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  • Discovery of New Catalytic Topoisomerase II Inhibitors for Anticancer Therapeutics

    Matias-Barrios, Victor M; Radaeva, Mariia; Song, Yi; Alperstein, Zaccary; Lee, Ahn R; Schmitt, Veronika; Lee, Joseph; Ban, Fuqiang; Xie, Ning; Qi, Jianfei; et al. (Frontiers Media S.A., 2021-02-01)
  • The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons

    Hossain Saad, Md Zubayer; Xiang, Liuruimin; Liao, Yan-Shin; Reznikov, Leah R; Du, Jianyang (Frontiers Media S.A., 2021-02-02)
    Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its binding sites in the pore region. We demonstrated that external protons block TRPM3 with an inhibitory pH50 of 5.5. whereas internal protons inhibit TRPM3 with an inhibitory pH50 of 6.9. We identified three titratable residues, D1059, D1062, and D1073, at the vestibule of the channel pore that contributes to pH sensitivity. The mutation of D1073Q reduced TRPM3 current by low external pH 5.5 from 62 ± 3% in wildtype to 25 ± 6.0% in D1073Q mutant. These results indicate that D1073 is essential for pH sensitivity. In addition, we found that a single mutation of D1059 or D1062 enhanced pH sensitivity. In summary, our findings identify molecular determinants respionsible for the pH regulation of TRPM3. The inhibition of TRPM3 by protons may indicate an endogenous mechanism governing TRPM3 gating and its physiological/pathological functions.
  • Physicochemical Effects of Niobic Acid Addition Into Dental Adhesives

    Garcia, Isadora Martini; Leitune, Vicente Castelo Branco; Balbinot, Gabrielade Souza; Balhaddad, Abdul Rahman A.; Melo, Mary Anne S.; Samuel, Susana Maria Werner; Collares, Fabrício Mezzomo (Frontiers Media S.A., 2021-02-02)
    The incorporation of metallic oxides in dental adhesives has been a strategy to confer improved radiopacity and physicochemical properties for polymers. Tailoring the structure of these fillers could contribute to their application in therapeutic strategies for dental restorations. The aim of this study was to evaluate the incorporation of niobic acid into experimental dental adhesives, and compare these adhesives to niobium pentoxide containing adhesives. A control group without Nb2O5·n H2O or Nb2O5 was also used for comparison. Niobium-based particles have been used as a feasible approach, mainly because of their bioactivity. In this study, hydrated niobium pentoxide, also called niobic acid (Nb2O5·n H2O), was incorporated into an experimental dental adhesive as a potential catalyst for monomer conversion. A base resin for dental adhesive was formulated with methacrylate monomers and photoinitiators. Two types of oxides were tested as filler for this adhesive: Nb2O5·n H2O or niobium pentoxide (Nb2O5). Both fillers were added separately into the experimental adhesive at 0, 2.5, 5, and 10 wt.%. One group without Nb2O5·n H2O or Nb2O5 (0 wt.% of filler addition) was used as a control group. The formulated materials were analyzed for radiopacity according to the ISO 4049 and used FTIR analysis to assess the degree of conversion (DC) and the maximum polymerization rate (RPmax). Mechanical properties were analyzed by ultimate tensile strength (UTS) in a testing machine. Softening in solvent was conducted by measuring Knoop microhardness before and after immersion of samples in ethanol. Normality of data was assessed with Shapiro-Wilk, and comparisons between factors were conducted with two-way ANOVA and Tukey at 5% of significance. Both fillers, Nb2O5 or Nb2O5·n H2O, increased the radiopacity of dental adhesives in comparison to the unfilled adhesive (p < 0.05). There were no differences among groups for the ultimate tensile strength (p > 0.05), and all groups containing Nb2O5 or Nb2O5·n H2O improved the resistance against softening in solvent (p < 0.05). The groups with 5 and 10 wt% addition of Nb2O5 showed decreased DC compared to the control group (p < 0.05), while the addition of Nb2O5·nH2O up to 10 wt% did not alter the DC (p > 0.05). The polymerization rate did not change among groups (p > 0.05). In conclusion, Nb2O5·n H2O is a promising filler to be incorporated into dental adhesives providing proper mechanical properties, improved resistance against solvents, and increased radiopacity, without changing the DC. © Copyright © 2021 Garcia, Leitune, Balbinot, Balhaddad, Melo, Samuel and Collares.
  • Non-cannabinoid metabolites of cannabis sativa l. With therapeutic potential

    Lowe, Henry; Steele, Blair; Bryant, Joseph; Toyang, Ngeh; Ngwa, Wilfred (MDPI AG, 2021-02-20)
    The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites—∆9-tetrahydrocannabinol (∆9-THC) and cannabidiol (CBD). Both ∆9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed. © 2021 by the authors.
  • A Brief Update on the Effect of the COVID-19 Pandemic on Hip and Knee Arthroplasty Patients in the United States: A Multicenter Update to a Previous Survey Study of Patients Postponed by the Pandemic

    Brown, Timothy S; Bedard, Nicholas A; Rojas, Edward O; Anthony, Christopher A; Schwarzkopf, Ran; Stambough, Jeffrey B; Nandi, Sumon; Prieto, Hernan; Parvizi, Javad; Bini, Stefano A; et al. (Elsevier Inc., 2020-12-03)
    Background: In March 2020, elective total hip and knee arthroplasty (THA and TKA) were suspended across the United States in response to the COVID-19 pandemic. We had previously published the results of a survey to the affected patients from 6 institutions. We now present the results of a larger distribution of this survey, through May and June 2020, to electively scheduled patients representing different regions of the United States. Methods: Fifteen centers identified through the American Association of Hip and Knee Surgeons Research Committee participated in a survey study of THA and TKA patients. Patients scheduled for primary elective THA or TKA but canceled due to the COVID-19 elective surgery stoppage (3/2020-5/2020) were included in the study. Descriptive statistics along with subgroup analysis with Wilcoxon rank were performed. Results: In total, surveys were distributed to 2135 patients and completed by 848 patients (40%) from 15 institutions. Most patients (728/848, 86%) had their surgery postponed or canceled by the surgeon or hospital. Unknown length of surgical delay remained the highest source of anxiety among survey participants. Male patients were more likely to be willing to proceed with surgery in spite of COVID-19. There were minimal regional differences in responses. Only 61 patients (7%) stated they will continue to delay surgery for fear of contracting COVID-19 while in the hospital. Conclusion: Similar to the previous study, the most anxiety-provoking thought was the uncertainty, over if and when the canceled joint replacement surgery could be rescheduled. Patients suffering from the daily pain of hip and knee arthritis who have been scheduled for elective arthroplasty remain eager to have their operation as soon as elective surgery is allowed to resume.
  • Characterization and implications of the initial estimated glomerular filtration rate 'dip' upon sodium-glucose cotransporter-2 inhibition with empagliflozin in the EMPA-REG OUTCOME trial

    Kraus, Bettina J; Weir, Matthew R; Bakris, George L; Mattheus, Michaela; Cherney, David Z I; Sattar, Naveed; Heerspink, Hiddo J L; Ritter, Ivana; von Eynatten, Maximilian; Zinman, Bernard; et al. (Elsevier B.V., 2020-11-10)
    Treatment with sodium-glucose co-transporter-2 inhibitors induces an initial 3-5 ml/min/1.73 m2 decline in estimated glomerular filtration rate (eGFR). Although considered to be of hemodynamic origin and largely reversible, this 'eGFR dip' may cause concern in clinical practice, which highlights the need to better understand its incidence and clinical implications. In this post hoc analysis of the EMPA-REG OUTCOME trial, 6,668 participants randomized to empagliflozin 10 mg, 25 mg or placebo with eGFR available at baseline and week four were categorized by initial eGFR change into three groups; over 10% decline ('eGFR dipper'), over 0 and up to 10% decline ('eGFR intermediate'), no eGFR decline ('eGFR non-dipper'). Baseline characteristics of 'eGFR intermediate' and 'eGFR non-dipper' were generally comparable. An initial 'eGFR dip' was observed in 28.3% of empagliflozin versus 13.4% of placebo-treated participants; odds ratio 2.7 [95% Confidence Interval 2.3-3.0]. In multivariate logistic regression, diuretic use and higher KDIGO risk category at baseline were independently predictive of an 'eGFR dip' in empagliflozin versus placebo. Safety and beneficial treatment effects with empagliflozin on cardiovascular and kidney outcomes were consistent across subgroups based on these predictive factors. The initial 'eGFR dip' did not have a major impact on the treatment effect of empagliflozin on subsequent cardiovascular death, hospitalization for heart failure, and incident or worsening kidney disease. Thus, patients with type 2 diabetes with more advanced kidney disease and/or on diuretic therapy were more likely to experience an 'eGFR dip' of over 10% with empagliflozin, but reduction in cardiovascular and kidney outcomes was not relevantly modified by such 'eGFR dip.'
  • Providing Ancillary Care in Clinical Research: A Case of Diffuse Large B-Cell Lymphoma during a Malaria Vaccine Trial in Equatorial Guinea

    Manock, Stephen R; Mtoro, Ali; Urbano Nsue Ndong, Vicente; Olotu, Ally; Chemba, Mwajuma; Sama Roca, Antonio E; Eburi, Esther; García, Guillermo A; Cortes Falla, Carlos; Niemczura de Carvalho, Julie; et al. (American Society of Tropical Medicine and Hygiene, 2020-11-23)
    Providing medical care for participants in clinical trials in resource-limited settings can be challenging and costly. Evaluation and treatment of a young man who developed cervical lymphadenopathy during a malaria vaccine trial in Equatorial Guinea required concerted efforts of a multinational, multidisciplinary team. Once a diagnosis of diffuse large B-cell lymphoma was made, the patient was taken to India to receive immunochemotherapy. This case demonstrates how high-quality medical care was provided for a serious illness that occurred during a trial that was conducted in a setting in which positron emission tomography for diagnostic staging, an oncologist for supervision of treatment, and an optimal therapeutic intervention were not available. Clinical researchers should anticipate the occurrence of medical conditions among study subjects, clearly delineate the extent to which health care will be provided, and set aside funds commensurate with those commitments.
  • Effect of SARS-CoV-2 infection in pregnancy on maternal and neonatal outcomes in Africa: An AFREhealth call for evidence through multicountry research collaboration

    Nachega, Jean B.; Sam-Agudu, Nadia A.; Budhram, Samantha; Taha, Taha E.; Vannevel, Valerie; Somapillay, Priya; Ishoso, Daniel Katuashi; Pipo, Michel Tshiasuma; Nswe, Christian Bongo Pasi; Ditekemena, John; et al. (American Society of Tropical Medicine and Hygiene, 2021-02-01)
    In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health's COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa.
  • Delayed stroke after hospitalization for coronavirus disease 2019 pneumonia from common and internal carotid artery thrombosis

    Hosseini, Motahar; Sahajwani, Sunny; Zhang, Jackie; Toursavadkohi, Shahab; Ucuzian, Areck A (Society for Vascular Surgery, 2020-11-10)
    Large vessel arterial thrombosis has been reported to complicate a subset of cases of coronavirus disease 2019 (COVID-19). Thrombosis of the extracranial carotid arterial system can lead to devastating stroke in some patients with COVID-19. We have presented the case of a patient previously hospitalized with COVID-19 for oxygen supplementation who had presented after discharge with delayed stroke from a right common carotid artery and internal carotid artery thrombosis. The thrombotic occlusion resolved with antithrombotic medications and no invasive intervention. The present report highlights the complicated and heterogeneous nature of COVID-19 and provides one approach to managing the devastating complication of stroke from carotid arterial thrombosis. © 2020 The Authors
  • Reply to Herbrecht and Colleagues.

    Baddley, John W; Morrissey, C Orla; Shaefer-Prokop, Cornelia; Chen, Sharon C-A; Pappas, Peter G; Donnelly, J Peter (Oxford University Press, 2020-03-02)
  • Prevalence and sociodemographic correlates of anogenital Human Papillomavirus (HPV) carriage in a cross-sectional, multi-ethnic, community-based Asian male population.

    Khoo, Su Pei; Shafii, Mohd Khairul Anwar; Bhoo-Pathy, Nirmala; Yap, Siew Hwei; Subramaniam, Shridevi; Nasir, Nazrila Hairizan; Lin, Zhang; Belinson, Jerome; Goh, Pik Pin; Qu, Xinfeng; et al. (Public Library of Science, 2021-01-20)
    Background Addressing the burden of HPV-associated diseases among men is increasingly becoming a public health issue. The main objective of this study was to determine HPV prevalence among a healthy community-based Malaysian men. Method This was a cross-sectional study that recruited 503 healthy males from 3 community-based clinics in Selangor, Malaysia. Genital and anal samples were collected from each participant for 14 high risk and 2 low risk HPV DNA detection and genotyping. All participants responded to a set of detailed sociodemographic and sexual behaviour questionnaire. Results The median age at enrolment was 40 years old (IQR: 31–50). The anogenital HPV6/11 prevalence was 3.2% whereas high risk HPV prevalence was 27.1%. The genital HPV prevalence for HPV6/11 was 2.9% while high risk HPV was 18.8%. HPV6/11 prevalence in the anal canal was 1.6% and high risk HPV was 12.7%. HPV 18 was the most prevalent genotype detected in the anogenital area. There was a significant independent association between genital and anal HPV infections. Conclusion Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.
  • Unusual Myoid Differentiation in a Canine Benign Mixed Mammary Tumour.

    Brunetti, Barbara; Muscatello, Luisa Vera; DeTolla, Louis J; Avallone, Giancarlo (Hindawi Ltd, 2021-01-23)
    This report describes an unusual mesenchymal differentiation in a canine benign mixed mammary tumour. A 13-year-old crossbreed female dog was submitted to surgery to remove an inguinal mammary nodule. The tumour was composed of mammary epithelium and mesenchymal populations, not only of cartilage and bone but also of myoid cells. PTAH demonstrated cross striation of striated muscle, and immunohistochemistry highlighted striated muscle expressing desmin and calponin, and smooth muscle expressing desmin, SMA, and calponin. The tumour was diagnosed as a benign mixed tumour with leio- and rhabdomyoid differentiation. There was no tumour recurrence after one year of clinical follow-up. In conclusion, the well-differentiated features of leiomyocytes and rhabdomyocytes and the growth pattern define the benign origin of the mesenchymal component, which has been confirmed by a benign outcome; therefore, the knowledge of this kind of differentiation is helpful to avoid misdiagnoses. © 2021 Barbara Brunetti et al.
  • A Severe Course of Relapsing-Remitting Acute-Onset Chronic Inflammatory Demyelinating Polyneuropathy in a Young Man

    Patnaik, Anna P.; Mininni, Joseph; Porter, Neil C.; Morris, Nicholas A. (S. Karger AG, 2021-01-01)
    Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is an immune mediated neuropathy characterized by progressive weakness and sensory impairment lasting over 2 months. Guillain-Barré-Strohl syndrome (GBS) is an immune mediated polyneuropathy with a similar presentation often over less than 4 weeks. While some have argued for the existence of recurrent GBS, most classify the syndrome as a form of relapsing-remitting CIDP. However, there are cases of GBS with treatment-related fluctuations that must be distinguished from A-CIDP as patients with A-CIDP require long-term immunotherapy. In this case report, we discuss a patient with multiple relapses over 3 years, who is more likely to have A-CIDP. His ganglioside profile, which has rarely been reported in A-CIDP, included high concentrations of anti-GM1, anti-GD1a, and anti-GD1b antibodies, which may account for his severe disease course. © 2021 S. Karger AG. All rights reserved.
  • Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

    Baden, Lindsey R; El Sahly, Hana M; Essink, Brandon; Kotloff, Karen; Frey, Sharon; Novak, Rick; Diemert, David; Spector, Stephen A; Rouphael, Nadine; Creech, C Buddy; et al. (Massachusetts Medical Society, 2020-12-30)
    BACKGROUND Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. METHODS This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. RESULTS The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups. CONCLUSIONS The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified.
  • The microRNA-195 - BDNF pathway and cognitive deficits in schizophrenia patients with minimal antipsychotic medication exposure.

    Pan, Shujuan; Feng, Wei; Li, Yanli; Huang, Junchao; Chen, Song; Cui, Yimin; Tian, Baopeng; Tan, Shuping; Wang, Zhiren; Yao, Shangwu; et al. (Springer Nature, 2021-02-08)
    Cognitive impairment is a core characteristic of schizophrenia, but its underlying neural mechanisms remain poorly understood. Reduced brain-derived neurotrophic factor (BDNF), a protein critical for neural plasticity and synaptic signaling, is one of the few molecules consistently associated with cognitive deficits in schizophrenia although the etiological pathway leading to BDNF reduction in schizophrenia is unclear. We examined microRNA-195 (miR-195), a known modulator of BDNF protein expression, as a potential mechanistic component. One-hundred and eighteen first-episode patients with schizophrenia either antipsychotic medication-naïve or within two weeks of antipsychotic medication exposure and forty-seven age- and sex-matched healthy controls were enrolled. MiR-195 and BDNF mRNA and BDNF protein levels in peripheral blood were tested. Cognitive function was assessed using the MATRICS Consensus Cognitive Battery (MCCB). MiR-195 was significantly higher (p = 0.01) whereas BDNF mRNA (p < 0.001) and protein (p = 0.016) levels were significantly lower in patients compared with controls. Higher miR-195 expression was significantly correlated to lower BDNF protein levels in patients (partial r = −0.28, p = 0.003) and lower BDNF protein levels were significantly associated with poorer overall cognitive performance by MCCB and also in speed of processing, working memory, and attention/vigilance domains composite score (p = 0.002–0.004). The subgroup of patients with high miR-195 and low BDNF protein showed the lowest level of cognitive functions, and miR-195 showed significant mediation effects on cognitive functions through BDNF protein. Elevated miR-195 may play a role in regulating BDNF protein expression thereby influencing cognitive impairments in schizophrenia, suggesting that development of cognition enhancing treatment for schizophrenia may consider a micro-RNA based strategy. © 2021, The Author(s).
  • Antiviral Activity of Jamaican Medicinal Plants and Isolated Bioactive Compounds.

    Lowe, Henry; Steele, Blair; Bryant, Joseph; Fouad, Emadelden; Toyang, Ngeh; Ngwa, Wilfred (MDPI AG, 2021-01-25)
    Plants have had historical significance in medicine since the beginning of civilization. The oldest medical pharmacopeias of the African, Arabian, and Asian countries solely utilize plants and herbs to treat pain, oral diseases, skin diseases, microbial infections, multiple types of cancers, reproductive disorders among a myriad of other ailments. The World Health Organization (WHO) estimates that over 65% of the world population solely utilize botanical preparations as medicine. Due to the abundance of plants, plant-derived medicines are more readily accessible, affordable, convenient, and have safer side-effect profiles than synthetic drugs. Plant-based decoctions have been a significant part of Jamaican traditional folklore medicine. Jamaica is of particular interest because it has approximately 52% of the established medicinal plants that exist on earth. This makes the island particularly welcoming for rigorous scientific research on the medicinal value of plants and the development of phytomedicine thereof. Viral infections caused by the human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), hepatitis virus B and C, influenza A virus, and the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) present a significant global burden. This is a review of some important Jamaican medicinal plants, with particular reference to their antiviral activity.
  • To Screen or Not to Screen for Carotid Stenosis: Is That the Question?

    Chaturvedi, Seemant (American Medical Association, 2021-02-02)
  • Global prevalence of hepatitis C virus in women of childbearing age in 2019: a modelling study

    Dugan, Ellen; Blach, Sarah; Biondi, Mia; Cai, Zongzhen; DePaola, Mindi; Estes, Chris; Feld, Jordan; Gamkrelidze, Ivane; Kottilil, Shyamasundaran; Ma, Siya; et al. (Elsevier Ltd., 2021-03-01)
    Background: Treatment for infection with hepatitis C virus (HCV) during pregnancy has not yet been approved; however, interventions specifically targeting women, especially those of childbearing age (15–49 years), could prevent vertical transmission and community spread. To assess the impact of such interventions, improved prevalence estimates in this group are needed. We aimed to estimate the global prevalence of viraemic HCV in 2019 among women of childbearing age. Methods: In this modelling study, we used previously developed models for 110 countries inputted with country-specific demographic and HCV epidemiology data. We did a literature review, searching PubMed, Embase, and grey literature for studies published between Jan 1, 2000, and June 30, 2018, reporting HCV antibody or viraemic prevalence in women of childbearing age. Studies from the literature review and studies in models were compared by use of a data quality scoring system and models were updated, as appropriate, when a better study was identified. We used these HCV disease burden models to calculate the 2019 prevalence of viraemic HCV in women of childbearing age. In countries without a model, prevalence was extrapolated by Global Burden of Disease (GBD) region. Findings: An estimated 14 860 000 (95% uncertainty interval [UI] 9 667 000–18 282 000) women aged 15–49 years had HCV infection worldwide in 2019, corresponding to a viraemic prevalence of 0·78% (95% UI 0·62–0·86). Globally, HCV prevalence increased with age, rising from 0·25% (95% UI 0·20–0·27) in women aged 15–19 years to 1·21% (0·97–1·34) in women aged 45–49 years. China (16% of total infections) and Pakistan (15%) had the greatest numbers of viraemic infections, but viraemic prevalence was highest in Mongolia (5·14%, 95% CI 3·46–6·28) and Burundi (4·91%, 3·80–18·75). Of the countries with 500 cases or more, viraemic prevalence was lowest in Chile (0·07%, 95% UI 0·04–0·12). Among the GBD regions, eastern Europe had the highest viraemic prevalence (3·39%, 95% UI 1·88–3·54). By WHO region, the Eastern Mediterranean region had the highest viraemic prevalence (1·75%, 95% UI 1·26– 1·90). Interpretation: Most research on HCV disease burden among women aged 15–49 years focuses on pregnant women. Using modelling, this analysis provides global and national estimates of HCV prevalence in all women of childbearing age. These data can inform preconception test-and-treat strategies to reduce vertical transmission and total disease burden. Funding: Gilead Sciences, John C Martin Foundation, private donors.
  • Lipid tethering of breast tumor cells reduces cell aggregation during mammosphere formation.

    Bhandary, Lekhana; Bailey, Patrick C; Chang, Katarina T; Underwood, Karen F; Lee, Cornell J; Whipple, Rebecca A; Jewell, Christopher M; Ory, Eleanor; Thompson, Keyata N; Ju, Julia A; et al. (Springer Nature, 2021-02-05)
    Mammosphere assays are widely used in vitro to identify prospective cancer-initiating stem cells that can propagate clonally to form spheres in free-floating conditions. However, the traditional mammosphere assay inevitably introduces cell aggregation that interferes with the measurement of true mammosphere forming efficiency. We developed a method to reduce tumor cell aggregation and increase the probability that the observed mammospheres formed are clonal in origin. Tethering individual tumor cells to lipid anchors prevents cell drift while maintaining free-floating characteristics. This enables real-time monitoring of single tumor cells as they divide to form mammospheres. Monitoring tethered breast cancer cells provided detailed size information that correlates directly to previously published single cell tracking data. We observed that 71% of the Day 7 spheres in lipid-coated wells were between 50 and 150 μm compared to only 37% in traditional low attachment plates. When an equal mixture of MCF7-GFP and MCF7-mCherry cells were seeded, 65% of the mammospheres in lipid-coated wells demonstrated single color expression whereas only 32% were single-colored in low attachment wells. These results indicate that using lipid tethering for mammosphere growth assays can reduce the confounding factor of cell aggregation and increase the formation of clonal mammospheres. © 2021, The Author(s).

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