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“جهاز المشروعات” ينفذ مشروعات كثيفة العمالة للمساهمة في تطوير المناطق العشوائية – موقع متناهي


The new PMC адрес is here! Learn more about navigating our updated article layout. The PMC legacy view will also be available for a limited time. Federal government websites often end in. The site is secure. Here we examined the effect of curcumin, the principal curcuminoid по этому адресу turmeric, on oral bioavailability of microdoses and affinity designer beta free download doses of sulphasalazine in humans.

Curcumin increased AUC 0—24 of affinity designer beta free download sulphasalazine 2. Non-linearity of the dose—exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine.

Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non-linearity in the dose—exposure relationship of sulphasalazine.

Drug-metabolizing enzymes and transporters form an essential detoxification system in the small intestine, and limit absorption of xenobiotic compounds including drugs into the circulation Wacher et al. Even for drugs in the market, these processes serve as potential sites causing non-linearity, and intersubject variation, due to drug—drug interactions, or genetic factors. Elucidation of the effect of such enzymes and transporters contributes to selection of candidates in drug development and to safety in drug therapy.

Subjects with this mutant allele show higher systemic exposure to topotecan Sparreboom et al. Because of the broad substrate specificity of BCRP, its effect on oral bioavailability of other substrate drugs and drug candidates is a matter of great concern.

There has been growing interest in inhibitors of drug transporters in vivosince the International Transporter Consortium published guidelines for the study of transporters in drug development, where the decision tree recommends a clinical drug—drug interaction study to elucidate the impact of transporters on the disposition and therapeutic efficacy of investigational drugs Giacomini et al. With regard to in vivo BCRP inhibitors, a multidrug resistance modifier GF, was the first compound to increase the oral absorption of topotecan by twofold in cancer patients Affinity designer beta free download et al.

More recently, gefitinib and curcumin was shown to greatly enhance the plasma concentration of sulphasalazine following oral administration, by inhibiting Bcrp in mice Zaher et al.

In spite of urgent needs, in vivo inhibitors of BCRP applicable to clinical studies have not been established. Curcumin, the principal curcuminoid of turmeric, is a naturally occurring polyphenol.

This low toxicity together with its high potency in inhibiting photolabelling of BCRP with [ I]iodoarylazidoprazosin Shukla affinity designer beta free download al. Therefore, this study aimed to assess the effect of curcumin using sulphasalazine as test substrate for BCRP, oral availability of which is limited by BCRP Yamasaki et al.

Clinical studies using microdoses aid rational selection of candidate drugs based on their pharmacokinetic behaviour in the early phase of drug development. To address this issue, we examined the effect of curcumin on the disposition of sulphasalazine both in windows home pro upgrade oem free microdose and in a therapeutic dose in this study. All animal care and experimental procedures complied with the regulations of the Committee on Ethics in the Care and use of Laboratory Animals of Hoshi University.

Kyoto, Japan. The studies of sulphasalazine 0. Sulphasalazine retained on the membrane filter was recovered in methanol by sonication for 15 min then vortexing for 10 min. Curcumin and sulphasalazine were dissolved in PBS containing 0. Blood was collected from the tail vein at 0. The ion spray interface was operated in the negative ion mode. This study was approved by the Ethics Committee of Osaka Pharmacology Clinical Research Hospital and Graduate School of Pharmaceutical Sciences, and was conducted in accordance with the Declaration of Helsinki and current Japanese ethical guidelines for clinical research.

Each subject was physically normal by clinical examination and routine clinical testing, and had no history of significant medical illness or hypersensitivity to any drugs. This was a single-arm and four-phase study. The first half of the study was the microdose pharmacokinetic study, and the second half was the pharmacokinetic study at a therapeutic dose. Assuming the volume of the intestinal affinity designer beta free download 2.

This dose of curcumin was lower than the highest dose 8 g per day for 3 months under which subjects did not display any adverse effects Cheng et al. Plasma concentrations of sulphasalazine were determined at the times shown. In period 2 and 4, the volunteers received 2 g curcumin 18 tablets 30 min before sulphasalazine administration. Blood samples were taken by direct venepuncture sodium heparin anticoagulant before dosing and at 0. After addition of the internal standard IS, probenecidsulphasalazine and IS in human plasma were extracted using t-butyl methyl ether followed by evaporation of the organic layer.

The turbo ion spray interface was operated in the negative ion mode. Curcumin and IS 4-hydroxybenzophenone in human plasma were extracted using ethyl acetate following protein precipitation followed by evaporation of the organic layer.

The residue was dissolved in distilled water containing acetonitrile and formic acid The mobile phase consisted of acetonitrile and 0. C max was obtained directly from the data.

The area under the curve AUC 0—24 was calculated by the linear trapezoidal rule. The Affinity designer beta free download e was estimated using least-squares regression analysis from the terminal post-distribution phase of the concentration—time curve.

The solubility of sulphasalazine was examined at different pH pH 4. After centrifugation and filtration through a 0. The OATP2B1 open reading frame inserted in the sense orientation was verified by direct sequencing affinity designer beta free download found to fully match the published reference sequence. The transfected cells were selected with Geneticin and affinity designer beta free download using the penicillin cup method.

The transport activity of the cloned cells was confirmed. Cells were seeded 72 h before the transport affinity designer beta free download in poly- l -lysine- and poly- l -ornithine-coated well plates at a density of 1. For the transport study, the cell culture medium was replaced with culture medium supplemented with 5 mM sodium butyrate 24 affinity designer beta free download before the transport assay to induce expression of the transporters. After termination of the uptake, cells were recovered in a test tube and sulphasalazine was extracted by acetonitrile.

Mobile phases were acetonitrile and 0. The horizontal line within each box represents the median and the box edges represent the lower and upper quartiles, respectively. The whiskers extend from the lower and upper quartiles to the furthest data points still within a distance of 1. Effect of curcumin on C max and AUC of sulphasalazine given orally at a microdose and at a therapeutic dose.

Values are expressed as box lower and upper quartiles and whisker the furthest data points still within a distance of 1. All other chemicals of the highest grade commercially available were obtained from Wako Pure Chemical Industries Kyoto, Japan. Curcumin tablets were manufactured by API Gifu, Japan and contained about mg of curcumin per tablet mg total weight of tablet and maltitol Curcumin inhibited the ATP-dependent uptake in a concentration-dependent manner with an IC 50 value of 1.

Using the previously reported K m of sulphasalazine 0. Membrane vesicles expressing hBCRP were incubated with sulphasalazine 0. A calculated curve is shown. The mean AUC 0—8 of plasma sulphasalazine concentrations was 8. No clinically undesirable signs and symptoms possibly attributable to the administration of sulphasalazine and curcumin were identified during the study.

All subjects successfully completed the study according to the protocol. During the study period, the concentrations of curcumin in the plasma samples were below 0. Curcumin treatment significantly elevated the plasma concentrations of sulphasalazine given either as a microdose or as a therapeutic dose orally Figure 3. Both C max and AUC 0—24 of sulphasalazine was significantly greater in the curcumin-treated group than in the control group in both the microdose and therapeutic dose studies Figure 4whereas there was no difference in the elimination constants K e Table 1.

The mean AUC 0—24 of plasma sulphasalazine concentrations were 3. The effect of BCRP inhibition was more prominent in the therapeutic dose подробнее на этой странице than in the microdose study Figure 4.

Effect узнать больше curcumin on the systemic exposure to sulphasalazine following oral administration in healthy subjects.

Pharmacokinetic parameters of sulphasalazine SASP given orally at a microdose MD and at a therapeutic dose ThD alone or after pretreatment with oral curcumin. When the plasma concentration-time profile of sulphasalazine was compared in both control groups, the dose-normalized plasma concentration was significantly higher at the microdose than at the therapeutic dose Figure 5.

AUC 0—24 was 7. Comparison of dose-normalized plasma concentration-time profile of sulphasalazine in the control groups. Plasma concentrations of sulphasalazine in subjects given an oral microdose MD and a therapeutic dose ThD of sulphasalazine alone, were divided by the doses. Data are taken from Figure читать. The solubility of sulphasalazine in the intestinal lumen affinity designer beta free download estimated by a conventional solubility test.

The maximum concentrations of sulphasalazine achievable were 0. The K i of atorvastatin has affinity designer beta free download reported to be 0. A The uptake of [ 3 H]oestronesulphate E3S; 0. The purpose of this study was to 10 1903 download free download the effect of curcumin on pharmacokinetics of oral sulphasalazine, a test substrate of BCRP in healthy subjects as well as experimental animals. A microdose and a therapeutic dose study in healthy subjects were designed to examine the linearity of pharmacokinetics of oral sulphasalazine, and dose dependence on the magnitude of affinity designer beta free download interaction.

The inhibitory potency of curcumin was examined in vitro and in vivo in mice. Consistent with previous mouse studies Zaher et al. It is also suggested that sulphasalazine undergoes active efflux by multidrug resistance-associated protein 2 MRP2 as well as Bcrp in rat intestine and Caco-2 cells Dahan and Amidon, Curcumin significantly elevated the plasma concentrations of sulphasalazine following oral administration at both microdose and therapeutic dose in healthy subjects Figure 3.

Notably, curcumin showed fold higher potency for in vivo inhibition of BCRP in humans than in mice. C max of sulphasalazine in the subjects given a therapeutic dose of sulphasalazine with pretreatment of oral curcumin was similar to the value detected in subjects homozygous for the BCRP SNP AA 49 vs.

The plasma concentration of curcumin was below the limit of quantification, which is in a good agreement with previous report Vareed et al. Therefore, curcumin is not suitable to inhibit BCRP involved affinity designer beta free download active efflux at the blood—brain barrier or systemic elimination by the liver and kidney at the current dose, although inhibition of BCRP in the liver during its first pass remains unclear. Overall, curcumin was an effective in vivo BCRP inhibitor and could be used to investigate the effect of BCRP on the absorption of drugs or drug candidates in clinical studies.

This type of study would help to understand the mechanism underlying poor oral absorption affinity designer beta free download inter-individual variation in the oral availability of BCRP substrate drugs. However the specificity of curcumin in terms of other transporters and enzymes affinity designer beta free download the small intestine must be considered.


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Download Download PDF. Translate PDF. Abstract: The present work describes the synthesis of a series of four novel biologically active 2-aminoarylazothiazole disperse dyes containing the sulfa drug nucleus.

The structures of the synthesized thiazole derivatives are confirmed using UV-spectrophotometry, infrared and nuclear magnetic resonance techniques and elemental analysis. The synthesized dyes are applied to polyester fabrics as disperse dyes and their fastness properties to washing, perspiration, rubbing, sublimation, and light are evaluated.

The synthesized compounds exhibit promising biological efficiency against selected Gram-positive and Gram-negative pathogenic bacteria as well as fungi. Keywords: azo dyes; 2-aminothiazole; sulfaguanidine; polyester; dyeing; antimicrobial activity 1.

Azo dyes have vivid colors in the yellow to blue-green region adjustable by varying between azo components with electron withdrawing groups and coupling components with electron donating groups. They have been reported in the literature as antimicrobial [4], antifungal [5], anti-inflammatory activity [6], anesthetic [7], anti-hypertesive [8] and antiviral drugs [9]. In continuation of our interest in the synthesis of arylazothiazole derivatives [14—16], this paper reports the synthesis of some 2-aminoarylazothiazoles and their application as disperse dyes on polyester fabrics.

In addition, the antibacterial activities of the synthesized dyes against various pathogenic bacteria and fungi were also investigated. Molecules , 21, ; doi Results and Discussion 2. Synthesis 2. Synthesis Treatment of 2-aminothiazole derivatives 1 with the diazonium chloride derived from Treatment sulfaguanidine of 2-aminothiazole 2 afforded derivatives the corresponding 1 with the diazonium 2-aminoarylazothiazole chloride4 derived derivatives and 5 as from shown insulfaguanidine Scheme 1. The2structures afforded the of corresponding 2-aminoarylazothiazole 4 and 5 were established on the basis of derivatives their elemental4 andanalyses 5 as shown and in Scheme spectral data.

The structures of these substituted thiazole dyes 6 and 7 were elucidated based on their shown in Scheme 1. The structures of these substituted thiazole dyes 6 and 7 were elucidated based elemental analyses and spectral data. The IR of the dye 6 showed absorption peaks at , , on their elemental analyses and spectral data. The 1H-NMR spectrum of dye 6 showed a triplet signal at 6.

The presence and 8. The ofpresence a doubletofat 8. Synthesis Scheme Synthesis of of 2-aminoarylazo-thiazole 2-aminoarylazo-thiazole disperse dispersedyes dyes4—7. Dyeing and Fastness Properties 2. Dyeing of polyester fabrics was assessed in terms of their fastness properties e. All results, provided in Table 1, reveal rubbing, that thesesublimation, dyes have good andfastness light via a standard properties methodperspiration, to washing, [17].

All results, provided rubbing in Table 1, reveal and sublimation. The use on process depends of polyester the chemicalfabric i. This proposal density, thus thewas in agreement presence with the observed of electron-donating results Table substituents 1 which should demonstrate increase the fading thatThis rate. Molecules , 21, 3 of 10 Table 1. Fastness properties of the synthetic dyes on polyester fabrics. Fastness 4—5 properties of the 3—4synthetic dyes 4—5on polyester4fabrics. Color Assessment 1These properties were evaluated using the grey scale 1—poor, 2—fair, 3—moderate, 4—good and Colors of polyesterThis 5—excellent.

A reflectance spectrophotometer Gretag Macbeth CE the dye substrate. Optical measurements of the synthetic dyes on polyester fabrics. Figure 1, illustrated the relationship between the dyeing bath concentrations and the strengths values.

Figure 1, illustrated the relationship between the dyeing bath concentrations and the strengths of the synthesized disperse of the synthesized dyes disperse dyes4—7, 4—7,under underhigh high temperature temperature dyeingdyeing conditions, conditions, wherewhere no direct no direct connection connection between between the relative the relative molecular molecular weight weight of these of these dyesdyes to to thethe build-upwas build-up wasclear.

FigureFigure 1. Comparison 1. Molecules , 21, 4 of 10 Molecules , 21, 4 of 10 Molecules , 21, 4 of 10 2. Antimicrobial Activity 2. Antimicrobial Activity Table 33 shows shows that that all all samples samples exhibited exhibited an an acceptable acceptable antimicrobial antimicrobial activity against the tested Table pathogenic 3 shows bacteria that at all samples different exhibited concentrations an 0.

At high are At high concentrations, mean regarding of C. The antifungal activity. At high activity. The an acceptable remarkable antifungal zone of all synthetic products was at range 0. The remarkable activity of the synthesized synthetic activity of the activity. Scanning Electron 2. Scanning Electron Microscopy Microscopy 2. Scanning Electron Microscopy Scanning Scanning electron electron microscopy microscopy was was used used toto observe observe the the morphological morphological alteration alteration of of the the cells cells after after Scanning treatment treatment withelectron with the microscopy the synthesized synthesized was used e.

As shown 7. As of the shown incells in after22 Figures Figures treatment and and 33,the with the S. Figure 2. Figure 3. Candida albicans in ethanol as control left ; Candida albicans treated with synthesized Figure 3.

Candida compound 7 right. Candida albicans in ethanol as control left ; Candida albicans treated with synthesized compound 7 right.

Gram-positive bacteria, Gram-negative bacteria as well as fungi. Molecules , 21, 5 of 10 Table 3. Control S.

Experimental Section 3. Materials and Methods 3. Debora Katz. Lucio Vilar. Sara Ortega. Jan Cap. Clinically non-functioning pituitary adenomas account for about one-third of pituitary tumors. The majority of them are pathologically classified as gonadotropinomas or null-cell adenomas without hormonal expression. The rest represent silent corticotroph adenomas and plurihormonal tumors. Conservative therapy with dopamine agonists is effective in some cases only depending on the expression of dopamine 2 receptors D2R.

The aim of this study was to quantitatively estimate D2R expression in clinically non-functioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. Out of the 87 adenomas investigated, 63 expressed gonadotropins, 7 were silent corticotroph adenomas, 7 were plurihormonal tumors, and only 6 did not express any pituitary hormone on immunohistochemical investigation.

The expression was very low in corticotroph adenomas relative median quantity after normalization to housekeeping gene 0. The difference between corticotroph adenomas and plurihormonal tumors in comparison with other pathological types was statistically significant. The expression of D2R did not depend on the presence or absence of gonadotropins.

We conclude that D2R expression is very low in corticotroph adenomas and significantly lower in plurihormonal tumors. The positivity of gonadotropins does not predict the D2R quantity. Ilinca Gussi. Vincenzo Esposito. Nelma Marques. Thyrotropin-secreting pituitary adenomas TSHomas represent a rare subtype of pituitary tumors.

Neurosurgery NCH is still considered the first-line therapy. In this study we aimed to investigate the outcome of different treatment modalities, including first line somatostatin analogs SSA treatment, with a specific focus on neurosurgery-related complications.

We retrospectively evaluated thirteen patients diagnosed for TSHomas 9 M; age range Ten patients had a magnetic resonance evidence of macroadenoma, three with slight visual field impairment.

Median TSH value at diagnosis was 3. Three patients two microadenoma were primarily treated with NCH and achieved disease remission, whereas ten patients nine macroadenomas were initially treated with SSA.

Despite the optim Keith Black , Patrizia Tunici. Andrea Lania , Giuseppe Reimondo , G. Ulrike Ernemann. Jacques Epelbaum. Vaclav Hana , Josef Vymazal. Antonio Desalles. John Monson. Mohammad Rifky. Beatrice Couzinet. Massimo Barberis. Diarmuid Smith. Salvador J Diaz-Cano. Yona Greenman.

Carmela Caputo. Michael Cusimano , Aydin Sav. Cord Dohrmann. Mohsen Javadpour. Elisa Verrua. Gianluigi Zona. Manish Kasliwal. Diane Stockton. Pascale Abrams. Ricardo Giorgi. Wouter Herder. Catherine Massart.

Mercedes Rigla. Log in with Facebook Log in with Google. Remember me on this computer. Enter the email address you signed up with and we’ll email you a reset link. Need an account? Click here to sign up. Download Free PDF. The use of beta-subunits of gonadotrophin hormones in the follow-up of clinically non-functioning pituitary tumours. Related Papers. British Journal of Radiology The role of somatostatin receptor scintigraphy in patients with pituitary adenoma or post-surgical recurrent tumours.

Pituitary Dopamine 2 receptor expression in various pathological types of clinically non-functioning pituitary adenomas. Chromogranin A as serum marker of pituitary adenomas.

Carly Hyland , a Patrick T. Bradshaw , b Robert B. Gunier , a Ana M. Patrick T. Robert B. Ana M. Sharon K. Author information Article notes Copyright and License information Disclaimer. E-mail: ude. Received Nov 24; Accepted Mar Published by Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution License 4. Associated Data Supplementary Materials eees Background: Studies suggest that exposure to pesticides during pregnancy and early childhood is associated with adverse child neurodevelopment.

Results: We observed mostly null associations between pesticide applications and neurobehavioral outcomes. Conclusions: We found only some subtle associations between some pesticides and neurobehavioral outcomes.

What this study adds Prenatal and early-life exposure to organophosphate pesticides has been associated with adverse child neurodevelopment; however, data gaps exist regarding the impact of exposure to mixtures of pesticides. Covariates At each study visit, bilingual study staff administered structured questionnaires to ascertain participant characteristics. Statistical analysis We implemented a two-stage BHM 19 , 33 — 39 to examine exposure—outcome associations with all pesticides included simultaneously.

Sensitivity analyses We examined the robustness of our results by conducting sensitivity analyses in which we varied the specification of the Z matrix. Table 1. Open in a separate window. Table 2. Associations with pesticide applications during prenatal period We observed largely negligible associations between pesticide use near the home during pregnancy and neurobehavioral outcomes. Table 3. Table 4. Associations with pesticide applications during the postnatal period The most consistent associations we observed for pesticide use during the postnatal period were for glyphosate and maternal- and youth-reported internalizing behaviors.

Table 5. Table 6. Sensitivity analyses Results from our sensitivity analyses were robust to variations of the specification of the Z matrix, and our overall interpretations were qualitatively the same data not shown. Discussion We observed mostly null associations of agricultural pesticide use near the home during critical periods of brain development and behavioral and emotional problems at ages 16 and 18 years among participants living in an intensive agricultural region.

Conclusion This is the first study to examine associations of applications of mixtures of neurotoxic pesticides near the home during pregnancy or early childhood, critical periods of brain development, and neurobehavioral outcomes assessed during adolescence or young adulthood. Supplementary Material Click here to view. Footnotes Published online 5 May A.

References 1. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide.

Prenatal residential proximity to agricultural pesticide use and IQ in 7-year-old children. Association between pesticide profiles used on agricultural fields near maternal residences during pregnancy and IQ at age 7 years. Environ Int. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Urinary 3,5,6-trichloropyridinol TCPY in pregnant women from Mexico City: distribution, temporal variability, and relationship with child attention and hyperactivity.

Int J Hyg Environ Health. Prenatal organophosphate pesticide exposure and traits related to autism spectrum disorders in a population living in proximity to agriculture. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. Environmental exposure mixtures: questions and methods to address them.

Curr Epidemiol Rep. US EPA. Environmental Protection Agency; Pyrethroid epidemiology: a quality-based review. Crit Rev Toxicol. Systemic insecticides neonicotinoids and fipronil : trends, uses, mode of action and metabolites. Environ Sci Pollut Res Int. Benbrook CM. Trends in glyphosate herbicide use in the United States and globally.

Environ Sci Eur. Greenland S. Hierarchical regression for epidemiologic analyses of multiple exposures. Bayesian methods for highly correlated exposure data. Applications of Bayesian methods to epidemiologic research. Greenland S, Poole C. Empirical-Bayes and semi-Bayes approaches to occupational and environmental hazard surveillance.

Arch Environ Health. When should epidemiologic regressions use random coefficients? Modern Epidemiology. Prenatal pesticide exposure and childhood leukemia – a California statewide case-control study.

Pesticides in dust from homes in an agricultural area. Environ Sci Technol. Determinants of agricultural pesticide concentrations in carpet dust. Causal diagrams for epidemiologic research.

Radloff LS. Appl Psychol Meas. Home Observation for Measurement of the Environment. Gestational exposure to endocrine-disrupting chemicals and reciprocal social, repetitive, and stereotypic behaviors in 4- and 5-year-old children: the HOME study. An application of hierarchical regression in the investigation of multiple paternal occupational exposures and neuroblastoma in offspring.

Am J Ind Med. Perinatal exposure to hazardous air pollutants and autism spectrum disorders at age 8. Exposure to multiple sources of polycyclic aromatic hydrocarbons and breast cancer incidence.

Examining the association of lung cancer and highly correlated fibre size-specific asbestos exposures with a hierarchical Bayesian model. Occup Environ Med. Prenatal phthalate exposures and childhood fat mass in a New York City Cohort. Hierarchical regression analysis applied to a study of multiple dietary exposures and breast cancer. Methods for epidemiologic analyses of multiple exposures: a review and comparative study of maximum-likelihood, preliminary-testing, and empirical-Bayes regression.

Stat Med. Markov chain Monte Carlo: an introduction for epidemiologists. Int J Epidemiol. Casella G, George EI. Explaining the Gibbs Sampler. Am Statistician. Plummer M. Geweke J. Getting it right: joint distribution tests of posterior simulators. J Am Statistical Assoc. Brooks SP, Gelman A.

General methods for monitoring convergence of iterative simulations. J Comput Graph Stat. Organophosphorus Cumulative Risk Assessment. Age of onset of mental disorders: a review of recent literature. Curr Opin Psychiatry. Prenatal exposure to organophosphorus pesticides and childhood neurodevelopmental phenotypes. Environ Res.


2023-01-23T04:44:15+04:00January 23rd, 2023|

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