By providing storage and computational resources at the network edge, which enables hosting applications closer to the mobile users, Multi-Access Edge Computing (MEC) uses the mobile backhaul, and the network core more efficiently, thereby reducing the overall latency. Fostering the synergy between 5G and MEC brings ultra-reliable low-latency in data transmission, and paves the way towards numerous latency-sensitive automotive use cases, with the ultimate goal of enabling autonomous driving. Despite the benefits of significant latency reduction, bringing MEC platforms into 5G-based vehicular networks imposes severe challenges towards poorly scalable network management, as MEC platforms usually represent a highly heterogeneous environment. Therefore, there is a strong need to perform network management and orchestration in an automated way, which, being supported by Software Defined Networking (SDN) and Network Function Virtualization (NFV), will further decrease the latency. With recent advances in SDN, along with NFV, which aim to facilitate management automation for tackling delay issues in vehicular communications, we study the closed-loop life-cycle management of network services, and map such cycle to the Management and Orchestration (MANO) systems, such as ETSI NFV MANO. In this paper, we provide a comprehensive overview of existing MANO solutions, studying their most important features to enable network service and resource orchestration in MEC-enhanced vehicular networks. Finally, using a real testbed setup, we conduct and present an extensive performance analysis of Open Baton and Open Source MANO that are, due to their lightweight resource footprint, and compliance to ETSI standards, suitable solutions for resource and service management and orchestration within the network edge.

Background Immune-related diarrhoea/colitis (ir-D/C) is a common adverse event of immune checkpoint inhibitor (ICI) therapy. Guidelines recommend corticosteroid (CS) treatment; however, the average treatment duration for ir-D/C remains poorly defined. Methods All advanced melanoma patients treated with ICI therapy at the Royal Marsden Hospital between 2011 and 2016 were reviewed to identify ir-D/C cases alongside clinical variables. Results 117 any-grade ir-D/C episodes occurred in 109 (21%) patients out of a total of 519 patients treated (ipilimumab=77 episodes, anti-PD1=17 (nivolumab or pembrolizumab), ipilimumab and nivolumab=23 (ipi+nivo)) (seven patients had ir-D/C more than once on different lines of treatment) and >/=grade 3 ir-D/C occurred most frequently (63/519 patients (12%) vs 29/519 (5%) grade 1, and 25/519 (5%) grade 2). Median onset (days) of all-grade ir-D/C after starting ICI therapy was 41 for ipilimumab (IQR 24 to 59, n=77), 91 for anti-PD1 (IQR 46 to 355, n=17) and 45 for ipi+nivo (IQR 24 to 67, n=23). In 71/117 (61%) patients, ir-D/C episodes were treated with CS (17% grade 2; 79% grade 3/4): 54 being steroid-responsive; 17 being steroid-refractory and received additional anti-tumor necrosis factor (TNF) treatment. Median grade 3 ir-D/C CS duration was similar across treatments, averaging 58 days. Median overall CS duration (days) was longer in the grade 3/4 D/C steroid-refractory group (94 vs 45 days). Infection developed in 11/71 (15%) CS recipients and in 6/17 (35%) anti-TNF recipients. In 65/117 (55%) patients, ir-D/C episodes were investigated with flexible sigmoidoscopy. Of these patients, 38/65 (58%) had macroscopic colitis and 12/65 (18%) had microscopic colitis. The steroid-refractory group had more macroscopic changes, 13/17 (76%), than the steroid-responsive group, 22/41 (54%). Conclusion Rates of grade 3 ir-D/C were higher than reported in clinical trials. The 58-day median duration of CS therapy for grade 3 ir-D/C places a significant number of patients at risk of complications. We demonstrate that microscopic colitis is an important subgroup, advocating biopsies in ir-D/C even with macroscopically normal bowel.

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 40,000 RT-qPCR results since its commencement at the beginning of April 2020. However, due to ongoing demand and competition for critical resources, alternative testing strategies were sought. In this work, we present a clinically-validated standard operating procedure (SOP) for high-throughput SARS- CoV-2 detection by RT-LAMP in 25 minutes that is robust, reliable, repeatable, sensitive, specific, and inexpensive.

Quercetin (QU), a hyperthermic sensitizer, when combined with cisplatin (CP) affects tumor growth. To determine the effects of QU and CP and their interactions, multimodal treatment in vitro and in vivo models under physiological and hyperthermic conditions was performed. In vitro, different sensitivity of T24 and UMUC human bladder cancer cells was observed after short-term exposure to QU (2 h) and CP (1 h). Effects of both compounds were investigated at low and high micromolar concentrations (1 and 50 µM, respectively) under both thermal conditions. QU acted in additive or synergistic manner in combination with CP between physiological condition and hyperthermia. As determined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, short-term application of QU and CP reduced cell viability. Clonal assay also indicated that combined treatment with QU and CP is lethal to bladder cancer cells in both conditions. In vivo, CP (5 or 10 mg kg−1) and QU (50 mg kg−1) acted synergistically with hyperthermia (43 °C) and inhibited tumor growth, activated immune effectors and increased mice survival. Our results demonstrate that combined treatment with CP and QU may increase death of tumor cells in physiological and hyperthermic conditions which could be clinically relevant in locoregional chemotherapy.

Reptiles, especially turtles, are becoming increasingly popular as pets. The haematological evaluation of turtles is an irreplaceable diagnostic tool in veterinary practice. However, the morphologic distinctiveness of turtle blood limits the use of electronic cell-counting devices, making time-consuming, manual counting techniques and evaluation of blood smears necessary. Many samples are dispatched to a laboratory over long distances, where a delay of 24 h or more may occur. At weekends, this interval may exceed 48 h. The objective of the present study was to determine the effect of storage duration at refrigerator temperature (4 °C) on the counts of red blood cells (RBC) and white blood cells (WBC), and on the mean corpuscular volume (MCV) and packed cell volume (PCV) in blood samples from healthy adult red-eared sliders. Blood samples were collected by venipuncture from the occipital venous sinus from six apparently healthy adult red-eared sliders, aged 2 to 4 years. Blood samples were analysed immediately after sampling to obtain the baseline value (BV) of the red blood cell count, white blood cell count and packed cell volume percentage. Blood was stored at 4 °C and the haematological analyses were performed after 24h, 48h and 72h. The results showed the same level of stability for RBC and WBC count, and MCV values during 72 hours of storage at 4 °C and for PCV during 48 hours. Handling of blood samples, and duration of storage of the blood samples can significantly influence the results/values of haematological tests. Consequently, the obtained values of the determined haematological parameters of improperly stored or handled blood samples can give a misleading interpretation of the results on the animal’s health status.

Background: Cochlear dysfunction can arise not only from various factors such as ear diseases but also from systemic disorders of the body. The occurrence of otologic symptoms such as hearing loss, dizziness, and tinnitus can be due to cardiovascular disorders. Therefore, current understandings in the field of the diagnosis and therapy of cardiovascular diseases (CVDs) should include, among others, evidence of otologic disorders. Objective: The aim of this study is to determine the association between risk factors for CVD and cochlear dysfunction. Methods: The cross-sectional study included 128 participants with major CVD risk factors who underwent auditory function examination (pure tone audiometry). Results: There were 52 women (40.6%) and 76 men (59.4%) in total. The mean age of the participants was 58 years (a range of 28–83 years). The mean age among participants with hearing loss was 60 (±10.88), whereas the mean age among participants that had normal hearing thresholds was 54 (±12.18). Sensorineural hearing loss (SNHL) was measured in 59% of participants, of most frequent mild degree hearing loss. The prevalence of SNHL was higher in participants with arterial hypertension (P < 0.001, OR = 5.881, 95% CI 2.694–12.837) and the most common among them was moderate degree hearing impairment (38%). There is also a statistically significant association of SNHL with dyslipidemia and elevated body mass index (P < 0.001, [OR]: 4.118, 95% [CI]: 1.873–9.053 and P< 0.001, [OR]: 1.517, 95% [CI]: 1.237–1.859 ) with moderate and profound hearing loss. Conclusion: Based on the data obtained, it seems that the presence of major cardiovascular risk factors was a significant predictor for cochlear dysfunction.

Recent catastrophic consequences of coronavirus pandemic stimulate some deeper analysis of present level of globalization, particularly connected with public health problems One definition of globalization may be that it is the integration of capital, technology, and information across national borders in a way that is creating a single global market and, to some degree, a global village Besides economic, it includes many different processes such as development of communications systems, the increase in human mobility, the integration of trade and investment across boundaries, the spread of democracy and human rights, the increasing role of nongovernmental organizations in international politics, the growing concern about global epidemics, and ecological matters such as climate change that are happening at the same time and in many cases reinforcing one another Up till now, in June 2020, there have been over 20,000 published scientific papers on Coronavirus Disease-2019 (COVID-19), which is an unprecedented level of interest in any topic in the entire history of science Besides the described effect of remdesivir on reducing the length of the illness and the announced research on the effect of dexamethasone on reducing the mortality rate, science has not offered any other news on medication effectiveness so far After the vaccine’s effectiveness in developing antibodies and protecting from COVID-19 is proven, then its safety will need to be proven Vaccines have to be harmless and their only effect on the organism should be the developing of permanent immunity to the novel coronavirus However, never have we in history, as humanity, had planned to simultaneously vaccinate 4 or 5 billion people Most of us welcomed positive globalization process, but with the recent pandemic of corona disease, we are introducing negative part of globalization with many unpredictable developments Indeed, globalization is both inevitable and usually desirable and contains advantageous and disadvantageous issues It is a source of both hope and of apprehension and is an accelerating process in flow of information, technology, goods and services, and production means Globalization has a complex influence on perinatal health The bonds that link perinatologists together transcend geographic, political, religious, and lingual differences, resulting in a globalization that optimizes perinatal care

Background: Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominantly inherited disorder caused by an accumulation of amyloid fibrils in tissues due to mutations in the transthyretin (TTR) gene. The prevalence of hATTR is still unclear and likely underestimated in many countries. In order to apply new therapies in a targeted manner, early diagnosis and knowledge of phenotype-genotype correlations are mandatory. This study aimed to assess the prevalence and phenotypic spectrum of hATTR in Austria. Methods: Within the period of 2014–2019, patients with ATTR-associated cardiomyopathy and/or unexplained progressive polyneuropathies were screened for mutations in the TTR gene. Results: We identified 43 cases from 22 families carrying 10 different TTR missense mutations and confirmed two mutational hot spots at c.323A>G (p.His108Arg) and c.337G>C (p.Val113Leu). Two further patients with late onset ATTR carried TTR variants of unknown significance. The majority of patients initially presented with heart failure symptoms that were subsequently accompanied by progressive polyneuropathy in most cases. A total of 55% had a history of carpal tunnel syndrome before the onset of other organ manifestations. Conclusions: Our study underlined the relevance of hATTR in the pathogenesis of amyloid-driven cardiomyopathy and axonal polyneuropathy and indicated considerable genetic heterogeneity of this disease in the Austrian population. The estimated prevalence of hATTR in Austria based on this study is 1:200,000 but a potentially higher number of unknown cases must be taken into account. With respect to new therapeutic approaches, we strongly propose genetic testing of the TTR gene in an extended cohort of patients with unexplained heart failure and progressive polyneuropathy.

Purpose: To report a rare occurrence of ocular dirofilariasis in Bosnia and Herzegovina and provide a short overview on clinical characteristics and treatment options for ocular dirofilariasis. Methods: A 75-year-old woman was admitted to the University Clinical Centre Tuzla with pain and redness in her left eye. A live, white, coiled, and active worm was noticed in subconjunctival space of bulbar conjunctiva. Results: After successful surgical extraction, the parasite was identified as the adult form of Dirofilaria repens. There were no signs of intraocular or systemic inflammation. Conclusion: Ophthalmologists should have in mind a possible infestation, especially in cases with repeated inflammatory reactions and swelling of the ocular region, which does not respond to conventional therapy.

BACKGROUND Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). METHODS We enrolled 4,735 patients (age 63.6 ± 11.3 yrs, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (n=1,992 patients) and adenosine (n=18); ≤2.0 for exercise (n=2,087) or dobutamine (n=638). RESULTS Force-based LVCR was obtained in all 4,735 pts. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57 % of patients with abnormal LVCR nevertheless showed increase in stroke volume. CONCLUSIONS Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Abstract In this article, we describe the Cayley graphs of pseudo-unitary homogeneous semigroups with zero 0, which are 0-disjoint unions of their subsets indexed by a groupoid.

Hercegovački pršut as a traditional dry-cured smoked ham (prosciutto) produced by using an open fire that can be potentially contaminated with polycyclic aromatic hydrocarbons (PAHs) and can pose a health risk for consumers. The aim of this research was to identify the types and concentrations of 16 PAHs in 34 samples of traditionally smoked prosciutto. Out of 16 investigated PAHs, identified in the EPA (Environmental Protection Agency) list of priority pollutants, 14 compounds were detected. Average levels of cancerogenic benzo[a]pyrene (BaP) and PAH4 (benzo[a]anthracene (BaA), benzo[b]fluoranthene (BbF), chrysene (Chry), and benzo[a]pyrene (BaP)) ranged from <LOQ (level of quantification) to 5.08 μg/kg and 0.45 μg/kg to 22.67 μg/kg. Two analyzed samples exceeded currently prescribed values according to the Bosnia and Herzegovina legislation for BaP concentrations and one sample for PAH4 content. PAH16 concentrations were on average between 2.92 μg/kg and 87.6 μg/kg. The highest PAH concentrations were found in samples from the Herzegovina-Neretva canton. The results of the research highlight the importance of standardizing smoking procedures and manufacturing practice, in the production of Hercegovački pršut, in order to reduce the PAH content.