor ions selected for MS/MS, with only one false positive due to co-fragmentation of a non-glycosylated peptide with a glycopeptide. We also demonstrate that by (1) identifying multiple series of glycoforms using high mass accuracy single stage MS spectra, and (2) performing product ion scans at optimized HCD collision energies, the identification of peptide + N-acetylhexosamine (HexNAc) ions (Y1 ions) can be readily achieved at <5 ppm mass measurement errors. These data allow base peptide sequences and glycan compositional information to be attained with high confidence, even for glycopeptides that produce weak precursor ion signals and/or low quality MS/MS spectra. The glycopeptides characterized from low fmol abundances using these methods allow two previously unreported glycosylation sites on the Gallus gallus protein ovoglycoprotein (amino acids 82 and 90) to be confirmed; considerable glycan heterogeneities at amino acid 90 of ovoglycoprotein, and amino acids 34 and 77 of Gallus gallus ovomucoid are also revealed.


Comparison of methods for measurement of interstitial fluid pressure in cat skin/subcutis and muscle.
Interstitial fluid pressure (IFP) in cats was measured with four techniques, i.e., hollow perforated and porous polyethylene capsules, wick in needle (WIN), and micropipettes. During control conditions, skin IFP of -1.5 +/- 0.4 (SD) mmHg (n = 53) was obtained with micropipettes, whereas pressures recorded in subcutis with perforated and porous capsules were -1.6 +/- 0.9 (n = 26) and -1.6 +/- 0.8 mmHg (n = 13), respectively. These were all significantly different from the -1.2 +/- 0.5 mmHg (n = 50) obtained in subcutis with WIN. In skeletal muscle, control IFP of -0.5, -0.5, and -1.1 mmHg was measured with micropipettes, WIN, and porous capsules, respectively. During peritoneal dialysis skin and muscle IFP recorded with micropipettes and WIN was reduced by 3-3.5 mmHg, whereas pressure in porous and perforated capsules fell by 7 and 10 mmHg, respectively. Intravenous Ringer infusion caused a marked transient rise in capsular pressures, not reflected by micropipettes and WIN, but similar pressures were obtained 210 min after infusion. In conclusion, all techniques reflect true IFP under steady-state conditions. Both capsules apparently act like osmometers in acute overhydration or dehydration and are, in addition, sensitive to pressure changes in local veins and are therefore not suitable for measurement of changes in IFP that take place in less than a few hours.


Is essential tremor symmetric? Observational data from a community-based study of essential tremor.
Essential tremor (ET) has been variably portrayed in the literature both as a symmetric arm tremor and as an asymmetric arm tremor. Few quantitative clinical or neurophysiological data specifically address the issue of tremor asymmetry in ET. To examine a community-dwelling cohort of subjects with ET to (1) estimate the prevalence of tremor asymmetry and (2) quantify the magnitude of tremor asymmetry. Fifty-four subjects with ET, identified in a community-based study of ET in New York City, underwent a Tremor Interview and a videotaped Tremor Examination. The examination included 6 tasks: sustained arm extension, pouring water, drinking water, using a spoon, finger-to-nose movements, and drawing spirals with each arm. Two neurologists rated the severity of tremor using a 0 to 3 clinical rating scale and a total tremor score was calculated (range, 0-36). Fourteen (25%) of 54 subjects also underwent quantitative computerized tremor analysis. The prevalence of asymmetry depended on the definition of asymmetry; small to moderate differences between sides were common. The mean side-to-side difference in clinical ratings for each of the 6 tasks was 0.54 of 3 points, which represented a 1.32-fold difference between sides. Clinical rating scores were higher in the nondominant arm in 39 subjects (72%), higher in the dominant arm in 9 (17%), and equal in 6 (11%). The 2 left-handed subjects had higher clinical ratings on the right. During quantitative computerized tremor analysis, there was a 1.71-fold mean difference between tremor amplitudes in the dominant and nondominant sides, and in 12 subjects (86%), the maximum tremor amplitude was in the nondominant arm. Small to moderate differences between sides were common in ET. In most community-dwelling subjects, tremor amplitude was greatest in the nondominant arm. In contrast, clinic-based studies have reported greater tremor in the dominant arm; those with ET who seek medical attention are more likely to exhibit severe tremor in their dominant arms. This study documents that mild asymmetry is a fundamental property of ET and that tremor is more severe in the nondominant arm.


Surgical correlation of preoperative MRI findings of trauma to tendons and ligaments of the foot and ankle.
The purpose of this study was to determine whether magnetic resonance imaging findings are accurate and can be confirmed surgically. Surgical correlation of preoperative magnetic resonance imaging findings of trauma to tendons and ligaments of the foot and ankle were retrospectively studied in 28 patients who had undergone surgical repair for tears of the Achilles tendon, posterior tibial tendon, peroneal tendons, collateral ligaments, and other pathology. This study corroborates that magnetic resonance imaging findings are confirmed surgically 83% of the time for tears of tendons and ligaments of the foot and ankle. Larger tendons (Achilles, posterior tibial tendon) have a 94% sensitivity and 6% specificity, respectively. Collateral ligament and high ankle sprains have a 73% sensitivity. There is a lower sensitivity of 57% for peroneus brevis and longus ruptures. This study revealed that peroneal trauma can be an isolated event and in some cases can occur with other traumatic pathology such as collateral ligament tears.


Chromatin remodeling and modification during HIV-1 Tat-activated transcription.
Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of AIDS. Following entry into the host cell, the viral RNA is reverse transcribed into DNA and subsequently integrated into the host genome as a chromatin template. Chromatin structure may be responsible for silencing retroviral gene expression. Transcriptional activation occurs after ATP-dependent chromatin remodeling complexes alter chromatin structure and positioning of nucleosomes. Histone acetyltransferases (HATs), histone deacetylases (HDACs), kinases, and methyltransferases (HMTs), covalently modify nucleosomes by adding or removing chemical moieties in the N-terminal tails of histones. Recent advances have indicated that HIV-1 encoded proteins interact with chromatin remodeling complexes and histone modifying enzymes, implying that chromatin remodeling plays an important role in the HIV-1 life cycle. Nucleosomes are positioned on the HIV-1 LTR and are barriers to transcription. Following cellular activation, these nucleosomes are modified and repositioned allowing for activation of viral gene expression. Tat recruits various HATs to the HIV-1 promoter region and can also be acetylated by some of these enzymes. Unmodified Tat is involved in binding to the CBP/p300 and cdk9/cyclin T complexes and facilitates transcription initiation. Acetylated Tat dissociates from the TAR RNA structure and recruits bromodomain-containing chromatin modifying complexes such as p/CAF and SWI/SNF to facilitate transcription elongation. This review summarizes our current knowledge and understanding of chromatin remodeling complexes and their regulation of HIV-1 replication, and highlights the important contributions HIV-1 research has made to further our understanding of the transcription process.


Newborn with severe epidermolysis bullosa: to treat or not to treat?
Epidermolysis bullosa (EB) is an inherited skin disease with four main subtypes that cannot be distinguished clinically at birth. All subtypes may present with widespread life-threatening blisters and fragile skin, making treatment and handling of the newborn with EB challenging. The prognosis of EB depends on the subtype, and therefore maximum treatment is necessary until the final diagnosis is known. In this case, it took 2 weeks before a final diagnosis was reached. In the meantime, we had several ethical discussions on the treatment level. The most important issues were management of pain and nutrition. For immediate pain relief, intranasal fentanyl worked best and gabapentin was successfully used for chronic pain. The feeding difficulties were handled first by a nasogastric feeding tube. Later a normal feeding bottle proved to be adequate.


Comparison between endobronchial ultrasound-guided transbronchial needle aspiration and 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of postoperative nodal recurrence in patients with lung cancer.
Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high diagnostic value for preoperative mediastinal staging in patients with lung cancer. In this study, the utility of EBUS-TBNA for the pathological diagnosis of postoperative lymph node recurrence was investigated and compared with that of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Patients who received both EBUS-TBNA and FDG-PET for the diagnosis of postoperative lymph node recurrence were retrospectively investigated. They underwent routine chest computed tomography (CT) follow-up after thoracotomy, and when hilar or mediastinal lymph nodes showed enlargement on CT compared with the previous chest CT, they were referred for FDG-PET and EBUS-TBNA. We compared the diagnostic performance of these two modalities. In addition, pathological findings of the biopsied sample were evaluated precisely and compared with the results of FDG-PET. Positivity for hypermetabolism on FDG-PET was defined as a standardized uptake value (SUV) greater than 2.5. A total of 40 patients were retrospectively reviewed. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA were 100% for each parameter, whereas those of FDG-PET were 95.8, 12.5, 62.2, 66.7 and 62.5%, respectively. The SUV of true-positive nodes was significantly higher than that of false-positive nodes (P = 0.001). Twenty-two of 24 patients who were confirmed for recurrence by EBUS-TBNA underwent anticancer treatment. The pathological diagnoses of 14 false-positive cases by FDG-PET were chronic inflammation in 12 and non-specific granuloma in 2. The diagnostic yield of EBUS-TBNA is higher than that of FDG-PET when postoperative lymph node recurrence is suspected.


Polyneuropathy possibly caused by 30 years of low exposure to n-hexane.
A slowly developing, mainly sensory, polyneuropathy was found in a 60-year-old man exposed to n-hexane (10-100 mg/m3) for 30 years in a mountain fuel stockpile. The nerve damage was verified by electromyography and sural nerve biopsy, and it is proposed that also a low-grade, but prolonged, exposure to n-hexane may cause polyneuropathy.


L-Dopa improves Restless Legs Syndrome and periodic limb movements in sleep but not Attention-Deficit-Hyperactivity Disorder in a double-blind trial in children.
In a previous open-label study, dopaminergic agents improved Restless Legs Syndrome (RLS) and Periodic Limb Movements in Sleep (PLMS), as well as Attention-Deficit-Hyperactivity Disorder (ADHD) in children with both disorders. We therefore conducted a double-blind placebo-controlled trial of L-DOPA in ADHD children with and without RLS/PLMS. Two groups of patients (total n = 29), those with ADHD only or those with ADHD and RLS/PLMS, were randomized to L-DOPA or placebo therapy. At baseline and after therapy patients were assessed with Conners' parent and teacher rating scales; polysomnography; RLS rating scale; and neuropsychometric measures of memory, learning, attention, and vigilance. L-DOPA improved RLS/PLMS symptoms in all patients with those disorders compared with placebo (p = .007). When assessed by the Conners' Scales before therapy, ADHD was more severe in children without RLS/PLMS than in children with RLS/PLMS (p = 0.006). L-DOPA had no effect on Conners' scales, sleep, or neuropsychometric tests when all patients treated with the drug were compared to those on placebo or when patients with ADHD only were compared to those with ADHD and RLS/PLMS. In this first double-blind study of a dopaminergic therapy in children with RLS/PLMS, L-Dopa significantly improved RLS/PLMS but not ADHD. These results, however, should be interpreted carefully since they may have been influenced by the relatively small sample size and the baseline differences in severity of ADHD symptoms. Further work needs to be done to elucidate the relationship between dopamine, ADHD and RLS/PLMS.


Loss of cardiomyocyte integrin-linked kinase produces an arrhythmogenic cardiomyopathy in mice.
Integrin-linked kinase (ILK), a serine/threonine protein kinase, has roles in cell signaling and molecular scaffolding. ILK mutation/deletion causes cardiomyopathic phenotypes, but the functional and electrophysiological features have not been characterized. This study investigated the structural, functional, ion channel, and electrophysiological changes associated with cardiomyocyte-directed ILK deletion in mice. Adult mice with cardiomyocyte-directed ILK knockout were compared with littermate controls. Knockout mice showed markedly increased mortality, with sudden death beginning after 5 weeks and 100% mortality at 18 weeks. In 10-week-old knockout mice, spontaneous and inducible ventricular tachyarrhythmias were common, occurring in 60% and 86%, respectively, and absent in controls (P<0.001, P<0.05 versus knockout mice). Ventricular refractoriness was prolonged, along with both QRS and QT interval. Action potentials were prolonged and displayed triggered activity. A wide range of ion currents were downregulated, including total, fast and slow components of transient outward K(+) current and inward rectifier K(+) current, along with corresponding ion channel subunit genes, providing a plausible explanation of action potential prolongation. At 5 weeks, only voltage-dependent K(+) currents were reduced, possibly related to direct ILK-Kv4.2 subunit interactions. Action potentials were prolonged, but no arrhythmias or cardiac dysfunction were noted. Structural remodeling was prominent at 10 weeks: connexin-43 was downregulated and redistributed to lateral cell margins, and left ventricular fibrosis occurred, with a strong regional distribution (predominating in the basal left ventricle). Conduction was slowed. High-throughput quantitative polymerase reaction gene-expression studies in 10-week-old ILK knockout showed upregulation of structural, remodeling and fibrosis-related genes, and downregulation of a wide range of ion channel and transporter subunits. Cardiomyocyte ILK deletion produces a lethal arrhythmogenic cardiomyopathy associated with important ion channel and structural remodeling.


[Effect of different threshold levels and injection rates on hepatic enhancement by using bolus tracking technique in helical CT].
To evaluate the influence of different injection rates and different threshold levels on hepatic enhancement using the bolus tracking technique. One hundred patients were included in this randomized and prospective study performed on a helical CT. Patients were assigned to one control and four study groups. Each group received 150 ml nonionic contrast medium. In the control group, used delay time and injection rate were 60 sec and 3 ml/sec, respectively. In the study groups, two different injection rates, 3 ml/sec (groups 1 and 2) and 5 mL/sec, respectively. In study groups, two different preselected thresholds, 40 HU (groups 1 and 3) and 50 HU (groups 2 and 4) were used. In these groups, delay times were determined individually by means of the bolus tracking technique. Peak enhancement time (PET), peak enhancement value (PEV), and mean hepatic enhancement (MHE) on CT scans was calculated for each group. PET was found to be significantly earlier in the study groups in which the injection rates were 5 mL/sec, compared to the other groups (p < 0.001). MHE was significantly higher in all study groups compared to the control group (p < 0.001). PEV was higher in study groups that the preselected threshold was 50 HU compared to only the control group (p < 0.01). Use of a bolus tracking program helps to achieve a greater level of hepatic enhancement. Increasing the injection rate shortens the time to peak hepatic enhancement. The threshold level of 50 HU achieves a great level of hepatic enhancement independent of injection rates in the bolus tracking technique. If the bolus tracking technique is not available, using an injection rate of 3 ml/sec and 70 sec delay time seems to be appropriate.


Microplastics as vectors for bioaccumulation of hydrophobic organic chemicals in the marine environment: A state-of-the-science review.
A state-of-the-science review was conducted to examine the potential for microplastics to sorb hydrophobic organic chemicals (HOCs) from the marine environment, for aquatic organisms to take up these HOCs from the microplastics, and for this exposure to result in adverse effects to ecological and human health. Despite concentrations of HOCs associated with microplastics that can be orders of magnitude greater than surrounding seawater, the relative importance of microplastics as a route of exposure is difficult to quantify because aquatic organisms are typically exposed to HOCs from various compartments, including water, sediment, and food. Results of laboratory experiments and modeling studies indicate that HOCs can partition from microplastics to organisms or from organisms to microplastics, depending on experimental conditions. Very little information is available to evaluate ecological or human health effects from this exposure. Most of the available studies measured biomarkers that are more indicative of exposure than effects, and no studies showed effects to ecologically relevant endpoints. Therefore, evidence is weak to support the occurrence of ecologically significant adverse effects on aquatic life as a result of exposure to HOCs sorbed to microplastics or to wildlife populations and humans from secondary exposure via the food chain. More data are needed to fully understand the relative importance of exposure to HOCs from microplastics compared with other exposure pathways. Environ Toxicol Chem 2016;35:1667-1676. © 2016 SETAC.


Lead poisoning in an art conservator.
A case of lead poisoning in a female art conservator is reported. The patient had experienced excessive lead exposure while restoring an antique Peruvian tapestry from the Chancay period (1000 to 1500 AD) using a powdered pigment (cinnabar), which had been recovered from the same tomb in which the tapestry was found. Over two months, prominent neurological, gastrointestinal, and diffuse muscular symptoms developed. Severe anemia accompanied by basophilic stippling of RBCs led to the diagnosis of lead poisoning, which was confirmed by markedly elevated blood lead levels (up to 130 micrograms/dL) and impairment of heme synthetic enzymes. The severity of the intoxication necessitated chelation therapy. Chemical analysis of the antique powdered pigment showed it to be the source of lead exposure, in that it contained about 1% lead.


The contribution made by lattice vacancies to the Wigner effect in radiation-damaged graphite.
Models for radiation damage in graphite are reviewed and compared, leading to a re-examination of the contribution made by vacancies to annealing processes. A method based on density functional theory, using large supercells with orthorhombic and hexagonal symmetry, is employed to calculate the properties and behaviour of lattice vacancies and displacement defects. It is concluded that annihilation of intimate Frenkel defects marks the onset of recovery in electrical resistivity, which occurs when the temperature exceeds about 160 K. The migration of isolated monovacancies is estimated to have an activation energy of E(a) ≈ 1.1 eV. Coalescence into divacancy defects occurs in several stages, with different barriers at each stage, depending on the path. The formation of pairs ultimately yields up to 8.9 eV energy, which is nearly 1.0 eV more than the formation energy for an isolated monovacancy. Processes resulting in vacancy coalescence and annihilation appear to be responsible for the main Wigner energy release peak in radiation-damaged graphite, occurring at about 475 K.


Prospective, longitudinal, multicenter study on the provision of information regarding sudden unexpected death in epilepsy to adults with epilepsy.
Despite increased awareness of the serious epilepsy complication sudden unexpected death in epilepsy (SUDEP), a substantial population of people with epilepsy (PWE) remain poorly informed. Physicians indicate concern that SUDEP information may adversely affect patients' health and quality of life. We examined SUDEP awareness and the immediate and long-term effects of providing SUDEP information to PWE. Baseline knowledge and behaviors among PWE and behavioral adjustments following the provision of SUDEP information were evaluated in a prospective, multicenter survey using the following validated scales: Neurological Disorders Depression Inventory for Epilepsy for depression symptoms, the EuroQoL five-dimension scale for health-related quality of life (HRQoL), a visual analog scale for overall health, the revised Epilepsy Stigma Scale for perceived stigma, and the Seizure Worry Scale for seizure-related worries. The prospective study collected data through semiquantitative interviews before (baseline), immediately after, and 3 months after the provision of SUDEP information. In total, 236 participants (mean age = 39.3 years, range = 18-77 years, 51.7% women) were enrolled, and 205 (86.9%) completed long-term, 3-month follow-up. One patient died from SUDEP before follow-up. No worsening symptoms from baseline to 3-month follow-up were observed on any scale. At baseline, 27.5% of participants were aware of SUDEP. More than 85% of participants were satisfied with receiving SUDEP information. Three quarters of participants were not concerned by the information, and >80% of participants recommended the provision of SUDEP information to all PWE. Although most patients reported no behavioral adjustments, 24.8% reported strong behavioral adjustments at 3-month follow-up. The provision of SUDEP information has no adverse effects on overall health, HRQoL, depressive symptoms, stigma, or seizure worry among PWE, who appreciate receiving information. SUDEP information provision might improve compliance among PWE and reduce but not eliminate the increased mortality risk.


Antiretroviral therapy and tuberculosis: does the regimen matter?
Infection with HIV is one of the strongest drivers of the incidence of tuberculosis. The use of potent combination antiretroviral therapy (cART) decreases the incidence of tuberculosis in HIV-infected patients. Data on whether this effect differs by type of initial antiretroviral drug or regimen are scarce. Studies are often not designed to address the potential effect of cART on tuberculosis incidence, and/or the diagnosis of tuberculosis is poorly validated. The paucity of data precludes recommendation on the initial cART regimen with respect to the incidence tuberculosis. Other well-described intervention like preventive therapy, and early start with cART are likely to have more effect on the prevention on tuberculosis in HIV-infected patients.


Protein requirements for assembly of virus-like particles of Junonia coenia densovirus in insect cells.
The coding sequences of four overlapping polypeptides starting at four different in-frame AUG codons and co-terminating at the stop codon of the cap gene of Junonia coenia densovirus (JcDNV) were inserted under the control of the p10 promoter of Autographa californica nucleopolyhedrovirus (AcMNPV) to generate AcMNPV-VP1 (four polypeptides), AcMNPV-VP2 (three polypeptides), AcMNPV-VP3 (two polypeptides), and AcMNPV-VP4 (one polypeptide) recombinant viruses. In all cases, infection of Spodoptera frugiperda cells (Sf9) by each of the four recombinant viruses resulted in the production of virus-like particles (VLPs) 22-25 nm in diameter. The VLPs produced by the three recombinants AcMNPV-VP2, AcMNPV-VP3 and AcMNPV-VP4 were abundant and contained three, two and one polypeptides, respectively. VP4, the shortest polypeptide, thus appears to be sufficient for assembly of VLPs morphologically similar to those formed with two to four polypeptides. The ratio of VPs did not appear to be critical for assembly of the particles. The polypeptide starting at the first AUG immediately downstream from the p10 promoter was always the most abundantly expressed in infected cells, regardless of the construct. In contrast, plaque-purified AcMNPV-VP1 recombinants were unstable and produced less than one-twentieth of the VLPs produced by the others. All VP transcripts started at the TAAG late motif of the p10 promoter and had a poly(A) tail 14 nt downstream of a poly(A) addition signal located 98 nucleotides downstream of the common stop codon. No significant transcription initiation inside the cap sequence of AcMNPV-VP2, AcMNPV-VP3 and AcMNPV-PV4 was observed.


A Comparison of Prenatal and Postnatal Models to Predict Outcomes at the Border of Viability.
To compare the accuracy of a prenatal outcomes calculator developed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) with a postnatal neonatal intensive care unit (NICU) prediction model for mechanically ventilated infants. Over a 3-year period, we identified 89 ventilated infants born in our NICU between 23 and 25 weeks gestation. We retrospectively determined the predicted morbidity and mortality for each infant using the prenatal NICHD Neonatal Research Network: Extremely Preterm Birth Outcome Data website calculator. For our postnatal prediction model, we assessed 2 factors while each infant was on mechanical ventilation: daily intuitions about whether the infant would die before NICU discharge and abnormal head ultrasound. We compared the prenatal and postnatal models for predicting outcomes at 2 years adjusted age. Of the 89 infants, 54 (61%) died or had neurologic developmental impairment (NDI) and 35 (39%) survived without NDI. The NICHD Neonatal Research Network: Extremely Preterm Birth Outcome Data website calculator predicted that 61 (69%) would either die or have NDI and that 28 (31%) would survive without NDI. Positive clinicians' intuitions about survival combined with normal head ultrasound scan results during a trial of therapy in the NICU predicted a 30% greater chance for survival without NDI than the prenatal tool. When infants at the border of viability are born and cared for in the NICU, they move from predictions for population-based outcomes into predictions based on individual trajectories and outcomes. A clinical trial of therapy provides additional prognostic information that can guide parental decisions made near the time of birth.


An R package for SNP marker-based parent-offspring tests.
With the advancement of genotyping technologies, whole genome and high-density SNP markers have been widely used for genotyping of mapping populations and for characterization of germplasm lines in many crops. Before conducting SNP data analysis, it is necessary to check the individuals to ensure the integrity of lines for further data analysis. We have developed an R package to conduct a parent-offspring test of individuals which are genotyped with a fixed set of SNP markers for further genetic studies. The program uses monomorphic SNP loci between parents and their progeny genotypes to calculate the similarity between each offspring and their parents. Based on the similarity of parents and individual offspring, the users can determine the threshold level for the individuals to be included for further data analysis. We used an F5-derived soybean population of '5601T' x PI 157440 that was genotyped with 1,536 SNPs to illustrate the procedure and its application. The R package 'ParentOffspring' coupled with the available SNP genotyping platforms could be used to detect the possible variants in a specific cross, as well as the potential errors in sample handling and genotyping processes. It can be used in any crop which is genotyped with a fixed set of SNP markers.


[Clinical evaluation of anaerobic infections in patients with bronchopulmonary infections diagnosed by transtracheal aspiration].
We evaluated the clinical and bacteriologic features in the patients with bronchopulmonary infections isolated anaerobes from transtracheal aspirates between April 1990 and March 1998. Some anaerobe was isolated in 42 (10.9%) in 387 patients whom we performed transtracheal aspiration (TTA), in 42 (15.7%) of 268 in whom some organism was isolated from TTA, or in 42 (16.3%) of 257 patients in whom some bacterium excluding acid-fast bacteria, fungi or mycoplasma from TTA. The isolation rate of anaerobic bacteria was 93.3% in the patients with lung abscess, 22.7% in the patients with nosocomial pneumonia, 19.4% in the patients with community-acquired pneumonia, 26.7% in the patients with acute exacerbation of chronic lower respiratory tract infection (CLRTI), 1.6% in the patients with persistent infection of CLRTI, and 3.0% in the patients with acute bronchitis, respectively. The major anaerobes, isolated from TTA, were Peptostreptococcus micros and Prevotella melaninogenica. The aerobic bacteria were isolated with anaerobic bacteria in 32 of 42 patients at the same time. The quantitive grade of colonial growth of anaerobes was equal to or more than aerobes in the patients with lung abscess and pneumonia. We mostly administrated 3rd generation cephems or carbapenems with or without clindamycin for the treatment of anaerobic infections. Forty-one of 42 patients were cured only by the therapy of antimicrobial agents, but pneumonia patient with lung cancer died in spite of adequate antimicrobial therapy. These results suggest that the anaerobic infections are important in the bronchopulmonary infections.


New insights on postglacial colonization in western Europe: the phylogeography of the Leisler's bat (Nyctalus leisleri).
Despite recent advances in the understanding of the interplay between a dynamic physical environment and phylogeography in Europe, the origins of contemporary Irish biota remain uncertain. Current thinking is that Ireland was colonized post-glacially from southern European refugia, following the end of the last glacial maximum (LGM), some 20 000 years BP. The Leisler's bat (Nyctalus leisleri), one of the few native Irish mammal species, is widely distributed throughout Europe but, with the exception of Ireland, is generally rare and considered vulnerable. We investigate the origins and phylogeographic relationships of Irish populations in relation to those across Europe, including the closely related species N. azoreum. We use a combination of approaches, including mitochondrial and nuclear DNA markers, in addition to approximate Bayesian computation and palaeo-climatic species distribution modelling. Molecular analyses revealed two distinct and diverse European mitochondrial DNA lineages, which probably diverged in separate glacial refugia. A western lineage, restricted to Ireland, Britain and the Azores, comprises Irish and British N. leisleri and N. azoreum specimens; an eastern lineage is distributed throughout mainland Europe. Palaeo-climatic projections indicate suitable habitats during the LGM, including known glacial refugia, in addition to potential novel cryptic refugia along the western fringe of Europe. These results may be applicable to populations of many species.


Tumor treating fields increases membrane permeability in glioblastoma cells.
Glioblastoma is the most common yet most lethal of primary brain cancers with a one-year post-diagnosis survival rate of 65% and a five-year survival rate of barely 5%. Recently the U.S. Food and Drug Administration approved a novel fourth approach (in addition to surgery, radiation therapy, and chemotherapy) to treating glioblastoma; namely, tumor treating fields (TTFields). TTFields involves the delivery of alternating electric fields to the tumor but its mechanisms of action are not fully understood. Current theories involve TTFields disrupting mitosis due to interference with proper mitotic spindle assembly. We show that TTFields also alters cellular membrane structure thus rendering it more permeant to chemotherapeutics. Increased membrane permeability through the imposition of TTFields was shown by several approaches. For example, increased permeability was indicated through increased bioluminescence with TTFields exposure or with the increased binding and ingress of membrane-associating reagents such as Dextran-FITC or ethidium D or with the demonstration by scanning electron microscopy of augmented number and sizes of holes on the cellular membrane. Further investigations showed that increases in bioluminescence and membrane hole production with TTFields exposure disappeared by 24 h after cessation of alternating electric fields thus demonstrating that this phenomenom is reversible. Preliminary investigations showed that TTFields did not induce membrane holes in normal human fibroblasts thus suggesting that the phenomenom was specific to cancer cells. With TTFields, we present evidence showing augmented membrane accessibility by compounds such as 5-aminolevulinic acid, a reagent used intraoperatively to delineate tumor from normal tissue in glioblastoma patients. In addition, this mechanism helps to explain previous reports of additive and synergistic effects between TTFields and other chemotherapies. These findings have implications for the design of combination therapies in glioblastoma and other cancers and may significantly alter standard of care strategies for these diseases.


Platelet inhibition by aspirin is diminished in patients during carotid surgery: a form of transient aspirin resistance?
The majority of patients who suffer peri-operative thromboembolic complication while undergoing vascular procedures do so despite taking aspirin. This study examined the antiplatelet effect of aspirin during surgery in patients undergoing carotid endarterectomy (CEA). Fifty patients undergoing CEA were standardised to 150 mg aspirin daily for > or =2 weeks. Platelet aggregation in response to arachidonic acid (AA) was measured in platelet rich plasma prepared from blood taken prior to, during, and at the end of surgery. Spontaneous platelet aggregation was also studied, as was the role of physiological agonists (ADP, collagen, thrombin, and epinephrine) in mediating the in vivo and in vitro responses to AA. Eighteen patients undergoing leg angioplasty, also on 150 mg aspirin, without general anaesthesia, served as a control group. In the CEA patients aggregation induced by AA (5 mM) increased significantly from 7.6 +/- 5.5% pre-surgery to 50.8 +/- 29.5% at the end of surgery (p <0.0001). Aggregation to AA was even greater in samples taken mid-surgery from a sub-set of patients (73.8+/-7.2%; p = 0.0001), but fell to 45.9 +/- 7.4% by the end of surgery. The increased aggregation in response to AA was not due to intra-operative release of physiological platelet agonists since addition of agents that block/neutralise the effects of ADP (apyrase; 4 micro g/ml), thrombin (hirudin; 10 units/ml), or epinephrine (yohimbine; 10 micro M/l) to the samples taken at the end of surgery did not block the increased aggregation. The patients undergoing angioplasty also showed a significant rise in the response to AA (5 mM), from 5.6 +/- 5.5% pre-angioplasty to 32.4 +/- 24.9% at the end of the procedure (p <0.0001), which fell significantly to 11.0 +/- 8.1% 4 hours later. The antiplatelet activity of aspirin, mediated by blockade of platelet arachidonic acid metabolism, diminished significantly during surgery, but was partially restored by the end of the procedure without additional aspirin treatment. This rapidly inducible and transient effect may explain why some patients undergoing cardiovascular surgery remain at risk of peri-operative stroke and myocardial infarction.


Primary structure of colicin M, an inhibitor of murein biosynthesis.
The DNA sequence of the colicin M activity gene cma was determined. A polypeptide consisting of 271 amino acids was deduced from the nucleotide sequence. The amino acid sequence agreed with the peptide sequences determined from the isolated colicin. The molecular weight of active colicin M was 29,453. The primary translation product was not processed. In the domain required for uptake into cells, colicin M contained the pentapeptide Glu-Thr-Leu-Thr-Val. A similar sequence was found in all colicins which are taken up by a TonB-dependent mechanism and in outer membrane receptor proteins which are constituents of TonB-dependent transport systems. The structure of colicin M in the carboxy-terminal activity domain had no resemblance to the pore-forming colicins or colicins with endonuclease activity. Instead, the activity domain contained a sequence which exhibited homology to the sequence around the serine residue in the active site of penicillin-binding proteins of Escherichia coli. The colicin M activity gene was regulated from an SOS box upstream of the adjacent colicin B activity gene on the natural plasmid pColBM-Cl139.


Identification of human immunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells, and macrophages.
Infectious recombinant viruses were constructed from three molecularly cloned human immunodeficiency virus (HIV) strains varying in cell tropism. All recombinants showed a high infectivity titer on phytohemagglutinin-stimulated normal T lymphocytes. However, a 120-bp region of the envelope gene including the area of the V3 hypervariable loop was found to influence infectivity titer on both clone 1022 CD4-positive HeLa cells and CD4-positive CEM leukemia cells. Infectivity for macrophages was more complex. All viruses replicated in macrophages to a low level, but viral sequences both inside and outside the V3 loop region influenced the efficiency of replication. Two experiments showed that the mechanism of restriction of infection of 1022 cells by HIV strain JR-CSF was related to lack of virus entry. First, productive virus infection occurred after transfection of 1022 cells with viral plasmid DNA. Second, the nonpermissive HIV strain JR-CSF could infect 1022 cells when pseudotyped with the envelope of other retroviruses, including human T-cell leukemia virus type I (HTLV-I), HTLV-II, and amphotropic murine leukemia virus. These results demonstrate the possibility that unexpected cell types might be infected with HIV in human patients coinfected with HIV and HTLV-I or HTLV-II.


A structural and functional analogue of a Bowman-Birk-type protease inhibitor from Odorrana schmackeri.
Frog skin secretions contain complex peptidomes and peptidic protease inhibitors that are one of the biologically and structurally described groups of components. In the present study, by use of molecular 'shotgun' cloning and LC MS/MS fractionation sequencing, a novel Bowman-Birk-type heptadecapeptide (AALKGCWTKSIPPKPCF-amide), named Odorrana schmackeriTrypsin Inhibitor (OSTI), with a canonical Cys6-Cys16 disulfide bridge, was isolated and identified in piebald odorous frog (O. schmackeri) skin secretion. A synthetic replicate of OSTI-exhibited trypsin inhibitory activity with a Ki value of 0.3 ± 0.04 nM and also a tryptase inhibitory effect with a Ki of 2.5 ± 0.6 μM. This is the first time that this property has been reported for a peptide originating from amphibian sources. In addition, substituting lysine (K) with phenylalanine (F) at the presumed P1 position, completely abrogated the trypsin and tryptase inhibition, but produced a strong chymotrypsin inhibition with a Ki of 1.0 ± 0.1 μM. Thus, the specificity of this peptidic protease inhibitor could be optimized through modifying the amino acid residue at the presumed P1 position and this novel native OSTI, along with its analogue, [Phe9]-OSTI, have expanded the potential drug discovery and development pipeline directed towards alleviation of serine protease-mediated pathologies.


Broadening Participation in Biology Education Research: Engaging Community College Students and Faculty.
Nearly half of all undergraduates are enrolled at community colleges (CCs), including the majority of U.S. students who represent groups underserved in the sciences. Yet only a small minority of studies published in discipline-based education research journals address CC biology students, faculty, courses, or authors. This marked underrepresentation of CC biology education research (BER) limits the availability of evidence that could be used to increase CC student success in biology programs. To address this issue, a diverse group of stakeholders convened at the Building Capacity for Biology Education Research at Community Colleges meeting to discuss how to increase the prevalence of CC BER and foster participation of CC faculty as BER collaborators and authors. The group identified characteristics of CCs that make them excellent environments for studying biology teaching and learning, including student diversity and institutional cultures that prioritize teaching, learning, and assessment. The group also identified constraints likely to impede BER at CCs: limited time, resources, support, and incentives, as well as misalignment between doing research and CC faculty identities as teachers. The meeting culminated with proposing strategies for faculty, administrators, journal editors, scientific societies, and funding agencies to better support CC BER.


Fractionation of Marek's disease virus-induced lymphoma by velocity sedimentation and association of infectivity with cellular fractions with and without tumor antigen expression.
Cell suspensions of lymphomas induced by Marek's disease (MD) virus were fractionated by sedimentation at unit gravity on a continuous gradient of bovine fetal serum. Cells in various fractions were examined for MD tumor-associated surface antigen (MATSA) by indirect immunofluorescence, using specific antibody, and for viral infectivity by cocultivating fractionated cells with permissive monolayer cells of duck embryo fibroblasts. Most MATSA-bearing cells in the lymphomas sedimented at a sedimentation velocity of greater than 3.0 mm/hour, whereas smaller, slow-sedimentating cells were generally devoid of MATSA expression. Viral infectivity was associated with MATSA-bearing and MATSA-lacking fractions. Within the limits of the experimental procedures used, this observation provided evidence that presence of MD virus genome in lymphocytes doses not result in concurrent expression of detectable MATSA and that MATSA likely represents another stage of interaction between MD virus and certain lymphocytes.


Air sac adenocarcinoma of the sternum in a Quaker parrot (Myiopsitta monachus).
Respiratory neoplasia is rarely reported in avian species. A 17-yr-old Quaker parrot (Myiopsitta monachus) was admitted with a 2-wk history of anorexia, depression, and respiratory distress. Clinical examination revealed a large, firm mass in the left pectoral muscle. Radiology showed a mass silhouetting the heart and the liver. Supportive treatment was provided, but the bird died during the seventh weekly visit to drain thoracic cavity fluid. Necropsy showed a white, 3 x 3 x 2-cm, hard, gritty sternal mass. Histology showed a nonencapsulated, moderately differentiated air sac carcinoma of the sternum. Immunohistochemically the neoplasm was cytokeratin positive and vimentin and calretinin negative. This is the first report of an air sac neoplasia in a Quaker parrot and one of few respiratory tumors in psittacines.


Expectations and experiences of older people and their carers in relation to emergency department arrival and care: A qualitative study in Australia.
Although older people frequently present to the emergency department (ED), little is known about their experiences in this setting, despite increasing attendance rates reported in this population internationally. This study explores the experiences of older people and their carers leading to and during ED care in a metropolitan university hospital in Sydney, Australia. The study forms part of a larger prospective exploratory study on this topic. Individual in-depth interviews were conducted with 10 people over 65 years of age who had a chronic illness and their carers one month after they presented to the ED. Interviews were transcribed verbatim and analyzed using general interpretive methods. The results revealed that the participants presented to the ED as a result of escalating symptoms and on their general practitioner's advice. Participants felt uninformed about ED procedures, therefore, families/carers felt the need to advocate for information and basic services. Participants were grateful for the care received and mindful of the busy environment. To meet the expectations of older people, nurses need to provide timely information and advise carers how they can assist.


Primary progressive myoclonus of aging.
Myoclonus in older individuals usually occurs in the context of associated neurologic features which allow the diagnosis of the underlying disorder. We encountered 7 patients with a newly recognized myoclonus syndrome; we use the term primary progressive myoclonus of aging (PPMA) for this syndrome. Our purpose was to characterize the clinical and electrophysiological properties of this syndrome. Our database was searched for the presence of "myoclonus" in the physical examination. Medical records and laboratory data were retrospectively reviewed, including electrophysiology data. We applied our criteria for PPMA: (1) asymmetric symptomatic action myoclonus, (2) >/=65 years of age, (3) cortical myoclonus physiology, (4) no dementia, (5) no associated features of defined neurodegenerative disorders, and (6) no secondary cause found. Seven patients fulfilled criteria. Age at presentation ranged from 70 to 87 years. Mean duration from myoclonus onset to last follow-up was 2.9 years. Electrophysiology showed positive-negative back-averaged transients, consistent with cortical myoclonus. No patient demonstrated dementia. Brain imaging in all cases was unremarkable. PPMA is a unique syndrome with characteristic findings that differentiate it from dementias and defined neurodegenerative syndromes. It is important to distinguish primary PPMA from other syndromes seen in older individuals to avoid diagnostic confusion. Some cases showed a response to levetiracetam.


Prognostic significance of immune-nutritional parameters for surgically resected elderly lung cancer patients: a multicentre retrospective study.
The world's population is rapidly ageing, and the age of patients with lung cancer will increase as well. The prognostic nutritional index, controlling nutritional status and the geriatric nutritional risk index (GNRI) are useful parameters for evaluating immune-nutritional status. We aimed to perform a multicentre retrospective study to investigate the correlations of these immune-nutritional parameters with postoperative comorbidities or surgical outcomes of elderly patients with non-small-cell lung cancer (NSCLC). We selected 272 consecutive patients with NSCLC aged >75 years treated from January 2005 to December 2012 and evaluated 3 preoperative immune-nutritional parameters as potential predictive factors of postoperative comorbidities or as prognostic factors for surgically resected elderly patients with NSCLC. Prognostic nutritional index, GNRI, sex and preoperative respiratory comorbidities were significantly associated with postoperative comorbidities. Multivariate analyses revealed that preoperative GNRI, sex, preoperative serum carcinoembryonic antigen levels, preoperative serum cytokeratin 19 fragment levels, pathological N factor and pleural invasion were significantly associated with overall survival (OS). Abnormal GNRI was significantly associated with histology and outcomes. The Kaplan-Meier analysis of OS as a function of preoperative GNRI revealed that patients with an abnormal GNRI experienced significantly shorter OS compared with those with normal GNRI (5-year OS, 45.15% vs 64.10%, respectively; P = 0.0007, log-rank test). The controlling nutritional status score was not significantly associated with postoperative comorbidities or surgical outcomes. Preoperative GNRI is a novel preoperative predictor of postoperative comorbidities and a prognostic factor that may identify high-risk elderly patients with NSCLC.


Controlled DNA Delivery Using Poly(lactide) Nanoparticles and Understanding the Binding Interactions.
Cationic polymer-based gene delivery vectors suffer from several limitations such as low DNA-loading capacity, poor transfection, toxicity, environmental degradations, etc. Again, very limited works are available addressing the binding interactions in detail at the atomic level explaining the loading capacity, protection ability against harsh environments, and controlled release behavior of the DNA-encapsulated vehicles. Here, a poly(l-lactide) (PLA) nanoparticle-based controlled DNA release system is proposed. The developed vehicle possesses a high DNA-loading capacity and can release the loaded DNA in a controlled manner. Spectroscopic, physicochemical, and molecular simulation techniques (AM1 and atomistic molecular dynamics) have been employed to understand the binding interactions between PLA and DNA molecules enabling high DNA loading, protection against external harsh environments, and controlled DNA release behavior. Methyl thiazolyl tetrazolium (MTT) assay experiments confirm the biocompatible nature of the vehicle. Cellular uptake efficiency and endo-lysosomal escape capabilities have been investigated against HeLA cells. This study, therefore, demonstrates the development of a promising nonviral DNA delivery vector and includes a detailed investigation of the atomic-level interaction behavior between PLA and DNA molecules.


The effect of chronic haloperidol treatment on dendritic spines in the rat striatum.
Previous studies have shown that schizophrenics, in comparison to controls, have reduced cortical spine density and smaller striatal spines. The current study in the rat was conducted to determine whether such differences could result from chronic neuroleptic treatment and whether they are correlated with neuroleptic-induced oral dyskinesias. Rats administered 1.5 mg/kg/day of haloperidol (HA) (n = 28) or water (n = 10) were tested for vacuous chewing movements (VCMs). After 6 months, rats were divided into low and high VCM groups; all but seven high VCM rats were sacrificed. These rats (withdrawn group) were withdrawn from HA for 4 weeks. Random electron micrographs of the striatum were analyzed for spine changes. Spine size was not significantly affected by HA (0.193 vs 0.174 microm2, HA and control, respectively) nor correlated with oral dyskinesias (0.191 vs 0.196 microm2, low and high VCM groups, respectively). These results suggest that smaller spines in schizophrenic striatum may be correlated with the disease rather than caused by neuroleptic treatment. Spine density decreased in the HA-treated group (32.7 +/- 9.5) in comparison to controls (53.7 +/- 7.3, P < 0.001) and remained low in the withdrawn group (35.0 +/- 4.2, P < 0.01). Spine density also decreased in both the low (37.3 +/- 9.9, P < 0.01) and the high (28.0 +/- 7.0, P < 0.000) VCM groups in comparison to controls. However, there was no significant difference between high and low VCM groups, suggesting that decreased spine density is independent of oral dyskinesias. These results suggest that the decreased spine density observed in schizophrenic cortex may be a result of neuroleptic treatment.


Impacts of clinicopathologic and operative factors on short-term and long-term survival in renal cell carcinoma with venous tumor thrombus extension: a multi-institutional retrospective study in Japan.
Although the percentage of patients with renal cell carcinoma (RCC) extending into venous systems is unexpectedly high, the prognostic impact and independency of venous tumor thrombus-related factors on overall survival (OS) remain controversial. Furthermore, the prognostic impact of various clinicopathologic factors including tumor thrombus-related factors on OS may change with elapsed years after the intervention and also with follow-up duration of participants. The aim of the study is to explore independent and universal predictive preoperative and intraoperative clinicopathologic factors on OS in patients with RCC extending into venous systems using subgroup analysis in terms of restricted follow-up duration and yearly-based survivors. Between 1980 and 2009, 292 patients diagnosed with RCC with venous tumor thrombus were retrospectively registered for this study. The prognostic impacts of various clinicopathologic and surgical treatment factors including levels of venous thrombus, venous wall invasion status and likelihood of aggressive cytoreductive operation, were investigated using Kaplan-Meier method and following multivariate Cox proportional hazards model for all patients and those still alive at 1, 2, and 3 years of follow-up. To investigate the impact of follow-up duration on the statistical analyses, multivariate logistic regression analyses were used to explore prognostic factors using restricted data until 1, 2, and 3 years of follow-up. The median follow-up duration was 40.4 months. The 5-year OS was 47.6%. Several independent predictive factors were identified in each subgroup analysis in terms of yearly-based survival and restricted follow-up duration. The presence of tumor thrombus invading to venous wall was independently related to OS in the full-range follow-up data and in survivors at 2 and 3 years of follow-up. Using restricted follow-up data until 1, 2, and 3 years of follow-up, many independent predictive factors changed with follow-up duration, but surgical category could be universal and independent predictive factors. The most universal factors affecting improvement both in short-term and long-term survivals could be cytoreductive surgery and absence of venous wall invasion. It may mean that feasible aggressive cytoreductive operation following more reliable preoperative imaging for predicting venous wall invasion status would improve OS for patients with RCC extending into venous systems.


Different monocyte reaction patterns in newly diagnosed, untreated rheumatoid arthritis and lupus patients probably confer disparate C-reactive protein levels.
To investigate the different capacities of monocytes to produce cytokines in newly diagnosed, untreated patients with rheumatoid arthritis (RA) or systemic lupus and to examine the possible correlation among serum C-reactive protein (CRP), cytokines, swollen joint counts, and erythrocyte sedimentation rates (ESR) in untreated RA patients. Monocytes from untreated RA or lupus patients were cultured in vitro with lipopolysaccharide (LPS, as bacterial infection) or immune complexes (as endogenous immune deviation) and supernatants were collected for cytokine determination. Sera from RA patients were assayed for interleukin-6 (IL-6), IL-1 beta, IL-10, tumor necrosis factor-alpha (TNF-alpha) and IL-1 receptor antagonist (IL-1ra). These cytokines were related to serum CRP, swollen joint counts, and ESR. RA monocytes uniformly produced IL-6, IL-1 beta, TNF-alpha, or IL-10 in vitro. In contrast, lupus monocytes could be divided into two subsets: (i) monocytes which produce cytokines on LPS stimulation but not on challenging with immune complexes; and (ii) monocytes which, interestingly, generate cytokines on stimulation by immune complexes but not LPS. These cytokines in turn stimulate the liver to synthesize CRP differently in the SLE subsets and RA patients. Moreover, serum IL-1ra levels correlated significantly with serum IL-6, IL-1 beta, and TNF-alpha concentrations (p = 0.005, 0.008, or 0.040, respectively), but not with IL-10 (p = 0.582) in RA patients. Two lupus subsets exist that react either to LPS or immune complexes to produce CRP-inducing cytokines, in contrast to homogeneous RA monocytes. This is the first report that different reaction patterns of CRP-inducing cytokine production in RA and lupus monocytes probably underlie the high CRP levels in RA versus low heterogeneity in lupus. The correlation of serum IL-1ra levels with serum IL-6, IL-1 beta, or TNF-alpha concentrations, and the borderline correlation of the former with CRP levels, demonstrate that IL-1ra is an acute phase reactant in RA as well as in SLE patients.


Stress-induced lncRNAs evade nuclear degradation and enter the translational machinery.
Long noncoding RNAs (lncRNAs) play important roles in the regulation of gene expression. In fission yeast, glucose starvation triggers a transcriptional cascade of polyadenylated lncRNAs in the upstream region of the fructose-1,6-bisphosphatase gene (fbp1(+) ), which is correlated with stepwise chromatin remodeling and necessary for the massive induction of fbp1(+) mRNA. Here, we show that these novel metabolic stress-induced lncRNAs (mlonRNAs) are 5'-capped, less stable than fbp1(+) mRNA and sensitive to a certain extent to the nuclear exosome cofactor Rrp6. However, most mlonRNAs seem to escape nuclear degradation and are exported to the cytoplasm, where they localize to polysomes precisely during glucose starvation-induced global translation inhibition. It is likely that ribosomes tend to accumulate in the upstream region of mlonRNAs. Although mlonRNAs contain an unusual amount of upstream AUGs (uAUGs) and small open reading frames (uORFs), they escape Upf1-mediated targeting to the non-sense-mediated decay (NMD) pathway. The deletion of Upf1 had no effect on mlonRNA stability, but considerably destabilized fbp1(+) mRNA, hinting toward a possible novel role of Upf1. Our findings suggest that the stability of mlonRNAs is distinctly regulated from mRNA and previously described noncoding transcripts.


Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study.
The Diabetes Control and Complications Trial (DCCT) demonstrated the benefits of intensive treatment of diabetes in reducing glycemic levels and slowing the progression of diabetic nephropathy. The DCCT cohort has been examined annually for another 8 years as part of the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. During the EDIC study, glycemic levels no longer differed substantially between the 2 original treatment groups. To determine the long-term effects of intensive vs conventional diabetes treatment during the DCCT on kidney function during the EDIC study. Observational study begun in 1993 (following DCCT closeout) in 28 medical centers in the United States and Canada. Participants were 1349 (of 1375) EDIC volunteers who had kidney evaluation at years 7 or 8. Development of microalbuminuria, clinical-grade albuminuria, hypertension, or increase in serum creatinine level. Results were analyzed by intention-to-treat analyses, comparing the 2 original DCCT treatment groups. New cases of microalbuminuria occurred during the EDIC study in 39 (6.8%) of the participants originally assigned to the intensive-treatment group vs 87 (15.8%) of those assigned to the conventional-treatment group, for a 59% (95% confidence interval [CI], 39%-73%) reduction in odds, adjusted for baseline values, compared with a 59% (95% CI, 36%-74%) reduction at the end of the DCCT (P<.001 for both comparisons). New cases of clinical albuminuria occurred in 9 (1.4%) of the participants in the original intensive-treatment group vs 59 (9.4%) of those in the original conventional-treatment group, representing an 84% reduction in odds (95% CI, 67%-92%), compared with a reduction of 57% (95% CI, -1% to +81%) at the end of the DCCT. Fewer cases of hypertension (prevalence at year 8, 29.9% vs 40.3%; P<.001) developed in the original intensive-treatment group. Significantly fewer participants reached a serum creatinine level of 2 mg/dL or greater in the intensive-treatment vs the conventional-treatment group (5 vs 19, P =.004), but there were no differences in mean log clearance values. Although small numbers of patients required dialysis and/or transplantation, fewer patients experienced either of these outcomes in the intensive group (4 vs 7, P =.36). The persistent beneficial effects on albumin excretion and the reduced incidence of hypertension 7 to 8 years after the end of the DCCT suggest that previous intensive treatment of diabetes with near-normal glycemia during the DCCT has an extended benefit in delaying progression of diabetic nephropathy.


Rapid lysis technique for mycobacterial species.
The lysis of mycobacterial cells typically has been difficult and time-consuming. We report a method for the physical rupture of Mycobacterium paratuberculosis and several other members of the family Mycobacteriaceae using a Mini-Beadbeater cell disrupter (Biospec Products; Bartlesville, Okla.) and zirconium beads, a process which yields DNA and RNA of high molecular weight and in greater quantity than that obtained by rupture in a Ribi pressure cell.


Molecular characterization and infectivity of Papaya leaf curl China virus infecting tomato in China.
Papaya leaf curl China virus (PaLCuCNV) was previously reported as a distinct begomovirus infecting papaya in southern China. Based on molecular diagnostic survey, 13 PaLCuCNV isolates were obtained from tomato plants showing leaf curl symptoms in Henan and Guangxi Provinces of China. Complete nucleotide sequences of 5 representative isolates (AJ558116, AJ558117, AJ704604, FN256260, and FN297834) were determined to be 2738-2751 nucleotides, which share 91.7%-97.9% sequence identities with PaLCuCNV isolate G2 (AJ558123). DNA-beta was not found to be associated with PaLCuCNV isolates. To investigate the infectivity of PaLCuCNV, an infectious clone of PaLCuCNV-[CN:HeNZM1] was constructed and agro-inoculated into Nicotiana benthamiana, N. tabacum Samsun, N. glutinosa, Solanum lycopersicum and Petunia hybrida plants, which induced severe leaf curling and crinkling symptoms in these plants. Southern blot analysis and polymerase chain reaction (PCR) indicated a systemic infection of test plants by the agro-infectious clone.


Oral cyclophosphamide therapy for patients with residual or relapsed indolent-type lymphoma after initial treatment for aggressive lymphomas. A sub-group of patients with apparent transformed indolent lymphoma.
Lymph node or bone marrow biopsy from sixty-one patients affected by aggressive non-Hodgkin lymphomas (NHL) were retrospectively evaluated to assess the histology at relapse. Eighteen cases (29.5%) were proven to have relapsed or persistent low-grade lymphoma after conventional therapy. In 5/18 patients association of low and high-grade lymphoma was detectable at diagnosis by bone marrow biopsy. In the remaining 13/18 no evidence of follicular lymphoma was detected at diagnosis. The outcome of these patients was compared to that of 43 patients relapsed without change in histology and treated by a second line therapy. Of these 43 patients, 13 were not responders (NR), 10 achieved a partial remission (PR) and 18 complete remission (CR). Two were lost during follow-up. The 18 patients with residual/relapsed indolent subtype received oral cyclophosphamide (100 mg/day for 15 days every month for six months): 3 of them had NR, 5 CR, and 10 PR. The overall survival (OS) median time was 39 months in low-grade resistant/relapsed patients and 20 months in patients with aggressive histology. OS at 24 months was 71 and 41%, respectively, (p < 0.02). Most of the patients with high-grade disease were refractory or relapsed after a median of five months, whereas cases with low-grade NHL showed a long lasting stable PR. We suggest that the higher grade patients with residual or relapsed low grade lymphoma were, in fact, transformed low-grade at diagnosis and, after removing the more aggressive component by chemotherapy, it is possible to manage these patients by conventional therapy for indolent lymphomas.


Value and limitations of computer analysis of digital subtraction angiography in the assessment of coronary flow reserve.
Conventional coronary angiography has significant limitations in quantifying the severity and functional significance of coronary stenoses. However, coronary reactive hyperemia is an excellent physiologic indicator of coronary reserve. Digital subtraction angiography offers the potential to analyze coronary blood flow dynamics quantitatively. Therefore we assessed the accuracy of digital angiographic methods to detect and quantify reductions in coronary flow reserve secondary to stenoses of varying magnitude in an experimental canine preparation. Studies were performed in nine anesthetized open-chest dogs with an electromagnetic flow (EMF) probe and two pneumatic occluders positioned on the left circumflex coronary artery. One occluder served to induce reactive hyperemia by temporary total occlusion, while the other served to produce variable gradations of stenosis. Digital angiography was performed after the subselective injection of contrast under basal conditions and during reactive hyperemia. Time-intensity curves were obtained from digital angiograms for both a coronary and a myocardial region of interest. Measurements included area under the curve, time to peak contrast, and contrast disappearance rate. An index of coronary reserve was computed as the ratio of hyperemic to basal measurements for each of these methods. Coronary blood flow ranged from 6.5 to 142 ml/min, with hyperemic to basal EMF flow ratios of 0.80 to 4.2:1. The index derived from contrast decay rate showed a poor correlation with EMF (r = .34). The correlation between measurements of time to peak myocardial contrast and coronary blood flow was r = .68 (y = 0.16 x + 0.97). The area under the time-intensity curve from a coronary region of interest showed a close correlation with coronary blood flow (y = 0.91 x + 0.1, r = .86). Thus estimates of coronary reserve by computer analysis of digital subtraction angiograms can yield information regarding the physiologic consequences of coronary stenoses.


Physiological Intra-Cytoplasmic Sperm Injection (PICSI) outcomes after oral pretreatment and semen incubation with myo-inositol in oligoasthenoteratozoospermic men: results from a prospective, randomized controlled trial.
The aim of the current study was to evaluate the effect of an oral pretreatment with a mix of myo-inositol (Myo-Ins), folic acid, vitamin E, L-carnitine, L-arginine and selenium (Folandrol, Exeltis, Hungary) and subsequent direct Myo-Ins incubation of spermatozoa before Physiological Intra-Cytoplasmic Sperm Injection (PICSI) procedures in infertile couples due to oligoasthenoteratozoospermia with previous failed PICSI procedures. We performed a prospective, randomized controlled trial at the Assisted Reproduction Unit of the Kaáli Institute (Győr, Hungary). The male partners were randomly assigned to two groups: the first one treated with a myo-Inositol-based supplement (Folandrol®, Exeltis, Hungary) for two months; the second one did not undergo any treatment in the same time range (controls). The semen of the treated group was incubated for 2 h with 2 mg/ml of MI (Andrositol Lab, Lo.Li. Pharma, Rome, Italy) for the PICSI protocol. There was no significant difference for mean female partner age (p = 0.17) and mean previous failed PICSI procedures (p = 0.65) between the two groups. Although there was no significant difference (p = 0.85) regarding the rate of mature oocytes and the fertilization index was significantly higher (p < 0.001) in the treatment group than control group. Also, despite the comparable average number of transferred embryos between the two groups (p = 0.55), in the treatment group there was a significantly higher rate of good quality embryos at day 3 after fertilization (p = 0.001). Finally, 11 pregnancies were obtained only in the treatment group (p = 0.001). The combination of oral supplementation and semen incubation with MI in oligoasthenoteratozoospermic men could improve PICSI outcomes.


Adhesion molecules in CNS disorders: biomarker and therapeutic targets.
Mounting evidence has been provided regarding the crucial role of leukocyte extravasation and subsequent inflammatory response in several central nervous system (CNS) disorders. The infiltrated leukocytes release proinflammatory mediators and activate resident cells, leading to tissue injury. Leukocyte-endothelia interaction is critical for leukocyte extravasation and migration from the intravascular space into the tissue during inflammation. The basic physiology of leukocyte-endothelia interaction has been investigated extensively. Traditionally, three kinds of adhesion molecules, selectin, integrin, and immunoglobulin families, are responsible for this multiple-step interaction. Furthermore, blocking adhesion molecule function by genetic knockout, antagonizing antibodies, or inhibitory pharmacological drugs provides neuroprotection, which is associated with a reduction in leukocyte accumulation within the tissue. Detection of the soluble form of adhesion molecules has also been proven to predict outcomes in CNS disorders. Lately, vascular adhesion protein-1, a novel adhesion molecule and endothelial cell surface enzyme, has been implicated as a brake in the rolling step of the adhesion cascade, and also a regulator of leukocyte transmigration step. In this review, we summarize the functions of traditional adhesion molecules as well as vascular adhesion protein-1in the leukocyte adhesion cascade. We also discuss the diagnostic and therapeutic potential of adhesion molecules in CNS disorders.


Night work, fatigued driving and traffic law: the case of police officers.
Given the well-known difficulties in defining and detecting fatigue, it is a real challenge to incorporate it into either traffic or criminal law. Finnish traffic law forbids fatigued driving "only" on a general level concerning the driver's fitness to drive. We present several comments from Finnish traffic and local police officers regarding their own experiences of driving while fatigued. The comments were extracted from a larger survey of traffic (N=129) and local (N=100) police officers, and prosecutors (N=96). Although the main topic of the survey was the application of the law that forbids fatigued driving, some police officers raised the issue of their own behavior in this respect. We argue that many shift workers, including police officers, break the law, especially when driving home after a night shift.


Sudden death and Wegener's granulomatosis of the pituitary.
Involvement of brain parenchyma or meninges in ANCA-associated small-vessel vasculitis such as Wegener's granulomatosis (WG) is not uncommon. In contrast, involvement of the pituitary is exceedingly rare with only a few cases reported so far. The diagnosis is usually made on the basis of imaging techniques and abnormal pituitary function tests in the setting of active systemic vasculitis. However, histology-proven involvement of the pituitary by WG has not been reported so far. We report a case of WG with histology-proven granulomatous necrotizing inflammation of the pituitary and hypothalamo-pituitary stalk, disclosed at autopsy after the patient had died suddenly and unexpectedly in his sleep. In a setting of histology-proven WG, these findings were regarded as a pituitary manifestation of the disorder. A distinct cause of death could not be found, hence we speculate that hypothalamo-pituitary inflammation due to WG may have caused the sudden death in this patient.


Dynamics in the tomato root transcriptome on infection with the potato cyst nematode Globodera rostochiensis.
Plant parasitic nematodes infect roots and trigger the formation of specialized feeding sites by substantial reprogramming of the developmental process of root cells. In this article, we describe the dynamic changes in the tomato root transcriptome during early interactions with the potato cyst nematode Globodera rostochiensis. Using amplified fragment length polymorphism-based mRNA fingerprinting (cDNA-AFLP), we monitored 17 600 transcript-derived fragments (TDFs) in infected and uninfected tomato roots, 1-14 days after inoculation with nematode larvae. Six hundred and twenty-four TDFs (3.5%) showed significant differential expression on nematode infection. We employed GenEST, a computer program which links gene expression profiles generated by cDNA-AFLP and databases of cDNA sequences, to identify 135 tomato sequences. These sequences were grouped into eight functional categories based on the presence of genes involved in hormone regulation, plant pathogen defence response, cell cycle and cytoskeleton regulation, cell wall modification, cellular signalling, transcriptional regulation, primary metabolism and allocation. The presence of unclassified genes was also taken into consideration. This article describes the responsiveness of numerous tomato genes hitherto uncharacterized during infection with endoparasitic cyst nematodes. The analysis of transcriptome profiles allowed the sequential order of expression to be dissected for many groups of genes and the genes to be connected with the biological processes involved in compatible interactions between the plant and nematode.


The association between Internet addiction and problematic alcohol use in adolescents: the problem behavior model.
This study aimed to a) evaluate the association between Internet addiction and problematic alcohol use; b) based on problem behavior theory, explore whether Internet addiction, as well as problematic alcohol use, correlated with the psychosocial proneness of problem behaviors among adolescents. A total of 2,114 high school students (1,204 male and 910 female) were recruited to complete the questionnaire assessing Internet addiction, problematic alcohol use, and associated psychosocial variables. The result revealed that Internet addiction was associated with problematic alcohol use. Besides, the psychosocial proneness of problem behaviors is associated with Internet addiction as well as problematic alcohol use in adolescents. These results suggest Internet addiction might be included in the organization of problem behavior theory, and it is suggested that prevention and intervention can best be carried out when grouped with other problem behaviors.


Potential role of cholinesterases in the invasive capacity of the freshwater bivalve, Anodonta woodiana (Bivalvia: Unionacea): a comparative study with the indigenous species of the genus, Anodonta sp.
To address the potential role of cholinesterase enzymes in the invasive capacity of species, the present study investigated ChE activity in the invasive freshwater bivalve Anodonta woodiana (Lea, 1834) comparing it with that of the indigenous species, Anodonta sp. (Linnaeus, 1758). The invasive capacity of pests has often been linked to their ecological plasticity and high intrinsic genetic variability; however the role played by molecular and cellular mechanisms, generally known as an organism's response to pollution, is unclear. Different substrates and selective ChE enzyme inhibitors were investigated in digestive gland, foot, gonad, adductor muscle and gill tissues while sensitivity to four organophosphate (OP) insecticides was investigated in vitro only in adductor muscle. The invasive species (A. woodiana) showed significantly greater (at least one order of magnitude) ChE activity than the endemic species (Anodonta sp.) (p<0.05) using acetylthiocholine (ASCh) as substrate and the activity was more widely distributed in tissues involved in movement (adductor muscle and foot), respiration, feeding (gills) and reproduction (gonads). Moreover, only the invasive species, A. woodiana, showed detectable ChE (vs. ASCh) activity in gill tissue. No substrate specificity was observed in any tissue of either species as already described for other bivalve species. ChE activity was not inhibited by Iso-OMPA but showed high sensitivity to BW248c51 and eserine. Both species showed moderate to low sensitivities in vitro to OP insecticides in the range 10(-7)-10(-2) M. Calculated IC(50) for fenitrothion and chlorpyrifos was in the range 10(-6)-10(-3) M in muscle of A. woodiana while a higher inhibition was observed for fenitrothion (10(-7) M) and lower for chlorpyrifos (10(-2) M) in the indigenous species Anodonta sp. Similar IC(50) of 10(-5)-10(-6) M were observed for DFP and azamethiphos in both species. The hypotheses of other authors that acetylcholinesterase (AChE) is involved in the control of many essential functions, such as frontal ciliary activity of gill epithelium, temperature resistance, ciliary activity for transport of suspended particulate, valve opening and embryo development, suggest that the high catalytic efficiency of the invasive species may endow it with a competitive advantage over the endemic species. In view of the peculiar reproductive strategy of these mussels, higher ChE vs. ASCh activity in gonads of the invasive species could also favour glochidium production and embryo development under a wider range of environmental conditions.


laying Farm: Up to Date Data on a Fowlpox Outbreak in Phylogenetic Analysis in Iran, 2018.
Fowlpox is an economically significant viral disease in poultry, characterized by two forms of clinical signs, including cutaneous and diphtheritic lesions. This infection can have several adverse effects on flock performance, such as a reduction in egg production and growth and an increase in mortality. In winter 2018, an infection suspected to fowlpox was reported from a Hy-line W-36 laying farm in Isfahan province, Iran. The birds were 38 weeks of age and showed obvious diphtheritic signs in mucous membranes with increased mortality and reduced egg production. In total, 20 samples were collected from diphtheritic lesions (Trachea and Esophagus) of infected birds. The Polymerase Chain Reaction method was used to amplify a 578 bp fragment of the poxvirus 4b core protein gene. Phylogenetic relationships of avian poxviruses are usually analyzed using the 4b core protein-coding gene sequences with molecular weights of 75.2 kDa. The major elements had the fowlpox genome, and sequencing was performed for one isolate as representative. The nucleotide sequence result showed that this isolate (FP\UT-POX-2018) had a similarity rate of 99.53% with the previous Iranian fowlpox isolate (FP\GHPCRLAB.3) sequenced in the GenBank.Moreover, there was a 100% similarity among the current isolate nucleotide sequence, FP/NobilisVarioleW, and FP/FPV-VR250. The derived phylogenetic tree showed that these isolates were clustered in A1 subclades. Therefore, Iranian isolates of fowlpox virus have remained in the same subclade of phylogenetic classification (subclade A1), and they show high genomic similarity with previous isolates of Iran. Veterinarians and farmers must not underestimate fowlpox. However, they should consider the importance of vaccination against this disease like any other disease care.


Effect of a deep inspiration on expiratory flow in normals and patients with chronic obstructive pulmonary disease.
Normal control subjects and individuals with chronic obstructive pulmonary disease (COPD) were studied by measuring routine lung function tests as well as maximal (MEFV) and partial expiratory flow-volume (PEFV) curves and lung elastic recoil (Pst,L) before and after a total lung capacity (TLC) volume history. In the normal subjects: before bronchodilators airflow increased significantly, whereas Pst,L and upstream segment resistance (Rus) decreased significantly following inspiration to TLC; after administration of inhaled bronchodilators, flow rates were higher on the PEFV than on MEFV curves; nevertheless, because Pst,L decreased substantially following a deep breath, post-bronchodilator Rus was still somewhat reduced by deep inspiration. In the subjects with COPD flow rates on PEFV curves were as high or exceeded flow rates on MEFV curves in 76/100 studies; the ratio of flow rates (PEFV)/flow rates (MEFV) increased as pulmonary function worsened; as in normal subjects, Pst,L diminished in COPD subjects following deep inspiration; although flow rates increased on both PEFV and MEFV curves after bronchodilators, the increments in flow were considerably larger on PEFV maneuvers.


Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation.
Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficiency with severely impaired FAO. Matings between LCAD +/- mice yielded an abnormally low number of LCAD +/- and -/- offspring, indicating frequent gestational loss. LCAD -/- mice that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria. Approximately 10% of adult LCAD -/- males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD -/- mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo.


Conceptually new low-calcemic oxime analogues of the hormone 1 alpha,25-dihydroxyvitamin D(3): synthesis and biological testing.
New chemical entities 16-ene-25-ketone 2b and the corresponding oxime 3b and oxime ether 4b, analogues of natural calcitriol (1), were rationally designed and synthesized on a milligram scale. Chemical introduction of the oxime ether functionality in analogue 4b was successful via direct oximation of an intact vitamin D conjugated triene system. Even though all three analogues are at least as antiproliferative in vitro as calcitriol (1) even at physiologically relevant low nanomolar concentrations, only side chain ketone 2b is more transcriptionally potent than calcitriol (1). Although oxime O-methyl ether 4b lacks the traditional side chain hydrogen bond-donating OH group of the natural hormone and lacks also the oxime-NOH group of analogue 3b, surprisingly, oxime ether 4b retains 20% of the transcriptional potency of natural calcitriol (1). In terms of in vivo toxicity (hypercalcemia), ketone 2b is strongly calcemic in rats, whereas oxime 3b and oxime ether 4b are considerably less calcemic (i.e., safer) than calcitriol (1).


High dose behind inhomogeneities during medium-energy x-ray irradiation.
Medium-energy x-rays from orthovoltage treatment units are used for a variety of radiotherapy treatments ranging from cutaneous malignancies in the head and neck region to bone metastases. It was the aim of the present study to investigate the dose distribution due to secondary electrons close behind inhomogeneities in these radiation qualities. The dose was assessed in a solid water phantom using three plane-parallel ionization chambers (NE 2532/2, 'Markus' and 'Attix' chamber) and sheets of aluminium, copper, zinc, platinum, lead and bone equivalent material. The depth dose distribution directly behind the inhomogeneity was assessed using sheets of 15 microm thick polyethylene foil. A dose increase was found directly behind inhomogeneities of high atomic number with a rapid dose fall-off over the first 100 microm. The dose downstream of the inhomogeneity was found to increase with increasing beam quality from 120 kVp (HVL 2.8 mm Al) to 250 kVp (HVL 2 mm Cu). In the latter the dose was increased directly behind lead and platinum sheets by up to a factor of eight compared with a solid water depth of similar attenuation. The results of the study demonstrate the importance of using appropriate materials if shielding is in contact with the patient.


The effect of the Maryland WIC 5-A-Day promotion program on participants' stages of change for fruit and vegetable consumption.
The Maryland Women, Infants and Children (WIC) 5-A-Day Promotion Program examined the effect of a multifaceted nutrition intervention on changing the fruit and vegetable consumption of low-income women in the WIC program in Maryland. The sample consisted of 3,122 participants (1,443 intervention and 1,679 control) with a mean age of 27.2. Fifty-six percent were Black/African American. This article focuses on the effect of the intervention on the stages of change of the participants. Intervention participants showed significantly greater positive movement through the stages than control participants. Stages of change were measured for two specific target behaviors: eating five servings of fruits and vegetables a day and eating more servings of fruit and vegetables a day. Results demonstrated significant differences in the stage status of intervention and control women and in movement through the stages. The effectiveness of the intervention across groups depended on which staging measure was used.


More than the sum of the parts: forest climate response from joint species distribution models.
The perceived threat of climate change is often evaluated from species distribution models that are fitted to many species independently and then added together. This approach ignores the fact that species are jointly distributed and limit one another. Species respond to the same underlying climatic variables, and the abundance of any one species can be constrained by competition; a large increase in one is inevitably linked to declines of others. Omitting this basic relationship explains why responses modeled independently do not agree with the species richness or basal areas of actual forests. We introduce a joint species distribution modeling approach (JSDM), which is unique in three ways, and apply it to forests of eastern North America. First, it accommodates the joint distribution of species. Second, this joint distribution includes both abundance and presence-absence data. We solve the common issue of large numbers of zeros in abundance data by accommodating zeros in both stem counts and basal area data, i.e., a new approach to zero inflation. Finally, inverse prediction can be applied to the joint distribution of predictions to integrate the role of climate risks across all species and identify geographic areas where communities will change most (in terms of changes in abundance) with climate change. Application to forests in the eastern United States shows that climate can have greatest impact in the Northeast, due to temperature, and in the Upper Midwest, due to temperature and precipitation. Thus, these are the regions experiencing the fastest warming and are also identified as most responsive at this scale.