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1.
Hum Mol Genet ; 32(15): 2485-2501, 2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37171606

RESUMEN

ATRX is a chromatin remodelling ATPase that is involved in transcriptional regulation, DNA damage repair and heterochromatin maintenance. It has been widely studied for its role in ALT-positive cancers, but its role in neurological function remains elusive. Hypomorphic mutations in the X-linked ATRX gene cause a rare form of intellectual disability combined with alpha-thalassemia called ATR-X syndrome in hemizygous males. Clinical features also include facial dysmorphism, microcephaly, short stature, musculoskeletal defects and genital abnormalities. As complete deletion of ATRX in mice results in early embryonic lethality, the field has largely relied on conditional knockout models to assess the role of ATRX in multiple tissues. Given that null alleles are not found in patients, a more patient-relevant model was needed. Here, we have produced and characterized the first patient mutation knock-in model of ATR-X syndrome, carrying the most common causative mutation, R246C. This is one of a cluster of missense mutations located in the chromatin-binding domain and disrupts its function. The knock-in mice recapitulate several aspects of the patient disorder, including craniofacial defects, microcephaly, reduced body size and impaired neurological function. They provide a powerful model for understanding the molecular mechanisms underlying ATR-X syndrome and testing potential therapeutic strategies.


Asunto(s)
Discapacidad Intelectual Ligada al Cromosoma X , Microcefalia , Talasemia alfa , Animales , Masculino , Ratones , Talasemia alfa/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Microcefalia/genética , Mutación , Proteínas Nucleares/genética , Proteína Nuclear Ligada al Cromosoma X/genética , Humanos
2.
J Adv Nurs ; 80(9): 3797-3811, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38268132

RESUMEN

AIM: The aim of this study is to explore how immigrant women and men from India construct mental health and mental illness in the perinatal period. DESIGN: Qualitative interpretive design. METHODS: Data were collected by conducting in-depth interviews with 19 participants. Photo elicitation, free listing and pile sorting were used during the interviews. Purposive sampling was used, and data were collected in 2018 and 2019. Data were analysed using thematic analysis. FINDING/RESULTS: One major theme and three subthemes were identified. 'We do not talk about it' was the major theme and the subthemes: (1) 'living peacefully and feeling happy' described the views on mental health; (2) 'that's the elephant in the room still' captures how participants felt when talking about mental illness; and (3) 'why don't we talk about it' offers reasons why the Indian community does not talk about mental health and illness. CONCLUSION: The findings of this study have highlighted the importance of understanding the impact of immigration and being culturally sensitive when assessing mental health in the perinatal period. IMPACT: The findings of this study identify some of the reasons for non-disclosure of mental health issues by immigrants. Incorporating these findings during psychosocial assessment by health professionals in the perinatal period will help translate the cultural aspects into more effective communication. PATIENT OR PUBLIC CONTRIBUTION: Patient and public contribution to the study was provided by the Community Stakeholders Group; these were members of the immigrant community from India who had expertise in mental health. They contributed to the study design and the key terms and phrases for the free list used in interviews.


Asunto(s)
Emigrantes e Inmigrantes , Trastornos Mentales , Salud Mental , Investigación Cualitativa , Humanos , Femenino , India/etnología , Trastornos Mentales/etnología , Trastornos Mentales/psicología , Adulto , Emigrantes e Inmigrantes/psicología , Masculino , Salud Mental/etnología , Embarazo , Adulto Joven
3.
Genome Res ; 30(4): 540-552, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32317254

RESUMEN

Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of Mecp2-null traits from screening 3177 Mecp2/Y genomes. Whole-exome sequencing, genetic crosses, and association analysis identified 22 candidate genes. Additional lesions in these candidate genes or pathway components associate variant alleles with phenotypic improvement in 30 lines. A network analysis shows that 63% of the genes cluster into the functional categories of transcriptional repression, chromatin modification, or DNA repair, delineating a pathway relationship with MECP2. Many mutations lie in genes that modulate synaptic signaling or lipid homeostasis. Mutations in genes that function in the DNA damage response (DDR) also improve phenotypes in Mecp2/Y mice. Association analysis was successful in resolving combinatorial effects of multiple loci. One line, which carries a suppressor mutation in a gene required for cholesterol synthesis, Sqle, carries a second mutation in retinoblastoma binding protein 8, endonuclease (Rbbp8, also known as CtIP), which regulates a DDR choice in double-stranded break (DSB) repair. Cells from Mecp2/Y mice have increased DSBs, so this finding suggests that the balance between homology-directed repair and nonhomologous end joining is important for neuronal cells. In this and other lines, two suppressor mutations confer greater improvement than one alone, suggesting that combination therapies could be effective in RTT.


Asunto(s)
Daño del ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Proteína 2 de Unión a Metil-CpG/genética , Síndrome de Rett/diagnóstico , Síndrome de Rett/genética , Supresión Genética , Alelos , Animales , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Genotipo , Homocigoto , Metabolismo de los Lípidos , Masculino , Proteína 2 de Unión a Metil-CpG/metabolismo , Ratones , Ratones Noqueados , Mutación , Fenotipo , Síndrome de Rett/metabolismo , Transducción de Señal , Secuenciación del Exoma
4.
Facial Plast Surg ; 39(6): 590-594, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37402402

RESUMEN

Patients often present with a complaint of nasal blockage, either primarily, or in conjunction with aesthetic concerns. The evaluation of the patient with nasal obstruction involves a comprehensive history and a detailed physical examination. The nose is an organ in which form and function are inseparable, and as such, examination of the patient with nasal obstruction must focus not only the internal structures that may cause obstruction of the nasal airway, but also the external structure of the nose as it impacts nasal breathing. Detailed facial analysis and a systematic nasal examination will reveal details regarding nasal obstruction due to internal sources such as septal deviation, turbinate hypertrophy, or nasal lining abnormalities, and structural abnormalities such as nasal valve collapse or external nasal deformity. This approach, in categorizing each component of the nasal exam and its findings, allows the surgeon to formulate an appropriate treatment plan that emerges from the details of the examination.


Asunto(s)
Obstrucción Nasal , Deformidades Adquiridas Nasales , Rinoplastia , Humanos , Obstrucción Nasal/diagnóstico , Obstrucción Nasal/etiología , Obstrucción Nasal/cirugía , Estética Dental , Tabique Nasal/cirugía , Deformidades Adquiridas Nasales/complicaciones , Deformidades Adquiridas Nasales/cirugía , Rinoplastia/efectos adversos
5.
J Pediatr Nurs ; 67: e234-e248, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35914989

RESUMEN

OBJECTIVE: To synthesize the literature regarding the experiences of new graduate nurses working in a pediatric setting. BACKGROUND: The transition experiences of new graduate nurses can be stressful and challenging. Pediatric settings may cause additional stress due to the unique nature of children's nursing and its' environment. INCLUSION CRITERIA: Qualitative studies of any design and qualitative components of mixed method studies that explored the experiences of new graduate nurses in a pediatric setting were included in this review: neonatal intensive care units and special care nurseries were excluded. METHODS: The JBI meta-aggregation approach for synthesizing qualitative data was followed. Databases searched were CINAHL, MEDLINE (Ovid), APA PsycInfo, Scopus, PubMed Central, ERIC, and ProQuest Dissertations and Theses. Studies published between January 2000 and January 2022 inclusive were considered. RESULTS: 2229 records were screened, and nine studies selected. From the nine studies 203 findings were included, resulting in 19 categories and five synthesized findings. The synthesized findings related to support, developing identity and role transition, working conditions and environment, fear and uncertainty, and career and goal planning. CONCLUSIONS: New graduates in a pediatric setting required support that took account of their development needs with consistent preceptorship. Being considered part of a team and the support of other team members were important in developing identity as a new graduate nurse in a pediatric setting. Working conditions for the new graduate needed to be safe, and new graduates also felt fearful and uncertain when it came to their new accountability and responsibilities.


Asunto(s)
Educación de Postgrado en Enfermería , Recién Nacido , Humanos , Niño , Investigación Cualitativa , Atención a la Salud
6.
Adv Neonatal Care ; 21(5): 418-424, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33427751

RESUMEN

BACKGROUND: Preterm infants routinely require enteral feeding via nasogastric or orogastric tubes as an alternative to oral feeding to meet their nutritional needs. Anecdotal evidence suggests variations in practice related to correct tube placement and assessment of feed intolerance. PURPOSE: To determine the current practices of enteral feeding tube placement confirmation and gastric residual (GR) aspiration of neonatal clinicians in Australia. METHODS: A cross-sectional online survey comprising 24 questions was distributed to nursing and medical health professionals working in Australian neonatal care units through 2 e-mail listservs made available by professional organizations. FINDINGS: The survey was completed by 129 clinicians. A single method was practiced by 50% of the clinicians in confirming tube placement, and most common practice was assessing the pH of GR aspirate. The majority of respondents (96%) reported that they relied on GR aspiration and clinical signs to determine feeding tolerance and subsequent decisions such as ceasing or decreasing feeds. However, the frequency of aspiration, the amount and color of aspirate considered to be normal/abnormal, and decisions on whether to replace gastric aspirate or whether aspiration should be performed during continuous tube feeding varied. IMPLICATION FOR PRACTICE: This study demonstrated considerable variability in clinical practice for enteral feeding tube placement confirmation and GR aspiration despite most respondents reporting using a unit-based clinical practice guideline. Our study findings highlight the need for not only developing evidence-based practice guidelines for safe and consistent clinical practice but also ensuring that these guidelines are followed by all clinicians. IMPLICATION FOR RESEARCH: Further research is needed to establish evidence-based methods both for enteral feeding tube placement confirmation and for the assessment of feeding intolerance during tube feeding. In addition, the reasons why evidence-based methods are not followed must be investigated.


Asunto(s)
Nutrición Enteral , Recien Nacido Prematuro , Australia , Estudios Transversales , Práctica Clínica Basada en la Evidencia , Humanos , Lactante , Recién Nacido , Intubación Gastrointestinal
7.
Crit Rev Food Sci Nutr ; 58(10): 1650-1659, 2018 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-28350175

RESUMEN

This workshop, jointly presented by the ILSI North America Technical Committees on Food Microbiology and Sodium, aimed to provide greater knowledge and appreciation of the opportunities and challenges facing the food industry in answering the public health community's call to reduce sodium levels in the food supply. One major challenge is finding effective substitutes for the various antimicrobial and functional roles that sodium plays across different food categories. Sodium plays a critical role in retarding the growth of pathogens and food spoilage bacteria. Moreover, taste is an important factor for consumers when they choose food products, and the flavor changes that occur when salt is reduced or replaced must be considered and ingredients and processes adjusted accordingly. The workshop provided a platform for a multidisciplinary discussion among the microbiology, food science, nutrition, and public health communities to share progress and propose solutions, including the formation of public-private partnerships, to develop coordinated and comprehensive strategies. This paper provides an overview of the issues raised, rather than a specific summary of workshop discussions. The Food and Drug Administration's Draft Guidance for Industry on voluntary sodium reduction and the 2015 US Dietary Guidelines for Americans were released subsequent to the workshop and are also discussed.


Asunto(s)
Abastecimiento de Alimentos , Sodio en la Dieta/administración & dosificación , Análisis de los Alimentos , Industria de Alimentos , Microbiología de Alimentos , Tecnología de Alimentos , Humanos , América del Norte , Política Nutricional , Fenómenos Fisiológicos de la Nutrición , Salud Pública , Cloruro de Sodio Dietético
9.
Cochrane Database Syst Rev ; 2: CD010331, 2017 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-28160271

RESUMEN

BACKGROUND: Hospitalised newborn neonates frequently undergo painful invasive procedures that involve penetration of the skin and other tissues by a needle. One intervention that can be used prior to a needle insertion procedure is application of a topical local anaesthetic. OBJECTIVES: To evaluate the efficacy and safety of topical anaesthetics such as amethocaine and EMLA in newborn term or preterm infants requiring an invasive procedure involving puncture of skin and other tissues with a needle. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase and CINAHL up to 15 May 2016; previous reviews including cross-references, abstracts, and conference proceedings. We contacted expert informants. We contacted authors directly to obtain additional data. We imposed no language restrictions. SELECTION CRITERIA: Randomised, quasi-randomised controlled trials, and cluster and cross-over randomised trials that compared the topical anaesthetics amethocaine and eutectic mixture of local anaesthetics (EMLA) in terms of anaesthetic efficacy and safety in newborn term or preterm infants requiring an invasive procedure involving puncture of skin and other tissues with a needle DATA COLLECTION AND ANALYSIS: From the reports of the clinical trials we extracted data regarding clinical outcomes including pain, number of infants with methaemoglobin level 5% and above, number of needle prick attempts prior to successful needle-related procedure, crying, time taken to complete the procedure, episodes of apnoea, episodes of bradycardia, episodes of oxygen desaturation, neurodevelopmental disability and other adverse events. MAIN RESULTS: Eight small randomised controlled trials met the inclusion criteria (n = 506). These studies compared either EMLA and placebo or amethocaine and placebo. No studies compared EMLA and amethocaine. We were unable to meta-analyse the outcome of pain due to differing outcome measures and methods of reporting. For EMLA, two individual studies reported a statistically significant reduction in pain compared to placebo during lumbar puncture and venepuncture. Three studies found no statistical difference between the groups during heel lancing. For amethocaine, three studies reported a statistically significant reduction in pain compared to placebo during venepuncture and one study reported a statistically significant reduction in pain compared to placebo during cannulation. One study reported no statistical difference between the two groups during intramuscular injection.One study reported no statistical difference between EMLA and the placebo group for successful venepuncture at first attempt. One study similarly reported no statistically significant difference between Amethocaine and the placebo group for successful cannulation at first attempt.Risk for local redness, swelling or blanching was significantly higher with EMLA (typical risk ratio (RR) 1.65, 95% confidence interval (CI) 1.24 to 2.19; typical risk difference (RD) 0.17, 95% CI 0.09 to 0.26; n = 272; number needed to treat for an additional harmful outcome (NNTH) 6, 95% CI 4 to 11; I2 = 92% indicating considerable heterogeneity) although not for amethocaine (typical RR 2.11, 95% CI 0.72 to 6.16; typical RD 0.05, 95% CI -0.02 to 0.11, n = 221). These local skin reactions for EMLA and amethocaine were reported as short-lasting. Two studies reported no methaemoglobinaemia with single application of EMLA. The quality of the evidence on outcomes assessed according to GRADE was low to moderate. AUTHORS' CONCLUSIONS: Overall, all the trials were small, and the effects of uncertain clinical significance. The evidence regarding the effectiveness or safety of the interventions studied is inadequate to support clinical recommendations. There has been no evaluation regarding any long-term effects of topical anaesthetics in newborn infants.High quality studies evaluating the efficacy and safety of topical anaesthetics such as amethocaine and EMLA for needle-related pain in newborn term or preterm infants are required. These studies should aim to determine efficacy of these topical anaesthetics and on homogenous groups of infants for gestational age. While there was no methaemoglobinaemia in the studies that reported methaemoglobin, the efficacy and safety of EMLA, especially in very preterm infants, and for repeated application, need to be further evaluated in future studies.


Asunto(s)
Anestesia Local , Anestésicos Locales/administración & dosificación , Dolor/prevención & control , Punciones/efectos adversos , Tetracaína/administración & dosificación , Anestesia Local/efectos adversos , Anestesia Local/métodos , Anestésicos Locales/efectos adversos , Cateterismo/efectos adversos , Combinación de Medicamentos , Humanos , Recién Nacido , Recien Nacido Prematuro , Agujas , Dolor/etiología , Dimensión del Dolor , Flebotomía/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Punción Espinal/efectos adversos
10.
J Clin Nurs ; 26(19-20): 3099-3110, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27875018

RESUMEN

AIMS AND OBJECTIVES: To describe the process and challenges from a project that aimed to develop processes, source new placements and place students primarily in the discipline of nursing, but also occupational therapy, physiotherapy, podiatry, social work, and speech therapy. BACKGROUND: Clinical experience in health facilities is an essential element of health professional education, yet globally, there is a lack of clinical placements to meet demands. Educational providers are seeking placements in nontraditional facilities, yet little has been reported on the challenges in the process of procuring clinical placements. DESIGN: The project used a descriptive approach within a quality implementation framework. METHODS: The project was guided by the quality implementation framework that included four critical steps: considerations of the host setting, structuring the implementation, supporting the implementation and improving future applications. RESULTS: A total of 115 new student placements were finalised across six health disciplines, including elderly care, nongovernment organisations and general practice. Sixty-two nursing students were placed in the new placements during the project. Challenges included communication, the time-consuming nature of the process and 'gatekeeping' blocks to obtaining placements. Recommendations included the importance of personal interaction in developing and maintaining relationships, and the need for clear communication processes and documentation. Potential areas for research are also given. CONCLUSIONS: There is great potential for growth in establishing new placements outside the traditional placement facilities for nursing and allied health and for expanding already existing nonhospital placements. RELEVANCE TO CLINICAL PRACTICE: Clinical professional experiences are essential to any nursing or allied health programme. There is an increasing demand for, and global lack of, clinical placements for nursing and allied health students. The results provide nursing and allied health educators and managers a framework for planning clinical placement procurement, and assisting in decision-making and developing strategies and processes for practice.


Asunto(s)
Empleos Relacionados con Salud/estadística & datos numéricos , Prácticas Clínicas/estadística & datos numéricos , Educación en Enfermería/organización & administración , Desarrollo de Programa , Estudiantes de Enfermería/estadística & datos numéricos , Empleos Relacionados con Salud/educación , Técnicos Medios en Salud/educación , Técnicos Medios en Salud/estadística & datos numéricos , Comunicación , Humanos , Relaciones Interprofesionales
11.
J Nutr ; 146(5): 1051-61, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27052537

RESUMEN

BACKGROUND: The 2007-2010 NHANES provides the first US nationally representative serum 25-hydroxyvitamin D [25(OH)D] concentrations measured by standardized liquid chromatography-tandem mass spectrometry. OBJECTIVE: We describe patterns for total 25(OH)D and individual metabolites in persons aged ≥1 y stratified by race-ethnicity and grouped by demographic, intake, physiologic, and lifestyle variables. METHODS: We measured 25-hydroxycholecalciferol [25(OH)D3], 25-hydroxyergocalciferol [25(OH)D2], and C3-epimer of 25(OH)D3 [C3-epi-25(OH)D3] in serum samples (n = 15,652) from the 2007-2010 cross-sectional NHANES [total 25(OH)D = 25(OH)D3 + 25(OH)D2]. RESULTS: Concentrations (median, detection rate) of 25(OH)D3 (63.6 nmol/L, 100%) and C3-epi-25(OH)D3 (3.40 nmol/L, 86%) were generally detectable; 25(OH)D2 was detectable in 19% of the population. Total 25(OH)D, 25(OH)D3, and C3-epi-25(OH)D3 displayed similar demographic patterns and were strongly correlated (Spearman's r > 0.70). Concentrations of 25(OH)D2 (90th percentile) were much higher in persons aged ≥60 y (17.3 nmol/L) than in younger age groups (≤4.88 nmol/L). We noted significant race-ethnicity differences in mean total 25(OH)D [non-Hispanic blacks (NHBs), Hispanics, and non-Hispanic whites (NHWs): 46.6, 57.2, and 75.2 nmol/L, respectively] and in the prevalence of total 25(OH)D <30 nmol/L overall (24% of NHBs, 6.4% of Hispanics, and 2.3% of NHWs) as well as stratified by season (winter months: 30% of NHBs, 7.5% of Hispanics, and 3.8% of NHWs; summer months: 17% of NHBs, 4.4% of Hispanics, and 1.6% of NHWs). Persons with higher vitamin D intakes (diet, supplements, or both) and those examined during May-October had significantly higher total 25(OH)D. Significant race-ethnicity interactions in a multiple linear regression model confirmed the necessity of providing race-ethnicity-specific estimates of total 25(OH)D. CONCLUSIONS: Race-ethnicity differences in the prevalence of low total 25(OH)D remained strong even after adjustment for season to account for the NHANES design imbalance between season, latitude, and race-ethnicity. The strong correlation between C3-epi-25(OH)D3 and 25(OH)D3 may be because the epimer is a metabolite of 25(OH)D3. The presence of 25(OH)D2 mainly in older persons is likely a result of high-dose prescription vitamin D2.


Asunto(s)
Negro o Afroamericano , Hispánicos o Latinos , Deficiencia de Vitamina D/epidemiología , Vitamina D/sangre , Población Blanca , 25-Hidroxivitamina D 2/sangre , Adolescente , Adulto , Factores de Edad , Anciano , Calcifediol/sangre , Niño , Preescolar , Cromatografía Líquida de Alta Presión/métodos , Dieta , Suplementos Dietéticos , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estaciones del Año , Espectrometría de Masas en Tándem/métodos , Estados Unidos/epidemiología , Vitamina D/análogos & derivados , Deficiencia de Vitamina D/sangre , Vitaminas/sangre , Adulto Joven
12.
Am J Public Health ; 106(1): 153-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26562128

RESUMEN

OBJECTIVES: We described the risk for maltreatment among toddlers of US Army soldiers over different deployment cycles to develop a systematic response within the US Army to provide families appropriate supports. METHODS: We conducted a person-time analysis of substantiated maltreatment reports and medical diagnoses among children of 112,325 deployed US Army soldiers between 2001 and 2007. RESULTS: Risk of maltreatment was elevated after deployment for children of soldiers deployed once but not for children of soldiers deployed twice. During the 6 months after deployment, children of soldiers deployed once had 4.43 substantiated maltreatment reports and 4.96 medical diagnoses per 10,000 child-months. The highest maltreatment rate among children of soldiers deployed twice occurred during the second deployment for substantiated maltreatment (4.83 episodes per 10,000 child-months) and before the first deployment for medical diagnoses of maltreatment (3.78 episodes per 10,000 child-months). CONCLUSIONS: We confirmed an elevated risk for child maltreatment during deployment but also found a previously unidentified high-risk period during the 6 months following deployment, indicating elevated stress within families of deployed and returning soldiers. These findings can inform efforts by the military to initiate and standardize support and preparation to families during periods of elevated risk.


Asunto(s)
Maltrato a los Niños/estadística & datos numéricos , Trastornos de Combate/psicología , Relaciones Familiares/psicología , Personal Militar/estadística & datos numéricos , Trastornos de Combate/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Personal Militar/psicología , Medición de Riesgo , Estados Unidos/epidemiología
13.
Angew Chem Int Ed Engl ; 55(33): 9601-5, 2016 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-27355874

RESUMEN

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A (11) C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding.


Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Neuroimagen , Oxazoles/farmacología , Tomografía de Emisión de Positrones , Inhibidores de Proteínas Quinasas/farmacología , Triazoles/farmacología , Proteínas tau/antagonistas & inhibidores , Encéfalo/metabolismo , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Humanos , Modelos Moleculares , Estructura Molecular , Oxazoles/síntesis química , Oxazoles/química , Fosforilación/efectos de los fármacos , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Triazoles/síntesis química , Triazoles/química , Proteínas tau/metabolismo
14.
Annu Rev Nutr ; 34: 401-19, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24819324

RESUMEN

Decisions related to a spectrum of nutrition-related public health and clinical concerns must consider many factors and are best informed by evaluating the totality and quality of the evidence. Systematic review (SR) is a structured process to evaluate, compare, and synthesize relevant evidence for the SR-specific question(s). Applications of SR are exemplified here through the discussion of four case studies: research agendas, nutrient reference intakes, dietary guidance, and practice guidelines. Concerns that SR cannot be effectively applied to nutrition evidence because of the lack of an unexposed comparator and the complex homeostasis in nutrition are discussed. Central to understanding the applicability of SR is its flexibility in defining key inclusion criteria and rigorous elements as appropriate for the SR-specific question(s). Through the reduction of bias and random error by explicit, reproducible, comprehensive, and rigorous examination of all of the evidence, SR informs the scientific judgment needed for sound evidence-based public health nutrition.


Asunto(s)
Medicina Basada en la Evidencia , Promoción de la Salud , Política Nutricional , Salud Pública , Animales , Técnicas de Apoyo para la Decisión , Humanos , Metaanálisis como Asunto , Guías de Práctica Clínica como Asunto , Salud Pública/tendencias , Literatura de Revisión como Asunto
15.
J Nutr ; 145(7): 1623-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25972526

RESUMEN

BACKGROUND: The purpose of food fortification is to affect those at the lower end of the distribution curve for nutrient status while avoiding unintended consequences for those at the high end of the distribution. Vitamin D presents challenges in this regard. OBJECTIVES: We used scenarios to model changes in concentrations of serum 25-hydroxyvitamin D [25(OH)D] based on increases made because of assumptions about fortification. We then examined the outcomes for balance between improving serum 25(OH)D status for those at risk of inadequacy while avoiding high concentrations for those not at risk. METHODS: Data from NHANES 2001-2006 served as baseline serum 25(OH)D concentrations and were used to model shifts in serum 25(OH)D distribution after application of 3 fortification scenarios, including conceptual scenarios and an experiential predictive scenario we developed with the use of statistical modeling of changes in NHANES serum folate concentrations between prefortification and postfortification time periods. RESULTS: All scenarios suggested the possibility of increasing serum 25(OH)D above 125 nmol/L among the proportion of the population at the high end of baseline serum 25(OH)D distribution. The scenario based on serum folate change struck a middle ground between the 2 conceptual scenarios. It predicted a prevalence of 11% <40 nmol/L serum 25(OH)D compared with 17% currently (study baseline), and 8% prevalence of serum 25(OH)D >125 nmol/L compared with <1% currently (study baseline). It also confirmed that fortification affects those at the low end of the status distribution curve differently from those at the high end. CONCLUSIONS: Nutrient inadequacy of the type demonstrated by vitamin D--in which the risk is not universal--requires a thorough exploration of the unintended consequences of the overall shift in the distribution of serum 25(OH)D if efforts are made to use fortification to increase the status of persons at risk of deficiency. Fortification is at best a blunt instrument that must be implemented with caution. Moreover, fortification must be preceded by more research to elucidate the dose-response relation between intake and changes in serum 25(OH)D.


Asunto(s)
Ácido Fólico/administración & dosificación , Alimentos Fortificados , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Transversales , Femenino , Ácido Fólico/sangre , Humanos , Lactante , Masculino , Desnutrición/sangre , Desnutrición/prevención & control , Persona de Mediana Edad , Modelos Estadísticos , Encuestas Nutricionales , Luz Solar , Vitamina D/administración & dosificación , Vitamina D/sangre , Adulto Joven
17.
J Nutr ; 144(5): 654-9, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24623845

RESUMEN

The discrepancy between the commonly used vitamin D status measures-intake and serum 25-hydroxyvitamin D [25(OH)D] concentrations--has been perplexing. Sun exposure increases serum 25(OH)D concentrations and is often used as an explanation for the higher population-based serum concentrations in the face of apparently low vitamin D intake. However, sun exposure may not be the total explanation. 25(OH)D, a metabolite of vitamin D, is known to be present in animal-based foods. It has been measured and reported only sporadically and is not currently factored into U.S. estimates of vitamin D intake. Previously unavailable preliminary USDA data specifying the 25(OH)D content of a subset of foods allowed exploration of the potential change in the reported overall vitamin D content of foods when the presence of 25(OH)D was included. The issue of 25(OH)D potency was addressed, and available commodity intake estimates were used to outline trends in projected vitamin D intake when 25(OH)D in foods was taken into account. Given the data available, there were notable increases in the total vitamin D content of a number of animal-based foods when potency-adjusted 25(OH)D was included, and in turn there was a potentially meaningful increase (1.7-2.9 µg or 15-30% of average requirement) in vitamin D intake estimates. The apparent increase could reduce discrepancies between intake estimates and serum 25(OH)D concentrations. The relevance to dietary interventions is discussed, and the need for continued exploration regarding 25(OH)D measurement is highlighted.


Asunto(s)
Suplementos Dietéticos , Alimentos Fortificados , Vitamina D/análogos & derivados , Vitaminas/administración & dosificación , Vitaminas/sangre , Adulto , Animales , Bovinos , Pollos , Huevos , Conducta Alimentaria , Femenino , Peces , Humanos , Masculino , Carne , Encuestas Nutricionales/estadística & datos numéricos , Aves de Corral , Ratas , Luz Solar , Vitamina D/administración & dosificación , Vitamina D/sangre , Adulto Joven
18.
JBI Evid Implement ; 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39360522

RESUMEN

INTRODUCTION: Ambulatory care settings are at high risk for errors when identifying patients and matching them to their intended care. OBJECTIVE: The objective of this project was to improve correct and consistent patient identification and matching to their intended care by nurses in ambulatory care settings. METHODS: The seven-phase JBI Evidence Implementation Framework was used to guide this project. JBI tools were used to audit current practices and implement best practices in four ambulatory care units. The implementation plan included a baseline audit and two follow-up audits. Feedback was obtained through interviews with ambulatory care nursing staff, educational sessions were conducted for nursing staff, and unit guidelines were developed. RESULTS: In the baseline audit, compliance with best practice criteria for patient matching and identification was below 62% for 7/13 criteria. After conducting education sessions and other strategies, 1/3 pre- and post-clinical intervention criteria improved in compliance, while 2 were unchanged. For blood product administration criteria, 2/5 improved, 1 was unchanged, and 2 were lower than baseline. Nurses' education in patient identification procedures improved (1/1) and knowing where to access relevant policies remained unchanged at 100%. Criteria for patients knowing the importance of patient identification (2/2) and the identification band following national standards (1/1) improved from baseline. CONCLUSIONS: The results support the use of education sessions and infrastructure changes to promote and sustain change in evidence-based practice in ambulatory care units. Not all criteria improved, and the audit team identified strategies to improve the implementation of evidence-based practice in ambulatory care units. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A275.

19.
Nutr Bull ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258404

RESUMEN

In 2023, 25% of adults in England, Wales and Northern Ireland experienced food insecurity. The concentration of food insecurity in both socioeconomically disadvantaged groups and households containing children raises concerns about its uneven nutritional and health impacts across different groups. In parallel with rising food insecurity over the past decade, concerns about the environmental consequences of human diets are intensifying, where urgent changes are needed to people's diets to avoid irreversible environmental damage. It is generally assumed that cost has a significant impact on people's ability to adopt more environmentally sustainable food practices. This UK Research Council-funded project seeks to gain insights into the ways in which low-income mothers (are able to) engage with environmentally sustainable food practices. RQ1 will examine the day-to-day food practices that mothers undertake for their families to offer insights into everyday food insecurity and the relevance of environmentally sustainable food practices. RQ2 will explore biographical experiences to highlight how mothers' life histories influence their familial food practices, including their current household food security and engagement with environmentally sustainable food practices. Finally, RQ3 will explore mothers' upcoming prospects of food insecurity and environmentally sustainable food practices. These research questions will be explored through a qualitative longitudinal, feminist study of 15 low-income mothers in Sheffield, UK, combining in-depth interviews with ethnographic elements. Gaining improved knowledge of mothers' food practices on a low income will be valuable to influence realistic, effective and meaningful philosophies, policies and practical action that prioritises equity, good nutrition and environmentally sustainable food practices.

20.
Nurse Educ Pract ; 80: 104130, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39307052

RESUMEN

AIM: To map the characteristics of nursing educators' competency standards for practice from the existing literature, examine the evidence and identify commonalities and differences. BACKGROUND: Many countries or regions have produced nursing educator standards, however, there is no common set of standards or competencies used globally. Mapping these nursing educator standards should identify a common set of standards that can be applied across any nursing educator practice setting. DESIGN: The review was conducted using the JBI methodology for scoping reviews and followed an a priori protocol. METHODS: A comprehensive search of studies or guidelines (2001-2022) was undertaken to identify specific nursing educator competencies from any practice setting and in any language. Preceptorship and mentorship studies were excluded from the search terms. Databases searched for relevant records and guidelines were CINAHL, ERIC, Medline (Ovid), Pubmed, Scopus, Google and targeted websites. After screening and selection, relevant data were extracted and summarized using an extraction guide. Characteristics of the reports were identified and all three levels of competency statements were mapped against commonly occurring categories derived from the data. RESULTS: 1145 evidence records were screened after removal of duplicates with 14 records included in the review. The included evidence sources were from various nursing educator practice settings and educator roles. All evidence sources had at least two levels of competency statements and 16 competency categories were identified. Common categories in the first two competency levels were: leadership and management; research and scholarship; professional values and professional development; and facilitating learning. Statements related to learner evaluation were also common in the level 2 competencies. Level 3 competencies were included in seven evidence sources and most of the sources included almost all categories. Low-occurring statements at all levels were in the 'Nursing skills' and 'Decision-making/strategic planning" categories. CONCLUSIONS: Common characteristics and categories were found between different evidence sources in this review. The most common competency review categories included leadership and management, professional development and facilitating learning. Few decision-making competencies were identified from the evidence sources. These results can inform educators and managers in developing globally-based nursing educator competencies, performance management tools and job descriptions.

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