Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase.

Despite the recent progress in the diagnosis of tuberculosis (TB), the chemotherapeutic management of TB continues to be challenging. Mycobacterium tuberculosis (Mtb), the etiological agent of TB, is classified as the 13th leading cause of death globally. In addition, 450,000 people were reported to develop multi-drug-resistant TB globally. The current project focuses on targeting methionine aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the excision of the N-terminal methionine (NME) during protein synthesis, allowing the enzyme to be an auspicious target for the development of novel therapeutic agents for the treatment of TB. Mtb possesses two MetAP1 isoforms, MtMetAP1a and MtMetAP1c, which are vital for Mtb viability and, hence, a promising chemotherapeutic target for Mtb therapy. In this study, we cloned and overexpressed recombinant MtMetAP1c. We investigated the in vitro inhibitory effect of the novel MetAP inhibitor, OJT008, on the cobalt ion- and nickel ion-activated MtMetAP1c, and the mechanism of action was elucidated through an in silico approach. The compound's potency against replicating and multi-drug-resistant (MDR) Mtb strains was also investigated. The induction of the overexpressed recombinant MtMetAP1c was optimized at 8 h with a final concentration of 1 mM Isopropyl ß-D-1-thiogalactopyranoside. The average yield from 1 L of Escherichia coli culture for MtMetAP1c was 4.65 mg. A preliminary MtMetAP1c metal dependency screen showed optimum activation with nickel and cobalt ions occurred at 100 µM. The half-maximal inhibitory concentration (IC50) values of OJT008 against MtMetAP1c activated with CoCl2 and NiCl2 were 11 µM and 40 µM, respectively. The in silico study showed OJT008 strongly binds to both metal-activated MtMetAP1c, as evidenced by strong molecular interactions and a higher binding score, thereby corroborating our result. This in silico study validated the pharmacophore's metal specificity. The potency of OJT008 against both active and MDR Mtb was <0.063 µg/mL. Our study reports OJT008 as an inhibitor of MtMetAP1c, which is potent at low micromolar concentrations against both active susceptible and MDR Mtb. These results suggest OJT008 is a potential lead compound for the development of novel small molecules for the therapeutic management of TB.

Racial Disparities in Preterm Birth among Pregnant Women with Obesity.

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.

Racial and Ethnic Disparities in Stillbirth among Pregnant Women with Obesity.

OBJECTIVE: The aim of this study was to examine the relationship between obesity and risk of stillbirth among pregnant women with obesity in the United States, with a focus on racial and ethnic disparities. STUDY DESIGN: We conducted a retrospective cross-sectional analysis of birth and fetal data from the 2014 to 2019 National Vital Statistics System (N = 14,938,384 total births) to examine associations between maternal body mass index (BMI) and risk of stillbirth. Cox's proportional hazards regression model was used to compute adjusted hazard ratios (HR) as a measure of risk of stillbirth in relation to maternal BMI. RESULTS: The stillbirth rate was 6.70 per 1,000 births among women with prepregnancy obesity, while the stillbirth rate among women with a normal (nonobese) prepregnancy BMI was 3.85 per 1,000 births. The risk of stillbirth was greater among women with obesity compared with women without obesity (HR: 1.39; 95% confidence interval [CI]: 1.37-1.41). Compared with non-Hispanic (NH) Whites, women identifying as NH-other (HR: 1.66; 95% CI: 1.61-1.72) and NH-Black (HR: 1.31; 95% CI: 1.26-1.35) were at higher risk of stillbirth, while Hispanic women had a decreased likelihood of stillbirth (HR: 0.38; 95% CI: 0.37-0.40). CONCLUSION: Obesity is a modifiable risk factor for stillbirth. Public health awareness campaigns and strategies targeting weight management in women of reproductive age and racial/ethnic populations at highest risk for stillbirth, are needed. KEY POINTS: · Stillbirth rates differ by race and ethnicity.. · Risk of stillbirth was greatest among women with obesity.. · Stillbirth rates rise with ascending prepregnancy BMI..

Inhibitory mechanism of clioquinol and its derivatives at the exopeptidase site of human angiotensin-converting enzyme-2 and receptor binding domain of SARS-CoV-2 viral spike.

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.

Impact of prophylactic antimalarials in pregnant women living with Human Immunodeficiency Virus on birth outcomes in Botswana.

OBJECTIVES: Until late 2015, Botswana recommended preventive treatment for pregnant women in malarial regions with chloroquine and proguanil (CP). The guideline change provided an opportunity to evaluate CP and adverse birth outcomes. METHODS: The Tsepamo Study performed birth outcomes surveillance at large delivery centres throughout Botswana. We evaluated adverse birth outcomes from 2015 to 2017 at three hospitals where 93% of CP use was recorded. Outcomes included neonatal death (NND), small for gestational age (SGA), very SGA, stillbirth (SB), preterm delivery (PTD) and very PTD. Logistic regression analysis (unadjusted and adjusted) was conducted for each adverse birth outcome. RESULTS: During the study period, 5883 (26%) of 23,033 deliveries were exposed to CP, with the majority (65%) in the most malaria-endemic region. At this site, there was a trend or an association between CP use and reduction of three adverse birth outcomes: PTD (aOR 0.85, 95% CI 0.76-0.96), vPTD (aOR 0.83, 95% CI 0.68-1.01) and NND (aOR 0.65, 95% CI 0.42-1.00). However, at the least malaria-endemic site, the association was in the opposite direction for SB (aOR 1.54, 95% CI 1.08-2.22), SGA (aOR 1.24, 95% CI 1.06-1.44) and vSGA (aOR 1.42, 95% CI 1.14-1.77). The association between CP and reduced PTD was present among women without HIV (aOR 0.77, 95% CI 0.67-0.89) but not among women with HIV (aOR 1.09, 95% CI 0.78-1.35). CONCLUSIONS: Antimalarial prophylaxis was associated with improved birth outcomes in the most malaria-endemic region of Botswana, but not elsewhere. This finding supports current WHO guidance to use prophylaxis strategies among pregnant women in highly malaria-endemic regions. Further studies of the risks and benefits of specific antimalarial regimens in pregnancy are warranted, particularly in areas with lower incidence of malaria.

A computational evaluation of structural stability of omicron and delta mutations of SARS-CoV-2 spike proteins and human ACE-2 interactions.

Several more infectious SARS-CoV-2 variants have emerged globally since SARS-CoV-2 pandemic and the discovery of the first D614G variant of SARS-CoV-2 spike proteins in 2020. Delta (B.1.617.2) and Omicron (B.1.1.529) variants have proven to be of major concern out of all the reported variants, considering their influence on the virus' transmissibility and severity. This study aimed at evaluating the impact of mutations on these two variants on stability and molecular interactions between the viral Spike protein and human angiotensin converting enzyme-2 (hACE-2). The spike proteins receptor binding domain (RBD) was docked with the hACE-2 using HADDOCK servers. To understand and establish the effects of the mutations on the structural stability and flexibility of the RBD-hACE-2 complex, molecular dynamic (MD) simulation of the docked complex was performed and evaluated. The findings from both molecular docking analysis and binding free energy showed that the Omicron (OM) variant has high receptiveness towards hACE-2 versus Delta variant (DT), thereby, responsible for its increase in transmission. The structural stability and flexibility evaluation of variants' systems showed that mutations on DT and OM variants disturbed the stability of either the spike protein or the RBD-hACE-2 complex, with DT variant having greater instability impact. This study, therefore, assumed this obvious instability observed in DT variant might be associated or responsible for the reported severity in DT variant disease over the OM variant disease. This study provides molecular insight into the effects of OM and DT variants on stability and interactions between SARS-CoV-2 protein and hACE-2.

HRSA-Funded MCH Pipeline Training Program: Advancing the MCH Pipeline and Workforce Through Research Collaborations.

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.

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results.

INTRODUCTION: The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from underrepresented minorities. We aimed to evaluate the success of this program based on three domains: (1) demographic characteristics, (2) academic and career development, and (3) attitudes towards the field of MCH and the training programs among graduates. METHODS: Three domains of success were determined through a collaborative effort between current program directors and the funding agency project officers. The survey with questions related to the three domains was distributed via an online platform to graduates from seven sites (one former site and six current sites). Data were analyzed and presented utilizing descriptive statistics. RESULTS: The survey was distributed to 550 graduates, 162 responded (37% response rate). Demographically, 78% were female, 54% were Black/African American, 22% were Latinx and 83% did not report any disability. Eighty percent of respondents applied to graduate/professional schools, 67% received admission. Graduates often continued to work in MCH fields (70%). Majority felt confident and knowledgeable in the field (89%) and agreed the faculty were supportive at their training sites (90%). CONCLUSION: The study highlights successes in recruiting from underrepresented minorities, particularly Black/African Americans and first-time college goers in the family into the MCH Pipeline Training Programs. Programs were successful in furthering academic and career development for most trainees. Attitudes towards MCH and the training programs were overwhelmingly positive. Continued support of these programs is critical in addressing health disparities and achieving health equity.

Metabolite Identification of a Novel Anti-Leishmanial Agent OJT007 in Rat Liver Microsomes Using LC-MS/MS.

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.

Inhibitory mechanism of Ambroxol and Bromhexine Hydrochlorides as potent blockers of molecular interaction between SARS-CoV-2 spike protein and human angiotensin-converting Enzyme-2.

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.

MCH Pipeline Training Program: Connecting with Academia to Build Capacity Through Mentoring.

INTRODUCTION: Efforts to recruit and retain diverse Maternal and Child Health (MCH) professionals are of paramount public health significance. Culturally congruent mentorship strategies are key to supporting a successful transition from undergraduate to graduate studies. METHODS: This mixed-method study evaluated a culturally congruent mentorship training used by one of the MCH Pipeline Training programs and described mentorship practices and lessons learned from the six MCH Pipeline programs. A retrospective pre-test post-test survey assessed mentorship competency skills following a mentoring workshop. All MCH Pipeline program leaders completed a questionnaire to elicit responses about mentoring training practices, mentor evaluation strategies, and lessons learned. RESULTS: Maternal and Child Health Pipeline Training Programs supported 1890 undergraduate scholars at universities and institutions nationally. Scholars at six MCH Pipeline Programs participated in MCH education and mentored experiential leadership opportunities in clinical practice, research, and public health education. Qualitative program-level mentor survey themes indicated the importance of creating a reflective space and building mentorship teams. Mean mentor self-assessed improvement in mentor competencies was 14.4 points, 95% CI [10.5, 18.3], p < .001 following completion of a mentoring training workshop implemented by one of the MCH Pipeline programs. DISCUSSION: The Health Resources and Services Administration's Maternal and Child Health Bureau recognized the need to support the development of the next generation of diverse MCH leaders. Pipeline programs that included mentoring workshops and building culturally congruent mentorship teams are two strategies to increase and retain diverse scholars in graduate school and leaders in the public health workforce.

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results.

INTRODUCTION: The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from underrepresented minorities. We aimed to evaluate the success of this program based on three domains: (1) demographic characteristics, (2) academic and career development, and (3) attitudes towards the field of MCH and the training programs among graduates. METHODS: Three domains of success were determined through a collaborative effort between current program directors and the funding agency project officers. The survey with questions related to the three domains was distributed via an online platform to graduates from seven sites (one former site and six current sites). Data were analyzed and presented utilizing descriptive statistics. RESULTS: The survey was distributed to 550 graduates, 162 responded (37% response rate). Demographically, 78% were female, 54% were Black/African American, 22% were Latinx and 83% did not report any disability. Eighty percent of respondents applied to graduate/professional schools, 67% received admission. Graduates often continued to work in MCH fields (70%). Majority felt confident and knowledgeable in the field (89%) and agreed the faculty were supportive at their training sites (90%). CONCLUSION: The study highlights successes in recruiting from underrepresented minorities, particularly Black/African Americans and first-time college goers in the family into the MCH Pipeline Training Programs. Programs were successful in furthering academic and career development for most trainees. Attitudes towards MCH and the training programs were overwhelmingly positive. Continued support of these programs is critical in addressing health disparities and achieving health equity.

Diabetes in pregnancy and risk of near-miss, maternal mortality and foetal outcomes in the USA: a retrospective cross-sectional analysis.

BACKGROUND: The prevalence of diabetes in pregnant women has increased in the USA over recent decades. The primary aim of this study was to assess the association between diabetes in pregnancy and maternal near-miss incident, maternal mortality and selected adverse foetal outcomes. METHODS: We conducted a retrospective, cross-sectional analysis among pregnancy-related hospitalizations in USA between 2002 and 2014. We examined the association between DM and GDM as exposures and maternal in-hospital mortality, maternal cardiac arrest, early onset of delivery, poor foetal growth and stillbirth as the outcome variables. RESULTS: Among the 57.3 million pregnant women in the study population, the prevalence of GDM and DM was 5.4 and 1.3%, respectively. We found that pregnant women with DM were three times more likely to experience cardiac arrest (OR = 3.21; 95% CI = 2.57-4.01) and in-hospital maternal death (OR = 3.05; 95% CI = 2.45-3.79), as compared to those without DM. Among pregnant women with GDM and DM, the risk for early onset of delivery was higher, compared to women without GDM or DM. CONCLUSION: A diagnosis of diabetes prior to pregnancy contributes significantly to the risk of maternal cardiac arrest, maternal mortality and adverse foetal outcomes.

Trends and Risk Factors for Leishmaniasis among Reproductive Aged Women in the United States.

BACKGROUND AND OBJECTIVE: Leishmaniasis, a neglected tropical disease, is endemic in several regions globally, but commonly regarded as a disease of travelers in the United States (US). The literature on leishmaniasis among hospitalized women in the US is very limited. The aim of this study was to explore trends and risk factors for leishmaniasis among hospitalized women of reproductive age within the US. METHODS: We analyzed hospital admissions data from the 2002-2017 Nationwide Inpatient Sample among women aged 15-49 years. We conducted descriptive statistics and bivariate analyses for factors associated with leishmaniasis. Utilizing logistic regression, we assessed the association between sociodemographic and hospital characteristics with leishmaniasis disease among hospitalized women of reproductive age in the US. Joinpoint regression was used to examine trends over time. RESULTS: We analyzed 131,529,239 hospitalizations; among these, 207 cases of leishmaniasis hospitalizations were identified, equivalent to an overall prevalence of 1.57 cases per million during the study period. The prevalence of leishmaniasis was greatest among older women of reproductive age (35-49 years), Hispanics, those with Medicare, and inpatient stay in large teaching hospitals in the Northeast of the US. Hispanic women experienced a statistically significant increased odds of leishmaniasis diagnosis (OR, 1.80; 95% CI, 1.19-4.06), compared to Non-Hispanic (NH) White women. Medicaid and Private Insurance appeared to serve as a protective factor in both unadjusted and adjusted models. We did not observe a statistically significant change in leishmaniasis rates over the study period. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Although the prevalence of leishmaniasis among women of reproductive age appears to be low in the US, some risk remains. Thus, appropriate educational, public health and policy initiatives are needed to increase clinical awareness and timely diagnosis/treatment of the disease.

A Framework for Protecting Pregnant Women in the Era of COVID-19 Pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for the coronavirus disease 2019 (COVID-19) pandemic, highlighted and compounded problems while posing new challenges for the pregnant population. Although individual organizations have provided disparate information, guidance, and updates on managing the pregnant population during the current COVID-19 pandemic, it is important to develop a collective model that highlights all the best practices needed to protect the pregnant population during the pandemic. To establish a standard for ensuring safety during the pandemic, we present a framework that describes best practices for the management of the pregnant population during the ongoing COVID-19 pandemic.

Development and Validation of a Sensitive, Specific and Reproducible UPLC-MS/MS Method for the Quantification of OJT007, A Novel Anti-Leishmanial Agent: Application to a Pharmacokinetic Study.

OJT007 is a methionine aminopeptidase 1 (MetAP1) inhibitor with potent anti-proliferative effects against Leishmania Major. In order to study its pharmacokinetics as a part of the drug development process, a sensitive, specific, and reproducible ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. Voriconazole was used as the internal standard to generate standard curves ranging from 5 to 1000 ng/mL. The separation was achieved using a UPLC system equipped with an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) with 0.1% formic acid in acetonitrile and 0.1% formic acid in water as the mobile phase under gradient elution at a flow rate of 0.4 mL/min. The mass analysis was performed with a 4000 QTRAP® mass spectrometer using multiple-ion reaction monitoring (MRM) in the positive mode, with the transition of m/z 325 → m/z 205 for OJT007 and m/z 350 → m/z 101 for voriconazole. The intra- and inter-day precision and accuracy were within ±15%. The mean extraction recovery and the matrix effect were 95.1% and 7.96%, respectively, suggesting no significant matrix interfering with the quantification of the drug in rat plasma. This study was successfully used for the pharmacokinetic evaluation of OJT007 using the rat as an animal model.

Discovery of Clioquinol and analogues as novel inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 infection, ACE2 and ACE2 - Spike protein interaction in vitro.

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.

The Global Alliance for Maternal and Child Health (GLAM): A Pioneer Organization for MCH Students.

Currently, there is an insufficient representation of racial/ethnic minority groups in the maternal and child health (MCH) workforce. A student-run outreach organization, the Global Alliance for Maternal and Child Health (GLAM), seeks to address this disparity by increasing the representation of racial/ethnic minority groups in MCH workforce. Founded by students at Texas Southern University in Houston, Texas, United States, GLAM, seeks to establish productive alliances and create programs that would help improve the well-being of mothers, infants, and children locally, nationally, and internationally by engaging an active cadre of students passionate about MCH. Through community outreach and global engagement using evidence-based strategies, GLAM is committed to the elimination of health disparities plaguing the MCH population.

Trends and Racial/Ethnic Disparities in the Rates of Pre-eclampsia by HIV Status in the US.

BACKGROUND: Preeclampsia and HIV account for a significant proportion of the global burden of disease and pose severe maternal-fetal risks. There is a dearth of literature regarding racial/ethnic disparities in preeclampsia associated with HIV/AIDS in the US. METHODS: We retrospectively analyzed data from the National Inpatient Sample (NIS) database from 2002 to 2015 on a cohort of hospitalized pregnant women with or without preeclampsia and HIV. Joinpoint regression models were used to identify trends in the rates of preeclampsia among pregnant women living with or without HIV, stratified by race/ethnicity over the study period. We also assessed the association between preeclampsia and various socio-demographic factors. RESULTS: We analyzed over 60 million pregnancy-related hospitalizations, of which 3665 had diagnoses of preeclampsia and HIV, corresponding to a rate of 0.61 per 10,000. There was an increasing trend in the diagnosis of preeclampsia among hospitalized, pregnant women without HIV across each racial/ethnic category. The highest prevalence of preeclampsia was among non-Hispanic (NH) Blacks, regardless of HIV status. CONCLUSION: The increase in rates of pre-eclampsia between 2002 and 2015 was mostly noted among pregnant women without HIV. Regardless of HIV status, NH-Blacks experienced the highest discharge prevalence of preeclampsia.

Racial/Ethnic Disparities in the Burden of HIV/Cervical Cancer Comorbidity and Related In-hospital Mortality in the USA.

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.