Recombination patterns around the breakpoints of a balanced 1;11 autosomal translocation associated with major mental illness.
The frequency and extent of pairing failure around human translocations are unknown. We have examined the pattern of recombination around the breakpoints of a balanced autosomal translocation t(1;11) (q43;q21) associated with major mental illness. DNA was available from 17 carriers and 10 non-translocation carriers with meioses involving four generations. The derivative 1 and 11 chromosomes were also isolated in somatic cell hybrids and used to confirm phase. We have genotyped pedigree members using 20 polymorphic markers within 10 cM on either side of both chromosome 1 and 11 breakpoints. We find no significant reduction of recombination in the vicinity of either breakpoint. However we estimate that there are insufficient meioses even in this large family to make a meaningful interpretation and suggest that sperm typing alone can answer these interesting questions.


A Family of ACO Routing Protocols for Mobile Ad Hoc Networks.
In this work, an ACO routing protocol for mobile ad hoc networks based on AntHocNet is specified. As its predecessor, this new protocol, called AntOR, is hybrid in the sense that it contains elements from both reactive and proactive routing. Specifically, it combines a reactive route setup process with a proactive route maintenance and improvement process. Key aspects of the AntOR protocol are the disjoint-link and disjoint-node routes, separation between the regular pheromone and the virtual pheromone in the diffusion process and the exploration of routes, taking into consideration the number of hops in the best routes. In this work, a family of ACO routing protocols based on AntOR is also specified. These protocols are based on protocol successive refinements. In this work, we also present a parallelized version of AntOR that we call PAntOR. Using programming multiprocessor architectures based on the shared memory protocol, PAntOR allows running tasks in parallel using threads. This parallelization is applicable in the route setup phase, route local repair process and link failure notification. In addition, a variant of PAntOR that consists of having more than one interface, which we call PAntOR-MI (PAntOR-Multiple Interface), is specified. This approach parallelizes the sending of broadcast messages by interface through threads.


[DEVELOPMENT AND CHALLENGES OF ANNULUS FIBROSUS TISSUE ENGINEERING].
To review the biomaterial and clinical prospects of annulus tibrosus tissue engineering. The recent literature concerning annulus fibrosus tissue engineering, including cell source, bioactive molecules, and biomaterial was extensively reviewed and summarized. Mesenchymal stem cells (MSCs) is an ideal seed cells. When annulus fibrosus cells and MSCs in the ratio of 2:1 are cultured, it shows the closest mRNA expression levels of annulus fibrosus-related markers. Bioactive molecules can be divided into 4 types: growth factors, morphogens, catabolic enzyme inhibitors, and intracellular regulators. They play an active role in promoting the synthesis of extracellular matrix, and maintaining intervertebral disc homeostasis and a balance between anabolic- and catabolic process in the disc. Based on the source, biological materials can be divided into natural materials, synthetic materials, and composite materials. The mechanical properties of the annulus fibrosus is an important basis for material design. Up to now, none of these scaffold materials is accepted as the most suitable one. The selection of scaffold materials is still to be further studied. The development of novel composite biomaterials is a trend. The annulus fibrosus tissue engineering for the anulus fibrosus regeneration and repair will bring very broad prospects for clinical application in future.


Influence of platelet-derived growth factor on lens epithelial cell proliferation and differentiation.
The expression pattern of platelet-derived growth factor (PDGF) and its receptor suggest a role in lens cell proliferation. PDGF is strongly expressed in the iris and ciliary body, situated opposite the proliferative cells of the lens epithelium which express the PDGF-alpha receptor. In this study, using lens epithelial explant cultures, we report that PDGF can induce a dose and time dependent increase in lens cell DNA synthesis. Culturing lens explants with both PDGF and FGF (a mitogen and differentiation factor for lens cells) resulted in responses greater than those induced by either growth factor alone. PDGF did not induce any changes typical of fibre differentiation; however, in combination with FGF it potentiated the fibre differentiating activity of FGF. Results obtained in this study support previous indications that PDGF has an important role in regulating lens cell proliferation. In addition, PDGF may have a role in potentiating FGF-induced lens fibre differentiation in vivo.


Is neck pain associated with worse health-related quality of life 6 months later? A population-based cohort study.
Current evidence suggests that neck pain is negatively associated with health-related quality of life (HRQoL). However, these studies are cross-sectional and do not inform the association between neck pain and future HRQoL. The purpose of this study was to investigate the association between increasing grades of neck pain severity and HRQoL 6 months later. In addition, this longitudinal study examines the crude association between the course of neck pain and HRQoL. This is a population-based cohort study. Eleven hundred randomly sampled Saskatchewan adults were included. Outcome measures were the mental component summary (MCS) and physical component summary (PCS) of the Short-Form-36 (SF-36) questionnaire. We formed a cohort of 1,100 randomly sampled Saskatchewan adults in September 1995. We used the Chronic Pain Questionnaire to measure neck pain and its related disability. The SF-36 questionnaire was used to measure physical and mental HRQoL 6 months later. Multivariable linear regression was used to measure the association between graded neck pain and HRQoL while controlling for confounding. Analysis of variance and t tests were used to measure the crude association among four possible courses of neck pain and HRQoL at 6 months. The neck pain trajectories over 6 months were no or mild neck pain, improving neck pain, worsening neck pain, and persistent neck pain. Finally, analysis of variance was used to examine changes in baseline to 6-month PCS and MCS scores among the four neck pain trajectory groups. The 6-month follow-up rate was 74.9%. We found an exposure-response relationship between neck pain and physical HRQoL after adjusting for age, education, arthritis, low back pain, and depressive symptomatology. Compared with participants without neck pain at baseline, those with mild (β=-1.53, 95% confidence interval [CI]=-2.83, -0.24), intense (β=-3.60, 95% CI=-5.76, -1.44), or disabling (β=-8.55, 95% CI=-11.68, -5.42) neck pain had worse physical HRQoL 6 months later. We did not find an association between neck pain and mental HRQoL. A worsening course of neck pain and persistent neck pain were associated with worse physical HRQoL. We found that neck pain was negatively associated with physical but not mental HRQoL. Our analysis suggests that neck pain may be a contributor of future poor physical HRQoL in the population. Raising awareness of the possible future impact of neck pain on physical HRQoL is important for health-care providers and policy makers with respect to the management of neck pain in populations.


Sputum smear microscopy result: a predictor for drug-resistant tuberculosis?
Until countries establish capacity for continuous surveillance systems, representative surveys of tuberculosis (TB) patients continue to improve our understanding of the burden of drug-resistant TB and help ensure appropriate allocation of resources. Although the available data are limited, the current recommendation of restricting surveys to sputum smear-positive patients is justified, given the greatly simplified logistics and only limited evidence in specific settings of an association between drug resistance and sputum smear status. Nonetheless, the relationship between drug resistance and sputum smear microscopy results may vary according to the setting and population under study. With the increasing availability and use of molecular diagnostics and the drive for universal drug susceptibility testing under the World Health Organization's End TB Strategy, substantially more data on drug resistance in the whole TB patient population should become available in the near future.


Physiological and acoustic characteristics of the male music theatre voice.
Six male music theatre singers were recorded in three different voice qualities: legit and two types of belt ("chesty" and "twangy"), on two vowels ([e] and [ɔ]), at four increasing pitches in the upper limit of each singer's belt range (∼250-440 Hz). The audio signal, the electroglottographic (EGG) signal, and the vocal tract impedance were all measured simultaneously. Voice samples were analyzed and then evaluated perceptually by 16 expert listeners. The three qualities were produced with significant differences at the physiological, acoustical, and perceptual levels: Singers produced belt qualities with a higher EGG contact quotient (CQEGG) and greater contacting speed quotient (Qcs), greater sound pressure level (SPL), and energy above 1 kHz (alpha ratio), and with higher frequencies of the first two vocal tract resonances (fR1, fR2), especially in the upper pitch range when compared to legit. Singers produced the chesty belt quality with higher CQEGG, Qcs, and SPL values and lower alpha ratios over the whole belt range, and with higher fR1 at the higher pitch range when compared to twangy belt. Consistent tuning of fR1 to the second voice harmonic (2f0) was observed in all three qualities and for both vowels. Expert listeners tended to identify all qualities based on the same acoustical and physiological variations as those observed in the singers' intended qualities.


Advanced glycation end products upregulate the endoplasmic reticulum stress in human periodontal ligament cells.
The accumulation of advanced glycation end products (AGEs) appears to be the main factor responsible for modulating periodontal inflammation in diabetes. The aim of this study is to examine the effects of AGEs on inflammation in human periodontal ligament cells and to investigate the mechanism with a specific emphasis on the role of endoplasmic reticulum (ER) stress-induced nuclear factor-kappa B (NF-κB) pathway. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expressions of ER markers and NF-κB were examined by Western blot analysis. The translocation of NF-κB was observed by immunofluorescence assay. Proinflammatory chemokine production was determined by enzyme-linked immunosorbent assay. Treatment with AGEs reduced cell viability in a concentration- and time-dependent manner. AGEs induced ER stress, as evidenced by survival molecules, such as glucose-regulated protein 78 (GRP78), double-stranded RNA-activated protein kinase-like ER kinase (PERK), and activating transcription factor 6 (ATF-6), and apoptotic molecules, such as CCAAT/enhancer binding protein homologous protein (CHOP) and caspase 12. AGEs upregulated the nucleoprotein expression of NF-κB, enhanced translocation of NF-κB from the cytoplasm to the nucleus, and increased the production of proinflammatory chemokines interleukin-6 and interleukin-8. AGEs mediate inflammation of human periodontal ligament cells via the ER stress-induced NF-κB pathway.


Onset and phoneme awareness and its relationship to letter knowledge in German-speaking preschool children.
The aim was to explore whether word-initial onset awareness is acquired before phoneme awareness and whether onset complexity influences performance on identification tasks. In addition, the relationship between onset and phoneme awareness and letter knowledge was investigated. In this study, 22 monolingual German-speaking preschool children aged 5;00-5;11 were tested. Onset, phoneme identification, and letter knowledge tasks were administered. The children were presented with pictures of word pairs. Both words in each pair shared a single-consonant onset, a two-consonant onset cluster or the first consonant of a consonant cluster. The children were asked to pronounce the shared sound(s). Additionally, they were asked to name all 26 upper-case letters. Onset awareness tasks were significantly easier to complete than phoneme awareness tasks. However, no influence of onset complexity on onset awareness performance was found. Moreover, letter knowledge correlated with all phonological awareness tasks. The results corroborate that phoneme awareness develops already at preschool age irrespective of explicit literacy tuition. Nevertheless, letter knowledge is closely related and should be linked to onset/phoneme awareness tasks.


Changes in Cerebral Oxygenation Associated with Intradialytic Blood Transfusion in Patients with Severe Anemia Undergoing Hemodialysis.
Hemodialysis (HD) patients frequently suffer from severe anemia caused by various hemorrhagic disorders in addition to renal anemia. Intradialytic blood transfusion is sometimes performed; however, the cerebral oxygenation changes associated with this procedure remain unclear. Sixteen HD patients with severe anemia who required intradialytic blood transfusion were included (12 men and 4 women; mean age, 64.8 ± 9.8 years). Cerebral regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy, and cerebral fractional oxygen extraction (FOE) was calculated before and after HD. Twenty-five HD patients with well-maintained hemoglobin (Hb) levels were included as a control group. Cerebral rSO2 values were significantly lower in HD patients with severe anemia than in the control group (42.4 ± 9.9 vs. 52.5 ± 8.5%, p = 0.001). Following intradialytic blood transfusion (385 ± 140 mL of concentrated red blood cells), Hb levels significantly increased (from 7.2 ± 0.9 to 9.1 ± 1.1 g/dL, p < 0.001), and cerebral rSO2 values significantly improved after HD (from 42.4 ± 9.9 to 46.3 ± 9.0%, p < 0.001). Cerebral FOE values before HD in patients with severe anemia were significantly higher than those in the control group (severe anemia, 0.56 ± 0.10; controls, 0.45 ± 0.08; p < 0.001). After HD with intradialytic blood transfusion, these values significantly decreased (0.52 ± 0.09 after HD versus 0.56 ± 0.10 before HD, p = 0.002). HD patients with severe anemia represented cerebral oxygen metabolism deterioration, which could be significantly improved by intradialytic blood transfusion.


Nearest level spacing statistics in open chaotic systems: generalization of the Wigner surmise.
We investigate the nearest level spacing statistics of open chaotic wave systems. To this end we derive the spacing distributions for the three Wigner ensembles in the one-channel case. The theoretical results give a clear physical meaning of the modifications on the spacing distributions produced by the coupling to the environment. Based on the analytical expressions obtained, we then propose general expressions of the spacing distributions for any number of channels, valid from weak to strong coupling. The latter expressions contain one free parameter. The surmise is successfully compared with numerical simulations of non-Hermitian random matrices and with experimental data obtained with a lossy electromagnetic chaotic cavity.


Endotoxin tolerance is associated with decreased prostaglandin H synthases-1 and -2.
Lipopolysaccharide (LPS) induces macrophage protein and eicosanoid synthesis. Previous studies have shown that LPS induction of eicosanoid metabolism is transcription dependent and that prostaglandin (PG) H synthase is the committed step in the conversion of arachidonic acid (AA) to thromboxane (Tx) B2. LPS tolerance induced by sublethal in vivo injections of LPS renders rats resistant to LPS in vivo and macrophages refractory to LPS-stimulated eicosanoid synthesis in vitro. This study examined potential activity and content changes in constitutive and mitogen inducible PGH synthase in LPS-stimulated control and tolerant macrophages. TxB2 levels were measured to evaluate basal PGH synthase activity and stimulation by Salmonella enteritidis LPS (50 micrograms/ml), calcium ionophore A-23187, and AA. All tolerant macrophage groups demonstrated decreased TxB2 synthesis. TxB2 synthesis stimulated by AA in tolerant cells was decreased by 70% (P < 0.05) compared with control macrophages. In subsequent studies changes in PGH synthase content were examined in rat peritoneal macrophages from tolerant and control rats incubated with and without LPS. Immunoblot analysis of PGH synthase-1 (constitutive) demonstrated no increase in cells stimulated with LPS compared with basal but was diminished by 62 +/- 9% (n = 4, P < 0.05) in tolerant macrophages compared with control cells. Immunoblot analysis of PGH synthase-2 (mitogen inducible) demonstrated induction in response to LPS that was maximal between 12 and 24 h. PGH synthase-2 was also induced in tolerant macrophages in response to LPS but was less than in control cells. The results demonstrate that endotoxin tolerance is associated with reduced activity and content of PGH synthase-1 and a decreased LPS induction of PGH synthase-2.(ABSTRACT TRUNCATED AT 250 WORDS)


Studies on the metabolism of diltiazem in man.
The human urinary metabolites of diltiazem were analyzed by thin-layer chromatography (TLC) and gas chromatography-mass spectrometry. Diltiazem was metabolized by deacetylation, N-demethylation, O-demethylation and conjugation. Metabolite MA, N- monodemethyl -diltiazem, was identified as a new major metabolite in human urine, and four metabolites were identified as deacetyl-diltiazem (M1), deacetyl-N- monodemethyl -diltiazem (M2), deacetyl-O-demethyl-diltiazem (M4), deacetyl-N,O-demethyl-diltiazem (M6) which were known as rat urinary metabolites. Metabolite M2, M4 and M6 were converted in part to glucuronides and/or sulfates. Unchanged diltiazem and metabolite MA were determined in human plasma and urine by TLC-densitometry. Diltiazem and metabolite MA excreted in 24-h urine were 44.4 and 48.5% of the total unconjugated form, respectively. The mean plasma level of metabolite MA was approximately one-third of diltiazem level. On the basis of these findings, a probable metabolic pathway of diltiazem in man is presented.


Hepatocyte DNA replication: effect of nutrients and intermediary metabolites.
Isolated adult rat liver parenchymal cells maintained in serum-free medium are stimulated by insulin and epidermal growth factor (EGF) to undergo DNA synthesis. Pyruvate, lactate, and, to a lesser extent, several other intermediary metabolites strikingly enhance DNA synthesis both under serum-free culture conditions and in the presence of dialyzed rat serum. High concentrations (2-50 mM) of these low-molecular-weight metabolites are necessary to produce optimal stimulation. Both alanine (greater than 2 mM) and glutamine (greater than 4 mM) are inhibitory under similar conditions. Glucose, although not required for hepatocyte maintenance or stimulation in the presence of insulin and EGF, acts synergistically with pyruvate to enhance DNA synthesis in a complete mixture.


Early Neurologic Deterioration after Stroke Depends on Vascular Territory and Stroke Etiology.
Early neurologic deterioration (END) occurs in up to one-third of patients with ischemic stroke and is associated with poor outcomes. The purpose of the present study was to determine which stroke etiologies and vascular distributions pose a greater threat of END in stroke patients. Using a single-center registry of prospectively maintained clinical data, adult ischemic stroke patients admitted (July 2008 to June 2014) within 48 hours of symptom onset were evaluated according to stroke etiology and vascular distribution using diffusion-weighted MRI. Major stroke etiologies were divided into cardioembolic, large vessel, small vessel, other, unknown source, and multiple possible etiologies. END was defined as a worsening of 2 or more points on the National Institutes of Health Stroke Scale during a 24-hour period of hospitalization. Crude and backward stepwise regression models were generated to associate stroke etiology and vascular distribution with END. Of the included 961 patients (median age 65 years, 47% female, 72% non-White), 323 (34%) experienced END. Strokes involving the internal carotid artery (ICA) were associated with a threefold higher odds of END in stepwise regression models (OR 3.0, 95% CI 1.4-6.6, P=0.006). Among stroke etiologies, those with unclear mechanisms had the lowest odds of END in the fully adjusted model (OR 0.6, 95% CI 0.4-1.0, P=0.029). In our single-center cohort of patients, ICA infarctions were independently associated with END whereas strokes of unknown etiology were least often associated with END. Larger cohorts are necessary to determine which steps, if any, can be taken to prevent END in these vulnerable populations.


Remodeling of dynamic structures of HIV-1 envelope proteins leads to synthetic antigen molecules inducing neutralizing antibodies.
A synthetic antigen targeting membrane-fusion mechanism of HIV-1 has a newly designed template with C3-symmetric linkers mimicking N36 trimeric form. The antiserum produced by immunization of the N36 trimeric form antigen showed structural preference in binding to N36 trimer and stronger inhibitory activity against HIV-1 infection than the N36 monomer. Our results suggest an effective strategy of HIV vaccine design based on a relationship to the native structure of proteins involved in HIV fusion mechanisms.


Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses.
To identify risk factors associated with development of clinical neurologic signs in horses exposed to equine herpesvirus-1 (EHV-1). 36 adult horses. Blood samples collected before and after challenge inoculation with nonneuropathogenic or neuropathogenic EHV-1 were analyzed for leukocyte-associated viremia, serum neutralizing antibody, and EHV-1-specific cytotoxic T-lymphocyte precursors (CTLPs). Associations between variables and neurologic disease and correlations between age category or breed and development of neurologic disease were examined. 9 horses developed CNS signs (ataxia, hind limb paresis or paralysis, bladder atony, or recumbency). Neurologic deficits were correlated with infection by a neuropathogenic strain of EHV-1, age>20 years, high postexposure viremic load, and low preexposure concentration of CTLPs. No significant correlations were observed between preinfection titers or horse breed and postinfection development of neurologic signs. Horses with high concentrations of preexisting CTLPs, regardless of age, strain of virus, or titer, were more likely to control the magnitude of postinfection leukocyte-associated viremia and subsequent development of neurologic disease; therefore, CTLPs appear to be a critical requirement for protective immunity against EHV-1-induced myeloencephalopathy. The importance of achieving immunity related to high concentrations of vaccine-induced CTLPs in horses at high risk for exposure to neuropathogenic strains of EHV-1 is indicated.


The influence of dietary protein on ascorbic acid metabolism in rats.
1. d-Glucuronolactone reductase, l-gulonolactone oxidase, uronolactonase, dehydroascorbatase, l-gulonate dehydrogenase and l-gulonate decarboxylase have been measured in the tissues of rats fed on diets containing variable amounts of protein. Rats fed on a protein-free or a 2% casein diet for 15 days showed a marked decline in the activities of d-glucuronolactone reductase, l-gulonolactone oxidase, uronolactonase and dehydroascorbatase in the liver, and no change in l-gulonate dehydrogenase and l-gulonate decarboxylase activities in the kidney when compared with rats fed on diets containing 9%, 18% or 25% casein. Giving diets containing 60% or 88% casein to rats did not appreciably alter the activities of uronolactonase, dehydroascorbatase, l-gulonate dehydrogenase and l-gulonate decarboxylase, but inhibited considerably the activities of d-glucuronolactone reductase and l-gulonolactone oxidase in the liver, resulting in decreased synthesis of ascorbic acid. 2. Rats fed on a 25% casein diet showed maximal weight gain, higher tissue reserve of ascorbic acid and higher urinary excretion of both ascorbic acid and glucuronic acid when compared with rats fed on diets containing lower or higher amounts of protein.


Evidence of a role for TRPC channels in VEGF-mediated increased vascular permeability in vivo.
Vascular endothelial growth factor (VEGF) increases vascular permeability by stimulating endothelial Ca(2+) influx. Here we provide evidence that links VEGF-mediated increased permeability and endothelial intracellular Ca(2+) concentration ([Ca(2+)](i)) with diacylglycerol (DAG)-mediated activation of the transient receptor potential channels (TRPCs). We used the Landis-Michel technique to measure changes in hydraulic conductivity (L(p)) and fluorescence photometry to quantify changes in endothelial [Ca(2+)](i) in individually perfused Rana mesenteric microvessels in vivo and transfected nonendothelial cells in vitro. The membrane-permeant DAG analog 1-oleoyl-2-acetyl-sn-glycerol (OAG, 100 microM), which is known to increase Ca(2+) influx through TRPCs, transiently increased L(p) 3.8 +/- 1.2-fold (from 1.6 +/- 0.8 to 9.8 +/- 2.7 x 10(-7) cm.s(-1).cmH(2)O(-1); P < 0.0001; n = 18). Protein kinase C inhibition by bisindolylmaleimide (1 microM) did not affect the OAG-induced increases in L(p). OAG also significantly increased microvascular endothelial [Ca(2+)](i) in vivo (n = 13; P < 0.0001), which again was not sensitive to protein kinase C inhibition. VEGF induced a transient increase in endothelial [Ca(2+)](i) in human embryonic kidney cells (HEK-293) that were cotransfected with VEGF receptor 2 and TRPC-6 but not with control, VEGF receptor 2, or TRPC-6 expression vector alone (P < 0.01; n = 9). Flufenamic acid, which has been shown to enhance activity of TRPC-6 but inhibit TRPC-3 and -7, enhanced the VEGF-mediated increase in L(p) in approximately half of the vessels tested but inhibited the response in the other half of the vessels. These data provide evidence consistent with the hypothesis that VEGF increases vascular permeability via DAG-mediated Ca(2+) entry through TRPCs. Although the exact identities of the TRPCs remain to be confirmed, TRPC-6 appears to be a likely candidate in approximately half of the vessels.


Use of 70% alcohol for the routine removal of microbial hard surface bioburden in life science cleanrooms.
Alcohol-based disinfectants are used for the removal of microbial hard surface bioburden in Life science Cleanrooms. Evidence for using formulations containing 70% alcohol has been lost over time but probably originates from historical observations of the activity of 60-70% alcohol. Tradition is no longer adequate to inform contemporary cleaning practice. We evaluated the efficacy of ethanol, isopropanol and trade-specific denatured alcohol 7 against vegetative Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Enterococcus hirae using standardized European Suspension and Hard Surface tests. All three alcohols were effective at lower concentrations than the 70% standard. This constitutes the first evaluation of disinfectant formulations containing ≤70% alcohol using standard methodology. The utility of trade-specific denatured alcohol #7 and evidence-based cleanroom practice warrant further validation.


Thiazole-Based σ1 Receptor Ligands: Diversity by Late-Stage C-H Arylation of Thiazoles, Structure-Affinity and Selectivity Relationships, and Molecular Interactions.
Spirocyclic thiophene derivatives represent promising σ1 ligands with high σ1 affinity and selectivity over the σ2 subtype. To increase ligand efficiency, the thiophene ring was replaced bioisosterically by a thiazole ring, and the pyran ring was opened. Late-stage diversification by regioselective C-H arylation of thiazoles 9 a-c resulted in a set of 53 compounds with high diversity. This set of compounds was analyzed with respect to σ1 affinity, σ1 /σ2 selectivity, lipophilicity (logD7.4 ), lipophilicity-corrected ligand efficiency (LELP), and molecular target interactions. The most promising candidates were pyridyl-substituted thiazole derivatives 33 c (2-(1-benzyl-4-ethoxypiperidin-4-yl)-5-(pyridin-3-yl)thiazole) and 34 c (2-(1-benzyl-4-ethoxypiperidin-4-yl)-5-(pyridin-4-yl)thiazole), possessing low-nanomolar σ1 affinity (Ki =1.3 and 1.9 nm), high σ1 /σ2 selectivity (>1500-fold), low lipophilicity (logD7.4 =1.8) and very good ligand efficiency (LELP=5.5), indicating promising pharmacodynamics and pharmacokinetics. Molecular simulation studies, including docking and deconvolution of the free binding energy into its major components, led to decreased hydrophobic stabilization of pyridyl derivatives 33 c and 34 c, which was compensated by lower desolvation energy.


[Characteristics of non-exertional heat-related illness in Japan].
This report shows characteristics of non-exertional heat-related illness in Japan. The findings are similar to those of previous reports in heatwaves of Europe and The United States. Eldery people with pre-existing diseases, homeless, living alone, poverty are independent risk factors of heatstoke and are strongly associated with severity and mortality.


Ambiguities in recurrence-based complex network representations of time series.
Recently, different approaches have been proposed for studying basic properties of time series from a complex network perspective. In this work, the corresponding potentials and limitations of networks based on recurrences in phase space are investigated in some detail. We discuss the main requirements that permit a feasible system-theoretic interpretation of network topology in terms of dynamically invariant phase-space properties. Possible artifacts induced by disregarding these requirements are pointed out and systematically studied. Finally, a rigorous interpretation of the clustering coefficient and the betweenness centrality in terms of invariant objects is proposed.


Partial purification of a stimulatory factor of RNA polymerase B in nonhistone proteins; correlation with nuclear protein kinase.
A stimulatory factor of DNA-dependent RNA polymerase B (nucleosidetriphosphate: RNA nucleotidyltransferase, EC 126.96.36.199) in nonhistone proteins was partially purified from rat liver nuclei on a column of daunomycin-CH Sepharose 4B and of phosphocellulose. In the process of purification, the stimulatory factor was separated from the main fraction of nuclear protein kinase (ATP: protein phosphotransferase, EC 220.127.116.11). This factor enhanced specifically the activity of RNA polymerase B on rat liver DNA as template and did not affect RNA polymerase A and Escherichia coli RNA polymerase at all. The polynucleotide elongation rate was increased by the addition of this factor.


3-(3-Fluoro-phenyl-sulfin-yl)-2,4,6,7-tetra-methyl-1-benzofuran.
In the title compound, C(18)H(17)FO(2)S, the 3-fluoro-phenyl ring makes a dihedral angle of 78.30 (5)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions.


Neonatal disseminated methicillin-resistant Staphylococcus aureus presenting as orbital cellulitis.
Orbital cellulitis and abscess are known complications of ethmoiditis in children, but they are very rare in the newborn. The authors report a case of orbital abscess caused by methicillin-resistant Staphylococcus aureus (MRSA) in a four-week-old neonate born four weeks prematurely.


A comparative analysis of lobular and ductal carcinoma of the breast: presentation, treatment, and outcomes.
Compared with invasive ductal carcinoma, invasive lobular carcinoma of the breast is considered by many to be a more indistinct and multicentric form of cancer that is detected later and is treated less optimally by breast-preservation techniques. This study analyzed the presentation, treatment trends, and survival rates of women who had invasive lobular and ductal breast carcinoma. The objective was to determine the utility of breast-preservation therapy for invasive lobular carcinoma by analysis of historic data on tumor features and survival. Data on 291,273 women diagnosed with invasive carcinoma between 1985 and 1993 were obtained from the National Cancer Data Base. Analysis included the patient's age at diagnosis; tumor histology, anatomic site, diameter, grade, and stage; treatment; and disease status 5 years after diagnosis. The mean patient age at diagnosis was 61.0 years for invasive ductal carcinoma, 63.0 years for invasive lobular carcinoma, and 60.6 years for tumors with combined histology. The anatomic location, tumor diameter, and tumor grade were similar for each histotype. Breast-preservation therapy was less frequent for invasive lobular carcinoma. The 5-year overall survival and local disease-free survival rates for women treated with breast preservation were similar for invasive ductal carcinoma (84% overall survival; 97% disease-free survival) and invasive lobular carcinoma (87% overall survival; 98% disease-free survival). Invasive lobular carcinoma presents with a similar age distribution, anatomic subsite, diameter, and grade as invasive ductal carcinoma. Breast preservation is selected less commonly for women who have invasive lobular carcinoma, but this choice of therapy does not compromise the disease-free or overall survival status of this group of patients.


A Structural Equation Model of Health-Related Quality of Life in Chinese Patients With Rheumatoid Arthritis.
Background: The aim of this study was to examine how body image, Disease Activity Score in 28 joints, the feeling of being anxious, depression, fatigue, quality of sleep, and pain influence the quality of life (QoL) in patients with rheumatoid arthritis (RA). Methods: A multicenter cross-sectional survey with convenience sampling was conducted from March 2019 and December 2019, 603 patients with RA from five hospitals were evaluated using the Body Image Disturbance Questionnaire, Disease Activity Score in 28 joints, Hospital Anxiety and Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Short Form 36 Health Survey, and Global Pain Scale. The relationship between quality of life and other variables was evaluated by using the structural equation model (SEM). Results: A total of 580 patients were recruited. SEM fitted the data very well with a root mean square error of approximation (RMSEA) of 0.072. Comparative fit index of 0.966, and Tucker-Lewis index of 0.936. The symptoms and the normalized factor load of six variables showed that the normalized factor load of pain was 0.99. Conclusions: The QoL model was used to fit an SEM to systematically verify and analyze the population disease data, biological factors, and the direct and indirect effects of the symptom group on the QoL, and the interactions between the symptoms. Therefore, the diagnosis, treatment and rehabilitation of RA is a long-term, dynamic, and complex practical process. Patients' personal symptoms, needs, and experiences also vary greatly. Comprehensive assessment of patients' symptoms, needs, and experiences, as well as the role of social support cannot be ignored, which can help to meet patients' nursing needs, improve their mood and pain-based symptom management, and ultimately improve patients' QoL.


[Lumboradiculalgia and calcified disk hernia].
In the context of a particular case report, the authors recall that calcified discs may be responsible for root pain, hyperalgic sciatica or lumbago. In the present case, the pain responded to intra-discal injection of long-acting corticosteroids. The authors compare this case to 10 other personal cases and 16 cases reported in the literature.


A new free radical scavenger, edaravone, ameliorates oxidative liver damage due to ischemia-reperfusion in vitro and in vivo.
Ischemia-reperfusion injury causes oxidative stress producing reactive oxygen species, which is a serious problem linked to morbidity and mortality in liver surgery. We investigated the effects of edaravone, a new free radical scavenger, on liver oxidative stress in vitro and in vivo. We employed a hypoxia-reoxygenation model of primary cultured hepatocytes using an AnaeroPack (Mitsubishi Gas Chemical Co., Tokyo, Japan). Hepatocytes were exposed to 3 or 4 hours of hypoxia and then returned to oxygenation. We analyzed the time course changes of aspartate aminotransferase (AST), phosphatidylcholine hydroperoxide (PCOOH), and adenosine triphosphate (ATP) content in hepatocytes of edaravone-treated groups or nontreated groups after reoxygenation. Edaravone significantly attenuated the elevation of the AST level of the medium and hepatocellular PCOOH and preserved the hepatocellular ATP level. In vivo, male Sprague-Dawley rats were subjected to 45 minutes of hepatic ischemia and 120 minutes of reperfusion. The rats were intravenously injected with vehicle or edaravone (3 mg/kg or 10 mg/kg) before reperfusion and 1 hour after reperfusion. Serum AST levels and hepatic PCOOH and energy charge were significantly improved in both edaravone groups compared with control. In conclusion, edaravone has the ability to eliminate intra-hepatocellular superoxide species and attenuate oxidative liver damage in liver surgery.


[Purification and Preliminary Research on the Immunogenicity of Inactivated Severe Fever with Thrombocytopenia Syndrome Bunyavirus].
To understand the immunogenicity of purified inactivated severe fever with thrombocytopenia syndrome bunyavirus (SFTSV), concentration by ultrafiltration as well as molecular-sieve chromatography (MSC) were used for purification of inactivated SFTSVs. Inactivated viruses in purified samples were analyzed and identified by western blotting and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the glycoprotein (GP) and nucleoprotein (NP) antigen titers of which were detected using a double-sandwich enzyme-linked immunosorbent assay (ELISA). Purified inactivated SFTSVs were enriched and observed by electron microscopy, and the total protein concentration detected using the bicinchoninic acid assay. Purified inactivated SFTSVs were applied to New Zealand rabbits via two immunization programs to evaluate immunogenicity and to compare the immune effect. After SFTSVs were inactivated and concentrated by ultrafiltration, MSC revealed two typical elution peaks. The sample of one peak was identified as inactivated virions, in which GP and NP were detected by SDS-PAGE, western blotting and ELISA. Main corponent of the other peak was NP. After concentration by ultrafiltration, purified inactivated SFTSVs with purity >90% and total protein concentration of 1. 1 mg/mL were obtained, and the typical electron microscopy of bunyavirus was observed. In the sera of animals immunized with purified inactivated SFTSVs, SFTSV-specific IgG antibody and neutralizing antibody were detected at high titers. However, antibody titers were affected by the immunization program. Effect of immunization on days 0, 14 and 28 was significantly better than that on days 0, 7 and 28. Our work revealed that cultivation of SFTSVs contained intact virus particles and large amounts of free NP. Using MSC, purified inactivated SFTSVs of high purity could be obtained. Purified inactivated SFTSVs induced high titers of neutralizing antibody and virus-specific IgG antibody showing satisfactory immunogenicity, which provides important clues for further study on a vaccine for the inactivated virus.


CXCL10/XCL1 fusokine elicits in vitro and in vivo chemotaxis.
Fusokines are proteins formed by the fusion of two cytokines. They have greater bioavailability and therapeutic potential than individual cytokines or a combination of different cytokines. Interferon-gamma-inducible protein 10 (CXCL10) and lymphotactin (XCL1) are members of the chemotactic family of cytokines, which induce tumor regression by eliciting immune-system cell chemotaxis. We engineered a replication-deficient adenoviral system expressing CXCL10/XCL1 fusokine (Ad FIL) and assessed its chemotactic response in vitro and in vivo. The CXCL10/XCL1 fusokine elicited a greater chemotactic effect in IL-2 stimulated lymphocytes than individual or combined cytokines in vitro. CXCL10/XCL1 fusokine biological activity was demonstrated in vivo by intratumoral chemoattraction of CXCR3+ cells. Thus, this novel CXCL10/XCL1 fusokine may represent a potential tool for gene therapy treatment of cancer and other illnesses that require triggering immune-system cell recruitment.


The effects of the dietary glycemic load on type 2 diabetes risk factors during weight loss.
To compare the effects of two calorie-restricted diets that differ in glycemic load (GL) on glucose tolerance and inflammation. Thirty-four healthy overweight adults, ages 24 to 42 years, were randomized to 30% provided calorie-restricted diets with high (HG) or low (LG) glycemic load for 6 months. Outcomes were changes in glucose-insulin dynamics and C-reactive protein (CRP) levels. Compared with baseline, levels of fasting insulin, homeostasis model assessment of insulin resistance, post-load insulin at 30 minutes, and incremental area-under-the-curve-insulin during the oral glucose tolerance test were significantly lower in both groups at 6 months (p range, 0.01 to 0.05), but after adjustment for baseline values and weight change, there were no differences between the two groups with regard to changes over time in any parameter. The mean percentage change in insulin sensitivity by a frequently sampled intravenous glucose tolerance test was +26% in the HG group and +24% in the LG group (p = 0.83); first-phase acute insulin release was -20% in the HG group and -21% in the LG group (p = 0.77). More participants on the LG diet (14 of 16 subjects) had a decline in serum CRP, compared with those on the HG diet (7 of 16 subjects) (p < 0.05). In healthy overweight adults provided with food for 6 months, the dietary GL did not seem to influence chronic adaptations in glucose-insulin dynamics above that associated with weight loss. This finding highlights the importance of absolute weight loss over the dietary macronutrient composition used to achieve weight loss. The finding of greater declines in CRP concentration after consumption of a low-GL diet warrants further investigation.


Barriers to Meaningful Participatory Mental Health Services Research and Priority Next Steps: Findings From a National Survey.
A growing consensus has emerged regarding the importance of stakeholder involvement in mental health services research. To identify barriers to and the extent of stakeholder involvement in participatory research, the authors undertook a mixed-methods study of researchers and community members who reported participation in such research. Eight consultative focus groups were conducted with diverse groups of stakeholders in mental health services research (N=51 unique participants, mostly service users), followed by a survey of service users, family members, community providers, and researchers (N=98) with participatory research experience. Focus groups helped identify facilitators and barriers to meaningful research collaboration, which were operationalized in the national survey. Participants were also asked about high-priority next steps. The barrier most strongly endorsed as a large or very large problem in the field was lack of funding for stakeholder-led mental health services research (76%), followed by lack of researcher training in participatory methods (74%) and insufficiently diverse backgrounds among stakeholders (69%). The two most frequently identified high-priority next steps were ensuring training and continuing education for researchers and stakeholders (33%) and authentically centering lived experience and reducing tokenism in research (26%). These findings suggest a need for increased attention to and investment in the development, implementation, and sustainment of participatory methods that prioritize collaboration with direct stakeholders, particularly service users, in U.S. mental health services research. The findings also underscore the presence and potentially important role of researchers who dually identify as service users and actively contribute a broader orientation from the service user-survivor movement.


The discrete phases of the cell cycle: autoradiographic, physical, and chemical evidences.
Recently the discrete model of the cell cycle, described as a series of metabolic progressions through four distinct phases, has been challenged by a few curves of percent labeled mitoses (PLM) and related autoradiographic data, which have been questionably interpreted in terms of a "continuous" cell cycle model. This conclusion is based in part on a few questionable observations which we summarize, along with our objections and explanations. We present a critical analysis of the autoradiographic data obtained with the PLM, in terms of the limitations and inconveniences of the technique itself. Some attention is paid to the usefulness of the "radioautographic transfer function," which seems an arbitrary mathematical expression of old autoradiographic observations. Finally, a review is presented of the old (by autoradiography) and new (by physical, chemical, and computer image analysis) evidences of the existence of dicrete phases in the cell cycle, which in turn support the idea of an all-or-none phenomenon for DNA synthesis, and which rule out the hypothesis of a continuous cell cycle model with a varying DNA synthesis rate function.


A short negative feedback mechanism regulating corticotropin-releasing hormone release.
The effect of ACTH administration on plasma CRH levels was studied. In five patients with Addison's disease and three patients with hypopituitarism, bolus iv injection of 0.25 and 0.5 mg ACTH-(1-24) reduced plasma CRH levels (that had become elevated 48 h after discontinuation of corticosteroid replacement) to near-normal levels at 30-60 min in a dose-dependent manner. Plasma immunoreactive beta-endorphin levels were similarly decreased in patients with Addison's disease. ACTH-(1-24) (0.25 and 0.5 mg) injection failed to inhibit plasma CRH levels in five normal subjects. Basal CRH release from the rat hypothalamic median eminence in vitro was inhibited by 0.22 and 2.2 nM ACTH-(1-24) and ACTH-(1-39) in a dose-dependent manner. These results suggest that in the absence of negative feedback control of ACTH secretion by glucocorticoids, ACTH can regulate its secretion by inhibition of hypothalamic CRH release.


Presence of leucocytes in prostatic secretions correlates with the severity of lower urinary tract symptoms.
We investigated the correlation between the presence of leucocytes in expressed prostatic secretion and the lower urinary tract symptom severity by retrospectively reviewing 699 men with lower urinary tract symptoms. The patients were evaluated by the International Prostate Symptoms Score and the Overactive Bladder Symptoms Score and underwent expressed prostatic secretion testing. Patients were classified into groups 1 and 2 based on the expressed prostatic secretion leucocyte count. The mean total and storage score of the International Prostate Symptoms Score, and mean total Overactive Bladder Symptoms Score were higher in group 1. Urine flow metrics showed that voided volume and maximum flow rate were lower in group 1. The scores for International Prostate Symptoms Score questions 4, 6 and 7 and Overactive Bladder Symptoms Score question 2 were higher in group 1 and showed a weak positive correlation with expressed prostatic secretion. Voided volume and maximum flow rate showed the strongest correlation, although International Prostate Symptoms Score question 7 and Overactive Bladder Symptoms Score question 2 were the only independent predictors of expressed prostatic secretion. Therefore, leucocytes in expressed prostatic secretion are associated with the lower urinary tract symptom severity, particularly nocturnal urination symptoms.


Review of Analytical Methods for Evaluating Azithromycin in the Context of Green Analytical Chemistry.
Azithromycin (AZT) is an antimicrobial available in different pharmaceutical forms and many people can have access to this medicine. Therefore, the existence of adequate and reliable analytical methods for evaluating the quality of AZT and AZT-based products is essential. The purpose of this review is to discuss the analytical methods for evaluating AZT present in the literature and official compendia in the context of Green Analytical Chemistry (GAC). Among the methods found in the literature for evaluating AZT, the most used method is HPLC (62%) followed by TLC (14%) and the microbiological method by agar diffusion (14%). Even pharmacopoeias recommend the analysis of AZT by HPLC or agar diffusion. Acetonitrile and methanol account for 35% of the most used solvents in the analyses, followed by buffer. AZT lacks analytical methods in the context of GAC. Both physical-chemical and microbiological methods can contemplate the environmentally friendly way to analyze AZT and AZT-based products, depending only on the chosen conditions. Ethanol, purified water, acetic acid instead of methanol, acetonitrile, buffer, formic acid in the physical-chemical methods are excellent alternatives. However, in the microbiological method, turbidimetry is a great option instead of agar diffusion.


Analysis of out-of-pocket costs associated with hospitalised injuries in Vietnam.
In Vietnam, over 39 000 people die and millions are hospitalised due to injuries every year. Injuries create a significant financial burden for families. In this study, we estimated out-of-pocket payment for medical care of injuries and the role of health insurance in containing such costs. A prospective cohort study of 892 hospitalised injury patients admitted to a provincial general hospital in 2010 in Vietnam was conducted. Data on demographic, injury characteristics and costs by specific categories paid out-of-pocket by patients were included in the analyses. Generalised linear models with log link and γ distribution were employed to examine the associations between insurance status and total costs. The average total medical care costs paid out-of-pocket by patients during hospitalisation were over US$ 270. Major drivers of the costs related to surgery (nearly 25%), diagnostic test/examination (24%) and drugs (23%). Burns incurred the highest total costs during hospitalisation ($321) and assault incurred the lowest ($167). Total costs were higher for more severe injuries and those that required a more complex surgery. Patients using health insurance paid less those who did not. However, there were no statistically significant associations between health insurance and total costs, costs for surgery, diagnostic tests/examinations or drugs. The study provides estimates and distribution of medical care costs for injuries in hospital. In addition to ongoing efforts in prevention, the study provides further evidence on the limited benefits of health insurance in protecting patients and their family from the high costs of hospitalisation in Vietnam.


[The diagnosis and treatment of injuries to the major vessels of the extremities and neck in wartime].
During the time of rendering special angiosurgical aid in the zone of military operations near the city of Gagra 28 wounded with gunshot injuries of major vessels of the neck and extremities were operated upon, which was 4.5% of all the wounded. Different procedures on the vessels were performed immediately after diagnosing the injuries within minimum terms after wounds in parallel with antishock measures. There was no intra- and postoperative lethality. Thrombosis of the restored arteries was noted in 4 out of all the patients operated upon. The extremity had to be amputated because of thrombosis of the operated artery in 2 cases only which made up 7.2% of all the interventions performed.


A new data management system for the French National Registry of human alveolar echinococcosis cases.
Alveolar echinococcosis (AE) is an endemic zoonosis in France due to the cestode Echinococcus multilocularis. The French National Reference Centre for Alveolar Echinococcosis (CNR-EA), connected to the FrancEchino network, is responsible for recording all AE cases diagnosed in France. Administrative, epidemiological and medical information on the French AE cases may currently be considered exhaustive only on the diagnosis time. To constitute a reference data set, an information system (IS) was developed thanks to a relational database management system (MySQL language). The current data set will evolve towards a dynamic surveillance system, including follow-up data (e.g. imaging, serology) and will be connected to environmental and parasitological data relative to E. multilocularis to better understand the pathogen transmission pathway. A particularly important goal is the possible interoperability of the IS with similar European and other databases abroad; this new IS could play a supporting role in the creation of new AE registries.


Interaction between cellular and viral genes in the expression of the RSV-induced transformation-specific cell-surface antigen VCSA.
Transformation of BHK hamster fibroblasts by an env- strain of Rous sarcoma virus (RSV) leads to the appearance at the cell surface of a virus-induced nonvirion antigen (VCSA), specific for transformation, whose expression is controlled by the transforming src gene. Previous work has shown that a rabbit anti-VCSA serum lyses specifically, in the presence of complement, 51Cr-labelled RSV-transformed cells from different animal species. Now, by competition experiments with a panel of different unlabelled cells we show that the VCSA expressed on RSV-transformed hamster fibroblasts is a complex of at least three distinct antigenic specificities: (1) one expressed on all RSV-transformed fibroblasts, regardless their species and the subgroup or strain of the transforming virus; (2) one cross-reacting with a cell-surface antigen (CSA) expressed at various degrees on untransformed avian fibroblasts, but not on mammalian fibroblasts; (3) one species-specific, present only on RSV-transformed hamster fibroblasts. It is concluded that VCSA is a complex of several antigenic determinants, and that some of these differ in different cells transformed by RSV. This observation indicates that VCSA expression at the cell surface is likely to be the result of the interaction between the viral src gene product pp60src with host cell gene(s) or gene product(s), rather than the simple expression of this molecule at the cell surface.


A simple in vitro screening test for blood compatibility of materials.
An in vitro closed-cell kinetic blood-coagulation test was developed and used to evaluate the blood compatibility of materials. The test compares the clotformation rate on a test surface to that of a control material, Silastic. This method avoids anticoagulants, blood flow variations, and the exposure to air and other foreign surfaces. Eight pairs of cells are sequentially evaluated as to the weight of thrombus formed, the amount of unclotted blood, and the reduction in platelet count of the blood exposed to both the test materials and the control. These data are used to calculate a relative index whereby materials can be rated quantitatively as to the rate of clot formation on their surface. The order of decreasing clot formation on one group of materials studied was as follows: biolized (Imai et al., Trans. Amer. Soc. Artif. Int. Organs, 17, 6, 1973) poly (ether urethane), segmented polyurethane, formaldehyde-treated pericardium, Hydron, glutaraldehyde-treated pericardium, biolized natural rubber, Hexsyn, heparinized natural rubber, Silastic, and natural rubber. Urethane and aldehyde-treated natural tissue had a lower percentage of red thrombus formation. These results generally correlate with in vivo observations.


Biomechanical comparison of short-segment posterior fixation including the fractured level and circumferential fixation for unstable burst fractures of the lumbar spine in a calf spine model.
OBJECTIVE There has been a transition from long- to short-segment instrumentation for unstable burst fractures to preserve motion segments. Circumferential fixation allows a stable short-segment construct, but the associated morbidity and complications are high. Posterior short-segment fixation spanning one level above and below the fractured vertebra has led to clinical failures. Augmentation of this method by including the fractured level in the posterior instrumentation has given promising clinical results. The purpose of this study is to compare the biomechanical stability of short-segment posterior fixation including the fractured level (SSPI) to circumferential fixation in thoracolumbar burst fractures. METHODS An unstable burst fracture was created in 10 fresh-frozen bovine thoracolumbar spine specimens, which were grouped into a Group A and a Group B. Group A specimens were instrumented with SSPI and Group B with circumferential fixation. Biomechanical characteristics including range of motion (ROM) and load-displacement curves were recorded for the intact and instrumented specimens using Universal Testing Device and stereophotogrammetry. RESULTS In Group A, ROM in flexion, extension, lateral flexion, and axial rotation was reduced by 46.9%, 52%, 49.3%, and 45.5%, respectively, compared with 58.1%, 46.5%, 66.6%, and 32.6% in Group B. Stiffness of the construct was increased by 77.8%, 59.8%, 67.8%, and 258.9% in flexion, extension, lateral flexion, and axial rotation, respectively, in Group A compared with 80.6%, 56.1%, 82.6%, and 121.2% in Group B; no statistical difference between the two groups was observed. CONCLUSIONS SSPI has comparable stiffness to that of circumferential fixation.


Anticoagulant therapy after prosthetic valve replacement -optimal PT-INR in Japanese patients-.
Values of the international normalized ratio of prothrombin time (PT-INR) were analyzed at the time when anticoagulant-related complications developed in patients undergoing prosthetic valve replacement so as to evaluate the optimal therapeutic range in PT-INR value in Japanese patients. A total of 102 patients with a prosthetic heart valve who have been followed up at our department during the past 25 years were enrolled in this study. PT-INRs were determined regularly in these patients for the period between October 1996 and March 1999. Although no thromboembolic complications occurred during the period of this study, hemorrhagic complications developed in 26 (25.5%) patients. Three (2.9%) patients suffered from life threatening bleeding, such as cerebral bleeding and gastrointestinal bleeding and were defined as the major hemorrhagic group. Another 23 (22.5%) patients had minor bleeding complications such as nasal, gingival or subcutaneous bleeding and were defined as the minor hemorrhagic group. Mean PT-INR values were 3.8 2.0 and 3.2 1.0 at the onset of the complications in major and minor hemorrhagic groups, respectively, and there was no significant difference between the two groups. However, mean PT-INR values in the minor bleeding group differed significantly from that in a patient group with no hemorrhagic complications (N=76). Among the cases with bleeding complications, only 19% of the patients belonged to the range below 2.5 of PT-INR value and 54% of the patients were included in the range from 2.5 to 3.5 (p<0.05). In conclusion, the optimal therapeutic range between 2.5 and 3.5 in PT-INR recommended by the American Heart Association for patients with a prosthetic heart value in Western countries may be too high in Japanese patients. PT-INR below 2.5 is considered to be safe to prevent hemorrhagic complications.


Histological study of intestinal atresia due to intrauterine intussusception.
Histological studies were conducted on 4 patients with intestinal atresia due to intrauterine intussusception. This atresia is characterized by a polypoid lesion as the remnant of the invaginated and necrotized intestine in the distal intestinal lumen. As the result of the histological survey in the affected intestine, we tentatively classified this atresia into two types, type A and B. In type A, the polypoid lesion is observed at the blind end, with relatively good preservation of the structure of the intestine. In type B, the polypoid lesion is located apart from the blind end, and the lesion is markedly necrotic. The interruption of intestinal blood flow seemed to be more severe in type B than in type A.


Sulthiame add-on treatment in children with epileptic encephalopathy with status epilepticus: an efficacy analysis in etiologic subgroups.
Sulthiame (STM) has been recommended as an effective antiepileptic drug (AED) in children with epileptic encephalopathy with status epilepticus in sleep (ESES). The aim of this study is to evaluate the efficacy of STM add-on treatment in children with pattern of ESES with respect to the etiologic subgroup. Twenty-nine children with ESES pattern with three different etiologic subgroups (epileptic syndromes: 14, structural/infectious: 9, unknown: 6) who were given STM as add-on treatment were included into the study. The efficacy of STM was evaluated in terms of seizure control, electroencephalography (EEG) findings, need of the new AEDs after add-on STM, and behavioral and cognitive improvement. The range of the follow-up duration after add-on STM treatment was between 5 and 51 months. At the end of 1 year of STM treatment, the most successful electrophysiologic improvement was identified in the well-defined epileptic syndrome group; epileptic syndrome, 71.4% (10/14); structural/infectious, 33.3% (3/9); and unknown, 0% (0/6). Patients who had complete response or persistent ESES pattern at the 3rd month were still in the same condition at the 6th and 12th months. However, the ESES pattern reappeared in 35.2% of the patients who had partial electrophysiological improvement at the 3rd month. In the epilepsy syndrome group, eight out of ten patients who had either complete or partial EEG response after 1 year of STM treatment displayed behavioral and cognitive improvement. Sulthiame might be a valid add-on treatment of ESES especially in children with epilepsy syndromes.


Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene.
Recombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We report the development of lentiviral vectors with the spleen focus forming virus (SF) promoter driving codon-optimized human RAG2 (RAG2co), which improved phenotype amelioration compared to native RAG2 in Rag2(-/-) mice. With the RAG2co therapeutic transgene, T-cell receptor (TCR) and immunoglobulin repertoire, T-cell mitogen responses, plasma immunoglobulin levels and T-cell dependent and independent specific antibody responses were restored. However, the thymus double positive T-cell population remained subnormal, possibly due to the SF virus derived element being sensitive to methylation/silencing in the thymus, which was prevented by replacing the SF promoter by the previously reported silencing resistant element (ubiquitous chromatin opening element (UCOE)), and also improved B-cell reconstitution to eventually near normal levels. Weak cellular promoters were effective in T-cell reconstitution, but deficient in B-cell reconstitution. We conclude that immune functions are corrected in Rag2(-/-) mice by genetic modification of stem cells using the UCOE driven codon-optimized RAG2, providing a valid optional vector for clinical implementation.


Cardiovascular safety profile of MA-2029, a novel motilin receptor antagonist.
The aim of this study was to assess the cardiovascular effect of MA-2029, a selective motilin receptor antagonist highly expected for the treatment of irritable bowel syndrome (IBS). MA-2029 inhibited the human ether-a-go-go-related gene (hERG) current at 100 microg/ml, but shortened action potential duration (APD) in isolated guinea pig papillary muscles at 10 and 100 microg/ml and the corrected QT (QTc) interval after oral administration of 30 and 300 mg/kg in conscious telemetered dogs. The discrepancy was probably caused by blockade of the Ca(2+) channel because MA-2029 inhibited the Ca(2+) current in isolated guinea pig myocytes. MA-2029 at 100 microg/ml also decreased the maximum rising velocity and action potential amplitude in the action potential study, indicating that MA-2029 has Na(+) channel blocking potential. In the cardiovascular study, MA-2029 at 30 mg/kg induced slight cardiovascular changes such as hypotension, QTc shortening, and PR prolongation possibly caused by Ca(2+) channel blockade. The plasma concentration at 4 hr after 30 mg/kg administration was 2.10 microg/ml, 200-fold higher than the effective concentration of MA-2029 as a motilin receptor antagonist. These results suggest that MA-2029 has sufficient cardiovascular safety although it inhibits multiple ion channels at supra-effective concentrations. On the other hand, cisapride, an effective IBS drug, showed clear hERG inhibition and APD prolongation at 100 ng/ml. Cisapride exhibited a narrow safety margin because it caused QT prolongation potential even at the therapeutic concentration. In conclusion, MA-2029 is a novel drug highly expected for the treatment of IBS with lower cardiovascular risk than cisapride.


Salvage with radiotherapy of postsurgical relapses of endometrial cancer.
From January 1960 to June 1974, 71 patients with a postsurgical relapse of endometrial adenocarcinoma have been referred to the Radiology Institute of the University of Florence. Eleven patients showed hematogenous metastases; the remaining 60 cases showed locoregional relapses and were treated with radiotherapy. Forty-eight patients, whose relapse was localized to the pelvis, vagina, inguinal nodes or perineal scar, were treated with a radical aim (4,500-6,000 rad in 5-6 weeks); the treatment was palliative in 12 cases with abdominal extrapelvic relapse. The therapeutic response was not evaluated in 8 patients lost to follow-up shortly after the treatment. In the cases treated with a radical scope, a complete regression was attained in 22 of 43 (51%); a survival rate of 16 of 43 (37%) was attained at 5 years. In 9 cases treated with a palliative aim, only subjective remission was attained, and no patient was alive one year after the therapy. The most favorable therapeutic response was attained in the vaginal relapses (50% survivors at 5 years) and the cases with a late recurrence (more than 3 years) after the initial surgery. No definite correlation was found between the prognosis of the relapse and the histological grading of the primary tumor.


Evaluation of eating habits by 7-day food record: web-PC vs. traditional paper format.
The aim of this study was to evaluate the validity of a web-based 7-day food-record using METADIETA-web link (Meteda s.r.l.) - a professional software used in nutritional practice and research - compared with the traditional paper format. Twenty-six healthy adults of both sexes were recruited in this cross-over study based on the number coming from the sample size calculation, and randomly assigned to start with METADIETA-web or traditional 7-Day Food-Diary. All the 7-day food-diaries were recorded in the Metadieta-software. The System Usability Scale (SUS) questionnaire was administered to evaluate the participants' preferences in terms of usability, acceptability, and feasibility. Differences in energy intake, nutrient composition, and SUS between the digital and traditional modalities were evaluated. Energy and nutrients were not significantly different between the two methods with a variation <15%, with alcohol intake showing the strongest relation (0.1% variation). The Interclass Correlation Coefficient showed a grade of consistency between the two methods excellent for alcohol, good for proteins, carbohydrates, and fibre, moderate for energy and saturated fat, and poor for total fat and cholesterol. SUS suggested that the web-based platform was in general well accepted, but highlighted some inconsistencies and complexity compared to the written food diary. The web-based 7-day food-record may allow an accurate and quicker analysis of food timing than conventional approaches, seeming reliable for energy and macronutrient composition, making it a potentially attractive tool for nutritional research. However, the reported inconsistencies and complexity must be considered and addressed.


Differential effects of modern immunosuppressive agents on the development of intimal hyperplasia.
Modern immunosuppressive agents such as tacrolimus and rapamycin are claimed to be associated with a reduction in vascular narrowing, a central feature of chronic rejection. This study assesses the effect of cyclosporine, tacrolimus and rapamycin on the development of intimal thickening, fibrosis-associated genes and deposition of extracellular matrix (ECM) proteins in a model of intimal hyperplasia. Male Sprague-Dawley rats received either no treatment or 5 mg/kg cyclosporine, 0.1 mg/kg tacrolimus or 0.05 mg/kg rapamycin. Animals underwent left common carotid balloon angioplasty, and intima medial ratios, pro-fibrotic gene expression and ECM accumulation were calculated at 14 and 28 days. Cyclosporine was associated with increased intimal thickening compared to controls ( P < 0.004). Tacrolimus had no effect on intimal thickening, whilst rapamycin significantly inhibited intimal thickening at both 14 and 28 days ( P < 0.004 and P < 0.026, respectively). All groups significantly inhibited matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, transforming growth factor (TGF)-beta and collagen III expression at 14 days ( P < 0.001), but increased ECM deposition. However, rapamycin marginally reduced ECM deposition compared to cyclosporine ( P < 0.06). Treatment with cyclosporine was associated with worsening of vascular narrowing, whilst rapamycin showed a beneficial reduction in intimal thickening. Treatment with all immunosuppressive agents resulted in increased ECM deposition. Rapamycin may halt the progression of vascular narrowing compared to both cyclosporine and tacrolimus.


A high normal ankle--brachial index is associated with electrocardiography-determined left ventricular hypertrophy: the Okinawa Peripheral Arterial Disease Study (OPADS).
We aimed to determine if the ankle--brachial index (ABI) increased with age as a result of increased arterial stiffness and wave reflection, and whether this was associated with left ventricular hypertrophy (LVH). An observational cross-sectional study was conducted in 13 396 participants aged 19-89 years who attended a health check-up. Brachial and ankle blood pressures were measured by an automatic oscillometric method. Electrocardiography-determined LVH (ECG-LVH) was defined by computer-interpreted Minnesota codes using resting 12-leads ECG. The mean age of the participants was 53 years (54% women). The prevalence of ECG-LVH was 13%; this was the lowest in participants with normal blood pressure and increased with an increase in the hypertension grade. The ABI was higher in participants with ECG-LVH than in those without (1.13± 0.07 vs. 1.15 ± 0.07, P < 0.001). The prevalence of ECG-LVH was the highest in participants with the highest quartile of ABI (16%), followed by those with the third quartile (14%), second quartile (12%), and the lowest quartile of ABI (9%). The odds ratio for ECG-LVH was significantly higher for participants with a higher quartile of ABI than those with the lowest, before and after adjustment for several covariates. Similar results were observed in sensitivity analysis of individuals with normal kidney function, younger than 65 years, and without diabetes mellitus, performed in order to reduce the influence of a medial arterial calcification-mediated increase in ABI. High ABI is a possible marker of arterial stiffness and/or wave reflection that, even in the normal range, is associated with ECG-LVH.


Vedolizumab for induction and maintenance of remission in Crohn's disease.
Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease. To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease. We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022. We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease. We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence. We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence). High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.


[Metformin--new treatment strategies for gynecologic neoplasms].
Metformin, a drug from the biguanide class, is now one of the most widely used drugs in the treatment of type 2 diabetes. This drug was also used in the treatment of polycystic ovarian syndrome and recent reports indicate the possibility of using this drug in oncology. Latest findings show that metformin has an anticancer effect. Influencing the transduction mechanisms primarily through activation of protein kinase activated by 5'AMP (AMPK) regulates the activity of the AMPK/mTOR signaling pathway. MTOR pathway dysregulation may be a factor in the pathogenesis of various human diseases, especially cancers. Overactivation of mTOR is observed in malignant cells and is associated with their resistance to treatment. It can therefore be concluded that metformin as an inhibitor of mTOR may be a factor that suppresses tumor development. There are also studies showing that metformin prevents the formation of metastases, reducing tumor vasculature and improves the effectiveness of anticancer drugs. The anticancer effect of metformin has been proven in the treatment of colorectal and breast cancer. The current studies reports the positive effects in the treatment of gynecological cancers such as ovarian, endometrial and cervical cancer. Incidence for these tumors in 2009 in Poland was: for ovarian cancer 11.01100000; for endometrial cancer 15.0/100000; for cervical cancer 10.5/100000. Metformin has antitumor activity in monotherapy and also synergistically with other anticancer agents. Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.


Common uses of nonradioactive drugs in nuclear medicine.
A variety of nonradioactive pharmaceuticals commonly used in patients who receive nuclear medicine diagnostic tests are described. Nonradioactive drugs used in thyroid, brain, hepatobiliary, cardiac, renal, Meckel's diverticulum, gallium, adrenal, and hematological studies are described. Pharmaceutical necessities used as disinfectants, diluents, and anticoagulants are also described. Hospital pharmacists should be familiar with the uses of commonly prescribed nonradioactive drugs in nuclear medicine studies.


Route to synthesize the sludge management processes.
A route for the synthesis of the treatment train of sewage sludge is proposed, and the conceptual design stage is demonstrated, using local sludge as an example.


Development of "personality" in the domestic cat: A longitudinal study.
Although individual differences in the behavior of animals, sometimes referred to as personality, have recently received considerable attention, the development of such differences remains understudied. We previously found consistent individual differences in behavior in four tests simulating everyday contexts in 74 preweaning age kittens from 16 litters of the domestic cat. To study the development of consistent among-individual differences in four behavioral traits in cats, we followed a subset of these same individuals and repeated the same tests at 6 and 12 months of age. Some individual differences in behavior became increasingly repeatable with age due to a combination of decreased individual-level variance (canalization) and increased among-individual variance; these changes in variance and repeatability continued into adulthood (12 months). We did not observe behavioral syndromes at any age, in contrast to our previous reports in a different population of adult cats. The mechanisms that underlie increased repeatability with age and the possibility of personality structure differing between populations in this species remain to be studied.


Posttraumatic stress symptoms between parents and their children following a natural disaster: An integrated model under a dyadic approach.
Various theories have been proposed to elucidate the mechanisms underlying the effect of parental posttraumatic stress symptoms (PTSSs) on their children. However, these theories focused on unique mechanisms for some factors and overlooked the combined role of different factors. This study aimed to construct a broad theoretical framework to comprehensively understand the mechanisms underlying the effect of parents' PTSSs on adolescents. We examined the combined role of parental PTSSs and marital conflict, and adolescents' self-differentiation, psychological inflexibility, and rumination after super typhoon Lekima. We used self-report questionnaires to investigate 1,218 parent-adolescent dyads in the area most affected by the disaster 3 months after the typhoon. Parents' PTSSs had a direct and positive association with adolescents' PTSSs. We also observed parents' PTSSs had an indirect relationship with adolescents' PTSSs through parental marital conflict and adolescents' self-differentiation, psychological inflexibility, and rumination. An effect of PTSSs may be found in the dyadic interaction between parents and their children. Children's psychological and behavioral changes resulting from impaired family relationship functioning exhibited by their posttraumatic parents also play an important role in the interpersonal effect of PTSSs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Lupus nephritis with cryoglobulinemic glomerulonephritis features: a diagnostic conundrum.
In this clinical case, we report an atypical and unique presentation of systemic lupus erythematosus (SLE) in a 39-year-old female with nephrotic syndrome. The patient exhibited class IV plus V lupus nephritis and extensive immune complex deposition within the intracapillary and arteriolar regions suggestive of cryoglobulinemic glomerulonephritis, despite no detectable circulating cryoglobulins. Electron microscopy revealed cryoglobulin-like deposit distribution in all glomerular examined compartments, namely subendothelial, intramembranous, subepithelial, and mesangial, apparently extending from the capillary hyaline thrombi. The case highlights the possibility of severe renal injury in SLE without circulating cryoglobulins and the diverse kidney manifestations associated with the disease. However, the impact on patient outcome was minimal, as classical treatment (id est National Institute of Health regimen) remained effective.


Screening and early detection of chronic kidney disease at primary healthcare.
Chronic kidney disease (CKD) represents a global public health concern and results in poor health outcomes. While the burden of CKD is accurately well defined in developed countries, increasing evidence indicates that the CKD burden may be even greater in developing countries. Primary care has an essential role in the early identification of CKD and the prompt integrated management between primary and secondary CKD care, with participation of the patient, should be done in high quality. Systematic screening for CKD in at-risk individuals is strongly indicated for timely intervention when needed and to perceive the impact of such policies on CKD incidence. Furthermore, failure to recognize a patient in stages 1-3 of CKD may result in high incidence of CKD complications and kidney failure, often leaving the patient unsuitable for different renal replacement therapies, such as dialysis and transplantation. Therefore, primary care early referral and consultation with a nephrologist can give a better chance for different dialysis procedures and minimize the rate of hospitalization and mortality.


[A Case of Dedifferentiated Liposarcoma of the Spermatic Cord].
A 63-year-old man was referred to our department because of painless hard mass in the right inguinal region. Abdominal computed tomography (CT) showed right spermatic cord mass measuring 25 mm in diameter. We performed right high orchiectomy. Histopathological diagnosis was dedifferentiated liposarcoma, which included myofibroblast components. He was alive 3 years postoperatively without recurrence.


Postcranial Skeletal Differences in Free-Range and Captive-Born Primates.
Skeletal morphology is important in evolutionary, genetic, developmental, physiological, and functional studies. Although samples from free-ranging individuals may be preferable, constraints of sample size, demography, or conservation status may necessitate the inclusion of captive-born individuals. Captivity may be associated with physical, physiological, or behavioral differences that may affect skeletal form. This study assesses differences in postcranial skeletal form between free-range and captive-born Macaca mulatta and Saguinus oedipus. Samples included free-range M. mulatta from Cayo Santiago (Caribbean Primate Research Center) and captive-born macaques from the Wisconsin National Primate Research Center. S. oedipus samples included free-range born and captive-born individuals from the Oak Ridge Associated Universities Marmoset Research Center. Twenty-four dimensions of various bones, including the scapula, upper limb, innominate and lower limb, were recorded for adults. Age of epiphyseal closure was recorded for immature captive-born M. mulatta. Analysis of variance and principal component analyses tested significant differences between free-range born and captive-born individuals in each species. Significant differences were present in size and shape of postcrania between free-range and captive-born within taxa. Free-range macaques were larger than captive-born macaques, but this pattern did not consistently carry over to the Saguinus samples. Shape differences, while present throughout the skeleton, were especially prominent in the scapula. Differences in developmental timing, nutrition, and physical activity can be expected to contribute to the observed differences in postcranial skeletal form. These differences should be considered when captive-born primates are included in morphological or evolutionary studies. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:761-774, 2019. © 2018 Wiley Periodicals, Inc.


Audience design through social interaction during group discussion.
This paper contrasts two accounts of audience design during multiparty communication: audience design as a strategic individual-level message adjustment or as a non-strategic interaction-level message adjustment. Using a non-interactive communication task, Experiment 1 showed that people distinguish between messages designed for oneself and messages designed for another person; consistent with strategic message design, messages designed for another person/s were longer (number of words) than those designed for oneself. However, audience size did not affect message length (messages designed for different sized audiences were similar in length). Using an interactive communication task Experiment 2 showed that as group size increased so too did communicative effort (number of words exchanged between interlocutors). Consistent with a non-strategic account, as group members were added more social interaction was necessary to coordinate the group's collective situation model. Experiment 3 validates and extends the production measures used in Experiment 1 and 2 using a comprehension task. Taken together, our results indicate that audience design arises as a non-strategic outcome of social interaction during group discussion.


Self-Collection for Primary HPV Testing: Perspectives on Implementation From Federally Qualified Health Centers.
Primary testing for high-risk human papillomavirus (HPV) by self-collection could result in higher rates of cervical cancer screening. Federally qualified health centers (FQHCs) in the US serve a large proportion of women who have low income and no health insurance and are medically underserved - risk factors for being insufficiently screened for cervical cancer. Although the implementation of self-collection for HPV testing is not yet widespread, health care entities need to prepare for its eventual approval by the US Food and Drug Administration. We conducted focus groups and interviews among clinical and administrative staff and leadership to gather data on key logistical concerns that must be addressed before implementing self-collection for HPV testing in FQHCs. We identified focus group and interview participants from 6 FQHCs in North Carolina. We conducted focus groups with clinical and administrative staff (N = 45) and semistructured interviews with chief executive officers, senior-level administrators, chief medical officers, and clinical data managers (N = 24). Transcripts were coded by using codebooks derived from research questions and notes taken during data collection. Themes emerged on implementation of self-collection for HPV testing. We applied the constructs from the Consolidated Framework for Implementation Research (CFIR) to themes to identify domains of potential barriers and facilitators to implementation. Clinical personnel reported that offering self-collection for HPV testing is acceptable and feasible and can increase cervical cancer screening rates. Uncertainties emerged about accuracy of results, workflow disruptions, financial implications, and effects on clinic quality measures. Implementing self-collection for HPV testing was considered feasible and acceptable by participants. However, important health service delivery considerations, including financial implications, must be addressed before integrating self-collection for HPV testing into the standard of care.


Genome Sequences of Vibrio navarrensis, a Potential Human Pathogen.
Vibrio navarrensis is an aquatic bacterium recently shown to be associated with human illness. We report the first genome sequences of three V. navarrensis strains obtained from clinical and environmental sources. Preliminary analyses of the sequences reveal that V. navarrensis contains genes commonly associated with virulence in other human pathogens.


Smart tattoo: technology for monitoring blood glucose in the future.
New ways of measuring blood glucose bring hope of easing the burden of diabetes management for patients living with the conditions. The smart tattoo is an innovation that represents a nascent nanotechnology, which is designed to be implanted within the skin to provide continuous and reliable glucose detection for individuals diagnosed with diabetes. The potential benefits of the smart tattoo are compelling not only due to the potential of these nanodevices to prevent diabetic complications and decrease the related social costs, but also due to ease of use and relative user comfort. However, despite the advantages of the smart tattoo, it is important that health professionals, in embracing nanotechnology, understand the ethical implications of using these innovative devices.


Resilience and Quality of Life in Breast Cancer Patients.
Many studies have shown that a relationship exists between quality of life (QoL) and resilience in breast cancer patients, but few studies present information on the nature of this relationship of resilience on QoL. Our aim was to examine the relationship between resilience and quality of life in breast cancer patients. QoL was measured in 218 consequent breast cancer patients, with EORTC - QLQ Core 30 questionnaire, and EORTC QLQ-BR23. The resilience was measured with Connor Davidson Resilience Scale. The global quality of life was positively correlated with the levels of resilience (R = 0.39 p < 0.001). All functional scales (physical, role, emotional, cognitive and social functioning was in a positive correlation with resilience. The symptoms severity (fatigue, nausea and vomitus, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) was in negative correlation with resilience. Less resilient breast cancer patients reported worse body image and future perspective and suffered from more severe adverse effects of systemic therapy, and arm/breast symptoms. Our findings show that psychological resilience affects different aspects of health-related quality of life. More resilient patients have significantly better quality of life in almost all aspects of QoL.


Influential factors on sexual function in infertile women with endometriosis: a path analysis.
Endometriosis have a negative influence on women's sexual life. The aim of the current study was to test a conceptual model considering the interrelated role of anxiety, depression, sleep quality, physical activity, BMI, stage of endometriosis, the intensity of dyspareunia and pelvic pain on sexual function (SF) in infertile women with endometriosis. Also test the mediating role of sleep quality, anxiety, and depression. In the present cross-sectional study, 220 infertile women with a laparoscopically confirmed endometriosis were recruited. Data were collected using a socio-demographic checklist, Female Sexual Function Index (FSFI), Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), Visual Analog Scale (VAS). We found that anxiety, depression, sleep quality, BMI, level of education, stage of endometriosis, and dyspareunia have a direct effect on women's SF. In our study, sleep quality, anxiety, pelvic pain, and depression were the four major mediators that the higher scores lead to a decrease in the SF of endometriosis patients. The intensity of pelvic pain with an effect on sleep quality (SQ) and dyspareunia change women's SF. The lower level of physical activity, and higher BMI with indirect effect thorough anxiety, and SQ can worsen SF. Also, a higher level of anxiety leads to poor SQ and depression. Anxiety with both direct and indirect effect impress women's SF. It seems that the main risk factors for sexual dysfunction in women with endometriosis are higher rates of anxiety, depression, poor sleep quality, pelvic pain, and dyspareunia. In the care of women with endometriosis, not only laparoscopy and medical treatment should be performed but also psychotherapeutic and psychosexual help should be offered.


Load-Induced Changes of Inter-Limb Asymmetries in Dynamic Postural Control in Healthy Subjects.
Inter-limb asymmetries are associated with a higher potential risk for non-contact injuries. Differences in function or performance between the limbs might lead to imbalances and promote instability, increasing the potential risk for injuries. Consequently, an investigation of inter-limb asymmetries should be included in injury risk assessment. Furthermore, since non-contact injuries mainly occur under loaded conditions, an investigation of load-induced changes of inter-limb asymmetries can provide additional information on the athlete's potential injury risk. Therefore, the current study aimed to investigate the influence of physical load on inter-limb asymmetries in dynamic postural control, which is essential in situations with a high risk for non-contact injuries such as landing, cutting, or stopping. In total, dynamic postural control of 128 active and healthy subjects (64 males and 64 females, age: 23.64 ± 2.44, height: 176.54 ± 8.96 cm, weight: 68.85 ± 10.98 kg) was examined. Dynamic postural control was tested with the Y-Balance Test (YBT) before and after a loading protocol on a bicycle ergometer or a treadmill. The results showed no significant increase of the inter-limb asymmetries in anterior direction [F (1, 126) = 4.44, p = 0.04, η2 p = 0.03]. Moreover, there is high variation between the subjects regarding the magnitude and the direction of the asymmetries and the changes due to load. Therefore, a more individual analysis considering the magnitude and the direction of the asymmetries is required. Thereby, considering different modifying factors, e.g., sex, injury history, and baseline level of asymmetries, can be helpful. Moreover, an analysis of the changes during load might provide further insights, reveal possible differences, and help detect the reasons and mechanisms underlying inter-limb asymmetries and asymmetrical loading.


Blur adaptation and myopia.
Previous studies have demonstrated a significant improvement in visual resolution during sustained periods of retinal defocus. This appears to result from perceptual adaptation designed to restore the perceived contrast of the degraded image. However, it is unclear whether perceptual adaptation to sustained blur is present in all individuals or only in certain subgroups, such as those who have been chronically exposed to sustained periods of blur due to uncorrected ametropia. Accordingly, the present study examined the effects of sustained retinal defocus on both high-and low-contrast visual acuity in emmetropes (n = 13) and myopes (n = 18). Subjects were required to view through +2.50-D spherical lenses worn over their distance refractive correction for a continuous 2-hour period. A significant improvement in both Landolt C and grating visual acuity measured through the fogging lenses was observed in both refractive groups. Although the mean change in grating visual acuity was significantly greater for the myopic subjects, the improvements in Landolt C acuity observed in the emmetropes and myopes were statistically equivalent. We hypothesize that the improvement in visual acuity results from perceptual adaptation to the blurred images, which may occur at central sites within the visual cortex.