Influence of supplemental oxygen on the physiological response to the PO2 aerobic exerciser.
Acute physiological responses to the "PO2-Aerobic Exerciser" (AE), a partial rebreathing device designed to stimulate training at altitudes, were studied in seven healthy men [mean VO2max = 56.1 +@- 10.1 (SD) ml X kg-1 X min-1] who performed cycle ergometer exercise to exhaustion in three experimental situations: a control test (C) breathing normal atmosphere: a test with the device (AE); and a test with the AE air supplemented with oxygen (AEO2'). Arterial oxygen saturation at rest for C, AE, and AEO2' studies was 97 +/- 1, 95 +/- 2, and 97 +/- 1%, respectively (P less than 0.05 for C vs AE and AE vs AEO2'), while at exhaustion it was 95 +/- 1, 87 +/- 2, and 95 +/- 1%, respectively (P less than 0.05 for C vs AE and AE vs AEO2'). Maximum work rate decreased from a control value of 1738 +/- 184 kg X min-1 to 1371 +/- 147 kg X min-1 during AE and remained below control levels during AEO2'; 1554 +/- 110 kg X min-1 (P less than 0.05). Beyond 60% of maximum work rate during AE, inspired CO2 increased to 0.026 +/- 0.005. Mouth pressure swings of up to -19.2 +/- 10.2 and 12.7 +/- 5.7 cm H2O were recorded during AE. While the PO2 aerobic exerciser induced a hypoxic stress, the pertubation imposed was not explained fully by arterial oxygen desaturation. Other factors such as hypercapnia and a flow resistive increase in the work of breathing appear to have influenced work capacity during the use of the device.


Diagnostic yield of an ambulatory patch monitor in patients with unexplained syncope after initial evaluation in the emergency department: the PATCH-ED study.
Diagnosing underlying arrhythmia in ED syncope patients remains problematic. This study investigates diagnostic yield, event prevalence, patient satisfaction and compliance, and influence on resource utilisation of an ambulatory patch monitor in unexplained ED syncope patients. Prospective pilot study conducted in a single tertiary ED in Scotland between 17 November 2015 and 16 June 2017 with a historical unmatched comparator group. Patients 16 years or over presenting within 6 hours of unexplained syncope were fitted in the ED with an ambulatory patch ECG recorder (Zio XT monitor), which continuously records a single-lead ECG for up to 14 days. Patients with an obvious underlying cause were excluded. An unmatched historical group of 603 syncope patients with no obvious diagnosis in ED, recruited to a prior cohort study (2007-2008), were used as a comparator. Primary endpoint was symptomatic significant arrhythmia at 90-day follow-up. During the prospective study period, 86 patients were recruited. 90-day diagnostic yield for symptomatic significant arrhythmia was 10.5% (95% CI 4.0 to 16.9; 9 of 86) versus 2.0% (95% CI 0.9 to 3.1; 12 of 603) in the comparator group. 24 patients (27.9%) had a significant arrhythmia (five serious); 26 patients (30.2%) had serious outcomes (major adverse cardiac event and/or death). Blinded patch report review suggested the patch would significantly reduce requirement for standard outpatient ambulatory ECG monitoring. 56 of 76 returned patches had a diagnostic finding within±45 s of a triggered/diary event (73.7% diagnostic utility; 95% CI 63.7 to 83.6); 34 of 56 (61%) for sinus rhythm or ectopic beats only. Routine, early ambulatory ECG monitoring in ED patients with unexplained syncope is probably warranted. A large-scale trial comparing this approach to standard care with cost-effectiveness and safety analysis is now required. NCT02683174.


Probing the mechanism of recognition of ssDNA by the Cdc13-DBD.
The Saccharomyces cerevisiae protein Cdc13 tightly and specifically binds the conserved G-rich single-stranded overhang at telomeres and plays an essential role in telomere end-protection and length regulation. The 200 residue DNA-binding domain of Cdc13 (Cdc13-DBD) binds an 11mer single-stranded representative of the yeast telomeric sequence [Tel11, d(GTGTGGGTGTG)] with a 3 pM affinity and specificity for three bases (underlined) at the 5' end. The structure of the Cdc13-DBD bound to Tel11 revealed a large, predominantly aromatic protein interface with several unusual features. The DNA adopts an irregular, extended structure, and the binding interface includes a long ( approximately 30 amino acids) structured loop between strands beta2-beta3 (L(2-3)) of an OB-fold. To investigate the mechanism of ssDNA binding, we studied the free and bound states of Cdc13-DBD using NMR spectroscopy. Chemical shift changes indicate that the basic topology of the domain, including L(2-3), is essentially intact in the free state. Changes in slow and intermediate time scale dynamics, however, occur in L(2-3), while conformational changes distant from the DNA interface suggest an induced fit mechanism for binding in the 'hot spot' for binding affinity and specificity. These data point to an overall binding mechanism well adapted to the heterogeneous nature of yeast telomeres.


Robust nonlinear system identification using neural-network models.
We study the problem of identification for nonlinear systems in the presence of unknown driving noise, using both feedforward multilayer neural network and radial basis function network models. Our objective is to resolve the difficulty associated with the persistency of excitation condition inherent to the standard schemes in the neural identification literature. This difficulty is circumvented here by a novel formulation and by using a new class of identification algorithms recently obtained by Didinsky et al. We show how these algorithms can be exploited to successfully identify the nonlinearity in the system using neural-network models. By embedding the original problem in one with noise-perturbed state measurements, we present a class of identifiers (under L1 and L2 cost criteria) which secure a good approximant for the system nonlinearity provided that some global optimization technique is used. In this respect, many available learning algorithms in the current neural-network literature, e.g., the backpropagation scheme and the genetic algorithms-based scheme, with slight modifications, can ensure the identification of the system nonlinearity. Subsequently, we address the same problem under a third, worst case L(infinity) criterion for an RBF modeling. We present a neural-network version of an H(infinity)-based identification algorithm from Didinsky et al and show how, along with an appropriate choice of control input to enhance excitation, under both full-state-derivative information (FSDI) and noise-perturbed full-state-information (NPFSI), it leads to satisfaction of a relevant persistency of excitation condition, and thereby to robust identification of the nonlinearity. Results from several simulation studies have been included to demonstrate the effectiveness of these algorithms.


Population impact of arthritis on disability in older adults.
Disability threatens the independence of older adults and has large economic and societal costs. This article examines the population impact of arthritis on disability incidence among older Americans. The present study used longitudinal data (1998-2000) from the Health and Retirement Study, a national probability sample of elderly Americans. Disability was defined by the inability to perform basic activities of daily living (ADL). A total of 7,758 participants ages > or =65 years with no ADL disability at baseline were included in the analyses. Multiple logistic regression was used to measure the impact of baseline arthritis (self reported) on incidence of subsequent ADL disability after controlling for baseline differences in demographics, health factors, health behaviors, and medical access. Older adults who had baseline arthritis had a substantially higher incidence of ADL disability compared with those without arthritis (9.3% versus 4.5%). The strong relationship of arthritis and ADL disability was partially explained by demographic, health, behavioral, and medical access factors. However, even after adjusting for all other risk factors, arthritis remained as an independent and significant predictor for developing ADL disability (adjusted odds ratio 1.5, 95% confidence interval 1.2-1.8). Almost 1 in every 4 new cases of ADL disability was due to arthritis (adjusted population attributable fraction: 23.7%). The high frequency of incident ADL disability attributable to arthritis points to the importance of intervention programs that address the entire spectrum of health and functional problems in persons with arthritis to prevent disability.


Chaotic phenomenon and the maximum predictable time scale of observation series of urban hourly water consumption.
The chaotic characteristics and maximum predictable time scale of the observation series of hourly water consumption in Hangzhou were investigated using the advanced algorithm presented here is based on the conventional Wolf's algorithm for the largest Lyapunov exponent. For comparison, the largest Lyapunov exponents of water consumption series with one-hour and 24-hour intervals were calculated respectively. The results indicated that chaotic characteristics obviously exist in the hourly water consumption system; and that observation series with 24-hour interval have longer maximum predictable scale than hourly series. These findings could have significant practical application for better prediction of urban hourly water consumption.


The Caulobacter crescentus ctrA P1 promoter is essential for the coordination of cell cycle events that prevent the overinitiation of DNA replication.
The master regulator CtrA oscillates during the Caulobacter cell cycle due to temporally regulated proteolysis and transcription. It is proteolysed during the G1-S transition and reaccumulates in predivisional cells as a result of transcription from two sequentially activated promoters, P1 and P2. CtrA reinforces its own synthesis by directly mediating the activation of P2 concurrently with repression of P1. To explore the role of P1 in cell cycle control, we engineered a mutation into the native ctrA locus that prevents transcription from P1 but not P2. As expected, the ctrA P1 mutant exhibits striking growth, morphological and DNA replication defects. Unexpectedly, we found CtrA and its antagonist SciP, but not DnaA, GcrA or CcrM accumulation to be dramatically reduced in the ctrA P1 mutant. SciP levels closely paralleled CtrA accumulation, suggesting that CtrA acts as a rheostat to modulate SciP abundance. Furthermore, the reappearance of CtrA and CcrM in predivisional cells was delayed in the P1 mutant by 0.125 cell cycle unit in synchronized cultures. High levels of ccrM transcription despite low levels of CtrA and increased transcription of ctrA P2 in the ctrA P1 mutant are two examples of robustness in the cell cycle. Thus, Caulobacter can adjust regulatory pathways to partially compensate for reduced and delayed CtrA accumulation in the ctrA P1 mutant.


A study of the emotional characteristics of temporomandibular disorder patients using SCL-90-R.
This study was conducted to identify the emotional characteristics of temporomandibular disorder patients. The authors applied one of the self-report modes of psychological measurement, Symptom Checklist-90-Revision. The subjects were 219 TM disorder patients who visited the Department of Oral Diagnosis and Oral Medicine, Seoul National University Hospital, during the period from December 1985 to September 1986. Patients were divided into subgroups according to sex, age, duration of symptoms, presence or absence of pain, and educational level. The mean values and distribution of T-scores of each symptom dimension and global index were then compared.


Exploring the intersection of adverse childhood experiences, pediatric chronic pain, and rheumatic disease.
While the general relationship between ACEs and the development of chronic pain has become increasingly clear, how ACEs may shape a child's clinical presentation with regards to chronic pain has yet to be fully expounded. We aimed to determine the association between ACEs and clinical manifestations of pediatric chronic pain and explore the interaction of ACEs and pediatric rheumatic disease among youth with chronic pain on health-related outcomes. We conducted a cross-sectional cohort study of patients aged ≤18 years with chronic pain seen in a pediatric rheumatology amplified pain clinic between August 2018 and July 2020. We stratified subjects into three groups: no ACEs, one ACE, and ≥ 2 ACEs. We assessed clinical signs and symptoms associated with the presence of ACEs using Chi-square or Wilcoxon-rank test. The association between ACEs as well as other variables of interest with functional impairment was tested using simple and multivariable linear regression. Of the 412 patients included, more than 75% of patients reported at least one ACE. Most frequent included history of mental illness in a first degree relative (56%) and parental divorce or separation (20%). Those with ≥2 ACEs had more somatic symptoms, worse functional disability, and a higher proportion of mental health conditions. There appeared to be a dose dependent interaction between ACEs and functional disability from co-morbid rheumatologic disease. In multivariable regression, higher verbal pain score, symptom severity score (SSS), and presence of autonomic changes were associated with estimated average increase in FDI score (β = 1.05, 1.95 and 4.76 respectively; all p < 0.01). Children with chronic pain and/or rheumatologic diseases who are exposed to ACEs are at increased risk of greater symptomatology, functional disability, and somatization of symptoms. Our findings indicate an ongoing need for systemic evaluation of ACEs in children with chronic pain and/or rheumatic disease and incorporation of trauma-based care.


Robust hepatic gene silencing for functional studies using helper-dependent adenoviral vectors.
RNA interference is currently envisioned as the basis of gene function and drug target validation studies. This novel technology has the advantage of providing a remarkably faster tool for gene silencing than traditional transgenic animal methodologies. In vivo administration of short interfering RNA (siRNA) typically results in reduced target gene expression for approximately 1 week. Viral vectors offer the possibility to express constitutive levels of short hairpin RNA (shRNA) so that the effects of knocking down the target gene can be studied for a few weeks, rather than a few days. Helper-dependent vectors have a significant advantage over previous generations of adenoviral vectors because of their much higher cloning capacity, potential for long-term transgene expression, and enhanced safety profiles on administration in vivo. Therefore, this advanced type of vector is an excellent tool to carry out in vivo studies directed at constitutive expression of shRNA. Here we show it is possible to obtain more than 90% target gene knockdown in an animal model of type 2 diabetes for several weeks, thereby consolidating this technology as an alternative to generating liver-specific knockout animals.


Acrylamide in gingerbread: critical factors for formation and possible ways for reduction.
The influence of ingredients, additives, and process conditions on acrylamide formation in gingerbread was investigated. The sources for reducing sugars and free asparagine were identified, and the effect of different baking agents on acrylamide formation was evaluated. Ammonium hydrogencarbonate strongly enhanced acrylamide formation, but its N atom was not incorporated into acrylamide, nor did acrylic acid form acrylamide in gingerbread. Acrylamide concentration and browning intensity both increased with baking time and correlated with each other. The use of sodium hydrogencarbonate as baking agent reduced the acrylamide concentration by >60%. Free asparagine was a limiting factor for acrylamide formation, but the acrylamide content could also be lowered by replacing reducing sugars with sucrose or by adding organic acids. It is concluded that a significant reduction of acrylamide in gingerbread can be achieved by using sodium hydrogencarbonate as baking agent, minimizing free asparagine, and avoiding prolonged baking.


Eye movements enhance memory for individuals who are strongly right-handed and harm it for individuals who are not.
Subjects who make repetitive saccadic eye movements before a memory test subsequently exhibit superior retrieval in comparison with subjects who do not move their eyes. It has been proposed that eye movements enhance retrieval by increasing interaction of the left and right cerebral hemispheres. To test this, we compared the effect of eye movements on subsequent recall (Experiment 1) and recognition (Experiment 2) in two groups thought to differ in baseline degree of hemispheric interaction-individuals who are strongly right-handed (SR) and individuals who are not (nSR). For SR subjects, who naturally may experience less hemispheric interaction than nSR subjects, eye movements enhanced retrieval. In contrast, depending on the measure, eye movements were either inconsequential or even detrimental for nSR subjects. These results partially support the hemispheric interaction account, but demand an amendment to explain the harmful effects of eye movements for nSR individuals.


Feasibility, Acceptability, and Preliminary Impacts of Web-Based Patient Education on Patients With Schizophrenia Spectrum Disorder: Quasi-Experimental Cluster Study.
Web-based interventions are promising tools for increasing the understanding of illness and treatment among patients with serious mental disorders. This study aimed to test the feasibility and acceptability of a Web-based patient education intervention using a quasi-experimental cluster design to report feedback on patient education sessions and the website used and to report preliminary evidence of the intervention's impact on patients with schizophrenia spectrum disorder. A single-blind, parallel, quasi-experimental cluster study over a 6-month period comparing Web-based education (n=33) with a nonequivalent control group (treatment as usual, n=24) for people with schizophrenia spectrum disorder was conducted. Participants (N=57) were recruited from one psychiatric hospital (6 wards). Feasibility was assessed by participants' commitment (refusal rate, dropout rate) to the study. Acceptability was assessed as participants' commitment to the intervention. Patient education sessions and website feedback were assessed by the patients and health care professionals. The preliminary impact of the sessions on patients' self-efficacy, self-esteem, illness cognition, and knowledge level was measured at baseline and follow-ups (8 weeks, 6 months) with self-rated questionnaires. The refusal rate among patients was high with no statistically significant difference (69% [74/107] in the intervention group, 76% [76/100] in the control group; P=.21). The same result was found for the dropout rates (48% [16/33] vs 58% [14/24]; P=.46). The acceptability of the intervention was good; 31 participants out of 33 (94%) completed all five sessions. Feedback on the intervention was mainly positive; three out of four subscales of session were rated above the midpoint of 4.0. Feedback on the website was also positive, with a grade of good for content (69%, 20/29 patients; 75%, 21/28 professionals), layout (62%, 18/29 patients; 61%, 17/28 professionals), and usability (62%, 18/29 patients; and 68%, 19/28 professionals). The patients using the intervention had significantly higher scores 6 months after the sessions in self-efficacy (baseline mean 26.12, SD 5.64 vs 6-month mean 29.24, SD 6.05; P=.003) and regarding knowledge level about schizophrenia (mean 11.39, SD 4.65 vs 6-month mean 15.06, SD 5.26; P=.002), and lower scores in the subscale of helplessness in illness cognition (mean 2.26, SD 0.96 vs 6-month mean 1.85, SD 0.59; P=.03). Differences from the control group were not significant. No differences were found in patients' self-esteem or other subscales in illness cognition. The patients were reluctant to participate in the study and tended to drop out before the follow-ups. Once they had participated, their acceptance of the intervention was high. A more effective recruitment strategy and monitoring method will be needed in future studies. To assess the impact of the intervention, a more rigorous study design with an adequately powered sample size will be used in cooperation with outpatient mental health services.


Association between acupuncture and grade 1 hypertension: A systematic review and meta-analysis.
Acupuncture is a traditional therapy that can be potentially effective for treating high blood pressure. Grade 1 hypertension is a relatively mild form of hypertension. This meta-analysis aims to assess the efficacy and safety of acupuncture in patients with grade 1 hypertension. We systematically searched the EMBASE, PubMed, Cochrane, China National Knowledge Infrastructure, and Wan Fang databases for randomised controlled trials investigating acupuncture therapy for grade 1 hypertension through March 2021. The primary outcomes were changes in blood pressure after acupuncture and efficacy of acupuncture. The secondary result was an adverse reaction to the treatment. Data were pooled and analysed using Review Manager 5.3 and Statistical Package for the Social Sciences software version 19.0. Ten randomised controlled trials involving 1196 patients were included. Our meta-analysis demonstrated that in terms of changes in systolic blood pressure (MD 3.62 mmHg; 95% CI, 1.34 to 5.90; I2 = 56%), diastolic blood pressure (MD 3.12 mmHg; 95% CI, 1.03 to 5.20; I2 = 77%), and treatment efficacy (RR 2.12; 95% CI, 1.38 to 3.26; I2 = 93%), acupuncture is more effective in treating grade 1 hypertension than a placebo, no treatment at all, or interventions that improve lifestyle alone, with a low incidence of adverse effects. However, we did not find a suitable subgroup to reduce heterogeneity. Interventions, acupuncture methods, and treatment courses were not the only sources of heterogeneity among the studies. Existing evidence shows that acupuncture could be used for treating hypertension; however, higher-quality randomised controlled trials are needed to better evaluate the safety and efficacy of acupuncture.


Large functional retroperitoneal paraganglioma: A surgical challenge.
Paraganglioma is relatively rare retroperitoneal tumors. If functional retroperitoneal paragangliomas are misdiagnosed, surgical intervention can precipitate intraoperative hypertensive crises which may have serious consequences. We present a case of a 40-year-old female who presented with a large functional right-sided retroperitoneal paraganglioma encasing the inferior vena cava (IVC). The patient underwent paraganglioma excision with IVC resection with right nephrectomy. Such complex multivisceral resections require surgical expertise and are feasible at high-volume centers experienced in performing retroperitoneal surgeries.


Estimating the depth and lifetime of a fluorescent inclusion in a turbid medium using a simple time-domain optical method.
A simple time-domain optical method for estimating the depth (d) and lifetime (tau) of fluorescent inclusions in a turbid medium is described. We demonstrate the method for depth and lifetime estimation of a fluorescent inclusion directly by fitting a monoexponential decay (tau(eff)) of the temporal position of the temporal point-spread function and the measurement of its maximum temporal position (t(max)). Since both of these measurements are intensity independent, this method provides a robust and efficient approach. This method is validated with experimental data.


In vitro exposure to triazoles used as fungicides impairs human granulosa cells steroidogenesis.
Triazoles are the main components of fungicides used in conventional agriculture. Some data suggests that they may be endocrine disruptors. Here, we found five triazoles, prothioconazole, metconazole, difenoconazole, tetraconazole, and cyproconazole, in soil or water from the Centre-Val de Loire region of France. We then studied their effects from 0.001 µM to 1000 µM for 48 h on the steroidogenesis and cytotoxicity of ovarian cells from patients in this region and the human granulosa line KGN. In addition, the expression of the aryl hydrocarbon receptor (AHR) nuclear receptor in KGN cells was studied. Overall, all triazoles reduced the secretion of progesterone, estradiol, or both at doses that were non-cytotoxic but higher than those found in the environment. This was mainly associated, depending on the triazole, with a decrease in the expression of CYP51, STAR, CYP11A1, CYP19A1, or HSD3B proteins, or a combination thereof, in hGCs and KGN cells and an increase in AHR in KGN cells.


[Binding of cortisol, fluocortolone and difluocortolone to human plasma proteins (author's transl)].
The binding properties of [3H]cortisol, [3H]fluocortolone and [3H]difluocortolone by human plasma, human albumin, human- beta- and gamma-globulins have been studied by equilibrium dialysis. Cortisol, in physiological concentrations (0,4 micromol/l), is 98% bound in human plasma at 25 degrees C, fluocortolone 96% and diflucortolone 85%. Uncer physiological conditions cortisol is mainly bound to the corticosteroid binding globulin (transcortin). 2/3 of fluocortolone is bound to transcortin and 1/3 to albumin and globulins, whereas difluocortolone is mainly bound to albumin and to globulins but not to transcortin. The binding affinities of beta- and gamma-globulins are -ery low for the corticoids investigated, but they are higher for fluocortolone and difluocortolone than for cortisol.


The values of talonavicular angles in patients with pes planus.
Talonavicular angles of 42 patients with flatfeet were measured using their weightbearing and nonweight-bearing anteroposterior and lateral radiographs. These patients were divided into two subgroups depending on the presence of pain. The normal feet of 22 people were included in this study to establish the control group. It was observed that, at the weightbearing position, the talonavicular angle increases. The talonavicular angle decreases in pes planus on the lateral radiographs. In patients presenting painful flatfeet, the talonavicular angle significantly reduces in the nonweightbearing anteroposterior x ray. The reason for pain may be enlargement of the medial border of the navicular bone or the presence of an accessory navicular bone. Relief of pain was observed in four patients following removal of the accessory navicular bone.


Can peripheral venous blood gases replace arterial blood gases in emergency department patients?
To determine if peripheral venous blood gas values for pH, partial pressure of carbon dioxide (Pco(2)) and the resultant calculated bicarbonate (HCO(3)) predict arterial values accurately enough to replace them in a clinical setting. This prospective observational study was performed in a university tertiary care emergency department from June to December 1998. Patients requiring arterial blood gas analysis were enrolled and underwent simultaneous venous blood gas sampling. The following data were prospectively recorded: age, sex, presenting complaint, vital signs, oxygen saturation, sample times, number of attempts and indication for testing. Correlation coefficients and mean differences with 95% confidence intervals (CIs) were calculated for pH, Pco(2) and HCO(3). A survey of 45 academic emergency physicians was performed to determine the minimal clinically important difference for each variable. The 218 subjects ranged in age from 15 to 90 (mean 60.4) years. The 2 blood samples were drawn within 10 minutes of each other for 205 (96%) of the 214 patients for whom data on timing were available. Pearson's product-moment correlation coefficients between arterial and venous values were as follows: pH, 0.913; Pco(2), 0.921; and HCO(3), 0.953. The mean differences (and 95% CIs) between arterial and venous samples were as follows: pH, 0.036 (0.030-0.042); Pco(2), 6.0 (5.0-7.0) mm Hg; and HCO(3), 1.5 (1.3-1.7) mEq/L. The mean differences (+/- 2 standard deviations) were greater than the minimum clinically important differences identified in the survey. Arterial and venous blood gas samples were strongly correlated, and there were only small differences between them. A survey of emergency physicians suggested that the differences are too large to allow for interchangeability of results; however, venous values may be valid if used in conjunction with a correction factor or for trending purposes.


Safety, tolerability, clinical, and joint structural outcomes of a single intra-articular injection of allogeneic mesenchymal precursor cells in patients following anterior cruciate ligament reconstruction: a controlled double-blind randomised trial.
Few clinical trials have investigated the safety and efficacy of mesenchymal stem cells for the management of post-traumatic osteoarthritis. The objectives of this pilot study were to determine the safety and tolerability and to explore the efficacy of a single intra-articular injection of allogeneic human mesenchymal precursor cells (MPCs) to improve clinical symptoms and retard joint structural deterioration over 24 months in patients following anterior cruciate ligament (ACL) reconstruction. In this phase Ib/IIa, double-blind, active comparator clinical study, 17 patients aged 18-40 years with unilateral ACL reconstruction were randomized (2:1) to receive either a single intra-articular injection of 75 million allogeneic MPCs suspended in hyaluronan (HA) (MPC + HA group) (n = 11) or HA alone (n = 6). Patients were monitored for adverse events. Immunogenicity was evaluated by anti-HLA panel reactive antibodies (PRA) against class I and II HLAs determined by flow cytometry. Pain, function, and quality of life were assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) and SF-36v2 scores. Joint space width was measured from radiographs, and tibial cartilage volume and bone area assessed from magnetic resonance imaging (MRI). Moderate arthralgia and swelling within 24 h following injection that subsided were observed in 4 out of 11 in the MPC + HA group and 0 out of 6 HA controls. No cell-related serious adverse effects were observed. Increases in class I PRA >10% were observed at week 4 in the MPC + HA group that decreased to baseline levels by week 104. Compared with the HA group, MPC + HA-treated patients showed greater improvements in KOOS pain, symptom, activities of daily living, and SF-36 bodily pain scores (p < 0.05). The MPC + HA group had reduced medial and lateral tibiofemoral joint space narrowing (p < 0.05), less tibial bone expansion (0.5% vs 4.0% over 26 weeks, p = 0.02), and a trend towards reduced tibial cartilage volume loss (0.7% vs -4.0% over 26 weeks, p = 0.10) than the HA controls. Intra-articular administration of a single allogeneic MPC injection following ACL reconstruction was safe, well tolerated, and may improve symptoms and structural outcomes. These findings suggest that MPCs warrant further investigations as they may modulate some of the pathological processes responsible for the development of post-traumatic osteoarthritis following ACL reconstruction. ClinicalTrials.gov ( NCT01088191 ) registration date: March 11, 2010.


The development of binocular function in infancy.
Binocular function in infancy can be assessed by means of the visual evoked potential (VEP) induced by a dynamic random dot pattern which alternates between a binocularly correlated and an anticorrelated state. A VEP time-locked to the alternation can only be produced by binocular interaction in the cortex. This interaction becomes detectable at around three months of age. Optokinetic nystagmus (OKN) in monocular viewing becomes symmetrical in nasal and temporal directions around the same age. Animal analogues and clinical cases suggest that this may also be an indicator of cortical binocularity. These techniques may be applicable to clinical assessment of binocular function in young infants.


Analytical studies of 'mixed sequence' oligodeoxyribonucleotides synthesized by competitive coupling of either methyl- or beta-cyanoethyl-N,N-diisopropylamino phosphoramidite reagents, including 2'-deoxyinosine.
High-performance liquid chromatography (HPLC) and 1H/31P nuclear magnetic resonance (NMR) spectroscopy were used to measure the molar ratio of oligodeoxyribonucleotide products in mixtures obtained with automated DNA synthesizers that employed competitive coupling of either standard methyl- or newer beta-cyanoethyl-N,N-diisopropylamino phosphoramidite reagents, which include deoxyinosine. Mixtures of these reagents when used as freshly prepared solutions afforded ratios of products that indicated negligibly small differences among the rates of the various competitive coupling reactions. However, studies of reagent stability in solution revealed that both types of the N-isobutyryl deoxyguanosine reagent decompose faster than their corresponding dA, dC, and dT phosphoramidites, which led to significantly lower proportions of dG-containing sequences. This problem was attenuated for the beta-cyanoethyl reagents due to their slower rate of decomposition.


Noninvasive Prenatal Diagnosis Significance of ERG Methylation as a Biomarker in Down's Syndrome.
BACKGROUND Down's syndrome (DS) is a genetic disease with chromosome abnormality due to the increasing chromosome 21. This study focused on the clinical application value of ERG methylation level in blood of pregnant women as a biomarker in Down's syndrome. MATERIAL AND METHODS The sham group consisted of 210 nonpregnant women, the positive control group consisted of 33 women with a delivery history of DS fetus, and the negative control group consisted of 60 women with eutocia history. A combination of restriction enzyme digestion experiment and PCR was performed to examine ERG methylation levels, methylation sites, and distribution in blood of pregnant women and in chorion tissues from abortion samples. Gene sequencing was performed to determine the ERG sequence in chromosome 21. Homology between normal tissues and chorion tissues from abortion samples was analyzed with bioinformatics technology. RESULTS ERG methylation in chorion tissues from 210 abortion samples at 8, 9, and 10 weeks gestational age were determined; however, no ERG methylation was determined in blood of pregnant women. Gene sequencing indicated that normal ERG sequence in chromosome 21 was in fetus chorion tissues, and these ERG sequences were aberrantly methylated. Bioinformatics result showed that homology and DNA methylation level was discrepancy in normal tissues and chorion tissues from abortion samples. CONCLUSIONS It was worthwhile to use ERG methylation as biomarker in noninvasive prenatal diagnosis, and ERG methylation should be applied with consent of pregnancy and her relatives.


Salinity and Temperature Influence Growth and Pigment Production in the Marine-Derived Fungal Strain Talaromyces albobiverticillius 30548.
Marine-derived fungi that inhabit severe changing environments have gained increasing interest for their ability to produce structurally unique natural products. Fungi belonging to the Talaromyces and the close Penicillium genera are among the most promising microbes for bioactive compound production, including colored metabolites. Coupling pigment producing capability with bioactive effectiveness would be a valuable challenge in some specific fields such as dyeing, cosmeceutical, or food industries. In this sense, Talaromyces albobiverticillius 30548, a red pigment producing strain, has been isolated from the marine environment of Reunion Island, Indian Ocean. In this research, we analyzed the effect of temperatures (21⁻27 °C) and salinity levels (0⁻9%) on fungal growth and pigment production. Maximum pigment yield was obtained in non-salted media, when cultured at 27 °C after 10 days of submerged fermentation in PDB. However, maximum dry biomass production was achieved at stressed condition with 9% sea salts concentrated media at the same temperature. The results indicate that salinity of the culture media positively influences the growth of the biomass. Inversely, pigment production decreases with increase in salinity over 6%. Color coordinates of secreted pigments were expressed in CIELAB color system. The hue angles (h°) ranged from red to yellow colors. This indicated that the color distribution of fungal pigments depends on the salinity in the culture media. This study emphasizes the impact of abiotic stress (salt and temperature) on the growth and metabolome of marine-derived fungal strains.


Resurrection of crushed magnetization and chaotic dynamics in solution NMR spectroscopy.
We show experimentally and theoretically that two readily observed effects in solution nuclear magnetic resonance (NMR)-radiation damping and the dipolar field-combine to generate bizarre spin dynamics (including chaotic evolution) even with extraordinarily simple sequences. For example, seemingly insignificant residual magnetization after a crusher gradient triggers exponential regrowth of the magnetization, followed by aperiodic turbulent spin motion. The estimated Lyapunov exponent suggests the onset of spatial-temporal chaos and the existence of chaotic attractors. This effect leads to highly irreproducible experimental decays that amplify minor nonuniformities such as temperature gradients. Imaging applications and consequences for other NMR studies are discussed.


Western honeybee drones and workers (Apis mellifera ligustica) have different olfactory mechanisms than eastern honeybees (Apis cerana cerana).
The honeybees Apis mellifera ligustica (Aml) and Apis cerana cerana (Acc) are two different western and eastern bee species that evolved in distinct ecologies and developed specific antennal olfactory systems for their survival. Knowledge of how their antennal olfactory systems function in regards to the success of each respective bee species is scarce. We compared the antennal morphology and proteome between respective sexually mature drones and foraging workers of both species using a scanning electron microscope, two-dimensional electrophoresis, mass spectrometry, bioinformatics, and quantitative real-time polymerase chain reaction. Despite the general similarities in antennal morphology of the drone and worker bees between the two species, a total of 106 and 100 proteins altered their expression in the drones' and the workers' antennae, respectively. This suggests that the differences in the olfactory function of each respective bee are supported by the change of their proteome. Of the 106 proteins that altered their expression in the drones, 72 (68%) and 34 (32%) were overexpressed in the drones of Aml and Acc, respectively. The antennae of the Aml drones were built up by the highly expressed proteins that were involved in carbohydrate metabolism and energy production, molecular transporters, antioxidation, and fatty acid metabolism in contrast to the Acc drones. This is believed to enhance the antennal olfactory functions of the Aml drones as compared to the Acc drones during their mating flight. Likewise, of the 100 proteins with expression changes between the worker bees of the two species, 67% were expressed in higher levels in the antennae of Aml worker contrasting to 33% in the Acc worker. The overall higher expressions of proteins related to carbohydrate metabolism and energy production, molecular transporters, and antioxidation in the Aml workers compared with the Acc workers indicate the Aml workers require more antennal proteins for their olfactory mechanisms to perform efficient foraging activities than do the Acc worker bees. These data decipher the mechanisms of the western and eastern drone and worker bees acting in response to their different olfactory system in their distinct ecosystem.


Diagnosis and treatment of diabetes mellitus in chronic pancreatitis.
Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus. It is a clinically relevant condition with a prevalence of 5%-10% among all diabetic subjects in Western populations. In nearly 80% of all type 3c diabetes mellitus cases, chronic pancreatitis seems to be the underlying disease. The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes mellitus, the endocrinopathy in type 3c is very complex. The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition. General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus (up to 90% of all cases) is rather good. However, in a patient first presenting with diabetes mellitus, chronic pancreatitis as a potential causative condition is seldom considered. Thus many patients are misdiagnosed. The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy. In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency, preventing or treating a lack of fat-soluble vitamins (especially vitamin D) and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.


Models of surgical procedures for multimodal image-guided neurosurgery.
Improvement of image guided surgery systems requires a better anticipation of the surgical procedure. This anticipation may be provided by a better understanding of surgical procedures and/or the use of information models related to neurosurgical procedures. We are introducing a generic model of surgical procedures in the context of multimodal image-guided craniotomies. The basic principle of the model is to break down the surgical procedure into a sequence of steps defining the surgical script. Each step is defined by an action; the model assigns to each surgical step a list of image entities extracted from multimodal preoperative images (anatomical and/or functional images) which are relevant to the performance of that particular step. The model has been built in two phases: creation and consolidation. Besides, a planning software prototype based on the generic model has been built. The resulting generic model is described by an UML class diagram and textual description. Some initial benefits of this approach can already be outlined: improvement of multimodal information management, enhancement of the preparation and the guidance of the surgical act.


Biocompatibility assessment of chemically modified GONRs with hemoglobin and histopathological studies for its toxicity evaluation.
Transition metal-Schiff base complexes are found to be important for biomedical applications but have demerits of being homogeneous complexes, thus their synthesis on the surface of graphene oxide nanoribbons (GONRs), materials of specific interest, can be beneficial for preparing advanced graphene-based materials for biomedical applications. Of foremost importance is their safety and biocompatibility with biological systems. In this study, a transition metal-Schiff base complex has been synthesized on the surface of a GONR (Ni-S-GNR) using 3-aminopropyltriethoxysilane and pyridine-2-carbaldehyde and complexing nickel. This Ni-S-GNR was characterized well by various physicochemical techniques. The evaluation of biocompatibility of Ni-S-GNR with hemoglobin confirmed binding interactions and influence on the native structure of hemoglobin. It was found that there was alteration in the secondary and tertiary structures of hemoglobin. In addition, histopathological studies on the liver and kidney cells of rats revealed non-toxicity of Ni-S-GNR towards these cells. Overall, Ni-S-GNR was found to be compatible with protein as the native structure was not destroyed and was non-toxic to cells.


Aripiprazole partial agonism at 5-HT2C: a comparison of weight gain associated with aripiprazole adjunctive to antidepressants with high versus low serotonergic activities.
5-HT2C receptor antagonists are thought to contribute toward increased appetite and obesity. Aripiprazole acts as a partial agonist at the 5-HT2C receptor; hence, it is thought to cause little or no significant weight gain when used alone. We theorize that, in the presence of antidepressants with high serotonergic activity, aripiprazole acts as an antagonist at the 5-HT2C receptor, thus increasing the potential for weight gain. Conversely, in environments with low serotonergic activity, aripiprazole acts as an agonist at the 5-HT2C receptor, therefore having less potential for weight gain. A retrospective electronic medical record chart review of the Veterans Integrated Service Network 22 Veterans Affairs database was performed comparing patients' weight and body mass index (BMI) while taking aripiprazole alone (n = 1,177), versus aripiprazole plus a high-serotonergic antidepressant (citalopram, fluoxetine, paroxetine, sertraline, or venlafaxine) (n = 145), versus aripiprazole plus a low-serotonergic antidepressant (bupropion) (n = 77) for a minimum continuous duration of 6 months of aripiprazole monotherapy or combination treatment. The study was conducted from January 2010 through June 2011. In our patient population, only the aripiprazole plus high-serotonergic antidepressants group had a statistically significant increase in weight (P = .0027) and BMI (P = .0016). Our data suggest that, in the presence of antidepressants with high serotonergic activity, aripiprazole may act as an antagonist at the 5-HT2C receptor, resulting in weight gain. Conversely, when aripiprazole is used in the presence of antidepressants with low serotonergic activity, it may act as an agonist and result in little or no weight gain. This varying effect at the 5-HT2C receptor may explain why aripiprazole has not been associated with significant weight gain in previous studies focusing on schizophrenia and bipolar disorder.


Rap1 binding to the talin 1 F0 domain makes a minimal contribution to murine platelet GPIIb-IIIa activation.
Activation of platelet glycoprotein IIb-IIIa (GPIIb-IIIa; integrin αIIbβ3) leads to high-affinity fibrinogen binding and platelet aggregation during hemostasis. Whereas GTP-bound Rap1 GTPase promotes talin 1 binding to the β3 cytoplasmic domain to activate platelet GPIIb-IIIa, the Rap1 effector that regulates talin association with β3 in platelets is unknown. Rap1 binding to the talin 1 F0 subdomain was proposed to forge the talin 1-Rap1 link in platelets. Here, we report a talin 1 point mutant (R35E) that significantly reduces Rap1 affinity without a significant effect on its structure or expression. Talin 1 head domain (THD) (R35E) was of similar potency to wild-type THD in activating αIIbβ3 in Chinese hamster ovary cells. Coexpression with activated Rap1b increased activation, and coexpression with Rap1GAP1 reduced activation caused by transfection of wild-type THD or THD(R35E). Furthermore, platelets from Tln1R35E/R35E mice showed similar GPIIb-IIIa activation to those from wild-type littermates in response to multiple agonists. Tln1R35E/R35E platelets exhibited slightly reduced platelet aggregation in response to low doses of agonists; however, there was not a significant hemostatic defect, as judged by tail bleeding times. Thus, the Rap1-talin 1 F0 interaction has little effect on platelet GPIIb-IIIa activation and hemostasis and cannot account for the dramatic effects of loss of Rap1 activity on these platelet functions.


Prevalence of antinuclear and anti-liver-kidney-microsome type-1 antibodies in patients with chronic hepatitis C in China.
Hepatitis C virus (HCV) infection may induce autoimmune response and autoantibodies can be detected in chronic hepatitis C (CHC) patients. However, the reported positive rate of autoantibodies in CHC patients in China varies considerably. In this study, we investigated the prevalence of antinuclear antibodies (ANA) and anti-liver-kidney-microsome type 1 autoantibodies (anti-LKM-1) in a large cohort of CHC patients, and analyzed the factors related to the presence of the autoantibodies. A total of 360 CHC patients were enrolled in this study. Serum ANA and anti-LKM-1 were detected by indirect immunofluorescence and enzyme-linked immunosorbent assay, respectively. Clinical analysis was performed to disclose the related factors to autoantibody production. The prevalence of ANA and anti-LKM-1 in CHC patients was 12.5% (45/360) and 2.5% (9/360), respectively. Women had a higher prevalence than men (18.9% vs 11.4%, P = 0.046). Patients with positive autoantibodies had lower HCV RNA levels (1.2 x 10(7) copies/L vs 7.2 x 10(7) copies/L, P < 0.05). Positive ANA was associated with higher serum globulin (P < 0.05). Stratified analysis showed that there were no significant differences in age, HCV genotype, disease course, clinical stage, prevalence of cirrhosis and interferon therapy between autoantibody-positive and -negative subgroups. Autoantibodies can be induced in the course of CHC, and some CHC patients can even develop autoimmune hepatitis.


Milestones of the last 10 years: CNS cancer.
For neuro-oncologists, much was accomplished in the last decade, including the establishment of the first standard of care (SOC) in this field of oncology. New treatment options boosted research in the whole field of neuro-oncology, as well clinical trials, translational and basic research. Accumulated data on molecular-genetic subgroups with distinct clinical outcomes in disease entities led to the establishment of new biomarkers and to the collaborative formulation of a new WHO classification of central nervous system tumors.


Communication: The ground electronic state of Si2C: Rovibrational level structure, quantum monodromy, and astrophysical implications.
We report the gas-phase optical detection of Si2C near 390 nm and the first experimental investigation of the rovibrational structure of its (1)A1 ground electronic state using mass-resolved and fluorescence spectroscopy and variational calculations performed on a high-level ab initio potential. From this joint study, it is possible to assign all observed Ka = 1 vibrational levels up to 3800 cm(-1) with confidence, as well as a number of levels in the Ka = 0, 2, and 3 manifolds. Dixon-dip plots for the bending coordinate (ν2) allow an experimental determination of a barrier to linearity of 783(48) cm(-1) (2σ), in good agreement with theory (802(9) cm(-1)). The calculated (Ka, ν2) eigenvalue lattice shows an archetypal example of quantum monodromy (absence of a globally valid set of quantum numbers) that is reflected by the experimentally observed rovibrational levels. The present study provides a solid foundation for infrared and optical surveys of Si2C in astronomical objects, particularly in the photosphere of N- and J-type carbon stars where the isovalent SiC2 molecule is known to be abundant.


FIS activates glnAp2 in Escherichia coli: role of a DNA bend centered at -55, upstream of the transcription start site.
A binding site for the Escherichia coli nucleoid binding protein FIS (factor for inversion stimulation) was identified upstream of a sigma54-dependent promoter, glnAp2. The binding and bending center of FIS is positioned at -55 with respect to the transcription start site (+1). Binding of FIS at this site activates the transcription of glnAp2 both in vivo and in vitro. Furthermore, we substituted the FIS-mediated DNA bending with other protein (cAMP receptor protein or integration host factor)-mediated DNA bending, without changing the position of the bending center. In vitro transcription assays indicated that all DNA bends centered at -55 activate transcriptional initiation of glnAp2, especially when linear templates were used.


Synthesis and electrochemical properties of copper(II), manganese(III) phthalocyanines bearing chalcone groups at peripheral or nonperipheral positions.
In this study, new chalcone compound 1 , new phthalonitrile derivatives 2 and 3, new copper(II), manganese(III) phthalocyanines bearing chalcone groups at peripheral or nonperipheral positions were synthesized. Electrochemistry of tetra-(4-{(2 E )-3-[2-fluoro-4-(trifluoromethyl)phenyl]prop-2-enoyl}phenoxy) substituted Co(II)Pc and Mn(III)Pcs were studied with cyclic voltammetry (CV) to determine the redox properties of the phthalocyanines. According to the results, while the CuPcs 2a and 3a showed two Pc based reduction reactions and one Pc based oxidation reaction, MnPcs 2b and 3b gave two metal-based reduction reactions. All the redox processes are shifted toward positive potentials as a result of the increased electron-withdrawing ability of the trifluoromethyl substituents.


Prostate cancer cell phenotypes based on AGR2 and CD10 expression.
The combination of expression patterns of AGR2 (anterior gradient 2) and CD10 by prostate cancer provided four phenotypes that correlated with clinical outcome. Based on immunophenotyping, CD10(low)AGR2(high), CD10(high)AGR2(high), CD10(low)AGR2(low), and CD10(high)AGR2(low) were distinguished. AGR2(+) tumors were associated with longer recurrence-free survival and CD10(+) tumors with shorter recurrence-free survival. In high-stage cases, the CD10(low)AGR2(high) phenotype was associated with a ninefold higher recurrence-free survival than the CD10(high)AGR2(low) phenotype. The CD10(high)AGR2(high) and CD10(low)AGR2(low) phenotypes were intermediate. The CD10(high)AGR2(low) phenotype was most frequent in high-grade primary tumors. Conversely, bone and other soft tissue metastases, and derivative xenografts, expressed more AGR2 and less CD10. AGR2 protein was readily detected in tumor metastases. The CD10(high)AGR2(low) phenotype in primary tumors is predictive of poor outcome; however, the CD10(low)AGR2(high) phenotype is more common in metastases. It appears that AGR2 has a protective function in primary tumors but may have a role in the distal spread of tumor cells.


Disability Policy Implementation From a Cross-Cultural Perspective.
Implementation of disability policy is influenced by social, political, and cultural factors. Based on published work, this article discusses four guidelines considered critical for successful policy implementation from a cross-cultural perspective. These guidelines are to: (a) base policy implementation on a contextual analysis, (b) employ a value-based approach, (c) align the service delivery system both vertically and horizontally, and (d) engage in a partnership in policy implementation. Public policy should be understood from a systems perspective that includes cross-cultural issues, such as how different stakeholders are acting and the way they plan and implement policy.


Modulation of human cytidine deaminase by specific aminoacids involved in the intersubunit interactions.
An investigation was made of the role exerted by some residues supposed to be involved in the intersubunit interaction and also in the catalytic site of homotetrameric human cytidine deaminase (T-CDA). Attention was focused on Y33, Y60, R68, and F137 residues that are a part of a conserved region in most T-CDAs. Hence, a series of site-directed mutagenesis experiments was set up obtaining seven mutants: Y60G, Y33G, Y33F Y33S, F137A, R68G, and R68Q. Each active purified mutant protein was characterized kinetically, with a series of substrates and inhibitors, and the effect of temperature on enzyme activity and stability was also investigated. Circular dichroism (CD) experiments at different temperatures and in presence of small amounts of sodium dodecyl sulphate (SDS) were performed in all the soluble mutant CDAs. The results obtained by site-directed mutagenesis studies were compared to the crystallographic data of B. subtilis CDA and E. coli CDA and to molecular modeling studies previously performed on human CDA. The mutation of Y60 to glycine produced an enzyme with a more compact quaternary structure with respect to the wild-type; this mutation did not have a dramatic effect on cytidine deamination, but it slightly affected the binding with the substrate. None of the mutant CDAs in Y33 showed enzymatic activity; they existed only as monomers, indicating that this residue, located at the intersubunit interface, may be responsible for the correct folding of human CDA. The insertion of an alanine instead of phenylalanine at position 137 led to a soluble but completely inactive enzyme unable to form a tetramer, suggesting that F137 residue may be important for the assembling of the tetramer and also for the arrangement of the CDA active site. Finally, R68G and R68Q mutations revealed that the presence of the amino group seems to be important for the catalytic process but not for substrate binding, as already shown in B. subtilis CDA. The quaternary structure of R68Q was not affected by the mutation, as shown by the SDS-induced dissociation experiments and CD studies, whereas R68G dissociated very easily in presence of small amounts of SDS. These experiments indicated that in the human CDA, the side chain of arginine 68 involved in the catalytic process in one subunit active site might come from another subunit. The data obtained from these studies confirmed the presence of a complicated set of intersubunit interactions in the active site of human CDA, as shown in other T-CDAs.


NF-κB and CREB are required for angiotensin II type 1 receptor upregulation in neurons.
Nuclear factor kappa B (NF-κB) and the Ets like gene-1 (Elk-1) are two transcription factors that have been previously established to contribute to the Angiotensin II mediated upregulation of Angiotensin II type 1 receptor (AT1R) in neurons. The cAMP response element binding protein (CREB) is another transcription factor that has also been implicated in AT1R gene transcription. The goal of the current study was to determine if NF-κB and CREB association was required for AT1R upregulation. We hypothesized that the transcription of the AT1R gene occurs via an orchestration of transcription factor interactions including NF-κB, CREB, and Elk-1. The synergistic role of CREB and NFκB in promoting AT1R gene expression was determined using siRNA-mediated silencing of CREB. Electrophorectic Mobility Shift Assay studies employing CREB and NF-κB demonstrated increased protein - DNA binding as a result of Ang II stimulation which was blunted by siRNA silencing of CREB. Upstream inhibition of p38 mitogen activated protein kinase (p38 MAPK) with SB203580 or inhibition of the calmodulin kinase (CAMK) pathway using KN-62 blunted changes in CREB and NF-κB expression. These findings suggest that Ang II may activate multiple signaling pathways involving p38 MAPK leading to the activation of NF-κB and CREB, which feed back to upregulate the AT1R gene. This study provides insight into the molecular mechanisms involving multiple transcription factor activation in a coordinated fashion which may be partially responsible for sympathoexcitation in clinical conditions associated with increased activation of the renin angiotensin system.


Patient satisfaction with hospitalists: facility-level analyses.
Despite concerns and disagreements about the impact of hospitalist models on health care, hospitalists are becoming the dominant means of providing inpatient care, and models continue to diversify. Understanding their impact and the factors that influence their adoption is essential. This study examined hospitalists' impact on patient satisfaction, considering a host of characteristics. Cross-sectional data received in calendar year 2008, aggregated to the facility level, represent 1777 hospitals (41% of which employed hospitalists) and 2 648 275 patients. Press Ganey's psychometrically sound inpatient satisfaction survey consists of 38 items (10 sections) rated on a 5-point Likert-type scale. Findings suggest that facilities with hospitalists may have an advantage regarding satisfaction with nursing and personal issues (eg, privacy, emotional needs, response to complaints), both of which may be related to broader communication issues. Moreover, teaching (overall satisfaction) and large facilities (satisfaction with admissions, nursing, and tests/treatments) might especially benefit from the presence of hospitalists. Exploring how specific hospitalist functions influence patient satisfaction may reap rewards.


Comparative reproducibility of dermal microvascular blood flow changes in response to acetylcholine iontophoresis, hyperthermia and reactive hyperaemia.
Laser Doppler fluxmetry (LDF) can non-invasively measure skin microvascular changes in response to acetylcholine (ACh), local heating of the skin and reactive hyperaemia following arterial occlusion. Various studies have used microvascular changes in response to these stimuli, especially ACh iontophoresis and local heating, as a surrogate marker of endothelial function. There are few data in the literature regarding the comparative reproducibility of microvascular perfusion changes induced by the three stimuli. The aim of this study was to systematically assess and compare the reproducibility of skin microcirculatory function in response to each of these challenges. Ten healthy non-smoking subjects (seven males) median age 36 years (range 23-46), with no history of hypertension, diabetes, coronary artery disease or any connective tissue disorder, were studied. Changes in skin microcirculation in response to ACh iontophoresis, local heating of the skin and post-occlusive reactive hyperaemia, on two separate days (median 31, range 11-42 days), were assessed in all subjects. We measured three parameters: the change in perfusion from baseline perfusion (peak minus baseline perfusion), the relative percentage change in perfusion from baseline (peak--baseline)/baseline x 100 (%) and also the time-to-peak perfusion. The reproducibility of the change in perfusion had coefficients of variation (CV) of 9.3% for local skin heating, 19.4% for reactive hyperaemia and 25.5% for ACh iontophoresis. The relative percentage change in perfusion from baseline was more variable with CVs ranging from 23% to 39%. The coefficient of variation of time-to-peak perfusion was 7.0% for heating, 15.1% for reactive hyperaemia and 10.4% for ACh iontophoresis. We have shown that microcirculatory changes measured by the change in perfusion from baseline and time-to-peak perfusion in response to ACh, post-occlusive reactive hyperaemia and local skin heating had good reproducibility when carried out in a controlled environment with a standardized protocol. Relative change in perfusion had relatively poor reproducibility. The change in perfusion and time-to-peak perfusion for local skin heating were the most reproducible overall.


Public health implications for adequate transitional care for HIV-infected prisoners: five essential components.
In the United States, 10 million inmates are released every year, and human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) prevalence is several-fold greater in criminal justice populations than in the community. Few effective linkage-to-the-community programs are currently available for prisoners infected with HIV. As a result, combination antiretroviral therapy (cART) is seldom continued after release, and virological and immunological outcomes worsen. Poor HIV treatment outcomes result from a myriad of obstacles that released prisoners face upon reentering the community, including homelessness, lack of medical insurance, relapse to drug and alcohol use, and mental illness. This article will focus on 5 distinct factors that contribute significantly to treatment outcomes for released prisoners infected with HIV and have profound individual and public health implications: (1) adaptation of case management services to facilitate linkage to care; (2) continuity of cART; (3) treatment of substance use disorders; (4) continuity of mental illness treatment; and (5) reducing HIV-associated risk-taking behaviors as part of secondary prevention.


Composite hip prosthesis design. I. Analysis.
An investigation was performed to study the mechanical performance of fiber-reinforced composite hip prostheses in a femur. The main objective of the study was to evaluate the effect of fiber orientation of a composite femoral implant on the response of the surrounding femoral bone. A three-dimensional finite element analysis was developed for analyzing a composite implant in the femur. A three-dimensional composite element was proposed to take into account ply drop-off due to a change of cross-section of the composite implant. The element could accommodate multidirectional layers and tapered composites. The material properties of the composite were treated as anisotropic and inhomogeneous while the properties of femoral bone were treated as anisotropic and homogenous. All the materials were assumed to behave linear-elastically. The thermoplastic graphite/PEEK material system was selected for the study. In this presentation, as the first part of the study, the development of the finite element analysis will be described. Numerical calculations were generated and compared with existing data and numerical results available from studies related to metal hip prostheses in the literature. Experiments on the composite hip implants were also conducted for further verification of the analysis and the computer simulations. In Part II, using the finite element code, an extensive study was performed to evaluate the stress/strain distributions, micromotions, and strain-energy density of the surrounding femoral bone, which have been related to initial fixation and long-term stability of the prosthesis in a femoral bone. Numerous fiber orientations were studied, and results of the calculations were compared with those generated by the prosthesis made of cobalt alloy and titanium alloy.


Anuphylactic reactions in the skin of the guinea pig with high and low molecular weight antibodies and gamma globulins.
High molecular weight (19S) gamma-globulin produces passive cutaneous anaphylaxis (PCA) reactions with its specific antiserum only when it is used as intravenous antigen. Reversed PCA reactions cannot be produced when the 19S protein is injected intradermally in contradistinction to the results with 7S gamma-globulin. Antibodies of the high molecular weight class, when injected intradermally, also failed to give PCA reactions following antigen injection. Heterophile antibodies from the sera of patients with infectious mononucleosis, demonstrated to be entirely of the 19S type, gave negative reactions, while 7S heterophile antibodies from guinea pig did give reactions following intravenous injection of sheep cells. Anti-B isoagglutinins of the 19S class failed to react, while those of the 7S class of similar titer gave clear reactions following the injection of B substance. Evidence was obtained that 19S antibodies were capable of inhibiting the PCA reactions obtained with the 7S type, indicating that interaction with antigen occurred. The failure to elicit PCA reactions appeared to be due to an inability to fix to guinea pig tissues in a manner similar to that known for 7S antibodies and gamma-globulin.


[Advances on the genome of algae].
Algae possess complex and diverse biology and evolutionary history. They play an important role in the ecosystem. A mass of unique genes and biological processes also make them attractive. The application of high-throughput sequencing approaches to algal research has greatly contributed to the development of algal genomics and transcriptomics, as well as enriched the gene information of algae. In this article, we summarize the advances of algal genomics and transcriptomics, describe and compare the characteristics of different algae genomes, and introduce the application of expression sequence tags (ESTs), microarray and RNA sequencing technique to algal transcriptomics research. Furthermore, the advances of algal gene expression and small RNA are also reviewed in detail. At last, we discuss the challenges and future development of this area.


Design and analysis of studies evaluating smoking cessation interventions where effects vary between practices or practitioners.
Patients grouped together in practices may share characteristics that cause them to have similar responses to an intervention. Sampling from such groups means that the power of a trial is less than when subjects are selected from the population at random. Knowledge of likely variation in outcome at the practice level is necessary to calculate the extent to which sample size would need to be inflated to maintain statistical power in the face of 'cluster effects'. To plan sample size and precision requirements of a clinical trial, we examined reports of primary care smoking cessation trials for information on outcomes at the level of clusters, and found them unhelpful. We therefore constructed hypothetical scenarios to quantity the potential importance of this effect. Scenarios of moderate and large inter cluster variation were compared with a sample where there was no difference in effect size at the level of practices. A study with 80% power to detect a difference of 20% versus 10% at a 5% significance level would need 200 patients in each arm in the absence of cluster effects. With moderate variation in outcome between clusters, over a thousand patients would be needed in the study to maintain this precision. With larger inter-cluster variation, close to 4000 subjects would be required. In the absence of detailed data from previous studies, hypothetical models can give insight into the statistical implications of possible cluster effects on study design and analysis. With even moderate inter-cluster variation, sample size will have to be inflated considerably to maintain the same statistical precision. Workers in this field will greatly assist those planning future research if they publish details of variation in outcome at the level of clusters.


Global trends and diversity in pentachlorophenol levels in the environment and in humans: a meta-analysis.
Pentachlorophenol (PCP) was banned or restricted in many countries worldwide because of its adverse effects on the ecological environment and humans. However, the endocrine disrupting effects caused by low environmental PCP exposure levels has warranted more analysis. We reviewed 80 studies conducted in 21 countries and published between 1967 and 2010, using meta-regression analysis to examine the time trends and regional differences in PCP levels. The results suggested that in indoor air, bodies of water, freshwater sediments in western countries, invertebrates and freshwater vertebrates, PCP levels had declined over time, with half-lives ranging from 2.0 years to 11.1 years. However, in marine sediments/vertebrates and Chinese surface water/sediments, PCP levels increased over time. PCP levels in human blood and urine had decreased since the 1970s, with population half-lives of 3.6 years and 5.7 years, respectively. The intervals for global population blood and urine reference values decreased to 1.1-6.3 μg/L (2002-2008) and 2.5-7 μg/L (1995-2003), respectively. The possible thyroid disrupting effects and other health risks correlated with low environmental PCP exposure should be concerning. This study can help to ascertain the effects of the banning/restriction policy, providing data for cost-benefit analysis in policy-making and further control of health risks caused by low environmental exposure to PCP.


[Eye involvement in rheumatoid arthritis in children and adults].
Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are systemic autoimmune diseases characterized by synovitis and a wide range of extraarticular manifestations. Ocular involvement occurs frequently in both diseases and it may affect all layers of the eyes. This review summarizes the clinical manifestations, the diagnostic tools and the therapeutic modalities of the various ocular features of patients with juvenile and adult rheumatoid arthritis.


Gabapentin in the treatment of uremic itch: an index case and a pilot evaluation.
The prevalence of renal itch in patients on dialysis is approximately 30%, but its treatment is often ineffective. We describe an index case of a hemodialysis (HD) patient suffering from painful diabetic neuropathy (PDN) treated with gabapentin; the first administration of the drug led to the complete remission of the concomitant uremic pruritus. Subsequently, we report the results of a pilot evaluation aimed at testing the effectiveness and safety of low gabapentin doses in HD patients with uremic pruritus. Five consecutive HD patients unresponsive to antihistamines received 4-week gabapentin treatment at a starting dose of 100 mg after every thrice-weekly HD, which was subsequently adjusted based on clinical response. Puritus severity was evaluated by means of a visual analogue scale (VAS) before each HD session on days 0, 2, 4, 7, 14, 21, 28 and 35. Safety was assessed using adverse event data. All patients experienced a rapid subjective improvement in pruritus, with the mean VAS score decreasing from 8.4-1.6 after the first drug administration. Three patients required a dose increase to 100 mg four times a week to obtain better itch control. Two patients experienced complete itch remission. Although a double-blind placebo-controlled clinical trial should be conducted to better elucidate the efficacy and toxicity of gabapentin in patients with uremic itch, our data suggest that gabapentin could be considered an effective and safe alternative treatment for uremic pruritus.


Cerebrospinal Fluid and Spinal Anesthesia Parameters in Healthy Individuals versus Opium-addict Patients during Lower Limb Surgery.
Studies have reported lower pain threshold, spinal anesthesia duration, and level of sensory block in addicts compared to non-addict patients undergoing spinal anesthesia for surgery. Moreover, blood gas and cerebrospinal fluid (CSF) were likely to be affected as well. The aim in the present study is to evaluate CSF and spinal parameters in addict versus non-addict patients during lower limb surgery. In this case-control study, 22 opium addicts and 22 sex- and age- matched non-addicts undergoing lower limb surgery under spinal anesthesia were included. The CSF parameters, venous blood gas (VBG), and sensory and motor block findings were compared between the groups. The addict and non-addict patients were similar regarding CSF and blood gas parameters except higher pH in VBG (7.39 ± 0.06 vs. 7.33 ± 0.11, P = 0.030) and CSF (7.39 ± 0.06 vs. 7.33 ± 0.11, P = 0.030) for addict patients. The addict patients had significantly later onset of sensory block (5.72 ± 1.57 vs. 3.16 ± 0.93 minutes, P < 0.001) and shorter motor block duration (137.72 ± 11.51 vs. 149.09 ± 14.44 minutes, P = 0.006), with no significant difference in the sensory block duration and motor block onset. Addict patients have delayed onset of sensory block with shorter duration of motor block and lower sensory block level. Among the blood gas and CSF markers, only pH was significantly higher in addict patients, needing further evaluations; however, it seems that addiction has no significant effect on these parameters.


Computational Study of the Interactions between Benzene and Crystalline Ice Ih : Ground and Excited States.
Ground-state geometries of benzene on crystalline ice cluster model surfaces (Ih ) are investigated. It is found that the binding energies of benzene-bound ice complexes are sensitive to the dangling features of the binding sites. We used time-dependent DFT to study the UV spectroscopy of benzene, ice clusters, and benzene-ice complexes, by employing the M06-2X functional. It is observed that the size of the ice cluster and the dangling features have minor effects on the UV spectral characteristics. Benzene-mediated electronic excitations of water towards longer wavelengths (above 170 nm) are noted in benzene-bound ice clusters, where the cross-section of photon absorption by water is negligible, in good agreement with recent experimental results (Thrower et al., J. Vac. Sci. Technol. A, 2008, 26, 919-924). The intensities of peaks associated with water excitations in benzene-ice complexes are found to be higher than in isolated ice clusters. The π→π* electronic transition of benzene in benzene-ice complexes undergoes a small redshift compared with the isolated benzene molecule, and this holds for all benzene-bound ice complexes.


Media analysis of early dissemination of Canadian child maltreatment surveillance data.
A media strategy was developed to disseminate Canadian child maltreatment surveillance data. Print media were systematically searched and 29 articles reporting on the data were retrieved. Using content analysis, the articles were analyzed to assess informational accuracy and to understand how the media framed the issue of maltreatment. This analysis permits the authors to share "lessons learned," which will be helpful for researchers disseminating child maltreatment data through the media.


Draft genome sequence of Thermococcus waiotapuensis WT1T, a thermophilic sulfur-dependent archaeon from the order Thermococcales.
Thermococcus waiotapuensis WT1T is a thermophilic, peptide, and amino acid-fermenting archaeon from the order Thermococcales. It was isolated from Waiotapu, Aotearoa-New Zealand, and has a genome size of 1.80 Mbp. The genome contains 2,000 total genes, of which 1,913 encode proteins and 46 encode tRNA.


Discovery of cashmere goat (Capra hircus) microRNAs in skin and hair follicles by Solexa sequencing.
MicroRNAs (miRNAs) are a large family of endogenous, non-coding RNAs, about 22 nucleotides long, which regulate gene expression through sequence-specific base pairing with target mRNAs. Extensive studies have shown that miRNA expression in the skin changes remarkably during distinct stages of the hair cycle in humans, mice, goats and sheep. In this study, the skin tissues were harvested from the three stages of hair follicle cycling (anagen, catagen and telogen) in a fibre-producing goat breed. In total, 63,109,004 raw reads were obtained by Solexa sequencing and 61,125,752 clean reads remained for the small RNA digitalisation analysis. This resulted in the identification of 399 conserved miRNAs; among these, 326 miRNAs were expressed in all three follicular cycling stages, whereas 3, 12 and 11 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. We also identified 172 potential novel miRNAs by Mireap, 36 miRNAs were expressed in all three cycling stages, whereas 23, 29 and 44 miRNAs were specifically expressed in anagen, catagen, and telogen, respectively. The expression level of five arbitrarily selected miRNAs was analyzed by quantitative PCR, and the results indicated that the expression patterns were consistent with the Solexa sequencing results. Gene Ontology and KEGG pathway analyses indicated that five major biological pathways (Metabolic pathways, Pathways in cancer, MAPK signalling pathway, Endocytosis and Focal adhesion) accounted for 23.08% of target genes among 278 biological functions, indicating that these pathways are likely to play significant roles during hair cycling. During all hair cycle stages of cashmere goats, a large number of conserved and novel miRNAs were identified through a high-throughput sequencing approach. This study enriches the Capra hircus miRNA databases and provides a comprehensive miRNA transcriptome profile in the skin of goats during the hair follicle cycle.


[Prevention of Post-Stroke Depression].
Post-stroke depression (PSD) is a clinically relevant complication of ischemic and hemorrhagic cerebral infarction that affects about 30% of all stroke survivors. It is associated with reduced quality of life as well as delayed recovery from neurological deficits and functional impairment, frequently leading to impeded rehabilitation. Suitable screening methods allow early detection of PSD. Timely initiation of treatment in patients with manifest PSD as well as implantation of effective prevention strategies can help reduce medical and socioeconomic burden associated with the disease. We reviewed the current literature on pharmacological and non-pharmacological prevention of PSD.


Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes.
Intracellular propulsion of Listeria monocytogenes is the best understood form of motility dependent on actin polymerization. We have used in vitro motility assays of Listeria in platelet and brain extracts to elucidate the function of the focal adhesion proteins of the Ena (Drosophila Enabled)/VASP (vasodilator-stimulated phosphoprotein) family in actin-based motility. Immunodepletion of VASP from platelet extracts and of Evl (Ena/VASP-like protein) from brain extracts of Mena knockout (-/-) mice combined with add-back of recombinant (bacterial or eukaryotic) VASP and Evl show that VASP, Mena, and Evl play interchangeable roles and are required to transform actin polymerization into active movement and propulsive force. The EVH1 (Ena/VASP homology 1) domain of VASP is in slow association-dissociation equilibrium high-affinity binding to the zyxin-homologous, proline-rich region of ActA. VASP also interacts with F-actin via its COOH-terminal EVH2 domain. Hence VASP/ Ena/Evl link the bacterium to the actin tail, which is required for movement. The affinity of VASP for F-actin is controlled by phosphorylation of serine 157 by cAMP-dependent protein kinase. Phospho-VASP binds with high affinity (0.5 x 10(8) M-1); dephospho-VASP binds 40-fold less tightly. We propose a molecular ratchet model for insertional polymerization of actin, within which frequent attachment-detachment of VASP to F-actin allows its sliding along the growing filament.


[FROM 'REMOTE CARDIAC REHABILITATION' TO CHRONIC DISEASE MANAGEMENT PROGRAMS BY DIGITAL MEANS - REVIEW OF THE NATIONAL PROGRAM AS A MODEL FOR MULTI-DISCIPLINARY DISEASE MANAGEMENT].
Cardiovascular diseases, often accompanied by many background diseases, are the main cause of morbidity and mortality globally. Cardiac rehabilitation programs are a key component of secondary prevention and lack of participation or adherence lead to significantly higher adverse event rates including hospitalization and mortality. Technological means have great potential for improving health care outcomes. Home-cardiac rehabilitation (H-CR) using technology implements the 'patient-centered' approach within the health services. Last year, the Israeli Ministry of Health approved the H-CR program for a low-risk patient and included it into medical coverage of the state. In accordance with the Ministry of Health circular, the H-CR program is implemented at the Sheba Medical Center since November 2018. The program incorporates innovative technology alongside multi-professional care. Implementation of the program enables studies about the methods to put into effect the therapeutic model in other chronic disease management, including home rehabilitation or hospitalization programs, while maintaining patient safety and securing medical information. The purpose of this article is to review the first H-CR program in Israel, its components, benefits, and challenges, as well as, to present the therapeutic model, its competence in multidisciplinary disease management and increased responsiveness to the treatment.


Involvement of protein kinase-C in the effect of angiotensin-II on adenosine 3',5'-monophosphate production in lactotroph cells.
When applied to rat anterior pituitary cells, angiotensin-II (AII) exerted two opposite effects on adenylate cyclase (AC) activity: a pertussis toxin (PTX)-sensitive inhibition of the enzyme with a maximal effect of -42 +/- 2% in crude cell membrane preparations, and, in contrast, a non-PTX-sensitive stimulation of cAMP production (maximal effect = 38 +/- 3%) in intact cells. The apparent affinity of both effects was equal to 1.8 nM. The stimulation of cAMP formation parallels the stimulation of PRL release. Under the same conditions, dopamine (DA) inhibited both membrane AC activity and cAMP formation in intact cells by a PTX-sensitive mechanism. After separation of pituitary cell types by sedimentation at unit gravity, the effects of AII and DA on intracellular cAMP and membrane AC activity coincided in the same fractions (those enriched in PRL cells). The stimulatory effect of AII on cAMP formation was about 5 times weaker than that of peptides positively coupled to AC as vasoactive intestinal peptide in total as well as in PRL-enriched cells. Since the AII receptor is also coupled to phospholipase-C (PLC) in a non-PTX-sensitive manner, we investigated whether protein kinase-C (PKC) could indirectly account for the positive effect of AII on cAMP formation. 12-O-Tetradecanolylphorbol 13-acetate (TPA), a stimulator of PKC was indeed able to increase intracellular cAMP; this effect was not additive with that of AII. conversely, application of the PKC inhibitors H7 [1-(5-isoquinolylsulfonyl)2-methyl-piperazine] and staurosporine or desensitization of PKC by long exposure of the cells to TPA abolished the cAMP response to TPA as well as that to AII. In addition, thyreoliberin, another activator of the PLC pathway, was able to stimulate cAMP formation in a PKC-dependent manner. DA inhibition of intracellular cAMP was not affected by any PKC inhibition. We conclude that in lactotroph cells, 1) the AII inhibitory coupling to AC observed in membrane preparations does not exist in intact cells, at least under basal conditions; and 2) the AII intracellular cAMP stimulation observed is not accounted for by a direct coupling with AC; it is due to a cross-talk of the PLC pathway mediated by PKC, an effect that might be shared by other PLC-stimulating mediators and may participate in the regulation of PRL release.


Early Life Stress as a Risk Factor for Substance use Disorders: Clinical and Neurobiological Substrates.
Early Life Stress (ELS) can profoundly influence an individual's genotype and phenotype. Effects of ELS can manifest in the short-term, late life and even in subsequent generations. ELS activate corticotrophin releasing factor (CRF); CRF influences drug seeking and addiction. The aim of this study was to examine the effects of endogenous elevated levels of CRF on addiction. Inducible forebrain over-expression of CRF mice (tetop-CRH x CaMKII-tTA) was used for this study. Morphine (10 mg/kg) was administered every other day for 10 days or with increasing doses of morphine: 20, 40, 60, 80, 100, and 100 mg/kg. The behavioral trials including morphine sensitization, Somatic Opiate Withdrawal Symptoms (SOWS) were conducted in a single, open field, activity. After behavioral trial, animals were perfused for immunohistochemistry analysis. CRF-over expressed (CRF-OE) mice showed increase in morphine sensitization and withdrawal symptoms after morphine administration compared to wild type (WT) mice. The two-way ANOVA in the morphine sensitization study showed a significant effect of treatment (P<0.05) and genotype for distance traveled (P<0.01). In the SOWS study, opiate withdrawal symptoms such as rearings, circling behavior, grooming, and jump in CRF-OE were amplified in parallel to WT mice. In the immunohistochemistry study, pro-dynorphine (PDYN) expression was increased after morphine administration in both amygdala and nucleus accumbens (NAcc). CRF-OE in the forebrain increases the sensitization and withdrawal symptoms in morphine treated mice. On exposure to morphine, in CRF-OE mice the PDYN protein expression was increased as compared to WT mice in the amygdala and NAcc.


[The relationship between workers' attitudes towards health, lifestyle and mental health].
In order to investigate the relationship between health practices, various psychosocial factors, and mental health, a survey was conducted by means of a self-rating questionnaire on 424 industrial workers. The questionnaire included items concerning Goldberg's 12 selected items from the Japanese version of the General Health Questionnaire, the Type A scale used in the Framingham study, Breslow's 7 health practices, and other original psychosocial, health practicing items. A total of 391 or 92.2% responded to the questionnaire. Among them, 354 (266 males and 88 females) complete responders to the GHQ were analysed for the present study. As a result, several factors such as decrease in age, perceived present illness, worsening of perceived health status, increase in anxiety concerning health, exacerbation of alcohol and smoking related behaviour, decrease in physical exercise, reduction of Breslow's 7 health practices, perceived stress and difficulty in dealing with stress, increase in stress content, negative and malfunctional coping strategies, and decrease in relaxation were, according to the GHQ scores, related to negative mental health. Furthermore, Type A scores were significantly correlated to GHQ scores, the number of stress factors, and Breslow's 7 health practices in males, but they were weak or had no correlation in females. It is considered that favorable health practices and attitudes towards health might help to maintain positive mental health, but further analysis is needed to determine their causal relationships because of the cross-sectional design of the present study.


Natural history of aging in Cornelia de Lange syndrome.
Observations about the natural history of aging in Cornelia de Lange syndrome (CdLS) are made, based on 49 patients from a multidisciplinary clinic for adolescents and adults. The mean age was 17 years. Although most patients remain small, obesity may develop. Gastroesophageal reflux persists or worsens, and there are early long-term sequelae, including Barrett esophagus in 10%; other gastrointestinal findings include risk for volvulus, rumination, and chronic constipation. Submucous cleft palate was found in 14%, most undetected before our evaluation. Chronic sinusitis was noted in 39%, often with nasal polyps. Blepharitis improves with age; cataracts and detached retina may occur. Decreased bone density is observed, with occasional fractures. One quarter have leg length discrepancy and 39% scoliosis. Most females have delayed or irregular menses but normal gynecologic exams and pap smears. Benign prostatic hypertrophy occurred in one male prior to 40 years. The phenotype is variable, but there is a distinct pattern of facial changes with aging. Premature gray hair is frequent; two patients had cutis verticis gyrata. Behavioral issues and specific psychiatric diagnoses, including self-injury, anxiety, attention-deficit disorder, autistic features, depression, and obsessive-compulsive behavior, often worsen with age. This work presents some evidence for accelerated aging in CdLS. Of 53% with mutation analysis, 55% demonstrate a detectable mutation in NIPBL or SMC1A. Although no specific genotype-phenotype correlations have been firmly established, individuals with missense mutations in NIPBL and SMC1A appear milder than those with other mutations. Based on these observations, recommendations for clinical management of adults with CdLS are made.


Synthesis and antimicrobial activity of some novel 4-(1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amines.
A new series of novel 4-(1H-benz[d]imidazol-2yl)-1,3-thiazol-2-amines 5a-d and 4-(1H-benz[d]imidazol-2yl)-3-alkyl-2,3-dihydro-1,3-thiazol-2-amine 8a-d has been synthesized by the cyclocondensation of 2-acetyl benzimidiazoles 4a-d and 2-bromo-1-(1-alkyl-1H-benzo[d]imidazol-2-yl)-1-ethanone 7a-d with thiourea respectively, and evaluated for their antibacterial and antifungal activity against clinical isolates of Gram-positive and Gram-negative bacteria. Some of these hybrids in these series exhibited antibacterial activity comparable to standard Streptomycin and Benzyl penicillin and antifungal activity against Fluconazole. All the newly synthesized compounds were characterized by their spectral data and further used to estimate their ability towards antimicrobial activity.


Evaluating and treating venous outflow stenoses is necessary for the successful open surgical treatment of arteriovenous fistula aneurysms.
Arteriovenous fistula (AVF) aneurysms (AVFAs) can lead to skin erosion, bleeding, difficult access while on hemodialysis, and poor cosmetic appearance. We reviewed our experience in treating patients with aneurysmal dilatation of their AVF. We reviewed clinical data of 48 patients (37 men; overall mean age, 55 years; range, 28-85 years) with an AVFA who underwent treatment during a 30-month period. Relevant clinical variables and treatment outcomes were analyzed. All patients underwent a fistulogram, and 90% required percutaneous angioplasty to improve outflow. Fifty-six percent of patients had one stenotic outflow lesion, and 44% had at least two tandem outflow stenoses that required treatment. Open repair with aneurysmorrhaphy was performed in one stage in 64% of patients and in two stages in 36%. A tunneled hemodialysis catheter was required in 11 patients (23%) until the surgically repaired AVF was ready for use again, comprising 10 patients treated with single-stage surgery and only one patient in the staged group. All AVFAs were effectively treated, and patients were able to maintain functional use of their access when healed. There is a high association of venous outflow stenoses and AVFA. Comprehensive therapy should encompass treatment of any venous outflow stenoses before open AVFA repair. A two-stage repair may decrease tunneled hemodialysis catheter use in patients with multiple aneurysms.


Absence of CC chemokine ligand 2 results in an altered Th1/Th2 cytokine balance and failure to expel Trichuris muris infection.
Despite a growing understanding of the role of cytokines in immunity to intestinal helminth infections, the importance of chemokines has been neglected. As a chemokine with both chemoattractive properties and an ability to shape the quality of the adaptive immune response, CC chemokine ligand 2 (CCL2) was investigated as an attractive candidate for controlling resistance to these types of infection, which require highly polarized Th cell responses. We show here for the first time that CCL2 plays an important role in the development of resistance to infection by the gastrointestinal nematode Trichuris muris. Thus, in the absence of CCL2, worm expulsion does not occur, and the lymph node draining the site of infection becomes a Th1-promoting environment. Elevated levels of IL-12 are produced by polarizing APCs, and the composition of the APC environment itself is perturbed, with reduced numbers of macrophages.


Revealing High Na-Content P2-Type Layered Oxides as Advanced Sodium-Ion Cathodes.
Layered Na-based oxides with the general composition of NaxTMO2 (TM: transition metal) have attracted significant attention for their high compositional diversity that provides tunable electrochemical performance for electrodes in sodium-ion batteries. The various compositions bring forward complex structural chemistry that is decisive for the layered stacking structure, Na-ion conductivity, and the redox activity, potentially promising new avenues in functional material properties. In this work, we have explored the maximum Na content in P2-type layered oxides and discovered that the high-content Na in the host enhances the structural stability; moreover, it promotes the oxidation of low-valent cations to their high oxidation states (in this case Ni2+). This can be rationalized by the increased hybridization of the O(2p)-TM(3d-eg*) states, affecting both the local TM environment as well as the interactions between the NaO2 and TMO2 layers. These properties are highly beneficial for the Na storage capabilities as required for cathode materials in sodium-ion batteries. It leads to excellent Na-ion mobility, a large storage capacity (>100 mAh g-1 between 2.0-4.0 V), yet preventing the detrimental sliding of the TMO2 layers (P2-O2 structural transition), as reflected by the ultralong cycle life (3000 (dis)charge cycles demonstrated). These findings expand the horizons of high Na-content P2-type materials, providing new insights of the electronic and structural chemistry for advanced cathode materials.


InfoFair: an annual computer and information event.
Since 1983, the Spencer S. Eccles Health Sciences Library has presented InfoFair, an annual event featuring presentations, exhibits, demonstrations, and workshops on computer and information topics of interest to health professionals and health information providers at the University of Utah Health Sciences Center and throughout Utah. The first InfoFair was held in response to an increasing number of inquiries from library users on how to search MEDLINE from their home or office computers. The focus of InfoFair has expanded and changed over the past nineteen years to reflect changes in library users' computer and information needs, concerns, and interests. While themes and programs have changed, a definite set of trends, guidelines, and procedures have developed based on the experience gained each year. The purpose of this paper is to review and evaluate the changes in InfoFair from 1983 to 2001 and to present information for use by other libraries for planning and presenting similar events.


[Research progress on the prevalence and harm of heated tobacco products].
Heated tobacco products (HTP) are a new type of tobacco product, also known as heat-not-burn (HnB) tobacco products. They are devices that use an electronic heat source to heat tobacco and produce aerosols containing nicotine for smokers to inhale. Currently, traditional combustible cigarettes and electronic nicotine delivery systems (ENDS) are increasingly being regulated under the Framework Convention on Tobacco Control. Tobacco companies have responded by actively promoting heated tobacco products worldwide, which pose new challenges to global tobacco control efforts and may become a challenge for tobacco control work in China. In reviewing the situation and the potential harm of heated tobacco products, it was noted that HTP are rapidly gaining popularity worldwide, and that their harmfulness may be underestimated. Compared to combustible cigarettes (CC) and ENDS, the long-term health effects of HTP are not fully understood, and they may pose new health risks. Potential health risks include an increase in smoking prevalence, the presence of harmful and potentially harmful compounds not found in CC, and the potential gateway effect on non-smokers. Due to differences in laws, regulations, health policies, institutions, and cultural factors related to the tobacco industry in different countries and regions, attitudes, and regulatory measures towards HTP also vary. It is essential for countries and regions around the world to develop appropriate policies to strengthen control of HTP and prevent their widespread use.