Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Crack Size and Undermatching Effects on Fracture Behavior of a Welded Joint.

Crack size and undermatching effects on fracture behavior of undermatched welded joints are presented and analyzed. Experimental and numerical analysis of the fracture behavior of high-strength low-alloyed (HSLA) steel welded joints with so-called small and large crack in undermatched weld metal and the base metal was performed, as a part of more extensive research previously conducted. J integral was determined by direct measurement using special instrumentation including strain gauges and a CMOD measuring device. Numerical analysis was performed by 3D finite element method (FEM) with different tensile properties in BM and WM. Results of J-CMOD curves evaluation for SUMITEN SM 80P HSLA steel and its weld metal (WM) are presented and analyzed for small and large cracks in tensile panels. This paper is focused on some new numerical results and observations on crack tip fields and constraint effects of undermatching and crack size keeping in mind previously performed experiments on the full-scale prototype. In this way, a unique combined approach of experimental investigation on the full-scale proto-type and tensile panels, as well as numerical investigation on mismatching and crack size effects, is achieved.

Endothelial Cell Adhesion Molecules- (un)Attainable Targets for Nanomedicines.

Endothelial cell adhesion molecules have long been proposed as promising targets in many pathologies. Despite promising preclinical data, several efforts to develop small molecule inhibitors or monoclonal antibodies (mAbs) against cell adhesion molecules (CAMs) ended in clinical-stage failure. In parallel, many well-validated approaches for targeting CAMs with nanomedicine (NM) were reported over the years. A wide range of potential applications has been demonstrated in various preclinical studies, from drug delivery to the tumor vasculature, imaging of the inflamed endothelium, or blocking immune cells infiltration. However, no NM drug candidate emerged further into clinical development. In this review, we will summarize the most advanced examples of CAM-targeted NMs and juxtapose them with known traditional drugs against CAMs, in an attempt to identify important translational hurdles. Most importantly, we will summarize the proposed strategies to enhance endothelial CAM targeting by NMs, in an attempt to offer a catalog of tools for further development.

The burden and health care use of patients with migraine and tension-type headache in post-conflict area of Serbia.

PURPOSE: The aim of the present study was to assess the burden and health care use of adult patients with migraine and tension type headache in a post-conflict area of Serbia. METHODS: This cross-sectional study was conducted on a representative sample of adults, living in predominantly Serb communities on the Kosovo and Metohija territory. The required data was obtained through a survey, utilizing a culturally-adapted questionnaire. The study sample comprised of 1,062 adults. RESULTS: In the year preceding the study, 49.7% of included subjects suffering from migraines and 27.5% of those experiencing tension type headache sought medical assistance for their condition. The majority (88.5%) of the respondents utilized non steroid antiinfammatory drugs as analgesic, while 14.2% used prophylactic treatment. Migraine sufferers reported losing on average 11.1 days in a 3-month period, while those experiencing tension type headache lost 4.7 days (p < 0.001) due to headaches, preventing them from partaking in professional, family and social activities. On headache-free days, 24.5% of the respondents were anxious or tense in anticipation of a headache onset, while 30% did not feel that the headache had completely resolved. Moreover, 11.5% of the sample reported never or rarely feeling in control of the headache, while 20% of the respondents were of view that their headaches were not taken seriously by their employer and co-workers and rarely discuss them. Adverse effect of headaches on education is more frequently noted by migraine sufferers than those experiencing tension type headache (p = 0.001), and this disparity persists in relation to career (p < 0.001) and family planning (p = 0.001). CONCLUSIONS: In Kosovo and Metohija, primary headaches exert a profound influence on the affected individuals and their community, and thus require recognition as one of the priorities of social initiatives aimed at the enhancement of public health.

Determination of the Actual Stress-Strain Diagram for Undermatching Welded Joint Using DIC and FEM.

This paper presents new methodology for determining the actual stress-strain diagram based on analytical equations, in combination with numerical and experimental data. The first step was to use the 3D digital image correlation (DIC) to estimate true stress-strain diagram by replacing common analytical expression for contraction with measured values. Next step was to estimate the stress concentration by using a new methodology, based on recently introduced analytical expressions and numerical verification by the finite element method (FEM), to obtain actual stress-strain diagrams, as named in this paper. The essence of new methodology is to introduce stress concentration factor into the procedure of actual stress evaluation. New methodology is then applied to determine actual stress-strain diagrams for two undermatched welded joints with different rectangular cross-section and groove shapes, made of martensitic steels X10 CrMoVNb 9-1 and Armox 500T. Results indicated that new methodology is a general one, since it is not dependent on welded joint material and geometry.

The first prevalence study of primary headaches in adults in a post-conflict area of Serbia.

AIM: The aim of the present study was to establish annual prevalence of primary headaches, migraine, and tension-type headache among adults in a post-conflict area of Serbia. METHODS: The data for this cross-sectional study was obtained via face-to-face interviews using questionnaires specifically designed for this purpose, in line with the available guidelines. The study sample included adults aged 18-65 years whose native language is Serbian with residence in six predominantly Serbian communities in Kosovo and Metohija. Relevant diagnoses were established according to the diagnostic criteria of the International Classification of Headache Disorders, 3rd edition. RESULTS: The study included 1062 adults. Analyses indicated 47.7% prevalence of primary headaches. The 1-year prevalence of migraine (with aura and without aura) and tension-type headache was established at 15.2% (3.3% and 11.9%), and 32.2%, respectively. One-year prevalence of chronic headache was calculated at 3.5%, while the prevalence of medication overuse headache was slightly lower at 2.9%. Primary headaches were more prevalent among women, participants residing south of the river Ibar, married or cohabiting individuals, as well as among interviewees (persons) who reported feeling unsafe in Kosovo and Metohija. This is the first study of the prevalence of primary headache disorders in Serbia. The obtained data is comparable to the data available for other countries, especially those in the Balkan region.

Say no to drugs: Bioactive macromolecular therapeutics without conventional drugs.

The vast majority of nanomedicines (NM) investigated today consists of a macromolecular carrier and a drug payload (conjugated or encapsulated), with a purpose of preferential delivery of the drug to the desired site of action, either through passive accumulation, or by active targeting via ligand-receptor interaction. Several drug delivery systems (DDS) have already been approved for clinical use. However, recent reports are corroborating the notion that NM do not necessarily need to include a drug payload, but can exert biological effects through specific binding/blocking of important target proteins at the site of action. The seminal work of Kopecek et al. on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers containing biorecognition motifs (peptides or oligonucleotides) for crosslinking cell surface non-internalizing receptors of malignant cells and inducing their apoptosis, without containing any low molecular weight drug, led to the definition of a special group of NM, termed Drug-Free Macromolecular Therapeutics (DFMT). Systems utilizing this approach are typically designed to employ pendant targeting-ligands on the same macromolecule to facilitate multivalent interactions with receptors. The lack of conventional small molecule drugs reduces toxicity and adverse effects at off-target sites. In this review, we describe different types of DFMT that possess biological activity without attached low molecular weight drugs. We classified the relevant research into several groups by their mechanisms of action, and compare the advantages and disadvantages of these different approaches. We show that identification of target sites, specificity of attached targeting ligands, binding affinity and the synthesis of carriers of defined size and ligand spacing are crucial aspects of DFMT development. We further discuss how knowledge in the field of NM accumulated in the past few decades can help in the design of a successful DFMT to speed up the translation into clinical practice.

Hyperbaric oxygen therapy in acute stroke: is it time for Justitia to open her eyes?

Hypoxia is a critical component of neuronal death in patients with stroke. Therefore increasing oxygenation of brain tissue seems to be a logical therapy against cerebral ischemia. Oxygen therapy exists in two modalities: normobaric hyperoxia therapy and hyperbaric oxygen therapy (HBO). HBO is a therapeutic procedure in which pure (100%) oxygen is administered at greater than atmospheric pressure in HBO therapy chambers. In this review article, we aimed to summarize the current knowledge regarding the therapeutic use of HBO in acute stroke patients. Literature review and electronic search were performed using PubMed, Medscape, and UpToDate with the keywords stroke, acute stroke, hyperbaric oxygen therapy, and hyperoxia. According to the reviewed literature, the use of HBO as routine stroke therapy cannot be justified in acute stage of stroke. More randomized, controlled studies are needed regarding safety and especially effectives of HBO in stroke patients. Also, standardized definitionof HBO should be proposed and used in all future studies.

Attenuation of neutrophil-mediated liver injury in mice by drug-free E-selectin binding polymer.

Inflammation with neutrophils infiltration is a prominent feature of alcohol-related liver disease (ARLD) and contributes to the severity of liver injury. Although an array of potential treatments has been studied, the standard treatment regimen is controversial and can induce severe side effects and infection-related complications. E-selectin, a cytokine inducible cell adhesion molecule, mediates the initial interaction of leucocytes with endothelial cells, and facilitates their further adhesion and extravasation into inflamed tissues. Given the important role of E-selectin in leukocytes trafficking, we hypothesized that a synthetic polymer presenting multiple copies of E-selectin binding peptide in a polyvalent manner (P-Esbp) may block the "roads" that facilitate neutrophil infiltration, inhibit the recruitment of neutrophils to the inflamed sites and reduce the extent of liver injury. We now demonstrate in vitro that P-Esbp reduced the recruitment of neutrophils (collected from blood of donors) on activated human umbilical vein endothelial cells (HUVEC) under flow conditions. Pre-treatment of mice with P-Esbp prior to alcohol binge attenuated alcohol-induced serum transaminase (ALT, AST) elevation, reduced pro-inflammatory cytokines (TNFα and IL-1ẞ) and chemokines (MIP-2/CXCL2 and MCP-1/CCL2) in National Institute on Alcohol Abuse and Alcoholism (NIAAA) model. Also, the up-regulation of neutrophil marker Ly6G and the number of MPO positive cells in the injured tissue was significantly reduced by the treatment, indicating diminished neutrophil infiltration. Moreover, as a result of P-Esbp treatment, E-selectin expression in the liver (mRNA and protein level) was downregulated, suggesting a potential to decrease ongoing local inflammatory response. Overall, our findings highlight the anti-inflammatory properties of the "drug-free" P-Esbp and its therapeutic potential to attenuate an excessive inflammation where infiltrating neutrophils can damage tissues and organs.

Is Balint training associated with the reduced burnout among primary health care doctors?

The aim of our study was to examine whether the participation in Balint group is associated with the reducing burnout syndrome among primary health care doctors. This investigation was conducted on a population of 210 doctors employed in primary health centers in Belgrade. Out of 210 doctors, 70 have completed Balint training for a period of at least 1 year, whereas 140 doctors have never attended this training (the Non-Balint group). The level of burnout among physicians was assessed with the Serbian translation of the original 22-item version of the Maslach Burnout Inventory - Human Services Survey which defines burnout in relation to emotional exhaustion, depersonalization and personal accomplishment. We found that 45.0% of the Non-Balint participants and 7.1% of the Balint-trained participants responded with symptoms of high level of emotional exhaustion, with a statistically significant difference (p < 0.001). In relation to depersonalization, 20% of the Non-Balint subjects were highly depersonalized compared to 4.4% of the Balint-trained subjects, with a statistically significant difference (p < 0.001). Regarding the personal accomplishment, 21.4% of the Non-Balint subjects and 7.1% of the Balint-trained subjects had a perception of low personal accomplishment, with a statistical significance (p < 0.001). In the multiple ordinal logistic model, with emotional exhaustion as a dependent variable, statistically significant predictor was female gender (OR = 2.51; p = 0.021), while Balint training was obtained as a protective factor (OR = 0.12; p < 0.001). Non-specialists were detected as a risk factor for depersonalization (OR = 2.14; p = 0.026) while Balint group was found as a protective factor (OR = 0.10; p < 0.001), according to the multiple ordinal logistic regression analysis. Regarding the reduced personal accomplishment, our results indicated that nonspecialists were at risk for this subdimension (OR = 2.09; p = 0.025), whereas Balint participants were protected (OR = 0.18; p < 0.001). Participation in Balint groups is associated with the reduced burnout syndrome among primary health care doctors.

How to use lasers for imaging attosecond dynamics of nuclear processes.

We identify a laser configuration in which attosecond electron wave packets are ionized, accelerated to multi-MeV energies, and refocused onto their parent ion. Magnetic focusing of the electron wave packet results in return currents comparable with large scale accelerator facilities. This technique opens an avenue towards imaging attosecond dynamics of nuclear processes.

Quantum theory of attosecond XUV pulse measurement by laser dressed photoionization.

The first reported measurements of single attosecond pulses use laser dressed single-photon extreme ultraviolet (XUV) ionization of gas atoms. The determination of XUV pulse duration from the electron spectrum is based on a classical theory. Although classical models are known to give a qualitatively correct description of strong laser atom interaction, the validity must be scrutinized by a quantum-mechanical analysis. We establish a theoretical framework for the accurate temporal characterization of attosecond XUV pulses. Our analysis reveals an improved scheme that allows for direct experimental discrimination between single and multiple attosecond pulses.

Numerical characterization of high harmonic attosecond pulses.

A numerical simulation of attosecond harmonic pulse generation in a three-dimensional field-ionizing gas is presented. Calculated harmonic efficiencies quantitatively reproduce experimental findings. This allows a quantitative characterization of attosecond pulse generation revealing information currently not accessible by experiment. The rapid phase variation and spatiotemporal distortions of harmonics are smaller than anticipated, allowing focusing of 30-nm, 750-as pulses to intensities in excess of 10(13) W/cm(2). Feasibility of such pulses brings novel applications such as extreme ultraviolet nonlinear optics and attosecond pump probe spectroscopy within reach.