Biotransformations of daunorubicin aglycones by rat liver microsomes.
Daunorubicin is biotransformed anaerobically by rat liver microsomes with a reduced nicotinamide adenine dinucleotide phosphate-generating system to form a series of aglycones. The first reaction, reductive cleavage of daunosamine (at C-7 in ring A) to form the 7- deoxyaglycone , is followed by reduction of the C-13 keto group. The 7- hydroxyaglycone may also form by hydrolytic cleavage of the amino sugar followed then by the same C-13 keto reduction. These reactions are not inhibited by beta- diethylaminoethyldiphenylpropyl acetate, whereas subsequent reactions in the D ring of the aglycones can be completely blocked by this cytochrome P-450 inhibitor: reductive and hydrolytic cleavage of the C-4 methoxy group. Thus, five reactions at three sites are described and theoretical pathways are proposed for the expected 12 aglycones from daunorubicin.


SMG7-AS1 as a prognostic biomarker and predictor of immunotherapy responses for skin cutaneous melanoma.
Skin cutaneous melanoma (SKCM) is the most life-threatening skin cancer and lacks early detection and effective treatment strategies. Many long noncoding RNAs are associated with the development of tumors and may serve as potential immunotherapeutic targets. In this study, microarray analysis was performed to screen for differentially expressed lncRNAs between SKCM and normal tissues, and SMG7-AS1 was identified as an upregulated lncRNA in SKCM. Subsequently, bioinformatic analysis revealed that dysregulation of SMG7-AS1 influences metastasis and immune infiltration. qRT-PCR of clinical samples demonstrated that the expression of SMG7-AS1 was higher in melanoma tissues. Flow cytometry showed that SMG7-AS1 plays a vital role in the cell cycle. Additionally, SMG7-AS1 was found to be associated with immunotherapy responses. To the best of our knowledge, this study is the first to report that SMG7-AS1 is associated with SKCM and may serve as a prognostic biomarker and predictor of immunotherapy responses in SKCM.


The inverse problem in electrocardiography: solutions in terms of equivalent sources.
This paper reviews those inverse electrocardiographic solutions that compute the electrical activity of the heart in terms of equivalent sources such as multipoles or multiple dipoles, as opposed to more realistic source formulations such as epicardial potentials. It treats, in succession, inverse solutions in terms of a single fixed-location dipole, a multipole series, moving dipoles, and, finally, multiple fixed-location dipoles. For each category of solution, simulation studies, animal experiments, and work involving human subjects are reviewed. Finally, more recent work that seeks to compute the cardiac activation isochrones, from the time integrals of the torso potentials during the QRS complex of the electrocardiogram, is described. The paper concludes with a discussion on the future of inverse electrocardiographic solutions in terms of equivalent sources.


"Default mode functional connectivity is associated with social functioning in schizophrenia": Correction to Fox et al. (2017).
Reports an error in "Default mode functional connectivity is associated with social functioning in schizophrenia" by Jaclyn M. Fox, Samantha V. Abram, James L. Reilly, Shaun Eack, Morris B. Goldman, John G. Csernansky, Lei Wang and Matthew J. Smith (Journal of Abnormal Psychology, 2017[May], Vol 126[4], 392-405). In the article, the email address of corresponding author Matthew J. Smith was set as email@example.com. It should have been firstname.lastname@example.com. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2017-14073-001.) Individuals with schizophrenia display notable deficits in social functioning. Research indicates that neural connectivity within the default mode network (DMN) is related to social cognition and social functioning in healthy and clinical populations. However, the association between DMN connectivity, social cognition, and social functioning has not been studied in schizophrenia. For the present study, the authors used resting-state neuroimaging data to evaluate connectivity between the main DMN hubs (i.e., the medial prefrontal cortex [mPFC] and the posterior cingulate cortex-anterior precuneus [PPC]) in individuals with schizophrenia (n = 28) and controls (n = 32). The authors also examined whether DMN connectivity was associated with social functioning via social attainment (measured by the Specific Levels of Functioning Scale) and social competence (measured by the Social Skills Performance Assessment), and if social cognition mediates the association between DMN connectivity and these measures of social functioning. Results revealed that DMN connectivity did not differ between individuals with schizophrenia and controls. However, connectivity between the mPFC and PCC hubs was significantly associated with social competence and social attainment in individuals with schizophrenia but not in controls as reflected by a significant group-by-connectivity interaction. Social cognition did not mediate the association between DMN connectivity and social functioning in individuals with schizophrenia. The findings suggest that fronto-parietal DMN connectivity in particular may be differentially associated with social functioning in schizophrenia and controls. As a result, DMN connectivity may be used as a neuroimaging marker to monitor treatment response or as a potential target for interventions that aim to enhance social functioning in schizophrenia. (PsycINFO Database Record


Developing force fields when experimental data is sparse: AMBER/GAFF-compatible parameters for inorganic and alkyl oxoanions.
We present a set of Lennard-Jones parameters for classical, all-atom models of acetate and various alkylated and non-alkylated forms of sulfate, sulfonate and phosphate ions, optimized to reproduce their interactions with water and with the physiologically relevant sodium, ammonium and methylammonium cations. The parameters are internally consistent and are fully compatible with the Generalized Amber Force Field (GAFF), the AMBER force field for proteins, the accompanying TIP3P water model and the sodium model of Joung and Cheatham. The parameters were developed primarily relying on experimental information - hydration free energies and solution activity derivatives at 0.5 m concentration - with ab initio, gas phase calculations being used for the cases where experimental information is missing. The ab initio parameterization scheme presented here is distinct from other approaches because it explicitly connects gas phase binding energies to intermolecular interactions in solution. We demonstrate that the original GAFF/AMBER parameters often overestimate anion-cation interactions, leading to an excessive number of contact ion pairs in solutions of carboxylate ions, and to aggregation in solutions of divalent ions. GAFF/AMBER parameters lead to excessive numbers of salt bridges in proteins and of contact ion pairs between sodium and acidic protein groups, issues that are resolved by using the optimized parameters presented here.


Milk-Fat Globule Membrane Plus Glucosamine Improves Joint Function and Physical Performance: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.
Care of the musculoskeletal system, including the muscles, joints, and bones, is important for a healthy life expectancy in today's aging society. The aim of this randomized, double-blind, placebo-controlled study was to investigate the effect of consumption of milk-fat globule membrane (MFGM) and glucosamine on joint function and physical performance. Participants were healthy Japanese men and women, aged 60-74 y, with a history of mild knee or low back pain at rest. They were randomized to receive tablets containing MFGM 1.0 g+glucosamine 1.5 g or placebo tablets for 8 wk. We assessed passive range of motion, active range of motion (self-reported VAS score), JKOM and JLEQ, and physical performance. Data were available for analysis for 25 participants in the active treatment group and 28 in the placebo group. The active group showed significant improvements in passive range of motion at the knee and active range of motion at both the knee and low back. The active group also showed significant improvements in some physical performance, including obstacle walking speed and speed of ascending stairs. The findings of this study suggest that consumption of a combination of MFGM and glucosamine may improve joint function and physical performance.


Somatomedins in pregnancy: a cross-sectional study of insulin-like growth factors I and II and somatomedin peptide content in normal human pregnancies.
To explore the role of the somatomedins (SM) during human pregnancy, we have measured plasma levels of insulin-like growth factor I (IGF-I), IGF-II, and SM peptide content (SMPC) in 79 women in various stages of normal pregnancies. IGF-I and IGF-II were measured by specific RIAs, and SMPC was measured by a radioreceptor assay using human placental membranes. IGF-I and SMPC rose during pregnancy, showing a significant positive correlation with the length of gestation. Plasma levels of IGF-I in the third trimester averaged 324 ng/ml, a 33% increase over the first trimester average of 243 ng/ml (P less than 0.05). Although IGF-II did not correlate with the length of gestation, the third trimester average was significantly higher than the first trimester average (780 vs. 630 ng/ml; P less than 0.05). After delivery, both IGF-I and IGF-II levels rapidly dropped to levels significantly below those seen in the third trimester. The gestational rise in SMPC and plasma levels of both IGF-I and IGF-II supports the hypothesis that SM play a role in the regulation of fetal growth.


Pravastatin Decreases Infarct Size Induced by Coronary Artery Ischemia/Reperfusion with Elevated eNOS Expression in Rats.
Our previous study showed that pravastatin prevents ischemia and reperfusion-induced lethal ventricular fibrillation in rats. This study explored whether pravastatin decreases myocardial infarct size and this effect is associated with endothelial nitric oxide synthase (eNOS) expression in myocardium. Rats were treated with ischemia (30 minutes) and reperfusion (60 minutes) after chronic oral administration of pravastatin, fluvastatin, or vehicle once daily for 22 days. Electrocardiograms and blood pressure were continuously recorded, myocardial infarct size was measured by TTC-staining, and eNOS expression was measured by western blot. The results showed that pravastatin and fluvastatin significantly reduced myocardial infarct size. No statistical differences were found in the areas at risk among all groups. However, a significant reduction in infarct size was observed in three pravastatin groups and one fluvastatin group compared to control. Both pravastatin and fluvastatin significantly increased eNOS protein expression in ischemic and non-ischemic tissues compared to control. Our results suggest that pravastatin decreases cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in reducing infarct size. These effects may be associated with elevation of eNOS expression.


WBN/Kob rats. A new spontaneously occurring model of chronic pancreatitis.
Chronic pancreatitis-like lesions are observed in 100% of male Wistar Bonn/Kobori rats. At 3 mo of age, histopathologic examinations of the pancreas revealed a distinct infiltration of inflammatory cells with interstitial edema in the acini. At the same time, periductal and interstitial fibrosis and adenomatous hyperplasia of the ductular epithelium were observed. Extensive fibrotic exudation developed rapidly with age, and irregular destruction of the parenchyma was noted. The only abnormality, prior to the appearance of glycosuria, that could be detected clinically was lower levels, compared to Wistar rats, of BT-PABA excreted in the urine after oral ingestion. These lower levels indicate a decrease in enzyme secretion in WBN/Kob rats. Ultrastructural observations in histologically normal areas at 2 mo of age showed a swelling of mitochondria, indicating that ischemia was associated with the early pancreatic lesions. Serial pancreatographies were performed at 2-8 mo of age. Irregular widenings of the main pancreatic duct and dilations of the smaller ducts were observed already at 2 mo of age, suggesting a stasis of pancreatic juice in the early stages of the disease. It seems that male WBN/Kob rats are a useful model of human chronic pancreatitis, with an unknown mechanism regulated by the sex hormones.


Serum levels of circulating intercellular adhesion molecule 1 in human malignant melanoma.
Current reports have suggested a role for intracellular adhesion molecule 1 (ICAM-1) in the progression of human malignant melanoma and other cancers. Stage I, II, and III patients with histologically diagnosed malignant melanoma had significantly increased serum levels of circulating ICAM-1 (cICAM-1) and a striking increase in the incidence of positive sera. In Stage II and III patients, the level of cICAM-1 was inversely correlated with survival. Patients with elevated levels of serum cICAM-1 (greater than 2 SD units above control mean) had a significantly shorter mean survival. We suggest that elevated levels of serum cICAM-1 may be of diagnostic and prognostic importance in patients with malignant cutaneous melanoma.


Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics.
A new generation of dual-target μ opioid receptor (MOR) agonist/dopamine D3 receptor (D3R) antagonist/partial agonists with optimized physicochemical properties was designed and synthesized. Combining in vitro cell-based on-target/off-target affinity screening, in silico computer-aided drug design, and BRET functional assays, we identified new structural scaffolds that achieved high affinity and agonist/antagonist potencies for MOR and D3R, respectively, improving the dopamine receptor subtype selectivity (e.g., D3R over D2R) and significantly enhancing central nervous system multiparameter optimization scores for predicted blood-brain barrier permeability. We identified the substituted trans-(2S,4R)-pyrrolidine and trans-phenylcyclopropyl amine as key dopaminergic moieties and tethered these to different opioid scaffolds, derived from the MOR agonists TRV130 (3) or loperamide (6). The lead compounds 46, 84, 114, and 121 have the potential of producing analgesic effects through MOR partial agonism with reduced opioid-misuse liability via D3R antagonism. Moreover, the peripherally limited derivatives could have therapeutic indications for inflammation and neuropathic pain.


Amniotic fluid and fetal urinary responses to severe placental insufficiency in sheep.
Our purpose was to test the hypothesis that severe placental insufficiency leads to reductions in fetal urine production and amniotic fluid volume in late-gestation fetal sheep. At 0.85 of gestation, chronically catheterized fetal sheep with ligated urachus were either embolized for 5 days by repeated injection of boluses of 15-microm microspheres into the common fetal umbilical artery until fetal arterial oxygen content was reduced by 50% (n = 6) or were infused with saline solution (n = 6). Amniotic fluid volume was measured daily before embolization by means of an indicator dilution technique and by drainage at autopsy. Fetal urine production, heart rate, and mean arterial blood pressure were measured continuously for 1 hour before embolization and 1 hour after embolization each day. Fetal arterial blood gases, oxygen content, electrolytes, and osmolality were also monitored. Five days of placental insufficiency, which reduced fetal arterial oxygen content by 50% and arrested fetal growth, resulted in a reduced amniotic fluid volume without a reduction in fetal urine production. Compared with that of controls, amniotic fluid volume was reduced over the 5-day period by 547 +/- 144 mL (-62%, P <.01). Amniotic fluid composition was also altered, with a significant increase in lactate and sodium concentrations and osmolality on days 4 to 5. On days 2 to 5, there was a progressive increase in amniotic fluid osmolality above that of controls, which paralleled the changes in amniotic fluid sodium concentration (P <.05). Fetuses became hypertensive on days 2 to 4 of embolization, although this response was attenuated by day 5. Chronic severe placental insufficiency caused a reduction in amniotic fluid volume not attributable to reduced fetal urine production. Changes in amniotic fluid composition induced by placental insufficiency suggest an excess intramembranous absorption of amniotic fluid water, in relation to solutes, into the fetal and maternal compartments, which may lead to the development of oligohydramnios.


Readability, Suitability and Health Content Assessment of Cancer Screening Announcements in Municipal Newspapers in Japan.
The objective of this study was to assess the readability, suitability, and health content of cancer screening information in municipal newspapers in Japan. Suitability Assessment of Materials (SAM) and the framework of Health Belief Model (HBM) were used for assessment of municipal newspapers that were published in central Tokyo (23 wards) from January to December 2013. The mean domain SAM scores of content, literacy demand, and layout/typography were considered superior. The SAM scores of interaction with readers, an indication of the models of desirable actions, and elaboration to enhance readers' self-efficacy were low. According to the HBM coding, messages of medical/clinical severity, of social severity, of social benefits, and of barriers of fear were scarce. The articles were generally well written and suitable. However, learning stimulation/motivation was scarce and the HBM constructs were not fully addressed. Articles can be improved to motivate readers to obtain cancer screening by increasing interaction with readers, introducing models of desirable actions and devices to raise readers' self-efficacy, and providing statements of perceived barriers of fear for pain and time constraints, perceived severity, and social benefits and losses.


Antenatal Bartter's syndrome with sensorineural deafness.
Bartter's syndrome is a group of inherited, salt-losing tubulopathies presenting as metabolic alkalosis with normotensive hyperreninemia and hyperaldosteronism. We report here the first case of a neonate with bilateral, sensorineural deafness, a variant of antenatal Bartter's syndrome from an Indian community.


[Sound injuries after surgery of otosclerosis].
Surgery for otosclerosis means that the sound protection due to the fixation of the footplate does not exist anymore. As the Corti hair cells have been fragilized by proteolytic enzymes, it is absolutely necessary to reconstruct the sound mechanism in order to maintain the vibration of the perilymph absolutely within acoustical physiologic limit of movement. The means to realize this reconstruction are presented in this paper, as well as the results.


Allowable imprecision for laboratory tests based on clinical and analytical test outcome criteria.
The allowable imprecision for laboratory tests has been estimated from criteria based on clinical and analytical test outcome. The analytical outcome criteria studied are the Clinical Laboratory Improvement Amendments (CLIA) criteria for proficiency testing. The clinical outcome criteria are estimates of medically significant changes in test results taken from a study in the literature. The estimates of allowable imprecision were obtained from quality-planning models that relate test outcome criteria to the allowable amount of imprecision and inaccuracy and to the quality control that is necessary to assure achievement of the desired outcome criteria in routine operation. These operating specifications for imprecision are consistently more demanding (require lower CVs) than the medically useful CVs originally recommended in the literature because the latter do not properly consider within-subject biological variation. In comparing estimates of allowable imprecision, the CLIA outcome criteria are more demanding than the clinical outcome criteria for aspartate aminotransferase (asymptomatic patients), cholesterol, creatinine (asymptomatic patients), glucose, thyroxine, total protein, urea nitrogen, hematocrit, and prothrombin time. The clinical outcome criteria are more demanding for bilirubin (acute illness), iron, potassium, urea nitrogen (acute illness), and leukocyte count. The estimates of allowable imprecision from analytical and clinical outcome criteria overlap for aspartate aminotransferase (acute illness), bilirubin (asymptomatic patients), calcium, creatinine (acute illness), sodium, triglyceride, and hemoglobin.


Developing Bovine Brain-Derived Extracellular Matrix Hydrogels: a Screen of Decellularization Methods for Their Impact on Biochemical and Mechanical Properties.
Tissue models that recapitulate the key biochemical and physical aspects of the brain have been highly pursued in neural tissue engineering. Decellularization of native organs offers the advantage of preserving the composition of native extracellular matrix (ECM). Brain ECM has distinct features which play a major role in neural cell behavior. Cell instructive ligands and mechanical properties take part in the regulation of cellular processes in homeostasis and diseases. One of the main challenges in decellularization is maintaining mechanical integrity in reconstituted hydrogels and achieving physiologically relevant stiffness. The effect of the decellularization process on different mechanical aspects, particularly the viscoelasticity of brain-derived hydrogels, has not been addressed. In this study, we developed bovine brain-derived hydrogels for the first time. We pursued seven protocols for decellularization and screened their effect on biochemical content, hydrogel formation, and mechanical characteristics. We show that bovine brain offers an easily accessible alternative for in vitro brain tissue modeling. Our data demonstrate that the choice of decellularization method strongly alters gelation as well as the stiffness and viscoelasticity of the resulting hydrogels. Lastly, we investigated the cytocompatibility of brain ECM hydrogels and the effect of modulated mechanical properties on the growth and morphological features of neuroblastoma cells.


Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-κB pathway in RAW264.7 cells.
Short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber contribute a significant proportion of daily energy requirement. Furthermore, these compounds are modulators of macrophage function and potential targets for the development of new drugs. The aims of this study were to evaluate the effects of three types of SCFAs (sodium acetate (NaAc), sodium propionate (NaP), and sodium butyrate (NaB)) on the production of NO and inducible nitric oxide synthase (iNOS) and proinflammatory and antiinflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin (IL-1, IL-6, and IL-10)) and to observe the effect of NaAc on inhibiting lipopolysaccharide (LPS)-induced NF-κB activation in LPS-stimulated RAW264.7 cells. The results show that three types of SCFAs (acetate, propionate, and butyrate) reduced the production of proinflammatory factors, including TNF-α, IL-1β, IL-6, and NO, and inhibited the vitality of iNOS. Meanwhile, SCFAs enhanced the production of antiinflammatory cytokine IL-10 in lower concentrations (1-1,200 μmol/L). Like NaB, NaAC inhibited LPS-induced NF-κB activation. These results may hold promise on the role that SCFAs have on the prevention and treatment of various inflammatory conditions.


[Relation between toxoplasmosis and orofacial clefts in children].
The authors performed a serological observation of toxoplasmosis by using the methods of IFT, CFT and ELISA in 118 mothers and their children with orofacial clefts. The results were compared with those gained in the control group of healthy mothers and their children. Titre means of toxoplasma antibodies in inflicted mothers and their children were higher than in the control group. The results were evaluated statistically. The authors assume that a certain proportion of orofacial clefts may be induced by toxoplasmosis. (Tab. 6, Ref. 13.).


A mathematical model of HIV dynamics treated with a population of gene-edited haematopoietic progenitor cells exhibiting threshold phenomenon.
The use of gene-editing technology has the potential to excise the CCR5 gene from haematopoietic progenitor cells, rendering their differentiated CD4-positive (CD4+) T cell descendants HIV resistant. In this manuscript, we describe the development of a mathematical model to mimic the therapeutic potential of gene editing of haematopoietic progenitor cells to produce a class of HIV-resistant CD4+ T cells. We define the requirements for the permanent suppression of viral infection using gene editing as a novel therapeutic approach. We develop non-linear ordinary differential equation models to replicate HIV production in an infected host, incorporating the most appropriate aspects found in the many existing clinical models of HIV infection, and extend this model to include compartments representing HIV-resistant immune cells. Through an analysis of model equilibria and stability and computation of $R_0$ for both treated and untreated infections, we show that the proposed therapy has the potential to suppress HIV infection indefinitely and return CD4+ T cell counts to normal levels. A computational study for this treatment shows the potential for a successful 'functional cure' of HIV. A sensitivity analysis illustrates the consistency of numerical results with theoretical results and highlights the parameters requiring better biological justification. Simulations of varying level production of HIV-resistant CD4+ T cells and varying immune enhancements as the result of these indicate a clear threshold response of the model and a range of treatment parameters resulting in a return to normal CD4+ T cell counts.


Workplace discrimination and autism spectrum disorders: The National EEOC Americans with Disabilities Act Research project.
Using the Integrated Mission System of the Equal Employment Opportunity Commission (EEOC), the employment discrimination experience of Americans with autism spectrum disorders (ASDs) is documented for Title I of the Americans with Disabilities Act. The researchers examine demographic characteristics of the charging parties; the industry designation, location, and size of employers against whom complaints are filed; the nature of discrimination (i.e., type of complaint) alleged to occur; and the legal outcome or resolution of these complaints. Researchers compare and contrast these key dimensions of workplace discrimination involving individuals with ASDs and persons with other physical, sensory, and neurological impairments. Researchers also attempt to discern whether or not the resolutions of the ASD charges can be predicted using the variables available for analysis. The comparative findings of this study indicate that individuals with ASDs were more likely to make charges of discrimination against Retail industry employers. Persons with ASDs were also more likely to make charges of discrimination when they were younger, male, and/or of Native American/Alaskan Native ethnicity. The predictive findings of this study indicate that the odds of ASD charges resulting in meritorious resolution (i.e., discrimination determined by the EEOC to have occurred) increase when the discrimination was encountered in Service industries and by larger employers. Implications for policy, advocacy and further research efforts are addressed.


Acquired factor VIII inhibitors in a patient associated with neurosurgery: case report and review of the literature.
Acquired factor VIII inhibitors in patients without hemophilia is rare event characterized by severe bleeding as a result of antibody against factor VIII. We describe a patient who developed subcutaneous and epidural bleeding after the clipping of an unruptured aneurysm. A 57-year-old man suddenly developed coagulopathy after undergoing a neurosurgical operation. Coagulation tests showed a prolongation of activated partial thromboplastin time and a marked reduction in factor VIII activity. Measurement of the factor VIII inhibitor level revealed 2 Bethesda units/ml. The hematoma was removed surgically, and bleeding was controlled with recombinant factor VIII. The patients then received prednisolone (80 mg/d) and cyclosporine. The laboratory tests normalized within 8 weeks. In the 5 years since cessation of corticosteroids, the clinical and laboratory courses of the patient have been uneventful. Autoimmune factor VIII inhibitors associated with a neurosurgical procedure are rare. Our case supports an association between surgery and the triggering of factor VIII inhibitors. This complication was probably the result of the surgical procedure or anesthetic agents or other drugs administrated during the perioperative period.


Checklist of earthworms (Oligochaeta: Lumbricidae) from Serbia: a review.
A checklist of the lumbricid earthworms in Serbia is presented. For the first time, comprehensive informations of all lumbricids in the country are given in order to establish the definitive list of known taxa from Serbia. The list underlines earthworm diversity and provides a general overview of their ecology, distribution in Serbia, and zoogeographical position. The complete list of earthworm taxa of Serbia comprises 74 species and subspecies of Lumbricidae, belonging to 15 genera. One third of earthworms in Serbia are endemics (26 taxa = 35.1%).


Genetic testing costs and compliance with clinical best practices.
We sought to determine the costs of genetic testing and compliance with published guidelines and clinical best practices at our institution. A cost analysis was performed comparing the costs of ordered tests to the cost of the recommended testing. This was an approved quality improvement project at a tertiary teaching hospital in California. We identified charts associated with the genetic testing billing codes for common genetic tests through our contracted laboratory (cystic fibrosis genotyping, Breast cancer susceptibility gene (BRCA 1&2), Methylenetetrahydrofolate reductase (MTHFR), factor V Leiden (FVL), prothrombin gene pathogenic variant, alpha-thalassemia, hemochromatosis, and cell-free fetal DNA). Charts were reviewed retrospectively by a licensed, certified genetic counselor to assess the compliance with published clinical practice guidelines identified on GeneReviews and the American College of Obstetricians and Gynecologists (ACOG). Tests were classified as: appropriate, misordered/not indicated, misordered/false reassurance, and misordered/inadequate. We performed a cost analysis for the recommended test changes. We reviewed 114 charts over a three-month period. Forty-four (38.6%) of the tests were misordered based on published clinical practice guidelines: 24 (21%) were misordered/not indicated, 8 (7%) were misordered/false reassurance, and 12 (10.5%) were misordered/inadequate. Costs of ordered testing ($75,177) were compared to recommended testing after review ($54,265), with a total cost savings of $20,912. In clinical practice, over one-third of genetic tests reviewed were misordered. As these tests are a small fraction of all genetic tests at our institution, future studies should broaden the scope of testing evaluated to understand the magnitude of this problem and potential cost savings. Genetic counselor review and involvement in genetic test ordering can decrease inappropriate healthcare expenditures and improve patient care.


Evaluation of pain relief sufficiency using the Cumulative Analgesic Consumption Score (CACS) and its modification (MACS).
Postoperative pain is one of the major complications in general and bariatric surgery, associated with ongoing problems such as ileus, pneumonia and prolonged mobilization. In this study, patients undergoing bariatric surgery were analyzed according to their postoperative pain relief regime. In one group patients were treated with a patient-controlled analgesia (PCA) device, while the other group was treated with oral and intravenous analgesic medication. The aim of this study was to analyze which postoperative pain relief therapy would be more appropriate. We chose the Cumulative Analgesic Consumption Score (CACS) and Numeric Rating Scale (NRS) for pain measurement. For better comparison, we performed a modification of CACS according to PCA treatment. We observed better pain relief in the PCA group. Furthermore, we observed an advantage of treatment with laxatives in patients treated with PCA. In conclusion, PCA devices are appropriate instruments for postoperative pain relief in bariatric patients. CACS is a practical tool for postoperative pain measurement, describing individual pain sensation more objectively, although holding further potential in modification.


Information-theoretic natural ultraviolet cutoff for spacetime.
Fields in spacetime could be simultaneously discrete and continuous, in the same way that information can. It has been shown that the amplitudes phi(x(n)) that a field takes at a generic discrete set of points x(n) can be sufficient to reconstruct the field phi(x) for all x, namely, if there exists a certain type of natural ultraviolet (UV) cutoff in nature, and if the average spacing of the sample points is at the UV-cutoff scale. Here, we generalize this information-theoretic framework to spacetimes themselves. We show that samples taken at a generic discrete set of points of a Euclidean-signature spacetime can allow one to reconstruct the shape of that spacetime everywhere, down to the cutoff scale. The resulting methods could be useful in various approaches to quantum gravity.


The upper limit of alveolar capillary recruitment in a young man with lung growth impairment.
In order to obtain further insight into the adaptive mechanisms relating to gas exchange in anatomically small lungs, tests of mechanical lung function and gas exchange were made in an active young man, whose lung growth had been severely impaired due to pectus excavatum developed in childhood. We found our patient to have small (total lung capacity, 59% of predicted) but mechanically normal lungs. He had a normal cardiac output, a normal single-breath diffusing capacity (100% pred), and a high diffusion coefficient (148% pred) associated with a high pulmonary capillary blood volume (131% pred) at rest. Pulmonary distensibility (K) and elastic recoil were normal. During steady-state exercise he was unable to recruit further reserves of pulmonary capillaries, but this was not reflected in a plateau for oxygen consumption, which was presumably the result of an increased pulmonary capillary blood flow rather than volume. The recruitment of pulmonary capillary reserves in this young man has enabled him to maintain a normal maximum exercise capacity. In addition, the high stroke volume and a haemoglobin level in the high normal range (176 g.l-1) may have maintained his maximal exercise function, despite fewer alveolar units. This study suggests that, contrary to previous findings, loss of a major proportion of lung tissue need not impair exercise capacity. Patients with either small lungs or following pneumonectomy may benefit from physical training sufficient to optimize both an increase in cardiac output and recruitment of their existing alveolar capillary reserves.


Lattice Boltzmann modeling of interfacial mass transfer in a multiphase system.
In the present study, a numerical model based on the lattice Boltzmann method (LBM) is proposed to simulate multiphase mass transfer, referred to as the CST-LB model. This model introduced continuum species transfer (CST) formulation by an additional collision term to model the mass transfer across the multiphase interface. The boundary condition treatment of this model is also discussed. In order to verify the applicability, the CST-LB model is combined with the pseudopotential multiphase model to simulate a series of benchmark cases, including concentration jump near the interface, gas dissolution in a closed system, species transport during drainage in a capillary tube, and multiphase species transport in the porous media. This CST-LB model can also be coupled with other multiphase LBMs since the model depends on the phase fraction field, which is not explicitly limited to specified multiphase models.


Multimodal MRI Analysis of Brain Metabolism in Maintenance Hemodialysis Patients Based on Cognitive Computing.
This paper investigates cognitive computation of brain metabolism in maintenance hemodialysis patients with multimodal MRI therapy assessment. This paper constructs a cross-individual emotion recognition method using dynamic sample entropy pattern learning. The cross-individual emotion recognition was carried out on subjects using the EEG emotion dataset SEED. The experimental results show that the proposed dynamic sample entropy-based pattern learning has better performance in cross-individual emotion recognition and exhibits better generalization and generalization ability when compared with the results of existing related studies. The constructed cognitive computing method for cross-individual emotion state recognition achieves optimization and innovation of EEG emotion pattern recognition, which can effectively predict people's mental emotion state from EEG signals. We also explore the value of diffusion-weighted magnetic resonance imaging and dynamic enhanced magnetic resonance imaging-based volumetric measurements in assessing the efficacy of neoadjuvant therapy in maintenance hemodialysis patients. We analyze and compare the results of different studies to find the best multimodal MRI to assess the efficacy of neoadjuvant therapy in maintenance hemodialysis patients. The use of ADC value growth rates to assess neoadjuvant efficacy provides the best diagnostic efficacy and allows the screening of patients who respond well to neoadjuvant therapy while avoiding the impact of two different b-value combinations commonly used to assess neoadjuvant efficacy.


Fostering collaborative research for customer experience - Connecting academic and practitioner worlds.
This editorial calls for greater use of academic-practitioner workshops to co-create value for academics, practitioners and wider network actors through promotion of research relevance and sharing of problems, ideas and data. It describes how one such workshop, the 2nd Academic-Practitioner Research with Impact Workshop focusing on the design and decision making for customer experience (CE), co-hosted in Manchester on 18th and 19th of June 2018 by Alliance Manchester Business School, the University of Manchester and Loughborough University's Centre for Service Management (CSM), was delivered. The key processes for success and issues to consider for future such events are discussed. The workshop resulted in 8 papers (six theoretical and two empirical). This Special Issue advances current understanding of CE through the research considering the role of technology (AI and big data) in CE research, atypical CE (vulnerability, deviance behaviours and service failure and recovery) and focusing on important organizational and B2B issues (business model innovation, and CE Management (CEM) in business markets).


Mothers and friends as listeners for adolescent anger narration: Distinct developmental affordances.
Narrating emotional experiences to important others contributes to socioemotional and self-development from early childhood through adulthood. However, to date, almost no work has explored the distinctive ways that different listeners might shape narration, and the socioemotional outcomes of narrating experience. The present study examines how early adolescents (n = 106, age range 12-14, 54 girls, 21% low-income, 7% Latinx, 3% non-White) narrate anger experiences to mothers and close same-sex friends. Our findings suggest that these two listeners provide distinct affordances for narration, with implications for emotions and learning. Mothers provide a more elaborative, emotion-focused narrative context, whereas friends provide a playful, creative narrative context. Friends elicit larger reductions in distress than mothers, although listener-associated differences in learning were more complex. Findings are discussed in terms of implications for narrative development specifically as well as more generally for relatively underexamined aspects of narrative across adolescence and adulthood. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Semantic Processing of Sentences in Preschoolers With Specific Language Impairment: Evidence From the N400 Effect.
Given the complexity of sentence processing and the specific problems that children with specific language impairment (SLI) experience, we investigated the time course and characteristics of semantic processing at the sentence level in Dutch preschoolers with SLI. We measured N400 responses to semantically congruent and incongruent spoken sentences (e.g., "My father is eating an apple/*blanket") in a group of 37 Dutch preschoolers with SLI and in a group of 25 typically developing (TD) peers. We compared the time course and amplitude of the N400 effect between the two groups. The TD group showed a strong posterior N400 effect in time windows 300-500 ms and 500-800 ms. In contrast, the SLI group demonstrated only a reliable N400 effect in the later time window, 500-800 ms, and did not show a stronger presence at posterior electrodes. The findings suggest that the neuronal processing of semantic information at sentence level is atypical in preschoolers with SLI compared with TD children.


Electrochemical Disposable Biosensor to Monitor Dabigatran in Point-of-Care Anticoagulation Therapy.
Dabigatran etexilate, an oral prodrug, is often used to treat complications linked to thrombosis. Dabigatran (DAB, active form) does not need to be monitored. However, there are several conditions, such as reduced renal function, traumatic bleeding, emergency surgery, the need for thrombolytic therapy in acute stroke, or the requirement to use other forms of anticoagulation, where knowing the concentration of DAB in the blood is indispensable. Unfortunately, there are no convenient DAB-specific point-of-care tests available. To solve this problem, two disposable sensors were constructed and optimised in this work to detect the anticoagulant drug DAB using novel co-facing disposable electrodes, which allows a calibration-free quantitation of the electroactive mediator concentration. A trypsin-based sensor was evaluated. This sensor performed well in a 10 mM Tris buffer (pH 8.8) solution. However, trypsin was inhibited by alpha-1 antitrypsin when a plasma sample was introduced into the sensor. This problem was overcome by plasma filtration. This sensor showed a detection limit of 50.7 ng mL-1 DAB in plasma and a quantification range of 177-500 ng mL-1. A thrombin-based sensor was also constructed. This sensor performed well in ten-fold diluted plasma, overcoming the filtration problem observed with the trypsin-based sensor. This sensor showed a detection limit of 9.6 ng mL-1 DAB in plasma and a quantification range of 11.5-140 ng mL-1. Its extensive pH stability range, the possibility of working at physiological pH, low volume, low cost, and fast turnaround response (less than 20 s) make the calibration-free thrombin-based sensor a suitable point-of-care test to measure DAB concentration in the blood.


Unique structural features in DNA polymerase IV enable efficient bypass of the N2 adduct induced by the nitrofurazone antibiotic.
The reduction in the efficacy of therapeutic antibiotics represents a global problem of increasing intensity and concern. Nitrofuran antibiotics act primarily through the formation of covalent adducts at the N(2) atom of the deoxyguanosine nucleotide in genomic DNA. These adducts inhibit replicative DNA polymerases (dPols), leading to the death of the prokaryote. N(2)-furfuryl-deoxyguanosine (fdG) represents a stable structural analog of the nitrofuran-induced adducts. Unlike other known dPols, DNA polymerase IV (PolIV) from E. coli can bypass the fdG adduct accurately with high catalytic efficiency. This property of PolIV is central to its role in reducing the sensitivity of E. coli toward nitrofuran antibiotics such as nitrofurazone (NFZ). We present the mechanism used by PolIV to bypass NFZ-induced adducts and thus improve viability of E. coli in the presence of NFZ. Our results can be used to develop specific inhibitors of PolIV that may potentiate the activity of nitrofuran antibiotics.


[Community acquired pneumonia in children].
In children, community acquired pneumonia represent less than 10% of respiratory tract infections. In infants and toddlers, the diagnosis is difficult as, at any age, in case of isolated fever. Typical features of pneumonia are rare. Chest radiograph is necessary for confirmation and mandatory in children under 2 years of age, other diagnosis suspision or recurrent pneumonia. Identification of risk factors and/or severity criteria will guide the hospitalisation decision. Epidemiological data have a collective usefulness but help very little for the individual decision. Pneumococcus is observed at any age. Before 3 years of age, viruses and pneumococcus are predominant. After 3 years of age pneumococcus, Mycoplasma pneumoniae and Chlamydia pneumoniae are possible. Viral or virobacterial co-infections exist in 15 up to 25% of cases. An empiric and rapid antibiotherapy is given, pending on age, national or regional epidemiology, initial severity, risk factors. A clinical evaluation is mandatory at H48-72. Routine vaccination with the 7-valent conjugate anti-pneumococcal vaccine will modify the strategy of use of antibiotics in children's pneumonia.


Transferrin Conjugated pH- and Redox-Responsive Poly(Amidoamine) Dendrimer Conjugate as an Efficient Drug Delivery Carrier for Cancer Therapy.
A multifunctional redox- and pH-responsive polymeric drug delivery system is designed and investigated for targeted anticancer drug delivery to liver cancer. The nanocarrier (His-PAMAM-ss-PEG-Tf, HP-ss-PEG-Tf) is constructed based on generation 4 polyamidoamine dendrimer (G4 PAMAM). Optimized amount of histidine (His) residues is grafted on the surface of PAMAM to obtain enhanced pH-sensitivity and proton-buffering capacity. Disulfide bonds (ss) are introduced between PAMAM and PEG to reach accelerated intracellular drug release. Transferrin (Tf) was applied to achieve active tumor targeting. Doxorubicin (DOX) is loaded in the hydrophobic cavity of the nanocarrier to exert its anti-tumor effect. The results obtained from in vitro and in vivo evaluation indicate that HP-ss-PEG-Tf/DOX complex has pH and redox dual-sensitive properties, and exhibit higher cellular uptake and cytotoxicity than the other control groups. Flow cytometry and confocal microscopy display internalization of HP-ss-PEG-Tf/DOX via clathrin mediated endocytosis and effective endosomal escape in HepG2 cancer cells. Additionally, cyanine 7 labeled HP-ss-PEG-Tf conjugate could quickly accumulate in the HepG2 tumor. Remarkably, HP-ss-PEG-Tf/DOX present superior anticancer activity, enhanced apoptotic activity and lower heart and kidney toxicity in vivo. Thus, HP-ss-PEG-Tf is proved to be a promising candidate for effective targeting delivery of DOX into the tumor.


The vanishing and the establishment of a new ecosystem on an oceanic island - Anthropogenic impacts with no return ticket.
A multiproxy approach was applied to a sediment core retrieved from the deep crater Lake Funda, located in the middle of the North Atlantic Ocean on Flores Island, Azores archipelago (Portugal). The purpose of this study was to determine how this ecosystem responded to natural and anthropogenic forces over the last millennium. We distinguished three main phases in lake evolution using multiproxy reconstructions and documentary sources. (A) Climate and lake catchment processes, as well as internal ones, were the main drivers of ecosystem variability before 1335 CE, when human disturbances were absent in the Lake Funda catchment. (B) The second phase is marked by unprecedented changes in all studied proxies between 1335 and 1560 CE, including abrupt changes in the composition and diversity of diatom and chironomid assemblages. Synergistic effects from high climate variability and the onset of human disturbances in the catchment (e.g., introduction of livestock) during the Medieval Climate Anomaly-Little Ice Age transition, led to an increase in lake trophic state from mesotrophic to eutrophic conditions. (C) In the last phase (1560 CE to the present), the eutrophic conditions in Lake Funda were maintained through a positive feedback loop between lake productivity and in-lake phosphorous recycling. Variability within the lake ecosystem was mainly associated with climate variability and internal lake dynamics (e.g., phosphorus remobilization). Our results show that a paleoecological approach is crucial to understanding lake ecological states in the present-day in order to develop locally adapted management and restoration strategies. A long-term perspective enables us to understand the harmful consequences of ongoing climate change and human disturbances on lake ecosystems.


Rational approach for design and evaluation of anti-aggregation agents for protein stabilization: A case study of trehalose phenylalaninate.
The present work introduces new anti-aggregation agent (AAA) derived through our new approach for design and evaluation of anti-aggregation agent as a multi-purpose excipient to combat protein aggregation. Therapeutic proteins undergo aggregation due to even minor changes in environmental conditions like temperature, pH, shear and stress. Excipients play a vital role in prevention of aggregation. To stabilize a protein formulation different classes of excipients are used in combination after carefully selecting through laborious and time consuming trial and error experiments. To resolve these concerns, we have developed a rational approach based on molecular docking analysis and have designed, synthesized AAAs, and validated the approach by experimental studies. Trehalose phenylalaninate (TPA) has been synthesized and evaluated for stabilization of Bovine serum albumin (BSA). TPA was found to be non-toxic with a LC50 of >80μg/ml. BSA solutions with and without TPA were subjected to thermal and agitation stress and aggregation was monitored using sophisticated analytical techniques. The helical structure of BSA was completely retained in stressed samples at 0.1% concentration of TPA. SEC-HPLC clearly demonstrated the absence of aggregates in presence of TPA. Although aggregation was not seen in fluorescence spectra but quenching due to TPA was evident. Moreover, molecular dynamics study on BSA-TPA complex showed lower RMSD.


Effects of Propofol Versus Sevoflurane on Postoperative Breast Cancer Prognosis: A Narrative Review.
Perioperative interventions produce substantial biologic perturbations which are associated with the risk of recurrence after cancer surgery. The changes of tumor microenvironment caused by anesthetic drugs received increasing attention. Till now, it's still unclear whether or not anesthetic drugs may exert positive or negative impact on cancer outcomes after surgery. Breast cancer is the most common tumor and the leading cause of cancer deaths in women. Propofol and sevoflurane are respectively the most commonly used intravenous and inhaled anesthetics. Debates regarding which of the two most commonly used anesthetics may relatively contribute to the recurrence and metastasis vulnerability of breast cancer postoperatively remain. This review aimed to provide a comprehensive view about the effect of propofol versus sevoflurane on the prognosis of breast cancer obtained from pre-clinical studies and clinical studies. Laboratory and animal studies have demonstrated that sevoflurane may enhance the recurrence and metastasis of breast cancer, while propofol is more likely to reduce the activity of breast cancer cells by attenuating the suppression of the immune system, promoting tumor cells apoptosis, and through other direct anti-tumor effects. However, retrospective clinical studies have shown contradictory results about the effects of propofol and sevoflurane on long-term survival in breast cancer patients. Furthermore, recent prospective studies did not identify significant differences between propofol and sevoflurane in breast cancer metastasis and recurrence. Therefore, more preclinical studies and randomized controlled studies are needed to guide the choice of anesthetics for breast cancer patients.


Molecular mechanisms involved in LH release by the ovine pituitary cells.
The luteinizing hormone-releasing hormone (LHRH) is a hypothalamic decapeptide and main positive regulator of luteinizing hormone (LH) secretion from pituitary cells. Insulin-like growth factor-I (IGF-1) also stimulates LH release and enhances the effect of LHRH. However, the molecular mechanisms involved in the interactions between LHRH and IGF-1 are unclear. Here, we first determined the effect of various types of LHRH [I (mammalian), II (chicken), III (lamprey), hyp9 and salmon] on both LH secretion and activation of MAPK (ERK1/2 and p38) in ovine pituitary cells. After 3h of treatment, LH secretion was significantly higher for LHRH-I than for the other LHRH tested. Interestingly, LHRH-III had no effect at any concentration used on the LH release by ovine pituitary cells. The phosphorylation of both MAPK ERK1/2 and p38 was also significantly higher after treatment with LHRH-I than LHRH-II, salmon LHRH or hyp9. These MAPKs were not activated or only very weakly activated by LHRH-III. We then used pharmacological inhibitors to show that MAPK ERK1/2 and PKCdelta participate in the LH release by ovine pituitary cells in response to LHRH-I. We identified the main substrates and signaling pathways [PI3K/Akt and MAPK (ERK1/2, p38 and JNK1/2] of IGF-1R and investigated the effect of IGF-1 on the stimulation of ovine pituitary cell LH secretion by the various LHRH. IGF-1 increases LH secretion in response to LHRH-I, LHRH-II, hyp9 and salmon LHRH but not the secretion after treatment with LHRH-III. Using specific inhibitors, we found that the MAPK ERK1/2 but not the PI3K/Akt signaling pathway is involved in the LH secretion in response to IGF-1. This is the first description of a common molecular mechanism, involving the MAPK ERK1/2, by which LHRH-R and IGF-1-R induce LH secretion in ovine pituitary cells.


Arterial embolization in the chest.
Transcatheter therapy is an effective technique in the treatment of vascular abnormalities in the chest. Pulmonary arteriovenous malformations, associated with the clinical sequellae of dyspnea, stroke, brain abscess, and hemoptysis, can be treated by transcatheter embolization with metallic coils or occlusion balloons. The results of treatment are excellent, with improvement seen in symptoms and physiologic parameters. The bronchial arteries and systemic nonbronchial collateral arteries supplying the tracheobronchial tree are most frequently involved in massive hemoptysis, a serious disorder with associated high rates of morbidity and mortality. Transcatheter embolization of these arteries is both safe and effective, requiring a thorough understanding of the arterial anatomy and technique of embolization.


An orthologous non-MHC locus in rats and mice is linked to CD4+ and CD8+ T-cell proportion.
CD4+ and CD8+ T cells have a central role in the immune system due to their ability to protect against infection and cancer development without targeting self. Consequently, changes in CD4+ and CD8+ T-cell homeostasis can be indicative of an array of serious illnesses, ranging from viral infections to autoimmune diseases. In addition to environmental influences, there is evidence for a genetic component regulating the proportion of CD4+ and CD8+ T cells in lymphoid organs. Indeed, identifying the genetic determinants defining the frequency of the T-cell subsets is critical as it may reveal a targetable genetic pathway to modulate CD4+ and CD8+ T-cell numbers, which could be of clinical relevance for multiple disease settings. In this study, we aim to uncover non-MHC genetic factors regulating the proportion of CD4+ and CD8+ T cells in lymphoid tissues. By investigating linkage analyses on three independent F2 cohorts, namely a rat F2 (BBDP × ACI.1U.LYP) cohort, a mouse 3A9 TCR transgenic F2 (B10.BR × NOD.H2k) cohort and a mouse F2 (C57BL/6 × FVB/N) cohort, we uncover an orthologous non-MHC locus on rat chromosome 1 and mouse chromosome 7 that is linked to T-cell proportion amongst total lymphocytes.


Gene transfer into mouse embryonic stem cell-derived cardiac myocytes mediated by recombinant adenovirus.
The main purpose of this study was to examine, for the first time, the ability of recombinant adenovirus to mediate gene transfer into cardiac myocytes derived from mouse embryonic stem (ES) cells differentiating in vitro. In addition, observations were made on the effect of adenovirus infection on cardiac myocyte differentiation and contractility in this in vitro system of cardiogenesis. ES cell cultures were infected at various times of differentiation with a recombinant adenovirus vector (AdCMVlacZ) containing the bacterial lacZ gene under the control of the cytomegalovirus (CMV) promoter. Expression of the lacZ reporter gene was determined by histochemical staining for beta-galactosidase activity. LacZ expression was not detected in undifferentiated ES cells infected with AdCMVlacZ. In contrast, infection of differentiating ES cell cultures showed increasing transgene expression with continued time in culture. Expression in ES-cell-derived cardiac myocytes was demonstrated by codetection of beta-galactosidase activity and troponin T with indirect immunofluorescence. At 24 h postinfection, approximately 27% of the cardiac myocytes were beta-galactosidase positive, and lacZ gene expression appeared to be stable for up to 21 d postinfection. Adenovirus infection had no apparent effect on the onset, extent, or duration of spontaneously contracting ES-cell-derived cardiomyocytes, indicating that cardiac differentiation and contractile function were not significantly altered in the infected cultures. The demonstration of adenovirus-mediated gene transfer into ES-cell-derived cardiac myocytes will aid studies of gene expression with this in vitro model of cardiogenesis and may facilitate future studies involving the use of these myocytes for grafting experiments in vivo.


Assessment of acute kidney injury in neurologically and traumatically injured intensive care patients receiving large vancomycin doses.
Previous reports note that in a mixed patient population, vancomycin doses >4 g/day are associated with increased rates of acute kidney injury (AKI). The objective of the study is to determine if vancomycin regimens >4 g/day are associated with a higher incidence of AKI in neurocritical care unit (NCCU) and trauma/burn Intensive Care Unit (TBICU) patients. This single-centered, retrospective study enrolled adult patients initiated on vancomycin in the NCCU and TBICU at an academic medical center during 2016. Based on maximum steady-state dose exposure, patients were separated into two groups: ≤4 g/day and >4 g/day. The primary outcome of incidence of AKI was defined by the AKI Network criteria. A total of 284 patients were screened for eligibility; 165 patients met inclusion criteria, 98 patients received ≤4 g/day and 67 patients received >4 g/day. The >4 g/day group had a lower mean age (32.6±11.1 vs. 47.8±16.2, P < 0.001), included more male patients (81% vs. 60%, P = 0.008), were more often treated for a central nervous system infection (31% vs. 11%, P = 0.001), had, on average, more concomitant use of nephrotoxic drugs (2.2±1.2 vs. 1.8±0.9, P = 0.02) and had a higher exposure to contrast (94% vs. 79%, P < 0.001). The primary outcome of AKI occurred in 14 patients receiving ≤4 g/day and five patients receiving >4 g/day which was not statistically significant (14% vs. 7%, P = 0.22). Our results indicate that administering >4 g/day of vancomycin to achieve therapeutic vancomycin troughs does not appear to lead to an increased incidence of AKI in a mixed NCCU and TBICU population.


Isolation and antimicrobial susceptibility of Aeromonas salmonicida in rainbow trout (Oncorhynchus mykiss) in turkey hatchery farms.
Three Aeromonas salmonicida strains were isolated from the livers of 265 rainbow trouts sampled. The antibiotic susceptibility test results showed that A. salmonicida strains were susceptible to streptomycine and ciprofloxacin. However, they were resistant to amoxycilline + clavulanic acid, penicillin, erythromycine, oxytetracycline and cefuroxime sodium.


Left ventricular echogenic focus in the fetal heart: pathologic correlation.
Echogenic foci within the left ventricle of the heart have been found in a minority of fetuses and generally are believed to be a normal variant. The cause and exact location of these foci have remained speculative, however. We identified three fetuses with this sonographic finding in whom pathologic correlation was available. The only consistent histologic finding present in all three fetuses was mineralization within a papillary muscle; the chordae tendineae were normal. One of the three fetuses had trisomy 21. Echogenic foci within the left ventricle of the fetal heart represent papillary muscle mineralization. Until more data are available to investigate any possible association with aneuploidy, an echogenic focus in the left ventricle should still be considered a normal variant.


Hemodynamic changes after acute and long-term combined alpha--beta-adrenoceptor blockade with labetalol as compared with beta-receptor blockade.
The hemodynamic pattern in hypertension varies according to the age of the subject and the stage of the hypertensive disorder. In the early stage, both cardiac output and systemic vascular resistance tend to be elevated. Already at that stage, mild degrees of left ventricular function disturbance can be detected. Advanced stages are characterized by a hypokinetic type of circulation with subnormal cardiac output and considerably increased systemic vascular resistance. Both cardioselective and nonselective beta-receptor antagonists lower cardiac output and tend to raise systemic vascular resistance. Even left ventricular filling pressures tend to be higher. While these effects are most distinct in the acute experiment, cardiac output remains always depressed and systemic vascular resistance stabilizes often at a higher level, compared with pretreatment values, even during long-term therapy. The antihypertensive action of beta-receptor blockers appears to be mainly due to the reduction of cardiac output. Combined alpha--beta-adrenergic blockade lowers blood pressure predominantly by alpha-adrenoceptor-mediated reduction of systemic vascular resistance both when induced acutely and during long-term administration. Owing to its beta-adrenoceptor blocking component, the increase of cardiac output is abolished: cardiac output is maintained at pretreatment levels, as is left ventricular filling pressure. Since a well-balanced blockade of both alpha- and beta-adrenergic receptors counteracts the hemodynamic changes occurring in the course of hypertension and tends to restore cardiovascular dynamics towards normal, combined alpha--beta-adrenoceptor blockade appears to be one of the most logical and rational therapeutical approaches to hypertension.


Heart failure in different occupational classes in Sweden.
The link between low socioeconomic status (SES) and coronary heart disease (CHD) is well established, but there is a paucity of data whether a similar relation exists for heart failure (HF). A total of 6999 men 47-55 years old, without a prior stroke or myocardial infarction, from a population sample of 9998 men, were investigated during 1970-73. Over a 28-year follow-up, 1004 men (14.3%) were discharged from hospital or died with a diagnosis of HF. There was an inverse relationship between SES, measured as an occupational class, and future risk of HF. Compared with men in the highest occupational class, men with intermediate non-manual occupations had a multiple-adjusted hazard ratio (HR) of 1.28, 95% confidence interval (CI) 0.98-1.67, lower officials and foremen had an HR of 1.57 (1.22-2.03), semiskilled and skilled workers 1.48 (1.15-1.89), and unskilled workers 1.72 (1.34-2.20). Results were similar if only men with a principal diagnosis of HF (n=516) were considered, irrespective of whether a diagnosis of acute myocardial infarction or coronary revascularization had been recorded at any time. Low SES is an independent risk factor for long-term risk of HF in men.


Health centers and the states. Partnership potential to address the fiscal crisis.
The 38-year-old federal Health Centers program funds community-owned preventive and primary health care for 14 million people, mostly from low-income and minority groups. Studies show that health centers provide quality health care efficiently and effectively. President Bush has begun a major program expansion to serve 6 million more people, but the states' fiscal crisis has forced funding cutbacks that could undermine the administration's initiative. The authors argue that states could actually save money by increasing their investment in health centers, given the health centers' record of reducing the need for high-cost specialty and hospital care and eliminating health disparities.


Relationships between selected gene polymorphisms and blood pressure sensitivity to weight loss in elderly persons with hypertension.
Salt sensitivity, the heterogeneity in the response of blood pressure (BP) to alterations in sodium intake, has been studied extensively, whereas weight sensitivity, the heterogeneity in BP response to weight change, has received scant attention. We examined the relationship of 21 gene polymorphisms previously found to be associated with hypertension, diabetes mellitus, or obesity, with weight sensitivity in the Trial of Nonpharmacologic Interventions in the Elderly, where participants with hypertension were randomized to receive intensive dietary intervention of sodium reduction, weight loss, both, or attention control, whereas pharmacological therapy was kept constant. After correcting for multiplicity, we identified significant associations of 3 polymorphisms with weight sensitivity of systolic BP (rs4646994, rs2820037, and rs1800629) and 3 polymorphisms for diastolic BP (rs4646994, rs2820037, and rs5744292). A recursive partitioning algorithm selected the combination of rs4646994, rs1800629, rs1982073, and rs1800896 as the set associated with the highest weight sensitivity. Polymorphisms related to hypertension, obesity, and diabetes mellitus are associated with weight sensitivity of BP.


Atypical Pneumococcal Isolate from Blood.
Pneumonia with bacteremia accounts for the majority (70%) of cases of invasive pneumococcal diseases. Laboratory characterization of pneumococci is routinely done by sensitivity to optochin. We identified an atypical presentation of optochin-resistant pneumococci in blood isolate of a patient with sepsis. Polymerase chain reaction for autolysin (lytA) and pneumolysin (ply) was positive in the bile soluble isolate. Gene sequencing revealed synonymous single nucleotide polymorphism type of functional mutation in lytA gene. There have been emerging reports of optochin-resistant pneumococci. Diminishing relevance and reliability of optochin sensitivity testing in identifying pneumococci in clinical samples has been highlighted by this case report.


Osteogenic Differentiation Evaluation of an Engineered Extracellular Matrix Based Tissue Sheet for Potential Periosteum Replacement.
Due to the indispensable role of periosteum in bone defect healing and regeneration, a promising method to enhance osteogenesis of bone grafts by using an engineered biomimetic periosteum would be highly beneficial. The stromal microenvironment of periosteum is composed of various highly organized extracellular matrix (ECM) fibers, so an aligned natural ECM sheet, derived from the human dermal fibroblast cell sheet, may be advantageous when applied for artificial periosteum fabrication. Human mesenchymal stem cells (hMSCs) have been used to replace the osteoprogenitor cell population in native periosteum due to hMSCs' great osteogenic potential and fast in vitro expansion capacity. The objective of this work is to investigate if the natural ECM sheet and the substrate alignment can promote in vitro osteogenesis of hMSCs. The conventional cell culture substrates collagen I-coated polydimethylsiloxane (PDMS) and tissue culture plastic (TCP) were used as controls. It was found that the ECM sheet significantly increased alkaline phosphatase activity and calcium deposition. The enhanced osteogenic potential was further confirmed by increased bone-specific gene expression. The ECM sheet can bind significantly higher amounts of growth factors including ANG-1, TGF-β1, bFGF, and VEGF, as well as calcium phosphate nanoparticles, which contributed to high osteogenesis of the hMSCs on ECM sheet. However, the alignment of the substrates did not show significant influence on osteogenic activity and growth factor binding. These results demonstrated the great potential of hMSC-seeded ECM sheet as a biomimetic periosteum to improve critical sized bone regeneration.


Common-mode plasmon sensing scheme as a high-sensitivity compact SPR sensor.
A deep metal grating enables quasi-phase-matched simultaneous excitation of two counterpropagating surface plasmon modes by means of its +1st and -2nd diffraction orders. The resulting angular reflection spectra of the scattered -1st and zeroth orders exhibit three interleaved zeros and maxima in a range centered around the Littrow angle. The spectra differ thoroughly from the usual reflection dip resulting from single-order plasmon coupling that produces strong absorption. The zeroth and -1st orders exhibit two crossing angles enabling high-sensitivity common-mode detection schemes designed to reject variations in source power and environmental noise. The proof of concept and experimental assessment of this new surface plasmon resonance (SPR) sensing scheme are demonstrated by monitoring gases in a pressure-controlled chamber. A limit of detection (LOD) of 2 × 10-7 refractive index unit (RIU) was achieved.


Response classes in the dorsal cochlear nucleus and its output tract in the chloralose-anesthetized cat.
Neurons in the dorsal cochlear nucleus (DCN) can be classified into three major physiological classes on the basis of responses to pure tone and broadband noise stimuli. A circuit diagram that associates these classes with different cell types has been proposed. According to this proposal, type II cells are inhibitory interneurons that respond well to tones and poorly to broadband noise, type IV cells are projection neurons with the opposite behavior, and type III cells are an inhomogeneous class with intermediate properties. To test the associations proposed, I compared the response type distribution in the DCN with its output tract, the dorsal acoustic stria (DAS), in chloralose-anesthetized cats. Axonal recordings in the DAS showed type III and IV responses as in DCN, but no type II responses. Compared with reports in decerebrate animals, fewer type IV neurons were encountered having sustained inhibition that generated strongly nonmonotonic responses to tones in both DCN and DAS. The presence of type II responses in the nucleus, but not in the output tract, offers strong support for the proposed association with DCN interneurons. On the other hand, the distinction between type III and IV responses needs refinement because the differences are only graded and because both types of responses occur in DAS, which shows that they are both associated with projection neurons.


Synthesis of poly(meth)acrylates with thioether and tertiary sulfonium groups by ARGET ATRP and their use as siRNA delivery agents.
The field of RNA interference depends on the development of safe and efficient carriers for short interfering ribonucleic acid (siRNA) delivery. Conventional cationic monomers for siRNA delivery have utilized the nitrogen heteroatom to produce cationic charges. Here, we polymerized cationic sulfonium (meth)acrylate by activators regenerated by electron transfer (ARGET) atom transfer radical polymerization (ATRP) to form polymers with narrow molecular weight distributions for siRNA delivery. The tertiary sulfonium species was stable toward dealkylation in water but less stable in the polar aprotic solvent dimethyl sulfoxide. Block copolymers poly(ethylene oxide) with poly(meth)acrylate containing sulfonium moieties were prepared as an siRNA delivery platform. Results suggested block copolymers were biocompatible up to 50 μg/mL in vitro and formed polyplexes with siRNA. Additionally, block copolymers protected siRNAs against endonuclease digestion and facilitated knockdown of glyceraldehyde 3-phosphate dehydrogenase (Gapdh) mRNA expression in murine calvarial preosteoblasts. The versatility, biocompatibility, and cationic nature of these tertiary sulfonium groups are expected to find widespread biological applications.


Large scale preparation and crystallization of neuron-specific enolase.
A simple method has been developed for the large scale purification of neuron-specific enolase [EC 18.104.22.168]. The method consists of ammonium sulfate fractionation of brain extract, and two subsequent column chromatography steps on DEAE Sephadex A-50. The chromatography was performed on a short (25 cm height) and thick (8.5 cm inside diameter) column unit that was specially devised for the large scale preparation. The purified enolase was crystallized in 0.05 M imidazole-HCl buffer containing 1.6 M ammonium sulfate (pH 6.39), with a yield of 0.9 g/kg of bovine brain tissue.


Detection of Mycobacterium tuberculosis in BACTEC 12B broth cultures by the Roche Amplicor PCR assay.
To evaluate the ability of the Amplicor MTB Assay to detect Mycobacterium tuberculosis complex (MTBC) organisms in BACTEC 12B broth cultures, 249 cultures with a growth index (GI) of > or = 20 from 160 patients were tested retrospectively. Specimens were processed by standard methods, and then BACTEC 12B vials and Middlebrook 7H11/7H115 plates were inoculated, incubated, and interpreted in accordance with the manufacturer's instructions and laboratory protocol. From 12B vials with a GI of > or = 20, and aliquot of broth was removed and frozen at -20 degrees C until assayed by PCR. PCR results were compared to those obtained by the usual laboratory protocol, whereby MTBC organisms were identified by a DNA probe assay performed on broth from 12B vials with a GI or > or = 300 or on colonies from solid medium. Of the 249 broth cultures evaluated, 142 contained mycobacteria, including 44 that contained MTBC organisms. Of these 44 cultures, 41 were PCR positive; the 3 that were PCR negative were blood specimens collected in an Isolator tube. All 98 cultures with nontuberculous mycobacteria and the 107 that did not contain mycobacteria were PCR negative. Thus, the sensitivity and specificity of PCR were 93 and 100%, respectively. For those culture sin which MTBC organisms were identified by both the DNA probe and PCR assays, the mean time from specimen inoculation to detection and identification of MTBC organisms was 16 (range, 4 to 26) days for the PCR and 28 (range, 13 to 43) days for the DNA probe assay (P < 0.0001). In summary, PCR is a rapid, reliable method for detection of MTBC organisms in BACTEC 12B broth cultures with a GI of > or = 20.


Metalloporphyrin polymer with temporally agile, broadband nonlinear absorption for optical limiting in the near infrared.
A lead bis(ethynyl)porphyrin polymer possesses strong nonlinear absorption with unprecedented spectral/temporal coverage as a result of broad, overlapping two-photon and excited-state absorption bands with favorable excited-state dynamics. Consequently, this material exhibits effective optical limiting over a range of about 500 nm in the near infrared (ca. 1050 - 1600 nm) and for laser pulsewidths spanning from 75 fs to 40 ns. Introduction of the material in a waveguide device geometry results in a strong optical limiting response.


Surgical treatment of a double splenic artery aneurysm.
Splenic artery aneurysms account for the majority of splanchnic artery aneurysms. These constitute a uncommon pathology, but with a mortality rate greater 70%. We report a case of a double symptomatic aneurysm of the splenic artery with a proximal and distal localization. The patient was a 65-year-old woman with chronic abdominal pain of the left hypochondrium, irradiating to the ipsilateral iliac fossa. In this case, the particular anatomical characteristics, which prevented a conservative endovascular treatment, were well suited to surgical treatment, performed successfully. In conclusion, in the case of a low-risk patient, in the presence of aneurysms with favourable anatomical characteristics one should prefer surgical rather than endovascular treatment, despite the widespread use of the latter.


Right and left ventricular mass development in early infancy: Correlation of electrocardiographic changes with echocardiographic measurements.
Right ventricular mass indexed to body surface area (RVMI) decreases and left ventricular mass index (LVMI) increases rapidly and substantially during early infancy. The relationship between these sizeable mass transformations and simultaneous electrocardiographic changes have not been previously delineated. Normal term infants (#45 initially enrolled) were prospectively evaluated at 2 days and at 2-week, 2-month, and 4-month clinic visits. Ventricular masses were estimated with 2D echocardiographic methods. QRS voltages were measured in leads V1, V6, I and aVF. Mean QRS axis shifted from 135 (95%CI 124, 146) to 65 degrees (95%CI 49, 81) and correlated with both RVMI decrease and LVMI increase (R = 0.46⁎ vs. 0.25†, respectively. *p < 0.01, †p < 0.05). As RVMI decreased from mean 28.1 (95%CI 27.1, 29.1) to 23.3 g/m2 (95%CI 21.4, 25.2) so did V1R and V6S voltages. RVMI changes correlated with V1R, V6S, and V1R + V6S voltages (R = 0.29*, 0.23† and 0.35*, respectively. *p < 0.01, †p < 0.05) but not with V1R/S ratio. As LVMI increased from 44.6 (95%CI 42.9, 46.3) to 55.4 g/m2 (95%CI 52.3, 58.5) V6R and V6Q increased but V1S voltage did not. LVMI changes correlated with V6R, V6R-S, and V6(Q + R)-S voltages (R = 0.31*, 0.34*, and 0.38* respectively. *p < 0.01) but not with V1S or V6R/S (R = 0.01 and 0.18 respectively, p = NS). During early infancy the RVMI decrease correlates best with the QRS axis shift and V1R + V6S voltage, and the LVMI increase correlates best with V6R-S and V6(Q + R)-S voltages.


Structure-oriented review of 14-3-3 protein isoforms in geriatric neuroscience.
This review focuses on the possible relevance of 14-3-3 proteins in geriatric neuroscience. 14-3-3 proteins are mainly localized in the synapses and neuronal cytoplasm. These proteins regulate intracellular signal cascades for differentiation, development, growth, apoptosis and survival. Seven isoforms have so far been identified in mammals. The binding motifs and potential functions of 14-3-3 proteins are now recognized to have a wide range of functional relevance. First, we provide a brief summary of the molecular structure and multiple functions of 14-3-3 proteins. Second, we review the involvement of 14-3-3 proteins in common diseases of geriatric neurology, such as Alzheimer's disease and tauopathies, Parkinson's disease and α-synucleinopathies, Huntington's disease and polyglutamine diseases, Creutzfeldt-Jakob disease and prion diseases, cerebral infarction, and atherosclerosis. Finally, we discuss the immunohistochemical localization of 14-3-3 proteins and its isoforms during the postnatal development of rat brains as a basis for understanding adult neurogenesis. The elucidation of the isoform-dependent functions of 14-3-3 proteins with regard to brain development might be promising for the future development of novel therapeutic interventions for common diseases of geriatric neurology.


Yale database for DNA sequence changes in mutagenesis.
The Yale database contains sequence changes in mutations induced in a number of bacterial, mammalian and yeast genes. It contains data in electronic form on more than 17,000 mutations (July, 1994), is periodically updated, and is available without cost on Internet and on diskettes. Researchers are invited to contribute additional results; a data entry program, MUSTIN, is provided to facilitate adding new data and to minimize errors.


Effect of light irradiation and primer application on polymerization of selfadhesive resin cements monitored by ultrasonic velocity.
In this study, we investigated the effect of light irradiation and primer/adhesive application on the polymerization reaction and elastic modulus (E) of self-adhesive resin cement (SAC) through ultrasonic velocity (V) measurements. The V values of longitudinal and shear waves were determined based on the transit time through the specimens and specimen thicknesses, and were used to calculate the E values. Analysis of variance and Tukey tests revealed that V increased rapidly, reaching a plateau at 2,700-2,900 m/s, when the SACs were light-irradiated. However, the increasing rate of V was retarded for the non-irradiated SACs. In addition, when the primer/adhesive was applied, higher E values were obtained after 24 h. Finally, the polymerization behavior of the SACs was affected by light irradiation and primer application, and the use of prime/adhesive might improve mechanical properties. In clinical situations, use of primer/adhesive is recommended for getting proper adhesion.


Ion transports in the middle ear epithelium.
Ion transports in the middle ear epithelium have been recently characterized. Experimental data using cell culture have found the existence of a sodium transepithelial transport that drives a water flow. This is thought to play a key role in the maintain of air-filled and fluid-free cavities. Impairment of this process is involved in the pathogenesis of secretory otitis media, which is the main cause of acquired hearing loss. Several modulations of this transport have been evidenced: (i) reactive oxygen species induced an endogenous synthesis of prostaglandin E2 (PGE2), which in turn increased the cAMP level and modulated ion transport rate; (ii) steroids increased the expression of the alpha subunit sodium channel mRNA, which changes paralleled the modulation of ion transport in the middle ear epithelium; (iii) moderate hypoxia selectively and reversibly decreased the rate of sodium transport, as a result of a parallel decrease in alpha epithelial sodium channel subunit mRNA level. These modulations may explain the course of middle ear pathology. However, the development of an in vivo model has become mandatory to assess the relevance of these data in the pathophysiology of the middle ear.


Substance use among children and young persons appearing in the Nairobi Juvenile Court, Kenya.
To estimate the prevalence and pattern of substance use among children and young persons appearing in the Nairobi Juvenile Court, Kenya. A point prevalence survey. The Nairobi Juvenile Court, Kenya. Ninety (sixty four males and twenty six females) children and young persons aged 8 to 18 years classified as criminal offenders, group I (60) and those for protection and discipline, group II (30), were selected. Socio-demographic and substance use questionnaires were administered to the subject. International classification of diseases, 10th Edition (ICD-10) diagnostic criteria were used. Crude rate for substance use in this study was found to be 39 out of the total sample of 90(43.3%), children and young persons. Of these thirty nine, 33 (85.8%) were males and six(14.2%) were females. Twenty nine (32.2%) used nicotine, 19(21.1%) used volatile hydrocarbons, 8(8.9%) used cannabis six (6.7%) used alcohol, five (5.6%) used khat and three (3.3%) used sedatives. Multiple substance use was also evident. This study has shown a high presence of substance use in children and young persons appearing in the Nairobi Juvenile Court.


Evaluation of the PI-RADS scoring system for classifying mpMRI findings in men with suspicion of prostate cancer.
To evaluate the ESUR scoring system (PI-RADS) for multiparametric MRI of the prostate in clinical routine and to define a reliable way to generate an overall PI-RADS score. Retrospective analysis of all patients with a history of negative prebiopsies, who underwent 3 Tesla multiparametric MRI from October 2011 to April 2013 (n = 143): PI-RADS scores for each single modality were defined. To generate the overall PI-RADS score, an algorithm based approach summing up each single-modality score to a sum-score was compared to a more subjective approach, weighting the single modalities dependent on the radiologist's impression. Because of ongoing cancer suspicion 73 patients underwent targeted mpMRI-ultrasound image fusion rebiopsy. For this group thresholds for tumor incidences and malignancy were calculated. 39 (53%) out of 73 targeted rebiopsies were cancer positive. The PI-RADS score correlated well with tumor incidence (AUC of 0.86, 95% CI 0.78 to 0.94) and malignancy (AUC 0.84, 95% CI 0.68 to 0.99). Regarding the sum-score a threshold of ≥ 10 turned out to be reliable for cancer detection (sensitivity 90%, specificity 62%) and for ≥ 13 for indicating higher malignancy (Gleason ≥ 4 + 3) (sensitivity 80%, specificity 86%). To generate the overall PI-RADS score, the use of an algorithm based approach was more reliable than that of the approach based on the radiologist's impression. The presented scoring system correlates well with tumor incidence and malignancy. To generate the overall PI-RADS score, it seems to be advisable to use an algorithm based instead of a subjective approach.


The effect of the cutoff frequency on the sound production of a clarinet-like instrument.
The input impedance of woodwind instruments is characterized by at least two bands due to the lattice of open toneholes, a stop band at low frequencies, and a pass band at higher frequencies where the acoustic energy is able to propagate past the first open tonehole and into the lattice. The cutoff frequency that separates these two bands is an approximate value that is determined by the geometry of the lattice of open toneholes. It is expected that the frequency at which the stop band transitions to the pass band affects the sound produced by the instrument, but it is not known how this frequency affects the competition between self-sustained oscillation and radiation. A simplified model of a clarinet-like resonator is conceived such that the first input impedance peak and the cutoff frequency can be independently chosen. Experimental prototypes are built and the measured impedance of these prototypes is compared with the simulations. Resonators with very similar low frequency behavior but very different cutoff frequencies are then compared using digital synthesis to evaluate the influence of the cutoff frequency on sound production. The cutoff frequency impacts the synthesized pressure and acoustic volume velocity in the mouthpiece, particularly regarding the spectral content at high frequencies.


Human immunodeficiency virus infection is a risk factor for adverse perinatal outcome.
The purpose of this study was to examine the relationship between maternal human immunodeficiency virus infection and adverse perinatal outcomes. A retrospective cohort study was conducted in a population of pregnant women who were delivered in a large inner-city hospital between January 1, 1988, and December 31, 1995. The study population consisted of 563 women who were human immunodeficiency virus seropositive and 2252 control subjects who were human immunodeficiency virus seronegative. Results were analyzed with descriptive statistics, chi2 tests, and logistic regression to adjust for potential confounders. Women who were seropositive were more likely than control subjects to deliver low birth weight infants (29.3% vs 16.3%; odds ratio, 2.11; 95% CI, 1.68-2.64), preterm infants (28.9% vs 18.2%; odds ratio, 1.83; 95% CI, 1.45-2.38), and intrauterine growth-restricted infants (16.5% vs 10.6%; odds ratio, 1.66; 95% CI, 1.26-2.19). They were also more likely to have perinatal deaths (11.5% vs 8.3% odds ratio, 1.41; 95% CI, 1.03-1.95). The risk of fetal malformations, fetal distress, and route of delivery were similar between the groups. After race, parity, alcohol use, prenatal care, diabetes mellitus, hypertension, percent ideal body weight, and sexually transmitted diseases were controlled with logistic regression, the increased risk of low birth weight (adjusted odds ratio, 1.45; 95% CI, 1.14-1.86) and preterm delivery (adjusted odds ratio, 1.32; 95% CI, 1.04-1.70) persisted. Parturients in our inner-city hospital who were infected with human immunodeficiency virus are at increased risk for delivery of low-birth-weight and premature infants.


First principles molecular dynamics study of nitrogen vacancy complexes in boronitrene.
We present the results of first principles molecular dynamics simulations of nitrogen vacancy complexes in monolayer hexagonal boron nitride. The threshold for local structure reconstruction is found to be sensitive to the presence of a substitutional carbon impurity. We show that activated nitrogen dynamics triggers the annihilation of defects in the layer through formation of Stone-Wales-type structures. The lowest energy state of nitrogen vacancy complexes is negatively charged and spin polarized. Using the divacancy complex, we show that their formation induces spontaneous magnetic moments, which is tunable by electron or hole injection. The Fermi level s-resonant defect state is identified as a unique signature of the ground state of the divacancy complex. Due to their ability to enhance structural cohesion, only the divacancy and the nitrogen vacancy carbon-antisite complexes are able to suppress the Fermi level resonant defect state to open a gap between the conduction and valence bands.


Assessment of symptomatic patients after endoscopic sinus surgery with special reference to the frontal sinus: comparative radiologic analysis.
To reveal the role of potential risk factors in frontal recess dissection (FRD), middle turbinate resection (MTR), sinonasal polyposis, and extension of disease in postoperative frontal sinus opacification by determining radiologic changes after endoscopic sinus surgery (ESS) in symptomatic cases using computed tomography (CT). Retrospective analysis of prospectively collected data from symptomatic patients after ESS. Postoperative CT scans were taken in all symptomatic patients during their least symptomatic period or after maximal medical therapy. The radiologic findings of each sinus were compared, and the outcome of ESS was statistically evaluated. Furthermore, FRD, MTR, sinonasal polyposis, and extension of disease were analyzed for postoperative frontal sinus opacification. In our study, 101 sinuses of 61 symptomatic patients were examined. A significant improvement in opacification in all sinuses was detected postoperatively. Multivariate analysis of all potential risk factors revealed that postoperative frontal sinus opacification was affected only by sinonasal polyposis (odds ratio [OR] 3.32; 95% confidence interval [CI] 1.04-10.58) and extension of disease (OR 16.93; 95% CI 4.33-66.23). Our study revealed that surgical procedures such as FRD and/or MTR may not directly affect postoperative frontal sinus opacification. On the contrary, sinonasal polyposis and extension of disease seemed to be the main risk factors of this issue.


An immunochemical study of delta-aminolevulinate synthase and delta-aminolevulinate dehydratase in liver and erythroid cells of rat.
The relationship between erythroid delta-aminolevulinate (ALA) synthase and hepatic ALA synthase in rat was analyzed immunochemically, using antibodies directed against rat liver ALA synthase and against chicken liver ALA synthase. Rat erythroid ALA synthase showed no cross-reactivity with anti-liver ALA synthase antibodies, but hepatic ALA synthases from rat, mouse, and chicken share substantial cross-reactivity with one another. These results clearly distinguish the isozyme relationship between erythroid ALA synthase and hepatic ALA synthase in rat and suggest that there may be at least two different ALA synthase genes in rat. ALA dehydratase in rat liver, on the other hand, could not be immunochemically distinguished from ALA dehydratase in rat erythroid cells when antibody against rat erythroid ALA dehydratase was used. The finding that erythroid ALA synthase is an entity different from hepatic ALA synthase may provide a clue to understanding the different features in hepatic and erythropoietic porphyrias.


Selection for Protein Kinetic Stability Connects Denaturation Temperatures to Organismal Temperatures and Provides Clues to Archaean Life.
The relationship between the denaturation temperatures of proteins (Tm values) and the living temperatures of their host organisms (environmental temperatures: TENV values) is poorly understood. Since different proteins in the same organism may show widely different Tm's, no simple universal relationship between Tm and TENV should hold, other than Tm≥TENV. Yet, when analyzing a set of homologous proteins from different hosts, Tm's are oftentimes found to correlate with TENV's but this correlation is shifted upward on the Tm axis. Supporting this trend, we recently reported Tm's for resurrected Precambrian thioredoxins that mirror a proposed environmental cooling over long geological time, while remaining a shocking ~50°C above the proposed ancestral ocean temperatures. Here, we show that natural selection for protein kinetic stability (denaturation rate) can produce a Tm↔TENV correlation with a large upward shift in Tm. A model for protein stability evolution suggests a link between the Tm shift and the in vivo lifetime of a protein and, more specifically, allows us to estimate ancestral environmental temperatures from experimental denaturation rates for resurrected Precambrian thioredoxins. The TENV values thus obtained match the proposed ancestral ocean cooling, support comparatively high Archaean temperatures, and are consistent with a recent proposal for the environmental temperature (above 75°C) that hosted the last universal common ancestor. More generally, this work provides a framework for understanding how features of protein stability reflect the environmental temperatures of the host organisms.


Neuronal intranuclear hyaline inclusion disease: report of a case and review of the literature.
A case of neuronal intranuclear hyaline inclusion disease (NIHID) is described. The patient was a 26-year-old man who died of a progressive neurologic disorder, the onset of which occurred at the age of 11 years. Clinically, the disease presented as juvenile parkinsonism, and pathologically it was characterized by multiple-system degeneration in conjunction with the ubiquitous presence of intranuclear hyaline inclusions in neurons of the central and peripheral nervous system including the autonomic ganglia. Smaller and less eosinophilic intranuclear inclusions were also present in a small number of glial cells. The neuronal inclusions emitted a strong yellow-green autofluorescence under ultraviolet light and were composed of filaments 10-15 nm in diameter. The glial inclusions also consisted of similar filaments but their autofluorescence could not be determined with certainty because of their small size and background autofluorescence. A review of the literature revealed 19 similar autopsy cases up to 1987. Since the clinical presentation and distribution of neuronal loss as well as the characteristics of the inclusions showed some differences among the cases, some authors speculated that NIHID represented more than one variant of a multiple-system degenerative disease. However, about half of the reported cases had favorable sites of neurodegeneration, such as the pallidum, substantia nigra, motor nuclei of the brain stem, anterior horn cells, Clarke's column and spinal ganglion as well as similarities among the inclusions. Thus, there seems to be a discrete group among cases of NIHID.


Histopathology of two serotypes of infectious bronchitis virus in laying hens vaccinated in the rearing phase.
The comparative histopathology of 2 different strains of infectious bronchitis virus (T and N1/ 88) in vaccinated hens was studied at 110 wk of age. The Harderian gland showed similar histopathology in T- and N1/88-infected hens. The trachea and kidney of challenged vaccinated hens were protected to a moderate extent, but the oviduct was protected to only a small extent. The severity and persistence of lesions were greater in tubular shell gland, shell gland pouch, and kidney of the T-infected hens, whereas, for the magnum, N1/88 had a greater effect.


Sequence determination of protected oligodeoxyribonucleotides containing phosphotriester linkages by californium-252 plasma desorption mass spectrometry.
A mass spectrometric method for determining the sequence and molecular weight of protected oligodeoxyribonucleotides is described. By using the method of 252Cf plasma desorption mass spectrometry [Macfarlane, R. D. & Torgerson, D. F. (1976) Science 191, 920--925], positive-ion mass spectra were obtained for a series of protected oligonucleotides extending to a decanucleotide; the spectra were dominated by the presence of the oligonucleotide molecular ion. The negative-ion mass spectra were characterized by a nested set of fragment ions extending from the 3'- or 5'-terminal nucleotide to the opposite terminal nucleotide, thereby identifying the sequence. The utility of this method has been demonstrated by the sequence determination of protected tetra-, penta-, and hexanucleotides synthesized by the improved phosphotriester method.