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1.
Cell ; 164(5): 859-71, 2016 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-26898329

RESUMEN

Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.


Asunto(s)
Desarrollo Infantil , Desnutrición/dietoterapia , Leche Humana/química , Leche/química , Oligosacáridos/metabolismo , Animales , Bacteroides fragilis/genética , Bifidobacterium/clasificación , Bifidobacterium/genética , Química Encefálica , Modelos Animales de Enfermedad , Escherichia coli/genética , Heces/microbiología , Vida Libre de Gérmenes , Humanos , Lactante , Malaui , Masculino , Metabolómica , Ratones , Ratones Endogámicos C57BL , Microbiota
2.
Health Res Policy Syst ; 22(1): 34, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38509612

RESUMEN

BACKGROUND: More than 35% of Aboriginal and Torres Strait Islander adults live with cardiovascular disease, diabetes, or chronic kidney disease. There is a pressing need for chronic disease prevention and management among Aboriginal and Torres Strait Islander people in Australia. Therefore, this review aimed to synthesise a decade of contemporary evidence to understand the barriers and enablers of chronic disease prevention and management for Aboriginal and Torres Strait Islander People with a view to developing policy and practice recommendations. METHODS: We systematically searched for peer-reviewed published articles between January 2014 to March 2023 where the search was performed using subject headings and keywords related to "Aboriginal and Torres Strait Islander peoples," "Chronic Disease," and "Primary Health Care". Quality assessment for all included studies was conducted using the Aboriginal and Torres Strait Islander Quality Appraisal Tool. The data were extracted and summarised using a conventional content analysis approach and applying strength-based approaches. RESULTS: Database searches identified 1653 articles where 26 met inclusion criteria. Studies varied in quality, primarily reporting on 14 criteria of the Aboriginal and Torres Strait Islander Quality Appraisal Tool. We identified six key domains of enablers and barriers of chronic disease prevention and management programs and implied a range of policy and practice options for improvement. These include culturally acceptable and safe services, patient-provider partnerships, chronic disease workforce, primary health care service attributes, clinical care pathways, and accessibility to primary health care services. This review also identified the need to address social and cultural determinants of health, develop the Aboriginal and Torres Strait Islander and non-Indigenous chronic disease workforce, support multidisciplinary teams through strengthening clinical care pathways, and engage Aboriginal and Torres Strait Islander communities in chronic disease prevention and management program design and delivery. CONCLUSION: Enabling place-based partnerships to develop contextual evidence-guided strategies that align with community priorities and aspirations, with the provision of funding mechanisms and models of care through policy and practice reforms will strengthen the chronic disease prevention and management program for Aboriginal and Torres Strait Islander people.


Asunto(s)
Aborigenas Australianos e Isleños del Estrecho de Torres , Servicios de Salud del Indígena , Adulto , Humanos , Atención a la Salud , Australia , Enfermedad Crónica , Atención Primaria de Salud
3.
BMC Med Educ ; 24(1): 260, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459497

RESUMEN

BACKGROUND: While there have been calls over the last 15 years for the inclusion of training in sex and gender-based medicine in medical school curricula and to sustain such improvements through a more gender responsive health system, little progress has been made. A related objective of the Australian National Men's Health Strategy (2020-30) is to improve practitioner core learning competencies in men's health as a critical step to reducing the burden of disease in men and disparities between men in health care access and outcomes. The aim of this study was therefore to obtain Australian medical student perspectives on the extent to which men's health and sex and gender-based medicine education is delivered in their curricula, their preparedness for engaging with men in clinical practice, and the men's health content they would have found useful during their training. METHODS: Eighty-three students (48% male) from 17 accredited medical schools, and in at least their fourth year of training, completed an online survey. The survey was co-designed by a multidisciplinary team of men's health researchers and clinicians, alongside a student representative. A mix of quantitative and qualitative survey items inquired about students' preparedness for men's health clinical practice, and coverage of men's health and sex- and gender-based medicine in their curricula. RESULTS: Most students reported minimal to no men's health coverage in their medical school education (65%). While few were offered optional men's health units (10.5%), the majority would have liked more formal training on the topic (78%). Accompanying qualitative findings substantiated a lack of preparedness among medical students to engage male patients, likely stemming from minimal coverage of men's health in their medical education. CONCLUSIONS: Australian medical students may feel underprepared for contemporary men's health clinical practice, as well as, albeit to a lesser extent, women's health clinical practice. There is a clear need and desire amongst medical students to enhance curricula with sex and gender-based medicine training.


Asunto(s)
Estudiantes de Medicina , Humanos , Masculino , Femenino , Salud del Hombre , Australia , Curriculum , Educación en Salud
4.
Anal Chem ; 95(21): 8223-8231, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37194568

RESUMEN

Mass spectrometry-based glycome analysis is a viable strategy for the compositional and functional exploration of glycosylation. However, the lack of generic tools for high-throughput and reliable glycan spectral interpretation largely hampers the broad usability of glycomic research. Here, we developed a generic and reliable glycomic tool, GlycoNote, for comprehensive and precise glycome analysis. GlycoNote supports interpretation of tandem-mass spectrometry glycomic data from any sample source, uses a novel target-decoy method with iterative decoy searching for highly reliable result output, and embeds an open-search component analysis mode for heterogeneity analysis of monosaccharides and modifications. We tested GlycoNote on several different large-scale glycomic datasets, including human milk oligosaccharides, N- and O-glycome from human cell lines, plant polysaccharides, and atypical glycans from Caenorhabditis elegans, demonstrating its high capacity for glycome analysis. An application of GlycoNote to the analysis of labeled and derived glycans further demonstrates its broad usability in glycomic studies. By enabling generic characterization of various glycan types and elucidation of component heterogeneity in glycomic samples, the freely available GlycoNote is a promising tool for facilitating glycomics in glycobiology research.


Asunto(s)
Glicómica , Polisacáridos/química , Glicómica/métodos , Humanos , Espectrometría de Masas en Tándem
5.
Fam Process ; 62(3): 976-992, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37114710

RESUMEN

Couple therapy has outperformed control conditions in randomized clinical trials (RCTs). However, there have been some questions whether couple treatment in naturalistic settings is as effective as those with more rigorous controls. The current meta-analysis examined 48 studies of couple therapy in non-randomized clinical trials. The pre-post effect size was Hedge's g = 0.522 for relational outcomes and Hedge's g = 0.587 for individual outcomes. However, there was significant heterogeneity in the results. Several moderators explained some of the variance in these estimates. For relationship outcomes, studies who had older couples and longer length of relationship had better outcomes. Studies with a higher percentage of racial/ethnic minority (REM) couples and studies in Veteran Affairs Medical Centers (VAMC) had lower relational outcomes. For individual outcomes, studies that had more sessions, older couples, and VAMC had better outcomes. Studies with a higher percentage of REM couples also had worse individual outcomes. Trainee status was not consistently related to relational or individual outcomes. Implications for research and practice are provided.


Asunto(s)
Terapia de Parejas , Humanos , Terapia de Parejas/métodos , Ensayos Clínicos Controlados no Aleatorios como Asunto
6.
Appl Environ Microbiol ; 88(2): e0170721, 2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34757822

RESUMEN

Human milk enriches members of the genus Bifidobacterium in the infant gut. One species, Bifidobacterium pseudocatenulatum, is found in the gastrointestinal tracts of adults and breastfed infants. In this study, B. pseudocatenulatum strains were isolated and characterized to identify genetic adaptations to the breastfed infant gut. During growth on pooled human milk oligosaccharides (HMOs), we observed two distinct groups of B. pseudocatenulatum, isolates that readily consumed HMOs and those that did not, a difference driven by variable catabolism of fucosylated HMOs. A conserved gene cluster for fucosylated HMO utilization was identified in several sequenced B. pseudocatenulatum strains. One isolate, B. pseudocatenulatum MP80, which uniquely possessed GH95 and GH29 α-fucosidases, consumed the majority of fucosylated HMOs tested. Furthermore, B. pseudocatenulatum SC585, which possesses only a single GH95 α-fucosidase, lacked the ability to consume the complete repertoire of linkages within the fucosylated HMO pool. Analysis of the purified GH29 and GH95 fucosidase activities directly on HMOs revealed complementing enzyme specificities with the GH95 enzyme preferring 1-2 fucosyl linkages and the GH29 enzyme favoring 1-3 and 1-4 linkages. The HMO-binding specificities of the family 1 solute-binding protein component linked to the fucosylated HMO gene cluster in both SC585 and MP80 are similar, suggesting differential transport of fucosylated HMO is not a driving factor in each strain's distinct HMO consumption pattern. Taken together, these data indicate the presence or absence of specific α-fucosidases directs the strain-specific fucosylated HMO utilization pattern among bifidobacteria and likely influences competitive behavior for HMO foraging in situ. IMPORTANCE Often isolated from the human gut, microbes from the bacterial family Bifidobacteriaceae commonly possess genes enabling carbohydrate utilization. Isolates from breastfed infants often grow on and possess genes for the catabolism of human milk oligosaccharides (HMOs), glycans found in human breast milk. However, catabolism of structurally diverse HMOs differs between bifidobacterial strains. This study identifies key gene differences between Bifidobacterium pseudocatenulatum isolates that may impact whether a microbe successfully colonizes an infant gut. In this case, the presence of complementary α-fucosidases may provide an advantage to microbes seeking residence in the infant gut. Such knowledge furthers our understanding of how diet drives bacterial colonization of the infant gut.


Asunto(s)
Bifidobacterium pseudocatenulatum , Leche Humana , Bifidobacterium pseudocatenulatum/metabolismo , Femenino , Humanos , Hidrolasas/metabolismo , Lactante , Leche Humana/química , Oligosacáridos/metabolismo , alfa-L-Fucosidasa/química , alfa-L-Fucosidasa/genética , alfa-L-Fucosidasa/metabolismo
7.
J Nutr ; 152(5): 1239-1253, 2022 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-35179194

RESUMEN

BACKGROUND: Human milk oligosaccharides (HMOs) are an abundant class of compounds found in human milk and have been linked to the development of the infant, and specifically the brain, immune system, and gut microbiome. OBJECTIVES: Advanced analytical methods were used to obtain relative quantitation of many structures in approximately 2000 samples from over 1000 mothers in urban, semirural, and rural sites across geographically diverse countries. METHODS: LC-MS-based analytical methods were used to profile the compounds with broad structural coverage and quantitative information. The profiles revealed their structural heterogeneity and their potential biological roles. Comparisons of HMO compositions were made between mothers of different age groups, lactation periods, infant sexes, and residing geographical locations. RESULTS: A common behavior found among all sites was a decrease in HMO abundances during lactation until approximately postnatal month 6, where they remained relatively constant. The greatest variations in structural abundances were associated with the presence of α(1,2)-fucosylated species. Genomic analyses of the mothers were not performed; instead, milk was phenotyped according to the abundances of α(1,2)-fucosylated structures. Mothers from the South American sites tended to have higher proportions of phenotypic secretors [mothers with relatively high concentrations of α(1,2)-fucosylated structures] in their populations compared to the rest of the globe, with Bolivia at ∼100% secretors, Peru at ∼97%, Brazil at ∼90%, and Argentina at ∼85%. Conversely, the cohort sampled in Africa manifested the lowest proportion of secretors (South Africa ∼ 63%, the Gambia ∼ 64%, and Malawi ∼ 75%). Furthermore, we compared total abundances of HMOs in secretors compared with nonsecretors and found that nonsecretors have lower abundances of HMOs compared to secretors, regardless of geographical location. We also observed compositional differences of the 50+ most abundant HMOs between milk types and geographical locations. CONCLUSIONS: This study represents the largest structural HMO study to date and reveals the general behavior of HMOs during lactation among different populations.


Asunto(s)
Leche Humana , Oligosacáridos , Lactancia Materna , Femenino , Humanos , Lactante , Lactancia , Malaui , Leche Humana/química , Oligosacáridos/química
8.
J Clin Psychol Med Settings ; 28(3): 543-552, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-32851553

RESUMEN

The aim of this mixed-methods study was to evaluate how providers in a busy urban practice with universal depression screening and co-located behavioral health services responded to positive screens and to explore patient expectations and attitudes towards positive screens. Semi-structured interviews of 20 pregnant women were conducted within 10 days of a positive depression screen or endorsement of suicidal ideation on the Edinburgh Perinatal Depression Scale and health record documentation was reviewed. Qualitative data were entered into a meta-matrix and cross-case analysis was used to reduce the data and determine prominent patterns and themes. Most participants reported discussing their mood with their provider, appreciated the discussion and were satisfied with the plan. Most had documentation of a discussion by their provider. Only 4 of 9 participants who endorsed thoughts of self-harm had documentation of a discussion regarding their response. While nearly all women were recommended for psychotherapy, most did not receive it. Participants expected follow-up but few had discussion of mood documented at the second prenatal visit, independent of seeing the same provider. Co-located behavioral health did not guarantee that services were utilized. There is a need to incorporate tested integrated care approaches to improve assessments and linkage to effective depression treatment.


Asunto(s)
Depresión , Trastorno Depresivo , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/terapia , Femenino , Humanos , Embarazo , Escalas de Valoración Psiquiátrica , Ideación Suicida , Encuestas y Cuestionarios
10.
Mol Cell Proteomics ; 15(9): 2987-3002, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27435585

RESUMEN

Glycans in breast milk are abundant and found as either free oligosaccharides or conjugated to proteins and lipids. Free human milk oligosaccharides (HMOs) function as prebiotics by stimulating the growth of beneficial bacteria while preventing the binding of harmful bacteria to intestinal epithelial cells. Bacteria have adapted to the glycan-rich environment of the gut by developing enzymes that catabolize glycans. The decrease in HMOs and the increase in glycan digestion products give indications of the active enzymes in the microbial population. In this study, we quantitated the disappearance of intact HMOs and characterized the glycan digestion products in the gut that are produced by the action of microbial enzymes on HMOs and glycoconjugates from breast milk. Oligosaccharides from fecal samples of exclusively breast-fed infants were extracted and profiled using nanoLC-MS. Intact HMOs were found in the fecal samples, additionally, other oligosaccharides were found corresponding to degraded HMOs and non-HMO based compounds. The latter compounds were fragments of N-glycans released through the cleavage of the linkage to the asparagine residue and through cleavage of the chitobiose core of the N-glycan. Marker gene sequencing of the fecal samples revealed bifidobacteria as the dominant inhabitants of the infant gastrointestinal tracts. A glycosidase from Bifidobacterium longum subsp. longum was then expressed to digest HMOs in vitro, which showed that the digested oligosaccharides in feces corresponded to the action of glycosidases on HMOs. Similar expression of endoglycosidases also showed that N-glycans were released by bacterial enzymes. Although bifidobacteria may dominate the gut, it is possible that specific minority species are also responsible for the major products observed in feces. Nonetheless, the enzymatic activity correlated well with the known glycosidases in the respective bacteria, suggesting a direct relationship between microbial abundances and catabolic activity.


Asunto(s)
Heces/química , Glicósido Hidrolasas/metabolismo , Leche Humana/química , Oligosacáridos/aislamiento & purificación , Proteínas Bacterianas/metabolismo , Bifidobacterium/enzimología , Bifidobacterium/genética , Bifidobacterium/aislamiento & purificación , Cromatografía Liquida , Heces/microbiología , Microbioma Gastrointestinal , Humanos , Lactante , Espectrometría de Masas
11.
J Nutr ; 147(1): 117-124, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27798342

RESUMEN

BACKGROUND: The quantitation of human milk oligosaccharides (HMOs) is challenging because of the structural complexity and lack of standards. OBJECTIVE: The objective of our study was to rapidly measure the absolute concentrations of HMOs in milk using LC-mass spectrometry (MS) and to determine the phenotypic secretor status of the mothers. METHODS: This quantitative method for measuring HMO concentration was developed by using ultraperformance LC multiple reaction monitoring MS. It was validated and applied to milk samples from Malawi (88 individuals; 88 samples from postnatal month 6) and the United States (Davis, California; 45 individuals, mean age: 32 y; 103 samples collected on postnatal days 10, 26, 71, or 120, repeated measures included). The concentrations of α(1,2)-fucosylated HMOs were used to determine the mothers' phenotypic secretor status with high sensitivity and specificity. We used Friedman's test and Wilcoxon's signed rank test to evaluate the change in HMO concentration during the course of lactation, and Student's t test was used to compare secretors and nonsecretors. RESULTS: A decrease (P < 0.05) in HMO concentration was observed during the course of lactation for the US mothers, corresponding to 19.3 ± 2.9 g/L for milk collected on postnatal day 10, decreasing to 8.53 ± 1.18 g/L on day 120 (repeated measures; n = 14). On postnatal day 180, the total concentration of HMOs in Malawi milk samples from secretors (6.46 ± 1.74 mg/mL) was higher (P < 0.05) than that in samples from nonsecretors (5.25 ± 2.55 mg/mL ). The same trend was observed for fucosylated species; the concentration was higher in Malawi milk samples from secretors (4.91 ± 1.22 mg/mL) than from nonsecretors (3.42 ± 2.27 mg/mL) (P < 0.05). CONCLUSIONS: HMOs significantly decrease during the course of lactation. Secretor milk contains higher concentrations of total and fucosylated HMOs than does nonsecretor milk. These HMO concentrations can be correlated to the health of breastfed infants in order to investigate the protective effects of milk components. The trials were registered at clinicaltrials.gov as NCT01817127 and NCT00524446.


Asunto(s)
Lactancia/fisiología , Leche Humana/química , Oligosacáridos/química , Adulto , Femenino , Humanos , Oligosacáridos/metabolismo
12.
J Nutr ; 147(10): 1867-1874, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28794206

RESUMEN

BACKGROUND: Human milk oligosaccharides (HMOs) and bioactive proteins are beneficial to infant health. Recent evidence suggests that maternal nutrition may affect the amount of HMOs and proteins in breast milk; however, the effect of nutrient supplementation on HMOs and bioactive proteins has not yet been well studied. OBJECTIVE: We aimed to determine whether lipid-based nutrient supplements (LNSs) affect milk bioactive protein and HMO concentrations at 6 mo postpartum in women in rural Malawi. These are secondary outcomes of a previously published randomized controlled trial. METHODS: Women were randomly assigned to consume either an iron and folic acid capsule (IFA) daily from ≤20 wk gestation until delivery, followed by placebo daily from delivery to 6 mo postpartum, or a multiple micronutrient (MMN) capsule or LNS daily from ≤20 wk gestation to 6 mo postpartum. Breast milk concentrations of total HMOs, sialylated HMOs, fucosylated HMOs, lactoferrin, lactalbumin, lysozymes, antitrypsin, immunoglobulin A, and osteopontin were analyzed at 6 mo postpartum (n = 647). Between-group differences in concentrations and in proportions of women classified as having low concentrations were tested. RESULTS: HMO and bioactive protein concentrations did not differ between groups (P > 0.10 for all comparisons). At 6 mo postpartum, the proportions of women with low HMOs or bioactive proteins were not different between groups except for osteopontin. A lower proportion of women in the IFA group had low osteopontin compared with the LNS group after adjusting for covariates (OR: 0.5; 95% CI: 0.3, 0.9; P = 0.016). CONCLUSION: The study findings do not support the hypothesis that supplementation with an LNS or MMN capsule during pregnancy and postpartum would increase HMO or bioactive milk proteins at 6 mo postpartum among Malawian women. This trial was registered at clinicaltrials.gov as NCT01239693.


Asunto(s)
Suplementos Dietéticos , Lípidos/administración & dosificación , Micronutrientes/administración & dosificación , Proteínas de la Leche/análisis , Leche Humana/química , Oligosacáridos/análisis , Adulto , Femenino , Humanos , Lactancia , Embarazo
13.
J Pediatr Gastroenterol Nutr ; 65(4): 449-455, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28945208

RESUMEN

OBJECTIVE: The aim of this study was to measure consumption and absorption of human milk oligosaccharides (HMOs) in a cohort of premature infants treated with probiotic Bifidobacterium breve. METHODS: Twenty-nine premature infants (median gestational age 28 weeks, range 23-32 weeks) cared for in the neonatal intensive care unit of the King Edward and Princess Margaret Hospital in Perth, Australia, were treated with B breve at a dose of 1.66 billion organisms per day. Samples of feces, urine, and milk were obtained at initiation of the probiotic and again 3 weeks later. 16S ribosomal RNA from the feces was analyzed by next-generation sequencing. Quantitation of HMO content of the milk, urine, and feces was performed using nano-high-performance liquid chromatography-chip/time-of-flight mass spectrometry. RESULTS: There was heterogeneity in colonization with bifidobacteria. "Responders" received milk with higher percentages of fucosylated HMOs and had higher percentages of bifidobacteria and lower percentages of Enterobacteriaceae in their feces than "nonresponders." Several individual HMOs in the milk were associated with changes in fecal bifidobacteria over time. Changes over time in milk, fecal, and urine HMOs suggested heterogeneity among HMO structures in consumption by microbes in the gut lumen and absorption from the intestine. CONCLUSIONS: Colonization of the premature infant intestinal tract with probiotic B breve is influenced by prebiotic HMOs. B breve is a selective consumer of HMOs in the premature infant.


Asunto(s)
Bifidobacterium breve , Digestión/fisiología , Microbioma Gastrointestinal/fisiología , Leche Humana/química , Oligosacáridos/química , Probióticos/uso terapéutico , Australia , Cromatografía Líquida de Alta Presión , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Masculino , Espectrometría de Masas , Leche Humana/fisiología , Oligosacáridos/fisiología
14.
J Biol Chem ; 289(41): 28554-68, 2014 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-25148684

RESUMEN

Sorting nexins (SNXs) or phox homology (PX) domain containing proteins are central regulators of cell trafficking and signaling. A subfamily of PX domain proteins possesses two unique PX-associated domains, as well as a regulator of G protein-coupled receptor signaling (RGS) domain that attenuates Gαs-coupled G protein-coupled receptor signaling. Here we delineate the structural organization of these RGS-PX proteins, revealing a protein family with a modular architecture that is conserved in all eukaryotes. The one exception to this is mammalian SNX19, which lacks the typical RGS structure but preserves all other domains. The PX domain is a sensor of membrane phosphoinositide lipids and we find that specific sequence alterations in the PX domains of the mammalian RGS-PX proteins, SNX13, SNX14, SNX19, and SNX25, confer differential phosphoinositide binding preferences. Although SNX13 and SNX19 PX domains bind the early endosomal lipid phosphatidylinositol 3-phosphate, SNX14 shows no membrane binding at all. Crystal structures of the SNX19 and SNX14 PX domains reveal key differences, with alterations in SNX14 leading to closure of the binding pocket to prevent phosphoinositide association. Our findings suggest a role for alternative membrane interactions in spatial control of RGS-PX proteins in cell signaling and trafficking.


Asunto(s)
Proteínas de Unión al GTP/metabolismo , Fosfatos de Fosfatidilinositol/química , Proteínas Recombinantes de Fusión/química , Nexinas de Clasificación/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Movimiento Celular , Secuencia Conservada , Cristalografía por Rayos X , Endosomas/química , Endosomas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Unión al GTP/genética , Expresión Génica , Regulación de la Expresión Génica , Células HeLa , Humanos , Ratones , Modelos Moleculares , Datos de Secuencia Molecular , Fosfatos de Fosfatidilinositol/metabolismo , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Alineación de Secuencia , Transducción de Señal , Nexinas de Clasificación/genética , Nexinas de Clasificación/metabolismo
15.
Anal Bioanal Chem ; 406(30): 7925-35, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25358913

RESUMEN

Glycomic analysis is the comprehensive determination of glycan (oligosaccharide) structures with quantitative information in a biological sample. Rapid-throughput glycomics is complicated due to the lack of a template, which has greatly facilitated analysis in the field of proteomics. Furthermore, the large similarities in structures make fragmentation spectra (as obtained in electron impact ionization and tandem mass spectrometry) less definitive for identification as it has been in metabolomics. In this study, we develop a concept of rapid-throughput glycomics on human milk oligosaccharides, which have proven to be an important bioactive component of breast milk, providing the infant with protection against pathogenic infection and supporting the establishment of a healthy microbiota. To better understand the relationship between diverse oligosaccharides structures and their biological function as anti-pathogenic and prebiotic compounds, large human studies are needed, which necessitate rapid- to high-throughput analytical platforms. Herein, a complete glycomics methodology is presented, evaluating the most effective human milk oligosaccharide (HMO) extraction protocols, the linearity and reproducibility of the nano-liquid chromatography chip time-of-flight mass spectrometry (nano-LC chip-TOF MS) method, and the efficacy of newly developed, in-house software for chromatographic peak alignment that allows for rapid data analysis. High instrument stability and retention time reproducibility, together with the successful automated alignment of hundreds of features in hundreds of milk samples, allow for the use of an HMO library for rapid assignment of fully annotated structures.


Asunto(s)
Glicómica/métodos , Espectrometría de Masas/métodos , Leche Humana/química , Oligosacáridos/análisis , Cromatografía Liquida/economía , Cromatografía Liquida/métodos , Femenino , Glicómica/economía , Humanos , Lactante , Espectrometría de Masas/economía , Reproducibilidad de los Resultados , Factores de Tiempo
16.
Environ Sci Technol ; 47(15): 8416-24, 2013 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-23796267

RESUMEN

In surface waters, two of the most commonly observed androgenic steroid hormones are androstenedione (AD) and testosterone (T). This study compares the photodegradation of dilute (<10 µg L(-1)) aqueous solutions of AD and T in natural sunlight, and evaluates the endocrine-disrupting potential of the resulting solutions. This study also examines the effect of dissolved organic matter (DOM) on AD photodegradation. During spring and summer at Henderson, NV, USA (latitude 36.04°N), AD and T underwent direct photodegradation, with half-lives ranging from 3.7 to 10.8 h. In three model DOM solutions, AD's half-life increased by 11% to 35%. Using screening factors to eliminate DOM's inner filter effect, quantum yield calculations suggested that light screening was primarily responsible for AD's increased half-life, and that physical quenching further inhibited AD's photodegradation in two out of three DOM solutions. In vitro androgenic activity of the AD and T solutions decreased approximately as fast as AD and T were removed, suggesting that solar photodegradation reduces the risk of endocrine disruption in surface waters impacted by AD or T, subject to continuing inputs. Reduced in vitro androgenic activity appears to be related to steroid ring cleavage and the formation of highly oxidized photoproducts.


Asunto(s)
Androstenodiona/química , Disruptores Endocrinos/química , Compuestos Orgánicos/química , Luz Solar , Testosterona/química , Disruptores Endocrinos/farmacología , Cinética , Oxidación-Reducción , Procesos Fotoquímicos , Estaciones del Año , Solubilidad
17.
Environ Sci Technol ; 46(12): 6698-704, 2012 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-22612278

RESUMEN

Isoflavones are plant-derived chemicals that are potential endocrine disruptors. Although some recent studies have detected isoflavones in natural waters, little is known about their aquatic fates. The photochemical behaviors of the isoflavones daidzein, formononetin, biochanin A, genistein, and equol were studied under simulated solar light and natural sunlight. All of these phytoestrogens were found to be photolabile under certain conditions. Daidzein and formononetin degraded primarily by direct photolysis. Their expected near-surface summer half-lives in pH 7 water at 47° latitude are expected to be 10 and 4.6 h, respectively. Biochanin A, genistein, and equol degraded relatively slowly by direct photolysis at environmentally realistic pH values, though they showed significant degradation rate enhancements in the presence of natural organic matter (NOM). The indirect photolysis rates for these compounds scaled with NOM concentration, and NOM from microbial origin was found to be a more potent photosensitizer than NOM from terrestrial sources. Mechanistic studies were performed to determine the indirect photolysis pathways responsible for the rate enhancements. Results of these studies implicate reaction with both singlet oxygen and excited state triplet NOM. Environmental half-lives for biochanin A, genistein, and equol are expected to vary on the basis of pH as well as NOM source and concentration.


Asunto(s)
Isoflavonas/química , Fotoquímica , Fitoestrógenos/química , Contaminantes Químicos del Agua/química , Concentración de Iones de Hidrógeno , Cinética , Espectrofotometría Ultravioleta
18.
Artículo en Inglés | MEDLINE | ID: mdl-22320690

RESUMEN

A computer-controlled mechanical chamber was used to control the contact between aluminum sheet samples laden with clay, and cotton sheet samples for the measurement of mass transfer. The contact parameters of pressure (20 to 60 kPa) and time (10 to 70 sec) were varied for 160 multiple experiments of mass soil transfer. Before log transformation the average transfer for 'First Transfer' of clay particles was 34.4 ± 6.3 mg/8.97 cm(2) while that for 'Total Transfer' was 36.1 ± 6.8 mg/8.97 cm(2). Second contact, therefore, resulted in an average transfer of 1.70 ± 0.76 mg/8.97 cm(2). These values are well above adherence values measured for potting soil and sand as reported for previous experiments using the same methodologies. Based on the univariate analysis and the multiple regression analysis we were able to see some effect of parameters on the clay adherence values. The effect of pressure increases was significant for the higher levels of 50 and 60 kPa. In addition, we observed that increases in temperature were significant for 'First Transfer,' and less so for 'Total Transfer'. Past experiments using potting soil and play sand show high adherence values to human cadaver skin over cotton sample; the same scenario would be expected for clay. This data set can be used to improve estimates of dermal exposure to dioxins found in ball clays often used by artisans in the making of pottery.


Asunto(s)
Silicatos de Aluminio/química , Cerámica , Dioxinas/análisis , Exposición Profesional/análisis , Piel/química , Contaminantes del Suelo/análisis , Aluminio , Silicatos de Aluminio/análisis , Arcilla , Sistemas de Computación , Fibra de Algodón
19.
Glob Public Health ; 17(9): 2190-2205, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35129083

RESUMEN

Conscientious objection to provide abortion has been enshrined in laws and policies globally. Insufficient attention has been paid to the direct and indirect ways in which conscientious objection compromises women's access to a lawful abortion. Using a systematic search strategy, this narrative literature review synthesises the literature exploring conscientious objection's impact on women's access to abortion in a range of countries. This narrative literature review builds on an extensive literature review published by Chavkin et al. (2013. Conscientious objection and refusal to provide reproductive healthcare: A white paper examining prevalence, health consequences, and policy responses. International Journal of Gynecology & Obstetrics, 123, S41-S56. https://doi.org/10.1016/S0020-7292(13)60002-8). Searches were undertaken on the Medline (Ovid), Global Health, CINAHL, Scopus and Science Direct databases. Thirty six papers were included for thematic analysis. Conscientious objection to abortion was found to impact women's access to abortion at three main levels: the practitioner level, the healthcare system level and the sociocultural environment level. Conscientious objection was found to impact access directly through attempts by health professionals to restrict access, and indirectly by exacerbating pre-existing barriers to access. Further research is required to better quantify the extent to which this impacts women and whether interventions are effective in reducing the barriers that conscientious objection creates and exacerbates.


Asunto(s)
Aborto Inducido , Negativa al Tratamiento , Actitud del Personal de Salud , Femenino , Salud Global , Personal de Salud , Humanos , Embarazo
20.
CVIR Endovasc ; 5(1): 66, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36536064

RESUMEN

BACKGROUND: Existing literature from around the world has shown that teaching of Interventional Radiology (IR) to medical students remains suboptimal. Despite calls for improvement at a "grass-roots" level, most IRs find that junior doctors have limited or no knowledge of IR, and thus reduced awareness of potential IR treatments for their patients or contemplating IR as a future career. The aim of this study was to survey current medical students to assess perception of whether a wider variety of medical schools are integrating IR into their curriculum, from universities all across Australia. This was a prospective cross-sectional study of members of the Australian Medical Students Association (AMSA) from across Australia. Students were given a 14-question survey of current university teaching and students' knowledge of the discipline of IR. The primary outcome was perception of current teaching and knowledge of IR. Secondary outcomes include awareness of technical, clinical, and other duties of IRs. RESULTS: Surveys were sent in a newsletter and posted on the AMSA Facebook page to their members. 82 responses were received via students from 20 out of 23 Australian medical schools. 61% of students described poor or no knowledge of IR. Teaching of IR was significantly worse than diagnostic radiology (p < 0.001), only 12% suggested that current IR teaching was adequate, and 99% suggested that IR teaching could be improved. Only 11% of students would consider a career in IR. CONCLUSIONS: Medical student perception of exposure to IR is poor compared to diagnostic radiology. Better awareness may lead to improved referral patterns for patients and more career interest in IR.

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