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Objectives: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D)., Methods: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95 % confidence intervals (CIs)., Results: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59 %) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95 % CI 0.89-1.04), ischemic stroke (RR 0.89; 95 % CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95 % CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95 % CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95 % CI 0.56-0.97)., Conclusion: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke., Competing Interests: Declaration of competing interest Dr. Sur has served as a consultant for Medtronic; receives research funding as the Evelyn F. McKnight Brain Institute Neurocognitive Scholar and the Florida Stroke Registry COHAN A-2; and serves on the editorial board for Stroke, JACC: Advances, and the Journal of Clinical and Translational Investigation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The key role of manganese (Mn) in the biogeochemical cycle of trace elements has been of great interest in recent years. Nevertheless, the redox properties of aqueous Mn(III) have been studied to a lesser extent. Mn(III) is not stable in solution by itself. However, when complexed with inorganic ligands, it has shown potential to oxidize and reduce trace elements. In the present study, we are exploring the redox characteristics of the complex Mn(III)-Pyrophosphate (Mn(III)-PP). This complex is stable over a wide range of pH values but requires the ratio of Mn:PP to be less than 1:6. Specifically, the redox reaction of chromium (Cr(III)) and Mn(III)-PP is investigated. A solid, Cr(OH) 3 , is used as a source of Cr(III).  For this reaction, environmentally relevant parameters, such as pH, ionic strength, ratio Mn(III)/Cr(III), and excess of ligand, were assessed. Results showed that Mn(III) can effectively oxidize Cr(III) to Cr(VI), taking about 15 days for the reaction to complete. This reaction occurs only under acidic conditions (pH 4), and with a low excess of Pyrophosphate. The initial Mn(III) concentration decreases as the Cr(VI) is produced, and Cr(VI) can be adsorbed back into the Cr(OH) 3 surface, limiting the mobility of this toxic species. Despite this adsorption, significant amounts of Cr(VI) are release in the aqueous phase. This study shows the importance of a mobile species (Mn-PP complex) in the oxidation of Cr(III) and the release of Cr(VI) to the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023. Published by Elsevier B.V.)

This study aimed to evaluate the effectiveness of the experimental formulation containing chlamydospores of Duddingtonia flagrans and Pochonia chlamydosporia fungi, against Moniezia expansa . Two experiments were carried out. The first experiment evaluated the in vitro efficacy using 1 g of the experimental formulation (V1) added to 100 M. expansa eggs and the control (V2) (without the fungal formulation). Intact eggs or eggs with alterations were counted in order to evaluate their effectiveness. The second experiment evaluated the action of the fungal formulation on M. expansa eggs after passing through the gastrointestinal tract of goats. Three groups were identified as B1, B2, and B3, which received 1.0, 1.5 g of experimental fungal formulation, and placebo, respectively. In experiment 1, all the eggs in V1 were subjected to the predatory action of fungi, while in V2, the eggs remained intact. In experiment 2, the reduction of eggs in groups B1 and B2 were 49% and 57% 24 h after ingestion, 60% and 63% 48 h after, and 48% and 58% 72 h after. The predatory capacity against M. expansa eggs shown in the tests demonstrated that experimental fungal formulation has the potential to be used on integrated helminth control programs.

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor.

Water contamination by antibiotics is an emerging global problem, with impacts on both public health and the environment. Erythromycin has been encountered in bodies of water throughout the world, which demands the development of efficient remediation technologies. We investigated the physiological responses and phytoremediation capacity of four species of aquatic macrophytes, two floating ( Salvinia molesta and Lemna minor ) and two submerged ( Myriophyllum aquaticum and Rotala rotundifolia ). The plants were exposed to relevant environmental concentrations of erythromycin (0 and 1.7 µg l -1 ) in artificially contaminated water for seven days. Physiological evaluations evidenced the ability of that antibiotic to promote oxidative events in those plants, such as the activation of antioxidant enzymes (ascorbate peroxidase and/or catalase). S. molesta exposed to erythromycin demonstrated accumulations of hydrogen peroxide and oxidative damage (lipid peroxidation) that was reflected in growth reductions. The erythromycin removal efficiency of floating plants varied from 9 to 12%, while submerged species varied from 31 to 44%. As such, submerged macrophyte species demonstrated the most efficient removal of erythromycin from contaminated waters, and are therefore more indicated for antibiotic phytoremediation projects.

Precis: The current study showed that glaucomatous eyes from patients with central visual field defects presented less negative disc-fovea angle compared with patients with peripheral defects., Purpose: The purpose of this study was to investigate the relationship between disc-fovea angle and visual field defect location in patients with glaucoma., Materials and Methods: This was a cross-sectional study including glaucoma patients divided into isolated central and isolated peripheral scotoma groups. The main outcome measure was disc-fovea angle measurement between groups. Secondary outcomes included disc-fovea distance, vertical disc diameter, and fovea vertical deviation., Results: We included 50 glaucoma patients (50 eyes; 27 with central scotoma and 23 with peripheral scotoma). Mean deviation from visual fields was -3.05±1.67 and -2.95±1.49 dB (P=0.829) (central and peripheral scotoma groups, respectively). We found that eyes in the central group had lower values of disc-fovea angle (-5.85±2.67 vs. -7.97±2.26 degrees, P=0.004), shorter disc-fovea distance (4.38±0.70 vs. 4.98±0.78 mm, P=0.006), and shorter fovea vertical deviation (-0.43±0.19 vs. -0.68±0.22 mm, P<0.001) compared with eyes in the peripheral group., Conclusions: This study showed an association between disc-fovea angle and central visual field defects in patients with glaucoma. Our findings suggest that eyes with a less negative disc-fovea angle should undergo a more careful investigation of the central visual field, even at early stages of the disease.

Teredinidae are a family of highly adapted wood-feeding and wood-boring bivalves, commonly known as shipworms, whose evolution is linked to the acquisition of cellulolytic gammaproteobacterial symbionts harbored in bacteriocytes within the gills. In the present work we applied metagenomics to characterize microbiomes of the gills and digestive tract of Neoteredo reynei, a mangrove-adapted shipworm species found over a large range of the Brazilian coast. Comparative metagenomics grouped the gill symbiont community of different N. reynei specimens, indicating closely related bacterial types are shared. Similarly, the intestine and digestive gland communities were related, yet were more diverse than and showed no overlap with the gill community. Annotation of assembled metagenomic contigs revealed that the gill symbiotic community of N. reynei encodes a plethora of plant cell wall polysaccharides degrading glycoside hydrolase encoding genes, and Biosynthetic Gene Clusters (BGCs). In contrast, the digestive tract microbiomes seem to play little role in wood digestion and secondary metabolites biosynthesis. Metagenome binning recovered the nearly complete genome sequences of two symbiotic Teredinibacter strains from the gills, a representative of Teredinibacter turnerae "clade I" strain, and a yet to be cultivated Teredinibacter sp. type. These Teredinibacter genomes, as well as un-binned gill-derived gammaproteobacteria contigs, also include an endo-β-1,4-xylanase/acetylxylan esterase multi-catalytic carbohydrate-active enzyme, and a trans-acyltransferase polyketide synthase (trans-AT PKS) gene cluster with the gene cassette for generating β-branching on complex polyketides. Finally, we use multivariate analyses to show that the secondary metabolome from the genomes of Teredinibacter representatives, including genomes binned from N. reynei gills' metagenomes presented herein, stands out within the Cellvibrionaceae family by size, and enrichments for polyketide, nonribosomal peptide and hybrid BGCs. Results presented here add to the growing characterization of shipworm symbiotic microbiomes and indicate that the N. reynei gill gammaproteobacterial community is a prolific source of biotechnologically relevant enzymes for wood-digestion and bioactive compounds production., Competing Interests: The authors have declared that no competing interests exist.

Aims: Currently, animal models of liver regeneration are based on extensive lesions of the native organ and on cellular approaches using biomaterials to host growth factors and extracellular components to create artificial liver systems. We report a polymeric biological platform, minimally invasive, that induced sequential proliferation of liver parenchyma inside the scaffold in mice., Main Methods: Porous discs of polyether-polyurethane were surgically placed under the left liver lobe and removed at days 4, 8, 12 and 25 after implantation. No exogenous growth factors or extracellular matrix components were added to the scaffold. Histological analysis of the implants was performed to identify hepatocytes, liver vascular structures and bile ducts in the newly formed tissue. In addition, systemic markers for hepatic function were determined., Key Findings: This biohybrid device provided a scaffold that was gradually filled with parenchymal and non-parenchymal liver tissue as detected by histological analysis. At day 4, the pores of the scaffold were filled with inflammatory cells and spindled-shaped like fibroblasts, and extracellular matrix components. At day 8, hepatocytes clusters, central lobular hepatic veins, portal space containing arteries, veins and biliary ducts were detected. By days 12 and 25 a liver-like structure filled 2/3 of the scaffold. Its organization resembled that of a mature liver. Serum concentration of ALT increased three-fold initially after implantation, returning gradually to control levels., Significance: The plain synthetic scaffold (without addition of exogenous molecules) placed under the intact left liver lobe exhibits the potential to investigate physiological mechanisms that regulate liver parenchyma proliferation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury., Methods: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR). Eight randomly assigned right kidneys constituted the control group. After 240 min of reperfusion, the left kidney was retrieved to evaluate histological changes, lipid peroxidation and antioxidant enzymes activity. Serum was collected to evaluate urea and creatinine., Results: IPC+TH+IR group revealed no difference to any other group subjected to ischemia in relation to histological changes, lipid peroxidation and antioxidant enzymes activity. Creatinine was lower in IPC+TH+IR group compared with IPC+IR, but showed no difference compared to TH+IR group., Conclusions: Combination of local ischemic preconditioning (IPC) and topical hypothermia conferred no protection in renal I/R injury. Moreover, local IPC solely followed by warm ischemia impaired renal function more than warm ischemia alone.

The purpose of this paper is to characterize the tiles placed on the walls of the Franciscan convent of "Santo Antônio" (Recife-PE) and to obtain information about the several expansions and structural reforms performed on the convent by dating the bricks. For this purpose, a portable energy dispersive x-ray fluorescence (EDXRF) was used to characterize the tiles. The dating of the bricks was performed using the Thermoluminescence (TL) technique. The results of the EDXRF analysis show that the dominant component of the white pigment is lead [2PbCO(3)·Pb(OH)(2)], used since the ancient times until the 20th century, while the dominant element of the blue pigment is cobalt (CoO·Al(2)O(3)), that has been used from 1807 until nowadays. The TL dating of bricks indicate that there were walls with different periods of construction, being one built around 1765, with a deviation of 28 years, whereas other was built later, around 1874, with a deviation of 15 years. These results provide new data towards understanding how and when the Recife Franciscan convent of "Santo Antônio" was designed and built, contributing to other research works presently underway on site., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

β-Lactam antimicrobials are known to have a low concentration/therapeutic response. However, extending the period in which β-lactam are free in the plasma does directly influence therapeutic outcomes. The objective of this study was to evaluate the influence of Pluronic® F68 on the antimicrobial activity of ceftazidime when admixed with aminophylline in parenteral solutions by the evaluation of its minimal inhibitory concentration (MIC) within 24 h. Ceftazidime, aminophylline, and Pluronics® F68 were evaluated using the MIC method against Escherichia coli and Pseudomonas aeruginosa, with these compounds individually and associated in the same parenteral solutions. When Pluronics® F68 was admixtured with ceftazidime alone or with ceftazidime and aminophylline, it was possible to observe lower MIC values not only at 24 h but also at 0 h for both microorganisms. This indicates that Pluronics® F68 may be able to enhance ceftazidime antimicrobial activity in the presence or absence of aminophylline. This fact suggests that Pluronics® F68 can be applied to allow the administration of ceftazidime under continuous infusion in parenteral solutions, beneficiating hospital pharmacotherapy. It may also be possible to reduce ceftazidime doses in formulations achieving the same therapeutic results., (Copyright © 2010 Wiley-Liss, Inc.)

Polylactic acid is a polymer of great technological interest, whose excellent mechanical properties, thermal plasticity, and bioresorbability render it potentially useful for environmental applications, as a biodegradable plastic and as a biocompatible material in biomedicine. This article discusses the synthesis and characterization of poly-L-lactic acid, obtained through two synthetic routes: direct polycondensation reactions without organic solvents, and in a supercritical medium. Tin complexes were used as catalysts in both polymerization reactions. The polymers were characterized by (1)HNMR, IR, GPC, DSC, and TGA techniques. In vitro biocompatibility tests were performed with human alveolar bone osteoblasts and there were assessed cell adhesion, proliferation and viability. The poly condensation reaction proved to be an excellent synthetic route to produce PLA polymers with different molar mass. The formation of polymers from lactic acid monomer was confirmed through techniques utilized. It was observed that cell adhesion and viability was not disturbed by the presence of the polymer, although the proliferation rate was decreased when compared to control.

We used an animal model of restrictive strabismus analogous to the fat adherence syndrome in humans to test the efficacy of topical intraoperative mitomycin-C (MMC) in preventing the development of restrictive scar tissue. A cicatricial adhesion was created between the inferior rectus muscle and the inferior orbital rim of each eye in eight rabbits, and passive forced ductions were quantitatively measured with a spring scale. Eight eyes were treated intraoperatively with topical MMC 0.5 mg/mL, the other eight with sterile water. Passive forced ductions were again measured 4 weeks postoperatively and representative orbits were exenterated for histopathologic examination. Significant restriction of motility was produced in six of the eight control eyes. Though prophylactic treatment with MMC may have been beneficial in some cases, on average, the restriction developing in these eyes did not significantly differ from that in the control eyes. In addition, longer exposure times to MMC led to marked orbital inflammation and severe restriction of ocular motility. Finally, histopathologic evaluation of the orbits of the MMC-treated eyes revealed marked fibrosis of perimuscular connective tissues. Although MMC may have a role in the management of fat adherence syndrome, further study is needed to establish safe and efficacious methods of delivery.