Factors influencing the increased 90Sr radioisotope migration in highly alkaline groundwater at Chornobyl NPP site.

This paper analyses the formation of high Sr2+ concentration in strong alkaline (pH = 9.5-12.5) groundwater using data of the 27 years of observations around the destroyed Chernobyl NPP Unit 4. It appears that the formation of strong alkaline groundwater in different monitoring wells is consistent with the distribution of 90Sr, pH and main ions. The reason for the increase in 90Sr concentrations is the process of its migration from the sources of contamination - leaks of highly active water localized in certain premises inside the «Shelter ¼ object. These computational experiments showed that for the groundwater in pH range 9.5-12.4, the concentration of strontium in the form of SrOH + increases and in the form of Sr2+ - decreases. In addition, the fraction of 90Sr in the form of a soluble neutral complex compound SrCO30, which is not sorbed, reaches 14-35%. Increased fractions of 90Sr in forms of SrOH+ and SrCO3 are factors which reduce the isotope ability to be sorbed by soils and therefore increase its migration ability. In strongly alkaline groundwater a sharp increase in 90Sr volumetric activity may also be caused by ionic strength (IS) increase above 5 mmol/L. Thus, the factors that influence the increase in 90Sr volumetric activity in strongly alkaline groundwater are the formation of its complex compounds and an increase in ionic strength (IS), which reduces the thickness of the double electric layer and, as a result, reduces the sorption capacity of soils.

Elution of Monomers From CAD-CAM Materials and Conventional Resin Composite in Distilled Water and Artificial Saliva.

PURPOSE: The purpose of this study was to evaluate the leaching pattern of different types of polymer computer-aided design and computer-aided manufacturing (CAD-CAM) materials with a conventional resin composite. METHODS AND MATERIALS: Specimens of three representatives by type of polymer CAD-CAM blocks and one conventional resin composite were suspended using a silk thread in distilled water and artificial saliva. After one day, seven days, 14 days, 30 days, and 60 days, the analysis of the eluates for the detection of bisphenol A (BPA), urethane dimethacrylate (UDMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A-glycidyl dimethacrylate (Bis-GMA) was quantified by utilizing high-performance liquid chromatography (HPLC). RESULTS: TEGDMA was the main eluted monomer for the polymer CAD-CAM materials for both solutions. However, there was a decreasing pattern throughout the tested period. On the contrary, there was a constant release of monomers from the conventional resin composite. Bisphenol-A was released only by the conventional resin composite and in both solutions chosen. CONCLUSIONS: Different types of polymer CAD-CAM materials release minimal or no monomers compared to the conventional resin composite material. The methods of fabrication of polymer CAD-CAM materials produces better properties than the conventional resin composite with a dramatic decrease of monomer elution.

Association of the advanced lung cancer inflammation index (ALI) with immune checkpoint inhibitor efficacy in patients with advanced non-small-cell lung cancer.

BACKGROUND: The advanced lung cancer inflammation index [ALI: body mass index × serum albumin/neutrophil-to-lymphocyte ratio (NLR)] reflects systemic host inflammation, and is easily reproducible. We hypothesized that ALI could assist guidance of non-small-cell lung cancer (NSCLC) treatment with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: This retrospective study included 672 stage IV NSCLC patients treated with programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy in 25 centers in Greece and Germany, and a control cohort of 444 stage IV NSCLC patients treated with platinum-based chemotherapy without subsequent targeted or immunotherapy drugs. The association of clinical outcomes with biomarkers was analyzed with Cox regression models, including cross-validation by calculation of the Harrell's C-index. RESULTS: High ALI values (>18) were significantly associated with longer overall survival (OS) for patients receiving ICI monotherapy [hazard ratio (HR) = 0.402, P < 0.0001, n = 460], but not chemo-immunotherapy (HR = 0.624, P = 0.111, n = 212). Similar positive correlations for ALI were observed for objective response rate (36% versus 24%, P = 0.008) and time-on-treatment (HR = 0.52, P < 0.001), in case of ICI monotherapy only. In the control cohort of chemotherapy, the association between ALI and OS was weaker (HR = 0.694, P = 0.0002), and showed a significant interaction with the type of treatment (ICI monotherapy versus chemotherapy, P < 0.0001) upon combined analysis of the two cohorts. In multivariate analysis, ALI had a stronger predictive effect than NLR, PD-L1 tumor proportion score, lung immune prognostic index, and EPSILoN scores. Among patients with PD-L1 tumor proportion score ≥50% receiving first-line ICI monotherapy, a high ALI score >18 identified a subset with longer OS and time-on-treatment (median 35 and 16 months, respectively), similar to these under chemo-immunotherapy. CONCLUSIONS: The ALI score is a powerful prognostic and predictive biomarker for patients with advanced NSCLC treated with PD-L1 inhibitors alone, but not in combination with chemotherapy. Its association with outcomes appears to be stronger than that of other widely used parameters. For PD-L1-high patients, an ALI score >18 could assist the selection of cases that do not need addition of chemotherapy.

Global CO2 emissions from dry inland waters share common drivers across ecosystems.

Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sediments are too scarce to upscale emissions for global estimates or to understand their fundamental drivers. Here, we present the results of a global survey covering 196 dry inland waters across diverse ecosystem types and climate zones. We show that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters. CO2 emissions were consistent across ecosystem types and climate zones, with local characteristics explaining much of the variability. Accounting for such emissions increases global estimates of carbon emissions from inland waters by 6% (~0.12 Pg C y-1). Our results indicate that emissions from dry inland waters represent a significant and likely increasing component of the inland waters carbon cycle.

α5ß1-Integrin promotes tension-dependent mammary epithelial cell invasion by engaging the fibronectin synergy site.

Tumors are fibrotic and characterized by abundant, remodeled, and cross-linked collagen that stiffens the extracellular matrix stroma. The stiffened collagenous stroma fosters malignant transformation of the tissue by increasing tumor cell tension to promote focal adhesion formation and potentiate growth factor receptor signaling through kinase. Importantly, collagen cross-linking requires fibronectin (FN). Fibrotic tumors contain abundant FN, and tumor cells frequently up-regulate the FN receptor α5ß1 integrin. Using transgenic and xenograft models and tunable two- and three-dimensional substrates, we show that FN-bound α5ß1 integrin promotes tension-dependent malignant transformation through engagement of the synergy site that enhances integrin adhesion force. We determined that ligation of the synergy site of FN permits tumor cells to engage a zyxin-stabilized, vinculin-linked scaffold that facilitates nucleation of phosphatidylinositol (3,4,5)-triphosphate at the plasma membrane to enhance phosphoinositide 3-kinase (PI3K)-dependent tumor cell invasion. The data explain why rigid collagen fibrils potentiate PI3K activation to promote malignancy and offer a perspective regarding the consistent up-regulation of α5ß1 integrin and FN in many tumors and their correlation with cancer aggression.

Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells.

The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs.

[Psychotic episode due to Hashimoto's thyroiditis].

Thyroid hormones are crucial in adult brain metabolic activity. As a result, abnormal thyroid gland function and in particular hypofunction, might cause principally depression and neurocognitive dysfunction. Psychosis, presented mainly with thought disorders and perceptual disturbances, is a much rarer manifestation of hypothyreoidism. A correlation between hypothyreoidism and psychosis has been described since 1888, especially in cases of advanced hypothyreoidism. A few years later (1949), Asher first added the terminology "myxedema madness" to the literature. Psychotic symptoms typically appear after the onset of physical symptoms, usually with a delay of months or years. The case of a female patient who presented a psychotic episode as a first manifestation of hypothyroidism will be described. NE, a 48 yearold female patient, was admitted for the first time to an inpatient mental health care unit due to delusions of persecution and reference, as well as auditory hallucinations that appeared a few weeks ago. After the patient admission, routine laboratory examination was conducted. In order to relieve the patient from her sense of discomfort and while awaiting laboratory results, olanzapine, 5 mg/day, was administered. Neurological examination and cranial computed tomography scan were unremarkable. Hormonal laboratory tests though revealed severe low thyroid hormone levels. Thyroid antibody testing certified Hashimoto's thyroiditis. Olanzapine was discontinued and the patient received thyroid hormone substitution, levothyroxine 75 µg/day, instead. The patient was discharged showing a significant improvement of psychotic symptoms after a 12-day hospitalization. A month later the patient was reevaluated. She had fully recovered from the psychotic episode. A year later, the patient continues to remain free from psychiatric symptoms, while thyroid hormone levels have been restored within normal range. The patient continues receiving only thyroid hormone substitution therapy with levothyroxine. Cases of acute psychosis associated with low levels of thyroid hormones in the context of primary hypothyreoidism have been repeatedly reported. The present case report emphasizes the importance of hypothyroidism exclusion as a secondary cause of psychosis. Thyroid disease treatment ameliorates psychotic disorder symptoms and recovers patients' mental condition.

Prevalence of ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms in Brazilian breast cancer-unaffected women

Polymorphisms of hormone receptor genes have been linked to modifications in reproductive factors and to an increased risk of breast cancer (BC). In the present study, we have determined the allelic and genotypic frequencies of the ERα-397 PvuII C/T, ERα-351 XbaI A/G and PGR PROGINS polymorphisms and investigated their relationship with mammographic density, body mass index (BMI) and other risk factors for BC. A consecutive and unselected sample of 750 Brazilian BC-unaffected women enrolled in a mammography screening program was recruited. The distribution of PGR PROGINS genotypic frequencies was 72.5, 25.5 and 2.0% for A1A1, A1A2 and A2A2, respectively, which was equivalent to that encountered in other studies with healthy women. The distribution of ERα genotypes was: ERα-397 PvuII C/T: 32.3% TT, 47.5% TC, and 20.2% CC; ERα-351 XbaI A/G: 46.3% AA, 41.7% AG and 12.0% GG. ERα haplotypes were 53.5% PX, 14.3% Px, 0.3% pX, and 32.0% px. These were significantly different from most previously published reports worldwide (P < 0.05). Overall, the PGR PROGINS genotypes A2A2 and A1A2 were associated with fatty and moderately fatty breast tissue. The same genotypes were also associated with a high BMI in postmenopausal women. In addition, the ERα-351 XbaI GG genotype was associated with menarche ≥12 years (P = 0.02). ERα and PGR polymorphisms have a phenotypic effect and may play an important role in BC risk determination. Finally, if confirmed in BC patients, these associations could have important implications for mammographic screening and strategies and may be helpful to identify women at higher risk for the disease.

Predictors of functional outcome after right hemisphere stroke in patients with or without thrombolytic treatment.

The purpose of this study was to assess the predictors of functional outcome after right hemisphere stroke at 6-month follow up in patients with or without thrombolytic treatment. Thrombolysis did not predict functional outcome in instrumental activities of daily living (IADL). Lower acute phase basic activities of daily living (ADL) measured by the Barthel Index was a statistically significant predictor of IADL when adjusted for age and education (p = .015) and had borderline significance (p = .076) as a predictor of functional outcome when adjusted for severity of stroke at admission. When stroke severity was taken into account also higher age became a statistically significant (p = .039) predictor of functional outcome. The acute phase neuropsychological symptoms predicted the functional outcome in unadjusted analyses but when adjusted for age, education, and severity of stroke no independent association was found.