Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 68
Filtrar
1.
Am J Infect Control ; 52(5): 509-516, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38218328

RESUMEN

BACKGROUND: The COVID-19 vaccine was initially offered to frontline health care workers (HCWs), due to the high risk of contracting COVID-19 through occupational exposure to patients. Low HCW vaccine uptake can impact overall community-level vaccine uptake. This study used the Diffusion of Innovation (DOI) Theory to understand factors related to COVID-19 vaccine uptake in HCWs. METHODS: We surveyed Pennsylvanian HCWs (excluding Philadelphia) from August 2022 to February 2023. Survey questions inquired about demographics, COVID-19 vaccination status, reasons for receiving/declining the COVID-19 vaccine, and sources of information about the vaccine. RESULTS: Participants (n = 3,490) were 85% female, 89% White, and 93% (n = 3,255) reported receiving at least one dose of a COVID-19 vaccine. HCWs were categorized into adopter categories of the DOI Theory: innovators (56%), early adopters (9%), early majority (11%), late majority (7%), and laggards (17%). The major reason that prompted participants to get the vaccine was to protect them against COVID-19 infection (78%), while the major reason for declining the vaccine was due to concern about possible side effects from the vaccine (78%). CONCLUSIONS: We applied the DOI Theory to characterize adopters and identify factors related to COVID-19 vaccine uptake in HCWs. As updated COVID-19 vaccines are approved for the United States market, our findings may be used to improve vaccine education and communication among HCWs to support vaccine uptake.

2.
Genes Brain Behav ; 22(6): e12870, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38123893

RESUMEN

In this issue, Griesius et al report that heterozygous Dlg2+/- rats showed a reversal learning impairment on a specific bowl-digging task, whereas other reversal tasks were unaffected. The study suggests that Dlg2 gene disruption, which has been linked to neuropsychiatric disorders, including schizophrenia, may cause relatively specific impairments in reversal learning, an important aspect of cognitive flexibility. The study draws attention to two important issues regarding the neuro-behavioral mechanisms of reversal learning, namely that hippocampal dysfunction, which is prominent in Dlg2+/- rats, may contribute to reversal learning impairments and that, depending on the task and previous experience, brain and behavioral mechanisms of reversal learning may differ.


Asunto(s)
Aprendizaje Inverso , Esquizofrenia , Humanos , Ratas , Animales , Esquizofrenia/genética , Heterocigoto
3.
Am J Pharm Educ ; 87(10): 100070, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37852681

RESUMEN

OBJECTIVE: A professional identity has been described as "an individual thinking, acting, and feeling" like a person within the profession. The objective of this study was to learn about professional identity formation (PIF) in recent graduates of a pharmacy program. METHODS: In-depth interviews were conducted with students graduating from a doctor of pharmacy degree program. Investigators performed a thematic content analysis of interview transcripts. RESULTS: Participants were from community pharmacy practice (4), residencies (4), industry (1), and ambulatory care (1). At the time of the interview, participants were a range of 5-13 months out from graduation. Analysis of the data revealed 4 thematic findings. First, thinking and acting like a pharmacist occurred frequently while in school but feeling like a pharmacist occurred mostly after graduation. Second, feeling like a pharmacist meant participants felt confident in their knowledge base and ability to independently make decisions. Third, real-world practice is critical to PIF, particularly through interactions with patients. Finally, feedback, mentoring, and reflection support PIF and can aid in reconciling the tensions between concepts taught in school and experiences in practice. CONCLUSIONS: In this qualitative analysis of data about PIF obtained from recent graduates from a pharmacy school, we found that thinking and acting like a pharmacist preceded feeling like a pharmacist; feeling like a pharmacist involved confidence in the ability to work autonomously; feedback, mentoring, and reflection on experiences supported PIF; and real-world experiences were critical to PIF.


Asunto(s)
Educación en Farmacia , Servicios Farmacéuticos , Farmacias , Farmacia , Humanos , Identificación Social
4.
Explor Res Clin Soc Pharm ; 11: 100306, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37521018

RESUMEN

Background: Students participating in student-run clinics (SRCs) have opportunities to develop and practice beneficial skill sets, including empathy and interprofessional collaboration. Objectives: This study aimed to assess whether participation in an underserved SRC impacts the development of empathy and interprofessional skills in pharmacy and medical students. Methods: This study assessed empathy and interprofessional skills development through a self-assessment survey. The survey included the Interpersonal Reactivity Index (IRI) to assess empathy, the Attitudes Towards Health Care Teams/Team Skills Scale (ATHCTS/TSS) to assess interprofessional team dynamics, and a free-text response section. Participants were grouped based on whether they participated in the SRC (intervention group) or did not participate in the SRC (control group). A subgroup analysis was performed based on the participants' discipline (medicine vs. pharmacy). To compare differences in IRI, ATHCTS, and TSS scores between study groups, independent samples t-tests were performed. A thematic analysis was used for qualitative data. Results: There were no statistically significant differences between intervention and control groups in IRI, ATHCTS, or TSS scores. Subgroup analyses showed no significant differences in scores of student pharmacists or medical students. For both disciplines, the thematic analysis revealed the most common positive themes identified were "real-world patient interaction and care," "impact on practice/career development." Alternatively, it revealed the highest reported negative themes identified as "time management and operational difficulties" and "concerns about the quality of/access to care". Conclusions: This study demonstrates that involvement in an SRC neither improves nor hinders a learner's development of empathy and interprofessional team skills. Qualitatively, students reported that participation in an SRC benefited their learning and helped develop their skills, like empathy and team dynamics, in an interprofessional setting. Future research with longitudinal monitoring or alternative assessment tools is recommended.

5.
Nurs Clin North Am ; 58(1): 25-34, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36731957

RESUMEN

The coronavirus disease-2019 pandemic disrupted traditional research practices with the cessation of face-to-face contact with study participants. Researchers needed to respond with alternative methods to continue nurse-led clinical research. A rapid pivot to remote processes for recruitment, enrollment, data collection, and participant incentives can enable research to continue despite restrictions on in-person activities. Technology offers innovative methods in meeting current research needs but is not without challenges and continued need for ethics evaluation.


Asunto(s)
COVID-19 , Enfermeras y Enfermeros , Investigación en Enfermería , Humanos , Pandemias
6.
Br J Clin Pharmacol ; 89(1): 11-19, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-32501602

RESUMEN

AIMS: To report on a retrospective study of individual funding request (IFR) submissions from a large tertiary hospital and describe gaps in current mechanisms for funding of high-cost medicines in England. METHODS: Data on the number and outcome of IFR submissions submitted to commissioners between 2014/15 and 2018/19 was extracted from the electronic patient health record and a local high-cost drug database. RESULTS: In total, 230 IFRs were submitted: 112 to NHS England and 118 to a Clinical Commissioning Group (CCG). The decline rate for IFRs was 71% for NHS England and 34% for CCGs. Lack of exceptionality was the primary reason cited for declining IFRs submitted between 2016-18 (n = 42/45; 93%). Half of the patients whose IFR was declined received treatment funded through other routes, the majority (13/23; 57%) from internal hospital budget. This was governed via a local high-cost drug panel. Positive clinical outcomes were observed in 50% (4/8) of patients who received NHS England IFR-funded treatment, 54% (19/35) who received CCG IFR-funded treatment and 91% (21/23) who were funded via other routes. CONCLUSION: The high rate of IFR decline signals inefficient use of resource expended in the IFR process. Gaps in access to high-cost medicines remain for patients with rare and refractory disease requiring urgent treatment, largely due to the demand for exceptionality from NHS commissioners. Local mechanisms address this unmet need but have limitations. An outcomes-based evaluation approach to commissioning and greater transparency of previous funding decisions by commissioners may improve efficiency and equity in the IFR system.


Asunto(s)
Medicina Estatal , Humanos , Estudios Retrospectivos , Centros de Atención Terciaria , Inglaterra
7.
Pharmacoecon Open ; 7(2): 175-187, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36315388

RESUMEN

BACKGROUND: The National Institute for Health and Care Excellence (NICE) is responsible for ensuring that patients in England and Wales can access clinically and cost-effective treatments. However, NICE's processes pose significant reimbursement challenges for treatments for rare diseases. While some orphan medicines have been appraised via the highly specialised technology route, most are appraised via the single technology appraisal programme, a route that is expected to be increasingly used given new more restrictive highly specialised technology criteria. This often results in delays to access owing to differences in applicable thresholds and the single technology appraisal approach being ill-equipped to deal with the inevitable decision uncertainty. NICE recently published their updated methods and process manual, which includes a new severity-of-disease modifier and an instruction to be more flexible when considering uncertainty in rare diseases. However, as the threshold gap between the single technology appraisal and highly specialised technology programmes remains, it is unlikely that these changes alone will address the problem. OBJECTIVE: We explored the potential impact of quality-adjusted life-year weights in decision making. METHODS: We explored the impact of NICE's new severity-of-disease modifier weighting and two alternative methods (the use of alternative quality-adjusted life-year weights and the fair rate of return), using three recent single technology appraisals of orphan medicines (caplacizumab, teduglutide and pirfenidone for mild idiopathic pulmonary fibrosis). RESULTS: Our results suggest NICE's severity-of-disease modifier would not have affected the recommendations. Using alternative methods, based upon achievement of an incremental cost-effectiveness ratio below standard thresholds, patients could have received access to caplacizumab approximately 5 months earlier, and the appraisals for teduglutide and pirfenidone would have resulted in a positive recommendation following appraisal consultation meeting 1 when neither of these products was available over 5 years from the initial submission. CONCLUSION: Ultimately, moving from a restrictive end-of-life modifier to one based on disease severity is a more equitable approach likely to benefit many therapies, including orphan products. However, NICE's single technology appraisal updates are unlikely to result in faster reimbursement of orphan medicines, nor will they address concerns around market access for orphan medicines in the UK.

8.
J Nurs Educ ; 61(7): 367-374, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35858129

RESUMEN

BACKGROUND: Nursing education influences medication administration practices, which involve clinical decision making and risk perceptions. METHOD: This mixed-methods concurrent nested study explored the relationship among knowledge, personality traits, and self-efficacy related to medication administration error in fourth-year, prelicen-sure nursing students (n = 60) who were recruited from three campuses of a large university. RESULTS: Results indicated low mean knowledge (70.75) and neuroticism (2.44) scores, and high mean self-efficacy and confidence (5.78) and conscientiousness (4.51) scores. Conscientiousness was correlated with both knowledge (r = .271, p = .036) and neuroticism (r = -.313, p = .015). Thematic analysis yielded four themes: nature of risk perceptions, more opportunities to learn, experiences with medication administration error, and intrinsic characteristics influence errors. Convergence was evident in both knowledge and personality data; self-efficacy/confidence and risk perceptions data diverged. CONCLUSION: Knowledge, personality traits, and self-efficacy appear to influence nursing students' risk perceptions of medication administration error, indicating an area for future research. [J Nurs Educ. 2022;61(7):367-374.].


Asunto(s)
Bachillerato en Enfermería , Estudiantes de Enfermería , Humanos , Conocimiento , Personalidad , Autoeficacia
10.
BMC Microbiol ; 22(1): 98, 2022 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-35410125

RESUMEN

BACKGROUND: Some people produce specific body odours that make them more attractive than others to mosquitoes, and consequently are at higher risk of contracting vector-borne diseases. The skin microbiome can break down carbohydrates, fatty acids and peptides on the skin into volatiles that mosquitoes can differentiate. RESULTS: Here, we examined how skin microbiome composition of women differs in relation to level of attractiveness to Anopheles coluzzii mosquitoes, to identify volatiles in body odour and metabolic pathways associated with individuals that tend to be poorly-attractive to mosquitoes. We used behavioural assays to measure attractiveness of participants to An. coluzzii mosquitoes, 16S rRNA amplicon sequencing of the bacteria sampled from the skin and gas chromatography of volatiles in body odour. We found differences in skin microbiome composition between the poorly- and highly-attractive groups, particularly eight Amplicon Sequence Variants (ASVs) belonging to the Proteobacteria, Actinobacteria and Firmicutes phyla. Staphylococcus 2 ASVs are four times as abundant in the highly-attractive compared to poorly-attractive group. Associations were found between these ASVs and volatiles known to be attractive to Anopheles mosquitoes. Propanoic pathways are enriched in the poorly-attractive participants compared to those found to be highly-attractive. CONCLUSIONS: Our findings suggest that variation in attractiveness of people to mosquitoes is related to the composition of the skin microbiota, knowledge that could improve odour-baited traps or other next generation vector control tools.


Asunto(s)
Anopheles , Microbiota , Animales , Bacterias/genética , Bacterias/metabolismo , Femenino , Humanos , Mosquitos Vectores , Odorantes/análisis , ARN Ribosómico 16S/genética
12.
Br J Nutr ; 127(9): 1352-1357, 2022 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-34719409

RESUMEN

In May 2021, the Scientific Advisory Committee on Nutrition (SACN) published a risk assessment on lower carbohydrate diets for adults with type 2 diabetes (T2D)(). The purpose of the report was to review the evidence on 'low'-carbohydrate diets compared with the current UK government advice on carbohydrate intake for adults with T2D. However, since there is no agreed and widely utilised definition of a 'low'-carbohydrate diet, comparisons in the report were between lower and higher carbohydrate diets. SACN's remit is to assess the risks and benefits of nutrients, dietary patterns, food or food components for health by evaluating scientific evidence and to make dietary recommendations for the UK based on its assessment(). SACN has a public health focus and only considers evidence in healthy populations unless specifically requested to do otherwise. Since the Committee does not usually make recommendations relating to clinical conditions, a joint working group (WG) was established in 2017 to consider this issue. The WG comprised members of SACN and members nominated by Diabetes UK, the British Dietetic Association, Royal College of Physicians and Royal College of General Practitioners. Representatives from NHS England and NHS Health Improvement, the National Institute for Health and Care Excellence and devolved health departments were also invited to observe the WG. The WG was jointly chaired by SACN and Diabetes UK.


Asunto(s)
Diabetes Mellitus Tipo 2 , Dietética , Adulto , Humanos , Dieta Baja en Carbohidratos , Carbohidratos , Inglaterra
13.
Br J Nutr ; 127(10): 1567-1587, 2022 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-34284830

RESUMEN

A multi-disciplinary expert group met to discuss vitamin D deficiency in the UK and strategies for improving population intakes and status. Changes to UK Government advice since the 1st Rank Forum on Vitamin D (2009) were discussed, including rationale for setting a reference nutrient intake (10 µg/d; 400 IU/d) for adults and children (4+ years). Current UK data show inadequate intakes among all age groups and high prevalence of low vitamin D status among specific groups (e.g. pregnant women and adolescent males/females). Evidence of widespread deficiency within some minority ethnic groups, resulting in nutritional rickets (particularly among Black and South Asian infants), raised particular concern. Latest data indicate that UK population vitamin D intakes and status reamain relatively unchanged since Government recommendations changed in 2016. Vitamin D food fortification was discussed as a potential strategy to increase population intakes. Data from dose-response and dietary modelling studies indicate dairy products, bread, hens' eggs and some meats as potential fortification vehicles. Vitamin D3 appears more effective than vitamin D2 for raising serum 25-hydroxyvitamin D concentration, which has implications for choice of fortificant. Other considerations for successful fortification strategies include: (i) need for 'real-world' cost information for use in modelling work; (ii) supportive food legislation; (iii) improved consumer and health professional understanding of vitamin D's importance; (iv) clinical consequences of inadequate vitamin D status and (v) consistent communication of Government advice across health/social care professions, and via the food industry. These areas urgently require further research to enable universal improvement in vitamin D intakes and status in the UK population.


Asunto(s)
Distinciones y Premios , Administración Financiera , Adolescente , Animales , Pollos , Femenino , Alimentos Fortificados , Humanos , Masculino , Embarazo , Reino Unido/epidemiología , Vitamina D , Vitaminas
14.
J Genet Couns ; 31(1): 41-48, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34251069

RESUMEN

State-based genetic counseling licensure creates standardization, ensures high-quality care, and supports the credentialing of genetic counselors (GCs) in the United States. However, it also has the unintended consequence of requiring substantial time and resources from genetic counselors who need to obtain licensure in multiple states. There is a wide range of variability among state licensure applications, required supporting documentation, verification processes, and cost-all of which are barriers for genetic counselors. New licensure laws are being passed on a regular basis, further complicating this process. Resources may be available to some genetic counselors such as employer reimbursement and administrative support; however, access to this support is not universal. This paper reviews the current condition of genetic counseling multi-state licensure, including barriers, unique challenges, and possible solutions for increased efficiencies, based on the authors' experiences and examples found in other healthcare fields.


Asunto(s)
Consejeros , Asesoramiento Genético , Recolección de Datos , Humanos , Calidad de la Atención de Salud , Estados Unidos
15.
J Am Pharm Assoc (2003) ; 62(1): 326-334, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34893443

RESUMEN

BACKGROUND: Central to effective public health policy and practice is the trust between the population served and the governmental body leading health efforts, but that trust has eroded in the years preceding the pandemic. Vaccine hesitancy among adults is also a growing concern across the United States. Recent data suggest that the trustworthiness of information about the coronavirus 2019 (COVID-19) vaccine was a larger concern than the vaccine's adverse effects or risks. OBJECTIVE: This study aims to describe the methods used to create a public health microinfluencer social media vaccine confidence campaign for the COVID-19 vaccine in underserved Tennessee communities. A secondary objective is to describe how the Social-Ecological Model (SEM) and Social Cognitive Theory may address vaccine hesitancy using community pharmacies. METHODS: In late 2020, 50 independent community pharmacies in underserved communities across Tennessee were involved in a public health project with the State of Tennessee Department of Health and the University of Tennessee Health Science Center College of Pharmacy. The project involved a 3-pronged, pharmacy-based COVID-19 vaccination outreach project, including (1) social media messaging (i.e., microinfluencer approach), (2) community partner collaboration, and (3) in-pharmacy promotion. Quantitative and qualitative data will assess the quality and effectiveness of the program. Social media outcomes will also be assessed to measure the impact of the microinfluencer social media training. RESULTS: Project implementation is planned for 6 months (January 2021 to June 2021) after an initial month of planning by the research team (December 2020) and preceding several months of assessment (July 2021 and beyond). CONCLUSIONS: Novel, theory-based approaches will be necessary to improve vaccine confidence. One approach to promoting public health, derived from the SEM, may be to use trusted microinfluencers on social media platforms, such as local community pharmacists and community leaders.


Asunto(s)
COVID-19 , Medios de Comunicación Sociales , Adulto , Vacunas contra la COVID-19 , Humanos , SARS-CoV-2 , Tennessee , Estados Unidos , Vacunación , Vacilación a la Vacunación
16.
Nurse Educ Pract ; 58: 103274, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34922091

RESUMEN

AIM: The purpose of this study was to explore and describe pre-licensure nursing students' perceptions of risk for medication administration errors in fourth-year baccalaureate student nurses from three campuses at a large central Pennsylvania university. BACKGROUND: Medication administration errors continue to be a significant safety concern in healthcare settings. Pre-licensure nursing education is a critical time period during which to have an impact on future medication administration practices. Perception of risk influences decision making and behavior, including nursing clinical decision making. DESIGN: This descriptive, exploratory study involved a qualitative design. METHODS: A thematic analysis of the qualitative data resulting from 60 individual, in-depth semi-structured interviews was conducted. RESULTS: The participants offered rich, detailed narratives which revealed the following themes: (1) the nature of risk perceptions, (2) more opportunities to learn, (3) experiences with medication administration error, and (4) intrinsic characteristics influence errors. CONCLUSIONS: The findings provide a broad description of the nature of student nurse risk perceptions for future medication administration errors. Recommendations for nursing education practice and pedagogy include additional clinical experiences, modified pharmacology curricula and instruction, and expanded simulations involving medication administration error.


Asunto(s)
Bachillerato en Enfermería , Educación en Enfermería , Estudiantes de Enfermería , Humanos , Aprendizaje , Investigación Cualitativa
17.
Future Oncol ; 17(5): 611-627, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33052055

RESUMEN

Aim: To estimate the comparative efficacy of cemiplimab, a programmed cell death protein 1 inhibitor, versus EGFR inhibitors, pembrolizumab and platinum-based chemotherapy in terms of overall survival (OS) and progression-free survival. Patients & methods: We performed an indirect treatment comparison of cemiplimab and other available systemic therapies for patients with advanced cutaneous squamous cell carcinoma. Results: Cemiplimab was associated with benefits in OS (hazard ratios range: 0.07-0.52) and progression-free survival (hazard ratios range: 0.30-0.67) versus EGFR inhibitors and pembrolizumab (data from KEYNOTE-629). Cemiplimab was more efficacious versus platinum-based chemotherapy in terms of OS. Conclusion: Cemiplimab may offer improvements in survival for advanced cutaneous squamous cell carcinoma patients compared with existing systemic therapies.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Carboplatino/farmacología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Cetuximab/farmacología , Cetuximab/uso terapéutico , Cisplatino/farmacología , Cisplatino/uso terapéutico , Ensayos Clínicos como Asunto , Receptores ErbB/antagonistas & inhibidores , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Estudios Observacionales como Asunto , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Supervivencia sin Progresión , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología
18.
Anticancer Res ; 40(2): 719-722, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014913

RESUMEN

AIM: A commercially available light emitting diode (LED) that transmitted narrow band ultraviolet B (UVB) radiation was evaluated for its efficacy and efficiency to produce vitamin D3 in human skin. MATERIALS AND METHODS: Human skin samples were obtained from surgical procedures. The LED had peak emission wavelength of 295 nm. Skin samples were exposed to the UVB-LED for varying times and then were analyzed by high-pressure liquid chromatography (HPLC) to determine the vitamin D3 content. RESULTS: There was a statistically significant time- and dose-dependent increase in the percent of 7-dehydrocholesterol that was converted to vitamin D3 in the skin type II samples; 1.3%±0.5, 2.3%±0.6 and 4.5%±1.67 after exposure to 0.75 (11.7 mJ/cm2), 1.5 (23.4 mJ/cm2) and 3 (46.8 mJ/cm2) minimal erythemal doses (MEDs), respectively. CONCLUSION: The UVB-LED was effective and efficient in generating vitamin D3 in human skin, in vitro. The amount of vitamin D3 production increased in a dose-dependent fashion with increased UVB energy. UVB-LEDs can be developed for devices that can efficiently produce vitamin D3 in human skin.


Asunto(s)
Colecalciferol/biosíntesis , Piel/metabolismo , Piel/efectos de la radiación , Rayos Ultravioleta , Colecalciferol/metabolismo , Cromatografía Líquida de Alta Presión , Deshidrocolesteroles/metabolismo , Relación Dosis-Respuesta en la Radiación , Humanos
19.
Anticancer Res ; 40(1): 535-543, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892609

RESUMEN

BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.


Asunto(s)
Suplementos Dietéticos , Genómica , Metabolómica , Vitamina D/farmacología , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Hormona Paratiroidea/sangre , Análisis de Componente Principal , Mapas de Interacción de Proteínas/efectos de los fármacos , Vitamina D/análogos & derivados , Vitamina D/sangre
20.
Plant Biotechnol J ; 18(2): 402-414, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31301102

RESUMEN

Plants can provide a cost-effective and scalable technology for production of therapeutic monoclonal antibodies, with the potential for precise engineering of glycosylation. Glycan structures in the antibody Fc region influence binding properties to Fc receptors, which opens opportunities for modulation of antibody effector functions. To test the impact of glycosylation in detail, on binding to human Fc receptors, different glycovariants of VRC01, a broadly neutralizing HIV monoclonal antibody, were generated in Nicotiana benthamiana and characterized. These include glycovariants lacking plant characteristic α1,3-fucose and ß1,2-xylose residues and glycans extended with terminal ß1,4-galactose. Surface plasmon resonance-based assays were established for kinetic/affinity evaluation of antibody-FcγR interactions, and revealed that antibodies with typical plant glycosylation have a limited capacity to engage FcγRI, FcγRIIa, FcγRIIb and FcγRIIIa; however, the binding characteristics can be restored and even improved with targeted glycoengineering. All plant-made glycovariants had a slightly reduced affinity to the neonatal Fc receptor (FcRn) compared with HEK cell-derived antibody. However, this was independent of plant glycosylation, but related to the oxidation status of two methionine residues in the Fc region. This points towards a need for process optimization to control oxidation levels and improve the quality of plant-produced antibodies.


Asunto(s)
Anticuerpos Anti-VIH , Fragmentos Fc de Inmunoglobulinas , Ingeniería de Proteínas , Anticuerpos Anti-VIH/metabolismo , Infecciones por VIH/inmunología , VIH-1 , Humanos , Fragmentos Fc de Inmunoglobulinas/metabolismo , Polisacáridos , Unión Proteica , Nicotiana/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...