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Clinical transplantology is a constantly evolving field of medicine. Kidney transplantation has become standard clinical practice, and it has a significant impact on reducing mortality and improving the quality of life of patients. Allogenic transplantation induces an immune response, which may lead to the rejection of the transplanted organ. The gold standard for evaluating rejection of the transplanted kidney by the recipient's organism is a biopsy of this organ. However, due to the high invasiveness of this procedure, alternative diagnostic methods are being sought. Therefore, the biomarkers may play an essential predictive role in transplant rejection. A review of the most promising biomarkers for early diagnosis and prognosis prediction of allogenic kidney transplant rejection summarizes novel data on neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), C-X-C motif chemokine 10 (CXCL-10), cystatin C (CysC), osteopontin (OPN), and clusterin (CLU) and analyses the dynamics of changes of the biomarkers mentioned above in kidney diseases and the mechanism of rejection of the transplanted kidney. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTI) represent one of the most common contagious diseases in humans. Uropathogenic Escherichia coli (UPEC) strains are recognized as the most frequent causative agent, and these express a range of virulence factors including the adhesins. Immune response to UPEC under immunosuppression has not been fully understood yet. Interleukin 1β (IL1β), 6 (IL6) and 17 (IL17) represent clinically relevant markers of inflammation. Aim: The study aimed to investigate the interplay between UPEC genotype and hosts' immune status in shaping local inflammatory response in the course of an UTI episode. The respective numbers of: 18 kidney recipients with UPEC UTI, 28 immunocompetent hosts with UPEC UTI and 29 healthy controls were involved. Urine IL1β, IL6, and IL17/creatinine ratios in relation to fimH, csgA, papC, tosA, and flu genes presence in UPEC isolated from the urine samples were analyzed. Apart from traditional statistics, also machine learning algorithms were applied. Results: The urine levels of IL1β and IL 6 were similar in kidney recipients and the immunocompetent hosts. IL1β levels were higher in both kidney recipients and immunocompetent hosts than in controls, while IL6 levels were higher only in immunocompetent hosts than in controls. In the machine learning classification model, high urine IL17 levels were significantly more prevalent in controls, while low IL17 levels in urines infected with Ag43-positive UPEC strains, regardless of the host's immune status. In the traditional statistical analysis, IL17 levels appeared significantly higher in urine samples from kidney recipients infected with Ag43–negative UPEC strains. Conclusions: In the UTI- affected patients, the combination of the immune status of an individual and Ag43 status of the UPEC strain determined urine IL17 level in the analyzed group. However, IL17 levels above median were overall more prevalent in controls. [ABSTRACT FROM AUTHOR]

Background: Anemia is the most common finding in patients with end-stage kidney disease undergoing renal replacement therapy. A certain percentage of patients does not respond adequately to erythropoietin (EPO) treatment, not being able to reach desirable hemoglobin levels even when treated with large-dose EPO and intravenous/oral iron. In our study, we wanted to further investigate how nutritional status is associated with erythropoietin responsiveness. To quantify EPO response, we used the Erythropoietin Resistance Index (ERI), which is defined as the weekly weight-adjusted dose of EPO divided by the hemoglobin level. Patients and methods: Seventy-eight patients undergoing hemodialysis were included. All of them were measured by a SECA mBCA body composition analyzer and evaluated by Kalantar-Zadeh's MIS score. Routine biochemical tests were also taken into account. The Shapiro-Wilk test was used to study the distributions of quantitative variables, which were significantly different from normal (p < 0.05). We used nonparametric Mann-Whitney U-test to compare groups. Correlations were studied by means of Spearman's rank correlation coefficient. Bonferroni correction for multiple testing was performed. To find independent determinants of ERI, we additionally performed multivariate analysis using the General Linear Model (GLM). Results: In terms of body composition, factors that are associated with high ERI are low BMI, low fat mass, low visceral fat volume, high total body water percentage, low phase angle and low fat-free mass. In addition to body composition parameters, total MIS score and IL-6 serum levels correlated positively with ERI value. IL-6 was an independent determinant of ERI value, based on multivariate analysis. After correction for multiple analysis, BMI and eGFR both remained significant factors associated with EPO response. Conclusions: It seems crucial to prevent inflammatory malnutrition as a part of a holistic approach to anemia treatment in dialysis patients. [ABSTRACT FROM AUTHOR]

Objectives and methods. The first aim of our study was to assess the detectability of women at risk of developing eo-PE depending on the algorithm used. All 801 patients had an estimated risk of eo-PE based on the Fetal Medicine Foundation algorithm. The patients were divided into four groups based on a risk calculation algorithm: 1) screening based on UtPI, MAP, and PlGF; 2) screening based on UtPI, MAP, PAPP-A, and PlGF; 3) screening based on UtPI, MAP, and PAPP-A; and 4) screening based on UtPI and MAP. The second aim was to explore how these groups changed depending on the cut-off points for the increased risk of eo-PE. We selected patients within groups where the risk of eo-PE was >1 : 150. Among them, the UtPI, MAP, PAPP-A, and PLGF values were compared taking into account the sizes of the groups. Results. For the cut-off point >1 : 150, 86 women at an increased risk of eo-PE using algorithm 1 were identified. Of these 86 patients, 83 (96%) were identified using algorithm 2, 62 (72%) using algorithm 3, and 60 (69%) using algorithm 4. In addition, it was demonstrated that between 21% and 29% of women at a low risk of eo-PE could be given acetylsalicylic acid if a screening test was used that did not account for PlGF. Conclusions. In order to provide the highest level of health care to pregnant women, it is extremely important that full screening for eo-PE should be ensured. The cheapest algorithm based only on MAP and UtPI resulted in our patients being unnecessarily exposed to complications. [ABSTRACT FROM AUTHOR]

Simple Summary: This study provided innovatory data regarding the role of EMMPRIN in long-term renal graft function and renal biopsy specimens in the form of interstitial fibrosis/tubular atrophy. The main cause of renal fibrosis is identified to be the activation and accumulation of fibroblasts and myofibroblasts in the interstitium, surrounded by increased amounts of extracellular matrix, and EMMPRIN has been proposed as a contributor factor. The study has evidenced that EMMPRIN displays adverse effects on renal graft survival in terms of the frequent occurrence of DGF, poorer short-term and long-term renal graft function, more profound fibrotic lesions in biopsy specimens, and the degree of proteinuria. This represents an opportunity for more accurate prediction of the post-transplant period and early, non-invasive detection of kidney graft dysfunction. Future studies need to further investigate the clinical significance of the presented results. Chronic kidney disease (CKD) is associated with renal fibrosis, and develops with the participation of fibroblasts and myofibroblasts from epithelial-to-mesenchymal transition (EMT). In cancer research, the key role of the glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in EMT has been proven. In this study, we evaluate how serum CD147/EMMPRIN affects long-term renal graft function and renal biopsy specimen lesions. In total, 49 renal graft recipients who had a renal biopsy within the last 18 months were retrospectively reviewed. At their most recent appointments, their serum concentrations of CD147/EMMPRIN and renal function were assessed. The occurrence of delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 1-year post-kidney transplantation (Tx) and the subsequent years of the follow-up period, and renal biopsy specimen lesions, mainly those related to renal fibrosis and tubular atrophy, were also evaluated. Results: CD147/EMMPRIN serum concentration correlated negatively with eGFR at the most recent appointment (ME 69 months) and with eGFR at 1 and 2 years after Tx (p < 0.05, R = −0.69, R = −0.39, and R = −0.40, respectively). CD147/EMMPRIN serum levels correlated positively with urine protein concentrations (p < 0.05, R = 0.73). A positive correlation was further found with the severity of renal biopsy specimen lesions such as interstitial fibrosis (CI), tubular atrophy (CT), double contours of the GBM (CG), mesangial matrix expansion (MM), and arteriolar hyalinosis (AH) (p < 0.05, R = 0.39, R = 0.29, R = 0.41, R = 0.32 and R = 0.40, respectively). Patients with a history of DGF had higher CD147/EMMPRIN serum concentrations (<0.05). Conclusions: CD147/EMMPRIN is linked to poorer long-term renal graft function. Additionally, a high serum concentration of CD147/EMMPRIN affects interstitial fibrosis tubular atrophy (IF/TA) lesions and proteinuria. [ABSTRACT FROM AUTHOR]

Obesity is a known factor in the development of preeclampsia. This paper links adipose tissue pathologies with aberrant placental development and the resulting preeclampsia. PPARγ, a transcription factor from the ligand-activated nuclear hormone receptor family, appears to be one common aspect of both pathologies. It is the master regulator of adipogenesis in humans. At the same time, its aberrantly low activity has been observed in placental pathologies. Overweight and obesity are very serious health problems worldwide. They have negative effects on the overall mortality rate. Very importantly, they are also conducive to diseases linked to impaired placental development, including preeclampsia. More and more people in Europe are suffering from overweight (35.2%) and obesity (16%) (EUROSTAT 2021 data), some of them young women planning pregnancy. As a result, we will be increasingly encountering obese pregnant women with a considerable risk of placental development disorders, including preeclampsia. An appreciation of the mechanisms shared by these two conditions may assist in their prevention and treatment. Clearly, it should not be forgotten that health education concerning the need for a proper diet and physical activity is of utmost importance here. [ABSTRACT FROM AUTHOR]

There are reports on the effects of excessive recipient body weight on renal graft function. Increased CCL2 (chemokine CC-mortif ligand 2) production is observed in patients with excessive body weight. CCL2 also exacerbates the inflammatory process in the renal graft. A total of 49 renal graft recipients of both sexes having undergone renal biopsy within the last 18 months were retrospectively reviewed. At their most recent appointment the patients' plasma concentrations of CCL2 were evaluated. Renal function was assessed retrospectively. CCL2 concentrations were higher in men than women (p < 0.047), while higher CCL2 levels were associated with a decrease in eGFR (estimated glomerular filtration rate) during the first year post Tx (kidney transplantation). CCL2 negatively correlated with eGFR at 5 years (R = −0.45, p < 0.040997) and positively correlated with the degree of tubular atrophy in renal biopsy specimens (R = 0.43, p < 0.027293) and with systolic pressure. Men showed significantly higher BMI (body mass index) values at the time of Tx and at their last appointment than women did (p < 0.000403; p < 0.000613, respectively). Men showed poorer long-term renal graft function, with significantly lower eGFR values at 4 and 5 years into the post-transplantation period. The male sex and excessive body weight have adverse effects on short- and long-term renal graft function, which is associated with increased levels of CCL2. [ABSTRACT FROM AUTHOR]

A semi-analytical model (CDOM-KD2) based on the light vertical attenuation coefficient (K d (λ)) has been developed for estimating the absorption by colored dissolved organic matter, a cdom (443), from ocean color remote sensing at global scale. The performance of this new inversion model together with that of former models by Shanmugam (2011) (S2011), Chen et al. (2017) (C2017) and Aurin et al. (2018) (A2018) was evaluated from in situ and matchup validation data sets gathering worldwide distributed samples. An overall consistency in the a cdom (443) estimated from S2011, C2017 and CDOM-KD2 models with a slightly better performance of the latter method was observed (MAPD of 27.42% and 30.85% for open ocean with in situ and satellite data, respectively), emphasizing the possible specific assessment of a cdom (443) dynamics from satellite remote sensing over the global ocean including the most oligotrophic waters. At 443 nm the global average relative contribution of a cdom (443) to the absorption by colored detrital matter, a cdm (443) is of 61% ± 14%, while the contribution of a cdom (443) to the non-water absorption, a nw (443), is of 35% ± 26%. Strong spatial disparities are however observed for both a cdom (443) temporal dynamics and relative contribution in the absorption budget. A decoupling is observed between a cdom (443) and particulate detrital (i.e. non-living) matter and phytoplankton in the gyre areas where a low temporal variability is globally observed. This is contrasting with water masses influenced by terrestrial inputs as well as in equatorial and subtropical areas impacted by main oceanic currents where CDOM loads and a cdom (443) contribution in the water absorption budget are more variable. • Development of a new model for estimating a cdom (443) at global scale from OCR. • CDOM global maps show its decoupling with detrital particles in the gyre areas. • CDOM's contribution to the total absorption budget shows great spatial variability. • CDOM's contribution to the total absorption budget is relatively stable in time. [ABSTRACT FROM AUTHOR]

We present a three-step inverse model (3SAA) for estimating the inherent optical properties (IOPs) of surface waters from the remote sensing reflectance spectra, R rs (λ). The derived IOPs include the total (a (λ)), phytoplankton (a phy (λ)), and colored detrital matter (a cdm (λ)), absorption coefficients, and the total (b b (λ)) and particulate (b bp (λ)) backscattering coefficients. The first step uses an improved neural network approach to estimate the diffuse attenuation coefficient of downwelling irradiance from R rs. a (λ) and b bp (λ) are then estimated using the LS2 model (Loisel et al., 2018), which does not require spectral assumptions on IOPs and hence can assess a (λ) and b b (λ) at any wavelength at which R rs (λ) is measured. Then, an inverse optimization algorithm is combined with an optical water class (OWC) approach to assess a phy (λ) and a cdm (λ) from a nw (λ).The proposed model is evaluated using an in situ dataset collected in open oceanic, coastal, and inland waters. Comparisons with other standard semi-analytical algorithms (QAA and GSM), as well as match-up exercises, have also been performed. The applicability of the algorithm on OLCI observations was assessed through the analysis of global IOPs spatial patterns derived from 3SAA and GSM. The good performance of 3SAA is manifested by median absolute percentage differences (MAPD) of 13%, 23%, 34% and 34% for b bp (443), a nw (443), a phy (443) and a cdm (443), respectively for oceanic waters. Due to the absence of spectral constraints on IOPs in the inversion of total IOPs, and the adoption of an OWC-based approach, the performance of 3SAA is only slightly degraded in bio-optical complex inland waters. • A class-based approach improves the IOP retrieval from OCR observations. • Validation using in situ, matchup, OLCI satellite and BGC-Argo data sets. • 3SAA shows good performance over marine et inland natural waters. [ABSTRACT FROM AUTHOR]

Simple Summary: Cardiac surgery associated acute kidney injury is a common complication of cardiac surgeries that worsens postoperative outcomes and the patient's prognosis. One of the main problems concerning this complication is its early diagnostics. In this study, the authors attempt to provide new data regarding the usage of novel kidney injury biomarkers in early detection of acute kidney injury and in the prognosis of the long-term postoperative kidney function. Perioperative factors that may influence kidney function were also analysed. It was concluded that biomarkers such as IL-6, IL-8, TNF-α, MMP-9 and NGAL are reliable acute kidney injury indicators. It was also demonstrated that intraoperative hypoperfusion secondary to hypovolemia is a main factor that damages the kidneys during cardiac surgeries. The authors hope that these findings will contribute to the development of new diagnostic protocols for acute kidney injury, which would involve novel renal biomarkers, thus enabling quicker diagnosis and more effective treatment of acute kidney injury. Background: There is a need for early diagnostic solutions for cardiac surgery associated acute kidney injury (CSA-AKI) as serum creatinine changes do not occur dynamically enough. Moreover, new approaches are needed for kidney protective strategy in patients undergoing cardiac surgery procedures; Methods: Samples of serum and urine were taken from the selected group of patients undergoing elective cardiac surgery procedures. The aim of this study was to assess the utility of specific inflammation and kidney injury biomarkers in the early diagnostic of CSA-AKI and in the prognosis of long-term postoperative kidney function; Results: At 6 h after weaning from cardiopulmonary bypass, there were significant differences in IL-6, IL-8, TNF-α, MMP-9 and NGAL concentrations in patients with CSA-AKI, compared to the control group. Serum IL-8 and urine NGAL 6 h after weaning from CPB proved to be independent acute kidney injury predictors. The TNF-α, MMP-9, IL-18, TIMP-1 and MMP-9/TIMP-1 ratio in the early postoperative period correlated with long-term kidney function impairment; Conclusions: Novel kidney injury biomarkers are an eligible tool for early diagnosis of CSA-AKI. They are also reliable indicators of long-term postoperative kidney function impairment risk after cardiac surgery procedures. [ABSTRACT FROM AUTHOR]

The exact pathogenesis and influence of various cytokines in patients with ovarian lesions remains unclear. Hence, this study aimed to investigate whether IL-6, IL-8, and TNF-α could be considered as new useful markers for diagnosis of ovarian cancer. 63 women diagnosed with ovarian cancer (OC) and 53 patients with benign ovarian cystic (BOC) lesions were included in this study. Serum levels of IL-6, IL-8, and TNF-α were measured using ELISA. Statistical comparisons were made using the Mann–Whitney U test and all correlations were evaluated by Spearman's ranks. The serum IL-8 and TNF-α concentration measured in the OC Group was significantly higher than in the BOC Group (p < 0.05). The cutoff level of IL-8 and TNF-α in the serum was set at 4.09 ng/mL and 2.63 ng/mL, respectively, with the sensitivity and specificity of 70% and 96% for IL-8 and 85.7% and 79.3% for TNF-α (p < 0.0001). These results suggest that IL-8 and TNF-α are useful biomarkers for predicting the malignant character of lesions of the ovary. The present study highlighted the importance of measuring the cytokines such as IL-8 and TNF-α in patients with ovarian lesions in predicting the clinical outcome. [ABSTRACT FROM AUTHOR]

The proxy for phytoplankton biomass, Chlorophyll a (Chl a), is an important variable to assess the health and state of the oceans which are under increasing anthropogenic pressures. Prior to the operational use of satellite ocean-colour Chl a to monitor the oceans, rigorous assessments of algorithm performance are necessary to select the most suitable products. Due to their inaccessibility, the oligotrophic open-ocean gyres are under-sampled and therefore under-represented in global in situ data sets. The Atlantic Meridional Transect (AMT) campaigns fill the sampling gap in Atlantic oligotrophic waters. In-water underway spectrophotometric data were collected on three AMT field campaigns in 2016, 2017 and 2018 to assess the performance of Sentinel-3A (S3-A) and Sentinel-3B (S3-B) Ocean and Land Colour Instrument (OLCI) products. Three Chl a algorithms for OLCI were compared: Processing baseline (pb) 2, which uses the ocean colour 4 band ratio algorithm (OC4Me); pb 3 (OL_L2M.003.00) which uses OC4Me and a colour index (CI); and POLYMER v4.8 which models atmosphere and water reflectance and retrieves Chl a as a part of its spectral matching inversion. The POLYMER Chl a for S-3A OLCI performed best. The S-3A OLCI pb 2 tended to under-estimate Chl a especially at low concentrations, while the updated OL_L2M.003.00 provided significant improvements at low concentrations. OLCI data were also compared to MODIS-Aqua (R2018 processing) and Suomi-NPP VIIRS standard products. MODIS-Aqua exhibited good performance similar to OLCI POLYMER whereas Suomi-NPP VIIRS exhibited a slight under-estimate at higher Chl a values. The reasons for the differences were that S-3A OLCI pb 2 R rs were over-estimated at blue bands which caused the under-estimate in Chl a. There were also some artefacts in the R rs spectral shape of VIIRS which caused Chl a to be under-estimated at values >0.1 mg m-3. In addition, using in situ R rs to compute Chl a with OC4Me we found a bias of 25% for these waters, related to the implementation of the OC4ME algorithm for S-3A OLCI. By comparison, the updated OLCI processor OL_L2M.003.00 significantly improved the Chl a retrievals at lower concentrations corresponding to the AMT measurements. S-3A and S-3B OLCI Chl a products were also compared during the Sentinel-3 mission tandem phase (the period when S-3A and S-3B were flying 30 sec apart along the same orbit). Both S-3A and S-3B OLCI pb 2 under-estimated Chl a especially at low values and the trend was greater for S-3A compared to S-3B. The performance of OLCI was improved by using either OL_L2M.003.00 or POLYMER Chl a. Analysis of coincident satellite images for S-3A OLCI, MODIS-Aqua and VIIRS as composites and over large areas illustrated that OLCI POLYMER gave the highest Chl a concentrations and percentage (%) coverage over the north and south Atlantic gyres, and OLCI pb 2 produced the lowest Chl a and % coverage. • Underway spectrophotometric Chl a were collected on 3 campaigns in the Atlantic. • Performance of Sentinel-3 OLCI, MODIS-Aqua, VIIRS ocean colour products assessed. • S-3A OLCI Chl a from POLYMER performed best; MODIS-Aqua also performed well. • Both S-3A and S-3B OLCI pb 2 under-estimated Chl a and was corrected using OL_L2M.003.00 and POLYMER. [ABSTRACT FROM AUTHOR]

To reduce the risk of infection of SARS-CoV-2 during commuting to the clinic or due to contact with medical staff, the American College of Obstetricians and Gynecologists has recommended arranging some appointments in the form of "telehealth". The aim of the study was to assess the access to medical care in pregnancy during the SARS-CoV-2 pandemic and the role of telehealth in the implementation of prenatal care standards. This is a cross-sectional study. The study group included 618 women who were pregnant and/or gave birth in Poland during the COVID-19 pandemic. The majority of the participants experienced difficulties accessing medical care because of the pandemic. The correlation between this experience and the use of the hybrid healthcare model was established. The affiliation to public or private healthcare was irrelevant. There was no relationship between healthcare (private/public or in-person/hybrid) and implementation of the prenatal care standards. To ensure safe access to prenatal care for pregnant women, recommendations for a hybrid pregnancy management model should be created with detailed information regarding which appointments patients must be present for in-person and which can be conducted remotely. To reduce the risks associated with movement and interpersonal contact, all visits during which tests and screenings take place should be conducted in-person; other appointments can be arranged in the form of telehealth. [ABSTRACT FROM AUTHOR]

Abnormally accelerated, premature placental senescence plays a crucial role in the genesis of pregnancy pathologies. Abnormal growth in the third trimester can present as small for gestational age fetuses or fetal growth restriction. One differs from the other by the presence of signs of placental insufficiency and the risk of stillbirth. The majority of stillbirths occur in normally grown fetuses and are classified as "unexplained", which often leads to conclusions that they were unpreventable. The main characteristic of aging is a gradual decline in the function of cells, tissues, and organs. These changes result in the accumulation of senescent cells in mitotic tissues. These cells begin the aging process that disrupts tissues' normal functions by affecting neighboring cells, degrading the extracellular matrix, and reducing tissues' regeneration capacity. Different degrees of abnormal placentation result in the severity of fetal growth restriction and its sequelae, including fetal death. This review aims to present the current knowledge and identify future research directions to understand better placental aging in late fetal growth restriction and unexplained stillbirth. We hypothesized that the final diagnosis of placental insufficiency can be made only using markers of placental senescence. [ABSTRACT FROM AUTHOR]

Background : The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). Methods : In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. Results : The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac ( p < 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. -3.6 mL/min; p = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. Conclusions : Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios.

Background: In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence of two genetic diseases, even with partially common symptoms, remains unusual. Therefore, targeted next-generation sequencing (NGS), along with genetic consultation and imaging studies, is essential for every patient with confirmed paraganglioma. In this report, we present two sisters diagnosed with multiple endocrine neoplasia type 2 (MEN2A) and familial paraganglioma syndrome type 1 (FPGL1)., Case Presentation: After presenting to the clinic with neck tumors persisting for several months, both patients underwent tumor removal procedures following imaging and laboratory studies. Pathological reports confirmed the diagnosis of paragangliomas. Subsequently, genetic testing, including NGS, revealed a mutation in the rearranged during transfection (RET) gene: the heterozygous change (c.2410G > A), (p.Val804Met), and a variant of the succinate dehydrogenase complex subunit D (SDHD) gene: (c.64 C > T), (p.Arg22Ter). Subsequently, thyroidectomy procedures were scheduled in both cases., Conclusion: To the best of our knowledge, this is the first report presenting these two mutations in two related patients, resulting in distinctive genetic syndromes with similar manifestations. This underscores that although infrequent, multiple hereditary disorders may co-occur in the same individual., (© 2024. The Author(s).)

Background: Kidneys play an essential role in the circulatory system, regulating blood pressure and intravascular volume. They are also set on maintaining an adequate filtration pressure in the glomerulus. During the CPB, a decrease in systemic blood pressure and hemoglobin concentration may lead to renal ischemia and subsequent acute kidney injury. Methods: One hundred nine adult patients were prospectively enrolled in this study. The intervention in this study was increasing the flow of the CPB pump to reach the target MAP of > 90 mmHg during the procedure. The control group had a standard pump flow of 2.4 L/min/m 2 . Results: Standard pump flow of 2.4 L/min/m 2 resulted in mean MAP < 90 mmHg during the CPB in most patients in the control group. Maintaining a higher MAP during CPB in this study population did not affect CSA-AKI incidence. However, it increased the intraoperative and postoperative diuresis and decreased renin release associated with CPB. Higher MAP during the CPB did not increase the incidence of cerebrovascular complications after the operation; patients in the highest MAP group had the lowest incidence of postoperative delirium, but the result did not obtain statistical significance. Conclusion: Maintaining MAP > 90 mmHg during the CPB positively impacts intraoperative and postoperative kidney function. It significantly reduces renal hypoperfusion during the procedure compared to MAP < 70 mmHg. MAP > 90 mmHg is safe for the central nervous system, and preliminary results suggest that it may have a beneficial impact on the incidence of postoperative delirium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Udzik, Pacholewicz, Biskupski, Safranow, Wojciechowska-Koszko, Kwiatkowski, Roszkowska, Rogulska, Dziedziejko, Marcinowska, Kwiatkowski and Kwiatkowska.)

Introduction: Physical activity during pregnancy is established to derive clinically meaningful improvements in pregnancy, childbirth, and postpartum health outcomes. Evidence-based pre-screening tools have been developed to support the implementation of physical activity programmes, and enhance communication between health care providers, exercise professionals and pregnant women. The Get Active Questionnaire for Pregnancy (GAQ-P) and the Health Care Provider Consultation Form for Prenatal Physical Activity (HCPCF) empower pregnant women to identify whether they require additional counselling from their obstetric health care provider in terms of physical activity. However, these tools are not available in Polish. This work details the process taken to translate the GAQ-P and HCPCF into Polish., Material and Methods: We followed the translation process outlined by the Translation and Cultural Adaptation International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines between August 2022 and August 2023. We formed an expert group that included representatives of the Polish Society of Sports Medicine, The Polish Society of Gynaecologists and Obstetricians, practitioners, and scientists in physical activity during pregnancy. We implemented 9 of the 10 steps recommended by ISOPR in the translation process. At the Cognitive Debriefing stage, we collected opinions on the Polish version of GAQ-P and HCPCF from 70 stakeholders on the clarity and cultural appropriateness of the translation., Results and Conclusions: Target users have positively evaluated the Polish version of GAQ-P and HCPCF. Thanks to the ISPOR methodology, we obtained a trustworthy, evidence-based screening tools, which can reduce the barriers for most women to be physically active during pregnancy.

During pregnancy, the placenta undergoes a natural aging process, which is considered normal. However, it has been hypothesized that an abnormally accelerated and premature aging of the placenta may contribute to placenta-related health issues. Placental senescence has been linked to several obstetric complications, including abnormal fetal growth, preeclampsia, preterm birth, and stillbirth, with stillbirth being the most challenging. A systematic search was conducted on Pubmed, Embase, and Scopus databases. Twenty-two full-text articles were identified for the final synthesis. Of these, 15 presented original research and 7 presented narrative reviews. There is a paucity of evidence in the literature on the role of placental aging in late small for gestational age (SGA), fetal growth restriction (FGR), and stillbirth. For future research, guidelines for both planning and reporting research must be implemented. The inclusion criteria should include clear differentiation between early and late SGA and FGR. As for stillbirths, only those with no other known cause of stillbirth should be included in the studies. This means excluding stillbirths due to congenital defects, infections, placental abruption, and maternal conditions affecting feto-maternal hemodynamics.

Preeclampsia (PE) is a multi-factorial disorder of pregnancy, and it continues to be one of the leading causes of fetal and maternal morbidity and mortality worldwide. Aspirin is universally recommended for high-risk women to reduce preeclampsia risk. The purpose of this review is to summarize the recommendations of various scientific societies on predicting preeclampsia and their indications for the inclusion of acetylsalicylic acid (ASA) prophylaxis. Fourteen guidelines were compared. The recommended dose, screening method, and gestational age at the start of the test vary depending on the recommendation. The societies are inclined to recommend using increasingly higher doses (>75 mg) of ASA, with many encouraging doses from 100 mg upward. Most societies indicate that the optimal time for implementing aspirin is prior to 16 weeks' gestation. Following the publication of the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial results and other papers evaluating the Fetal Medicine Foundation (FMF) screening model, a large number of societies have changed their recommendations from those based on risk factors alone to the ones based on the risk assessment proposed by the FMF. This allows for the detection of a high-risk pregnancy population in whom aspirin will be remarkably effective in preventing preterm PE, thereby decreasing maternal and fetal morbidity.

Acute kidney injury (AKI) can result from multiple factors. The main cause is reduced renal perfusion. Kidneys are susceptible to ischemia due to the anatomy of microcirculation that wraps around the renal tubules-peritubular capillary (PTC) network. Cortical and medullary superficial tubules have a large share in transport and require the supply of oxygen for ATP production, while it is the cortex that receives almost 100% of the blood flowing through the kidneys and the medulla only accounts for 5-10% of it. This difference makes the tubules present in the superficial layer of the medulla very susceptible to ischemia. Impaired blood flow causes damage to the endothelium, with an increase in its prothrombotic and pro-adhesive properties. This causes congestion in the microcirculation of the renal medulla. The next stage is the migration of pericytes with the disintegration of these vessels. The phenomenon of destruction of small vessels is called peritubular rarefaction, attributed as the main cause of further irreversible changes in the damaged kidney leading to the development of chronic kidney disease. In this article, we will present the characteristic structure of renal microcirculation, its regulation, and the mechanism of damage in acute ischemia, and we will try to find methods of prevention with particular emphasis on the inhibition of the renin-angiotensin-aldosterone system.

Background: Hemodialyzed patients with poor erythropoietin response tend to have low volume of visceral adipose tissue and score high on malnutrition-inflammation score. This study investigates in-depth the role of leptin and chosen cytokines in the development of malnutrition-inflammation syndrome (MIS) and erythropoietin resistance., Methods: Eighty-one hemodialyzed patients with erythropoietin-treated anemia were enrolled in the study. Their body composition was measured. Erythropoietin resistance index was calculated. Blood samples for leptin, IL-6, IL-18, TNF-alpha, and IL-1-alpha serum levels were drawn., Results: Leptin showed negative correlation with erythropoietin resistance index (ERI), whilst IL-6 showed the opposite. IL-6 seemed to be linked more to HD parameters and vintage, while TNF-alpha and leptin were more dependent on body composition. IL-18 and IL-1-alpha did not affect nutritional parameters nor ERI., Conclusion: Modulation of adipokine- and cytokine-related signaling is a promising target in tempering malnutrition in hemodialyzed, and thus achieving better outcomes in anemia treatment. Large clinical studies that target the inflammatory response in hemodialysis, especially regarding IL-6, TNF-alpha, and leptin, would be of great worth.

(1) Aim: Ultrasound is the gold standard for assessing fetal growth disorders. The relationship between high sFlt-1/PlGF scores and LBW (low birth weight) was described. In this study, we attempted to assess whether uric acid could be used as a secondary marker in estimating the pregnancy risk associated with LBW. (2) Material and methods: 665 pregnant women with a suspected or confirmed form of placental insufficiency were enrolled. In each of the patients, sFlt-1 and PlGF and uric acid levels were determined. Patients were divided into two groups according to birth weight below and above the third percentile for the given gestational age with the criteria of the neonatal definition of FGR (fetal growth restriction). (3) Results: A significant negative correlation between neonatal birth weight and the uric acid level across the entire study group was observed. We found a significant negative correlation between neonatal birth weight and the uric acid level with birth weights < 3rd percentile. (4) Conclusions: There is a significant link between the uric acid concentration and LBW in the group with placental insufficiency. Uric acid can improve the prediction of LBW. An algorithm for LBW prognosis that makes use of biophysical (ultrasound) and biochemical (uric acid level, angiogenesis markers) parameters yields better results than using these parameters separately from each other.

Tacrolimus, in combination with mycophenolate mofetil and glucocorticoids, is the basis of immunosuppressive therapy after renal transplantation. Tacrolimus intrapatient variability (IPV) and the blood concentration normalized by the dose (concentration/dose ratio, C/D ratio) both have an effect on the function of the transplanted kidney. In this study, we examined whether the metabolism rate affected IPV, whether the C/D ratio value was stable in the long-term follow-up, and whether it could be used for IPV measurements. In addition, our study population was examined for the effect of the C/D ratio and IPV on long-term renal function. The C/D ratio and IPV were examined in 170 patients at appointments held at 3, 6, 12 and 24 months after RTx. The average time post renal transplantation was 70 months. Renal function defined as creatinine concentration at the last appointment was examined. Results: the mean C/D ratio in the study group was 1.63. A negative correlation between the C/D ratio and creatinine concentration at the end of the follow-up was observed. Between the C/D ratio < and ≥1.63 groups, significant differences in creatinine concentration at the last appointment were found. No relationship was identified between the mean C/D ratio and IPV. The C/D ratio values increased significantly over a longer post-transplant period (12, 24, 60 and 120 m). We did not find a correlation between the mean IPV and the creatinine concentration from the last appointment. Our study group was divided into terciles according to IPV, while no renal graft function differences were found at the same appointment. Conclusion: the C/D ratio is useful for assessing the effects of the metabolism rate of tacrolimus on the long-term renal graft function. The C/D ratio does not affect the IPV value. IPV calculated from variability of the C/D ratio does not influence transplanted kidney function. The C/D changes over time.

Despite many available treatments, infants born to preeclamptic mothers continue to pose a serious clinical problem. The present study focuses on the evaluation of infants born to preeclamptic mothers for the occurrence of early-onset complications and attempts to link the clinical status of such infants to the angiogenesis markers in maternal blood (sFlt-1, PlGF). The study included 77 newborns and their mothers diagnosed with preeclampsia. The infants were assessed for their perinatal outcomes, with an emphasis on adverse neonatal outcomes such us infections, RDS, PDA, NEC, IVH, ROP, or BPD during the hospitalization period. The cutoff point was established using the ROC curve for the occurrence of any adverse neonatal outcome and it was 204 for the sFlt-1/PlGF and 32 birth week with AOC 0.644 and 0.91, respectively. The newborns born to mothers with high ratios had longer hospitalization times and, generally, were more frequently diagnosed with any of the aforementioned adverse neonatal outcomes. Also, the neonates born prior to or at 32 wkGA with higher sFlt-1/PlGF ratios were statistically significantly more common to be diagnosed with any of the adverse neonatal outcomes compared to those with lower ratio born prior to or at 32 wkGA. The sFlt-1/PlGF ratio can be a useful tool in predicting short-term adverse neonatal outcomes. Infants born after a full 33 weeks gestation developed almost no severe neonatal complications. Appropriate screening and preventive healthcare for preeclampsia can contribute significantly to reducing the incidence of neonatal complications.

Background/aims: Chronic kidney disease CKD patients on intermittent hemodialysis IHD are exposed to SARS-CoV-2 infection and carry a risk of developing severe symptoms. The aim of this study was to evaluate the humoral and cellular immunity induced by two doses of mRNA vaccines, the Pfizer-BioNTech (Comirnaty) COVID-19 Vaccine and the Moderna (mRNA-1273) COVID-19 vaccine., Patients and Methods: The study included 281 patients from five dialysis centers in northern Poland. Within 2 weeks prior to the first dose of the vaccine, a blood sample was collected for an evaluation of SARS-CoV-2 antibodies. Thirty to forty-five days after the second dose of the vaccine, a blood sample was taken to evaluate humoral and cellular response., Results: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate. The strongest factors influencing the antibodies AB level after vaccination were a pre-vaccination history of SARS-CoV-2 infection, age, the neutrophil-to-lymphocyte ratio NLR, neutrophil absolute count, and the hemoglobin level. Cellular immunity was higher in patients with a pre-vaccination history of SARS-CoV-2 infection. Cellular immunity depended on the albumin level. Positive cellular response to vaccination was a positive factor reducing all-cause mortality, except for COVID-19 mortality (no such deaths were reported during our follow-up). Cellular immunity and humoral immunity were positively mutually dependent. High levels of albumin and hemoglobin, low neutrophil count, and a reduced NLR, translated into better response to vaccination., Conclusions: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate and a good rate of cellular immunity. The factors that change with exacerbating inflammation and malnutrition (albumin, hemoglobin, neutrophil count, the NLR) affected the efficacy of the vaccination.

Introduction: Angiogenic markers (sFLt1 and PlGF) are altered in preeclampsia and related placental insufficiency syndromes. The utility of these markers in various types of placental insufficiency is still not well known., Aims: We analyzed blood specimens from 918 women with suspected or confirmed preeclampsia, HELLP syndrome, abruptio placenta, SGA, gestational hypertension for angiogenic markers - sFLT1, PlGF, sFlT1/PlGF ratios and studied them at various gestational windows., Results: sFlt-1/PLGF ratio shows high sensitivity and specificity in all placental insufficiency cases independent of clinical forms below 34 weeks (AUC 0.964 respectively 0.834 34-37 weeks' and 0.843 >37 weeks). In preeclampsia or HELLP, they maintain a high specificity and sensitivity also after 34 weeks of gestation. SGA prior to 34 weeks' gestation displayed severe placental angiogenesis disorders, with their share amounting to 78%. After 34 weeks, this share dropped to only slightly above 50%, and after the 37th week, a mere 38%., Conclusions: Placental angiogenesis markers may be useful in diagnosing many forms of placental ischemia syndromes, particularly when the disease presents early in gestation. In late-onset SGA cases, assessment of the diagnostic value of angiogenesis markers requires further analysis., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19-26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and the secretion of drugs from the basolateral surface into the tubular lumen; (2) tubular obstruction by crystals or casts containing drugs and their metabolites (a dose-dependent mechanism); (3) interstitial nephritis induced by drugs and their metabolites (a dose-independent mechanism). In this article, the mechanisms of the individual types of injury will be described. Specific groups of drugs will be linked to specific injuries. Additionally, the risk factors for the development of AKI and the methods for preventing and/or treating the condition will be discussed.

Prematurity has been one of the greatest challenges faced by perinatal medicine for many years. The recommended therapy for women with threatened preterm labor at 24 to 34 weeks' gestation is a single course of glucocorticoids. The greatest benefits have been proven when labor occurs at least 24 hours, but no later than 7 days after steroid administration. Applied treatment is not without influence on neonates' development., Aim: The aim of this study is to analyze the time between the administration of a course of glucocorticoids to patients with threatened preterm labor between 24 and 34 weeks of gestation and labor., Materials and Methods: 459 deliveries by patients between 24 and 34 weeks' gestation who had received betamethasone (two 12 mg doses) or dexamethasone (four 6 mg doses) were analyzed. Their indications for glucocorticoid therapy were divided into four categories: the signs of threatened preterm labor, premature rupture of membranes, iatrogenic prematurity and cervical incompetence. The neonates (n=530) were divided into two main groups: group 1 of those born within the first 7 days (n1=127) and group 2 of those born more than 7 days (n2=403) after the glucocorticoids therapy. Statistical analysis was performed using the Statistica 13.3 software with calculations performed using the Mann- Whitney U and χ2 tests, assuming the level of statistical significance of <0.05 (p<0.05)., Results: The neonates born within the first 7 days after the glucocorticoid therapy accounted for 23.96% (127 children). The average time of delay between the course of glucocorticoids and labor was 33 days, with the longest interval being 116 days. The most common indications for glucocorticoids were iatrogenic causes in group 1 (35.40%) and the signs of threatened preterm labor (67.63%) in group 2., Conclusions: The percentage of births at the recommended time after steroidotherapy (not later than 7 days) was lower than expected. The prenatal steroid therapy qualification methods, should be reanalyzed, especially when signs of preterm labor are observed., (© 2020 MEDPRESS.)

Preeclampsia (PE) is a disorder that affects 3-5% of normal pregnancies. It was believed for a long time that the kidney, similarly to all vessels in the whole system, only sustained endothelial damage. The current knowledge gives rise to a presumption that the main role in the development of proteinuria is played by damage to the podocytes and their slit diaphragm. The podocyte damage mechanism in preeclampsia is connected to free VEGF and nitric oxide (NO) deficiency, and an increased concentration of endothelin-1 and oxidative stress. From national cohort studies, we know that women who had preeclampsia in at least one pregnancy carried five times the risk of developing end-stage renal disease (ESRD) when compared to women with physiological pregnancies. The focal segmental glomerulosclerosis (FSGS) is the dominant histopathological lesion in women with a history of PE. The kidney's podocytes are not subject to replacement or proliferation. Podocyte depletion exceeding 20% resulted in FSGS, which is a reason for the later development of ESRD. In this review, we present the mechanism of kidney (especially podocytes) injury in preeclampsia. We try to explain how this damage affects further changes in the morphology and function of the kidneys after pregnancy.

BACKGROUND Spinal hematomas can be post-traumatic, iatrogenic, or spontaneous. A spontaneous spinal hematoma is a rare finding, but one with very serious clinical implications. There are some risk factors linked to its occurrence, e.g. arteriovenous malformations, lumbar puncture, coagulopathy, neoplasms, or therapeutic anticoagulation. At present, only a few cases of spontaneous spinal hematoma (SSH) associated with new oral anticoagulants (NOACs) have been described, three of which were linked with rivaroxaban. CASE REPORT We report the case of an 82-year-old Caucasian woman with persistent atrial fibrillation treated with rivaroxaban, who presented to the Urology Department with acute-onset back pain which was thought to be due to urolithiasis. No kidney stones were found, but her creatinine serum level was elevated, so she was transferred to our clinic for further treatment. During hospitalization she quickly developed paraplegia with urine and stool retention. MRI was performed, and demonstrated an acute epidural hemorrhage in her thoracic and lumbar spine. The neurosurgeons disqualified this patient from surgical intervention due to the extent of the hematoma and its location. The patient was referred to the Neurology Department for treatment and rehabilitation, but, to the best of our knowledge, she did not recover her motor function. CONCLUSIONS Although rivaroxaban has been shown to be more effective than warfarin in stroke prevention in patients with atrial fibrillation, physicians must remember that its use also carries the risk of major bleeding. SSH occurrence should be taken into account in a patient taking NOACs who develops paraplegia, even if there is no history of trauma prior to admission.

Background/aims: Tacrolimus is an immunosuppressive drug. Its C0 concentration, commonly used for monitoring, does not always correspond to its pharmacologic effect. Thölking et al developed an indicator, the C/D ratio, that describes the drug's metabolism rate. Our purpose was to determine whether the points dividing the patients into fast, intermediate, and slow metabolizers that were assumed by those authors would be similar for long-term follow-up after renal transplantation (RTx)., Methods: We examined the C/D ratio in 571 patients at their most recent appointments-1 year and more after renal transplantation. The mean time after RTx was 84 months. We studied kidney function both at the most recent appointment and early after RTx., Results: The median C/D ratio for our group was 1.68. Our observations revealed a negative correlation between the C/D ratio and creatinine concentration and a positive correlation between the C/D ratio and eGFR concentration long term after RTx. We formulated a C/D ratio cutoff point between an eGFR < and ≥ 60 mL/min/1.73 m 2 and came up with the value of 1.53. It was found that between the < 1.53 and ≥ 1.53 groups, there were significant differences in creatinine and eGFR concentrations at the most recent appointment, as well as differences in how creatinine and eGFR levels varied over time between RTx and the most recent observation., Conclusions: The C/D ratio is useful for assessing the effect of the tacrolimus metabolism rate on long-term renal function. We propose the C/D ratio value of 1.53 as the cutoff point below which the ratio provides a negative prognosis for long-term renal function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Urokinase-type plasminogen activator receptor (uPAR) is found in a variety of cell types including monocytes, lymphocytes, macrophages, and endothelial cells and plays an important role in fibrinolysis and in the activation and chemotaxis of neutrophils and lymphocytes. In this study, we examined the correlation between uPAR plasma concentration and kidney allograft function., Aims: This study enrolled 78 Caucasian deceased-donor renal transplant recipients., Methods: Plasma concentrations of uPAR were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits., Results: We observed elevated with borderline significance (p = 0.095) uPAR plasma concentrations in patients with tubular atrophy. Plasma concentrations of uPAR showed strong statistically significant positive correlations with serum creatinine or urea and strong negative correlation with estimated glomerular filtration rate (eGFR). There was also a borderline positive correlation between uPAR plasma concentration and protein concentration in urine as well as the duration of hemodialysis., Conclusions: The results of our study indicate that uPAR plasma concentrations in kidney allograft recipients are significantly negatively correlated with graft function and may be elevated in patients with tubular atrophy.

We explored whether there was a relationship between the sFlt-1/PlGF ratio in early-late and late-onset SGA patients and whether it is associated with neonatal birth weight., Material/methods: 110 patients who were diagnosed with a fetal weight below the 10th percentile for gestational age and who at the same time delivered neonates with a birth weight below the 10th percentile for gestational age. For each of the patients sFlt-1, PlGF and the sFlt-1/PlGF ratio were studied and uterine artery (UtA) and umbilical artery (UA) Doppler were performed., Results: sFlt-1/PlGF ratios and neonatal birth weight which showed significant negative correlation across the entire population studied (R = -0.46, p < 0.001). In late-onset SGA patients this negative correlation was observed, as well (R = -0.54, p < 0.001) In the group of patients with pregnancies older than 34 weeks and an sFlt-1/PlGF ratio ≥38, we observed a significantly lower neonatal birth weight when compared to the same gestational age group with an sFlt-1/PlGF ratio <38 (2045 g vs 2405 g, p < 0.001)., Conclusion: Late-onset SGA syndromes are characterized by lower sFlt-1/PlGF ratios, which indicates a lower degree of placental function impairment. The sFlt-1/PlGF ratio can be a predictor of more significant growth disorders and a lower neonatal birth weight. The sFlt-1/PlGF ratio can be helpful in distinguishing between disordered angiogenesis-dependent and other causes of late-onset SGA cases., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Although solar retinopathy is characterised by a mild course in most cases, it can lead to permanent vision impairment and significantly restrict patient's ability to perform daily activities. The authors discuss the pathomechanism as well as signs and symptoms of solar retinopathy, additionally presenting the overview of diagnostic, armamentarium, differential diagnosis, prognosis and prevention.

The paper reports the case series of solar retinopathy. High definition optical coherence tomography examinations performed within 2 days after solar light-induced injury indicated a characteristic retinal disorder - a curved, hyper-reflective lesion extending from the retinal pigment epithelium at the fovea to the parafoveal outer plexiform layer. The findings correspond to the layout of photoreceptor cells whose injury in patients with solar retinopathy is confirmed by histological studies reported in available publications.

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

Tubulointerstitial nephritis and uveitis syndrome is a rare autoimmune disease of incompletely understood pathogenesis. Over 250 cases have been reported in the literature till now, yet the diagnostic process can still be confusing, as the symptoms may occur randomly and vary. Here we report a case of a 52-year-old male with a very atypical clinical manifestation of tubulointerstitial nephritis and uveitis syndrome. Typically, the onset of the syndrome is marked with anterior uveitis concomitant with tubulointerstitial nephritis. In the reported case, though, retinitis persisted for a relatively long time and only after a few years the patient developed symptoms of anterior uveitis.

Objectives: The aim of our study was to evaluate urinary excretion of three brush border enzymes: gamma-glutamyl transferase, alanine aminopeptidase, and leucyl aminopeptidase in pregnant women with various types of hypertensive disorders., Material and Methods: The study included 120 pregnant women, further subdivided into four groups: 41 women at ≥ 20 weeks gestation with gestational hypertension, 28 women > 20 weeks of pregnancy with preeclampsia, 21 women with chronic hypertension identified > 20 weeks of pregnancy and 30 healthy pregnant controls., Results: No significant differences in urinary levels of all three of the brush border enzymes were found between the groups. Also, there was no correlation between enzyme concentration in the urine and blood pressure values in any of the analyzed groups of pregnant women., Conclusions: The obtained results suggest no damage to the brush border of the proximal kidney tubules in the early stages of disorders associated with increased blood pressure during pregnancy.

Background: Cytokines are key mediators of the immune response after transplantation. The interleukin (IL)-2 cytokine family, which includes IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21, is of particular interest because of its importance in the allogenic response. The aim of this study was to examine the association between the rs6822844 gene polymorphism in the IL2-IL21 region and allograft function after kidney transplantation., Methods: The study enrolled 270 Caucasian kidney allograft recipients (166 males and 104 females, mean age 47.63 ± 12.96 years). Following parameters were recorded in each case: recipient's age, delayed graft function (DGF), occurrence and number of episodes of acute rejection (AR), and chronic allograft dysfunction (CAD). Genotyping of the rs6822844 IL2-IL21 cluster gene polymorphism was performed using real-time PCR assay., Results: There were no statistically significant differences in the genotypes and alleles of the rs6822844 IL2-IL21 cluster gene polymorphism among patients with DGF (p = 0.72), AR (p = 0.69) and CAD (p = 0.77), or in creatinine concentrations 1, 3, 6, 12, 24 or 36 months after transplantation (p = 0.46, p = 0.58, p = 0.6, p = 0.72, p = 0.7, p = 0.76, respectively)., Conclusion: It seems that the rs6822844 IL2-IL21 gene cluster polymorphism is of little importance in allograft function after kidney transplantation.

p19(INK4d) (CDKN2D) is a negative regulator of the cell cycle. Little is known of its role in cancer development and prognosis. We aimed to evaluate the clinical significance of p19(INK4d) expression in ovarian carcinomas with respect to the TP53 accumulation status, as well as the frequency of CDKN2D mutations. p19(INK4d) and TP53 expression was evaluated immunohistochemically in 445 ovarian carcinomas: 246 patients were treated with platinum-cyclophosphamide (PC/PAC), while 199 were treated with taxane-platinum agents (TP). CDKN2D gene expression (mRNA) was examined in 106 carcinomas, while CDKN2D mutations in 68 tumors. Uni- and multivariate statistical analyses (logistic regression and the Cox proportional hazards model) were performed for patient groups divided according to the chemotherapeutic regimen administered, and in subgroups with and without TP53 accumulation. High p19(INK4d) expression increased the risk of death, but only in patients with the TP53-negative carcinomas (HR 1.61, P = 0.049 for PC/PAC-treated patients, HR 2.00, P = 0.015 for TP-treated patients). This result was confirmed by the mRNA analysis (HR 4.24, P = 0.001 for TP-treated group). High p19(INK4d) protein expression associated with adverse clinicopathological factors. We found no alterations in the CDKN2D gene; the c.90C>G (p.R30R; rs1968445) polymorphism was detected in 10% of tumors. Our results suggest that p19(INK4d) expression is a poor prognostic factor in ovarian cancer patients. Analyses of tumor groups according to the TP53 accumulation status facilitate the identification of cancer biomarkers.

Alterations of the PIK3CA gene occur in endometrial carcinomas, but their role in the carcinogenesis of those malignancies is still poorly understood. In this study, PIK3CA mutations and amplification in 196 endometrioid endometrial carcinomas and 20 endometrial hyperplasias were assessed by single-strand conformation polymorphism (PCR-SSCP), sequencing, and quantitative polymerase chain reaction. Results were correlated with mutations in the PTEN, KRAS, and CTNNB1 genes and with the clinicopathologic parameters of the tumors. PIK3CA mutations were found in 39 (20%) carcinomas. Six new mutations were identified. No PIK3CA mutations were found in endometrial hyperplasias. PIK3CA amplification was observed in 24 (12.2%) carcinomas and in 2 (10%) hyperplasias. The PIK3CA mutations and amplifications (with the exception of 6 cases) occurred independently. PIK3CA mutations were significantly associated with PTEN mutations (P = .0414) and tended to be associated with CTNNB1 (P = .0833), but not with KRAS mutations. Conversely, the PIK3CA amplifications significantly negatively correlated with PTEN mutations (P = .0038) and did not coexist with CTNNB1 and KRAS mutations. The PIK3CA mutations were significantly associated with poorly differentiated tumors (P = .0423). Interestingly, PIK3CA amplifications, but not mutations, were strongly associated with older age (≥63 years, P = .0018). Our data show that mutations and amplification of PIK3CA are significant genetic alterations in endometrioid endometrial carcinomas associated with adverse clinicopathologic parameters (grade and stage). These data also demonstrate that PIK3CA mutations cooperate with PTEN mutations, suggesting an additive effect to PTEN, whereas PIK3CA amplification can, as an isolated event, enable the development of those tumors. Moreover, for the first time, a possible role of PIK3CA amplification in initiation and progression of endometrial carcinomas in older women is suggested, but this preliminary suggestion requires further research., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Despite the development of immunosuppressive regimens in kidney transplantation, long-term graft survival rates have not increased significantly. One of the causes of long-term graft loss is ischemia-reperfusion insult. Hepatocyte growth factor (HGF) is a regenerative factor produced in response to injury., Objectives: Our aim was to assess the effect of HGF and xanthine oxidase (indicators of ischemia/reperfusion insult) on early and late kidney function., Patients and Methods: In 17 patients, HGF levels in urine and xanthine oxidase activity in blood were examined 1, 7, 14, 30 days, 3 and 6 months after kidney transplantation. We also measured 24-hour diuresis and serum creatinine levels after transplantation., Results: Urinary HGF levels were highest 1 day after transplantation. During the following week, it rapidly decreased and was maintained at similar levels in the later period. Creatinine at 1 day showed a positive correlation with urinary HGF levels at 1 day and at 3 months (R = 0.54, P <0.05 and R = 0.82, P <0.01, respectively). Creatinine at 7 days positively correlated with HGF levels at 6 months (R = 0.82, P <0.05). HGF levels at 1 day and at 6 months positively correlated with xanthine oxidase activity at 1 day (R = 0.73, P <0.001 and R = 0.77, P <0.02, respectively). A negative correlation was observed between HGF levels at 6 months and diuresis 1 and 7 days after transplantation (R = -0.99, P <0.00 001 and R = -0.77, P <0.05, respectively)., Conclusions: Urinary HGF is a good marker of perioperative kidney damage and may affect long-term graft function.

We describe the development of a new suite of aerosol models for the retrieval of atmospheric and oceanic optical properties from the SeaWiFS and MODIS sensors, including aerosol optical thickness (τ), angstrom coefficient (α), and water-leaving radiance (L(w)). The new aerosol models are derived from Aerosol Robotic Network (AERONET) observations and have bimodal lognormal distributions that are narrower than previous models used by the Ocean Biology Processing Group. We analyzed AERONET data over open ocean and coastal regions and found that the seasonal variability in the modal radii, particularly in the coastal region, was related to the relative humidity. These findings were incorporated into the models by making the modal radii, as well as the refractive indices, explicitly dependent on relative humidity. From these findings, we constructed a new suite of aerosol models. We considered eight relative humidity values (30%, 50%, 70%, 75%, 80%, 85%, 90%, and 95%) and, for each relative humidity value, we constructed ten distributions by varying the fine-mode fraction from zero to 1. In all, 80 distributions (8 Rh×10 fine-mode fractions) were created to process the satellite data. We also assumed that the coarse-mode particles were nonabsorbing (sea salt) and that all observed absorptions were entirely due to fine-mode particles. The composition of the fine mode was varied to ensure that the new models exhibited the same spectral dependence of single scattering albedo as observed in the AERONET data. The reprocessing of the SeaWiFS data show that, over deep ocean, the average τ(865) values retrieved from the new aerosol models was 0.100±0.004, which was closer to the average AERONET value of 0.086±0.066 for τ(870) for the eight open-ocean sites used in this study. The average τ(865) value from the old models was 0.131±0.005. The comparison of monthly mean aerosol optical thickness retrieved from the SeaWiFS sensor with AERONET data over Bermuda and Wallops Island show very good agreement with one another. In fact, 81% of the data points over Bermuda and 78% of the data points over Wallops Island fall within an uncertainty of ±0.02 in optical thickness. As a part of the reprocessing effort of the SeaWiFS data, we also revised the vicarious calibration gain factors, which resulted in significant improvement in angstrom coefficient (α) retrievals. The average value of α from the new models over Bermuda is 0.841±0.171, which is in good agreement with the AERONET value of 0.891±0.211. The average value of α retrieved using old models is 0.394±0.087, which is significantly lower than the AERONET value.

Introduction: Accumulation of reactive oxygen species (ROS) takes place in patients with chronic renal failure (CRF). Oxidative stress causes disorders in the activity of the sodium-proton exchanger (NHE). Studies on NHE in CRF produced results that are discrepant and difficult to interpret. The aim of this study was to demonstrate that oxidative stress had an effect on the activity of NHE., Methods: We enrolled 87 subjects divided into 4 groups: patients with CRF treated conservatively; patients with CRF hemodialyzed without glucose--HD-g(-); patients with CRF hemodialyzed with glucose--HD-g(+); controls (C). The activity of NHE, the rate of proton efflux V(max), Michaelis constant (Km), and the concentration of thiobarbituric acid-reactive substances (TBARS, an indicator of oxidative stress) in plasma, as well as the concentration of reduced glutathione in blood were determined., Results: The concentration of TBARS was significantly higher in hemodialyzed patients before and after dialysis and in patients with CRF on conservative treatment in comparison with group C. TBARS in plasma correlated negatively with VpH(i)6.4 in group C and with V(max) and VpH(i)6.4 after HD in group HD-g(-). We found that the concentration of creatinine correlated with TBARS (p < 0.0001; r = +0.51) in the conservatively treated group., Conclusion: We observed a marked oxidative stress and decreased NHE activity when dialysis was done without glucose, whereas patients dialyzed with glucose demonstrated a relatively low intensity of oxidative stress.

Background: Our research focused on the relations between the age at onset of bilateral breast cancer and the prevalence of selected hereditary BRCA1, BRCA2 and CHEK2 gene mutations with reference to their positive family history of cancer., Methods: The DNA of peripheral blood lymphocytes of patients was examined for the presence of selected hereditary mutations in the BRCA1, BRCA2 and CHEK2 genes, using molecular biology techniques. The family history of neoplasms was also analyzed., Results: The following mutations in the BRCA1 gene were identified: 185delAG, C61G, 5382insC, 3875 del11ins7, and R1751X. In the BRCA2 gene, the 9631delC and A9599T mutations were found. In the CHEK2 gene, the 1100delC and I157T mutations were identified. BRCA1/2 gene mutations were identified in 19.4% of patients and CHEK2 gene mutations in 7%., Conclusions: It was shown that the presence of the mutations in the BRCA1/2 genes among patients with bilateral breast cancer is associated with an earlier occurrence of the first and the second breast cancer than in patients without hereditary mutations in these genes (a difference of 7.2-8.4 years). In patients with CHEK2 gene mutations, breast cancer occurred 2.1-3.8 years earlier than in patients without mutations in the CHEK2 gene., (Copyright 2009 S. Karger AG, Basel.)