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Abstract Background Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity’s impact on EV secretion from human AT remains limited. Methods We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography–mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry. Results EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation. Conclusions We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.

Summary: Background: Abdominal obesity increases the risk for non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: To elucidate the directional cell-type level biological mechanisms underlying the association between abdominal obesity and MASLD, we integrated adipose and liver single nucleus RNA-sequencing and bulk cis-expression quantitative trait locus (eQTL) data with the UK Biobank genome-wide association study (GWAS) data using colocalization. Then we used colocalized cis-eQTL variants as instrumental variables in Mendelian randomization (MR) analyses, followed by functional validation experiments on the target genes of the cis-eQTL variants. Findings: We identified 17 colocalized abdominal obesity GWAS variants, regulating 17 adipose cell-type marker genes. Incorporating these 17 variants into MR discovers a putative tissue-of-origin, cell-type-aware causal effect of abdominal obesity on MASLD consistently with multiple MR methods without significant evidence for pleiotropy or heterogeneity. Single cell data confirm the adipocyte-enriched mean expression of the 17 genes. Our cellular experiments across human adipogenesis identify risk variant -specific epigenetic and transcriptional mechanisms. Knocking down two of the 17 genes, PPP2R5A and SH3PXD2B, shows a marked decrease in adipocyte lipidation and significantly alters adipocyte function and adipogenesis regulator genes, including DGAT2, LPL, ADIPOQ, PPARG, and SREBF1. Furthermore, the 17 genes capture a characteristic MASLD expression signature in subcutaneous adipose tissue. Interpretation: Overall, we discover a significant cell-type level effect of abdominal obesity on MASLD and trace its biological effect to adipogenesis. Funding: NIH grants R01HG010505, R01DK132775, and R01HL170604; the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant No. 802825), Academy of Finland (Grants Nos. 333021), the Finnish Foundation for Cardiovascular Research the Sigrid Jusélius Foundation and the Jane and Aatos Erkko Foundation; American Association for the Study of Liver Diseases (AASLD) Advanced Transplant Hepatology award and NIH/NIDDK (P30DK41301) Pilot and Feasibility award; NIH/NIEHS F32 award (F32ES034668); Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005-2021), the Academy of Finland grant (Contract no. 138006); Academy of Finland (Grant Nos 335443, 314383, 272376 and 266286), Sigrid Jusélius Foundation, Finnish Medical Foundation, Finnish Diabetes Research Foundation, Novo Nordisk Foundation (#NNF20OC0060547, NNF17OC0027232, NNF10OC1013354) and Government Research Funds to Helsinki University Hospital; Orion Research Foundation, Maud Kuistila Foundation, Finish Medical Foundation, and University of Helsinki.

Background and Aims: Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta (PPP1R3B) rs4240624 genotype to decreased bile acid levels in bile. In this study, we investigated whether these individuals had an increased risk for GSD as well as the differences in the lipid composition of the gallbladder bile of these individuals compared to controls and patients with GSD. Methods: Bile acids, cholesterol, and phospholipid levels in gallbladder bile samples were enzymatically measured in 46 patients (34 female, age 45.7 ± 9.8 years, BMI 41.3 ± 4.4 kg/m2) who underwent elective laparoscopic Roux-en-Y gastric bypass. The lipidome of gallbladder bile was analyzed using high-performance liquid chromatography-mass spectrometry. Gallstone status was evaluated using abdominal ultrasonography before the surgery. Results: The G allele of PPP1R3B rs4240624 was significantly associated with GSD in patients with obesity. We validated this association in the UK Biobank. Bile lipidomics demonstrated that 13 of the 17 minor lipid classes measured were higher in individuals with the G allele. The concentrations of bile acids, cholesterol, and phospholipids, as well as the cholesterol saturation index, were lower in patients with GSD than in those without gallstones. GSD had an effect similar to that of PPP1R3B genotype on minor lipids. Conclusion: The PPP1R3B rs4240624 genotype is associated with gallstones and with changes in gallbladder bile similar to those observed in patients with gallstones, suggesting that the PPP1R3B genotype contributes to the risk of gallstones by altering the bile lipidome.

Summary: Recent studies demonstrate that liver secretory proteins, also known as hepatokines, regulate normal development, obesity, and simple steatosis to non-alcoholic steatohepatitis (NASH) progression. Using a panel of ∼100 diverse inbred strains of mice and a cohort of bariatric surgery patients, we found that one such hepatokine, inter-trypsin inhibitor heavy chain 3 (ITIH3), was progressively lower in severe non-alcoholic fatty liver disease (NAFLD) disease states highlighting an inverse relationship between Itih3/ITIH3 expression and NAFLD severity. Follow-up animal and cell culture models demonstrated that hepatic ITIH3 overexpression lowered liver triglyceride and lipid droplet accumulation, respectively. Conversely, ITIH3 knockdown in mice increased the liver triglyceride in two independent NAFLD models. Mechanistically, ITIH3 reduced mitochondrial respiration and this, in turn, reduced liver triglycerides, via downregulated de novo lipogenesis. This was accompanied by increased STAT1 signaling and Stat3 expression, both of which are known to protect against NAFLD/NASH. Our findings indicate hepatokine ITIH3 as a potential biomarker and/or treatment for NAFLD.

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD. Methods: MASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks. In addition to the dietary change, the intervention group received genetically engineered E. coli Nissle expressing aldafermin, while control groups received either E. coli Nissle vehicle or no treatment. MASLD-related plasma biomarkers were measured using an automated clinical chemistry analyzer. The liver steatosis was assessed by histology and bioimaging analysis using Fiji (ImageJ) software. The effects of the intervention in the liver were also evaluated by RNA sequencing and liquid-chromatography-based non-targeted metabolomics analysis. Pathway enrichment studies were conducted by integrating the differentially expressed genes from the transcriptomics findings with the metabolites from the metabolomics results using Ingenuity pathway analysis. Results: After the intervention, E. coli Nissle expressing aldafermin along with dietary changes reduced body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels compared to the two control groups. The integration of transcriptomics with non-targeted metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways potentially implicated in the reduction of hepatic steatosis and insulin resistance. Moreover, the downregulation of pathways linked to lipid metabolism and changes in amino acid-related pathways suggested an overall reduction of oxidative stress in the liver. Conclusions: These data support the potential for using engineered microbial therapeutics in combination with dietary changes for managing MASLD.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a complex disease involving both genetic and environmental factors in its onset and progression. We analyzed NASH phenotypes in a genetically diverse cohort of mice, the Hybrid Mouse Diversity Panel, to identify genes contributing to disease susceptibility. Methods: A “systems genetics” approach, involving integration of genetic, transcriptomic, and phenotypic data, was used to identify candidate genes and pathways in a mouse model of NASH. The causal role of Matrix Gla Protein (MGP) was validated using heterozygous MGP knockout (Mgp+/-) mice. The mechanistic role of MGP in transforming growth factor-beta (TGF-β) signaling was examined in the LX-2 stellate cell line by using a loss of function approach. Results: Local cis-acting regulation of MGP was correlated with fibrosis, suggesting a causal role in NASH, and this was validated using loss of function experiments in 2 models of diet-induced NASH. Using single-cell RNA sequencing, Mgp was found to be primarily expressed in hepatic stellate cells and dendritic cells in mice. Knockdown of MGP expression in stellate LX-2 cells led to a blunted response to TGF-β stimulation. This was associated with reduced regulatory SMAD phosphorylation and TGF-β receptor ALK1 expression as well as increased expression of inhibitory SMAD6. Hepatic MGP expression was found to be significantly correlated with the severity of fibrosis in livers of patients with NASH, suggesting relevance to human disease. Conclusions: MGP regulates liver fibrosis and TGF-β signaling in hepatic stellate cells and contributes to NASH pathogenesis.

Peripheral neurological complications are seen after SARS-CoV-2 infections. These are mostly immune-mediated such as Guillaine–Barré syndrome or chronic inflammatory demyelinating polyneuropathy. We present a 39-year-old man treated with a right sciatic nerve allotransplantation with subsequent clinical and electrophysiological improvement within 30 months of observation. After SARS-CoV-2 infection, he developed clinical deterioration with selective sciatic nerve demyelination in a nerve conduction study. Nerve conduction velocity returned to previous values within six months of treatment. Intravenous immunoglobulins were used at standard dosage. The inflammatory immune process seemed to be a cause of peripheral demyelination isolated to a nerve allograft with good reaction for intravenous immunoglobulin treatment.

Summary: Background: Non-alcoholic fatty liver disease (NAFLD) is a fast-growing, underdiagnosed, epidemic. We hypothesise that obesity-related inflammation compromises adipose tissue functions, preventing efficient fat storage, and thus driving ectopic fat accumulation into the liver. Methods: To identify adipose-based mechanisms and potential serum biomarker candidates (SBCs) for NAFLD, we utilise dual-tissue RNA-sequencing (RNA-seq) data in adipose tissue and liver, paired with histology-based NAFLD diagnosis, from the same individuals in a cohort of obese individuals. We first scan for genes that are differentially expressed (DE) for NAFLD in obese individuals’ subcutaneous adipose tissue but not in their liver; encode proteins secreted to serum; and show preferential adipose expression. Then the identified genes are filtered to key adipose-origin NAFLD genes by best subset analysis, knockdown experiments during human preadipocyte differentiation, recombinant protein treatment experiments in human liver HepG2 cells, and genetic analysis. Findings: We discover a set of genes, including 10 SBCs, that may modulate NAFLD pathogenesis by impacting adipose tissue function. Based on best subset analysis, we further follow-up on two SBCs CCDC80 and SOD3 by knockdown in human preadipocytes and subsequent differentiation experiments, which show that they modulate crucial adipogenesis genes, LPL, SREBPF1, and LEP. We also show that treatment of the liver HepG2 cells with the CCDC80 and SOD3 recombinant proteins impacts genes related to steatosis and lipid processing, including PPARA, NFE2L2, and RNF128. Finally, utilizing the adipose NAFLD DE gene cis-regulatory variants associated with serum triglycerides (TGs) in extensive genome-wide association studies (GWASs), we demonstrate a unidirectional effect of serum TGs on NAFLD with Mendelian Randomization (MR) analysis. We also demonstrate that a single SNP regulating one of the SBC genes, rs2845885, produces a significant MR result by itself. This supports the conclusion that genetically regulated adipose expression of the NAFLD DE genes may contribute to NAFLD through changes in serum TG levels. Interpretation: Our results from the dual-tissue transcriptomics screening improve the understanding of obesity-related NAFLD by providing a targeted set of 10 adipose tissue-active genes as new serum biomarker candidates for the currently grossly underdiagnosed fatty liver disease. Funding: The work was supported by NIH grants R01HG010505 and R01DK132775. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The KOBS study (J. P.) was supported by the Finnish Diabetes Research Foundation, Kuopio University Hospital Project grant (EVO/VTR grants 2005–2019), and the Academy of Finland grant (Contract no. 138006). This study was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation program (Grant No. 802825 to M. U. K.). K. H. P. was funded by the Academy of Finland (grant numbers 272376, 266286, 314383, and 335443), the Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation (grant numbers NNF10OC1013354, NNF17OC0027232, and NNF20OC0060547), Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, University of Helsinki, and Helsinki University Hospital and Government Research Funds. I. S. was funded by the Instrumentarium Science Foundation. Personal grants to U. T. A. were received from the Matti and Vappu Maukonen Foundation, Ella och Georg Ehrnrooths Stiftelse and the Finnish Foundation for Cardiovascular Research.

Virtual reality (VR) is a well-established technology in medicine. Head-mounted displays (HMDs) have made VR more accessible in many branches of medical research. However, its application in balance evaluation has been vague, and comprehensive literature on possible applications of VR in posture measurement is scarce. The aim of this review is to conduct a literature search on the application of immersive VR delivered using a head-mounted display in posturographic measurements. A systematic search of two databases, PubMed and Scopus, using the keywords “virtual reality” and “posturography,” was performed following PRISMA guidelines for systematic reviews. Initial search results returned 89 non-duplicate records. Two reviewers independently screened the abstracts. Sixteen papers fulfilled the inclusion criteria and none of the exclusion criteria and were selected for complete text retrieval. An additional 16 records were identified from citation searching. Ultimately, 21 studies were included in this review. virtual reality is often used as additional visual stimuli in static and dynamic posturography evaluation. Only one study has attempted to evaluate a VR environment in a head-mounted display as an independent method in the assessment of posture. Further research should be conducted to assess HMD VR as a standalone posturography replacement.

Alternative methods of killing microbes have been extensively researched in connection with the widespread appearance of antibiotic resistance among pathogenic bacteria. In this study, we report on in vitro antimicrobial phototoxicity research of cationic phthalocyanine with 2-(4-N-methylmorpholin-4-ium-4-yl)ethoxy substituents against selected clinical strains of Pseudomonas aeruginosa isolated from the lower respiratory tract and chronic wounds. The microorganisms tested in the research were analyzed in terms of drug resistance and biofilm formation. The photocytotoxic effect of phthalocyanine was determined by the reduction factor of bacteria. The studied cationic phthalocyanine at a concentration of 1.0 × 10−4 M, when activated by light, revealed a significant reduction factor, ranging from nearly 4 to 6 log, of P. aeruginosa cells when compared to the untreated control group. After single irradiation, a decrease in the number of bacteria in biofilm ranging from 1.3 to 4.2 log was observed, whereas the second treatment significantly improved the bacterial reduction factor from 3.4 to 5.5 log. It is worth mentioning that a boosted cell-death response was observed after the third irradiation, with a bacterial reduction factor ranging from 4.6 to 6.4 log. According to the obtained results, the tested photosensitizer can be considered as a potential antimicrobial photodynamic therapy against multidrug-resistant P. aeruginosa.

Abstract Knowing about the antibiotic resistance, serotypes, and virulence-associated genes of Group B Streptococcus for epidemiological and vaccine development is very important. We have determined antimicrobial susceptibility patterns, serotype, and virulence profiles. The antibiotic susceptibility was assessed for a total of 421 Streptococcus agalactiae strains, isolated from pregnant women and neonates. Then, 89 erythromycin and/or clindamycin-resistant strains (82 isolates obtained from pregnant women and seven isolates derived from neonates) were assessed in detail. PCR techniques were used to identify the studied strains, perform serotyping, and assess genes encoding selected virulence factors. Phenotypic and genotypic methods determined the mechanisms of resistance. All tested strains were sensitive to penicillin and levofloxacin. The constitutive MLSB mechanism (78.2%), inducible MLSB mechanism (14.9%), and M phenotype (6.9%) were identified in the macrolide-resistant strains. It was found that macrolide resistance is strongly associated with the presence of the ermB gene and serotype V. FbsA, fbsB, fbsC, scpB, and lmb formed the most recurring pattern of genes among the nine surface proteins whose genes were analysed. A minority (7.9%) of the GBS isolates exhibited resistance to lincosamides and macrolides, or either, including those that comprised the hypervirulent clone ST-17. The representative antibiotic resistance pattern consisted of erythromycin, clindamycin, and tetracycline resistance (71.9%). An increase in the fraction of strains resistant to macrolides and lincosamides indicates the need for monitoring both the susceptibility of these strains and the presence of the ST-17 clone.

Abstract Global interest in applying virtual reality (VR) in research and medicine has grown significantly, with potential benefits for patients suffering from balance disorders, instability, and a high risk of falling. This exploratory study assesses the impact of immersive VR (IVR) delivered through a head-mounted display (HMD) on balance and explores the feasibility of using the HMD VR unit as a standalone posturography tool. Using the Meta Quest 2 HMD and a mid-range Android smartphone equipped with standard sensors, the research employed a VR environment that simulated a ship at sea, with thirty-eight healthy participants with no otoneurologic abnormalities. Measurements were conducted in repeated trials, including static assessments on both stable ground and foam, as well as a 3-m walk. This was conducted in two settings: one within a VR environment with three different intensity levels and the other in non-VR settings. Statistical analysis and clinical evaluation revealed that IVR with HMD influences head-level sway velocity, which correlates with increased visual disturbance, suggesting its potential as a low-risk standalone posturography tool.

This article explores the relevance of universal design and empathic design in education. The universal design focuses on creating accessible and usable products, environments, and systems for individuals with diverse abilities. Empathy, on the other hand, involves understanding and sharing the feelings of others, encompassing cognitive, emotional, and compassionate empathy. The article investigates the application of empathy in design, particularly its importance for engineers. Teaching empathy to engineers is emphasized as a crucial aspect. By developing empathic skills, engineers gain a deeper understanding of user needs and perspectives, leading to more inclusive and user-centered design solutions. Effective communication techniques such as asking open-ended questions, active listening, observation, and perspective-taking are explored to enhance empathy in communication. The article also explores methods for measuring empathy, thus enabling engineers to assess the effectiveness of their empathic design approaches. The challenges facing students, teachers, and university authorities in implementing such courses are also bulleted. Med Pr. 2023;74(3):211–25

The lack of empathy towards disability is a significant societal issue that hampers inclusivity and understanding. Many struggle to comprehend the daily challenges and experiences faced by people with disabilities, leading to ignorance, prejudice, and exclusion. However, empathy plays a pivotal role in addressing this problem and serves as the foundation for developing and creating better products, services, and environments. This article explores the potential of developing virtual reality (VR) applications to enhance students’ empathy towards individuals with disabilities. By increasing empathy levels, students are expected to gain significant qualifications in universal design (UD). The full application development process covers the most suitable head-mounted display (HMD) set. The implementation methodology using the Unity programming platform, the approach adopted for conducting classes using the developed VR application, and the deployment stage. Testing was successfully conducted on a student population, receiving positive user feedback. Through the integration of VR technology, the authors thoroughly describe how to address the empathy gap and equip students with essential skills for inclusive and accessible design. The findings presented in this study provide valuable guidance for educators and developers interested in harnessing VR’s potential to foster empathy and advance universal design practices. With the presented methodology and proposed application, the authors demonstrate the effectiveness of VR applications in elevating students’ empathy levels, consequently enhancing their qualifications in universal design. Med Pr. 2023;74(3):199–210

(1) Background: Donor nephrectomy for living donor kidney transplantation using minimally invasive techniques is a safe procedure that has been used for more than 20 years with excellent results. The total laparoscopic approach offers decreased postoperative pain, less incisional morbidity, and a shorter recovery time. (2) Methods: We present the results of a series of 43 laparoscopic donor nephrectomies performed in a single center. The procedures were performed in a systematic approach with transperitoneal access using four ports. The main renal artery and vein were ligated using a linear stapler fixed with an alternate triple row of titanium staples. The specimen was extracted in an endoscopic bag through an additional incision. (3) Results: All procedures were performed laparoscopically without conversion to open surgery. The average warm ischemia time was 4.73 min. In all recipients, immediate kidney allograft function was observed. (4) Conclusions: Total laparoscopic living donor nephrectomy is a safe procedure. It was performed successfully in all cases with a short surgical time, low morbidity, and 0% mortality.

Abstract Acute kidney injury (AKI) in kidney transplant recipients (KTRs) is a common, yet poorly investigated, complication of urinary tract infections (UTI) and urosepsis. A retrospective comparative analysis was performed, recruiting 101 KTRs with urosepsis, 100 KTRs with UTI, and 100 KTRs without history of UTI or sepsis. The incidences of AKI in the urosepsis and UTI groups were 75.2% and 41%, respectively. The urosepsis group has also presented with a significantly higher prevalence of AKI stage 2 and 3 than the UTI group. The rates of recovery from AKI stages 1, 2 and 3, were 75,6%, 55% and 26.1%, respectively. Factors independently associated with renal recovery from AKI were: AKI severity grade (AKI stage 2 with OR = 0.25 and AKI stage 3 with OR = 0.1), transfusion of red blood cells (RBC) (OR = 0.22), and the use of steroid bolus in the acute phase of treatment (OR = 4). The septic status (urosepsis vs UTI) did not influence the rates of renal recovery from AKI after adjustment for the remaining variables. The dominant cause of RBC transfusions in the whole population was upper GI-bleeding. In multivariable analyses, the occurrence of AKI was also independently associated with a greater decline of eGFR at 1-year post-discharge and with a greater risk of graft loss. In KTRs with both urosepsis and UTI, the occurrence of AKI portends poor transplantation outcomes. The local transfusion policy, modulation of immunosuppression and stress ulcer prophylaxis (which is not routinely administered in KTRs) in the acute setting may be modifiable factors that significantly impact long-term transplantation outcomes.

Abstract Despite improvement in the care of diabetes over the years, pregnancy complicated by type 1 diabetes (T1DM) is still associated with adverse maternal and neonatal outcomes. To date, proteomics studies have been conducted to identify T1DM biomarkers in non-pregnant women, however, no studies included T1DM pregnant women. In this study serum proteomic profiling was conducted in pregnant women with T1DM in the late third trimester. Serum samples were collected from 40 women with T1DM and 38 healthy controls within 3 days before delivery at term pregnancy. Significant differences between serum proteomic patterns were revealed, showing discriminative peaks for complement C3 and C4-A, kininogen-1, and fibrinogen alpha chain. Quantification of selected discriminative proteins by ELISA kits was also performed. The serum concentration of kininogen-1 was significantly lower in women with T1DM than in controls. There were no significant differences in serum concentrations of complement C3 and complement C4-A between study groups. These data indicate that pregnant women with T1DM have a distinct proteomic profile involving proteins in the coagulation and inflammatory pathways. However, their utility as biomarkers of pregnancy complications in women with T1DM warrants further investigation.

Throughout the years, much progress has been made in the field of renal transplantation; however, along with new developments, new problems have arisen. While transplantation is the optimal choice in patients suffering from end-stage renal disease, it is always connected to certain commonly associated risks, in particular those caused by opportunistic infections. One such risk includes the reactivation of cytomegalovirus (CMV), an issue commonly affecting all kinds of transplant recipients. Similarly, with the rise of the ever-evolving global SARS-CoV-2 pandemic, patients must be constantly monitored for any respiratory symptoms, and observed closely under the care of their attending physician. Treating these patients has become extremely difficult due to limitations caused by COVID-19 protocols (for instance, the reduction of immunosuppression dosages and the avoidance of lymphocyte-depleting induction therapy) and the lack of knowledge surrounding this relatively new and worsening risk factor. In order to give patients optimal care, these arising problems need to be studied and addressed.

Immunocompromised patients with respiratory viral infections are at increased risk of fungal superinfections, including Pneumocystosis. Within the scope of the COVID-19 pandemic, Pneumocystis jirovecii co-infections are being increasingly reported. Differential diagnosis often creates a dilemma, due to multiple overlapping clinical and radiographic features. Awareness of fungal co-infections in the context of the COVID-19 pandemic is crucial to initiate prophylactic measures, especially in high-risk individuals. We report the second case of Pneumocystis jirovecii pneumonia and COVID-19 co-infection in a renal transplant recipient in Poland.

The popularity of living-donor organ donation has increased recently as an alternative to deceased-organ donation due to the growing need for organs and a shortage of deceased-donor organs. This procedure requires an in-depth health assessment of candidates, who must be in excellent physical and mental health. We present a potential living-kidney donor withdrawn from donation due to a newly diagnosed Paget’s disease of bone (PDB). The patient underwent computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, and bone densitometry with trabecular bone score (TBS) assessment. The sole lumbar vertebra affected by PDB was investigated comprehensively, non-invasively, quantitatively, and qualitatively.

The purpose of this article is to assess the present knowledge about chronic active (CA) T-cell mediated rejection (TCMR) of a kidney. In the research authors review current Banff diagnostic criteria used in kidney rejection, focus on their possible future evolution, and investigate the role of currently available molecular methods that could be implemented into the diagnostic scheme. Research also points out previously and currently available treatment methods applied to CA TCMR and takes into account possible side effects consequent upon the therapy. Moreover, attention is being paid to the CA TCMR coincidence with other kidney rejection types such as antibody-mediated rejection (ABMR) and its influence on the treatment approach. Authors also mark the possibility of non-HLA antibodies coexistence in patients with CA TCMR and describe its possible resonance on kidney allograft function. Nonetheless, it seems that current knowledge about CA TCMR is not sufficient and requires further investigation.

Higher educational institutions in Western Balkan countries strive for continuous development of their teaching and learning processes. One of the priorities is employing state-of-the-art technology to facilitate experience-based learning, and virtual and augmented reality are two of the most effective solutions to providing the opportunity to practice the acquired theoretical knowledge. This report presents (apart from the theoretical introduction to the issue) an overall picture of the knowledge of AR and VR technology in education in Western Balkan universities. It is based on a semi-structured online questionnaire whose recipients were academic staff and students from universities in Albania, Kosovo, and North Macedonia. The questionnaire differed for each target group; the version for academics comprised 11 questions for 710 respondents, and the version for students comprised 10 questions for 2217 respondents. This paper presents and discusses the results for each question with the aim to illustrate Western Balkan countries’ current state of VR and AR application in education.

Background: Molnupiravir demonstrated an in vitro antiviral activity against positive-sense RNA viruses, including SARS-CoV-2. The study aimed to present the results of outpatient molnupiravir use in kidney transplant recipients and hemodialysis patients during the first months of 2022 in Poland. Methods: The retrospective observational cohort study at one kidney transplant center included 36 patients diagnosed with COVID-19 with an automated nucleic acid amplification test on nasopharyngeal swab specimens. All patients received molnupiravir for home-based therapy at a dose of 800 mg every 12 h orally for 5 days. Both kidney transplant recipients (n = 16) and hemodialysis patients (n = 20) presented a lot of comorbidities with a Charlson comorbidity index of 4.1 and 5.1, respectively. Results: Patients presented with fever, cough, and weakness followed by muscle and joint pain. Five kidney transplant recipients experienced acute kidney injury with a rise in serum creatinine level from 0.4 to 1.9 mg/dL. No serious side effects of molnupiravir therapy or interactions with immunosuppressive medications were observed. Symptoms of COVID-19 improved rapidly or resolved within 24–48 h of starting treatment. Conclusion: The study suggests the safety and efficacy of molnupiravir therapy alone early after the onset of SARS-CoV-2 infection, but further investigations should be performed to confirm our preliminary results. To the best of the authors’ knowledge, it is the first published report on molnupiravir use in end-stage kidney disease (ESKD) patients on hemodialysis and the third concerning kidney transplant recipients.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with a robust immune response. The development of systemic inflammation leads to a hyperinflammatory state due to cytokine release syndrome during severe COVID-19. The emergence of many new SARS-CoV-2 variants across the world deteriorates the protective antiviral immunity induced after infection or vaccination. The innate immune response to SARS-CoV-2 is crucial for determining the fate of COVID-19 symptomatology. T cell-mediated immunity is the main factor of the antiviral immune response; moreover, SARS-CoV-2 infection initiates a rapid B-cell response. In this paper, we present the current state of knowledge on immunity after COVID-19 infection and vaccination. We discuss the mechanisms of immune response to various types of vaccines (nucleoside-modified, adenovirus-vectored, inactivated virus vaccines and recombinant protein adjuvanted formulations). This includes specific aspects of vaccination in selected patient populations with altered immune activity (the elderly, children, pregnant women, solid organ transplant recipients, patients with systemic rheumatic diseases or malignancies). We also present diagnostic and research tools available to study the anti-SARS-CoV-2 cellular and humoral immune responses.

The need for objective data-driven usability testing of VR applications is becoming more tangible with the rapid development of numerous VR applications and their increased accessibility. Traditional methods of testing are too time and resource consuming and might provide results that are highly subjective. Thus, the aim of this article is to explore the possibility of automation of usability testing of VR applications by using objective features such as HMD built-in head and hands tracking, EEG sensor, video recording, and other measurable parameters in addition to automated analysis of subjective data provided in questionnaires. For this purpose, a simple VR application was created which comprised relatively easy tasks that did not generate stress for the users. Fourteen volunteers took part in the study and their signals were monitored to acquire objective automated data. At the same time the observer was taking notes of subjects’ behaviour, and their subjective opinions about the experience were recorded in a post-experiment questionnaire. The results acquired from signal monitoring and questionnaires were juxtaposed with observation and post-interview results to confirm the validity and efficacy of automated usability testing. The results were very promising, proving that automated usability testing of VR applications is potentially achievable.