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Lejla Ramić, P. Sator

Topical therapy plays an important role in the treatment of psoriasis. It is the gold standard in mild psoriasis cases and is also recommended in addition to UV and systemic therapy in cases of moderate to severe psoriasis. In this overview article we summarize the current therapeutic options, taking into account special localizations (scalp, facial, intertriginous/genital, or palmoplantar lesions) and situations (hyperkeratotic or inflammatory forms), as well as the therapy options during pregnancy and breastfeeding. In the initial phase, the combination of topical corticosteroids and vitamin D analogues has proven to be the therapy of choice, as well as monotherapy in each case. In maintenance therapy, fixed combination therapy is recommended once or twice a week.

Monika Hezareh Rothmann, P. Møller, Y. Essig, L. Gren, V. Malmborg, M. Tunér, J. Pagels, A. Krais et al.

Biofuel is an attractive substitute for petrodiesel because of its lower environmental footprint. For instance, the polycyclic aromatic hydrocarbons (PAH) emission per fuel energy content is lower for rapeseed methyl ester (RME) than for petrodiesel. The present study assesses genotoxicity by extractable organic matter (EOM) of exhaust particles from combustion of petrodiesel, RME and hydrogenated vegetable oil (HVO) in lung epithelial (A549) cells. Genotoxicity was assessed as DNA strand breaks by the alkaline comet assay. EOM from combustion of petrodiesel and RME generated the same level of DNA strand breaks based on equal concentration of total PAH (i.e. net increases of 0.13 [95% confidence interval (CI): 0.002, 0.259 and 0.12 [95% CI: 0.01, 0.24] lesions per million base pairs, respectively). In comparison, the positive control (etoposide) generated much higher level of DNA strand breaks (i.e. 0.84, 95% CI: 0.72, 0.97) lesions per million base pairs). Relatively low concentrations of EOM from RME and HVO combustion particles (<116 ng/ml total PAH) did not cause DNA strand breaks in A549 cells, whereas benzo[a]pyrene and PAH-rich EOM from petrodiesel combusted using low oxygen inlet concentration were genotoxic. The genotoxicity was attributed to high molecular weight PAH isomers with 5-6 rings. In summary, the results show that EOM from combustion of petrodiesel and RME generate the same level of DNA strand breaks on equal total PAH basis. However, the genotoxic hazard of engine exhaust from on-road vehicles is lower for RME than petrodiesel because of lower PAH emission per fuel energy content.

Debarpan Dhar, S. Mehanovic, Walter N. Moss, C. Miller

Mammalian orthoreovirus (MRV) is a prototypic member of the Spinareoviridae family and has ten double-stranded RNA segments. One copy of each segment must be faithfully packaged into the mature virion, and prior literature suggests that nucleotides (nts) at the terminal ends of each gene likely facilitate their packaging. However, little is known about the precise packaging sequences required or how the packaging process is coordinated. Using a novel approach, we have determined that 200 nts at each terminus, inclusive of untranslated regions (UTR) and parts of the open reading frame (ORF), are sufficient for packaging each S gene segment (S1-S4) individually and together into replicating virus. Further, we mapped the minimal sequences required for packaging the S1 gene segment to 25 5′ nts and 50 3′ nts. The S1 UTRs alone are not sufficient, but are necessary for packaging, as mutations of the 5′ or 3′ UTRs led to a complete loss of virus recovery. Using a second novel assay, we determined that 50 5′nts and 50 3′ nts of S1 are sufficient to package a non-viral gene segment into MRV. The 5′ and 3′ termini of the S1 gene are predicted to form a panhandle structure and specific mutations within the predicted stem of the panhandle region led to a significant decrease in viral recovery. Additionally, mutation of six nts that are conserved in the three major serotypes of MRV and are predicted to form an unpaired loop in the S1 3′UTR, led to a complete loss of viral recovery. Overall, our data provide strong experimental proof that MRV packaging signals lie at the terminal ends of the S gene segments and offer support that the sequence requirements for efficient packaging of the S1 segment include a predicted panhandle structure and specific sequences within an unpaired loop in the 3′ UTR.

B. Katana, Amra Mačak Hadžiomerović, Eldad Kaljić, Adnan Mujezionović, Sead Kojić, Bojana Stanišić, Jasmina Bajrović, M. Míková et al.

Introduction: Knee osteoarthritis (OA) develops gradually and causes pain, a decrease in range of motion, muscle mass, and strength and leads to a decrease in physical activity and a poor quality of life for the patient. The aim of this study was to investigate the effects of different physiotherapy programs on pain intensity, range of motion, and quality of life in people with knee OA. Methods: The study was designed as a prospective, experimental, and randomized trial. Sixty subjects of both sexes and all ages with OA of the knee were enrolled in the study. In the studied Group I (n = 30), in addition to the standard protocol, high induction electromagnetic stimulation was applied using a Salus Talent device with a strength of 3 T and a frequency of up to 50 Hz for 10 min. In the test Group II (n = 30), in addition to the standard protocol, high-intensity laser therapy (HILT) with a power of 5 J was applied with the help of the Ilux Yag 1064 device for 7 min. The therapy protocol for both test groups lasted 8 weeks, with subjects treated once a week. Results: Analysis of the mean scores on the VAS scale shows that in both groups, the lowest mean scores were recorded in the III measurement (4.35) and the highest in the I measurement (7.96). In all three measurements, there was a difference in the extent of mobility of internal rotation in the form of a higher average range of motion in the test group II, in which HILT was applied. Analysis of the mean scores on the knee injury and osteoarthritis outcome score quality of life scale showed that in both groups, the lowest mean scores were recorded at the first measurement (14.84), with the mean score increasing at the second (32.95) and third measurements (41.08). Conclusion: Both methods showed significant results in reducing pain intensity, improving knee mobility, activities of daily living, and quality of life in people with knee OA. The obtained data do not give preference to any method but indicate them as adequate physiotherapy protocols to improve the function and quality of life of people with knee OA.

A. Mujanović, F. Ng, T. Meinel, T. Dobrocky, E. Piechowiak, C. Kurmann, D. Seiffge, S. Wegener et al.

Background: The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion. Aim: The aim of this analysis was to summarize the available clinical evidence on no-reflow in patients with acute ischemic stroke. Methods: A systematic literature review and a meta-analysis of clinical data on definition, rates, and impact of the no-reflow phenomenon after reperfusion therapy was carried out. A predefined research strategy was formulated according to the Population, Intervention, Comparison, and Outcome (PICO) model and was used to screen for articles in PubMed, MEDLINE, and Embase up to 8 September 2022. Whenever possible, quantitative data were summarized using a random-effects model. Results: Thirteen studies with a total of 719 patients were included in the final analysis. Most studies (n = 10/13) used variations of the Thrombolysis in Cerebral Infarction scale to evaluate macrovascular reperfusion, whereas microvascular reperfusion and no-reflow were mostly assessed on perfusion maps (n = 9/13). In one-third of stroke patients with successful macrovascular reperfusion (29%, 95% confidence interval (CI), 21–37%), the no-reflow phenomenon was observed. Pooled analysis showed that no-reflow was consistently associated with reduced rates of functional independence (odds ratio (OR), 0.21, 95% CI, 0.15–0.31). Conclusion: The definition of no-reflow varied substantially across studies, but it appears to be a common phenomenon. Some of the no-reflow cases may simply represent remaining vessel occlusions, and it remains unclear whether no-reflow is an epiphenomenon of the infarcted parenchyma or causes infarction. Future studies should focus on standardizing the definition of no-reflow with more consistent definitions of successful macrovascular reperfusion and experimental set-ups that could detect the causality of the observed findings.

N. Malanović, D. Vejzović

The continuous use of antibiotics is associated with the spread of antimicrobial resistances and the not yet clear link to cancer development. Many conventional antibiotics have already shown different effects on a variety of cancer types raising questions for their rational use in cancer. However, discrepancy in the observed trend for some antibiotics reducing cancer development and being associated with higher risk of cancer underscores the lack of understanding the complex link between antibiotics and cancer. Here, we briefly summarize the possible antibiotic-mediated effects on cancer and conclude that those effects can be direct via i) specific targeting of tumor/cancer, ii) antimicrobial activity and iii) immunomodulatory activity whereby iv) indirectly caused effects primarily affect immune equilibrium between bacteria, cancer and immune cells. Furthermore, we also conclude that there is a great need for bulk profiling, comprehensive screening programs in all countries and in-depth studies to understand the risks and benefits of antibiotic use.

G. Aad, B. Abbott, K. Abeling, N. J. Abicht, S. Abidi, A. Aboulhorma, H. Abramowicz, H. Abreu et al.

Thanh N. Nguyen, Muhammad M. Qureshi, D. Strambo, D. Strbian, S. Räty, C. Herweh, M. Abdalkader, M. Olivé-Gadea et al.

Background: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. Methods: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. Results: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64–82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3–10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85–1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35–2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07–2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0–2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). Conclusions: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The fibrosis of the LA, which is characteristic of AF, causes mechanical dysfunction of the LA and may also be present in patients without LA enlargement. LA strain represents a surrogate marker of this mechanical dysfunction. Early detection of LA dysfunction may be crucial in identifying patients who are more likely to experience AF recurrence following cardioversion and ablation. Before cardioversion and ablation, the probability of AF recurrence might be predicted, which could lead to better patient selection, an individualized therapeutic strategy with reduced risk and focused follow-up. Purpose The aim of this study was to evaluate the additional predictive value of LA function assessed by using strain echocardiography for early AF recurrence after cardioversion and ablation. Methods 94 patients diagnosed with symptomatic persistent atrial fibrillation (EHRA symptom score ≥3 (mean age 59.4 ± 12.2 years, 58% male, 42%female), preserved LV ejection fraction were prospectively analyzed. In 39 (41,5%) patients pharmacological cardioversion was done after saturation with antiarhythmic drugs,in 27 (28,7%) patients planed electrical cardioversion was done after medical saturation with antiarrhythmic drugs and failure of pharmacological cardioversion, and in 28 (29,8%) patients planed RF ablation was performed. Complete echocardiography evaluation including strain and volume index LA was performed before cardioversion and ablation. The rhythm evaluation was done in the first month after cardioversion and RF ablation (35±5 days). The primary endpoint was persistent AF recurrence. Results 29 (30,8%) patients had AF recurrence in the overall study population, independently of duration of AF or method of rhythm control. Peak atrial longitudinal strain (PALS) ≤15% had the highest incremental predictive value for AF recurrence (HR =8.42, 95% CI: 3.17–25.12, p < 0.001). In patients with non-dilated LA, PALS≤15% remained an independent predictor of AF recurrence (HR = 5.32, 95% CI: 1.77–17.42, p = 0.005). Conclusion This study shown that, in addition to LA dilatation, LA function as determined by PALS can provide a prognostic value for early AF recurrence after cardioversion or ablation. PALS also predicted AF recurrence in patients with nondilated LA. These findings highlight the additional prognostic usefulness of LA strain and recommend its implementation in the systematic assessment of AF patients prior to the choice of rhythm/rate control.

In the strong-field ionization of atomic and molecular systems, the photoelectron is exposed to the long-range Coulomb force which is neglected in the standard theories based on the strong-field approximation (SFA). We introduce an ansatz which takes into account the Coulomb effects and at the same time is as simple as the standard SFA. Our Coulomb distorted plane wave-Volkov approximation provides analytical expressions for the relevant matrix elements. We also present a generalization of this approximation taking into account first-order term of an expansion in the atomic potential. Similarly as in the standard improved SFA, this generalized approximation describes well the rescattering plateau and the cutoff observed in the photoelectron spectra. Our new approximation is illustrated with numerical examples of strong-field ionization of the hydrogen atom exposed to linearly and circularly polarized laser pulses. The spectra obtained are slightly flatten in comparison with the SFA spectra and this effect is stronger for shorter laser wavelengths.

A. Beganović, B. Petrovic, M. Surić Mihić

Occupational exposure in Bosnia and Herzegovina is regulated by the national regulation on radiation protection for occupational and public exposure. All radiation workers are required to be monitored using whole body passive thermoluminescent dosemeters and, in case of non-uniform external exposures, by dosemeters that would indicate dose to the most affected body parts. Exposed workers are almost exclusively employed in the medical field, and some of them work in nuclear medicine departments where they handle unsealed radioactive sources. Introduction of the positron emission tomography-computed tomography (PET-CT) in two largest clinical centers in the country was expected to cause the increase of equivalent doses to hands received by staff handling the positron emitting radionuclides. Hence, routine monitoring of finger doses became a necessity. The purpose of this study was to evaluate the available data on monitoring with ring dosemeters during PET-CT procedure in two hospitals in Bosnia and Herzegovina and compare them with other practices in the nuclear medicine department, as well as with the results of monitoring in other countries. In general, results confirm that effective doses, as well as equivalent doses to hands, are well below annual dose limits. Finger dosemeters have been proven to be an invaluable asset in the incidental situations that sometimes occur in nuclear medicine departments. Different number of patients and differences in injection methodologies are identified as a possible source of differences between doses in two hospitals. Overall, routine evaluation of doses to hands provides a sound basis for possible optimization processes, as well as confirmation of good practices.

G. Spinetti, Martina Mutoli, S. Greco, Federica Riccio, S. Ben-Aicha, Franziska Kenneweg, A. Jusic, D. de Gonzalo-Calvo et al.

Diabetes mellitus, a group of metabolic disorders characterized by high levels of blood glucose caused by insulin defect or impairment, is a major risk factor for cardiovascular diseases and related mortality. Patients with diabetes experience a state of chronic or intermittent hyperglycemia resulting in damage to the vasculature, leading to micro- and macro-vascular diseases. These conditions are associated with low-grade chronic inflammation and accelerated atherosclerosis. Several classes of leukocytes have been implicated in diabetic cardiovascular impairment. Although the molecular pathways through which diabetes elicits an inflammatory response have attracted significant attention, how they contribute to altering cardiovascular homeostasis is still incompletely understood. In this respect, non-coding RNAs (ncRNAs) are a still largely under-investigated class of transcripts that may play a fundamental role. This review article gathers the current knowledge on the function of ncRNAs in the crosstalk between immune and cardiovascular cells in the context of diabetic complications, highlighting the influence of biological sex in such mechanisms and exploring the potential role of ncRNAs as biomarkers and targets for treatments. The discussion closes by offering an overview of the ncRNAs involved in the increased cardiovascular risk suffered by patients with diabetes facing Sars-CoV-2 infection. Graphical Abstract

Žana Stanić, R. Fureš, M. Vulić, E. Čečuk, M. Plazibat, Z. Hrgović, A. Cerovac

7. Cabrera C, Radolec M, Prescott A, De La Cruz C, Beck S. Interdisciplinary approach for the medical management of gestational gigantomastia. AJP Rep. 2020;10(03):e304e308. 8. Lesavoy MA, GomezGarcia A, Nejdl R, Yospur G, Syiau TJ, Chang P. Axillary breast tissue: clinical presentation and surgical treatment. Ann Plast Surg. 1995;35(4):356360. 9. Fletcher MB, Corsini LM, Meyer MD, Osswald SS. Gestational gigantomastia: a case report and brief review of the literature. JAAD Case Rep. 2020;6(11):11591161. 10. Mangla M, Chhatwal J, Nautiyal R, Prasad D. Gestational gigantomastia in the setting of myasthenia gravis. J Obstet Gynaecol India. 2019;69(S1):8487. 11. Husain M, Khan S, Bhat A, Hajini F. Accessory breast tissue mimicking pedunculated lipoma. BMJ Case Rep. 2014;2014:bcr20142 04990. 12. Khan RN, Parvaiz MA, Khan AI, Loya A. Invasive carcinoma in accessory axillary breast tissue: a case report. Int J Surg Case Rep. 2019;59:152155. 13. Lokuhetty MD, Saparamadu PA, AlSajee DM, AlAjmi R. Gigantomastia in pregnancy with an accessory axillary mass masquerading as inflammatory carcinoma. Diagn Cytopathol. 2011;39(2): 141143. 14. Swelstad MR, Swelstad BB, Rao VK, Gutowski KA. Management of gestational gigantomastia. Plast Reconstr Surg. 2006;118(4): 840848. 15. Antevski BM, Smilevski DA, Stojovski MZ, Filipovski VA, Banev SG. Extreme gigantomastia in pregnancy: case report and review of literature. Arch Gynecol Obstet. 2007;275(2):149153. 16. Alhindi N, Mortada H, Alzaid W, Al Qurashi AA, Awan B. A systematic literature review of the clinical presentation, management, and outcome of gestational gigantomastia in the 21st century. Aesthetic Plast Surg. 2022;47:1029. 17. Hassayoune N, Mhallem Gziri M, Lentini A, et al. Severe gestational gigantomastia: from mastectomy to staged autologous breast reconstruction. A case report. JPRAS Open. 2021;29:6570. 18. Lapid O. Breast reconstruction after mastectomy for gestational gigantomastia. Aesthetic Plast Surg. 2013;37(2):388391. 19. Qin F, Si L, Zhang H, et al. Management of gestational gigantomastia with breast reconstruction after mastectomy: case report and literature review. J Int Med Res. 2020;48(6):030006052092046.

I. Burazor, O. Djokić, M. Perić, T. Bilic, O. Subic, T. Rankovic-Nenezic, N. Tasić, D. Tasić et al.

Type of funding sources: None. Obesity and overweight play a key role in the development of cardiovascular disease or myocardial ischemia, particularly today, as does their relationship to traditional and non-traditional risk factors. Despite, diet and weight management are grossly under-met per desired body mass index (BMI) threshold goals among very high-risk patients with established atherosclerotic cardiovascular disease (ASCVD). Thus, we aimed to investigate the presence of overweight and obesity in patients with established atherosclerotic cardiovascular disease who were admitted to our center. Patients and methods: Out of 790 patients admitted in our center between May and October 2021, we analyzed 341 patients who underwent isolated coronary artery by-pass surgery. Risk factors were noted as well as previous drug therapy, previous COVID 19 infection and vaccination. Anthropometric data were measured and BMI was determined. Obesity was defined as a BMI >_30 kg/m2 and overweight as a BMI between 25 and 30 kg/m2 . Patients with a BMI >_40 kg/m2 were considered morbidly obese. Early cardiac rehabilitation (phase 1) was performed by using personalized approach in all patients. Out of 341 patients (64.68±7.91 years of age), 275 were males (80.6%). The total of 97 (28.44%) had previous myocardial infarction. Blood pressure was well controlled. Majority of the patients reached the step 2 goals according to EAPC Guidelines on prevention (130.7±6.45/75.27±6.54mmHg), and were adherent to prescribed drugs. Mean heart rate was 65±5.65/minute. Only 27% of females and 22% of males had normal weight with BMI between 18.5 and 24.9.kg/m2. The mean BMI was 27.76 kg/m2. 50% of males and females were overweight. Obesity was noted in 23% of females and 27% of males (0.7% morbidly obese. Early cardiac rehabilitation was performed in all patients and they were all referred to participate the phase 2 programs. Diet and body weight reduction in overweight and obese ASCVD patients should continue to be a priority given the impact on cardiovascular risk. There is a potential for optimizing management of overweight and obesity in patients. In addition to a better risk factor profile, weight loss also leads to a better quality of life. Cardiovascular prevention and rehabilitation programs should include weight loss intervention. Different forms of self-support and use of digital health might be used as a specific component of a comprehensive intervention to reduce total cardiovascular risk, extend life expectancy, and improve quality of life.

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