The gradual deterioration of articular cartilage was thought to be the central event in osteoarthritis (OA), but recent studies demonstrated the importance of low-grade synovitis in the progression of OA. The Syndecan (SDC) family of membrane proteoglycans is known to be involved in the regulation of inflammation, but there is limited evidence considering the role of syndecans in OA synovitis. Our study aimed to investigate the hip OA synovial membrane expression patterns of SDC1, SDC2 and SDC4, as well as exostosins and sulfotransferases (enzymes involved in the polymerisation and modification of syndecans’ heparan sulphate chains). Synovial membrane samples of patients with OA (24) were divided into two groups according to their Krenn synovitis score severity. The immunohistochemical expressions of SDC1, SDC2, SDC4, EXT1, EXT2, NDST1 and NDST2 in synovial intima and subintima were then analysed and compared with the control group (patients with femoral neck fracture). According to our study, the immunoexpression of SDC1, NDST1 and EXT2 is significantly increased in the intimal cells of OA synovial membrane in patients with lower histological synovitis scores and SDC4 in patients with higher synovitis scores, in comparison with non-OA controls. The difference in the expression of SDC2 among the OA and non-OA groups was insignificant. SDC1, SDC4, NDST1 and EXT2 seem to be involved as inflammation moderators in low-grade OA synovitis and, therefore, should be further investigated as potential markers of disease progression and therapeutic goals.

Background: this study aimed to determine the expression of RNA-binding oncofetal proteins IMP3 and LIN28A in extravillous (EVT) and villous trophoblast (VT) cells of placentas from pre-eclamptic (PE) pregnancies to better understand the pathogenesis of PE. Methods: placental tissue of 10 patients with PE with severe features, 10 patients with PE without severe features and 20 age-matched healthy pregnancy controls were analyzed by immunohistochemistry, double immunofluorescence and qPCR. Results: We found a decreased percentage of IMP3-positive EVT cells in PE with and without severe features compared to that of the healthy control (p < 0.001). IMP3 expression was significantly low in VT of PE placentas compared to that of the healthy control (p = 0.002). There was no significant difference in LIN28A expression between groups of PE and the control group. Additionally, we noticed the trend toward downregulation of IMP3 mRNA and LIN28A mRNA in severe PE compared to that of healthy controls. Conclusions: We demonstrated that IMP3 expression is decreased in EVT and VT cells of placentas from pregnancies complicated with both PE with and without severe features. However, additional functional investigations are needed to clarify the role of IMP3 as a potential therapeutic target in the management of PE.

Background: The recognition of comorbidities is relevant for asthma management, especially if these conditions/diseases are treatable traits such as anxiety. This study aimed to explore the associations between asthma severity and child and parent asthma-related anxiety and to recognize the most common specific fears. Methods: This cross-sectional study consisted of 150 parents and their children diagnosed with asthma, and was conducted at the Pediatric Clinic of the University Hospital Center Split in Croatia. All children, from ages 3 to 17 years, underwent a thorough clinical examination. A total of 150 parents and 108 children filled out an asthma-related anxiety questionnaire in paper form. Results: Parents of children with moderate and severe asthma had higher asthma-related anxiety due to restrictions related to asthma symptoms (p = 0.032), and children diagnosed with moderate and severe asthma had greater anxiety due to restrictions related to asthma symptoms than children diagnosed with mild asthma (p = 0.004). Children’s anxiety was the highest when they experienced an asthmatic attack during physical activity (PA), and they fear that they will not be successful in sports or dancing due to asthma. Parents commonly reported the fear of an asthma attack without warning signs (p < 0.001), fear of drug side effects (p < 0.001), fear of absence from school (p = 0.006), and fear of an asthma attack during PA (p < 0.001). Conclusions: The current study reports findings of increased parental levels of anxiety when compared to their children, related to fear of an asthma attack occurring without warning signs, fear of side effects and fear of absence from school, as well as the fear of an asthma attack occurring during sports activities. When assessing individual items on anxiety associated with asthma, children most commonly reported concern related to physical activity.

The purpose of this study was to evaluate the effects of Dab1 gene silencing on the immunoexpression of light chain 3 beta (Lc3b), glucose regulating protein 78 (Grp78), heat shock cognate 71 (Hsc70), mammalian target of rapamycin (mTOR) and lysosomal-associated membrane protein 2A (Lamp2a) in the lung tissue of developing yotari (Dab1−/−) and wild-type (wt) mice. The lung epithelium and mesenchyme of the embryos at gestational days E13.5 and E15.5 were examined using immunofluorescence and semi-quantitative methods. In the pulmonary mesenchyme and epithelium, Grp78 and Lc3b of moderate fluorescence reactivity was demonstrated in wt mice for both evaluated time points, while yotari mice exhibited only epithelial reactivity for the same markers. Mild punctate expression of Hsc70 was observed for both genotypes. A significant difference was present when analyzing mTOR expression, where wt mice showed strong perinuclear staining in the epithelium. According to our data, Dab1 gene silencing may result in autophagy abnormalities, which could then cause respiratory system pathologies via defective lung cell degradation by lysosome-dependent cell elimination.

UBASH3A and UBASH3B are protein families of atypical protein tyrosine phosphatases that function as regulators of various cellular processes during mammalian development. As UBASH3A has only mild phosphatase activity, its regulatory effects are based on the phosphatase-independent mechanisms. On the contrary, UBASH3B has strong phosphatase activity, and the suppression of its receptor signalling is mediated by Syk and Zap-70 kinases. The regulatory functions of UBASH3A and UBASH3B are particularly evident in the lymphoid tissues and kidney development. These tyrosine phosphatases are also known to play key roles in autoimmunity and neoplasms. However, their involvement in mammalian development and its regulatory functions are largely unknown and are discussed in this review.

While clear cell renal cell carcinoma (ccRCC) is curable, advanced metastatic (mRCC) remains a clinical challenge. We analyzed clinical, pathohistological, and molecular data (Receptor Interacting Protein 5—RIP5 and Vestigial Like Family Member 4—VGLL4 expression) of 55 mRCC patients treated with first-line treatment with sunitinib. The trend of linear increase in the protein expression of RIP5 was observed with the progression of tumor grade. Overall, 80% of RIP5-positive cells were in the control kidneys and high-grade mRCC. On the contrary, RIP5 displayed low expression in grade 2 mRCC (5.63%). The trend of linear decrease in the expression of VGLL4 was observed with the progression of tumor grade. The highest protein expression of VGLL4 was observed in grade 2 (87.82%) in comparison to grade 3 and 4 and control. High expression of RIP5 mRNA was associated with longer first-line overall survival and longer progression-free survival in mRCC. In addition, a high VGLL4 mRNA expression showed better overall survival in patients with ccRCC. In conclusion, high mRNA expression of RIP5 and VGLL4 are important markers of better survival rates in mRCC patients.

Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

We aimed to investigate expression of the novel susceptibility genes for CAKUT, DLG1 and KIF12, proposed by a systematic in silico approach, in developing and postnatal healthy human kidneys to provide information about their spatiotemporal expression pattern. We analyzed expression of their protein products by immunohistochemistry and immunofluorescence and quantified relative mRNA levels by RT-qPCR. Statistically significant differences in expression patterns were observed between certain developmental stages. Strong expression of DLG1 was observed in the developing kidney, with a gradual decrease from the first phase of kidney development (Ph1) until the third phase (Ph3), when most nephrons are formed; at later stages, the highest expression was observed in the tubules. KIF12 was highly expressed in the developing structures, especially in Ph1, with a gradual decrease until the postnatal phase, which would indicate a significant role in nephrogenesis. Co-localization of DLG1 and KIF12 was pronounced in Ph1, especially on the apical side of the tubular epithelial cells. Thereafter, their expression gradually became weaker and was only visible as punctate staining in Ph4. The direct association of DLG1 with KIF12 as control genes of normal kidney development may reveal their new functional aspect in renal tubular epithelial cells.

One major challenge during the COVID-19 pandemic was the limited accessibility to healthcare facilities, especially for the older population. The aim of the current study was the exploration of the extent to which the healthcare systems responded to the healthcare needs of the older people with or without cognitive impairment and their caregivers in the Adrion/Ionian region. Data were collected through e-questionnaires regarding the adequacy of the healthcare system and were anonymously administered to older individuals and stakeholder providers in the following countries: Slovenia, Italy (Calabria), Croatia, Bosnia and Herzegovina, Greece, Montenegro, and Serbia. Overall, 722 older people and 267 healthcare stakeholders participated in the study. During the COVID-19 pandemic, both healthcare stakeholders and the older population claimed that the healthcare needs of the older people and their caregivers increased dramatically in all countries, especially in Italy (Calabria), Croatia and BiH. According to our results, countries from the Adrion/Ionian regions faced significant challenges to adjust to the special needs of the older people during the COVID-19 pandemic, which was possibly due to limited accessibility opportunities to healthcare facilities. These results highlight the need for the development of alternative ways of providing medical assistance and supervision when in-person care is not possible.

The SI4CARE project is a transnational project which aims to develop both strategy and action plans to improve health and social care in the Adriatic–Ionian region. Starting from a survey of the status quo, each partner has developed some pilots to support the development and monitoring of the policy actions. In particular, partner number three, the Municipality of Miglierina, designed and developed a pilot related to the use of wearable devices for monitoring elderly patients in rural areas. With the collaboration of the complex unity of primary care (UCCP) of the Reventino area, the pilot is based on the use of smart wearable devices to monitor some parameters of older adults after their vaccinations for flu and covid. This paper focused on the design and implementation of the system. It describes its application in the Municipality of Miglierina. Presentation of the results and a discussion of the strengths and weaknesses will be presented, in detail, in future work. Finally, the possibility of extending the experiment to other Adriatic–Ionian regions is addressed.

Slovenians like new technologies. However, they hold specific fears that robots will take their working places. Robots represent opportunities for providing service as the population grows old, and robots will be needed to help old people. Especially in fields where workers are scarce, such as healthcare, knowledge of the interaction human-cobot will be needed. Robots have been present in highly supervised and stable environments for decades. Due to extreme progress in robotics, they have moved among people, in less predictable environments, and have a more human-like appearance. The purpose of our paper is to present cases of cobots in Slovenian hospitals. We use qualitative methodology. Results of our desktop research are presented. Our paper researches contemporary management challenges in healthcare. Before, and after the COVID-19 pandemic, the demand for healthcare professionals was a critical challenge as the nursing staff was overburdened. It is hard to fill all the necessary nursing positions in hospitals. The problem seems to be getting even bigger due to the growing trend of the elderly population around the world. In the theoretical part, we present the interaction between human being-robot. In the empirical part, we present three examples of the incorporation of robots in hospitals in Slovenia and expose some of the current challenges, benefits, and difficulties of working with robots.