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Aims The coronavirus disease‐2019 (COVID‐19) pandemic has changed the landscape of medical care delivery worldwide. We aimed to assess the influence of COVID‐19 pandemic on hospital admissions and in‐hospital mortality rate in patients with acute heart failure (AHF) in a retrospective, multicentre study. Methods and results From 1 January 2019 to 31 December 2020, a total of 101 433 patients were hospitalized in 24 Cardiology Departments in Poland. The number of patients admitted due to AHF decreased by 23.4% from 9853 in 2019 to 7546 in 2020 (P

The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase–associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition–induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM inhibition in cell lines and patient-derived primary lymphoma cells decreased MYC levels as well as expression of multiple MYC-dependent genes, including PLK1. Chemical and genetic PIM inhibition upregulated surface CD20 levels in an MYC-dependent fashion. Consistently, MEN1703 and other clinically available pan-PIM inhibitors synergized with the anti-CD20 monoclonal antibody rituximab in vitro, increasing complement-dependent cytotoxicity and antibody-mediated phagocytosis. Combined treatment with PIM inhibitor and rituximab suppressed tumor growth in lymphoma xenografts more efficiently than either drug alone. Taken together, these results show that targeting PIM in DLBCL exhibits pleiotropic effects that combine direct cytotoxicity with potentiated susceptibility to anti-CD20 antibodies, justifying further clinical development of such combinatorial strategies. Significance: These findings demonstrate that inhibition of PIM induces DLBCL cell death via MYC-dependent and -independent mechanisms and enhances the therapeutic response to anti-CD20 antibodies by increasing CD20 expression.

Coronary-artery bypass graft (CABG) surgery is known to improve cardiac function and decrease mortality, albeit, this method of treatment is also associated with a neuropsychiatric complications including postoperative delirium. The pathophysiology of delirium after cardiac surgery remains poorly understood. Thus, the purpose of this study was to investigate whether oxidative stress reflected by decreased preoperative and postoperative plasma antioxidant activity is independently associated with delirium after cardiac surgery. The second aim was to assess whether decreased antioxidant activity is stress-related or mediated by other pathologies such as major depressive disorder (MDD), anxiety disorders, and cognitive impairment. Furthermore, the putative relationship between pre- and postoperative soluble receptor for advanced glycation end-products (sRAGE) overexpression and plasma antioxidant capacity was evaluated. The patients cognitive status was assessed 1 day preoperatively with the use of the Mini-Mental State Examination Test and the Clock Drawing Test. A diagnosis of MDD and anxiety disorders was established on the basis of DSM-5 criteria. Blood samples for antioxidant capacity and sRAGE levels were collected both preoperatively and postoperatively. The Confusion Assessment Method for the Intensive Care Unit was used within the first 5 days postoperatively to screen for a diagnosis of delirium. Postoperative delirium was diagnosed in 34% (61 of 177) of individuals. Multivariate logistic regression analysis revealed that low baseline antioxidant capacity was independently associated with postoperative delirium development. Moreover, increased risk of delirium was observed among patients with a preoperative diagnosis of MDD associated with antioxidant capacity decreased postoperatively. According to receiver operating characteristic analysis, the most optimal cutoff values of the preoperative and postoperative antioxidant capacity that predict the development of delirium were 1.72 mM and 1.89 mM, respectively. Pre- and postoperative antioxidant capacity levels were negatively correlated with postoperative sRAGE concentration (Spearman's Rank Correlation − 0.198 and − 0.158, p

Orbital telorism, the interocular distance, is a clinically informative and in extremes is considered a minor physical anomaly. While its extremes, hypo- and hypertelorism, have been linked to disorders often related to cognitive ability, little is known about the neural correlates of normal variation of telorism within the general population. We derived measures of orbital telorism from cranial magnetic resonance imaging (MRI) by calculating the distance between the eyeball center of gravity in two population-based datasets (N=5,653, N=29,824, Mean age 64.66, 63.75 years). This measure was found to be related grey matter tissue density within numerous regions of the brain, including, but surprisingly not limited to, the frontal regions, in both positive and negative directions. Additionally, telorism was related to several cognitive functions, such as Perdue Pegboard test (Beta, P-value, (CI95%) −0.02, 1.63×10-7(−0.03;-0.01)) and fluid intelligence (0.02, 4.75×10-06(0.01:0.02)), with some relationships driven by individuals with a smaller orbital telorism. This is reflective of the higher prevalence of hypo-telorism in developmental disorders, specifically those that accompany lower cognitive lower functioning. This study suggests, despite previous links only made in clinical extremes, that orbital telorism holds some relation to structural brain development and cognitive function in the general population. This relationship is likely driven by shared developmental periods.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. Objectives In this study AD characteristics and its atopic comorbidities are compared in smoking and nonsmoking AD patients. Methods TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included into TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analyzed comparing AD disease characteristics and comorbidities in smokers versus non-smokers. Results Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n=352; 38.8%) and nonsmokers, however lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to nonsmoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than nonsmokers. Total IgE levels were more elevated in smokers and they displayed a younger age at initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to nonsmokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. Conclusions German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Introduction We aimed to search the literature for global surgical curricula, assess if published resources align with existing competency frameworks in global health and surgical education, and determine if there is consensus around a fundamental set of competencies for the developing field of academic global surgery. Methods We reviewed SciVerse SCOPUS, PubMed, African Medicus Index, African Journals Online (AJOL), SciELO, Latin American and Caribbean Health Sciences Literature (LILACS) and Bioline for manuscripts on global surgery curricula and evaluated the results using existing competency frameworks in global health and surgical education from Consortium of the Universities for Global Health (CUGH) and Accreditation Council for Graduate Medical Education (ACGME) professional competencies. Results Our search generated 250 publications, of which 18 were eligible: (1) a total of 10 reported existing competency-based curricula that were concurrent with international experiences, (2) two reported existing pre-departure competency-based curricula, (3) six proposed theoretical competency-based curricula for future global surgery education. All, but one, were based in high-income countries (HICs) and focused on the needs of HIC trainees. None met all 17 competencies, none cited the CUGH competency on “Health Equity and Social Justice” and only two mentioned “Social and Environmental Determinants of Health.” Only 22% (n = 4) were available as open-access. Conclusion Currently, there is no universally accepted set of competencies on the fundamentals of academic global surgery. Existing literature are predominantly by and for HIC institutions and trainees. Current frameworks are inadequate for this emerging academic field. The field needs competencies with explicit input from LMIC experts to ensure creation of educational resources that are accessible and relevant to trainees from around the world.

Interoception, the ability to perceive internal bodily sensations, and heart rate variability (HRV) share common physiological pathways, including the baroreflex feedback loop. The baroreflex can be activated by resonance breathing, wherein respiration is paced at 6 times per minute (0.1 Hz), eliciting immediate physiological changes and longer-term therapeutic responses. This registered report characterizes baroreflex functioning as a cardiac mechanism of interoception in a two-session study (n = 67). The heartbeat discrimination task was used to obtain indices of interoceptive accuracy, sensibility and metacognition. Baroreflex functioning was measured as HRV at 0.1 Hz and baroreflex sensitivity (BRS); high frequency (HF) HRV was calculated as a control. Cardiovascular indices were measured at baseline and during active and control paced breathing after which changes in interoception were measured. The first hypothesis was that baseline baroreflex functioning would predict individual differences in interoceptive awareness. The second hypothesis was that resonance breathing would increase participants' ability to detect their own heartbeats, and that this effect would be mediated by increases in 0.1 Hz HRV and BRS. Data were collected upon in principle acceptance of the manuscript. We found a negative relationship of interoceptive accuracy with baseline HF HRV and BRS, and a positive relationship between metacognitive interoception and 0.1HZ HRV, BRS and HF HRV. We found that changes in 0.1 Hz HRV and BRS during resonance breathing positively correlate with increases in interoceptive accuracy. Our results show that the extent to which breathing recruits the resonant properties of the cardiovascular system can facilitate the conscious perception of participants' heartbeats. We interpret this as an increase in vagal afferent signaling and baroreflex functioning following resonance breathing. We put forward an alternative explanation that HRV modulation can reduce interoceptive prediction errors, facilitating the conscious perception of interoceptive signals, and consider the role of resonance breathing on mental health from an interoceptive inference perspective.

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented disruptions in fellowship training programs worldwide. In gastroenterology, the strain in healthcare service provision and the emphasis on preventing viral transmission has adversely impacted hands-on training opportunities, with trainees facing the constant pressure to meet training requirements under the continuous threat of viral transmission. Emerging evidence highlight the scale of the problem, specifically with regard to endoscopy competence due to cancellation of elective endoscopic procedures, provision of inpatient and outpatient consultative care as well as academic education and the mental well-being of trainees. As such, it has been necessary for trainees, trainers and training programs collectively to adapt to these challenges and incorporate novel and adaptive solutions to circumvent these training barriers. This review aims to summarise data on the global impact of COVID-19 on gastroenterology training and the practical interventions that could be implemented.

Purpose Lorlatinib is a third-generation tyrosine kinase inhibitor currently approved for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer. This open-label, phase 1, randomized two-sequence, two-treatment, two-period, crossover study investigated the absolute oral bioavailability of lorlatinib in healthy participants. Methods Eligible participants were randomized to receive two treatments in one of two sequences: lorlatinib 100 mg single oral dose followed by lorlatinib 50 mg intravenous (IV) dose, or lorlatinib IV dose followed by lorlatinib oral dose, each with at least a 10-day washout between successive lorlatinib doses. Blood samples for pharmacokinetics were collected for up to 144 hours (h) after dosing. Validated liquid chromatographic-tandem mass spectrometry was used to determine plasma concentrations of lorlatinib and its benzoic acid metabolite PF-06895751. Results In total, 11 participants were enrolled (mean age 37.6 years, all male). The adjusted geometric mean (90% confidence interval) for the absolute oral bioavailability was 80.78% (75.73–86.16%). Using non-compartmental analysis, the estimated arithmetic mean elimination plasma half-life of lorlatinib was 25.5 and 27.0 h after the oral and IV doses, respectively. No deaths, serious adverse events (AEs), or severe AEs were reported, and most treatment-emergent AEs were mild in severity, with two events of transaminase increase of moderate severity. All treatment-emergent AEs were resolved by the end of the study. Conclusion Both oral and IV lorlatinib were well-tolerated in healthy participants and oral lorlatinib is highly bioavailable after oral administration.

Introduction Alveolar macrophages (AMs) are lung-resident immune cells that phagocytose inhaled particles and pathogens, and help coordinate the lung’s immune response to infection. Little is known about the impact of chronic e-cigarette use (ie, vaping) on this important pulmonary cell type. Thus, we determined the effect of vaping on AM phenotype and gene expression. Aims and Methods We recruited never-smokers, smokers, and e-cigarette users (vapers) and performed research bronchoscopies to isolate AMs from bronchoalveolar lavage fluid samples and epithelial cells from bronchial brushings. We then performed morphological analyses and used the Nanostring platform to look for changes in gene expression. Results AMs obtained from smokers and vapers were phenotypically distinct from those obtained from nonsmokers, and from each other. Immunocytochemistry revealed that vapers AMs had significantly elevated inducible nitric oxide synthase (M1) expression and significantly reduced CD301a (M2) expression compared with nonsmokers or smokers. Vapers’ AMs and bronchial epithelia exhibited unique changes in gene expression compared with nonsmokers or smokers. Moreover, vapers’ AMs were the most affected of all groups and had 124 genes uniquely downregulated. Gene ontology analysis revealed that vapers and smokers had opposing changes in biological processes. Conclusions These data indicate that vaping causes unique changes to AMs and bronchial epithelia compared with nonsmokers and smokers which may impact pulmonary host defense. Implications These data indicate that normal “healthy” vapers have altered AMs and may be at risk of developing abnormal immune responses to inflammatory stimuli.

Casirivimab and imdevimab (REGN-COV-2) are investigational monoclonal antibodies approved in November 2020 by the Food and Drug Administration for emergency use in mild and moderate COVID-19. These two noncompeting human IgG1 monoclonal antibodies can target the receptor-binding domain of the spike protein of SARSCoV-2, prevent its entry into human cells, and reduce viral load. The antibodies can be administered intravenously for mild-to-moderate COVID-19 patients who do not require hospitalization and supplemental oxygen. The purpose of the study is to review the latest available data on COVID-19 treatment using casirivimab and imdevimab. According to recent preclinical studies, the antibody cocktail presents optimal antiviral strength and has the potential to minimize the chances of the virus escaping. It was shown in animal studies that the cocktail reduces the pathological consequences caused by viruses, decreases the number of viruses in the respiratory system, and reduces lung titers and pneumonia symptoms. Casirivimab and imdevimab as a cocktail also prevents the rapid appearance of treatment-resistant mutants. In the clinical trial, REGN-COV-2 decreased viral load, particularly in patients with a non-initiated immune response (serum antibody-negative) and with high viral load at baseline. The adverse effects were comparable in the combined REGN-COV2 dose groups (2.4 g and 8.0 g), as well as in the placebo group. The cocktail caused few and mainly low-grade toxic effects. Casirivimab and imdevimab seem to be effective and safe antiviral therapy for nonhospitalized patients with COVID-19. Further observations and research are extremely necessary to assess the efficacy, security and indications in a wider group of patients.

Background and Objectives: Liver metastases might not be detected by computed tomography (CT) and magnetic resonance imaging (MRI) due to their small size, but they can be detected by EUS. Furthermore, EUS-FNA has a significant impact on improving the diagnostic accuracy of EUS. The purpose of this study was to assess the feasibility of EUS in detection of occult small hepatic focal lesions at the time of primary tumor staging, not seen by CT or MRI. Methods: This prospective study included 730 patients who underwent EUS for staging or sampling of gastrointestinal, pancreatic, or thoracic malignancy. The liver was examined thoroughly for detection of occult lesions. CT or MRI was done within 1 week of EUS examination. Results: EUS examination of the liver detected focal lesions in 150 patients (20.5%) and metastases in 118 patients (16.2%); meanwhile, CT and MRI detected focal lesions in 99 patients (13.6%) and metastases in 82 patients (11.2%). EUS missed focal lesions in 7 patients, 6 of which were liver metastases (1.0% and 0.8%, respectively), while CT and MRI missed focal lesions in 58 patients, 42 of which were metastases (7.9% and 5.8%, respectively), which were detected by EUS. Conclusion: Thorough dedicated EUS examination of the liver is a feasible useful tool for detection of small hepatic lesions missed by CT and MRI. It is not considered an extra financial burden to the patient or health-care system because those patients are indicated for EUS examination for evaluation of their original lesion in the first place. Furthermore, EUS-FNA can add another advantage in diagnosing the etiology of such lesions.

Objectives The main aim of this work is to assess the level of knowledge about diabetes prevention and the consequences of untreated diabetes in the Polish society, as well as to indicate the variables that have a significant impact on that knowledge. Material and Methods The analysis is based on the results of the National Multicenter Health Survey – WOBASZ II. The number of subjects surveyed was 6170, including 2760 men and 3410 women, aged 20–74 years. Data on socio-demographic variables, lifestyle and subjective health assessment were collected using the face-to-face technique. Results The results obtained in the WOBASZ II project showed that >85% of the respondents had an unsatisfactory level of knowledge about diabetes prevention methods and approximately to 85% of the respondents – about the consequences of untreated diabetes. Moreover, one-fourth of the respondents were unable to identify a single way of preventing diabetes, and more than one-third could not identify a single disease caused by diabetes. The risk of a lack of knowledge about diabetes prevention and the consequences of untreated diabetes is more common for men, people with a low level of education, not married, non-diabetic, and without diagnosed diabetes in the family. Conclusions The presented results indicate that there is an prevailing lack of knowledge about diabetes prevention and the consequences of untreated diabetes in the Polish society. It is associated with several variables like: sex, level of education, age, marital status, subjective health assessment and diabetes diagnosed in the respondent and/or in the respondent’s family. Int J Occup Med Environ Health. 2021;34(5):667–78

Background The COVID-19 pandemic has created unprecedented challenges in all fields of society with social, economic, and health-related consequences worldwide. In this context, gastroenterology patients and healthcare systems and professionals have seen their routines changed and were forced to adapt, adopting measures to minimize the risk of infection while guaranteeing continuous medical care to chronic patients. Objective At this point, it is important to evaluate the impact of the pandemic on this field to further improve the quality of the services provided in this context. Methods/results/conclusion We performed a literature review that summarizes the main aspects to consider in gastroenterology, during the pandemic crisis, and includes a deep discussion on the main changes affecting gastroenterology patients and healthcare systems, anticipating the pandemic recovery scenario with future practices and policies.

Digestate is a nutrient-rich substance produced by anaerobic digestion that contains organic, inorganic, and biological matter. The European Nitrates Directive (91/676/EEC) provides regulations regarding the wider implementation of the digestate. Owing to a significant amount of organic matter in the digestate, it can be utilised as a solid biofuel, soil amendment substance, or substrate for activated carbon production. However, the solid by-products of the anaerobic digestion of the municipal solid waste wet fraction cannot be used for such applications because it is still considered a waste. Hydrothermal carbonisation (HTC) was investigated as a pre-treatment method for the digestate obtained by anaerobic digestion of the municipal solid waste wet fraction. HTC was carried out at temperatures of 180, 200 and 230 °C and residence times of 30, 60 and 120 min. The value of pressure was determined based on water temperature and partial pressure of the gaseous by-products. The HTC process resulted in changes in the physical and chemical properties of the hydrochars compared to those of the raw materials. A temperature of 200 °C and residence time of 60 min during HTC were optimal for energy consumption; this hydrochar exhibited the best combustion parameters and physical properties (specific surface area).

BACKGROUND AND AIM The proper visibility of mucosa during esophagogastroduodenoscopy (EGD) is crucial for the detection of early upper gastrointestinal tract lesions. In contrast to colonoscopy, no validated scoring system for the assessment of upper gastrointestinal mucosal cleanliness has been developed so far. The aim of the study was to create and validate standardized grading system (POLPREP) to assess the mucosal cleanliness during EGD. METHODS To assess the visibility of mucosa during EGD, 4-point scale was developed (0-3). Twelve operators assessed 18 images of esophagus, stomach, and duodenum twice (in 2 weeks interval). In validation round, the images and endoscopy reports of 443 EGDs performed in six centers were assessed. RESULTS The inter-observer accordance of POLPREP was 0.8 (intra-class correlation coefficient; 0.79 consultants, 0.85 trainees). The intra-observer repeatability was 0.64 (Fleiss kappa value; 0.64 consultants, 0.64 trainees). The lesions detection rate was significantly higher in clean (scores 2 and 3; 19.7%) than in "unclean" segments (score 1; 7.7%, P = 0.049). Score 3 was associated with over three-fold higher lesion detection than score 1 (odds ratio 3.2, 95% confidence interval 1.1-9; P = 0.03). CONCLUSIONS The proposed POLPREP scale allows for unified assessment of upper gastrointestinal tract mucosal cleanliness. The higher cleanliness scores are related with greater upper gastrointestinal pathologies detection.

[Abstract] Aims. This study aimed to assess age‐ and sex‐related differences in management and 1‐year risk for all‐cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results. Of 16 354 patients included in the European Society of Cardiology Heart Failure Long‐Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline‐directed medical therapy (GDMT) were high (angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, beta‐blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1‐year follow‐up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all‐cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all‐cause hospitalization (21.9% vs. 27.3%; P < 0.001) and there were no differences in causes of death. All‐cause mortality and all‐cause hospitalization increased with greater age in both sexes. Sex was not an independent predictor of 1‐year all‐cause mortality (restricted to patients with LVEF ≤45%). Mortality risk was significantly lower in patients of younger age, compared to patients aged >75 years. Conclusions. There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all‐cause mortality in patients with LVEF ≤45%.

It has been reported that altered dopaminergic neurotransmission may contribute to the development of aggressive behaviors and emotional intelligence (EI) impairment. However, less is known about the impact of polymorphisms in dopaminergic genes on the level of aggression and EI. Therefore, we aimed to investigate the association between the catechol-O-methyltransferase (COMT) rs6277 gene polymorphism and the dopamine 2 receptor (DRD2) rs4680 gene polymorphism as well as the level of aggression and EI in adolescents with conduct disorder. Participants were 144 adolescents with conduct disorder recruited at the youth sociotherapy centre. The Buss-Perry Aggression Questionnaire (BPAQ) was administered to record the level of aggression while the Popular Emotional Intelligence Questionnaire (PEIQ) and the Schutte Self-Report Inventory (SSRI) were used to assess EI. We found no significant associations between selected polymorphisms and the scores of BPAQ, PEIQ and SSRI. Our findings do not support the role of the COMT and the DRD2 gene polymorphisms in shaping aggressive behaviors and EI in adolescents with conduct disorder. Longitudinal studies on larger populations are needed to confirm these results.

Jolanta Kolasa,1 Magdalena Lisiak,2 Marcin Grabowski,3 Ewa A Jankowska,4 Malgorzata Lelonek,5 Jadwiga Nessler,6 Agnieszka Pawlak,7 Izabella Uchmanowicz2 1Medical Unit Cardiology, Novartis Poland Sp. z o.o, Warsaw, Poland; 2Department of Clinical Nursing, Faculty of Health Sciences, Wroclaw Medical University, Wroclaw, Poland, and Centre for Heart Diseases, University Hospital, Wroclaw, Poland; 3 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland; 4Centre for Heart Diseases, University Hospital, Wroclaw, Poland, and Department of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland; 5Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland; 6Department of Coronary Disease and Heart Failure, Jagiellonian University Medical College, John Paul II Hospital, Krakow, Poland; 7Department of Invasive Cardiology, Centre of Postgraduate Medical Education, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland, and Department of Applied Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, PolandCorrespondence: Jolanta KolasaMedical Unit Cardiology, Novartis Poland Sp. z o.o, Marynarska 15, Warsaw, 02-674, PolandTel +48 22 375 48 88Email jolanta.kolasa@novartis.comPurpose: As insufficient adherence to recommendations is a major cause of poor health outcomes in patients with heart failure (HF), it is important to identify the factors that improve disease knowledge and self-care behaviors. We aimed to identify factors associated with HF knowledge and self-care behaviors in patients hospitalized due to acute decompensated heart failure (ADHF) in Poland.Patients and Methods: This was a secondary analysis of data from a multi-center, prospective, non-randomized educational program named “The Weak Heart”, which was conducted in 14 cardiology centers in Poland. The level of HF knowledge was assessed using a questionnaire developed by the research team, and self-care behaviors were evaluated using the European Heart Failure Self-care Behaviour Scale (9-EHFScBS) questionnaire.Results: The study included 259 patients admitted to the hospital with ADHF. The mean HF knowledge and 9-EHFScBS questionnaire scores were 8.25± 4.34 and 25.2± 9.5, respectively. The patients’ level of education (P = 0.002), number of prior HF hospitalizations (P = 0.008), and previous disease education (P < 0.001) were independently associated with better HF knowledge. Age (P = 0.03) and disease education (P = 0.02) were independently associated with self-care behaviors.Conclusion: The adherence to self-care recommendations among patients with ADHF is insufficient. Disease education positively influenced both HF knowledge and self-care abilities. To improve patients’ adherence to HF recommendations, well-designed models of education based on HF management guidelines should be implemented.Keywords: adherence, heart failure, health education, self-care behaviors

Introduction. In 2018, another update of the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/ Sedation, Delirium, Immobilization and Sleep Disorders in Adult Patients Treated in Intensive Care Units (ICUs) was released. Aim. The study is aimed at presenting current recommendations concerning pain management in patients treated in ICU, and presenting the algorithm of pain assessment and monitoring in patients treated in ICU, using a Polish version of the BPS (Behavioural Pain Scale). The guidelines were prepared based on a systematic review of the literature published in the years 2013-2018. Material and methods. The search for scientific publications was carried out using electronic databases in English and Polish. The following keywords and their combinations were used in the searches: pain, assessment, monitoring, nurse, intensive care, adult patient, unable to communicate. Initially, 758 papers were identified with the use of keywords. After excluding duplicates and preliminary checking and selecting the titles of publications and abstracts, 85 papers were qualified for the analysis of full text. Conclusions. Access to effective pain treatment is a fundamental human right. Recommendations of the Polish Association of Anaesthesia and Intensive Care Nurses, concerning pain monitoring in ICU using a Polish version of the Behavioural Pain Scale (BPS), developed by the Task Force for Practice, are intended to provide a specific guideline for developing effective local pain management strategies in ICU.

Background An acute inguinal hernia remains a common emergency surgical condition worldwide. While emergency surgery has a major role to play in treatment of acute hernias, not all patients are fit for emergency surgery, nor are facilities for such surgery always available. Taxis is the manual reduction of incarcerated tissues from the hernia sack to its natural compartment, and can help delay the need for surgery from days to months. The aim of this study was to prepare a safe algorithm for performing manual reduction of incarcerated inguinal hernias in adults. Methods Medline, Scopus, Ovid and Embase were searched for papers related to emergency inguinal hernias and manual reduction. In addition, the British National Formulary and Safe Sedation Practice for Healthcare Procedures: Standards and Guidance were reviewed. Results A safe technique of manual reduction of an acute inguinal hernia, called GPS (Gentle, Prepared and Safe) Taxis, is described. It should be performed within 24 h from the onset of a painful irreducible lump in groin, and when concomitant symptoms and signs of bowel strangulation are absent. Conscious sedation guidelines should be followed. The most popular drug combination is of intravenous morphine and short-acting benzodiazepine, both titrated carefully for optimal and safe effect. The dose of drugs must be individualised, and the smallest effective dosage should be used to avoid oversedation. Following successful taxis, the patient should undergo a short period of observation. Urgent surgery can be undertaken during the same admission or up to several weeks later. Conclusions Taxis is a benign/non-invasive method for patients with an acute, non-strangulated inguinal hernias. It likely reduces the risk and complications of anaesthesia and surgery in the emergency settings. GPS Taxis should be considered as first line treatment in the majority of patients presenting with an acute inguinal hernia when existing bowel infarction is unlikely. Supplementary Information The online version contains supplementary material available at 10.1007/s10029-021-02429-1.

Sparse studies have shown that specific biomarkers of a global DNA methylation status may be related to various mental diseases and states, including: bipolar disorder (BD), anxiety and major depression disorder (MDD). The objective of this study was to analyze potential variation of the above mentioned global methylation status in women with depression. 38 women with a current and clinically confirmed depressive episode suffering from BD type I, type II or MDD and 71 women from the general population and at similar age were recruited for the study. Alu and LINE-1 methylation was assayed with the quantitative methylation-specific PCR technique with TaqMan probes, while the 5-mC and 5-hmC level was determined using the ELISA-based method. Significantly higher levels of 5-mC, Alu and LINE-1 methylation were observed in the women with depression as compared to the controls; while the 5-hmC level revealed to be significantly lower. The BD type I patients presented the highest level of 5-mC of all the women with a depressive episode. 5-mC level in the patients was positively and significantly correlated with the severity of the symptoms of depression. Relationships between Alu or LINE-1 methylation and 5-mC level were statistically significant only in the case of the control women. Alu and LINE-1 methylation do not constitute suitable biomarkers of global DNA methylation in the investigated patients. These findings require confirmation in case-control and prospective epidemiological studies.

PawlakAngelika,RękaGabriela,OlszewskaAnna,WarchulińskaJoanna,Piecewicz-SzczęsnaHalina. Methods of assessing body composition and anthropometric measurements – a review of the literature.Journal of Education, Health and Sport. 2021;11(4):18-27. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2021.11.04.002 https://apcz.umk.pl/czasopisma/index.php/JEHS/article/view/JEHS.2021.11.04.002 https://zenodo.org/record/4671483 The journal has had 5 points in Ministry of Science and Higher Education parametric evaluation. § 8. 2) and § 12. 1. 2) 22.02.2019. © The Authors 2021; This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 21.03.2021. Revised: 26.03.2021. Accepted: 08.04.2021. Methods of assessing body composition and anthropometric measurements – a review of the literature Angelika Pawlak ORCID iD https://orcid.org/0000-0003-4130-2593 Affiliation Students’ Scientific Association of Chair and Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin Country Poland Bio Statement — Principal contact for editorial correspondence. Gabriela Ręka ORCID iD https://orcid.org/0000-0001-9728-5281 Affiliation Students’ Scientific Association of Chair and Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin Country Poland Bio Statement — Anna Olszewska ORCID iD https://orcid.org/0000-0002-9787-0373 Affiliation Chair and Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin Country Poland Bio Statement — Joanna Warchulińska ORCID iD https://orcid.org/0000-0001-8814-7231 Affiliation Chair and Department of Human Physiology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin Country Poland Bio Statement — Halina Piecewicz-Szczęsna ORCID iD https://orcid.org/0000-0002-0573-7226 Affiliation Chair and Department of Epidemiology and Clinical Research Methodology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin Country Poland Bio Statement — Abstract Introduction and purpose Body composition assessment is an important element in determining the health of the body, which enables us to estimate the percent content of particular tissues in the body. Measured parameters include the amount of adipose tissue, muscle, bone tissue, and hydration. The aim of the study is to present a differentiation of methods of assessing body composition and anthropometric measurements after analysis of 29 scientific publications from Pubmed and Google Scholar. A brief description of the state of knowledge Bioelectrical impedance analysis, densitometry, magnetic resonance imaging, computed tomography, and air displacement plethysmography are methods that enable us to assess body composition and hydration. These methods differ from each other in equipment which is used, accuracy, test price, and technique of measurement. The differences in the accuracy of measurements result from the lack of correlation between the methods given. Skinfold thickness, body mass index, waist to hip circumference ratio, and growth charts in children are methods of assessing anthropometric measurements. The research shows the use of individual methods of assessing body composition and methods of anthropometric measurements among different age groups. Conclusions There are many devices and methods for measuring body composition and for anthropometric measurements, which can be used in different age groups. They are important in assessing human growth, development, and health status and can be used in clinical practice. Keywords: body composition; measures; weights; bioelectrical impedance

Personalised therapy is currently a promising method of treatment for cancer patients. The dynamic development of molecular biology enabled identification of molecular subtypes of neoplasms, allowing determination of the optimal therapeutic management for the patient. Molecular diagnostics is also essential for cancer diagnosis, predicting disease development and prognosis. In the case of lung cancer, which is one of the most common malignant neoplasms, the main candidates for targeted treatment are patients with stage III and IV of the disease and with no possibility of radical local treatment. In clinical practice, the most proven therapeutic agents are inhibitors of tyrosine kinase, i.e. a receptor of the epithelial growth factor (TKI-EGFR), inhibitors of ALK, ROS1, BRAF and others, as well as immunotherapy applying monoclonal antibodies against immunological system checkpoints in cases of high level expression of programmed death receptor type 1 (PD-1) or its ligand (PD-L1), but also in cases of the high tumour mutational burden (TMB). As compared to chemotherapy, targeted therapy undoubtedly improves the treatment outcomes and, due to its lower toxicity, improves the quality of life of advanced non-small cell lung cancer patients. The aim of this paper is to characterise molecular tests which are currently applied in qualification of non-small cell lung cancer patients for targeted therapies.

Abstract Glioblastoma is the most common and malignant primary brain tumour, with a poor prognosis. Introduction of new treatment options is critically important. The study aimed to assess the appropriateness of escalation doses and toxicity of [225Ac]Ac-DOTA-SP therapy. Material and methods A total of 21 patients (age of 43.0 ± 9.5 years), with histologically confirmed recurrent or conversion glioblastoma grade 4 following a standard therapy, have been included in the study. One to 2 intracavitary port-a-cath systems were stereotactically inserted. Patients were treated with escalation dose protocol with 10, 20 and 30 MBq per cycle totally 1–6 doses of [225Ac]Ac-DOTA-SP in 2-month intervals. Therapeutic response was monitored by clinical performance status and MRI imaging. Results Treatment was well tolerated with mostly mild temporary adverse effects (oedema, epileptic seizures, aphasia, hemiparesis) mainly in the group of patients treated with 30 MBq of [225Ac]Ac-DOTA-SP. Only one patient treated with 30 MBq revealed thrombopenia grade 3. There was no other grade 3 and 4 toxicity related to [225Ac]Ac-DOTA-treatment in all groups. The median overall survival time from the primary diagnosis (OS-d) was 35.0 months and from the diagnosis of the recurrence/conversion (OS-r/c) was 13.2 months. From the start of treatment with [225Ac]Ac-DOTA-SP, the median PFS was 2.4 months, and the OS-t was 9.0 months. There were no statistically significant differences between the investigated dose escalation groups. Conclusions Treatment of recurrent glioblastoma with [225Ac]Ac-DOTA-SP is safe and well tolerated up to 30 MBq per cycle. The escalation dose protocol showed good tolerability. Only mild temporary adverse effects were observed. No remarkable haematological, kidney and liver toxicity was seen.

Contains fulltext : 251528.pdf (Publisher’s version ) (Open Access) The interocular distance, or orbital telorism, is a distinctive craniofacial trait that also serves as a clinically informative measure. While its extremes, hypo- and hypertelorism, have been linked to monogenic disorders and are often syndromic, little is known about the genetic determinants of interocular distance within the general population. We derived orbital telorism measures from cranial magnetic resonance imaging by calculating the distance between the eyeballs' centre of gravity, which showed a good reproducibility with an intraclass correlation coefficient of 0.991 (95% confidence interval 0.985-0.994). Heritability estimates were 76% (standard error = 12%) with a family-based method (N = 364) and 39% (standard error = 2.4%) with a single nucleotide polymorphism-based method (N = 34 130) and were unaffected by adjustment for height (model II) and intracranial volume (model III) or head width (model IV). Genome-wide association studies in 34 130 European individuals identified 56 significantly associated genomic loci (P

Although recent years have seen a growing interest in positive emotions in second or foreign language learning and teaching, negative emotions are always present in the classroom and they deserve to be investigated in their own right. The article focuses on boredom, a construct that has been explored in educational psychology but has received only scant attention from second language acquisition researchers. It reports a study which examined the changes in the levels of boredom experienced by 13 English majors in four EFL classes and the factors accounting for such changes. Using data obtained from a few different sources (i.e., boredom grids, narratives, interviews, class evaluations and lesson plans), it was found that although boredom can be attributed to different constellations of factors, it was mainly traced to repetitiveness, monotony and predictability of what transpired during a particular class.

In the era of personalized medicine, the ability of pre-selecting individualized therapeutic options and pre-defining their suitability in advance of clinical treatment might facilitate decision making in breast cancer treatment and hence, improve patient outcome. In order to preclinically validate anti-cancer drug efficacy, it is crucial to design a model system that reveals the influence of cellular interactions of the tumor microenvironment and cellular heterogeneity on drug response. Within the PRIMO (Personalized Medicine for tailored cancer therapies) project, such a 3D preclinical model system comprised of patient-derived microtumors (PDM) and autologous tumor-infiltrating lymphocytes (TILs) isolated from fresh primary breast cancer tissue using limited digestion and subsequent culture in defined media in the absence of serum is established. Herein, the heterogeneous cellular composition of isolated PDM is analyzed by FFPE immunohistochemistry and compared to corresponding primary tumor tissue. The composition of autologous TILs influencing individual treatment responses is characterized by multi-color flow cytometry detecting different cell populations, such as tumor-specific CD8+ or regulatory CD4+ T-cells. By using the DigiWest technology, a proprietary high throughput immune assay screening tool, in-depth protein profiling of up to 200 analytes from low amounts of PDM material is performed. The generated protein profiles of PDM are compared to their corresponding primary tumor tissue as well as the pathological receptor grading. Furthermore, differences in activation of key signal transduction pathways are detected and related to treatment responses to small molecules, chemotherapeutics as well as immunotherapeutic agents within PDM and PDM-TIL co-cultures assessed by a functional viability assay in a microplate format. To expand this preclinical model system, we established PDM-co-cultures adding further immune cell types including natural killer (NK) cells or dendritic cells (DC). In summary, immunohistochemical analyses combined with protein profiling of breast cancer PDM enables drug-mode-of-action analyses, biomarker identification together with personalized therapeutic sensitivity prediction. The platform presented here expands the preclinical repertoire of relevant test systems for efficacy testing of drugs and investigational compounds, pre-identified by protein pathways as well as genetic profiling in personalized medicine of breast cancer. Citation Format: Nicole Anderle, Felix Ruoff, Simge Yuez, André Koch, Andreas Hartkopf, Sara Brucker, Michael Pawlak, Markus Templin, Christian Schmees. A fast and effective 3D preclinical assay system comprised of patient derived breast cancer microtumors combined with DigiWest protein signaling pathway analyses for therapeutic response prediction (Project PRIMO) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-42.

BACKGROUND Despite the progress in the treatment of heart failure with reduced ejection fraction (HFrEF), the prognosis remains unfavorable. OBJECTIVES To evaluate the effectiveness, tolerance and safety after one-year follow-up of Polish patients with stable chronic HFrEF treated with sacubitril/valsartan. MATERIAL AND METHODS This was an observational multicenter study conducted in 3 centers (Krakow, Łodź and Warszawa) specializing in heart failure (HF). We enrolled 89 HFrEF patients (aged 59.3 ±13.5 years, 82% males) in NYHA class II-IV (ambulatory). Clinical, laboratory and echocardiographic parameters were evaluated at baseline and after a one-year follow-up. The composite endpoint was defined as death or urgent HF hospitalization. RESULTS After 1 year, 80% of patients used 50% or more of the target dose of sacubitril/valsartan. After a year of treatment, there were significant improvements of HF symptoms, N-terminal prohormone B-type natriuretic peptide (NT proBNP), ejection fraction (EF), and distance in six-minute walk test (6MWP) (all p < 0.001). Patients treated with the highest dose of sacubitril/valsartan exhibited the greatest benefits. The safety profile was favorable and consistent with that previously reported; however, therapy discontinuation due to side effects occurred in 11% of patients. The independent predictors for composite endpoint (n = 24, 26.9%) were history of HF hospitalization, tricuspid annular plane systolic excursion (TAPSE) and angiotensin-converting-enzyme inhibitor (ACEI)-naive patients. CONCLUSIONS Treatment of chronic HFrEF patients with sacubitril/valsartan is safe and is associated with significant clinical and objective improvement. The non-survivors had more advanced HF, so the initiation and uptitration of sacubitril/valsartan should be done early.

Despite a growing focus on positive psychology in recent years, negative emotions have not ceased to play a crucial role in learning additional languages in the classroom. This paper reports a study that investigated one such negative emotion – boredom – as experienced by 115 advanced learners of English. They were asked to write a descriptive paragraph about boredom that they experienced during English classes. Qualitative analysis resulted in the identification of five broad categories of factors responsible for student boredom – namely, language tasks, the teacher, modes of class organization, class components and others. On that basis, some boredom-coping solutions are offered.

Allergy is the result of the body’s intolerance to harmless antigens. In the treatment of respiratory allergies, allergen immunotherapy (AIT) is a causal method of treating allergies. It can be carried out via the subcutaneous route (SCIT) or the sublingual route (SLIT) – in the form of drops or tablets. Desensitisation is recommended from the age of 5 years, and the doses of the drug should be repeated gradually so that the body acquires immunological tolerance to allergens. Thirty-six current publications from the PubMed and Google Scholar platforms were reviewed. A series of studies confirming the safety, efficacy, and good tolerability of both types of AIT in children and adults were referred to. The results presented in the review show the similarities and differences between the desensitisation methods. They differ, among other things, in the convenience of use, the price, the frequency of side effects of treatment, and the dosage.

Cystic endometrial hyperplasia-pyometra complex (CEH/P) significantly perturbs the reproductive performance of affected bitches and ovariohysterectomy (OHE) is a commonly applied treatment. Thus the only way to take advantage of the genetic potential of valuable females is application of assisted reproductive techniques (ART) mainly in vitro embryo production (IVP) or in some exceptional cases animal cloning by somatic cell nuclear transfer (SCNT). The aim of our study was to examine a potential effect of the CEH/P status on the quality of oocytes from females subjected to OHE. In total, 828 immature oocytes collected from ovaries of 33 bitches (21 control, 12 CEH/P) were subjected to genetic analyses (mRNA expression of two maternal-effect genes: GDF-9, OCT4 and mitochondrial DNA (mtDNA) content). Oocytes of CEH/P females were characterized by a higher mtDNA content (471 696) than gametes of their healthy counterparts (368 175; P

Background: In recent years, food allergy has been diagnosed more frequently in children and adolescents. The environment is more toxic and chemical substances that are additives to food dominate the diet. Also, a changing lifestyle, exposure to stress, and a poorly balanced diet may have an impact on the occurrence of allergies. In society, more children suffer from food allergies than adults, and food allergies are becoming an increasingly serious social and medical problem. Aim of the study: The aim of this study is to review the subject of food allergies in children, with a focus on the social and medical problems associated with this condition. Material and methods: 31 studies, published in the last 10 years, were found in databases such as the Polish Medical Bibliography, PubMed Medline, and Google Scholar, using the following keywords: “food allergy”, “risk factors”, “diet”, “psychology”, “social aspects”. Conclusions: Given the potentially serious medical and social consequences resulting from allergic diseases, the increasing incidence of allergies among children and young people should motivate medical personnel and educators to receive additional training and to conduct further research in this area.

Inhalation of tobacco smoke has been linked to increased risk of viral infection, such as influenza. Inhalation of electronic-cigarette (e-cigarette) aerosol has also recently been linked to immune suppression within the respiratory tract, specifically the nasal mucosa. We propose that changes in the nasal mucosal immune response modify antiviral host-defense responses in e-cigarette users. Nonsmokers, cigarette smokers, and e-cigarette users were inoculated with live-attenuated influenza virus (LAIV) to safely examine the innate immune response to influenza infection. Before and after LAIV inoculation, we collected nasal epithelial-lining fluid, nasal lavage fluid, nasal-scrape biopsy specimens, urine, and blood. Endpoints examined include cytokines and chemokines, influenza-specific IgA, immune-gene expression, and markers of viral load. Statistical analysis included primary comparisons of cigarette and e-cigarette groups with nonsmokers, as well as secondary analysis of demographic factors as potential modifiers. Markers of viral load did not differ among the three groups. Nasal-lavage-fluid anti-LAIV IgA levels increased in nonsmokers after LAIV inoculation but did not increase in e-cigarette users and cigarette smokers. LAIV-induced gene-expression changes in nasal biopsy specimens differed in cigarette smokers and e-cigarette users as compared with nonsmokers, with a greater number of genes changed in e-cigarette users, mostly resulting in decreased expression. The top downregulated genes in cigarette smokers were SMPD3, NOS2A, and KLRB1, and the top downregulated genes in e-cigarette users were MR1, NT5E, and HRAS. Similarly, LAIV-induced cytokine levels in nasal epithelial-lining fluid differed among the three groups, including decreased antiviral host-defense mediators (IFNγ, IL6, and IL12p40). We also detected that sex interacted with tobacco-product exposure to modify LAIV-induced immune-gene expression. Our results demonstrate that e-cigarette use altered nasal LAIV-induced immune responses, including gene expression, cytokine and chemokine release, and LAIV-specific IgA levels. Together, these data suggest that e-cigarette use induces changes in the nasal mucosa that are consistent with the potential for altered respiratory antiviral host-defense function. Clinical trial registered with www.clinicaltrials.gov (NCT 02019745).

Background Tryptophan metabolism via the kynurenine pathway is considered the link between the immune and endocrine systems. Dysregulation of serotonergic transmission can stem from the direct influence of interferon-α on the activity of serotonergic receptors 5-HT1A and 5-HT2A, and from its indirect effect on tryptophan metabolism. Induction of the kynurenine pathway increases the concentration of neurotoxic kynurenine metabolites, and the activity of kynurenine derivatives is linked to the onset of depression. The aim of our study was to evaluate the relationships between depressive symptoms and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, indolamine 2,3-dioxygenase (IDO) activity and tryptophan availability to the brain. Methods The study followed a prospective longitudinal cohort design. We evaluated 101 patients with chronic hepatitis C who were treated with pegylated interferon-α2a, and 40 controls who were awaiting treatment. We evaluated the relationships between total score on the Montgomery–Asberg Depression Rating Scale and kynurenine, tryptophan, anthranilic acid and kynurenic acid concentrations, IDO activity and tryptophan availability to the brain. A logistic regression model was adapted for the diagnosis of major depressive disorder at each time point, taking into account changes in parameters of the kynurenine pathway between a given time point and the baseline measurement. Results Of the treated patients, 44% fulfilled the criteria for major depressive disorder at least once during the 24 weeks of treatment. Anthranilic acid concentrations were significantly increased compared to baseline for all time points except week 2. Tryptophan availability showed a significant decrease (β = −0.09, p = 0.01) only in week 12 of treatment. Over time, kynurenine, tryptophan and anthranilic acid concentrations, as well as IDO activity and tryptophan availability to the brain, were significantly associated with total score on the Montgomery–Asberg Depression Rating Scale. A logistic regression model revealed that participants with decreased tryptophan availability to the brain at 12 weeks of treatment and participants with increased anthranilic acid concentrations at week 24 of treatment were at increased risk for diagnosis of major depressive disorder (odds ratios 2.92 and 3.59, respectively). Limitations This study had an open-label design in a population receiving naturalistic treatment. Conclusion The present study provides the first direct evidence of the role of anthranilic acid in the pathogenesis of inflammation-induced major depressive disorder during treatment for hepatitis C with pegylated interferon-α2a.

INTRODUCTION Peritraumatic distress is a syndrome that involves negative emotions, such as anxiety, helplessness and horror, experienced during and shortly after a traumatic event. The intensity of peritraumatic distress is significantly linked to the intensity of post-traumatic stress syndrome (PTSD) symptoms. The aim of the study was to study the intensity of peritraumatic distress symptoms in the mothers of severely ill children and the relationship between peritraumatic distress and psychological, socio-demographic and medical coefficients in the mothers. MATERIAL AND METHODS An anonymous survey was performed in a group of 135 mothers of children with a perinatal medical history and mothers of children hospitalized in an intensive care unit and an oncology unit. The demographic questionnaire was compiled by the authors along with several standardized research tools. RESULTS Intensity of peritraumatic distress correlates strongly positively with anxiety, ρ = 0.50; P < 0.001, and moderately positively with intrusion ρ = 0.39; P < 0.00, arousal, ρ = 0.38; P < 0.001, PTSD intensification, ρ = 0.40; P < 0.001, depression, ρ = 0.49; P < 0.001. Significant predictors of peritraumatic distress include the use of such coping strategies as acceptance, β = -0.44; P = 0.001, denial, β = 0.20; P = 0.019, planning, β = -0.26; P = 0.012 and humour, β = -0.29; P = 0.048, as well as the possibility to obtain self-worth support, β = -0.07; P = 0.029 (R2 corrected = 0,32; F(5.33) = 9.43; P < 0.001). CONCLUSIONS Coping strategies are a potentially modifiable factor, thus, implementing prevention programmes concerning the strategies should be considered.

MM-129 is a novel inhibitor targeting BTK/PI3K/AKT/mTOR and PD-L1, as it possesses antitumor activity against colon cancer. To evaluate the safety profile of MM-129, we conducted a toxicity study using the zebrafish and rodent model. MM-129 was also assessed for pharmacokinetics features through an in vivo study on Wistar rats. The results revealed that MM-129 exhibited favorable pharmacokinetics with quick absorption and 68.6% of bioavailability after intraperitoneal administration. No serious adverse events were reported for the use of MM-129, confirming a favorable safety profile for this compound. It was not fatal and toxic to mice at an anticancer effective dose of 10 μmol/kg. At the end of 14 days of administering hematological and biochemical parameters, liver and renal functions were all at normal levels. No sublethal effects were either detected in zebrafish embryos treated with a concentration of 10 μM. MM-129 has the potential as a safe and well-tolerated anticancer formulation for future treatment of patients with colon cancer.

PLs bilayers coating the major synovial joints such as knees and hips as the lubricant are responsible for the lubrication of articular cartilage. Lamellar-repulsive effect has been considered as a lubrication mechanism but it is likely that lubricin and hyaluronan with PLs participate in the lubrication process. The molecules of lubricin and hyaluronan adsorbed by PLs have a supportive role and provide the efficient lubrication of synovial joints via the hydration mechanism (~ 80% water content). Lipid profiles of injured and healthy knees’ synovial fluids show significant differences. The phospholipid content in synovial fluid (SF) during joint inflammation, osteoarthritis is significantly higher (2 to 3 times) above the normal concentration of PL, and has a poor boundary-lubricating ability because of deactivated PL molecules. Deactivated PL molecule has no ability to form bilayers, lamellar phases, and liposomes.

The first case of the coronavirus SARS-CoV-2 infection was confirmed in December 2019 in Wuhan, China, from whence the virus spread across the world within several weeks. Due to the alarming level of infections, the World Health Organisation (WHO) announced a SARS-CoV-2 pandemic on 12 March. This dynamic and unprecedented epidemiological situation created an urgent need to carry out SARS-CoV-2 tests in individuals meeting the criteria defined for COVID-19 suspect cases. According to the current WHO recommendations, active SARS-CoV-2 infection diagnostics is based on molecular method using a real-time reverse transcription – polymerase chain reaction (real-time RT-PCR). Highly specific and sensitive, this method makes it possible to detect even a small amount of RNA particles of the virus in the tested sample. Undoubtedly, the launch of new COVID laboratories and the implementation of adequate procedures increases the effectiveness of activities aimed at directly combatting the SARS-CoV-2 pandemic. The population of oncological patients is particularly exposed to the risk of complications and death resulting from the SARS-CoV-2 infection; therefore it is essential to ensure them the possibility of quick testing for COVID-19. This article presents the authors’ own experiences as well as technical and formal issues related to the launching of a SARS-CoV-2 laboratory.

CD4+T helper (Th) cells are critical in homeostasis and host defense but are also central to the development of various autoimmune diseases if they become dysregulated. Specifically, pathogenic Th1 and Th17 cells contribute to autoimmune inflammation whereas Treg and Tr1 cells are important for maintaining immune tolerance and resolution of inflammation, respectively. Cytokines trigger signaling pathways in naive T cells that induce lineage-defining transcription factors that direct their differentiation into the distinct T helper cell subsets. It has become clear that the differentiation of T helper cells is not only influenced by the cytokine milieu but also by their metabolic state, cues from the microbiota and the tissue they reside in. A comprehensive understanding how these various stimuli contribute to T helper cell differentiation and phenotype could potentially provide novel ways for therapeutic intervention in autoimmunity and tissue inflammation.

Anophthalmia and microphthalmia (A/M) represent severe developmental ocular malformations, corresponding, respectively, to absent eyeball or reduced size of the eye. Both anophthalmia and microphthalmia may occur in isolation or as part of a syndrome. Genetic heterogeneity has been demonstrated, and many genes have been reported to be associated with A/M. The advances in high-throughput sequencing have proven highly effective in defining the molecular basis of A/M. Nevertheless, there are still many patients with unsolved genetic background of the disease, who pose a significant challenge in the molecular diagnostics of A/M. Here we describe a family, with three males affected with the non-syndromic A/M. Whole exome-sequencing performed in Patient 1, revealed the presence of a novel probably pathogenic variant c.734A>G, (p.[Tyr245Cys]) in the PORCN gene. Pedigree analysis and segregation of the identified variant in the family confirmed the X-linked recessive pattern of inheritance. This is the first report of X-linked recessive non-syndromic A/M. Until now, pathogenic variants in the PORCN gene have been identified in the patients with Goltz syndrome, but they were inherited in X-linked dominant mode. The ocular phenotype is the only finding observed in the patients, which allows to exclude the diagnosis of Goltz syndrome.