ABSTRACT Between autumn 1943 and autumn 1944, the Wehrmacht’s 2nd Panzer Army applied novel methods to stem the ever-growing tide of Yugoslavia’s partisan movement. During the first two years of the uprising, the German doctrine for combating the guerrillas was based almost entirely on brute force; in battlefield terms, this amounted to persistent use of classic large-scale encirclement operations aimed at breaking particularly dangerous enemy concentrations. After it had become clear that this wasn’t working, the Germans slowly began applying a more diversified approach in late 1943, including more reliance on small unit tactics, flexible operational planning, and subversive propaganda. Although initially successful, these methods came too late to make a strategic impact on the course of the Yugoslavia campaign. Furthermore, they could not offset the effects of Berlin’s long-standing refusal to dedicate more resources to this secondary theater of war.

Isolation of Staphylococcus aureus is quite common in both the general population and hospital environment. The heterogeneity of the disease and the unique ability of S. aureus to develop resistance to the most recently discovered antibacterial drugs points to its ability to adapt and survive in different conditions. CA-MRSA is different from hospital strains of MRSA by its epidemiological, phenotypic and genotypic characteristics. The emergence of MRSA in the community suggests the need for a new approach to managing the indications and the certification of staphylococcal infections, with special emphasis on the selection of empiric antibiotic therapy. In the study, we analised of MRSA from 4341 samples taken from patients from the general population of Sarajevo Canton in the six-month period of follow-up processed at the Public Health Institute of Sarajevo Canton. We determined the epidemiological characteristics of the isolated strains. Methicillin resistance was determined by phenotypic methods. The following molecular methods were used for the confirmation of methicillin resistance: determination of the mecA gene, PFGE profile, genetic type of MRSA being determined by spa typing, the distribution of SCCmec types being examined, and the detected gene for PVL. The study stresses the need for national monitoring of spreading of the existing epidemic strains, as well as the monitoring of emergence of new strains which would enable the inclusion of our country in the international network of monitoring bacterial resistance.

Abstract:This paper analyses impact of aircraft noise on community around Podgorica Airport, Montenegro. The airport is located 12 km from the city centre of the Montenegro capital, Podgorica. It served 1.3 million passengers and 7.5 thousand operations in 2019. The noise impact assessment is conducted in IMPACT web-based modelling platform using the distribution of operations by aircraft types, time of the day, and radar tracks for the busiest day (August 15) in 2019. Noise contours are assessed for Lden and Lnight indicators. They were merged with the Global Human Settlement Layer to assess the number of people exposed to different noise levels. In addition, based on the World Health Organization recommended exposure levels related to their health implications, the percentages of the population highly annoyed and highly sleep-disturbed are estimated. Furthermore, facilities of public importance (schools, hospitals, churches, etc.) are assessed against compatibility with the requirements set for the Zones with increased noise protection in national regulations. The results show that the exposure of community around Podgorica Airport to aircraft noise is still not a serious issue. The near vicinity of the airport is industrial zone and the number of people highly annoyed by noise is approximately 3.2% of the total city population. Nevertheless, it is crucial to draw attention to planners to preserve airport neighbourhood from potential inhabiting, to avoid problems that some airports in the region are facing nowadays.

Chronic inflammatory lung diseases are characterized by uncontrolled immune response in the airways as their main pathophysiological manifestation. The lack of specific diagnostic and therapeutic biomarkers for many pulmonary diseases represents a major challenge for pulmonologists. The majority of the currently approved therapeutic approaches are focused on achieving disease remission, although there is no guarantee of complete recovery. It is known that angiotensin-converting enzyme 2 (ACE2), an important counter-regulatory component of the renin–angiotensin–aldosterone system (RAAS), is expressed in the airways. It has been shown that ACE2 plays a role in systemic regulation of the cardiovascular and renal systems, lungs and liver by acting on blood pressure, electrolyte balance control mechanisms and inflammation. Its protective role in the lungs has also been presented, but the exact pathophysiological mechanism of action is still elusive. The aim of this study is to review and discuss recent findings about ACE2, including its potential role in the pathophysiology of chronic inflammatory lung diseases:, i.e., chronic obstructive pulmonary disease, asthma, and pulmonary hypertension. Additionally, in the light of the coronavirus 2019 disease (COVID-19), we will discuss the role of ACE2 in the pathophysiology of this disease, mainly represented by different grades of pulmonary problems. We believe that these insights will open up new perspectives for the future use of ACE2 as a potential biomarker for early diagnosis and monitoring of chronic inflammatory lung diseases.

Summary Stress at the work place was declared by the World Health Organization as a worldwide epidemic. The stress caused by work appears when the balance between one’s own possibilities and the environment demands is disturbed, which leads to a poor mental state. The fact is that the majority of dentists find they are under constant stress, which is caused by the nature of dental work. Literature describes dentistry as an extremely stressful profession. The main stressors include the tendency toward technical perfection, the causation of pain in patients, the lack of patient cooperation during dental treatment, the failure to maintain the given appointments. Adequate education and preparation, even during dental studies, non-neglect of symptoms and difficulties at the work place, adequate and timely response to the identification of the cause and its elimination or balancing, have a key role in solving this great problem in modern dentistry.

The heritability of methylation patterns in tumor cells, as shown in recent studies, suggests that tumor heterogeneity and progression can be interpreted and predicted in the context of methylation changes. To elucidate methylation-based evolution trajectory in tumors, we introduce a novel computational method for methylation phylogeny reconstruction leveraging single cell bisulfite treated whole genome sequencing data (scBS-seq), incorporating additional copy number information inferred independently from matched single cell RNA sequencing (scRNA-seq) data, when available. We validate our method with the scBS-seq data of multi-regionally sampled colorectal cancer cells, and demonstrate that the cell lineages constructed by our method strongly correlate with original sampling regions. Our method consists of three components: (i) noise-minimizing site selection, (ii) likelihood-based sequencing error correction, and (iii) pairwise expected distance calculation for cells, all designed to mitigate the effect of noise and uncertainty due to data sparsity commonly observed in scBS-seq data. In (i), we present an integer linear program-based biclustering formulation to select a set of CpG-sites and cells so that the number of CpG-sites with non-zero coverage in the selected cells is maximized. This procedure filters out cells with read information in too few sites and CpG-sites with read information in too few cells. In (ii), we address the sequencing errors commonly encountered in currently available platforms with a maximum log likelihood approach to correct likely sequencing errors in scBS-seq reads, incorporating CpG-site copy number information in case it can be orthogonally obtained. Given the copy number and read information for a site in a cell, together with the overall sequencing error probability, we compute the log likelihood for all possible underlying allele statuses. If the mixed read statuses at the CpG-site for the cell are more likely due to sequencing error on homozygous alleles as opposed to the presence of alleles mixed methylation statuses, we correct the reads of the minority methylation status to the majority one. In (iii), we introduce a formulation to estimate distances between any pair of cells. As scBS-seq data is typically characterized by shallow read coverage, there is rarely read count evidence for two (or more, depending on CNV status) alleles at a CpG-site. Since allele-specific methylation has been shown to have increased frequency in cancer tissues, given the reads at a CpG-site, it is especially important to consider the possibility of unobserved alleles and their methylation status when determining the CpG-site9s possible methylation zygosities. Our method incorporates copy number information when available, and for each CpG-site in a cell, we compute a probability distribution across all possible methylation zygosities. Then, given specific distance values between pairs of distinct zygosities and the likelihood of each possible zygosity for each shared CpG-site in both cells, we compute the expected total distance between any pair of cells as the mean of expected distances across all shared CpG-sites. We leverage such pairwise distances in methylation phylogeny construction. Citation Format: Xuan C. Li, Yuelin Liu, Farid Rashidi, Salem Malikic, Stephen M. Mount, Eytan Ruppin, Kenneth Aldape, Cenk Sahinalp. Epigenomic tumor evolution modeling with single-cell methylation data profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB020.

As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, rather than discrete transcripts from the m14, m15 and m16 genes as annotated, there are five 3′-coterminal transcripts expressed over this region, all utilising a consensus polyA tail at the end of the m16 gene. Functional inactivation of any one of these genes had no measurable impact on viral replication. However, disruption of all five transcripts led to significantly attenuated dissemination to, and replication in, the salivary glands of multiple strains of mice, but normal growth during acute infection. Disruption of the m15 locus was associated with heightened NK cell responses, including enhanced proliferation and IFNγ production. Depletion of NK cells, but not T cells, rescued salivary gland replication and viral shedding. These data demonstrate the identification of multiple transcripts expressed by a single locus which modulate, perhaps in a concerted fashion, the function of anti-viral NK cells.

This study intends to valorize by-products of the industrial processing of tobacco to obtain nicotine and phenolics as value-added compounds. Three influential parameters of the microwave-assisted extraction-MAE (temperature, treatment time, and solvent/solid ratio) were studied for the optimization of the extraction protocol for tobacco leaves and three types of waste—scrap, dust, and midrib, respectively. Nicotine was the dominant bioactive compound in all extracts, ranging from 1.512 to 5.480% in leaves, 1.886 to 3.709% in scrap, 2.628 to 4.840% dust, and 0.867 to 1.783% in midrib extracts. Five phenolic compounds were identified and quantified, predominated by chlorogenic acid and rutin. Additionally, total phenol content and antioxidant activity were determined using spectrophotometric assays. Optimization was performed in two aspects: to obtain a maximum extraction yield with minimum nicotine content and to obtain a maximum extraction yield with maximum nicotine content. These findings demonstrate that tobacco waste is a valuable source of bioactive compounds and MAE can be a promising alternative technique to obtain extracts rich in targeted bioactive compounds, especially nicotine.