Identification of a heat shock cognate protein 70 gene in Chinese soft-shell turtle (Pelodiscus sinensis) and its expression profiles under thermal stress.
The heat shock cognate protein 70 (Hsc70) is a member of a 70-kDa heat shock protein (HSP70) family that functions as molecular chaperones. In this study, a novel Hsc70 gene from Chinese soft-shelled turtle (Pelodiscus sinensis) (tHsc70) was identified. The tHsc70 full-length complementary DNA (cDNA) is 2272 bp long with a 1941-bp open reading frame (ORF) encoding 646 amino acids. Three characteristic signature regions of the HSP70 family, two major domains of an adenosine triphosphate (ATP)/guanosine triphosphate (GTP) binding domain (ABD), and a substrate-binding domain (SBD) were present in the predicted tHsc70 amino acid sequence. The tHsc70 gene was expressed in Escherichia coli BL21 and the expression product reacted with the anti-Hsc70 mouse monoclonal antibody by Western blotting. Homology analysis revealed that tHsc70 shared identity from 53.9% to 87.7% at the nucleotide level, and 49.1% to 99.5% at the amino acid level with the known Hsc70s. Phylogenetic analysis showed that tHsc70 was clustered together with the Hsc70 gene of another reptile species (Alligator mississippiensis). The tHsc70 was expressed in the liver, lung, heart, and skeletal muscle. The expression patterns of tHsc70 messenger RNA (mRNA) differed among different tissues under different durations of heat stress at 40 °C. Adaptation at 25 °C for 1 h after heat stress was also different among tissues and length of heat stress. Irrespective of different profiles of expression under heat stress, tHsc70 may play roles in protecting turtles from thermal stress.


Directional terahertz emission from corrugated InAs structures.
The terahertz (THz) radiation from transient dipoles, formed by distinct diffusion coefficients between oppositely charged carriers as often observed in low band gap semiconductors, propagates with an anisotropic amplitude distribution perpendicular to the dipole axis along the diffusive motion. By directionally adjusting the electronic diffusion, we conceptualize groove-patterned THz emitters based on (100) InAs thin films and demonstrate the unidirectional radiation. Line-of-sight emission along the surface-normal direction is greatly enhanced in a distributed asymmetric trapezoid with its period similar to the electronic diffusion length of InAs. This directional enhancement is in clear contrast to the constant emission amplitude along the lateral direction, regardless of pattern scale, which manifests the role of groove patterns as microscale reflectors in laterally corrugating the carrier density. In contrast to the rather limited nonlinearity in (100) plane, the azimuthal angle dependence of the THz field amplitude in corrugated samples shows a combined effect of diffusive transport and second-order nonlinearity, whose compositional contributions varies in different structures.


Seminoma with tubular, microcystic, and related patterns: a study of 28 cases of unusual morphologic variants that often cause confusion with yolk sac tumor.
We report 28 testicular seminomas with cystic spaces of variable nature, sometimes accompanied by solid and hollow tubular patterns (12 cases). The spaces often suggested reticular or microcystic patterns of yolk sac tumor, and the solid and hollow tubular patterns often added to the diagnostic confusion. The tumors occurred in men 21 to 55 years old and on gross examination had the typical appearance of seminoma. On microscopic examination, the spaces ranged from small, closely packed and relatively regular to dilated, more dispersed and somewhat irregular. The hollow tubules appeared to result from central discohesion within nests of tumor. The spaces, particularly when large, often contained occasional tumor cells or inflammatory cells within pale edema fluid. The cytologic appearance of the cells lining the spaces, and in the surrounding tumor, retained the typical features of seminoma cells. Thirteen tumors (46%) either lacked (8 cases) or had very scant (5 cases) lymphocytes in the cystic and tubular areas, and hyaline globules were absent. Thirteen of 13 tumors were immunopositive for OCT-3/4 in the nontypical and typical areas; 9 of 10 were placental alkaline phosphatase positive, and 7 of 10 were c-Kit (CD117) positive. The same 13 cases were negative with cytokeratin (AE1/AE3) and alpha-fetoprotein stains. Distinction from yolk sac tumor is aided by the observation that the spaces of yolk sac tumor are often more irregular in their individual shapes and frequently form anastomosing channels. Additionally, the spaces of yolk sac tumor randomly merge with various other yolk sac tumor patterns. The cells lining spaces in yolk sac tumor are often flattened with compressed nuclei and lack the typical prominent nucleoli of seminoma cells. Paucity of lymphocytes and intracystic edema, however, are not differentially helpful, although basophilic fluid favors yolk sac tumor. A panel of immunostains (AE1/AE3, OCT-3/4, and alpha-fetoprotein) is helpful in the differential with yolk sac tumor in especially problematic cases. The edema and paucity of lymphocytes may suggest spermatocytic seminoma, but the varied cell types of that neoplasm are absent.


A novel extracellular esterase from Bacillus subtilis and its conversion to a monoacylglycerol hydrolase.
A novel gene lipB, which encodes an extracellular lipolytic enzyme, was identified in the Bacillus subtilis genomic DNA sequence. We have cloned and overexpressed lipB in B. subtilis and Escherichia coli and have also purified the enzyme from a B. subtilis culture supernatant to electrophoretic homogeneity. Four different lipase assays were used to determine its catalytic activity: pH-stat, spectrophotometry, fluorimetry and the monomolecular film technique. LipB preferentially hydrolysed triacylglycerol-esters and p-nitrophenyl-esters of fatty acids with short chain lengths of </= 10 carbon atoms. Triolein, which is a typical substrate for true lipases, was not hydrolysed at all. These results led us to classify LipB as an esterase rather than a lipase. The catalytic triad of LipB consists of residues Ser78, Asp134, and His157 as demonstrated by amino-acid sequence alignments and site-directed mutagenesis. The nucleophile Ser78 is located in a lipase-specific consensus sequence, which is Ala-X-Ser-X-Gly for most Bacillus lipases. All other bacterial lipases contain a glycine residue instead of the alanine at position-2 with respect to the catalytic serine. We have investigated the role of this alanine residue by constructing LipB variant A76G, thereby restoring the lipase-specific consensus motif. When compared with LipB this variant showed a markedly reduced thermostability but an increased stability at pH 5-7. Determination of the specific activities of wild-type LipB and variant A76G using a monomolecular film of the substrate monoolein revealed an interesting result: the A76G substitution had converted the esterase LipB into a monoacylglycerol hydrolase.


Two cases of pediatric primary immunodeficiency caused by a familial moesin(MSN)gene mutation.
We investigated two brothers who presented with repeated lung infections after 6 months of age. Lymphocytes and neutrophils were significantly decreased, and both had bronchiectasis and emphysema. We sought to characterize the complete picture of lung injury in some types of primary immunodeficiency disease, followed by verification and analysis. We performed immune function determination, a complete examination of the respiratory system, genetic analysis, and literature research. The levels of lymphocytes, neutrophils, monocytes, and natural killer cells in the brothers were significantly decreased. The IgM and IgG levels of the older brother were decreased, while the IgM and IgA levels of the younger brother were decreased. Both brothers had bronchial wall erosion with a worm-eaten appearance and decreased lung function. Genetic testing revealed a hemizygous missense mutation (c.511C > T:p.R171W) in exon 5 of the MSN gene, which was inherited from the mother. A literature review showed that the primary immunodeficiency caused by MSN gene mutations is an X-linked recessive genetic disease with four known gene mutation sites, including nonsense and missense mutations. Nonsense mutations result in a higher incidence of autoimmune diseases and a lower degree of immune function impairment. Nonsense mutations closer to the front of the MSN gene may cause more severe disease. Neonatal disease screening can improve the early diagnosis rate, but hematopoietic stem cell transplantation (HSCT) treatment is controversial. The primary immunodeficiency disease caused by MSN gene mutation is an X-linked recessive genetic disease that involves structural and functional damage to the respiratory system, and the worm-eaten appearance of the bronchial wall under endoscopy may be a relatively specific sign. The general manifestations of this disease are recurrent infections from 1 month to 6 months after birth, significantly reduced counts of lymphocytes and neutrophils, and decreased cellular and humoral immune function. Different types of MSN gene mutations and nonsense mutations at different sites have different clinical phenotypes. This study enriches the known spectrum of this disease.


You may need a nerve to treat pain: the neurobiological rationale for vagal nerve activation in pain management.
Pain is a complex common health problem, with important implications for quality of life and with huge economic consequences. Pain can be elicited due to tissue damage, as well as other multiple factors such as inflammation and oxidative stress. Can there be 1 therapeutic pathway that may target multiple etiologic factors in pain? In the present article, we review evidence for the relationships between vagal nerve activity and pain, and between vagal nerve activity and 5 factors that are etiologic to or protective in pain. Vagal nerve activity inhibits inflammation, oxidative stress, and sympathetic activity, activates brain regions that can oppose the brain "pain matrix," and finally it might influence the analgesic effects of opioids. Together, these can explain the antinociceptive effects of vagal nerve activation or of acetylcholine, the principal vagal nerve neurotransmitter. These findings form an evidence-based neurobiological rationale for testing and possibly implementing different vagal nerve-activating treatments in pain conditions. In this article, we show evidence for the relationships between vagal nerve activity and pain, and between vagal nerve activity and 5 factors that are etiologic to pain. Given the evidence and effects of the vagus nerve activation in pain, people involved in pain therapy may need to seriously consider activation of this nerve.


Temsirolimus activates autophagy and ameliorates cardiomyopathy caused by lamin A/C gene mutation.
Mutations in the lamin A/C gene (LMNA), which encodes A-type lamins, cause a diverse range of diseases collectively called laminopathies, the most common of which is dilated cardiomyopathy. Emerging evidence suggests that LMNA mutations cause disease by altering cell signaling pathways, but the specific mechanisms are poorly understood. We show that the AKT-mammalian target of rapamycin pathway is hyperactivated in hearts of mice with cardiomyopathy caused by Lmna mutation and that in vivo administration of the rapamycin analog temsirolimus prevents deterioration of cardiac function. We also show defective autophagy in hearts of these mice and demonstrate that improvement in heart function induced by pharmacological interventions is correlated with enhanced autophagy. These findings provide a rationale for treatment of LMNA cardiomyopathy with rapalogs and implicate defective autophagy as a pathogenic mechanism of cardiomyopathy arising from LMNA mutation.


Determination of agricultural land suitability with a multiple-criteria decision-making method in Northwestern Turkey.
This study was carried out in the district of Lapseki in Çanakkale, Turkey. The suitability of land in Lapseki for agriculture was evaluated by using an analytic hierarchy process. In the study, the basic parameters were determined by using the soil map and the Shuttle Radar Topography Mission data. Land use capability classes, soil depth, erosion risk and other soil properties (limiting factors) were obtained from the soil map, while slope, elevation and aspect were obtained from the Shuttle Radar Topography Mission data. To determine the weight of the parameters in the analytic hierarchy process, the opinions of the public institutions and experts were obtained. The obtained data were analyzed with the analytic hierarchy process and mapped with geographic information systems techniques, and a land suitability map was generated. The agricultural land suitability map demonstrated that 2.95% (2557 ha) of the lands in the study area were highly suitable; 10.37% (8989 ha) were moderately suitable; 53.47% (46,336 ha) were marginally suitable; and 33.21% (28,775 ha) were not suitable for agricultural use. The data from the agricultural land suitability map were compared with the Coordination of Information on the Environment 2012 data. As a result of comparison, 14.12% (361 ha) of highly suitable lands for agriculture and 2.25% (202 ha) of moderate suitable lands for agriculture are urbanized. It was seen that 45.71% (24,837 ha) of the lands that are marginally suitable for agriculture and 18.76% (5397 ha) of the not suitable lands had current land use for agriculture.


[Congenital neuropathy caused by hypomyelination].
A 9 year-old girl with congenital hypomyelination neuropathy is reported. Clinical features were delayed motor development, disturbances of gait, deep sensory defect, areflexia and mild distal palsy with claw feet. E.M.G. revealed dramatically diminished motor conduction velocities. C.S.F. protein was normal. Histological examination of the right sural nerve revealed a severe loss of myelinated fibers. On electron microscopy, poorly myelinated and large amyelinated axons were enclosed by normal Schwann cells and surrounded by multiple single or double layered basement membranes which were concentrically arranged in an onion bulb pattern. This case of congenital hypomyelination neuropathy is compared with ten similar cases in the literature.


Metabolic requirements of red drum, Sciaenops ocellatus, for protein and energy based on weight gain and body composition.
Precise formulation of diets that meet but do not greatly exceed nutritional requirements should assist in lowering feed costs for commercial aquaculture of red drum, Sciaenops ocellatus. In this study, protein and energy requirements of red drum for maintenance and maximum gain were determined by feeding a diet containing digestible protein (DP) at 36.5% and 14.2 kJ digestible energy (DE) per gram at various rates for 8 wk in two separate experiments. Changes in weight and whole-body energy and protein were measured and regressed against protein or energy fed using a nonlinear procedure. In the first experiment, juvenile fish [ approximately 3. 4 g initial body weight (BW)] were either starved or fed at one of the following g/(100 g BW.d): 0.5, 1, 2, 4, 6, or 8. The second experiment utilized larger red drum (approximately 5.5 g initial weight), fed 0.75, 1.5, 3, 5, 5.5, 6, 6.5 or 7 g/(100 g BW.d) to confirm and refine results from the first experiment. Based on maintenance of body weight in both experiments, red drum had a protein maintenance requirement of 1.5 and 2.5 g DP/(kg BW.d) whereas estimates based on maintenance of whole-body protein were 0.5 and 2.2 g DP/(kg BW.d). Energy requirements for maintenance of weight and body energy ranged from 58 to 93 and 92 to 97 kJ DE/(kg BW.d), respectively. Protein requirements for maximum weight gain and change in body protein ranged from 20 to 25 g DP/(kg BW.d), whereas energy requirements for maximum weight gain and whole-body deposition ranged from 776 to 958 and 914 to 985 kJ DE/(kg BW.d), respectively. These requirements for maintenance and maximum gain of red drum should assist in formulation of diets for a variety of desired feeding strategies.


FCTP-WSRC: Protein-Protein Interactions Prediction via Weighted Sparse Representation Based Classification.
The task of predicting protein-protein interactions (PPIs) has been essential in the context of understanding biological processes. This paper proposes a novel computational model namely FCTP-WSRC to predict PPIs effectively. Initially, combinations of the F-vector, composition (C) and transition (T) are used to map each protein sequence onto numeric feature vectors. Afterwards, an effective feature extraction method PCA (principal component analysis) is employed to reconstruct the most discriminative feature subspaces, which is subsequently used as input in weighted sparse representation based classification (WSRC) for prediction. The FCTP-WSRC model achieves accuracies of 96.67%, 99.82%, and 98.09% for H. pylori, Human and Yeast datasets respectively. Furthermore, the FCTP-WSRC model performs well when predicting three significant PPIs networks: the single-core network (CD9), the multiple-core network (Ras-Raf-Mek-Erk-Elk-Srf pathway), and the cross-connection network (Wnt-related Network). Consequently, the promising results show that the proposed method can be a powerful tool for PPIs prediction with excellent performance and less time.


The KCNH2-IVS9-28A/G mutation causes aberrant isoform expression and hERG trafficking defect in cardiomyocytes derived from patients affected by Long QT Syndrome type 2.
Long QT Syndrome type 2 (LQT2) is caused by mutations in the KCNH2 gene that encodes for the α-subunit (hERG) of the ion channel conducting the rapid delayed rectifier potassium current (IKr). We have previously identified a disease causing mutation (IVS9-28A/G) in the branch point of the splicing of KCNH2 intron 9. However, the mechanism through which this mutation causes the disease is unknown. We generated human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from fibroblasts of two IVS9-28A/G mutation carriers. IVS9-28A/G iPSC-CMs showed prolonged repolarization time, mimicking what observed at the ECG level in the same patients. The expression of the full-length ERG1a isoform resulted reduced, whereas the C-terminally truncated ERG1aUSO isoform was upregulated in mutant iPSC-CMs, with consequent alteration of the physiological ERG1aUSO/ERG1a ratio. Importantly, we observed an impairment of hERG trafficking to the cell membrane. The severity of the alterations in hERG expression and trafficking correlated with the clinical severity of the disease in the two patients under study. Finally, we were able to revert the trafficking defect and reduce the repolarization duration in LQT2 iPSC-CMs using the proteasome inhibitor ALLN. Our results highlight the key role of the KCNH2 intron 9 branch point in the regulation of KCNH2 isoform expression and hERG channel function, and allow to categorize the IVS9-28A/G mutation as LQT2 class 2 mutation. These findings may result in a more personalized clinical management of IVS9-28A/G mutation carriers.


End-Of-Life Care in the Time of COVID-19: Communication Matters More Than Ever.
The COVID-19 pandemic resulted in visitation restrictions across most health care settings, necessitating the use of remote communication to facilitate communication among families, patients and health care teams. To examine the impact of remote communication on families' evaluation of end-of-life care during the COVID-19 pandemic. Retrospective, cross-sectional, mixed methods study using data from an after-death survey administered from March 17-June 30, 2020. The primary outcome was the next of kin's global assessment of care during the Veteran's last month of life. Data were obtained from the next-of-kin of 328 Veterans who died in an inpatient unit (i.e., acute care, intensive care, nursing home, hospice units) in one of 37 VA medical centers with the highest numbers of COVID-19 cases. The adjusted percentage of bereaved families reporting excellent overall end-of-life care was statistically significantly higher among those reporting Very Effective remote communication compared to those reporting that remote communication was Mostly, Somewhat, or Not at All Effective (69.5% vs. 35.7%). Similar differences were observed in evaluations of remote communication effectiveness with the health care team. Overall, 81.3% of family members who offered positive comments about communication with either the Veteran or the health care team reported excellent overall end-of-life care vs. 28.4% who made negative comments. Effective remote communication with the patient and the health care team was associated with significantly better ratings of the overall experience of end-of-life care by bereaved family members. Our findings offer timely insights into the importance of remote communication strategies.


Adenine base editor-mediated splicing remodeling activates noncanonical splice sites.
Adenine base editors (ABEs) are genome-editing tools that have been harnessed to introduce precise A•T to G•C conversion. The discovery of split genes revealed that all introns contain two highly conserved dinucleotides, canonical "AG" (acceptor) and "GT" (donor) splice sites. ABE can directly edit splice acceptor sites of the adenine (A) base, leading to aberrant gene splicing, which may be further adopted to remodel splicing. However, spliced isoforms triggered with ABE have not been well explored. To address it, we initially generated a cell line harboring C-terminal enhanced GFP (eGFP)-tagged β-actin (ACTB), in which the eGFP signal can track endogenous β-actin expression. Expectedly, after the editing of splice acceptor sites, we observed a dramatical decrease in the percentage of eGFP-positive cells and generation of splicing products with the noncanonical splice site. Furthermore, we manipulated Peroxidasin in mouse embryos with ABE, in which a noncanonical acceptor was activated to remodel splicing, successfully generating a mouse disease model of anophthalmia and severely malformed microphthalmia. Collectively, we demonstrate that ABE-mediated splicing remodeling can activate a noncanonical acceptor to manipulate human and mouse genomes, which will facilitate the investigation of basic and translational medicine studies.


Imbalance in extracellular matrix degradation in urethral stricture.
Extracellular matrix degradation may play an important role in the etiology of urethral stricture. MMP1 and TIMP1 are involved in extracellular matrix degradation. The aim of this study was to investigate the roles of MMP1, TIMP1, and MMP1:TIMP1 ratio at the remodeling phase of urethral stricture in an animal model. This research was carried out in collaboration between the Bogor Institute of Agriculture, Universitas Indonesia, and the Eijkman Institute Indonesia. This was an experimental in vivo study in adult male New Zealand rabbits, divided into two groups: a urethral stricture group and a control group. Euthanasia was performed in four rabbits of each group on days 7, 14, 21, 28, and 56. Urethral stricture was confirmed with an 8 F urethral catheter. Several laboratory examinations were done, including H&E and Masson trichrome staining, immunohistochemistry, and ELISA, to determine levels of MMP1 and TIMP1. Percentages of total collagen and collagen type 1 were counted with ImageJ 1.46q software. A general linear model was used for statistic analysis. We found that the level of MMP1 was lower, TIMP1 higher, and MMP1:TIMP1 ratio lower in the urethral stricture group than the control group. There was a correlation between MMP1 level with total collagen percentage (r=0.561, P=0.010) and no correlation between TIMP1 and total collagen (r=0.307, P=0.188). Imbalance in extracellular matrix degradation was marked by decreased MMP1 level and MMP1:TIMP1 ratio and increased TIMP1 level. This results showed that urethral stricture is not only caused by collagen decomposition, but also by the imbalance of extracellular matrix degradation.


Visualising reactive oxygen species in live mammals and revealing of ROS-related system.
Of all the aerobic respiration by-products, cytotoxic superoxide derived from mitochondrial-leaked electrons, is the only one known to be disposed of intracellularly. Is this fate the only destiny for mitochondrial-leaked electrons? When Cynomolgus monkeys were injected intravenously with reactive oxygen species (ROS) indicators, the connective tissues of dura mater, facial fascia, pericardium, linea alba, dorsa fascia and other body parts, emitted specific and intense fluorescent signals. Moreover, the fluorescent signals along the linea alba of SD rats, did not result from the local presence of ROS but from the interaction of ROS indicators with electrons flowing through this tissue. Furthermore, the electrons travelling along the linea alba of mice were revealed to originate from mitochondria. These data suggest that mitochondrial-leaked electrons may be transported extracellularly to a hitherto undescribed system of connective tissues, which is pervasively networked, electrically conductive and metabolically related.


Proteomic analysis of plasma-purified VLDL, LDL, and HDL fractions from atherosclerotic patients undergoing carotid endarterectomy: identification of serum amyloid A as a potential marker.
Apolipoproteins are very heterogeneous protein family, implicated in plasma lipoprotein structural stabilization, lipid metabolism, inflammation, or immunity. Obtaining detailed information on apolipoprotein composition and structure may contribute to elucidating lipoprotein roles in atherogenesis and to developing new therapeutic strategies for the treatment of lipoprotein-associated disorders. This study aimed at developing a comprehensive method for characterizing the apolipoprotein component of plasma VLDL, LDL, and HDL fractions from patients undergoing carotid endarterectomy, by means of two-dimensional electrophoresis (2-DE) coupled with Mass Spectrometry analysis, useful for identifying potential markers of plaque presence and vulnerability. The adopted method allowed obtaining reproducible 2-DE maps of exchangeable apolipoproteins from VLDL, LDL, and HDL. Twenty-three protein isoforms were identified by peptide mass fingerprinting analysis. Differential proteomic analysis allowed for identifying increased levels of acute-phase serum amyloid A protein (AP SAA) in all lipoprotein fractions, especially in LDL from atherosclerotic patients. Results have been confirmed by western blotting analysis on each lipoprotein fraction using apo AI levels for data normalization. The higher levels of AP SAA found in patients suggest a role of LDL as AP SAA carrier into the subendothelial space of artery wall, where AP SAA accumulates and may exert noxious effects.


[Microorganisms isolated from outpatient urine samples and antimicrobial susceptibility over a 12-year period].
This study aimed to determine the prevalence of microorganisms isolated from urine samples from outpatients and the resistance of the pathogens isolated to antimicrobial agents used in the province of Cordoba, Spain, which has a Health Area of approximately 776,000 inhabitants. It was a retrospective descriptive study covering a 12-year period (1992-2003). All samples were sent from primary care to the microbiology laboratory. The laboratory techniques and criteria for evaluation were the same in all cases. Escherichia coli was the most frequently isolated of the Gram-negative bacteria (64%), while Enterococcus faecalis was the most frequently isolated of the Gram-positive bacteria (6.9%). A decrease in susceptibility of the isolates to the most empirically used antimicrobial drugs was observed.


Preschool onset attention-deficit/hyperactivity disorder: course and predictors of stability over 24 months.
The present study examined the course of ADHD over 24 months in a preschool population. n=48 preschoolers with ADHD, aged 3.0-5.11 years, subjects included in a larger sample of preschoolers with depression and other disorders (n=306) were comprehensively assessed at 3 annual time points over 24 months in a prospective longitudinal follow-up study. Baseline diagnoses of preschool MDD, ODD, and CD were risk factors for ADHD diagnosis over 24 months in this preschool population. Among older preschoolers and after controlling for key demographic variables, ADHD predicted later ADHD diagnosis, along with other significant risk factors - baseline diagnosis of ODD, and/or family history of disruptive disorders, and stressful life events. ADHD showed greater homotypic continuity at later rather than earlier preschool ages. Other disruptive comorbidities also emerged as key predictors of stable ADHD course. Study findings may help to inform which preschool ADHD populations to target for early intervention. Larger sample sizes are needed to confirm these findings and to further explore the stability, course, and predictors of outcome of preschool onset ADHD.


Absence of significant sodium-hydrogen exchange by rabbit erythrocyte sodium-lithium countertransporter.
Red blood cells of several mammalian species (e.g., human, rabbit, bovine) possess a countertransport system for Li and Na. We have used rabbit red blood cells to determine the extent of sodium-proton exchange by this countertransporter. Ouabain-insensitive 22Na efflux into phosphate-buffered K-acetate media of varying Na concentrations was determined at extracellular pH 7.5 and 6.9. To maintain the intracellular pH at approximately 7.2, most of the acetate in the pH 6.9 medium was replaced by gluconate, a nonpenetrating anion. Extracellular Na strongly (greater than 10-fold) stimulated the 22Na efflux in both high- and low-pH media, but the K1/2 for this stimulation was higher at pH 6.9. This is consistent with a competitive binding of H to the outward-facing transport site. However, the lower pH itself, in a Na-free medium, stimulated the 22Na efflux only very slightly. The 22Na efflux stimulated by lowering the extracellular pH to 6.9 was less than 1% of the stimulation produced by 100 mM extracellular Na. It is concluded that, although H appears to bind to the substrate site of the Na-Li exchanger, there is no significant H transport in the physiological pH range.


Construction of nano-silica particle clusters and their effects on the shear thickening properties of liquids.
It is of great research significance to prepare a new shear thickening fluid (STF) with a simple process, remarkable thickening effect and excellent impact resistance from the properties of the particles. Inspired by the shear thickening mechanism, nano-silica particle clusters (SPC) with different morphological structures were prepared by the reaction of amino-modified silica with polyethylene glycol diglycidyl ether (PEGDGE), and the structure models of particle clusters were designed through theoretical analysis. The structure of SPC was affected by the degree of amination modification and the molecular weight of PEGDGE, which was analyzed by DLS and TEM. The shear thickening behavior of the fluid was evaluated by steady-state rheology and dynamic-state rheology analysis. The shear thickening behavior of the fluid composed of SPC also changed greatly with the influence of the degree of amination modification and the molecular weight of PEGDGE. In addition, compared with the STF contained original silica, the STF contained SPC could produce a faster and stronger shear thickening response. Therefore, silica particle clusters are not only a promising candidate for the preparation of high-performance shear thickening fluids, but can also be better applied to industrial and scientific fields such as impact protection and shock absorption.


The complete type of suprapatellar plica and lipoma arborescens: a case report.
Lipoma arborescens is a rare intra-articular benign lesion. It is characterized by villous lipomatous proliferation of the synovial tissue and its etiology is not certain. Clinical presentation is usually long-standing, painless and slowly progressive swelling of the related joint. Magnetic resonance imaging plays an important role in diagnosis. Diagnosis can be determined by hypertrophied synovial tissue with synovial lining cells containing adipose tissue on examination using a light microscope. The synovial plica of the knee is formed during the embryogenic phase of development. This development is incomplete in many individuals. When the synovial plica of the knee persists, it is transformed into an embryonic relic that is located in either the suprapatellar or midpatellar region of the knee. We present a rare case with both a complete type of suprapatellar plica and a symptomatic lipoma arborescens in the suprapatellar recess.


Ranolazine therapy in drug-refractory ventricular arrhythmias.
Ranolazine is an antiischemic and antianginal agent, but experimental and preclinical data provided evidence of additional antiarrhythmic properties. The aim of this study was to evaluate the safety and efficacy of ranolazine in reducing episodes of ventricular arrhythmias in patients with recurrent antiarrhythmic drug-refractory ventricular arrhythmias or with chronic angina. Seventeen implantable cardioverter defibrillator (ICD) recipients, who had experienced a worsening of their ventricular arrhythmia burden, and 12 ICD recipients with angina were enrolled. Patients were followed up for 6 months after the addition of ranolazine (postranolazine). Data were compared with before its administration (preranolazine). In the Arrhythmias group, a significant reduction was found in the median number of ventricular tachycardia episodes per patient (4 vs. 0, P = 0.01), and in ICD interventions in terms of both antitachycardia pacing (2 vs. 0, P = 0.04) and shock delivery (2 vs. 0, P = 0.02) after the addition of ranolazine. Moreover, fewer patients experienced episodes of nonsustained ventricular tachycardia (71 vs. 41%, P = 0.04), ventricular tachycardia (76 vs. 24%, P = 0.01), ICD antitachycardia pacing (47 vs. 18%, P = 0.02), and ICD shocks (47 vs. 6%, P = 0.03). In the Angina group, none of the patients developed major ventricular arrhythmias while on ranolazine treatment. No adverse effects were observed. In this small study, ranolazine proved to be effective, well tolerated, and safe in reducing ventricular arrhythmia episodes and ICD interventions in patients with recurrent antiarrhythmic drug-refractory events. In addition, none of the patients with chronic angina developed major ventricular arrhythmias.


Effects of dexamethasone, progesterone, and testosterone on IOP and GAGs in the rabbit eye.
The effects of steroids on intraocular pressure and on aqueous outflow pathway (AOP) and adjacent anterior segment tissue glycosaminoglycans (GAGs) were studied in New Zealand Red rabbits treated for 4 wk with dexamethasone, hydroxymethyl-progesterone and methyl-testosterone. Only topical administration of dexamethasone resulted in a significant increase in intraocular pressure. The eyes were labeled in vitro for 1 hr with GAG precursors, [3H]-glucosamine and [35S]-sulfate, and maintained as whole organ cultures. The GAGs were biochemically isolated, fractionated by gel filtration chromatography and subjected to selective GAG degradative procedures. The total content of hyaluronic acid and chondroitin sulfate was analyzed by high performance liquid chromatography. In dexamethasone-treated eyes, the total content of hyaluronic acid was decreased in the AOP, although the specific activity of [3H]-glucosamine did not change. The total content of chondroitin sulfate was increased in the AOP and iris-ciliary body, while the specific activity of the [35S]-label was decreased in the AOP, iris-ciliary body, and sclera. The changes in the AOP GAGs in dexamethasone-treated eyes may be important factors for the development of dexamethasone-induced ocular hypertension in the rabbit.


The Anatomical Basis of Cellulite Dimple Formation: An Ultrasound-Based Examination.
Cellulite is a common aesthetic condition that affects the majority of women. It is characterized by the inhomogeneous appearance of the skin overlying the gluteal and the posterior thigh region. Despite a wide array of treatment options, little has been done to evaluate the anatomical basis of cellulite formation. This study used ultrasound to visualize subcutaneous changes of cellulite to aid with treatment guidance and complication avoidance. Cellulite dimples were examined on the bilateral thigh and buttock regions of 50 consecutive women and each dimple was scored with the Hexsel Cellulite Scoring System based on severity. Cellulite dimples were then analyzed by ultrasound to identify the presence, orientation, and origination of subcutaneous fibrous bands and the presence of associated vascular structures. Two hundred total sites were examined, with 173 dimples identified. Of these, 169 demonstrated the presence of fibrous bands (97.6 percent). The majority of bands demonstrated an oblique (versus perpendicular) orientation to the skin (84.4 percent), with the majority (90.2 percent) taking origin from the superficial fascia (versus the deep fascia). Overall, 11 percent of bands had an associated vascular structure. When stratified by body mass index, overweight and obese patients had a higher likelihood of having an associated blood vessel visualized (p = 0.01). Results were similar for dimples in the thigh compared to those located in the buttock region. Ultrasound appears to be a valid technique to image the subcutaneous architecture of cellulite. This technology can help guide surgeons in real time to improve outcomes and minimize complications while performing cellulite treatments.


Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives.
Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 15% of severe cases require an intensive care unit (ICU) admission and mechanical ventilation due to development of acute respiratory distress syndrome (ARDS). Tetracyclines (TCs) are a group of bacteriostatic antibiotics, like tetracycline, minocycline, and doxycycline, effective against aerobic and anaerobic bacteria as well as Gram-positive and Gram-negative bacteria. Based on available evidences, TCs may be effective against coronaviruses and thus useful to treat COVID-19. Thus, this review aims to provide a brief overview on the uses of TCs for COVID-19 management. SARS-CoV-2 and other coronaviruses depend mainly on the matrix metalloproteinases (MMPs) for their proliferation, cell adhesion, and infiltration. The anti-inflammatory mechanisms of TCs are linked to different pathways. Briefly, TCs inhibit mitochondrial cytochrome c and caspase pathway with improvement of lymphopenia in early COVID-19. Specifically, minocycline is effective in reducing COVID-19-related complications, through attenuation of cytokine storm as apparent by reduction of interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF)-α. Different clinical trials recommend the replacement of azithromycin by minocycline in the management of COVID-19 patients at high risk due to two main reasons: 1) minocycline does not prolong the QT interval and even inhibits ischemia-induced arrhythmia; 2) minocycline displays synergistic effect with chloroquine against SARS-CoV-2. Taken together, the data presented here show that TCs, mainly doxycycline or minocycline, may be potential partners in COVID-19 management, derived pneumonia, and related complications, such as acute lung injury (ALI) and ARDS.


Executive dysfunction in frontotemporal dementia and corticobasal syndrome.
To determine the pattern of executive dysfunction in frontotemporal dementia (FTD) and corticobasal syndrome (CBS) and to determine the brain areas associated with executive dysfunction in these illnesses. We administered the Delis-Kaplan Executive Function System (D-KEFS), a collection of standardized executive function tests, to 51 patients with behavioral-variant FTD and 50 patients with CBS. We also performed a discriminant analysis on the D-KEFS to determine which executive function tests best distinguished the clinical diagnoses of FTD and CBS. Finally, we used voxel-based morphometry (VBM) to determine regional gray matter volume loss associated with executive dysfunction. Patients with FTD and patients with CBS showed executive dysfunction greater than memory dysfunction. Executive function was better preserved in the patients with CBS than the patients with FTD with the exception of tests that required motor, visuospatial ability, or both. In patients with CBS, dorsal frontal and parietal and temporal-parietal cortex was associated with executive function. In FTD, tests with a language component (Verbal Fluency) were associated with left perisylvian cortex, sorting with the left dorsolateral prefrontal cortex, and reasoning (the Twenty Questions task) with the left anterior frontal cortex. The Twenty Questions test best distinguished the clinical diagnoses of CBS and FTD. The neuroanatomic findings (especially in frontotemporal dementia [FTD]) agree with the previous literature on this topic. Patients with FTD and patients with corticobasal syndrome (CBS) show disparate performance on higher-order executive functions, especially the Twenty Questions test. It may be difficult to distinguish motor and visuospatial ability from executive function in patients with CBS using tests with significant motor and visuospatial demands such as Trail Making.


Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infection.
Parental exposure to pathogens can prime offspring immunity in diverse organisms. The mechanisms by which this heritable priming occurs are largely unknown. Here we report that the soil bacteria Pseudomonas vranovensis is a natural pathogen of the nematode Caenorhabditis elegans and that parental exposure of animals to P. vranovensis promotes offspring resistance to infection. Furthermore, we demonstrate a multigenerational enhancement of progeny survival when three consecutive generations of animals are exposed to P. vranovensis. By investigating the mechanisms by which animals heritably adapt to P. vranovensis infection, we found that parental infection by P. vranovensis results in increased expression of the cysteine synthases cysl-1 and cysl-2 and the regulator of hypoxia inducible factor rhy-1 in progeny, and that these three genes are required for adaptation to P. vranovensis. These observations establish a CYSL-1, CYSL-2, and RHY-1 dependent mechanism by which animals heritably adapt to infection.


[Immunoreactivity in suppurative keratitis].
Immunologic analysis of blood serum of 40 patients with purulent keratitis has shown disturbances in T- and B-systems of immunity, especially in moderate and severe degrees of the disease. This dictates a necessity of further studies in this direction by using immunocorrective therapy.


Health departments do it better: prenatal care site and prone infant sleep position.
Reduction of prone infant sleep position has been the main public health effort to reduce the incidence of Sudden Infant Death Syndrome (SIDS). Oregon Pregnancy Risk Assessment Monitoring System (PRAMS) surveys a stratified random sample of women after a live birth. In 1998-1999, 1867 women completed the survey (64.0% unweighted response; 73.5% weighted response). Overall, 9.2% of all women "usually" chose prone infant sleep position, while 24.2% chose side and 66.5% chose supine position. Women receiving care from private physicians or HMOs more often chose prone position (10.6%) than women receiving prenatal care from health department clinics (2.5%), hospital clinics (6.1%) or other sites (8.3%). Compared to health department prenatal clinic patients, private prenatal patients were more likely to choose prone infant sleep position, adjusted odds ratio = 4.78 (95% confidence interval [CI] 1.64-13.92). Health Department clinics have done a better job than private physicians in educating mothers about putting infants to sleep on their backs. Providers-especially private providers-should continue to stress the importance of supine sleep position for infants.


[Cardiovascular pathology in dermatomyositis].
Among 110 patients with dermatomyositis cardiovascular pathology was found in 77, and only in 37 of them it was attributable to the underlying pathology. In all of these patients myocardial lesions were found, that manifested themselves most frequently by non-specific ECG changes. Cardiac insufficiency and arrhythmias were revealed less frequently, mainly during exacerbations of the pathological process. Only in one patient endocarditis was diagnosed, and in two others elements of chronic cor pulmonale due to pneumonitis. In 18 patients signs of moderate myocardial dystrophy developed after a long-term therapy with corticosteroid hormones. A study of the central haemodynamics in 20 patients with dermatomyositis revealed a tendency towards a hyperkinetic state of the circulation in those patients who had the most sereve muscle syndrome. Angioscopy of the bulbar conjunctiva revealed the changes that persisted even during the remission period, achieved by means of active steroid therapy.


Outcomes after Proton Beam Irradiation in Patients with Choroidal Melanoma Eligible for Investigational AU-011 Treatment.
Vision loss is common in patients treated with radiotherapy for uveal melanoma. With proton beam irradiation (PBI), the prescribed dose is delivered to the tumor with a sharp dose reduction outside the target volume. However, radiation complications are likely to develop when tumors are located near the optic nerve or fovea. Treatment with light-activated AU-011 (belzupacap sarotalocan), an investigational drug which specifically targets tumor cells, may avoid these complications. We evaluated outcomes in a historical group of patients who fit eligibility criteria for AU-011 therapy and were treated with PBI. A consecutive series of patients who received PBI for small choroidal melanoma at a single center between 1986 and 2016 were identified. Consistent with eligibility criteria in clinical trials of AU-011, patients were included when tumor dimensions did not exceed 2.5 mm in maximum thickness and 10.0 mm in largest basal diameter (LBD). Snellen visual acuities were converted to logMAR for analysis. Visual acuity outcomes were analyzed in patients with an initial acuity of logMAR 0.7 or better (equivalent to Snellen 20/100). Rates of visual acuity loss and mortality were calculated using the Kaplan-Meier method. Acuity loss by tumor location was compared using log-rank testing. Rates of tumor recurrence, neovascular glaucoma (NVG), and eye loss were also described. Two hundred and 22 patients were included in the study. The median age was 60.7 years (range 21.3-94.8 years). Median tumor thickness was 2.0 mm (range 1.2-2.5 mm), and median LBD was 8.0 mm (range 4.0-10.0 mm). Median follow-up was 6.9 years (range 1.0-30.2 years). In 204 patients with a baseline logMAR visual acuity of 0.7 or better, the mean baseline acuity was 0.15 (equivalent to Snellen 20/25), which decreased to 0.52 (approximately Snellen 20/70) by 5 years after PBI. Visual outcomes were significantly worse for patients with tumors located within 3 mm of the optic disc and/or fovea. Tumor recurrence (1.4%), NVG (4.5%), and eye loss (2.7%) were uncommon. Despite the advantageous dose distribution of protons, over half of patients with small choroidal melanomas located near the optic disc or fovea had a visual acuity equivalent to 20/80 or worse at 5 years after PBI. Treatment with AU-011 may allow better vision preservation in small tumors that carry a high risk of vision loss with radiotherapy.


Combined transcript and metabolite analysis reveals genes involved in spider mite induced volatile formation in cucumber plants.
Many plants have an indirect defense against herbivores by emitting volatiles that attract carnivorous enemies of the herbivores. In cucumber (Cucumis sativus) the production of carnivore attractants can be induced by herbivory or jasmonic acid spraying. From the leaves of cucumber plants with and without spider mite infestation, two subtractive cDNA libraries were made that were enriched in cDNA fragments up- or down-regulated by spider mite infestation. A total of 713 randomly selected clones from these libraries were used to make a cDNA microarray. Subsequently, cucumber plants were sprayed with jasmonic acid, mechanically damaged, infested with spider mites, or left untreated (control). Leaf samples were taken at a range of different time points, and induced volatile compounds and mRNA (from the same leaves) were collected. cDNAs prepared from the mRNA were hybridized to the clones on the microarray. The resulting gene expression profiles were analyzed in combination with volatile production data in order to gain insight in the possible involvement of the studied genes in the synthesis of those volatiles. The clones on the microarray and the induced cucumber volatiles could be grouped into a number of clusters in which specific biosynthetic genes clustered with the product of that pathway. For example, lipoxygenase cDNA clones clustered with the volatile (Z)-3-hexenyl acetate and the volatile sesquiterpene (E,E)- alpha-farnesene clustered with an up-regulated sesquiterpene synthase fragment. This fragment was used to screen a cDNA library which resulted in the cloning of the cucumber (E,E)-alpha-farnesene and (E)-beta-caryophyllene synthases. The use of combined global gene expression analysis and metabolite analysis for the discovery of genes involved in specific biosynthetic processes is discussed.


Fractional exhaled nitric oxide and impulse oscillometry in children with allergic rhinitis.
Airway inflammation, bronchial hyper-responsiveness (BHR), and bronchodilator response (BDR) are representative characteristics of asthma. Because allergic rhinitis (AR) is a risk factor for asthma development, we evaluated these 3 characteristics in AR using measurement of fractional exhaled nitric oxide (FeNO), a methacholine challenge test (MCT), and impulse oscillometry (IOS). This study included 112 children with asthma (asthma group), 196 children with AR (AR group), and 32 control subjects (control group). We compared pulmonary function parameters and FeNO levels among the 3 groups. The AR group was subdivided into 2 categories: the AR group with BHR and the AR group without, and again pulmonary function and FeNO levels were compared between the 2 subgroups. FeNO levels were more increased in the AR and asthma groups than in the control group; within the AR group, FeNO was higher in the AR group with BHR than in the AR group without. The BDR was more increased in the AR group than in the control group when percent changes in reactance at 5 Hz (Δ X5) and reactance area (Δ AX) were compared. In the AR group, however, there was no difference in Δ X5 and Δ AX between the AR group with BHR and the AR group without. Reversible airway obstruction on IOS and elevated FeNO levels were observed in children with AR. Because elevated FeNO levels can indicate airway inflammation and because chronic inflammation may lead to BHR, FeNO levels may be associated with BHR in AR. IOS can be a useful tool for detecting lower airway involvement of AR independent of BHR assessed in the MCT.


Comparison of the saccules and lagenae in six macrourid fishes from different deep-sea habitatsa).
There are substantial interspecific differences in the morphology of the ears of the more than 34 000 living fish species. However, almost nothing is known about the functional significance of these differences. One reason is that most comparative studies have been conducted on shallow-water species with far less focus on the numerous species that inhabit the depths of the oceans. Thus, to get a better sense of ear diversity in fishes and its potential role in hearing, this study focuses on the saccule and lagena, the primary auditory end organs, in six species of the family Macrouridae (rattails), a large group of fishes that typically inhabit depths from 1000 to 4000 m. The inner ears and, particularly, the saccules and lagenae in these species are large with the saccule resembling that of other Gadiformes. The lagenae of all macrourids studied here have serrated edge otoliths and highly diverse hair cell ciliary bundle shapes. The differences found in the inner ear anatomy of macrourids likely reflect the sensory advantages in different habitats that are related to the benefits and constraints at different depths, the fish's particular lifestyle, and the trade-off among different sensory systems.


Isolation and molecular characterization of spermatogonia from male Sprague-Dawley rats exposed in utero and postnatally to dibutyl phthalate or acrylamide.
The increased incidence of testicular disorders in young men and the possible influence of environmental chemicals, such as dibutyl phthalate (DBP) and acrylamide (AA), requires experimental models for identifying modes of action. Most published reproductive toxicologic studies use RNA samples from the total testis to evaluate testicular gene expression; however, analyses of isolated cell types could provide a more specific tool. Among testicular germ cells, spermatogonia are critical since they represent the onset of spermatogenesis. This study aimed, (1) to establish a technique for spermatogonia isolation; (2) to apply this isolation technique to verify possible gene expression alterations (Pou5f1, Kitlg, Mki-67, Bak1 and Spry4) in prepubertal post-natal day, (PND24) and pubertal (PND45) testes after in utero and postnatal exposure to DBP or AA. The technique was efficient for isolation of a majority of spermatogonia. In utero DBP exposure led to reduced litter body weight at birth, reduced anogenital distance of male pups on PND4, and increased frequency of male nipple retention on PND14 compared to controls. DBP-exposed relative testes weights were reduced only at PND24 compared to control but they did not differ at PND45. DBP-exposed animals showed reduced expression levels of Pou5f1 and Mki67 on PND24, and reduced expression of Pou5f1 and Spry4 on PND45. AA exposure reduced expression of Pou5f1, Mki67, and Spry4 at PND45 although not significantly. Our results suggest that DBP acts by reducing cell proliferation and impairing differentiation in prepubertal and pubertal testes.


Dietary protein energy supplementation of pregnant Asian mothers at Sorrento, Birmingham. II: Selective during third trimester only.
Unselective dietary protein energy supplementation of Asian mothers at Sorrento Maternity Hospital did not enhance intrauterine growth. The effect of selective supplementation was therefore studied. Forty-five mothers who at 28 weeks were known to be nutritionally at risk (triceps increment less than or equal to 20 microns/week between 18 and 28 weeks) received one of three supplements during the third trimester: (a) vitamins only--a multivitamin sachet daily containing vitamins A, B, C, and D; (b) energy--42-125 MJ (10 000-30 000 kcal), all from carbohydrate, plus vitamins; (c) protein energy--energy and vitamins as before, but with 5-10% of energy from milk protein. Eighty-three mothers regarded as adequately nourished at 28 weeks also received one of the three supplements. In the nutritionally at-risk mothers the protein energy supplement was associated with a heavier crude birth weight and heavier weight for gestational age. Supplementation did not lead to improved intrauterine growth in those mothers who were adequately nourished. The differential effect of supplementation depending on the mothers' nutritional state during the second trimester may explain apparently conflicting results of other studies where some have shown a substantial effect of supplementation and others only a small effect. This effect of intervention is further evidence that "poor nutrition" contributes to poor intrauterine growth in selected mothers, even in developed countries.


Medical waste autoclaves: not just a lot of hot air.
Over the past ten years, the treatment of medical waste has received much attention. During this time, an entire new industry to develop "alternate medical waste treatment technologies" has emerged. Much of this has been in response to increasingly stringent air quality standards along with public sentiment opposed to incineration, with a resultant decline in the use of on-site medical waste incinerators. However, in between incinerators and alternative treatment systems is a technology that is as much a part of American healthcare as hospitals themselves. Medical waste regulation in all fifty states recognize steam sterilization as an acceptable method of treatment prior to disposal. Within this category of medical waste treatment technology, there is a wide array of systems available, many of which have altered the basic, simple principles of steam treatment to make it more conducive to this application. This Professional Development Series reviews some the basic and newer innovative techniques of steam treatment of medical waste.


Monte Carlo phase diagram for diblock copolymer melts.
The phase diagram for diblock copolymer melts is evaluated from lattice-based Monte Carlo simulations using parallel tempering, improving upon earlier simulations that used sequential temperature scans. This new approach locates the order-disorder transition (ODT) far more accurately by the occurrence of a sharp spike in the heat capacity. The present study also performs a more thorough investigation of finite-size effects, which reveals that the gyroid (G) morphology spontaneously forms in place of the perforated-lamellar (PL) phase identified in the earlier study. Nevertheless, there still remains a small region where the PL phase appears to be stable. Interestingly, the lamellar (L) phase next to this region exhibits a small population of transient perforations, which may explain previous scattering experiments suggesting a modulated-lamellar (ML) phase.


Antibacterial activity and osseointegration of silver-coated poly(ether ether ketone) prepared using the polydopamine-assisted deposition technique.
Poly(ether ether ketone) (PEEK) is a popular orthopaedic implant material due to the outstanding biocompatibility and mechanical properties. However, bacterial infections and aseptic loosening during implantation can cause many clinical problems that may eventually lead to implant failure. Therefore, endowing implants with antibacterial functions plays an important role in promoting integration between implants and bone tissue and ultimately, in successful implantation. This study aimed to develop a biocompatible and antibacterial coating for PEEK implants using polydopamine (PDA)-based surface modification technology and subsequent deposition of silver (Ag) nanoparticles (PEEK-PDA-Ag). Formation of Ag nanoparticles was clearly observed on the surface of PEEK-PDA-Ag using scanning electron microscopy. PEEK-PDA-Ag showed low toxicity to MC3T3-E1 cells. It exhibited outstanding antibacterial properties against both S. aureus and E. coli in vitro as well as decent antibacterial performance in vivo. In addition, in vivo studies demonstrated good osseointegration of PEEK-PDA-Ag implants, as shown by micro-CT evaluation and push-out tests. Together, the findings from this study indicate that the facilely prepared PEEK-PDA-Ag substrates possess considerable biocompatibility and antibacterial properties, permitting their potential use as a promising orthopaedic implant material.


Comparative assessment of distance processing and hemispheric specialization in humans and baboons (Papio papio).
This comparative study explored the ability to process distance and its lateralization in humans and baboons. Using a conditional matching-to-sample procedure in a divided-field format, subjects had to decide whether or not the distance between a line and a dot belonged to a short- or a long-distance category. Experiments 1, 2, and 4 demonstrated the ability of baboons to process and categorize distances. Moreover, humans showed better distance processing for right visual field/left hemisphere presentations than for left visual field/right hemisphere (LVF-RH) displays (Experiments 1-2). The same bias was found in baboons (Experiment 1), but in a weaker way. In Experiment 3, naive human individuals were tested and the difficulty of the discrimination was enhanced. There was a LVF-RH advantage which vanished with practice. Results are discussed by referring to theories (i.e., Kosslyn, 1987) of visuospatial processing for coordinate and categorical judgments.


Does structural commonality of metal complex formation by PAC-1 (anticancer), DHBNH (anti-HIV), AHL (autoinducer), and UCS1025A (anticancer) denote mechanistic similarity? Signal transduction and medical aspects.
There is an urgent need of novel approaches to drugs in the cancer, HIV, and bacterial areas. Increasing resistance to conventional therapies is observed. This minireview provides novel insights for drugs in these three areas. The agents PAC-1 (anticancer), DHBNH (anti-HIV), AHL (autoinducer), and UCS1025A (anticancer) have recently attracted attention due to considerable potential based on new approaches. PAC-1 activates procaspase-3 to caspase-3, resulting in induction of apoptosis in tumor cells. DHBNH binds to a newly revealed site on HIV reverse transcriptase. The drug mainly inhibits RNase H (RNA-cleaving). AHLs comprise an important class that participates in bacterial cell communication. UCS1025A is a fungus-derived inhibitor of the enzyme telomerase, present in cancer cells, which is crucially involved in tumor cell immortality. All four agents possess chelating sites for metal binding, which has not been appreciated. In PAC-1 and DHBNH, the coordinating portion is similar to salicylaldehyde semicarbazone. For AHL and UCS1025A, the metal-binding moiety is a beta -ketoamide. Metal complexes of heavier metals are well-known electron transfer (ET) functionalities that can generate reactive oxygen species. Hence, it is reasonable to hypothesize a commonality in mechanism based on metal ET. Differences in receptor binding can result, in part, in diverse physiological responses. There is considerable literature that addresses involvement of signal transduction with the various physiologically active agents discussed herein. Thus, cell communication appears to play an important role in the biochemistry of these endogenous and exogenous substances. Details of cell signaling are presented for complexes of metals (Fe, Cu, Ni, and As), telomerase, caspase-3, and RNase. In addition, practical medical aspects are discussed.


Patient Education and Discharge Planning to Prevent Functional Decline in the Older Adult.
The population in the United States is aging, and persons older than 65 years account for over 50% of healthcare costs. Preventing functional decline in older adults through patient education and optimal discharge planning is one way we can succeed in decreasing healthcare costs, readmissions, and mortality in this population. The aim of this article is to present viable healthcare policy options to prevent or minimize functional decline in the older adult, regardless of what health-related facility the person enters. Policy objectives include mandating functional screening tests on all persons 65 years and older, addressing functional status as a required element of discharge planning, tracking and reporting patient outcomes, and utilizing advanced practice nurses to the full extent of their education and scope of practice. Three policy options are presented, analyzed, and compared. The summary concludes with a recommended policy option.


Virulence of pPst+ and pPst- strains of Yersinia pestis for guinea-pigs.
Guinea-pigs were infected subcutaneously or by respiratory challenge with plasmid-containing (pPst+pCad+pFra+) Yersinia pestis strain 358 and its pPst-pCad+pFra+, pPst+pCad+pFra- and pPst-pCad+pFra- derivatives, grown in vitro at 28 degrees C or at 37 degrees C. Lack of plasmid pPst did not lead to an increase in LD50 with either route of challenge. When the virulence of the four Y. pestis strains grown at the two temperatures was compared, the LD50 values of those grown at 37 degrees C were lower. Respiratory challenge with cultures grown at 37 degrees C mimics the man-to-man pneumonic plague cycle. The average LD50 values decreased c. two-fold and 10-fold for pPst+ and pPst- Y. pestis variants, respectively. The data suggest that historical epidemic outbreaks of pneumonic plague in the human population residing in the Caucasus region where there are natural plague foci in common voles may have been caused by pPst- Y. pestis strains.


Effect of Rotation on Scaffold Motion and Cell Growth in Rotating Bioreactors.
Efficient use of different bioreactor designs to improve cell growth in three-dimensional scaffolds requires an understanding of their mechanism of action. To address this for rotating wall vessel bioreactors, fluid and scaffold motion were investigated experimentally at different rotation speeds and vessel fill volumes. Low cost bioreactors with single and dual axis rotation were developed to investigate the effect of these systems on human osteoblast proliferation in free floating and constrained collagen-glycosaminoglycan porous scaffolds. A range of scaffold motions (free fall, periodic oscillation, and orbital motion) were observed at the rotation speeds and vessel fluid/air ratios used, with 85% fluid fill and an outer vessel wall velocity of ∼14 mm s-1 producing a scaffold in a free fall state. The cell proliferation results showed that after 14 and 21 days of culture, this combination of fluid fill and speed of rotation produced significantly greater cell numbers in the scaffolds than when lower or higher rotation speeds (p < 0.002) or when the chamber was 60% or 100% full (p < 0.01). The fluid flow and scaffold motion experiments show that biaxial rotation would not improve the mass transfer of medium into the scaffold as the second axis of rotation can only transition the scaffold toward oscillatory or orbital motion and, hence, reduce mass transport to the scaffold. The cell culture results confirmed that there was no benefit to the second axis of rotation with no significant difference in cell proliferation either when the scaffolds were free floating or constrained (p > 0.05).


Extrarenal nephroblastic proliferation in spinal dysraphism. A report of 4 cases.
Four cases of extrarenal nephrogenic proliferation in the sacrococcygeal region with spinal dysraphism are presented. In two of the cases, features of Wilm's or incipient Wilm's tumor were present. The previous literature on sacrococcygeal nephrogenic tissue is reviewed, and the impact of these findings on the histogenesis of extrarenal sacrococcygeal Wilm's tumor is discussed.


Synthesis, neutralization and blocking procedures of organic/inorganic hybrid scaffolds for bone tissue engineering applications.
Bioactive glasses (BaG) can bind to human bone tissues and have been used in many biomedical applications for the last 30 years. However they usually are weak and brittle. On the other hand, composites that combine polymers and BaG are of particular interest, since they often show an excellent balance between stiffness and toughness. Bioactive glass-poly(vinyl alcohol) foams to be used in tissue engineering applications were previously developed by our group, using the sol-gel route. Since bioactive glass-polymer composite derived from the sol-gel process cannot be submitted to thermal treatments at high temperatures (above 400 degrees C), they usually have unreacted species that can cause cytotoxicity. This work reports a technique for stabilizing the sol-gel derived bioactive glass/poly(vinyl alcohol) hybrids by using glutaraldehyde (GA), NH(4)OH solutions and a blocking solution containing bovine serum albumin. PVA/BaG/GA hybrids were characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM/EDX) analyses. Moreover, MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide) biocompatibility and cytotoxicity assays were also conducted. The hybrids exhibited pore size varying from 80 to 820 mum. After treatments, no major changes in the pore structure were observed and high levels of cell viability were obtained.


Dietary effects on brain serotonin synthesis: relationship to appetite regulation.
This review summarizes evidence showing that: 1) the synthesis of serotonin in the brain depends directly on the amount of tryptophan available to it from the circulation; 2) tryptophan uptake into brain depends on the blood levels not only of tryptophan, but also of other aromatic and branched-chain amino acids that compete with tryptophan for a common transport carrier into brain; and 3) dietary factors that influence the blood levels of tryptophan and these other amino acids can modify tryptophan uptake into brain, and consequently the rate of serotonin formation. Additionally, data are reviewed that attempt to show that appetite for protein and/or carbohydrates is dependent on the relationship between food intake, plasma amino acid pattern, brain tryptophan uptake, and serotonin synthesis.


Systematic comparison of graph embedding methods in practical tasks.
Network embedding techniques aim to represent structural properties of graphs in geometric space. Those representations are considered useful in downstream tasks such as link prediction and clustering. However, the number of graph embedding methods available on the market is large, and practitioners face the nontrivial choice of selecting the proper approach for a given application. The present work attempts to close this gap of knowledge through a systematic comparison of 11 different methods for graph embedding. We consider methods for embedding networks in the hyperbolic and Euclidean metric spaces, as well as nonmetric community-based embedding methods. We apply these methods to embed more than 100 real-world and synthetic networks. Three common downstream tasks - mapping accuracy, greedy routing, and link prediction - are considered to evaluate the quality of the various embedding methods. Our results show that some Euclidean embedding methods excel in greedy routing. As for link prediction, community-based and hyperbolic embedding methods yield an overall performance that is superior to that of Euclidean-space-based approaches. We compare the running time for different methods and further analyze the impact of different network characteristics such as degree distribution, modularity, and clustering coefficients on the quality of the embedding results. We release our evaluation framework to provide a standardized benchmark for arbitrary embedding methods.


Rate of and risk factors for acute inpatient mortality after orthopaedic surgery.
Orthopaedic surgeons operate on a diverse group of patients, and many of these patients have concomitant medical problems. The purpose of this study was to identify the rate of mortality and to evaluate the risk factors associated with mortality after orthopaedic surgery. Data from the National Hospital Discharge Survey, a nationwide sample of hospital admissions, were obtained for the years 1995 through 1997. The study was limited to hospital admissions. Univariate and multivariate analyses were performed. The 43,215 inpatient orthopaedic operations that we evaluated were associated with a mortality rate of 0.92%. Seventy-seven percent of all deaths occurred after procedures performed for patients who were more than seventy years old, and 50% of all deaths occurred after operations performed for the treatment of hip fractures. The independent preoperative medical risk factors for death included chronic renal failure, congestive heart failure, metastasis to bone, atrial fibrillation, chronic obstructive pulmonary disease, and osteomyelitis. The risk factors of diabetes, coronary artery disease, peripheral vascular disease, septic arthritis, and rheumatoid arthritis did not achieve significance. Among orthopaedic subspecialty categories, operations for tumors, trauma, and infection were associated with elevated mortality rates. In a predictive model, five critical risk factors were identified as most helpful in identifying patients at risk for death: chronic renal failure, congestive heart failure, chronic obstructive pulmonary disease, hip fracture, and an age of greater than seventy years. The mortality rate was 0.25% for patients with no critical risk factors. A linear increase in mortality was seen with increasing numbers of critical risk factors (p < 0.005). Death is rare after orthopaedic operations. In the United States, the rate of acute mortality after inpatient orthopaedic surgical procedures is approximately 1% for all patients, 3.1% for patients with a hip fracture, and 0.5% for patients without a hip fracture. These data will aid orthopaedic surgeons in predicting operative mortality for their patients.


Effects of relaxation with guided imagery on surgical stress and wound healing.
The purpose of this experiment was to determine the effects of an audiotape series employing Relaxation with Guided Imagery (RGI) on the psychophysiologic stress response and wound healing in surgical patients. Twenty-four patients undergoing cholecystectomy were randomly assigned to either RGI or control (quiet period) conditions and measured against three indexes of recovery: state anxiety, urinary cortisol levels, and wound inflammatory responses. An analysis of variance for repeated measures revealed that the RGI group demonstrated significantly less state anxiety, lower cortisol levels one day following surgery, and less surgical wound erythema than the control group. Thus, the RGI tapes demonstrated stress-relieving outcomes closely associated with healing.


The analgesic efficacy of pectoral nerve block for breast augmentation: a meta-analysis of randomized controlled studies.
Many patients suffered from serious pain after breast augmentation, but the analgesic efficacy of pectoral nerve block for these patients was not well established. Thus, this meta-analysis was intended to study the analgesic efficacy of pectoral nerve block for breast augmentation. Several databases including PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases were searched, and we included randomized controlled trials (RCTs) regarding the analgesic efficacy of pectoral nerve block for breast augmentation. Six RCTs were ultimately included in this meta-analysis. Compared with control intervention for breast augmentation, pectoral nerve block could significantly reduce pain scores at 1 h (mean difference [MD] = -2.28; 95% confidence interval [CI] = -3.71 to -0.85; P = 0.002), 2 h (MD = -3.08; 95% CI = -3.95 to -2.20; P < 0.00001), 4 h (MD = -2.95; 95% CI = -3.32 to -2.58; P < 0.00001), 6-8 h (MD = -2.68; 95% CI = -3.24 to -2.11; P < 0.00001), 24 h (MD = -2.04; 95% CI = -2.41 to -1.67; P < 0.00001), the number of analgesic requirement (odd ratio [OR] = 0.20; 95% CI = 0.09 to 0.45; P = 0.0001), and the incidence of nausea (OR = 0.21; 95% CI = 0.08 to 0.54; P = 0.001) and vomiting (OR = 0.15; 95% CI = 0.05 to 0.39; P = 0.0001). Conclusions: Pectoral nerve block may be effective for pain relief after breast augmentation.


Interrater reliability of measurements of comorbid illness should be reported.
Comorbidity indices are commonly used to stratify patients to control for treatment selection bias. The objectives here were to review the reporting of interrater reliability when studies use comorbidity indices in clinical research publications and to report the interrater reliability of four common indices in a particular research setting. Four trained abstractors reviewed the same 40 charts of patients with squamous cell carcinoma of the head and neck from a regional cancer center. Scores for the Charlson Index, the Index of Co-existent Disease, the Cumulative Illness Rating Scale, and the Kaplan-Feinstein Classification were calculated, and the intraclass correlation coefficient was used to assess interrater reliability. The details on the training of abstractors and the results of interrater reliability tests are not commonly reported. In our study setting, the Charlson Index had excellent reliability and the others had acceptable reliability. If the quality of a study using an index or scale is to be assessed, the reliability and interrater reliability of the score assignment process should be reported.


Bacterial Transformation Buffers Environmental Fluctuations through the Reversible Integration of Mobile Genetic Elements.
Horizontal gene transfer (HGT) promotes the spread of genes within bacterial communities. Among the HGT mechanisms, natural transformation stands out as being encoded by the bacterial core genome. Natural transformation is often viewed as a way to acquire new genes and to generate genetic mixing within bacterial populations. Another recently proposed function is the curing of bacterial genomes of their infectious parasitic mobile genetic elements (MGEs). Here, we propose that these seemingly opposing theoretical points of view can be unified. Although costly for bacterial cells, MGEs can carry functions that are at points in time beneficial to bacteria under stressful conditions (e.g., antibiotic resistance genes). Using computational modeling, we show that, in stochastic environments, an intermediate transformation rate maximizes bacterial fitness by allowing the reversible integration of MGEs carrying resistance genes, although these MGEs are costly for host cell replication. Based on this dual function (MGE acquisition and removal), transformation would be a key mechanism for stabilizing the bacterial genome in the long term, and this would explain its striking conservation.IMPORTANCE Natural transformation is the acquisition, controlled by bacteria, of extracellular DNA and is one of the most common mechanisms of horizontal gene transfer, promoting the spread of resistance genes. However, its evolutionary function remains elusive, and two main roles have been proposed: (i) the new gene acquisition and genetic mixing within bacterial populations and (ii) the removal of infectious parasitic mobile genetic elements (MGEs). While the first one promotes genetic diversification, the other one promotes the removal of foreign DNA and thus genome stability, making these two functions apparently antagonistic. Using a computational model, we show that intermediate transformation rates, commonly observed in bacteria, allow the acquisition then removal of MGEs. The transient acquisition of costly MGEs with resistance genes maximizes bacterial fitness in environments with stochastic stress exposure. Thus, transformation would ensure both a strong dynamic of the bacterial genome in the short term and its long-term stabilization.


Excessive trading, a gambling disorder in its own right? A case study on a French disordered gamblers cohort.
Trading and gambling appear to share some similarities. Indeed, traders can get professionally involved in high-risk types of trading as if it were gambling. This research explores whether excessive trading can be conceptualized as a subset of gambling disorders. To better acknowledge the existence of an addictive-like trading behavior and to discuss its phenomenological similarities with gambling disorders. The data of 8 excessive traders out of a cohort of 221 outpatients seeking treatment in our Problem Gambling unit were analyzed. Our case series revealed important similarities with gambling disorders in terms of diagnosis, trajectory and comorbidities. Like many disordered gamblers, excessive traders of this study experienced a number of small early wins, chased their losses, and ended up losing control over the money they invested. All of them invested in very risky stocks associated with short-term trading leading to potential large gains, but also with very significant losses. The structure itself of the two activities (gambling and trading) is very close. Our results tended to support the idea of an addictive-like trading behavior as a subset of gambling disorders. Investing is not a form of gambling, but some people gamble with investments. Several observations and recommendations can be made: (i) conduct researches; (ii) build and validate specific assessment tools; (iii) develop strategies for prevention and treatment; and (iv) conduct more rigorous studies to clarify what we named an addictive-like trading behavior.


Impacts of imperfect geometry structure on the nonlinear and chromatic dispersion properties of a microstructure fiber.
We numerically investigated the impacts of the imperfect geometry structure on the nonlinear and chromatic dispersion properties of a microstructure fiber (MF). The statistical results show that the imperfect geometry structure degrades the high nonlinearity and fluctuates the chromatic dispersion in a MF. Moreover, the smaller air holes and the larger pitch are more likely to maintain the properties of nonlinearity and chromatic dispersion. Finally, the nonlinearity and chromatic dispersion are more insensitive to air-hole nonuniformity than to air-hole disorder. All of these will provide references for designing and fabricating MF.


Energetics and power output of isolated fish fast muscle fibres performing oscillatory work.
Fast myotomal muscle fibres were isolated from the cod (Gadus morhua L.) and the energy cost of contraction was measured under conditions simulating swimming. Fibre bundles were subjected to sinusoidal cycles of shortening and lengthening about their in situ fibre length, and stimulated at selected phases in each cycle. The preparations were poisoned with iodoacetic acid and bubbled with nitrogen to block the synthesis of ATP. After an initial rapid decline over the first 10 cycles, force and net work remained steady in some cases for up to 64 oscillatory length cycles, but more commonly declined slowly after about 30 cycles. The total mechanical work performed increased largely in proportion to the number of work cycles. At the end of each experiment fibres were frozen in isopentane cooled in liquid nitrogen and metabolite concentrations determined by high performance liquid chromatography (HPLC) and enzymatic analysis. Concentrations of adenylates did not differ significantly from control values, although a significant increase in IMP concentrations at 64 cycles accounted for the maintenance of relatively high energy charge values. Creatine (C) concentrations increased and creatine phosphate (CP) concentrations decreased, implying a tight coupling of the ATP/ADP reaction to the CP/C reaction. Muscle economy was calculated as the positive work performed during a work cycle divided by the total chemical energy expended. These values (approx. 7 mJ mumol-1) were found to be independent of the number of work cycles performed, although a trend to increase was observed. Muscle efficiency values, calculated assuming a Gibb's force free energy change for CP splitting in vivo of 55 kJ mol-1, were in the range 12-23%.


Cl-Amidine Improves Survival and Attenuates Kidney Injury in a Rabbit Model of Endotoxic Shock.
Objective: Sepsis causes millions of deaths on a global scale annually. Activation of peptidylarginine deiminase (PAD) enzymes in sepsis causes citrullination of histones, which results in neutrophil extracellular trap formation and sepsis progression. This study evaluates pan-PAD inhibitor, Cl-amidine, in a model of lipopolysaccharide (LPS)-induced endotoxic shock in rabbits. We hypothesized that Cl-amidine would improve survival and attenuate kidney injury. Methods: In the survival model, rabbits were injected injected intravenously with 1 mg/kg of LPS, and then randomly assigned either to receive dimethyl sulfoxide (DMSO; 1 mcL/g) or Cl-amidine (10 mg/kg diluted in 1 mcL/g DMSO). They were then monitored for 14 days to evaluate survival. In the non-survival experiment, the same insult and treatment were administered, however; the animals were euthanized 12 hours after LPS injection for kidney harvest. Acute kidney injury (AKI) scoring was performed by a histopathologist who was blinded to the group assignment. Serial blood samples were also collected and compared. Results: Rabbits that received Cl-amidine had a higher survival (72%) compared with the rabbits that received DMSO (14%; p < 0.05). Cl-amidine-treated rabbits had lower (p < 0.05) histopathologic AKI scores, as well as plasma creatinine and blood urea nitrogen (BUN) levels 12 hours after insult. Conclusions: Pan-PAD inhibitor Cl-amidine improves survival and attenuates kidney injury in LPS-induced endotoxic shock in rabbits.


IMGT, the international ImMunoGeneTics information system for Immunoinformatics. Methods for querying IMGT databases, tools, and Web resources in the context of immunoinformatics.
IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), was created in 1989 by the Laboratoire d'lmmunoGénétique Moléculaire (LIGM) (Université Montpellier II and CNRS) at Montpellier, France, in order to standardize and manage the complexity of immunogenetics data. IMGT is recognized as the international reference in immunogenetics and immunoinformatics. IMGT is a high quality integrated knowledge resource, specialized in (i) the immunoglobulin (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates; (ii) proteins that belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF); and (iii) related proteins of the immune systems (RPI) of any species. IMGT provides a common access to standardized data from genome, proteome, genetics, and three-dimensional (3D) structures for the IG, TR, MHC, IgSF, MhcSF, and RPI. IMGT interactive on-line tools are provided for genome, sequence, and 3D structure analysis. IMGT Web resources comprise 8,000 HTML pages of synthesis and knowledge (IMGT Scientific chart, IMGT Repertoire, IMGT Education, etc.) and external links (IMGT Bloc-notes and IMGT other accesses).


Regulation of C4-phosphoenolpyruvate carboxylase activity by ambient CO2.
Light activation of phosphoenolpyruvate carboxylase from the leaves of the C4 plant Setaria verticillata (L.) is more pronounced at low CO2 levels. The 2-fold activation observed at physiological ambient CO2 becomes 3.64-fold at 5 μL/L and completely abolished above 700 μL/L. When the stomata close under the influence of abscisic acid at 330 μL/L CO2, the extent of light activation is high (3.59-fold), probably because the increased diffusive resistance keeps the internal CO2 at much lower levels. Under darkness. CO2 and absicisic acid do not affect the extractable phosphoenolpyruvate carboxylase activity. Internal CO2 levels may determine phosphoenolpyruvate concentratio in the cytoplasm through the control of its utilization by phosphoenolpyruvate carboxylase. We have recently proposed (Samaras et al. 1988) that photosynthetically produced phosphoenolpyruvate could be an activator of the enzyme. It is therefore suggested that CO2 indirectly affects the activation state of phosphoenolpyruvate carboxylase by controlling the levels of phosphoenolpyruvate which may act as an activator.


The nature of cancer and the mechanisms of its control: a review.
Observations on the nature of spontaneous tumours of mammary gland origin in mice, published over a 60-year period in 320 papers, are reviewed. Data presented are (1) development of adequate experimental mice; (2) comparative studies on transplantable, chemically induced and spontaneous tumours by diverse genetic procedures, and (3) tumour regressions obtained with nucleosides. The fundamental conclusion derived from these data is that a genetic change, comparable to a somatic mutation, is involved in the origin of cancer. Nucleosides, especially 5-methyl cytidine (a mild mutagen), have been indicated in the controlling mechanism for this genetic change. The nucleosides appear to be involved in the stabilization of the helical formation of the chromatid strand. The concept of induced stability of chromosome behaviour is discussed, and a number of other aspects including viral and endocrine influence, and histocompatibility.


[Superoxide dismutase in plant cells].
Superoxide dismutase (SOD) is one of the key components of defense system, which protect cells and tissues from oxidative destruction. The unique nature of this enzyme among other antioxidants, its localization in different intracellular compartment are reviewed in addition to enzyme behaviour under unflavourable influences. Besides, we considered questions of regulation of SOD activity, participation of such intracellular macromolecules as reactive oxygen species, calcium iones, phytogormones, and nitric oxide in this regulation, as well as phosphoralation/dephosphorylation process.


Multicenter prospective study of the humoral autoimmune response in bullous pemphigoid.
Bullous pemphigoid (BP) is an autoimmune bullous disease, associated with autoantibodies directed against the hemidesmosomal components BP180 and BP230. In this study for the first time different laboratories have analyzed the autoantibody profile in the same group of 49 prospectively recruited BP patients. The results show that: 1) disease severity and activity correlated with levels of IgG against the BP180-NC16A domain, but also against a COOH-terminal epitope of BP180, 2) distinct epitopes of the BP180 ectodomain other than BP180-NC16A were recognized by 96% of the BP sera; and 3) the combined use of BP180 and BP230 ELISA led to the detection of IgG autoantibodies in all the BP sera. These results demonstrate the usefulness of the combined ELISAs based on various BP180 and BP230 fragments in establishing the diagnosis of BP and support the concept that BP180 is the major autoantigen of BP.


Ionoregulatory changes during metamorphosis and salinity exposure of juvenile sea lamprey (Petromyzon marinus L.).
Ammocoetes of the anadromous sea lamprey Petromyzon marinus L. spend many years in freshwater before metamorphosing and migrating to sea. Metamorphosis involves the radical transformation from a substrate-dwelling, filter feeder into a free-swimming, parasitic feeder. In the present work we examined osmoregulatory differences between ammocoetes and transformers (metamorphic juveniles), and the effects of salinity acclimation. We measured the expression of key ion-transporting proteins [Na(+)/K(+)-ATPase, vacuolar (V)-type H(+)-ATPase and carbonic anhydrase (CA)] as well as a number of relevant blood parameters (hematocrit, [Na(+)] and [Cl(-)]). In addition, immunofluorescence microscopy was used to identify and characterize the distributions of Na(+)/K(+)-ATPase, V-type H(+)-ATPase and CA immunoreactive cells in the gill. Ammocoetes did not survive in the experiments with salinities greater than 10 per thousand, whereas survival in high salinity (> or =25-35 per thousand) increased with increased degree of metamorphosis in transformers. Plasma [Na(+)] and [Cl(-)] of ammocoetes in freshwater was lower than transformers and increased markedly at 10 per thousand. In transformers, plasma ions increased only at high salinity (>25 per thousand). Branchial Na(+)/K(+)-ATPase levels were approximately tenfold higher in transformers compared to ammocoetes and salinity did not affect expression in either group. However, branchial H(+)-ATPase expression showed a negative correlation with salinity in both groups. Na(+)/K(+)-ATPase immunoreactivity was strongest in transformers and associated with clusters of cells in the interlamellar spaces. H(+)-ATPase (B subunit) immunoreactivity was localized to epithelial cells not expressing high Na(+)/K(+)-ATPase immunoreactivity and having a similar tissue distribution as carbonic anhydrase. The results indicate that branchial Na(+)/K(+)-ATPase and salinity tolerance increase in metamorphosing lampreys, and that branchial H(+)-ATPase is downregulated by salinity.


Moderate alcohol consumption on the risk of stroke in the Million Veteran Program.
There is inconsistent evidence on the association of moderate alcohol consumption and stroke risk in the general population and is not well studied among U.S. Veterans. Furthermore, it is unclear whether primarily drinking beer, wine, or liquor is associated with a difference in stroke risk. The study included 185,323 Million Veteran Program participants who self-reported alcohol consumption on the Lifestyle Survey. Moderate consumption was defined as 1-2 drinks/day and beverage preference of beer, wine or liquor was defined if ≥ 50% of total drinks consumed were from a single type of beverage. Strokes were defined using ICD-9 and ICD-10 codes from the participants' electronic health record. The mean (sd) age of the sample was 64 (13) years and 11% were women. We observed 4,339 (94% ischemic; 6% hemorrhagic) strokes over a median follow-up of 5.2 years. In Cox models adjusted for age, sex, race, education, income, body mass index, smoking, exercise, diet, cholesterol, prevalent diabetes, prevalent hypertension, lipid-lowering medication, antihypertensive medication, and diabetes medication, moderate alcohol consumption (1-2 drinks/day) was associated with a 22% lower risk of total stroke compared with never drinking [Hazards ratio (HR) 95% confidence interval (CI): 0.78 (0.67, 0.92)]. When stratifying by stroke type, we observed a similar protective association with moderate consumption and ischemic stroke [HR (95% CI): 0.76 (0.65, 0.90)], but a non-statistically significant higher risk of hemorrhagic stroke [HR (95% CI): 1.29 (0.64, 2.61)]. We did not observe a difference in ischemic or hemorrhagic stroke risk among those who preferred beer, liquor or wine vs. no beverage preference. When stratifying by prior number of hospital visits (≤ 15, 16-33, 34-64, ≥ 65) as a proxy for health status, we observed attenuation of the protective association with greater number of visits [HR (95% CI): 0.87 (0.63, 1.19) for ≥ 65 visits vs. 0.80 (0.59, 1.08) for ≤ 15 visits]. We observed a lower risk of ischemic stroke, but not hemorrhagic stroke with moderate alcohol consumption and did not observe substantial differences in risk by beverage preference among a sample of U.S. Veterans. Healthy user bias of moderate alcohol consumption may be driving some of the observed protective association.


Practice-Based Knowledge Discovery for Comparative Effectiveness Research: An Organizing Framework.
Electronic health information systems can increase the ability of health-care organizations to investigate the effects of clinical interventions. The authors present an organizing framework that integrates outcomes and informatics research paradigms to guide knowledge discovery in electronic clinical databases. They illustrate its application using the example of hospital acquired pressure ulcers (HAPU). The Knowledge Discovery through Informatics for Comparative Effectiveness Research (KDI-CER) framework was conceived as a heuristic to conceptualize study designs and address potential methodological limitations imposed by using a single research perspective. Advances in informatics research can play a complementary role in advancing the field of outcomes research including CER. The KDI-CER framework can be used to facilitate knowledge discovery from routinely collected electronic clinical data.