Evaluation of toluene dependence and cross-sensitization to diazepam.
Acute effects of the abused inhalant toluene resemble those of CNS depressant drugs. Since abuse of toluene involves repeated use, the purpose of the present study was to evaluate the effects of repeated or continuous exposure to toluene and to compare these effects to those of other inhalants and depressants. In experiment 1, ICR mice exposed continuously to 250 ppm toluene via inhalation for four days developed mild dependence upon termination that was characterized by an increase in severity of handling-induced convulsions. However, administration of the convulsants, N-methyl-D-aspartate (NMDA) or pentylenetetrazole (PTZ), did not differentially affect toluene- vs. air-exposed mice. In experiment 2, CFW mice (but not ICR mice) developed cross-sensitization to the initial locomotor stimulatory effects of toluene following four days of injections with 10 mg/kg/day diazepam. Previous findings have shown that 1,1,1-trichloroethane (TCE) produced robust dependence and cross-sensitization to diazepam's locomotor effects when tested under similar conditions. The present results suggest that the dependence and cross-sensitization with diazepam produced by toluene are milder than those induced by TCE. Further, these studies add to increasing evidence that abused inhalants do not have identical pharmacological effects.


Raoultella electrica sp. nov., isolated from anodic biofilms of a glucose-fed microbial fuel cell.
A Gram-stain-negative, non-spore-forming, rod-shaped bacterium, designated strain 1GB(T), was isolated from anodic biofilms of a glucose-fed microbial fuel cell. Strain 1GB(T) was facultatively anaerobic and chemo-organotrophic, having both a respiratory and a fermentative type of metabolism, and utilized a wide variety of sugars as carbon and energy sources. Cells grown aerobically contained Q-8 as the major quinone, but excreted Q-9 and a small amount of Q-10 when cultured with an electrode serving as the sole electron acceptor. The G+C content of the genomic DNA of 1GB(T) was 54.5 mol%. Multilocus sequence typing (MLST) analysis showed that strain 1GB(T) represented a distinct lineage within the genus Raoultella (98.5-99.4 % 16S rRNA gene sequence similarity and 94.0-96.5 % sequence similarity based on the three concatenated housekeeping genes gyrA, rpoB and parC. Strain 1GB(T) exhibited DNA-DNA hybridization relatedness of 7-43 % with type strains of all established species of the genus Raoultella. On the basis of these phenotypic, phylogenetic and genotypic data, the name Raoultella electrica sp. nov. is proposed for strain 1GB(T). The type strain is 1GB(T) ( = NBRC 109676(T) = KCTC 32430(T)).


What Is a Chronic Disease? A Contribution Based on the Secondary Use of 161 Million Discharge Records.
Several definitions of chronic diseases exist. The objective is to reuse a nationwide medical-administrative database (PMSI) to estimate the lifespan of diagnostic codes, hence the chronicity of the corresponding diseases. We analyzed 162 million inpatient stays from 2008 to 2014, and estimate the lifespan of every ICD-10 code for every patient, identified by a unique imprint. We calculated 200 indicators for different time and survival values, and selected the ones that maximized the area under the ROC curve (AUC) drawn by comparison against 4 chronic disease classifications: CCI, ALD, result from the analysis of ICD-10 labels, and a handmade list. The best indicator was the time to reach a survival of 4.5%. It enables to get the following AUC: 78.9% compared with CCI, 90.3% compared with ALD, 75.1% compared with labels analysis, and 91.5% compared with the handmade list. This indicator enables to classify 23,349 ICD-10 codes from "most chronic" to "most acute". The 100 most chronic codes are listed.


Characterization of the gut-liver-muscle axis in cirrhotic patients with sarcopenia.
Sarcopenia is frequent in cirrhosis and is associated with unfavourable outcomes. The role of the gut-liver-muscle axis in this setting has been poorly investigated. The aim of this study was to identify gut microbiota, metabolic and inflammatory signatures associated with sarcopenia in cirrhotic patients. Fifty cirrhotic patients assessed for the presence of sarcopenia by the quantification of muscle mass and strength were compared with age- and sex-matched controls. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, was performed. The gut microbiota of sarcopenic cirrhotic patients was poor in bacteria associated with physical function (Methanobrevibacter, Prevotella and Akkermansia), and was enriched in Eggerthella, a gut microbial marker of frailty. The abundance of potentially pathogenic bacteria, such as Klebsiella, was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levels of pro-inflammatory mediators and of fibroblast growth factor 21 (FGF21) in cirrhotic patients. Gut microbiota metabolic pathways involved in amino acid, protein and branched-chain amino acid metabolism were up-regulated, in addition to ethanol, trimethylamine and dimethylamine production. Correlation networks and clusters of variables associated with sarcopenia were identified, including one centred on Klebsiella/ethanol/FGF21/Eggerthella/Prevotella. Alterations in the gut-liver-muscle axis are associated with sarcopenia in patients with cirrhosis. Detrimental but also compensatory functions are involved in this complex network.


[Non-steroid anti-inflammatory agents and gastrointestinal protection: adequate prescription in primary care?].
To find the frequency of prescription of gastro-intestinal protectors (GIP) at the same time as non-steroidal anti-inflammatory drugs (NSAID). To find certain characteristics linked to their use in primary care. To evaluate how correctly they are prescribed. A crossover descriptive study. A base urban health area. Patients over 14, who attended in 1994, who had a medical history and were treated with NSAID. 1,115 medical histories were obtained by simple randomised sampling, of whom 205 were under treatment with NSAID. A questionnaire was used to evaluate: age, sex, NSAID treatment, GIP, history of peptic ulcer, corticoid or acenocoumarol treatment, tobacco, alcohol and related pathology. After a complete bibliographic review, some criteria were fixed for when it is correct to give GIP-NSAID. The prevalence of NSAID prescription was 18.39%. 34 patients treated with NSAID received GIP at the same time. Aceclophenac was the most widely prescribed NSAID; and H2 antihistamines, the drugs most commonly used as GIP.


Prospective assessment of patients' knowledge and informational needs and of surgeon-to-patient information transfer before and after knee or hip arthroplasty.
Patients are playing an increasingly large role in their own management and must therefore receive clear, complete, and comprehensible information. In the field of hip and knee arthroplasty, little is known about the level of patient knowledge and effectiveness of surgeon-to-patient information transfer. We therefore designed a prospective observational study with the objective of assessing four factors: patient knowledge during management, quality of information transfer, informational needs, and factors associated with the level of knowledge. The level of patient knowledge changes during the management process. A prospective single-centre study was conducted between January 2014 and March 2015 during the outpatient visits and inpatient stays of 63 patients who underwent arthroplasty of the hip (n=36) or knee (n=27). A single observer attended all patient visits and recorded the information provided by the surgeon. Each patient completed a self-questionnaire after the outpatient visit (T1), at admission (T2), and at discharge after surgery (T3). Semi-quantitative scores were used to assess knowledge and informational needs. The effectiveness of information transfer was evaluated by comparing the information provided by the surgeon to the replies made by the patients. The mean overall knowledge score (on a 0-42 scale) increased from 17.22±6.33 at T1 to 19.44±6.89 at T3 (P=0.0028). In contrast, knowledge about complications was better at T1 than at T3 (2.67±1.98 vs. 2.19±1.91; P<0.05). Agreement between information given by the surgeon and replies made by patients varied across items from 23% to 100%. The mean informational needs score (on a scale from 0 to 21) ranged from 3.67 to 4.83 and was higher at T3 than at T2 (4.83±3.77 vs. 3.67±4.86; P=0.03). The proportion of patients who wanted written information was higher at T3. Most patients sought information before the outpatient visit. At each step of the management process, the main areas about which the patients wanted information were the surgical procedure, the rehabilitation programme, and the prosthesis. Several socio-demographic or management-related factors influenced the level of knowledge. Thus, older age and lower educational attainment were associated with lower knowledge scores, whereas previous lower-limb orthopaedic surgery and amount of information provided by the surgeon were associated with higher knowledge scores. Knowledge scores were not associated with being employed vs. retired, gender, replacement of a hip vs. a knee, the surgeon, or being accompanied by another person. Our study is original in that we assessed changes in patient knowledge during the management process for hip or knee arthroplasty. The level of patient knowledge was fairly low and varied considerably across individuals and time points in the management process. These data highlight the importance of providing patients with information throughout their management and particularly at discharge, when the desire for information seems greatest. IV, prospective observational study with no control group.


Horizontal transmission of Nosema ceranae (Microsporidia) from worker honeybees to queens (Apis mellifera).
Horizontal transmission from worker honeybees to queens is confirmed in a laboratory essay as a possible route of Nosema ceranae infection in field colonies and pathological repercussions on honeybee queens are described. Lesions are only detected in the epithelial ventricular layer of the infected queens and death occurs within 3 weeks when the nurse workers are experimentally and collectively infected with approximately 5000 viable spores per bee. These data suggest that the higher number of infected house bees, the higher risk of transmission to queens. The presented data may explain the role of house honeybees in natural queen infection, although it is probably that a high proportion of infected house bees must be required to infect the queen.


Low plasma renalase concentration in hypertensive patients after surgical repair of coarctation of aorta.
The study aimed to evaluate plasma renalase level, a recently discovered kidney-derived catecholamine-metabolizing enzyme in patients after successful repair of aortic coarctation, with special consideration of arterial hypertension in the context of underlying process of arterial remodeling. This case-control study covered 50 consecutive patients after Dacron patch repair of aortic coarctation (31 men; median age 33 [26; 40]; age at surgery 10 [5; 16] years), matched in terms of age and gender with 50 controls. Both groups were stratified depending on the presence of hypertension and assessed in terms of renalase, C-reactive protein, and carotid intima-media thickness. Additionally ultrasound and tonometric markers of vascular remodeling were obtained in the study group. Hypertension was found in 21 patients (42%) in the study group and 29 (58%) in the control group (P = .11). Renalase level was significantly lower in patients in the study than control group (5825.1 vs. 6592.7 ng/mL; P = .041). Significant difference in terms of renalase concentration between hypertensive and normotensive patients was confirmed both in subjects with coarctation of aorta (P = .027) and in control group (P < .0001). Renalase level inversely correlated with serum creatinine (r = -0.36) and arterial blood pressure in the whole population, and with central systolic (r = -0.29) and diastolic pressure (r = -0.35) in study group. Multivariate regression revealed that serum creatinine and pulse pressure were independent predictors of renalase. Surgical intervention >7 years was linked to lower renalase (P = .018) and unfavorable vascular parameters. Renalase level <4958 ng/mL accurately predicted presence of hypertension in patients after coarctation of aorta repair (odds ratio, 3.8; P = .032). Renalase deficiency is associated with the presence of hypertension in both patients after surgical repair of aortic coarctation and the control group. In coarctation of aorta, its action is probably parallel to underlying arterial remodeling.


Expression of a dominant negative I kappa B-alpha modulates hypersensitivity of ataxia telangiectasia fibroblasts to streptonigrin-induced apoptosis.
Ataxia telangiectasia (AT) cells exhibit greater levels of apoptosis than normal fibroblasts following exposure to X-rays or radiomimetic drugs. In this study, we investigated apoptosis in AT cells whose radiation sensitivity has been altered by transfection with a cDNA expressing truncated I kappa B-alpha (delta I kappa B-alpha). delta I kappa B-alpha functions as a dominant negative regulatory protein of NF-kappa B. The transfected cells (ATCL11) were compared to parental cells after treatment with the radiomimetic drug streptonigrin. ATCL11 cells exposed to streptonigrin demonstrated less apoptosis (approximately 2%) at 24 hr than did parental AT cells (approximately 24%). These data indicate that the mechanisms underlying apoptosis induction by streptonigrin are modulated by regulation of NF-kappa B.


Cubic nonlinear squeezing and its decoherence.
Squeezed states of the harmonic oscillator are a common resource in applications of quantum technology. If the noise is suppressed in a nonlinear combination of quadrature operators below threshold for all possible up-to-quadratic Hamiltonians, the quantum states are non-Gaussian and we refer to the noise reduction as nonlinear squeezing. Non-Gaussian aspects of quantum states are often more vulnerable to decoherence due to imperfections appearing in realistic experimental implementations. Therefore, a stability of nonlinear squeezing is essential. We analyze the behavior of quantum states with cubic nonlinear squeezing under loss and dephasing. The properties of nonlinear squeezed states depend on their initial parameters which can be optimized and adjusted to achieve the maximal robustness for the potential applications.


Imaging Features and Interventional Treatment for Liver Injuries and Their Complications.
Liver injury is a common consequence of blunt abdominopelvic trauma. Contrast-enhanced CT allows for the rapid detection and evaluation of liver injury. The treatment strategy for blunt liver injury has shifted from surgical to nonoperative management, which has been widely complemented by interventional management to treat both liver injury and its complications. In this article, we review the major imaging features of liver injury and the role of interventional management for the treatment of liver injury.


Artificial Intelligence-Based Diagnostic Model for Detecting Keratoconus Using Videos of Corneal Force Deformation.
To develop a novel method based on biomechanical parameters calculated from raw corneal dynamic deformation videos to quickly and accurately diagnose keratoconus using machine learning. The keratoconus group was included according to Rabinowitz's criteria, and the normal group included corneal refractive surgery candidates. Independent biomechanical parameters were calculated from dynamic corneal deformation videos. A novel neural network model was trained to diagnose keratoconus. Tenfold cross-validation was performed, and the sample set was divided into a training set for training, a validation set for parameter validation, and a testing set for performance evaluation. External validation was performed to evaluate the model's generalizability. A novel intelligent diagnostic model for keratoconus based on a five-layer feedforward network was constructed by calculating four biomechanical characteristics, including time of the first applanation, deformation amplitude at the highest concavity, central corneal thickness, and radius at the highest concavity. The model was able to diagnose keratoconus with 99.6% accuracy, 99.3% sensitivity, 100% specificity, and 100% precision in the sample set (n = 276), and it achieved an accuracy of 98.7%, sensitivity of 97.4%, specificity of 100%, and precision of 100% in the external validation set (n = 78). In the absence of corneal topographic examination, rapid and accurate diagnosis of keratoconus is possible with the aid of machine learning. Our study provides a new potential approach and sheds light on the diagnosis of keratoconus from a purely corneal biomechanical perspective. Our findings could help improve the diagnosis of keratoconus based on corneal biomechanical properties.


Cystic Fibrosis below the Diaphragm: Abdominal Findings in Adult Patients.
Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in the white population. Mutation of the CF transmembrane conductance regulator gene on chromosome 7 results in production of abnormally viscous mucus and secretions in the lungs of patients with CF. A similar pathologic process occurs in the gastrointestinal tract, pancreas, and hepatobiliary system. Inspissated mucus causes luminal obstruction and resultant clinical and radiologic complications associated with the disease process. Pancreatic involvement can result in exocrine and endocrine insufficiency, pancreatic atrophy, fatty replacement, or lipomatous pseudohypertrophy. Acute and chronic pancreatitis, pancreatic calcification, cysts, and cystosis also occur. Hepatic manifestations include hepatic steatosis, focal biliary and multilobular cirrhosis, and portal hypertension. Biliary complications include cholelithiasis, microgallbladder, and sclerosing cholangitis. The entire digestive tract can be involved. Distal ileal obstruction syndrome, intussusception, appendicitis, chronic constipation, colonic wall thickening, fibrosing colonopathy, pneumatosis intestinalis, gastroesophageal reflux, and peptic ulcer disease have been described. Renal manifestations include nephrolithiasis and secondary amyloidosis. The educational objectives of this review are to reveal the abdominal manifestations of CF to facilitate focused analysis of cross-sectional imaging in adult patients. Life expectancy in patients with CF continues to improve because of a combination of aggressive antibiotic treatment, improved emphasis on nutrition and physiotherapy, and development of promising new CF transmembrane conductance regulator modulators. As lung function and survival improve, extrapulmonary conditions, including hepatic and gastrointestinal malignancy, will be an increasing cause of morbidity and mortality. Awareness of the expected abdominal manifestations of CF may assist radiologists in identifying acute inflammatory or neoplastic conditions. (©)RSNA, 2015.


MiR-223-3p Regulates Autophagy and Inflammation by Targeting ATG16L1 in Fusarium solani-Induced Keratitis.
Increasing evidence suggested that microRNAs (miRs) are implicated in the regulation of the inflammatory response and autophagy in multiple diseases. The present study aimed to explore the effect of miR-223-3p on inflammation and autophagy in fungal keratitis (FK). An FK mouse model was established, and primary corneal stromal cells were isolated by inoculation with Fusarium solani. The expression of miR-223-3p was determined by quantitative RT-PCR. Subsequently, the target gene of miR-223-3p was identified by a dual-luciferase reporter assay. The levels of miR-223-3p were altered by transfecting miR agomir/antagomir to evaluate its effects. Slit-lamp biomicroscopy and hematoxylin and eosin staining were employed to detect corneal damage. The levels of autophagy were assessed by immunofluorescence, Western blotting, mRFP-GFP-LC3 fluorescence microscopy, and electron microscopy. In addition, inflammation was demonstrated by determining the proinflammatory mediators IL-1β and TNF-ɑ. Our data suggested that miR-223-3p was increased and that autophagic flux was impaired in mouse FK. Then, we confirmed that autophagy-related gene 16L1 (ATG16L1) was a potential target of miR-223-3p and that this miR negatively regulated the expression of ATG16L1. The inhibition of miR-223-3p attenuated inflammation in FK, reduced P62 expression, and increased the ratio of LC3-II/LC3-I, whereas the overexpression of miR-223-3p displayed the opposite results. Taken together, miR-223-3p might regulate autophagy via targeting ATG16L1 in experimental F. solani keratitis and is associated with the inflammatory response. MiR-223-3p might be a potential therapeutic target for FK.


Curcumin abolishes mutant TDP-43 induced excitability in a motoneuron-like cellular model of ALS.
Mutation of TAR DNA-binding protein-43 (TDP-43) is detected in familial and sporadic amyotrophic lateral sclerosis (FALS and SALS). TDP-43-positive cytoplasmic inclusions are present in both neuron and glia of ALS, although not in mutant Cu/Zn-superoxide dismutase (mSOD1)-related or RNA binding protein Fused in sarcoma (FUS)-related ALS. Previous studies have established that cortical hyper-excitability is common to both FALS and SALS patients. Much of our current understanding of neuron excitability has come from studying the subtype of mSOD1-related ALS. Thus, we evaluated the excitable capability through analyzing properties of action potentials (APs) and voltage-gated sodium (Nav) channels on the cellular model, motoneuron-like cell lines that were steadily transfected with mutant Q331K and wild-type TDP-43. We found that wild-type TDP-43 increased firing frequency of APs, but the presence of mutant Q331K TDP-43 enhanced firing frequency and decreased the threshold of APs to a higher level. Further, we observed that mutant Q331K and wild-type TDP-43 induced more rapid speed of recovery from fast and slow inactivation of Nav channels and resulted in a reduction of voltage dependency of slow inactivation. These results provide evidence for high excitability that resulted from the presence of mutant and wild-type TDP-43, and more toxicity of mutant TDP-43 than wild-type. Other studies suggest that Nav channel activity can be increased directly by different oxidative species and, we have shown previously that oxidative stress and mitochondrial dysfunction occurs simultaneously in the cellular model of mutant TDP-43 and can be ameliorated by dimethoxy curcumin (DMC), a safe and effective antioxidant. In the present study we found that the abnormities of APs and Nav channels were significantly ameliorated when treated with DMC (15μM) for 24h, suggesting a dropping-excitability state. Taken together, mutant Q331K TDP-43 induces high excitability in a motoneuron-like cellular model, and this abnormal state is rescued by DMC which may act through alleviation of oxidative stress and mitochondrial dysfunction.


Effects of end-capped acceptors subject to subtle structural changes on solution-processable small molecules for organic solar cells.
Self-assembly is crucial for small molecular organic solar cells, which are extremely sensitive to the molecular structure. In this work, three subtle structural changed end-capped acceptors with increased electron withdrawing ability, named octyl 2-cyanoacetate (=CNCOOC8H17), 3-oxoundecanenitrile (=CNCOC8H17), and 2-(octylsulfonyl) acetonitrile (=CNSOOC8H17), were synthesized and introduced into a planar conjugated backbone using ethylhexyl-thiophene substituted benzodithiophene (TBDT) as a core and trithiophene as a π-bridge (labelled M1, M2 and M3, respectively). Their effects on absorption, thermal properties, and morphologies were studied and compared. In particular, the molecular packing of the three materials varied significantly, and the hole mobilities differed by orders of magnitude. As a result, the fill factors of devices varied from 52% to 72%. Combining the effects of electron-withdrawing capability and molecular packing, the power conversion efficiencies of the optimized devices increased from 3.0% for M3 to 6.4% for M1 and M2. The relationship between end-capped acceptors and photovoltaic properties would generate valuable insights into further producing more efficient solution-processable organic solar cells.


Neuropsychiatric disorders associated with streptococcal infection: a case-control study among privately insured children.
To assess whether antecedent streptococcal infection(s) increase the risk of subsequent diagnosis of obsessive-compulsive disorder (OCD), Tourette syndrome (TS), other tic disorders, attention-deficit/hyperactivity disorder (ADHD), or major depressive disorder (MDD) in a national sample of privately insured children. Using health insurance claims data, we compared the prior year's occurrence of streptococcal infection in children ages 4 to 13 years with OCD, TS, or tic disorder newly diagnosed between January 1998 and December 2004 to that of a cohort of matched controls. Conditional logistic regression models were used to determine the association of prior streptococcal sore throat or scarlet fever with a diagnosis of OCD, TS, or tic disorder. We repeated the analyses for two other infectious diseases (otitis media and sinusitis) and one noninfectious condition (migraine). We also investigated the potential specificity of this association by performing similar analyses focused on newly diagnosed ADHD and newly diagnosed MDD. Subjects with newly diagnosed OCD, TS, or tic disorder were more likely than controls to have had a diagnosis of streptococcal infection in the previous year (odds ratio 1.54, 95% confidence interval 1.29-2.15). Prior streptococcal infection was also associated with incident diagnoses of ADHD (odds ratio 1.20, 95% confidence interval 1.06-1.35) and MDD (odds ratio 1.63, 95% confidence interval 1.12-2.30). These findings provide epidemiologic evidence that some pediatric-onset neuropsychiatric disorders, including OCD, tic disorders, ADHD, and MDD, may be temporally related to prior streptococcal infections. Whether this is the result of a nonspecific stress response or secondary to an activation of the immune system remains to be determined.


Magnesium Signaling in Plants.
Free magnesium (Mg2+) is a signal of the adenylate (ATP+ADP+AMP) status in the cells. It results from the equilibrium of adenylate kinase (AK), which uses Mg-chelated and Mg-free adenylates as substrates in both directions of its reaction. The AK-mediated primary control of intracellular [Mg2+] is finely interwoven with the operation of membrane-bound adenylate- and Mg2+-translocators, which in a given compartment control the supply of free adenylates and Mg2+ for the AK-mediated equilibration. As a result, [Mg2+] itself varies both between and within the compartments, depending on their energetic status and environmental clues. Other key nucleotide-utilizing/producing enzymes (e.g., nucleoside diphosphate kinase) may also be involved in fine-tuning of the intracellular [Mg2+]. Changes in [Mg2+] regulate activities of myriads of Mg-utilizing/requiring enzymes, affecting metabolism under both normal and stress conditions, and impacting photosynthetic performance, respiration, phloem loading and other processes. In compartments controlled by AK equilibrium (cytosol, chloroplasts, mitochondria, nucleus), the intracellular [Mg2+] can be calculated from total adenylate contents, based on the dependence of the apparent equilibrium constant of AK on [Mg2+]. Magnesium signaling, reflecting cellular adenylate status, is likely widespread in all eukaryotic and prokaryotic organisms, due simply to the omnipresent nature of AK and to its involvement in adenylate equilibration.


Clinical predictors of severe malarial anaemia in a holoendemic Plasmodium falciparum transmission area.
Severe malarial anaemia (SMA) is a common complication of Plasmodium falciparum infections, resulting in mortality rates that may exceed 30% in paediatric populations residing in holoendemic transmission areas. One strategy for reducing the morbidity and mortality associated with SMA is to identify clinical predictors that can be readily recognized by caregivers for prompt therapeutic interventions. To determine clinical predictors of SMA, Kenyan children (3-36 months, n = 671) presenting with acute illness at a rural hospital in Siaya District were recruited. Demographic, clinical, laboratory and haematological parameters were measured upon enrolment. As human immunodeficiency virus-1 and bacteraemia promote reduced haemoglobin (Hb) concentrations, children with these infections were excluded from the analyses. Children with P. falciparum mono-infections (n = 355) were stratified into three groups: uncomplicated malaria (Hb >or= 110 g/l); non-SMA (60 <or= Hb < 109), and SMA (Hb < 60 g/l). SMA was characterized by a younger age, monocytosis, thrombocytopenia, reticulocytosis, reduced erythropoiesis, elevated pigment-containing monocytes (PCM), respiratory distress, conjunctival and palmar pallor, splenomegaly, signs of malnutrition, and protracted fever and emesis. Logistic regression analysis demonstrated that age, reticulocyte count, presence of PCM and conjunctival and palmar pallor were significant predictors of SMA. Recognition of these clinical signs in children residing in resource-poor settings may help to guide the identification and management of SMA.


[Clinical aspects and diagnosis of metastatic pericarditis in cancer patients].
Metastatic pericarditis was identified in 74 out of 240 cancer patients suffering from secondary tumor lesions in the heart (30.8%). It involved quick accumulation of exudate which led to grave heart failure due to cardiac tamponade development in 39%. Liquid in the heart sac was detected by X-rays in 20, ECG-39, and echocardiography--in 83% of patients. Application of echocardiography provides a means for ascertaining the extent of pericardial involvement and monitoring changes in tumor process occurring in the course of therapy.


Tuning of Kalman filter parameters via genetic algorithm for state-of-charge estimation in battery management system.
In this work, a state-space battery model is derived mathematically to estimate the state-of-charge (SoC) of a battery system. Subsequently, Kalman filter (KF) is applied to predict the dynamical behavior of the battery model. Results show an accurate prediction as the accumulated error, in terms of root-mean-square (RMS), is a very small value. From this work, it is found that different sets of Q and R values (KF's parameters) can be applied for better performance and hence lower RMS error. This is the motivation for the application of a metaheuristic algorithm. Hence, the result is further improved by applying a genetic algorithm (GA) to tune Q and R parameters of the KF. In an online application, a GA can be applied to obtain the optimal parameters of the KF before its application to a real plant (system). This simply means that the instantaneous response of the KF is not affected by the time consuming GA as this approach is applied only once to obtain the optimal parameters. The relevant workable MATLAB source codes are given in the appendix to ease future work and analysis in this area.


The evaluation of the inverted supinator reflex in asymptomatic patients.
A prospective study was undertaken over a 6-month period to determine the incidence of the inverted supinator reflex in asymptomatic, neurologically normal individuals. The objective of our study is to assess asymptomatic patients for the presence of the inverted radial reflex and to determine its clinical relevance. The inverted radial reflex sign is commonly used in clinical practice to assess cervical myelopathy. It is unknown whether the sign correlates with the presence or severity of myelopathy, and no consensus exists regarding the significance of a positive sign in asymptomatic individuals. Patients attending the Trauma Clinic at our institution were invited to participate. Each patient was examined neurologically and specifically for the presence or absence of the Babinski test, Hoffman's sign, the finger escape sign, static and dynamic Romberg's test, and the inverted supinator reflex. Patients were excluded if they had any history of neck pain, any history of neurosurgical procedure or spinal surgery, any known neurologic disorder or deficit, or if there was any outstanding medicolegal case. We examined 277 patients in 6-month period. The male to female ratio was 1.1:1. The mean age was 27 years (range, 16-78). The incidence of the inverted supinator reflex was 27.6% (75/271). Of the 75 positive patients, the inverted supinator reflex was present bilaterally in 39% (29/75). Nine of 75 patients (10%) had an associated positive Hoffman's sign but had no other signs suggestive of myelopathy. The proportion of patients with a positive inverted supinator reflex reduced with increasing age (Pearson correlation coefficient > 0.80). This study demonstrates that an isolated, inverted supinator reflex may be a variation of normal clinical examination. We believe that an isolated inverted supinator reflex, in the absence of other clinical findings, is not a reliable sign of cervical myelopathy; however, it must be interpreted with caution in the older patient.


Effect of isotonic and isokinetic exercise on muscle activity and balance of the ankle joint.
[Purpose] This study was performed to examine how the balance of lower limbs and the muscle activities of the tibialis anterior (TA), the medial gastrocnemius (GCM), and the peroneus longus (PL) are influenced by isotonic and isokinetic exercise of the ankle joint. [Subjects] The subjects of this study were healthy adults (n=20), and they were divided into two groups (isotonic=10, isokinetic=10). [Methods] Isotonic group performed 3 sets of 10 contractions at 50% of MVIC and Isokinetic group performed 3 sets of 60°/sec. Muscle activity was measured by EMG and balance was measured by one-leg standing test. [Results] For muscle activity, a main effect of group was found in the non-dominant TA, and the dominant TA, GCM and PL. For balance, a main effect of time was found in both groups for the sway area measured support was provided by the non-dominant side. [Conclusion] In terms of muscle activity, the two groups showed a significant difference, and the isokinetic group showed higher muscle activities. In terms of balance, there was a significant difference between the pre-test and the post-test. The results of this study may help in the selection of exercises for physical therapy, because they show that muscle activity and balance vary according to the type of exercise.


[The input of the chemical potential gradient of the water in the medium to the energy balance of terrestrial vascular plants].
One of the characteristic feature of activity of plant organism vital functions is a speed of its inner water flow. The main source of energy providing the transport of water is gradient of water chemical potential between soil and atmosphere. In case of equal potentials of these surroundings, the plant organism have additional energetic expenses to compensate the energy of external source. Series of experiments to investigate the influence of saturation of atmosphere with water (equilibrium of potentials) to energetic balance of plant were carried out. The results shows that: 1) etiolate seedlings in this conditions waste 10-15 percent energy per unit of new formation more than under 70-80 percent humidity; 2) saturation of atmosphere with water above plants with well developed transpiration surface leads to the decrease in their heat content; 3) equilibrium of water chemical potentials of different environments increases the intensity of intact root transpiration, i.e. intensifies "the burning" of organic matter. Thus, gradient of water chemical potential existing in nature between environments of different organs if sufficient source of energy for a plant.


[Morphologic characteristics of secondary tubulointerstitial nephritis in humans and in rabbit experiments].
Tubulo-stromal relationships were studied in rabbit and human kidneys in secondary tubulo-interstitial nephritis (TIN) of immune genesis to establish the species differences in the course and manifestations of this disease. TIN of rabbits was studied on the model of serum disease (13 animals) and in humans on renal biopsies from patients with mesangioproliferative GN (22 cases). The correlation of relative volumes of tubule structural elements characteristic for each species undergoes changes when pathologic process develops; new correlations are similar in both humans and rabbits, although the time of involvement of tubular part of nephron into the pathologic process is different. Immunohistochemically and electron-microscopically a diffuse character of the damage is shown.


ABCB1 (MDR1) polymorphisms and antidepressant response in geriatric depression.
Variation in the ATP-binding cassette, subfamily B, member 1 transporter (ABCB1) (multidrug-resistance gene 1) gene has been investigated as a predictor of response to treatment with a variety of medications such as antiarrhythmics, chemotherapeutic agents, anti-HIV medications, and some psychotropics. The ABCB1 gene product, P-glycoprotein, affects the transport of drugs out of many cell types, including endothelial cells at the blood-brain barrier. We sought to determine if ABCB1 polymorphisms predict response to antidepressant treatment in geriatric patients. We compared the effects of ABCB1 genetic variation on the therapeutic response to paroxetine, a P-glycoprotein substrate, and to mirtazapine, which is not thought to be transported by ABCB1, in a sample of 246 elderly patients with major depression treated in a clinical trial setting. A total of 15 single nucleotide polymorphisms in the ABCB1 gene were assessed in each patient. Two of these ABCB1 single nucleotide polymorphisms were earlier reported to predict treatment response in patients prescribed with P-glycoprotein substrate antidepressants. The two earlier identified ABCB1 markers for antidepressant response predicted time to remission in our paroxetine-treated patients, but not in the mirtazapine-treated patients. These results replicate the published findings of others. If a Bonferroni correction for type I error is made, our results do not reach the criteria for statistical significance. However, the Bonferroni correction may be too conservative given the strong linkage disequilibrium among some of the markers and our aim to replicate the earlier published findings. Our study provides confirmation that certain ABCB1 polymorphisms predict response to substrate medications in geriatric patients.


Does a Large (>24 mm) Follicle Yield a Competent Oocyte/Embryo?
To evaluate the effect of large follicular size (≥24 mm) at day of oocyte retrieval on oocyte/embryo quality. A cohort study was conducted in a single tertiary medical center between July 2018 and May 2019. Before ultrasound-guided follicular aspiration, follicles were measured and divided into 2 groups according to their maximal dimensional size: large: ≥24 mm and normal: <24 mm. Microscopic examination of the follicular aspirates was performed by an embryologist. Each follicle aspirated was evaluated for oocyte maturation, oocyte fertilization, and embryo quality. 428 follicles were measured, including 383 (62.81%) in the normal and 45 (14.06%) in the large follicle groups. Oocytes were achieved during aspiration from 297 (75.5%) and 29 (64.4%) of the normal and large follicle groups, respectively (p = 0.05). No in-between group differences were observed in mature oocyte (MII), fertilization, and top-quality embryo (TQE) rates. Nevertheless, once a zygote (2PN) was achieved, a trend toward a higher TQE rate/2PN was found in the large follicle group (16/19 [84.2%] vs. 115/171 [67.3%]; p = 0.062). While a nonsignificant decrease in oocyte recovery rate was found in follicles ≥24 mm, the zygote and TQE per follicle were comparable.


Risperidone effects in the presence/absence of psychostimulant medicine in children with ADHD, other disruptive behavior disorders, and subaverage IQ.
The aim of this study was to examine the safety and efficacy of risperidone, with or without concomitant psychostimulant use, in the treatment of children with conduct disorder (CD) or other disruptive behavior disorders [oppositional defiant disorder (ODD), disruptive behavior disorder-not otherwise specified (DBD-NOS)], and comorbid attention-deficit hyperactivity disorder (ADHD). Data from two 6-week placebo-controlled trials assessing risperidone therapy in children with subaverage IQs and CD, ODD, DBD-NOS were combined, and patients with comorbid ADHD were selected for this post hoc analysis. Patients were grouped according to randomized drug therapy (risperidone or placebo), and then subgrouped according to their use of a concomitant psychostimulant. Safety outcomes included adverse events and weight change, while efficacy outcomes included changes in scores on disruptive behavior and hyperactivity-based subscales of two behavior-rating instruments (Nisonger Child Behavior Rating Form and the Aberrant Behavior Checklist). The analysis included 155 of 208 originally tested children divided into four sub-groups (35-43 patients each). There was no significant difference in the frequency of adverse events in patients who received risperidone alone and those who received risperidone plus a stimulant. The most common adverse events in risperidone-treated patients were somnolence, headache, dyspepsia, rhinitis, and vomiting. Within each randomized treatment group, actual weight gain was comparable, regardless of concomitant stimulant use. Risperidone-treated patients had clinically and statistically significant reductions in both disruptive behavior and hyperactivity subscale scores, compared to placebo, regardless of concomitant stimulant use. The addition of risperidone to a psychostimulant resulted in significantly better control of hyperactivity (p < 0.001) than was achieved with stimulant treatment alone, without causing an increase in adverse events. Risperidone was a safe and effective treatment, with or without a combined psychostimulant, for both disruptive behavior disorders and comorbid ADHD in children.


Intrapleural Fibrinolysis for the Treatment of Indwelling Pleural Catheter-Related Symptomatic Loculations: A Multicenter Observational Study.
Indwelling pleural catheters (IPCs) are an effective option in the management of malignant pleural effusion. Up to 14% of patients with IPCs develop symptomatic pleural loculations causing ineffective fluid drainage and breathlessness. To our knowledge, this is the first study to describe intrapleural fibrinolytic therapy for IPC-related symptomatic loculations. All patients who received intrapleural fibrinolytic therapy for symptomatic loculations between January 1, 2002, and June 30, 2014, in four established IPC centers were retrospectively included. Patient outcomes, treatment effectiveness, and adverse events were recorded. Sixty-six patients (mean age, 64.7 ± 14.2 years; 52% women) were included. Lung cancer (31.3%) and malignant pleural mesothelioma (20.3%) were the most common malignancies. Fibrinolytic instillation was performed in outpatient (61%) and inpatient settings. Tissue-plasminogen activator (n = 52), urokinase (n = 12), and streptokinase (n = 2) were used. The majority (69.7%) received only one fibrinolytic dose (range, one to six). Pleural fluid drainage increased in 93% of patients, and dyspnea improved in 83% following therapy. The median cumulative pleural fluid volume drained at 24 h posttreatment was 500 mL (interquartile range 300-1,034 mL). The area of opacity caused by pleural effusion on chest radiograph decreased from (mean, SD) 52% (14%) to 31% (21%) of the hemithorax (n = 13; P = .001). There were two cases of nonfatal pleural bleed (3%). Intrapleural fibrinolytic therapy can improve pleural fluid drainage and symptoms in selected patients with IPC and symptomatic loculation, but it carries a small risk of pleural bleeding. There is significant heterogeneity in its use currently, and further studies are needed to determine patient selection and optimal dosing regimen and to define its safety profile.


Clinical Factors Associated with Lamina Cribrosa Thickness in Patients with Glaucoma, as Measured with Swept Source Optical Coherence Tomography.
To investigate the influence of various risk factors on thinning of the lamina cribrosa (LC), as measured with swept-source optical coherence tomography (SS-OCT; Topcon). This retrospective study comprised 150 eyes of 150 patients: 22 normal subjects, 28 preperimetric glaucoma (PPG) patients, and 100 open-angle glaucoma patients. Average LC thickness was determined in a 3 x 3 mm cube scan of the optic disc, over which a 4 x 4 grid of 16 points was superimposed (interpoint distance: 175 μm), centered on the circular Bruch's membrane opening. The borders of the LC were defined as the visible limits of the LC pores. The correlation of LC thickness with Humphrey field analyzer-measured mean deviation (MD; SITA standard 24-2), circumpapillary retinal nerve fiber layer thickness (cpRNFLT), the vertical cup-to-disc (C/D) ratio, and tissue mean blur rate (MBR) was determined with Spearman's rank correlation coefficient. The relationship of LC thickness with age, axial length, intraocular pressure (IOP), MD, the vertical C/D ratio, central corneal thickness (CCT), and tissue MBR was determined with multiple regression analysis. Average LC thickness and the correlation between LC thickness and MD were compared in patients with the glaucomatous enlargement (GE) optic disc type and those with non-GE disc types, as classified with Nicolela's method. We found that average LC thickness in the 16 grid points was significantly associated with overall LC thickness (r = 0.77, P < 0.001). The measurement time for this area was 12.4 ± 2.4 minutes. Average LC thickness in this area had a correlation coefficient of 0.57 with cpRNFLT (P < 0.001) and 0.46 (P < 0.001) with MD. Average LC thickness differed significantly between the groups (normal: 268 ± 23 μm, PPG: 248 ± 13 μm, OAG: 233 ± 20 μm). Multiple regression analysis showed that MD (β = 0.29, P = 0.013), vertical C/D ratio (β = -0.25, P = 0.020) and tissue MBR (β = 0.20, P = 0.034) were independent variables significantly affecting LC thickness, but age, axial length, IOP, and CCT were not. LC thickness was significantly lower in the GE patients (233.9 ± 17.3 μm) than the non-GE patients (243.6 ± 19.5 μm, P = 0.040). The correlation coefficient between MD and LC thickness was 0.58 (P < 0.001) in the GE patients and 0.39 (P = 0.013) in the non-GE patients. Cupping formation and tissue blood flow were independently correlated to LC thinning. Glaucoma patients with the GE disc type, who predominantly have large cupping, had lower LC thickness even with similar glaucoma severity.


Hepatotoxicity associated with protease inhibitor-based antiretroviral regimens with or without concurrent ritonavir.
To determine the incidence of significant liver enzyme elevations following the initiation of protease inhibitor (PI)-based antiretroviral therapy (ART) with or without pharmacokinetic boosting with ritonavir (RTV), and to define the role of chronic viral hepatitis in its development. Prospective, cohort analysis of 1161 PI-naive, HIV-infected patients receiving RTV-boosted (lopinavir, indinavir and saquinavir) and unboosted PI-based ART (indinavir, nelfinavir) that had at least one liver enzyme measurement before and during therapy. The incidence of grade 3 and 4 liver enzyme elevations among persons with and without hepatitis B and/or C co-infection treated with PI-based ART were compared. Severe hepatotoxicity was defined as an increase in serum liver enzyme >/= 5-times the upper limit of the normal range or 3.5-times an elevated baseline level. The incidence of grade 3 or 4 elevations among PI-naive patients was: nelfinavir, 11%; lopinavir/RTV (200 mg/day), 9%; indinavir, 13%; indinavir/RTV (200-400 mg/day), 12.8%; and saquinavir/RTV (800 mg/day), 17.2%. The risk was significantly greater among persons with chronic viral hepatitis (63% of cases); however, the majority of hepatitis C virus (HCV)-infected patients treated with nelfinavir (84%), saquinavir/RTV (74%), indinavir, 86%, indinavir/RTV (90%) or lopinavir/RTV (87%) did not develop hepatotoxicity. Our data suggest that the lopinavir/RTV is not associated with a significantly increased risk of hepatotoxity among HCV-infected and uninfected patients compared with an alternative PI-based regimen, nelfinavir. Accordingly, other medication-related factors (e.g, efficacy and non-hepatic toxicity) should guide individual treatment decisions.


A comparison of the discriminative stimulus effects of delta(9)-tetrahydrocannabinol and O-1812, a potent and metabolically stable anandamide analog, in rats.
Efforts to determine whether Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and anandamide elicit similar discriminative stimulus effects have yielded conflicting results. The difficulty in establishing a discriminative cue to anandamide may be due to its metabolic instability. Rats were trained to discriminate either Delta(9)-THC or O-1812, a metabolically stable anandamide analog, from vehicle to avoid this issue. O-1812 and Delta(9)-THC substituted for each other; however, both drugs were more potent in the O-1812-trained rats. Further, O-1812 only substituted for Delta(9)-THC at response rate decreasing doses. The CB(1) antagonist, SR141716A, blocked the discriminative stimulus effects of both drugs but augmented their rate effects. O-1839, a VR(1) agonist, failed to substitute for either cannabinoid. These results suggest that the discriminative stimulus effects of Delta(9)-THC and O-1812 are similar, but subtle differences also exist.


Detection of viruses and virus-like particles in four species of wild and farmed bivalve molluscs in Alaska, U.S.A., from 1987 to 2009.
The U.S. Alaska Department of Fish and Game has regulatory oversight of the mariculture industry that is partially administered through a statewide shellfish health policy. Possession and transport of bivalve molluscs require development of indigenous pathogen histories from diagnostic examinations of wild and farmed populations. These examinations have resulted in the detection of various infectious agents and parasites including viruses: an aquareovirus and aquabirna-like virus isolated by fish cell culture, and papilloma- or polyoma- and herpes-like virus particles within bivalve cell intranuclear inclusion bodies observed by electron microscopy. This study summarizes these results in samples examined from 1987 to 2009 and is the first description of poikilothermic viruses from Alaskan waters isolated from or observed within the tissues of 4 species of bivalve molluscs: geoduck clam Panope abrupta, native littleneck clam Protothaca staminea, purple-hinged rock scallop Crassadoma gigantea and Pacific oyster Crassostrea gigas.


Cross-cultural adaptation of the Maltreatment and Abuse Chronology of Exposure (MACE) scale to Brazilian Portuguese.
There is strong evidence to indicate that childhood maltreatment can negatively affect both physical and mental health and there is increasing interest in understanding the occurrence and consequences of such experiences. While several tools have been developed to retrospectively investigate childhood maltreatment experiences, most of them do not investigate the experience of witnessing family violence during childhood or bullying exposure. Moreover, the majority of scales do not identify when these experiences may have occurred, who was involved or the feelings evoked, such as helplessness or terror. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was developed to overcome these limitations. In view of the improvements over previous self-report instruments that this new tool offers and of the small number of self-report questionnaires for childhood maltreatment assessment available in Brazil, this study was conducted to conduct cross-cultural adaptation of the MACE scale for Brazilian Portuguese. The following steps were performed: translation, back-translation, committee review for semantic and conceptual evaluation, and acceptability trial for equivalence. Semantic and structural changes were made to the interview to adapt it for the Brazilian culture and all 75 of the items that comprise the longer version of MACE were translated. The results of the acceptability trial suggest that the items are comprehensible. The MACE scales may be useful tools for investigation of childhood maltreatment and make a valuable contribution to research in Brazil. Future studies should consider testing the availability and reliability of the three versions of the instrument translated into Brazilian Portuguese.


The conserved portion of the putative virulence region contributes to virulence of avian pathogenic Escherichia coli.
Colibacillosis is a common systemic disease of worldwide economic importance in poultry, caused by Escherichia coli. E. coli are normally found in the intestines of poultry, but some strains are able to cause extraintestinal disease. Plasmid pVM01 is essential for virulence in avian pathogenic Escherichia coli (APEC) strain E3 in chickens after aerosol exposure and contains the virulence-associated genes iucA, iss and tsh in distinct regions. The determination of the complete sequence of this plasmid identified many ORFs that were highly similar to genes found in the APEC O1 plasmid, as well as many hypothetical ORFs. Truncated versions of pVM01 were constructed and introduced into avirulent APEC strain E3/2.4 and the pathogenicity of these strains was assessed by aerosol exposure. The function of the region of pVM01 that contains the genes for conjugation was confirmed. Strains carrying the truncated plasmids appeared to be of intermediate virulence compared to the wild-type APEC strain E3. The conserved portion of the putative virulence region was found to contribute to the colonization of and generation of lesions in the air sacs. Both the conserved and variable portions of the putative virulence region were shown to contribute to the colonization of the trachea, but the variable portion of the putative virulence region was not required for the strain to confer a virulent phenotype. These results reveal that deletion of the conserved portion of the putative virulence region, but not the variable portion of the putative virulence region, is associated with a decrease in virulence of APEC.


A mild form of adenylosuccinate lyase deficiency in absence of typical brain MRI features diagnosed by whole exome sequencing.
Adenylosuccinate lyase (ADSL) deficiency is a defect of purine metabolism affecting purinosome assembly and reducing metabolite fluxes through purine de novo synthesis and purine nucleotide recycling pathways. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The most severe form is characterized by neonatal encephalopathy, absence of spontaneous movement, respiratory failure, intractable seizures, and early death within the first weeks of life. More commonly, ADSL presents purely neurologic clinical picture characterized by severe psychomotor retardation, microcephaly, early onset of seizures, and autistic features (type I) or a more slowly progressing form with later onset, and major features including slight to moderate psychomotor retardation, and transient contact disturbances (type II). Diagnostic markers are the presence of succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (SAdo) in extracellular fluids. ADSL is a rare disorder, although its prevalence remains unknown. Of note, the wide range of essentially nonspecific manifestations and lack of awareness of the condition often prevent diagnosis. We present here the case of particularly mild, late onset ADSL that has been unsuccessfully investigated until whole exome sequencing (WES) was performed. Besides emphasizing the valuable diagnostic value of WES, this report provides new data further documenting the relatively wide clinical manifestation of ADSL.


Mutational analysis of K28 preprotoxin processing in the yeast Saccharomyces cerevisiae.
K28 killer strains of Saccharomyces cerevisiae are permanently infected with a cytoplasmic persisting dsRNA virus encoding a secreted alpha/beta heterodimeric protein toxin that kills sensitive cells by cell-cycle arrest and inhibition of DNA synthesis. In vivo processing of the 345 aa toxin precursor (preprotoxin; pptox) involves multiple internal and carboxy-terminal cleavage events by the prohormone convertases Kex2p and Kex1p. By site-directed mutagenesis of the preprotoxin gene and phenotypic analysis of its in vivo effects it is now demonstrated that secretion of a biological active virus toxin requires signal peptidase cleavage after Gly(36) and Kex2p-mediated processing at the alpha subunit N terminus (after Glu-Arg(49)), the alpha subunit C terminus (after Ser-Arg(149)) and at the beta subunit N terminus (after Lys-Arg(245)). The mature C terminus of the beta subunit is trimmed by Kex1p, which removes the terminal Arg(345) residue, thus uncovering the toxin's endoplasmic reticulum targeting signal (HDEL) which--in a sensitive target cell--is essential for retrograde toxin transport. Interestingly, both toxin subunits are covalently linked by a single disulfide bond between alpha-Cys(56) and beta-Cys(340), and expression of a mutant toxin in which beta-Cys(340) had been replaced by Ser(340) resulted in the secretion of a non-toxic alpha/beta heterodimer that is blocked in retrograde transport and incapable of entering the yeast cell cytosol, indicating that one important in vivo function of beta-Cys(340) might be to ensure accessibility of the toxin's beta subunit C terminus to the HDEL receptor of the target cell.


Antioxidant Properties and Oxidative Transformation of Different Chromone Derivatives.
Nowadays, there is an increase in the application of natural products for the prevention of different disorders or adjuvant substances next to pharmacological treatment. Phytochemicals include different chromone derivatives, which possess a wide spectrum of biological activity. The aim of the present study was the investigation of the antioxidant activity, cytotoxicity and oxidative transformation of nine chromone derivatives. First, we investigated the radical scavenging activity (ABTS), the oxygen radical absorption capacity (ORAC) and the ferric reducing antioxidant power (FRAP) of the investigated molecules. The cytotoxic effects of the compounds were tested on H9c2 cell cultures by the MTT assay. Each compound showed a significant ORAC value compared to the reference. However, the compound 865 possess significantly higher FRAP and ABTS activity in comparison with the reference and other tested molecules, respectively. Based on these assays, the compound 865 was selected for further analysis. In these experiments, we investigated the oxidative metabolism of the compound in vitro. The molecule was oxidized by the Fenton reaction, artificial porphyrin and electrochemistry; then, the formed products were identified by mass spectrometry. Four possible metabolites were detected. The results revealed the compound 865 to possess good antioxidant properties and to be stable metabolically; hence, it is worth investigating its effects in vivo.


Cerebrovascular Biology and the various neural barriers: challenges and future directions.
DESPITE MAJOR ADVANCES in neuroscience, potential therapeutic options for the treatment of central nervous system diseases often cannot be optimized secondary to the presence of the blood-brain barrier (BBB). During the next decade of inquiry, it is crucial that basic science and clinical research that is focused on overcoming the BBB, to optimize delivery to the central nervous system, be identified and supported as a priority topic. For this reason, the third international Cerebrovascular Biology and Blood-Brain Barrier Conference was convened in March 1998 in Gleneden Beach, OR. This meeting brought together basic science and clinical researchers from around the world to analyze BBB function and to discuss delivery of effective agents to the central nervous system for treatment of brain disease. This report summarizes the information presented at the meeting and the discussions that ensued. The current state of knowledge, obstacles to further understanding the BBB, and research priorities are identified.


Comparative molecular analysis of Haemophilus influenzae isolates from young children with acute lower respiratory tract infections and meningitis in Hanoi, Vietnam.
Thirty-seven Haemophilus influenzae strains from nasopharyngeal swabs (NP) and 44 H. influenzae strains from cerebrospinal fluid (CSF) were investigated. Of the 37 H. influenzae isolates from NP, the serotypes of 30 isolates were nontypeable, 4 were type b, 2 were type c, and 1 was type a, whereas all of the 44 isolates from CSF were type b. The MICs of 16 antibiotics for the H. influenzae isolates from NP and CSF were similar, and no beta-lactamase-negative ampicillin-resistant strain was found. Molecular typing by pulsed-field gel electrophoresis (PFGE) showed that the 37 H. influenzae strains from NP had 22 PFGE patterns, with none predominating, and the 44 H. influenzae strains from CSF had 9 PFGE patterns, with patterns alpha (22 isolates) and beta (12 isolates) predominating. Our results indicate that two predominant types of H. influenzae type b strains have the potential to spread among children with meningitis in Hanoi, Vietnam.


Improved delineation of ventricular shunt catheters using fast steady-state gradient recalled-echo sequences in a rapid brain MR imaging protocol in nonsedated pediatric patients.
Rapid brain MR imaging is often substituted for head CT in multiply imaged patients with shunted hydrocephalus. Fast TSE-T2 sequences are commonly used in these protocols. One limitation of TSE-T2 sequences is the decreased catheter delineation compared with CT. The aim of this study was to compare fast TSE-T2 with rapid SS-GRE sequences in the evaluation of intracranial shunt catheter delineation as part of a rapid nonsedated pediatric brain MR imaging protocol. We evaluated the findings from 179 consecutive patients who underwent routine clinical imaging according to the rapid nonsedated pediatric brain MR imaging protocol. Comparison of the quality of intracranial shunt catheter localization on SS-GRE versus TSE-T2 was performed. Of the total of 179 rapid nonsedated pediatric brain MR images that were reviewed, 62 (35%) had an intracranial shunt catheter. The shunt catheter tip was better localized on the SS-GRE than on the TSE-T2 images in 49/62 (79%) of these patients. Of the remaining 13/62 (21%), the TSE-T2 was either better or equivalent in localizing the shunt catheter tip. Our study shows that rapid SS-GRE sequences can provide better delineation of standard intracranial shunt catheters than standard rapid MR imaging protocols containing only fast TSE-T2 sequences.


Ketogenic therapy in neurodegenerative and psychiatric disorders: From mice to men.
Ketogenic diet is a low carbohydrate and high fat diet that has been used for over 100 years in the management of childhood refractory epilepsy. More recently, ketogenic diet has been investigated for a number of metabolic, neurodegenerative and neurodevelopmental disorders. In this comprehensive review, we critically examine the potential therapeutic benefits of ketogenic diet and ketogenic agents on neurodegenerative and psychiatric disorders in humans and translationally valid animal models. The preclinical literature provides strong support for the efficacy of ketogenic diet in a variety of diverse animal models of neuropsychiatric disorders. However, the evidence from clinical studies, while encouraging, particularly in Alzheimer's disease, psychotic and autism spectrum disorders, is limited to case studies and small pilot trials. Firm conclusion on the efficacy of ketogenic diet in psychiatric disorders cannot be drawn due to the lack of randomised, controlled clinical trials. The potential mechanisms of action of ketogenic therapy in these disorders with diverse pathophysiology may include energy metabolism, oxidative stress and immune/inflammatory processes. In conclusion, while ketogenic diet and ketogenic substances hold promise pre-clinically in a variety of neurodegenerative and psychiatric disorders, further studies, particularly randomised controlled clinical trials, are warranted to better understand their clinical efficacy and potential side effects.


Identification and its vicissitudes.
This paper attempts to understand the vicissitudes of identification within the co-ordinates of narcissism and the object relation. Firstly the dialectic pair primary identification/secondary identification are studied, and primary narcissism is suggested as the hypothesis which best explains them. The complex identification processes in the primary scene are considered next and the importance of the introjection of the oedipal parents for the formation of the superego is underlined. The importance of the structuring function of the introjection and projection mechanisms becomes embodied in the concept of projective identification, which comes to question the postulate of primary narcissism. The theory of projective-introjective identification is an extremely powerful instrument for explaining phenomena, however it obliges one to accept that the first introjections are radically different from the others. They have nothing to do with mourning but rather with primitive mechanisms which question the subject/object polarity and, so this author believes, spring basically from envy. Lastly, it is maintained that envy and libido are factors of a dialectic from which the object relation and the earliest processes of identification, previous to the Oedipus complex, proceed at one and the same time.


Growth performance, carcass characteristics, meat quality, and tissue histology of growing pigs fed crude glycerin-supplemented diets.
The effects of dietary crude glycerin on growth performance, carcass characteristics, meat quality indices, and tissue histology in growing pigs were determined in a 138-d feeding trial. Crude glycerin utilized in the trial contained 84.51% glycerin, 11.95% water, 2.91% sodium chloride, and 0.32% methanol. Eight days postweaning, 96 pigs (48 barrows and 48 gilts, average BW of 7.9 +/- 0.4 kg) were allotted to 24 pens (4 pigs/pen), with sex and BW balanced at the start of the experiment. Dietary treatments were 0, 5, and 10% crude glycerin inclusion in corn-soybean meal-based diets and were randomly assigned to pens. Diets were offered ad libitum in meal form and formulated to be equal in ME, sodium, chloride, and Lys, with other AA balanced on an ideal AA basis. Pigs and feeders were weighed every other week to determine ADG, ADFI, and G:F. At the end of the trial, all pigs were scanned using real-time ultrasound and subsequently slaughtered at a commercial abattoir. Blood samples were collected pretransport and at the time of slaughter for plasma metabolite analysis. In addition, kidney, liver, and eye tissues were collected for subsequent examination for lesions characteristic of methanol toxicity. After an overnight chilling of the carcass, loins were removed for meat quality, sensory evaluation, and fatty acid profile analysis. Pig growth, feed intake, and G:F were not affected by dietary treatment. Dietary treatment did not affect 10th-rib backfat, LM area, percent fat free lean, meat quality, or sensory evaluation. Loin ultimate pH was increased (P = 0.06) in pigs fed the 5 and 10% crude glycerin compared with pigs fed no crude glycerin (5.65 and 5.65 versus 5.57, respectively). Fatty acid profile of the LM was slightly changed by diet with the LM from pigs fed 10% crude glycerin having less linoleic acid (P < 0.01) and more eicosapentaenoic acid (P = 0.02) than pigs fed the 0 or 5% crude glycerin diets. Dietary treatment did not affect blood metabolites or frequency of lesions in the examined tissues. This experiment demonstrated that pigs can be fed up to 10% crude glycerin with no effect on pig performance, carcass composition, meat quality, or lesion scores.


[Angiographic study of the ejection fraction by thirds of systole in coronary patients].
The parameters of myocardial function in the initial phase of ventricular ejection are theoretically more sensitive than the indices calculated over the total systolic ejection period. The object of this study was to evaluate whether the calculation of the ejection fraction by thirds of systole, giving a separate assessment of left ventricular performance at the beginning, the middle and end of ejection, could reliably detect minor changes in ventricular function unrecognised by the usual holosystolic indices. Seventy left ventricular angiograms were analysed in 20 normal subjects (Group I) and 50 patients with coronary artery disease whose ventricular function estimated by the usual parameters was either decreased (Group II, 20 patients) or normal (Group III, 30 patients). In Group I, the ejection fraction in the first third of systole (FE1/3) was much higher than the ejection fraction in the second third (FE2/3). On the other hand, in Groups II and III, all patients had a FE1/3 lower than the FE2/3 (specificity: 100 p. 100). In these two groups, the reduction of FE1/3 and the increase of FE2/3 were very significant compared to Groupe I (p less than 0,001). The ejection fraction of the lest third was identical in the 3 groups. This abnormal distribution of ejection was detected in all coronary patients and was the only alteration of ventricular performance in each of the 30 patients in Group III. In this group, this abnormality was detected equally in patients with triple vessel disease (Subgroup III a, 20 patients) and in patients with isolated left anterior descending disease (Subgroup III b, 10 patients) illustrating the high sensitivity of this index for the detection of a minor abnormality of myocardial function.


Induction of phytoalexin synthesis in soybean. Stereospecific 3,9-dihydroxypterocarpan 6a-hydroxylase from elicitor-induced soybean cell cultures.
A microsomal preparation from elicitor-challenged soybean cell suspension cultures catalyzes an NADPH-dependent and dioxygen-dependent 6a-hydroxylation of 3,9-dihydroxypterocarpan to 3,6a,9-trihydroxypterocarpan. The latter is a precursor for the soybean phytoalexin glyceollin. No reaction is observed with NADH. The 6a-hydroxylase is inhibited by cytochrome c. Optical rotatory dispersion spectra of the enzymatic product formed from racemic dihydroxypterocarpan and of the remaining unreacted substrate proved that the product has the natural (6aS, 11aS)-configuration and that hydroxylation proceeds with retention of configuration. The 6a-hydroxylase was also found in elicitor-challenged soybean seedlings. The results indicate that the 6a-hydroxylase is specifically involved in the biosynthesis of glyceollin.


An Experimental Approach to Rigorously Assess Paneth Cell α-Defensin (Defa) mRNA Expression in C57BL/6 Mice.
Abundant evidence from many laboratories supports the premise that α-defensin peptides secreted from Paneth cells are key mediators of host-microbe interactions in the small intestine that contribute to host defense and homeostasis. α-defensins are among the most highly expressed antimicrobial peptides at this mucosal surface in many mammals, including humans and mice; however, there is striking variation among species in the number and primary structure of α-defensin paralogs. Studies of these biomolecules in vivo are further complicated by striking variations between laboratory mouse strains. Herein, we report an experimental approach to determine with precision and specificity expression levels of α-defensin (Defa) mRNA in the small intestine of C57BL/6 mice through an optimized set of oligonucleotide primers for qRT-PCR assays and cloned cDNA plasmids corresponding to the Defa paralogs. This approach demonstrated marked differences in α-defensin expression in C57BL/6 mice with respect to proximal/distal anatomical location and developmental stage, which have not been described previously. These data underscore the importance of careful attention to method (primer choice, proximal vs. distal location, and developmental stage) in analysis of antimicrobial peptide expression and their impact.


Use of compressed sensing to expedite high-throughput diagnostic testing for COVID-19 and beyond.
The rapid spread of SARS-CoV-2 has placed a significant burden on public health systems to provide rapid and accurate diagnostic testing highlighting the critical need for innovative testing approaches for future pandemics. In this study, we present a novel sample pooling procedure based on compressed sensing theory to accurately identify virally infected patients at high prevalence rates utilizing an innovative viral RNA extraction process to minimize sample dilution. At prevalence rates ranging from 0-14.3%, the number of tests required to identify the infection status of all patients was reduced by 75.6% as compared to conventional testing in primary human SARS-CoV-2 nasopharyngeal swabs and a coronavirus model system. Additionally, our modified pooling and RNA extraction process minimized sample dilution which remained constant as pool sizes increased. Our use of compressed sensing can be adapted to a wide variety of diagnostic testing applications to increase throughput for routine laboratory testing as well as a means to increase testing throughput to combat future pandemics.


Strain specificity of clinical isolates of herpes simplex virus.
Herpes simplex virus (HSV) produces a wide variety of ocular disease in man. Although host factors are important in determining this variation, it is possible that the different clinical patterns of herpetic ocular disease may be attributed at least partially to the differing biological behavior of specific strains of HSV. To test this theory, we compared the anterior segment disease produced by infecting rabbit corneas with seven different strains of HSV. We found that these seven different strains produced different patterns of ocular disease in the rabbit eye. This also may occur in humans, and we hope to define the biological differences that cause one strain to produce disease more severe than that produced by another strain.


Fetal hyperinsulinemia and protein turnover in fetal rat tissues.
The effects of fetal hyperinsulinemia on protein turnover in various tissues of fetal rats were determined after transuteral injection of insulin to rat fetuses at day 19 of gestation. Tissue protein content was measured on the subsequent days of gestation (days 20-22), and protein synthesis was determined at day 20 of gestation in fetal tissues after intravenous injection of [3H]phenylalanine into the maternal circulation, followed by measurements of tissue free and protein-bound phenylalanine specific radioactivity in fetal diaphragm, brain, heart, and liver. Rates of protein degradation in these fetal tissues were calculated by subtracting protein accretion rates from rates of protein synthesis. The injection of insulin to rat fetuses at day 19 of gestation resulted in relative macrosomia versus saline-injected controls from the same litter (body wt at day 20 of gestation, 3.26 +/- 0.15 g for saline-injected fetuses and 3.60 +/- 0.25 g for insulin-injected fetuses, P less than 0.001) and increased protein and RNA content of brain, heart, and liver. Although fractional rates of protein synthesis were not significantly elevated in tissues from the hyperinsulinemic fetuses, absolute rates of protein synthesis were increased in brain, heart, and liver of hyperinsulinemic fetuses. Hyperinsulinemia did not reduce calculated rates of protein breakdown in fetal brain, heart, or liver but did in fetal diaphragm. We conclude that the major effect of fetal hyperinsulinemia on protein turnover in rats is to increase protein synthesis in selected tissues without simultaneously affecting protein breakdown.


Genotypic characterization of xanthomonad strains isolated from passion fruit plants (Passiflora spp.) and their relatedness to different Xanthomonas species.
The genetic diversity of 55 xanthomonad strains isolated from passion fruit plants (Passiflora spp.) and identified as Xanthomonas campestris pv. passiflorae was initially assessed by randomly amplified polymorphic DNA (RAPD) analysis. The strains showed a high level of polymorphism with almost unique fingerprints. Fifteen clusters with a similarity of approximately 70% were identified, three of which were prevalent. There was a correlation between the clusters and the geographic origin of the strains. A representative strain of each cluster, together with the pathovar reference strain, were used to verify the relationships of these strains to 18 Xanthomonas species and Pseudomonas syringae pv. passiflorae. All Xanthomonas species yielded a unique RAPD profile and no consistent relatedness to the X. campestris pv. passiflorae strains was observed. Amplification products were also analysed by repetitive (rep) primers (BOX, ERIC and REP), RFLP of the 16S-23S rDNA intergenic spacer and SDS-PAGE of whole-cell proteins. All of these approaches generated profiles characteristic for each Xanthomonas species but the taxonomic position of the X. campestris pv. passiflorae strains could not be unequivocally assigned. Finally, DNA-DNA hybridization allowed a sound taxonomic allocation of the strains to Xanthomonas axonopodis pv. passiflorae.


Inter-arm blood pressure difference and mortality: a cohort study in an asymptomatic primary care population at elevated cardiovascular risk.
Differences in blood pressure between arms are associated with increased cardiovascular mortality in cohorts with established vascular disease or substantially elevated cardiovascular risk. To explore the association of inter-arm difference (IAD) with mortality in a community-dwelling cohort that is free of cardiovascular disease. Cohort analysis of a randomised controlled trial in central Scotland, from April 1998 to October 2008. Volunteers from Lanarkshire, Glasgow, and Edinburgh, free of pre-existing vascular disease and with an ankle-brachial index ≤0.95, had systolic blood pressure measured in both arms at recruitment. Inter-arm blood pressure differences were calculated and examined for cross-sectional associations and differences in prospective survival. Outcome measures were cardiovascular events and all-cause mortality during mean follow-up of 8.2 years. Based on a single pair of measurements, 60% of 3350 participants had a systolic IAD ≥5 mmHg and 38% ≥10 mmHg. An IAD ≥5 mmHg was associated with increased cardiovascular mortality (adjusted hazard ratio [HR] 1.91, 95% confidence interval [CI] = 1.19 to 3.07) and all-cause mortality (adjusted HR 1.44, 95% CI = 1.15 to 1.79). Within the subgroup of 764 participants who had hypertension, IADs of ≥5 mmHg or ≥10 mmHg were associated with both cardiovascular mortality (adjusted HR 2.63, 95% CI = 0.97 to 7.02, and adjusted HR 2.96, 95% CI = 1.27 to 6.88, respectively) and all-cause mortality (adjusted HR 1.67, 95% CI = 1.05 to 2.66, and adjusted HR 1.63, 95% CI = 1.06 to 2.50, respectively). IADs ≥15 mmHg were not associated with survival differences in this population. Systolic IADs in blood pressure are associated with increased risk of cardiovascular events, including mortality, in a large cohort of people free of pre-existing vascular disease.


Pathogenicity of O. circumcincta, O. ostertagi and H. contortus in weanling stag fawns (Cervus elaphus).
Groups of four stag fawns, weighing 51 +/- 0.8 kg, were-infected with 30,000 larvae of one of three nematode parasites: O.circumcincta, O.ostertagia, or H.contortus. A further four remained as control. Individual feed intake, body-weight, faecal egg count and plasma pepsinogen concentration were measured during seven weeks after infection. Only infection with H.contortus caused significant elevation of pepsinogen concentration to 380ml/ L and consistent depression of feed intake (15%). Worm egg counts were below 300 e.p.g. in deer infected with all worm species. It is concluded that while resistance to development of parasites common to other species appears to be high further investigation of the susceptibility of deer to H. contortus infection would be justifiable.


Genome sequences of three koi herpesvirus isolates representing the expanding distribution of an emerging disease threatening koi and common carp worldwide.
Since the mid-1990s, lethal infections of koi herpesvirus (KHV) have been spreading, threatening the worldwide production of common carp and koi (both Cyprinus carpio). The complete genome sequences of three KHV strains from Japan, the United States, and Israel revealed a 295-kbp genome containing a 22-kbp terminal direct repeat. The finding that 15 KHV genes have clear homologs in the distantly related channel catfish virus (ictalurid herpesvirus 1) confirms the proposed place of KHV in the family Herpesviridae, specifically in the branch with fish and amphibian hosts. KHV thus has the largest genome reported to date for this family. The three strains were interpreted as having arisen from a wild-type parent encoding 156 unique protein-coding genes, 8 of which are duplicated in the terminal repeat. In each strain, four to seven genes from among a set of nine are fragmented by frameshifts likely to render the encoded proteins nonfunctional. Six of the affected genes encode predicted membrane glycoproteins. Frameshifts or other mutations close to the 3' ends of coding sequences were identified in a further six genes. The conclusion that at least some of these mutations occurred in vivo prompts the hypothesis that loss of gene functions might be associated with emergence of the disease and provides a basis for further investigations into the molecular epidemiology of the virus.


Snorkel/Chimney Stent Morphology Predicts Renal Dysfunction after Complex Endovascular Aneurysm Repair.
Despite the high technical success and midterm patency of snorkel stents, concerns remain about structural durability and its effect on long-term renal function. We sought to evaluate the luminal stability of renal snorkel stents to investigate morphologic predictive factors of renal dysfunction after snorkel/chimney endovascular aneurysm repair (sn-EVAR). Patients with high quality computer tomography angiography after sn-EVAR between 2009 and 2013 were included for analysis. Luminal diameters of renal snorkel stents were measured on a 3-dimensional workstation at the proximal, main-body junction, and distal locations. Creatinine values and estimated glomerular filtration rates (eGFR) were recorded throughout the preoperative, perioperative, and postoperative course. Acute kidney injury (AKI) and chronic renal decline were evaluated using the risk, injury, failure, loss of function, end stage renal disease (RIFLE) criteria and chronic kidney disease (CKD) staging system, respectively. 52 patients underwent sn-EVAR (33 double renal, 19 single renal) with a 2-year primary patency of 95% at a mean follow-up of 21 months, of which 34 had suitable imaging protocols. In this subset, snorkel stents had mean deformations of -0.14 ± 0.52 (2.8%), -0.23 ± 0.52 (4.6%) and -0.04 ± 0.16 mm (1.8%) at the proximal, junction, and distal segments. Four cases of significant >50% stent collapse occurred during follow-up, all of which occurred at the junctional segment. In the total cohort, 17 (32.6%) and 16 (30.7%) patients developed AKI and chronic renal decline, respectively. Multivariate regression identified larger proximal luminal diameters at latest follow-up (odds ratio 0.67; confidence interval [CI] 0.006-0.740; P = 0.037) as the only protective morphologic risk factor for developing chronic renal decline. No independent predictor factors for AKI were found. Rates of renal decline were significantly worse with smaller measured proximal lumens with a 1-year freedom from renal decline of 50% vs. 77-83% for diameters measured less than 4 mm vs. greater than 4 mm (P = 0.010). Degree of oversizing also affected rates of decline with greater oversizing associated with improved freedom from renal decline at 1 year of 100% vs. 57% (P = 0.012). Using a multivariate Cox model, stent oversizing (hazard ratio [HR], 0.039; P = 0.018) and baseline CKD (HR 0.033, P = 0.004) were the only independent factors, both of which resulted in slower rates of renal decline during follow-up. Renal snorkel stent grafts maintain a high degree of patency and luminal stability at 2-year follow-up. However, stent collapse remains a rare but concerning risk, with the junctional segment most prone to significant stent deformation. Renal snorkel stents must be critically sized relative to native renal anatomy, and we recommend using at least stents sized ≥6 mm to minimize the risk of renal dysfunction. Frequent and regular radiographic and laboratory follow-up remains important as we further optimize the approach to complex EVAR.


Foxtail Millet [Setaria italica (L.) Beauv.] Grown under Low Nitrogen Shows a Smaller Root System, Enhanced Biomass Accumulation, and Nitrate Transporter Expression.
Foxtail millet (FM) [Setaria italica (L.) Beauv.] is a grain and forage crop well adapted to nutrient-poor soils. To date little is known how FM adapts to low nitrogen (LN) at the morphological, physiological, and molecular levels. Using the FM variety Yugu1, we found that LN led to lower chlorophyll contents and N concentrations, and higher root/shoot and C/N ratios and N utilization efficiencies under hydroponic culture. Importantly, enhanced biomass accumulation in the root under LN was in contrast to a smaller root system, as indicated by significant decreases in total root length; crown root number and length; and lateral root number, length, and density. Enhanced carbon allocation toward the root was rather for significant increases in average diameter of the LN root, potentially favorable for wider xylem vessels or other anatomical alterations facilitating nutrient transport. Lower levels of IAA and CKs were consistent with a smaller root system and higher levels of GA may promote root thickening under LN. Further, up-regulation of SiNRT1.1, SiNRT2.1, and SiNAR2.1 expression and nitrate influx in the root and that of SiNRT1.11 and SiNRT1.12 expression in the shoot probably favored nitrate uptake and remobilization as a whole. Lastly, more soluble proteins accumulated in the N-deficient root likely as a result of increases of N utilization efficiencies. Such "excessive" protein-N was possibly available for shoot delivery. Thus, FM may preferentially transport carbon toward the root facilitating root thickening/nutrient transport and allocate N toward the shoot maximizing photosynthesis/carbon fixation as a primary adaptive strategy to N limitation.


Human serum alpha 1-antichymotrypsin is an inhibitor of pancreatic elastases.
Incubation of human serum alpha 1-antichymotrypsin with human pancreatic elastase 2 or porcine pancreatic elastase results in the complete inhibition of each enzyme as determined by spectrophotometric assays. alpha 1-Antichymotrypsin reacts much more rapidly with the human than with the porcine enzyme. The inhibitor: enzyme molar ratio, required to obtain full inhibition of enzymatic activity, is equal to 1.25/1 when alpha 1-antichymotrypsin reacts with human pancreatic elastase 2 while it is markedly higher with porcine pancreatic elastase (5.5/1). Patterns obtained by SDS/polyacrylamide gel electrophoresis of the reaction products show the formation with both enzymes of an equimolar complex (Mr near 77 000) and the release of a fragment migrating as a peptide of Mr near 5000. Moreover a free proteolytically modified form of alpha 1-antichymotrypsin, electrophoretically identical with that obtained in the reaction with cathepsin G or bovine chymotrypsin, is produced in the reaction with each elastase but in a much greater amount when alpha 1-antichymotrypsin reacts with porcine elastase than with human elastase. As a consequence of our findings, the specificity of alpha 1-antichymotrypsin, so far limited to the inhibition of chymotrypsin-like enzymes from pancreas and leukocyte origin, has to be extended to the two pancreatic elastases investigated in this work. A contribution of alpha 1-antichymotrypsin to the regulatory balance between plasma inhibitors and human pancreatic elastase 2 in pancreatic diseases is suggested.


Regeneration of breeding tubercles on zebrafish pectoral fins requires androgens and two waves of revascularization.
Sexually dimorphic breeding tubercles (BTs) are keratinized epidermal structures that form clusters on the dorsal surface of the anterior rays of zebrafish male pectoral fins. BTs appear during sexual maturation and are maintained through regular shedding and renewal of the keratinized surface. Following pectoral fin amputation, BT clusters regenerate after the initiation of revascularization, but concomitantly with a second wave of angiogenesis. This second wave of regeneration forms a web-like blood vessel network that penetrates the supportive epidermis of BTs. Upon analyzing the effects of sex steroids and their inhibitors, we show that androgens induce and estrogens inhibit BT cluster formation in intact and regenerating pectoral fins. Androgen-induced BT formation in females is accompanied by the formation of a male-like blood vessel network. Treatment of females with both androgens and an angiogenesis inhibitor results in the formation of undersized BT clusters when compared with females treated with androgens alone. Overall, the growth and regeneration of large BTs requires a hormonal stimulus and the presence of an additional blood vessel network that is naturally found in males.


Advances in understanding and treating dystrophic epidermolysis bullosa.
Epidermolysis bullosa is a group of inherited disorders that can be both systemic and life-threatening. Standard treatments for the most severe forms of this disorder, typically limited to palliative care, are ineffective in reducing the morbidity and mortality due to complications of the disease. Emerging therapies-such as the use of allogeneic cellular therapy, gene therapy, and protein therapy-have all shown promise, but it is likely that several approaches will need to be combined to realize a cure. For recessive dystrophic epidermolysis bullosa, each particular therapeutic approach has added to our understanding of type VII collagen (C7) function and the basic biology surrounding the disease. The efficacy of these therapies and the mechanisms by which they function also give us insight into developing future strategies for treating this and other extracellular matrix disorders.


[Glucose, glycotoxins, and protein glycation products: the role in pathogensis].
Arteriosclerosis and atheromatosis are etiologically and pathogenetically different non-physiological processes in atherosclerosis localized in the proximal segments of the arterial bed and elastic-type arteries; both affect the structure and function of the arterial wall. They cause an inflammatory reaction with subsequent compaction (sclerosing) of the walls of large and mid-size arteries, the loss of their elasticity due to structural changes in the loose connective tissue of intima-media, impaired elasticity and enhanced rigidity of the wall, inflammation, fibrosis, and increased pulse wave conduction velocity. Arteriosclerosis is initiated by long-term hyperglycemia, chemical collagen and elastin glycation by glucose and its metabolites (glycotoxins glyoxal and methylglyoxal) forming cross-links between collagen and elastin fibers. In contrast, atheromatosis as the main manifestation of atherosclerosis affects elastic-type arteries via accumulation of intimal lipids (cholesterol-esterified essential unsaturated and polyenic fatty acids, plaque formation at the sites of macrophage deposition in intima, necrotic and calcinotic foci. Atheromatosis does not affect collageous and elastic structures in the arterial wall. Arteriosclerosis and atheromatosis are two independent pathological processes in the walls of elastic-type arteries. Arteriosclerosis results from glycation of collagen and elastin chains in muscular-type arterioles, postarterioles, endothelium, and pericytes of exchangeable capillaries. Microangiopathy initiates only glycation and glycotoxin action because muscular-type arterioles have no intima, an interstitial tissue for the collection and utilization of biological "rubbish" from blood and intravascular pool of intercellular medium.


Ecological momentary assessment of various tobacco product use among young adults.
Young adults are at high risk for using traditional and novel tobacco products. However, little is known about daily/weekly use patterns or psychosocial triggers for using various tobacco products. This ecological momentary assessment (EMA) study examined timing, tobacco cravings, affect, social context, and other substance use (alcohol, marijuana) in relation to use of cigarettes, electronic nicotine delivery systems (ENDS), and any tobacco product (i.e., cigarettes, ENDS, cigars, hookah), respectively. We also examined interactions between these predictors, sex, and race/ethnicity. From a longitudinal study of 3418 18-25 year-olds from seven Georgia colleges/universities, we recruited 72 reporting current tobacco use to participate in the 21-day EMA study; 43 participated, of which 31 completed ≥66% assessments and were analyzed. Cravings, affect, social context, and substance use were assessed daily across four four-hour windows. Of the 31 participants, average age was 21.10 years (SD = 1.95), 45.2% were female, and 71.0% non-Hispanic White; 71.0% used cigarettes, 58.1% ENDS, 38.7% cigars, and 25.8% hookah (25.6% used one product, 46.5% two, 27.9% ≥ three). Predictors of cigarette use included higher anxiety, greater odds of marijuana and alcohol use, and higher boredom levels among women. Predictors of ENDS use included being non-White and greater odds of marijuana use, as well as higher tobacco cravings among women and higher boredom among men. Predictors of any tobacco product use included being non-White, higher boredom levels, and greater odds of marijuana and alcohol use. Distinct interventions may be needed to address use of differing tobacco products among young adults.


Evaluation of a New Criterion for Detecting Prion Disease With Diffusion Magnetic Resonance Imaging.
Early diagnosis is a requirement for future treatment of prion diseases. Magnetic resonance imaging (MRI) with diffusion-weighted images and improved real-time quaking-induced conversion (RT-QuIC) in cerebrospinal fluid (CSF) have emerged as reliable tests. To assess the sensitivity and specificity of diffusion MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) with a new criterion (index test) of at least 1 positive brain region among the cortex of the frontal, parietal, temporal, and occipital lobes; the caudate; the putamen; and the thalamus. This diagnostic study with a prospective and a retrospective arm was performed from January 1, 2003, to October 31, 2018. MRIs were collected from 1387 patients with suspected sCJD consecutively referred to the National Prion Disease Pathology Surveillance Center as part of a consultation service. Magnetic resonance imaging. Four neuroradiologists blinded to the diagnosis scored the MRIs of 200 randomly selected patients. One neuroradiologist scored the MRIs of all patients. Sensitivity and specificity of the index test compared with currently used criteria and CSF diagnostic (improved RT-QuIC, 14-3-3, and tau CSF tests). A total of 872 patients matched the inclusion criteria (diffusion MRI and autopsy-confirmed diagnosis), with 619 having sCJD, 102 having other prion diseases, and 151 having nonprion disease. The primary analysis included 200 patients (mean [SD] age, 63.6 [12.9] years; 100 [50.0%] male). Sensitivity of the index test of 4 neuroradiologists was 90% to 95% and superior to sensitivity of current MRI criteria (69%-76%), whereas specificity was 90% to 100% and unchanged. Interrater reliability of the 4 neuroradiologists was high (κ = 0.81), and individual intrarater reliability was excellent (κ ≥0.87). The sensitivity of the index test of 1 neuroradiologist for 770 patients was 92.1% (95% CI, 89.7%-94.1%) and the specificity was 97.4% (95% CI, 93.4%-99.3%) compared with a sensitivity of 69.8% (95% CI, 66.0%-73.4%; P < .001) and a specificity of 98.0% (95% CI, 94.3%-99.6%; P > .99) according to the current criteria. For 88 patients, index test sensitivity (94.9%; 95% CI, 87.5%-98.6%) and specificity (100%; 95% CI, 66.4%-100%) were similar to those of improved RT-QuIC (86.1% [95% CI, 76.5%-92.8%] and 100% [95% CI, 66.4%-100%], respectively). Lower specificities were found for 14-3-3 and tau CSF tests in 452 patients. In this study, the diagnostic performance of diffusion MRI with the new criterion was superior to that of current standard criteria and similar to that of improved RT-QuIC. These results may have important clinical implications because MRI is noninvasive and typically prescribed at disease presentation.


Evaluation of restriction endonuclease cleavage of plant nuclear DNA using contaminating chloroplast DNA.
Plant DNA is often contaminated by chloroplast DNA. The contamination was used here with advantage to check restriction endonuclease cleavage of plant DNA. This method is based on hybridization of Southern blots of digested plant DNA with cloned fragments of chloroplast DNA as a probe. Advantages of this method are demonstrated.