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1.
Infect Dis (Lond) ; : 1-15, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38922811

RESUMEN

Neglected tropical diseases continue to cause a significant burden worldwide, with Africa accounting for more than one-third of the global burden. Over the past decade, progress has been made in eliminating, controlling, and eradicating these diseases in Africa. By December 2022, 47 out of 54 African countries had eliminated at least one neglected tropical disease, and more countries were close to achieving this milestone. Between 2020 and 2021, there was an 80 million reduction in people requiring intervention. However, continued efforts are needed to manage neglected tropical diseases and address their social and economic burden, as they deepen marginalisation and stigmatisation. Wastewater-based epidemiology involves analyzing wastewater to detect and quantify biomarkers of disease-causing pathogens. This approach can complement current disease surveillance systems in Africa and provide an additional layer of information for monitoring disease spread and detecting outbreaks. This is particularly important in Africa due to limited traditional surveillance methods. Wastewater-based epidemiology also provides a tsunami-like warning system for neglected tropical disease outbreaks and can facilitate timely intervention and optimised resource allocation, providing an unbiased reflection of the community's health compared to traditional surveillance systems. In this review, we highlight the potential of wastewater-based epidemiology as an innovative approach for monitoring neglected tropical disease transmission within African communities and improving existing surveillance systems. Our analysis shows that wastewater-based epidemiology can enhance surveillance of neglected tropical diseases in Africa, improving early detection and management of Buruli ulcers, hookworm infections, ascariasis, schistosomiasis, dengue, chikungunya, echinococcosis, rabies, and cysticercosis for better disease control.

2.
PeerJ ; 12: e17198, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915381

RESUMEN

In this review, we examine the current landscape of point-of-care testing (POCT) diagnostic tools designed for poverty-related infectious diseases (PRIDs) in sub-Saharan Africa (sSA) while delineating key avenues for future advancements. Our analysis encompasses both established and emerging diagnostic methods for PRIDs, addressing the persistent challenges in POCT tool development and deployment, such as cost, accessibility, and reliability. We emphasize recent advancements in POCT diagnostic tools as well as platforms poised to enhance diagnostic testing in sSA. Recognizing the urgency for affordable and widely accessible POCT diagnostic tools to detect PRIDs in sSA, we advocate for a multidisciplinary approach. This approach integrates current and emerging diagnostic methods, explicitly addressing challenges hindering point-of-care (POC) tool development. Furthermore, it recognizes the profound impact of misdiagnosis on public and global health, emphasizing the need for effective tools. To facilitate the successful development and implementation of POCT diagnostic tools in sSA, we propose strategies including the creation of multi-analyte detection POCT tools, the implementation of education and training programs, community engagement initiatives, fostering public-private collaborations, and the establishment of reliable supply chains. Through these concerted efforts, we aim to accelerate the development of POCT in the sSA region, ensuring its effectiveness and accessibility in addressing the diagnostic challenges associated with PRIDs.


Asunto(s)
Enfermedades Transmisibles , Pruebas en el Punto de Atención , Pobreza , Humanos , África del Sur del Sahara/epidemiología , Pruebas en el Punto de Atención/economía , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/epidemiología , Análisis Costo-Beneficio , Sistemas de Atención de Punto/economía
3.
Clin Biochem ; 126: 110747, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38484829

RESUMEN

BACKGROUND: Immunoassays are important for routine clinical testing and medical diagnosis. However, they are limited by cross-reactivity especially at low analyte concentrations. There is a critical need to investigate compounds that can interfere with immunoassays. Herein, we describe the identification of canrenone, a spironolactone metabolite that falsely increases progesterone concentrations on the Abbott Architect i2000 Immunoassay. METHODS: Serum samples and assay diluents were spiked with spironolactone or canrenone and progesterone concentrations were measured on the Architect i2000 and Immulite XPi immunoassay platforms. Blood samples from patients taking spironolactone were analyzed with liquid chromatography-tandem mass spectrometry to evaluate the intrinsic response of progesterone concentrations to the presence of canrenone. RESULTS: We measured approximately 10-fold higher progesterone concentrations on the Abbott Architect i2000 compared to reference immunoassay analyzers (Siemens Immulite XPi and Roche Cobas e601/602), suggesting an analytical error which is unique to the Architect i2000 antibody and/or assay conditions. By measuring serum progesterone after addition of spironolactone or canrenone to serum samples, we found that canrenone falsely increased progesterone on the Architect i2000 immunoassay. However, this interference was more pronounced at low serum progesterone concentrations. Moreover, a strong positive correlation was seen between canrenone and measured serum progesterone concentrations. CONCLUSIONS: Our investigations are important for individuals who require progesterone measurements using the Architect i2000 immunoassay, especially because it is unlikely for clinicians to order canrenone measurements alongside progesterone measurements for individuals taking spironolactone. Further research is needed to determine whether canrenone can influence progesterone measurements on other immunoassay systems.


Asunto(s)
Canrenona , Espironolactona , Humanos , Espironolactona/metabolismo , Canrenona/metabolismo , Progesterona , Digoxina , Inmunoensayo/métodos
4.
Afr J Lab Med ; 12(1): 2225, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38116518

RESUMEN

Background: Haemoglobinopathies, including sickle cell disease and ß-thalassaemia, are monogenic disorders with a relatively higher prevalence among malaria-endemic areas in Africa. Despite this prevalence, most African countries lack the necessary resources for diagnosing and managing these debilitating conditions. Aim: This study provides a critical review of newborn screening for detecting haemoglobinopathies in Africa, highlighting challenges and proposing strategies for improved diagnosis and management. Methods: A literature search on haemoglobinopathies in Africa was conducted in PubMed, Google Scholar and ScienceDirect, using specific keywords and Boolean operators, including articles published from January 1981 to December 2022. Results: The data show that sickle cell disease is prevalent among populations in Central and West Africa; however, ß-thalassaemia is prevalent among people in the northern parts of Africa. Newborn screening pilot initiatives for haemoglobinopathies were being implemented in Angola, Nigeria, Ghana, the Democratic Republic of Congo and the Republic of Benin. The cost of testing, lack of sufficient and accessible medical records, and inadequacy in healthcare infrastructure pose significant challenges in bridging the gaps in newborn screening. Furthermore, the stigmatisation and lack of awareness of haemoglobinopathies and access to newborn screening programmes pose additional challenges. Conclusion: This review highlights the challenges associated with haemoglobinopathy testing, effective strategies for mitigating these challenges, and future perspectives for expanding efforts toward detecting and managing these disorders across Africa. Providing affordable diagnostic tools, mobile clinics, government subsidies, education campaigns, and the implementation of electronic medical records systems could help bridge the gaps in newborn screening in Africa. What this study adds: The study presents a comprehensive view of newborn screening of haemoglobinopathies in Africa, provides a detailed outline of the challenges faced by newborn screening for haemoglobinopathies in Africa, and offers strategies for better diagnosis and care.

5.
Genes (Basel) ; 14(4)2023 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-37107558

RESUMEN

An inverse comorbidity has been observed between Down syndrome (DS) and solid tumors such as breast and lung cancers, and it is posited that the overexpression of genes within the Down Syndrome Critical Region (DSCR) of human chromosome 21 may account for this phenomenon. By analyzing publicly available DS mouse model transcriptomics data, we aimed to identify DSCR genes that may protect against human breast and lung cancers. Gene expression analyses with GEPIA2 and UALCAN showed that DSCR genes ETS2 and RCAN1 are significantly downregulated in breast and lung cancers, and their expression levels are higher in triple-negative compared to luminal and HER2-positive breast cancers. KM Plotter showed that low levels of ETS2 and RCAN1 are associated with poor survival outcomes in breast and lung cancers. Correlation analyses using OncoDB revealed that both genes are positively correlated in breast and lung cancers, suggesting that they are co-expressed and perhaps have complementary functions. Functional enrichment analyses using LinkedOmics also demonstrated that ETS2 and RCAN1 expression correlates with T-cell receptor signaling, regulation of immunological synapses, TGF-ß signaling, EGFR signaling, IFN-γ signaling, TNF signaling, angiogenesis, and the p53 pathway. Altogether, ETS2 and RCAN1 may be essential for the development of breast and lung cancers. Experimental validation of their biological functions may further unravel their roles in DS and breast and lung cancers.


Asunto(s)
Síndrome de Down , Neoplasias Pulmonares , Ratones , Animales , Humanos , Síndrome de Down/epidemiología , Síndrome de Down/genética , Síndrome de Down/complicaciones , Factores de Transcripción , Transducción de Señal/genética , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética
6.
J Environ Manage ; 337: 117556, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36958281

RESUMEN

To achieve sustainable production and consumption patterns in the modern world, emerging countries are concentrating more on how economic variables may employ carbon neutrality targets appropriately. Using renewable energy, structural changes initiative, and imposing environmental taxes are all part of the plan to achieve the carbon neutrality goal in terms of reduced carbon emissions (CO2), haze pollutants, and greenhouse gases (GHG). Environmental taxation, renewable energy, structural changes, trade openness, and foreign direct investment (FDI) are aspects taken into account in this study, along with the long-term viability of the natural ecology in the E7 (China, Turkey, India, Russia, Brazil, Indonesia, and Mexico) economies. The Driscoll Kraay fixed effect OLS technique and the Method-of-Moment quantile (MMQ) regression technique were adopted for the baseline analysis for the data span of 2000 to 2020. From the empirical analysis, it was discovered that environmental Tax, structure change, and renewable energy have a negative connection with carbon emissions for the understudy countries. Moreover, the pollutant haven hypothesis (PHH) was confirmed since the findings discovered a positively significant relation involving FDI and carbon emission. Similarly, trade openness was seen to have a positive connection with carbon emissions. Thus, it is concluded that effective environmental taxation, renewable energy enhancement, and structure changes mitigate pollution while trade openness and FDI inflow enhance carbon emission for the E7 economies. According to the results, rigorous environmental tax rules will enable enterprises to transition manufacturing to green and sustainable alternatives. Finally, the report recommends that transferring tax money to research and development of sustainable technology programmes will enable governments to meet the SDG-7 and SDG-13 objectives of the United Nations.


Asunto(s)
Dióxido de Carbono , Desarrollo Económico , Dióxido de Carbono/análisis , Contaminación Ambiental/análisis , Internacionalidad , Inversiones en Salud , Impuestos , Energía Renovable , Carbono
7.
Environ Sci Pollut Res Int ; 30(18): 51726-51739, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36820978

RESUMEN

The main cause of environmental degradation is carbon emissions, which puts environmental sustainability in jeopardy. This ecological worry, the obligation for which falls on all economic actors, has not gone undetected, and so in 2021, the Glasgow Climate Pact (COP: 26) was organized, with the primary aim of decreasing global carbon emissions. Because the Post-Glasgow Agreement goals represent a significant challenge to achieving ecological responsibility, pressure is applied to the participating nations. However, earlier literature lacked sufficient investigation of factors useful for the mitigation of carbon emissions in E7 (China, Turkey, India, Russia, Brazil, Indonesia, and Mexico) economies. Hence, we aim to fill this research vacuum by predicting the impact of clean fuels and cooking technology availability, renewable energy, and environmental taxes on E7 economies' carbon emissions from 2000 to 2020, while taking urbanization and population expansion into account. Evaluation is done using four different cross-sectional dependence (CSD) methods, as well as unit root tests (CIPS and CADF), cointegration analysis (Westerlund and Kao), and the Driscoll-Kraay and quantile-on-quantile long-run factor estimate methods. The long-run analysis revealed from our findings that environmental tax, renewable energy, and access to clean fuels and technologies for cooking decrease carbon emission for the E7 economies. On the other hand, urbanization and population growth enhance emissions for the E7 economies. Finally, our results hold up under a variety of policy interpretations that would aid in reducing carbon emissions and their negative effects on the environment.


Asunto(s)
Dióxido de Carbono , Desarrollo Económico , Estudios Transversales , Impuestos , Energía Renovable
8.
Diagnostics (Basel) ; 12(11)2022 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-36359413

RESUMEN

The COVID-19 pandemic has had a significant impact on many lives and the economies of many countries since late December 2019. Early detection with high accuracy is essential to help break the chain of transmission. Several radiological methodologies, such as CT scan and chest X-ray, have been employed in diagnosing and monitoring COVID-19 disease. Still, these methodologies are time-consuming and require trial and error. Machine learning techniques are currently being applied by several studies to deal with COVID-19. This study exploits the latent embeddings of variational autoencoders combined with ensemble techniques to propose three effective EVAE-Net models to detect COVID-19 disease. Two encoders are trained on chest X-ray images to generate two feature maps. The feature maps are concatenated and passed to either a combined or individual reparameterization phase to generate latent embeddings by sampling from a distribution. The latent embeddings are concatenated and passed to a classification head for classification. The COVID-19 Radiography Dataset from Kaggle is the source of chest X-ray images. The performances of the three models are evaluated. The proposed model shows satisfactory performance, with the best model achieving 99.19% and 98.66% accuracy on four classes and three classes, respectively.

9.
Trauma Violence Abuse ; 23(1): 255-264, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-32686611

RESUMEN

OBJECTIVES: This article summarizes the rate of mental health disorders of foster children, the specific types of disorders faced by this population, and how factors such as type of abuse or placement variables can affect mental health outcomes. METHOD: A search in PsycInfo Ovid, EMBASE Elsevier, and Cochrane Library Wiley resulted in 5,042 manuscripts that were independently reviewed by two authors, yielding 25 articles. INCLUSION CRITERIA: Published in or after 2000, written in English, and having a population sample of foster children (ages 0-18) in Western countries including the United States, Norway, Australia, and Canada. RESULTS: Foster children have higher rates of mental health disorders than those of the general population. The most common diagnoses include oppositional defiant disorder/conduct disorder, major depressive disorder, post-traumatic stress disorder, and reactive attachment disorder. Variables such as type of maltreatment and type of placement predicted mental health outcomes. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Children in foster care experience more mental health disorders, as a response to either the circumstances that led to being removed from their homes or the experience of being placed in foster care. These results demonstrate the necessity for providers to consider mental health issues when caring for children in foster care and to perform appropriate screenings and assessments. With adequate trauma-informed training, providers can quickly become comfortable and competent in identifying mental health needs of children in foster care who have experienced trauma.


Asunto(s)
Maltrato a los Niños , Trastorno Depresivo Mayor , Trastornos Mentales , Trastornos por Estrés Postraumático , Adolescente , Niño , Preescolar , Cuidados en el Hogar de Adopción , Humanos , Lactante , Recién Nacido , Trastornos Mentales/epidemiología , Salud Mental , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/epidemiología , Estados Unidos
10.
Afr Health Sci ; 21(4): 1509-1517, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35283940

RESUMEN

Corona virus disease 2019 (COVID-19) remains an incurable, progressive pneumonia-like illness characterized by fever, dry cough, fatigue, and headache during its early stages. COVID-19 has ultimately resulted in mortality in at least 2 million people worldwide. Millions of people globally have already been affected by this disease, and the numbers are expected to increase, perhaps until an effective cure or vaccine is identified. Although Africa was initially purported by the World Health Organization (WHO) to be severely hit by the pandemic, Africa recorded the least number of cases during the first wave, with lowest rates of infections, compared to Asia, Europe, and the Americas. This statistic might be attributed to the low testing capacity, existing public health awareness and lessons learnt during Ebola epidemic. Nonetheless, the relatively low rate of infection should be an opportunity for Africa to be better prepared to overcome this and future epidemics. In this paper, the authors provide insights into the dynamics and transmission of the severe acute respiratory syndrome corona virus (SARS-CoV-2) during the first wave of the pandemic; possible explanations into the relatively low rates of infection recorded in Africa; with recommendations for Africa to continue to fight Covid-19; and position itself to effectively manage future pandemics.


Asunto(s)
COVID-19 , Pandemias , África/epidemiología , COVID-19/epidemiología , Brotes de Enfermedades/prevención & control , Humanos , Pandemias/prevención & control , SARS-CoV-2
11.
J Pediatric Infect Dis Soc ; 9(2): 194-201, 2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-30849175

RESUMEN

BACKGROUND: MMR II (M-M-R II [Merck & Co, Inc.]) is currently the only measles, mumps, and rubella (MMR) vaccine licensed in the United States. A second MMR vaccine would mitigate the potential risk of vaccine supply shortage or delay. In this study, we assessed the immunogenicity and safety of another MMR vaccine (MMR-RIT [Priorix, GlaxoSmithKline]) compared with those of the MMR II in 12- to 15-month-old children who received it as a first dose. METHODS: In this phase III, observer-blinded, noninferiority, lot-to-lot consistency clinical trial (ClinicalTrials.gov identifier NCT01702428), 5003 healthy children were randomly assigned to receive 1 dose of MMR-RIT (1 of 3 production lots) or MMR II along with other age-recommended routine vaccines. We evaluated the immunogenicity of all vaccines in terms of antibody concentrations (by using an enzyme-linked immunosorbent assay or electrochemiluminescence assay) and/or seroresponse rates 43 days after vaccination. We also assessed the reactogenicity and safety of the vaccines. RESULTS: Immunoresponses after vaccination with MMR-RIT were robust and noninferior to those after vaccination with the MMR II. Immunogenicity of the 3 production lots of MMR-RIT was consistent; more than 97% of the children had a seroresponse to MMR components. The coadministered vaccines elicited similar immunoresponses in the MMR-RIT and MMR II groups. Both MMR vaccines resulted in comparable reactogenicity profiles, and no safety concerns were detected. CONCLUSIONS: If licensed, the MMR-RIT could provide a valid option for the prevention of measles, mumps, and rubella in children in the United States and would reduce potential risks of a vaccine shortage.


Asunto(s)
Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Exantema/etiología , Femenino , Fiebre/etiología , Regulación Gubernamental , Humanos , Lactante , Masculino , Sarampión/inmunología , Sarampión/prevención & control , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos , Paperas/inmunología , Paperas/prevención & control , Rubéola (Sarampión Alemán)/inmunología , Rubéola (Sarampión Alemán)/prevención & control , Método Simple Ciego , Estados Unidos , Vacunación
12.
Sci Total Environ ; 688: 701-707, 2019 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-31254836

RESUMEN

Disposal of concentrate from brackish water desalination is limited by concerns of salt leaching into fresh water sources. Prevention of salt from leaching can greatly increase desalination concentrate management costs, as there are few options to recover those costs. An option for concentrate disposal is to grow halophyte crops using the concentrate as irrigation water. The purpose of this study was to determine how much of the Ca, Mg, Na, and K taken up by Atriplex species during growth can be stabilized by pyrolysis, thus preventing those cations from returning into the soil solution after harvest. Results show that salts in the biomass are concentrated into the biochars and that pyrolysis conditions affect the amount of salt that can be leached with water. Ca was the most retained of the cations: 100% and 94% were retained in A. canescens biochars and A. lentiformis 600 °C biochar, respectively. Mg retention was similar: 100% and 93% retained for A. canescens and A. lentiformis 600 °C biochars, respectively. Increasing pyrolysis temperature increased the retention of Ca and Mg; trends for K and Na were inconsistent. Soil application of these biochars will still be problematic due to low retention of Na against short-term leaching, thus limiting the potential for on-site sequestration to enable land utilization for crop production. With more understanding of the salt formation and retention mechanisms within biomass, higher amounts of salt might be sequestered longer, while taking advantage of the carbon sequestration and soil quality benefits of biochars.


Asunto(s)
Carbón Orgánico/química , Modelos Químicos , Sales (Química)/química , Atriplex
13.
Int J Pediatr Otorhinolaryngol ; 108: 95-99, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29605375

RESUMEN

While various forms of facial trauma, bruising, burns, and fractures are frequently seen in cases of child abuse, purposeful nasal erosion has rarely been identified as a form of abusive injury. Progressive destruction of nasal tissue in children provokes a wide differential diagnosis crossing multiple subspecialties: infectious, primary immunodeficiencies, inflammatory conditions, malignancy, and genetic disorders. Progressive nasal erosion also can be a manifestation of child abuse. The proposed mechanism is repetitive mechanical denudation of the soft tissue and cartilage resulting in chronic inflammation, bleeding, and ultimately destruction of the insulted tissue. We report 6 cases of child abuse manifesting as overt nasal destruction.


Asunto(s)
Maltrato a los Niños/diagnóstico , Traumatismos Faciales/etiología , Nariz/lesiones , Niño , Preescolar , Contusiones/etiología , Diagnóstico Diferencial , Traumatismos Faciales/diagnóstico , Femenino , Fracturas Óseas/diagnóstico , Fracturas Óseas/etiología , Humanos , Lactante , Masculino , Tomografía Computarizada por Rayos X
14.
J Pediatric Infect Dis Soc ; 6(1): 9-19, 2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-28062552

RESUMEN

BACKGROUND.: Children under 3 years of age may benefit from a double-dose of inactivated quadrivalent influenza vaccine (IIV4) instead of the standard-dose. METHODS.: We compared the only United States-licensed standard-dose IIV4 (0.25 mL, 7.5 µg hemagglutinin per influenza strain) versus double-dose IIV4 manufactured by a different process (0.5 mL, 15 µg per strain) in a phase III, randomized, observer-blind trial in children 6-35 months of age (NCT02242643). The primary objective was to demonstrate immunogenic noninferiority of the double-dose for all vaccine strains 28 days after last vaccination. Immunogenic superiority of the double-dose was evaluated post hoc. Immunogenicity was assessed in the per-protocol cohort (N = 2041), and safety was assessed in the intent-to-treat cohort (N = 2424). RESULTS.: Immunogenic noninferiority of double-dose versus standard-dose IIV4 was demonstrated in terms of geometric mean titer (GMT) ratio and seroconversion rate difference. Superior immunogenicity against both vaccine B strains was observed with double-dose IIV4 in children 6-17 months of age (GMT ratio = 1.89, 95% confidence interval [CI] = 1.64-2.17, B/Yamagata; GMT ratio = 2.13, 95% CI = 1.82-2.50, B/Victoria) and in unprimed children of any age (GMT ratio = 1.85, 95% CI = 1.59-2.13, B/Yamagata; GMT ratio = 2.04, 95% CI = 1.79-2.33, B/Victoria). Safety and reactogenicity, including fever, were similar despite the higher antigen content and volume of the double-dose IIV4. There were no attributable serious adverse events. CONCLUSIONS.: Double-dose IIV4 may improve protection against influenza B in some young children and simplifies annual influenza vaccination by allowing the same vaccine dose to be used for all eligible children and adults.


Asunto(s)
Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Preescolar , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Estudios de Equivalencia como Asunto , Femenino , Humanos , Inmunización Secundaria , Lactante , Virus de la Influenza B/inmunología , Masculino
15.
Anal Biochem ; 521: 55-58, 2017 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-28088451

RESUMEN

A major challenge in attaching fluorophores or other handles to proteins is the availability of a site-specific labeling strategy that provides stoichiometric modification without compromising protein integrity. We developed a simple approach that combines TEV protease cleavage, sortase modification and affinity purification to N-terminally label proteins. To achieve stoichiometrically-labeled protein, we included a short affinity tag in the fluorophore-containing peptide for post-labeling purification of the modified protein. This strategy can be easily applied to any recombinant protein with a TEV site and we demonstrate this on Epidermal Growth Factor Receptor (EGFR) and Membrane Scaffold Protein (MSP) constructs.


Asunto(s)
Aminoaciltransferasas/metabolismo , Proteínas Bacterianas/metabolismo , Cisteína Endopeptidasas/metabolismo , Proteínas del Citoesqueleto/química , Endopeptidasas/metabolismo , Receptores ErbB/química , Proteínas de la Membrana/química , Fragmentos de Péptidos/metabolismo , Proteínas Recombinantes de Fusión/química , Cromatografía de Afinidad/métodos , Proteínas del Citoesqueleto/aislamiento & purificación , Proteínas del Citoesqueleto/metabolismo , Receptores ErbB/aislamiento & purificación , Receptores ErbB/metabolismo , Humanos , Proteínas de la Membrana/aislamiento & purificación , Proteínas de la Membrana/metabolismo , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , Staphylococcus aureus/enzimología
16.
Pediatr Infect Dis J ; 36(2): 202-208, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27846058

RESUMEN

BACKGROUND: This multicenter phase III study (NCT01340937) evaluated the consistency of immune responses to 3 separate lots of diphtheria-tetanus toxoids-acellular pertussis 5, inactivated poliovirus vaccine, Haemophilus influenzae type b, and hepatitis B (DTaP5-IPV-Hib-HepB), an investigational hexavalent vaccine (HV). METHODS: Healthy infants were randomized (2:2:2:1) to receive HV or Pentacel (Control). Groups 1, 2 and 3 received HV at 2, 4 and 6 months, and Control at 15 months. Group 4 received Control at 2, 4, 6 and 15 months, plus Recombivax HB (HepB) at 2 and 6 months. Concomitant Prevnar 13 was given to all groups at 2, 4, 6 and 15 months; pentavalent rotavirus vaccine (RV5) was given to all groups at 2, 4 and 6 months. Blood specimens (3-5 mL) were collected immediately before administration of dose 1, postdose 3, immediately before toddler dose, and after toddler dose. Adverse events were recorded after each vaccination. RESULTS: The 3 manufacturing lots of HV induced consistent antibody responses to all antigens. Immunogenicity of HV was noninferior to Control for all antibodies, except for pertussis filamentous hemagglutinin geometric mean concentration postdose 3, and pertussis pertactin (PRN) geometric mean concentration after toddler dose. Postdose 3 immunogenicity of concomitantly administered Prevnar 13 was generally similar (except for serotype 6B) when given with HV or Control. Adverse events of HV were similar to Control, except for a higher rate of fever ≥38.0°C [49.2% vs. 35.4%, estimated difference 13.7% (8.4, 18.8)]. CONCLUSIONS: HV demonstrated lot-to-lot manufacturing consistency; safety and immunogenicity were comparable with the licensed vaccines. HV provides a new combination vaccine option within the US 2-month, 4-month and 6-month vaccine series.


Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/normas , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Vacunas contra Haemophilus/normas , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/inmunología , Vacuna Antipolio de Virus Inactivados/normas , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Fiebre/epidemiología , Humanos , Esquemas de Inmunización , Lactante , Masculino , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/normas
17.
J Biol Chem ; 292(2): 597-610, 2017 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-27872189

RESUMEN

The epidermal growth factor receptor (EGFR)/ErbB family of receptor tyrosine kinases includes oncogenes important in the progression of breast and other cancers, and they are targets for many drug development strategies. Each member of the ErbB family possesses a unique, structurally uncharacterized C-terminal tail that plays an important role in autophosphorylation and signal propagation. To determine whether these C-terminal tails are intrinsically disordered regions, we conducted a battery of biophysical experiments on the EGFR and HER3 tails. Using hydrogen/deuterium exchange mass spectrometry, we measured the conformational dynamics of intracellular half constructs and compared the tails with the ordered kinase domains. The C-terminal tails demonstrate more rapid deuterium exchange behavior when compared with the kinase domains. Next, we expressed and purified EGFR and HER3 tail-only constructs. Results from circular dichroism spectroscopy, size exclusion chromatography with multiangle light scattering, dynamic light scattering, analytical ultracentrifugation, and small angle X-ray scattering each provide evidence that the EGFR and HER3 C-terminal tails are intrinsically disordered with extended, non-globular structure in solution. The intrinsic disorder and extended conformation of these tails may be important for their function by increasing the capture radius and reducing the thermodynamic barriers for binding of downstream signaling proteins.


Asunto(s)
Receptores ErbB/química , Receptor ErbB-3/química , Dicroismo Circular , Medición de Intercambio de Deuterio , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Cinética , Dominios Proteicos , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , Difracción de Rayos X
18.
Matern Child Health J ; 20(Suppl 1): 154-163, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27316631

RESUMEN

Introduction The objective of this qualitative study was to assess healthcare providers' acceptability of an ongoing postpartum human papillomavirus (HPV) vaccination program in Southeast Texas and its integration into everyday clinical care. Methods In 2012, the Department of Obstetrics & Gynecology at the University of Texas Medical Branch (UTMB) began offering HPV vaccination as part of standard postpartum care to increase vaccination rates among young women in Galveston County. Initial vaccine doses were offered on the postpartum unit while subsequent doses were coordinated with postpartum and well-baby visits. Thirty months after project initiation, semi-structured interviews of physicians (n = 12) and nurses (n = 6) involved in postpartum and pediatric care at UTMB were conducted. Interview transcripts were analyzed using thematic analysis in Nvivo10. Results Overall, providers demonstrated "pro-vaccine" attitudes and stated the program was an effective strategy for vaccinating hard-to-reach women. Cancer prevention was the main perceived benefit while follow-up compliance was the primary perceived patient barrier. The initial challenges with integrating postpartum HPV vaccination included miscommunication between providers regarding vaccine orders and coordination issues with well-baby visits for follow-up doses. One novel finding was providers' beliefs that women's personal HPV vaccine practices may positively impact their decisions about later vaccinating their children against HPV. Providers' suggestions to improve the program included: enhancing postpartum HPV vaccine education for patients, offering more continuing education for providers, and increasing community awareness of HPV vaccination. Discussion These findings can help providers of postpartum care understand how to integrate postpartum HPV vaccination into their current practices and how to overcome perceived vaccination barriers.


Asunto(s)
Actitud del Personal de Salud , Personal de Salud/psicología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Atención Posnatal , Adolescente , Adulto , Femenino , Conocimientos, Actitudes y Práctica en Salud , Accesibilidad a los Servicios de Salud , Humanos , Entrevistas como Asunto , Aceptación de la Atención de Salud , Embarazo , Evaluación de Programas y Proyectos de Salud , Investigación Cualitativa , Salud de la Mujer
19.
Hum Vaccin Immunother ; 12(8): 1965-1971, 2016 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-27002930

RESUMEN

Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination is recommended for all women during each pregnancy to prevent pertussis in young infants. However, data on the safety of this protective measure are limited and conflicting. To assess maternal and infant outcomes associated with administration of this vaccine during pregnancy, we reviewed medical records of 1,759 women who delivered a singleton infant at a southeast Texas public hospital between November 1, 2012 and June 30, 2014. After excluding women who had inadequate prenatal care or who delivered at <27 weeks gestation, we used multivariable logistic regression analyses to compare 13 outcomes between those who did and did not receive the Tdap vaccine. We examined 6 maternal outcomes (chorioamnionitis, postpartum endometritis, preterm delivery, preterm premature rupture of membranes, induced labor, and mode of delivery) and 7 infant outcomes (low birth weight, very low birth weight, small for gestational age, 5-minute Apgar score, birth defects, and neonatal intensive care unit admission). Maternal Tdap vaccination was associated with decreased odds of cesarean delivery. No associations between maternal Tdap vaccination and infant outcomes were observed. This study demonstrates that Tdap vaccination during pregnancy does not increase the risk of adverse outcomes.


Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Transmisión de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/prevención & control , Tos Ferina/prevención & control , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Estudios Retrospectivos , Texas , Resultado del Tratamiento , Adulto Joven
20.
Am J Obstet Gynecol ; 215(3): 318.e1-9, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-26899907

RESUMEN

BACKGROUND: Effective interventions are needed to address the low rate of human papillomavirus (HPV) vaccination in the United States, particularly among girls and women 16-26 years old. Counseling and offering the vaccine to postpartum patients could be an effective strategy to increase uptake among young women who did not complete the 3-dose series at an earlier age. OBJECTIVE: The purpose of this evaluation was to assess the effectiveness of a multicomponent program designed for postpartum women that used patient navigators (PNs) and reminders for follow-up visits to improve uptake and completion of the HPV vaccine series. STUDY DESIGN: As part of standard care, patients ≤26 years of age from Galveston County, Texas, who delivered an infant from November 2012 through June 2014 at a public hospital were counseled and offered the HPV vaccine postpartum. PNs assisted with scheduling follow-up injections during postpartum or well-child visits. A program evaluation was conducted after 20 months. RESULTS: Of 1038 patients approached, only 161 (15.5%) had previously completed the vaccine series. Of the 877 patients who had not completed the series, 661 (75.4%) received at least 1 dose postpartum, with 575 patients receiving their first dose and 86 receiving their second or third doses. By April 2015, initiation rates had increased as a result of this program from 25.4% before the program was initiated to 80.8% and completion rates from 15.5-65.1%. Missed appointments for injections were less likely among those who received text message reminders and more likely among those with ≥2 prior pregnancies. Those who were Hispanic or had received an influenza vaccination in the last year were more likely to initiate and complete the series through this program. Patients who missed ≥1 follow-up appointments were less likely to complete the vaccine series. CONCLUSION: Offering the HPV vaccine postpartum dramatically increased initiation rates among postpartum patients. PN and text messages ensured that a high percentage completed all 3 doses.


Asunto(s)
Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/uso terapéutico , Aceptación de la Atención de Salud , Periodo Posparto , Vacunación , Adolescente , Adulto , Femenino , Humanos , Vacunas contra Papillomavirus/administración & dosificación , Pobreza , Evaluación de Programas y Proyectos de Salud , Salud Pública , Texas , Envío de Mensajes de Texto , Estados Unidos , Salud de la Mujer , Adulto Joven
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