Diabetic nephropathy (DN) is one of the most perilous side effects of diabetes mellitus type 1 and type 2 (T1DM and T2DM).). It is known that sodium/glucose cotransporter 2 inhibitors (SGLT 2i) and glucagone like peptide-1 receptor agonists (GLP-1 RAs) have renoprotective effects, but the molecular mechanisms are still unknown. In clinical trials GLP-1 analogs exerted important impact on renal composite outcomes, primarily on macroalbuminuria, possibly through suppression of inflammation-related pathways, however enhancement of natriuresis and diuresis is also one of possible mechanisms of nephroprotection. Dapagliflozin, canagliflozin, and empagliflozin are SGLT2i drugs, useful in reducing hyperglycemia and in their potential renoprotective mechanisms, which include blood pressure control, body weight loss, intraglomerular pressure reduction, and a decrease in urinary proximal tubular injury biomarkers. In this review we have discussed the potential synergistic and/or additive effects of GLP 1 RA and SGLT2 inhibitors on the primary onset and progression of kidney disease, and the potential implications on current guidelines of diabetes type 2 management.

Over the past decade, immune checkpoint inhibitors (ICI) have revolutionized the treatment of advanced melanoma and ensured significant improvement in overall survival versus chemotherapy. ICI or targeted therapy are now the first line treatment in advanced melanoma, depending on the tumor v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutational status. While these new approaches have changed the outcomes for many patients, a significant proportion of them still experience lack of response, known as primary resistance. Mechanisms of primary drug resistance are not fully elucidated. However, many alterations have been found in ICI-resistant melanomas and possibly contribute to that outcome. Furthermore, some tumors which initially responded to ICI treatment ultimately developed mechanisms of acquired resistance and subsequent tumor progression. In this review, we give an overview of tumor primary and acquired resistance mechanisms to ICI and discuss future perspectives with regards to new molecular targets and combinatorial therapies.

The World Health Organisation predicts a lack of 15 million health professionals by 2030. The lack of licenced professionals is a problem that keeps emerging and is carefully studied on a global level. Strategic objectives aimed at stimulating employment, improving working conditions, and keeping the nurses on board greatly depends on identifying factors that contribute to their turnover. The aim of this study was to present a conceptual model based on predictors of nurses’ turnover intention. Methods: A quantitative, non-experimental research design was used. A total of 308 registered nurses (RNs) took part in the study. The Multidimensional Work Motivation Scale (MWMS) and Practice Environment Scale of the Nursing Work Index (PES-NWI) were used. Results: The conceptual model, based on the binary regression models, relies on two direct significant predictors and four indirect significant predictors of turnover intention. The direct predictors are job satisfaction (OR = 0.23) and absenteeism (OR = 2.5). Indirect predictors that affect turnover intention via job satisfaction are: amotivation (OR = 0.59), identified regulation (OR = 0.54), intrinsic motivation (OR = 1.67), and nurse manager ability, leadership and support of nurses (OR = 1.51). Conclusions: The results of the study indicate strategic issues that need to be addressed to retain the nursing workforce. There is a need to ensure positive perceptions and support from managers, maintain intrinsic motivation, and promote even higher levels of motivation to achieve satisfactory levels of job satisfaction.

Chronic rhinosinusitis (CRS) is a prevalent, multifaceted inflammatory condition affecting the nasal cavity and the paranasal sinuses, frequently accompanied by formation of nasal polyps (CRSwNP). This apparently uniform clinical entity is preceded by heterogeneous changes in cellular and molecular patterns, suggesting the presence of multiple CRS endotypes and a diverse etiology. Alterations of the upper airway innate defense mechanisms, including antimicrobial and antioxidant capacity, have been implicated in CRSwNP etiology. The aim of this study was to investigate mRNA expression patterns of antioxidative enzymes, including superoxide dismutase (SOD) and peroxiredoxin-2 (PRDX2), and innate immune system defense players, namely the bactericidal/permeability-increasing fold-containing family A, member 1 (BPIFA1) and PACAP family members, particularly adenylate-cyclase-activating polypeptide receptor 1 (ADCYAP1) in nasal mucosa and nasal polyps from CRSwNP patients. Additional stratification based on age, sex, allergic comorbidity, and disease severity was applied. The results showed that ADCYAP1, BPIFA1, and PRDX2 transcripts are differentially expressed in nasal mucosa and scale with radiologically assessed disease severity in CRSwNP patients. Sinonasal transcriptome is not associated with age, sex, and smoking in CRSwNP. Surgical and postoperative corticosteroid (CS) therapy improves endoscopic appearance of the mucosa, but variably reverses target gene expression patterns in the nasal cavity of CRSwNP patients. Transcriptional cross-correlations analysis revealed an increased level of connectedness among differentially expressed genes under inflammatory conditions and restoration of basic network following CS treatment. Although results of the present study imply a possible engagement of ADCYAP1 and BPIFA1 as biomarkers for CRSwNP, a more profound study taking into account disease severity and CRSwNP endotypes prior to the treatment would provide additional information on their sensitivity.

Urolithiasis is characterized by the formation and retention of solid crystals within the urinary tract. Kidney stones are mostly composed of calcium oxalate, which predominantly generates free radicals that are toxic to renal tubular cells. The aim of the study is to explore possible effects of antioxidant pre-treatment on inhibition of oxidative stress. Three cell lines were used as in vitro model of urolithiasis: MDCK I, MDCK II and LLC-PK1. Oxidative stress was induced by exposure of cells to sodium oxalate in concentration of 8 mM. In order to prevent oxidative stress, cells were pre-treated with three different concentrations of l-arginine and vitamin E. Oxidative stress was evaluated by determining the expression of superoxide dismutase (SOD), osteopontin (OPN), and by the concentration of glutathione (GSH). In all three cell lines, pre-treatment of antioxidants increased cell survival. Positive correlation of SOD and OPN expression as well as GSH concentration was observed in all groups of cells. Our results indicate that an antioxidant pre-treatment with l-arginine and vitamin E is able to hamper oxalate-induced oxidative stress in kidney epithelial cells and as such could play a role in prevention of urolithiasis.

Nephrolithiasis is a pathological condition characterized by the formation of solid crystals in the kidneys or other parts of urinary tract. Kidney stones are a serious public health issue and financial burden for health care system, as well as a painful and uncomfortable condition for patients, resulting in renal tissue injury in severe cases. Dietary habits, low fluid and high salt intake predominantly, contribute to the development of kidney stones. Current research suggests that polyphenols have a protective effect in the pathogenesis of kidney stones. Polyphenols are a group of naturally occurring compounds found in plant-based foods such as fruits, vegetables, tea, and coffee. In this review, we explore mechanisms underlying the beneficial effects of polyphenols, such as oxidative stress reduction and modulation of inflammatory pathways, in various in vitro models of nephrolithiasis. Additionally, certain polyphenols, such as catechins found in green tea, have been shown to inhibit the formation and growth of kidney stones in animal studies. This review highlights the antioxidant and anti-inflammatory effects, as well as the inhibition of crystal formation, as results of polyphenol treatment in vitro. Further research is required to determine the specific effects of polyphenols on kidney stone formation in humans; however, current knowledge implicates that incorporating a variety of polyphenol-rich foods into the diet may be a beneficial strategy for individuals at risk of developing nephrolithiasis.