Presents case reports of two psychiatric patients who suddenly deteriorated and burned in a severe psychiatric condition due to the circumstances they faced due to the COVID-19 pandemic, which required urgent admission and intensive psychiatric treatment. In the first case report, pandemic and restrictive measures were the predisposing factors for suicide attempt of the patient who is the war veteran with diagnosed complex PTSD, while the precipitating factors for the suicide attempt were impaired physician-patient communication, fear of losing a job and existential issues. There is a need to raise awareness in society that rising unemployment is associated with an increased number of suicides, as well as responsible and balanced media coverage of the COVID-19 pandemic. In the second case report, our patient with bipolar disorder got into relapse of disease with psychotic symptoms during the pandemic of COVID-19 after changes the work structure and after she illegally visited her son who was self-isolated after returning to B&H from abroad, with no self-protected equipment. Overall, both case studies illustrate the psychological potential that the crisis caused by the COVID-19 pandemic has on at-risk groups of psychiatric patients. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

: Understanding the role of religious communities in Croatia and Bosnia and Her-zegovina’s post-Communist societies is very important for grasping the nature and history of democratic development in these two countries. A close investigation reveals that the relationship between the political and religious elites is cruci-al, but also subject to change given the shifting nature of social developments. Three stages in this relationship can be observed. The first phase started with the collapse of Yugoslavia and Communism in 1991-1992 and lasted until the early 2000s. This was a formative stage for the new societies, and religion played a key role in the national homogenisation and construction of new identities. The second phase, which started in the early 2000s and lasted most of the decade, was a period of relative economic prosperity, with a weakening of the nationalist political elites’ sway, and consequently a weakening of the role of the religious organisations. The third phase, which started with the financial crisis of 2008 and is still ongoing, is marked by a renewed populist and rightist agenda in politics, which has also resulted in a strengthening of the public role of organised religion in both countries.

Background and aim Striving for harmonisation of specialty training and excellence of care in rheumatology, the European League Against Rheumatism (EULAR) established a task force to develop points to consider (PtCs) for the assessment of competences during rheumatology specialty training. Methods A systematic literature review on the performance of methods for the assessment of competences in rheumatology specialty training was conducted. This was followed by focus groups in five selected countries to gather information on assessment practices and priorities. Combining the collected evidence with expert opinion, the PtCs were formulated by the multidisciplinary task force, including rheumatologists, medical educationalists, and people with rheumatic and musculoskeletal diseases. The level of agreement (LoA) for each PtC was anonymously voted online. Results Four overarching principles and 10 PtCs were formulated. The overarching principles highlighted the importance of assessments being closely linked to the rheumatology training programme and protecting sufficient time and resources to ensure effective implementation. In the PtCs, two were related to overall assessment strategy (PtCs 1 and 5); three focused on formative assessment and portfolio (PtCs 2–4); three focused on the assessment of knowledge, skills or professionalism (PtCs 6–8); one focused on trainees at risk of failure (PtC 9); and one focused on training the trainers (PtC 10). The LoA (0–10) ranged from 8.75 to 9.9. Conclusion These EULAR PtCs provide European guidance on assessment methods throughout rheumatology training programmes. These can be used to benchmark current practices and to develop future strategies, thereby fostering continuous improvement in rheumatology learning and, ultimately, in patient care.

Parkinson`s disease (PD) is a progressive neurodegenerative disorder involving dopaminergic neurons from the substantia nigra. The loss of dopaminergic neurons results in decreased dopamine (DA) release in the striatum and thus impaired motor functions. DA is one of the key neurotransmitters monitored for the diagnosis, and during the progression and treatment of PD. Therefore, sensitive and selective DA detection methods are of high clinical relevance. In this study, a new microfluidic device utilized for electrochemical DA detection is reported. The microfluidic sensing device operates in the range of 0.1 - 1000 nM DA requiring only ~ 2.4 µL sample volume, which corresponds to detectable 240 amol of DA. Using this sensor, we were able to monitor the changes in DA levels in cerebrospinal fluid (CSF) and plasma of a mouse model of PD and following the treatment of drug L-3,4-dihydroxyphenylalanine (L-DOPA), which reversed the parkinsonian symptoms in PD mice.

People suffering from hearing impairment often have difficulties participating in conversations in so-called cocktail party scenarios where multiple individuals are simultaneously talking. Although advanced algorithms exist to suppress background noise in these situations, a hearing device also needs information about which speaker a user actually aims to attend to. The voice of the correct (attended) speaker can then be enhanced through this information, and all other speakers can be treated as background noise. Recent neuroscientific advances have shown that it is possible to determine the focus of auditory attention through noninvasive neurorecording techniques, such as electroencephalography (EEG). Based on these insights, a multitude of auditory attention decoding (AAD) algorithms has been proposed, which could, combined with appropriate speaker separation algorithms and miniaturized EEG sensors, lead to so-called neurosteered hearing devices. In this article, we provide a broad review and a statistically grounded comparative study of EEG-based AAD algorithms and address the main signal processing challenges in this field.

Supplemental Digital Content is available in the text. Checkpoint inhibitors (CPIs) have demonstrated a heterogenous spectrum of response and disease progression that may not be fully captured by conventional response criteria, such as a limited degree of progression, known as oligoprogression, which could benefit from local treatment. We retrospectively analyzed data from all patients diagnosed with metastatic melanoma, who received CPI between January 2006 and March 2018 at Royal Marsden. We enrolled 36 patients who experienced progression in a maximum of 3 metastatic sites, after achieving disease control from therapy with CPI, and were radically treated with the locoregional approach. We carried out Kaplan-Meier analysis to obtain progression free-survival post-first oligoprogression (PFS-PO1), overall survival (OS) post-first oligoprogression, and OS estimates. The median time to oligoprogression from the start of CPI was 12 months. At a median follow-up of 34 months, the median PFS-PO1 was 32 months, with 50% of patients not progressed at the time of the data cutoff. The median OS-post-first oligoprogression was not reached. At a median follow-up of 52 months (from the first cycle of CPI), the median OS was not reached, with 75% of patients alive at the time of analysis. Univariate and multivariate analyses demonstrated that baseline American Joint Committee on Cancer stage IV M1a or M1b is associated with a longer PFS-PO1 compared with stage M1c or M1d. We observed that local therapy for oligoprogression after CPI can result in durable disease control, suggesting that locoregional treatment should be considered in patients being treated with immunotherapy. However, prospective evaluation, perhaps in randomized trials, is needed.

Abstract Background Conventional miltefosine dosing (2.5 mg/kg/day) for treatment of visceral leishmaniasis (VL) is less effective in children than in adults. A higher allometric dose (median 3.2 mg/kg/day) was therefore investigated in paediatric VL patients in Eastern Africa. Results of this trial showed an unforeseen, lower than dose-proportional increase in exposure. Therefore, we performed a pooled model-based analysis of the paediatric data available from both dosing regimens to characterize observed non-linearities in miltefosine pharmacokinetics (PK). Methods Fifty-one children with VL were included in this analysis, treated with either a conventional (n = 21) or allometric (n = 30) miltefosine dosing regimen. PK data were analysed using non-linear mixed-effects modelling. Results A two-compartment model following first-order absorption and linear elimination, with two separate effects on relative oral bioavailability, was found to fit these data best. A 69% lower bioavailability at treatment start was estimated, presumably due to initial malnourishment and malabsorption. Stagnation in miltefosine accumulation in plasma, hampering increased drug exposure, was related to the increase in cumulative dose (mg/kg/day). However, the allometric regimen increased exposure 1.7-fold in the first treatment week and reduced the time to reach the PK target by 17.4%. Conclusions Miltefosine PK in children suffering from VL are characterized by dose-dependent non-linearities that obstruct the initially expected exposure levels. Bioavailability appeared to be affected by the cumulative dose, possibly as a consequence of impaired absorption. Despite this, allometric dosing led to a faster target achievement and increased exposure compared with conventional dosing.

Background: Age-related epigenetic dysregulations are associated with several diseases, including cancer. The number of stochastic epigenetic mutations (SEM) has been suggested as a biomarker of life-course accumulation of exposure-related DNA damage; however, the predictive role of SEMs in cancer has seldom been investigated. Methods: A SEM, at a given CpG site, was defined as an extreme outlier of DNA methylation value distribution across individuals. We investigated the association of the total number of SEMs with the risk of eight cancers in 4,497 case–control pairs nested in three prospective cohorts. Furthermore, we investigated whether SEMs were randomly distributed across the genome or enriched in functional genomic regions. Results: In the three-study meta-analysis, the estimated ORs per one-unit increase in log(SEM) from logistic regression models adjusted for age and cancer risk factors were 1.25; 95% confidence interval (CI), 1.11–1.41 for breast cancer, and 1.23; 95% CI, 1.07–1.42 for lung cancer. In the Melbourne Collaborative Cohort Study, the OR for mature B-cell neoplasm was 1.46; 95% CI, 1.25–1.71. Enrichment analyses indicated that SEMs frequently occur in silenced genomic regions and in transcription factor binding sites regulated by EZH2 and SUZ12 (P < 0.0001 and P = 0.0005, respectively): two components of the polycomb repressive complex 2 (PCR2). Finally, we showed that PCR2-specific SEMs are generally more stable over time compared with SEMs occurring in the whole genome. Conclusions: The number of SEMs is associated with a higher risk of different cancers in prediagnostic blood samples. Impact: We identified a candidate biomarker for cancer early detection, and we described a carcinogenesis mechanism involving PCR2 complex proteins worthy of further investigations.

Over the past few decades, nanotechnology has increasingly been considered to be attractive technology that has revolutionized the food sector. Nanomaterials, unlike conventional microscale materials, having novel characteristics can improve sensory quality of foods by imparting novel texture, colour, appearance, processability and stability during shelf life. The physicochemical characteristics of a nanomaterial are important as they can affect the outcome of the risk assessment. This paper provides an overview of the application of nanotechnology in the field of food processing and packaging. In addition, this paper also discussed toxic effects of nanomaterials and food labeling. The results of this paper shows that today there is a divided opinion on the use of nanotechnology in food processing and packaging because on the one hand there are the results of the study which reveal that the majority of consumers prefer the use of nanotechnology-based solutions, while on the other hand there is immense public concern regarding the toxicity and environmental effect of these nanoparticles.

Based on the strong-field approximation, we report results for high-order harmonic generation by bi-elliptical orthogonally polarized two-color (BEOTC) fields with frequency ratios of 2:1 and 3:1 and fundamental wavelengths of 800 and 1800 nm. A BEOTC field denotes the superposition of two copropagating counter-rotating elliptically polarized fields with different wavelengths and orthogonal semimajor axes. Its two limiting cases are the bicircular field and the linearly polarized orthogonal two-color field [D. B. Milo\ifmmode \check{s}\else \v{s}\fi{}evi\ifmmode \acute{c}\else \'{c}\fi{} and W. Becker, Phys. Rev. A 100, 031401(R) (2019)]. A detailed analysis of the high-order harmonic intensities and ellipticities as functions of the harmonic order, the ellipticity, and the relative phase between the two driving-field components is presented. Regions of the parameter space are identified where the harmonic ellipticities are very high. Surprisingly, this can be the case already for very small ellipticity (as small as $\ensuremath{\varepsilon}=0.01$) of the driving field. This can be important for practical applications. In the opposite limit where the BEOTC field is close to bicircular, the selection rules that govern the latter case can also be very quickly invalidated. For the 2:1 case, this can result in an apparent shift of the selection rules by one harmonic order.

The purpose of this paper is to analyze and compare two different business models called business to business and business to consumer. The first model -business to business or B2B is defined as the transfer of goods and services between businesses or firms without the interference of consumers. The second model, business to consumer or B2C is customer-oriented in which the goods and services are sold immediately to customers in the market. This research focuses on the performance of these two business models in North Macedonia and Serbia. Our analysis tries to provide information regarding the countries’ development in different sectors within B2B and B2C models that are affected by specific indicators such as net salaries, total employment level, investment and exports, and research&innovation. Furthermore, besides the analysis of these indicators separately for each country, the paper will show the results and compare the performance differences among listed developing countries.