An assessment of intra-individual variability in carotid artery longitudinal wall motion: recommendations for data acquisition.
To assess the intra-individual variation in carotid artery longitudinal wall motion (CALM) in healthy adults in order to determine the amount of data required to generate a representative measurement of CALM. We conducted an analysis of 27 healthy men to determine whether calculation of resting individual CALM outcomes is dependent on the number of averaged heart cycles. CALM was assessed at rest, 1-2 cm proximal to the right carotid bifurcation during a breath hold and was segmented into three motion displacements: systolic anterograde CALM, systolic retrograde CALM, and diastolic CALM. A 2D measure of total carotid artery motion (RALength) was also determined from the longitudinal and radial displacements. Outcomes were averaged discretely using two, three, four, five, and six consecutive heart cycles to assess the impact of additional data on intra-individual coefficients of variation (CV%) and intra-class correlations (ICC). Calculated means were similar between all heart cycle averaging for CALM displacements (all P > 0.05), though the two-heart cycle average of RALength (P = 0.06) was reduced in comparison to all other averages. Averaging data from four heart cycles was sufficient to generate a plateau in the variability in resting CALM displacements, such that within-subject ICC values all reached >0.90 and CV% were similar to previously reported day-to-day variability in healthy adults. There is variability in beat-to-beat measures of CALM that should be considered when designing protocols for data collection and analysis. We suggest that four consecutive heart cycles should be averaged to generate representative resting CALM outcomes in humans. While indices of variability were reduced when assessing outcomes generated from two to four heart cycles, no further improvements were observed when more heart cycles were included, indicating that averaging more than four heart cycles is likely not required.


In Vitro Evaluation of Antioxidant, Anti-Inflammatory, Antimicrobial and Wound Healing Potential of Thymus Sipyleus Boiss. Subsp. Rosulans (Borbas) Jalas.
Thymus sipyleus Boiss. subsp. rosulans (Borbas) Jalas (TS) is a commonly used plant in the treatment of various complaints, including skin wounds in Turkish folk medicine. Despite the widespread traditional use of TS, there is not any scientific report confirming the effectiveness of this plant on the healing process. This research aimed to investigate the effects of different extracts obtained from TS on biological events during wound healing, on a cellular basis. In this context, proliferative activities of the extracts, as well as the effects on wound closure and hydroxyproline synthesis, were determined. In addition to wound healing properties, the antioxidant, antibacterial and anti-inflammatory activities of the extracts were evaluated. Decoction (D) and infusion (I) extracts contained the highest amount of phenolic content and showed the most potent activity against DPPH radical. All extracts exhibited complete protection against the damage induced by hydrogen peroxide (H2O2) by increasing cell viability compared to only H2O2-treated groups, both in co-treatment and pre-treatment protocols. None of the extracts exhibited cytotoxic activity, and most of the extracts from the TS stimulated fibroblast proliferation and migration. All TS extracts exert anti-inflammatory activity by suppressing the overproduction of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO). The most pronounced activity on hydroxyproline synthesis was observed in D extract. In summary, it was observed that TS extracts can promote the healing process by enhancing fibroblast migration, proliferation and collagen synthesis as well as suppressing pro-inflammatory cytokines. The obtained data in this work support the traditional use of TS as a valuable plant-based compound for the treatment of wounds.


Perceptual Transitions between Object Rigidity & Non-rigidity: Competition and cooperation between motion-energy, feature-tracking and shape-based priors.
Why do moving objects appear rigid when projected retinal images are deformed non-rigidly? We used rotating rigid objects that can appear rigid or non-rigid to test whether shape features contribute to rigidity perception. When two circular rings were rigidly linked at an angle and jointly rotated at moderate speeds, observers reported that the rings wobbled and were not linked rigidly but rigid rotation was reported at slow speeds. When gaps, paint or vertices were added, the rings appeared rigidly rotating even at moderate speeds. At high speeds, all configurations appeared non-rigid. Salient features thus contribute to rigidity at slow and moderate speeds, but not at high speeds. Simulated responses of arrays of motion-energy cells showed that motion flow vectors are predominantly orthogonal to the contours of the rings, not parallel to the rotation direction. A convolutional neural network trained to distinguish flow patterns for wobbling versus rotation, gave a high probability of wobbling for the motion-energy flows. However, the CNN gave high probabilities of rotation for motion flows generated by tracking features with arrays of MT pattern-motion cells and corner detectors. In addition, circular rings can appear to spin and roll despite the absence of any sensory evidence, and this illusion is prevented by vertices, gaps, and painted segments, showing the effects of rotational symmetry and shape. Combining CNN outputs that give greater weight to motion energy at fast speeds and to feature tracking at slow, with the shape-based priors for wobbling and rolling, explained rigid and nonrigid percepts across shapes and speeds (R 2 =0.95). The results demonstrate how cooperation and competition between different neuronal classes leads to specific states of visual perception and to transitions between the states.


Corneal stromal cell plasticity: in vitro regulation of cell phenotype through cell-cell interactions in a three-dimensional model.
In vivo, epithelial cells are connected both anatomically and functionally with stromal keratocytes. Co-culturing aims at recapturing this cellular anatomy and functionality by bringing together two or more cell types within the same culture environment. Corneal stromal cells were activated to their injury phenotype (fibroblasts) and expanded before being encapsulated in type I collagen hydrogels constructs. Three different epithelial-stromal co-culture methods were then examined: epithelial explant; transwell; and the use of conditioned media. The aim was to determine whether the native, inactivated keratocyte cell phenotype could be restored in vitro. Media supplementation with transforming growth factor beta-1 (TGF-β1) was then used to determine whether the inactivated stromal cells retained their plasticity in vitro and could be re-activated to the fibroblast phenotype. Finally, media supplementation with wortmannin was used to inhibit epithelial-stromal cell interactions. Two different nondestructive techniques, spherical indentation and optical coherence tomography, were used to reveal how epithelial-stromal co-culturing with TGF-β1, and wortmannin media supplementation, respectively, affect stromal cell behavior and differentiation in terms of construct contraction and elastic modulus measurement. Cell viability, phenotype, morphology, and protein expression were investigated to corroborate our mechanical findings. It was shown that activated stromal cells could be inactivated to a keratocyte phenotype via co-culturing and that they retained their plasticity in vitro. Activated corneal stromal cells that were fibroblastic in phenotype were successfully reverted to a nonactivated keratocyte cell lineage in terms of behavior and biological properties; and then back again via TGF-β1 media supplementation. It was then revealed that epithelial-stromal interactions can be blocked via the use of wortmannin inhibition. A greater understanding of stromal-epithelial interactions and what mediates them offers great pharmacological potential in the regulation of corneal wound healing, with the potential to treat corneal diseases and injury by which such interactions are vital.


[Rapid diagnosis in infectious diseases].
Rapid detection of infectious agents has recently received a lot of interest. The aim of this article is to review its various aspects in terms of real impact on the medical handling of the infected patient as well as economical impact. Few examples are developed in detail, including technical strategies: sexually transmitted diseases due to Chlamydia trachomatis; gastroenteritis due to rotavirus and adenovirus, bacterial pneumonia and meningitis, and acute tonsillitis due to beta-hemolytic group A streptococci.


PKA phosphorylates and inactivates AMPKalpha to promote efficient lipolysis.
The mobilization of metabolic energy from adipocytes depends on a tightly regulated balance between hydrolysis and resynthesis of triacylglycerides (TAGs). Hydrolysis is stimulated by beta-adrenergic signalling to PKA that mediates phosphorylation of lipolytic enzymes, including hormone-sensitive lipase (HSL). TAG resynthesis is associated with high-energy consumption, which when inordinate, leads to increased AMPK activity that acts to restrain hydrolysis of TAGs by inhibiting PKA-mediated activation of HSL. Here, we report that in primary mouse adipocytes, PKA associates with and phosphorylates AMPKalpha1 at Ser-173 to impede threonine (Thr-172) phosphorylation and thus activation of AMPKalpha1 by LKB1 in response to lipolytic signals. Activation of AMPKalpha1 by LKB1 is also blocked by PKA-mediated phosphorylation of AMPKalpha1 in vitro. Functional analysis of an AMPKalpha1 species carrying a non-phosphorylatable mutation at Ser-173 revealed a critical function of this phosphorylation for efficient release of free fatty acids and glycerol in response to PKA-activating signals. These results suggest a new mechanism of negative regulation of AMPK activity by PKA that is important for converting a lipolytic signal into an effective lipolytic response.


A multicenter, randomized, open study to evaluate the impact of an electronic data capture system on the care of patients with rheumatoid arthritis.
To examine the impact of an electronic data capture system on patient satisfaction and patient-physician interactions in a rheumatology clinical setting. In this multicenter study, 1079 patients with rheumatoid arthritis completed questionnaires quarterly about their health and satisfaction with care using a computer. At 6 months, 901 eligible patients were randomized 2:1 to receive or not to receive graphical summarized health information or Health Tracker (HT) reports. Data collected at each visit included patient satisfaction with care; patient-physician interaction assessments; a 56-joint self-assessment for patients; a 28-joint assessment for physicians; patient pain, fatigue, and global assessments (visual analogue scale, physician global assessment, Health Assessment Questionnaire, and Short Form-12) all of which were cumulatively recorded in the HT report. Patient demographics at baseline were similar between groups. Changes from baseline to 1 year showed that patients in the HT-viewers group were significantly more satisfied with their care (p < 0.001) than those in the HT-nonviewers group (p = 0.131). Physicians reported improved interactions with patients at 1 year in both the HT-viewers (p < 0.001) and HT-nonviewers groups (p = 0.002); however, the improvement was significantly larger for the HT-viewers group than for the HT-nonviewers group (p < 0.001). Adverse events were comparable between groups. Patient access to systematically collected patient data reports promoted self-involvement and improved patient satisfaction and patient-physician interactions more in the HT-viewers than in HT-nonviewers groups at 1 year (p < 0.001). This was an open, observational study; no formal hypothesis testing was conducted. The HT system was not validated and some bias may have existed with respect to patient comfort level with a computer, user error, and timing of data entry of the physicians' assessments.


Reactions of CH3SH and CH3SSCH3 with gas-phase hydrated radical anions (H2O)n(•-), CO2(•-)(H2O)n, and O2(•-)(H2O)n.
The chemistry of (H(2)O)(n)(•-), CO(2)(•-)(H(2)O)(n), and O(2)(•-)(H(2)O)(n) with small sulfur-containing molecules was studied in the gas phase by Fourier transform ion cyclotron resonance mass spectrometry. With hydrated electrons and hydrated carbon dioxide radical anions, two reactions with relevance for biological radiation damage were observed, cleavage of the disulfide bond of CH(3)SSCH(3) and activation of the thiol group of CH(3)SH. No reactions were observed with CH(3)SCH(3). The hydrated superoxide radical anion, usually viewed as major source of oxidative stress, did not react with any of the compounds. Nanocalorimetry and quantum chemical calculations give a consistent picture of the reaction mechanism. The results indicate that the conversion of e(-) and CO(2)(•-) to O(2)(•-) deactivates highly reactive species and may actually reduce oxidative stress. For reactions of (H(2)O)(n)(•-) with CH(3)SH as well as CO(2)(•-)(H(2)O)(n) with CH(3)SSCH(3), the reaction products in the gas phase are different from those reported in the literature from pulse radiolysis studies. This observation is rationalized with the reduced cage effect in reactions of gas-phase clusters.


Smoker's Paradox in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.
Prior studies have found that smokers undergoing thrombolytic therapy for ST-segment elevation myocardial infarction have lower in-hospital mortality than nonsmokers, a phenomenon called the "smoker's paradox." Evidence, however, has been conflicting regarding whether this paradoxical association persists in the era of primary percutaneous coronary intervention. We used the 2003-2012 National Inpatient Sample databases to identify all patients aged ≥18 years who underwent primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Multivariable logistic regression was used to compare in-hospital mortality between smokers (current and former) and nonsmokers. Of the 985 174 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, 438 954 (44.6%) were smokers. Smokers were younger, were more often men, and were less likely to have traditional vascular risk factors than nonsmokers. Smokers had lower observed in-hospital mortality compared with nonsmokers (2.0% versus 5.9%; unadjusted odds ratio 0.32, 95% CI 0.31-0.33, P<0.001). Although the association between smoking and lower in-hospital mortality was partly attenuated after baseline risk adjustment, a significant residual association remained (adjusted odds ratio 0.60, 95% CI 0.58-0.62, P<0.001). This association largely persisted in age-stratified analyses. Smoking status was also associated with shorter average length of stay (3.5 versus 4.5 days, P<0.001) and lower incidence of postprocedure hemorrhage (4.2% versus 6.1%; adjusted odds ratio 0.81, 95% CI 0.80-0.83, P<0.001) and in-hospital cardiac arrest (1.3% versus 2.1%; adjusted OR 0.78, 95% CI 0.76-0.81, P<0.001). In this nationwide cohort of patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, we observed significantly lower risk-adjusted in-hospital mortality in smokers, suggesting that the smoker's paradox also applies to ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.


How Common is Eosinophilia in Tuberculosis? Case Report.
Though peripheral blood eosinophilia is common due to allergic diseases, drugs, parasitic infections, and malignancies, it is rarely reported due to tuberculosis (TB). The association between eosinophilia and TB is not well known. We have a case of the 9-year-old female present with abdominal pain in the right upper quadrant which is non-radiating associated with decreased appetite, weight loss, malaise and low-grade fever and vomiting of ingested of two weeks. On examination, she had severe wasting and hepatomegaly. On investigations, she had leukocytosis with 50% of eosinophilia, high ESR, multiple liver cysts (abdominal ultrasound and CT) and biopsy suggestive of TB. Finally, the patient started on anti-TB and her response was followed by clinical and laboratory parameters. After three weeks of treatment with anti-TB, she starts to gain weight, improve abdominal pain, appetite loss, and the investigation also normalized (leukocyte and the eosinophil become normalized, ESR corrected). The patient was to follow up for two years in the clinic and finally discharged. The coexistence of eosinophilia and TB in our patient is suggested because of the biopsy results in conjunction with the improvement of peripheral blood eosinophilia with anti-TB treatment. This example hopefully will encourage future investigations and researchers to look at the prevalence and a clear association of TB and peripheral eosinophilia.


A Dual SILAC Proteomic Labeling Strategy for Quantifying Constitutive and Cell-Cell Induced Protein Secretion.
Recent evidence suggests that the extracellular protein milieu is much more complex than previously assumed as various secretome analyses from different cell types described the release of hundreds to thousands of proteins. The extracellular function of many of these proteins has yet to be determined particularly in the context of three-dimensional tissues with abundant cell-cell contacts. Toward this goal, we developed a strategy of dual SILAC labeling astrocytic cultures for in silico exclusion of unlabeled proteins from serum or neurons used for stimulation. For constitutive secretion, this strategy allowed the precise quantification of the extra-to-intracellular protein ratio of more than 2000 identified proteins. Ratios covered 4 orders of magnitude indicating that the intracellular vs extracellular contributions of different proteins can be variable. Functionally, the secretome of labeled forebrain astrocytic cultures specifically changed within hours after adding unlabeled, "physiological" forebrain neurons. "Nonphysiological" cerebellar hindbrain neurons, however, elicited a different, highly repulsive secretory response. Our data also suggest a significant association of constitutive secretion with the classical secretion pathway and regulated secretion with unconventional pathways. We conclude that quantitative proteomics can help to elucidate general principles of cellular secretion and provide functional insight into the abundant extracellular presence of proteins.


[Anti-arrhythmia activity of derinat in an experiment].
The acute toxicity of the immunostimulant derinat is very low: the LD50 value for intraperitoneal administration exceeds 1000 mg/kg. The drug effectively prevents from acute arrhythmia development upon occlusion in cats and produces antifibrillator effect on a model of reperfusive arrhythmia in a dose of 7.5 mg/kg. Derinat also exhibits the antiarrhythmic activity on the model of adrenalin-induced rhythm violations, but appears ineffective on the calcium chloride model.


Maternal Metformin Treatment Improves Developmental and Metabolic Traits of IUGR Fetuses.
Metformin is an anti-hyperglycemic drug widely used for the treatment of insulin resistance and glucose intolerance and is currently considered for preventing large-for-gestational-age (LGA) offspring in pregnant women affected by obesity or diabetes. Our hypothesis was the opposite-metformin may be used for improving the development of offspring affected by intrauterine growth restriction (IUGR) and preventing the appearance of small-for-gestational-age (SGA) neonates in non-obese and non-diabetic but malnourished pregnancies. The current study, performed in a swine preclinical model of IUGR by undernutrition, showed that fetuses in the treated group showed no significant increases in body-weight, but showed a significantly higher weight of the brain, the total thoracic and abdominal viscera, the liver, the kidneys, the spleen, and the adrenal glands. Maternal metformin treatment was also related to significant increases in the fetal plasma concentration of parameters indicative of glycemic (glucose and fructosamine) and lipid profiles (triglycerides). Overall, these results suggest a protective effect of the treatment on the developmental competence of the fetuses. These findings may be of high value for human medicine in case of maternal malnutrition, since metformin is a cheap drug easily available, but also in case of placental deficiency, since metformin seems to improve placental development and function.


A pair of Bacillus subtilis ribosomal protein genes mapping outside the principal ribosomal protein cluster.
Before now, the only ribosomal protein gene loci to be identified in Bacillus subtilis map within the principal ribosomal protein gene cluster at about 10 degrees on the linkage map. Using mutants with alterations in large subunit ribosomal proteins L20 or L24, I mapped the corresponding genes near leuA at approximately 240 degrees. The data were fully consistent with the fact that the genes for the two proteins were close together but not near any other ribosomal protein genes, as is also the case with the genes for the corresponding proteins of Escherichia coli.


Analysis of the TCR beta variable gene repertoire in chimpanzees: identification of functional homologs to human pseudogenes.
Chimpanzees are used for a variety of disease models such as hepatitis C virus (HCV) infection, where Ag-specific T cells are thought to be critical for resolution of infection. The variable segments of the TCR alphabeta genes are polymorphic and contain putative binding sites for MHC class I and II molecules. In this study, we performed a comprehensive analysis of genes that comprise the TCR beta variable gene (TCRBV) repertoire of the common chimpanzee Pan troglodytes. We identified 42 P. troglodytes TCRBV sequences representative of 25 known human TCRBV families. BV5, BV6, and BV7 are multigene TCRBV families in humans and homologs of most family members were found in the chimpanzee TCRBV repertoire. Some of the chimpanzee TCRBV sequences were identical with their human counterparts at the amino acid level. Notably four successfully rearranged TCRBV sequences in the chimpanzees corresponded to human pseudogenes. One of these TCR sequences was used by a cell line directed against a viral CTL epitope in an HCV-infected animal indicating the functionality of this V region in the context of immune defense against pathogens. These data indicate that some TCRBV genes maintained in the chimpanzee have been lost in humans within a brief evolutionary time frame despite remarkable conservation of the chimpanzee and human TCRBV repertoires. Our results predict that the diversity of TCR clonotypes responding to pathogens like HCV will be very similar in both species and will facilitate a molecular dissection of the immune response in chimpanzee models of human diseases.


Nonsurgical Therapy for Solitary Rectal Ulcer Syndrome.
The treatment of solitary rectal ulcer syndrome (SRUS) remains problematic and is less than ideal. Prospective, well-designed studies assessing the efficacy of treatment for SRUS are few; most of the knowledge imparted for treating SRUS is experiential. As such, firm treatment recommendations can not be made. Rather, a conservative, stepwise, individualized approach must be employed. Diagnostic modalities should be incorporated in the management scheme to direct treatment when indicated. Management must include patient reassurance that the underlying lesion is benign, because complete "cures" are uncommon in those with SRUS. The goals of therapy should be discussed with the patient prior to initiating treatment. Although the ultimate goal is macroscopic and microscopic healing, a realistic goal is cessation or minimization of symptoms. We outline a reasonable approach to the management of SRUS. Histologic confirmation of SRUS should prompt a discussion of the presumed pathogenic mechanisms with the patient. Conservative therapy with dietary fiber, bowel retraining, and bulk laxatives should be employed. If symptoms persist, the patient should receive a trial of sucralfate enemas for 6 weeks. Individuals who respond should continue conservative therapy. However, if symptoms persist, defecography can be done to assess for inappropriate puborectalis contraction and occult rectal mucosal prolapse. Patients with inappropriate contraction of the puborectalis can be offered biofeedback. Patients with occult rectal mucosal prolapse can be considered for surgery. However, the risks, benefits, and success rates of surgery should be discussed at length, prior to any procedure being performed. Rectopexy or Delorme's procedure offer the best success rates to date; however, the choice of surgical procedure must take into account the experience of the surgeon and wishes of the patient.


The dialog between psychoanalysis and neuroscience: what does philosophy of mind say?
To briefly review how the main monist and dualist currents of philosophy of mind approach the mind-body problem and to describe their association with arguments for and against a closer dialog between psychoanalysis and neuroscience. The literature was reviewed for studies in the fields of psychology, psychoanalysis, neuroscience, and philosophy of mind. Some currents are incompatible with a closer dialog between psychoanalysis and neurosciences: interactionism and psychophysical parallelism, because they do not account for current knowledge about the brain; epiphenomenalism, which claims that the mind is a mere byproduct of the brain; and analytical behaviorism, eliminative materialism, reductive materialism and functionalism, because they ignore subjective experiences. In contrast, emergentism claims that mental states are dependent on brain states, but have properties that go beyond the field of neurobiology. Only emergentism is compatible with a closer dialog between psychoanalysis and neuroscience.


Return to Play After Symptomatic Lumbar Disc Herniation in Elite Athletes: A Systematic Review and Meta-analysis of Operative Versus Nonoperative Treatment.
The prevalence of symptomatic lumbar disc herniation (LDH) in athletes can be as high as 75%. For elite athletes diagnosed with LDH, return to play (RTP) is a major concern, and thus comparing surgical with nonoperative care is essential to guide practitioners and athletes, not just in terms of recovery rates but also speed of recovery. The purpose of this systematic review is to provide an update on RTP outcomes for elite athletes after lumbar discectomy versus nonoperative treatment of LDHs. A search of the literature was conducted using 3 online databases (MEDLINE, EMBASE, and PubMed) to identify pertinent studies. Yielded studies were screened according to the inclusion criteria. Systematic review with meta-analysis. Level 4. Relevant data were extracted. A meta-analysis was performed comparing RTP rate for all comparative studies. Twenty studies met the inclusion criteria and were included in this review. Overall, 663 out of 799 patients (83.0%) returned to play in the surgical group and 251 out of 308 patients (81.5%) returned to play in the nonoperative group. No statistically significant difference for RTP rate was found (odds ratio, 1.39; 95% CI, 0.58-3.34; P = 0.46; I2, 71%). The mean time to RTP for patients undergoing lumbar discectomy was 5.19 months (range 1.00-8.70 months), and 4.11 months (range 3.60-5.70 months) for those treated conservatively. There was no significant difference in RTP rate between athletes treated with operative or nonoperative management of LDHs, nor did operative management have a faster time to RTP. Athletes should consider the lack of difference in RTP rate in addition to the potential risks associated with spinal surgery when choosing a treatment option. Future randomized controlled trials are needed on this topic to allow for high-powered conclusions.


Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor.
Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor (NSF). NO inhibits NSF disassembly of soluble NSF attachment protein receptor (SNARE) complexes by nitrosylating critical cysteine residues of NSF. NO may regulate exocytosis in a variety of physiological processes, including vascular inflammation, neurotransmission, thrombosis, and cytotoxic T lymphocyte cell killing.


Comparison of the effects of three persimmon cultivars on lipid and glucose metabolism in high-fat diet-fed mice.
We compared the effects of three persimmon cultivars, one nonastringent-type fruit (Fuyu) and two astringent-type fruits (Hiratanenashi and Hachiya), on the lipid and glucose metabolism of high-fat diet-fed mice. Persimmon samples prepared from young fruits of the three cultivars contained around 80% dietary fiber and differed in their bile acid-binding abilities and tannin contents. C57BL/6J mice were fed a modified AIN76 high-fat diet supplemented with 2% of each persimmon sample instead of cellulose for 10 wk. All cultivars significantly accelerated fecal bile acid secretion, depending on the bile acid-binding ability of the cultivars. Hiratanenashi and Hachiya, the cultivars with a strong bile acid-binding ability, prevented any increase in fasting blood glucose and plasma nonesterified fatty acid levels. Hachiya, the cultivar with the highest tannin content, also tended to prevent an increase in plasma non-high-density lipoprotein cholesterol levels. However, Fuyu, the cultivar with the lowest bile acid-binding ability and tannin content, had no effect on lipid or glucose metabolism. These effects linked to expression of the genes related to lipid and energy metabolism, including the cytochrome P450 7A1 gene in the liver and the uncoupling protein 3 gene in the brown adipose tissue. These results indicate that the beneficial effects of these cultivars on lipid and glucose metabolism are closely related to their bile acid-binding ability and tannin content.


A pyroelectric infrared biometric system for real-time walker recognition by use of a maximum likelihood principal components estimation (MLPCE) method.
This paper presents a novel biometric system for real-time walker recognition using a pyroelectric infrared sensor, a Fresnel lens array and signal processing based on the linear regression of sensor signal spectra. In the model training stage, the maximum likelihood principal components estimation (MLPCE) method is utilized to obtain the regression vector for each registered human subject. Receiver operating characteristic (ROC) curves are also investigated to select a suitable threshold for maximizing subject recognition rate. The experimental results demonstrate the effectiveness of the proposed pyroelectric sensor system in recognizing registered subjects and rejecting unknown subjects.


Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B.
For patients undergoing liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease, the current standard of care for preventing reinfection of the allograft is nucleoside analogue therapy combined with hepatitis B immune globulin (HBIG). Entecavir has demonstrated high efficacy and a favorable safety profile for chronic hepatitis B (CHB) treatment, but data for patients undergoing HBV-related LT are limited. This study assessed the safety and efficacy of entecavir combined with various HBIG regimens after CHB-related LT. In this phase 3b, single-arm, open-label study, 65 patients undergoing LT for CHB-related liver disease with an HBV DNA load <172 IU/mL at LT received entecavir (1.0 mg daily) for 72 weeks after LT. The primary endpoint was the proportion of evaluable patients (treated for ≥4 weeks) with virological recurrence (HBV DNA level ≥50 IU/mL) through week 72. Concomitant HBIG therapy was received by 64 of the 65 enrolled patients, and 44% of these patients received high-dose HBIG (any HBIG dose in the specified interval ≥10,000 IU). Through week 72, all 61 patients evaluable for the efficacy analysis had undetectable HBV DNA. The Kaplan-Meier estimate of patients without hepatitis B surface antigen (HBsAg) recurrence at week 72 was 0.9655. Two patients experienced a reappearance of HBsAg, but both remained HBV DNA(-) until the last follow-up. The frequency and nature of adverse events were consistent with those expected for this patient population. Serum creatinine increments ≥0.3 mg/dL and ≥0.5 mg/dL occurred in 62% and 39% of the patients, respectively, and all of these patients received calcineurin inhibitor therapy. In conclusion, in this population of patients treated with entecavir after CHB-related LT, entecavir was well tolerated and effective in maintaining viral suppression, even in individuals who experienced a reappearance of HBsAg.


Comparative trial of Nutrizym in chronic pancreatic insufficiency.
A cross-over trial of pancreatic replacement therapy was carried out in 12 adults with chronic pancreatic insufficiency. The standard enteric-coated preparation, Pancrex V forte, was compared with Nutrizym, which has an enteric-coated core of pancreatic extract and a shell of bromelains-a mixture of proteolytic enzymes derived from the stem of the pineapple.Nutrizym was significantly more effective than Pancrex V forte in improving fat absorption, and reduced faecal weight. Protein digestion was assessed by measuring the urinary excretion of hydroxyproline after a gelatin meal. Nutrizym produced an earlier and significantly higher peak in hydroxyproline excretion than Pancrex V forte, but the cumulative effect was similar. The value of bromelains was investigated by including a period on the Nutrizym core alone. This was similar to Pancrex V forte in improving fat absorption but had less effect on protein digestion, suggesting that the beneficial effect of Nutrizym compared with Pancrex V forte was due to the added bromelains, and not to differences in enzyme content or enteric coating.


Effects of perinatal polychlorinated biphenyls on adult female rat reproduction: development, reproductive physiology, and second generational effects.
Perinatal exposures to endocrine-disrupting chemicals, such as polychlorinated biphenyls (PCBs), can cause latent effects on reproductive function. Here, we tested whether PCBs administered during late pregnancy would compromise reproductive physiology in both the fetally exposed female offspring (F1 generation), as well as in their female offspring (F2 generation). Pregnant Sprague-Dawley rats were treated with the PCB mixture, Aroclor 1221 (A1221; 0, 0.1, 1, or 10 mg/kg), on Embryonic Days 16 and 18. Somatic and reproductive development of F1 and their F2 female offspring were monitored, including ages of eye opening, pubertal landmarks, and serum reproductive hormones. The results showed that low doses of A1221 given during this critical period of neuroendocrine development caused differential effects of A1221 on F1 and F2 female rats. In both generations, litter sex ratio was skewed toward females. In the F1 generation, additional effects were found, including a significant alteration of serum LH in the 1 mg/kg A1221 group. The F2 generation showed more profound alterations, particularly with respect to fluctuations in hormones and reproductive tract tissues across the estrous cycle. On proestrus, the day of the preovulatory GnRH/gonadotropin surge, F2 females whose mothers had been exposed perinatally to A1221 exhibited substantially suppressed LH and progesterone concentrations, and correspondingly smaller uterine and ovarian weights on estrus, compared with F2 descendants of control rats. These latter changes suggest a dysregulation of reproductive physiology. Thus, low levels of exposure to PCBs during late fetal development cause significant effects on the maturation and physiology of two generations of female offspring. These findings have implications for reproductive health and fertility of wildlife and humans.


The relationship between MTHFR gene polymorphisms, plasma homocysteine levels and diabetic retinopathy in type 2 diabetes mellitus.
To evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine levels in patients with type 2 diabetes mellitus and diabetic retinopathy (DR). Total of 208 patients with type 2 diabetes mellitus and 57 controls were recruited into the study. MTHFR genetic C677T polymorphisms were determined by PCR-RFLP. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. The frequencies of MTHFR TT homogeneous type, CT heterogeneous type and allele T (28.18%, 41.82%, 49.09%) were significantly higher in the type 2 diabetes mellitus with diabetic retinopathy group than those without retinopathy (18.37%, 29.59%, 33.16%) and those of controls (17.54%, 28.07%, 31.58%). The presence of the T allele appeared to have a strong association with the development of diabetic retinopathy. The odds ratio was 1.94 with a 95% confidence interval of 1.31 - 2.88. Moreover, plasma homocysteine levels were remarkably higher in patients with TT or CT genotype than in patients with the CC genotype. MTHFR gene C677T mutation associated with a predisposition to increased plasma homocysteine levels may be considered as a genetic risk factor for diabetic microangiopathy (such as DR) in Chinese patients with type 2 diabetes mellitus.


Perceived social support moderates the link between threat-related amygdala reactivity and trait anxiety.
Several lines of research have illustrated that negative environments can precipitate psychopathology, particularly in the context of relatively increased biological risk, while social resources can buffer the effects of these environments. However, little research has examined how social resources might buffer proximal biological risk for psychopathology or the neurobiological pathways through which such buffering may be mediated. Here we report that the expression of trait anxiety as a function of threat-related amygdala reactivity is moderated by perceived social support, a resource for coping with adversity. A significant positive correlation between amygdala reactivity and trait anxiety was evident in individuals reporting below average levels of support but not in those reporting average or above average levels. These results were consistent across multiple measures of trait anxiety and were specific to anxiety in that they did not extend to measures of broad negative or positive affect. Our findings illuminate a biological pathway, namely moderation of amygdala-related anxiety, through which social support may confer resilience to psychopathology. Moreover, our results indicate that links between neural reactivity and behavior are not static but rather may be contingent on social resources.


Bevacizumab and Aflibercept Activate Platelets via FcγRIIa.
To confirm the formation of a drug-growth factor complex and investigate the effects of three VEGF inhibitors in the activation of platelets. Growth factors and individual drugs were mixed and incubated. Scattered light intensity was measured by dynamic light scattering (DLS) to monitor the formation of drug-growth factor complex. Blood samples were obtained from 16 subjects (5 AMD patients and 11 healthy volunteers). Platelets obtained from the platelet-rich fraction by centrifugation were washed and resuspended in HEPES/Tyrode buffer. Platelet aggregability was assessed using a light transmission aggregometer in the presence of VEGF inhibitors and growth factors. In DLS study, a mixture of bevacizumab and VEGF-A showed one peak with a relatively gentle slope, indicating a heterogeneous mixture of multimeric bevacizumab-VEGF-A complexes. In aggregation study, no detectable aggregation was observed in the presence of ranibizumab, while significant aggregation was observed in the presence of VEGF-A and bevacizumab in five cases (one AMD patient and four healthy volunteers), VEGF-B and aflibercept in two cases (two volunteers), and placental growth factor (PlGF) and aflibercept in one case (one volunteer). No aggregation was observed when FcγRIIa antibody was added beforehand. A complex composed of bevacizumab or aflibercept, but not ranibizumab, and growth factors activates platelets via FcγRIIa.


Concurrent lymphoma and pancreatic adenocarcinoma.
Retroperitoneal lymph node enlargement in patients with pancreatic cancer is sometimes treated as incurable disease. Non-metastatic causes of lymphadenopathy should however be considered. Two cases of significant retroperitoneal lymphadenopathy in the setting of pancreatic cancer, treated by pancreaticoduodenectomy and lymph node dissection are described. Both cases had a final diagnosis of concurrent pancreatic cancer and lymphoma with no evidence of pancreatic lymph node metastasis on histopathology. We discuss the patterns of normal lymph node involvement in pancreatic cancer and lymphoma. Interpretation of staging imaging is important in patients with pancreatic cancer. Not all enlarged lymph node should be attributed to pancreatic cancer.


Evaluation of Ca2+ Binding Sites in Tacrolimus by Infrared Multiple Photon Dissociation Spectroscopy.
Tacrolimus (TAC) is an efficient immunosuppressant used in organ transplantation procedures. There is an intrinsic correlation between TAC and Ca2+ because of the dependence of its action mechanism on calcium and calcineurin, and the role of ion coordination on TAC identification and quantitation. To depict the Ca2+ binding sites in TAC, this work carried out gas-phase vibrational infrared multiple photon dissociation spectroscopy of [Ca(TAC)]2+ and of three other TAC mimetic molecules (probes 1-3). Density functional theory (DFT) and Monte Carlo (MC) simulations were also used to support the experimental data assignment, and natural bond orbital (NBO) analysis was carried out to depict the coordination sphere. PM3 and B3LYP/6-31G(d) levels of theory displayed similar trends during the MC simulations, suggesting that PM3 is a viable alternative to more expensive DFT calculations, at least during the conformational analysis step. Infrared spectroscopy of the [Ca(probe X)1]2+ and [Ca(probe X)3]2+ ( X = 1-3) complexes allowed for a useful guide for building guess geometries and for the band assignment of the [Ca(TAC)]2+ complex. Nevertheless, the MC approach was particularly useful for exploring the potential energy surface. The lowest energy conformation for [Ca(TAC)]2+ was found by MC simulations and is 32.92 kJ mol-1 lower in energy than the one found by comparing the results obtained for Ca2+ coordination in probes, despite the calculated spectra being virtually identical. Both approaches are good ways to depict the coordination sites, and these results suggest that using small molecules as models is a reliable approach to depict the geometry or coordination sites of extensive ions, yielding a robust correlation between experimental and theoretical spectra. Furthermore, MC survey produced a lower energy conformation with a good match to the experimental results. Both methods depict the Ca2+ coordination sphere as a hexacoordinated environment where the main coordination centers are carbonyl groups.


Active Predictive Coding: A Unifying Neural Model for Active Perception, Compositional Learning, and Hierarchical Planning.
There is growing interest in predictive coding as a model of how the brain learns through predictions and prediction errors. Predictive coding models have traditionally focused on sensory coding and perception. Here we introduce active predictive coding (APC) as a unifying model for perception, action, and cognition. The APC model addresses important open problems in cognitive science and AI, including (1) how we learn compositional representations (e.g., part-whole hierarchies for equivariant vision) and (2) how we solve large-scale planning problems, which are hard for traditional reinforcement learning, by composing complex state dynamics and abstract actions from simpler dynamics and primitive actions. By using hypernetworks, self-supervised learning, and reinforcement learning, APC learns hierarchical world models by combining task-invariant state transition networks and task-dependent policy networks at multiple abstraction levels. We illustrate the applicability of the APC model to active visual perception and hierarchical planning. Our results represent, to our knowledge, the first proof-of-concept demonstration of a unified approach to addressing the part-whole learning problem in vision, the nested reference frames learning problem in cognition, and the integrated state-action hierarchy learning problem in reinforcement learning.


Neuropharmacological effects of methotrexate perfused through the cerebrospinal fluid system of the rhesus monkey.
Thirteen adult Rhesus monkeys were repeatedly perfused through the ventriculocisternal or ventriculolumbar spaces with Elliott's B solution containing various concentrations of methotrexate (MTX) and trace amounts of [3H]MTX and [carboxy-14C]inulin. The concentrations of MTX ranged from 4.8 to 0.15 mg/ml representing perfusion dosages of 551 mg/sq m to 16 mg/sq m. The average steady-state concentration out-concentration in (Co/Ci) value for MTX was 0.78 +/- 0.04 for the ventriculocisternal and 0.66 +/- 0.01 for the ventriculolumbar routes. MTX treatments did not significantly affect mean inulin steady-state Co/Ci values or CSF formation rate. With the exception of a monkey perfused with MTX at an inflow concentration of 4.8 mg/ml, body weight, food intake, and urine output, analyzed at weekly intervals, generally were not remarkably affected by MTX perfusions. In five monkeys perfused with MTX in concentrations of 4.8 to 0.6 mg/ml, gross neurological toxicity was observed, principally in the form of seizures and hypokinesia during perfusion series with occasional residual motor deficit. Significant cerebral damage was associated with the brains of two monkeys perfused with MTX at concentrations of 2.4 and 0.6 mg/ml and two monkeys perfused at concentrations of 1.2 and 0.3 mg/ml; there of the four animals displayed signs of gross neurotoxicity, and two animals developed permanent motor deficits. However, the extent to which neurotoxic signs could be attributed solely to MTX was difficult to judge because some changes in central nervous system morphology were associated with the mechanical aspects of the procedure. Overall behavioral performance as measured by a visual pattern discrimination reinforced by avoidance or escape from an electric shock was not significantly affected by repeated perfusions of MTX (0.6 mg/ml) in two monkeys not otherwise studied in detail.


Power-Up for Mucoadhesiveness: Two Generations of Thiolated Surfactants for Enhanced Sticky Nanoemulsions.
Nanoemulsions can be tuned toward enhanced gastro-intestinal retention time by incorporating thiolated surfactants into their surface. Tailoring the chemical reactivity of the thiol headgroup has major influence on mucoadhesive features of the nanoemulsion. Two generations of thiolated surfactants were synthetically derived from PEG-40-stearate featuring either a free thiol group or an S-protected thiol group. The surfactants were characterized regarding critical micelle concentration (CMC), hemolytic activity, and cytotoxicity. Subsequently, they were incorporated into nanoemulsions and the resulting nanoemulsions were characterized regarding particle size, polydispersity index (PDI), zeta potential, and time-dependent stability. Afterward, mucosal interactions as well as mucoadhesion on porcine intestinal mucosa were investigated. Successful synthesis of Cysteine-PEG-40-stearate (CYS-PEG-40-stearate) and MNA-Cysteine-PEG-40-stearate (MNA-CYS-PEG-40-stearate) was confirmed by 1H NMR spectroscopy. Both chemical modifications led to slightly elevated CMC values while preserving low cytotoxicity and hemotoxicity. Incorporation into nanoemulsions had minor influence on overall physical particle characteristics, while interactions with mucus and mucoadhesiveness of the nanoemulsions were drastically improved resulting in the rank order PEG-40-stearate < CYS-PEG-40-stearate < MNA-CYS-PEG-40-stearate. Accordingly, thiolated surfactants, especially S-protected derivatives, are versatile tools to generate highly mucoadhesive nanoemulsions.


Templated mineralization of synthetic hydrogels for bone-like composite materials: role of matrix hydrophobicity.
Bone-mimetic mineral-polymer composite materials have several applications ranging from artificial bone grafts to scaffolds for bone tissue engineering; templated mineralization is an effective approach to fabricate such composites. In this study, we synthesized bone-like composites using synthetic hydrogels having pendant side chains terminating with carboxyl groups as a template for mineralization. The role of matrix hydrophobicity on mineralization was examined using poly(ethylene glycol) hydrogels modified with varying lengths of anionic pendant side chains (CH(2) horizontal lineCHCONH(CH(2))(n)COOH, where n = 1, 3, 5, and 7). The ability of these hydrogels to undergo templated mineralization was found to be strongly dependent upon the length of the pendant side chain as is evident from the extent of calcification and morphology of the minerals. Moreover, mineralized phases formed on the hydrogels were confirmed to resemble apatite-like structures. In addition to demonstrating the importance of material hydrophobicity as a design parameter for the development of bone-like synthetic materials, our study also provides a potential explanation for the in vitro differences between the apatite-nucleating capacity of aspartate-rich osteopontin and glutamate-rich bone sialoprotein.


Endovascular Treatment of the Ruptured Pseudoaneurysm of Common Femoral Artery in Behcet's Disease: Report of a Case with Four Years of Follow-Up.
Behcet's disease (BD) is a vasculitic condition that affects arteries and veins of all sizes. Arterial pseudoaneurysm is a rare but life-threatening complication of BD. We reported a 41-year-old man with 20 years history of BD and 5 years history of bilateral blindness. The patient presented with sudden onset of pain and swelling in his left groin and was diagnosed with the ruptured pseudoaneurysm of the left common femoral artery (CFA), which extended into the origins of superficial and deep femoral arteries. The patient was in the active phase of BD; therefore, he was initially treated with corticosteroids and cyclophosphamide pulse therapies and subsequently underwent stent graft placement. Post stenting angiography and postprocedural ultrasonography confirmed the successful exclusion of pseudoaneurysm without any evident complication. Four years of follow-up was uneventful.


[Antigenic affinity of meningococci and human A- and B-group erythrocytes].
The use of the modified method of isohemagglutinin adsorption by microbial antigens in experiments with the causative agent of meningococcal infection has led, for the first time, to the detection of meningococcal antigens affined to the antigens of human erythrocytes, groups A and B. The antigenic affinity of group A erythrocytes and meningococci has proved to be more pronounced in meningococcal strains isolated from the spinal fluid of patients than in cultures obtained from the nasopharynx of healthy persons. The detection of the affinity of these antigens makes it possible to explain the mechanism of differences in the susceptibility of persons with different blood groups to meningococcal infection by "antigenic mimicry".


Pan msr gene deleted strain of Salmonella Typhimurium suffers oxidative stress, depicts macromolecular damage and attenuated virulence.
Salmonella encounters but survives host inflammatory response. To defend host-generated oxidants, Salmonella encodes primary antioxidants and protein repair enzymes. Methionine (Met) residues are highly prone to oxidation and convert into methionine sulfoxide (Met-SO) which compromises protein functions and subsequently cellular survival. However, by reducing Met-SO to Met, methionine sulfoxide reductases (Msrs) enhance cellular survival under stress conditions. Salmonella encodes five Msrs which are specific for particular Met-SO (free/protein bound), and 'R'/'S' types. Earlier studies assessed the effect of deletions of one or two msrs on the stress physiology of S. Typhimurium. We generated a pan msr gene deletion (Δ5msr) strain in S. Typhimurium. The Δ5msr mutant strain shows an initial lag in in vitro growth. However, the Δ5msr mutant strain depicts very high sensitivity (p < 0.0001) to hypochlorous acid (HOCl), chloramine T (ChT) and superoxide-generating oxidant paraquat. Further, the Δ5msr mutant strain shows high levels of malondialdehyde (MDA), protein carbonyls, and protein aggregation. On the other side, the Δ5msr mutant strain exhibits lower levels of free amines. Further, the Δ5msr mutant strain is highly susceptible to neutrophils and shows defective fitness in the spleen and liver of mice. The results of the current study suggest that the deletions of all msrs render S. Typhimurium highly prone to oxidative stress and attenuate its virulence.


Calorimetric determination of the energetics of the molten globule intermediate in protein folding: apo-alpha-lactalbumin.
High-sensitivity differential scanning calorimetry has been used to characterize the energetics of the molten globule state of apo-alpha-lactalbumin. This characterization has been possible by performing temperature scans at different guanidine hydrochloride (GuHCl) concentrations in order to experimentally define the temperature-GuHCl stability surface of the protein. Multidimensional analysis of the heat capacity surface has allowed simultaneous resolution of the energetics of the unfolded and molten globule states. These experiments indicate that the intrinsic enthalpy difference (i.e., excluding additional contributions such as those arising from differential GuHCl binding) between the unfolded and native states is 31.8 kcal/mol at 25 degrees C whereas that of the molten globule and native states is only 7.7 kcal/mol. At the same temperature, the entropy changes are 99.2 and 23.7 cal/K.mol and the heat capacity changes are 1821 and 326 cal/K.mol, respectively. Analysis of the thermodynamic data indicates that in passing from the native to the molten globule state only approximately 19% of the hydrogen bonds are broken. In addition, the magnitude of delta Cp for the molten globule suggests that water does not largely penetrate into the interior of the molten globule, implying that significant hydrophobic interactions are still present in this state. These parameters provide precise energetic constraints to the allowed structural conformations of the molten globule.


Profiles of coagulase-positive and -negative staphylococci in retail pork: prevalence, antimicrobial resistance, enterotoxigenicity, and virulence factors.
The present study aimed to investigate the occurrence and species of coagulasepositive staphylococci (CoPS) and coagulase-negative staphylococci (CoNS) in retail pork meat samples collected during nationwide monitoring. The staphylococcal isolates were characterized for antimicrobial and zinc chloride resistance and enterotoxigenic potential. A total of 260 pre-packaged pork meat samples were collected from 35 retail markets in 8 provinces in Korea for isolation of staphylococci. Antimicrobial and zinc chloride resistance phenotypes, and genes associated with the resistance phenotypes were determined on the isolates. Furthermore, the presence and distribution of 19 staphylococcal enterotoxin (SE) genes and enterotoxin-like genes among the pork-associated staphylococci were determined by multiplex polymerase chain reaction-based assays using the specific primer sets. A total of 29 staphylococcal strains (29/260, 11.1%) were isolated from samples of retail pork meat, 24 (83%) of which were CoNS. The four CoNS species identified were S. saprophyticus (n = 16, 55%), S. sciuri (n = 3, 10%), S. warneri (n = 3, 10%), and S. epidermidis (n = 2, 7%). Among the 29 isolates, four methicillin-resistant CoNS (MR-CoNS; three S. sciuri and one S. epidermidis) and one methicillin-resistant CoPS (MR-CoPS; one S. aureus) were identified. In addition, a relatively high level of tetracycline (TET) resistance (52%) was confirmed in CoNS, along with a predominant distribution of tet(K). The most prevalent SEs were sep (45%), and sen (28%), which were carried by 81% of S. saprophyticus. These findings suggest that CoNS, especially S. saprophyticus strains, in raw pork meat could be a potential risk factor for staphylococcal food poisoning (SFP), and therefore, requires further investigation to elucidate the role of SEls in SFP and virulence of the pathogen. Our results also suggest that CoNS from raw pork meat may act as a source for transmission of antimicrobial resistance genes such as staphylococcal cassette chromosome mec and tet(K).


Gender Disparity in Host Responses to Hepatitis B-Related Hepatocellular Carcinoma: A Case Series.
Chronic hepatitis B virus (HBV) infection is one of the most common causes of hepatocellular carcinoma (HCC), a malignant tumor with high mortality worldwide. One remarkable clinical feature of HBV-related HCC is that the risk of development is higher in males and postmenopausal females compared to other females. Increasing evidence also indicates that the prognosis of HBV-associated HCC may involve gender disparity, with females having more favorable outcomes. The proposed mechanism of this gender disparity is thought to be complex and multifactorial. Attributions have been made to gender differences in behavioral risk factors, host stress, immune response, psychology, metabolic risk factors, tumor biology, and hormonal factors. Gender disparities in hormonal factors and stress with consequent incited inflammation and hepatocarcinogenesis in HBV-related HCC is a particularly burgeoning area of investigation. Clarifying these mechanisms could provide insight into HBV-related HCC pathogenesis, and potentially provide a target for prevention and treatment of this disease. Reported herein is a case series involving two families affected by vertically transmitted chronic hepatitis B, longitudinally observed over multiple decades, with family members demonstrating discordant outcomes related to HCC, with worse outcomes among affected males. As a supplement to this case, we review the currently available literature on gender differences in outcomes from HBV-related HCC. In reporting this case series, we aim to add our important observation to the current literature and highlight the need for further research in the mechanisms involved in gender disparity in the prognosis of HBV-related HCC.


Cell death and cell-cycle arrest induced by incorporation of [3H]thymidine into human haemopoietic cell lines.
To investigate the influence of [methyl-3H]thymidine ([3H]Tdr) incorporated into human haemopoietic cell lines. HL-60, Molt-4, Jurkat, Raji and SKW6-CL4 cells were incubated in the presence of [3H]Tdr. Cell proliferation, cell viability, DNA fragmentation and expression of caspase-3 and Bcl-2 families were examined. The cell-cycle of HL-60 was analysed using flow cytometry. In HL-60, Molt-4 and Jurkat, cell death was accompanied by DNA nucleosomal fragmentation and activation of caspase-3. In Raji and SKW6-CL4, it was accompanied by neither. Protein levels of Bcl-2 and Bad in HL-60 and Molt-4 did not significantly change, and that of Bax was decreased after a 3-day incubation. HL-60 incubated in the presence of 74 or 185 kBq/ml [3H]Tdr arrested at G2/M phase, and then underwent apoptosis. In 7.4 kBq/ml, the cell-cycle progressed after the delay in S-phase. Two different modes of cell death were observed when [3H]Tdr was incorporated into the human haemopoietic cell lines. Incorporation into HL-60 cells resulted in delay of S-phase progression, arrest at G2/M and apoptosis.


Pediatrician-recommended use of sports drinks and dental caries in 3-year-old children.
To determine whether children advised by a pediatrician to take sports drinks consume them more frequently than do other children and whether these children have an increased risk of dental caries. The subjects were 522 mother/child pairs who attended a dental checkup for 3-year-olds at one of ten community health centers in Nagasaki, Japan. Pearson's chi-square test was used to compare the prevalence of children with or without dental caries according to child-related variables. Multiple logistic regression was performed to assess the relationship between the presence of dental caries and child-related variables taken from a dental checkup and a questionnaire. A high frequency of sports drink consumption was strongly associated with dental caries in children. The highest proportion of mothers answered that they were advised by a pediatrician to give sports drinks to their children. However, these children consumed sports drinks significantly less frequently than did children who did so for reasons other than pediatrician recommendations. In addition, these children were significantly less likely to have dental caries than were children who consumed sports drinks for otherreasons. Pediatrician-recommended consumption of sports drinks does not lead to more frequent consumption of these beverages or to dental caries in 3-year-old children.


Previously hidden chromosome aberrations in T(12;15)-positive BALB/c plasmacytomas uncovered by multicolor spectral karyotyping.
The majority of BALB/c mouse plasmacytomas harbor a balanced T(12;15) chromosomal translocation deregulating the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, the possible contribution of additional chromosomal aberrations to the progression of plasmacytoma development has been largely ignored. Here we use multicolor spectral karyotyping (SKY) to evaluate 10 established BALB/c plasmacytomas in which the T(12;15) had been previously detected by G banding. SKY readily confirmed the presence of this translocation in all of these tumors and in three plasmacytomas newly identified secondary cytogenetic changes of the c-myc-deregulating chromosome (Chr) T(12;15). In addition, numerous previously unknown aberrations were found to be scattered throughout the genome, which was interpreted to reflect the general genomic instability of plasmacytomas. Instability of this sort was not uniform, however, because only half of the tumors were heavily rearranged. Seven apparent hot spots of chromosomal rearrangements (40% incidence) were identified and mapped to Chrs 1B, 1G-H, 2G-H1, 4C7-D2, 12D, 14C-D2, and XE-F1. Two of these regions, Chr 1B and Chr 4C7-D2, are suspected to harbor plasmacytoma susceptibility loci; Pctr1 and Pctr2 on Chr 4C7-D2 and as yet unnamed loci on Chr 1B. These results suggest that secondary chromosomal rearrangements contribute to plasmacytoma progression in BALB/c mice. To evaluate the biological significance of these rearrangements, SKY will be used in follow-up experiments to search for the presence of recurrent and/or consistent secondary cytogenetic aberrations in primary BALB/c plasmacytomas.


[Involvement of bacterial microflora in etiopathogenesis of chronic sinusitis].
We used the method of amplification of RNA 16S genes in combination with discriminating hybridization of amplification products with species-specific probes in DNA-chip format to identify bacterial flora in patients with chronic sinusitis. A total of 34 samples from 33 patients suffering from chronic sinusitis have been tested. Biopsy specimens of sinus mucosa served as material for sinus microflora studies in the absence of sinusitis exacerbation. It was found that in the exacerbation-free period the samples contained no bacterial RNA 16S while human RNA was isolated from all the samples. Moreover, we isolated and typed fragments of 16S RNA E.fecalis genes from tested in parallel sample of the wall of the oroantral fistula. This confirmed significance and effectiveness of the above method. We came to the conclusion that sinus mucosa is sterile in chronic hyperplastic sinusitis.


Rationale for routine collection of patient reported outcomes during integrative medicine consultation visits.
Integrative medicine (IM) is whole-person care utilizing complementary health approaches to address numerous physical or emotional influences that can impact an individual's health. Patient-reported outcomes (PRO) are subjective measures that quantify patients' perception of their quality of life. While PRO measures have been routinely assessed in specific oncology clinics, our objective was to assess the ability and utility of routine collection of PRO measures in an IM clinic. Patients receiving a clinical consultation in an ambulatory IM clinic completed the PROMIS Global Health Form in the clinic waiting room. From November 2013 through October 2016, the PROMIS Global Health Form (PROMIS-10) was administered during 59% of IM provider consultation visits (7172/12,207), representing 3473 unique patients. Most patients were female (81%), White (93%), middle-aged (49.2; SD 15.4) and had commercial health insurance (66%). Baseline Mental (44.9; SD 9.1) and Physical Health (44.2; SD 8.6) scores were roughly 0.5 standard deviation below the national mean values (50; SD 10). Factors such as age, race and non-commercial insurance were associated with lower PROMIS-10 scores. Patients completing at least two PROMIS-10 questionnaires (n = 1541) exhibited increases of 2.3% and 2.8% from first to last PROMIS-10 assessment in Mental and Physical Heath scores respectively. It is possible to routinely collect PRO measures in large IM clinic and longitudinal improvements in Mental and Physical Health scores were observed. Future research should focus on understanding how providers can utilize PRO results in real-time to improve patients' clinical outcomes and potentially decrease healthcare utilization.


Effect of economic recession and impact of health and social protection expenditures on adult mortality: a longitudinal analysis of 5565 Brazilian municipalities.
Economic recession might worsen health in low-income and middle-income countries with precarious job markets and weak social protection systems. Between 2014-16, a major economic crisis occurred in Brazil. We aimed to assess the association between economic recession and adult mortality in Brazil and to ascertain whether health and social welfare programmes in the country had a protective effect against the negative impact of this recession. In this longitudinal analysis, we obtained data from the Brazilian Ministry of Health, the Brazilian Institute for Geography and Statistics, the Ministry of Social Development and Fight Against Hunger, and the Information System for the Public Budget in Health to assess changes in state unemployment level and mortality among adults (aged ≥15 years) in Brazil between 2012 and 2017. Outcomes were municipal all-cause and cause-specific mortality rates for all adults and across population subgroups stratified by age, sex, and race. We used fixed-effect panel regression models with quarterly timepoints to assess the association between recession and changes in mortality. Mortality and unemployment rates were detrended using Hodrick-Prescott filters to assess cyclical variation and control for underlying trends. We tested interactions between unemployment and terciles of municipal social protection and health-care expenditure to assess whether the relationship between unemployment and mortality varied. Between 2012 and 2017, 7 069 242 deaths were recorded among adults (aged ≥15 years) in 5565 municipalities in Brazil. During this time period, the mean crude municipal adult mortality rate increased by 8·0% from 143·1 deaths per 100 000 in 2012 to 154·5 deaths per 100 000 in 2017. An increase in unemployment rate of 1 percentage-point was associated with a 0·50 increase per 100 000 population per rter (95% CI 0·09-0·91) in all-cause mortality, mainly due to cancer and cardiovascular disease. Between 2012 and 2017, higher unemployment accounted for 31 415 excess deaths (95% CI 29 698-33 132). All-cause mortality increased among black or mixed race (pardo) Brazilians (a 0·46 increase [95% CI 0·15-0·80]), men (0·67 [0·22-1·13]), and individuals aged 30-59 years (0·43 [0·16-0·69] per 1 percentage-point increase in the unemployment rate. No significant association was identified between unemployment and all-cause mortality for white Brazilian, women, adolescents (aged 15-29 years), or older and retired individuals (aged ≥60 years). In municipalities with high expenditure on health and social protection programmes, no significant increases in recession-related mortality were observed. The Brazilian recession contributed to increases in mortality. However, health and social protection expenditure seemed to mitigate detrimental health effects, especially among vulnerable populations. This evidence provides support for stronger health and social protection systems globally. None.


Phydbac2: improved inference of gene function using interactive phylogenomic profiling and chromosomal location analysis.
Phydbac (phylogenomic display of bacterial genes) implemented a method of phylogenomic profiling using a distance measure based on normalized BLAST scores. This method was able to increase the predictive power of phylogenomic profiling by about 25% when compared to the classical approach based on Hamming distances. Here we present a major extension of Phydbac (named here Phydbac2), that extends both the concept and the functionality of the original web-service. While phylogenomic profiles remain the central focus of Phydbac2, it now integrates chromosomal proximity and gene fusion analyses as two additional non-similarity-based indicators for inferring pairwise gene functional relationships. Moreover, all presently available (January 2004) fully sequenced bacterial genomes and those of three lower eukaryotes are now included in the profiling process, thus increasing the initial number of reference genomes (71 in Phydbac) to 150 in Phydbac2. Using the KEGG metabolic pathway database as a benchmark, we show that the predictive power of Phydbac2 is improved by 27% over the previous version. This gain is accounted for on one hand, by the increased number of reference genomes (11%) and on the other hand, as a result of including chromosomal proximity into the distance measure (16%). The expanded functionality of Phydbac2 now allows the user to query more than 50 different genomes, including at least one member of each major bacterial group, most major pathogens and potential bio-terrorism agents. The search for co-evolving genes based on consensus profiles from multiple organisms, the display of Phydbac2 profiles side by side with COG information, the inclusion of KEGG metabolic pathway maps the production of chromosomal proximity maps, and the possibility of collecting and processing results from different Phydbac queries in a common shopping cart are the main new features of Phydbac2. The Phydbac2 web server is available at http://igs-server.cnrs-mrs.fr/phydbac/.


[Internal medicine: challenges and opportunities at the beginning of a new century].
Internal medicine was born at the end of the nineteenth century as the result of the great amount of medical knowledge that accrued. The word "internal" has a great meaning and symbolism that underscores a holistic view of the patient. After some years of fruitful work, internal medicine experienced the appearance of subspecialties. This meant a great technological advance but increased the costs of services and deteriorated patient-physician relationship. These tactics along with world sanitary changes, offer a unique opportunity for the resurgence of Internal Medicine. Nowadays the internist has the image of an expert able to treat patients with diseases that involve several organs or systems or to serve as a consultant for complex medical problems. The new threats of the specialty are Family Medicine and hospital physicians. The areas in which the internist should acquire expertise to cope with the new sanitary requirements are also analyzed.


Nanoplasmonic Paper-Based Platform for General Screening of Biomacromolecules.
Hygiene assessment in industrial and clinical environments is crucial in the prevention of health risks. Current technologies for routine cleanliness evaluation rely on the detection of specific biomolecules, thus requiring more than one test for broad-range screening. Herein, the modulation of the catalytic activity of gold nanoparticles (AuNPs) by biomacromolecules was employed to develop a nanoplasmonic platform for general hygiene screening. AuNPs were immobilized on cellulose paper by simple adsorption. When ferricyanide was dispensed onto the paper, the AuNPs catalysed the ferricyanide's dissociation, releasing free cyanide ions that dissolved them. The AuNP dissolution produced an intense colour shift detectable with the naked eye. When biomacromolecules (e.g., proteins and polysaccharides) were present, they spontaneously attached to AuNPs, forming a biomolecular corona (biocorona), reducing their catalytic activity until complete suppression when the NPs were fully covered by molecules. The concentration-dependent decrease in the catalytic activity was here used to quantify biomacromolecules and complex samples such as milk, eggs, soy sauce and yeast extract (in 20 min), with detection limits comparable to those of standard methods, i.e., 0.25 µg mL-1 for albumin. This nano-enabled technology may be applied as a broad-range (unspecific) alert system for inexpensive cleanliness evaluation, with potential applications in sensitive sectors including productive industries and hospitals.


Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus.
The 2009/2010 pandemic influenza virus (H1N1pdm) contains an avian-lineage PB2 gene that lacks E627K and D701N substitutions important in the pathogenesis and transmission of avian-origin viruses in humans or other mammals. Previous studies have shown that PB2-627K is not necessary because of a compensatory Q591R substitution. The role that PB2-701N plays in the H1N1pdm phenotype is not well understood. Therefore, PB2-D701N was introduced into an H1N1pdm virus (A/New York/1682/2009 (NY1682)) and analyzed in vitro and in vivo. Mini-genome replication assay, in vitro replication characteristics in cell lines, and analysis in the mouse and ferret models demonstrated that PB2-D701N increased virus replication rates and resulted in more severe pathogenicity in mice and more efficient transmission in ferrets. In addition, compared to the NY1682-WT virus, the NY1682-D701N mutant virus induced less IFN-λ and replicated to a higher titer in primary human alveolar epithelial cells. These findings suggest that the acquisition of the PB2-701N substitution by H1N1pdm viruses may result in more severe disease or increase transmission in humans.


Clinical and Radiographic Evaluation of Procedural Accidents and Errors during Root Canal Therapy.
Root canal therapy (RCT)_like other dental practices_ can be accompanied with some accidents or unpredictable conditions that are called "procedural accidents". Having the knowledge about these accidents and their etiology is essential to have RCT completion and to prevent the repeat of these accidents. This study was designed to evaluate accidents occurring during RCT in patients referred to endodontic department of Shaheed Beheshti dental school during 2002. This study was conducted via descriptive method. Data were collected from observation, clinical examination and oral radiographs, and were recorded in questionnaires, 150 cases from the patients referred to endodontic department were selected randomly and different observed RCT errors were analyzed by SPSS software. The Chi-square and Fisher exact tests were used for analysis. The study showed that 101 patients (67.3%) had one type of RCT errors, and remaining (32.7%) were error free. From the errors studied the most prevalent were "void" which was observed in 41 patients (27.3%), and "ledge" in 39 patients (26%) respectively. The prevalence of other accidents were underfilling in 35 patients (23.3%), poor shaping in 30 patients (20%), overfilling in 23 patients (15.3%), transportation in 13 patients (8.7%), zipping in 3 patients (2%), gouging in 1 patients (0.7%), and strip perforation in 1 patients (0.7%), while no case of broken instruments, vertical fracture, furcation and cervical perforation was observed. The most prevalent errors were found in instrumentation and obturation steps, therefore more care and attention must be paid to instructor observation and the education of these stages.


Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The tumor microenvironment content, particularly the presence of macrophages, was described as crucial for the development of the disease. This work aimed at studying the involvement of the M-CSF (CSF-1)/IL-34/CSF-1R pathway in the formation of macrophages in MPM, using samples from patients. Pleural effusions (PEs), frozen tumors, primary MPM cells and MPM cell lines used in this study belong to biocollections associated with clinical databases. Cytokine expressions were studied using real-time PCR and ELISA. The Cancer Genome Atlas database was used to confirm our results on an independent cohort. An original three-dimensional (3D) coculture model including MPM cells, monocytes from healthy donors and a tumor antigen-specific cytotoxic CD8 T cell clone was used. We observed that high interleukin (IL)-34 levels in PE were significantly associated with a shorter survival of patients. In tumors, expression of CSF1 was correlated with 'M2-like macrophages' markers, whereas this was not the case with IL34 expression, suggesting two distinct modes of action of these cytokines. Expression of IL34 was higher in MPM cells compared with primary mesothelial cells. Particularly, high expression of IL34 was observed in MPM cells with an alteration of CDKN2A. Finally, using 3D coculture model, we demonstrated the direct involvement of MPM cells in the formation of immunosuppressive macrophages, through activation of the colony stimulating factor-1 receptor (CSF1-R) pathway, causing the inhibition of cytotoxicity of tumor antigen-specific CD8+ T cells. The M-CSF/IL-34/CSF-1R pathway seems strongly implicated in MPM and could constitute a therapeutic target to act on immunosuppression and to support immunotherapeutic strategies.


Demographic and dietary risk factors in relation to urinary metabolites of organophosphate flame retardants in toddlers.
Organophosphate flame retardants (OPFRs), including Tris (1,3-dichloro-isopropyl) phosphate (TDCPP), triphenyl phosphate (TPP), and isopropylated triphenyl phosphate (ITP), are increasingly used in consumer products because of the recent phase out of polybrominated diphenyl ether (PBDE) flame retardants. OPFRs have been widely detected in adults and have been linked to reproductive and endocrine changes in adult males. Carcinogenicity and damage to immunologic, neurologic and developmental systems have been observed in human cell lines. Young children are especially vulnerable to OPFR exposure, but little is known about exposure levels or exposure risk factors in this population. We examined parent-reported demographic and dietary survey data in relation to OPFR urinary metabolite concentrations in 15- to 18-month old toddlers (n = 41). OPFR metabolites were detected in 100% of subjects. The metabolite of TPP, diphenyl phosphate (DPP) was detected most commonly (100%), with TDCPP metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), detected in 85-95% of samples, and ITP metabolite, monoisopropylphenyl phenyl phosphate (ip-DPP), detected in 81% of samples (n = 21). Toddlers of mothers earning <$10,000 annually had geometric mean DPP concentrations 66% higher (p = 0.05) than toddlers of mothers earning >$10,000/year (7.8 ng/mL, 95% CI 5.03, 12.11 and 4.69 ng/mL, 95% CI 3.65-6.04, respectively). While no dietary factors were significantly associated with OPFR metabolite concentrations, results suggested meat and fish consumption may be associated with higher DPP and BDCPP levels while increased dairy and fresh food consumption may be associated with lower DPP, BDCPP, and ip-DPP levels. Research with larger sample sizes and more detailed dietary data is required to confirm these preliminary findings.


Maternal risk factors in cleft lip and palate: case control study.
Three hundred and six mothers who gave birth to babies with cleft lip, or palate, or both, were matched with 306 who gave birth to healthy babies in the same area during the same time period. Significantly more babies in the cleft group had a family history of clefts (48/306 compared with 7/306, P<0.0001). In the cases studied, combined cleft lip and palate was significantly more common among boys (82/157 compared with 57/149, P=0.02) and cleft palate alone among girls (48/149 compared with 22/157, P=0.0002). Significantly more mothers reported some sort of illness during early pregnancy (101/306 compared with 74/306, P=0.02). There were no differences between the groups as far as dietary preferences were concerned but during early pregnancy the mothers who gave birth to babies with defects tended to drink less alcohol (<1 unit/week) (236 compared with 199, P=0.001) and less coffee (<1 cup/week) (159/306 compared with 131, P=0.03). However, in each case similar proportions gave up once the pregnancy was confirmed. Large multicentre studies are required to confirm or refute these findings.


West Nile Virus-Inclusive Single-Cell RNA Sequencing Reveals Heterogeneity in the Type I Interferon Response within Single Cells.
West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus of global importance. Neuroinvasive WNV infection results in encephalitis and can lead to prolonged neurological impairment or death. Type I interferon (IFN-I) is crucial for promoting antiviral defenses through the induction of antiviral effectors, which function to restrict viral replication and spread. However, our understanding of the antiviral response to WNV infection is mostly derived from analysis of bulk cell populations. It is becoming increasingly apparent that substantial heterogeneity in cellular processes exists among individual cells, even within a seemingly homogenous cell population. Here, we present WNV-inclusive single-cell RNA sequencing (scRNA-seq), an approach to examine the transcriptional variation and viral RNA burden across single cells. We observed that only a few cells within the bulk population displayed robust transcription of IFN-β mRNA, and this did not appear to depend on viral RNA abundance within the same cell. Furthermore, we observed considerable transcriptional heterogeneity in the IFN-I response, with genes displaying high unimodal and bimodal expression patterns. Broadly, IFN-stimulated genes negatively correlated with viral RNA abundance, corresponding with a precipitous decline in expression in cells with high viral RNA levels. Altogether, we demonstrated the feasibility and utility of WNV-inclusive scRNA-seq as a high-throughput technique for single-cell transcriptomics and WNV RNA detection. This approach can be implemented in other models to provide insights into the cellular features of protective immunity and identify novel therapeutic targets.IMPORTANCE West Nile virus (WNV) is a clinically relevant pathogen responsible for recurrent epidemics of neuroinvasive disease. Type I interferon is essential for promoting an antiviral response against WNV infection; however, it is unclear how heterogeneity in the antiviral response at the single-cell level impacts viral control. Specifically, conventional approaches lack the ability to distinguish differences across cells with varying viral abundance. The significance of our research is to demonstrate a new technique for studying WNV infection at the single-cell level. We discovered extensive variation in antiviral gene expression and viral abundance across cells. This protocol can be applied to primary cells or in vivo models to better understand the underlying cellular heterogeneity following WNV infection for the development of targeted therapeutic strategies.


Molecular-level engineering of protein physical hydrogels for predictive sol-gel phase behavior.
Predictable tuning of bulk mechanics from the molecular level remains elusive in many physical hydrogel systems because of the reliance on nonspecific and nonstoichiometric chain interactions for network formation. We describe a mixing-induced two-component hydrogel (MITCH) system, in which network assembly is driven by specific and stoichiometric peptide-peptide binding interactions. By integrating protein science methodologies with a simple polymer physics model, we manipulate the polypeptide binding interactions and demonstrate the direct ability to predict the resulting effects on network cross-linking density, sol-gel phase behavior, and gel mechanics.


Demographic and clinical characteristics of new patients presenting to a community teaching clinic.
We compare patient populations attending chiropractors in the field to those in teaching clinics to allow educational institutions to determine if students are exposed to a similar case mix. The purpose of our study was to describe and compare descriptively the clinical case mix of a recently opened community-based teaching clinic to previously published practice data. A retrospective descriptive cross-sectional study was conducted using new patient records completed at a clinic. Data were extracted using a specifically designed abstraction form. We manually abstracted 649 files. A total of 580 new patient files was included in the analysis, among which 57.7% included female patients with a mean age of 43 years (SD 18), and 42.1% presented with a chief complaint of more than one year in duration. The vast majority of patients complained of spinal pain (81.4%), most commonly low back pain. Almost 92% of the diagnoses were classified as simple (sprain/strain). The average number of visits per patient was 7.4 (SD 11.3); 54.7% received spinal manipulation on their first visit. The majority of patients were referred by the treating intern (64.8%) and about 24% of patients were local residents. Our study contributed to the few studies detailing patients attending chiropractic academic teaching clinics. It provided benchmark demographic and clinical data that may be used for operational planning. Our study suggested that the case mix of this teaching clinic provides interns with appropriate learning opportunities to achieve entry to practice competencies.


Financial hardship and health in a refugee population in Australia: A longitudinal study.
Refugees and asylum seekers are at a higher risk than the host population to poor health and financial stress. This study uses a unique longitudinal panel from Australia, the Building a New life in Australia (BNLA cohort) to understand the relationship over time between the social determinants of health, health, and financial hardship in refugees and asylum seekers. We employ a longitudinal; dynamic multivariate logistic regression to firstly estimate the relationship between the social determinants of health and poor physical and mental health. Next, we include variables related to financial hardship in our model to determine if there is an association independent of the social determinants of health. Finally, we estimate if there is a relationship between the number of financial hardships and poor physical and mental health. The results show that migrants from North Africa, the Middle East, and Sub-Sahara Africa and women are more likely to suffer from poor health. Financial hardship has an independent association with poor health. We find that going without meals had the highest odds of suffering from poor health. There was evidence of a dose response of financial hardship for those suffering from a limiting long-term health condition and post-traumatic stress syndrome. These findings suggest that refugees in Australia may need additional support past their first year to help them assimilate and contribute to economic productivity.


Changes in brain activity during action observation and motor imagery: Their relationship with motor learning.
Many studies have demonstrated that training utilizing action observation and/or motor imagery improves motor performance. These two techniques are widely used in sports and in the rehabilitation of movement-related disorders. Motor imagery has also been used for brain-machine/computer interfaces (BMI/BCI). During both action observation and motor imagery, motor-related regions such as the premotor cortex and inferior parietal lobule are activated. This is common to actual execution and are involved with the underlying mechanisms of motor learning without execution. Since it is easier to record brain activity during action observation and motor imagery than that during actual sport movements, action observation, and motor imagery of sports skills or complex whole body movements have been utilized to investigate how neural mechanisms differ across the performance spectrum ranging from beginner to expert. However, brain activity during action observation and motor imagery is influenced by task complexity (i.e., simple vs complex movements). Furthermore, temporal changes in brain activity during actual execution along the long time course of motor learning are likely nonlinear and would be different from that during action observation or motor imagery. Activity in motor-related regions during action observation and motor imagery is typically greater in experts than in nonexperts, while the activity during actual execution is often smaller in experts than in nonexperts.


Visual cluster analysis in support of clinical decision intelligence.
Electronic health records (EHRs) contain a wealth of information about patients. In addition to providing efficient and accurate records for individual patients, large databases of EHRs contain valuable information about overall patient populations. While statistical insights describing an overall population are beneficial, they are often not specific enough to use as the basis for individualized patient-centric decisions. To address this challenge, we describe an approach based on patient similarity which analyzes an EHR database to extract a cohort of patient records most similar to a specific target patient. Clusters of similar patients are then visualized to allow interactive visual refinement by human experts. Statistics are then extracted from the refined patient clusters and displayed to users. The statistical insights taken from these refined clusters provide personalized guidance for complex decisions. This paper focuses on the cluster refinement stage where an expert user must interactively (a) judge the quality and contents of automatically generated similar patient clusters, and (b) refine the clusters based on his/her expertise. We describe the DICON visualization tool which allows users to interactively view and refine multidimensional similar patient clusters. We also present results from a preliminary evaluation where two medical doctors provided feedback on our approach.


[Intestinal parasites in two periurban populations in La Plata, Argentina].
The prevalence of intestinal parasites was studied in two urban neighborhoods with different socioeconomic conditions in La Plata, Argentina. Age, sex, and environmental factors were considered. One hundred and one hundred one children up to 14 years old were examined by coproparasitologic analysis. Giardia lamblia was the most frequent species. Overall prevalences (73.0% and 54.4%), frequencies of polyparasitism (45.0% and 14.8%), and prevalences of helminthic infection (48.0% and 12.7%) were highest in the population having significantly inferior sanitary and environmental conditions. A correlation with age was observed. It is necessary to apply management practices for the control of enteroparasitoses, in accordance with the corresponding characteristics of the environmental and sociocultural ecosistem.


Protective effect of taurine on TNBS-induced inflammatory bowel disease in rats.
We had previously reported that the protective effect of taurine against indomethacin-induced gastric mucosal injury was due to its antioxidant effects, which inhibited lipid peroxidation and neutrophil activation. In this study, we examined the effect of taurine on reducing the inflammatory parameters of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease (IBD) in rats. In order to induce IBD, ethanolic TNBS was given to rats intracolonically. Then they received 500 mg/kg/day of taurine orally and were sacrificed one week after IBD induction. While ulceration and inflammation of distal colon with formation of granuloma in the vehicle-treated IBD rats two days after administration of TNBS were observed, treatment with taurine ameliorated colonic damage and decreased the incidence of diarrhea and adhesion. Also, colon weight as an index of tissue edema, which was markedly increased in the IBD rats, became significantly lower after taurine treatment. Myeloperoxidase (MPO) activity in the vehicle-treated IBD rats was substantially increased, compared with that of normal control. The taurine-treated animals significantly reduced MPO activity (35% lower) when compared with that of the vehicle-treated animals. Taurine treatment decreased both basal and formyl-methionyl leucyl phenylalanine-stimulated reactive oxygen generation from colonic tissue in the IBD rats. These results suggest that the administration of taurine reduce the inflammatory parameters in this IBD rat model by increasing defending capacity against oxidative damage.


A 66-year-old woman with fever, cough, and a tongue lesion.
A 66-year-old woman presented with acute onset of fever, chills, and productive cough associated with right-sided chest pain. During a recent hospitalization for dyspnea, she had been diagnosed with Coombs-positive autoimmune hemolytic anemia and had been taking a tapering dose of prednisone starting approximately 6 weeks prior to admission. In the interim, her dyspnea had resolved on treatment with steroids. At the time of presentation, her prednisone dose was 40 mg. Additional medical history included VTE, for which the patient was receiving anticoagulation therapy, and steroid-induced diabetes mellitus. Many years earlier, she had been treated for TB in her home country. The patient had immigrated to Queens, New York, from a Nepalese village 8 years prior. While still in Nepal, she had worked on a farm and had been in close proximity to cows. In Queens, she lived with her family in a house with a small garden but had no pets. Recent travel included a visit to Nepal 9 months ago and a trip to Syracuse, New York, one month prior to presentation. She was a never smoker and did not consume alcohol.


Antibodies to distinct polypeptides of RNA polymerase I in sera from patients with rheumatic autoimmune disease.
Sera from patients with rheumatic autoimmune diseases were screened for antibodies directed against RNA polymerase I by using a solid-phase radioimmunoassay. Significant levels of the antibodies were detected in the sera of all patients with either systemic lupus erythematosus or mixed connective tissue disease and in 78% of the individuals with rheumatoid arthritis. No detectable anti-RNA polymerase I antibodies were found in the sera from healthy subjects. Individuals taking hydralazine, three of whom exhibited symptoms of drug-induced lupus, had barely detectable levels of the antibodies. Immunoglobulins obtained from sera containing anti-RNA polymerase I antibodies, as determined by the radioimmunoassay, could inhibit RNA polymerase I activity in vitro. Sera from patients with systemic lupus erythematosus contained immunoglobulins directed against the polymerase I-associated polypeptide of Mr 65,000 as well as against the polypeptides of Mr 120,000 or Mr 25,000, or both. Sera from individuals with rheumatoid arthritis reacted with the polypeptide of Mr 65,000 only. The antibodies in the sera of patients with mixed connective tissue disease were directed against the Mr 42,000 polypeptide or a combination of the Mr 65,000, 42,000, and 25,000 polypeptides. These data suggest that the production of anti-RNA polymerase I antibodies may be a unique characteristic of individuals with rheumatic autoimmune diseases and that the production of antibodies against specific polypeptides of RNA polymerase I may be indicative of the particular class of disease.


Prognostic Factors of Local Control and Survival in Patients Irradiated for Glioblastoma Multiforme (GBM).
Standard treatment of glioblastoma multiforme (GBM) includes resection, longer-course radiotherapy and chemotherapy. Some patients cannot tolerate these regimens and may benefit from personalized treatments. This study aims to contribute to treatment personalization by identifying predictors of outcomes after longer-course radiotherapy. In 91 patients, number/site/diameter of lesions, Ki-67, MGMT promoter methylation, Karnofsky performance score (KPS), symptoms, gender, age and resection were evaluated for local control and survival. On univariate analyses, gross resection (p=0.029) was significantly associated with improved local control. It maintained significance in the multivariate analysis [hazard ratio (HR)=1.64, p=0.025]. MGMT-methylation (p=0.004), KPS ≥80 (p=0.022) and resection (p<0.001) were significantly associated with improved survival on univariate analyses, unifocal GBM (p=0.056) showed a trend. In the multivariate analyses, MGMT-methylation (HR=3.63, p=0.009), KPS (HR=2.01, p=0.018) and resection (HR=3.29, p<0.001) were significant. Predictors of local control and survival were identified that may guide physicians when tailoring treatments to patients with GBM.