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1.
Int J Neonatal Screen ; 10(1)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38535125

RESUMO

Hemoglobinopathies are the commonest monogenic disorder worldwide, with approximately seven percent of the world population being carriers of hemoglobinopathies. The healthcare utilization impact of thalassemia has resulted in global public health initiatives to screen for hemoglobinopathies, especially sickle cell disease (SCD). The Iowa Newborn Screening Program (INSP) has been in place for more than 50 years with a primary focus on detecting SCD. Recent changes in migration patterns have led to a global distribution of hemoglobinopathies in the western world, which has translated to an increase in the diagnosis of SCD and the incidental detection of non-sickling hemoglobinopathies within the INSP. This study documents the birth prevalence of hemoglobinopathies diagnosed in newborns through the INSP and highlights the need for newborn screening programs to evolve to meet the healthcare needs of underserved, minority populations.

2.
Hum Vaccin Immunother ; 19(3): 2267295, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37885158

RESUMO

In the field of immunology, a systems biology approach is crucial to understanding the immune response to infection and vaccination considering the complex interplay between genetic, epigenetic, and environmental factors. Significant progress has been made in understanding the innate immune response, including cell players and critical signaling pathways, but many questions remain unanswered, including how the innate immune response dictates host/pathogen responses and responses to vaccines. To complicate things further, it is becoming increasingly clear that the innate immune response is not a linear pathway but is formed from complex networks and interactions. To further our understanding of the crosstalk and complexities, systems-level analyses and expanded experimental technologies are now needed. In this review, we discuss the most recent immunoprofiling techniques and discuss systems approaches to studying the global innate immune landscape which will inform on the development of personalized medicine and innovative vaccine strategies.


Assuntos
Vacinas , Imunidade Inata , Vacinação , Biologia de Sistemas
3.
Commun Biol ; 6(1): 188, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36805684

RESUMO

Herein, we studied the impact of empty LNP (eLNP), component of mRNA-based vaccine, on anti-viral pathways and immune function of cells from young and aged individuals. eLNP induced maturation of monocyte derived dendritic cells (MDDCs). We further show that eLNP upregulated CD40 and induced cytokine production in multiple DC subsets and monocytes. This coincided with phosphorylation of TANK binding kinase 1 (pTBK1) and interferon response factor 7 (pIRF7). In response to eLNP, healthy older adults (>65 yrs) have decreased CD40 expression, and IFN-γ output compared to young adults (<65 yrs). Additionally, cells from older adults have a dysregulated anti-viral signaling response to eLNP stimulation, measured by the defect in type I IFN production, and phagocytosis. Overall, our data show function of eLNP in eliciting DC maturation and innate immune signaling pathways that is impaired in older adults resulting in lower immune responses to SARS-CoV-2 mRNA-based vaccines.


Assuntos
COVID-19 , Adulto Jovem , Humanos , Idoso , SARS-CoV-2 , Células Apresentadoras de Antígenos , Antígenos CD40 , RNA Mensageiro
4.
Res Sq ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36380763

RESUMO

Despite the overwhelming success of mRNA-based vaccine in protecting against SARS-CoV-2 infection and reducing disease severity and hospitalization, little is known about the role lipid nanoparticles (LNP) play in initiating immune response. In this report we studied the adjuvantive impact of empty LNP with no mRNA cargo (eLNP) on anti-viral pathways and immune function of cells from young and aged individuals. We found that eLNP induced maturation of monocyte derived dendritic cells by measuring the expression of CD40, CD80, HLA-DR and production of cytokines including IFN-α,IL-6, IFN-γ, IL-12, and IL-21. Flow cytometry analysis of specific dendritic cell subsets showed that eLNP can induce CD40 expression and cytokine production in cDC1, cDC2 and monocytes. Empty LNP (eLNP) effects on dendritic cells and monocytes coincided with induction pIRF7 and pTBK1, which are both important in mitigating innate immune signaling. Interestingly our data show that in response to eLNP stimulus at 6 and 24 hrs, aged individuals have decreased CD40 expression and reduced IFN- γ output compared to young adults. Furthermore, we show that cDC1, cDC2, and CD14 dim CD16 + monocytes from healthy aged individuals have dysregulated anti-viral signaling response to eLNP stimulation as measured by the defect in type I IFN production, phosphorylation of IRF7, TBK-1, and immune function like phagocytosis. These data showed a novel function of eLNP in eliciting DC maturation and innate immune signaling pathways and that some of these functions are impaired in older individuals providing some suggestion of why older individuals (> 65 yrs of age) respond display lower immune responses and adverse events to SARS-CoV-2 mRNA-based vaccines.

5.
PeerJ ; 10: e13277, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573180

RESUMO

Importance: The rise of novel, more infectious SARS-CoV-2 variants has made clear the need to rapidly deploy large-scale testing for COVID-19 to protect public health. However, testing remains limited due to shortages of personal protective equipment (PPE), naso- and oropharyngeal swabs, and healthcare workers. Simple test methods are needed to enhance COVID-19 screening. Here, we describe a simple, and inexpensive spit-test for COVID-19 screening called Patient Self-Collection of Sample-CoV2 (PSCS-CoV2). Objective: To evaluate an affordable and convenient test for COVID-19. Methods: The collection method relies on deep throat sputum (DTS) self-collected by the subject without the use of swabs, and was hence termed the Self-Collection of Sample for SARS-CoV-2 (abbreviated PSCS-CoV2). We used a phenol-chloroform extraction method for the viral RNA. We then tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction with primers against at least two coding regions of the viral nucleocapsid protein (N1 and N2 or E) of SARS-CoV-2. We evaluted the sensitivity and specificity of our protocol. In addition we assess the limit of detection, and efficacy of our Viral Inactivating Solution. We also evaluated our protocol, and pooling strategy from volunteers on a local college campus. Results: We show that the PSCS-CoV2 method accurately identified 42 confirmed COVID-19 positives, which were confirmed through the nasopharyngeal swabbing method of an FDA approved testing facility. For samples negative for COVID-19, we show that the cycle threshold for N1, N2, and RP are similar between the PSCS-CoV2 and nasopharynx swab collection method (n = 30). We found a sensitivity of 100% (95% Confidence Interval [CI], 92-100) and specifity of 100% (95% CI, 89-100) for our PSCS-CoV2 method. We determined our protocol has a limit of detection of 1/10,000 for DTS from a COVID-19 patient. In addition, we show field data of the PSCS-CoV2 method on a college campus. Ten of the twelve volunteers (N1 < 30) that we tested as positive were subsequently tested positive by an independent laboratory. Finally, we show proof of concept of a pooling strategy to test for COVID-19, and recommend pool sizes of four if the positivity rate is less than 15%. Conclusion and Relevance: We developed a DTS-based protocol for COVID-19 testing with high sensitivity and specificity. This protocol can be used by non-debilitated adults without the assistance of another adult, or by non-debilitated children with the assistance of a parent or guardian. We also discuss pooling strategies based on estimated positivity rates to help conserve resources, time, and increase throughput. The PSCS-CoV2 method can be a key component of community-wide efforts to slow the spread of COVID-19.


Assuntos
COVID-19 , Adulto , Criança , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Teste para COVID-19 , Faringe , Escarro
6.
Geroscience ; 43(1): 31-51, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33569701

RESUMO

The SARS-CoV-2 pandemic has almost 56 million confirmed cases resulting in over 1.3 million deaths as of November 2020. This infection has proved more deadly to older adults (those >65 years of age) and those with immunocompromising conditions. The worldwide population aged 65 years and older is increasing, and the total number of aged individuals will outnumber those younger than 65 years by the year 2050. Aging is associated with a decline in immune function and chronic activation of inflammation that contributes to enhanced viral susceptibility and reduced responses to vaccination. Here we briefly review the pathogenicity of the virus, epidemiology and clinical response, and the underlying mechanisms of human aging in improving vaccination. We review current methods to improve vaccination in the older adults using novel vaccine platforms and adjuvant systems. We conclude by summarizing the existing clinical trials for a SARS-CoV-2 vaccine and discussing how to address the unique challenges for vaccine development presented with an aging immune system.


Assuntos
COVID-19 , Vacinas , Idoso , Envelhecimento , Vacinas contra COVID-19 , Humanos , SARS-CoV-2
7.
AIDS ; 27 Suppl 2: S169-77, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24361626

RESUMO

There is consensus on the benefits for all infants of exclusive breastfeeding for 6 months and introduction of appropriate complementary foods at 6 months, followed by continued breastfeeding. However, guidelines on infant and young child feeding (IYCF) for HIV-positive mothers have changed continually since 2000. This article explores issues and evidence related to IYCF for the prevention and care of paediatric HIV in resource-limited settings in light of new HIV treatment guidelines, implementation challenges and knowledge gaps.In 2010 the impact of antiretroviral drugs (ARVs) on reducing the risk of mother-to-child transmission of HIV moved WHO to urge countries to endorse either avoidance of all breastfeeding or exclusive breastfeeding for the first 6 months while taking ARVs, depending on which strategy could give their infants the greatest chance of HIV-free survival. Implementation of the 2010 recommendations is challenged by lack of healthcare provider training, weak clinic-community linkages to support mother/infant pairs and lack of national monitoring and reporting on infant feeding indicators.More evidence is needed to inform prevention and treatment of malnutrition among HIV-exposed and HIV-infected children. Knowledge gaps include the effects of prolonged ARV exposure, the cause of HIV-associated growth faltering, the effects of early infant testing on continuation of breastfeeding and specific nutrition interventions needed for HIV-infected children.Significant progress has been made toward keeping mothers alive and reducing paediatric HIV infection, but sustained political, financial and scientific commitment are required to ensure meaningful interventions to eliminate postnatal transmission and meet the nutritional needs of HIV-exposed and HIV-infected children.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Transtornos da Nutrição Infantil/prevenção & controle , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Alimentação com Mamadeira , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Contraindicações , Medicina Baseada em Evidências , Comportamento Alimentar , Feminino , Saúde Global , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/imunologia , Implementação de Plano de Saúde , Humanos , Lactente , Recém-Nascido , Estado Nutricional , Cuidado Pós-Natal/métodos , Cuidado Pós-Natal/normas , Guias de Prática Clínica como Assunto , Gravidez , Medição de Risco , Desmame
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