Immunoexpression Patterns of Megalin, Cubilin, Caveolin-1, Gipc1 and Dab2IP in the Embryonic and Postnatal Development of the Kidneys in Yotari (Dab1-/-) Mice.

Our study examines the immunoexpression patterns of Megalin, Cubilin, Caveolin-1, Gipc1 and Dab2IP in the embryonic development (E) and postnatal (P) mouse kidney, with a focus on differentiating patterns between wild-type (wt) and yotari, Dab1-/- (yot) mice. Immunofluorescence revealed raised immunoexpression of receptors Megalin and Cubilin at the ampulla/collecting ducts and convoluted tubules across all developmental stages, with the most prominent immunoexpression observed in the convoluted tubules and the parietal epithelium of the Bowman's capsule. Quantitative analysis showed a higher percentage of Megalin and Cubilin in wt compared to yot mice at E13.5. Co-expression of Megalin and Cubilin was observed at the apical membrane of convoluted tubules and the parietal layer of the Bowman's capsule. The staining intensity of Megalin varied across developmental stages, with the strongest reactivity observed at the ampulla and collecting ducts at embryonic day (E) 13.5 in wt mice. In contrast, Caveolin-1 exhibited high immunoexpression in the metanephric mesenchyme, blood vessels, and the border area between the metanephric mesenchyme and renal vesicle, with a decrease in immunoexpression as development progressed. Gipc1 showed diffuse cytoplasmic staining in metanephric mesenchyme, convoluted tubules and collecting ducts, with significant differences in immunoexpression between wild-type and yot mice at both investigated embryonic time points. Dab2IP immunofluorescent staining was most prominent in renal vesicle/glomeruli and ampulla/collecting ducts at E13.5, with mild staining intensity observed in the distal convoluted tubules postnatally. Our findings elucidate distinct immunoexpression of patterns and potential parts of these proteins in the development and function of the kidney, highlighting the importance of further investigation into their regulatory mechanisms.

Biological characteristics and clinical management of uveal and conjunctival melanoma.

Uveal and conjunctival melanomas are relatively rare tumors; nonetheless, they pose a significant risk of mortality for a large number of affected individuals. The pathogenesis of melanoma at different sites is very similar, however, the prognosis for patients with ocular melanoma remains unfavourable, primarily due to its distinctive genetic profile and tumor microenvironment. Regardless of considerable advances in understanding the genetic characteristics and biological behaviour, the treatment of uveal and conjunctival melanoma remains a formidable challenge. To enhance the prospect of success, collaborative efforts involving medical professionals and researchers in the fields of ocular biology and oncology are essential. Current data show a lack of well-designed randomized clinical trials and limited benefits in current forms of treatment for these tumors. Despite advancements in the development of effective melanoma therapeutic strategies, all current treatments for uveal melanoma (UM) and conjunctival melanoma (CoM) remain unsatisfactory, resulting in a poor long-term prognosis. Ongoing trials offer hope for positive outcomes in advanced and metastatic tumors. A more comprehensive understanding of the genetic and molecular abnormalities involved in the development and progression of ocular melanomas opens the way for the development of personalized therapy, with various potential therapeutic targets currently under consideration. Increased comprehension of the molecular pathogenesis of UM and CoM and their specificities may aid in the development of new and more effective systemic therapeutic agents, with the hope of improving the prognosis for patients with metastatic disease.

Non-Medical Factors Associated with the Outcome of Treatment of Chronic Non-Malignant Pain: A Cross-Sectional Study.

BACKGROUND: Chronic pain is a global public health issue with increasing prevalence. Chronic pain causes sleep disorder, reactive anxiety, and depression, impairs the quality of life; it burdens the individual and society as a whole. The aim of this study was to examine non-medical factors related to the outcome of the treatment of chronic non-malignant pain. METHODS: A cross-sectional study with two groups of patients was conducted using a questionnaire with biological, psychological, and social characteristics of patients. Since this study was cross-sectional, it was not possible to determine whether some factors were the cause or the consequence of unsuccessful treatment outcome, which is at the same time one of the disadvantages of cross-sectional studies. RESULTS: The poor outcome of the treatment of chronic non-malignant pain in a multivariate binary logistic regression model was statistically significantly associated with the lower quality of life (OR = 0.95 (95% CI: 0.91-0.99; p = 0.009), and higher depression level OR = 1.08 (95% CI: 1.02-1.14; p = 0.009). The outcome of the treatment was not directly related to social support measured by the multivariate binary logistic regression model (OR = 1.04, 95% CI: 0.95-1.15, p = 0.395), but solitary life (without partner) was (OR = 2.16 (95% CI: 1.03-4.53; p = 0.043). CONCLUSION: The typical patient with a poor pain management outcome is retired, presents depressive behavior; their pain disturbs general activity and sleeping. Moreover, they have a physically disturbed quality of life and require self-treatment due to the inaccessibility of doctors and therapies. The principle of treatment of patients with chronic, non-malignant pain should take into account a biopsychosocial approach with individually adjusted procedures.

Anti-TNF Therapy and the Risk of Malignancies and Infections in Inflammatory Rheumatic Diseases - Our Experience.

BACKGROUND: Early diagnosis is the key to successful treatment of inflammatory rheumatic diseases and the use of conventional disease-modifying antirheumatic drugs (csDMARD) and biologic disease-modifying antirheumatic drugs (bDMARD) or biologics have substantially contributed to better disease control. Biological drugs have been approved for the treatment of rheumatoid arthritis (RA), juvenile arthritis (JIA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). SUBJECTS AND METHODS: The study involved 79 adult patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), psoriatic arthritis (PsA) or undifferentiated spondyloarthropathy (USpA) - the last three clinical entities belong to a common group called spondyloarthropathies (SpA); receiving anti-TNF therapy at the department of Rheumatology and Rehabilitation, Clinical Hospital Center Zagreb. The duration of therapy was a minimum of 1 month, with the mean duration of 32.0±24.0 months. The infections recorded were infections that appeared during treatment or soon after the treatment was stopped. RESULTS: During the course of therapy 17 patients (21.5%) experienced an infection, with the total number of 21 infections. This resulted in an overall incidence rate (IR) of 9.9/100 patient-years. Of the patients with RA 76.5% developed an infection, which was significantly higher than for patients with SpA (p<0.001). The IR/100 patient-years for all infections in RA patients was 23.7 compared to 2.8 in patients with SpA. Female gender was associated with a significantly higher infection rate (70.6%, p=0.005). There were 8 infections that were considered serious, yielding an IR of 3.8/100 patient-years. There was only one malignancy case in our study. CONCLUSION: Every fifth patient developed an infection during the course of anti-TNF therapy, and more than one third of all infections were serious. RA and female gender was associated with a significantly increased number of infections.

A Homozygous Dab1-/- Is a Potential Novel Cause of Autosomal Recessive Congenital Anomalies of the Mice Kidney and Urinary Tract.

This study aimed to explore morphology changes in the kidneys of Dab1-/- (yotari) mice, as well as expression patterns of reelin, NOTCH2, LC3B, and cleaved caspase3 (CASP3) proteins, as potential determinants of normal kidney formation and function. We assumed that Dab1 functional inactivation may cause disorder in a wide spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). Animals were sacrificed at postnatal days P4, P11, and P14. Paraffin-embedded kidney tissues were sectioned and analyzed by immunohistochemistry using specific antibodies. Kidney specimens were examined by bright-field, fluorescence, and electron microscopy. Data were analyzed by two-way ANOVA and t-tests. We noticed that yotari kidneys were smaller in size with a reduced diameter of nephron segments and thinner cortex. TEM microphotographs revealed foot process effacement in the glomeruli (G) of yotari mice, whereas aberrations in the structure of proximal convoluted tubules (PCT) and distal convoluted tubules (DCT) were not observed. A significant increase in reelin expression, NOTCH2, LC3B and cleaved CASP3 proteins was observed in the glomeruli of yotari mice. Renal hypoplasia in conjunction with foot process effacement and elevation in the expression of examined proteins in the glomeruli revealed CAKUT phenotype and loss of functional kidney tissue of yotari.

Religiousness, Anxiety and Depression in Patients with Glaucoma, Age-Related Macular Degeneration and Diabetic Retinopathy.

BACKGROUND: Many chronic medical conditions such as glaucoma, senile macular degeneration and diabetic retinopathy are further complicated by emotional and psychological disorders. Religiousness represents a part of a social culture and has a significant role in the prevention of mental difficulties of the patients, especially those belonging to older population. The aim of this study was to investigate the connection between religiousness, anxiety, and depression in patients with glaucoma, age-related macular degeneration and diabetic retinopathy and to test their connection related to different diagnosis. SUBJECTS AND METHODS: This cross-sectional study included 163 patients divided into three groups (glaucoma group, senile macular degeneration group and diabetic retinopathy group). Respondents voluntarily agreed to participate in the study and with assistance they fully completed the Scale of Religiousness, Hospital Anxiety and Depression Scale, General Health Questionnaire and demographic information (age, gender, education, employment and marital status). RESULTS: The results showed noticeable religiosity of the respondents (M=18.31, SD=5.28), but also the presence of anxiety (M=7.55, SD=3.73), especially in patients with glaucoma, as well as impaired mental health in AMD patients (M=19.56, SD=4.14). No differences were found in the severity of anxiety, depression, general health and religiosity between groups, but the presence of depression in subjects with age-related macular degeneration significantly affects the level of religiosity (p=0.032). CONCLUSION: These results unequivocally point to the need for further research and raising awareness of all health professionals about the importance of a holistic approach to the patient regardless of his diagnosis in order to identify the possible effective ways to deal with chronic disease considering all levels of patient's needs.