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Background: We aimed to assess the extent to which the buffy coat DNA methylome is representative of methylation patterns in constitutive white blood cell (WBC) types in normal pregnancy.Methods: A comparison of differential methylation of buffy coat DNA vs DNA isolated from polymorphonuclear (PMN) and lymphocytic fractions was performed for each blood sample obtained within 24 h prior to delivery from 29 normotensive pregnant women. Methylation profiles were obtained using an Illumina Human Methylation 450 BeadChip and CHaMP bioinformatics pipeline. A subset of differentially methylated probes (DMPs) showing discordant methylation were further investigated using statistical modeling and enrichment analysis.Results: The smallest number of DMPs was found between the buffy coat and the PMN fraction (2.96%). Pathway enrichment analysis of the DMPs identified biological pathways involved in the particular leukocyte lineage, consistent with perturbations during isolation. The comparisons between the buffy coat and the isolated fractions as a group using linear modeling yielded a small number of probes (∼29,000) with discordant methylation. Demethylation of probes in the buffy coat compared to derived cell lines was more common and was prevalent in shelf and open sea regions.Conclusion: Buffy coat is representative of methylation patterns in WBC types in normal pregnancy. The differential methylations are consistent with perturbations during isolation of constituent cells and likely originate in vitro due to the physical stress during cell separation and are of no physiological relevance. These findings help the interpretation of DNA methylation profiling in pregnancy and numerous other conditions.

Scope: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with poor therapeutic strategies. Mastiha possesses antioxidant/anti-inflammatory and lipid-lowering properties. The authors investigate the effectiveness of Mastiha as a nonpharmacological intervention in NAFLD. Methods and Results: Ninety-eight patients with NAFLD in three countries (Greece, Italy, Serbia) are randomly allocated to either Mastiha or Placebo for 6 months, as part of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The authors assess NAFLD severity via magnetic resonance imaging (MRI) scanning and LiverMultiScan technique and evaluate the effectiveness of Mastiha through medical, anthropometric, biochemical, metabolomic, and microbiota assessment. Mastiha is not superior to Placebo on changes in iron-corrected T1 (cT1) and Liver Inflammation Fibrosis score (LIF) in entire patient population; however, after BMI stratification (BMI ≤ 35 kg m-2 and BMI > 35 kg m-2), severely obese patients show an improvement in cT1 and LIF in Mastiha versus Placebo. Mastiha increases dissimilarity of gut microbiota, as shown by the Bray-Curtis index, downregulates Flavonifractor, a known inflammatory taxon and decreases Lysophosphatidylcholines-(LysoPC) 18:1, Lysophosphatidylethanolamines-(LysoPE) 18:1, and cholic acid compared to Placebo. Conclusion: Mastiha supplementation improves microbiota dysbiosis and lipid metabolite levels in patients with NAFLD, although it reduces parameters of liver inflammation/fibrosis only in severely obese patients. © 2021 Wiley-VCH GmbH

The importance of aging effects analysis in VLSI circuits increases with nowadays fast scaling of integrated circuits manufacturing technologies. Delays along paths in a digital circuit are crucial parameters that define the circuit working frequency. They degrade over time resulting in delay faults and circuit failures. The prediction of circuit long-term behavior is useful mechanism for ensuring a VLSI's lifetime reliability. In particular, paths in a digital circuit that have the largest delays are the most sensitive to gates' delay fluctuations, and consequently aging. Delay of those paths can be obtained using either aging sensors or through statistical analysis of accelerated aging experiments, but such approaches can be very difficult, time consuming and expensive for implementation. This paper suggests a new methodology capable to estimate the aging effect to digital circuit delays along multiple paths, simultaneously. The proposed technique has been developed for circuits described at a gate level, and implemented within a standard logic simulator, which enables aging analysis in initial phases of system design process. Results show that proposed methodology can efficiently estimate the long-term timing behavior of the digital circuit in a very early design stages with a small computational effort, helping the designer in selection of most reliable design choices.

This paper presents an exploratory case study of clinician-patient communications in a specific clinical environment. It describes how intensive care unit (ICU) clinicians' technical and social categorizations of patients and families shape the flow of communication in these acute care settings. Drawing on evidence from a year-long ethnographic study of four ICUs, we develop a typology of patients and families as viewed by the clinicians who care for them. Each type, or category, of patient is associated with differing communication strategies, with compliant patients and families engaged in greater depth. In an era that prioritizes patient engagement through communication for all patients, our findings suggest that ICU teams need to develop new strategies for engaging and communicating with not just compliant patients and families, but those who are difficult as well. We discuss innovative methods for developing such strategies.

Background Long-term treatment with biologic therapy alongside with immunomodulators in patients with inflammatory bowel disease (IBD) can be associated with severe side effects. Nowadays, there is not a clear recommendation for de-escalation of therapy in patients on biologic treatment. The aim of the study was to evaluate relapse rate in 4 ili 2 years follow-up in patients with mucosal healing after two years of anti-TNF treatment, regardless achieved histological remission. Methods 52 patients with IBD after two years treatment with anti-TNF agents (Infliksimab (IFX) and Adalimumab (ADA)) and achieved mucosal healing, were enrolled in this retrospective study. Mayo endoscopic sub-score (0,1) and SES ( Results From 52 patients 40.38% (21/52) patients had UC, and 59.61 % (31/52) had CD with an average disease duration of 11.57 (SD ± 6.28) years. Gender distribution was relatively equal, 46% men (24/52), with an average age of 40.66 (SD ± 11.15) years. All of the patients were on anti-TNF therapy and had mucosal healing at the moment of discontinuation, 55% (29/52) were on IFX, 35% (23/52) were on ADA, respectively. 48.07% (25/52), were with pathohistological remission of disease. In 4 years follow-up after anti-TNF therapy discontinuation, 59.61% (31/52) relapsed, with an estimated period of relapse time of 15.4 (SD ± 9.83) months. Using Spearman`s correlation moderate relation was revealed between histological activity and relapse (rho 0.467, p < 0.001). Probability of relapse within 4 years in this group of patients with histologically active disease was higher (p < 0.01, OR 2.72, 95% Cl 1.24–5.92). Conclusion Achieving both, endoscopic and histological remission, may be a good parameter in making a decision when to de-escalate anti-TNF therapy.

BACKGROUND Integrating palliative care into intensive care requires active involvement of bedside nurses in discussions of patients' prognosis and goals of care. OBJECTIVE To improve critical care nurses' skills and confidence to engage in discussions with patients' families and physicians about prognosis and goals of care by using a focused educational intervention. METHODS An 8-hour-long workshop was developed for critical care nurses. Key roles and skills of nurses in communication about prognosis and goals of care were defined. Participants practiced skills during facilitated role-plays. A reflection session addressed burnout, distress, and self-care. Participants completed surveys before, immediately after, and 3 months after their workshop, rating their confidence and skill in performing key tasks. Use of a participant focus group and open-response items in the surveys further elucidated the impact of the workshop. RESULTS Between March 2011 and April 2013, a total of 82 critical care nurses completed a workshop. Compared with before the workshop, after the workshop, nurses reported greater skill and confidence for 14 survey items (P < .001), including assessing families' understanding of prognosis and goals of care, addressing families' emotional needs, and contributing to family meetings. Increases were sustained 3 months after the workshop. CONCLUSION Defining roles and providing opportunities for skills practice and reflection can enhance nurses' confidence to engage in discussions about prognosis and goals of care.

BACKGROUND: Pulmonary rehabilitation programs document outcomes to prepare for program certification, to demonstrate the value of the program to upper management, and to provide feedback to pulmonary rehabilitation staff regarding the efficacy of the program. The overall goal of this study was to evaluate the feasibility of using non-research-generated clinical data to report long-term outcomes following a pulmonary rehabilitation program. METHODS: Using a longitudinal descriptive design, all subjects who completed pulmonary rehabilitation at one community-based pulmonary rehabilitation program in the San Francisco Bay Area were asked to complete a 6-month and subsequent yearly questionnaires. Adherence to pulmonary rehabilitation techniques was described for 7 y following pulmonary rehabilitation participation, health-care utilization from 1 y before pulmonary rehabilitation was compared with subsequent years, and health-care utilization was compared between those who participated in ongoing regular exercise after pulmonary rehabilitation and those who did not exercise. RESULTS: More than 70% of subjects who completed the questionnaire reported adherence to pulmonary rehabilitation techniques, including exercise for at least 7 y following pulmonary rehabilitation. Health-care utilization declined after pulmonary rehabilitation. Subjects who did not exercise regularly required significantly more health care than those who exercised regularly ( P < .05). CONCLUSIONS: This study demonstrated the ability of one pulmonary rehabilitation program to accurately monitor extended long-term follow-up after pulmonary rehabilitation. Implementing this long-term monitoring methodology consistently in pulmonary rehabilitation programs could contribute to evaluation of the comparative effectiveness of various treatment options.

This paper aims toward joining the ideas of OBT (oscillation-based testing) and DFT (design for testability). It gives insight into an optimization process that provides testability if one chooses to use the OBT. The optimization procedure is exemplified on a timer device NE555. Utilization of a timer circuit allows avoidance of a specific design of the feed-back loop. The optimization procedure is based on the Monte Carlo analysis. Once a device Spice model is acquired with all the elements of the model designed in a certain parameter tolerance space, one can move to the optimization for testability. Total derivatives of the function of oscillation frequency due to parameters values are estimated. The point that corresponds to the maximal total derivative is chosen as the appropriate set of parameter values for DFT. After the optimization procedure described in this paper has been performed on a Spice model, one can use the model parameters to set the goals of the IC design and manufacturing process of the device.

BACKGROUND Integrating palliative care into intensive care units (ICUs) requires involvement of bedside nurses, who report inadequate education in palliative care. OBJECTIVE To implement and evaluate a palliative care professional development program for ICU bedside nurses. METHODS From May 2013 to January 2015, palliative care advanced practice nurses and nurse educators in 5 academic medical centers completed a 3-day train-the-trainer program followed by 2 years of mentoring to implement the initiative. The program consisted of 8-hour communication workshops for bedside nurses and structured rounds in ICUs, where nurse leaders coached bedside nurses in identifying and addressing palliative care needs. Primary outcomes were nurses' ratings of their palliative care communication skills in surveys, and nurses' identification of palliative care needs during coaching rounds. RESULTS Each center held at least 6 workshops, training 428 bedside nurses. Nurses rated their skill level higher after the workshop for 15 tasks (eg, responding to family distress, ensuring families understand information in family meetings, all P < .01 vs preworkshop). Coaching rounds in each ICU took a mean of 3 hours per month. For 82% of 1110 patients discussed in rounds, bedside nurses identified palliative care needs and created plans to address them. CONCLUSIONS Communication skills training workshops increased nurses' ratings of their palliative care communication skills. Coaching rounds supported nurses in identifying and addressing palliative care needs.

This paper presents a context-aware mobile framework (or middleware), intended to support the implementation of context-aware mobile services. The overview of basic concepts, architecture and components of context-aware mobile framework is given. The mobile framework provide acquisition and management of context, where raw data sensed from physical (hardware) sensors and virtual (software) sensors are combined, processed and analyzed to provide high-level context and situation of the user to the mobile context-aware applications in near real-time. Using demo mobile health application, its most important components and functions, such as these supposed to detect urgent or alarming health conditions of a mobile user and to initiate appropriate actions demonstrated.

Background Several studies have suggested that combining radiotherapy (RT) to immunotherapy (IO) may be synergistic but many questions are still pending regarding the radiation modalities to optimize this combination, such as the choice of the lesion to irradiate. Radiomics consists in the analysis of quantitative data extracted from standard medical imaging to generate imaging biomarkers. A previous study published in The Lancet Oncology has shown that a radiomic signature could predict the CD8 cells infiltration, which is associated with the activity of anti-PD-1/PD-L1. We aimed to assess whether this biomarker could help to guide IO-RT combinations. Methods Patients from three clinical studies of IO-RT combinations with advanced solid tumors in two institutions were screened. Patients with available baseline (E0) and first evaluation (E1) CTs were included. Immunotherapy consisted in 4 different drugs. Hypofractionated conformal RT or stereotactic RT of one tumor lesion was delivered after the start of IO for most of the patients. The irradiated lesion and a sample of non-irradiated lesions were delineated from E0 and E1 CTs. Radiomics features were extracted and the published radiomic signature was applied to estimate the CD8 cells. Results 84 patients were included. 244 tumor lesions were delineated on the E0 CT, including the 84 lesions which were selected for irradiation. Median time between IO and RT start was 21 days (IQR: 9-24), and 2.4 mo between E0 and E1 (IQR: 1.3 - 3). 80 irradiated lesions and 152 non irradiated lesions remained at E1. At baseline, the volume and the radiomic score of TIL (RS) were not different between the two groups (irradiation or no) (p = 0.94 and 0.50). While the mean volume of the analyzed lesions was not different from E1 to E0 (p = 0.15), irradiated lesions were significantly smaller at E1 (p = 0.03). A high RS in the irradiated lesion at E1 (compared to the median value) was associated with PFS (HR = 0.57, IC95%: 0.345-0.95, p = 0.031) irrespective of the volume in multivariate analysis but was not significantly associated with OS. Conclusions Radiomic score of the irradiated lesion was associated with PFS. Such biomarker may help to guide the selection of the lesion to irradiate in IO-RT combinations. Legal entity responsible for the study Gustave Roussy Cancer Campus. Funding Fondation pour la Recherche Medicale, SIRIC-SOCRATE 2.0, Fondation ARC, Amazon. Disclosure R. Sun: Travel / Accommodation / Expenses: AstraZeneca. N.L. Sundahl: Travel / Accommodation / Expenses: Merck Sharpe & Dohme; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Bayer; Travel / Accommodation / Expenses: Bristol-Myers Squibb. P. Ost: Research grant / Funding (institution): Merck Sharpe & Dohme; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Janssen; Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Travel / Accommodation / Expenses: Ferring Pharmaceuticals; Honoraria (self): Bayer. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Jansen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Orion. E. Deutsch: Advisory / Consultancy, Research grant / Funding (institution): Roche Genentech; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD. All other authors have declared no conflicts of interest.

The 60 K plateau of the YBa 2 Cu 3 O 6+ x high- T c superconducting compound has traditionally been known as a horizontal section in its T c ( x ) characteristics within which the critical temperature maintains at a constant level T c ≈ 60 K. However, recent experiments on a series of high quality single crystals samples of the YBa 2 Cu 3 O 6+ x compound (produced by improved techniques of sample preparation) have shown the 60 K plateau does not manifest itself anymore as a horizontal section of the T c ( x ), but emerges as a section over which T c ( x ) keeps on continuously rising (the “quasi” 60 K plateau). Here we propose a theoretical model that explains how the classical (horizontal) 60 K plateau naturally evolves into the “quasi” 60 K plateau, due to the improved orthorhombicity in the high quality single crystal material accompanied by longer CuO chains. The model assumes that short CuO chains do not contribute to the hole transfer from chains to CuO 2 layers, but only chains whose length is greater than, or equal to, a certain threshold length l cr . Our calculations point to a conclusion that this minimal number of oxygen atoms in a CuO chain, that is required to trigger the hole transfer, is equal to four. The calculated values for T c ( x ) are in a very good correlation with the corresponding experimentally obtained results.

Objective: Veterans evaluated at the WRIISC present with multiple and chronic health conditions such as posttraumatic stress disorder (PTSD), pain, and fatigue. These patients often experience poor symptom relief. A pilot project was designed to determine whether such veterans would practice yoga as an adjunct to conventional medical care. We also used a range of standard screening measures to examine the health profile of individuals. Methods: Veterans were referred by VA clinicians to a WRIISC yoga clinic established in 2009. Two classes were offered per week. Veterans were assessed at baseline and after 12 classes with the PTSD Ch ecklist (PCL), Short F orm McGill Pain Questionnaire (SF-12), and the Flinders Fatigue Scale (FFS). Results: There have been 293 patient referrals so far and more than 1,824 yoga contact hours. Detailed data were collected on 10 veterans age 53–85 yrs (6 males). The screening instruments revealed nonsignificant benefits of yoga across the classes (p > .05). Furthermore, the PCL scores showed that four patients (40%) screened positive for PTSD (mean severity score = 40.9, range = 18–70). In addition, the PCL showed positive correlations with measures of pain (FS-12; Spearman’s rho = .76, p < .01), and chronic fatigue (FFS; Spearman’s rho = .94, p < .001). Similar results were found for equivalent correlations after 12 yoga classes. Conclusion: This pilot study demonstrates that veterans accept yoga as a complementary treatment to their regular medical care. Of possible significance is the observation that 40% of the patients screened positive for PTSD. The reasons for this are not clear but may be because such patients were referred at a higher rate. It is also possible that PTSD patients seek out yoga classes as an effective means of treating their symptoms. The strong correlations between measures of PTSD, pain, and fatigue suggest far-reaching implications for the integration of yoga in the treatment of veterans with a broad array of disorders exacerbated by stress. 2. Yoga-based Psychotherapy Group With Urban Youth Exposed to Trauma

Pre-eclampsia (PE) is a pregnancy-specific hypertensive disorder that has been associated with cardiovascular risk factors and vascular changes, such as acute atherosis in placental blood vessels, similar to early-stage atherosclerosis. The objective of this study was to determine whether women with PE have increased atherosclerotic burden, as determined by the carotid intima-media thickness (CIMT), compared with women without PE.We conducted a systematic review and meta-analysis of studies that reported CIMT, a non-invasive, ultrasound-based measure of subclinical atherosclerosis, in women who did vs those who did not have PE. Studies were eligible if they had been conducted during pregnancy or during the first decade postpartum, and if CIMT was measured in the common carotid artery. Studies published before 7 March 2016 were identified through PubMed, EMBASE and Web of Science. Two reviewers used predefined forms and protocols to evaluate independently the eligibility of studies based on titles and abstracts and to perform full-text screening, data abstraction and quality assessment. Heterogeneity was assessed using the IFourteen studies were included in the meta-analysis. Seven studies were carried out during pregnancy complicated by PE, 10 were carried out up to 10 years postpartum and three included measurements obtained at both time periods. Women who had PE had significantly higher CIMT than did those who did not have PE, both at the time of diagnosis (SMD, 1.10 (95% CI, 0.73-1.48); P0.001) and in the first decade postpartum (SMD, 0.58 (95% CI, 0.36-0.79); P0.001).Atherosclerotic load is present at the time of PE and may be a mechanism associated with the disease. Measurement of CIMT may offer an opportunity for the early identification of premenopausal women with atherosclerotic burden after a PE pregnancy. Copyright © 2016 ISUOG. Published by John WileySons Ltd.La preeclampsia (PE) es un trastorno hipertensivo específico del embarazo que ha sido asociada con factores de riesgo cardiovascular y cambios vasculares, tales como aterosis aguda en los vasos sanguíneos de la placenta, similares a las primeras etapas de la aterosclerosis. El objetivo de este estudio fue determinar si las mujeres con PE han aumentado la carga aterosclerótica, según lo determinado por el espesor del complejo íntima-media de la arteria carótida (CIMT, por sus siglas en inglés), en comparación con las mujeres sin PE. MÉTODOS: Se realizó una revisión sistemática y un metaanálisis de estudios que reportaron el CIMT, una medida no invasiva de la aterosclerosis subclínica obtenida mediante ecografía, comparando mujeres con PE y mujeres sin ella. Solo se incluyeron estudios llevados a cabo durante el embarazo o durante la primera década después del parto, y en los que se midió el CIMT en la arteria carótida común. Se usaron las bases de datos de PubMed, EMBASE y Web of Science para identificar estudios publicados antes del 7 marzo de 2016. Dos revisores utilizaron formularios y protocolos preestablecidos para evaluar de forma independiente la elegibilidad de los estudios, a partir de los títulos y los resúmenes, y para realizar un cribado del texto completo, un resumen de los datos y una evaluación de calidad. La heterogeneidad se evaluó mediante el test estadístico IEn el metaanálisis se incluyeron catorce estudios. Siete de los estudios se llevaron a cabo durante embarazos complicados por PE, 10 se realizaron hasta 10 años después del parto y tres incluyeron mediciones tomadas en ambos períodos. Las mujeres con PE tuvieron un CIMT significativamente mayor que aquellas que no la tenían, tanto en el momento del diagnóstico (SMD 1,10 (I 95%, 0,73-1,48), P0,001) como en la primera década después del parto (SMD 0,58 (IC 95%, 0,36-0,79), P0,001).La carga aterosclerótica está presente en el momento de la PE y podría ser un mecanismo asociado con esta enfermedad. La medición del CIMT puede ofrecer una oportunidad para la identificación temprana de mujeres premenopáusicas con carga aterosclerótica después de un embarazo con PE. : (pre-eclampsia,PE),,,。-(carotid intima-media thickness,CIMT),PEPE,。 : PEPECIMTmeta,CIMT、。:10CIMT。PubMed、EMBASEWeb of Science,201637。,,、。I2 。(SMD)。 : meta14。7PE,1010,3。PEPE,[SMD,1.10(95% CI,0.73~1.48);P0.001]10[SMD,0.58(95% CI,0.36~0.79);P0.001] CIMT。 : PE,。CIMT,PE。.

Experimental results available in the literature were employed to study the high pressure dependence of the superconducting transition temperature T c of YBa2Cu3O x high-T c superconductor in a wide range of oxygen concentrations x. By the use of simple phenomenological model, we determined the T c (x) dependences at different constant values of pressure P to 35 GPa. We found that maximum T c which can be attained in YBa2Cu3O x material is approximately 131 K, and it is achieved for P≈18 GPa in the sample with x≈6.74 and with zero pressure hole concentration n h,0≈0.11.

An extended ASYNNNI model, that beside nearest-neighbour and next-nearest neighbour O-O interactions in the basal plane also includes interactions between the three nearest oxygen atoms, is used to describe the statistics of CuO chain fragmentation and to calculate doping and T c in YBa2Cu3O6+x . Calculations were made by the Monte Carlo method employing the recently proposed charge transfer model that assumes only chains whose length is equal to, or exceeds, a characteristic (critical) length, l cr, can provide holes to the layers and contribute to doping p. The obtained p(x) is then combined with a universal T c versus p relation to yield T c(x) characteristics that correlate remarkably with those reported in recent experiments. The best coordination between theoretical and experimental T c(x) characteristics has been achieved for l cr = 2, implying that only isolated basal plane oxygen atoms (trivial chains) do not contribute holes to CuO2 layers.

Inflammation, cardiometabolic risk (CMR) factors, and autonomic imbalance have been independently associated with cognitive declines in aging, but their interactive effect on cognition remains unclear. We quantified the magnitude of their associations with cognitive function and the extent to which links were synergistic. In eighty dementia-free participants (mean = 73.6 years), cognitive function was assessed with the Montreal Cognitive Assessment (MoCA) and CMR was ascertained using principal components analysis on nine serum and blood pressure (BP) measures. Autonomic balance was estimated by delta-BP between 10-min exercise and 1-min cool-down. Beta-adrenergic receptor-mediated inflammation control (BARIC) was quantified by co-incubating immune cells with lipopolysaccharide and beta-agonist for monocyte TNF-alpha expression. Data were analyzed using multivariate linear regression. Of 76 participants who completed MoCA, cognition was impaired in 21 (27.6%; MoCA ⩽ 23) and correlated with age (beta = −0.30, t = −2.56, p = 0.013), but not BMI or gender. Impaired BARIC and higher delta-BP were independently associated with lower MoCA scores (beta = −1.14, t = −2.94, p = 0.005; beta = 0.86, t = 2.32, p = 0.025), adjusted for CMR. For CMR factors, the first component explained 31.5% of total variance, for which higher values reflected hyperglycemia and hyperlipidemia, and significantly predicted lower MoCA scores (beta = −1.20, t = −2.92,p = 0.005). Furthermore, a synergistic effect of BARIC and CMR on MoCA scores was observed (beta = −1.01, t = −3.62, p 0.001). Sympathoadrenal regulation of inflammation, CMR factors, and autonomic balance exert both independent and synergistic effects on cognitive function in older adults, highlighting a critical role of ANS-immune interactions in aging and cognition.

Summary Trichinella spiralis is a helminth that provokes Th2 and anti-inflammatory type responses in an infected host. Our previous studies using Dark Agouti (DA) rats indicated that T. spiralis infection reduced experimental autoimmune encephalomyelitis (EAE) severity in rats. The aim of this study was to analyse the mechanisms underlying EAE suppression driven by T. spiralis infection. Reduced clinical and histological manifestations of the disease were accompanied by increased IL-4 and IL-10 production and decreased IFN-γ and IL-17 production in draining lymph node cells. This indicates that T. spiralis infection successfully maintains a Th2 cytokine bias regardless of EAE induction. High IL-10 signifies parasite-induced anti-inflammatory and/or regulatory cell responses. Transfer of splenic T cell-enriched population of cells from T. spiralis-infected rats into EAE immunized rats caused amelioration of EAE and in some cases protection from disease development. This population of cells contained higher proportion of CD4+ CD25+ Foxp3+ regulatory cells and produced high level of IL-10 when compared with uninfected rats.

The aim of this study was to evaluate and analyze the incidence and features of headaches in patients undergoing hemodialysis.In this prospective study 318 patients, 119 women and 199 men, undergoing chronic HD in four hemodialysis centers in Serbia, were questioned about their problems with headaches using a questionary designed according to the diagnostic criteria of the International Headache Classification of Headache Disorders (ICHD) from 2004. Patients were distributed in two groups according to the presence of hemodialysis headaches (HDH). The groups were compared regarding sex, age, duration of HD, primary diseases that lead to ESRD, arterial systolic and diastolic blood pressure (BP) and serum levels of hemoglobin, urea nitrogen, creatinine, sodium, potassium, calcium, phosphates, albumin, glucose and calcium-phosphate product. We also analyzed features of HDH. The results were statistically compared.Patients with HDH had significantly lower serum glucose, but higher serum phosphates and albumin than patients without headaches. Furthermore, HDH patients had higher calcium phosphate product and systolic blood pressure than non-HDH patients. Out of 318 patients included in the study, 21 (6.6%) patients had HDH. According to our results, HDH appeared more frequently in men, during the 3rd hour of HD in more than a half of the patients and lasted less then 4 h in the majority of HDH patients. In the majority of patients HDH was bilateral, non-pulsating, without associated symptoms and it appeared mostly during HD. Personal history was negative for primary headaches in all patients with HDH.We believe that the results of our investigation of more than 300 HD patients pointed to some biochemical changes, possibly implicated by pathophysiology of HDH and disclose some specific HDH features that might contribute to a better understanding of this secondary headache disorder.

We present our results with botulinum-A toxin transperineal pelvic floor/external sphincter injection combined with behavioral and biofeedback reeducation in children with voiding dysfunction who had been resistant to previously applied therapies.Eight boys and 12 girls between 7 and 12 years old (mean age 9) with recurrent urinary tract infection, an interrupted or fractional voiding pattern and high post-void residual urine in whom behavioral, short biofeedback and alpha-blocker therapies had failed were included in the study. They were treated with botulinum-A toxin at a dose of 50 to 100 U. Botulinum-A toxin was injected transperineally into the pelvic floor and/or external sphincter in all patients. In boys the sphincter was localized endoscopically before injection (endoscopically assisted transperineal approach). Behavioral and biofeedback reeducation started 15 days after injection.Followup was between 9 and 14 months. All patients were without urinary tract infection and fever, while 5 were still on chemoprophylaxis. Six months after treatment residual urine decreased in 17 of 20 patients by 0 to 130 ml (mean +/- SD 45.75 +/- 32.17 ml, t = 6.360, p0.001). Nine patients reestablished a normal voiding curve and 8 showed improvement. Three did not manifest any significant improvement. In 1 girl transitory incontinence resolved spontaneously within 48 hours. There were no other complications.The effect of botulinum is transitory. However, it can break the circle of detrusor-sphincter dyssynergia and the period when it is sustained can be used for retraining the patient in normal voiding. At this moment botulinum-A toxin is one of last options in refractory cases of voiding dysfunction.

A cluster variation method (CVM) has been used to calculate the phase diagram of oxygen ordering in YBa2Cu3O6+2c in terms of two dimensional Ising model that, besides of repulsive nearest-neighbor (NN) interaction V1 > 0 and two types of next-to-nearest neighbor (NNN) pair interactions V2 0, includes additional three-atom effective interaction Vth coupling two NNN oxygen atoms already bounded by V2 (through Cu(1) ion) with the third O atom that is connected with one of these two by the repulsive NNN Coulomb interaction V3 > 0. Phase diagrams were calculated for several different sets of interaction constants V1, V2, V3, and Vth together with the corresponding phase diagrams obtained for Vth = 0. The arrangement of main orthorhombic structures in (c, T) space and the nature of the phase transition curves between them is found to be in a very good agreement with those of the corresponding phase diagrams of the well-known ASYNNNI model, which had already proven itself as accurately reproducing the number of experimental findings on the structural phase diagram of YBa2Cu3O6+2c. On the other hand, unlike to the predictions of the ASYNNNI model (Vth = 0), it is shown that inclusion of three-atom interaction Vth results in significant increase of the number of isolated basal plane oxygen ions which are generally considered as not giving rise to the charge transfer process and the onset of superconductivity. The importance of obtained oxygen superstructures of low temperature oxygen ordering and its possible impact on existence of plateaus in Tc(c) dependence has been discussed.

The antioxidative properties of bulb, leaf and stalk of leeks, Allium sphaerocephalon L., were investigated. Activities of the antioxidant enzymes superoxide dismutase, catalase, peroxidase, glutathione peroxidase, the quantities of malonyldialdehyde, superoxide and hydroxyl radicals and reduced glutathione and the content of flavonoids, chlorophylls, carotenoids, vitamin C and soluble proteins were determined. Results indicated that extracts from all plant organs exhibited antioxidant activity. The highest antioxidant activity was observed in the leaves. Furthermore, ESR signal of PBN-OH radical adducts in the presence of leaves phosphate buffer (pH 7) extract was reduced for 64.51%.

An accumulation of various cardiovascular risk factors has been noted to occur within the clinical diagnosis of metabolic syndrome. However, it remains unclear whether specific risk factors aggregate following a predefined pattern or whether this happens by chance.This cross-sectional study involved 1715 adults, 37% males and 63% females, aged 34-80 years, who were consecutively recruited from cardiology and endocrinology outpatient clinics, and from internal medicine specialists in the primary healthcare physician office setting in Serbia, on a one-third basis. According to the AHA/NHLBI criteria, the actual prevalence of a combination of 3 or more of the following risk factors was determined: abnormal waist circumference, hypertension, high triglycerides, low high-density lipoprotein cholesterol, and abnormal fasting glucose. In addition, the prevalence of a corresponding combination of 3 factors was predicted from the prevalence of each factor in a given population, assuming that their combination occurred as the result of chance.The most frequent risk factor was hypertension (87%), followed by waist circumference (60%), dyslipidemia (55%), and abnormal fasting glucose level (50%). Metabolic syndrome was identified in 1135 participants (66.2%). The actual prevalence of the combination of increased waist circumference, elevated blood sugar and hypertension was found to be 5 times more frequent than would be expected to occur by chance (10% actual vs. 2% predicted; p0.0001).A predefined aggregation pattern of risk factors within the metabolic syndrome was found for abdominal obesity, abnormal fasting glucose and hypertension. These risk factors do cluster more frequently than coincidental phenomena in the subjects of the given population, implying common underlying pathophysiological mechanisms.

Background. Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes.Methods. Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate.Results. The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired.Conclusions. Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.

Effect of the long term illumination of the YBa2Cu3O6+x with visible light or ultraviolet irradiation on its superconducting properties was studied in the frame of a simple theoretical model, which assumes that photodoping triggers rearrangement of oxygen monomers in the chain layers thus causing the enhancement of the average chain length, l(av). Since, according to the model of charge transfer mechanism, long CuO chains are better electronic hole donors than the short ones, increase of the average chain length induces additional holes transfer from chain layers to the superconducting CuO2 planes which in turn leads to the increase of the superconducting transition temperature T-c. By the use of the expression for the chain length probability distribution and numerically calculated values for the average chain length in the non-excited system, we were able to estimate the doping p (number of holes per one Cu atom in the superconducting CuO2 planes) and T-c enhancement due to photo-induced oxygen reordering. The theoretical results are compared with available experimental data. (C) 2011 Elsevier B.V. All rights reserved. 5th International Conference on Elementary Processes in Atomic Systems (CEPAS), Jun 21-25, 2011, Belgrade, Serbia

In the present study, we have employed two dimensional ASYNNNI model and the numerical Monte Carlo simulations to investigate the effect of visible light or ultraviolet radiation on the doping p of the superconducting CuO2 planes, and consequently on the superconducting transition temperature T-c, in YBa2Cu3O6+x high-T-c superconductor. It was shown that, depending on the oxygen concentration, x, three regions of different critical temperatures T-c behavior could be distinguished. In the first region where x LT 0.6 the critical temperature increases rapidly with oxygen depletion, in the second region, 0.6 LT x LT 0.75, the total T-c change, delta T-c, is almost independent of the oxygen content thus forming some kind of plateau, while in the third region, 0.75 LT x LT 1.0, the T-c does not increase significantly. Such a theoretically obtained behavior of T-c is in general agreement with the experimentally established facts on the delta 7(c), vs. x dependence. (C) 2011 Elsevier B.V. All rights reserved. 5th International Conference on Elementary Processes in Atomic Systems (CEPAS), Jun 21-25, 2011, Belgrade, Serbia

In the present study, we have employed two dimensional ASYNNNI model to investigate how the Ortho-II structure formation influences doping, p , of the superconducting CuO 2 planes in YBa 2 Cu 3 O 6+ x high- T c superconductor. It was shown, that if the direct repulsive interaction between next nearest oxygen atoms ( V 3 ), present in the Hamiltonian of the ASYNNNI model, is neglected, the Ortho-II ordering is destroyed and doping p becomes a linearly increasing function of oxygen concentration x in the range 0.50 ⩽ x ⩽ 0.65, for any choice of critical chain length l cr (defined so that CuO chains of length l l cr cannot transfer holes to the CuO 2 planes). Consequently, the T c ( x ) dependence, obtained by the employment of the universal T c vs. p relation, does not exhibit experimentally observed “60 K plateau”. The results presented here confirm that establishment of Ortho-II structural phase is a key factor for the “60 K plateau” formation in the T c ( x ) dependence.

Trichinella spiralis is a helminth that provokes Th2 and anti-inflammatory type responses in an infected host. Our previous studies using Dark Agouti (DA) rats indicated that T. spiralis infection reduced experimental autoimmune encephalomyelitis (EAE) severity in rats. The aim of this study was to analyse the mechanisms underlying EAE suppression driven by T. spiralis infection. Reduced clinical and histological manifestations of the disease were accompanied by increased IL-4 and IL-10 production and decreased IFN-gamma and IL-17 production in draining lymph node cells. This indicates that T. spiralis infection successfully maintains a Th2 cytokine bias regardless of EAE induction. High IL-10 signifies parasite-induced anti-inflammatory and/or regulatory cell responses. Transfer of splenic T cell-enriched population of cells from T. spiralis-infected rats into EAE immunized rats caused amelioration of EAE and in some cases protection from disease development. This population of cells contained higher proportion of CD4(+) CD25(+) Foxp3(+) regulatory cells and produced high level of IL-10 when compared with uninfected rats.

The article investigates availability and quality of drinking water along with possibilities of rainwater harvesting, as an element of sustainable development on four Croatian islands. Investigated islands, represent two main regions: northern and southern Adriatic coast. This division corresponds with gravity to two main macro regional centers on the coast and it is common in demographic, economic and sociological research. Data on local water resources, conditions and type of water supply, quality of water, prices, consumption of water, number and condition of cisterns and demographic records are collected and analyzed. Also, meteorological data on annual rainfall in past 26 years are collected and analyzed. Drinking water quality corresponds with Croatian law regarding physical and chemical parameters, while most of microbiological parameters are unacceptable. The results point out modest possibility of developing public water supply on islands. Average annual rainfall indicates that harvesting of rainwater should be integrated as additional water source on investigated islands which would save great quantities of the drinking water that are used as technical water and for the other purposes such as agriculture or forest fires. Also that would lower the household expenses for the water and diminish water crisis during the tourist season months. Natural water resources on Croatian islands are scarce and it is our ethical obligation to preserve them in favor of existing eco systems and long term exploitation.

An expression for the chain length probability distribution p(l) of a one dimensional Ising chain was derived using the cluster variation method formalism, the p(l) being expressed through the pair cluster probabilities. It was shown numerically that the same expression also applies in the case of one dimensional chains formed along one of the next-nearest neighbor interactions included in the two dimensional ASYNNNI (Asymmetric Next-Nearest Neighbor Ising) model, widely used to describe the statistics of oxygen ordering in the basal CuOx planes of the YBa2Cu3O6+x type high-Tc superconducting materials. Equivalency between ASYNNNI and 1d Ising model is discussed.

Distribution of CuO chains in YBa 2 Cu 3 O 6+2 c , with respect to different chain lengths, has been studied in terms of the two dimensional asymmetric next-nearest-neighbor Ising (ASYNNNI) model, for the case of orthorhombic-I structural phase. If p ( l ) stands for the fraction of CuO chains of length l ( l equals to number of oxygen atoms that are linked in the chain), the results obtained show that p ( l ) decreases monotonically with l , very accurately fitting to p ( l ) = AB l , as at very low temperatures so at a very high temperatures as well (ranking from ≈300 K to 1800 K), and at all values of oxygen concentration c . Both parameters A and B were found to depend on ( c , T ) only through a single quantity—the average length l av ( c , T ) of CuO chains in the system. The expressions for A ( l av ) = A ( l av ( c , T )) and B ( l av ) = B ( l av ( c , T )), that were derived out of extensive Monte Carlo (MC) numerical simulations on the chain probability distribution p ( l ) and independently obtained values of l av were found to be very accurately fulfilled at all calculated points of ( c , T ) space. The particular behavior of p ( l ) dependance has been assigned to 1 d Ising model type of oxygen atom fluctuations along cooper mediated V 2 b crystallographic axes). The importance of knowing the exact form of p ( l ), for evaluation of the number of transferred electronic holes from CuO chains to superconducting CuO 2 layers, has been discussed together with its possible impact on the two-plateaus shape of T c ( c ) dependance.

Background: Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. Methods: Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+ TLs, CD4+ TLs, and CD8+ TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O-2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. Results: Elastase positive cells accounted for the 7.04% +/- 1.1 of total cells, CD68+ cells for the 16.6% +/- 2, CD3+ TLs for the 28.8% +/- 7, CD4+ TLs for the 14.5 +/- 4 and CD8+ TLs for the 13.8 +/- 4. CD8+ TLs correlated inversely with FVC % predicted (r(s) = -0.67, p = 0.01), TLC % predicted (r(s) = -0.68, p = 0.01), DLCO % predicted (r(s) = -0.61, p = 0.04), and PaO2 (r(s) = -0.60, p = 0.04). Positive correlations were found between CD8+ TLs and P(A-a)O-2 (r(s) = 0.65, p = 0.02) and CD8+ TLs and MRC score (r(s) = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (r(s) = -0.80, p = 0.002) and FEV1 % predicted (r(s) = -0.68, p = 0.01). Conclusion: In UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.

Background: Surgical biopsy specimens have shown that T lymphocytes (TLs) infiltrate lung parenchyma in patients with idiopathic pulmonary fibrosis (IPF) and might play a pathogenetic role. BAIL, a far less invasive technique, has also been used for the investigation of IPF pathogenesis. However, controversy exists whether the BAL fluid cellular profile reflects the cellular composition of the lung parenchyma. Study objective: To compare infiltrating TLs subpopulations (CD4+, CD8+, and CD4+/CD8+ ratio) in lung tissue and BAL fluid. Patients and methods: Immunohistochemistry was performed according to the streptavidin-biotin method on the surgical biopsy specimens 4 12 untreated patients with IPF. The number of CD3+, CD4+, and CD8+ TLs was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor; Meylan, France). In BAL fluid, the same TLs subpopulations were evaluated by flow cytometry. Results: In lung tissue, CD3+ TLs accounted for a mean (+/- SEM) of 28.8 +/- 7% of total cells, CD4+ TLs accounted for 14.5 +/- 4% of total cells (50.1 +/- 4% of CD3+ TLs), and CD8+ TLs accounted for 13.8 +/- 4% of total cells (47.4 +/- 4% of CD3+ TLs). In BAL fluid, lymphocytes accounted for 9.8 +/- 2.5% of total cells, CD4+ TLs accounted for 51.8 +/- 4% of CD3+ TLs, and CD8+ TLs accounted for 42.2 +/- 4% of CD3+ TLs. Tissue CD4+ and CD8+ TLs (expressed as a percentage of CD3+ TLs) correlated significantly with the number of CD4+ and CD8+ TLs in BAIL fluid (r = 0.846 and p = 0.001 vs; r = 0.692 and p = 0.013, respectively). A significant positive correlation was also found between the mean CD4+/CD8+ ratio found in tissue and BAL fluid (1.05 +/- 0.21 and 1.5 +/- 0.27, respectively; r = 0.832; p = 0.01). Conclusion: The results suggest that in patients with IPF, the TL subpopulations in BAL fluid reflect the pattern of lymphocytic infiltration in pulmonary parenchyma.

Fluctuations in tetragonal phase of YBa2Cu3O6+2c compound are analyzed in terms of the two-dimensional asymmetric next-nearest-neighbor Ising (ASYNNNI) model. For several sets of interaction constants between oxygen atoms, VI GT 0. V-2 LT 0 and V-3 GT 0, we calculated equidistant mu (c, T) = constant curves to show that largest fluctuations of oxygen concentration in tetragonal phase occur for chemical potential mu approximate to mu (g1), where mu (g1) = -8V(1) - 4V(3). We argue that this is a general property of the ASYNNNI model: it holds for all temperatures and different values of interaction constants. Analyzing the experimental results on isothermal susceptibility, chi = sigmac/sigma mu for six different temperatures ranging from 673 to 923 K, we found that the top of chi occurs for approximately the same value of oxygen chemical potential in gas phase which corresponds to mu (gi) of the ASYNNNI model. By comparison with experiment, we obtained the relation, 4 \V-2\ - epsilon = 82 mRy, where epsilon is the on-site energy of the basal plane oxygen atoms. (C) 2001 Elsevier Science B.V. All rights reserved.

We proposed a two-dimensional Ising model for oxygen ordering in YBa2Cu3Ox material in which an effective O-O interaction energy with Cull) ion in between, besides the occupation of the two oxygen sites, also depends on occupancy of the surrounding oxygen sites. We have shown that the Hamiltonian of the model reduces to that of the anisotropic next-nearest-neighbor Ising (ASYNNNI) model with additional term, for three-atom interaction (characterized by the parameter omega). We have shown that, for omega GT /V-2//4 (where V-2 LT 0 denotes copper mediated O-O interaction of the ASYNNNI model), the model includes all three major structural phases, tetragonal, OI, and OII, as ground states at x = 0, x = 6.5, and x = 7.0, respectively, while at off-stoichiometry 6.5 LT x LT 7, the model stabilizes the so-called fragmented-chain structure of Zaanen et al. [J. Zaanen, A.T. Paxton, O. Jepsen, O.K. Anderson, Phys. Rev. Lett. 60 (1988) 2685]. We calculated the fractions of 2-fold (n(2)), 3-fold (n(3)) and 4-fold (n(4)) coordinated Cu(1) ions as a function of oxygen content x at constant low temperatures (proportional to 300 K) and obtained characteristic plateaus in n(2)(x) and n(4)(x), while n(3)(x) is very large (proportional to 0.36) for x = 6.75. We discussed the impact of the fragmented chain statistics on charge transfer process from Cu(1)-O(1) chains to superconducting CuO2 sheets and its relevance for occurrence of 60 and 90 K plateaus in T-c versus x dependence. (C) 2000 Elsevier Science B.V. All rights reserved.

Low-temperature thermodynamics of the asymmetric next-nearest-neighbor Ising (ASYNNNI) model is analyzed. It is demonstrated that this model at low temperatures is equivalent to one-dimensional (1D) NN Ising model in zero external field with the NN interaction being a copper mediated NNN interaction of the ASYNNNI model, ${V}_{2}l0.$ It is also shown that the spin correlation function ${\ensuremath{\xi}}_{{V}_{2}}(r)=〈{\ensuremath{\sigma}}_{i}{\ensuremath{\sigma}}_{i+r}〉$ $\ensuremath{-}〈{\ensuremath{\sigma}}_{i}{〉}^{2}$ along Cu-O(1) chains decays exponentially with interspin distance r at $T\ensuremath{\approx}0.$

According to the charge transfer model of Kudinov et a]. the photoinduced enhancement of conductivity in YBa2Cu3O6+x material can be explained by the photoexcitation of electron-hole pairs, and the subsequent transfer of electrons to the oxygen deficient CuOx planes where they become trapped in the CuO chain fragments, while the holes remain free in the superconducting CUO2 planes contributing to the superconducting current. In this paper we have employed the numerical cluster variation method (CVM) and the recently established relation between chain probability distribution p(n) and the average chain length n(av), to calculate the number of electrons being captured in the unoccupied p orbitals of O- ions incorporated in the CuO chains, thus producing the free holes in the CUO2 planes. Our results support the standing that several processes make contribution to the effects of persistent photoconductivity and photoinduced superconductivity. (C) 2007 Elsevier B.V. All rights reserved. 8th International Conference on Materials and Mechanisms of Superconductivity and High Temperature Superconductors, Jul 09-14, 2006, Dresden, Germany