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rder to improve perinatal outcomes.Soil contamination related to industrial and agricultural activities were associated with many adverse health effects and climate change could exacerbate this effect. However, the evidence on this topic in low and middle-income countries (LMICs) is still scarce. We, therefore, aimed to investigate the heavy metals (HMs) concentrations in topsoil around Lake Urmia (which dried about 50 % of it in recent years). Accordingly, 96 surface soil samples were collected from an area of about 4000 km2 in 2019. An inductively coupled plasma-atomic emission spectrometry (ICP-AES) was used to measure the HMs concentrations, including cadmium (Cd), arsenic (As), chromium (Cr), cobalt (Co), nickel (Ni), copper (Cu), lead (Pb) and zinc (Zn). Health risk assessment of exposure to HMs was performed using Monte Carlo simulations technique. The mean concentrations of Zn, Cu, Ni, Co, Pb, Cr, As and Cd were 68.66, 35, 31.66, 15, 14.4, 11.2, 7.04, and 0.26 mg/kg, respectively, which was in the allowable range of USEPA guideline. The mean enrichment factor (EF) values for Zn, Cd, Cu, Cr, Ni, Pb, Co and As were1.3, 1.9, 1, 1.2, 1.7, 2.8, 1.8 and 2, respectively. Carcinogenic risks of exposure to HMs for inhalation, dermal and ingestion exposure pathways were at safe level. Similarly, the hazard index (HI) was at safe level (HI less then 1). The sensitivity analysis indicated that the exposure duration (ED) for As, exposure frequency (EF) for Cd and Ni, concentration (Csoi) for Cr and Pb had the highest impact on ELCR values. Our finding confirmed that HMs concentrations around Lake Urmia had no health risk for inhabitants.The present study relies on the air quality evaluation during COVID-19 pandemic in Avellino, described in the last years and for several consecutive years, among the worst Italian cities in this context. The main purpose of this manuscript was to investigate the effects of quarantine and lockdown measures on air pollution. The concentrations of the main atmospheric pollutants (Carbon monoxide (CO), Ozone (O3), Fine Particulate (PM2.5 and PM10), Benzene (C6H6) and Nitrogen dioxide (NO2) were recorded during the period January-December 2020 using two stationary monitoring stations (AV1 and AV2) of the Regional Environmental Protection Agency (ARPAC). During the lockdown period (March 9-May 18, 2020), results indicated significant reductions only in the levels of CO, benzene and NO2, while for PM10 the limit of 50 μg m-3 was passed 8 times for AV1 and 13 times for AV2. The results showed the not predominant role of traffic on air quality in Avellino regards to PM levels and make it necessary a serious reflection about important and not extendable decisions to improve the air quality.Human epidermal growth factor receptor 2 (HER2)-positive classic invasive lobular carcinoma (ILC) is a rare entity, and its specific pathological characteristics and clinical behavior are unclear. Therefore, we retrospectively investigated the clinicopathological features of HER2-positive classic ILC and described HER2-targeted neoadjuvant chemotherapy outcome. Fourteen HER2-positive classic ILC cases were identified, their clinicopathological data were collected, and their clinical management was investigated. In general, HER2 positivity is associated with higher grade carcinoma in ductal lesions; however, our 14 cases had typical morphologic features of classic ILC. We did not identify unique morphologic features in HER2-positive classic ILC with the clinicopathological parameters examined, including age, menopausal status, histological grade, and hormone receptor status. Four of six patients who received HER2-targeted neoadjuvant chemotherapy had a pathological complete or partial response. Based on our findings, clinicopathological features of classic ILC may not predict HER2 overexpression or amplification. HER2-targeted neoadjuvant chemotherapy was effective against some HER2-positive classic ILCs. Taken together, these results demonstrate that HER2 immunohistochemistry and fluorescence in situ hybridization should be considered for all ILC patients regardless of subtype.Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) blockade is a promising therapy for hematological malignancies. However, the association of PD-L1 expression with the clinicopathological features and prognosis in pediatric ALK-positive anaplastic large cell lymphoma (ALCL) remains unclear. Using PD-L1/ALK immunofluorescence double staining, we evaluated the PD-L1 expression on tumor cells/tumor-infiltrating immune cells (TIICs) and the quantity of TIICs in 54 children with ALK-positive ALCL treated with the ALCL99 protocol. The percentages of PD-L1-positive tumor cells were significantly lower in patients with skin/mediastinum involvement, clinical high-risk group, present minimal disseminated disease (MDD), and a low ALK-antibody titer. The percentages of PD-L1-positive TIICs were significantly higher in patients with absent MDD. The percentages of TIICs were significantly lower in patients with absent MDD and a common morphological pattern. We classified patients according to the PD-L1 expression on tumor cells (Tumor-PD-L1), PD-L1 expression on TIICs (TIIC-PD-L1), and quantity of TIICs (TIIC-quantity). The progression-free survival (PFS) did not differ between Tumor-PD-L1high and Tumor-PD-L1low ALCL; TIIC-PD-L1high and TIIC-PD-L1low ALCL; and TIIC-quantityhigh and TIIC-quantitylow ALCL. According to the combined parameters of Tumor-PD-L1 and TIIC-quantity, Tumor-PD-L1high/TIIC-quantityhigh ALCL had a worse 5-year PFS than other ALCL (50% versus 83%; P = .009). Tumor-PD-L1high/TIIC-quantityhigh ALCL remained a significant prognostic factor in multivariate analysis (P = .044). This is the first study to demonstrate that a high tumoral PD-L1 expression with a high quantity of TIICs was associated with a poor prognosis in pediatric ALK-positive ALCL. The tumor microenvironment of ALK-positive ALCL may be relevant to the clinicopathological features and prognosis.Patients with Sjӧgren's syndrome (SS) have dry eye associated with meibomian gland dysfunction (MGD). The meibum from donors with dry eye due to MGD but without SS (MMGD) presents with lower levels of cholesteryl ester, less straight chains, and more ordered hydrocarbon chains compared with meibum from donors without MGD (Mn). The aim of the current study was to compare the composition and hydrocarbon chain conformation of meibum from donors with Sjögren's syndrome (Mss) to Mn and MMGD. Meibum was expressed from patients with SS using an ILUX instrument (Alcon Inc., Fort Worth TX). All of the nine meibum donors with SS were female. Meibum composition was characterized using 1H-NMR and meibum hydrocarbon chain conformation was measured using fourier transform infrared spectroscopy. Meibum from every donor with SS measured contained a significantly (P 0.05, for Mss compared with Mn. Nor was the CH3/CH2 band height ratio used to estimate the number of hydrocarbon CH3 and CH2 moieties different, P = 0.22, for Mss compared with Mn. In conclusion, the compositional differences between Mss compared with Mn did not result in differences in any of the nine meibum lipid phase transitional parameters measured. The compositional differences observed between Mss and Mn could be markers for or contribute to SS as the differences could lead to tear film lipid packing differences other than conformational differences.Manganese (Mn2+) has been reported to activate macrophages and NK cells, and to induce the production of type-I interferons (IFNs) by activating the cGAS-STING pathway. Few studies have been conducted on its adjuvanticity to microbial vaccines, and on the involvement of the interferon regulatory factor (IRF) 5 signaling pathway in the adjuvanticity. Selleck Raf inhibitor In this study, we demonstrated that Mn2+ could facilitate various microbial vaccines to induce enhanced antibody responses, and facilitate the influenza virus vaccine to induce protective immunity against the influenza virus challenge. When formulated in vaccines, Mn2+ could activate murine CD4+ T cells, CD8+ T cells, B cells and DCs, and induce the expression and phosphorylation of TANK-binding kinase 1 (TBK1) and IRF5 in the splenocytes of the immunized mice, resulting in the increased expression of type-I IFNs, TNF-α, B cell-activating factor of the TNF family (BAFF) and B lymphocyte-induced maturation protein-1 (Blimp-1). The induced TBK1 could recruit and bind the IRF5. Furthermore, the Mn2+ induced expression of IRF5 and Blimp-1 was prohibited by a IRF5 interfering oligonucleotide. The data suggest the Mn2+ could be used as a novel type of adjuvants for microbial vaccines, and the activation of IRF5 signaling pathway might involve in the adjuvanticity.G protein-coupled estrogen receptor (GPER) is important for maintaining normal blood vessel function by preventing endothelial cell dysfunction. It has been reported that G-1, an agonist of GPER, increases nitric oxide (NO) production through the phosphorylation of endothelial nitric oxide synthase (eNOS). However, the effect of GPER activation on eNOS expression has not been studied. Our results show that G-1 significantly increased the expression of eNOS and Kruppel-like factor 2 (KLF2) in human endothelial EA.hy926 cells. The individual silences of KLF2 and GPER attenuated G-1-induced eNOS expression. In addition, inhibition of the Gαq and Gβγ suppressed G-1-induced the expression of eNOS and KLF2 in EA.hy926 cells. Interestingly, these effects were similar in HUVECs. Furthermore, we found that GPER-mediated Ca2+ signaling increased the phosphorylation of CaMKKβ, AMPK, and CaMKIIα in the cells. The phosphorylation of histone deacetylase 5 (HDAC5) by activation of AMPK and CaMKIIα increased the expression of eNOS via transcriptional activity of KLF2. We further demonstrate that GPER activation increased the phosphorylation of Src, EGFR, ERK5, and MEF2C and consequently induced the expression of eNOS and KLF2. Meanwhile, inhibition of ERK5 and HDAC5 suppressed the expression of eNOS and KLF2 induced by G-1 in the cells. These findings suggest that GPER provides a novel mechanism for understanding the regulation of eNOS expression and is an essential therapeutic target in preventing cardiovascular-related endothelial dysfunction.

High risk (HR) factors have been shown to have increased rates of mortality following Stage 1 palliation (S1P) for single ventricle physiology. It remains unclear how initial HR status affects longitudinal outcomes following subsequent Stage 2 (S2P) and Stage 3 (S3P) palliation.

Single ventricle patients undergoing S1P between July of 2004 and October of 2018 at a single institution were included. Patients having ≥ 1 HR factor were considered HR status, with all others classified as low risk (LR). Longitudinal survival stratified by risk status was compared following each palliative stage, in addition to re-admission and length of stay (LOS). Proportional hazard modeling was used to determine risk factors for longitudinal mortality.

Of 132 patients presenting during the study for S1P, 57 (43.2%) were classified as HR. Overall 10-year survival was decreased in the HR cohort (p=0.001). HR patients were at significantly increased risk of death during Interstage I (p=0.01) and Interstage II (p=0.01), but survival was similar to LR patients following S3P (p=0.