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.
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.
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.
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.
Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by Leishmania parasites. Previous studies speculated that augmenting cytokines associated with a type 1 T-helper cell (Th1) response is necessary to combat severe forms of leishmaniasis, and it has been hypothesized that the antileishmanial drug miltefosine is capable of immunomodulation and induction of Th1 cytokines. ABSTRACT Host immune responses are pivotal for the successful treatment of the leishmaniases, a spectrum of infections caused by Leishmania parasites. Previous studies speculated that augmenting cytokines associated with a type 1 T-helper cell (Th1) response is necessary to combat severe forms of leishmaniasis, and it has been hypothesized that the antileishmanial drug miltefosine is capable of immunomodulation and induction of Th1 cytokines. A better understanding of the immunomodulatory effects of miltefosine is central to providing a rationale regarding synergistic mechanisms of activity to combine miltefosine optimally with other conventional and future antileishmanials that are currently under development. Therefore, a systematic literature search was performed to evaluate to what extent and how miltefosine influences the host Th1 response. Miltefosine’s effects observed in both a preclinical and a clinical context associated with immunomodulation in the treatment of leishmaniasis are evaluated in this review. A total of 27 studies were included in the analysis. Based on the current evidence, miltefosine is not only capable of inducing direct parasite killing but also of modulating the host immunity. Our findings suggest that miltefosine-induced activation of Th1 cytokines, particularly represented by increased gamma interferon (IFN-γ) and interleukin 12 (IL-12), is essential to prevail over the Leishmania-driven Th2 response. Differences in miltefosine-induced host-mediated effects between in vitro, ex vivo, animal model, and human studies are further discussed. All things considered, an effective treatment with miltefosine is acquired by enhanced functional Th1 cytokine responses and may further be enhanced in combination with immunostimulatory agents.
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.
Sexting has recently attracted the attention of researchers. The aim of this study was twofold: (a) to investigate the prevalence of sexting among boys and girls, and b) to examine the relationship between different types of sexting and emotional difficulties in high school pupils. The research was conducted on a sample of 711 adolescents aged 14-19 years. The Sexting Behavior Questionnaire was used to assess sexting, while the Depression Anxiety and Stress Scales and the item of suicidality were used to assess emotional difficulties. The results of the study show that the most frequently reported type of sexting is sending sexually explicit content and the rarest is posting sexually explicit content. Boys are more frequently engaged in sexting compared to girls. Furthermore, pupils involved in sexting think about suicidal thoughts and suicide more often. The obtained results suggest that youth do participate in sexting and those who do have some negative thoughts, which emphasize the necessary for both a prevention and intervention approach for this population.
The idea of chatbots firstly appeared in the 1960s. But only after more than half a century passed the world became ready for their implementation into the real life, this being a result of the rapid progress in natural language processing, artificial intelligence, and the global presence of text messaging applications. Today, specialized chatbots exist in different domains, thus helping organizations handle large amount of inquiries. Idea of this project was to develop one friendly chatbot with whom you can talk about politics, movies, weather, sport, emotions and similar everyday things. Friendly chatbot named Zeka, is a web-based chatbot developed with the help of Chatterbot library. Chatbot relies on different natural processing and machine learning algorithms altered by its developers to increase its performance.
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