LATS1 Is a Mediator of Melanogenesis in Response to Oxidative Stress and Regulator of Melanoma Growth.

The LATS1 kinase has been described as a tumor suppressor in various cancers. However, its role in melanoma has not been fully elucidated. There are several processes involved in tumorigenesis, including melanin production. Melanin content positively correlates with the level of reactive oxygen species (ROS) inside the cell. Accordingly, the purpose of the study was to assess the role of LATS1 in melanogenesis and oxidative stress and its influence on tumor growth. We have knocked down LATS1 in primary melanocytes and melanoma cells and found that its expression is crucial for melanin synthesis, ROS production, and oxidative stress response. We showed that LATS1 ablation significantly decreased the melanogenesis markers' expression and melanin synthesis in melanocyte and melanoma cell lines. Moreover, silencing LATS1 resulted in enhanced oxidative stress. Reduced melanin content in LATS1 knocked down tumors was associated with increased tumor growth, pointing to melanin's protective role in this process. The study demonstrated that LATS1 is highly engaged in melanogenesis and oxidative stress control and affects melanoma growth. Our results may find the implications in the diagnosis and treatment of pigmentation disorders, including melanoma.

"Sure I'll help-I've just been sitting around doing nothing at school all day": Cognitive flexibility and child irony interpretation.

Successful peer relations in older children depend on proficiency with banter, which in turn frequently involves verbal irony. Individual differences in successful irony interpretation have traditionally been attributed to theory of mind. Our premise was that the key factor might in fact be cognitive flexibility, that is, the ability to switch between different perspectives (here, on the same utterance). We also wished to extend the focus of previous irony studies, which have almost exclusively examined simple irony, where the literal meaning conflicts with observable physical evidence (e.g., "Great day for a picnic" when viewing a downpour). Therefore, we also examined how children interpreted more complex irony, where listeners must consider at a deeper level the common ground shared with the speakers (e.g., general knowledge/cultural common ground or information about the particular speaker). In Study 1, we found that for 6- to 8-year-olds, both cognitive flexibility and theory of mind contributed unique variance to simple irony interpretation while statistically controlling for nonverbal reasoning and structural language standardized scores. Neither inhibitory control, nor working memory, nor general knowledge correlated with irony interpretation. The 6- to 8-year-olds were at floor for complex irony. In Study 2, we found that cognitive flexibility contributed unique variance to how 10- to 12-year-olds interpreted complex irony while controlling for nonverbal reasoning, structural language, and specific knowledge required. We are the first to examine the relationship with cognitive flexibility and conclude that it must be taken into account when investigating the relationship between theory of mind and irony interpretation.

Using shared knowledge to determine ironic intent; a conversational response paradigm.

Mentalising has long been suggested to play an important role in irony interpretation. We hypothesised that another important cognitive underpinning of irony interpretation is likely to be children's capacity for mental set switching - the ability to switch flexibly between different approaches to the same task. We experimentally manipulated mentalising and set switching to investigate their effects on the ability of 7-year-olds to determine if an utterance is intended ironically or literally. The component of mentalising examined was whether the speaker and listener shared requisite knowledge.We developed a paradigm in which children had to select how a listener might reply, depending on whether the listener shared knowledge needed to interpret the utterance as ironic. Our manipulation of requisite set switching found null results. However, we are the first to show experimentally that children as young as seven years use mentalising to determine whether an utterance is intended ironically or literally.

Tumor microenvironment - Unknown niche with powerful therapeutic potential.

Head and neck squamous cell carcinomas (HNSCC) are in a group of cancers that are the most resistant to treatment. The survival rate of HNSCC patients has been still very low since last 20 years. The existence of relationship between oncogenic and surrounding cells is probably the reason for a poor response to treatment. Fibroblasts are an important element of tumor stroma which increases tumor cells ability to proliferate. Another highly resistance, tumorigenic and metastatic cell population in tumor microenvironment are cancer initiating cells (CICs). The population of cancer initiating cells can be found regardless of differentiation status of cancer and they seem to be crucial for HNSCC development. In this review, we describe the current state of knowledge about HNSCC biological and physiological tumor microenvironment.

Intraoperative contrast-enhanced urosonography during endoscopic treatment of vesicoureteral reflux in children.

BACKGROUND: There are many controversies surrounding the effectiveness of endoscopic treatment of vesicouretheral reflux (VUR) in children, thus it is of highest priority to analyze factors influencing the outcome of therapy and to search for new methods that would increase the success rate and reduce the number of reinjections. OBJECTIVE: The aim of the study was to analyze whether intraoperative contrast-enhanced urosonography (ce-US) may increase the effectiveness of endoscopic anti-reflux therapy. MATERIALS AND METHODS: Intraoperative contrast-enhanced urosonography (ce-US) with SonoVue® was performed in 17 patients (25 ureteral units) undergoing endoscopic treatment of VUR. Ce-US was performed in the operating room before the procedure and after injection of the bulking material. When VUR persisted, the operator repeated the injection, which was followed by ce-US. The results were compared with those obtained from a control group (15 patients; 22 ureteral units). RESULTS: A repeat injection during a single endoscopic treatment was required in 24% of cases. The overall success rate confirmed at 6-12 months' follow-ups was 84%. The success rate was significantly higher in comparison to the control group (success: 64%). CONCLUSION: Intraoperative ce-US performed during endoscopic treatment of VUR enables immediate monitoring of outcome and provides the opportunity for repeat injection during the same procedure, thus increasing the efficacy of the procedure and reducing the number of reinjections.

Serum fibroblast growth factor 23 and calcium-phosphorus metabolism parameters in children with chronic kidney disease - preliminary report.

INTRODUCTION: In chronic kidney disease (CKD) the function of all factors regulating mineral metabolism is disturbed, leading inevitably to renal osteodystrophy and vascular calcification. The aimof the study is to assess concentrations of fibroblast growth factor 23 (FGF 23), osteoprotegerin (OPG) and other parameters of calcium-phosphate metabolism in children with CKD. MATERIAL AND METHODS: 37 children with CKD 3-5, aged 1.6-17 years were included in the study. In all children serum levels of calcium (sCa), phosphate (sP), creatinine, alkaline phosphatase (ALP), FGF 23, intact parathormone (PTH), OPG and receptor activator nuclear factor κB ligand (RANKL) were measured. RESULTS: Total calcium concentration was within normal limits in all children included in this study. Hyperphosphatemia was found in 2 children from group CKD 3 (12%), 6 from CKD 4 (54%) and 1 from CKD 5 (11%). FGF 23 level increased consecutively in subsequent CKD stages achieving the highest values in CKD 5 group. In all children with CKD, serum levels of OPG were correlated with FGF 23. In children with CKD 3-4 negative correlation between FGF 23 and PTH (r=-0.45; p=0.02) and positive correlation between FGF 23 and RANKL (r=0,59; p=0.006) has been found. Positive correlation between OPG concentration and HCO3 -and BE levels has been observed, as well as negative correlation between RANKL/OPG ratio and HCO3 -and BE levels. CONCLUSION: Despite maintaining serum calcium, phosphorus and PTH levels within recommended limits, elevated levels of FGF 23 and OPG were observed in children with chronic kidney disease, especially in it's end-stage.

Anxiety in children and adolescents with chronic kidney disease--multicenter national study results.

BACKGROUND/AIMS: Chronic medical illness is a significant risk factor for the development of psychiatric disorders. The aims of the study were: to investigate the level of anxiety in children with chronic kidney disease (CKD) and to identify factors associated with the presence of that emotional problem. METHODS: CKD children on hemodialysis (HD, n=22), peritoneal dialysis (PD, n=20,) and on conservative treatment (CT, n=95) were enrolled in the study. We used State-Trait Anxiety Inventory (STAI) for adolescents and STAI-C for children. Socio-demographic and physical factors were assessed. RESULTS: There was a significantly higher level of anxiety-state among HD children (8-12 years) compared with other groups of participants of the same age and Polish population norms. The level of anxiety among adolescents (13-18 years), both anxiety-state and anxiety-trait, was significantly higher in the HD group compared with other groups, which did not differ among themselves. In the HD adolescents, there was a correlation between the anxiety-state and the duration of the disease as well as with the number of hospitalizations. PD adolescents in the mainstream education had higher levels of anxiety-state and anxiety-trait compared with home schooled patients. CONCLUSIONS: Even though children and adolescents with CKD are at risk of developing a variety of emotional disorders, the level of anxiety among the researched group, with the exception of HD patients, was not significantly different than the level of anxiety among healthy subjects. Adolescents on HD who present a high level of anxiety should undergo long-term psychological treatment.

Psychosocial aspects of children and families of children treated with automated peritoneal dialysis.

BACKGROUND: The aim of this study was to analyze psychosocial aspects of chronic kidney disease (CKD) in children treated with automated peritoneal dialysis (APD). METHODS: The study assessed 41 children > 2 (range 2.1-18) years of age and their parents. Data concerning the illness and sociodemographic parameters were collected. Patients completed the Paediatric Quality of Life Inventory (PedsQL) and their parents the PedsQL-proxy version, General Health Questionnaire (GHQ-12), Berlin Social Support Scales (BSSS), and Caregiver's Burden Scale (CBS). RESULTS: Parents rated their children's overall health-related quality of life (QoL) as well as their physical and emotional functioning lower than the patients themselves. The majority of primary caregivers had a medium level of the total burden index in the CBS and higher values in the scales need for support and perceived available support than in the received support (BSSS). In the GHQ-12, 51.2% of primary caregivers had scores >2 points, which indicated the possible occurrence of abnormal mental functioning. CONCLUSIONS: Financial support for patients' families is necessary. Parents who provide primary care to children on PD require, above all, emotional support and assistance in self-fulfilment. More than half of them may have impaired mental function. There is the strong need to provide continuous psychological care for caregivers. Differences in perception of the children's activity in varied areas by the patients themselves and their caregivers may contribute to further problems within families.

Perception of health-related quality of life in children with chronic kidney disease by the patients and their caregivers: multicentre national study results.

OBJECTIVE: The aim of the study was to analyse the health-related quality of life (HRQoL) in Polish children with chronic kidney disease (CKD) dependant on the CKD stage, treatment modality and selected social life elements in families of the patients. Furthermore, potential differences between self-report and parent/proxy reports and the factors influencing them were assessed. METHODS: A total of 203 CKD children (on haemodialysis (HD), peritoneal dialysis (PD) and conservative treatment (CT)) and their 388 parent/proxies were enrolled into a cross-sectional national study. The demographic and social data were evaluated. We used the Paediatric Quality of Life Inventory 4.0 Generic Core Scales to assess the HRQoL in children. RESULTS: Health-related quality of life scores for all CKD groups were significantly lower in all domains compared with population norms, the lowest one being in the HD group. In CT children, HRQoL did not depend on the CKD stage. Both parents assessed the HRQoL of their children differently depending on their involvement in the care. There are differences between the HRQoL scores of the children and their parents. CONCLUSION: The HRQoL in children with CKD is lower than in healthy children. This is already observed in the early stages of the disease. The disease itself influences the child's mental state. Children on HD require special support on account of the lowest demonstrated overall HRQoL. Children's lower rating of the quality of life observed by their parents may render the patients unmotivated and adversely affect their adjustment to life in later years. It may also create conflicts between the parents and the children.

Sarcasm use in Turkish: The roles of personality, age, gender, and self-esteem.

This study examined how self-reported sarcasm use is related to individual differences in non-Western adults. A sample of 329 Turkish speakers of high socioeconomic status completed an online survey including measures of self-reported sarcasm use, personality traits, positive and negative affect, self-presentation styles, self-esteem, as well as age and gender. Participants who reported being more likely to use sarcasm in social situations had scores indicating that they were less agreeable, less conscientious, and less emotional stable (i.e., more neurotic). Also, those who reported using sarcasm more often tended to be younger and had lower self-esteem. Self-reported sarcasm use was also positively related to both the self-promoting and the self-depreciating presentation styles. In addition to highlighting the complex relationship between individual differences and language production, these findings underscore the importance of expanding sarcasm research to include non-Western samples.

Phenological changes and reduced seasonal synchrony in western Poland.

Botanical gardens offer continuity for phenological recording in observers, protocols and plant specimens that may not be achievable from other sources. Here, we examine phenological change and synchrony from one such garden in western Poland. We analysed 66 botanical phenophases and 18 interphase intervals recorded between 1977 and 2007 from the Poznan Botanical Garden. These were examined for trends through time and responsiveness to temperature. Furthermore, we derived measures of synchrony for start of spring and end of autumn events to assess if these had changed over time. All 39 events with a mean date before mid-July demonstrated a significant negative relationship with temperature. Where autumn events were significantly related to temperature, they indicated a positive relationship. Typically, spring events showed an advance over time and autumn events a delay. Interphase intervals tended to lengthen over the study period. The measures of synchrony changed significantly over time suggesting less synchrony among spring events and also among autumn events. In combination, these results suggest increases in growing season length. However, responses to a changing climate were species-specific. Thus, the transitions from winter into spring and from autumn into winter are becoming less clearly defined.

2D and 3D cell cultures - a comparison of different types of cancer cell cultures.

Cell culture is a widely used in vitro tool for improving our understanding of cell biology, tissue morphology, and mechanisms of diseases, drug action, protein production and the development of tissue engineering. Most research regarding cancer biology is based on experiments using two-dimensional (2D) cell cultures in vitro. However, 2D cultures have many limitations, such as the disturbance of interactions between the cellular and extracellular environments, changes in cell morphology, polarity, and method of division. These disadvantages led to the creation of models which are more closely able to mimic conditions in vivo. One such method is three-dimensional culture (3D). Optimisation of the culture conditions may allow for a better understanding of cancer biology and facilitate the study of biomarkers and targeting therapies. In this review, we compare 2D and 3D cultures in vitro as well as different versions of 3D cultures.

Two-dimensional (2D), three-dimensional static (3D) and real-time (4D) contrast enhanced voiding urosonography (ceVUS) versus voiding cystourethrography (VCUG) in children with vesicoureteral reflux.

BACKGROUND: Two-dimensional (2DUS) contrast enhanced voiding urosonography has been used in the diagnosis and treatment monitoring of the vesicoureteral reflux in children for over 15 years. The opportunity of performing this examination with the use of three-dimensional static (3DUS) and real-time (4DUS) techniques opens up new diagnostic horizons. OBJECTIVE: To analyze if 3DUS/4DUS bring additional information leading to an increased detection rate or change in the grading of reflux compared to 2DUS and voiding cystouretrography. MATERIAL AND METHODS: We evaluated 69 patients (mean 4.1 years) who underwent 2DUS/3DUS/4DUS contrast enhanced voiding urosonography (ceVUS) and voiding cystourethrography (VCUG) for the diagnosis and grading of vesicoureteral reflux. RESULTS: 2DUS and 3DUS/4DUS urosonography diagnosed 10 more refluxes (7.25%) than cystourethrography and in 3 refluxes (2.17%) detected a higher grade. In 9 refluxes (6.52%) 3DUS/4DUS urosonography and cystourethrography diagnosed a higher grade than 2DUS. There was a statistically significant difference between cystourethrography and 3DUS/4DUS urosonography when the number of detected refluxes and differences in grading were compared. 4DUS enabled a better visualization of reflux than 3DUS. CONCLUSIONS: 3DUS/4DUS techniques bring additional information leading to a change in reflux grading compared to 2DUS and a detect higher number of refluxes compared to cystourethrography.

Color Doppler dynamic tissue perfusion measurement: a novel tool in the assessment of renal parenchymal perfusion in children with vesicoureteral reflux.

INTRODUCTION: Vesicoureteral reflux (VUR) occurs in 20-50% of children suffering from recurrent urinary tract infections (UTIs) and is associated with an increased risk of renal scarring and impaired renal function. Early detection of renal perfusion deterioration would allow for the implementation of more aggressive treatment and potentially prevent further damage to the renal parenchyma. The aim of the study was to assess renal parenchymal perfusions in children with recurrent UTIs with and without coexisting VUR, and compare the findings with the results of healthy patients. MATERIAL AND METHODS: Color Doppler sonographic dynamic renal parenchymal perfusion measurements were performed with PixelFlux (Chameleon-Software, Germany) software in 77 children with recurrent UTIs and coexisting VUR and in 30 children with UTIs without VUR. The findings were compared with the results of 53 healthy children. RESULTS: Cortical parenchymal perfusion of children suffering from UTIs and VUR was significantly reduced when compared to the control group. Statistically significant differences (p < 0.05) were found in all perfusion parameters (i.e. mean velocity (v mix ), mean perfused area (A mix ), mean perfusion intensity (I mix ), tissue pulsatility index (TPI), and tissue resistance index (TRI)) between the control group and children suffering from UTIs and VUR, particularly VUR grades III and IV. There were no significant differences between the UTI group and the control group. No differences were found between the controls and VUR grade II. CONCLUSIONS: Renal parenchymal perfusion decreases significantly with higher grades of VUR.

Disease-related social situation in family of children with chronic kidney disease--parents` assessment. A multicentre study.

INTRODUCTION AND OBJECTIVE: Chronic kidney disease (CKD) in children burdens life of patients and their families. Little is known about parents` assessment of families' social situation. However, the knowledge of the details of a patient's and his family's life standards might influence modification and optimization of applied therapy. Therefore, the main goal of the present study was to explore the selected elements of life situation of patients suffering with CKD as well as their parents, depending on the CKD stage and appropriate treatment. MATERIALS AND METHODS: Cross-sectional national study was conducted. A total of 203 children with CKD and 388 their parent-proxies (196 women and 192 men) were enrolled into this study. Patient data and questionnaires filled by both parents, concerning social-demographic parameters and assessment of changes in families after CKD diagnosis in the child, were analysed. RESULTS: CKD children are being brought up in proper families whose financial situation is not good. Children need help in process of education. Perception of current situation differed between both parents in the change of the income source, taking care of CKD child, change in social relations and evaluating relations with medical staff. Parents do not obtain proper support from social workers. CONCLUSION: Families of CKD children require support in area of financial and educational help for school children. The discrepancies in evaluation of family situation between mothers and fathers of ill children might be the source of conflicts possibly resulting in worsening the outcome for CKD children.

2D/3D/4D contrast-enhanced voiding urosonography in the diagnosis and monitoring of treatment of vesicoureteral reflux in children - can it replace voiding cystourethrography?

INTRODUCTION: Vesicoureteral reflux appears in 20-50% of pediatric patients with recurrent urinary tract infections. The most common method of diagnosing this disease is voiding cystourethrography. However, contemporary pediatric radiology does not favor this method due to exposure to X-radiation. AIM: The aim of this study was to assess the usefulness of 2D/3D/4D contrast-enhanced voiding urosonography in the diagnosis and treatment monitoring of vesicoureteral reflux in children and the possibility of using contrast-enhanced voiding urosonography to replace voiding cystourethrography. MATERIAL AND METHODS: Voiding cystourethrography and contrast-enhanced voiding urosonography were conducted in 80 pediatric patients in order to assess sensitivity, specificity, positive and negative predictive values as well as the number of vesicoureteral refluxes detected by each of the two methods. The second stage of the study involved performing voiding urosonography in an extended protocol in 58 children in order to determine the usefulness of three-dimensional (3D/4D) examinations in the assessment of vesicoureteral reflux and the ability to assess the urethra. RESULTS: The concordance between the two methods was 86.95%. The sensitivity of voiding urosonography was 84.51%, specificity - 90.99%, positive predictive value - 85.71% and negative predictive value - 90.17%. A 3D/4D assessment of the urinary bladder and transperineal 2D morphological assessment of the urethra were possible in all patients (100%). Assessment of the urethra during micturition with the use of 2D/3D/4D techniques was possible in all patients in whom voiding was elicited (95.83%), and 3D/4D assessment of vesicoureteral reflux was possible in all patients with reflux (100%). Although the application of 3D/4D techniques allowed accurate specification of the grade of reflux in all cases (100%), it appeared particularly useful in differentiating between grades II and III (70.97%). CONCLUSIONS: Contrast-enhanced voiding urosonography allows the diagnosis and monitoring of treatment of vesicoureteral reflux in pediatric patients as well as assessment of the urethra in both girls and boys. The method is characterized by high sensitivity and specificity. Moreover, it is safe, relatively inexpensive and can replace voiding cystourethrography.

Does a late referral to a nephrologist constitute a problem in children starting renal replacement therapy in Poland?--a nationwide study.

BACKGROUND: It is estimated that 20-50% of adult patients start chronic dialysis therapy without prior contact with a nephrologist. The aim of this nationwide study was to assess clinical and metabolic status of children at the start of chronic dialysis in Poland with regard to the timing of the referral to a nephrologist. METHODS: We studied data of 180 children (mean age 14+/-6 years) undergoing chronic dialysis in 13 (out of 14) dialysis pediatric centres in Poland. Patients were classified as early referrals (ERs) when they entered the dialysis programme at least 1 month after the first referral to a nephrologist or late referrals (LRs) when the dialysis was introduced within 1 month from the first visit. RESULTS: Seventy-nine percent of pediatric patients were referred early (ER) to the dialysis centre and 21% were referred late (LR) and had to start dialysis within a month. When starting dialysis, LR patients had significantly higher levels of urea and phosphate as well as lower calcium and haemoglobin in comparison with ERs. Hypertension, pulmonary oedema, fluid overload, treatment in the intensive care unit (ICU) and body mass index (BMI) below 10th percentile turned out to be more frequent in the LR group. Peritoneal dialysis (PD) was used as the first method of dialysis in 59% of ERs and 46% of LRs. The majority of ER patients was treated in the predialysis period with calcitriol, phosphate binders and low protein diet (84%, 89%, 92% of all children, respectively), and 20% of them received epoetin. In the up to 3 years observation of our initial cohort, we also found that the patients who were referred late were less likely to receive kidney transplant (P = 0.02). CONCLUSION: The results of the study indicate that the LR to a pediatric nephrologist was associated with poorer clinical and metabolic status of children entering chronic dialysis programmes.

Hypertension in dialysed children: the prevalence and therapeutic approach in Poland--a nationwide survey.

BACKGROUND: The aim of this nationwide analysis was to assess the incidence and current treatment profile of arterial hypertension in children undergoing chronic haemodialysis or peritoneal dialysis and attitudes of paediatric nephrologists towards the choice of antihypertensive drugs in their patients. METHODS: The study group consisted of 134 children (89 males, 45 females, mean age 10.7+/-5 years) from all 13 paediatric dialysis centres in Poland. The data were gathered through a questionnaire for each patient dialysed in November 2004. RESULTS: The overall incidence of hypertension in the study group was 55% (74 of 134 patients; 47 males, 27 females). The incidence rate was similar in boys and girls (53 vs 60%) and in those on haemodialysis and peritoneal dialysis (56 vs 54%). Chronic glomerulonephritis as an underlying renal disease was significantly more frequent in the hypertensive than in the normotensive subjects (37 vs 10%, P = 0.004). Residual urine output was higher in normotensives (41 vs 10 ml/kg body weight; P < 0.001). Among those treated with antihypertensives: 32% were treated by monotherapy, 36% received two drugs, 22% received three drugs, while 7% received > or = 4 drugs. The therapy was effective in only 57% of subjects. We observed no differences in biochemical and clinical parameters between those who responded to the therapy and those who failed to do so. Calcium channel blockers constituted the most frequently administered class of drugs [73% of children; in 43 out of 48 (90%) combined with other drugs, but in 11 out of 24 (46%) as a monotherapy]. In monotherapy, angiotensin-converting enzyme inhibitors and calcium channel blockers were administered most frequently. CONCLUSION: We conclude that the incidence of hypertension in dialysis children in Poland is high (55%). The effectiveness of antihypertensive treatment is rather low (58%) and the choice of drugs is limited.

Urinary iodine excretion in inhabitants of rural region living in the Lublin Province.

Iodine is the element necessary for the human organism to function properly. Iodine is essential especially for the synthesis of thyroid hormones that regulate the cellular metabolism of the whole organism. The purpose of the work was to estimate the concentration of iodine in urine among the inhabitants of a typical agricultural region as a simple method of detecting deficiency of iodine in the human organism. The biggest iodine excretion was observed in a group above 40 years of age. The amount of the excretion of iodine together with urine was similar among men and women up to 40 years old. Monitoring of iodine concentration in urine is a sensitive marker of iodine deficiency in the human organism.