Septic systems drive nutrient enrichment of groundwaters and eutrophication in the urbanized Indian River Lagoon, Florida.

Effluent from septic systems can pollute groundwater and surface waters in coastal watersheds. These effects are unknown for the highly urbanized central Indian River Lagoon (CIRL), Florida, where septic systems represent > 50% of wastewater disposal. To better understand these impacts, water quality was assessed along both canals and a tributary that drain into the CIRL. Dissolved nutrient concentrations were higher near septic systems than in natural areas. δ15N values of groundwater (+7.2‰), surface water (+5.5‰), and macrophytes (+9.7‰) were within the range for wastewater (>+3‰), as were surface water concentrations of the artificial sweetener sucralose (100 to 1700 ng/L) and fecal indicator bacteria density. These results indicate that septic systems are promoting eutrophication in the CIRL by contributing nutrient pollution to surface water via groundwater. This study demonstrates the need to reduce reliance on septic systems in urbanized coastal communities to improve water quality and subsequently mitigate harmful algal blooms.

Trichostatin A Inhibits Rhabdomyosarcoma Proliferation and Induces Differentiation through MyomiR Reactivation.

Rhabdomyosarcoma (RMS) is a malignant tumour of soft tissues, occurring mainly in children and young adults. RMS cells derive from muscle cells, which due to mutations and epigenetic modifications have lost their ability to differentiate. Epigenetic modifications regulate expression of genes responsible for cell proliferation, maturation, differentiation and apoptosis. HDAC inhibitors suppress histone acetylation; therefore, they are a promising tool used in cancer therapy. Trichostatin A (TsA) is a pan-inhibitor of HDAC. In our study, we investigated the effect of TsA on RMS cell biology. Our findings strongly suggest that TsA inhibits RMS cell proliferation, induces cell apoptosis, and reactivates tumour cell differentiation. TsA up-regulates miR-27b expression, which is involved in the process of myogenesis. Moreover, TsA increases susceptibility of RMS cells to routinely used chemotherapeutics. In conclusion, TsA exhibits anti-cancer properties, triggers differentiation, and thereby can complement an existing spectrum of chemotherapeutics used in RMS therapy.

Predictive and concurrent validity of the Malnutrition Universal Screening Tool using mid-upper arm circumference instead of body mass index.

BACKGROUND: Considering the difficulty in obtaining weight and height measurements of patients at hospital admission, the Malnutrition Universal Screening Tool (MUST) proposes the use of mid-upper arm circumference (MUAC) instead of body mass index (BMI) as an alternative for screening of malnutrition risk. The present study aimed to evaluate the performance of MUST with MUAC in place of BMI to identify nutritional risk and predict prolonged hospitalisation and mortality in hospitalised patients. METHODS: The prospective cohort study involved ambulant patients aged ≥18 years who were admitted to the emergency department of a public hospital. A questionnaire concerning clinical and socio-demographic data was applied and anthropometric measurements were performed (weight, height, BMI and MUAC). Nutritional risk screening was performed using the original MUST (BMI) and MUST-MUAC tools. The outcomes were length of hospital stay and death. RESULTS: Seven hundred and fifty-two patients were included and followed-up for 13.5 (interquartile range 3.00-19.00) days. The frequency of patients at nutritional risk was higher according to MUST-MUAC (48.9%) compared to the original MUST (37.1%). MUST-MUAC showed concurrent validity, demonstrating good agreement with the original MUST (k = 0.690), high sensitivity (95.3%) and accuracy (area under the curve = 0.868; 95% confidence interval = 0.841-0.895) with respect to identifying nutritional risk. The presence of nutritional risk detected by the MUST-MUAC increased the chance of prolonged hospital stay by 1.9 (95% CI. 1.4-2.7)-fold and mortality by 3.2 (95% CI. 1.1-9.4)-fold. CONCLUSIONS: MUST-MUAC showed satisfactory concurrent and predictive validity. Considering that MUAC measurement is easier to perform than BMI, the MUST-MUAC should be used for screening of nutritional risk in hospitalised patients.

KCNJ11 and KCNQ1 Gene Polymorphisms Are Not Associated with Post-Transplant Diabetes Mellitus in Kidney Allograft Recipients Treated with Tacrolimus.

Post-transplant diabetes mellitus (PTDM) is a metabolic disorder occurring after solid organ transplantation during the therapy with calcineurin inhibitors. ATP-sensitive potassium channels KCNJ11 and KCNQ1 play an important role in the regulation of insulin secretion by ß cells and development of diabetes mellitus. Numerous studies have confirmed the association between KCNJ11 and KCNQ1 gene polymorphisms and type 2 diabetes. The aim of this study was to examine the association between KCNJ11 and KCNQ1 gene polymorphisms and posttransplant diabetes mellitus in kidney allograft recipients treated with tacrolimus. The study included 201 patients who received kidney transplants. The patients were subdivided into two subgroups: patients with PTDM (N = 35) and patients without PTDM (N = 166). The association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes was studied in three models of univariate Cox regression analysis, i.e., additive, dominant and recessive. In these three models there were no statistically significant associations between KCNJ11 and KCNQ1 gene polymorphisms and PTDM. The results of this study suggest lack of association between KCNJ11 and KCNQ1 gene polymorphisms and post-transplant diabetes mellitus in kidney allograft recipients treated with tacrolimus in the Polish population.

CDC123/CAMK1D gene rs12779790 polymorphism and rs10811661 polymorphism upstream of the CDKN2A/2B gene in women with gestational diabetes.

OBJECTIVE: Gestational diabetes mellitus (GDM) is carbohydrate intolerance occurring in pregnant women. CDC123/CAMK1D and CDKN2A/2B are associated with increased risk of type 2 diabetes and may affect pancreatic beta cell function. The aim of this study was to examine the association between CDKN2A/2B rs10811661 and CDC123/CAMK1D rs12779790 gene polymorphisms and GDM. STUDY DESIGN: This study included 411 pregnant women. The diagnosis of GDM was based on the International Association of Diabetes and Pregnancy Study Groups criteria. According to the results of their oral glucose tolerance test, the women were divided into two groups: 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. RESULTS: There were no statistically significant differences in the distribution of CDC123/CAMK1D rs12779790 genotypes and alleles between women with GDM and healthy pregnant women. However, there was a statistically significant association between the C allele of CDKN2A/2B rs10811661 polymorphism and reduced risk of GDM (C vs T, OR 0.53, 95% CI 0.36 to 0.79, P=0.0014). In the multivariate logistic regression analysis, older age and higher body mass index before pregnancy were independent significant predictors of a higher risk of GDM, while higher number of C alleles (CDKN2A/2B rs10811661) was a protective factor against GDM. CONCLUSION: The results of this study suggest an association between CDKN2A/2B gene rs10811661 polymorphism and GDM.

Hematopoietically expressed homeobox (HHEX) gene polymorphism (rs5015480) is associated with increased risk of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a metabolic disorder that occurs during pregnancy. HHEX and PROX1 are genetic loci associated with diabetes mellitus type 2. HHEX and PROX1 play significant roles in carbohydrate intolerance and diabetes because these transcription factors may be involved in the regulation of insulin secretion and in glucose and lipid metabolism. The aim of this study was to examine the association between HHEX (rs5015480) and PROX1 (rs340874) gene polymorphisms and GDM. This study included 204 pregnant women with GDM and 207 pregnant women with the normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test at 24-28 weeks' gestation. There was a statistically significant prevalence of the HHEX rs5015480 CC genotype and C allele among women with GDM (C vs T allele, p = 0.021, odds ratio OR = 1.40, 95% CI: 1.05-1.87). Statistically significant higher increase of body mass and BMI during pregnancy was found in women with the HHEX rs5015480 CC genotype. The results of our study suggest an association between the HHEX gene rs5015480 polymorphism and risk of GDM. The HHEX gene rs5015480 C allele may be a risk allele of GDM that is associated with increased BMI during pregnancy.

The effect of low levels of lead (Pb) in the blood on levels of sphingosine-1-phosphate (S1P) and expression of S1P receptor 1 in the brain of the rat in the perinatal period.

Sphingolipids are the main components of the lipid membrane. They also perform structural functions and participate in many signal transmission processes. One of the bioactive sphingolipids is sphingosine-1-phosphate (S1P), a ligand for five G protein-coupled receptors (S1PRs1-5), which can also act as an intracellular second messenger. S1P is responsible for the stimulation of progenitor cells in the brain, but it can also induce apoptosis of mature neurons. This study is aimed at assessing the effect of pre- and neonatal exposure to permissible Pb concentrations on S1P levels and S1PR1 (EDG1) expression in the prefrontal cortex, cerebellum, and hippocampus of rats. The concentrations of S1P were determined by RP-HPLC, S1PR1 expression was determined by RT PCR and Western Blot, and receptor immunolocalization was determined by immunohistochemistry method. Our results showed that even low blood Pb concentrations, i.e. within the acceptable limit of 10 µg/dL caused changes in the concentration of S1P in the cerebellum, prefrontal cortex, and hippocampus. Our data also showed a significant decrease in the level of S1PR1 in all studied part of brain, without significant changes in S1PR1 gene expression. Pre- and neonatal exposure to Pb also resulted in a decrease in the expression of S1PR1 in glial cells in all regions of the Cornu Ammonis (CA1-CA4) and Dentate Gyrus in the hippocampus, as well as in all layers of the cerebellum and prefrontal cortex, compared to the unexposed control group.

Experimental reconstruction of the Berry curvature in a Floquet Bloch band.

Topological properties lie at the heart of many fascinating phenomena in solid-state systems such as quantum Hall systems or Chern insulators. The topology of the bands can be captured by the distribution of Berry curvature, which describes the geometry of the eigenstates across the Brillouin zone. Using fermionic ultracold atoms in a hexagonal optical lattice, we engineered the Berry curvature of the Bloch bands using resonant driving and show a full momentum-resolved measurement of the ensuing Berry curvature. Our results pave the way to explore intriguing phases of matter with interactions in topological band structures.

Study on size effect of the silica nanospheres with solid core and mesoporous shell on cellular uptake.

The properties of mesoporous silica nanoparticles including large surface area, large pore volume, easy surface functionalization and control of structure and pore size has made them promising drug carriers. In this study, the effect of different diameters (50 nm, 70 nm, 90 nm, 110 nm and 140 nm) of silica nanospheres with a solid core and mesoporous shell (mSiO2/SiO2) on cellular internalization in mouse fibroblast cells (L929) was evaluated. The physical properties of the nanostructures were characterized with various methods, such as transmission electron microscopy with x-ray dispersion spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy and zeta potential. In order to define the cellular uptake, the nanostructures were labelled with fluorescent dye Alexa647, and imaging and quantitative methods were applied: laser scanning confocal microscopy, flow cytometry and thermogravimetry. Our results indicate that cellular uptake of the studied nanospheres is size-dependent, and nanospheres of 90 nm in diameter showed the most efficient cell internalization. Thus, particle size is an important parameter that determines cellular uptake of nanoparticles and should be considered in designing drug delivery carriers.

Mechanisms of cancer metastasis: involvement of cancer stem cells?

The leading cause of death from cancer is tumor expansion, which usually leads to dissemination and metastasis of malignant cells. Accumulating evidence suggests growing tumors contain some very rare primitive cells that are mobile and thus endowed with metastatic potential. If these cells survive radio/chemotherapy, they are responsible for tumor re-growth after treatment. In this review, we discuss the origin of these cells, which: 1) are true cancer stem cells (CSCs) that initiate tumor growth and are subsequently responsible for metastatic dissemination; or 2) are derived from transformed tumor cells by the epithelial mesenchymal transition phenomenon. We also address major molecular mechanisms involved in trafficking of these cells during metastasis, paying special attention to the underappreciated side effects of radio/chemotherapy that may induce pro-metastatic environments in various organs. Overall, we envision that the process of pathological metastasis of cancer cells reflects a physiological property of normal SCs for their ability to migrate, as seen during embryogenesis. Finally, we discovered highly migratory, very small embryonic-like SCs that are deposited during development in adult tissues. As we hypothesize, these cells could: 1) give rise to some primitive types of tumors; and 2) may have a direct role in cancer expansion by being involved in tumor angiogenesis and formation of tumor stroma.