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1.
Front Neurol ; 15: 1384480, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915800

RESUMEN

Huntington's disease (HD) is a debilitating neurodegenerative condition characterized by motor, cognitive and psychiatric abnormalities. Immune dysregulation, prominently featuring increased immune activity, plays a significant role in HD pathogenesis. In addition to the central nervous system (CNS), systemic innate immune activation and inflammation are observed in HD patients, exacerbating the effects of the Huntingtin (HTT) gene mutation. Recent attention to sex differences in HD symptom severity underscores the need to consider gender as a biological variable in neurodegenerative disease research. Understanding sex-specific immune responses holds promise for elucidating HD pathophysiology and informing targeted treatment strategies to mitigate cognitive and functional decline. This perspective will highlight the importance of investigating gender influence in HD, particularly focusing on sex-specific immune responses predisposing individuals to disease.

2.
bioRxiv ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38746319

RESUMEN

Discovery of synaptic nanostructures suggests a molecular logic for the flexibility of synaptic function. We still have little understanding of how functionally diverse synapses in the brain organize their nanoarchitecture due to challenges associated with super-resolution imaging in complex brain tissue. Here, we characterized single-domain camelid nanobodies for the 3D quantitative multiplex imaging of synaptic nano-organization in 6 µm brain cryosections using STED nanoscopy. We focused on thalamocortical (TC) and corticocortical (CC) synapses along the apical-basal axis of layer 5 pyramidal neurons as models of functionally diverse glutamatergic synapses in the brain. Spines receiving TC input were larger than CC spines in all layers examined. However, TC synapses on apical and basal dendrites conformed to different organizational principles. TC afferents on apical dendrites frequently contacted spines with multiple aligned PSD-95/Bassoon nanomodules, which are larger. TC spines on basal dendrites contained mostly one aligned PSD-95/Bassoon nanocluster. However, PSD-95 nanoclusters were larger and scaled with spine volume. The nano-organization of CC synapses did not change across cortical layers. These results highlight striking nanoscale diversity of functionally distinct glutamatergic synapses, relying on afferent input and sub-cellular localization of individual synaptic connections.

3.
J Neurosci ; 44(17)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38438258

RESUMEN

Acetylcholine (ACh) is released from basal forebrain cholinergic neurons in response to salient stimuli and engages brain states supporting attention and memory. These high ACh states are associated with theta oscillations, which synchronize neuronal ensembles. Theta oscillations in the basolateral amygdala (BLA) in both humans and rodents have been shown to underlie emotional memory, yet their mechanism remains unclear. Here, using brain slice electrophysiology in male and female mice, we show large ACh stimuli evoke prolonged theta oscillations in BLA local field potentials that depend upon M3 muscarinic receptor activation of cholecystokinin (CCK) interneurons (INs) without the need for external glutamate signaling. Somatostatin (SOM) INs inhibit CCK INs and are themselves inhibited by ACh, providing a functional SOM→CCK IN circuit connection gating BLA theta. Parvalbumin (PV) INs, which can drive BLA oscillations in baseline states, are not involved in the generation of ACh-induced theta, highlighting that ACh induces a cellular switch in the control of BLA oscillatory activity and establishes an internally BLA-driven theta oscillation through CCK INs. Theta activity is more readily evoked in BLA over the cortex or hippocampus, suggesting preferential activation of the BLA during high ACh states. These data reveal a SOM→CCK IN circuit in the BLA that gates internal theta oscillations and suggest a mechanism by which salient stimuli acting through ACh switch the BLA into a network state enabling emotional memory.


Asunto(s)
Acetilcolina , Colecistoquinina , Ratones Endogámicos C57BL , Ritmo Teta , Ritmo Teta/efectos de los fármacos , Ritmo Teta/fisiología , Animales , Masculino , Ratones , Femenino , Acetilcolina/farmacología , Acetilcolina/metabolismo , Colecistoquinina/farmacología , Colecistoquinina/metabolismo , Interneuronas/fisiología , Interneuronas/efectos de los fármacos , Somatostatina/metabolismo , Somatostatina/farmacología , Amígdala del Cerebelo/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Complejo Nuclear Basolateral/fisiología , Complejo Nuclear Basolateral/efectos de los fármacos , Red Nerviosa/fisiología , Red Nerviosa/efectos de los fármacos , Receptor Muscarínico M3/fisiología , Receptor Muscarínico M3/metabolismo , Parvalbúminas/metabolismo
4.
J Cell Sci ; 136(24)2023 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-38149870

RESUMEN

Skeletal muscle stem cells (MuSCs, also called satellite cells) are the source of the robust regenerative capability of this tissue. The hallmark property of MuSCs at homeostasis is quiescence, a reversible state of cell cycle arrest required for long-term preservation of the stem cell population. MuSCs reside between an individual myofiber and an enwrapping basal lamina, defining the immediate MuSC niche. Additional cell types outside the basal lamina, in the interstitial space, also contribute to niche function. Quiescence is actively maintained by multiple niche-derived signals, including adhesion molecules presented from the myofiber surface and basal lamina, as well as soluble signaling factors produced by myofibers and interstitial cell types. In this Cell Science at a Glance article and accompanying poster, we present the most recent information on how niche signals promote MuSC quiescence and provide perspectives for further research.


Asunto(s)
Músculo Esquelético , Células Satélite del Músculo Esquelético , Nicho de Células Madre , Fibras Musculares Esqueléticas , División Celular , Células Madre/metabolismo
5.
BMJ Nutr Prev Health ; 6(1): 6-13, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37559965

RESUMEN

Background: Hands-on culinary medicine education for medical trainees has emerged as a promising tool for cardiovascular health promotion. Purpose: To determine whether virtual culinary medicine programming associates with Mediterranean diet (MedDiet) adherence and lifestyle medicine competencies among medical trainees across the USA. Method: A total of 1433 medical trainees across 19 sites over a 12-month period were included. The Cooking for Health Optimisation with Patients-Medical Trainees survey composed of 61 questions regarding demographics, nutritional attitudes, dietary habits including MedDiet score and lifestyle medicine counselling competencies. Multivariable logistic regression assessed the association of virtual culinary medicine education with MedDiet intake and nutritional attitudes. Results: There were 519 medical trainees who participated in virtual culinary medicine education and 914 medical trainees who participated in their standard nutrition curricula. More than one-half of participants were women (n=759) and the mean age was 27 years old. Compared with students enrolled in traditional nutrition curricula, participants in virtual culinary medicine education were 37% more likely to adhere to MedDiet guidelines for fruit intake (OR 1.37, 95% CI 1.03 to 1.83, p=0.03). Virtual culinary medicine education was associated with higher proficiency in lifestyle medicine counselling categories, notably recommendations involving fibre (OR 4.03; 95% CI 3.05 to 5.34), type 2 diabetes prevention (OR 4.69; 95% CI 3.51 to 6.27) and omega fatty acids (OR 5.21; 95% CI 3.87 to 7.02). Virtual culinary medicine education had a similar, although higher magnitude association with MedDiet counselling competency (OR 5.73, 95% CI 4.26 to 7.70) when compared with historical data previously reported using hands-on, in-person culinary medicine courseware (OR 4.97, 95% CI 3.89 to 6.36). Conclusions: Compared with traditional nutritional educational curricula, virtual culinary medicine education is associated with higher MedDiet adherence and lifestyle medicine counselling competencies among medical trainees. Both virtual and hands-on culinary medicine education may be useful for cardiovascular health promotion.

6.
J Neurosci ; 43(5): 722-735, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36535767

RESUMEN

The amygdalar anterior basolateral nucleus (BLa) plays a vital role in emotional behaviors. This region receives dense cholinergic projections from basal forebrain which are critical in regulating neuronal activity in BLa. Cholinergic signaling in BLa has also been shown to modulate afferent glutamatergic inputs to this region. However, these studies, which have used cholinergic agonists or prolonged optogenetic stimulation of cholinergic fibers, may not reflect the effect of physiological acetylcholine release in the BLa. To better understand these effects of acetylcholine, we have used electrophysiology and optogenetics in male and female mouse brain slices to examine cholinergic regulation of afferent BLa input from cortex and midline thalamic nuclei. Phasic ACh release evoked by single pulse stimulation of cholinergic terminals had a biphasic effect on transmission at cortical input, producing rapid nicotinic receptor-mediated facilitation followed by slower mAChR-mediated depression. In contrast, at this same input, sustained ACh elevation through application of the cholinesterase inhibitor physostigmine suppressed glutamatergic transmission through mAChRs only. This suppression was not observed at midline thalamic nuclei inputs to BLa. In agreement with this pathway specificity, the mAChR agonist, muscarine more potently suppressed transmission at inputs from prelimbic cortex than thalamus. Muscarinic inhibition at prelimbic cortex input required presynaptic M4 mAChRs, while at thalamic input it depended on M3 mAChR-mediated stimulation of retrograde endocannabinoid signaling. Muscarinic inhibition at both pathways was frequency-dependent, allowing only high-frequency activity to pass. These findings demonstrate complex cholinergic regulation of afferent input to BLa that is pathway-specific and frequency-dependent.SIGNIFICANCE STATEMENT Cholinergic modulation of the basolateral amygdala regulates formation of emotional memories, but the underlying mechanisms are not well understood. Here, we show, using mouse brain slices, that ACh differentially regulates afferent transmission to the BLa from cortex and midline thalamic nuclei. Fast, phasic ACh release from a single optical stimulation biphasically regulates glutamatergic transmission at cortical inputs through nicotinic and muscarinic receptors, suggesting that cholinergic neuromodulation can serve precise, computational roles in the BLa. In contrast, sustained ACh elevation regulates cortical input through muscarinic receptors only. This muscarinic regulation is pathway-specific with cortical input inhibited more strongly than midline thalamic nuclei input. Specific targeting of these cholinergic receptors may thus provide a therapeutic strategy to bias amygdalar processing and regulate emotional memory.


Asunto(s)
Acetilcolina , Complejo Nuclear Basolateral , Ratones , Animales , Masculino , Femenino , Acetilcolina/metabolismo , Complejo Nuclear Basolateral/metabolismo , Receptores Colinérgicos/metabolismo , Tálamo/fisiología , Colinérgicos/farmacología , Receptores Muscarínicos/metabolismo , Transmisión Sináptica/fisiología
7.
Matern Child Health J ; 26(9): 1907-1916, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35871121

RESUMEN

OBJECTIVES: To inform updates to the Pregnancy Risk Assessment Monitoring System (PRAMS) design and processes, African American/Black and Hispanic/Latina women in Florida provided feedback on their awareness and perceptions of the PRAMS survey, and preferences for survey distribution, completion, design and content. METHODS: Focus groups were conducted in English and Spanish with 29 women in two large metropolitan counties. Participants completed a brief survey, reviewed the PRAMS questionnaire and recruitment materials, engaged in discussion, and gave feedback directly onto cover design posters. RESULTS: Participants reported limited awareness of PRAMS. Preferences for survey distribution and completion varied by participant lifestyle. Interest in topics covered by PRAMS was as a motivator for completion, while distrust and confidentiality concerns were deterrents. Participants were least comfortable answering questions about income, illegal drug use, and pregnancy loss/infant death. Changes to the length of the survey, distribution methods, and incentives/rewards for completion were recommended. CONCLUSIONS FOR PRACTICE: Results highlight the need to increase PRAMS awareness, build trust, and consider the design, length and modality for questionnaire completion as possible avenues to improve PRAMS response rates.


Asunto(s)
Vigilancia de la Población , Femenino , Florida , Humanos , Vigilancia de la Población/métodos , Embarazo , Medición de Riesgo , Encuestas y Cuestionarios
8.
J Psychopharmacol ; 36(12): 1350-1361, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35772419

RESUMEN

BACKGROUND: Adolescence is characterised by psychological and neural development. Cannabis harms may be accentuated during adolescence. We hypothesised that adolescents would be more vulnerable to the associations between cannabis use and mental health and addiction problems than adults. METHOD: As part of the 'CannTeen' study, we conducted a cross-sectional analysis. There were 274 participants: split into groups of adolescent users (n = 76; 16-17 years old) and controls (n = 63), and adult users (n = 71; 26-29 years old) and controls (n = 64). Among users, cannabis use frequency ranged from 1 to 7 days/week, while controls had 0-10 lifetime exposures to cannabis. Adolescent and adult cannabis users were matched on cannabis use frequency (mean=4 days/week). We measured Diagnostic and Statistical Manual (DSM-5) Cannabis Use Disorder (CUD), Beck Depression Inventory, Beck Anxiety Inventory and Psychotomimetic States Inventory-adapted. RESULTS: After adjustment for covariates, adolescent users were more likely to have severe CUD than adult users (odd ratio = 3.474, 95% confidence interval (CI) = 1.501-8.036). Users reported greater psychotic-like symptoms than controls (b = 6.004, 95% CI = 1.211-10.796) and adolescents reported greater psychotic-like symptoms than adults (b = 5.509, 95% CI = 1.070-9.947). User-group was not associated with depression or anxiety. No significant interactions between age-group and user-group were identified. Exploratory analyses suggested that cannabis users with severe CUD had greater depression and anxiety levels than cannabis users without severe CUD. CONCLUSION: Adolescent cannabis users are more likely than adult cannabis users to have severe CUD. Adolescent cannabis users have greater psychotic-like symptoms than adult cannabis users and adolescent controls, through an additive effect. There was no evidence of an amplified vulnerability to cannabis-related increases in subclinical depression, anxiety or psychotic-like symptoms in adolescence. However, poorer mental health was associated with the presence of severe CUD.


Asunto(s)
Ansiedad , Depresión , Abuso de Marihuana , Trastornos Psicóticos , Adolescente , Adulto , Humanos , Ansiedad/epidemiología , Estudios Transversales , Depresión/epidemiología , Abuso de Marihuana/epidemiología , Trastornos Psicóticos/epidemiología , Estudios de Casos y Controles
9.
Nutrients ; 14(7)2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35406045

RESUMEN

Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (-0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.


Asunto(s)
Ceramidas , Fructosa , Obesidad Infantil , Biomarcadores/metabolismo , Factores de Riesgo Cardiometabólico , Ceramidas/metabolismo , Niño , Fructosa/administración & dosificación , Humanos , Resistencia a la Insulina/fisiología , Lipogénesis , Hígado/metabolismo
10.
Protein Sci ; 29(12): 2387-2397, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33020946

RESUMEN

During adaptive metabolic evolution a native glycerol dehydrogenase (GDH) acquired a d-lactate dehydrogenase (LDH) activity. Two active-site amino acid changes were detected in the altered protein. Biochemical studies along with comparative structure analysis using an X-ray crystallographic structure model of the protein with the two different amino acids allowed prediction of pyruvate binding into the active site. We propose that the F245S alteration increased the capacity of the glycerol binding site and facilitated hydrogen bonding between the S245 γ-O and the C1 carboxylate of pyruvate. To our knowledge, this is the first GDH to gain LDH activity due to an active site amino acid change, a desired result of in vivo enzyme evolution.


Asunto(s)
Bacillus , Proteínas Bacterianas , L-Iditol 2-Deshidrogenasa , Lactato Deshidrogenasas , Bacillus/enzimología , Bacillus/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Sitios de Unión , Cristalografía por Rayos X , Cinética , L-Iditol 2-Deshidrogenasa/química , L-Iditol 2-Deshidrogenasa/genética , Lactato Deshidrogenasas/química , Lactato Deshidrogenasas/genética , Mutagénesis Sitio-Dirigida
11.
Animals (Basel) ; 10(4)2020 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-32244374

RESUMEN

The infrequency of a total solar eclipse renders the event novel to those animals that experience its effects and, consequently, may induce anomalous behavioral responses. However, historical information on the responses of animals to eclipses is scant and often conflicting. In this study, we qualitatively document the responses of 17 vertebrate taxa (including mammals, birds, and reptiles) to the 2017 total solar eclipse as it passed over Riverbanks Zoo and Garden in Columbia, South Carolina. In the days leading up to the eclipse, several focal teams, each consisting of researchers, animal keepers, and student/zoo volunteers conducted baseline observations using a combination of continuous ad libitum and scan sampling of each animal during closely matched seasonal conditions. These same focal teams used the same protocol to observe the animals in the hours preceding, during, and immediately following the eclipse. Additionally, for one species-siamangs (Symphalangus syndactylus)-live video/audio capture was also employed throughout observations to capture behavior during vocalizations for subsequent quantitative analysis. Behavioral responses were classified into one or more of four overarching behavioral categories: normal (baseline), evening, apparent anxiety, and novel. Thirteen of seventeen observed taxa exhibited behaviors during the eclipse that differed from all other observation times, with the majority (8) of these animals engaging in behaviors associated with their evening or nighttime routines. The second predominant behavior was apparent anxiety, documented in five genera: baboons (Papio hamadryas), gorillas (Gorilla gorilla gorilla), giraffes (Giraffa cf. camelopardalis), flamingos (Phoenicopterus ruber), and lorikeets (Trichoglossus moluccanus and Trichoglossus haematodus). Novel behaviors characterized by an increase in otherwise nearly sedentary activity were observed only in the reptiles, the Galapagos tortoise (Chelonoidis nigra) and the Komodo dragon (Varanus komodoensis). While the anthropogenic influences on animal behaviors-particularly those relating to anxiety-cannot be discounted, these observations provide novel insight into the observed responses of a diverse vertebrate sample during a unique meteorological stimulus, insights that supplement the rare observations of behavior during this phenomenon for contextualizing future studies.

12.
J Lipid Res ; 61(3): 455-463, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31888979

RESUMEN

Elevated levels of triglyceride-rich lipoproteins (TRLs), both fasting and postprandial, are associated with increased risk for atherosclerosis. However, guidelines for treatment are defined solely by fasting lipid levels, even though postprandial lipids may be more informative. In the postprandial state, circulating lipids consist of dietary fat transported from the intestine in chylomicrons (CMs; containing ApoB48) and fat transported from the liver in VLDL (containing ApoB100). Research into the roles of endogenous versus dietary fat has been hindered because of the difficulty in separating these particles by ultracentrifugation. CM fractions have considerable contamination from VLDL (purity, 10%). To separate CMs from VLDL, we produced polyclonal antibodies against ApoB100 and generated immunoaffinity columns. TRLs isolated by ultracentrifugation of plasma were applied to these columns, and highly purified CMs were collected (purity, 90-94%). Overall eight healthy unmedicated adult volunteers (BMI, 27.2 ± 1.4 kg/m2; fasting triacylglycerol, 102.6 ± 19.5 mg/dl) participated in a feeding study, which contained an oral stable-isotope tracer (1-13C acetate). We then used this technique on plasma samples freshly collected during an 8 h human feeding study from a subset of four subjects. We analyzed fractionated lipoproteins by Western blot, isolated and derivatized triacylglycerols, and calculated fractional de novo lipogenesis. The results demonstrated effective separation of postprandial lipoproteins and substantially improved purity compared with ultracentrifugation protocols, using the immunoaffinity method. This method can be used to better delineate the role of dietary sugar and fat on postprandial lipids in cardiovascular risk and explore the potential role of CM remnants in atherosclerosis.


Asunto(s)
Apolipoproteína B-100/química , Quilomicrones/aislamiento & purificación , Lipoproteínas/aislamiento & purificación , Triglicéridos/aislamiento & purificación , Cromatografía de Afinidad , Quilomicrones/química , Femenino , Voluntarios Sanos , Humanos , Inmunoprecipitación , Lipoproteínas/química , Masculino , Periodo Posprandial , Triglicéridos/química
13.
Brain Res ; 1722: 146349, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31348911

RESUMEN

Although it is known that acetylcholine acting through M1 muscarinic receptors (M1Rs) is essential for memory consolidation in the anterior basolateral nucleus of the amygdala (BLa), virtually nothing is known about the circuits involved. In the hippocampus M1R activation facilitates long-term potentiation (LTP) by potentiating NMDA glutamate receptor (NMDAR) currents. The majority of NMDAR+ profiles in the BLa are spines. Since about half of dendritic spines of BLa pyramidal neurons (PNs) receiving glutamatergic inputs are M1R-immunoreactive (M1R+) it is possible that the role of M1Rs in BLa mnemonic functions also involves potentiation of NMDAR currents in spines. However, the finding that only about half of BLa spines are M1R+ suggests that this proposed mechanism may only apply to a subset of glutamatergic inputs. As a first step in the identification of differential glutamatergic inputs to M1R+ spines in the BLa, the present electron microscopic study used antibodies to two different vesicular glutamate transporter proteins (VGluTs) to label two different subsets of glutamatergic inputs to M1R+ spines. These inputs are largely complimentary with VGluT1+ inputs arising mainly from cortical structures and the basolateral nucleus, and VGluT2+ inputs arising mainly from the thalamus. It was found that about one-half of the spines that were postsynaptic to VGluT1+ or VGluT2+ terminals were M1R+. In addition, a subset of the VGluT1+ or VGluT2+ axon terminals were M1R+, including those that synapsed with M1R+ spines. These results suggest that acetylcholine can modulate glutamatergic inputs to BLa spines by presynaptic as well as postsynaptic M1R-mediated mechanisms.


Asunto(s)
Complejo Nuclear Basolateral/ultraestructura , Neuronas/ultraestructura , Receptor Muscarínico M1/análisis , Proteína 1 de Transporte Vesicular de Glutamato/análisis , Proteína 2 de Transporte Vesicular de Glutamato/análisis , Animales , Espinas Dendríticas/metabolismo , Espinas Dendríticas/ultraestructura , Masculino , Ratones , Neuronas/metabolismo , Terminales Presinápticos/metabolismo , Terminales Presinápticos/ultraestructura
14.
Mol Psychiatry ; 24(5): 710-725, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30214043

RESUMEN

Noradrenergic signaling plays a well-established role in promoting the stress response. Here we identify a subpopulation of noradrenergic neurons, defined by developmental expression of Hoxb1, that has a unique role in modulating stress-related behavior. Using an intersectional chemogenetic strategy, in combination with behavioral and physiological analyses, we show that activation of Hoxb1-noradrenergic (Hoxb1-NE) neurons decreases anxiety-like behavior and promotes an active coping strategy in response to acute stressors. In addition, we use cerebral blood volume-weighted functional magnetic resonance imaging to show that chemoactivation of Hoxb1-NE neurons results in reduced activity in stress-related brain regions, including the bed nucleus of the stria terminalis, amygdala, and locus coeruleus. Thus, the actions of Hoxb1-NE neurons are distinct from the well-documented functions of the locus coeruleus in promoting the stress response, demonstrating that the noradrenergic system contains multiple functionally distinct subpopulations.


Asunto(s)
Neuronas Adrenérgicas/fisiología , Proteínas de Homeodominio/genética , Estrés Fisiológico/genética , Adaptación Psicológica/fisiología , Neuronas Adrenérgicas/metabolismo , Amígdala del Cerebelo/metabolismo , Animales , Ansiedad/genética , Ansiedad/metabolismo , Conducta Animal/fisiología , Encéfalo/metabolismo , Femenino , Proteínas de Homeodominio/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neuronas/metabolismo
15.
Gastroenterology ; 153(3): 743-752, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28579536

RESUMEN

BACKGROUND & AIMS: Consumption of sugar is associated with obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis [DNL]) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/d). METHODS: Children (9-18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child. RESULTS: Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (interquartile range [IQR], 2.5%-14.8%) to 3.8% (IQR, 1.7%-15.5%) (P < .001) and VAT decreased from 123 cm3 (IQR, 85-145 cm3) to 110 cm3 (IQR, 84-134 cm3) (P < .001). The DNL area under the curve decreased from 68% (IQR, 46%-83%) to 26% (IQR, 16%-37%) (P < .001). Insulin kinetics improved (P < .001). These changes occurred irrespective of baseline liver fat. CONCLUSIONS: Short-term (9 days) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov Number: NCT01200043.


Asunto(s)
Carbohidratos de la Dieta/administración & dosificación , Fructosa/administración & dosificación , Insulina/metabolismo , Grasa Intraabdominal , Lipogénesis , Obesidad Infantil/fisiopatología , Adolescente , Negro o Afroamericano , Niño , Femenino , Prueba de Tolerancia a la Glucosa , Hispánicos o Latinos , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Hígado/diagnóstico por imagen , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/fisiopatología , Obesidad Infantil/complicaciones , Grasa Subcutánea/diagnóstico por imagen
16.
Am J Surg ; 213(4): 631-636, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28038715

RESUMEN

INTRODUCTION: Skills decay is a known risk for surgical residents who have dedicated research time. We hypothesize that simulation-based assessments will reveal significant differences in perceived skill decay when assessing a variety of clinical scenarios in a longitudinal fashion. METHODS: Residents (N = 46; Returning: n = 16, New: n = 30) completed four simulated procedures: urinary catheterization, central line, bowel anastomosis, and laparoscopic ventral hernia repair. Perception surveys were administered pre- and post-simulation. RESULTS: Perceptions of skill decay and task difficulty were similar for both groups across three procedures pre- and post-simulation. Due to a simulation modification, new residents were more confident in urinary catheterization than returning residents (F(1,4) = 11.44, p = 0.002). In addition, when assessing expectations for skill reduction, returning residents perceived greater skill reduction upon reassessment when compared to first time residents (t(35) = 2.37, p = 0.023). CONCLUSION: Research residents may benefit from longitudinal skills assessments and a wider variety of simulation scenarios during their research years. TABLE OF CONTENTS SUMMARY: As part of a longitudinal study, we assessed research residents' confidence, perceptions of task difficulty and surgical skill reduction. Residents completed surveys pre- and post-experience with four simulated procedures: urinary catheterization, subclavian central line insertion, bowel anastomosis, and laparoscopic ventral hernia repair. Returning residents perceived greater skill reduction upon reassessment when compared to residents participating for the first time. In addition, modification of the clinical scenarios affected perceptions of skills decay.


Asunto(s)
Competencia Clínica , Internado y Residencia , Entrenamiento Simulado , Anastomosis Quirúrgica , Cateterismo Venoso Central , Evaluación Educacional , Femenino , Cirugía General/educación , Hernia Ventral/cirugía , Humanos , Intestinos/cirugía , Laparoscopía , Estudios Longitudinales , Masculino , Medio Oeste de Estados Unidos , Refuerzo en Psicología , Autoeficacia , Cateterismo Urinario
17.
J Appl Commun Res ; 44(1): 22-39, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26949274

RESUMEN

Changes to the United States Preventive Services Task Force (USPSTF) recommendations for cervical cancer preventive services have led to patient confusion, especially in medically underserved populations. We investigated how patient uncertainty concerning cervical cancer screening guidelines is appraised and managed through communication with healthcare providers by conducting in-depth, face-to-face interviews with 24 adult women between the ages of 24 and 65 (m = 41, SD = 14) living in Appalachia Kentucky. In general, participants expressed a high degree of uncertainty about the updated cervical cancer screening guidelines and appraised this uncertainty as both a danger and an opportunity. Communication with healthcare providers served both to exacerbate and to mitigate patient uncertainty. The study identifies how health care providers may use the change in USPSTF guidelines as a 'teachable moment' to productively counsel patients on the importance of timely screening, the typical progression of certain types of high-risk HPV infection to cervical cancer, and the importance of follow-up care.

18.
J Surg Res ; 199(1): 23-31, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26197949

RESUMEN

BACKGROUND: Surgery residents may take years away from clinical responsibilities for dedicated research time. As part of a longitudinal project, the study aim was to investigate residents' perceptions of clinical skill reduction during dedicated research time. Our hypothesis was that residents would perceive a greater potential reduction in skill during research time for procedures they were less confident in performing. MATERIALS AND METHODS: Surgical residents engaged in dedicated research training at multiple training programs participated in four simulated procedures: urinary catheterization, subclavian central line, bowel anastomosis, and laparoscopic ventral hernia (LVH) repair. Using preprocedure and postprocedure surveys, participants rated procedures for confidence and difficulty. Residents also indicated the perceived level of skills reduction for the four procedures as a result of time in the laboratory. RESULTS: Thirty-eight residents (55% female) completed the four clinical simulators. Participants had between 0-36 mo in a laboratory (M = 9.29 mo, standard deviation = 9.38). Preprocedure surveys noted lower confidence and higher perceived difficulty for performing the LVH repair followed by bowel anastomosis, central line insertion, and urinary catheterization (P < 0.05). Residents perceived the greatest reduction in bowel anastomosis and LVH repair skills compared with urinary catheterization and subclavian central line insertion (P < 0.001). Postprocedure surveys showed significant effects of the simulation scenarios on resident perception for urinary catheterization (P < 0.05) and LVH repair (P < 0.05). CONCLUSIONS: Residents in this study expected greater skills decay for the procedures they had lower confidence performing and greater perceived difficulty. In addition, carefully adapted simulation scenarios had a significant effect on resident perception and may provide a mechanism for maintaining skills and keeping confidence grounded in experience.


Asunto(s)
Investigación Biomédica/educación , Competencia Clínica , Educación de Postgrado en Medicina/métodos , Cirugía General/educación , Internado y Residencia/métodos , Curva de Aprendizaje , Chicago , Femenino , Humanos , Masculino , Minnesota , Percepción , Procedimientos Quirúrgicos Operativos/educación , Factores de Tiempo , Wisconsin
19.
Am J Surg ; 210(4): 618-23, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26198334

RESUMEN

BACKGROUND: The aim of this study was to evaluate recommendation patterns of different specialties for the work-up of a palpable breast mass using simulated scenarios and clinical breast examination models. METHODS: Study participants were a convenience sample of physicians (n = 318) attending annual surgical, family practice, and obstetrics and gynecology (OB/GYN) conferences. Two different silicone-based breast models (superficial mass vs chest wall mass) were used to test clinical breast examination skills and recommendation patterns (imaging, tissue sampling, and follow-up). RESULTS: Participants were more likely to recommend mammography (P < .001) and core biopsy (P < .0001) and less likely to recommend needle aspiration (P < .043) and 1-month follow-up (P < .001) for the chest wall mass compared with the superficial mass. Family practitioners were less likely to recommend ultrasound (P < .001) and obstetrics and gynecologists were less likely to recommend mammogram (P < .006) across models. Surgeons were more likely to recommend core biopsy and less likely to recommend needle aspiration across models (P < .001). CONCLUSIONS: Recommendation patterns differed across the 2 models in line with existing practice guidelines. Additionally, differences in practice patterns between primary care and specialty providers may represent varying clinician capabilities, healthcare resources, and individual preferences. Our work shows that simulation may be used to track adherence to practice guidelines for breast masses.


Asunto(s)
Biopsia con Aguja , Neoplasias de la Mama/diagnóstico , Medicina Familiar y Comunitaria , Mamografía , Palpación , Especialidades Quirúrgicas , Ultrasonografía Mamaria , Competencia Clínica , Toma de Decisiones Clínicas , Femenino , Humanos , Masculino , Modelos Anatómicos , Modelos Biológicos , Derivación y Consulta , Entrenamiento Simulado , Espera Vigilante
20.
J Nat Prod ; 77(2): 402-5, 2014 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-24467367

RESUMEN

Methyl farnesoate, [methyl (2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienoate (1)] has not been thought be present in the hemolymph of insects, although it is the immediate biosynthetic precursor of the circulating insect hormone juvenile hormone III (methyl (2E,6E)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate) (2). Compound 1 was identified from the hemolymph obtained from five orders of insects. Identification of 1 from the American bird grasshopper was facilitated using both electron impact and chemical-ionization GC-MS, GC-FTIR, and 2D NMR techniques. The identifications from other insects were made using GC-MS, and the amounts of all were quantified using LIM-CI-GC-MS. The ratios of 1 and 2 varied in these insects during different developmental stages. The present results underscore the need for further studies on methyl farnesoate (1) as a circulating hormone in insects.


Asunto(s)
Ácidos Grasos Insaturados/aislamiento & purificación , Saltamontes/química , Hemolinfa/química , Sesquiterpenos/aislamiento & purificación , Animales , Ácidos Grasos Insaturados/química , Ácidos Grasos Insaturados/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Saltamontes/metabolismo , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Sesquiterpenos/química , Sesquiterpenos/metabolismo
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