[Participation of chromatin proteins in the binding of glucocorticoid receptor complexes by the cell nucleus].
The binding of the purified glucocorticoid-receptor complexes from rat liver cytosol with partially deproteinized and partially reconstituted chromatins from rats liver and brain has been investigated. The chromatin was deproteinized by stepwise extraction of nuclei with NaC1 solution of raised molarity. The partial chromatin reconstruction was accomplished by the addition of individual fractions of extracted proteins to DNA-cellulose. It has been shown that in both test-systems used some fractions of nuclear proteins in particular the fractions of loosely associated with chromatin nonhistone proteins are capable of modulating specifically (mainly positively) the binding of glucocorticoid-receptor complexes with chromatin.


Exploring the equilibrium and dynamic phase transition properties of the Ising ferromagnet on a decorated triangular lattice.
We study the equilibrium and dynamic phase transition properties of a two-dimensional Ising model on a decorated triangular lattice under the influence of a time-dependent magnetic field composed of a periodic square wave part plus a time-independent bias term. Using Monte Carlo simulations with a standard Metropolis algorithm, we determine the equilibrium critical behavior in zero field. At a fixed temperature corresponding to the multidroplet regime, we locate the relaxation time and the dynamic critical half period at which a dynamic phase transition takes place between ferromagnetic and paramagnetic states. Benefiting from finite-size scaling theory, we estimate the dynamic critical exponent ratios for the dynamic order parameter and its scaled variance, respectively. The response function of the average energy is found to follow a logarithmic scaling as a function of lattice size. At the critical half period and in the vicinity of a small bias field regime, the average of the dynamic order parameter obeys a scaling relation with a dynamic scaling exponent which is very close to the equilibrium critical isotherm value. Finally, in the slow critical dynamics regime, investigation of metamagnetic fluctuations in the presence of bias field reveals a symmetric double-peak behavior for the scaled variance contours of the dynamic order parameter and average energy. Our results strongly resemble those previously reported for kinetic Ising models.


Site-directed mutagenesis of human soluble calcium-activated nucleotidase 1 (hSCAN-1): identification of residues essential for enzyme activity and the Ca(2+)-induced conformational change.
Human soluble calcium-activated nucleotidase 1 (hSCAN-1) is the human homologue of soluble apyrases found in blood-sucking insects. This family of nucleotidases is unrelated in sequence to more well-studied nucleotidases, and very little is known about the enzymatic mechanism. By multiple sequence alignment, eight regions that are highly conserved in the hSCAN-1 family were identified and named. To identify amino acids important for catalytic activity and enzyme specificity, seven point mutations were constructed, expressed in bacteria, refolded, purified, and characterized. Substitution of glutamic acid 130 with tyrosine resulted in dramatically increased nucleotidase activities, while mutagenesis of aspartic acid 151 to alanine and aspartic acid 84 to alanine completely abolished activity. Mutagenesis of arginine 133 and arginine 271 resulted in enzymes with very little nucleotidase activity. Mutagenesis of aspartic acid 175 to alanine and glycine 122 to glutamic acid had smaller negative effects on enzyme activities. Previously, our laboratory showed that calcium triggers a conformational change in hSCAN-1 necessary for nucleotidase activity. Here we show that several mutants (D84A, R133A, and D151A) that lost most of their activity were unable to undergo the conformational change induced by Ca(2+), as shown by Cibacron blue binding, limited proteolysis, and tryptophan fluorescence. We conclude that aspartic acid residues 84 and 151, as well as arginine residue 133, are essential for the Ca(2+)-induced conformational change that is necessary for enzyme activity. Aspartic acid 175 and glutamic acid 130 are important for determining substrate specificity. In addition, we show that Sr(2+), unlike Mg(2+) and other divalent cations, can substitute for Ca(2+) to induce the conformational change necessary for enzyme activity. However, Sr(2+) cannot substitute for Ca(2+) to support nucleotide hydrolysis, presumably because Sr(2+) cannot substitute for Ca(2+) in its second role as a nucleotide cosubstrate. The ramifications of our results on the interpretation of a recently published crystal structure are discussed. This information will facilitate future engineering of this enzyme designed to enhance its ability to hydrolyze ADP and thus increase its potential for therapeutic use in the treatment of pathological ischemic events triggered via activation of platelets by ADP.


Impact of two CO(2) laser heatings for damage repairing on fused silica surface.
CO(2) laser is an interesting tool to repair defects on silica optics. We studied UV nanosecond laser-induced damage in fused silica after CO(2) laser heating. The localization of damage sites and the laser damage threshold are closely related to stress area in silica induced by heating. By applying a suitable second laser heating, we managed to eliminate the debris issued from redeposited silica and to modify the stress area. As a consequence, a significant increase of laser resistance has been observed. This process offers the possibility to improve damage repairing sufficiently to extend the lifetime of the silica components.


Work-related stress and psychological distress in emergency medical technicians.
Emergency medical technicians (N = 65) participated in a study on work environment characteristics, work-related stress, and psychological distress. Data were collected at baseline and 6 months. Work-related stress was associated with lower work group support and poor supervisory behavior. Work-related stress was strongly related to psychological distress. Changes in work-related stress were significantly related to changes in psychological distress. Findings support the work-related stress, psychological distress model.


Maximum likelihood estimation of protein kinetic parameters under weak assumptions from unfolding force spectroscopy experiments.
Single molecule force spectroscopy (SMFS) is extensively used to characterize the mechanical unfolding behavior of individual protein domains under applied force by pulling chimeric polyproteins consisting of identical tandem repeats. Constant velocity unfolding SMFS data can be employed to reconstruct the protein unfolding energy landscape and kinetics. The methods applied so far require the specification of a single stretching force increase function, either theoretically derived or experimentally inferred, which must then be assumed to accurately describe the entirety of the experimental data. The very existence of a suitable optimal force model, even in the context of a single experimental data set, is still questioned. Herein, we propose a maximum likelihood (ML) framework for the estimation of protein kinetic parameters which can accommodate all the established theoretical force increase models. Our framework does not presuppose the existence of a single force characteristic function. Rather, it can be used with a heterogeneous set of functions, each describing the protein behavior in the stretching time range leading to one rupture event. We propose a simple way of constructing such a set of functions via piecewise linear approximation of the SMFS force vs time data and we prove the suitability of the approach both with synthetic data and experimentally. Additionally, when the spontaneous unfolding rate is the only unknown parameter, we find a correction factor that eliminates the bias of the ML estimator while also reducing its variance. Finally, we investigate which of several time-constrained experiment designs leads to better estimators.


Management of idiopathic pulmonary fibrosis: prognostic indicators.
There now exists a number of approaches that can be used to predict likely responses to therapy and disease progression in idiopathic pulmonary fibrosis. These tools should be used in management decisions. It must be remembered that destroyed, fixed fibrotic lung will not improve and that the computed tomography pattern and extent of the "fibrotic" pattern should be used to determine if the best response to treatment that can be expected is a prevention of deterioration rather than improvement.


Life-threatening endocrine emergencies during pregnancy - management and therapeutic features.
Endocrine emergencies during pregnancy may be life-threatening events for both mother and fetus. Besides pregnancy-associated endocrine disorders, several pre-existing endocrinopathies such as type-1 diabetes and Grave's disease or adrenal failure may acutely deteriorate during pregnancy. Since "classical" signs are often modified by pregnancy, early diagnosis and management may be hampered. In addition, laboratory tests show altered physiologic ranges and pharmacologic options are limited while therapeutic goals are mostly tighter than in the non-pregnant patient. Though subclinical endocrinopathies are more frequent and worth consideration due to their related adverse sequelae, this article focuses on endocrine emergencies complicating pregnancy.


Trauma histories among justice-involved youth: findings from the National Child Traumatic Stress Network.
Up to 90% of justice-involved youth report exposure to some type of traumatic event. On average, 70% of youth meet criteria for a mental health disorder with approximately 30% of youth meeting criteria for post-traumatic stress disorder (PTSD). Justice-involved youth are also at risk for substance use and academic problems, and child welfare involvement. Yet, less is known about the details of their trauma histories, and associations among trauma details, mental health problems, and associated risk factors. This study describes detailed trauma histories, mental health problems, and associated risk factors (i.e., academic problems, substance/alcohol use, and concurrent child welfare involvement) among adolescents with recent involvement in the juvenile justice system. The National Child Traumatic Stress Network Core Data Set (NCTSN-CDS) is used to address these aims, among which 658 adolescents report recent involvement in the juvenile justice system as indexed by being detained or under community supervision by the juvenile court. Age of onset of trauma exposure was within the first 5 years of life for 62% of youth and approximately one-third of youth report exposure to multiple or co-occurring trauma types each year into adolescence. Mental health problems are prevalent with 23.6% of youth meeting criteria for PTSD, 66.1% in the clinical range for externalizing problems, and 45.5% in the clinical range for internalizing problems. Early age of onset of trauma exposure was differentially associated with mental health problems and related risk factors among males and females. The results indicate that justice-involved youth report high rates of trauma exposure and that this trauma typically begins early in life, is often in multiple contexts, and persists over time. Findings provide support for establishing trauma-informed juvenile justice systems that can respond to the needs of traumatized youth.


Bronchoscopy versus empirical therapy in HIV-infected patients with presumptive Pneumocystis carinii pneumonia. A decision analysis.
The outcomes of alternative strategies for the management of pulmonary complications in patients infected with the human immunodeficiency virus (HIV) and with suspected Pneumocystis carinii pneumonia were compared using a decision analysis model. A decision tree was constructed using baseline probabilities derived from published data and expert opinion. The case scenario analyzed was that of a patient not currently receiving anti-Pneumocystis prophylaxis who presents with moderate pulmonary symptoms and fulfills the Centers for Disease Control (CDC) criteria for presumptive P. carinii pneumonia. Two strategies were compared: (1) early bronchoscopy with appropriate therapy based on the results, and (2) empiric treatment for P. carinii (trimethoprim/sulfamethoxazole or pentamidine, and steroids) with delayed bronchoscopy in those not responding to 5 days of empiric therapy. The expected 1-month survival rate (with and without quality of life adjustment) was found to be essentially the same for the two strategies using the baseline probabilities, and the decision remained a toss-up within the clinically relevant range of published probabilities for P. carinii pneumonia in patients fulfilling the CDC criteria. Because early bronchoscopy does not offer any additional survival benefits and is associated with greater costs and disutility, empiric therapy would appear to be the superior management strategy in this scenario.


Associations of physical activity with self-rated health and well-being in middle-aged Finnish men.
We examined the associations of physical activity (PA) frequency with self-rated health (SRH), self-rated well-being (SRW) and depressive symptoms, in middle-aged men in Finland. The cross-sectional study comprised 665 men (mean age 41 ± 3 SD years; body mass index (BMI) 26.8 ± 4.2 SD kg/m(2)), who had completed the screening questionnaire of an intervention for men with cardiovascular risk factors. Their weekly frequency of PA was assessed by a questionnaire, SRH and SRW by visual analog scales (VAS), and depressive symptoms by the Patient Health Questionnaire-2 (PHQ-2). The mean SRH ± SD (range of scale 0-100) by PA frequency categories was 56.2 ± 18.5 for PA sometimes or never, 63.8 ± 16.2 for PA about 1-2 times/week, and 71.1 ± 15.5 for PA at least 3 times/week. The mean SRW ± SD (range of scale 0-100) was 59.0 ± 20.4, 65.6 ± 17.6, and 68.9 ± 17.1, respectively. The mean PHQ-2 score ± SD (range of scale 0-6) by PA categories was 1.83 ± 1.40 for PA sometimes or never, 1.68 ± 1.28 for PA about 1-2 times/week, and 1.60 ± 1.31 for the PA at least 3 times/week group. SRH and SRW improved linearly with increasing PA frequency (both p < 0.001), and the results remained similar after adjustment for BMI, education and smoking status. No association existed between PA frequency and PHQ-2. More frequent PA was linearly associated with better SRH and SRW, but not with depressive symptoms that were measured by a brief depression screening tool.


Parkinson's disease and working capacity.
The purpose of the present study was to establish how Parkinson's disease (PD) affects working capacity. Altogether, 937 (70%) of 1,343 working-aged members of the Finnish Parkinson Association participated in a questionnaire study. The ages of the subjects were between 29 and 65 years, median 59.0 years; 508 (54%) were men. The median (quartile range) duration of PD symptoms was 7.3 (4.3-11.3) years, and the median self-estimated severity of the disease on the Hoehn & Yahr scale was 2. Only 150 of 937 subjects (16%) were still working: 112 (12%) full-time and 38 (4%) part-time. Among those 343 (37%) who had retired purely because of PD at a median age of 53.4 years, the median working time was 1.7 years after established diagnosis. In part-time work, PD patients had been able to continue for a median of 4.3 years. PD often leads to early retirement; compared with the general Finnish population of similar age, PD patients had retired on the average 6 years earlier. Young age, mild symptoms, and short duration of the disease as well as adjustments enabling easier employment were associated with the possibility to continue longer in the work force.


Diabetes mellitus related biomarker: The predictive role of growth-differentiation factor-15.
Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine, which belongs to super family of the transforming growth factor beta. GDF-15 is widely presented in the various cells (macrophages, vascular smooth muscle cells, adipocytes, cardiomyocytes, endothelial cells, fibroblasts), tissues (adipose tissue, vessels, tissues of central and peripheral nervous system) and organs (heart, brain, liver, placenta) and it plays an important role in the regulation of the inflammatory response, growth and cell differentiation. Elevated GDF-15 was found in patients with established CV diseases including hypertension, stable coronary artery disease, acute coronary syndrome, myocardial infarction, ischemic and none ischemic-induced cardiomyopathies, heart failure, atrial fibrillation, as well as stroke, type two diabetes mellitus (T2DM), chronic kidney disease, infection, liver cirrhosis, malignancy. Therefore, aging, smoking, and various environmental factors, i.e. chemical pollutants are other risk factors that might increase serum GDF-15 level. Although GDF-15 has been reported to be involved in energy homoeostasis and weight loss, to have anti-inflammatory properties, and to predict CV diseases and CV events in general or established CV disease population, there is no large of body of evidence regarding predictive role of elevated GDF-15 in T2DM subjects. The mini review is clarified the role of GDF-15 in T2DM subjects.


[Experiences of voluntary visitors with nonverbal communication in interaction with confused elderly patients in nursing homes].
20 confused elderly in nursing homes (average age 82), who were socially isolated and dependent of nursing care resulting from dementia and institutional factors, were visited by students of social work and student nurses of the elderly. The voluntary visitors were trained in client-centered therapy, reality orientation, non-verbal communication, sensory training, reinforcing daily functions and occupational therapy. The experiences with verbal and non-verbal communication (visual and hearing contact and touching) and with difficulties with the confused elderly, with feelings and the environmental factors are described. The visiting results in better understanding of the confused elderly and in increasing of supporting relationship. Confusion was ameliorated only in some confused elderly. Recommendations are given for voluntary visitors.


Some problems in learning to do "good psychotherapy".
In a discussion of some problems that psychiatric residents encounter in learning to do good psychotherapy, the author compares learning techniques of medicine and those of psychiatry. He concludes that one of the most difficult experiences for the psychiatric resident is learning tolerance for ambiguity and uncertainty.


Effect of Acetic Acid and Lactic Acid at Low pH in Growth and Azole Resistance of Candida albicans and Candida glabrata.
Successful colonization of the acidic vaginal niche by C. glabrata and C. albicans depends on their ability to cope with the presence of lactic and acetic acids produced by commensal microbiota. As such, the inhibitory effect of these acids at a low pH in growth of C. glabrata and C. albicans was investigated. The effect of the presence of these organic acids in tolerance of the two Candida species to azoles used in treatment of vaginal infections was also investigated including eventual synergistic effects. Under the different experimental conditions tested lactic acid exerted no significant inhibitory effect against C. albicans or C. glabrata, contrasting with the generalized impression that the production of this acid is on the basis of the protective effect exerted by vaginal lactobacilii. Differently, C. glabrata and C. albicans exhibited susceptibility to acetic acid, more prominent at lower pHs and stronger for the latter species. Synergism between acetic acid and azoles was observed both for C. albicans and C. glabrata, while lactic acid-azole synergism was only efficient against C. albicans. Altogether our in vitro results indicate that tolerance to acetic acid at a low pH may play a more relevant role than tolerance to lactic acid in determining competitiveness in the vaginal tract of C. albicans and C. glabrata including under azole stress. Treatment of vaginal candidiasis with azoles may depend on the level of acetic and lactic acids present and improvements could be achieved synergizing the azole with these acids.


The theory of encephalization.
The theory of encephalization is developed from elementary dimensional requirements for the construction of a brain of given size. The basic assumption in the theory is that most of the brain in vertebrates is constructed as a series of mappings repeated at various levels. Encephalization is seen as a composite of an amplification factor for the repeated mappings (identical with the encephalization quotient EQ) and a factor associated with "added" tissue. The latter may be viewed as tissue that corresponds to new functions. The relation of the theory to allometric analysis is a relationship of theory to empirical estimation of "expected" brain size at a given body size. But body size is not fundamental to the theory. It is merely one of several possible sources of a measure of the area of a basic mapping, as it were, which is then subject to the amplification factor. Issues in the use of encephalization to assess behavioral capacities are reviewed briefly, as are the neurobiological correlates of encephalization and brain size.


Functional analysis of a nonsyndromic hearing loss-associated mutation in the transmembrane II domain of the GJC3 gene.
In a previous study, we identified a novel missense mutation, p.W77S, in the GJC3 gene encoding connexin30.2/connexin31.3 (CX30.2/CX31.3) from patients with hearing loss. The functional alteration of CX30.2/CX31.3 caused by the p.W77S mutant of GJC3 gene, however, remains unclear. In the current study, our result indicated that the p.W77 is localized at the second membrane-spanning segments (TM2) and near border of the E1 domain of the CX30.2/CX31.3 protein and highly conserved (Conseq score = 8~9) in all species. The p.W77S missense mutation proteins in the intracellular distribution are different CX30.2/CX31.3WT and an accumulation of the mutant protein in the endoplasmic reticulum (ER) of the HeLa cell. Furthermore, co-expression of WT and p.W77S mutant chimerae proteins showed that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the WT proteins' expression in the cell membranes. In addition, we found that CX30.2/CX31.3W77S missense mutant proteins were degraded by lysosomes and proteosomes in the transfected HeLa cell. Based on these findings, we suggest that p.W77S mutant has a dominant negative effect on the formation and function of the gap junction. These results give a novel molecular elucidation for the mutation of GJC3 in the development of hearing loss.


Reconstructing Native American migrations from whole-genome and whole-exome data.
There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern American ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations.


Clinical and Psychosocial Outcomes Associated With a Tele-behavioral Health Platform for Families: Retrospective Study.
The burden of pediatric mental illness in the United States has steadily worsened over the past decade. A recent increase in employer-sponsored behavioral health programs has focused on the needs of the general population. However, these programs do not provide the specialty mental health care required for children, adolescents, and their families. This study aimed to evaluate the effects of a technology-enabled pediatric and family behavioral health service on clinical outcomes among children and caregiver strain. The service is available to commercially insured populations and provides educational content; tele-behavioral health care, including coaching, therapy, and psychiatry; and care escalation and coordination. A retrospective cohort analysis of members using the service between February and September 2022 was conducted. Clinical outcomes for children and their caregivers were collected using the Pediatric Symptom Checklist-17 (PSC-17), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire 8-item (PHQ-8), and Caregiver Strain Questionnaire-Short Form 7 (CGSQ-SF7). Rates of reliable improvement were determined by calculating the reliable change index for each outcome. Paired, 2-tailed t tests were used to evaluate significant changes in assessment scores at follow-up compared to baseline. Of the 4139 participants who enrolled with the service, 48 (1.2%) were referred out for more intensive care, 2393 (57.8%) were referred to coaching, and 1698 (41%) were referred to therapy and psychiatry. Among the 703 members who completed the intervention and provided pre- and postintervention outcomes data, 386 (54.9%) used psychoeducational content, 345 (49.1%) received coaching, and 358 (50.9%) received therapy and psychiatry. In coaching, 75% (183/244) of participants showed reliable improvement on the PSC-17 total score, 72.5% (177/244) on the PSC-17 internalizing score, and 31.5% (105/333) on the CGSQ-SF7 total score (average improvement: PSC-17 total score, 3.37 points; P<.001; PSC-17 internalizing score, 1.58 points; P<.001; and CGSQ-SF7 total score, 1.02 points; P<.001). In therapy and psychiatry, 68.8% (232/337) of participants showed reliable improvement on the PSC-17 total score, 70.6% (238/337) on the PSC-17 internalizing score, 65.2% (219/336) on the CGSQ-SF7 total score, 70.7% (82/116) on the GAD-7 score, and 67.5% (77/114) on the PHQ-8 score (average improvement: PSC-17 total score, 3.16 points; P<.001; PSC-17 internalizing score, 1.66 points; P<.001; CGSQ-SF7 total score, 1.06 points; P<.001; GAD-7 score, 3.00 points; P<.001; and PHQ-8 score, 2.91 points; P<.001). Tele-behavioral health offerings can be effective in improving caregiver strain and psychosocial functioning and depression and anxiety symptoms in a pediatric population. Moreover, these digital mental health offerings may provide a scalable solution to children and their families who lack access to essential pediatric mental health services.


Improved γ-Linolenic Acid Production from Cellulose in Mucor circinelloides via Coexpression of Cellobiohydrolase and Delta-6 Desaturase.
The present study was aimed at facilitating the production of γ-linolenic acid (GLA) from the cellulosic substrate with the engineered oleaginous fungus Mucor circinelloides WJ11. Here, the homologous recombination technology was used to overexpress the cellobiohydrolase (CBH2) derived from Trichoderma longibrachiatum and the original delta-6 fatty acid desaturase (D6) in M. circinelloides to construct genetically engineered strains capable of effectively using cellulose to enhance GLA synthesis. When cultivated in modified K&R medium supplemented with microcrystalline cellulose, the CBH2 and D6 coexpressing strains led to increases in the biomass (up to 12.8 g/L) and lipid yield (up to 3.7 g/L) of 87% and 2.4-fold, respectively, compared to that of the control strain. Notably, when CBH2 and D6 were coexpressed in M. circinelloides, the yield of GLA reached 608 mg/L, which was a dramatic increase of 3.9-fold compared to that of the control strain. This is the first report on promoting the GLA production from the cellulosic substrate via coexpression of CBH2 and delta-6 desaturase. This work provides a theoretical basis for efficient transformation from the cellulosic substrate to functional GLA by CBH2 and D6 coexpressing strains, which might play a positive role in promoting the sustainable development of biological industry.


Prosthetic valve endocarditis caused by Propionibacterium species: a national registry-based study of 51 Swedish cases.
Propionibacterium spp. are a rare cause of infective endocarditis (IE). The diagnosis is difficult because the bacteria are slow-growing and growth in blood cultures is often misinterpreted as contamination from the skin flora. The aim of this study was to describe all cases of Propionibacterium spp. endocarditis in the Swedish national registry of IE. The registry was searched for all cases of IE from 1995 to 2016 caused by Propionibacterium spp. Data concerning clinical characteristics, treatment, and outcome were registered. A total of 51 episodes of definitive prosthetic valve endocarditis (PVE) caused by Propionibacterium spp. were identified, comprising 8% of cases of PVE during the study period. Almost all cases (n = 50) were male. The median time from surgery to diagnosis of IE was 3 years. Most patients were treated mainly with beta-lactams, partly in combination with aminoglycosides. Benzyl-penicillin was the most frequently used beta-lactam. A total of 32 patients (63%) underwent surgery. Overall, 47 patients (92.1%) were cured, 3 (5.9%) suffered relapse, and 1 (2.0%) died during treatment. IE caused by Propionibacterium spp. almost exclusively affects men with a prosthetic valve and findings of Propionibacterium spp. in blood cultures in such patients favors suspicion of a possible diagnosis of IE. In patients with prosthetic valves, prolonged incubation of blood cultures up to 14 days is recommended. The prognosis was favorable, although a majority of patients required cardiac surgery during treatment. Benzyl-penicillin should be the first-line antibiotic treatment option for IE caused by Propionibacterium spp.


A role for the Wnt gene family in hematopoiesis: expansion of multilineage progenitor cells.
The microenvironment is a key regulator of hematopoietic stem cells (HSCs) and is a likely source of extracellular factors that control stem cell fate. A better understanding of these microenvironmental factors may come from investigations of developmental cell fate determination in which the critical roles of cell-cell interactions of multipotential cells have been shown. The Wnt gene family is known to regulate the cell fate and cell-cell interactions of multipotential cells in a variety of tissues. Expression of Wnts and of their putative receptors encoded by murine homologs of the Drosophila frizzled gene in hematopoietic tissues was examined by reverse transcriptase-polymerase chain reaction. Wnt-5a and Wnt-10b were expressed in day-11 murine yolk sac, day-14 fetal liver, and fetal liver AA4+ cells. The expression profiles of four murine frizzled homologs, Mfz3-7, were nearly identical to that of Wnt-5a and Wnt-10b. Notably, Wnt-10b was expressed in the fetal liver AA4+ Sca+ c-kit+ flASK) HSC population. A role for Wnts in HSC fate determination was studied by treatment of HSC populations in culture with soluble WNT proteins. The addition of conditioned media from cells transfected with Wnt-1, Wnt-5a, or Wnt-10b cDNAs to cultures of flASK cells stimulated a sevenfold, eightfold, and 11-fold expansion in cell number, respectively, relative to control media. Removal of WNT-5a from this media by immunodepletion depleted the stimulatory activity from the media, whereas addition of a partially purified WNT-5a stimulated a fivefold expansion relative to control cells. Transduction of flASK cells with a retrovirus bearing a Wnt-5a cDNA enhanced proliferation. We conclude that WNTs stimulate the survival/proliferation of hematopoietic progenitors, demonstrating that WNTs comprise a novel class of hematopoietic cell regulators.


Transforming growth factor B1 decreases uptake of glutathione precursor amino acids in bovine pulmonary artery endothelial cells.
We have previously observed that transforming growth factor beta 1 (TGF beta 1) produces a pro-oxidant effect and decreases cellular glutathione (GSH) levels of cultured bovine pulmonary artery endothelial cells (BPAEC) (White A. C., S. K. Das, and B. L. Fanburg. Am. J. Respir. Cell Mol. Biol. 6:364-368, 1992). In the present studies we demonstrate that 2 ng/ml TGF beta 1 reduces the uptake of two GSH precursor amino acids (cystine and glutamate) by 50% (cystine; control 359.35 +/- 100, TGF beta 1 187.7 +/- 26 pmol/10 min/10(6) cells, p < 0.05; glutamate; control 215.15 +/- 18, TGF beta 1 110.2 +/- 16 pmol/10 min/10(6) cells, p < 0.001). The inhibitory effect of TGF beta 1 on the uptake of GSH precursor amino acids persisted in the presence of buthionine sulfoximine (inhibits gamma-glutamyl cysteine synthetase, the rate limiting step in GSH synthesis) or acivicin (inhibits gamma-glutamyl transpeptidase). The uptake of leucine, an amino acid that does not serve as a precursor for GSH, was unaffected by TGF beta 1. In additional experiments TGF beta 1 decreased the levels of cellular and medium GSH-indicating that TGF beta 1 did not increase efflux of GSH from BPAEC. We propose from these observations that TGF beta 1 decreases cellular glutathione, at least in part, through down regulation of precursor amino acid transport and, thereby, its rate of synthesis.


Rapid production of metal-organic frameworks via microwave-assisted solvothermal synthesis.
This paper describes a very rapid technique for the production of metal-organic frameworks (MOF). The method uses a conventional microwave to nucleate crystal growth. A MOF synthesis that used to take hours or days can now be completed in 30 s to 2 min. The yield goes from approximately 30% to over 90%. Novel MOFs can be made, since the growth process is no longer dependent on the walls or dust particles for nucleation. Particle sizes have a narrower distribution. Further, the particle size can be controlled by varying the precursor concentration.


Learning strategies used by cardiology residents: assessment of learning styles and their correlations.
To identify the learning styles of a group of cardiology residents (R) undergoing a training program at the University of Buenos Aires and to identify correlations of these styles. Statistical data were obtained through a 120-question survey developed by Vermunt and colleagues, which identified four different learning styles: construction-directed; reproduction-directed; application-directed; and undirected. Four variables were identified [gender, previous experience as a teaching assistant (TA) in medical school, university final average (FA) and the public or private institution/centre of origin] in order to analyse level of correlation with learning styles (LS). Between April 2001 and April 2002, 149 residents (R) completed the survey. Average age was 29 (+/-2.7) years old; with 63% being men. The predominant LS were oriented toward knowledge application. In terms of variables, no differences regarding gender were detected; the R with TA showed undirected LS characteristics; those with a low FA registered a tendency towards reproduction-directed LS; and those residents at public/state medical centres indicated construction-directed LS tendencies. An application-directed learning style predominates in this group of residents. Information regarding learning styles can provide foundations upon which arguments can be made for changes in education that are traditionally not evidence-based.


Long non-coding RNA profiling links subgroup classification of endometrioid endometrial carcinomas with trithorax and polycomb complex aberrations.
Integrative analysis of endometrioid endometrial carcinoma (EEC) using multiple platforms has distinguished four molecular subgroups. However, the landscape of expressed long non-coding RNAs (lncRNA) and their role in charting EEC subgroups and determining clinical aggressiveness remain largely unknown. Using stringent criteria, we identified 1,931 expressed lncRNAs and predicted potential drivers through integrative analysis. Unsupervised clustering of lncRNA expression revealed three robust categories: basal-like, luminal-like and CTNNB1-enriched subgroups. Basal-like subgroup was enriched for aggressive tumors with higher pathological grade (p < 0.0001), TNM stage (p = 0.01), and somatic mutations in trithorax-group genes (MLL, MLL2 and MLL3); and it overexpressed polycomb genes EZH2 and CBX2. In contrast to the luminal-like subgroup, progesterone (PGR) and estrogen receptor (ESR1) genes were highly down-regulated in the EEC basal-like subgroup. Consistent with its enrichment for CTNNB1 mutations (69%), lncRNA profile of the CTNNB1-enriched EEC subgroup was highly similar to that of the CTNNB1-enriched liver cancer subgroup. We performed integrative analysis of lncRNAs in EEC using The Cancer Genome Atlas (TCGA) molecular RNAseq profiles of 191 primary tumors for which genomic data were also available. We established lncRNA subgroup classification, correlated it with chromatin modifying gene expression, and described correlations between our lncRNA classification and clinico-genomic tumor features. Our results reveal the utility of systematic characterization of clinically annotated EEC in three clinically relevant subgroups. They also highlight the convergence of aberrations in polycomb- and trithorax-group genes in aggressive basal EEC subtypes, providing a rationale for further investigation of epigenetic therapy in this setting.


Oxidative stress and decreased Nrf2 level in pediatric patients with COVID-19.
The aim of this study was to investigate the change in nuclear factor erythroid 2-related factor (Nrf2), which plays a critical role in cytoprotection against oxidative stress, in pediatric patients with coronavirus disease 2019 (COVID-19) infection positivity, and to evaluate the relationship between Nrf2 and oxidative balance. The study included 40 children with confirmed COVID-19 infection and 35 healthy children. The groups were compared in respect of Nrf2, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), in addition to clinical findings of fever, cough, shortness of breath, contact history, and demographic data of age and gender. The mean Nrf2 values and TAS levels were determined to be statistically significantly low (p < 0.001) and the TOS level and OSI were statistically significantly high in the children with COVID-19 compared to the control group. A significant positive correlation was determined between Nrf2 and TAS (p < 0.01); as the Nrf2 value increased, so the TAS value increased. A significant negative correlation was determined between Nrf2 and TOS and OSI (p < 0.01); as the Nrf2 value increased, there was determined to be a significant decrease in the TOS and OSI values. COVID-19 infection in pediatric patients causes a decrease in the Nrf2 level. By causing a decrease in the TAS level and an increase in the TOS and OSI levels, the decrease in Nrf2 may explain the tissue damage which can be caused by COVID-19.


Stimulation of energy metabolism by alpha-adrenergic agonists in primary cultures of astrocytes.
Noradrenaline effects on glucose oxidation were studied in primary cultures of astrocytes. CO2 formation from labeled glucose was enhanced in the presence of noradrenaline. The stimulatory effect by noradrenaline was exerted both on lactate formation (approximately 20%) and on tricarboxylic acid activity (CO2 production from glutamate) (approximately 40%). The effect was, at least partly, exerted on the alpha-ketoglutarate dehydrogenase step. The EC50 value for noradrenaline on lactate formation was significantly lower (60 nM) than that on oxidative metabolism (1,900 nM). Studies with specific adrenergic agonists and antagonists showed that various receptor subtypes are involved. Thus, the effect on lactate formation was mediated exclusively by stimulation of an alpha 1 receptor whereas oxidative metabolism was enhanced by both alpha 1 and alpha 2 receptor stimulation. No effects were exerted by beta receptor agonists or antagonists.


Ultrastructural localization of Thorotrast (thorium dioxide) in human liver by analytical scanning electron microscope.
The distribution of thorium dioxide (Thorotrast) in the liver from a Thorotrast-administered autopsy case was examined stereographically by analytical scanning electron microscopy. Thorium particles were detected in the macrophages of the portal triad and hepatic sinusoid. These macrophages were irregularly shaped and tended to be aggregated. In the sinusoid, accumulation of the macrophages formed a thrombus-like structure. Furthermore, observed in the sinusoid were free Thorotrast particles that appeared to have been released into the sinusoid as a result of breakdown of the macrophages (Kupffer cells).


Adaptations of semen characteristics and sperm motility to harsh salinity: Extreme situations encountered by the euryhaline tilapia Sarotherodon melanotheron heudelotii (Dumeril, 1859).
In most teleost fishes, sperm cells are quiescent in the seminal plasma and are activated by either a drop (fresh water fish) or an increase in osmolality (marine fish) when released in the water. It is most interesting to examine how the mechanisms of sperm motility activation can adapt to a broad range of salinities, as applies to some euryhaline species, and particularly to the tilapia Sarotherodon melanotheron heudelotii, which can reproduce at salinities from 0 up to 120 in the wild. Here, the gonado-somatic index, semen characteristics, and the osmotic and ionic requirements of sperm motility activation were compared in S. m. heudelotii reared in fresh water (FW), sea water (SW), or hypersaline water (HW; salinities of 0, 35, and 70, respectively). No salinity-dependent differences were found in gonado-somatic index or semen characteristics, except for an increase of seminal plasma osmolality with increasing salinity (from 318 to 349 mOsm kg(-1) in FW and HW fish, respectively). The osmolality range allowing the highest percentages of sperm activation broadened and shifted toward higher values with increasing fish ambient salinity (150-300, 300-800, and 500-1200 mOsm kg(-1), for FW, SW, and HW fish, respectively). Nevertheless, at the three fish rearing salinities, sperm could be activated in media that were hypotonic, isotonic, or hypertonic relative to the seminal plasma, at least when some calcium was present above a threshold concentration. The [Ca(2+)] required for the activation of S. m. heudelotii sperm is (1) higher in fish reared at a higher salinity (2) higher in hypertonic than that in hypotonic activation media, whatever the fish rearing salinity, and (3) higher in the presence of Na(+) or K(+), the negative effects of which increased with an increase in fish rearing salinity. The [Ca(2+)]/[Na(+)]  ratios allowing for maximal sperm motility in SW or HW fish are close to those observed in natural environments, either in sea or hypersaline waters. In comparison to most teleosts with external fertilization, the total duration of sperm motility in S. m. heudelotii was exceptionally long (>2 hours regardless the fish rearing salinities). The decrease in sperm activity with increasing time since activation did not result from limiting energy reserves, as the addition of calcium in the activation medium caused most spermatozoa to become motile again. The comparison of sperm characteristics of S. m. heudelotii acclimated from FW to SW or HW with those of fish maintained all lifelong at their native salinity showed that adaptive responses were completed within 2 months or less.


Pattern of the haemoglobinopathy in the endemic and nearby provinces in Thailand, a note from then GIS pattern.
In Thailand, high prevalence of haemoglobin disorders has been reported. Millions of Thai people suffer from these diseases. This problem affects not only public health but also the economy of the country. Carrier detection, genetic counselling and prenatal diagnosis should be encouraged. Most of the programmes have been launched to the endemic provinces in the southern part of northeastern region of Thailand. However, due to the recent industrialisation in Thailand, the migration of the Thai population affects the pattern of haemoglobin disorder in this area. Here, the author performs a spatial analysis by Geographical Information System (GIS) using ArcExplorer Program on the database of the recorded prevalence of haemoglobin disorder in the endemic area and nearby provinces. The drift of the high prevalence from the central endemic area to the nearby provinces can be seen and support the migration effect of the population. Of interest, this observation can support the recent report on the rising prevalence of haemoglobin disorders in the non-endemic area of Thailand.


Suspected adverse drug reactions in the Hungarian veterinary practice between 1982 and 1992.
The most characteristic adverse drug reactions observed after the use of home-manufactured or imported veterinary medicinal products in Hungary between 1982 and 1992 included toxicosis, severe local reaction, lack of efficacy, and presence of residues in the edible tissues of food animals. The causes of adverse drug reactions comprised manufacturing defects, lack of chemical or microbiological stability, misuse or extra label use, and neglecting the warnings in the directions for use. Collection and analysis of data relating to adverse drug reactions are indispensable for the prevention of similar cases. The authorities can facilitate data collection by supplying veterinary practitioners with the necessary report forms.


Effect of Exogenous Proline on Metabolic Response of Tetragenococcus halophilus under Salt Stress.
This study investigated the effect of proline addition on the salt tolerance of Tetragenococcus halophilus. Salt stress led to the accumulation of intracellular proline in T. halophilus. When 0.5 g/l proline was added to hyperhaline medium, the biomass increased 34.6% (12% NaCl) and 27.7% (18% NaCl) compared with the control (without proline addition), respectively. A metabolomic approach was employed to reveal the cellular metabolic responses and protective mechanisms of proline upon salt stress. The results showed that both the cellular membrane fatty acid composition and metabolite profiling responded by increasing unsaturated and cyclopropane fatty acid proportions, as well as accumulating some specific intracellular metabolites (environmental stress protector). Higher contents of intermediates involved in glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway were observed in the cells supplemented with proline. In addition, addition of proline resulted in increased concentrations of many organic osmolytes, including glutamate, alanine, citrulline, N-acetyl-tryptophan, and mannitol, which may be beneficial for osmotic homeostasis. Taken together, results in this study suggested that proline plays a protective role in improving the salt tolerance of T. halophilus by regulating the related metabolic pathways.


The history of esophageal surgery.
Esophageal surgery has always been considered extremely demanding, given the surgical experience and skills required, due to the anatomic location of the esophagus as well as the impact of such extensive operations on patients' homeostasis. The intention of the present study is to review all historical time points of esophageal surgery, from its inception to the modern era of minimally invasive esophageal surgery. The first clear description of esophageal surgery is dated back to 1738, in an attempt to remove a foreign body from the thoracic esophagus. However, the high morbidity and mortality rates of esophageal surgical operations led to the invention and application of less invasive surgical procedures. Esophageal surgery has evolved from extensive surgical operations to minimally invasive esophagectomies, aiming exclusively to reduce perioperative morbidity and mortality, while maintaining surgical effectiveness. Despite the fact that benign esophageal pathologies were the main stimulus for this evolution, minimally invasive esophageal surgery is now applied even in patients with esophageal cancer, with outcomes comparable to those of traditional surgical approaches. It would be interesting to see how all these new surgical techniques may evolve, altering further the current status of esophageal surgery in the future.


IL-10 Receptor Neutralization-Induced Colitis in Mice: A Comprehensive Guide.
Interleukin-10 (IL-10) and its receptor (IL-10R) have been foremost targets to understand inflammatory bowel disease (IBD) pathogenesis. For the past several decades, IL-10-deficient (Il10-/- ) mice were considered one of the best models to study immune-mediated colitis. Several physiologic limitations with this model, e.g., delayed and varied disease onset, have hindered investigators in testing new clinical therapies for IBD. In this article, we provide comprehensive guidance for using anti-IL-10R monoclonal antibody (αIL-10R mAb) neutralization as a superior alternative model to study IBD. This article describes the feasibility of using αIL-10R mAb to induce chronic colitis (within 4 weeks), perform time-dependent mechanistic studies, and assess the efficacy of IBD therapeutics. This article also delineates protocols for in-house assays to critically assess colitis and associated inflammatory parameters. Overall, we underscore αIL-10R mAb neutralization as a relevant immune-mediated murine colitis model to study human Crohn's disease. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Induction of chronic colitis in mice via αIL-10R mAb neutralization Basic Protocol 2: Biochemical evaluation of αIL-10R mAb neutralization-induced chronic colitis Support Protocol 1: Stool analysis and scoring Support Protocol 2: Swiss roll method.


[Sensorineural hearing loss in childhood: evaluation of economic impact in view of vaccine prevention of cases due to congenital cytomegalovirus infection].
Sensorineural hearing loss (SNHL) is a serious public health problem which affects 1-3% per hundred live born babies in developed countries. The congenital cytomegalovirus (CMV) infection is its most important non-genetic cause. The evaluation of the effectiveness of future programs of anti-CMV vaccination requires an assessment of the present costs of SNHL. Direct costs for the Italian public system were calculated per prosthesis child until his full age and turned out to add up to 260,000 euro. Private costs are difficult to be assessed and anyhow are highly dependent from the socio-economic level. This preliminary assessment suggests that the vaccination would be cost-saving if SNHL cases due to congenital CMV were more than 21 per year, corresponding to a congenital infection prevalence higher than 0.21%o.


A Comprehensive Review of COVID-19 Virology, Vaccines, Variants, and Therapeutics.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the coronavirus disease 2019 (COVID-19), has caused more than 179 million infections and 3.8 million deaths worldwide. Throughout the past year, multiple vaccines have already been developed and used, while some others are in the process of being developed. However, the emergence of new mutant strains of SARS-CoV-2 that have demonstrated immune-evading characteristics and an increase in infective capabilities leads to potential ineffectiveness of the vaccines against these variants. The purpose of this review article is to highlight the current understanding of the immunological mechanisms of the virus and vaccines, as well as to investigate some key variants and mutations of the virus driving the current pandemic and their impacts on current management guidelines. We also discussed new technologies being developed for the prevention, treatment, and detection of SARS-CoV-2. In this paper, we thoroughly reviewed and provided crucial information on SARS-CoV-2 virology, vaccines and drugs being used and developed for its prevention and treatment, as well as important variant strains. Our review paper will be beneficial to health care professionals and researchers so they can have a better understanding of the basic sciences, prevention, and clinical treatment of COVID-19 during the pandemic. This paper consists of the most updated information that has been available as of June 21, 2021.


An overlooked cause of resistant hypertension: upper airway resistance syndrome - preliminary results.
Upper airway resistance syndrome is a sleep-disordered breathing syndrome that is characterized by repetitive arousals resulting in sympathetic overactivity. We aimed to determine whether upper airway resistance syndrome was associated with poorly controlled hypertension. A total of 40 patients with resistant hypertension were enrolled in the study. All of the patients underwent polysomnographic examinations and 24-hour ambulatory blood pressure monitoring to exclude white coat syndrome and to monitor treatment efficiency. Among 14 upper airway resistance syndrome patients, 2 patients had surgically correctable upper airway pathologies, while 12 patients were given positive airway pressure therapy. All patients underwent polysomnographic examinations; 22 patients (55%) were diagnosed with obstructive sleep apnea and 14 patients (35%) were diagnosed with upper airway resistance syndrome, according to American Sleep Disorders Association criteria. The patients with upper airway resistance syndrome were younger and had a lower body mass index compared with other patients, while there were no difference between the blood pressure levels and the number of antihypertensive drugs. The arousal index was positively correlated with systolic blood pressure level (p=0.034; rs=0.746), while the Epworth score and AHI were independent of disease severity (p=0.435, rs=0.323 and p=0.819, rs=-0.097, respectively). Eight patients were treated with positive airway pressure treatment and blood pressure control was achieved in all of them, whereas no pressure reduction was observed in four untreated patients. We conclude that upper airway resistance syndrome is a possible secondary cause of resistant hypertension and that its proper treatment could result in dramatic blood pressure control.


RF system of the SPring-8 storage ring.
Construction of three RF stations in the storage ring of SPring-8 has been completed. The design concept concentrates on avoiding a coupled-bunch instability which limits the stored current or makes the synchrotron radiation beam unstable. The cavity is bell-shaped to reduce the coupling impedance of the higher-order modes. The cavity dimensions are trimmed systematically to distribute the higher-order mode frequencies. Each cavity has two movable tuners. The temperature of the cavity cooling water is controlled within 0.02 K and the water flow is kept constant. The construction and commissioning of the SPring-8 storage ring RF system is reported.


Serum Uric Acid, Alzheimer-Related Brain Changes, and Cognitive Impairment.
Despite known associations of lower serum uric acid (UA) with Alzheimer's disease (AD) dementia or AD-related cognitive impairment, little is known regarding the underlying patho-mechanisms. We aimed to examine the relationships of serum UA with in vivo AD pathologies including cerebral beta-amyloid (Aβ) and tau deposition, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensities (WMH). We also investigated the association between serum UA and cognitive performance, and then assessed whether such an association is mediated by the brain pathologies. A total of 430 non-demented older adults underwent comprehensive clinical assessments, measurement of serum UA level, and multimodal brain imaging, including Pittsburgh compound B-positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and magnetic resonance imaging scans. Mini-Mental State Examination (MMSE) and word list recall (WLR) test scores were used to measure cognitive performance. Serum UA level was significantly associated with AD-CM, but not with Aβ deposition, tau deposition, or WMH volume. Serum UA levels also had significant association with WLR and marginal association with MMSE; such associations disappeared when AD-CM was controlled as a covariate, indicating that AD-CM has a mediating effect. The findings of the present study indicate that there is an association of low serum UA with AD-related cerebral hypometabolism, and whether this represents a causal relationship remains to be determined.


The Impact of Campus-Level Factors on Peers' Perceived Ability to Support a Survivor.
Campus sexual violence is a complex issue that has led to a proliferation of federal legislation and best practices with the intent to better support student survivors. Despite these efforts, research suggests that many survivors do not disclose to formal resources on campus, but rather, to their peers. While there is growing theoretical and empirical support for the role of peer-level influences on both preventing and responding to sexual violence on college campuses, our understanding of students' confidence in knowing how to respond is limited. Furthermore, disclosure research has yet to assess the impact of broader campus-level factors on students' confidence in being able to support survivors. In the present exploratory study, undergraduate students responded to a survey, which included questions about receiving disclosures and perceived ability to respond as well as measures of individual-level correlates (gender, race, prior victimization) and campus community factors (perceptions of the university's responsiveness, exposure to information, awareness of resources). Bivariate analyses were conducted to examine whether certain students were more likely to receive a disclosure on campus. To look at the impact of individual- and community-level factors, a series of hierarchical logistic regression models were estimated. Ability to respond to a disclosure was measured using three separate dichotomous variables. Findings show that 34% of our sample has received at least one disclosure of sexual violence from a peer since coming to campus. In addition, results show that above and beyond individual correlates, campus-level factors impacted students' confidence in their roles as disclosure recipients. These results have significant implications for sexual violence programs on campus. Suggestions for future research are also discussed.


Sphingosylphosphorylcholine stimulates human monocyte-derived dendritic cell chemotaxis.
To investigate the effects of sphingosylphosphorylcholine (SPC) on human monocyte-derived dendritic cell (DC) chemotaxis. Human DC were generated from peripheral blood monocytes by culturing them with granulocyte macrophage-colony stimulating factor and interleukin-4. The effect of SPC on the DC chemotactic migration was measured by chemotaxis assay. Intracellular signaling event involved in the SPC-induced DC chemotaxis was investigated with several inhibitors for specific kinase. The expression of the SPC receptors was examined by reverse transcription polymerase chain reaction. We found that SPC induced chemotactic migration in immature DC (iDC) and mature DC (mDC). In terms of SPC-induced signaling events, mitogen activated protein kinase activation and Akt activation in iDC and mDC were stimulated. SPC-induced chemotaxis was mediated by extracellular signal-regulated protein kinase and phosphoino-sitide-3-kinase, but not by calcium in both iDC and mDC. Although mDC express ovarian cancer G protein-coupled receptor 1, but not G protein-coupled receptor 4, iDC do not express any of these receptors. To examine the involvement of sphingosine-1-phosphate (S1P) receptors, we checked the effect of an S1P receptor antagonist (VPC23019) on SPC-induced DC chemotaxis. VPC23019 did not affect SPC-induced DC chemotaxis. The results suggest that SPC may play a role in regulating DC trafficking during phagocytosis and the T cell-stimulating phase, and the unique SPC receptor, which is different from S1P receptors, is involved in SPC-induced chemotaxis.


[Sensitization to pollen in the asthmatic child. A study of 86 cases].
This retrospective study was designed to determine the place of pollen sensibilization in asthmatic child and to assess its epidemiological and clinical characteristics. 86 from 638 asthmatic child were allergic to pollen and included in the study. The mean age was 4 years (extremes : 1-12 years). The mean age of first respiratory manifestations was 1 and half years. The male/female ratio was 1.46. Asthmatic attacks was noted in 77% of cases, chronic cough was the only allergic manifestation in 16% of cases. Associated rhinitis or conjunctivitis were found in 55% of cases, atopic dermatitis was found in 4 patients (4.6% of cases). Atopic asthma was per annual in 78% of cases. Pollinic asthma was diagnosed in 51 child. Other sensibilization were found in 60% of cases. 26 child (32%) were allergic to pollen only and 18 child to sample pollen. The gramineae pollen sensibilization is the most common allergy, followed by olive tree and cypress tree and herbaceous pollens.


PSGL-1: A New Player in the Immune Checkpoint Landscape.
P-selectin glycoprotein ligand-1 (PSGL-1) has long been studied as an adhesion molecule involved in immune cell trafficking and is recognized as a regulator of many facets of immune responses by myeloid cells. PSGL-1 also regulates T cell migration during homeostasis and inflammatory settings. However, recent findings indicate that PSGL-1 can also negatively regulate T cell function. Because T cell differentiation is finely tuned by multiple positive and negative regulatory signals that appropriately scale the magnitude of the immune response, PSGL-1 has emerged as an important checkpoint during this process. We summarize what is known regarding PSGL-1 structure and function and highlight how it may act as an immune checkpoint inhibitor in T cells.


Epigenetic changes and their relationship to somaclonal variation: a need to monitor the micropropagation of plantation crops.
Chromatin modulation plays important roles in gene expression regulation and genome activities. In plants, epigenetic changes, including variations in histone modification and DNA methylation, are linked to alterations in gene expression. Despite the significance and potential of in vitro cell and tissue culture systems in fundamental research and marketable applications, these systems threaten the genetic and epigenetic networks of intact plant organs and tissues. Cell and tissue culture applications can lead to DNA variations, methylation alterations, transposon activation, and finally, somaclonal variations. In this review, we discuss the status of the current understanding of epigenomic changes that occur under in vitro conditions in plantation crops, including coconut, oil palm, rubber, cotton, coffee and tea. It is hoped that comprehensive knowledge of the molecular basis of these epigenomic variations will help researchers develop strategies to enhance the totipotent and embryogenic capabilities of tissue culture systems for plantation crops.


Herpes simplex virus shedding in genital secretions.
Nine women and eight men with a history of genital herpes had cultures taken for 60 consecutive days to assess the frequency and duration of viral shedding in the absence of symptoms. Daily self-obtained specimens (cervical-vaginal swabs from women and urethral swabs from men) were submitted for viral isolation. Five of 972 samples were found to contain infectious virus; two of the positive specimens correlated with overt disease. The other three positive cultures, two from the same individual, were not clearly associated with a genital infection. Thus, the overall frequency of asymptomatic viral shedding was 0.31% and occurred in two of 17 individuals. It is concluded that prolonged continuous sampling may be necessary to assess the risk of asymptomatic shedding. Infectious virus was not present in the genital secretions of most individuals (15 of 17) in the absence of a lesion, even when cultured on a daily basis for 60 days.


Mechanical properties of organic nanofibers.
Intrinsic elastic and inelastic mechanical properties of individual, self-assembled, quasi-single-crystalline para-hexaphenylene nanofibers supported on substrates with different hydrophobicities are investigated as well as the interplay between the fibers and the underlying substrates. We find from atomic-force-microscopy-based rupture experiments a rupture shear stress of about 2 x 10(7) Pa for an individual fiber. Deflecting a nanofiber suspended across a gap results in a Young's modulus of 0.65 GPa. Translational motion of intact nanofibers across the surface is demonstrated for fibers on a silicon substrate with a low-adhesion coating, whereas such motion on a noncoated substrate is limited to very short (sub-micrometer) nanofiber pieces due to strong adhesive forces.


Oral health and systemic inflammatory, cardiac and nitroxid biomarkers in hemodialysis patients.
Periodontal diseases have systemic inflammatory effects and have been adversely associated with cardiovascular diseases, which are also the most frequent cause of death in the end-stage renal disease. The aim of this cross-sectional study was to investigate the oral health and serum biomarkers among the hemodialysis (HD) patients in Slovenia. 111 HD patients were periodontally examined and their sera were assayed for C reactive protein (CRP), cardiac troponin T (TnT), nitrite/nitrate (NOx) and antibody levels to A. actinomycetemcomitans and P. gingivalis. The association of oral health with systemic response was analyzed with Kruskal-Wallis test, Fisher's exact test and multivariate linear regression. Bleeding on probing without periodontal pockets was present in 5.2%, calculus without periodontal pockets in 42.1%, shallow periodontal pockets in 39.5% and deep periodontal pockets in 13.2% of dentate patients. There were 28.8% edentulous participants. 63.1% of the patients had CRP levels higher than 3 mg/L and 34.2% higher than 10 mg/L. TnT was detectable in all participants, with 25.2% exhibiting levels higher than 100 ng/L. The median level of NOx was 43.1 µmol/L. Participants with higher CRP were more likely to be edentulous and have higher TnT levels. A direct association of oral health with TnT or NOx was not detected. HD patients in Slovenia have compromised oral health and increased serum inflammatory and cardiac biomarkers. Edentulousness was an independent predictor for the increased CRP, indicating a need for improved dental care to retain the teeth as long as possible.


Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma.
Despite the introduction of 13-cis-retinoic acid (13-cis-RA) into the current chemotherapy, more than half of high-risk neuroblastoma patients have experienced tumor relapses driven by chemoresistant cancer stem cells (CSCs) that can be isolated by their ability to grow as spheres. Although aldehyde dehydrogenase (ALDH) has been used to characterize CSCs in certain cancers, ALDH remains elusive in neuroblastoma. In the present study, we determined ALDH activity and expression of its 19 isoforms in spheres and parental cells of neuroblastoma. ALDH activity and several ALDH isoforms were consistently induced in spheres of different neuroblastoma cells. While ALDH1A2, ALDH1L1 and ALDH3B2 expression was consistently induced in spheres and associated with the sphere and colony formation, only ALDH1A2 expression was significantly correlated with the poor prognosis of neuroblastoma patients. ALDH1A2 expression was further associated with the growth and undifferentiation of neuroblastoma xenografts and the resistance of neuroblastoma cells to 13-cis-RA. These results suggest that ALDH1A2 is involved in the regulation of CSC properties in neuroblastoma.


Reserve Accumulation Is Prioritized Over Growth Following Single or Combined Injuries in Three Common North American Urban Tree Species.
Trees that grow in urban areas are confronted with a wide variety of stresses that undermine their long-term survival. These include mechanical damage to the crown, root reduction and stem injury, all of which remove significant parts of plant tissues. The single or combined effects of these stresses generate a complex array of growth and ecophysiological responses that are hard to predict. Here we evaluated the effects of different individual and combined damage on the dynamics of non-structural carbohydrates (NSC, low weight sugars plus starch) concentration and new tissue growth (diameter increment) in young trees. We hypothesized that (i) tissue damage will induce larger reductions in diameter growth than in NSC concentrations and (ii) combinations of stress treatments that minimally alter the "functional equilibrium" (e.g., similar reductions of leaf and root area) would have the least impact on NSC concentrations (although not on growth) helping to maintain tree health and integrity. To test these hypotheses, we set up a manipulative field experiment with 10-year-old trees of common urban species (Celtis occidentalis, Fraxinus pennsylvanica, and Tilia cordata). These trees were treated with a complete array of mechanical damage combinations at different levels of intensity (i.e., three levels of defoliation and root reduction, and two levels of stem damage). We found that tree growth declined in relation to the total amount of stress inflicted on the trees, i.e., when the combined highest level of stress was applied, but NSC concentrations were either not affected or, in some cases, increased with an increasing level of stress. We did not find a consistent response in concentration of reserves in relation to the combined stress treatments. Therefore, trees appear to reach a new "functional equilibrium" that allows them to adjust their levels of carbohydrate reserves, especially in stems and roots, to meet their metabolic demand under stressful situations. Our results provide a unique insight into the carbon economy of trees facing multiple urban stress conditions in order to better predict long-term tree performance and vitality.


Photolithographic patterning on multi-wavelength quantum dot film of the improved conversion efficiency for digital holography.
A triple-wavelength patterned quantum dot film was fabricated for the light source of digital holography to improve both the axial measurement range and noise reduction. The patterned quantum dot film was fabricated after optimizing the photolithography process condition based on the UV-curable quantum dot solution, which was capable of multiple patterning processes. In addition, an optimized pattern structure was developed by adding TiO2 nanoparticles to both the quantum dot and bank layers to increase the scattering effect for the improved photoluminescence intensity. Finally, the newly developed light source with the balanced spectral distribution was applied to the digital holography, rendering it applicable as an improved light source.


Clinical features of Japanese children and adolescents with systemic lupus erythematosus: results of 1980-1994 survey.
Marked advances have been made in the past decade in the management of adults with systemic lupus erythematosus (SLE). Therefore, a nationwide retrospective survey was conducted between 1980 and 1994 to investigate the clinical manifestations of SLE in Japanese children and adolescents. Questionnaires were sent to 340 hospitals. Of 405 patients reported by 176 hospitals, 373 patients, diagnosed by the criteria established by the Pediatric Study Group of the Japanese Ministry of Health and Welfare in 1985, were enrolled in the study. Forty-nine of the 354 patients (13.8%) had relatives with a connective tissue disease within the third degree of consanguinity. The frequent manifestations in 373 patients were the presence of antinuclear antibody (98.9%), immunologic disorders (93.0%), hypocomplementemia (87.1%), malar rash (79.6%) and fever (74.0%). Lupus nephritis was present in 148 of the 309 patients (47.9%) at their first visit to a clinic, and 261 of the 373 patients (70.0%) developed renal involvement during the observation period. Of 370 patients, 92 patients (24.9%) exhibited central nervous system lupus. Of 368 patients, 192 patients (52.2%) were treated by methylprednisolone pulse therapy and 148 patients (40.2%) received immunosuppressants in combination with steroid therapy at some stage during the observation period, Survival rate at 5 years from onset was 95.9%. Management of infection, coagulopathies, and central nervous system involvement is essential to improve the prognosis of SLE in Japanese children and adolescents.


Upper Eyelid Silicone Oil Migration after Sutureless 23-gauge Vitrectomy.
To report a case of upper eyelid swelling and ptosis caused by silicone oil migration in a patient after sutureless 23-gauge pars plana vitrectomy and silicone oil injection. A 36-year-old female was referred to eye clinic with total retinal detachment (RD) and superotemporal giant dialysis secondary to trauma in the left eye. Transconjunctival sutureless 23-gauge pars plana vitrectomy and intraocular silicone oil (1300 centistokes) injection were performed. After about 5 months, she came back with the left upper eyelid and periorbital swelling. Palpation of the eyelid revealed soft and mobile subcutaneous small lumps that were not attached to the skin. Computed tomography scan of the orbit showed an 11 mm × 8 mm soft tissue density mass in lateral aspect of the left orbit. Transcutaneously surgical exploration was performed. The patient was seen after 1 week postoperatively and there was a significant improvement of the ptosis. Eyelid swelling and ptosis caused by silicone oil migration after RD surgery are very rare and this is one of the few reports in literature.


The Relationship Between Open Access Article Publishing and Short-Term Citations in Otolaryngology.
The purpose of this study is to compare the number of citations received by open access articles versus subscription access articles in subscription journals in the Otolaryngology literature. Using the Dimensions research database, we examined articles indexed to PubMed with at least 5 citations published in 2018. Articles were included from Otolaryngology-Head and Neck Surgery, The Laryngoscope, JAMA Otolaryngology-Head and Neck Surgery, Annals of Otology, Rhinology, and Laryngology, and American Journal of Otolaryngology. Multivariate Poisson regression modeling was used to adjust for journal, article type, and topic. Practice guidelines, position statements, or retractions were excluded as potential outliers. 137 open access articles and 337 subscription access articles meeting inclusion criteria were identified, with a median citation number of 8 (IQR 6-11). The most common article type was original investigation (82.5%), and the most common study topic was head and neck (28.9%). Open access articles had a higher median number of citations at 9 (IQR 6-13) when compared to subscription access articles at 7 (IQR 6-10) (P = .032). Open access status was significantly associated with a higher number of citations than subscription access articles when adjusting for journal, article type, and topic (β = .272, CI 0.194-0.500, P < .001). Although comprising a minority of articles examined in this study of subscription journals, open access articles were associated with a higher number of citations than subscription access articles. Open access publishing may facilitate the spread of novel findings in Otolaryngology.


The complex role of triglycerides in cardiovascular disease.
The objectives of the present work were to obtain a summary estimate of the magnitude of association between triglycerides and cardiovascular disease in the general population based on currently available data. Our goal was to determine whether this relationship is independent of other risk factors, particularly high density lipoprotein cholesterol (HDL-C), using semi-quantitative meta-analysis. We only included studies reporting the association between fasting triglyceride levels and incident cardiovascular disease endpoints. Twenty-one studies including 65,863 men and 11,089 women were selected for the analysis from population-based prospective studies using standard meta-analysis calculations, relative risks (RR) and 95% confidence intervals (CI). Multivariable adjusted RRs were determined only for the studies reporting adjustment for HDL-C (9 studies in men, 2 studies in women). These analyses indicate plasma triglycerides are an independent predictor of cardiovascular disease.


Regional development of glutamate-N-methyl-D-aspartate receptor sites in asphyxiated newborn infants.
The N-methyl-D-aspartate (NMDA) subclass of glutamate receptors was examined in newborn infants dying between 25 weeks' gestation and term, either from acute cerebral hypoxia, or from other noncerebral conditions incompatible with life. Frontal, occipital, temporal, and motor cortex tissue samples were obtained at autopsy (post mortem delay: median, 45.9 hr; range, 24-96 hr) and frozen for subsequent [3H]MK801 homogenate binding assays. Whereas no significant variation was observed in ligand affinity (KD), in all cases receptor density (BMAX) increased with gestational age, in occipital cortex (27 weeks, BMAX = 222 +/- 44 fmol x mg protein(-1); 39 weeks, 439 +/- 42 fmol x mg protein[-1]), but not in motor or temporal cortex. The gestational-age increase also occurred in control frontal cortex (27 weeks, 284 +/- 80; 39 weeks, 567 +/- 40 fmol x mg protein[-1]), but was significantly less marked in frontal cortex in hypoxia cases (27 weeks, 226 +/- 90; 39 weeks, 326 +/- 47 fmol x mg protein[-1]). In all cortical areas except temporal, the maximal response to glutamate did not vary across case groups. Hypoxia cases showed an increased response to glutamate enhancement selectively in temporal cortex. Binding site density did not correlate with degree of hypoxia as assessed pathologically, suggesting that receptor differences preceded the hypoxic episode. Regional differences in glutamate-NMDA receptor sites may underlie increased vulnerability to hypoxia at birth.


Stocking density effects on growth performance and processing yields of heavy broilers.
This study examined responses of male broilers during a 49-d production cycle to 4 placement densities in 2 trials. Trials were pooled because no treatment x trial interaction occurred. In each trial, 1,488 male chicks were randomly placed into 32 floor pens to simulate final densities of 30 (37 chicks/pen), 35 (43 chicks/ pen), 40 (50 chicks/pen), and 45 (56 chicks/pen) kg of BW/m2 of floor space based on a projected final BW of 3.29 kg. Growth rate and nutrient utilization were similar (P > or = 0.05) among the treatments from 1 to 32 d of age. From 1 to 49 d, BW gain (P = 0.011) and feed consumption (P = 0.029) were adversely affected by increasing the placement density from 30 to 45 kg of BW/m2 of floor space. The reduction in cumulative BW gain due to placement density can be partially explained by less feed consumption as evidenced by 95.4% of the sums of squares of BW gain being attributable to feed consumption. Litter moisture content (P = 0.025) and foot pad lesion score (P = 0.001) increased linearly with increasing placement density. Upon processing, whole carcass and breast meat yields relative to BW were not affected (P > or = 0.05) as density increased from 30 to 45 kg/m2. The proportion of whole carcasses with scratches, but not tears, on the back and thighs increased (P = 0.021) as density increased. These results indicate that increasing the density beyond 30 kg/m2 elicited some negative effects on live performance of heavy broilers.


Liberal use of axillary artery cannulation for aortic and complex cardiac surgery.
Axillary artery cannulation for cardiopulmonary bypass has been described previously as a safe and reliable technique, with a low risk of atheroemboli, avoidance of malperfusion in aortic dissection and facilitation of selective antegrade cerebral perfusion during hypothermic circulatory arrest. The aim of this study was to document the broad applicability of axillary cannulation and its associated morbidity and identify where it was not possible to use planned axillary cannulation. A retrospective review of a single surgeon's 10-year experience of axillary cannulation using the side-graft technique in 184 consecutive patients (age 22-92 years) in aortic and complex cardiac surgery from July 2002 to June 2012. There were no intraoperative deaths and no major complications related to axillary artery use. There were six postoperative deaths unrelated to axillary artery cannulation. Six patients (3.3%) had minor complications as a direct result of axillary cannulation including seroma, haematoma, chronic pain and pectoralis major muscle atrophy. There were 10 cases where planned axillary cannulation was abandoned, due to inadequate size of the axillary artery in 8 patients and axillary artery dissection and morbid obesity in 1 patient each. Axillary artery cannulation is an ideal arterial inflow site in cases where the ascending aorta is unsuitable as it is safe, reliable and reduces the risks of atheroembolization and malperfusion. Major complications are rare with this meticulous technique and it is our standard practice in complex cardiac and aortic surgery.


Onset of maternal psychiatric disorders after the birth of a child with intellectual disability: a retrospective cohort study.
Mothers of a child with intellectual disability (ID) have more psychiatric disorders after the birth of their child than other mothers. However, it is unclear if this is because they have more psychiatric disorders before the birth or if the increase is related to the burden of caring for the child. We aimed to calculate the rate of new psychiatric disorders in mothers after the birth of their eldest child with ID born between 1983 and 2005 and to compare these with rates in women with a child with no ID or autism spectrum disorder (ASD) born during the same period. By linking data from Western Australian population-based registries, we selected women with no psychiatric history who survived the birth of their live-born child (N = 277,559) and compared rates of psychiatric disorders for women with a child with ID and women without a child with or ASD. Negative binomial regression with STATA 12 was used for all analyses. Mothers of children with mild-moderate ID of unknown cause had around two to three and a half times the rate of psychiatric disorders of mothers of children without ID or ASD. Mothers of children with Down syndrome and no pre-existing psychiatric disorder showed resilience and had no impairments in their mental health. Interventions and services are needed for mothers of other children with ID to improve their mental health. Further research is implicated to explore the mental health of mothers of children with ID and a pre-existing psychiatric disorder.


Correlation of cell volume fractions with cell concentrations in fermentation media.
Cell volume fractions and cell concentrations were measured in submerged cultures of Saccharomyces cerevisiae, Escherichia coli, and Penicillium chrysogenum. Correlations for cell volume fractions with cell concentrations in fermentation media of the microorganisms were established accordingly. Other key properties of microorganisms, such as cell water content, wet cell density, and dry cell density, can also be obtained with the use of the current method. The results are in good agreement with data available in the literature.


Degradation of fluorotelomer alcohols: a likely atmospheric source of perfluorinated carboxylic acids.
Human and animal tissues collected in urban and remote global locations contain persistent and bioaccumulative perfluorinated carboxylic acids (PFCAs). The source of PFCAs was previously unknown. Here we present smog chamber studies that indicate fluorotelomer alcohols (FTOHs) can degrade in the atmosphere to yield a homologous series of PFCAs. Atmospheric degradation of FTOHs is likely to contribute to the widespread dissemination of PFCAs. After their bioaccumulation potential is accounted for, the pattern of PFCAs yielded from FTOHs could account for the distinct contamination profile of PFCAs observed in arctic animals. Furthermore, polar bear liver was shown to contain predominately linear isomers (>99%) of perfluorononanoic acid (PFNA), while both branched and linear isomers were observed for perfluorooctanoic acid, strongly suggesting a sole input of PFNA from "telomer"-based products. The significance of the gas-phase peroxy radical cross reactions that produce PFCAs has not been recognized previously. Such reactions are expected to occur during the atmospheric degradation of all polyfluorinated materials, necessitating a reexamination of the environmental fate and impact of this important class of industrial chemicals.


Is the Association Between Obesity and Hip Osteoarthritis Surgery Explained by Familial Confounding?
Familial confounding is confounding due to genetics or environmental exposures shared by family members. We aimed to study whether familial confounding explains the association between body mass index (BMI) and severe hip osteoarthritis (OA). We linked data from the Norwegian Arthroplasty Registry with the Norwegian Twin Registry on the National ID-number in 2014, generating a population-based prospective cohort study of same-sex twins born between 1915 and 1960 (53.4% females). BMI was calculated from self-reported height/weight. The outcome was incident hip arthroplasty due to OA (follow-up time, 1987-2014; 424 914 person-years). We performed sex-specific co-twin control analyses of dizygotic (N = 5,226) and monozygotic (MZ, N = 3,803) twin pairs using Cox regression models and explored reasons for any familial confounding using bivariate twin models. The mean (SD) BMI was 22.6 (2.96), peak lifetime BMI 25.6 (2.61), and N = 614 had hip surgery due to OA. In cohort analyses, BMI was associated with hip OA for women and men (hazard ratio [HR] = 1.09, 95% confidence intervals [CIs] = 1.06 to 1.11 and HR = 1.08, 95% CI = 1.04 to 1.12, respectively). When adjusting for familial confounding within MZ twins, the association got stronger for women (HR = 1.19; 95% CI = 1.05 to 1.36) but weaker for men (HR = 0.93; 95% CI = 0.75 to 1.16). There was no genetic overlap between BMI and hip OA, yet the familial confounding in men provides suggestive evidence that the association could be explained by shared environmental factors. The association between BMI and hip OA may be explained by familial confounding for men. For women, there was no evidence for familial confounding, consistent with a causal association. See video abstract at, http://links.lww.com/EDE/B336.


[Current evidence based interventions for preventing fall and fall-related hip fracture of the older people].
For older people, the consequences of falling include injury, fear of falling, decreased activity, functional deterioration, reduced quality of life, and death. According to reliable systematic reviews and guidelines, exercise programs including balance and strength training, multifactorial interventions, and home safety assessment and modification interventions are effective at reducing the rates of falls and risks of falling among community-dwelling elderly people. Taking vitamin D supplements might be effective for reducing falls in older people who exhibit lower vitamin D levels in the blood. Hip protectors apparently reduce the risk of hip fractures in frail older residents of care facilities. Taking vitamin D with calcium supplements might reduce the risk of hip fractures.


Positron emission tomography of lung tumors and mediastinal lymph nodes using [18F]fluorodeoxyglucose. The Members of the PET-Lung Tumor Study Group.
Positron emission tomography detects increased glucose uptake in malignant tissue using the glucose analogue [2-18F]fluoro-2-deoxy-D-glucose. We reviewed the scans obtained in 62 patients with lung tumors. All had undergone computed tomography and had tissue-based diagnoses: 22 had adenocarcinomas, 12 had squamous cell carcinomas, 13 had other malignancies, 1 had organizing pneumonia, 1 had a hamartoma, and 13 had granulomas. Positron emission tomography with [2-18F]fluoro-2-deoxy-D-glucose identified 44 of 47 malignancies. Two of three false-negative findings were tumors that were 1 cm2 or less and the other was a bronchioloalveolar carcinoma. All three false-positive findings were granulomas. The sensitivity and specificity of the technique were 93.6% and 80%, respectively, and the positive and negative predictive values were 93.6% and 80%, respectively. The differential uptake ratio was determined in all 62 patients. The mean differential uptake ratio (+/- the standard error of the mean) for malignant tumors was 6.4 +/- 0.56 and that for benign tumors was 1.14 +/- 0.26 (p < 0.0001, t test). Twenty-five of the patients had N2 lymph nodes evaluated pathologically. Positron emission tomography with [2-18F]fluoro-2-deoxy-D-glucose identified negative N2 nodes in 19 of 22 patients (86%) with negative nodes and positive N2 nodes in 2 of 3 patients (66%) with positive nodes, including one instance missed by computed tomography.(ABSTRACT TRUNCATED AT 250 WORDS)


Reliability, Responsiveness, and Criterion Validity of the Kiio Sensor, a New Tool for Assessment of Muscle Function.
Musculoskeletal injuries are a leading cause of disability in both the general population and military, and the ability to effectively quantify musculoskeletal function remains problematic. The aim of the current study is to investigate the reliability, responsiveness, and criterion validity of the kiio Sensor for measurement of muscle strength, a key aspect of comprehensive functional assessment. Forty-four (24 male, 20 female) physically active civilian adults (mean [SD] = 21.2 [1.5] years of age) with no history of upper extremity injuries in the last year and no current complaints of pain, weakness, or functional limitation completed two sessions of maximum shoulder external rotation contractions. The forces were measured with a kiio Sensor and isokinetic dynamometer. The devices showed strong correlation (r = 0.89) and no significant mean difference (0.3 ± 3.3 lb, p = 0.47). Intrasession reliability for both devices was analyzed using intraclass correlation coefficients (ICC3,1 = 0.96 [95% confidence interval = 0.93-0.98)], with the kiio Sensor having slightly less standard error and trial-to-trial variability. The kiio Sensor 7-day reliability was ICC3,3 = 0.97 (95% confidence interval = 0.94-0.98). The kiio Sensor demonstrates excellent reliability, responsiveness, and validity compared with a gold standard isokinetic dynamometer. Several key attributes contributing to this technology's military relevance are discussed.


Deep learning based adaptive sequential data augmentation technique for the optical network traffic synthesis.
The lack of the sufficient and diverse training data is one of the main challenges limiting performances of the machine learning enabled applications in optical networks. Here, we propose a deep learning based sequential data augmentation technique for the aggregate traffic data augmentation for diverse optical network scenarios. A generative adversarial network (GAN) model is trained with the experimental traffic data to automatically extract the substantial characteristics of the experimental traffic data through the zero-sum game theory and then augment the traffic data adaptively. The statistical evaluation parameters of the augmented traffic are mean, variance and Hurst exponent. To add comparisons, two other classical generative models including the statistical parameter configuration (SPC) model and the variational autoencoder (VAE) model are also adopted to generate the traffic data that are similar to the actual traffic data. The comprehensive comparisons among the proposed GAN, the SPC and VAE show that the performances of the GAN exceed those of the SPC and the VAE obviously. The mean and the variance of the augmented traffic data from the GAN are almost equal to those of the experimental traffic data, where the average deviations are both within 2%. The Hurst exponent of the augmented traffic data from the GAN is respectively near 90% and 96% of those of the experimental traffic data in the access network and the core network. To estimate the similarity intuitively, the well-known k-mean algorithm is used to cluster the augmented traffic data according to the centroids determined by the corresponding experimental traffic data and the clustering accuracies are all higher than 95% for 6 kinds of typical traffic types in the optical networks. These results demonstrate that the proposed GAN is able to effectively generate the traffic data that is very close to the experimental traffic data and is difficult to be distinguished for diverse traffic types. Moreover, a relatively small dataset with a few hundred pieces of experimental traffic data is required and the amount of the augmented traffic data from the GAN is unlimited in theory, which can be augmented as much as we need. The proposed traffic data augmentation technique also has the potential to be utilized in other sequential data augmentation applications for the optical networks.


[Progressive cerebellar ataxia with euthyroid Hashimoto's disease--implication of autoantibodies associated with Hashimoto's disease in progressive cerebellar ataxia].
To determine the frequency of cerebellar ataxia patients with autoantibodies for Hashimoto's disease, we analyzed 68 patients who were examined serum test for autoantibodies of Hashimoto disease among 178 cerebellar ataxia patients who visited our neurology clinic from January 2005 until December 2007. In these 68 patients, 8 had autoantibodies for Hashimoto's disease. Five of these 8 patients were diagnosed with hereditary spinocerebellar ataxia by genetic analysis. Moreover, one patient was diagnosed with probable multiple system atrophy by neurological examination. Cerebellar ataxic disease of known causes was ruled out for the remaining two cases; they were euthyroid and their cerebellar ataxia was slowly progressive and were diagnosed with cortical cerebellar atrophy. Although Hashimoto's disease may associate with cerebellar ataxia because cortical cerebellar atrophy is a heterogeneous condition, this association is not clear at present.


Usefulness of a Cardiovascular Polypill in the Treatment of Secondary Prevention Patients in Spain: A Cost-effectiveness Study.
To estimate the health benefits and cost-effectiveness of a polypill intervention (aspirin 100 mg, atorvastatin 20 mg, ramipril 10 mg) compared with multiple monotherapy for secondary prevention of cardiovascular events in adults with a history of myocardial infarction from the perspective of the Spanish National Health System. An adapted version of a recently published Markov model developed and validated in Microsoft Excel was used to compare the cost-effectiveness of the polypill with that of its combined monocomponents over a 10-year time horizon. The population included in the model had a mean age of 64.7 years; most were male and had a history of myocardial infarction. The input parameters were obtained from a systematic literature review examining efficacy, adherence, utilities, and costs. The results of the model are expressed in events avoided, incremental costs, incremental life years, incremental quality-adjusted life years, and the incremental cost-effectiveness ratio. Over a 10-year period, use of the cardiovascular polypill instead of its monocomponents simultaneously would avoid 46 nonfatal and 11 fatal cardiovascular events per 1000 patients treated. The polypill would also be a more effective and cheaper strategy. Probabilistic analysis of the base case found a 90.9% probability that the polypill would be a cost-effective strategy compared with multiple monotherapy at a willingness-to-pay of 30 000 euros per quality-adjusted life year. The polypill would be a cost-effective strategy for the Spanish National Health System with potential clinical benefits.


Bacterial diversity in fumarole environments of the Paricutín volcano, Michoacán (Mexico).
Active volcanoes are among the most extreme environments on Earth. The extreme temperatures, presence of toxic heavy metals and low nutrient bioavailability favor the development of extremophiles. We characterized the physical-chemical parameters of and bacterial communities (T-RFLP and 16S rRNA gene libraries) inhabiting fumarole niches of the Paricutín volcano located in Michoacán (Mexico). This volcano, which surged in 1943, is one of the youngest volcanoes on Earth and the microbial diversity in this area is yet to be characterized. The sampling stations were characterized in a pH range from 5.34 to 7.89 and showed different temperatures (soil, 27-87 °C; air, 13.6-56 °C) with high concentrations of metals such as iron and arsenic. The most abundant bacterial populations, confirmed by T-RFLP and 16S rRNA gene libraries, were related to members of Firmicutes and Proteobacteria phyla including sequences associated with thermophiles and sulfate reducing bacteria. Overall, the Paricutín volcano showed low bacterial diversity and its prokaryotic diversity was characterized by the impossibility of amplifying Archaea-related sequences.