Examining student perceptions of an inter-institutional interprofessional stroke simulation activity.
Integration of interprofessional educational (IPE) activities into health professions' curricula aims to promote collaborative practice with a goal of improving patient care. An interprofessional stroke simulation involving standardised patients was organised for IPE student learners from a number of different health professions programmes based across several different institutions. In this article, we describe the development of an inter-institutional IPE activity and examine the outcomes of this activity on student interprofessional growth. Using a pre-post-study design, all participants were invited to anonymously respond to the 16-question IPEC Competency Self-Assessment tool to examine self-assessed interprofessional interactions and values as a result of the simulation. The questionnaire was available to the students using an online platform, and paired t-tests were used to analyse the responses. Quantitative data revealed significant positive changes in both the values and interaction domains of the assessment from pre- to post-simulation experience (p < 0.0001 and p = 0.0003, respectively). Student reflections identified new realisations around the concepts of leadership and team member roles in the context of patient care. Results of this endeavour support the effectiveness of this activity for developing interprofessional competencies among students, suggest that the self-assessment tool may be used as a means to detect these changes, and lend support to our methods for establishing inter-institutional IPE partnerships.


New species of Caromiobenella Jeon, Lee & Soh, 2018 (Crustacea, Copepoda, Monstrilloida) from Chuja Island, Korea.
Male monstrilloid copepods belonging to the genus Caromiobenella Jeon, Lee & Soh, 2018 were collected from Chuja Island, Jeju, Korea, using a light trap. This paper describes a new species, Caromiobenellaohtsukai sp. n., based on the display of reduced, knob-like fifth legs on the ventral side of the first urosomal somite. A unique combination of male genitalia features and number of caudal setae further confirms its specificity. Molecular analysis based on two partial gene sequences of mitochondrial cytochrome c oxidase subunit I (mtCOI) and 28S ribosomal RNA (28S rRNA) also supports the designation of this species by showing a relevant divergence from known congeners. Caromiobenellaohtsukai sp. n. is the ninth member of this genus and also the ninth monstrilloid reported from Korea.


Combined Use of Ex Vivo Dermoscopy and Histopathology for the Diagnosis of Melanocytic Tumors.
Dermoscopy can be applied to fixed tissues, and dermoscopic patterns correlate with microscopic findings. Data on the influence of ex vivo dermoscopy on pathologic diagnosis of melanocytic lesions are limited. Therefore, we aimed to determine whether this technique could aid on the histopathological evaluation of melanocytic neoplasms. Sequential cutaneous excisional biopsies of melanocytic lesions and their corresponding ex vivo dermoscopic images were prospectively analyzed. Additional sectioning was executed in areas of dermoscopic concern, having, by reference, a dermoscopic mapping of the sectioned specimens. Diagnostic differences before and after analyzing the new dermoscopy-guided sections were registered. A total of 564 melanocytic lesions were examined, and additional cuts were considered necessary in 84 (14.9%) cases. Of these, 11 lesions (13.1%) had a different final diagnosis after dermoscopy-guided specimen sectioning, including 3 lesions that were reclassified as melanomas and 2 melanomas that were restaged. We found that the combined use of ex vivo dermoscopy and histopathology improves clinical-pathological correlation and allows selection of representative areas for sectioning. Altogether, this technique may improve diagnostic confidence and accuracy in the histopathological evaluation of melanocytic lesions.


MORPHOLOGY AND MOLECULAR PHYLOGENY OF ANKISTRODINIUM GEN. NOV. (DINOPHYCEAE), A NEW GENUS OF MARINE SAND-DWELLING DINOFLAGELLATES FORMERLY CLASSIFIED WITHIN AMPHIDINIUM(1).
The classical athecate dinoflagellate genera (Amphidinium, Gymnodinium, Gyrodinium) have long been recognized to be polyphyletic. Amphidinium sensu lato is the most diverse of all marine benthic dinoflagellate genera; however, following the redefinition of this genus ∼100 species remain now of uncertain or unknown generic affiliation. In an effort to improve our taxonomic and phylogenetic understanding of one of these species, namely Amphidinium semilunatum, we re-investigated organisms from several distant sites around the world using light and scanning electron microscopy and molecular phylogenetic methods. Our results enabled us to describe this species within a new heterotrophic genus, Ankistrodinium. Cells of A. semilunatum were strongly laterally flattened, rounded-quadrangular to oval in lateral view, and possessed a small asymmetrical epicone. The sulcus was wide and characteristically deeply incised on the hypocone running around the antapex and reaching the dorsal side. The straight acrobase with hook-shaped end started at the sulcal extension and continued onto the epicone. The molecular phylogenetic results clearly showed that A. semilunatum is a distinct taxon and is only distantly related to species within the genus Amphidinium sensu stricto. The nearest sister group to Ankistrodinium could not be reliably determined.


Human Pol ζ purified with accessory subunits is active in translesion DNA synthesis and complements Pol η in cisplatin bypass.
DNA polymerase ζ (Pol ζ) is a eukaryotic B-family DNA polymerase that specializes in translesion synthesis and is essential for normal embryogenesis. At a minimum, Pol ζ consists of a catalytic subunit Rev3 and an accessory subunit Rev7. Mammalian Rev3 contains >3,000 residues and is twice as large as the yeast homolog. To date, no vertebrate Pol ζ has been purified for biochemical characterization. Here we report purification of a series of human Rev3 deletion constructs expressed in HEK293 cells and identification of a minimally catalytically active human Pol ζ variant. With a tagged form of an active Pol ζ variant, we isolated two additional accessory subunits of human Pol ζ, PolD2 and PolD3. The purified four-subunit Pol ζ4 (Rev3-Rev7-PolD2-PolD3) is much more efficient and more processive at bypassing a 1,2-intrastrand d(GpG)-cisplatin cross-link than the two-subunit Pol ζ2 (Rev3-Rev7). We show that complete bypass of cisplatin lesions requires Pol η to insert dCTP opposite the 3' guanine and Pol ζ4 to extend the primers.


Behavioral assessment of chronic orofacial pain.
Orofacial pain is usually evaluated and treated from a biomedical perspective. There is no question that the large majority of individuals having acute orofacial pain benefit from timely and appropriate medical intervention. When orofacial pain persists, however, the likelihood that this pain can influence and be influenced by behavioral factors increases. While some individuals are able to adapt and cope with chronic orofacial pain, others develop significant behavioral problems. These problems may include an overly sedentary lifestyle, dependence on habit-forming narcotic medications, or severe depression or anxiety. The hallmark of the behavioral perspective on chronic pain is the insistence that a careful assessment and treatment of such behavioral problems is just as important as appropriate biomedical intervention.(1)


Mortality after Respiratory Isolation of Nontuberculous Mycobacteria. A Comparison of Patients Who Did and Did Not Meet Disease Criteria.
The mortality of patients with respiratory tract isolates of nontuberculous mycobacteria (NTM) and their risk factors for death are not well described. To determine age-adjusted mortality rates for patients with respiratory NTM isolates and their causes of death and to examine whether American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) diagnostic criteria identify those at higher risk of death after NTM isolation. We linked vital records registries with a previously identified Oregon population-based cohort of patients with NTM respiratory isolation. We excluded patients with Mycobacterium gordonae (n = 33) and those who died (n = 21) at the time of first isolation. We calculated 5-year age-adjusted mortality rates. We used Kaplan-Meier and Cox proportional hazards analysis to examine the association of ATS/IDSA criteria and other risk factors with death. Of 368 subjects with respiratory NTM isolates in 2005-2006, 316 were included in the survival analysis. Most (84%) of their cultures isolated Mycobacterium avium complex. 35.1% died in the 5 years following respiratory isolation. Five-year age-adjusted mortality rates were slightly higher for those meeting (28.7/1,000) versus not meeting (23.4/1,000) ATS/IDSA criteria. In multivariate analysis, older age (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.04-1.07) and lung cancer (aHR, 2.77; 95% CI, 1.51-5.07) were associated with an increased risk of death. A trend was noted between meeting ATS/IDSA criteria and subsequent death (aHR, 1.37; 95% CI, 0.95-1.97). Among cases, male sex, older age, and immunosuppressive therapy use were independent risk factors for death. In the State of Oregon, patients with NTM respiratory isolates have high mortality, regardless of whether they meet ATS/IDSA criteria for pulmonary NTM disease. Most patients die as a result of causes other than NTM infection.


Halogenation of bisphenol-A, triclosan, and phenols in chlorinated waters containing iodide.
Free chlorine reacts with the iodide (I(-)) present in disinfected waters to produce free iodine. Past research has indicated that this nonchlorinated oxidant exhibits greater reactivity and potentially produces more toxic byproducts than free chlorine alone. In this study, we examined the reactivity of the phenolic compounds 2,4-dichlorophenol, triclosan, and bisphenol A in chlorinated waters containing I(-). The free iodine mediated reactions were probed as a function of the initial I(-) concentration and the solution pH. Over the pH range of 5.5 to 10 for an initial I(-) concentration of 10 μM, the observed transformation kinetics of 2,4-dichlorophenol were generally 2-15× faster than reactions with free chlorine alone, while for triclosan and bisphenol A the free iodine mediated transformations were ≈3-20× and ≈230-660× faster, respectively. A comprehensive reaction model that simultaneously accounts for free chlorine and free iodine reactivity in these systems was developed to determine second-order rate constants for the chlorinated and iodinated oxidants. For all test compounds, iodinated daughter products are rapidly produced when free chlorine reacts in the presence of I(-).


Preliminary X-ray crystallographic analysis of the D-xylulose 5-phosphate phosphoketolase from Lactococcus lactis.
Phosphoketolases are thiamine diphosphate-dependent enzymes which play a central role in the pentose-phosphate pathway of heterofermentative lactic acid bacteria. They belong to the family of aldehyde-lyases and in the presence of phosphate ion cleave the carbon-carbon bond of the specific substrate D-xylulose 5-phosphate (or D-fructose 6-phosphate) to give acetyl phosphate and D-glyceraldehyde 3-phosphate (or D-erythrose 4-phosphate). Structural information about phosphoketolases is particularly important in order to fully understand their mechanism as well as the steric course of phosphoketolase-catalyzed reactions. Here, the purification, preliminary crystallization and crystallographic characterization of D-xylulose 5-phosphate phosphoketolase from Lactococcus lactis are reported. The presence of thiamine diphosphate during purification was essential for the enzymatic activity of the purified protein. The crystals belonged to the monoclinic space group P2(1). Diffraction data were obtained to a resolution of 2.2 A.


Bioactivity of Methoxylated and Methylated 1-Hydroxynaphthalene-2-Carboxanilides: Comparative Molecular Surface Analysis.
A series of twenty-six methoxylated and methylated N-aryl-1-hydroxynaphthalene- 2-carboxanilides was prepared and characterized as potential anti-invasive agents. The molecular structure of N-(2,5-dimethylphenyl)-1-hydroxynaphthalene-2-carboxamide as a model compound was determined by single-crystal X-ray diffraction. All the analysed compounds were tested against the reference strain Staphylococcus aureus and three clinical isolates of methicillin-resistant S. aureus as well as against Mycobacterium tuberculosis and M. kansasii. In addition, the inhibitory profile of photosynthetic electron transport in spinach (Spinacia oleracea L.) chloroplasts was specified. In vitro cytotoxicity of the most effective compounds was tested on the human monocytic leukaemia THP-1 cell line. The activities of N-(3,5-dimethylphenyl)-, N-(3-fluoro-5-methoxy-phenyl)- and N-(3,5-dimethoxyphenyl)-1-hydroxynaphthalene-2-carbox- amide were comparable with or even better than the commonly used standards ampicillin and isoniazid. All promising compounds did not show any cytotoxic effect at the concentration >30 µM. Moreover, an in silico evaluation of clogP features was performed for the entire set of the carboxamides using a range of software lipophilicity predictors, and cross-comparison with the experimentally determined lipophilicity (log k), in consensus lipophilicity estimation, was conducted as well. Principal component analysis was employed to illustrate noticeable variations with respect to the molecular lipophilicity (theoretical/experimental) and rule-of-five violations. Additionally, ligand-oriented studies for the assessment of the three-dimensional quantitative structure-activity relationship profile were carried out with the comparative molecular surface analysis to determine electron and/or steric factors that potentially contribute to the biological activities of the investigated compounds.


Human natural killer cells: their origin, receptors and function.
The term of "natural killer" (NK) cells was originally assigned on a merely functional basis to lymphoid cells capable of lysing certain tumors in the absence of prior stimulation. However, both their origin and the molecular mechanism(s) involved in their function remained a mystery for many years 1. Regarding their origin, clear evidence has now been provided both in mouse and in man that NK and T cells may derive from a common precursor 2-5. Thus, mature NK cells can be obtained in vitro from CD34(+) cells isolated from umbilical cord blood, bone marrow (BM) and even human thymus 6 when cultured in the presence of appropriate feeder cells or IL-15. The molecular mechanism allowing NK cells to discriminate between normal and tumor cells, predicted by the "missing self hypothesis" 7, has been clarified only in recent years. Thus, NK cells recognize MHC class I molecules through surface receptors delivering signals that inhibit, rather than activate, NK cells. As a consequence, NK cells lyse target cells that have lost (or express insufficient amounts of) MHC class I molecules, as frequently occurs in tumors and in cells infected by certain viruses.


Polaribacter gangjinensis sp. nov., isolated from seawater.
A strictly aerobic, orange-pigmented and Gram-staining-negative bacterium, designated K17-16(T), was isolated from seawater of Gangjin Bay, Korea. Comparative 16S rRNA gene sequence analysis revealed that strain K17-16(T) was a member of the genus Polaribacter in the family Flavobacteriaceae and showed 94.0-95.6 % sequence similarity with the type strains of recognized species of the genus Polaribacter. The G+C content of the genomic DNA was 34.6 mol% and the major respiratory lipoquinone was MK-6. The major polar lipids detected were phosphatidylethanolamine, three unidentified amino-group-containing lipids and an unidentified aminophospholipid. The predominant cellular fatty acids were iso-C(15 : 0) (15.4 %), C(15 : 0) (12.4 %), summed feature 3 (comprising iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c; 10.6 %), C(15 : 1)ω6c (9.8 %) and iso-C(15 : 0) 3-OH (8.6 %). On the basis of phenotypic and genotypic data, strain K17-16(T) represents a novel species in the genus Polaribacter, for which the name Polaribacter gangjinensis sp. nov. is proposed. The type strain is K17-16(T) ( = KCTC 22729(T) = JCM 16152(T)).


Complex formation and vectorization of a phosphorothioate oligonucleotide with an amphipathic leucine- and lysine-rich peptide: study at molecular and cellular levels.
Optical spectroscopic techniques such as CD, Raman scattering, and fluorescence imaging allowed us to analyze the complex formation and vectorization of a single-stranded 20-mer phosphorothioate oligodeoxynucleotide with a 15-mer amphipathic peptide at molecular and cellular levels. Different solvent mixtures (methanol and water) and molecular ratios of peptide/oligodeoxynucleotide complexes were tested in order to overcome the problems related to solubility. Optimal conditions for both spectroscopic and cellular experiments were obtained with the molecular ratio peptide/oligodeoxynucleotide equal to 21:4, corresponding to a 7:5 ratio for their respective +/- charge ratio. At the molecular level, CD and Raman spectra were consistent with a alpha-helix conformation of the peptide in water or in a methanol-water mixture. The presence of methanol increased considerably the solubility of the peptide without altering its alpha-helix conformation, as evidenced by CD and Raman spectroscopies. UV absorption melting profile of the oligodeoxynucleotide gave rise to a flat melting profile, corresponding to its random structure in solution. Raman spectra of oligodeoxynucleotide/peptide complexes could only be studied in methanol/water mixture solutions. Drastic changes observed in Raman spectra have undoubtedly shown: (a) the perturbation occurred in the peptide secondary structure, and (b) possible interaction between the lysine residues of the peptide and the oligodeoxynucleotide. At the cellular level, the complex was prepared in a mixture of 10% methanol and 90% cell medium. Cellular uptake in optimal conditions for the oligodeoxynucleotide delivery with low cytotoxicity was controlled by fluorescence imaging allowing to specifically locate the compacted oligonucleotide labeled with fluorescein at its 5'-terminus with the peptide into human glioma cells after 1 h of incubation at 37 degrees C.


Regulatory GTP-binding proteins: emerging concepts on their role in cell function.
The last few years have evidenced a tremendous expansion in our appreciation of the role of regulatory GTP-binding proteins in cellular activation. The availability of cholera and pertussis toxins to detect G proteins as well as methodological advances in the study of cellular function has afforded the opportunity to examine G protein participation in many cellular events. Regulation of adenylyl cyclase and cyclic GMP phosphodiesterase by G proteins has been demonstrated. Phosphatidylinositol-4,5-biphosphate specific phospholipase C activity appears to be subject to G protein control. G proteins regulate inward K+ and Ca2+ channels through a mechanism which may be independent of effects on the above mentioned enzymes. Certainly, the number of G proteins which have been identified from sequencing of complementary DNA affords the potential for G protein involvement in many cellular events. Only three G proteins have however been isolated and functionally characterized, Gs, Gi and transducin. Whether all the functions of these proteins have been identified remains to be seen.


HIV risk and multiple sources of heterosexism among young Black men who have sex with men.
This study examined whether the association between social support and condom self-efficacy would be moderated by (a) internalized heterosexism among and (b) enacted heterosexism experienced by young Black men who have sex with men (YBMSM), who contend with high HIV incidence, heterosexism, and low uptake of preexposure prophylaxis. Participants were 1,210 YBMSM (ages 18-29) who completed measures of social support, internalized and enacted heterosexism, and condom self-efficacy in 2 large cities in the southern United States as part of a community-level HIV-prevention study. A significant 3-way interaction between social support and both hypothesized moderators, internalized and enacted heterosexism, showed that social support was positively associated with condom self-efficacy when both internalized and enacted heterosexism were high (1 SD above the mean; b = .177, 95% confidence interval [CI: .088, .266]). However, social support was not associated with condom self-efficacy when scores were low (1 SD below the mean) on both internalized and enacted heterosexism (b = .024, 95% CI [-.054, .101]), low on internalized and high on enacted heterosexism (b = .058, 95% CI [-.061, .117]), or high on internalized and low on enacted heterosexism (b = .039, 95% CI [-.083, .161]). YBMSM who are high in both internalized and enacted heterosexism may see greater benefits from social support on condom self-efficacy than would YBMSM who grapple with less heterosexism. In addition to promoting social support, interventions should aim to assess and reduce multiple forms of stigma. (PsycINFO Database Record


[The prognostic factors and evolution of the quality of life in primary biliary cirrhosis].
The prognostic factors and the evolution of the quality of life were evaluated in 38 patients with primary biliary cirrhosis (94.7% females, mean age 52.6 +/- 2.0 years) followed up for more than 36 months (mean 65.3 +/- 3.7 months). Karnofsky's index significantly declined during follow up (p less than 0.05) in a parallel fashion to modified Child's hepatic functional class (p less than 0.05) and to the days of hospital readmission (p less than 0.05). Eleven patients (28.9%) died, and the median survival was 88.7 months. The comparison of the actuarial curves showed the following to be significant poor prognostic factors at the time of diagnosis: a) clinical: more than one associated autoimmune disease, weight loss of more than 10% of the ideal weight, jaundice, upper gastrointestinal hemorrhage associated with portal hypertension, portal-systemic encephalopathy and a modified Child's hepatic functional class of 9 or more; b) biochemical: serum albumin lower than 3.5 g/dl and bilirubin higher than 2 mg/dl; c) histological: Total histological activity index of 10 or more and erosive necrosis index of 2 or more (Knodell et al.), lobular granulomas, and stage IV (Ludwig et al). A significant correlation was found (p less than 0.001) between the R index of the Mayo Clinic and the mean survival time of our patients. As a temporary policy, we indicate hepatic transplant when R is 9.2 or higher (life expectancy lower than 24 months), awaiting our own probabilistic prognostic model with the inclusion of quality of life criteria.


Ethanol inhibits development of dendrites and synapses in rat hippocampal pyramidal neuron cultures.
Evidence suggests that some neuropathologic manifestations of Fetal Alcohol Syndrome (FAS) result from the disruption of neuromorphogenesis and synapse formation in the hippocampus. Prior research in this laboratory has shown that ethanol in the medium during the first 24 h in culture increases the number of minor processes (the precursors of axons and dendrites) and accelerates the rate at which axons are formed in low-density cultures of embryonic rat hippocampal neurons. The current study examined the effects of ethanol on the subsequent development of dendrites and synapses in these cultures. Quantitative morphometric analysis utilized double-immunofluorescent staining for MAP2 and synapsin I to visualize dendrites and synaptic specializations, respectively. Six days of ethanol (200, 400 or 600 mg/dl) in the medium, beginning at the time of plating, resulted in decreases in total dendritic length per cell, dendrite number per cell, length of individual dendrites and synapse number per innervated dendrite but had no effect on cell survival. The decrease in synapse number was correlated with dendrite length, suggesting that ethanol's effects on synapse number are secondary to its effects on dendritogenesis. Taken together with our previous findings, these results are the first to demonstrate that ethanol has differential effects on axonal and dendritic growth in a culture model of neurons that are vulnerable to ethanol-induced cytoarchitectural abnormalities during development in vivo.


Diagnostic value of anti-Sa and anticitrullinated protein antibodies in rheumatoid arthritis.
To determine the diagnostic value of anticitrullinated protein antibodies, second generation (ACPA2), by electrochemiluminescent immunoassay (ECLIA) and anti-Sa by ELISA in a large cohort of Chinese patients with early rheumatoid arthritis (RA). One hundred ninety-eight patients with early RA (< 1 yr duration), 112 with other rheumatic diseases, and 60 healthy individuals were studied. The combination of anti-Sa and ACPA2 positivity had the highest specificity (99.42%), but it had a rather low sensitivity (50.0%). The combination of anti-rheumatoid factor (RF) and ACPA2 showed the highest sensitivity (80.30%), with specificity of 95.93%. The mean titer of ACPA2 and RF was significantly higher in the anti-Sa-positive group compared to the negative group (ACPA2, p <0.001; RF, p = 0.007). The 28-joint Disease Activity Scores of the anti-Sa-positive patients were significantly higher than those of the negative group (p = 0.01). The anti-Sa had no significant correlation with age, sex, antinuclear antibody, SSA, SSB, erythrocyte sedimentation rate, C-reactive protein, immunoglobulin A (IgA), IgG, IgM, C3, and C4. Our results come from a newly developed ECLIA for detection of ACPA2 and the anti-Sa-antibody-based ELISA system. The combined application of ACPA2 and anti-Sa tests can improve the laboratory diagnosis of early RA.


Replacement of cetyltrimethylammoniumbromide bilayer on gold nanorod by alkanethiol crosslinker for enhanced plasmon resonance sensitivity.
Surface modification of gold nanorods (GNRs) is often problematic due to tightly packed cetyltrimethylammoniumbromide (CTAB) bilayer. Herein, we performed a double phase transfer ligand exchange to achieve displacement of CTAB on nanorods. During the removal, 11-mercaptoundecanoic acid (MUDA) crosslinker is simultaneously assembled on nanorod surfaces to prevent aggregation. The resulting MUDA-GNRs retain the shape and position of plasmon peaks similar to CTAB-capped GNRs. The introduction of carboxyl groups allows covalent conjugation of biological receptors in a facile fashion to construct a robust, label-free biosensor based on localized surface plasmon resonance (LSPR) transduction of biomolecular interaction. More importantly, smaller MUDA layer on the GNRs reduces the distance of target binding to the plasmonic nanostructure interface, leading to a significant enhancement in LSPR assay sensitivity and specificity. Compared to modification using conventional electropolymer adsorption, MUDA-coated gold nanosensor exhibits five times lower detection limit for cardiac troponin I assay with a high selectivity.


Regression-based norms for the FAS phonemic fluency test for ages 40-84 based on a Norwegian sample.
The FAS phonemic fluency test is a commonly used neuropsychological test of executive function and processing speed. Although Norwegian discrete norms have been developed for the FAS test, American regression-based norms are frequently used by clinicians in Norway.However, language and cultural differences impact performance on the FAS test, and using foreign norms may not be appropriate. Moreover, while discrete norming relies on stratified subgroups of demographics, regression-based norming uses the entire sample to estimate the influence of demographics on performance and may thus improve normative estimates. Here we develop regression-based norms for the FAS phonemic fluency test based on n = 204 healthy Norwegian controls between the ages 40-84 from the Norwegian Dementia Disease Initiation cohort (DDI). We compare the proposed regression norms to published Norwegian discrete norms and American regression-based norms in an independent sample of n = 182 cognitively healthy adults reporting subjective cognitive decline (SCD). We found that years of education was the only significant predictor of FAS performance in our normative sample, accounting for 14.9% of the variance. Both the proposed regression-based norms and previously published discrete norms adequately adjusted for demographics in the independent sample. In contrast, the American norms underestimated the effect of education and overestimated the effect of age. While both the proposed Norwegian regression norms and the previously published discrete norms are suitable for use in Norway, the proposed regression norms may be less vulnerable to sub-stratification sample characteristics posed by discrete norming procedures, and thereby improve normative estimation.


Inhibition of murine relapsing experimental autoimmune encephalomyelitis by immune tolerance to proteolipid protein and its encephalitogenic peptides.
Tolerization of SJL/J mice with splenocytes coupled with proteolipid protein (PLP), the major protein component of central nervous system myelin, resulted in dramatic inhibition of relapsing experimental autoimmune encephalomyelitis (R-EAE) induced by mouse spinal cord homogenate (MSCH). Mice tolerized with splenocytes coupled with MSCH (a complex mixture of neuroantigens) or with purified PLP, but not purified myelin basic protein, were resistant to the development of clinical and histologic R-EAE. In addition, mice rendered tolerant to an encephalitogenic peptide of PLP were significantly protected, whereas mice tolerized to a nonencephalitogenic peptide of PLP were highly susceptible, to the induction of MSCH-induced R-EAE. Thus, immune responses directed against encephalitogenic regions of PLP appear to play a major role in the development of R-EAE induced by MSCH in SJL/J mice. These results also indicate that determinant-specific immune tolerance is a feasible approach to the regulation of a disease that involves autoimmune responses to a variety of Ag.


A small peptide inhibitor of the low voltage-activated calcium channel Cav3.1.
The calcium channel gamma(6) subunit modulates low voltage-activated (LVA) calcium current in both human embryonic kidney (HEK) cells and cardiomyocytes, although the mechanism of modulation is unknown. We recently showed that gamma(6) contains a critical GxxxA motif in the first transmembrane domain (TM1) that is essential for its inhibition of the Cav3.1 (LVA) calcium current. In this study, we tested the hypothesis that an eight-amino acid peptide that contains the GxxxA motif from gamma(6) TM1 can act as a novel pharmacological inhibitor of the Cav3.1 calcium current by performing whole-cell electrophysiology. Our results demonstrate that the peptide inhibits Cav3.1 current by dynamically binding and dissociating from the Cav3.1 channel in a concentration-dependent but largely voltage-independent manner. By selectively substituting residues within the peptide, we show that both the GxxxA framework and surrounding aliphatic side-chains contribute to the presumably interhelical interactions between gamma(6) TM1 and the Cav3.1 channel. The fast kinetics of the interaction supports the view that gamma(6) acts as an endogenous LVA channel antagonist within the plasma membrane, suggesting a mechanism other than regulation of surface expression or membrane trafficking of the pore-forming subunit of the channel. We also demonstrate that the peptide has different affinities for Cav3.1 and Cav1.2 calcium currents, which is consistent with the selective effect of gamma(6) on LVA and high voltage-activated calcium currents in vivo.


Cyclic electron flow around photosystem I via chloroplast NAD(P)H dehydrogenase (NDH) complex performs a significant physiological role during photosynthesis and plant growth at low temperature in rice.
The role of NAD(P)H dehydrogenase (NDH)-dependent cyclic electron flow around photosystem I in photosynthetic regulation and plant growth at several temperatures was examined in rice (Oryza sativa) that is defective in CHLORORESPIRATORY REDUCTION 6 (CRR6), which is required for accumulation of sub-complex A of the chloroplast NDH complex (crr6). NdhK was not detected by Western blot analysis in crr6 mutants, resulting in lack of a transient post-illumination increase in chlorophyll fluorescence, and confirming that crr6 mutants lack NDH activity. When plants were grown at 28 or 35°C, all examined photosynthetic parameters, including the CO(2) assimilation rate and the electron transport rate around photosystems I and II, at each growth temperature at light intensities above growth light (i.e. 800 μmol photons m(-2) sec(-1)), were similar between crr6 mutants and control plants. However, when plants were grown at 20°C, all the examined photosynthetic parameters were significantly lower in crr6 mutants than control plants, and this effect on photosynthesis caused a corresponding reduction in plant biomass. The F(v)/F(m) ratio was only slightly lower in crr6 mutants than in control plants after short-term strong light treatment at 20°C. However, after long-term acclimation to the low temperature, impairment of cyclic electron flow suppressed non-photochemical quenching and promoted reduction of the plastoquinone pool in crr6 mutants. Taken together, our experiments show that NDH-dependent cyclic electron flow plays a significant physiological role in rice during photosynthesis and plant growth at low temperature.


Biochemical and haematologic effects of intake of Macrotermes nigeriensis fortified functional diet.
Twenty-four male albino rats, 4 weeks old were randomly distributed into 4 groups (A-D) and fed growers' mash as the control diet and 25, 50 and 75% oven-dried, ground Macrotermes nigeriensis fortified diets respectively for a total period of 28 days. The effects of the diets on hepatic, renal and haematologic function indices of albino rats were studied. The animals fed the fortified diets had non-significantly (p > 0.05) lesser body weight gains than the control animals. The fortified diets elicited dose-dependent increases in the levels of blood total protein, albumin, packed cell volume, hemoglobin and red blood cell counts as well as on the calculated red cell indices. The fortified diets did not significantly (p > 0.05) alter the activities of plasma alanine and aspartate aminotransferases as well as the concentrations of total bilirubin, urea and creatinine. The results indicate that the fortified diets do not have detrimental hepatic, renal or haematologic effects but rather may be recommended for fortification of human and animal food, especially in weaning diets of growing children and nursing mothers to combat food insecurity and malnutrition.


[Carbohydrate tolerance in patients with myocardial infarct according to prednisolone-glucose tolerance test].
Sensitivity to carbohydrates was studied in 100 patients in the subacute period of myocardial infarction by the prednisolne-glucose tolerance test with parallel determination of the content of sugar and pyruvic and lactic acids. Latent, predominantly mild disorders of carbohydrate metabolism were revealed in most patients. Considerably diminished glucose tolerance (diabetic-type sugar curve) was encountered in 12.5% of patients with normal and in 17.9% of those with excessive body weight. The prednisolone-glucose tolerance test and the tests for the content of pyruvic and lactic acids conducted in dynamics showed a statistically reliable increase in the pyruvate level on a fasting stomach and after glucose loads and of the lactate level on a fasting stomach and at the end of the examination. In diabetictype glycemic curves, however, the peak sugar levels were paralleled by normal content of pyruvic and lactic acids. The glycemia indices revealed in dynamics of the prednisolone-glucose tolerance test were significantly higher in patients with an increased blood sugar content in the acute period of myocardial infarction.


Marine debris in harbour porpoises and seals from German waters.
Records of marine debris in and attached to stranded harbour porpoises (Phocoena phocoena), harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) were studied comprising information on 6587 carcasses collected along the German coast between 1990 and 2014, the decomposition state allowed for necropsy in 1622 cases. Marine debris items were recorded in 31 carcasses including 14 entanglements (5 harbour porpoises, 6 harbour seals, 3 grey seals) and 17 cases of ingestion (4 harbour porpoises, 10 harbour seals, 3 grey seals). Objects comprised general debris (35.1%) and fishing related debris (64.9%). Injuries associated with marine debris included lesions, suppurative ulcerative dermatitis, perforation of the digestive tract, abscessation, suppurative peritonitis and septicaemia. This study is the first investigation of marine debris findings in all three marine mammal species from German waters. It demonstrates the health impacts marine debris can have, including severe suffering and death. The results provide needed information on debris burdens in the North and Baltic Seas for implementing management directives, such as the Marine Strategy Framework Directive (MSFD).


Life expectancies of cigarette smokers and nonsmokers in the United States.
This research employs the National Health Interview and the National Mortality Followback Surveys to calculate life expectancies by age and sex for white nonsmokers, former smokers, and current smokers in the United States in 1986. In general, life expectancies are higher for never smokers than for former smokers, and higher for former smokers than for current smokers. Heavy smokers have lower life expectancies than persons with all other smoking statuses; indeed, compared to never smokers, heavy smokers at age 25 can expect at least a 25% shorter life. Gender differences in life expectancies were found to persist even with the elimination of smoking. Differences in life expectancy by sex thus appear to be due, in part, to cigarette smoking, but also to occupational, environmental, and sociodemographic factors.


Cutaneous manifestations of sarcoidosis. Relationships to other organ system involvement, abnormal laboratory measurements, and disease course.
The charts of 329 patients with sarcoidosis were reviewed to determine if there were significant associations between the presence of sarcoidosis skin lesions and other abnormalities. Sixty-four patients had either biopsy specimen-documented cutaneous granulomata or erythema nodosum (EN). Respiratory symptoms occurred in 41% of patients with skin lesions compared with 63% of patients with sarcoidosis without skin lesions. Among patients with skin lesions other than EN, splenomegaly occurred in 38%, hepatomegaly in 32%, and lymphadenopathy in 31% compared with 10%, 11%, and 56%, respectively, for patients with sarcoidosis without skin lesions. Thirty-two percent of patients with EN had progressive disease compared with 72% of patients with skin lesions other than EN; however, improved prognosis with EN was limited to white patients.


Antibodies in bovine serum and lacteal secretions to capsular antigens of Staphylococcus aureus.
Pregnant cows were immunized systemically with an encapsulated strain of Staphylococcus aureus (Smith diffuse strain). Antibodies in serum and colostrum were detectable by enzyme-linked immunosorbent assay and prevented capsule production by the Smith diffuse strain in a soft agar medium. Antibody in milk, although detectable by enzyme-linked immunosorbent assay, did not affect the production of capsule in vitro. Antibodies were absorbed from milk and serum, using staphylococcal surface antigen. In a 2nd experiment, lactating cows were immunized, using Smith diffuse strain antigens in the form of a bacterin or as a surface extract; the bacterin or extract was emulsified in Freund's incomplete adjuvant. Antibody titers in the milk of cows given bacterin were significantly (P less than 0.001) greater than titers in the milk of animals immunized with surface extract. The soft agar technique was insufficiently sensitive to detect antibody in the milk of any of the cattle.


C-reactive protein improves the ability to detect cardiometabolic risk in mild-to-moderate obstructive sleep apnea.
Obstructive sleep apnea (OSA), particularly in the mild-to-moderate range, affects up to 40% of the adult general population. While it is clear that treatment should be pursued in severe cases of OSA, when and how to best treat OSA in the mild-to-moderate range remains complicated, despite its high prevalence. The aim of this study was to compare the relative utility of apnea/hypopnea index (AHI) versus a biomarker of inflammation, C-reactive protein (CRP), in identifying the presence and severity of hypertension and hyperglycemia. Middle-aged (n = 60) adults with mild-to-moderate OSA (AHI between 5 and 29 events per hour) underwent 8-h polysomnography, a physical examination including measures of blood pressure and body mass index, and a fasting morning blood draw for glucose and CRP CRP levels were associated with greater odds for having hypertension and hyperglycemia compared to AHI Receiver-operating characteristics (ROC) curves revealed that adding CRP to standard clinical factors (age, sex, and BMI) yielded moderately good to strong risk models for the disorders (AUC = 0.721 and AUC = 0.813, respectively). These preliminary findings suggest that including a measure of CRP improves the ability for clinicians to detect cases of mild-to-moderate OSA with true cardiometabolic risk, with implications in improving prognosis and treatment within this clinically gray area.


Morphine Suppository versus Indomethacin Suppository in the Management of Renal Colic: Randomized Clinical Trial.
Background. Renal colic is a medical emergency due to the rapid onset and devastating nature of its pain. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are both used as first-line choices in its management. Aim. This study aimed to compare the efficacy and safety of opioids and NSAIDs in the management of acute renal colic. Methods. One hundred and fifty-eight patients were divided into two groups (n = 79) and received either 10 mg morphine or 100 mg indomethacin suppositories. The severity of pain was measured using verbal numeric rating scale at baseline and 20, 40, 60, and 90 minutes after the administration of analgesics. Drug side effects as well as patients' vital signs were also recorded. Results. The mean decrease in the pain score during the first 20 minutes was significantly higher among those who received morphine suppository. However, no significant difference was observed between the two groups regarding the mean decrease in pain score during the first 40, 60, and 90 minutes after the admission. Prevalence of drug side effects or changes in the vital signs was not significantly different between the two groups. Conclusions. Morphine suppositories seem to be more efficient in achieving rapid pain relief comparing to indomethacin.


How N-Acetylcysteine Supplementation Affects Redox Regulation, Especially at Mitohormesis and Sarcohormesis Level: Current Perspective.
Exercise frequently alters the metabolic processes of oxidative metabolism in athletes, including exposure to extreme reactive oxygen species impairing exercise performance. Therefore, both researchers and athletes have been consistently investigating the possible strategies to improve metabolic adaptations to exercise-induced oxidative stress. N-acetylcysteine (NAC) has been applied as a therapeutic agent in treating many diseases in humans due to its precursory role in the production of hepatic glutathione, a natural antioxidant. Several studies have investigated NAC's possible therapeutic role in oxidative metabolism and adaptive response to exercise in the athletic population. However, still conflicting questions regarding NAC supplementation need to be clarified. This narrative review aims to re-evaluate the metabolic effects of NAC on exercise-induced oxidative stress and adaptive response developed by athletes against the exercise, especially mitohormetic and sarcohormetic response.


Is Pd(II)-promoted σ-bond metathesis mechanism operative for the Pd-PEPPSI complex-catalyzed amination of chlorobenzene with aniline? Experiment and theory.
Reduction of the Pd-PEPPSI precatalyst to a Pd(0) species is generally thought to be essential to drive Buchwald-Hartwig amination reactions through the well-documented Pd(0)/Pd(II) catalytic cycle and little attention has been paid to other possible mechanisms. Considered here is the Pd-PEPPSI-catalyzed aryl amination of chlorobenzene with aniline. A neat reaction system was used in new experiments, from which the potentially reductive roles of the solvent and labile ligand of the PEPPSI complex in leading to Pd(0) species are ruled out. Computational results demonstrate that anilido-containing Pd(II) intermediates involving σ-bond metathesis in pathways leading to the diphenylamine product have relatively low barriers. Such pathways are more favorable energetically than the corresponding reductive elimination reactions resulting in Pd(0) species and other putative routes, such as the Pd(II)/Pd(IV) mechanism, single electron transfer mechanism, and halide atom transfer mechanism. In some special cases, if reactants/additives are inadequate to reduce a Pd(II) precatalyst, a Pd(II)-involved σ-bond metathesis mechanism might be feasible to drive the Buchwald-Hartwig amination reactions.


Placental malaria and perinatal transmission of human immunodeficiency virus type 1.
Prevalence of placental malaria in human immunodeficiency virus (HIV) type 1-infected and -uninfected women and the effect of placental malaria on genital shedding and perinatal transmission of HIV-1 were examined. Genital samples for HIV-1 DNA RNA were collected during labor. Infants were tested for HIV-1 at 1 day and 6 weeks postpartum. Placental malaria was diagnosed by histopathological examination: 372 placentas of HIV-1-infected women and 277 of HIV-1-uninfected women were processed. A higher prevalence of placental malaria was seen in HIV-1-infected women. No association was found between placental malaria and either maternal virus load, genital HIV-1 DNA, or HIV-1 RNA. Placental malaria did not correlate with in utero or peripartal transmission of HIV-1.


[Role of duration and intensity of activation of afferent fibers in regulating morphologic shifts in a neuron].
The afferent impulsation has a regulating influence on morphological and histochemical shifts in the neuron. The size and staining of spinal motoneurons of the frog are changed depending on the force and duration of the applied high frequency stimulation of afferent fibres. The threshold 10-minute-long activation results in the increased size and lighter staining of nerve cells. An increased force of high frequency stimuli causes darker staining and a decreased size of the motoneurons under study. One-minute-long activation of the afferent fibres by electric stimuli of 50 imp/sec failed to cause changes in the size and staining of nerve cells. Prolongation of the activation till 10 minutes results in a sharp decrease of the neuron size. Further activation of the afferent fibres for 2 hours causes pathological shifts in the structure of motoneurons: their vacuolization and melting. Besides, there appears a great number of dark stretched intensively stained nerve cells.


Sensing Ability of Ferroelectric Oxide Nanowires Grown in Templates of Nanopores.
Nanowires of ferroelectric potassium niobate were grown by filling nanoporous templates of both side opened anodic aluminum oxide (AAO) through radiofrequency vacuum sputtering for multisensor fabrication. The precise geometrical ordering of the AAO matrix led to well defined single axis oriented wire-shaped material inside the pores. The sensing abilities of the samples were studied and analyzed in terms of piezoelectric and pyroelectric response and the results were compared for different length of the nanopores (nanotubes)-1.3 µm, 6.3 µm and 10 µm. Based on scanning electronic microscopy, elemental and microstructural analyses, as well as electrical measurements at bending and heating, the overall sensing performance of the devices was estimated. It was found that the produced membrane type elements, consisting potassium niobate grown in AAO template exhibited excellent piezoelectric response due to the increased specific area as compared to non-structured films, and could be further enhanced with the nanowires length. The piezoelectric voltage increased linearly with 16 mV per micrometer of nanowire's length. At the same time the pyroelectric voltage was found to be less sensitive to the nanowires length, changing its value at 400 nV/µm. This paper provides a simple and low-cost approach for nanostructuring ferroelectric oxides with multisensing application, and serves as a base for further optimization of template based nanostructured devices.


Serum Endocan Levels on Admission Are Associated With Worse Clinical Outcomes in COVID-19 Patients: A Pilot Study.
Thrombotic and embolic complications in the cardiovascular system are evident and associated with worse prognosis in coronavirus disease 2019 (COVID-19) patients. Endothelial-specific molecule 1 (endocan) plays a role in vascular pathology. We hypothesized serum endocan levels on admission are associated with primary composite end point (mortality and intensive care unit hospitalization) in COVID-19 patients. Patients (n = 80) with laboratory, clinical, and radiological confirmed COVID-19 were included in this cross-sectional study. Ten milliliter of peripheral venous blood were drawn within 24 hours of admission to estimate serum endocan levels. Data were analyzed using SPSS version 26.0 (IBM). Patients with the primary composite end point had significantly higher serum endocan levels than patients without (852.2 ± 522.7 vs 550.2 ± 440.8 ng/L, respectively; P < .01). In the logistic regression analysis, only increased serum endocan levels and increase in age were independent predictors of the primary composite end point (P < .05). In the receiver operating characteristics curve analysis, we found that a serum endocan level of 276.4 ng/L had a 97% sensitivity and 85% specificity for prediction of the primary composite end point. Baseline serum endocan levels may prove useful as a prognostic factor in patients hospitalized for COVID-19.


New perspectives on proanthocyanidin biochemistry and molecular regulation.
Our understanding of proanthocyanidin (syn. condensed tannin) synthesis has been recently extended by substantial developments concerning both structural and regulatory genes. A gene encoding leucoanthocyanidin reductase has been obtained from the tropical forage, Desmodium uncinatum, with the latter enzyme catalyzing formation of (+)-catechin. The BANYULS gene in Arabidopsis thaliana, previously proposed to encode leucoanthocyanidin reductase or to regulate proanthocyanidin biosynthesis, has been shown instead to encode anthocyanidin reductase, which in turn converts anthocyanidins (pelargonidin, cyanidin, or delphinidin) into 2,3-cis-2R,3R-flavan-3-ols (respectively, (-)-epiafzelechin, (-)-epicatechin and (-)-epigallocatechin). However, the enzyme which catalyzes the polymerization reaction remains unknown. Nevertheless, a vacuolar transmembrane protein TT12, defined by the Arabidopsis tt12 mutant, is involved in transport of proanthocyanidin polymer into the vacuole for accumulation. Six different types of regulatory elements, e.g. TFIIIA-like, WD-40-like, WRKY-like, MADS-box-like, myb-like, and bHLH (myc-like), have been cloned and identified using mutants from Arabidopsis (tt1, ttg1, ttg2, tt2, tt16, tt2, tt8) and two other species (Hordeum vulgare [ant13] and Lotus spp [tan1]). Accordingly, increases in proanthocyanidin levels have been induced in the the world's major forage, alfalfa. These advances may now lead to a detailed understanding of how PA synthesis is controlled and to useful alterations in proanthocyanidin concentration for the improvement of forage species, pulses, and other crop plants.


Composition dependence of X-ray stability and degradation mechanisms at lead halide perovskite single crystal surfaces.
The multiple applications of lead halide perovskite materials and the extensive use of X-ray based techniques to characterize them highlight a need to understand their stability under X-ray irradiation. Here, we present a study where the X-ray stability of five different lead halide perovskite compositions (MAPbI3, MAPbCl3, MAPbBr3, FAPbBr3, CsPbBr3) was investigated using photoelectron spectroscopy. To exclude effects of thin film formation on the observed degradation behaviors, we studied clean surfaces of single crystals. Different X-ray resistance and degradation mechanisms were observed depending on the crystal composition. Overall, perovskites based on the MA+ cation were found to be less stable than those based on FA+ or Cs+. Metallic lead formed most easily in the chloride perovskite, followed by bromide, and only very little metallic lead formation was observed for MAPbI3. MAPbI3 showed one main degradation process, which was the radiolysis of MAI. Multiple simultaneous degradation processes were identified for the bromide compositions. These processes include ion migration towards the perovskite surface and the formation of volatile and solid products in addition to metallic lead. Lastly, CsBr formed as a solid degradation product on the surface of CsPbBr3.


Completion of the Chloroplast Genomes of Five Chinese Juglans and Their Contribution to Chloroplast Phylogeny.
Juglans L. (walnuts and butternuts) is an economically and ecologically important genus in the family Juglandaceae. All Juglans are important nut and timber trees. Juglans regia (Common walnut), J. sigillata (Iron walnut), J. cathayensis (Chinese walnut), J. hopeiensis (Ma walnut), and J. mandshurica (Manchurian walnut) are native to or naturalized in China. A strongly supported phylogeny of these five species is not available due to a lack of informative molecular markers. We compared complete chloroplast genomes and determined the phylogenetic relationships among the five Chinese Juglans using IIumina sequencing. The plastid genomes ranged from 159,714 to 160,367 bp encoding 128 functional genes, including 88 protein-coding genes and 40 tRNA genes each. A complete map of the variability across the genomes of the five Juglans species was produced that included single nucleotide variants, indels (insertions and deletions), and large structural variants, as well as differences in simple sequence repeats (SSR) and repeat sequences. Molecular phylogeny strongly supported division of the five walnut species into two previously recognized sections (Juglans/Dioscaryon and Cardiocaryon) with a 100% bootstrap (BS) value using the complete cp genomes, protein coding sequences (CDS), and the introns and spacers (IGS) data. The availability of these genomes will provide genetic information for identifying species and hybrids, taxonomy, phylogeny, and evolution in Juglans, and also provide insight into utilization of Juglans plants.


Distinct modes of functional connectivity induced by movie-watching.
A fundamental question in systems neuroscience is how endogenous neuronal activity self-organizes during particular brain states. Recent neuroimaging studies have demonstrated systematic relationships between resting-state and task-induced functional connectivity (FC). In particular, continuous task studies, such as movie watching, speak to alterations in coupling among cortical regions and enhanced fluctuations in FC compared to the resting-state. This suggests that FC may reflect systematic and large-scale reorganization of functionally integrated responses while subjects are watching movies. In this study, we characterized fluctuations in FC during resting-state and movie-watching conditions. We found that the FC patterns induced systematically by movie-watching can be explained with a single principal component. These condition-specific FC fluctuations overlapped with inter-subject synchronization patterns in occipital and temporal brain regions. However, unlike inter-subject synchronization, condition-specific FC patterns were characterized by increased correlations within frontal brain regions and reduced correlations between frontal-parietal brain regions. We investigated these condition-specific functional variations as a shorter time scale, using time-resolved FC. The time-resolved FC showed condition-specificity over time; notably when subjects watched both the same and different movies. To explain self-organisation of global FC through the alterations in local dynamics, we used a large-scale computational model. We found that condition-specific reorganization of FC could be explained by local changes that engendered changes in FC among higher-order association regions, mainly in frontal and parietal cortices.


Evaluation of the concept of "hypoxic fraction" as a descriptor of tumor oxygenation status.
The presence and significance of tumor hypoxia has been recognized since the 1950's. Hypoxic cells in vitro and in animal tumors in vivo are documented to be three times more resistant to radiation-induced killing compared to aerobic cells. There is now evidence that tumor hypoxia is treatment-limiting in many human cancers. One common way to describe the extent of hypoxia in individual and groups of tumors is the "hypoxic fraction." This measurement infers that cells are present in only two radiobiologically significant states: oxygenated and hypoxic. In this paper, we demonstrate the qualitative and quantitative presence of hypoxic tumor cells using the oxygen dependent metabolism of the 2-nitroimidazole, EF5. Two assumptions concerning the calculation and interpretation of the hypoxic fraction are considered. The first is the use of multiple animals to describe the radiation response at a given radiation dose. We hypothesize that the presence of intertumor variability in radiation response due to hypoxia could negatively influenced the characterization of the change in slope required to calculate the hypoxic fraction. The studies presented herein demonstrate heterogeneity of radioresponse due to hypoxic fraction within and between tumor lines. The 9L subcutaneous tumor studied in air-breathing rats demonstrates a 2 log variation in surviving fraction at 17 Gy. The Morris 7777 hepatoma, in contrast, showed little variability of radiation response. Our second question addresses the limitations of using the "hypoxic fraction" to describe the radiation response of a tumor. This calculated value infers that radiobiological hypoxia is a binary measurement: that a tumor contains two cell populations, aerobic cells with maximal radiosensitivity and hypoxic cells with maximal radioresistance. The classic work of Thomlinson and Gray, however, implies the presence of an oxygen gradient from tumors vessel through the tissues. In both the 9L and Q7 tumors, flow cytometric analysis of EF5 binding demonstrates a continuous range of cellular pO2 levels. These studies suggest that: 1) there is extensive intertumor variability of radiation response in certain tumor lines; 2) the variability in radiation response between individual tumors in a group may affect the ability to describe a particular tumor type's "hypoxic fraction" and 3) The oxygen status of tumor cells is a continuum. This realization affects the ability to apply a binary concept such as the "hypoxic fraction" effectively in radiobiology.


The prognostic significance of leukocytosis in cervical cancer.
Cervical cancer is a frequent tumor with established prognostic factors such as FIGO stage and hemoglobin levels among others. Despite the fact that paraneoplastic leukocytosis is relatively common in many solid tumors, only isolated cases of cervical cancer patients presenting this abnormality have been published; hence, the clinical significance of leukocytosis is unknown in this tumor type. Retrospective review on the medical records of 294 consecutive newly diagnosed and untreated locally advanced cervical cancer patients who received radiotherapy and concurrent cisplatin was conducted. Leukocytosis was defined as a persistent white blood cell count exceeding 10,800/microL, determined at least twice before commencing chemoradiation providing that patients were free of any active acute or chronic infection or any other condition known to elevate the leukocyte count. The frequency of leukocytosis and their correlation with clinicopathologic features were investigated, as well as their impact on tumor response and survival. Leukocytosis with a median value of 13,300/microL (11,100-28,800) was observed in 35 (11.9%) patients at diagnosis. Leukocytosis was statistically associated only with advanced stages. Clinical complete response was observed in 57% versus 86% of the patients with and without leukocytosis, respectively. In the univariate analysis, leukocytosis, stage, and hemoglobin levels were significant predictors of survival; however, only leukocytosis and the hemoglobin level remained significant predictors of survival in the multivariate analysis. Leukocytosis is common in cervical cancer patients and has a negative prognostic significance.


Four-dimensional orthogonal electrophoresis system for screening protein complexes and protein-protein interactions combined with mass spectrometry.
Most current approaches for purification and identification of protein complexes adopt affinity purifications combined with mass spectrometry, such as co-immunoprecipitation and tandem affinity purification. Herein, we propose a new approach, termed as the four-dimensional orthogonal electrophoresis (4-DE) system, to find and analyze the cytoplasmic protein complexes. 4-DE system is composed of two parts: nondenaturing part (Part I) and denaturing part (Part II). Through Part I and decision procedure separations, six protein complex candidates 20S core particle of proteasome (CP), hemoglobin (Hb, α2β2), Hb (α2δ2), peroxiredoxin-2 (PRDX2), carbonic anhydrase-1 (CAH1), and heat shock protein 60 (HSP60) were separated. CP, Hb (α2β2), PRDX2, and HSP60 with different MWs and pI's were chosen for Part II proteomic analysis. The results indicate that 4-DE is not only suitable for studying protein complexes and protein-protein interactions as well as structural proteomics from complex biological samples, but can also be easy to separate and concentrate intact protein complexes from dilute complex samples.


Primary carcinoma of the fallopian tube.
Carcinoma of the fallopian tube is the least common of the gynecologic malignancies. Because of its rarity and the absence of typical symptoms, preoperative diagnosis is seldom made. Patient as well as physician delay in diagnosis is often considerable. There are no reliable laboratory aids available to enhance the discovery of this tumor. However, routine periodic pelvic examinations with laparoscopic examination of any significant adnexal enlargement in postmenopausal women should decrease the discovery time. Certainly, unexplained vaginal discharge or bleeding particularly when associated with a pelvic mass, should increase one's suspicion. Conventional surgical treatment can be curative if the tumor has not exceeded the confines of the tube and has not involved the serosa. Regardless, the prognosis for patients with primary carcinoma of the fallopian tube is grim.


In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe.
Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases, although the exact mechanism is yet to be explored. Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care. The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe. Herein, we report the first in vivo CB2R-targeted NIR inflammation imaging study using a synthetic fluorescent probe developed in our laboratory, NIR760-mbc94. In vitro binding assay and fluorescence microscopy study indicate NIR760-mbc94 specifically binds towards CB2R in mouse RAW264.7 macrophage cells. Furthermore, in vivo imaging was performed using a Complete Freund's Adjuvant (CFA)-induced inflammation mouse model. NIR760-mbc94 successfully identified inflamed tissues and the probe uptake was blocked by a CB2R ligand, SR144528. Additionally, immunofluorescence staining in cryosectioned tissues validated the NIR760-mbc94 uptake in inflamed tissues. In conclusion, this study reports the first in vivo CB2R-targeted inflammation imaging using an NIR fluorescent probe. Specific targeting of NIR760-mbc94 has been demonstrated in macrophage cells, as well as a CFA-induced inflammation mouse model. The combined evidence indicates that NIR760-mbc94 is a promising inflammation imaging probe. Moreover, in vivo CB2R-targeted fluorescence imaging may have potential in the study of inflammation-related diseases.


Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning.
The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane fusion during virus entry and is part of a broadly neutralizing epitope. However, sequence determinants at the fusion peptide and its adjacent regions for pathogenicity and antigenicity remain elusive. In this study, we performed a series of deep mutational scanning (DMS) experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 in different cell lines and in the presence of broadly neutralizing antibodies. We identified mutations at residue 813 of the spike protein that reduced TMPRSS2-mediated entry with decreased virulence. In addition, we showed that an F823Y mutation, present in bat betacoronavirus HKU9 spike protein, confers resistance to broadly neutralizing antibodies. Our findings provide mechanistic insights into SARS-CoV-2 pathogenicity and also highlight a potential challenge in developing broadly protective S2-based coronavirus vaccines.


Consumptive coagulopathy in severe preeclampsia.
Our experience with consumptive coagulopathy associated with preeclampsia at North Carolina Baptist Hospital is presented. All cases of recognized consumptive coagulopathy on the obstetric service from 1969 to 1975 are reviewed and the associated obstetric entities given. Two cases of consumptive coagulopathy complicating severe preeclampsia are presented. Consumptive coagulopathy occurred in 9.1% of eclamptic patients and in 2.6% of severe preeclamptic patients. No previous incidence figures were found in the literature.


Combination of skin flap and silicone prosthesis for rehabilitation of a large orbital defect: A case report.
Exenteration surgery greatly affects a person in terms of function, esthetics, and psychological trauma. In such cases, restoration by silicone orbital prosthesis is a well-accepted treatment option. However, this is a difficult task, necessitating personalized design of method for each patient. This case report describes the technique for fabrication of a silicone orbital prosthesis for a male patient with left orbital defect due to exenteration of a Grade 3 squamous cell carcinoma of the left eye and surrounding tissues. The patient was delivered with a satisfactory silicone orbital prosthesis having good retention and finish. Multidisciplinary management and team approach are crucial in providing precise and effective rehabilitation for improving the patient's quality of life and help them return to their normal social life.


[The psychophysiological status of school children going to educational establishments of different kinds].
The paper presents the results of hygienic studies of the psychophysiological status of school children going to educational establishments of different kinds, which have established the best psychophysiological status in intensively taught schoolchildren.


Biogeography and potential exchanges among the atlantic Equatorial belt cold-seep faunas.
Like hydrothermal vents along oceanic ridges, cold seeps are patchy and isolated ecosystems along continental margins, extending from bathyal to abyssal depths. The Atlantic Equatorial Belt (AEB), from the Gulf of Mexico to the Gulf of Guinea, was one focus of the Census of Marine Life ChEss (Chemosynthetic Ecosystems) program to study biogeography of seep and vent fauna. We present a review and analysis of collections from five seep regions along the AEB: the Gulf of Mexico where extensive faunal sampling has been conducted from 400 to 3300 m, the Barbados accretionary prism, the Blake ridge diapir, and in the Eastern Atlantic from the Congo and Gabon margins and the recently explored Nigeria margin. Of the 72 taxa identified at the species level, a total of 9 species or species complexes are identified as amphi-Atlantic. Similarity analyses based on both Bray Curtis and Hellinger distances among 9 faunal collections, and principal component analysis based on presence/absence of megafauna species at these sites, suggest that within the AEB seep megafauna community structure is influenced primarily by depth rather than by geographic distance. Depth segregation is observed between 1000 and 2000 m, with the middle slope sites either grouped with those deeper than 2000 m or with the shallower sites. The highest level of community similarity was found between the seeps of the Florida escarpment and Congo margin. In the western Atlantic, the highest degree of similarity is observed between the shallowest sites of the Barbados prism and of the Louisiana slope. The high number of amphi-atlantic cold-seep species that do not cluster according to biogeographic regions, and the importance of depth in structuring AEB cold-seep communities are the major conclusions of this study. The hydrothermal vent sites along the Mid Atlantic Ridge (MAR) did not appear as "stepping stones" for dispersal of the AEB seep fauna, however, the south MAR and off axis regions should be further explored to more fully test this hypothesis.


A flight surgeon's personal view of an emerging illness.
The personal experience of a retired Air Force flight surgeon and instrument-rated civilian pilot with an illness that has achieved recent prominence in both the popular and medical press is recounted. The author believes that the illness is widely prevalent and its incidence is increasing. His experience and conviction is that, during certain phases of the illness, both cognitive dysfunction and orthostatic intolerance occur that can pose grave safety risks in the aviation environment, and must be taken seriously by the practicing flight surgeon. As in all emerging illnesses, clinical experience and judgment must precede more definitive proof of the effects of this illness.


Injury versus noninjury factors as predictors of postconcussive symptoms following mild traumatic brain injury in children.
To examine the relative contributions of injury characteristics and noninjury child and family factors as predictors of postconcussive symptoms (PCS) following mild traumatic brain injury (TBI) in children. Participants were 8- to 15-year-old children, 186 with mild TBI and 99 with mild orthopedic injuries (OI). Parents and children rated PCS shortly after injury and at 1, 3, and 12 months postinjury. Hierarchical regression analyses were conducted to predict PCS from (1) demographic variables; (2) premorbid child factors (WASI IQ; WRAT-3 Reading; Child Behavior Checklist; ratings of preinjury PCS); (3) family factors (Family Assessment Device General Functioning Scale; Brief Symptom Inventory; and Life Stressors and Social Resources Inventory); and (4) injury group (OI, mild TBI with loss of consciousness [LOC] and associated injuries [AI], mild TBI with LOC but without AI, mild TBI without LOC but with AI, and mild TBI without LOC or AI). Injury group predicted parent and child ratings of PCS but showed a decreasing contribution over time. Demographic variables consistently predicted symptom ratings across time. Premorbid child factors, especially retrospective ratings of premorbid symptoms, accounted for the most variance in symptom ratings. Family factors, particularly parent adjustment, consistently predicted parent, but not child, ratings of PCS. Injury characteristics predict PCS in the first months following mild TBI but show a decreasing contribution over time. In contrast, noninjury factors are more consistently related to persistent PCS.


Emergence and development of stress-induced analgesia and concomitant behavioral changes in mice exposed to social conflict.
Mice of the inbred strain DBA/2, when exposed to a social conflict, developed a low intensity, naloxone-insensitive analgesia after 15 bites, and a more pronounced naloxone-sensitive analgesia after 45 bites. The effective inhibition of the antinociceptive response following low and high number of bites by the alkylating opiate antagonist beta-chlornaltrexamine suggests participation of opioid mechanisms at both stress levels. Emergence of an increased tail-flick latency was indicated by the occurrence of defensive upright postures upon contact with the opponent, while animals displaying full analgesic response during the period of bite 31-45 increased their escape reactions without being in contact with the aggressor. Suppression of social conflict analgesia in mice by pretreatment with opiate antagonists facilitated the occurrence of these escape reactions. The display of panic escape responses is discussed in the context of increased fear and helplessness that developed under conditions of sustained attacks.


The relationship between collagen and C1q biosynthesis in cultured human fibroblasts.
The relationship between collagen and C1q biosynthesis has been investigated in cultured human fibroblasts. This was done by measuring the effects of variation in cell density, inhibition of prolyl hydroxylase and complexing of C1q on synthesis and/or secretion of both proteins. It was found that synthesis and secretion of both proteins were not co-ordinate, and that therefore regulation of expression of both proteins is probably not linked. However complexing of C1q did result in marked stimulation in collagen synthesis, suggesting that the fibrosis which follows inflammation may result from binding of C1q to the immune complexes formed in the inflammatory process.


Atmospheric movement of microorganisms in clouds of desert dust and implications for human health.
Billions of tons of desert dust move through the atmosphere each year. The primary source regions, which include the Sahara and Sahel regions of North Africa and the Gobi and Takla Makan regions of Asia, are capable of dispersing significant quantities of desert dust across the traditionally viewed oceanic barriers. While a considerable amount of research by scientists has addressed atmospheric pathways and aerosol chemistry, very few studies to determine the numbers and types of microorganisms transported within these desert dust clouds and the roles that they may play in human health have been conducted. This review is a summary of the current state of knowledge of desert dust microbiology and the health impact that desert dust and its microbial constituents may have in downwind environments both close to and far from their sources.


Clinical skills problems. A valid instrument for assessing competence?
Physician assistants are required to take the clinical skills problems (CSP) portion of the National Certifying Examination administered by the National Commission on Certification of Physician's Assistants (NCCPA). No comparable section exists in entry-level physician certification examinations because studies have shown that this type of examination is neither a valid nor a reliable indicator of clinical competence. A published account of the studies used to implement the CSP portion of the National Certifying Examination contained serious flaws, calling the research into question. Denial of certification based solely on failure on the CSP portion of the National Certifying Examination could be challenged legally. The CSP is invalid and unreliable, and should be eliminated.


Pubertal stage and the prevalence of violence and social/relational aggression.
We examined associations between pubertal stage and violent adolescent behavior and social/relational aggression. The International Youth Development Study comprises statewide representative student samples in grades 5, 7, and 9 (N = 5769) in Washington State and Victoria, Australia, drawn as a 2-stage cluster sample in each state. We used a school-administered, self-report student survey to measure previous-year violent behavior (ie, attacking or beating up another person) and social/relational aggression (excluding peers from the group, threatening to spread lies or rumors), as well as risk and protective factors and pubertal development. Cross-sectional data were analyzed. Compared with early puberty, the odds of violent behavior were approximately threefold higher in midpuberty (odds ratio [OR]: 2.87 [95% confidence interval (CI): 1.81-4.55]) and late puberty (OR: 3.79 [95% CI: 2.25-6.39]) after adjustment for demographic factors. For social/relational aggression, there were weaker overall associations after adjustment, but these associations included an interaction between pubertal stage and age, and stronger associations with pubertal stage at younger age were shown (P = .003; midpuberty OR: 1.78 [95% CI: 1.20-2.63]; late puberty OR: 3.00 [95% CI: 1.95-4.63]). Associations between pubertal stage and violent behavior and social/relational aggression remained after the inclusion of social contextual mediators in the analyses. Pubertal stage was associated with higher rates of violent behavior and social/relational aggression, with the latter association seen only at younger ages. Puberty is an important phase at which to implement prevention programs to reduce adolescent violent and antisocial behaviors.


[The multifariousness of the gene differentiation of taxa at the species and genus levels and the biological heterogeneity of mammalian orders].
Correlation analysis revealed close relationships between genetic differentiation (measured by percent of fixed gene differences of species and genera) and some biological indexes reflecting the peculiarities of ontogenesis, age, fecundity, body size, and taxonomic structure at the level of order. The most strong relationships were found between paleontological age of order, polytypic character of genera, linear body size, and duration of ontogenesis. The least significant were correlations of genetic differentiation with fecundity as well as with biological age of orders. The factors determining decrease in genetic differentiation among species and genera in large mammals, are 1) the young age of orders which determines the ranks of lower taxa; 2) the overestimation of taxonomic rank of orders of larger mammals in comparison with smaller ones.


The development and validation of a novel questionnaire to measure patient and family satisfaction with end-of-life care: the Canadian Health Care Evaluation Project (CANHELP) Questionnaire.
The purpose of this study was to further validate a novel instrument to measure satisfaction with end-of-life care, called the Canadian Health Care Evaluation Project (CANHELP) questionnaire. Data were collected by a cross-sectional survey of patients who had advanced, life-limiting illnesses and their family caregivers, and who completed CANHELP, a global rating of satisfaction, and a quality of life questionnaire. We conducted factor analysis, assessed internal consistency using Cronbach's alpha, and evaluated construct validity by describing the correlation amongst CANHELP, global rating of satisfaction and the quality of life questionnaire scores. There were 361 patient and 193 family questionnaires available for analysis. In the factor analysis, we identified six easily interpretable factors which explained 55.4% and 60.2% of the variance for the patient and caregiver questionnaire, respectively. For the patient version, the subscales derived from these factors were Relationship with Doctors, Illness Management, Communication, Decision-Making, Role of the Family, and Your Well-being. For the family questionnaire, the factors were Relationship with Doctors, Characteristics of Doctors and Nurses, Illness Management, Communication and Decision-Making, Your Involvement, and Your Well-being. Each subscale for each questionnaire had acceptable to excellent internal consistency (Cronbach's alpha ranged from 0.69-0.94). We observed good correlations between the CANHELP overall satisfaction score and global rating of satisfaction (correlation coefficient 0.49 and 0.63 for patient and family, respectively) which was greater than the correlations between CANHELP and the quality of life instruments. We conclude that the CANHELP Questionnaire is a valid and internally consistent instrument to measure satisfaction with end-of-life care.


Generalized block-lifting factorization of M-channel biorthogonal filter banks for lossy-to-lossless image coding.
Generalized block-lifting factorization of M-channel (M > 2) biorthogonal filter banks (BOFBs) for lossy-to-lossless image coding is presented in this paper. Since the proposed block-lifting structure is more general than the conventional lifting factorizations and does NOT require many restrictions such as paraunitary, number of channels, and McMillan degree in each building block unlike the conventional lifting factorizations, its coding gain is higher than that of the previous methods. Several proposed BOFBs are designed and applied to image coding. Comparing the results with conventional lossy-to-lossless image coding structures, including the 5/3- and 9/7-tap discrete wavelet transforms in JPEG 2000 and a 4 × 8 hierarchical lapped biorthogonal transform in JPEG XR, the proposed BOFBs achieve better result in both objective measure and perceptual visual quality for the images with a lot of high-frequency components.


Improved energy bound accuracy enhances the efficiency of continuous protein design.
Flexibility and dynamics are important for protein function and a protein's ability to accommodate amino acid substitutions. However, when computational protein design algorithms search over protein structures, the allowed flexibility is often reduced to a relatively small set of discrete side-chain and backbone conformations. While simplifications in scoring functions and protein flexibility are currently necessary to computationally search the vast protein sequence and conformational space, a rigid representation of a protein causes the search to become brittle and miss low-energy structures. Continuous rotamers more closely represent the allowed movement of a side chain within its torsional well and have been successfully incorporated into the protein design framework to design biomedically relevant protein systems. The use of continuous rotamers in protein design enables algorithms to search a larger conformational space than previously possible, but adds additional complexity to the design search. To design large, complex systems with continuous rotamers, new algorithms are needed to increase the efficiency of the search. We present two methods, PartCR and HOT, that greatly increase the speed and efficiency of protein design with continuous rotamers. These methods specifically target the large errors in energetic terms that are used to bound pairwise energies during the design search. By tightening the energy bounds, additional pruning of the conformation space can be achieved, and the number of conformations that must be enumerated to find the global minimum energy conformation is greatly reduced.


Assessment of executive functioning in brain injury: collaboration between speech-language pathology and neuropsychology for an integrative neuropsychological perspective.
Executive functioning (EF) deficits are common sequelae of traumatic brain injury (TBI). These deficits extend beyond the acute stages of recovery and pose a significant challenge in rehabilitation efforts. Current theories of EF propose a multidimensional construct. This paper provides an integrative theoretical framework with interactive dimensions for the assessment and treatment of EF that can assist the interdisciplinary team to successfully manage EF deficits secondary to TBI. This paper is a review of pertinent literature related to assessment of EF. It concludes with a case presentation that illustrates the utility of the proposed theoretical framework in the rehabilitation context. Formal neuropsychological, standardized psychometric measures and informal clinical observations, particularly as they relate to contextual assessment, should be incorporated in order to effectively assess EF difficulties in survivors of TBI. The paper concludes with recommendations for effective assessment and treatment of EF by the interdisciplinary team consisting of speech-language pathologists and neuropsychologists.


Prolonged treatment of human osteoarthritic chondrocytes with insulin-like growth factor-I stimulates proteoglycan synthesis but not proteoglycan matrix accumulation in alginate cultures.
To determine the level of anabolic response when chondrocytes isolated from human osteoarthritic cartilage are stimulated with 2 doses of insulin-like growth factor-I (IGF-I) for extended culture periods. Human chondrocytes were isolated from knee cartilage removed at the time of joint replacement surgery for osteoarthritis (OA). The cells were cultured in alginate beads under serum-free conditions and treated with 100 ng/ml or 1000 ng/ml of human recombinant IGF-I. Response was measured during culture periods of 1 to 28 days by determining the level of radiolabeled sulfate incorporated into alcian blue precipitable material and by measuring the level of total proteoglycan accumulation using the dimethylmethylene blue (DMB) assay. For the latter assay, cultures treated with osteogenic protein-1 (OP-1) were used for comparison to IGF-I. Results were normalized to cell numbers using DNA measurements. The level of IGF-I stimulated sulfate incorporation relative to untreated controls increased with time in culture, with a peak response occurring between days 7 and 14 of culture. There was no significant difference between the 2 IGF-I doses. Despite the stimulation of sulfate incorporation, the DMB assay did not reveal a significant accumulation of proteoglycans in the cell-associated and further-removed matrix with either dose of IGF-I in cultures carried out to 21 days. In contrast, compared to controls, OP-1 at 100 ng/ml stimulated a 3-fold increase in matrix proteoglycan at day 21 of culture. Prolonged IGF-I treatment of human OA chondrocytes in serum-free alginate cultures stimulated sulfate incorporation without significant accumulation of a proteoglycan matrix in longterm cultures. However, significant proteoglycan accumulation was seen in cultures treated with OP-1, suggesting it is a better stimulator of proteoglycan production by OA chondrocytes.


Accidental Heart Murmurs.
Accidental murmurs occur in anatomically and physiologically normal heart. Accidental (innocent) murmurs have their own clearly defined clinical characteristics (asymptomatic, they require minimal follow-up care). To point out the significance of auscultation of the heart in the differentiation of heart murmurs and show clinical characteristics of accidental heart murmurs. Article presents review of literature which deals with the issue of accidental heart murmurs in the pediatric cardiology. In the group of accidental murmurs we include classic vibratory parasternal-precordial Stills murmur, pulmonary ejection murmur, the systolic murmur of pulmonary flow in neonates, venous hum, carotid bruit, Potaine murmur, benign cephalic murmur and mammary souffle. Accidental heart murmurs are revealed by auscultation in over 50% of children and youth, with a peak occurrence between 3-6 years or 8-12 years of life. Reducing the frequency of murmurs in the later period can be related to poor conduction of the murmur, although the disappearance of murmur in principle is not expected. It is the most common reason of cardiac treatment of the child, and is a common cause of unreasonable concern of parents.


Early intervention for toddlers with language delays: a randomized controlled trial.
Early interventions for toddlers with expressive and receptive language delays have not resulted in positive expressive language outcomes. This randomized controlled trial tested the effects on language outcomes of a caregiver-implemented communication intervention targeting toddlers at risk for persistent language delays. Participants included 97 toddlers, who were between 24 and 42 months with language scores at least 1.33 SDs below the normative mean and no other developmental delays, and their caregivers. Toddlers were randomly assigned to the caregiver-implemented intervention or a usual-care control group. Caregivers and children participated in 28 sessions in which caregivers were taught to implement the intervention. The primary outcome was the Preschool Language Scale, Fourth Edition, a broad-based measure of language. Outcome measurement was not blinded. Caregivers in the intervention improved their use of all language facilitation strategies, such as matched turns (adjusted mean difference, intervention-control, 40; 95% confidence interval 34 to 46; P < .01). Children in the intervention group had significantly better receptive language skills (5.3; 95% confidence interval 0.15 to 10.4), but not broad-based expressive language skills (0.37, 95% confidence interval -4.5 to 5.3; P = .88). This trial provides preliminary evidence of the short-term effects of systematic caregiver instruction on caregiver use of language facilitation strategies and subsequent changes in children's language skills. Future research should investigate the ideal dosage levels for optimizing child outcomes and determine which language facilitation strategies are associated with specific child outcomes. Research on adaptations for families from culturally and linguistically diverse backgrounds is needed.


Prevalence of Metabolic Syndrome among Psychiatric Inpatients: A Hospital Based Study from Kashmir.
Over the last fifty years there has been dramatic change in the human environment, behaviours and way-of-life. These changes have resulted in escalating rates of metabolic syndrome not only in general population but also among people with mental illness. Various factors, like the lack of exercise, use of psychotropic medications and inadequate medical care leads to the increased risk of metabolic changes among people with mental illness. Hence, there is a greater need to evaluate metabolic syndrome in this population. To find the prevalence of metabolic syndrome among psychiatric inpatients in Tertiary Care Hospital in Kashmir region of North India. It was a cross-sectional study conducted at the Institute of Mental Health and Neurosciences, Kashmir, India. A total of 213 in-patients with a primary psychiatric diagnosis as per The International Classification of Diseases, Tenth Revision (ICD 10) Classification of Mental and Behavioural Disorders criteria were evaluated for the presence of metabolic syndrome. A modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criterion for the diagnosis of metabolic syndrome was used. All the intergroup comparisons for parametric data were done by Student's t-test, whereas non-parametric data were analysed by Chi-square tests. A p-value <0.05 was considered statistically significant. The overall prevalence of metabolic syndrome was 34.74%. The prevalence was higher in females (43.3%) than males (28.5%) (p<0.05) and it increased with age, with the highest prevalence in the age group >50 years (p<0.05). Among the diagnostic subgroups, the prevalence was highest among patients with unipolar depression (45.0%), while it was lesser in patients with bipolar disorders (37.88%) and psychotic disorders (30.95%). Prevalence of metabolic syndrome was significantly higher (63.64%) among patients taking second generation antipsychotics (p<0.05). Our study shows that metabolic syndrome is highly prevalent among psychiatric inpatients and needs to be addressed to prevent the risk for cardiovascular diseases.


Protection provided by hepatitis B vaccine in a Yupik Eskimo population--results of a 10-year study.
A hepatitis B virus vaccine demonstration project was conducted in southwest Alaska in 1981-1982 to determine the immunogenicity and efficacy of the vaccine. A total of 1630 susceptible persons in the Alaskan Native population were vaccinated with the recommended three-dose regimen of plasma-derived hepatitis B vaccine, and 94% demonstrated antibody to hepatitis B surface antigen (anti-HBs) at levels > or = 10 mIU/mL. After 10 years of follow-up, 76% of those immunized had anti-HBs levels > or = 10 mIU. During the 10 years following the first dose of vaccine, 13 study participants developed antibody to hepatitis B core antigen (10 vaccine responders, 3 nonresponders), and none developed sustained HBs positivity or had clinical hepatitis. These data suggest that immunization with hepatitis B vaccine continues to provide high levels of protection from clinical disease for at least 10 years.


Dissolution enhancement of glibenclamide by solid dispersion: solvent evaporation versus a supercritical fluid-based solvent -antisolvent technique.
Glibenclamide (GLIB) is a poorly soluble drug with formulation-dependent bioavailability. Therefore, we attempted in this study to improve GLIB dissolution rate by preparing drug solid dispersions by solvent evaporation (SE) and supercritical fluid solvent-antisolvent techniques (SCF-SAS). A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE. The ratios of carriers used in SCF-SAS method were HPMCE5 (fixed at 60%), PEG6000 (20-40%), and Poloxamer407 (0-20%). A constant drug: carrier weight ratio of 1:10 was used in all experiments. The SDs obtained were physically characterized and subjected to the dissolution study. The major GLIB bands in FTIR spectra were indicative of drug integrity. The reduced intensity and the fewer number of peaks observed in X-ray diffractograms (XRD) of GLIB formulations was the indicative of at least partial transformation of crystalline to amorphous GLIB. This change and/or dilution of drug in much higher amounts of carriers present caused disappearance of distinctive endothermic peaks in differential scanning calorimetry thermograms of GLIB formulations. The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances. As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix.


Syntrophomonas zehnderi sp. nov., an anaerobe that degrades long-chain fatty acids in co-culture with Methanobacterium formicicum.
An anaerobic, mesophilic, syntrophic fatty-acid-oxidizing bacterium, designated strain OL-4(T), was isolated as a co-culture with Methanobacterium formicicum DSM 1535(NT) from an anaerobic expanded granular sludge bed reactor used to treat an oleate-based effluent. Strain OL-4(T) degraded oleate, a mono-unsaturated fatty acid, and straight-chain fatty acids C(4 : 0)-C(18 : 0) in syntrophic association with Methanobacterium formicicum DSM 1535(NT). Even-numbered fatty acids were degraded to acetate and methane whereas odd-numbered fatty acids were degraded to acetate, propionate and methane. Branched-chain fatty acids were not degraded. The bacterium could not grow axenically with any other substrate tested and therefore is considered to be obligately syntrophic. Fumarate, sulfate, thiosulfate, sulfur and nitrate could not serve as electron acceptors for strain OL-4(T) to degrade oleate or butyrate. Cells of strain OL-4(T) were curved rods, formed spores and showed a variable response to Gram staining. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain OL-4(T) was most closely related to the fatty-acid-oxidizing, syntrophic bacterium Syntrophomonas sp. TB-6 (95 % similarity), Syntrophomonas wolfei subsp. wolfei DSM 2245(T) (94 % similarity) and Syntrophomonas erecta DSM 16215(T) (93 % similarity). In addition to this moderate similarity, phenotypic and physiological characteristics, such as obligate syntrophy, spore formation and utilization of a broader substrate range, differentiated strain OL-4(T) from these Syntrophomonas species. Therefore strain OL-4(T) represents a novel species, for which the name Syntrophomonas zehnderi sp. nov. is proposed. The type strain is OL-4(T) (=DSM 17840(T)=JCM 13948(T)).