Improving treatment of patients with psychosis in low-and-middle-income countries in Southeast Europe: Results from a hybrid effectiveness-implementation, pragmatic, cluster-randomized clinical trial (IMPULSE).

BACKGROUND: In Southeast Europe (SEE) standard treatment of patients with psychosis is largely based on pharmacotherapy with psychosocial interventions rarely available. DIALOG+ is a digital psychosocial intervention designed to make routine care therapeutically effective. This trial simultaneously examined effectiveness of DIALOG+ versus standard care on clinical and social outcomes (Aim 1) and explored intervention fidelity (Aim 2). METHODS: A hybrid type II effectiveness-implementation, cluster-randomized trial was conducted in five SEE countries: Bosnia and Herzegovina, Kosovo*, Montenegro, North Macedonia, and Serbia. The intervention was offered to patients six times across 12 months instead of routine care. The outcomes were subjective quality of life (primary), clinical symptoms, satisfaction with services, and economic costs. Intervention fidelity was operationalized as adherence to the protocol in terms of frequency, duration, content, and coverage. Data were analyzed using multilevel regression. RESULTS: A total of 81 clinicians and 468 patients with psychosis were randomized to DIALOG+ or standard care. The intervention was delivered with high fidelity. The average number of delivered sessions was 5.5 (SD = 2.3) across 12 months. Patients in the intervention arm had better quality of life (MANSA) at 6 months (p = 0.03). No difference was found for other outcomes at 6 months. Due to disruptions caused by the COVID-19 pandemic, 12-month data were not interpretable. CONCLUSIONS: DIALOG+ improved subjective quality of life of individuals with psychosis at 6 months (after four sessions), albeit with small effect size. The intervention has the potential to contribute to holistic care of patients with psychosis.

Morphological study of the rainbow scattering of protons by graphene.

We have studied metamorphoses of the angular rainbow pattern generated by classical rainbow scattering of protons by graphene. To analyze the rainbow pattern, a morphological method was developed. It focuses on the shape of the rainbow pattern rather than on the exact position of rainbow lines or the particle count. It comprises elements of the catastrophe theory, which provides a local model of the rainbow pattern and the reduced potential and an index theory of algebraic topology that allows the evolution of the rainbow pattern to be linked with bifurcations of critical points of the reduced potential. The obtained insight is summarized into five principles that allow an experimentalist to sketch a qualitatively correct rainbow pattern in the impact parameter plane and the distribution of the reduced potential critical points, just by observing the evolution of the angular rainbows. The morphological method should be applicable for the analysis of all structurally stable patterns in nature.

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum.

AIMS: Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene-environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. METHODS: The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). RESULTS: Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene-environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. CONCLUSIONS: The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

On the phase-space catastrophes in dynamics of the quantum particle in an optical lattice potential.

We have investigated the dynamics of a quantum particle in the optical lattice potential. Initially, the quantum particle was represented by a Gaussian wave packet, located in the center of the well. The corresponding Schrödinger equation was solved explicitly by the method of the Chebyshev global propagation. Obtained solutions were also used for the construction of the Wigner functions. We found a great number of local abrupt changes of the solution shape. To explain this behavior, we used the fact that structurally stable systems, which form the largest class of the low dimensional dynamical systems, can be modeled and classified according to the catastrophe theory. All important features of the exact solution were explained on the basis of the mathematical properties of the catastrophic model. Such an approach enabled us to extract relevant information out of numerical solutions without employing any kind of approximations. We have investigated the influence of the Wigner catastrophes on the details of the quantum-classical correspondence breakdown. The wave packet was found to expand rapidly, filling the whole classically available area of the phase space. It was found that its self-interference pattern saturates quickly. A region of the phase space emerges in which the Wigner function oscillations transform into the singularity driven fluctuations. Once this region covers the whole area of the phase space, a wave packet dynamics enters into the new regime where its Wigner function fluctuates around the ergodic average. It will be shown that all mentioned processes are caused by the proliferation of the catastrophes and their mutual interactions.

CUSHING'S SYNDROME, A RISK FACTOR FOR VENOUS THROMBOEMBOLISM IS A CANDIDATE FOR GUIDELINES.

OBJECTIVES: The present paper aims to review important contemporary information about VTE risk in endogenous and exogenous CS, as a substantial discrepancy exists between the results of a recent meta-analysis confirming the increased risk for VTE and the absence of CS in VTE guidelines. METHODS: An extensive search of relevant databases (e.g. PubMed, Google Scholar, and Scopus) was performed in order to establish the interconnectedness of the following terms: Cushing's syndrome, venous thromboembolism, deep vein thrombosis, pulmonary embolism. RESULTS: The analysis demonstrated that patients with CS have about ten times the risk for VTE, particularly during the first year following the diagnosis of CS. Oral glucocorticoid users (with iatrogenic CS) have a 3-fold increase in risk of VTE in comparison with non-users. The most recent 2019 meta-analysis encompassed 7142 patients with endogenous CS (including Cushing's disease) undergoing transsphenoidal surgery or adrenalectomy, and their risk of unprovoked VTE was almost 18 times higher in comparison with a healthy population. CONCLUSION: Over the past 50 years considerable evidence of increased VTE risk in CS has been accumulated. It pertains to both endogenous and exogenous type of CS and has been confirmed in the vast majority, if not all the available studies, including meta-analyses. Nevertheless, official CS guidelines make no mention of CS as a VTE risk factor, even though it is important that not only physicians who treat CS, but also physicians who manage patients with suspected VTE be aware of increased VTE risk.

Coordinated self-interference of wave packets: a new route towards classicality for structurally stable systems.

This is a study of proton transmission through planar channels of tungsten, where a proton beam is treated as an ensemble of noninteracting wave packets. For this system, the structural stability manifests in an appearance of caustic lines, and as an equivalence of self-interference produced waveforms with canonical diffraction patterns. We will show that coordination between particle self-interference is an additional manifestation of the structural stability existing only in ensembles. The main focus of the analysis was on the ability of the coordination to produce classical structures. We have found that the structures produced by the self-interference are organized in a very different manner. The coordination can enhance or suppress the quantum aspects of the dynamics. This behavior is explained by distributions of inflection, undulation, and singular points of the ensemble phase function, and their bifurcations. We have shown that the coordination has a topological origin which allows classical and quantum levels of reality to exist simultaneously. The classical behavior of the ensemble emerges out of the quantum dynamics without a need for reduction of the quantum to the classical laws of motion.

Optical Properties and Structure of As-Sb Chalcohalide Glasses by Raman Scattering and Density Functional Theory Calculations.

We report an investigation of the optical properties, structure, and vibrational modes of SbxAs37-xS48I15 glasses (0 at. % < x < 37 at. %). Optical parameters such as the refractive index, the absorption coefficient, and the optical band gap are correlated with the glass composition. All parameters were found to follow an almost linear dependence with the antimony content x. Both the refractive index and the absorption edge wavelength exhibit a systematic increase against x. Off-resonant Raman spectra of the glasses spectra were measured and analyzed. Structural units, representative of the glass structure, were optimized by density functional theory (DFT) calculations, providing vibrational spectra in agreement with the experiments. Raman spectra were interpreted based on the harmonic frequencies and the activities of vibrational modes obtained by the DFT analysis. The results showed evidence in favor of statistical mixing of iodine atoms, among the various pyramidal units, hence discarding structural models suggesting the presence of isolated pyramidal molecules of the types AsI3/SbI3. Both experimental data and DFT results suggested that iodine atoms exhibit much higher propensity to replace sulfur atoms in antimony than in arsenic-based pyramids. In addition, comparison of experimental and simulated spectra of selected clusters in mixed glasses indicates that it is more probable to find corner-sharing Sb-based pyramids than As-based ones.

Green synthesis and characterization of nontoxic L-methionine capped silver and gold nanoparticles.

The simple green method for synthesis of stable L-Methionine (L-Met) capped silver (Ag@LM NPs) and gold (Au@LM NPs) nanoparticles (NPs) without adding any additional reduction agent or stabilizer was developed. Colloidal dispersions were characterized by UV-Vis spectrophotometry. The size and spherical shape of NPs were evaluated by transmission electron microscopy. Their surface covering was confirmed by atomic force microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential measurements. Density functional theory calculations pointed that the preferential adsorption mode of L-Met on both Ag and Au surfaces was a vertical binding geometry via -NH2 group, while horizontal binding mode via S and -NH2 groups is also possible. The genotoxicity (evaluated by the micronucleus assay) of NPs, as well as their effects on some oxidative stress parameters (catalase activity, malondialdehyde level), were assessed in vitro using human peripheral blood cells as a model system. The influence of NPs on the morphology of lymphocyte cells studied using atomic force microscopy revealed that the membrane of cells remained unaffected after the treatment with NPs. When considering the effects of NPs on catalase activity and malondialdehyde level, neither particle type promoted oxidative stress. However, the treatment of lymphocytes with Ag@LM NPs induced a concentration-dependent enhancement of the micronuclei incidence and suppression of the cell proliferation while Au@LM NPs promoted cell proliferation, with no significant effects on micronuclei formation. The Ag@LM NPs were more prone to induce DNA damage than Au@LM NPs, which makes the latter type more suitable for further studies in nano-medicine.

Retrospective analysis of routine use of a double heat cycle (DHC) during radiofrequency segmental ablation (ClosureFAST(™) ) of saphenous veins.

BACKGROUND: Recent experimental evidence suggests that increasing energy delivered during radiofrequency segmental ablation (RFSA) of varicose veins might further improve outcomes. OBJECTIVES: To evaluate occlusion rates and safety of the routine use of double heat cycle (DHC) during RFSA of incompetent saphenous veins up to 3 years after the initial treatment. METHODS: Retrospective review of prospectively collected duplex ultrasound (DUS) and complication rate data of successive patients from the Viennese, Lower Austrian and Slovenian regions treated for incompetent saphenous veins, followed up on a yearly basis for up to 3 years after the procedure. RESULTS: Between 2007 and 2011, 258 patients (389 veins; 322 great saphenous veins (GSV)] had been treated with DHC ClosureFast. Patients' return was 46% (122 subjects) 3 years after RFSA [140 GSV and 31 small saphenous veins (SSV)] with a mean follow-up time of 24.93 ± 11.77 months. At 36 months Kaplan-Meier survival analysis showed the occlusion probability of 98.6% (95% CI: 1.005-0.966). All SSV were closed. Except for three cases of dysaesthesia which disappeared within a year, there have not been major side-effects. CONCLUSIONS: Results of the retrospective analysis indicate that the routine use of DHC during RFSA for incompetent saphenous veins is equally safe but potentially more efficacious considering mid-term venous closure rates.

High variability of indoor radon concentrations in uraniferous bedrock areas in the Balkan region.

In this work the strong influence of geological factors on the variability of indoor radon is found in two of three geologically very different regions of South-Eastern Europe. A method to estimate the annual mean concentration when one seasonal measurement is missing is proposed. Large differences of radon concentrations in different rooms of the same house and significant difference in radon concentrations in one season comparing it to the others are noted in certain cases. Geological factors that can lead to such behavior are discussed.

Effect of sex hormones on plasma phospholipid fatty acid composition in intact rats and rats with bilaterally occluded carotid arteries.

The effects of 8-days treatment with 17alpha-estradiol (33.3 microg/kg) and progesterone (1.7 mg/kg) on plasma lipids and fatty acid composition of plasma phospholipids were examined in intact (INT) and bilaterally common carotid arteries occluded (BCO) male Wistar rats. Significant decrease of triglyceride level was found in BCO rats after the estradiol treatment. Both hormones elevated proportion of 18:1n-7 fatty acid in INT, but they failed to have such an effect in BCO. Estradiol increased 22:5n-3 and total n-3 polyunsaturated fatty acids (PUFA) in intact, and decreased 18:2n-6 in BCO rats. Significantly lower level of total n-3 was found in progesterone-treated than in estradiol-treated BCO rats. Given that n-3 PUFA have many beneficial effects on cell and tissue function, while n-6 PUFA have mostly the opposite effects, estradiol, rather than progesterone, was seen to improve plasma lipids and phospholipids FA profiles in INT and BCO animals. Estradiol significantly elevated the estimated activity of delta9-desaturases and progesterone of delta5-desaturase in BCO group, with no effects in INT rats.

Extensive myelitis after oral polio vaccination: MRI features.

A 7-year-old boy presented with fever and ataxia 20 days after oral polio vaccination. Magnetic resonance imaging showed extensive myelitis, involving both anterior and posterior horns of the gray matter. Complete posttreatment recovery was evident. Postvaccinal myelitis after oral polio vaccination, of either infectious or immune mediated etiology, is very rare entity that should be promptly recognized in order to initiate adequate treatment.

Treatment of chronic venous disease with flavonoids: recommendations for treatment and further studies.

OBJECTIVES: A variety of studies have suggested that flavonoids are effective for the treatment of CVD. However, many questions remain about their mechanism of action and when, how, and for what signs and symptoms they should be used. METHOD: A panel of experts in CVD met in Budapest, Hungary in December 2011 to discuss the current state of knowledge of CVD and the role of flavonoids in its treatment. The discussion was based on a literature search in the current databases. The goals of this paper are recommendations for further studies on the use of flavonoids in the treatment of CVD. RESULTS: There is good evidence to recommend the use of flavonoids in the treatment of CVD. However, because of the poor quality of some older clinical trials, inadequate reporting, and insufficient information, much work is still needed to firmly establish their clinical efficacy and to determine when and how they should be employed. In particular, long-term randomized, placebo-controlled, double-blind studies are needed to establish the efficacy and safety of flavonoids. Additional studies are also needed to establish their mechanism of action, pharmacokinetics, toxicity, and cost-effectiveness. CONCLUSIONS: Aside from good evidence for the use of flavonoids in CVD further studies are indicated to establish long term treatment in this indication.

Simple external manual manoeuvres to pass the radiofrequency catheter through a bending segment of a saphenous vein.

Smooth passage of a catheter through a varicose saphenous vein during radiofrequency ablation may prove a challenging task. Various types of venous bending in the transverse and sagittal planes and their combinations within the saphenous compartment may be pretty well appreciated by ultrasound examination. Several simple manual manoeuvres like stretching, pushing or lifting along with limb re-positioning may often help the surgeon to advance the catheter through the segments by temporarily changing their special configuration. In this way the number of patients otherwise considered unsuitable for endovascular catheter procedures like radiofrequency or laser ablation may be considerably reduced.

Telangiectasias resistant to sclerotherapy are commonly connected to a perforating vessel.

Leg telangiectasias resistant to repeated courses of sclerotherapy in patients without deep and superficial venous incompetence are not uncommon. Little is known about factors which may underlie the resistance. Among 26 patients with such telangiectasias we found a direct communication of the vessels with deep and saphenous veins in 65% of patients. Ultrasound-guided injection of 0.5% polidocanol foam into the feeding veins or their perforating segments led to clearance of all the telanagiectasias. In 23% of cases no feeding veins could have been identified by ultrasound. Direct injections of a sclerosant into perforating feeding veins may clear refractory telangiectasias in a majority of patients though it is obvious that other factors may contribute to the failure of sclerotherapy in others.

Early granulomatous foreign body reactions to a novel alginate dermal filler: the system's failure?

BACKGROUND: Cutaneous granulomas after a soft filler injection represent one of the worst scenarios for both patient and injector. OBJECTIVES: To present clinical and histopathological features of granulomatous nodular reactions induced by a new alginate-based dermal filler (Novabel(®)), and put it in context of the process of injectable soft tissue fillers approval and promotion in the EU. METHODS: A case series of four patients injected with Novabel(®) for volume restoration of the face and hands, who developed severe foreign body reactions. RESULTS: Four patients injected with Novabel(®) into tear troughs and/or dorsa of hands developed severe granulomatous reactions within months after injections. As we injected with the new filler into a total of 10 patients, a high incidence of 40% of the disfiguring adverse effect was observed. The inadequate response of manufacturer to our reporting the side-effects along with the available data on registration process of dermal fillers confirmed that the area is not well-regulated. CONCLUSIONS: The status of dermal fillers as class III medical devices, and the process of their approval and marketing in the EU need to be seriously reconsidered to avoid unnecessary and serious adverse reactions.