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1.
Diabetes Res Clin Pract ; 212: 111608, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38574894

RESUMEN

AIMS: To examine, among youth and young adults (YYA) with type 1 diabetes (T1D), the association of household food insecurity (HFI) with: 1) HbA1c and 2) episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia. METHODS: HFI was assessed using the U.S. Household Food Security Survey Module in SEARCH for Diabetes in Youth participants with T1D between 2016 and 2019. Linear and logistic regression models adjusted for age, diabetes duration, sex, race, ethnicity, clinic site, parent/participant education, household income, health insurance, and diabetes technology use. RESULTS: Of 1830 participants (mean age 20.8 ± 5.0 years, 70.0 % non-Hispanic White), HbA1c was collected for 1060 individuals (mean HbA1c 9.2 % ± 2.0 %). The prevalence of HFI was 16.4 %. In the past 12 months, 18.2 % and 9.9 % reported an episode of DKA or severe hypoglycemia, respectively. Compared to participants who were food secure, HFI was associated with a 0.33 % (95 % CI 0.003, 0.657) higher HbA1c level. Those with HFI had 1.58 (95 % CI 1.13, 2.21) times the adjusted odds of an episode of DKA and 1.53 (95 % CI 0.99, 2.37) times the adjusted odds of an episode of severe hypoglycemia as those without HFI. CONCLUSIONS: HFI is associated with higher HbA1c levels and increased odds of DKA in YYA with T1D.


Asunto(s)
Diabetes Mellitus Tipo 1 , Inseguridad Alimentaria , Hemoglobina Glucada , Humanos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/complicaciones , Masculino , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Femenino , Adolescente , Adulto Joven , Adulto , Hipoglucemia/epidemiología , Hipoglucemia/sangre , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/etiología , Estudios Transversales , Prevalencia
2.
J Phys Act Health ; 21(1): 77-84, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37922896

RESUMEN

BACKGROUND: Physical activity (PA) is essential for optimal diabetes management. Household food insecurity (HFI) may negatively affect diabetes management behaviors. The purpose of this study was to cross-sectionally examine the association between HFI and PA in youth and young adults (YYA) with type 1 (N = 1998) and type 2 (N = 391) diabetes from the SEARCH for Diabetes in Youth Study. METHODS: HFI was measured with the US Household Food Security Survey Module. PA was measured with the International Physical Activity Questionnaire Short Form. Walking, moderate-intensity PA (excluding walking), vigorous-intensity PA, moderate- to vigorous-intensity PA, and total PA were estimated as minutes per week, while time spent sitting was assessed in minutes per day. All were modeled with median regression. Meeting PA guidelines or not was modeled using logistic regression. RESULTS: YYA with type 1 diabetes who experienced HFI spent more time walking than those who were food secure. YYA with type 2 diabetes who experienced HFI spent more time sitting than those who were food secure. CONCLUSIONS: Future research should examine walking for leisure versus other domains of walking in relation to HFI and use objective PA measures to corroborate associations between HFI and PA in YYA with diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Adolescente , Adulto Joven , Estudios Transversales , Ejercicio Físico , Abastecimiento de Alimentos , Inseguridad Alimentaria
3.
Am J Orthopsychiatry ; 94(1): 61-76, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37768607

RESUMEN

Racism has been declared a public health threat. With increased direct and vicarious exposure to racism-based violence through social media, we explored the associations between racism-based events and traumatic stress symptomatology, as well as self- and collective care (inclusive of coping, activism, and ethnic and racial identity) through a mixed-methods approach. A total of 104 racism-based events were reported across 43 Black and/or Latine/x emerging adults in the sample, with a majority endorsing racism-based stress or traumatic stress (i.e., the symptomatology associated with a racism-based event). Individuals who reported higher racism-based traumatic stress symptoms immediately following a racism-based event also reported higher ethnic identity resolution scores. Further, 19%-42% of participants reported racism-based traumatic stress and racism-based stress more recently (respectively), showing that racism-based events may be traumatic stressors with long-term mental health consequences. Participants provided thick descriptions of how they defined and engaged in self- and collective care as wellness and activism and reported engaging in cultural, ancestral, spiritual, and religious practices in an attempt to heal. The findings of this study underscore the importance of radical hope and radical healing for Black and Latine/x communities. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Racismo , Adulto , Humanos , Habilidades de Afrontamiento , Salud Mental
4.
J Acad Nutr Diet ; 123(8): 1162-1172.e1, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36990427

RESUMEN

BACKGROUND: Household food insecurity is associated with poor dietary intake in the general population, but little is known about this association in persons with diabetes. OBJECTIVE: We examined the degree of adherence to the dietary reference intakes and 2020-2025 Dietary Guidelines for Americans overall and according to food security status and diabetes type among youth and young adults (YYA) with youth-onset diabetes. DESIGN, PARTICIPANTS, AND SETTING: The SEARCH for Diabetes in Youth study includes 1,197 YYA with type 1 diabetes (mean age = 21 ± 5 years) and 319 YYA with type 2 diabetes (25 ± 4 years). Participants (or parents if younger than age 18 years) completed the US Department of Agriculture Household Food Security Survey Module, wherein ≥3 affirmations indicate food insecurity. MAIN OUTCOME MEASURES: Diet was assessed via food frequency questionnaire and compared with age- and sex-specific dietary reference intakes for 10 nutrients and dietary components (calcium; fiber; magnesium; potassium; sodium; vitamins C, D, and E; added sugar; and saturated fat). STATISTICAL ANALYSES PERFORMED: Median regression models controlled for sex- and type-specific means for age, diabetes duration, and daily energy intake. RESULTS: Prevalence of guideline adherence was overarchingly poor, with <40% of participants meeting recommendations for eight of 10 nutrients and dietary components; however, higher adherence (>47%) was observed for vitamin C and added sugars. YYA with type 1 diabetes who were food insecure were more likely to meet recommendations for calcium, magnesium, and vitamin E (P < 0.05), and less likely for sodium (P < 0.05) than those with food security. In adjusted models, YYA with type 1 diabetes who were food secure had closer median adherence to sodium (P = 0.002) and fiber (P = 0.042) guidelines than those food insecure. No associations were observed in YYA with type 2 diabetes. CONCLUSIONS: Food insecurity is associated with lesser adherence to fiber and sodium guidelines in YYA with type 1 diabetes, which may lead to diabetes complications and other chronic diseases.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Masculino , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 1/epidemiología , Magnesio , Calcio , Abastecimiento de Alimentos , Dieta , Vitaminas , Ácido Ascórbico , Calcio de la Dieta , Ingestión de Alimentos , Inseguridad Alimentaria , Sodio
5.
Diabetes Care ; 46(2): 262-269, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35771776

RESUMEN

OBJECTIVE: To evaluate the relation between household food insecurity (HFI) and fear of hypoglycemia among young adults with type 1 and type 2 diabetes and adolescents with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS: We analyzed cross-sectional data of 1,676 young adults with youth-onset diabetes (84% type 1, 16% type 2) and 568 adolescents (<18 years old; mean age 15.1 years) with type 1 diabetes from the SEARCH for Diabetes in Youth study. Adult participants and parents of adolescent participants completed the U.S. Household Food Security Survey Module. Adults, adolescents, and parents of adolescents completed the Hypoglycemia Fear Survey, where answers range from 1 to 4. The outcomes were mean score for fear of hypoglycemia and the behavior and worry subscale scores. Linear regression models identified associations between HFI and fear of hypoglycemia scores. RESULTS: Adults with type 1 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.22 units higher for behavior, 0.55 units for worry, 0.40 units for total; all P < 0.0001) than those without HFI. No differences by HFI status were found for adolescents with type 1 diabetes. Parents of adolescents reporting HFI had a 0.18 unit higher worry score than those not reporting HFI (P < 0.05). Adults with type 2 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.19 units higher for behavior, 0.35 units for worry, 0.28 units for total; all P < 0.05) than those in food secure households. CONCLUSIONS: Screening for HFI and fear of hypoglycemia among people with diabetes can help providers tailor diabetes education for those who have HFI and therefore fear hypoglycemia.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglucemia , Humanos , Adolescente , Adulto Joven , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Abastecimiento de Alimentos , Miedo , Inseguridad Alimentaria , Padres
6.
Pediatr Diabetes ; 23(7): 982-990, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35752872

RESUMEN

OBJECTIVE: To examine the association between household food insecurity (HFI), glycemic control, severe hypoglycemia and diabetic ketoacidosis (DKA) among youth and young adults (YYA) with youth-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional study included 395 YYA with type 2 diabetes from the SEARCH for Diabetes in Youth Study (2015-2019). HFI was reported by young adult participants or parents of minor participants via the US Household Food Security Survey Module. Glycemic control was assessed by HbA1c and analyzed as a continuous and categorical variable (optimal: <7.0%, suboptimal: ≥7.0%-9.0%, poor: >9.0%). Acute complications included self-reported severe hypoglycemia or DKA in the last 12 months. Adjusted logistic and linear regression were used for binary and continuous outcomes, respectively. RESULTS: Approximately 31% reported HFI in the past 12 months. Mean HbA1c among those with HFI was 9.2% compared to 9.5% without HFI. Of those with HFI, 56% had an HbA1c >9.0% compared to 55% without HFI. Adjusted models showed no associations between HFI and glycemic control. Of those with HFI, 14.4% reported experiencing DKA and 4.7% reported severe hypoglycemia. YYA with HFI had 3.08 times (95% CI: 1.18-8.06) the odds of experiencing DKA as those without HFI. There was no association between HFI and severe hypoglycemia. CONCLUSIONS: HFI was associated with markedly increased odds of DKA but not with glycemic control or severe hypoglycemia. Future research among YYA with type 2 diabetes should evaluate longitudinally whether alleviating HFI reduces DKA.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cetoacidosis Diabética , Hipoglucemia , Adolescente , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Cetoacidosis Diabética/complicaciones , Cetoacidosis Diabética/etiología , Inseguridad Alimentaria , Hemoglobina Glucada/análisis , Control Glucémico , Humanos , Hipoglucemia/epidemiología , Hipoglucemia/etiología , Hipoglucemia/prevención & control , Adulto Joven
7.
Chem Sci ; 13(7): 1957-1971, 2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35308859

RESUMEN

Understanding the conformational ensembles of intrinsically disordered proteins and peptides (IDPs) in their various biological environments is essential for understanding their mechanisms and functional roles in the proteome, leading to a greater knowledge of, and potential treatments for, a broad range of diseases. To determine whether molecular simulation is able to generate accurate conformational ensembles of IDPs, we explore the structural landscape of the PLP peptide (an intrinsically disordered region of the proteolipid membrane protein) in aqueous and membrane-mimicking solvents, using replica exchange with solute scaling (REST2), and examine the ability of four force fields (ff14SB, ff14IDPSFF, CHARMM36 and CHARMM36m) to reproduce literature circular dichroism (CD) data. Results from variable temperature (VT) 1H and Rotating frame Overhauser Effect SpectroscopY (ROESY) nuclear magnetic resonance (NMR) experiments are also presented and are consistent with the structural observations obtained from the simulations and CD. We also apply the optimum simulation protocol to TP2 and ONEG (a cell-penetrating peptide (CPP) and a negative control peptide, respectively) to gain insight into the structural differences that may account for the observed difference in their membrane-penetrating abilities. Of the tested force fields, we find that CHARMM36 and CHARMM36m are best suited to the study of IDPs, and accurately predict a disordered to helical conformational transition of the PLP peptide accompanying the change from aqueous to membrane-mimicking solvents. We also identify an α-helical structure of TP2 in the membrane-mimicking solvents and provide a discussion of the mechanistic implications of this observation with reference to the previous literature on the peptide. From these results, we recommend the use of CHARMM36m with the REST2 protocol for the study of environment-specific IDP conformations. We believe that the simulation protocol will allow the study of a broad range of IDPs that undergo conformational transitions in different biological environments.

8.
J Audiol Otol ; 26(2): 90-96, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35196447

RESUMEN

BACKGROUND AND OBJECTIVES: Otalgia can be primary/otogenic or secondary as a referred pain from another site, which can be difficult to establish owing to various causes and the complex innervation of the ear. In our center, we observed a large group of patients with unexplained otalgia that had a higher prevalence of migraine. We hypothesized that migraine may cause secondary otalgia. This study then aimed to determine the prevalence of migraine-associated otalgia and evaluate the efficacy of migraine treatment. SUBJECTS AND METHODS: This 2-year retrospective study was conducted at a busy otology clinic. Patients were identified using diagnostic codes corresponding to otalgia. The prevalence of migraine-associated otalgia was determined, and the efficacy of migraine treatment was evaluated in these patients. The interventions included prophylactic and abortive migraine treatments. Statistical analysis was conducted to compare between the pre- and post-treatment symptoms. RESULTS: A total of 208 patients with otalgia were identified. Sixty-four out of ninety patients with unexplained otalgia met the criteria for migraine; of them, 30 patients had an adequate follow-up and were thus included in the evaluation of treatment efficacy. Otalgia improved in 87% of the patients who received migraine treatment. After treatment, the mean pain score and headache frequency significantly decreased from 7 to 2 and from 27 to 9 days per month, respectively (p<0.001). CONCLUSIONS: Migraine should be considered as a source of secondary otalgia, and patients should receive treatment as they often respond to migraine treatment.

9.
J Chem Inf Model ; 61(7): 3172-3196, 2021 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-34165973

RESUMEN

The evolution of antibiotic-resistant bacteria is an ongoing and troubling development that has increased the number of diseases and infections that risk going untreated. There is an urgent need to develop alternative strategies and treatments to address this issue. One class of molecules that is attracting significant interest is that of antimicrobial peptides (AMPs). Their design and development has been aided considerably by the applications of molecular models, and we review these here. These methods include the use of tools to explore the relationships between their structures, dynamics, and functions and the increasing application of machine learning and molecular dynamics simulations. This review compiles resources such as AMP databases, AMP-related web servers, and commonly used techniques, together aimed at aiding researchers in the area toward complementing experimental studies with computational approaches.


Asunto(s)
Antibacterianos , Péptidos Catiónicos Antimicrobianos , Antibacterianos/farmacología , Bacterias , Humanos , Simulación de Dinámica Molecular , Proteínas Citotóxicas Formadoras de Poros
10.
Cleft Palate Craniofac J ; 58(11): 1438-1442, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33784859

RESUMEN

OBJECTIVE: Advancements have been made in the care of patients with Treacher Collins syndrome (TCS), but epidemiological data are lacking given its rarity. A national database provides a valuable opportunity for studying the incidence of rare craniofacial conditions. We sought to evaluate disease incidence of phenotypically severe cases and the frequency of the most common associated diagnoses and interventions. DESIGN: The 2016 Kids' Inpatient Database (KID), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality was the first version to include updated International Classification of Diseases-Tenth Edition (ICD-10) coding encompassing a unique code for TCS. The 2016 KID was queried for the unique code. Incidence was calculated using national estimates. Diagnosis and procedure codes were pooled and analyzed. PATIENTS: A total of 266 discharge cases with a diagnosis code for TCS (Q75.4). MAIN OUTCOMES: Disease incidence and the most frequent diagnosis and procedure codes. RESULTS: The estimated incidence of children born with a diagnosis of TCS was approximately 1 in 80,000. Two of the three most common ICD-10 diagnosis codes were tracheostomy status and obstructive sleep apnea. The most common procedures performed were airway examination procedures. CONCLUSIONS: Treacher Collins syndrome is a rare craniofacial disorder requiring complex multidisciplinary management. Phenotypically severe cases requiring inpatient management may be rarer than previous estimates suggest. Inpatient airway interventions are very common, and multidisciplinary team members should anticipate the degree of potential airway risk these patients pose.


Asunto(s)
Disostosis Mandibulofacial , Apnea Obstructiva del Sueño , Niño , Bases de Datos Factuales , Humanos , Incidencia , Pacientes Internos , Disostosis Mandibulofacial/epidemiología , Disostosis Mandibulofacial/terapia , Estados Unidos/epidemiología
11.
Rapid Commun Mass Spectrom ; 35(4): e9006, 2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33201519

RESUMEN

RATIONALE: The stable carbon isotopic (δ13 C) reference material (RM) LSVEC Li2 CO3 has been found to be unsuitable for δ13 C standardization work because its δ13 C value increases with exposure to atmospheric CO2 . A new CaCO3 RM, USGS44, has been prepared to alleviate this situation. METHODS: USGS44 was prepared from 8 kg of Merck high-purity CaCO3 . Two sets of δ13 C values of USGS44 were determined. The first set of values was determined by online combustion, continuous-flow (CF) isotope-ratio mass spectrometry (IRMS) of NBS 19 CaCO3 (δ13 CVPDB = +1.95 milliurey (mUr) exactly, where mUr = 0.001 = 1‰), and LSVEC Li2 CO3 (δ13 CVPDB = -46.6 mUr exactly), and normalized to the two-anchor δ13 CVPDB-LSVEC isotope-delta scale. The second set of values was obtained by dual-inlet (DI)-IRMS of CO2 evolved by reaction of H3 PO4 with carbonates, corrected for cross contamination, and normalized to the single-anchor δ13 CVPDB scale. RESULTS: USGS44 is stable and isotopically homogeneous to within 0.02 mUr in 100-µg amounts. It has a δ13 CVPDB-LSVEC value of -42.21 ± 0.05 mUr. Single-anchor δ13 CVPDB values of -42.08 ± 0.01 and -41.99 ± 0.02 mUr were determined by DI-IRMS with corrections for cross contamination. CONCLUSIONS: The new high-purity, well-homogenized calcium carbonate isotopic reference material USGS44 is stable and has a δ13 CVPDB-LSVEC value of -42.21 ± 0.05 mUr for both EA/IRMS and DI-IRMS measurements. As a carbonate relatively depleted in 13 C, it is intended for daily use as a secondary isotopic reference material to normalize stable carbon isotope delta measurements to the δ13 CVPDB-LSVEC scale. It is useful in quantifying drift with time, determining mass-dependent isotopic fractionation (linearity correction), and adjusting isotope-ratio-scale contraction. Due to its fine grain size (smaller than 63 µm), it is not suitable as a δ18 O reference material. A δ13 CVPDB-LSVEC value of -29.99 ± 0.05 mUr was determined for NBS 22 oil.

12.
Front Cardiovasc Med ; 7: 595011, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33195484

RESUMEN

Introduction: Abdominal aortic aneurysms (AAA) are characterized by localized inflammation, extracellular matrix degradation, and apoptosis of smooth muscle cells, which together lead to progressive and irreversible aortic dilation. Major risk factors for AAA include smoking and aging, both of which prominently alter gene expression via epigenetic mechanisms, including histone methylation (me) and acetylation (ac).However, little is known about epigenomic dynamics during AAA formation. Here, we profiled histone modification patterns in aortic tissues during AAA formation in two distinct mouse models; (1) angiotensin II (AngII) infusion in low density lipoprotein receptor (LDLR) knockout (KO) mice, and (2) calcium chloride (CaCl2) application in wild type mice. Methods and Results: AAA formed in both models, in conjunction with enhanced macrophage infiltration, elastin degradation and matrix metalloproteinases expression as evaluated by immunohistochemistry. To investigate the histone modification patterns during AAA formation, total histone proteins were extracted from AAA tissues, and histone H3 modifications were quantified using profiling kits. Intriguingly, we observed dynamic changes in histone H3 modifications of lysine (K) residues at different time points during AAA formation. In mature aneurysmal tissues at 3 weeks after AngII infusion, we detected reduced K4/K27/K36 monomethylation, K9 trimethylation K9, and K9/K56 acetylation (<70%), and increased K4 trimethylation (>130%). Conversely, in CaCl2-induced AAA, K4/K9/K27/K36/K79 monomethylation and K9/K18/K56 acetylation were reduced in AAA tissues, whereas K27 di-/tri-methylation and K14 acetylation were upregulated. Interestingly, K4/K27/K36 monomethylation, K9 trimethylation, and K9/K56 acetylation were commonly downregulated in both animal models, while no H3 modifications were uniformly upregulated. Western blot of AAA tissues confirmed markedly reduced levels of key H3 modifications, including H3K4me1, H3K9me3, and H3K56ac. Furthermore, pathway enrichment analysis using an integrative bioinformatics approach identified specific molecular pathways, including endocytosis, exon guidance and focal adhesion signaling, that may potentially be linked to these histone H3 modifications during AAA formation. Conclusions: Dynamic modifications of histone H3 occur during AAA formation in both animal models. We identified 6 discreet H3 modifications that are consistently downregulated in both models, suggesting a possible role in AAA pathobiology. Identifying the functional mechanisms may facilitate development of novel strategies for AAA prevention or treatment.

13.
J Agric Food Chem ; 68(39): 10852-10864, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-32893631

RESUMEN

An international project developed, quality-tested, and measured isotope-delta values of 10 new food matrix reference materials (RMs) for hydrogen, carbon, nitrogen, oxygen, and sulfur stable isotope-ratio measurements to support food authenticity testing and food provenance verification. These new RMs, USGS82 to USGS91, will enable users to normalize measurements of samples to isotope-delta scales. The RMs include (i) two honeys from Canada and tropical Vietnam, (ii) two flours from C3 (rice) and C4 (millet) plants, (iii) four vegetable oils from C3 (olive, peanut) and C4 (corn) plants, and (iv) two collagen powders from marine fish and terrestrial mammal origins. An errors-in-variables regression model included the uncertainty associated with the measured and assigned values of the RMs, and it was applied centrally to normalize results and obtain consensus values and measurement uncertainties. Utilization of these new RMs should facilitate mutual compatibility of stable isotope data if accepted normalization procedures are applied and documented.


Asunto(s)
Colágeno/análisis , Deuterio/análisis , Harina/análisis , Miel/análisis , Isótopos de Nitrógeno/análisis , Isótopos de Oxígeno/análisis , Aceites de Plantas/química , Isótopos de Azufre/análisis , Animales , Proteínas de Peces/análisis , Peces
14.
Cardiovasc Res ; 116(14): 2226-2238, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31710686

RESUMEN

AIMS: Chronic adventitial and medial infiltration of immune cells play an important role in the pathogenesis of abdominal aortic aneurysms (AAAs). Nicotinic acid (niacin) was shown to inhibit atherosclerosis by activating the anti-inflammatory G protein-coupled receptor GPR109A [also known as hydroxycarboxylic acid receptor 2 (HCA2)] expressed on immune cells, blunting immune activation and adventitial inflammatory cell infiltration. Here, we investigated the role of niacin and GPR109A in regulating AAA formation. METHODS AND RESULTS: Mice were supplemented with niacin or nicotinamide, and AAA was induced by angiotensin II (AngII) infusion or calcium chloride (CaCl2) application. Niacin markedly reduced AAA formation in both AngII and CaCl2 models, diminishing adventitial immune cell infiltration, concomitant inflammatory responses, and matrix degradation. Unexpectedly, GPR109A gene deletion did not abrogate the protective effects of niacin against AAA formation, suggesting GPR109A-independent mechanisms. Interestingly, nicotinamide, which does not activate GPR109A, also inhibited AAA formation and phenocopied the effects of niacin. Mechanistically, both niacin and nicotinamide supplementation increased nicotinamide adenine dinucleotide (NAD+) levels and NAD+-dependent Sirt1 activity, which were reduced in AAA tissues. Furthermore, pharmacological inhibition of Sirt1 abrogated the protective effect of nicotinamide against AAA formation. CONCLUSION: Niacin protects against AAA formation independent of GPR109A, most likely by serving as an NAD+ precursor. Supplementation of NAD+ using nicotinamide-related biomolecules may represent an effective and well-tolerated approach to preventing or treating AAA.


Asunto(s)
Aorta Abdominal/efectos de los fármacos , Aneurisma de la Aorta Abdominal/prevención & control , NAD/metabolismo , Niacina/farmacología , Niacinamida/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Angiotensina II , Animales , Aorta Abdominal/metabolismo , Aorta Abdominal/patología , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/metabolismo , Aneurisma de la Aorta Abdominal/patología , Cloruro de Calcio , Células Cultivadas , Dilatación Patológica , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores Acoplados a Proteínas G/genética , Receptores de LDL/genética , Receptores de LDL/metabolismo , Transducción de Señal , Sirtuina 1/metabolismo
15.
Drug Discov Today ; 24(9): 1821-1835, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31229665

RESUMEN

Cell-penetrating peptides (CPPs) offer an exciting approach to tackle the pharmacokinetic challenges associated with the delivery of large, polar molecules to intracellular targets. Since the discovery of the first CPPs in the early 1990s, vast amounts of research have been undertaken to characterise their cellular uptake mechanisms. Despite this, the precise mechanisms of cellular internalisation of many CPPs remain elusive owing to inconsistent experimental results. Molecular dynamics (MD) simulations provide an approach to probe specific aspects of the internalisation process and many published CPP studies have incorporated simulation data. This review provides a critical evaluation of the current approaches that are being used to simulate CPPs interacting with artificial lipid bilayers.


Asunto(s)
Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/metabolismo , Simulación de Dinámica Molecular , Transporte Biológico , Membrana Celular/química , Permeabilidad de la Membrana Celular , Endocitosis , Humanos , Membrana Dobles de Lípidos , Transporte de Proteínas
16.
Pediatr Diabetes ; 20(3): 321-329, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30666775

RESUMEN

Affordability and geographic accessibility are key health care access characteristics. We used data from 481 youth and young adults (YYA) with diabetes (389 type 1, 92 type 2) to understand the association between health care access and glycemic control as measured by HbA1c values. In multivariate models, YYA with state or federal health insurance had HbA1c percentage values 0.68 higher (P = 0.0025) than the privately insured, and those without insurance 1.34 higher (P < 0.0001). Not having a routine diabetes care provider was associated with a 0.51 higher HbA1c (P = 0.048) compared to having specialist care, but HbA1c did not differ significantly (P = 0.069) between primary vs specialty care. Distance to utilized provider was not associated with HbA1c among YYA with a provider (P = 0.11). These findings underscore the central role of health insurance and indicate a need to better understand the root causes of poorer glycemic control in YYA with state/federal insurance.


Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Hemoglobina Glucada/metabolismo , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Adolescente , Adulto , Glucemia/análisis , Glucemia/metabolismo , Niño , Servicios de Salud del Niño/estadística & datos numéricos , Diabetes Mellitus Tipo 1/economía , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/terapia , Femenino , Hemoglobina Glucada/análisis , Accesibilidad a los Servicios de Salud/economía , Accesibilidad a los Servicios de Salud/normas , Humanos , Cobertura del Seguro , Seguro de Salud/clasificación , Seguro de Salud/legislación & jurisprudencia , Seguro de Salud/estadística & datos numéricos , Masculino , Patient Protection and Affordable Care Act , South Carolina/epidemiología , Adulto Joven
17.
Cardiovasc Drugs Ther ; 32(5): 503-510, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30097828

RESUMEN

PURPOSE: Perivascular adipose tissue (PVAT) surrounds the arterial adventitia and plays an important role in vascular homeostasis. PVAT expands in obesity, and inflamed PVAT can locally promote endothelial dysfunction and atherosclerosis. Here, using adipose tissue transplantation, we tested the hypothesis that expansion of PVAT can also remotely exacerbate vascular disease. METHODS: Fifty milligrams of abdominal aortic PVAT was isolated from high-fat diet (HFD)-fed wild-type mice and transplanted onto the abdominal aorta of lean LDL receptor knockout mice. Subcutaneous and visceral adipose tissues were used as controls. After HFD feeding for 10 weeks, body weight, glucose/insulin sensitivity, and lipid levels were measured. Adipocytokine gene expression was assessed in the transplanted adipose tissues, and the thoracic aorta was harvested to quantify atherosclerotic lesions by Oil-Red O staining and to assess vasorelaxation by wire myography. RESULTS: PVAT transplantation did not influence body weight, fat composition, lipid levels, or glucose/insulin sensitivity. However, as compared with controls, transplantation of PVAT onto the abdominal aorta increased thoracic aortic atherosclerosis. Furthermore, PVAT transplantation onto the abdominal aorta inhibited endothelium-dependent relaxation in the thoracic aorta. MCP-1 and TNF-α expression was elevated, while adiponectin expression was reduced, in the transplanted PVAT tissue, suggesting augmented inflammation as a potential mechanism for the remote vascular effects of transplanted PVAT. CONCLUSIONS: These data suggest that PVAT expansion and inflammation in obesity can remotely induce endothelial dysfunction and augment atherosclerosis. Identifying the underlying mechanisms may lead to novel approaches for risk assessment and treatment of obesity-related vascular disease.


Asunto(s)
Tejido Adiposo Blanco/trasplante , Aorta Abdominal/metabolismo , Aorta Abdominal/cirugía , Aorta Torácica/metabolismo , Aterosclerosis/metabolismo , Comunicación Paracrina , Placa Aterosclerótica , Adiponectina/metabolismo , Tejido Adiposo Blanco/metabolismo , Adiposidad , Animales , Aorta Abdominal/patología , Aorta Abdominal/fisiopatología , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Aterosclerosis/genética , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Quimiocina CCL2/metabolismo , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Mediadores de Inflamación/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de LDL/deficiencia , Receptores de LDL/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Vasodilatación
18.
PLoS One ; 12(11): e0188242, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29155845

RESUMEN

This study examined the effects of the ActiGraph's (AG) low-frequency extension (LFE) filter on steps and physical activity classification in the free-living environment. Thirty-four African-American women (age, 24.5±5.2 years; BMI, 24.9±4.5 kg/m2) had daily activity measured simultaneously with an AG-GT3X+ accelerometer and a New Lifestyles NL-800 pedometer for seven days. Steps per day (steps/day) and time (minutes/day) spent in sedentary, light, and moderate-to-vigorous physical activity (MVPA) were examined with and without the LFE filter (AG-LFE and AG-N, respectively). The AG-LFE recorded more total steps (13,723±4,983 steps/day) compared to AG-N and NL-800 (6,172±2,838 and 5,817±3,037 steps/day, respectively; p<0.001). Compared to the AG-N, the AG-LFE estimated less time in sedentary behaviors (518.7±92.1 vs. 504.2±105.4 min/day, respectively; p<0.001), and more time in light (247.7±70.4 vs. 279.1±74.7 min/day, respectively; p<0.001) and MVPA (18.9±16.9 vs. 21.5±18.2 min/day, respectively; p<0.001), respectively. These data suggest that steps and physical activity classifications will be affected when using the ActiGraph with and without the LFE filter. Future research should investigate the accuracy of these measures using the LFE filter.


Asunto(s)
Acelerometría/métodos , Actigrafía/métodos , Metabolismo Energético/fisiología , Ejercicio Físico/fisiología , Monitoreo Ambulatorio/métodos , Conducta Sedentaria , Acelerometría/instrumentación , Actigrafía/instrumentación , Adulto , Negro o Afroamericano , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Monitoreo Ambulatorio/instrumentación , Caminata
19.
JMIR Hum Factors ; 4(4): e28, 2017 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-29054836

RESUMEN

BACKGROUND: Sedentary behavior (SB) is a significant risk factor for heart disease, diabetes, obesity, and early mortality, particularly among women, and the health consequences associated with SB are independent of physical activity status. Interventions utilizing wearable technologies can improve SB, but their effectiveness is influenced by individual preferences, device engagement strategies, and technological features, which may affect user compliance. Gathering a priori insight from target populations on their preferences for program tools and strategies may assist researchers in identifying effective methods to improve the efficacy of SB interventions. OBJECTIVE: The objective of this study was to (1) explore the likeability (likes and dislikes) and usability (engagement intentions and navigation) of a wearable device (Movband) and its accompanying website (dashboard), (2) examine social incentive preferences (teammates), and (3) assess the feasibility (participants' experiences during an activity-monitoring period) of these tools for use in an intervention to reduce SB in girls and women. METHODS: A total of 9 girls (mean age: 8.9 years, standard deviation [SD] 1.1 years) and 11 college-aged women (mean age: 22.6 years, SD 3.2 years) participated in this study. Separate focus groups were held for girls and women, and all participants attended one before and the other following a 7-day activity-monitoring period. During the focus groups, participants were prompted with questions to address the study aims, and the nominal group technique was used to compile lists of group-specific preferences for the activity-monitoring system. The top three ranking likes and dislikes were reverse coded to determine likeability. RESULTS: The top-ranking responses for the girls and women were the following: visual display of movements and ease of navigation (dashboard like), boring to look at and no calorie-tracking function (dashboard dislike), backlight and long battery life (Movband like), and color and not waterproof (tied for girls) and vertical time display (Movband dislike). Additionally, participants identified several aesthetic preferences and functional limitations. At the second focus group visit, the majority of the participants self-reported less SB during the previous week. Objective data from the activity-monitoring period revealed that the average steps per day for girls and women were 12,373.4 (SD 2617.6) and 8515.8 (SD 3076.7), respectively. CONCLUSIONS: These results suggest that the girls and women liked many features of the Movband and dashboard. However, several dislikes were mentioned, which may negatively influence compliance and the effectiveness of the activity-monitoring system and require improvements before using in an SB intervention.

20.
Opt Express ; 25(16): 19251-19262, 2017 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-29041118

RESUMEN

A multi-GHz frequency comb (astrocomb) is typically realized by filtering modes of a sub-GHz frequency comb (source comb) in a Fabry-Pérot etalon, which can lead to ambiguities in determining which subset of source comb modes has been filtered. Here we demonstrate a broadband Fourier-transform spectrometer (FTS) with a resolving power of R = 430,000 at 550 nm, and apply it to the identification of comb subsets from a filtered 1­GHz supercontinuum. After apodization the FTS demonstrated an instrument line shape width of 1.26 GHz which enabled individual comb-line positions to be identified with an uncertainty of 17.6 MHz, a relative precision of 5 × 10-8. Correcting for air dispersion allowed the instrument to determine the comb-mode spacing to an accuracy of 300 Hz and filtered subsets of source comb modes to be uniquely distingished across the entire comb bandwidth from 550 to 900 nm. The inherently broadband design of the FTS makes it suitable in future applications for calibrating ultra-broadband astrocombs employed by instruments such as ELT HIRES.

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