Репозиторий Университета

Background: Although the relationship between acute alcohol consumption and injuries is well recognized, studies exploring how the time of day the drinking commences affects alcohol-related injuries have been scarce. This contribution examines the associations between the time at which the drinking began and the duration of the drinking, the volume of alcohol consumed, the injury type, and the blood alcohol concentration (BAC) level. Method: This study employed a cross-sectional survey, which was conducted in two hospital emergency departments (ED) in Chiangmai Province, Thailand. The sample was composed of 519 injured patients aged 18 years and older. Outcome measures included the BAC and type of injury. Exposures included the quantity of alcohol consumed, the time the drinking commenced, and the pattern of drinking involved. Results: The injured patients who drank alcohol within six hours prior to sustaining their injury were more likely to get injured and present themselves at the ED at night (20:00–04:00) compared to those who sustained an injury but did not drink in the hours prior. However, this relationship was only true for unintentional injuries, not intentional ones. The majority of participants consumed their first drink between 16:00 and 20:00. On average, among the 104 patients who drank prior to sustaining an injury, the total amount of alcohol consumed was 6.9 drinks, the duration of drinking was 2.6 h, the rate of drinking was 6.0 drinks/hour, and the BAC was 0.119 gm%. Every drink increased the BAC by 0.012 gm% and each year of increasing age increased the BAC by 0.003 gm%. People who were older, less educated, and drank more frequently tended to have their first drink earlier than other drinkers. An earlier start to their drinking resulted in a faster pace of drinking and a higher BAC. Conclusions: BAC increased with the total amount of alcohol consumed and the age of the drinker. Different groups of people had their first drink at different times of the day, resulting in differences in the rate of drinking, the BAC, the time of injury, and the time they presented to the ED after injury.

Purpose: To assess the clinical and radiographic success rate of microsurgical endodontic treatment of upper molar teeth in relationship with the maxillary sinus, with 12 months follow-up. Methods: Patients treated with microsurgical endodontic treatment of upper molar teeth in the period between 2017 and 2019 were recruited from two dental clinics according to specific selection criteria. The outcomes were determined based on clinical and radiographic results taken three, six and 12 months post-operatively, compared with those taken immediately before and after surgery. Clinical and radiographic outcomes were recorded. The distance between the most apical part of the root and of the lesion to the maxillary sinus was measured on CBCT images before the surgery. Patient-related outcomes were recorded. Results: Out of 35 patients evaluated, 21 were selected according with the selection criteria for a total of 27 roots and 29 canals treated. After 12 months, 18 patients showed a complete healing whereas three demonstrated incomplete healing. Consequently, the success rate in this study was 85.7% after one year. In 28.5% (6 patients) there was a perforation of the Schneiderian membrane that didn’t seem to affect the outcome. All patients kept the molar one year later. The pain level decreased significantly over the time during the first week after surgery. Conclusion: Microsurgical Endodontic treatment of the upper molar teeth should be considered a valid and predictable treatment option even in case of Schneiderian membrane perforation. Future clinical studies with a larger sample size are needed to compare the results obtained.

Purpose: To assess the clinical and radiographic success rate of microsurgical endodontic treatment of upper molar teeth in relationship with the maxillary sinus, with 12 months follow-up. Methods: Patients treated with microsurgical endodontic treatment of upper molar teeth in the period between 2017 and 2019 were recruited from two dental clinics according to specific selection criteria. The outcomes were determined based on clinical and radiographic results taken three, six and 12 months post-operatively, compared with those taken immediately before and after surgery. Clinical and radiographic outcomes were recorded. The distance between the most apical part of the root and of the lesion to the maxillary sinus was measured on CBCT images before the surgery. Patient-related outcomes were recorded. Results: Out of 35 patients evaluated, 21 were selected according with the selection criteria for a total of 27 roots and 29 canals treated. After 12 months, 18 patients showed a complete healing whereas three demonstrated incomplete healing. Consequently, the success rate in this study was 85.7% after one year. In 28.5% (6 patients) there was a perforation of the Schneiderian membrane that didn’t seem to affect the outcome. All patients kept the molar one year later. The pain level decreased significantly over the time during the first week after surgery. Conclusion: Microsurgical Endodontic treatment of the upper molar teeth should be considered a valid and predictable treatment option even in case of Schneiderian membrane perforation. Future clinical studies with a larger sample size are needed to compare the results obtained.

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

Background: Low endometrial receptivity is one of the major factors affecting successful implantation in assisted reproductive technologies (ART). Infertile patients with thin endometrium have a significantly lower cumulative clinical pregnancy rate than patients with normal endometrium. Molecular pathophysiology of low receptivity of thin endometrium remains understudied. We have investigated composition of glycocalyx of the apical surface of luminal and glandular epithelial cells in thin endometrium of infertile women. Methods: Thirty-two patients with tubal-peritoneal infertility undergoing in vitro fertilization (IVF) were included in the study. Endometrial samples were obtained in a natural menstrual cycle. Patients were divided into two groups: patients with normal endometrium (≥8 mm) and with thin endometrium (< 8 mm). Histochemical and immunohistochemical analysis of paraffin-embedded endometrial samples was performed using six biotinylated lectins (UEA-I, MAL-II, SNA, VVL, ECL, Con A) and anti-Le  and MECA-79 monoclonal antibodies (MAbs). Results: Complex glycans analysis taking into account the adjusted specificity of glycan-binding MAbs revealed 1.3 times less expression of MECA-79 glycans on the apical surface of the luminal epithelial cells of thin endometrium compared to normal endometrium; this deficiency may adversely affect implantation, since MECA-79 glycans are a ligand of L-selectin and mediate intercellular interactions. The glycans containing a type-2 unit Galβ1-4GlcNAcβ (LacNAc) but lacking sulfo-residues at 6-OH of GlcNAcβ, and binding to MECA-79 MAbs were found; they can be considered as potential markers of endometrium receptivity. Expression of the lectins-stained glycans on the apical surfaces of the luminal and glandular epithelial cells did not differ significantly. Correlation between the expression of difucosylated oligosaccharide Le  on the apical surfaces of the luminal and glandular epithelial cells was found in patients with thin endometrium and recurrent implantation failure. A similar relationship was shown for mannose-rich glycans. Conclusions: Specific features of key glycans expression in epithelial compartments of thin endometrium may be essential for morphogenesis of the endometrial functional layer and explain its low receptivity. Y Y

Objective: The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods: Female F1 hybrid mice (C Bl/  x DBA/2) and male and female linear mice C BL/  were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results: The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment. Conclusion: The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269. 57 6 57 6

Objective: The current scientific research direction is development of drugs with a targeted effect on malignant tumors. One of the promising groups is indolocarbazoles and their derivatives, which can initiate various tumor cell death pathways. Russian scientists from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation has developed a new experimental drug form of the original compound LCS 1269 with cytotoxic and antiangiogenic properties, blocking vasculogenic mimicry in tumor. The study aim is the experimental drug form LCS 1269 antitumor activity on models of transplantable mouse tumors B-16 melanoma and Lewis epidermoid lung carcinoma (LLC) with different routes and modes of administration. Material and methods: Female F1 hybrid mice (C Bl/  x DBA/2) and male and female linear mice C BL/  were used for management of tumor strains. Mice were obtained from N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russian Federation vivarium. The antitumor effect was assessed by tumor growth inhibition (TGI) and increase of treated animal’s life span (ILS) compared to the control. Results: The experimental drug form showed high antitumor activity when administered intravenously once at doses of 100 and 120 mg/kg (TGI = 98–82% and TGI = 95–77%, respectively, ILS = 24%, p < 0.05) on melanoma B-16 mice. On LLC mice, the experimental drug form showed that the intravenous administration route was effective in the range of doses from 60 to 80 mg/kg with a 5 day administration regimen with an interval of 24 h. A dose of 70 mg/kg had maximum effect at the level of TGI = 96–77% (p < 0.05) with its retention for 20 days after the end of treatment. Conclusion: The studies have shown that the new compound LCS 1269 in the original drug form, has a pronounced antitumor activity and significantly reduces the volume of tumor mass both on melanoma B-16 and on LLC. It allows us to recommend continue the search for sensitivity of animal transplantable tumors to LCS 1269. 57 6 57 6

The current consensus on prevention of re-establishment of malaria is based on the following principles: (1) Fundamental role of general health services; (2) Surveillance; (3) Vector control; (4) Border actions; (5) Intersectoral collaboration. These principles are critically reviewed, and it is pointed out that alertness of the general health services to suspected malaria (vigilance) needs to be maintained everywhere, while health education is rational only if targeting high-risk sub-populations. It is argued that prevention of re-establishment of malaria transmission should be integrated with prevention of malaria mortality in cases of imported malaria, and that this requires collaboration with entities dealing with travellers’ health and the availability of chemoprophylaxis and other measures for travellers to malaria endemic countries.

The current consensus on prevention of re-establishment of malaria is based on the following principles: (1) Fundamental role of general health services; (2) Surveillance; (3) Vector control; (4) Border actions; (5) Intersectoral collaboration. These principles are critically reviewed, and it is pointed out that alertness of the general health services to suspected malaria (vigilance) needs to be maintained everywhere, while health education is rational only if targeting high-risk sub-populations. It is argued that prevention of re-establishment of malaria transmission should be integrated with prevention of malaria mortality in cases of imported malaria, and that this requires collaboration with entities dealing with travellers’ health and the availability of chemoprophylaxis and other measures for travellers to malaria endemic countries.

Background: Lifting The Burden (LTB) and European Headache Federation (EHF) have developed a set of headache service quality indicators, successfully tested in specialist headache centres. Their intended application includes all levels of care. Here we assess their implementation in primary care. Methods: We included 28 primary-care clinics in Germany (4), Turkey (4), Latvia (5) and Portugal (15). To implement the indicators, we interviewed 111 doctors, 92 nurses and medical assistants, 70 secretaries, 27 service managers and 493 patients, using the questionnaires developed by LTB and EHF. In addition, we evaluated 675 patients’ records. Enquiries were in nine domains: diagnosis, individualized management, referral pathways, patient education and reassurance, convenience and comfort, patient satisfaction, equity and efficiency of headache care, outcome assessment and safety. Results: The principal finding was that Implementation proved feasible and practical in primary care. In the process, we identified significant quality deficits. Almost everywhere, histories of headache, especially temporal profiles, were captured and/or assessed inaccurately. A substantial proportion (20%) of patients received non-specific ICD codes such as R51 (“headache”) rather than specific headache diagnoses. Headache-related disability and quality of life were not part of routine clinical enquiry. Headache diaries and calendars were not in use. Waiting times were long (e.g., about 60 min in Germany). Nevertheless, most patients (> 85%) expressed satisfaction with their care. Almost all the participating clinics provided equitable and easy access to treatment, and follow-up for most headache patients, without unnecessary barriers. Conclusions: The study demonstrated that headache service quality indicators can be used in primary care, proving both practical and fit for purpose. It also uncovered quality deficits leading to suboptimal treatment, often due to a lack of knowledge among the general practitioners. There were failures of process also. These findings signal the need for additional training in headache diagnosis and management in primary care, where most headache patients are necessarily treated. More generally, they underline the importance of headache service quality evaluation in primary care, not only to identify-quality failings but also to guide improvements. This study also demonstrated that patients’ satisfaction is not, on its own, a good indicator of service quality.

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell’s history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells.

In recent decades, a new method of cellular immunotherapy was introduced based on engineering and empowering the immune effector cells. In this type of immunotherapy, the immune effector cells are equipped with chimeric antigen receptor (CAR) to specifically target cancer cells. In much of the trials and experiments, CAR-modified T cell immunotherapy has achieved very promising therapeutic results in the treatment of some types of cancers and infectious diseases. However, there are also some considerable drawbacks in the clinical application of CAR-T cells although much effort is in progress to rectify the issues. In some conditions, CAR-T cells initiate over-activated and strong immune responses, therefore, causing unexpected side-effects such as systemic cytokine toxicity (i.e., cytokine release syndrome), neurotoxicity, on-target, off-tumor toxicity, and graft-versus-host disease (GvHD). To overcome these limitations in CAR-T cell immunotherapy, NK cells as an alternative source of immune effector cells have been utilized for CAR-engineering. Natural killer cells are key players of the innate immune system that can destroy virus-infected cells, tumor cells, or other aberrant cells with their efficient recognizing capability. Compared to T cells, CAR-transduced NK cells (CAR-NK) have several advantages, such as safety in clinical use, non-MHC-restricted recognition of tumor cells, and renewable and easy cell sources for their preparation. In this review, we will discuss the recent preclinical and clinical studies, different sources of NK cells, transduction methods, possible limitations and challenges, and clinical considerations.

Background: It remains unclear whether alcohol use disorders (AUDs) can be characterized by specific levels of average daily alcohol consumption. The aim of the current study was to model the distributions of average daily alcohol consumption among those who consume alcohol and those with alcohol dependence, the most severe AUD, using various clustering techniques. Methods: Data from Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used in the current analyses. Clustering algorithms were applied in order to group a set of data points that represent the average daily amount of alcohol consumed. Gaussian Mixture Models (GMMs) were then used to estimate the likelihood of a data point belonging to one of the mixture distributions. Individuals were assigned to the clusters which had the highest posterior probabilities from the GMMs, and their treatment utilization rate was examined for each of the clusters. Results: Modeling alcohol consumption via clustering techniques was feasible. The clusters identified did not point to alcohol dependence as a separate cluster characterized by a higher level of alcohol consumption. Among both females and males with alcohol dependence, daily alcohol consumption was relatively low. Conclusions: Overall, we found little evidence for clusters of people with the same drinking distribution, which could be characterized as clinically relevant for people with alcohol use disorders as currently defined.

Background: Malaria is a disease annually causing over 400,000 deaths. Deep understanding of molecular and genetic processes underlying its life cycle and pathogenicity is required to efficiently resist it. RNA interference is a mechanism of the gene expression regulation typical for a wide variety of species. Even though the existence of this phenomenon in Plasmodium falciparum has long been rejected, several recent works pose hypotheses and provide direct and indirect evidence of the existence of mechanisms similar to RNA interference in this organism. In particular, the possibility of regulation of P. falciparum gene expression through human microRNAs is of great importance both for fundamental biology and for medicine. In the present work we address the problem of possibility of the existence in the P. falciparum genome of the nucleotide sequences such that mRNAs transcribed from genes containing these sequences could form duplexes with human microRNAs. Using bioinformatics methods we have analysed genomes of 15 P. falciparum isolates for sequences homological to these microRNAs. Results: The analysis has demonstrated the existence of a vast number of genes that could potentially be regulated by the human microRNAs in the plasmodial genome. Conclusions: Despite the fact that the numbers of homological intervals vary significantly between isolates, the hsa-miR-451a and hsa-miR-223-3p microRNAs are expected to make the most notable contribution to the pathogenesis of P. falciparum malaria. The majority of homological intervals occur in genes encoding cell adhesion proteins.

Background: The aim of this paper was to systematically review the root canal configuration (RCC) and morphology literature of the mandibular second premolar (Mn2P). Methods: Systematic research of five electronic databases was performed to identify published literature concerning the root canal configuration (RCC) of the Mn2P up through July 2020. Studies were selected according to predefined search terms and keywords inclusion criteria: “root canal configuration”, “root canal system”, “root canal morphology”, “mandibular second premolar”, “mandibular premolars”, “morphology” and “anatomy”. Further possible studies were identified by cross-referencing and screening the bibliographies of the selected articles. Results: From 1622 retrieved studies, 44 studies investigating the internal morphology of 17,839 Mn2Ps were included. Most examined Mn2Ps were single-rooted (89.5–100%); two-rooted (0.1–8%) and three-rooted (0.1–3.5%) Mn2Ps at lower frequency. Most frequent RCCs reported were 1–1–1/1 (55.3–99.6%) followed by 1–1–2/2 (0.5–57%) and 2–2–2/2 (0.6–18%). The meta-analysis of seven studies demonstrated that a significantly higher number of RCC type 1–2–1/1 (OR [95%CI] = 2.05 [1.27, 3.33]) and 2–2–2/2 (OR [95%CI] = 2.32 [0.65, 8.63]) were observed in male than in female patients. Conclusions: Different RCC research methods have been reported. Whereas clearing and radiographs were commonly used in the past, CBCT has been prevalent in recent years. A globally high frequency of a 1–1–1/1 RCC in the Mn2P has been reported. Nevertheless, the probability that different, more complicated RCCs can appear in Mn2Ps should not be underestimated and, thus, should be taken into consideration when making decisions during an endodontic treatment.

Background: The existing data demonstrate the potential role of trace elements in nasal mucociliary clearance, although the association between trace element and mineral status and ciliary function in children with chronic rhinosinusitis is insufficiently studied. Therefore, the objective of the present study is evaluation of trace element and mineral status and mucociliary function in pediatric CRS patients before and after functional endoscopic sinus surgery. Methods: The present study involved 30 children with chronic rhinosinusitis without nasal polyps. During this follow-up the patients were examined preoperatively (point 0), underwent functional endoscopic sinus surgery, and were repeatedly examined at three months postoperatively (point 1). At both points the patients were subjected to quality-of-life assessment using SNOT-20 questionnaire; endoscopic and computer tomography examination of the nasal sinuses; evaluation of ciliary function and mucosal cytology using high-speed videomicroscopy; assessment of blood count and inflammatory markers; as well as analysis of trace element and mineral levels in whole blood, serum, and hair using inductively-coupled plasma mass-spectrometry. Results: The obtained data demonstrate that endoscopic sinus surgery significantly improved sinonasal pathology in children with chronic rhinosinusitis, as evidenced by significantly reduced Lund-Mackay, Lund-Kennedy, and SNOT-20 scores. At the same time, no significant improvement of ciliary functions or mucosal cytology was observed postoperatively. Trace element status assessment demonstrated that postoperative serum Zn, whole blood Mg and Cu were significantly lower as compared to preoperative values. In contrast, serum Mn and Cr, as well as whole blood Cr and hair Se were characterized by a significant increase at three months postoperatively. Multiple linear regression analysis demonstrated that serum Zn is significantly associated with the number of ciliated cells and cell viability, whereas serum Mn and whole blood Cu concentrations are inversely associated with cell viability and ciliary length, respectively. Hair Se was found to be associated with the number of neutrophils in the mucosa biopsy. Conclusion: Redistribution of trace elements and minerals may at least partially mediate prolonged recovery of mucosal ciliary function in children with chronic rhinosinusitis in three months after functional sinus surgery, although the particular mechanisms of these alterations in trace element levels are to be discovered.

Background: The existing data demonstrate the potential role of trace elements in nasal mucociliary clearance, although the association between trace element and mineral status and ciliary function in children with chronic rhinosinusitis is insufficiently studied. Therefore, the objective of the present study is evaluation of trace element and mineral status and mucociliary function in pediatric CRS patients before and after functional endoscopic sinus surgery. Methods: The present study involved 30 children with chronic rhinosinusitis without nasal polyps. During this follow-up the patients were examined preoperatively (point 0), underwent functional endoscopic sinus surgery, and were repeatedly examined at three months postoperatively (point 1). At both points the patients were subjected to quality-of-life assessment using SNOT-20 questionnaire; endoscopic and computer tomography examination of the nasal sinuses; evaluation of ciliary function and mucosal cytology using high-speed videomicroscopy; assessment of blood count and inflammatory markers; as well as analysis of trace element and mineral levels in whole blood, serum, and hair using inductively-coupled plasma mass-spectrometry. Results: The obtained data demonstrate that endoscopic sinus surgery significantly improved sinonasal pathology in children with chronic rhinosinusitis, as evidenced by significantly reduced Lund-Mackay, Lund-Kennedy, and SNOT-20 scores. At the same time, no significant improvement of ciliary functions or mucosal cytology was observed postoperatively. Trace element status assessment demonstrated that postoperative serum Zn, whole blood Mg and Cu were significantly lower as compared to preoperative values. In contrast, serum Mn and Cr, as well as whole blood Cr and hair Se were characterized by a significant increase at three months postoperatively. Multiple linear regression analysis demonstrated that serum Zn is significantly associated with the number of ciliated cells and cell viability, whereas serum Mn and whole blood Cu concentrations are inversely associated with cell viability and ciliary length, respectively. Hair Se was found to be associated with the number of neutrophils in the mucosa biopsy. Conclusion: Redistribution of trace elements and minerals may at least partially mediate prolonged recovery of mucosal ciliary function in children with chronic rhinosinusitis in three months after functional sinus surgery, although the particular mechanisms of these alterations in trace element levels are to be discovered.

Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR’s potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies.

Background: During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH). Results: Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control. Conclusions: Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.

Background: During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH). Results: Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control. Conclusions: Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.