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1.
Am J Respir Crit Care Med ; 207(6): 693-703, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36457159

RESUMO

Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post-COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP-COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP-COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83-155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05-1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00-1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07-1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6-9.5), rising to 11.7% (95% CrI, 10.3-13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19-related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.


Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , Teorema de Bayes , Pulmão/diagnóstico por imagem , Hospitalização
2.
Nurs Outlook ; 71(2): 101907, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36623984

RESUMO

BACKGROUND: Lesbian, gay, bisexual, transgender, and queer plus (LGBTQ) people experience discrimination and health disparities compared to heterosexual cisgender people. Clinicians report discomfort and insufficient preparation for providing care to LGBTQ people and nursing has been slow to integrate LGBTQ health into curricula. PURPOSE: Conduct a systematic review to examine and critically appraise peer-reviewed literature on nursing student knowledge, skills, and attitudes (KSAs) regarding LGBTQ health and the development/evaluation of LGBTQ health content in nursing curricula. METHODS: A systematic review was conducted (N = 1275 articles from PubMed, LGBT Health, CINAHL, ERIC, and Health Source-Nursing/Academic Edition). FINDINGS: Twenty articles met inclusion criteria. Twelve studies described curricular interventions; however, there were few validated tools to evaluate content coverage or KSAs. Four themes emerged specific to LGBTQ health content inclusion. DISCUSSION: While an emerging science of LGBTQ nursing education has been identified, more work is needed to build and evaluate a comprehensive curricular approach for full programmatic integration of LGBTQ health. CONCLUSION: As nursing programs build LGBTQ content into nursing curricula, care must be taken to integrate this content fully with the depth of curricular content in population health, social determinants of health, social justice, intersectionality, cultural competence, and political advocacy. TWEETABLE ABSTRACT: Greater integration of LGBTQ health content into nursing education should be a priority for nursing education.


Assuntos
Educação em Enfermagem , Minorias Sexuais e de Gênero , Estudantes de Enfermagem , Feminino , Humanos , Comportamento Sexual , Educação de Pós-Graduação
3.
Nurs Outlook ; 71(3): 101950, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36924597

RESUMO

BACKGROUND: In the US, sexual and gender minority (SGM) individuals continue to experience health inequities, and nursing curricula content and nursing faculty with SGM health expertise in the US remain limited. Addressing health disparities begins with the preparation of future nurses-US nursing faculty must be supported to meet these growing needs. PURPOSE: To describe, appraise, and synthesize research from 2000-2020 on US nursing faculty knowledge, awareness, inclusion, and perceived importance of SGM health content. METHODS: Following PRISMA 2020 guidelines, we registered a systematic review and appraisal protocol in PROSPERO, and then executed the protocol and synthesized the literature. DISCUSSION: We found an empirical evidence base surrounding US nursing faculty and SGM health much more limited than expected. Only four cross-sectional, descriptive empirical articles fit the a priori inclusion criteria. The studies were of moderate quality at best and often relied on unvalidated or older measures. In general, the studies focused on examining characteristics of nursing programs, faculty comfort with content, faculty perceptions of content importance, and hours dedicated to content. CONCLUSION: Since the close of the review, new commentaries and editorials expanding the call for change in the US were published-the time for commentary has passed. It remains unclear whether US nursing faculty are adequately prepared to educate future nurses about SGM health issues-and an unprepared healthcare workforce is yet another barrier to SGM health equity. The evidence base supporting US nursing faculty development desperately needs more studies using rigorous methodologies.


Assuntos
Docentes de Enfermagem , Minorias Sexuais e de Gênero , Humanos , Estudos Transversais , Identidade de Gênero , Currículo
4.
Build Environ ; 240: 110422, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37251109

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, the virus that causes the coronavirus disease (COVID)-19, is primarily transmitted through respiratory droplets which linger in enclosed spaces, often exacerbated by HVAC systems. Although research to improve HVAC handling of SARS-CoV-2 is progressing, currently installed HVAC systems cause problems because they recirculate air and use ineffective filters against virus. This paper details the process of developing a novel method of eliminating air pollutants and suspended pathogens in enclosed spaces using Photocatalytic Oxidation (PCO) technology. It has been previously employed to remove organic contaminants and compounds from air streams using the irradiation of titanium dioxide (TiO2) surfaces with ultraviolet (UV) lights causing the disintegration of organic compounds by reactions with oxygen (O) and hydroxyl radicals (OH). The outcome was two functional prototypes that demonstrate the operation of PCO-based air purification principle. These prototypes comprise a novel TiO2 coated fibre mop system, which provide very large surface area for UV irradiation. Four commercially accessible materials were used for the construction of the mop: Tampico, Brass, Coco, and Natural synthetic. Two types of UV lights were used: 365 nm (UVA) and 270 nm (UVC). A series of tests were conducted that proved the prototype's functionality and its efficiency in lowering volatile organic compounds (VOCs) and formaldehyde (HCHO). The results shown that a MopFan with rotary mop constructed with Coco fibres and utilising UVC light achieves the best VOC and HCHO purification performance. Within 2 h, this combination lowered HCHO by 50% and VOCs by 23% approximately.

5.
Nurs Outlook ; 70(3): 513-524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35430056

RESUMO

BACKGROUND: Lesbian, gay, bisexual, transgender and queer (LGBTQ) people, also commonly referred to as sexual and gender minorities (SGMs), live in every part of the United States and encompass all races and/or ethnicities, religions, and social classes. Major reports from various sources document higher rates of health issues (e.g., substance abuse, depression, suicidality, cardiovascular disease) among SGMs than heterosexuals. Chronic stress related to marginalization and discrimination is a key contributor to these disparities. The nursing profession has paid relatively little attention to SGM health issues. PURPOSE AND METHODS: To address these gaps, the first National Nursing LGBTQ Health Summit brought together nursing deans, leaders of national nursing organizations, and other participants from across the United States. FINDINGS: Participants agreed that increasing SGM-specific content in nursing curricula, practice guidelines, faculty development, and research is necessary to improve the health of SGM people. DISCUSSION: The Summit ended with a call to action for the nursing profession to prioritize SGM health through innovations in education, research, and practice.


Assuntos
Minorias Sexuais e de Gênero , Pessoas Transgênero , Currículo , Feminino , Identidade de Gênero , Humanos , Comportamento Sexual , Estados Unidos
6.
J Virol ; 94(21)2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32817221

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and has rapidly caused a pandemic, with over 20 million recorded COVID-19 cases in August 2020 (https://covid19.who.int/). There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA-approved drugs. Rapid development and human testing of potential antivirals is urgently needed. Numerous drugs are already approved for human use, and subsequently, there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). We found that 17 of these inhibit SARS-CoV-2 at non-cytotoxic concentrations. We directly followed up seven of these to demonstrate that all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found that both drugs protect mice from clinical disease.IMPORTANCE There are no FDA-approved antivirals for any coronavirus, including SARS-CoV-2. Numerous drugs are already approved for human use that may have antiviral activity and therefore could potentially be rapidly repurposed as antivirals. Here, we present data assessing the antiviral activity of 20 FDA-approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV in vitro We found that 17 of these inhibit SARS-CoV-2, suggesting that they may have pan-anti-coronaviral activity. We directly followed up seven of these and found that they all inhibit infectious-SARS-CoV-2 production. Moreover, we evaluated chloroquine and chlorpromazine in vivo using mouse-adapted SARS-CoV. We found that neither drug inhibited viral replication in the lungs, but both protected against clinical disease.


Assuntos
Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Células A549 , Animais , COVID-19 , Cloroquina/farmacologia , Clorpromazina/farmacologia , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Pandemias , SARS-CoV-2 , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration , Replicação Viral/efeitos dos fármacos , Tratamento Farmacológico da COVID-19
7.
Molecules ; 26(3)2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33498976

RESUMO

Molecular magnets attached to carbon nanotubes (CNT) are being studied as potential candidates for developing spintronic and quantum technologies. However, the functionalization routes used to develop these hybrid systems can drastically affect their respective physiochemical properties. Due to the complexity of this systems, little work has been directed at establishing the correlation between the degree of functionalization and the magnetic character. Here, we demonstrate the chemical functionalization degree associated with molecular magnet loading can be utilized for controlled tuning the magnetic properties of a CNT-lanthanide hybrid complex. CNT functionalization degree was evaluated by interpreting minor Raman phonon modes in relation to the controlled reaction conditions. These findings were exploited in attaching a rare-earth-based molecular magnet (Gd-DTPA) to the CNTs. Inductively coupled plasma mass spectrometry, time-of-flight secondary ion mass spectrometry and super conducting quantum interference device (SQUID) measurements were used to elucidate the variation of magnetic character across the samples. This controlled Gd-DTPA loading on the CNT surface has led to a significant change in the nanotube intrinsic diamagnetism, showing antiferromagnetic coupling with increase in the Weiss temperature with respect to increased loading. This indicates that synthesis of a highly correlated spin system for developing novel spintronic technologies can be realized through a carbon-based hybrid material.


Assuntos
Elementos da Série dos Lantanídeos/química , Imãs/química , Nanotubos de Carbono/química , Gadolínio DTPA/química , Fenômenos Magnéticos , Microscopia Eletrônica de Transmissão , Nanotubos de Carbono/ultraestrutura , Espectrometria de Massa de Íon Secundário , Análise Espectral Raman
8.
J Virol ; 91(12)2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28404843

RESUMO

Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses.IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection.


Assuntos
Receptores ErbB/metabolismo , Pulmão/patologia , Fibrose Pulmonar/virologia , Síndrome Respiratória Aguda Grave/metabolismo , Síndrome Respiratória Aguda Grave/patologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , Anfirregulina/administração & dosagem , Anfirregulina/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Pulmão/virologia , Camundongos , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia , Síndrome Respiratória Aguda Grave/virologia , Transdução de Sinais , Cicatrização/efeitos dos fármacos
9.
J Virol ; 91(2)2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27807241

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 and is a highly pathogenic respiratory virus. There are no treatment options against MERS-CoV for humans or animals, and there are no large-scale clinical trials for therapies against MERS-CoV. To address this need, we developed an inactivated rabies virus (RABV) that contains the MERS-CoV spike (S) protein expressed on its surface. Our initial recombinant vaccine, BNSP333-S, expresses a full-length wild-type MERS-CoV S protein; however, it showed significantly reduced viral titers compared to those of the parental RABV strain and only low-level incorporation of full-length MERS-CoV S into RABV particles. Therefore, we developed a RABV-MERS vector that contained the MERS-CoV S1 domain of the MERS-CoV S protein fused to the RABV G protein C terminus (BNSP333-S1). BNSP333-S1 grew to titers similar to those of the parental vaccine vector BNSP333, and the RABV G-MERS-CoV S1 fusion protein was efficiently expressed and incorporated into RABV particles. When we vaccinated mice, chemically inactivated BNSP333-S1 induced high-titer neutralizing antibodies. Next, we challenged both vaccinated mice and control mice with MERS-CoV after adenovirus transduction of the human dipeptidyl peptidase 4 (hDPP4) receptor and then analyzed the ability of mice to control MERS-CoV infection. Our results demonstrated that vaccinated mice were fully protected from the MERS-CoV challenge, as indicated by the significantly lower MERS-CoV titers and MERS-CoV and mRNA levels in challenged mice than those in unvaccinated controls. These data establish that an inactivated RABV-MERS S-based vaccine may be effective for use in animals and humans in areas where MERS-CoV is endemic. IMPORTANCE: Rabies virus-based vectors have been proven to be efficient dual vaccines against rabies and emergent infectious diseases such as Ebola virus. Here we show that inactivated rabies virus particles containing the MERS-CoV S1 protein induce potent immune responses against MERS-CoV and RABV. This novel vaccine is easy to produce and may be useful to protect target animals, such as camels, as well as humans from deadly MERS-CoV and RABV infections. Our results indicate that this vaccine approach can prevent disease, and the RABV-based vaccine platform may be a valuable tool for timely vaccine development against emerging infectious diseases.


Assuntos
Infecções por Coronavirus/imunologia , Proteção Cruzada/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Vírus da Raiva/imunologia , Raiva/imunologia , Vacinas Virais/imunologia , Animais , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Regulação Viral da Expressão Gênica , Humanos , Imunização , Camundongos , Interações Microbianas , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Raiva/prevenção & controle , Raiva/virologia , Vírus da Raiva/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Atenuadas , Vacinas Sintéticas , Proteínas Virais/genética , Proteínas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Virais/genética , Montagem de Vírus
10.
J Virol ; 91(1)2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27795435

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is an important emerging pathogen that was first described in 2012. While the cell surface receptor for MERS-CoV has been identified as dipeptidyl peptidase 4 (DPP4), the mouse DPP4 homologue does not allow virus entry into cells. Therefore, development of mouse models of MERS-CoV has been hampered by the fact that MERS-CoV does not replicate in commonly available mouse strains. We have previously described a mouse model in which mDPP4 was replaced with hDPP4 such that hDPP4 is expressed under the endogenous mDPP4 promoter. In this study, we used this mouse model to analyze the host response to MERS-CoV infection using immunological assays and transcriptome analysis. Depletion of CD4+ T cells, CD8+ T cells, or macrophages has no effect on MERS-CoV replication in the lungs of infected mice. However, we found that depletion of CD8+ T cells protects and depletion of macrophages exacerbates MERS-CoV-induced pathology and clinical symptoms of disease. Overall, we demonstrate an important role for the inflammatory response in regulating MERS-CoV pathogenesis in vivo IMPORTANCE: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic respiratory virus that emerged from zoonotic sources in 2012. Human infections are still occurring throughout Saudi Arabia at a 38% case fatality rate, with the potential for worldwide spread via air travel. In this work, we identify the host response to the virus and identify inflammatory pathways and cell populations that are critical for protection from severe lung disease. By understanding the immune response to MERS-CoV we can develop targeted therapies to inhibit pathogenesis in the future.


Assuntos
Linfócitos T CD8-Positivos/virologia , Infecções por Coronavirus/imunologia , Dipeptidil Peptidase 4/genética , Macrófagos/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Receptores Virais/genética , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Dipeptidil Peptidase 4/imunologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Pulmão/imunologia , Pulmão/virologia , Depleção Linfocítica , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Regiões Promotoras Genéticas , Receptores Virais/imunologia , Transcriptoma , Transgenes , Internalização do Vírus , Replicação Viral
11.
Proc Natl Acad Sci U S A ; 112(28): 8738-43, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-26124093

RESUMO

Traditional approaches to antimicrobial drug development are poorly suited to combatting the emergence of novel pathogens. Additionally, the lack of small animal models for these infections hinders the in vivo testing of potential therapeutics. Here we demonstrate the use of the VelocImmune technology (a mouse that expresses human antibody-variable heavy chains and κ light chains) alongside the VelociGene technology (which allows for rapid engineering of the mouse genome) to quickly develop and evaluate antibodies against an emerging viral disease. Specifically, we show the rapid generation of fully human neutralizing antibodies against the recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) and development of a humanized mouse model for MERS-CoV infection, which was used to demonstrate the therapeutic efficacy of the isolated antibodies. The VelocImmune and VelociGene technologies are powerful platforms that can be used to rapidly respond to emerging epidemics.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , Infecções por Coronavirus/terapia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Células HEK293 , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia
12.
Issues Ment Health Nurs ; 39(1): 46-52, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29333887

RESUMO

Little is known about abuse experienced among African American men who have sex with men (MSM) who are 50 years and older. A series of focus groups were conducted to examine perspectives of seropositive African American MSM age 50 years and older who reported experiencing some form of psychological or physical abuse. Thirty African American MSM were divided into four focus groups and four themes emerged: "Fear Being Gay," "No One Else to Love Me," "Nowhere to Turn," and "Sexual Risk & Control." The data suggest there is a need to develop culturally tailored interventions for this population.


Assuntos
Negro ou Afro-Americano/psicologia , Soropositividade para HIV/psicologia , Homossexualidade Masculina/etnologia , Homossexualidade Masculina/psicologia , Abuso Físico/etnologia , Idoso , Medo , Grupos Focais , Comportamentos de Risco à Saúde , Humanos , Solidão , Masculino , Pessoa de Meia-Idade , Abuso Físico/psicologia
13.
J Virol ; 90(19): 8924-33, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27466418

RESUMO

UNLABELLED: The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) cause significant morbidity and morality. There is currently no approved therapeutic for highly pathogenic coronaviruses, even as MERS-CoV is spreading throughout the Middle East. We previously screened a library of FDA-approved drugs for inhibitors of coronavirus replication in which we identified Abelson (Abl) kinase inhibitors, including the anticancer drug imatinib, as inhibitors of both SARS-CoV and MERS-CoV in vitro Here we show that the anti-CoV activity of imatinib occurs at the early stages of infection, after internalization and endosomal trafficking, by inhibiting fusion of the virions at the endosomal membrane. We specifically identified the imatinib target, Abelson tyrosine-protein kinase 2 (Abl2), as required for efficient SARS-CoV and MERS-CoV replication in vitro These data demonstrate that specific approved drugs can be characterized in vitro for their anticoronavirus activity and used to identify host proteins required for coronavirus replication. This type of study is an important step in the repurposing of approved drugs for treatment of emerging coronaviruses. IMPORTANCE: Both SARS-CoV and MERS-CoV are zoonotic infections, with bats as the primary source. The 2003 SARS-CoV outbreak began in Guangdong Province in China and spread to humans via civet cats and raccoon dogs in the wet markets before spreading to 37 countries. The virus caused 8,096 confirmed cases of SARS and 774 deaths (a case fatality rate of ∼10%). The MERS-CoV outbreak began in Saudi Arabia and has spread to 27 countries. MERS-CoV is believed to have emerged from bats and passed into humans via camels. The ongoing outbreak of MERS-CoV has resulted in 1,791 cases of MERS and 640 deaths (a case fatality rate of 36%). The emergence of SARS-CoV and MERS-CoV provides evidence that coronaviruses are currently spreading from zoonotic sources and can be highly pathogenic, causing serious morbidity and mortality in humans. Treatment of SARS-CoV and MERS-CoV infection is limited to providing supportive therapy consistent with any serious lung disease, as no specific drugs have been approved as therapeutics. Highly pathogenic coronaviruses are rare and appear to emerge and disappear within just a few years. Currently, MERS-CoV is still spreading, as new infections continue to be reported. The outbreaks of SARS-CoV and MERS-CoV and the continuing diagnosis of new MERS cases highlight the need for finding therapeutics for these diseases and potential future coronavirus outbreaks. Screening FDA-approved drugs streamlines the pipeline for this process, as these drugs have already been tested for safety in humans.


Assuntos
Antivirais/farmacologia , Mesilato de Imatinib/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Animais , Linhagem Celular , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia
14.
Appl Nurs Res ; 33: 138-141, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28096007

RESUMO

The primary aim of this descriptive correlational study was to determine which domains of health related quality of life (HRQOL) after controlling for demographic correlates predict depressive symptoms among N=70 seropositive African American men and women on Active Antiretroviral Therapy (ART). A demographic questionnaire, the Center for Epidemiological Studies Depression Scale (CESD-D), and the SF-36 Health Related Quality of Life (HRQOL) scale were administered. The regression analyses resulted in three models. The first model indicated that emotional well-being explained 38% of the variance in depressive symptoms (P=0.000) and in model two, emotional well-being and role limitations on emotional health explained 50% of the variance (P=0.000) and in the final and best fitting model emotional well-being, role limitations on emotional health and pain explained 53% of the variance in depressive symptoms (P=0.000) respectively. The findings underscore the need to explore the impact of HRQOL on mental health, and to also screen and treat seropositive African American men and women on (ART) for depressive symptoms.


Assuntos
Negro ou Afro-Americano , Depressão/etiologia , Infecções por HIV/fisiopatologia , Qualidade de Vida , Fármacos Anti-HIV/uso terapêutico , Depressão/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Humanos
15.
J Gerontol Nurs ; 43(12): 29-34, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28661541

RESUMO

The current article discusses the importance of implementing HIV and AIDS education, prevention, and intervention programs that are tailored to women 50 and older and to determine HIV risk factors for this population. A literature search was performed, resulting in 41 relevant articles. The literature underscored the significance of increasing awareness of HIV/AIDS, particularly among older women. HIV risk behaviors and the effect that these behaviors have on HIV transmission and prevention among women 50 and older are described. Prior research findings identified risk categories of older women that may contribute to the transmission of HIV among this particular population, including heterosexual relations, perceived HIV risk, ageism and HIV transmission, biological factors, transfusions, sexual enhancement aids, and health care providers and prevention messages. In addition, previous findings indicate that health care providers have not traditionally targeted women 50 and older for HIV prevention. Health care providers should incorporate discussion of HIV risk and transmission during clinic visits and implement prevention programs that target this population. [Journal of Gerontological Nursing, 43(12), 29-34.].


Assuntos
Infecções por HIV/prevenção & controle , Recursos Humanos de Enfermagem , Adulto , Idoso , Feminino , Infecções por HIV/fisiopatologia , Infecções por HIV/terapia , Humanos , Pessoa de Meia-Idade , Assunção de Riscos
16.
Issues Ment Health Nurs ; 38(6): 486-492, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28605244

RESUMO

It has nearly been more than three decades; yet, the research on aging seropositive African American men who have sex with men (MSM) is scarce. Exploring issues for an aging population of seropositive MSM is critical given that earlier epidemiological data suggested that by 2015, half of the AIDS cases will be in adults aged 50 years and older. A qualitative approach with the aim to examine perspectives about HIV risk from a group of seropositive African American MSM 50 years of age and older was conducted. Two separate focus groups with a total N  =  30 were conducted. Four themes emerged: feeling left out, no place to call home, not a priority, and no one to grow older with.


Assuntos
Atitude/etnologia , Negro ou Afro-Americano/psicologia , Infecções por HIV/etnologia , Infecções por HIV/psicologia , Homossexualidade Masculina/etnologia , Homossexualidade Masculina/psicologia , Fatores Etários , Idoso , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade
17.
J Virol ; 89(23): 11820-33, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26378163

RESUMO

UNLABELLED: Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PLPro), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2. IMPORTANCE: The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function.


Assuntos
Antígenos CD/fisiologia , Glicosilação , Fases de Leitura Aberta/genética , Síndrome Respiratória Aguda Grave/virologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia , Vírion/fisiologia , Ligação Viral , Animais , Chlorocebus aethiops , Cromatografia de Afinidade , Clonagem Molecular , Proteases 3C de Coronavírus , Cisteína Endopeptidases/genética , Primers do DNA/genética , Citometria de Fluxo , Proteínas Ligadas por GPI/fisiologia , Células HEK293 , Humanos , Imunoprecipitação , Microscopia Confocal , Microscopia Eletrônica , Fases de Leitura Aberta/fisiologia , RNA Polimerase Dependente de RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Vero , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética
18.
Arch Psychiatr Nurs ; 30(6): 736-739, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27888968

RESUMO

The purpose of this descriptive correlational study was to describe predictors of depressive symptoms among N=70 seropositive Botswana men and women residing in Gaborne, Botswana. A demographic questionnaire, the Center for Epidemiologic Studies Depression Scale, (CESD-D), and the SF-36 [Quality of life] were administered. The questionnaires were translated and back translated in Setswana and administered by Batswana men and women. The results of the regression analyses resulted in two calculated models. In the first Model energy/fatigue explained 46% of the variance in depressive symptoms (P=.000), and in the second Model energy/fatigue and role limitations on emotional well-being explained 50% of the variance in depressive symptoms respectively. The study findings underscore the need for mental health services for seropositive Batswana men and women.


Assuntos
Depressão/epidemiologia , Depressão/psicologia , Soropositividade para HIV , Adulto , Botsuana , Fadiga/etiologia , Feminino , Humanos , Masculino , Saúde Mental , Qualidade de Vida , Inquéritos e Questionários
19.
Issues Ment Health Nurs ; 37(10): 727-733, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27715353

RESUMO

The purpose of this study was to describe the correlates of condom use among a sample of N = 60 substance using seropositive men who have sex with (MSM). The mean age of the study participants was 52 ranging 50-75 years of age. Seventy-percent of study participants reporting smoking marijuana, 62% using cocaine, 25% heroin, 37% alcohol, and 30% amphetamines. Among those reporting substance use, 75% reported it was a hassle to use condoms, 42% indicated pleasure decreased with condom use, 72% indicated safer sex is boring, 72% reported the idea of using condoms is unappealing, 78% reported condoms ruined sex, and 71% said condoms interfered with romance. A multiple logistic regression analysis revealed low self-esteem, relationship status, attitudes towards condom use, and depression predicted condom use χ2 = 20.79, df = 6, ρ =.002. The study findings have implications for mental health nursing practice with seropositive African American MSM.


Assuntos
Preservativos , Infecções por HIV/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Homossexualidade Masculina/psicologia , Sexo Seguro , Transtornos Relacionados ao Uso de Substâncias/psicologia , Idoso , Humanos , Masculino , Serviços de Saúde Mental , Pessoa de Meia-Idade , Autoimagem
20.
J Virol ; 88(10): 5209-12, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24600003

RESUMO

The identification of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 reaffirmed the importance of understanding how coronaviruses emerge, infect, and cause disease. By comparing what is known about severe acute respiratory syndrome coronavirus (SARS-CoV) to what has recently been found for MERS-CoV, researchers are discovering similarities and differences that may be important for pathogenesis. Here we discuss what is known about each virus and what gaps remain in our understanding, especially concerning MERS-CoV.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Coronaviridae/isolamento & purificação , Infecções por Coronavirus/virologia , Pesquisa Biomédica/tendências , Coronaviridae/patogenicidade , Humanos
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