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OBJECTIVES: We assessed the impact of obesity and racial disparities on preterm birth (PTB) in the United States and sought to determine whether obesity widens the racial-ethnic disparity gap in preterm birth with a focus on non-Hispanic Black and White women. METHODS: Using birth data for the years 2014-2019 made publicly available by the Centers for Disease Control and Prevention and obtained from the National Vital Statistics System, we conducted a cross-sectional cohort study analyzing a total of 14,864,844 births from 2014 to 2019. RESULTS: We observed dose-dependent changes in obesity and PTB by defining obesity in subgroups and PTB in a stratified method. PTB occurred more among non-Hispanic Black women than their non-Hispanic White and Hispanic counterparts. We observed a consistent trend of increased PTB among women with high body mass index. Racial disparity existed in PTB among pregnant obese women, with non-Hispanic Black women exhibiting the greatest risk for PTB. CONCLUSIONS: Our work further contributes to the growing knowledge of the existence of health disparity among the Black population.
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Disparidades en el Estado de Salud , Nacimiento Prematuro , Femenino , Humanos , Recién Nacido , Embarazo , Negro o Afroamericano , Estudios Transversales , Obesidad/epidemiología , Parto , Mujeres Embarazadas , Nacimiento Prematuro/epidemiología , Estados Unidos/epidemiología , BlancoRESUMEN
PURPOSE: Presently, there are six undergraduate HRSA-funded MCH pipeline training programs (MCHPTP) in the nation and they have gained significant momentum since inception by recruiting, training and mentoring undergraduate students in a comprehensive MCH-focused approach. This article describes the outcomes from the 6 training programs; and primarily Baylor College of Medicine-Texas Southern University (BCM-TSU's) collaborative strategy focusing on the MCH research training and outcomes, which align with HRSA's MCH bureau's missions. DESCRIPTION: Each MCHPTP offers trainees interdisciplinary MCH research experiences through intra/inter-institutional collaborations and partnerships, but BCM-TSU's MCHPTP was the only one with the primary focus to be research. As a case study, the BCM-TSU Program developed an innovative research curriculum integrated with MCH Foundations Course that comprised 2 hour weekly meetings. Students were split into collaborative research groups of 4-5 students, with multidisciplinary peer-mentors, clinical fellows and MCH research faculty from institutions at the world-renowned Texas Medical Center. ASSESSMENT: Since the inception of the MCH mentorship programs, all six MCHPTPs have enrolled up to 1890 trainees and/or interns. BCM-TSU Program trainees are defined as undergraduate students in their 1st or 2nd year of college while research interns are upper classmen in their 3rd or 4th year of college. The case study showed that BCM-TSU Program trainees demonstrated outstanding accomplishments in the area of research through primary and co-authorships of 13 peer-reviewed journal publications by 78 trainees, over a period of 3 years, in addition to dozens of presentations at local, regional and national conferences. CONCLUSIONS: The research productivity of students in the six MCHPTPs is strongly indicative of the success of integrating MCH research mentoring into MCH didactic training. The development of a diverse and robust MCH mentorship program promotes and strengthens research activities in areas of high priority such as addressing health disparities in MCH morbidity and mortality in the U.S.
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Tutoría , Mentores , Curriculum , Humanos , Evaluación de Programas y Proyectos de Salud , Recursos HumanosRESUMEN
The purpose of this study was to identify potential metabolic pathways and metabolites of OJT007, a methionine aminopeptidase 1 (MetAP1) inhibitor. OJT007 is a novel drug with potent antiproliferative effects against Leishmania Major. We conducted in vitro Phase I oxidation and Phase II glucuronidation assays on OJT007 using rat liver microsomes. Four unknown metabolites were initially identified using a UPLC-UV system from microsomal incubated samples. LC-MS/MS analysis was then used to identify the structural characteristics of these metabolites via precursor ion scan, neutral loss scan, and product ion scan. A glucuronide metabolite was further confirmed by ß-glucuronidase hydrolysis. The kinetic parameters of OJT007 glucuronidation demonstrated that OJT007 undergoes rapid metabolism. These results demonstrate the liver's microsomal ability to mediate three mono-oxidated metabolites and one mono-glucuronide metabolite. This suggests hepatic glucuronidation metabolism of OJT007 may be the cause of its poor oral bioavailability.
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Microsomas Hepáticos , Espectrometría de Masas en Tándem , Animales , Cromatografía Liquida , Glucuronidasa/metabolismo , Glucurónidos/farmacología , Microsomas/metabolismo , Microsomas Hepáticos/metabolismo , RatasRESUMEN
This study highlights the role of time-dependent hydrolysis of ionic liquid anion, [BF4]-, of ionic liquid (IL), 1-ethyl-3-methylimidazolium tetrafluoroborate, [C2mim][BF4], which results in ever-changing pH conditions. Such pH changes along with the ionic interactions bring conformational changes in bovine serum albumin (BSA), leading to the formation of amyloid fibers at 37 °C without external control of pH or addition of electrolyte. The fibrillation of BSA occurs spontaneously with the addition of IL; however, the highest growth rate has been observed in aqueous solution of 10% IL (v/v %) among investigated systems. Thioflavin T (ThT) fluorescence emission has been employed to monitor the growth and development of ß-sheet content in amyloid fibrils. The structural alterations in BSA have also been investigated using intrinsic fluorescence measurements. Circular dichroism (CD) measurements confirmed the formation of amyloid fibrils. Transmission electron microscopy (TEM) has been explored to establish the morphologies of BSA fibrils at different intervals of time, whereas atomic force microscopy (AFM) has established the helically twisted nature of grown amyloid fibrils. The docking studies have been utilized to understand the insertion of IL ions in different domains of BSA, which along with decreased pH cause the unfolding and growth of BSA into amyloid fibrils. It is expected that the results obtained from this study would help to understand the impact of IL containing [BF4]- anion on protein stability and aggregation along with providing a new platform to control the formation of amyloid fibrils and other biomaterials driven via ionic interactions and alterations in pH.
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Líquidos Iónicos , Albúmina Sérica Bovina , Amiloide , Dicroismo Circular , Hidrólisis , TemperaturaRESUMEN
Considering the remarkable applicability of ionic liquids (ILs) in bio-catalysis involving enzymes, herein, we report new IL based aqueous microemulsions as a catalytic reactor for cytochrome c (Cyt-c). Microemulsions (µEs), comprising water as the polar component, imidazolium (cation) and dioctylsulfosuccinate (AOT) (anion) based biamphiphilic ionic liquid (BAIL) as the surfactant and a hydrophobic ionic liquid (HIL) as the non-polar component have been prepared and characterized. The use of BAIL has promoted the formation of µEs without any co-surfactant, owing to its higher surface activity. The effect of ester- or amide-functionalization of the alkyl chain of the imidazolium cation of BAILs on the phase behavior of µEs has been investigated. The prepared µEs have been characterized via conductivity, dynamic light scattering (DLS), UV-vis absorption and steady-state fluorescence (using external polarity probes) techniques. The prepared µEs have been employed as nano-reactors for exploring the catalytic activity of Cyt-c. The formed BAIL-water nano-interfaces in reverse µEs have exerted a positive effect on the catalytic activity of Cyt-c stored in a water pool of reverse µEs. A five-fold higher rate constant in µEs as compared to buffer establishes µEs as a better catalytic medium. Furthermore, the differing nature of nano-interfaces created by BAILs and water in reverse µEs, depending on the functionalization of the alkyl chain of the cationic part of BAIL, has exerted varying influence on the catalytic activity of Cyt-c. It is expected that the present work will result in providing a versatile platform for the creation of new IL and water based µEs for bio-catalytic applications.
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Citocromos c/química , Emulsiones/química , Líquidos Iónicos/química , Tensoactivos/química , Animales , Catálisis , Ácido Dioctil Sulfosuccínico/química , Guayacol/química , Caballos , Peróxido de Hidrógeno/química , Imidazoles/química , Oxidación-Reducción , Agua/químicaRESUMEN
The development of new strategies for thermal stability and storage of enzymes is very important, considering the nonretention of catalytic activity by enzymes under harsh conditions of temperature. Following this, herein, a new approach based on the interfacial adsorption of lysozyme (LYZ) at nanointerfaces of ionic liquid (IL)-based microemulsions, for enhanced thermal stability of LYZ, is reported. Microemulsions (MEs) composed of dialkyl imidazolium-based surface active ILs (SAILs) as surfactants, ILs as the nonpolar phase, and ethylene glycol (EG) as the polar phase, without any cosurfactants, have been prepared and characterized in detail. Various regions corresponding to polar-in-IL, bicontinuous, and IL-in-polar phases have been characterized using conductivity measurements. Dynamic light scattering (DLS) measurements have provided insights into the size distribution of microdroplets, whereas temperature-dependent DLS measurements established the thermal stability of the MEs. Nanointerfaces formed by SAILs with EG in thermally stable reverse MEs act as fluid scaffolds to adsorb and provide thermal stability, up to 120 °C, to LYZ. Thermally treated LYZ upon extraction into a buffer shows enzyme activity owing to negligible change in the active site of LYZ, as marked by retention of microenvironment of Trp residues present in the active site of LYZ. The present work is expected to establish a new platform for the development of novel nanointerfaces utilizing biobased components for other biomedical applications.
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Líquidos Iónicos/química , Nanotecnología , Temperatura , Emulsiones/química , Estabilidad de Enzimas , Muramidasa/química , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Surface active ionic liquid (SAIL) induced hydrogelation, in the absence of additives, is important considering the properties of soft-hydrogels that can be utilized in different applications. The present study is concerned with the phase behavior and hydrogelation of a SAIL, 1-hexadecyl-3-methylimidazolium p-toluenesulfonate, [C16mim][PTS]. The obtained information about the phase behavior along with the surfactant like behavior of the SAIL was exploited for effective exfoliation of graphene-flakes from graphite in aqueous medium that remain stable for at least one month. Thus the obtained dispersion of graphene-flakes was subsequently hydrogelated exploiting the observations made from the phase behavior of the SAIL, via entanglement of long worm-like micelles of the SAIL formed at higher concentration. The obtained graphene-flake based hydrogels were found to be equally stable as compared to the blank hydrogel as well as against centrifugation. The low melting point of hydrogel facilitates the extraction of graphene-flakes from the hydrogel matrix by heating and diluting the gel and there is no sign of agglomeration in the extracted graphene-flakes even if the extraction is carried out after a period of three months. The present work is an exemplary study on exfoliation, hydrogelation and extraction of graphene-flakes from a hydrogel, when required, using a SAIL and is expected to provide a new platform for utilization of SAILs for efficient graphene exfoliation and subsequent preparation of functional materials.
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UNLABELLED: Anxiety, depression, and altered memory are associated with intestinal diseases, including inflammatory bowel disease (IBD). Understanding the link between these behavioral changes and IBD is important clinically since concomitant mood disorders often increase a patient's risk of requiring surgery and developing secondary functional gastrointestinal diseases. Anxiety-like behavior (light/dark box test) and recognition memory (novel object recognition task) were determined at the peak and during resolution of inflammation in the dextran sodium sulfate (DSS) mouse model of acute colitis. DSS (5 days) was administered via drinking water followed by 3 or 9 days of normal drinking water to assess behavior during active or resolving inflammation, respectively. Disease (weight, colon length, and histology) was assessed and the composition of the gut microbiota was characterized by using qPCR on fecal pellet DNA. In a subset of mice, pretreatment with probiotics was started 1 wk prior to commencing DSS. During active inflammation (8 days), mice demonstrated impaired recognition memory and exhibited anxiety-like behavior vs. CONTROLS: These behavioral defects were normalized by 14 days post-DSS. Shifts in the composition of the gut microbiota were evident during active inflammation, notably as decreases in lactobacilli and segmented filamentous bacteria, which were also reversed once the disease had resolved. Administration of probiotics could prevent the behavioral defects seen in acute DSS. Taken together, our findings indicate that changes in mood and behavior are present during acute inflammation in murine IBD and associated with dysbiosis and that these outcomes can be prevented by the administration of probiotics.
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Ansiedad/terapia , Colitis Ulcerosa/terapia , Probióticos/uso terapéutico , Animales , Ansiedad/etiología , Ansiedad/microbiología , Encéfalo/fisiopatología , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/microbiología , Femenino , Intestinos/microbiología , Intestinos/patología , Masculino , Memoria , Ratones , Ratones Endogámicos C57BLRESUMEN
Microemulsions (µEs), comprising water as polar component, pluronic (normal, L35 and reverse, 10R5) as surfactant and a hydrophobic ionic liquid (HIL) as non-polar component have been prepared and characterized. Owing to higher surface activity, pluronics have promoted the formation of µEs without the use of co-surfactant. Thus prepared µEs have been utilized as nano-reactors for the oxidation of guaiacol in the presence of Cytochrome-c (Cyt-c) at 15, 20, and 25 °C. A 3.2- and 1.3-fold increase in the rate of formation of product of enzymatic catalysis in direct µE (HIL-in-water) with reverse pluronic (10R5) is observed at 15 and 20 °C as compared to that in buffer. However, negligible enzymatic activity is observed in the direct µE formed by normal pluronic (L35). The catalytic activity of Cyt-c decreases in reverse µEs (water-in-HIL) as compared to direct µEs irrespective of the nature of pluronic used. The contrasting nature of nano-interfaces formed by pluronics in µEs and the extent of hydration of these nano-interfaces controlled by temperature exerts varying influence on the catalytic activity of Cyt-c. It is expected that the present work would result in providing a versatile platform for the creation of new IL and pluronic-based µEs for bio-catalytic applications, which have never been reported.
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Líquidos Iónicos , Poloxámero , Poloxámero/química , Líquidos Iónicos/química , Citocromos c/química , Agua/química , Tensoactivos/químicaRESUMEN
The outbreak of SARS-CoV-2 infections around the world has prompted scientists to explore different approaches to develop therapeutics against COVID-19. This study focused on investigating the mechanism of inhibition of clioquinol (CLQ) and its derivatives (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ), 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) against the viral glycoprotein, and human angiotensin-converting enzyme-2 (hACE-2) involved in SARS-CoV-2 entry. The drugs were docked at the exopeptidase site of hACE-2 and receptor binding domain (RBD) sites of SARS-CoV-2 Sgp to calculate the binding affinity of the drugs. To understand and establish the inhibitory characteristics of the drugs, molecular dynamic (MD) simulation of the best fit docking complex performed. Evaluation of the binding energies of the drugs to hACE-2 after 100 ns MD simulations revealed CLQ to have the highest binding energy value of -40.4 kcal/mol close to MLN-7640 (-45.4 kcal/mol), and higher than the exhibited values for its derivatives: CLBQ (-34.5 kcal/mol) and CLCQ (-24.8 kcal/mol). This suggests that CLQ and CLBQ bind more strongly at the exopeptidase site than CLCQ. Nevertheless, the evaluation of binding affinity of the drugs to SARS-CoV-2 Sgp showed the drugs are weakly bound at the RBD site, with CLBQ, CLCQ, CLQ exhibiting relatively low energy values of -16.8 kcal/mol, -16.34 kcal/mol, -12.5 kcal/mol, respectively compared to the reference drug, Bisoxatin (BSX), with a value of -25.8 kcal/mol. The structural analysis further suggests decrease in systems stability and explain the mechanism of inhibition of clioquinol against SARS-CoV-2 as reported in previous in vitro study.Communicated by Ramaswamy H. Sarma.
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COVID-19 , Clioquinol , Humanos , SARS-CoV-2 , Exopeptidasas , AngiotensinasRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects the host cells through interaction of its spike protein with human angiotensin-converting enzyme 2 (hACE-2). High binding affinity between the viral spike protein and host cells hACE-2 receptor has been reported to enhance the viral infection. Thus, the disruption of this molecular interaction will lead to reduction in viral infectivity. This study, therefore, aimed to analyze the inhibitory potentials of two mucolytic drugs; Ambroxol hydrochlorides (AMB) and Bromhexine hydrochlorides (BHH), to serve as potent blockers of these molecular interactions and alters the binding affinity/efficiency between the proteins employing computational techniques. The study examined the effects of binding of each drug at the receptor binding domain (RBD) of the spike protein and the exopeptidase site of hACE-2 on the binding affinity (ΔGbind) and molecular interactions between the two proteins. Binding affinity revealed that the binding of the two drugs at the RBD-ACE-2 site does not alter the binding affinity and molecular interaction between the proteins. However, the binding of AMB (-56.931 kcal/mol) and BHH (-46.354 kcal/mol) at the exopeptidase site of hACE-2, significantly reduced the binding affinities between the proteins compared to the unbound, ACE-2-RBD complex (-64.856 kcal/mol). The result further showed the two compounds have good affinity at the hACE-2 site, inferring they might be potent inhibitors of hACE-2. Residue interaction networks analysis further revealed the binding of the two drugs at the exopeptidase site of hACE-2 reduced the number of interacting amino residues, subsequently leading to loss of interactions between the two proteins, with BHH showing better reduction in the molecular interaction and binding affinity than AMB. The result of the structural analyses additionally, revealed that the binding of the drugs considerably influences the dynamic of the complexes when compared to the unbound complex. The findings from this study suggest the binding of the two drugs at the exopeptidase site reduces the binding effectiveness of the proteins than their binding at the RBD site, and consequently might inhibit viral attachment and entry.
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Ambroxol , Bromhexina , Tratamiento Farmacológico de COVID-19 , Enzima Convertidora de Angiotensina 2 , Angiotensinas/metabolismo , Humanos , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/químicaRESUMEN
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease 2019 (COVID-19), has resulted in an ongoing pandemic. Presently, there are no clinically approved drugs for COVID-19. Hence, there is an urgent need to accelerate the development of effective antivirals. Herein, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a Food and Drug Administration (FDA) approved drug, and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection-induced cytopathic effect in vitro. In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin-converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. CLQ displayed the highest potency in the low micromolar range, with its antiviral activity showing a strong correlation with inhibition of rhACE2 and rhACE2-RBD interaction. Altogether, our findings provide a new mode of action and molecular target for CLQ and validates this pharmacophore as a promising lead series for the clinical development of potential therapeutics for COVID-19.
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OBJECTIVE: The purpose of this study was to determine whether cervical cancer is a risk factor for early mortality among women with HIV and whether racial/ethnic disparity predicted in-hospital death among women living with HIV and diagnosed with cervical cancer. METHODS: We conducted a population-based study using the National Inpatient Sample (NIS) database comprising hospitalized HIV-positive women with or without cervical cancer diagnosis, from 2003 through 2015. We compared trends in the rates of cervical cancer, in-hospital death, and years of potential life lost (YPLL) by race/ethnicity. RESULTS: We identified 2,613,696 women with HIV, and among them, 5398 had cervical cancer. The prevalence of cervical cancer (per 10,000) was 9.3 for NH-Whites, 30.9 among NH-Blacks, and 30.2 for Hispanics. Rates of cervical cancer over time diminished significantly only among NH-Whites (average annual percent change (AAPC), - 5.8 (- 9.7, - 1.8)), and YPLL in women with cervical cancer decreased significantly only in NH-Whites (AAPC, - 6.2 (- 10.1, - 2.0)). Cervical cancer was associated with increased odds of in-hospital death overall (OR 2.24 (1.59-3.15)) and among NH-Blacks (OR 2.03 (1.30-3.18)) only. CONCLUSIONS: NH-Blacks and Hispanics with HIV remain at increased risk for concurrent diagnosis of cervical cancer compared with NH-Whites. Moreover, NH-Black women with HIV and cervical cancer are at greatest risk for in-hospital death. The findings emphasize the need for a more robust prevention strategy among minority women to reduce the high burden of HIV/cervical cancer and related mortality.
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Negro o Afroamericano/estadística & datos numéricos , Infecciones por VIH/etnología , Disparidades en el Estado de Salud , Hispánicos o Latinos/estadística & datos numéricos , Mortalidad Hospitalaria/etnología , Neoplasias del Cuello Uterino/etnología , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), enters the host cells through two main pathways, both involving key interactions between viral envelope-anchored spike glycoprotein of the novel coronavirus and the host receptor, angiotensin-converting enzyme 2 (ACE2). To date, SARS-CoV-2 has infected up to 26 million people worldwide; yet, there is no clinically approved drug or vaccine available. Therefore, a rapid and coordinated effort to re-purpose clinically approved drugs that prevent or disrupt these critical entry pathways of SARS-CoV-2 spike glycoprotein interaction with human ACE2, could potentially accelerate the identification and clinical advancement of prophylactic and/or treatment options against COVID-19, thus providing possible countermeasures against viral entry, pathogenesis and survival. Herein, we discovered that Ambroxol hydrochloride (AMB), and its progenitor, Bromhexine hydrochloride (BHH), both clinically approved drugs are potent effective modulators of the key interaction between the receptor binding domain (RBD) of SARS-CoV-2 spike protein and human ACE2. We also found that both compounds inhibited SARS-CoV-2 infection-induced cytopathic effect at micromolar concentrations. Therefore, in addition to the known TMPRSS2 activity of BHH; we report for the first time that the BHH and AMB pharmacophore has the capacity to target and modulate yet another key protein-protein interaction essential for the two known SARS-CoV-2 entry pathways into host cells. Altogether, the potent efficacy, excellent safety and pharmacologic profile of both drugs along with their affordability and availability, makes them promising candidates for drug repurposing as possible prophylactic and/or treatment options against SARS-CoV-2 infection.
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Detailed physicochemical and computational investigation are made to explore different aspects of complexation between bovine serum albumin (BSA) and three structurally different surface active ionic liquids (SAILs), 1-dodecyl-3-methylimidazolium chloride, [C12mim][Cl]; 3-(2-(dodecylamino)-2-oxoethyl)-1-methyl-1H-imidazol-3-ium chloride, [C12Amim][Cl] and 3-methyl-1-dodecyloxy carbonyl methylimidazolium chloride, [C12Emim][Cl]. The interfacial and bulk complexation behavior has been monitored using tensiometry, conductivity, steady-state fluorescence and turbidity measurements. Thermodynamic insights about complexation have been obtained using isothermal titration calorimetry (ITC) measurements whereas molecular docking studies were used to predict the possible binding sites of SAILs on BSA. The information obtained from these studies helped in establishing the formed BSA-SAIL complex as a pH dependent colloidal transport system for controlled transport of a lipophilic dye, Rhodamine 6G (R6G), in aqueous phase, which is supported by confocal laser scanning microscopy (CLSM). In the present work, the effect of functionalization over the alkyl chain of SAILs, modulating the colloidal properties of SAIL-BSA systems, has been explored along with the utilization of these complexes as a pH dependent reversible carrier of lipophilic molecules. It is expected that besides providing basic understanding of colloidal complexes of BSA with SAILs, the present work is expected to be helpful in extending the applications of such colloidal systems for material transport.
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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease 2019 (COVID-19), has emerged as an ongoing global pandemic. Presently, there are no clinically approved vaccines nor drugs for COVID-19. Hence, there is an urgent need to accelerate the development of effective antivirals. Here in, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a FDA approved drug and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection induced cytopathic effect in vitro . In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. CLQ displayed the highest potency in the low micromolar range, with its antiviral activity showing strong correlation with inhibition of rhACE2 and rhACE2-RBD interaction. Altogether, our findings provide a new mode of action and molecular target for CLQ and validates this pharmacophore as a promising lead series for clinical development of potential therapeutics for COVID-19.
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Bio-based surface-active ionic liquids (SAILs) have been synthesized and investigated for their complexation with lysozyme (LYZ) in an aqueous medium to develop antimicrobial SAIL-LYZ colloidal complexes. The synthesized SAILs, [Cho][Sar] and [Cho][Doc], are comprised of choline ([Cho]+) and lauryl sarcosinate ([Sar]-) or deoxycholate ([Doc]-). The constituent anions of the investigated SAILs are structurally dissimilar and thus resulted in contrasting complexation behavior toward LYZ, as suggested by the results obtained from different techniques. The interfacial behavior is monitored using tensiometry. Zeta-potential, turbidity, and dynamic light scattering results provide insights into the complexation phenomenon in bulk. The observations made from fluorescence and circular dichroism (CD) spectroscopy give information about the alterations in the inherent structure of LYZ. The thermodynamics of the binding of SAILs with LYZ is monitored using isothermal titration calorimetry (ITC). Computer simulations have been utilized to determine the preferential binding site of SAILs on LYZ, which supports the results obtained from different techniques. Interestingly, LYZ complexed with the investigated SAILs, which are non-antimicrobial, is found to exhibit enhanced antimicrobial activity depending upon the concentration regime of the used SAIL. In this way, we have developed new antimicrobial colloidal complexes of SAILs and LYZ. The present study provides useful insights to synthesize new bio-based SAILs to be utilized for creating colloidal formulations applicable in enzyme/protein stabilization, storage, and other biomedical applications.
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Antiinfecciosos , Líquidos Iónicos , Muramidasa , Termodinámica , AguaRESUMEN
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent for coronavirus disease 2019 (COVID-19), and its ensuing mitigation measures have negatively affected the Maternal and Child Health (MCH) population. There is currently no surveillance system established to enhance our understanding of SARS-CoV-2 transmission to guide policy decision making to protect the MCH population in this pandemic. Based on reports of community and household spread of this novel infection, we present an approach to a robust family-centered surveillance system for the MCH population. The surveillance system encapsulates data at the individual and community levels to inform stakeholders, policy makers, health officials and the general public about SARS-CoV-2 transmission dynamics within the MCH population.
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BACKGROUND: American trypanosomiasis, commonly referred to as Chagas disease, is caused by a single cell protozoan known as Trypanosoma cruzi (T. cruzi). Although those affected are mainly in Latin America, Chagas has been detected in the United States (US), Canada and in many European countries due to migration. Few studies have explored the epidemiology of Chagas within the US or changes in disease burden over the past decade. The objective of this study was to explore the trends and associated characteristics for Chagas disease among hospitalized women of reproductive age in the US. METHODS: We analyzed admissions data including socio-demographic and hospital characteristics for inpatient hospitalization for women of reproductive age (15-49 years) in the US from 2002 through 2017. We employed Joinpoint regression analysis to determine trends in the prevalence of Chagas disease over this period. RESULTS: A total of 487 hospitalizations of Chagas disease were identified, corresponding to 3.7 per million hospitalizations over the study period. The rate statistically increased from 1.6 per million in 2002 to 7.6 per million hospitalizations in 2017. Chagas was most prevalent among older women, Hispanics and those in the highest zip income bracket. The in-hospital mortality rate was about 10 times greater among women with Chagas compared to those without the condition (3.1% versus 0.3%), and the condition tended to be clustered in women treated at large, urban teaching hospitals in the Northeastern region of the US. CONCLUSION: Chagas disease diagnosis appears to be increasing among hospitalized women of reproductive age in the US with a 10-fold elevated risk of mortality.
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Ionic liquid (IL), 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, [C2mim] [Tf2N], as a non-polar phase in conjunction with polar ethylene glycol (EG) forms microemulsions stabilized by surface active ionic liquids (SAILs), N-methyl-N-alkylimidazolium chlorides, [Cnmim] [Cl], where nâ¯=â¯8, 12 and 16 in conjunction with decanol as co-surfactant. The phase behaviour of the ternary systems has been investigated and three regions of microemulsions - polar-in-ionic liquid, bicontinuous and ionic liquid-in-polar, have been identified using electrical conductivity measurements. The effect of alkyl chain length on the phase behavior has been discussed in detail. The one-phase microemulsion region is found to decrease with the increase in the alkyl chain length of the SAILs. The microstructural characteristics have been investigated by using FTIR and NMR spectroscopy. The micropolarity of reverse micelles present in the microemulsions has been investigated using UV-Vis spectroscopy employing methyl orange as a polarity probe. The dynamics of solvent relaxation in microemulsions have been investigated by steady-state and time-resolved fluorescence spectroscopy using coumarin 153 (C-153) as fluorescence probe at different compositions of microemulsions. The dynamic light scattering measurements (DLS) reveals the expansion of reverse micelles formed by [Cnmim][Cl] in non polar [C2mim] [Tf2N] upon the addition of polar component. Interestingly, the microemulsions have been found to be thermally stable in a wide temperature range as revealed from temperature dependence UV-Vis, fluorescence and DLS measurements.