Two siblings with alternate unbalanced recombinants derived from a large cryptic maternal pericentric inversion of chromosome 20.
Two brothers, with dissimilar clinical features, were each found to have different abnormalities of chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since chromosome 20 is a metacentric chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal chromosome 20 homologs, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, approximately 900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, approximately 1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e., between RP11-93B14 and proximal BAC RP11-765G16).


The role of cellular interactions in joint erosions.
Maintenance of the normal integrity of articular cartilage is due to a balance between the synthesis and degradation of the extracellular matrix. This balance is maintained as a result of the anabolic and catabolic activities of the indigenous cells, the chondrocytes. It is becoming understood that the metabolic activity of the chondrocytes can be modified by certain intercellular messengers. To date, two such intercellular messengers have been recognized and partially characterized: the interleukins and the catabolins. These messengers are probably part of a much wider family of proteins that function in the control of connective tissue structure in general. In terms of the arthritic diseases, the catabolins seem likely to play a role in the early stages of chondrocyte-mediated matrix degradation in osteoarthritis, (OA), while in rheumatoid arthritis (RA) the catabolins, probably coming from the fibroblastic cells of the synovium, and the interleukins, probably originating from the inflammatory cells of the pannus, may work in association with extrinsic proteinases secreted by a number of component cells of the inflammatory synovium. Recognition of the role of intercellular messengers in both the physiology and pathology of articular tissues provides new and exciting possibilities in pharmacodynamic systems for prevention of joint damage.


Inhibition of vesicular stomatitis virus mRNA synthesis by human MxA protein.
The interferon-induced human MxA protein inhibits the multiplication of influenza virus and vesicular stomatitis virus (VSV) by an unknown mechanism. Here we show that MxA protein interferes with VSV mRNA synthesis. Transfected Swiss 3T3 mouse cells constitutively expressing MxA protein and control cells were infected with VSV, and viral RNA and protein synthesis was monitored. Viral macromolecules were very abundant in control cells at 4 h postinfection, whereas the pools of VSV proteins and RNAs were more than 50-fold reduced in cells expressing MxA. To determine whether MxA inhibited VSV primary transcription, we infected the cells in the presence of the protein synthesis inhibitor cycloheximide and measured the pools of the five viral mRNAs at 4 h postinfection. VSV L mRNA concentration was more than 20-fold reduced, VSV G mRNA concentration was about 10-fold reduced, and the other viral mRNAs were three- to fivefold less abundant in MxA-expressing cells than in control cells. Our results thus indicate that MxA interferes with normal VSV mRNA synthesis either directly by inhibiting the activity of the viral polymerase complex or indirectly by reducing the stability of the VSV mRNAs.


Management of Croup in the Emergency Department: The Role of Multidose Nebulized Epinephrine.
Croup occasionally requires medical intervention for respiratory distress. Mainstays of treatment are corticosteroids and nebulized epinephrine. Diagnosis and assessment of severity remain clinical. Safety of discharge from an emergency department (ED) after treatment with corticosteroids and 1 nebulized epinephrine has been established. No evidence exists regarding risk associated with discharge after multidose nebulized epinephrine. Many patients requiring multidose nebulized epinephrine are reflexively admitted. The purpose of this study was to provide a descriptive analysis of the current management of croup, specifically patients requiring multidose nebulized epinephrine. The Pediatric Health Information System was used to extract information on patients diagnosed with croup age 0 to 11 years, evaluated in pediatric EDs from 2004 to 2014, who received corticosteroids and at least 1 nebulized epinephrine. We retrospectively assessed patients requiring multidose nebulized epinephrine, evaluating risk of return for additional care associated with discharges and reviewing admissions for markers of disease severity. A total of 95,403 patients were identified. Those requiring corticosteroids and multidose nebulized epinephrine (N = 8084) were less likely to return for further care if discharged from the ED (5.4% return single dose, 0.8% return multidose: P < 0.0001) and were admitted at a higher rate (10.7% admission single dose, 70.5% admission multidose: P < 0.0001). Of those admitted, only 31.7% received more than 2 treatments. Patients requiring single-dose nebulized epinephrine are managed differently than those requiring multidose nebulized epinephrine. There is likely a role for multidose nebulized epinephrine in the outpatient management of croup. A prospective study is needed.


Transient delayed facial nerve palsy after inferior alveolar nerve block anesthesia.
Facial nerve palsy, as a complication of an inferior alveolar nerve block anesthesia, is a rarely reported incident. Based on the time elapsed, from the moment of the injection to the onset of the symptoms, the paralysis could be either immediate or delayed. The purpose of this article is to report a case of delayed facial palsy as a result of inferior alveolar nerve block, which occurred 24 hours after the anesthetic administration and subsided in about 8 weeks. The pathogenesis, treatment, and results of an 8-week follow-up for a 20-year-old patient referred to a private maxillofacial clinic are presented and discussed. The patient's previous medical history was unremarkable. On clinical examination the patient exhibited generalized weakness of the left side of her face with a flat and expressionless appearance, and she was unable to close her left eye. One day before the onset of the symptoms, the patient had visited her dentist for a routine restorative procedure on the lower left first molar and an inferior alveolar block anesthesia was administered. The patient's medical history, clinical appearance, and complete examinations led to the diagnosis of delayed facial nerve palsy. Although neurologic occurrences are rare, dentists should keep in mind that certain dental procedures, such as inferior alveolar block anesthesia, could initiate facial nerve palsy. Attention should be paid during the administration of the anesthetic solution.


Epigenetic changes in fibroblasts drive cancer metabolism and differentiation.
Genomic changes that drive cancer initiation and progression contribute to the co-evolution of the adjacent stroma. The nature of the stromal reprogramming involves differential DNA methylation patterns and levels that change in response to the tumor and systemic therapeutic intervention. Epigenetic reprogramming in carcinoma-associated fibroblasts are robust biomarkers for cancer progression and have a transcriptional impact that support cancer epithelial progression in a paracrine manner. For prostate cancer, promoter hypermethylation and silencing of the RasGAP, RASAL3 that resulted in the activation of Ras signaling in carcinoma-associated fibroblasts. Stromal Ras activity initiated a process of macropinocytosis that provided prostate cancer epithelia with abundant glutamine for metabolic conversion to fuel its proliferation and a signal to transdifferentiate into a neuroendocrine phenotype. This epigenetic oncogenic metabolic/signaling axis seemed to be further potentiated by androgen receptor signaling antagonists and contributed to therapeutic resistance. Intervention of stromal signaling may complement conventional therapies targeting the cancer cell.


An extra maternally derived X chromosome is deleterious to early mouse development.
An extra copy of the X chromosome, unlike autosomes, exerts only minor effects on development in mammals including man and mice, because all X chromosomes except one are genetically inactivated. Contrary to this contention, we found that an additional maternally derived X (XM) chromosome, but probably not a paternally derived one (XP), consistently contributes to early death of 41,XXY and 41,XXX embryos in mice. Because of imprinted resistance to inactivation, two doses of XM remain active in the trophectoderm, and seem to be responsible for the failure in the development of the ectoplacental cone and extraembryonic ectoderm, and hence, from early embryonic death. Discordant observations in man indicating viability of XMXMXP and XMXMY individuals suggest that imprinting on the human X chromosome is either weak, unstable or erased before the initiation of X-inactivation in progenitors of extraembryonic membranes.


Changes in functional capacity of patients two years after coronary artery bypass grafting surgery.
To check changes in the functional capacity of patients undergoing coronary artery bypass grafting (CABG) by testing six-minute walk test (6MWT) following two years. A prospective cohort study where 215 patients were enrolled who underwent CABG, 13 did not meet the criteria for inclusion. 202 patients were evaluated preoperatively, 13 died during hospitalization and 6 in the follow up of two years. Four patients were considered lost follow up. This study followed 179 patients for two years classified into active and sedentary, according to physical activity in leisure time and to the 6MWT preoperatively and 2 years later. One hundred and twenty patients were evaluated in the day before CABGS, being 67% male with an average age of 63 (+/- 9.75) years. Before surgery and 2 years later, 52 were active and the 6MWT distances performed had been 359m (+/- 164.47) and 439m (+/- 171.34), respectively; P= 0.016. Forty five patients were classified as sedentary before and 2 years after surgery. The 6MWT distances walked before and after surgery had been 255m (+/- 172.15) and 376m (+/- 210.92), respectively; P < 0.001. Eighty two patients transited between these two groups, 71 passed from sedentary to active and had walked before and after surgery 289m (+/- 157.15) and 380m (+/- 125.44), respectively; P= 0.001. The 11 patients who were active and passed to the sedentary group walked 221m (+/- 191.91) and 384m (+/- 63.73), respectively; P= 0.007. The functional capacity of the patients submitted to CABGS had a significant improvement in a medium period of follow-up.


Recent advances in computational actinoid chemistry.
We briefly review advances in computational actinoid (An) chemistry during the past ten years in regard to two issues: the geometrical and electronic structures, and reactions. The former addresses the An-O, An-C, and M-An (M is a metal atom including An) bonds in the actinoid molecular systems, including actinoid oxo and oxide species, actinoid-carbenoid, dinuclear and diatomic systems, and the latter the hydration and ligand exchange, the disproportionation, the oxidation, the reduction of uranyl, hydroamination, and the photolysis of uranium azide. Concerning their relevance to the electronic structures and reactions of actinoids and their importance in the development of an advanced nuclear fuel cycle, we also mentioned the work on actinoid carbides and nitrides, which have been proposed to be candidates of the next generation of nuclear fuel, and the oxidation of PuO(x), which is important to understand the speciation of actinoids in the environment, followed by a brief discussion on the urgent need for a heavier involvement of computational actinoid chemistry in developing advanced reprocessing protocols of spent nuclear fuel. The paper is concluded with an outlook.


[Antiretroviral drug toxicity in human immunodeficiency virus infected children].
Paediatric Human Immunodeficiency Virus infection (HIV) nowadays is a chronic disease with an excellent long term prognosis, but lifelong combined antiretroviral treatment is required. However, an improved quality of life in this population is limited by adverse drug effects. The highest risk of treatment toxicity is developing a complete metabolic syndrome including: Hyperlipemia, lipodystrophy, insulin resistance, lactic acidosis, osteopenia, hypertension, and specific system and organ toxicity, such as the kidney, liver, CNS or bone marrow. The risk of cardiovascular disease adult life and also definitive bone mass damage are the most significant metabolic costs that have to paid for increased survival. Most of these toxicities were able to be adequately treated but, pharmacological interferences, patient intolerance and the high number of drugs are the problems that limit the adherence to treatment, which is essential for a good therapeutical efficacy. In this article, we present four HIV paediatric patients who presented with almost the whole range of metabolic toxicities, and a practical overview of therapeutical management.


Effects of veratrine on the in situ dog heart: evidence for increased ventricular fibrillation threshold.
The present work studied the effect of veratrine on electrical stability of the mammalian ventricles. In a group of anesthetized open-chest dogs we determined the effects of veratrine (0.001-0.3 mg/kg) on the threshold for ventricular fibrillation (VFT), both during sinus rhythm (SR) and during atrial drive (AD) at 166 +/- 7 beats/min. Veratrine (0.3 mg/kg) increased the VFT during SR from control levels of 33 +/- 5 mA to 56 +/- 4 mA (P less than .05) and during AD from 34 +/- 6 to 57 +/- 9 mA (P less than .05). VFTs after infusion of veratrine were higher than in a control group of dogs given the saline diluent in which VFT during SR was 26 +/- 3 mA (P less than .001) and during AD was 24 +/- 3 mA (P less than .005). The increase in VFT during SR was independent of the decrease in heart rate, which fell from 147 +/- 8 to 106 +/- 6 beats/min (P less than .001). It was associated, however, with an increase in the QT interval during SR from control values of 254 +/- 13 to 308 +/- 19 msec (P less than .02) and during AD from 238 +/- 8 to 267 +/- 8 msec (P less than .005). We conclude that small doses of veratrine increase the electrical stability of the ventricles in the normal dog heart.


Chronic subdural hematoma in the cerebellopontine angle.
A 32-year-old man had the clinical and radiological features of a mass lesion in the left cerebellopontine angle. Surgical exploration revealed a cyst containing 20 ml of altered blood. Microscopic examination of the cyst wall showed the structure of an organizing hematoma in the subdural space. The patient, on repeated questioning, denied a history of head injury.


Binding of small, acid-soluble spore proteins to DNA plays a significant role in the resistance of Bacillus subtilis spores to hydrogen peroxide.
Dormant spores of Bacillus subtilis which lack the majority of the alpha/beta-type small, acid-soluble proteins (SASP) (termed alpha- beta- spores) that coat the DNA in wild-type spores are significantly more sensitive to hydrogen peroxide than are wild-type spores. Hydrogen peroxide treatment of alpha- beta- spores causes DNA strand breaks more readily than does comparable treatment of wild-type spores, and alpha- beta- spores, but not wild-type spores, which survive hydrogen peroxide treatment have acquired a significant number of mutations. The hydrogen peroxide resistance of wild-type spores appears to be acquired in at least two incremental steps during sporulation. The first increment is acquired at about the time of alpha/beta-type SASP synthesis, and the second increment is acquired approximately 2 h later, at about the time of dipicolinic acid accumulation. During sporulation of the alpha- beta- strain, only the second increment of hydrogen peroxide resistance is acquired. In contrast, sporulation mutants which accumulate alpha/beta-type SASP but progress no further in sporulation acquire only the first increment of hydrogen peroxide resistance. These findings strongly suggest that binding of alpha/beta-type SASP to DNA provides one increment of spore hydrogen peroxide resistance. Indeed, binding of alpha/beta-type SASP to DNA in vitro provides strong protection against cleavage of DNA by hydrogen peroxide.


Proteomic analysis of chicken embryonic trachea and kidney tissues after infection in ovo by avian infectious bronchitis coronavirus.
Avian infectious bronchitis (IB) is one of the most serious diseases of economic importance in chickens; it is caused by the avian infectious coronavirus (IBV). Information remains limited about the comparative protein expression profiles of chicken embryonic tissues in response to IBV infection in ovo. In this study, we analyzed the changes of protein expression in trachea and kidney tissues from chicken embryos, following IBV infection in ovo, using two-dimensional gel electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS). 17 differentially expressed proteins from tracheal tissues and 19 differentially expressed proteins from kidney tissues were identified. These proteins mostly related to the cytoskeleton, binding of calcium ions, the stress response, anti-oxidative, and macromolecular metabolism. Some of these altered proteins were confirmed further at the mRNA level using real-time RT-PCR. Moreover, western blotting analysis further confirmed the changes of annexin A5 and HSPB1 during IBV infection. To the best of our knowledge, we have performed the first analysis of the proteomic changes in chicken embryonic trachea and kidney tissues during IBV infection in ovo. The data obtained should facilitate a better understanding of the pathogenesis of IBV infection.


Modeling multi-sensory feedback control of zebrafish in a flow.
Understanding how animals navigate complex environments is a fundamental challenge in biology and a source of inspiration for the design of autonomous systems in engineering. Animal orientation and navigation is a complex process that integrates multiple senses, whose function and contribution are yet to be fully clarified. Here, we propose a data-driven mathematical model of adult zebrafish engaging in counter-flow swimming, an innate behavior known as rheotaxis. Zebrafish locomotion in a two-dimensional fluid flow is described within the finite-dipole model, which consists of a pair of vortices separated by a constant distance. The strength of these vortices is adjusted in real time by the fish to afford orientation and navigation control, in response to of the multi-sensory input from vision, lateral line, and touch. Model parameters for the resulting stochastic differential equations are calibrated through a series of experiments, in which zebrafish swam in a water channel under different illumination conditions. The accuracy of the model is validated through the study of a series of measures of rheotactic behavior, contrasting results of real and in-silico experiments. Our results point at a critical role of hydromechanical feedback during rheotaxis, in the form of a gradient-following strategy.


Copper(I)- and copper(0)-promoted homocoupling and homocoupling-hydrodehalogenation reactions of dihalogenoclathrochelate precursors for C-C conjugated iron(II) bis-cage complexes.
Iron(II) dibromo- and diiodoclathrochelates undergo copper(I)-promoted reductive homocoupling in HMPA at 70-80 °C leading to C-C conjugated dibromo- and diiodo-bis-clathrochelates in high yields. Under the same conditions, their dichloroclathrochelate analog does not undergo the same homocoupling reaction, so the target dichloro-bis-cage product was obtained in high yield via dimerization of its heterodihalogenide iodochloromonomacrobicyclic precursor. The use of NMP as a solvent at 120-140 °C gave the mixture of bis-clathrochelates resulting from a tandem homocoupling-hydrodehalogenation reaction: the initial acetonitrile copper(I) solvato-complex at a high temperature underwent re-solvatation and disproportionation leading to Cu(II) ions and nano-copper, which promoted the hydrodehalogenation process even at room temperature. The most probable pathway of this reaction in situ includes hydrodehalogenation of the already formed dihalogeno-bis-clathrochelate via the formation of reduced anion radical intermediates. As a result, chemical transformations of the iron(II) dihalogenoclathrochelates in the presence of an acetonitrile copper(I) solvato-complex were found to depend both on the nature of halogen atoms in their ribbed chelate fragments and on reaction conditions (i.e. solvent and temperature). The C-C conjugated iron(II) dihalogeno-bis-clathrochelates easily undergo nucleophilic substitution with various N,S-nucleophiles giving ribbed-functionalized bis-cage species. These iron(II) complexes were characterized by elemental analysis, MALDI-TOF mass spectrometry, IR, UV-Vis, (1)H and (13)C NMR spectroscopy, and by X-ray diffraction; their electrochemical properties were studied by cyclic voltammetry. The isomeric shift values in (57)Fe Mössbauer spectra of such cage compounds allowed identifying them as low-spin iron(II) complexes, while those of the quadrupole splitting are the evidence for a significant TP distortion of their FeN6-coordination polyhedra. As follows from CV data, the C-C conjugated iron(II) bis-clathrochelates undergo stepwise electrochemical reduction and oxidation giving mixed-valence Fe(II)Fe(I) and Fe(II)Fe(III) bis-cage intermediates.


p21Ras activation by the guanine nucleotide exchange factor Sos, requires the Sos/Grb2 interaction and a second ligand-dependent signal involving the Sos N-terminus.
It has been suggested that a key event in growth factor-induced p21Ras activation by the guanine nucleotide exchange factor Sos, is the recruitment of Sos to the plasma membrane by its interaction with the adaptor protein Grb2. However, other evidence argues that the sub cellular localisation of Sos is independent of Grb2, and that the Sos/Grb2 interaction can be dispensed with for p21Ras activation. To clarify the role of the Sos/Grb2 interaction in ligand-stimulated p21Ras activation, we have utilised the observation that overexpression of the Sos C-terminal domain can effectively inhibit p21Ras-dependent signalling in three different mammalian systems. We have shown that concurrent expression of Grb2, but not SH2 or SH3 domain mutants of Grb2, or the alternative adaptor protein Nck, can rescue this inhibitory effect of the C-terminus. This shows that the Grb2/Sos interaction is required to mediate growth factor-dependent activation of p21Ras, and requires the presence of intact SH2 and SH3 domains of Grb2. This approach was also used for a functional analysis of Sos which revealed that growth factor dependent signals are transmitted through both the N-terminal and C-terminal domains.


Unravelling adolescent girls' aspirations in Nepal: Status and associations with individual-, household-, and community-level characteristics.
Adolescents' aspirations have potential to influence their present and future well-being. Limited knowledge exists on adolescent girls' aspirations and their determinants, particularly in low-income contexts. Using cross-sectional data, collected in 2018 in Nepal, within the Suaahara II Adolescent Panel Survey, (n = 840), adolescent girls' aspirations in several domains-education, occupation, marriage, fertility, health, and nutrition-were described. Regression models were estimated to explore associations between individual, household and community characteristics and these aspirations for all adolescents and separately for younger (10-14 years) and older (15-19 years) girls. Age, school attendance, and self-efficacy, as well as household wealth, caste/ethnicity, size, and agro-ecological zone of residence were significantly associated with aspirations, although effect sizes and significance varied by aspiration domain and age group. Findings underscore the curtailing effect of poverty on aspirations and the dynamic nature of aspirations. Initiatives to foster girls' aspirations must address both individual and contextual factors.


The salivary proteome profile in patients affected by SAPHO syndrome characterized by a top-down RP-HPLC-ESI-MS platform.
SAPHO syndrome is a rare and often unrecognized disease with prominent inflammatory cutaneous and articular symptoms characterized by musculoskeletal manifestations (synovitis, hyperostosis, osteomyelitis) associated with dermatological conditions (severe acne and pustulosis). The acidic soluble fraction of whole saliva from 10 adult women affected by SAPHO syndrome and from a group of 28 healthy women was analysed by RP-HPLC-ESI-MS with the aim of discovering salivary biomarkers of the disorder. The levels of the oral proteins and peptides were correlated with clinical data. The following proteins showed a significant decreased concentration in saliva of SAPHO subjects with respect to controls: cystatin S1 and SN, histatins, the major acidic PRPs, P-C and P-B peptides. The cystatin SN abundance lowered according to the disease duration and histatins showed positive correlations with the C reactive protein. Statistical analysis performed excluding one patient with a different pattern of salivary proteins/peptides highlighted a positive relationship between cystatin S1, histatins 3, histatin 5, and the neutrophil count. Moreover, histatin 3 correlated positively with the total white cell count and negatively with the erythrocyte sedimentation rate. Levels and frequency of S100A12 protein showed a trend to increase in SAPHO patients. The high expression of this pro-inflammatory protein is probably related to the inflammatory response and to the altered neutrophil responses to functional stimuli that characterize SAPHO syndrome suggesting a possible application as a salivary biomarker.


Centroid displacement statistics of the eye aberration.
We discuss a method for the study of the spatial statistics of the ocular aberrations, based on the direct use of the Hartmann-Shack centroid displacements, avoiding the wavefront reconstruction step. Centroid diagrams are introduced as a helpful aid to visualize basic properties of the aberration datasets, and slope-related second-order statistical functions are applied to check the compatibility between the experimental data and different models for the aberration statistics. Preliminary results suggest that no single power-law spectrum (e.g., Kolmogorov's) is able to represent the whole range of spatial statistics of individual eye fluctuations and that more elaborated models, including at least the contribution of a relevant defocus fluctuation term, are required. This centroid-based approach allows for an easier intercomparison of results between laboratories and avoids the bias and information loss associated with the estimation of a reduced number of Zernike coefficients from a much wider slope data set.


Male sex workers in three Australian cities: socio-demographic and sex work characteristics.
This article describes the socio-demographic and sex work characteristics of sex workers in Sydney, Melbourne, and Brisbane. A total of 185 male sex workers completed the questionnaire component of the study. The results of this study serve to debunk many of the myths surrounding the popular view of the male sex worker (MSW). The respondents in this study were on average 27 years old, and the majority had completed secondary education, with 30% having gained some form of tertiary qualification. Interestingly, those MSWs who had not completed secondary education were mostly street workers and were generally aged under 25 years. The majority of sex workers lived in rented accommodation, with only 6% reporting to be homeless. Half of all respondents identified as being "gay," 31% as "bisexual" and 5.5% as "straight." More than half of the respondents were in a permanent relationship. Only 7.3% of this group reported using heroin daily, although the majority consumed alcohol, tobacco, marijuana, and ecstasy. The majority of sex workers had been in the profession for less than six months, although some had been working in the industry for more than ten years. Most of the sex workers reported having taken an HIV test and a preference to offer safer sex. The article highlights ways in which the work context of MSW can be better understood and supported by education and public policy programs.


Molecular map of the Chlamydomonas reinhardtii nuclear genome.
We have prepared a molecular map of the Chlamydomonas reinhardtii genome anchored to the genetic map. The map consists of 264 markers, including sequence-tagged sites (STS), scored by use of PCR and agarose gel electrophoresis, and restriction fragment length polymorphism markers, scored by use of Southern blot hybridization. All molecular markers tested map to one of the 17 known linkage groups of C. reinhardtii. The map covers approximately 1,000 centimorgans (cM). Any position on the C. reinhardtii genetic map is, on average, within 2 cM of a mapped molecular marker. This molecular map, in combination with the ongoing mapping of bacterial artificial chromosome (BAC) clones and the forthcoming sequence of the C. reinhardtii nuclear genome, should greatly facilitate isolation of genes of interest by using positional cloning methods. In addition, the presence of easily assayed STS markers on each arm of each linkage group should be very useful in mapping new mutations in preparation for positional cloning.


"What was meant to be" versus "what might have been": Effects of culture and control on counterfactual thinking.
Counterfactual thinking is a ubiquitous feature of daily life with links to causal reasoning. Therefore, we argue that cultures that vary in perceptions of what controls important life outcomes may also vary in counterfactual thought. Investigating White American and United Arab Emirates-based Arab participants' counterfactual potency and spontaneous counterfactual thinking, we found that Arab participants endorsed counterfactual thoughts less than White Americans, and were unaffected by the routine nature of action when negative outcomes were severe. Differences in counterfactual endorsement in response to severe negative outcomes were linked to greater beliefs in divine control and fate in Arab participants, and not to religiosity, reinforcing an important role of perceptions of control in counterfactual thought. However, although reporting less counterfactual endorsement overall, Arabs showed a similar pattern of counterfactual thought to White Americans when negative outcomes were mild, or when reporting spontaneous thought. Arabs likewise showed a similar pattern of regret as White Americans regardless of event severity, reporting more regret when outcomes resulted from unusual action. These patterns suggest a dissociation between affect and cognition, and between what kind of outcomes are subject to counterfactual scrutiny in Arab participants. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Functional Identification of a Nuclear Localization Signal of MYB2 Protein in Giardia lamblia.
MYB2 protein was identified as a transcription factor that showed encystation-induced expression in Giardia lamblia. Although nuclear import is essential for the functioning of a transcription factor, an evident nuclear localization signal (NLS) of G. lamblia MYB2 (GlMYB2) has not been defined. Based on putative GlMYB2 NLSs predicted by 2 programs, a series of plasmids expressing hemagglutinin (HA)-tagged GlMYB2 from the promoter of G. lamblia glutamate dehydrogenase were constructed and transfected into Giardia trophozoites. Immunofluorescence assays using anti-HA antibodies indicated that GlMYB2 amino acid sequence #507-#530 was required for the nuclear localization of GlMYB2, and this sequence was named as NLSGlMYB2. We further verified this finding by demonstrating the nuclear location of a protein obtained by the fusion of NLSGlMYB2 and G. lamblia glyceraldehyde 3-phosphate dehydrogenase, a non-nuclear protein. Our data on GlMYB2 will expand our understanding on NLSs functioning in G. lamblia.


Association of Factor V Leiden G1691A and Prothrombin gene G20210A mutations with adverse pregnancy outcomes.
To determine the association of Factor V Leiden / prothrombin gene mutation in Pakistani women with adverse pregnancy outcomes. The prospective study was conducted at the Aga Khan University Hospital, Karachi, from January 1 to December 31, 2016, and comprised females > 40 years having history of two or more foetal losses with no apparent aetiology. Restriction fragment length polymorphism- Polymerase chain reaction was performed using MnlI and HindIII restriction enzymes for factor V Leiden G1691A and prothrombin gene mutation G20210A. Females with two or more consecutive normal pregnancies were enrolled as the control group. Data was analysed using SPSS 19. Of the 172 participants with a mean age of 29.3±5.9 years (range: 19-38 years). 86(50%) each were healthy controls and those with recurrent pregnancy loss. There were 238 livebirths among the controls compared to 13 in the other group. Factor V Leiden G1691A was identified in 2(2.3%) women, and prothrombin gene mutation G20210A in 1(1.2%) woman in the patient group, while no mutation was identified in the control group. The prevalence of Factor V Leiden / prothrombin gene mutation in women with recurrent pregnancy loss was found to be very low.


Brief report: error pattern in an autistic savant calendar calculator.
Special ability in computing the day of the week from given dates was observed in a 18 years old male, L.E., suffering from autism. Neuropsychological testing revealed severe deficits in all cognitive domains and poor explicit knowledge of calendar structure. The subject scored well above the chance level on dates of the past and future decades. Error rate and response latency increased with temporal remoteness of dates. Most of errors were in indicating the weekday before or after that of date stimulus. The performance and error pattern suggest that L.E. used "encapsulated" computation algorithm(s) for the day of week task.


Validation of current practice and a near patient testing method for oral-anticoagulant control in general practice.
When oral anticoagulant control is monitored in general practice, venous blood samples are usually transported to a central laboratory for determination of international normalized ratio (INR). An alternative is near patient testing by a commercial method. In a rural general practice 27 km from a central haematology laboratory, whole blood samples were drawn from patients receiving oral anticoagulants and analysed by three methods: after centrifugation, plasma separated and frozen in liquid nitrogen, transported to the laboratory, thawed and immediately analysed (control); courier transport of citrated sample to the laboratory for analysis (routine); near patient testing of whole blood sample (NPT). Maximum temperature achieved and time to analysis for routine samples were recorded. 306 complete sets of data were obtained. Comparison between the routine method and the control method revealed acceptable agreement. On multiple regression analysis, maximum temperature achieved did not contribute to differences observed but time to analysis of over 5 hours did make a significant contribution. Comparison between the NPT method and control method showed acceptable agreement, with persistent under-recording by the NPT method. The routine method for INR determination was validated as robust and reproducible with the proviso that needle-to-analysis time should be kept below 5 hours. The NPT method was valid under conditions of normal general practice. Strict quality control of NPT methods is essential if performance is to be comparable with that of established methods.


Intestinal fibrosis: ready to be reversed.
Intestinal fibrosis is a common complication of several enteropathies, with inflammatory bowel disease (IBD) being the major cause. Intestinal fibrosis affects both ulcerative colitis and Crohn's disease, and no specific antifibrotic therapy exists. This review highlights recent developments in this area. The pathophysiology of intestinal stricture formation includes inflammation-dependent and inflammation-independent mechanisms. A better understanding of the mechanisms of intestinal fibrogenesis and the availability of compounds for other nonintestinal fibrotic diseases bring clincial trials in stricturing Crohn's disease within reach. Improved understanding of its mechanisms and ongoing development of clinical trial endpoints for intestinal fibrosis will allow the testing of novel antifibrotic compounds in IBD.


Diffusion-weighted magnetic resonance imaging in non-invasive monitoring of antiangiogenic therapy in experimental tumor model.
To show usefulness of diffusion-weighted magnetic resonance imaging (MRI) for non-invasive assessment of experimental tumor after antiangiogenic treatment. M1 sarcoma was implanted to the peritoneal cavity of the rat and allowed to grow to a palpable tumor size. Animal was treated with a single injection of endothelial growth factor antibody Bevacizumab (Avastin). Serial MRI scanning including diffusion-weighted sequence was performed before and up to 100 h after treatment. Animal was sacrificed thereafter and MRI data were correlated with morphology. Apparent diffusion coefficient (ADC) maps derived tumor necrotic area correlated well with histology-derived tumor necrotic area. ADC threshold of 1.39 x 10(-3) mm(2)/s appeared to be optimal for tumor necrosis quantification in this tumor model and allowed to follow temporal changes of tumor internal structure after treatment. Diffusion-weighted MRI permits non-invasive tissue characterization without the need for exogenous contrast agents and, therefore, may be used to individualise therapy and to monitor tumor response.


Cardiac fibroblasts in pressure overload hypertrophy: the enemy within?
Cardiac fibroblasts have been long recognized as active participants in heart disease; however, their exact physiological and pathological roles remain elusive, mainly due to the lack of specific markers. In this issue of the JCI, Moore-Morris and colleagues used a fibroblast-specific collagen1a1-GFP reporter to demonstrate that fibroblast accumulation after aortic banding in murine hearts arises almost exclusively from proliferation of resident fibroblasts originating from both the epicardium and a previously unrecognized source, the endocardium. Further characterization of fibroblast origin and function in different types and stages of heart disease could lead to development of improved fibroblast-targeted cardiac therapies.


Management of metastatic bone disease of melanoma.
One of the most aggressive tumors arising from the skin, mucosa, and uvea is malignant melanoma, which easily metastasizes. Bone tissue is one of the most typical locations for distant metastasis, and around 5%-20% of patients eventually acquired skeletal metastases. For decades, the incidence of bone metastases was higher, bringing greater burden on the family, society, and healthcare system owing to the progress of targeted therapy and immunotherapy, which prolonging the survival time substantially. Moreover, bone metastases result in skeletal-related events, which influence the quality of life, obviously. Appropriate intervention is therefore crucial. To obtain the optimum cost-effectiveness, existing treatment algorithm must be integrated, which is still controversial. We have aimed to throw light on current views concerning the formation, biological and clinical features, and treatment protocol of melanoma bone metastases to guide the decision-making process.


Structure, Topology, and Dynamics of Membrane-Inserted Polypeptides and Lipids by Solid-State NMR Spectroscopy: Investigations of the Transmembrane Domains of the DQ Beta-1 Subunit of the MHC II Receptor and of the COP I Protein p24.
MHC class II receptors carry important function in adaptive immunity and their malfunctioning is associated with diabetes type I, chronic inflammatory diseases and other autoimmune diseases. The protein assembles from the DQ alpha-1 and DQ beta-1 subunits where the transmembrane domains of these type I membrane proteins have been shown to be involved in homo- and heterodimer formation. Furthermore, the DQ alpha 1 chain carries a sequence motif that has been first identified in the context of p24, a protein involved in the formation of COPI vesicles of the intracellular transport machinery, to specifically interact with sphingomyelin-C18 (SM-C18). Here we investigated the membrane interactions and dynamics of DQ beta-1 in liquid crystalline POPC phospholipid bilayers by oriented 15N solid-state NMR spectroscopy. The 15N resonances are indicative of a helical tilt angle of the membrane anchor sequence around 20°. Two populations can be distinguished by their differential dynamics probably corresponding the DQ beta-1 mono- and homodimer. Whereas, this equilibrium is hardly affected by the addition of 5 mole% SM-C18 a single population is visible in DMPC lipid bilayers suggesting that the lipid saturation is an important parameter. Furthermore, the DQ alpha-1, DQ beta-1 and p24 transmembrane helical domains were reconstituted into POPC or POPC/SM-C18 lipid bilayers where the fatty acyl chain of either the phosphatidylcholine or of the sphingolipid have been deuterated. Interestingly in the presence of both sphingolipid and polypeptide a strong decrease in the innermost membrane order of the POPC palmitoyl chain is observed, an effect that is strongest for DQ beta-1. In contrast, for the first time the polypeptide interactions were monitored by deuteration of the stearoyl chain of SM-C18. The resulting 2H solid-state NMR spectra show an increase in order for p24 and DQ alpha-1 which both carry the SM recognition motif. Thereby the data are suggestive that SM-C18 together with the transmembrane domains form structures imposing positive curvature strain on the surrounding POPC lipids. This effect is attenuated when SM-C18 is recognized by the protein.


Hybrid 99mTc-magnetite tracer for dual modality sentinel lymph node mapping.
Accuracy of sentinel lymph node identification using radioactive tracers in non-superficial cancers can be limited by radiation shine through and low spatial resolution of detection systems such as intraoperative gamma probes. By utilising a dual radioactive/magnetic tracer, sensitive lymphoscintigraphy can be paired with high spatial resolution intraoperative magnetometer probes to improve the accuracy of sentinel node detection in cancers with complex multidirectional lymphatic drainage. Dextran-coated magnetite nanoparticles (33 nm mean hydrodynamic diameter) were labelled with 99mTc and applied as a lymphotropic tracer in small and large animal models. The dual tracer could be radiolabelled with 98 ± 2% efficiency after 10 min of incubation at room temperature. Biodistribution studies of the tracer were conducted in normal rats (subdermal and intravenous tail delivery, n = 3) and swine (subdermal hind limb delivery, n = 5). In rats the dual tracer migrated through four tiers of lymph node, 20 min after subdermal injection. Results from intravenous biodistribution test for radiocolloids demonstrated no aggregation in vivo, however indicated the presence of some lower-molecular weight radioactive impurities (99mTc-dextran). In swine, the dual tracer could be effectively used to map lymphatic drainage from hind hoof to popliteal and inguinal basins using intraoperative gamma and magnetometer probes. Of the eight primary nodes excised, eight were positively identified by gamma probe and seven by magnetometer probe. The high-purity dual tracer shows early promise for sentinel node identification in complex lymphatic environments by combining sensitive preoperative lymphoscintigraphy with a high-resolution intraoperative magnetometer probe.


Growing Magnetotactic Bacteria of the Genus Magnetospirillum: Strains MSR-1, AMB-1 and MS-1.
Magnetotactic bacteria are Gram-negative, motile, mainly aquatic prokaryotes ubiquitous in freshwater and marine habitats. They are characterized by their ability to biomineralize magnetosomes, which are magnetic nanometer-sized crystals of magnetite (Fe3O4) or greigite (Fe3S4) surrounded by a lipid bilayer membrane, within their cytoplasm. For most known magnetotactic bacteria, magnetosomes are assembled in chains inside the cytoplasm, thereby conferring a permanent magnetic dipole moment to the cells and causing them to align passively with external magnetic fields. Because of these specific features, magnetotactic bacteria have a great potential for commercial and medical applications. However, most species are microaerophilic and have specific O2 concentration requirements, making them more difficult to grow routinely than many other bacteria such as Escherichia coli. Here we present detailed protocols for growing three of the most widely studied strains of magnetotactic bacteria, all belonging to the genus Magnetospirillum. These methods allow for precise control of the O2 concentration made available to the bacteria, in order to ensure that they grow normally and synthesize magnetosomes. Growing magnetotactic bacteria for further studies using these procedures does not require the experimentalist to be an expert in microbiology. The general methods presented in this article may also be used to isolate and culture other magnetotactic bacteria, although it is likely that growth media chemical composition will need to be modified.


N-Acetylglucosamine-asparagine levels in tissues of patients with aspartylglycosaminuria.
The levels of the main glycoprotein-derived storage compound, N-acetylglucosamine-asparagine, in various post mortem tissues of three adult patients with inherited deficiency of lysosomal 1-aspartamido-beta-N-acetylglucosamine amidohydrolase (aspartylglycosaminuria) were measured by gas-liquid chromatography. All aspartylglycosaminuria tissues studied contained significant amounts of N-acetylglucosamine-asparagine, whereas none of the corresponding control tissues contained detectable amounts of this compound. High levels of N-acetylglucosamine-asparagine were found in the liver (3.65 mg/g wet weight), spleen (2.24) and thyroid (2.18), and lower levels in the kidney (0.89), brain (0.53), spinal cord (0.32), sciatic nerve (0.34) and skeletal muscle (0.16). The results show that N-acetylglucosamine-asparagine accumulates chiefly in tissues with important functions in glycoprotein metabolism and/or high endocytic activity. Correlation of the results to the clinical manifestations of aspartylglycosaminuria did not reveal a direct relationship between the amount of N-acetylglucosamine-asparagine stored and the degree of organ dysfunction.


Dual peroxidase and colloidal gold-labeling study of angiotensin converting enzyme and angiotensin-like immunoreactivity in the rat subfornical organ.
The cellular relationships between angiotensin converting enzyme (ACE) (EC 184.108.40.206) and angiotensin-like immunoreactivity (AGLI) were examined in the subfornical organ (SFO). Brains from adult rats were fixed by vascular perfusion with 3.75% acrolein and 2% paraformaldehyde. The region containing the SFO was then sectioned on a vibrating microtome. Partially permeabilized sections were immunocytochemically labeled using the peroxidase-antiperoxidase (PAP) or combined PAP and immunogold methods. Goat antiserum to ACE was localized to both non-neuronal and neuronal cells within the SFO. Intense peroxidase immunoreactivity for ACE was associated with the ventricular and basal surface of ependymal cells, the luminal surface of the vascular endothelium, portions of glial membranes exposed to extracellular spaces, and membranous organelles within neuronal processes. Two antisera raised in rabbits against angiotensin II showed peroxidase immunoreactivity within the extracellular spaces and throughout the cytoplasm of numerous axon terminals and a few perikarya and dendrites in the SFO. Axon terminals and dendrites also showed aggregates of AGLI in smooth membranes and vesicles near the plasmalemma. Gold labeling for AGLI was evident in only 6% of the axon terminals and in a smaller number of dendrites containing peroxidase immunoreactivity for ACE. The low incidence of terminals containing both markers appeared to at least partially reflect limited penetration of the 10 nm gold particles. These results provide the first ultrastructural evidence that ACE is associated with the plasmalemma and membranous organelles strategically located for interaction with precursors of angiotensin II or other peptides within the cerebrospinal fluid, extracellular spaces and neurons of the SFO.


Experimental infection of the skin in the hamster simulating human impetigo. III. Interaction between staphylococci and group A streptococci.
The interaction between staphylococci and Group A beta hemolytic streptococci in mixed lesions was investigated in an experimental impetigo model. A strain of staphylococcus of phage Type 71, which has been shown in vitro to produce a bacteriocin for streptococci and other Gram-positive organisms, eliminates or reduces Group A streptococci in mixed lesions. In contrast, staphylococcal strains of phage Types 75 and 81, which do not produce a demonstrable bacteriocin in vitro, exhibit no such effect. Some variation was noted in the in vivo response of two different streptococcal M Types to the bactericidal effect of phage Type 71 staphylococci. Bacterial antagonism is more pronounced when staphylococci and streptococci are injected simultaneously into animals than when staphylococci are superimposed on preexisting streptococcal lesions. Marked variations were found in the numbers of viable streptococci (colony-forming units) recovered from individual lesions containing identical mixtures of streptococci and phage Type 71 staphylococci. The frequency of a demonstrable bactericidal effect was related to the number of streptococci injected. With small inocula of streptococci, the tendency towards an all-or-none effect was particularly striking. No evidence of selection of streptococcal or staphylococcal mutants which might explain this phenomenon was obtained. These observations suggest that the bactericidal effect of phage Type 71 staphylococci on other Gram-positive organisms, previously demonstrated in vitro, appears to operate also in vivo.


SERS-Active Printable Hydrogel for 3D Cell Culture and Imaging.
Hydrogel-based three-dimensional (3D) cell culture systems mimic the salient elements of extracellular matrices and promote native cell function. However, high-resolution 3D cell imaging that can provide biological information about multiple features of individual cells is yet to be realized. In this context, we incorporated plasmonic gold nanoparticles (AuNPs) into an alginate/gelatin hydrogel to produce surface-enhanced Raman spectroscopy (SERS)-active hydrogel inks for the 3D printing and culturing of Vero cells. Dense incorporation of AuNPs enables production of a printed 3D grid structure with 3D SERS performance, but with no measurable adverse effects on cell growth. Label-free SERS spectra were collected within a hydrogel, and a random forest binary classifier was developed to discriminate Vero cell signals from the hydrogel background with an accuracy of 87.5%. The results suggest that SERS signals from cellular components, such as proteins, lipids, and carbohydrates, account for this discrimination. We demonstrate visualization of cell shape, location, and density by combining predicted binary maps with peak feature intensity maps in 2D and 3D. SERS images with a resolution of ≈3 μm match well with the microscopy images and show clear increases in intensity with incubation time. We suggest that 3D SERS cell imaging is a promising means to examine the effect of external cell stimuli on cellular behavior for diagnostic purposes.


Radiographic diagnosis of breast implant rupture: current status and comparison of techniques.
Rupture of a breast implant is a recognized complication of augmentation mammaplasty and reconstructive breast surgery. Due to concerns over the extravasation of silicone gel within adjacent tissue and distant body sites, considerable attention has been given to the radiographic detection of mammary implant rupture. A metaanalysis comparing the accuracy of various currently available imaging modalities was conducted and an algorithm suggested to guide clinicians in the detection of breast implant rupture. Advantages and limitations of mammography, xeromammography, ultrasonography, MRI, and CT are outlined as well as some of the most specific radiographic signs of each with illustrative examples from patients evaluated at our institution. Results of our retrospective analysis corroborated by a review of the most recent literature reveal that mammography supplemented with ultrasonography constitutes the most cost-effective initial study, followed by MRI if these are equivocal. MRI is the most sensitive and specific study to evaluate breast implant rupture.


Broad range detection of viral and bacterial pathogens in bronchoalveolar lavage fluid of children to identify the cause of lower respiratory tract infections.
Knowledge on the etiology of LRTIs is essential for improvement of the clinical diagnosis and accurate treatment. Molecular detection methods were applied to identify a broad range of bacterial and viral pathogens in a large set of bronchial alveolar lavage (BAL) fluid samples. The patterns of detected pathogens were correlated to the clinical symptoms. BAL fluid samples and clinical data were collected from 573 hospitalized children between 1 month and 14 years of age with LRTIs, enrolled from January to December 2018. Pathogens were detected using standardized clinical diagnostics, with a sensitive, high-throughput GeXP-based multiplex PCR and with multiplex qPCR. Data were analyzed to describe the correlation between the severity of respiratory tract disease and the pathogens identified. The pathogen detection rate with GeXP-based PCR and multiplex qPCR was significantly higher than by clinical routine diagnostics (76.09% VS 36.13%,χ2 = 8.191, P = 0.004). The most frequently detected pathogens in the BAL fluid were human adenovirus (HADV)(21.82%), Mycoplasma pneumoniae (20.24%), human rhinovirus (13.96%), Streptococcus pneumoniae (8.90%) and Haemophilus influenzae (8.90%). In 16.4% of the cases co-detection with two or three different pathogens was found. Viral detection rates declined with age, while atypical pathogen detection rates increased with age. Oxygen supply in the HADV and Influenza H1N1 infected patients was more frequent (49.43%) than in patients infected with other pathogens. Broad range detection of viral and bacterial pathogens using molecular methods is a promising and implementable approach to improve clinical diagnosis and accurate treatment of LRTI in children.


Different imprinting status of IGF-2 in epithelial ovarian tumors.
To explore whether the imprinting status of IGF-2 in the malignant epithelial ovarian tumors is different from that in benign tumors, the target sequences (DNA and RNA) which contain a polymorphism site for ApaI restriction endonuclease digestion were amplified with PCR and RT-PCR methods. Then the PCR/RT-PCR products were digested by ApaI. The IGF-2 transcriptional pattern came out from the results of endonucleases digestion. Among the 36 cases of benign epithelial ovarian tumors, 20 were heterozygous for ApaI locus and all showed genomic imprinting. While in the malignant group, 22 were heterozygous for ApaI locus but six were found to lose imprinting. Significant differences existed between the two groups (P < 0.05). Loss of imprinting of IGF-2 may serve as a marker for differentiating the malignant ovarian cancers from the benign ones. In a new field of molecular genetics, our research provides an experimental basis for genetic diagnosis and treatment of the ovarian cancers.


Acute cardioembolic cerebral infarction: answers to clinical questions.
Cardioembolic cerebral infarction (CI) is the most severe subtype of ischaemic stroke but some clinical aspects of this condition are still unclear. This article provides the reader with an overview and up-date of relevant aspects related to clinical features, specific cardiac disorders and prognosis of CI. CI accounts for 14-30% of ischemic strokes; patients with CI are prone to early and long-term stroke recurrence, although recurrences may be preventable by appropriate treatment during the acute phase and strict control at follow-up. Certain clinical features are suggestive of CI, including sudden onset to maximal deficit, decreased level of consciousness at onset, Wernicke's aphasia or global aphasia without hemiparesis, a Valsalva manoeuvre at the time of stroke onset, and co-occurrence of cerebral and systemic emboli. Lacunar clinical presentations, a lacunar infarct and especially multiple lacunar infarcts, make cardioembolic origin unlikely. The most common disorders associated with a high risk of cardioembolism include atrial fibrillation, recent myocardial infarction, mechanical prosthetic valve, dilated myocardiopathy and mitral rheumatic stenosis. Patent foramen ovale and complex atheromatosis of the aortic arch are potentially emerging sources of cardioembolic infarction. Mitral annular calcification can be a marker of complex aortic atheroma in stroke patients of unkown etiology. Transthoracic and transesophageal echocardiogram can disclose structural heart diseases. Paroxysmal atrial dysrhythmia can be detected by Holter monitoring. Magnetic resonance imaging, transcranial Doppler, and electrophysiological studies are useful to document the source of cardioembolism. In-hospital mortality in cardioembolic stroke (27.3%, in our series) is the highest as compared with other subtypes of cerebral infarction. Secondary prevention with anticoagulants should be started immediately if possible in patients at high risk for recurrent cardioembolic stroke in which contraindications, such as falls, poor compliance, uncontrolled epilepsy or gastrointestinal bleeding are absent. Dabigatran has been shown to be non-inferior to warfarin in the prevention of stroke or systemic embolism. All significant structural defects, such as atrial septal defects, vegetations on valve or severe aortic disease should be treated. Aspirin is recommended in stroke patients with a patent foramen ovale and indications of closure should be individualized. CI is an important topic in the frontier between cardiology and vascular neurology, occurs frequently in daily practice, has a high impact for patients, and health care systems and merits an update review of current clinical issues, advances and controversies.


Rapid identification and source-tracking of Listeria monocytogenes using MALDI-TOF mass spectrometry.
Listeria monocytogenes is an important foodborne pathogen responsible for the sometimes fatal disease listeriosis. Public health concerns and stringent regulations associated with the presence of this pathogen in food and food processing environments underline the need for rapid and reliable detection and subtyping techniques. In the current study, the application of matrix assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS) as a single identification and source-tracking tool for a collection of L. monocytogenes isolates, obtained predominantly from dairy sources within Australia, was explored. The isolates were cultured on different growth media and analysed using MALDI-TOF MS at two incubation times (24 and 48 h). Whilst reliable genus-level identification was achieved from most media, identification at the species level was found to be dependent on culture conditions. Successful speciation was highest for isolates cultured on the chromogenic Agar Listeria Ottaviani Agosti agar (ALOA, 91% of isolates) and non-selective horse blood agar (HBA, 89%) for 24h. Chemometric statistical analysis of the MALDI-TOF MS data enabled source-tracking of L. monocytogenes isolates obtained from four different dairy sources. Strain-level discrimination was also observed to be influenced by culture conditions. In addition, t-test/analysis of variance (ANOVA) was used to identify potential biomarker peaks that differentiated the isolates according to their source of isolation. Source-tracking using MALDI-TOF MS was compared and correlated with the gold standard pulsed-field gel electrophoresis (PFGE) technique. The discriminatory index and the congruence between both techniques were compared using the Simpsons Diversity Index and adjusted Rand and Wallace coefficients. Overall, MALDI-TOF MS based source-tracking (using data obtained by culturing the isolates on HBA) and PFGE demonstrated good congruence with a Wallace coefficient of 0.71 and comparable discriminatory indices of 0.89 and 0.86, respectively. MALDI-TOF MS thus represents a rapid and cost-effective source-tracking technique for L. monocytogenes.


Measured concentrations of consumer product chemicals in California house dust: Implications for sources, exposure, and toxicity potential.
Household dust is a reservoir of various consumer product chemicals. Thus, characterizing comprehensive chemical profiles of house dust may help improve our understanding of residential chemical exposure. We have previously developed a method for detecting a broad spectrum of chemicals in dust by applying a combination of target, suspect screening, and non-target methods with mass spectrometry preceded by liquid chromatography and gas chromatography. Building upon a previous study that detected 271 compounds in 38 dust samples, we presented concentrations of 144 compounds that were confirmed and quantified by standards in the same set of samples. Ten compounds were measured with median concentrations greater than 10 000 ng/g of dust: cis-hexadec-6-enoic acid, squalene, cholesterol, vitamin E, bis(2-ethylhexyl) phthalate, dioctyl terephthalate, linoleic acid, tricaprylin, tris(1-chloroisopropyl) phosphate, and oxybenzone. We also reviewed in vitro toxicity screening data to identify compounds that were not previously detected in indoor dust but have potential for adverse health effects. Among 119 newly detected compounds, 13 had endocrine-disrupting potential and 7 had neurotoxic potential. Toxicity screening data were not available for eight biocides, which may adversely affect health. Our results strive to provide more comprehensive chemical profiles of house dust and identified information gaps for future health studies.


[Expression and intranuclear distribution of nucleolin in estrogen receptor-negative and estrogen receptor-positive breast cancers in women measured by laser scanning cytometry].
Nucleolin (NU) is one of the most abundant nucleolar proteins. Nucleolin is mainly involved in ribosome biogenesis that is supported by the ability of NU to bind rDNA and modify the structure of chromatin by binding to histon H1. Estrogen receptor alpha (ERalpha) is a DNA-binding transcriptional factor. It is estimated that 69-85% of breast cancers in women are ERalpha-positive. The aim of the study was to assess the expression and intranuclear distribution of NU in invasive ductal and lobular breast cancers in women and their relationship to ERalpha-status, histologic type and grade of breast cancer, and lymph node status. For this purpose, laser scanning cytometry (LSC) was used. Measurements were done in cytospins of cancer cells of 87 ductal and 11 lobular invasive breast cancers. The cells were labeled with mouse anti-human NU antibody followed by F(ab')2 fragments of FITC-conjugated goat anti-mouse antibody. Nuclei were counterstained with 5 microg/mL of propidium iodide in the presence of 100 microg/mL of RNase A. All measurements were performed using LSC. The following parameters of individual cancer cells were calculated: NU fluorescence within the nucleus, within nucleolin aggregates (NUA) and in the remaining karyoplasm, number of NUA, area of the nucleus and NUA. The percentage of ER-positive breast cancer cells was calculated in parallel by the automated image analysis in formalin-fixed sections using immunohistochemistry with anti-ERalpha antibody. The cut-off value for ER-negative tumors was set at 10% of positively stained nuclei. Statistical analysis was done using the Statistica 5.0 software. P values less than 0.05 were considered statistically significant. The mean area of the nucleus of ductal cancer cells was significantly higher and NU expression lower in ERalpha-negative cancers than in ERalpha-positive ones (p = 0.007 and p = 0.04, respectively). The mean area of NUA and NU expression in ductal cancers were higher than in lobular cancers (p = 0.03 and p = 0.02, respectively). The expression of NU within the nucleus and within the karyoplasm besides NUA was significantly higher in ductal than in lobular cancers (p = 0.02 and p = 0.04, respectively). The expression of NU in the remaining karioplasm of tumor cells of lymph node-positive cancers was lower than in node-negative ones (p = 0.04). The same relation was found for ductal cancers (p = 0.02). The differences in nucleolin expression and its intranuclear distribution in ERalpha-negative and ERalpha-positive breast cancers, as well as ductal and lobular cancers point to biologic differences between these carcinomas. The method used in the study may be applied to measurements of expression and intranuclear distribution of other nuclear proteins or to simultaneous measurement of expression and distribution of nuclear and cytoplasmic proteins.


Mouse models and methods for studying human disease, acute kidney injury (AKI).
Acute kidney injury (AKI) is serious complication in hospitalized patients with high level of mortality. There is not much progress made for the past 50 years in reducing the mortality rate despite advances in understanding disease pathology. Using variety of animal models of acute kidney injury, scientist studies the pathogenic mechanism of AKI and to test therapeutic drugs, which may reduce renal injury. Among them, renal pedicle clamping and cisplatin induced nephrotoxicity in mice are most prominently used, mainly due to the availability of gene knockouts to study specific gene functions, inexpensive and availability of the inbred strain with less genetic variability. However, ischemic mouse model is highly variable and require excellent surgical skills to reduce variation in the observation. In this chapter, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion and cisplatin induced nephrotoxicity. We also discuss the protocol for the isolation and analysis of infiltrated inflammatory cell into the kidney by flow cytometry. Information provided in this chapter will help scientist who wants to start research on AKI and want to establish the mouse model for ischemic and toxic kidney injury.


External quality assessment for clinical microbiology in Norway 1986-1987.
During the period 1986-1987 eight external quality assessment tests for clinical microbiology were performed, each consisting of four simulated clinical specimens. The results are reported, evaluated and some problem areas discussed.


Urodynamic findings in children with isolated epispadias.
The exstrophy-epispadias complex represents a spectrum of anomalies with variable implications for upper and lower urinary tract function. Successful treatment of incontinence in this population is challenging and often elusive. To date few studies have focused on urodynamic findings specific to primary epispadias. We retrospectively reviewed the records of patients presenting with primary epispadias in the absence of bladder exstrophy. We identified 18 boys and 12 girls, of whom 16 underwent formal urodynamic evaluation before (5), after (6) or before and after (5) surgical narrowing of the bladder neck. Bladder capacity was recorded as percent of expected capacity for age. Bladders were considered hypertonic when end filling pressure was greater than 20 cm. water. End filling pressure was defined as the pressure at which urinary leakage was noted or the patient had discomfort. Uninhibited contractions were considered significant when the amplitude was greater than 15 cm water. The ability of the detrusor to generate a voiding contraction at the end of the filling phase was also recorded. Urodynamic studies were performed with a balloon catheter occluding the incompetent bladder neck or with a standard urodynamic catheter after formal bladder neck repair. Before bladder neck repair average bladder capacity was 157 ml (range 55 to 450), corresponding to 52% (range 22 to 100) of expected capacity. Significant uninhibited contractions were noted in 2 patients. In 7 of the 9 evaluable patients (78%) a voiding contraction was generated. In children in whom urodynamic studies were done after surgery mean bladder capacity was 260 ml (range 77 to 660), corresponding to 76% (range 36 to 147) of expected capacity. Hypertonicity and hyperreflexia were noted in 3 and 2 patients, respectively. In 5 of the 11 cases (46%) a voiding bladder contraction was generated. Of the 5 patients who underwent urodynamic evaluation before and after bladder neck repair the percent increase in bladder capacity was significantly greater in the 2 boys (67 and 110%, respectively) than in the 3 girls (-20, 10 and 20, respectively). The most frequently noted urodynamic pattern before surgical correction of the bladder neck in patients with isolated epispadias is a low capacity, highly compliant bladder with minimal detrusor dysfunction. Postoperatively capacity increases, albeit to a greater extent in boys than in girls, and the incidence of detrusor dysfunction increases as well. In some patients classic bladder neck repair may result in detrimental bladder dynamics due to as yet poorly elucidated mechanisms.


Discussing sentinel lymph node biopsy with your melanoma patients.
Sentinel lymph node biopsy, indicated for stage 1B/2 melanoma may be an underutilized diagnostic modality. Experts in the field agree that sentinel lymph node biopsy should be offered to patients with T1 melanomas with primary tumor ulceration, a mitotic rate greater than or equal to 1/mm2, and/or Clark level IV/V invasion especially if tumor thickness exceeds 0.75 mm. It is the responsibility of practitioners to characterize patients as eligible or non-eligible for the sentinel node procedure. Furthermore, it is important to obtain a fully informed consent and explain to patients the statistics of the progonostic information garnered by the test.


Exercise training improves outcomes of a dyspnea self-management program.
The purpose of this study was twofold: (1) to determine whether exercise training adds to the benefit of a dyspnea self-management (DM) program; and (2) to determine if there is a "dose response" to supervised exercise training (0, 4, or 24 sessions) in dyspnea, exercise performance, and health-related quality of life. Subjects with chronic obstructive pulmonary disease (n = 103, 46 men, 57 women; age 66 +/- 8 years; forced expiratory volume in 1 second 44.8 +/- 14% predicted) were randomized to DM, DM-exposure, or DM-training. Dyspnea self-management included individualized education about dyspnea management strategies, a home-walking prescription, and daily logs. Outcomes were measured at baseline and 2 months as part of a 1-year longitudinal randomized clinical trial. Outcomes included dyspnea during laboratory exercise and with activities of daily living (Chronic Respiratory Questionnaire [CRQ]), Shortness of Breath Questionnaire, Baseline/Transitional Dyspnea Index), exercise performance (incremental treadmill tests (ITTs) and endurance treadmill tests (ETTs), 6-minute walk (6MW), and health-related quality of life (SF-36). The DM-training group had significantly greater improvements than the DM-exposure and the DM groups in dyspnea at isotime during ITT (P =.006); exercise performance during ITT (P =.005), ETT (P =.003), and 6MW (P =.01); SF-36 Vitality (P =.031); and CRQ mastery (P =.007). There was a dose-dependent improvement in CRQ dyspnea scores (P <.05) with significant improvements only in the DM-training and DM-exposure groups. Exercise training substantially improved the impact of a dyspnea self-management program with a home walking prescription (DM). This impact tended to be dependent on the "dose" of exercise.


Structural stability of Bacillus thuringiensis delta-endotoxin homolog-scanning mutants determined by susceptibility to proteases.
Forty homolog-scanning (double-reciprocal-crossover) mutant proteins of two Bacillus thuringiensis delta-endotoxin genes (cryIAa and cryIAc) were examined for potential structural alterations by a series of proteolytic assays. Three groups of mutants could be identified. Group 1, consisting of 13 mutants, showed no delta-endotoxin present during overexpression conditions in Escherichia coli (48 h at 37 degrees C, with a ptac promoter). These mutants produced full-sized delta-endotoxin detectable by polyacrylamide gel electrophoresis with Coomassie blue staining or Western immunoanalysis after 24 h of growth but not after 48 h, suggesting sensitivity to intracellular proteases. Group 2 consisted of 13 mutants that produced stable delta-endotoxins that were completely digested by 2% bovine trypsin. In contrast, native delta-endotoxin produces a 65,000-Da trypsin-resistant peptide, which is the active toxin. Group 3 mutants expressed delta-endotoxin and trypsin-stable toxins, similar to the wild type. In this study, 12 group 3 mutant toxins were compared with wild type toxins by thermolysin digestion at a range of temperatures. The two wild-type toxins exhibited significant differences in thermolysin digestion midpoints. Among the group 3 mutants, most possessed significantly different protein stabilities relative to their parental toxins. Two of the group 3 mutants were observed to have exchanged the thermolysin sensitivity properties of the parental toxins.


Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice.
Western pattern diets induce neuroinflammation and impair cognitive behavior in humans and animals. Neuroinflammation and cognitive impairment have been associated with microbiota dysbiosis, through the gut-brain axis. Furthermore, microbiota-accessible carbohydrates (MACs) found in dietary fiber are important in shaping the microbial ecosystem and have the potential to improve the gut-brain-axis. However, the effects of MACs on neuroinflammation and cognition in an obese condition have not yet been investigated. The present study aimed to evaluate the effect of MACs on the microbiota-gut-brain axis and cognitive function in obese mice induced by a high-fat and fiber deficient (HF-FD) diet. C57Bl/6 J male mice were fed with either a control HF-FD or a HF-MAC diet for 15 weeks. Moreover, an additional group was fed with the HF-MAC diet in combination with an antibiotic cocktail (HF-MAC + AB). Following the 15-week treatment, cognitive behavior was investigated; blood, cecum content, colon, and brain samples were collected to determine metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology. We report MACs supplementation prevented HF-FD-induced cognitive impairment in nesting building and temporal order memory tests. MACs prevented gut microbiota dysbiosis, including increasing richness, α-diversity and composition shift, especially in Bacteroidetes and its lower taxa. Furthermore, MACs increased colonic mucus thickness, tight junction protein expression, reduced endotoxemia, and decreased colonic and systemic inflammation. In the hippocampus, MACs suppressed HF-FD-induced neuroglia activation and inflammation, improved insulin IRS-pAKT-pGSK3β-pTau synapse signaling, in addition to the synaptic ultrastructure and associated proteins. Furthermore, MACs' effects on improving colon-cognitive parameters were eliminated by wide spectrum antibiotic microbiota ablation. These results suggest that MACs improve cognitive impairments via the gut microbiota-brain axis induced by the consumption of an HF-FD. Supplemental MACs to combat obesity-related gut and brain dysfunction offer a promising approach to prevent neurodegenerative diseases associated with Westernized dietary patterns and obesity.


[Combined treatment of myodystonic pain syndromes by manual therapy and acupuncture].
Combination of manual therapy (++post-isometric relaxation) and acupuncture in the treatment of myodystonic syndromes is based from the standpoint of realization of the neurophysiological components of the pathogenesis of myofascicular hypertonus. The controlled afferent flow created by ++post-isometric relaxation and acupuncture exerts a varying effect on the structural and functional levels of the nervous system. The therapeutic effect of manual therapy is realized at the special segmental level, that of acupuncture with participation of the suprasegmental systems.


Pharmacokinetics of delta-9-tetrahydrocannabinol following acute cannabis smoke exposure in mice; effects of sex, age, and strain.
Increased use of cannabis and cannabinoids for recreational and medical purposes has led to a growth in research on their effects in animal models. The majority of this work has employed cannabinoid injections; however, smoking remains the most common route of cannabis consumption. To better model real-world cannabis use, we exposed mice to cannabis smoke to establish the pharmacokinetics of Δ9THC and its metabolites in plasma and brain. To determine the time course of Δ9THC and two major metabolites [11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (11-COOH-THC)], male and female C57BL/6J mice were exposed to smoke from sequentially burning 5 cannabis cigarettes. Following smoke exposure, trunk blood and brains were collected at 6 time points (10-240 min). Plasma and brain homogenates were analyzed for Δ9THC and metabolites using a validated ultraperformance liquid chromatography-tandem mass spectrometry method. To assess effects of age, sex, and mouse strain, we exposed mice of four strains (C57BL/6J, FVB, Swiss Webster, and 129S6/SvEv, aged 4-24 months) to cannabis using the same smoke regimen. Samples were collected 10 and 40 min following exposure. Lastly, to assess effects of dose, C57BL/6J mice were exposed to smoke from burning 3 or 5 cannabis cigarettes, with samples collected 40 min following exposure. The pharmacokinetic study revealed that maximum plasma Δ9THC concentrations (Cmax) were achieved at 10 and 40 min for males and females, respectively, while Cmax for brain Δ9THC was observed at 20 and 40 min for males and females, respectively. There were no age or strain differences in plasma Δ9THC concentrations at 10 or 40 min; however, 129S6/SvEv mice had significantly higher brain Δ9THC concentrations than FVB mice. Additionally, 3 cigarettes produced significantly lower plasma 11-COOH-THC concentrations compared to 5 cigarettes, although dose differences were not evident in plasma or brain concentrations of Δ9THC or 11-OH-THC. Across all experiments, females had higher levels of 11-COOH-THC in plasma compared to males. The results reveal robust sex differences in Δ9THC pharmacokinetics, and lay the groundwork for future studies using mice to model the pharmacodynamics of smoked cannabis.


[Visceral lesions in hypereosinophilia].
The hypereosinophilic syndrome is an ill-defined nosological entity with predominant risks of cardiac and/or neurological lesions. In the light of new data on the effector cytotoxic effects of eosinophils, we have tried to establish new criteria of severity by purifying the circulating eosinophils of 14 patients with hypereosinophilic syndrome and testing their toxicity. This study has revealed the existence of low density ("hypodense") eosinophils with potential cytotoxicity in vitro. The worst clinical forms of the syndrome were observed in the group of patients with positive eosinophil toxicity tests. The significance of these cellular changes (hypodensity, eosinotoxicity) and their relationship with the clinical manifestations are discussed.


Extracellular Vesicles Isolated from Familial Alzheimer's Disease Neuronal Cultures Induce Aberrant Tau Phosphorylation in the Wild-Type Mouse Brain.
Extracellular vesicles (EVs) are a heterogeneous group of secreted particles consisting of microvesicles, which are released by budding of the cellular membrane, and exosomes, which are secreted through exocytosis from multivesicular bodies. EV cargo consists of a wide range of proteins and nucleic acids that can be transferred between cells. Importantly, EVs may be pathogenically involved in neurodegenerative diseases such as Alzheimer's disease (AD). While EVs derived from AD neurons have been found to be neurotoxic in vitro, little is known about the pathological consequences of AD EVs in vivo. Furthermore, although all known familial AD (fAD) mutations involve either amyloid-β protein precursor (AβPP) or the machinery that processes AβPP, hyperphosphorylation of the microtubule associated protein tau appears to play a critical role in fAD-associated neurodegeneration, and previous reports suggest EVs may propagate tau pathology in the AD brain. Therefore, we hypothesized that fAD EVs may have a mechanistic involvement in the development of fAD-associated tau pathology. To test this, we isolated EVs from iPSC-derived neuronal cultures generated from an fAD patient harboring a A246E mutation to presenilin-1 and stereotactically injected these EVs into the hippocampi of wild-type C57BL/6 mice. Five weeks after injection, mice were euthanized and pathology evaluated. Mice injected with fAD EVs displayed increased tau phosphorylation at multiple sites relative to PBS and non-disease control EV injected groups. Moreover, fAD EV injected hippocampi contained significantly more tau inclusions in the CA1 hippocampal neuronal field than controls. In total, these findings identify EVs as a potential mediator of fAD-associated tau dysregulation and warrant future studies to investigate the therapeutic potential of EV-targeted treatments for fAD.


Patient-specific quantification of respiratory motion-induced dose uncertainty for step-and-shoot IMRT of lung cancer.
The objective of this study was to quantify respiratory motion-induced dose uncertainty at the planning stage for step-and-shoot intensity-modulated radiation therapy (IMRT) using an analytical technique. Ten patients with stage II∕III lung cancer who had undergone a planning four-dimensional (4D) computed tomographic scan and step-and-shoot IMRT planning were selected with a mix of motion and tumor size for this retrospective study. A step-and-shoot IMRT plan was generated for each patient. The maximum and minimum doses with respiratory motion were calculated for each plan, and the mean deviation from the 4D dose was calculated, taking delivery time, fractionation, and patient breathing cycle into consideration. For all patients evaluated in this study, the mean deviation from the 4D dose in the planning target volume (PTV) was <2.5%, with a standard deviation <1.2%, and maximum point dose variation from the 4D dose was <6.2% in the PTV assuming delivery dose rate of 200 MU∕min and patient breathing cycle of 8 s. The motion-induced dose uncertainty is a function of motion, fractionation, MU (plan modulation), dose rate, and patient breathing cycle. Respiratory motion-induced dose uncertainty varies from patient to patient. Therefore, it is important to evaluate the dose uncertainty on a patient-specific basis, which could be useful for plan evaluation and treatment strategy determination for selected patients.


The conserved histone chaperone LIN-53 is required for normal lifespan and maintenance of muscle integrity in Caenorhabditis elegans.
Whether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and aspects of healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different biological processes. The epigenetic factor LIN-53 (RBBP4/7) associates with different chromatin-regulating complexes to safeguard cell identities in Caenorhabditis elegans as well as mammals, and has a role in preventing memory loss and premature aging in humans. We show that LIN-53 interacts with the nucleosome remodeling and deacetylase (NuRD) complex in C. elegans muscles to ensure functional muscles during postembryonic development and in adults. While mutants for other NuRD members show a normal lifespan, animals lacking LIN-53 die early because LIN-53 depletion affects also the histone deacetylase complex Sin3, which is required for a normal lifespan. To determine why lin-53 and sin-3 mutants die early, we performed transcriptome and metabolomic analysis revealing that levels of the disaccharide trehalose are significantly decreased in both mutants. As trehalose is required for normal lifespan in C. elegans, lin-53 and sin-3 mutants could be rescued by either feeding with trehalose or increasing trehalose levels via the insulin/IGF1 signaling pathway. Overall, our findings suggest that LIN-53 is required for maintaining lifespan and muscle integrity through discrete chromatin regulatory mechanisms. Since both LIN-53 and its mammalian homologs safeguard cell identities, it is conceivable that its implication in lifespan regulation is also evolutionarily conserved.


Muscle Function, Body Composition, Insulin Sensitivity and Physical Activity in Adolescents Born Preterm: Impact of Gestation and Vitamin D Status.
Whilst several studies have explored adolescent metabolic and cognitive function after preterm birth, few have explored muscle function and physical activity. We set out to examine the relationship between gestational age and muscle metabolism in a cohort of adolescents who were born preterm. Participants were recruited from the Newcastle preterm birth growth study cohort. They did not have severe neurological disease and were not on daily medication. Participants underwent an assessment of oxidative muscle function using phosphorus magnetic resonance spectroscopy that included the half-time for recovery of equilibrium of phosphocreatine, τ½PCr. In addition, we measured key variables that might affect muscle function including physical activity levels determined by 3-day accelerometry, body composition using air displacement plethysmography, insulin sensitivity using the homeostatic model assessment/Matsuda index and serum vitamin D concentrations. 60 adolescents (35F) median age 15.6 years (range 12.1−18.8) with a median gestation of 31 weeks (range 24 to 34 weeks) underwent a single assessment. Males were more active and spent less time in sedentary mode. Time spent in light activity was associated with insulin sensitivity (IS) (Matsuda Index; p < 0.05) but there were no strong correlations between activity levels and gestational age. Greater fat mass, waist circumference and body mass index were all associated with lower IS. Gestational age was negatively associated with adjusted measures of oxidative muscle function (τ½PCr). In a stepwise multivariate linear regression model, gestational age at birth was the most significant predictor of oxidative muscle function (p = 0.005). Higher serum vitamin D levels were also associated with faster phosphocreatine recovery time (p = 0.045). Oxidative function in the skeletal muscle of adolescents born preterm is associated with gestational age and vitamin D concentrations. Our study suggests that being born preterm may have a long-term impact on muscle metabolism.


Formation mechanism of polycyclic aromatic hydrocarbons in benzene combustion: Quantum chemical molecular dynamics simulations.
High temperature quantum chemical molecular dynamics simulations on the polycyclic aromatic hydrocarbon (PAH) formation during combustion of benzene were performed using the density-functional tight-binding (DFTB) method. Systems with varying H/C of 0.8, 0.6, 0.4, and 0.2 and temperatures of T(n)=2500 K and T(n)=3000 K were employed for the study of the PAH formation and growth mechanism, and trajectories were analyzed by recording average C:H compositions, common elementary reactions and molecular species, ring count, and other characteristic quantities as functions of time. We found that at H/C=0.8 mostly short polyacetylenic hydrocarbons were formed, and no significant PAH growth was found. At lower H/C ratio, longer polyacetylenic chains started to form and new five- and six-membered rings were created due to chain entanglement. Significant PAH growth forming only pericondensed PAHs was observed at lower H/C ratios of 0.4 and 0.2. In addition, smaller hydrocarbon species, such as C(2)H(2), C(2)H, and C(2), are constantly produced by fragmentation of hydrocarbons (unimolecular reactions) and remain common species, although they are simultaneously consumed by the H-abstraction-C(2)H(2)-addition growth mechanism. Hydrogen is found to have a clear inhibitive effect on PAH and carbon cluster growth in general, in agreement with recent experimental observations.


[Undetermined family diagnosis--uncertain diagnosis].
The results of testing convergence- and discriminance-validity of the central dimensions "cohesion" and "control" for family diagnostics and therapy are presented in this paper by means of a multitrait-multimethod matrix which includes five known family diagnostic instruments from seven studies published up until the end of 1995. The main result demonstrates that both discriminance- and convergence-validity cannot be considered safe from "cohesion" or "control".


Mild cognitive impairment in combination with comorbid diabetes mellitus and hypertension is negatively associated with health-related quality of life among older persons in Taiwan.
To fill the gap in knowledge about associations of health-related quality of life (HRQoL) with comorbid diabetes mellitus (DM), hypertension (HTN), and/or mild cognitive impairment (MCI) in the elderly, we explored associations of comorbid DM, HTN, and/or MCI with HRQoL. Data for this study were from a population-based cross-sectional survey of elderly Taiwanese (≥ 65 years old). Participants (N = 4,634; 47.9% male) were categorized into eight chronic-illness groups: DM only (n = 224); HTN only (n = 1226); DM and HTN (n = 365); MCI only (n = 497); DM and MCI (n = 58); HTN and MCI (n = 303); DM, HTN, and MCI (n = 101); and none (healthy; n = 1860). Associations were examined between the eight chronic-illness groups and HRQoL (measured by EQ-5D scores) using binary logistic regression analyses and generalized linear models adjusted for covariates. Index scores were calculated from EQ-5D scores using Taiwan's general population-preference weights. Compared to the healthy group, after adjusting covariates, MCI alone or with other comorbidities was significantly, negatively associated with HRQoL. Among all chronic-illness groups, comorbid DM, HTN, and MCI exhibited the lowest HRQoL. After adjusting covariates, between-group odds ratios for index scores were significant when comparing comorbid DM and MCI to DM only, comparing comorbid HTN and MCI to HTN only and comorbid DM, comparing HTN and MCI to comorbid DM and HTN, suggesting that MCI additively affects HRQoL. HRQoL of older Taiwanese adults was negatively associated with having MCI. Thus, clinicians managing older persons with chronic illnesses should assess their cognitive function to identify high-risk groups needing HRQoL assistance.


Contrast enhanced ultrasound for the characterization of focal liver lesions.
to present the practice of two experienced centres concerning the use of contrast enhanced ultrasound (CEUS) in the characterization of focal liver lesions (FLL). A prospective, bicentric study, between 09.2009-09.2010 was undertaken and 729 FLL (506-Center A, 223-Center B) were evaluated. A CEUS examination was considered conclusive, if the FLL had a typical enhancement pattern according to EFSUMB Guidelines. From the 729 cases with FLL, 389 (53.4%) were patients without known and 340 (46.6%) with known chronic liver disease. CEUS was conclusive for the diagnosis in 597/729 cases (82%) and allowed the positive diagnosis of benign vs. malignant lesion in 662/729 (90.8%) FLL. For each center independently (Center A vs. Center B) the situation was as follows: conclusive for the diagnosis 390/506 (77.1%) vs 207/223 (92.8%) (p<0.0001), conclusive for the differentiation benign/malignant 449/506 (88.7%) vs. 213/223 (95.5%) (p=0.0032). In our bicentric study, CEUS was conclusive for diagnosis in 82% of FLL and the benign or malignant character of a lesion was demonstrated in 90.8% of cases. Thus, when faced with an uncharacteristic FLL on standard ultrasound, our local strategy in both centers was to perform CEUS as a first-line investigation thus avoiding other expensive examinations.


The intramolecular interaction of thiophene and furan with aromatic and fluoroaromatic systems in some [3.3]meta(heterocyclo)paracyclophanes: a combined computational and NMR spectroscopic study.
Four thiophene- and furan-containing [3.3]meta(heterocyclo)paracyclophanes were designed and synthesized to study the intramolecular interaction between standard heteroaromatic rings and tetra-H- or tetra-F-substituted benzenes. A complete conformational analysis, carried out by DFT calculations and variable-temperature NMR techniques, showed that, despite their structural similarity, these adducts have different conformational preferences and undergo different types of isomerizations depending on the nature of the heterocycle. The thiophene-derived adducts adopted a parallel stacked arrangement of the aromatic systems in the ground-state conformations. Their isomerization pathways involved a thiophene ring-flip process passing through an edge-to-face arranged transition state in which the heterocycle is perpendicular to the benzene platform and its sulfur atom points toward the center of that ring. The threshold energy barrier to the ring-flip process was higher by 10 kJ mol(-1) in the case of the adduct featuring the perfluorinated benzene. This difference was rationalized by assuming that the ground-state conformations of the H- and F-substituted compounds have different stability. On the contrary, the furan-derived adducts were shown by calculations and NMR spectroscopy to adopt, in their ground-state conformations, a perpendicular edge-to-face disposition of the rings with the oxygen atom pointing toward the benzene platform. The adoption of this arrangement was confirmed by X-ray crystallography. In the case of these compounds, the isomerization process involved distortion of the CH(2)SCH(2) bridges connecting the aromatic systems and the adoption of transition-state geometries for which the rings were arranged in a parallel-stacked orientation. Once again a very nice agreement was observed between the predicted and the experimentally determined geometries and pathways. In the case of the furan-containing compounds, the threshold barriers were found to be much lower in energy that those observed for the thiophene derivatives. Remarkably, they were virtually independent of the presence of fluorine atoms on the platform benzene ring.


More severe impairment of manual dexterity in bipolar disorder compared to unipolar major depression.
Mood disorders are associated with various neurocognitive deficits. However, few studies have reported the impairment of motor dexterity in unipolar depression and bipolar disorder. In the present study, manual dexterity was compared between unipolar major depression, bipolar disorder, and healthy controls. Manual dexterity was assessed by the Purdue pegboard test in 98 patients with unipolar major depression, 48 euthymic or depressed patients with bipolar disorder, and 158 healthy controls, matched for age and gender. Compared to healthy controls, sum of the scores of right, left, and both hands subtests (R+L+B) was significantly lower in both patients with unipolar depression and bipolar disorder (P=0.0034 and P<0.0001, respectively). Furthermore, R+L+B was significantly lower in bipolar disorder compared to unipolar depression (P=0.0016). Lithium dose and chlorpromazine equivalent dose of antipsychotics were significantly negatively correlated with some of the subtest scores. On the other hand, depression severity did not significantly correlate with any of the subtest scores. Difference in R+L+B between unipolar depression and bipolar disorder remained statistically significant even after controlling for gender, age, lithium dose, and chlorpromazine equivalent dose (P=0.0028). Limitations Bipolar patients during manic episode were not included in the study. Gross movement dexterity was impaired in both patients with unipolar depression and bipolar disorder. The severity of impairment was significantly greater in patients with bipolar disorder. The functional difference between unipolar and bipolar patients may suggest different pathological conditions between the two depressive disorders.