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.

Introduction: A Holter blood pressure monitoring is a basic method for the diagnosis and evaluation of hypertension therapy. Hypertension in children and adolescents is defined as an increase of systolic/diastolic pressure, which is equal, or above 95th percentile blood pressure for sex, age, and height. Aim: The aim of this study is to analyze the etiology of arterial hypertension (AH) in the pediatric population. Methods: Research had descriptive and retrospective character. During the period from March 2006 to April 2020, 1527 registered continuous Holters of blood pressure were analyzed. Data were taken from the medical documentation of patients that were hospitalized on Pediatric Clinic (register of continuous Holter of blood pressure). Results: Out of the total number of registered and analyzed patients 833 were male (54.5%) with dominant age 15–19 years of life 774 (50.6%), school-age children 660 (43.2%), preschool children 93 (6.1%). We had 902 (59%) first registrations and 626 (41%) control registrations. AH was verified in 52 patients (387 records of continuous Holter of blood pressure were performed to them). Primary AH was verified in 27 patients and secondary AH in 25 patients. Forty patients (76.9%) were treated with monotherapy while combined therapy was used in 12 (23.1%) of cases. Renal cause was in 28% patients, endocrine in 24%, cardiovascular in 24%, neurological in 16%, and rheumatic in 8% of patients with secondary AH. Conclusion: Continuous Holter of blood pressure represents useful diagnostic method and method of control of high blood pressure in children and adolescents. It should be routine method in everyday pediatric clinical practice especially in pediatric cardiology.

Contemporary wireless networks dramatically enhance data rates and latency to become a key enabler of massive communication among various low-cost devices of limited computational power, standardized by the Long-Term Evolution (LTE) downscaled derivations LTE-M or narrowband Internet of Things (NB IoT), in particular. Specifically, assessment of the physical-layer transmission performance is important for higher-layer protocols determining the extent of the potential error recovery escalation upwards the protocol stack. Thereby, it is needed that the end-points of low processing capacity most efficiently estimate the residual bit error rate (BER) solely determined by the main orthogonal frequency-division multiplexing (OFDM) impairment–carrier frequency offset (CFO), specifically in small cells, where the signal-to-noise ratio is large enough, as well as the OFDM symbol cyclic prefix, preventing inter-symbol interference. However, in contrast to earlier analytical models with computationally demanding estimation of BER from the phase deviation caused by CFO, in this paper, after identifying the optimal sample instant in a power delay profile, we abstract the CFO by equivalent time dispersion (i.e., by additional spreading of the power delay profile that would produce the same BER degradation as the CFO). The proposed BER estimation is verified by means of the industry-standard LTE software simulator.

© The Author(s) 2020. Published by ARDA. Abstract Background: The subject of this research is the creation of an optimal school bench design with the aim of determining the most favorable posture of students while sitting, taking into account the relevant ergonometric and biomechanical characteristics of the human body. For the proposed model of the school bench which allows adjusting the different slopes of its surface, the corresponding computer model of the student and the table was first created, and then biomechanical and RULA analysis was performed in order to determine the maximum load in the lumbar part. Next, for each test subject of given weight, it was necessary to determine the amount of maximum load in lumbar zone L3/L4 for different slope angles and to determine the critical angles at which the maximum permissible load of 3400 N is reached.

The present study was conducted to investigate the water quality of the Trstionica River, Bosnia and Herzegovina. The physicochemical properties (temperature, pH, conductivity, total solids after evaporation at 105 °C), content of metals (calcium (Ca), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), sodium (Na), nickel (Ni), lead (Pb) and zinc (Zn)), and anions (chloride (Cl−), and phosphate (PO4)) were determined in water samples collected at seven locations during two sampling periods: unstable weather conditions (precipitation), and stable weather conditions (without precipitation). There was a significant difference in the content of individual parameters in the river water depending on the sampling time. For determination of metals concentrations, which were below the limit of detection, a preconcentration method using an ion-exchange resin was applied. The metals concentrations during the rainy day were in the order Ca > Mg > Na > Fe > Cu > Zn > Pb > Mn with mean values of 343, 6.03, 1.94, 0.18, 0.20, 0.03, 0.02, 0.01 mg dm−3, respectively, and during stable weather conditions: Ca > Mg > Na > Cu > Fe > Mn > Zn with mean values of 288, 7.62, 2.38, 0.11, 0.10, 0.01, 0.01 mg dm−3, respectively. Cd, Cr, and Ni concentrations were below limit of detection in both cases. Obtained values were compared with World Health Organization (WHO) regulations. The results showed that the Trstionica River in the investigated part of the stream meets most of the parameters required by the regulations. The correlation between analysed parameters was assessed, as well. Based on the calculated water quality index values, the water of Trstionica River falls into the category of excellent water.

Cervical cancer is the fourth most common malignancy in women worldwide and a leading cause of cancer-related mortality in developing countries. Important etiological factors in this cancer are high-risk human papillomaviruses (HPV), as roughly 96% of cervical cancer cases are positive for these oncoviruses. On the other hand, it has been recently pointed out that E6/E7 oncoproteins of high-risk HPV can upregulate the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) axis. Likewise, several recent reports showed that checkpoint blockades targeting PD-1/PD-L1 pathways have achieved efficient clinical responses via suppressing cancer progression and improving survival in several types of human cancers including metastatic cervical cancer. In this review, we summarize recent advances in our understanding of the PD-1/PD-L1 signaling pathway and its interaction with high-risk HPV and their oncoproteins, which could have an important impact on the management of HPV-associated cancers including cervical.

Već sedamdesetih godina dvadesetoga stoljeća razvijeni su prvi koncepti suvremenoga pojma medijske pismenosti. Nakon toga uslijedilo je nekoliko inicijativa da bi se bolje prepoznala važnost učenja i nužnost razvoja medijske pismenosti. Devedesetih godina dolazi do institucionalizacije medijske pismenosti i do definiranja osnovnih smjernica i elemenata potrebnih za razvoj i implementaciju medijske pismenosti u društvu. Otada pa sve do danas koncept medijske pismenosti ubrzano se mijenjao. Dinamičan i ubrzan razvoj informacijskih i komunikacijskih tehnologija, pojava novih medija i medijskih navika konzumenata doveli su do promjene samoga koncepta i razumijevanja medijske pismenosti. Dotad se medijska pismenost prepoznavala kao instrument za zaštitu konzumenata od negativnih medijskih poruka i sadržaja (najčešće djece i mladih), a potom i kao instrument za zaštitu konzumenata od tehnologije te kao preduvjet za bolju građansku participaciju. Danas tumačenje pojma medijske pismenosti promatramo i u zavisnosti od društva i konteksta u kojem se medijska pismenost koristi i na način kako se razvija. Prema tome, koncept i primjena u ovisnosti su o geografskom i tehnološkom pristupu medijima, a samim time i o evaluaciji i načinu na koji komuniciramo preko različitih medija. Stoga bi današnji koncept medijske pismenosti predstavljao oružje ili oruđe za borbu protiv negativnih medijskih sadržaja, manipulacije, lažnih vijesti, obmana, propagande, dezinformacija, a u svrhu kritičkoga i kreativnog izražavanja i bolje građanske participacije.

Recent studies have been showed important role of elevated iron levels in pathogenesis of Type 2 Diabetes mellitus (T2D) and insulin resistance. The aim of this study was to determine serum of free iron concentration in T2D patients and find out associations with lipid profile. The study included 51 participants (27 healthy control and 24 no treated diabetes patients), with ages from 45 to 65 45-65 ages and both gender. As expected, concentrations of serum iron were elevated in diabetic patients compare to healthy subjects while statistical significant difference were shown between iron levels in control group and group with good control of glycaemia (p<0.05). In addition, there was a significant positive correlation between free iron concentration and LDL cholesterol levels and negative significant correlation between iron concentrations with HDL cholesterol in diabetics (p<0.05). These findings suggest that increase serum of free iron concentrations may have an important role and influence in development of disease, especially in lipid metabolism and profile as well in risk of further complications of diabetes.

From the point of welding procedure evaluation, it is important to analyse welds for their impact toughness and transition temperature for three main zones: weld metal, heat-affected zone and base metal. This paper covers butt welds of two QT steel grades, 690 and 890, with thicknesses of 30 mm and 20 mm, respectively. They are interesting regarding yield strength and characteristic weld zones. Basic details of GMAW process used in experiment are provided, with temperatures for impact toughness tests of weld zones varied from +20 °C down to -60 °C. Based on acquired experimental results of impact toughness, fitting curves were developed by use of Oldfield model, i.e. hyperbolic tangent function. Acquired transition temperatures (TT) from fitting curves show mostly allowable values for all three weld zones. As expected, lower strength grade 690 possess higher impact toughness, in comparison to higher strength grade 890. The standardized criteria of minimal absorbed energy of 30 J (KV) and 50% of shear fracture (SF) show different transition temperatures (TT-30J and TT-50%SF), while general dependence of impact toughness to shear fracture (KV vs. SF) shows a reasonable trend. Finally, used GMAW procedures may be considered as acceptable, since for both steel grades (690 and 890) all three weld zones show better TT-30J values than minimal required by standard (TT-30J=-40 °C) for QT structural steels.

Introduction: Needlestick injuries (NSIs) are one of the most frequent routes of the transmission of bloodborne pathogens in health care settings and the substantial source of occupationally acquired bloodborne infections. They remain a significant problem for developing countries that lack the ability to implement more reliable technologies and available guidance because of the economic situation. The objectives of the study were to determine the frequency of NSIs among healthcare workers (HCWs) and supporting staff in primary health care, to investigate the factors that caused these injuries and to evaluate a set of implemented guides. Methods: A retrospective study of the Department of infection control records of NSIs between January 2003 and January 2016 was conducted. Incidence proportion (rate of injury risk) was calculated for each profession with reported NSIs. Results: A total of 156 NSIs and sharp injuries were reported to the Department of infection control during the 12-year period. Among the group of HCWs, medical nurses/technicians (54.49%) were the most common injured workers, and the lowest numbers were reported by a physical therapist and dental technicians (0.64%). In a total number of cases, support staff accounted for 16.67%. The most incidents occurred during the use of needles, in 146 (90.6%) cases. Calculated incidence proportion for medical doctors is 0.24%, 5.33% for dentists, and 13.8% for medical and dental nurses/technicians and laboratory technicians. For support staff, the calculated rate is 6.04%. Conclusions: At the primary health care level, the NSIs frequency among all employee profiles is lower and it is suggesting the possibility of underreporting cases. Healthcare facility management should consider introducing new and more reliable technologies to reduce the number of NSIs especially among nurses/technicians, laboratory technicians, and cleaning staff. Additional training and preventive measures should be directed towards the proper disposal of medical waste. Management of the Institution presented engagement to prevent the occurrence of NSIs, and it is a positive example for all countries in transition.