ABSTRACT Introduction: In recent years, immunotherapy for the treatment of solid cancer has emerged as a promising therapeutic alternative. Adoptive cell therapy (ACT), especially T cell-based, has been found to cause tumor regression and even cure in a percentage of treated patients. Checkpoint inhibitors further underscore the potential of the T cell compartment in the treatment of cancer. Not all patients respond to these treatments; however, many challenges remain. Areas covered: This review covers the challenges and progress in tumor antigen target identification and selection, and cell product manufacturing for T cell ACT. Tumor immune escape mechanisms and strategies to overcome those in the context of T cell ACT are also discussed. Expert opinion: The immunotherapy toolbox is rapidly expanding and improving, and the future promises further breakthroughs in the T cell ACT field. The heterogeneity of the tumor microenvironment and the multiplicity of tumor immune escape mechanisms pose formidable challenges to successful T cell immunotherapy in solid tumors, however. Individualized approaches and strategies combining treatments targeting different immunotherapeutic aspects will be needed in order to expand the applicability and improve the response rates in future.

INTRODUCTION Chronic diseases with disabilities have a huge pharmacoeconomic impact on the health budget, especially in countries with recent history of social and economic transition. The aim of this study was to identify total costs of treating patients with lumbar pain in medical facilities in the central part of the Republic of Serbia. MATERIAL AND METHODS This study was designed as a cost of illness study, using a bottom-up approach and it was conducted from a societal perspective. This study included 97 patients with lumbar syndrome who were treated in outpatient facilities in the Central part of Serbia. RESULTS Total costs of treating lumbar pain were about €200.40 ± €86.65 per patient per year, where the largest volume of direct costs were costs due to visits to specialists in primary health care institutions (€9.39 ± €6.66). Total indirect costs were €182.00 ± €78.66. DISCUSSION Our findings highlight the need to estimate the total costs of treating lumbar pain and evaluate the correlation between costs and other variables for larger population of these patients. CONCLUSION This study distinguished two important pharmacoeconomic aspects of treating lumbar pain. Firstly, indirect costs represent major part of total costs of treating lumbar syndrome. Secondly, differences in valuing medical services between countries with recent history of social and economic transition and countries within European Union are one of crucial reasons for difference in total costs of treating low back pain among patients in neighboring regions.

Cytological analysis of urine sediment is an integral part of urine analysis and a useful, cost-effective diagnostic tool for all routine clinical examinations, which can sometimes be overlooked in veterinary practice. Proper handling and timely urine sample analysis are essential for valid microscopic analysis. Microscopic urinary sediment testing is usually carried out with stained or unstained specimen. A common urine may contain a small number of cells (erythrocytes and leukocytes, epithelial cells) of several crystals, spermatozoids (male animals). In contrast, a large number of cells or casts, the presence of unusual types of crystals, neoplastic cells, parasites, and microorganisms include abnormal findings, requiring a specialized diagnostic approach. Correct identification of organic components of the urinary sediment are crucial for accurate and timely diagnosis of kidney disorders. Laboratory experts should be trained to properly identify and classify organic components of the urinary tract.

Bites of laboratory animals are treated as the bites of any other animals since the possibility of existence of pathogenic microorganisms, unfavorable for human health, in the rooms where these animals reside, is not excluded. A rare case of a laboratory rat bite, used for scientific research and previously infected with Pseudomonas aeruginosa , is presented here. The patient's wound was located on the forefinger of his hand and was 1 cm long and up to 0.2 cm deep. The antitetanus prophylaxis was administered in an ambulance, including antibiotic therapy with amoxicillin-clavulanate per os. There exists a need for checks and special guidelines for the handling and retention of laboratory animals. The patient has successfully remedied the wound, thanks to consistent antibiotic therapy and antitetanus prophylaxis, and possible inflammatory complications were prevented .

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection”. Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. The contribution of this study is to provide the first large-scale, international, multi-center variability assessment of the “virtual dissection” of the pyramidal tract (PyT). Eleven (11) experts and thirteen (13) non-experts in neuroanatomy and “virtual dissection” were asked to perform 30 PyT segmentation and their results were compared using various voxel-wise and streamline-wise measures. Overall the voxel representation is always more reproducible than streamlines (≈70% and ≈35% overlap respectively) and distances between segmentations are also lower for voxel-wise than streamline-wise measures (¾3mm and ¾ûmm respectively). This needs to be seriously considered before using tract-based measures (e.g. bundle volume versus streamline count) for an analysis. We show and argue that future bundle segmentation protocols need to be designed to be more robust to human subjectivity. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction techniques in this era of open and collaborative science.

Cattle farming, as one of the most important branches of livestock production, has longbeen confronted with the chronic problem of the decline in reproductive performances. In 2005, thenumber of cattle around the world amounted to about 1,370,000,000 heads of cattle, while in 2012this number was just over a billion, which indicates the importance of applying differentreproductive protocols in order to increase production. Heat stress leads to disorders of thephysiological and reproductive processes, as the rise in body temperature caused by heat stress hasdirect negative consequences on numerous cell functions. The study included a total of 54 Holstein-Friesian cows, 28 experimental and 26 control cows from PD Butmir farm with 5 lactations onaverage. Hormone protocols for estrus and ovulation were used in June and July 2013. Cows in theexperimental group were subjected to a Presynch + 5dCoS2 protocol. Cows that did not conceiveafter this protocol were immediately subjected to resynchronization with Cosynch -72 protocol. Thesuccess rate of the Presynch + 5dCoS2 protocol was 19%, while in the case of Cosynch 72 it was33%, which was statistically significant (p <0,05). The first presynchronization and synchronizationprotocol (5dCoS2) did not significantly help to improve the conception rate after the firstinsemination postpartum, but it is evident that they had a positive effect on another protocol (COS72)in the form of reduction in embryonic mortality in the summer months when embryonic loss is thegreatest.The COS72 protocol provides satisfactory results in the summer, but good fitness and healthmanagement, as well as heat stress reduction in accordance with the location and farm design arethe preconditions for a successful estrus and ovulation synchronization program prior to artificialinsemination.

Utjecaj gljiva truležnica roda Heterobasidion i Armillaria na pojavu truleži na stablima obične smreke provedeno je na Šumskogospodarskom području “Gornjebosansko”, gospodarska jedinica “Gornja Stavnja”, odjeljenje 65. Utvrđivanje prisutnosti truleži vršeno je na srušenim stablima obične smreke na premjernim površinama koje su raspoređene u sistematski postavljenoj mreži 100 m x 100 m. Uzorci su prikupljeni sa tri mjesta na dijelu debla zahvaćenom procesom truleži (početak zone truleži, sredina i vršna zona truleži). Na mjestima uzorkovanja uzimani su kolutovi drva debljine 5 cm. Analize uzoraka su provedene u laboratorijima Šumarskog fakulteta Univerziteta u Sarajevu. Za izravnu izolaciju gljivične DNA su pripremljeni uzroci drva mase 10-20 mg. Za amplifikaciju ciljanog segmenta DNK korištene su tubice s pripremljenim reagensima, proizvod ReadyToGo PCR beads tvrtke Amersham, Bioscience. Za amplifikaciju ciljanog segmenta ITS regije za rod Heterobasidion su korišteni početnice MJ-F, MJ-R, KJ-F i KJ-R, pomoću kojih je utvrđena međuvrsna raznolikost (tablica 2). Za amplifikaciju ciljanog segmenta ITS regiona za rod Armillaria su korišteni početnice ITS-1 i ITS-4, pomoću kojih je utvrđena samo pripadnost rodu. Za međuvrsnu raznolikost je vršena amplifikacija ciljanog segmenta IGS regiona za rod Armillaria pomoću početnice LR12 i O-1, te razgradnja endonukleazom AluI (tablica 3). Uspješnost amplifikacije je provjerena elektroforezom na agaroznom gelu. Interpretacija profila je izvršena pomoću molekularnog markera poznate veličine (100 bp) (slika 1). Na osnovi provedenih istraživanja unutar istraživane sastojine utvrđeno je 9 stabala s gljivom H. parviporum, 2 stabla s gljivom A. ostoyae, 1 stablo s gljivom A. cepistipes, te 17 stabala čiju trulež su uzrokovale ostale gljive truležnice (tablica 4). Gljiva H. annosum je uspješno identificirana iz plodišta. Na osnovi svega navedenog, može se zaključiti da je molekularnim analizama moguće utvrđivati međuvrsnu raznolikost gljiva ova dva roda iz uzoraka drveta sa truleži i plodišta gljiva.

Introduction: The main aim of the study was to examine the interdependence of values of the nutrition index, the use of medicaments, and alcohol consumption in the group of subjects with post-traumatic stress disorder (PTSD) and in control group without PTSD. Methods: To determine the interdependence of different indices of nutrition and the alcohol and drug consumption in both groups, the crosstab model was used. Results: In both of the tested groups, medicament users had higher average values for nutritional indexes compared to the subjects that are not the consumers of medicaments, but the confirmed differences were not statistically significant. The subjects with PTSD who consume alcohol had lower average values for nutritional indexes compared to the subjects who do not consume alcohol. In the control group, subjects who consumed alcohol had higher mean values for nutritional indexes than those who did not consume alcohol. Differences in the values of the nutrition index between alcohol and non-alcohol subjects were not statistically significant either in the PTSD group or in the control group. The subjects with PTSD had less average values of all the used nutrition indexes compared to the control group subjects, but the confirmed differences were not statistically significant. Conclusion: Our results indicate that medicaments use and alcohol consumption do not exert a statistically significant effect on the values of the nutrition index in any of the study groups. Possible concomitant use of drugs with the opposite effect on the monitored parameter (nitrazepam and amitriptyline vs. SSRI and bupropion) can lead to findings like this. We recommend further research to eliminate influence of pharmacodynamic effects of alcohol, drugs, and stress on the development of weight gain or loss.

Govedarstvo kao jedna od najznačajnijih grana stočarske proizvodnje se dugosuočava sa hroničnim problemom pada reproduktivnih performansi. U 2005 godini broj govedaširom svijeta je iznosio oko 1.370.000.000 grla, dok je u 2012 taj broj iznosio tek nešto iznadmilijarde, što govori o važnosti primjene različitih reproduktivnih protokola u cilju povećanjabrojnosti proizvodnih jedinki. Toplotni stres dovodi do poremećaja fizioloških i reproduktivnihprocesa, jer rast tjelesne temperature uzrokovan toplotnim stresom ima direktne negativne posljedicena brojne ćelijske funkcije. U istraživanje je bilo uključeno ukupno 54 krave Holštajn-Frizijskepasmine, 28 eksperimentalnih i 26 kontrolnih krava, uzgojenih na PD Butmir sa prosječnomiskoristljivošću od 5. laktacija. Hormonalni protokoli sinhronizacije estrusa i ovulacije su korišteniu mjesecima juni i juli 2013. godine. Krave u eksperimentalnoj grupi su podvrgavanepresynch+5dCoS2 hormonalnom protokolu. Krave koje nisu ostale gravidne nakon ovog protokolaodmah su podvrgnute resinhronizaciji sa hormonalnim protokolom Cosynch 72. Uspješnostpresynch+5dCoS2 hormonalnog protokola je bila 19%, dok je u slućaju Cosynch 72 ona iznosila33%, a što je bilo statistički signifikantno (p< 0,05). Prvi presinhronizacijski i sinhronizacijskiprotokol (5dCoS2) nisu značajnije pomogli u poboljšanju koncepcije nakon prvog osjemenjavanjapostpartum, ali na osnovu rezultata evidentno je da su imali pozitivni efekt na drugi protokol(COS72) u vidu smanjenja embrionalnog mortaliteta u ljetnim mjesecima, kada je on najizražajniji.Protokol COS72, daje zadovoljavajuće rezultate u ljetnom periodu, ali preduvjeti za uspješanprogram sinhronizacije estrusa i ovulacije uoči vještačkih osjemenjavanja su dobra kondicija izdravstveni menadžment, kao i smanjenje toplotnog stresa u skladu s lokacijom i dizajnom farme.

BackgroundSensitization to airborne molds may be a risk factor for severe asthma and direct cause of asthma exacerbation (AE).MethodsA prospective, 1-year (April 2016–March 2017) study, done in Kuwait Allergy Centre, investigated the link between AEs with exposure to outdoor molds and the role of meteorological parameters in mold sensitized patients and compared with non-allergic asthma patients who had asthma deterioration. The total of 676 adult asthmatics with moderate-severe AEs were included and divided into atopic (85.65%) and non-atopic group. Atopy was defined by positive skin prick test (SPT) to at least one inhalant allergen. Data regarding atopy and asthma severity were collected from patient’s records. Patients with symptoms and signs of acute respiratory infection and patient sensitized to indoor allergens only were excluded. Daily count of local pollens (Salsola kali, Bermuda grass) and molds (Aspergillus, Alternaria and Cladosporium) were obtained from the Aerobiology department. Daily metrological parameters (atmospheric pressure-AP, temperature-T and relative humidity-RH) were provided by Kuwait Environment Public Authority. Count of spores/m3 and weather variable are shown on weekly basis. The year circle was divided into 4 Seasons (1, 2, 3, 4) accordingly to typical desert climate.ResultsSensitization to molds was relatively high but significantly less (25.0%) if compared to the pollens sensitization. The highest number of AEs was in season 4 for both molds and pollens sensitized patients. Seasonal patterns for both allergens were significant and positively correlated with RH and AP. In season 1 only, mold sensitized patients showed higher rate of AEs. Non-atopic patients have been less sensitive to increased RH than atopic. Negative correlation with T was similar in both atopic and non-atopic patients.ConclusionDespite of high rate of sensitization to molds, their significant role in triggering AE was not found in desert environment. Typical desert climate and high allergencity of local weeds outweigh the influence of the molds.