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Polychlorinated biphenyls (PCBs) are chemicals that have become ubiquitous environmental pollutants due to their past use, persistence, and long-range transport thus requiring continuous monitoring. Therefore, this research was carried out to investigate spatial and temporal trends of seven indicator PCBs and two others (PCB 105 and PCB 156) in the Nairobi River. Levels of PCBs ranged from below detection limit (bdl) to 157.64 ± 1.52 ng g-1 and bdl to 718.78 ± 1.71 ng L-1 for sediment and water, respectively. PCBs 28, 138, and 153 were the most dominant contributing 33.4%, 17.9%, and 14.5% to the total PCBs in sediments and 54.6%, 19.3%, and 14.1% to the total PCBs in water. There was a general increase in ΣPCBs from 18.89 to 151.18 ng g-1 for sediments and 275.52 to 429.84 ng L-1 for water as the River flowed downstream. The dry season recorded the highest ΣPCB in sediments while the rainy season recorded the highest ΣPCBs in water, with levels exceeding the WHO water quality guidelines. Risk assessment revealed that populations living downstream are exposed to high levels of PCBs through the consumption of water. Levels of ΣPCBs downstream also exceeded the sediment quality guidelines meaning that aquatic organisms are threatened.

Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. The loss of death domain-associated protein (DAXX) and α-thalassemia/mental retardation X-linked protein (ATRX) plays a role in telomere lengthening and stability. This study aims to evaluate the prognostic significance of telomere length (TL) and its association with DAXX and ATRX proteins in breast cancer (BC). Our study used the FISH technique to detect peptide nucleic acid (PNA) in the peripheral blood cells of a cohort of BC patients (n = 220) and a control group of apparently healthy individuals (n = 100). Expression of DAXX and ATRX proteins was evaluated using immunohistochemistry (IHC) in all BC tissues.

Patients with a shorter TL had worse disease-free survival (DFS) and overall survival (OS). There were significant associations between shorter TL and advanced disease stages, lymph node metastasis, and positive HER2/neu expression. DAXX protein expression was significantly correlated with TL. Lower DAXX expression was significantly with shorter DFS.

Assessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.

Assessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.Enterococcus faecalis infections represent a health concern, mainly in oral diseases, in which treatments with chlorhexidine solution (0.2%) are often used; however, it presents high toxicity degree and several side effects. Based on this, the use of natural products as an alternative to treatment has been explored. Nonetheless, plant extracts have poor organoleptic characteristics that impair theirs in natura use. Therefore, this work aimed to evaluate the analytical profile, biological activity, and cytotoxicity in vitro of S. brasiliensis-loaded chitosan microparticles (CMSb) produced using different aspersion flow rates. The analytical fingerprint was obtained by FTIR and NIR spectra. Principal components analysis (PCA) was used to verify the similarity between the samples. The crystallinity degree was evaluated by X-ray diffraction (XRD). Phytochemical screening (PS) was performed to quantify phytocompounds. Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC). Antibiofilm activity and bactericidal kinetics against E. faecalis (ATCC 29212 and MB 146-clinical isolated) were also assessed. The hemolytic potential was performed to evaluate the cytotoxicity. Data provided by FTIR, NIR, and PCA analyses revealed chemical similarity between all CMSb. Furthermore, the results from XRD analysis showed that the obtained CMSb present amorphous characteristic. find more and polyphenols were accurately quantified by the PS, but methodology limitations did not allow the flavonoid quantification. The low hemolytic potential assay indicates that all samples are safe. Antimicrobial assays revealed that CMSb were able to inhibit not only the E. faecalis ATCC growth but also the biofilm formation. Only one CMSb sample was able to inhibit the clinical strain. These results highlighted the CMSb antimicrobial potential and revealed this system as a promising product to treat infections caused by E. faecalis.Ethylmorphine hydrochloride (EtM) is a derivative of morphine used as analgesic to treat severe pain in case of cancer and bone injury. This study aimed to formulate and evaluate core in cup tablets containing 2 doses of EtM, the cup was formulated as lyophilized oro-dispersible tablet (ODT) for immediate release (IR), and the core was formulated as directly compressed tablet for sustained release (SR). #link# Factorial design was adopted for the optimization of tablets prepared via lyophilized form and direct compression techniques a 41.22 design was used for the former, while a 32 one was used for the latter. All prepared tablets showed acceptable physical properties which were in accordance with pharmacopeial standards. Two lyophilized ODTs (F9 and F10) formulae were selected as the cup for instant release. While one directly compressed tablet formula (S6) was selected based on the in vitro release profile to represent the sustained core, the outcome was 2 core in cup tablets, namely B1 and B2 which were evaluated for their in vivo absorption and showed a maximum plasma concentration (Cpmax) of 354.12 ± 17.55 ng/mL and 350.82 ± 12.15 ng/mL respectively attained after 3.0 h which were twofolds significantly higher in comparison to the market tablet with Cpmax of only 172.05 ± 12.53 ng/mL attained after 2.20 ± 0.24 h.Seven new species of Urocleidoides from the gills and skin of nine Neotropical fish hosts (Anostomidae, Parodontidae, and Gymnotidae) are described Urocleidoides digitabulum n. sp. on Leporinus friderici, Leporinus octofasciatus, and Megaleporinus elongatus (Anostomidae); Urocleidoides solarivaginatus n. sp. on L. friderici, L. octofasciatus, and Leporinus striatus (Anostomidae); Urocleidoides falxus n. sp. and Urocleidoides sapucaiensis n. sp. on M. elongatus; Urocleidoides tenuis n. sp. on Apareiodon piracicabae and Apareiodon affinis (Parodontidae); Urocleidoides sinus n. sp. on L. striatus, Schizodon nasutus, and Schizodon intermedius (Anostomidae); and Urocleidoides uncinus n. link2 sp. link3 on Gymnotus sylvius (Gymnotidae). Urocleidoides paradoxus was also found in this study on L. friderici and included in the phylogenetic analysis. Molecular data (partial 28S rDNA and mitochondrial cytochrome oxidase subunit I) were obtained for U. digitabulum n. sp., U. tenuis n. sp., U. sinus n. sp., and U. uncinus n. sp. The identification of Urocleidoides is amended herein to include all taxonomic modifications observed in this genus over time and add new characteristics observed in the species in the present study. Phylogenetic analysis revealed Urocleidoides digitabulum n. sp. and Urocleidoides sinus n. sp. (parasites of anostomids) closely related in the tree topologies. Furthermore, the new species described herein parasitized phylogenetically distant host species (Characiformes and Gymnotiformes), suggesting the effect of the dynamic process of ecological fitting.

This study investigated the correlation of nucleophosmin 1 (NPM1) expression with

F-fluorodeoxyglucose (

F-FDG) positron emission tomography/computerised tomography scan (PET/CT)-related parameters and compared the diagnostic value of NPM1 with that of the positive biomarker TTF1 in lung adenocarcinoma patients.

Forty-six lung adenocarcinoma patients who underwent

F-FDG PET/CT before pulmonary surgery were retrospectively analysed. Metabolic parameters including SUV

, SUV

, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from

F-FDG PET imaging data. The expression levels of NPM1 and TTF1 were assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumour tissues and adjacent normal lung tissues. We examined the association between the frequency of NPM1 and TTF1 expression and the metabolic parameters.

Lung adenocarcinoma samples expressed higher levels of NPM1 than adjacent normal lung epithelial tissues. NPM1 showed higher specificity and sensitivity for lung adenocarcinoma compared with TTF1 (p < 0.001). SUV

, SUV

and TLG correlated with NPM1 expression (p < 0.001). MTV was inversely correlated with TTF1 (p < 0.01). SUV

was the primary predictor of NPM1 expression by lung adenocarcinoma (p < 0.01). A cutoff value for the SUV

of 3.93 allowed 90.9% sensitivity and 84.6% specificity for predicting NPM1 overexpression in lung adenocarcinoma.

NPM1 overexpression correlated with

F-FDG PET/CT metabolic parameters and improved diagnostic accuracy in lung adenocarcinoma. SUV

on

F-FDG PET/CT may estimate NPM1 expression for targeted therapy of lung adenocarcinoma.

NPM1 overexpression correlated with 18F-FDG PET/CT metabolic parameters and improved diagnostic accuracy in lung adenocarcinoma. SUVmax on 18F-FDG PET/CT may estimate NPM1 expression for targeted therapy of lung adenocarcinoma.

More accurate prediction of the extent of drug brain exposure in early drug discovery and understanding potential species differences could help to guide medicinal chemistry and avoid unnecessary animal studies. Hence, the aim of the current study was to validate the use of a P-gp transfected LLC-PK1 model to predict the unbound brain-to-plasma concentration ratio (Kp

) in rats and humans.

MOCK-, Mdr1a- and MDR1-transfected LLC-PK1 monolayers were applied in a transwell setup to quantify the bidirectional transport for 12 specific P-gp substrates, 48 UCB drug discovery compounds, 11 compounds with reported rat in situ brain perfusion data and 6 compounds with reported human Kp

values. The in vitro transport data were introduced in a minimal PBPK model (SIVA®) to determine the transport parameters. These parameters were combined with the differences between in vitro and in vivo passive permeability as well as P-gp expression levels (as determined by LC-MS/MS), to predict the Kp

.

A 10-fold difference between in vitro and in vivo passive permeability was observed. Incorporation of the differences between in vitro and in vivo passive permeability and P-gp expression levels resulted in an improved prediction of rat (AAFE 2.17) and human Kp

(AAFE 2.10).

We have succesfully validated a methodology to use a P-gp overexpressing LLC-PK1 cell line to predict both rat and human Kp

by correcting for both passive permeability and P-gp expression levels.

We have succesfully validated a methodology to use a P-gp overexpressing LLC-PK1 cell line to predict both rat and human Kpuu,brain by correcting for both passive permeability and P-gp expression levels.

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