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1.
Am J Emerg Med ; 53: 208-214, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35074684

RESUMEN

OBJECTIVES: The effectiveness of current assessment tools for cervical fracture are mixed with respect to elderly patients. We aim to examine utility of history and physical exam to assess for cervical fracture for elderly patients suffering a ground-level fall. METHODS: Retrospective cohort from a tertiary-care ED for patients ≥65 years, including dementia, after ground-level fall. Logistic regression was used to examine predictability of various clinical factors. Neurologic deficits were considered a hard sign for imaging and were not assessed. RESULTS: Of 1035 patient encounters analyzed, 683 had CT cervical-spine (C-spine) imaging (66.0%) and 16 (1.5%) had cervical fracture. C-spine tenderness (OR 4.7, 95% CI 1.5-14.1), neck pain (OR 10.5, 95% CI 3.4-32.5), altered mental status (AMS) (OR 5.1, 95% CI 1.7-15.6), and external trauma above the clavicles (ETC) (OR 3.8, 95% CI 1.2-12.3) predicted cervical fracture. C-spine tenderness and neck pain were collinear and run-in separate models. Dementia (OR 0.2, 95% CI 0.4-0.9) did not predict cervical fracture in this population. A combination of ETC, C-spine tenderness, and AMS had a sensitivity = 100% and specificity = 40.0% for detection of cervical fracture. ETC was found in all but two fractures requiring intervention with negative predictive value = 99.3%. CONCLUSIONS: Clinical assessment for elderly patients without neurologic signs, together with the absence of ETC, cervical tenderness, and AMS may be reliable in ruling out cervical fracture after a ground-level fall, including patients with history of dementia. Fractures requiring intervention were rare in patients without ETC. However, findings are retrospective and prospective validation is required.


Asunto(s)
Demencia , Fracturas Óseas , Traumatismos del Cuello , Fracturas de la Columna Vertebral , Heridas no Penetrantes , Anciano , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/lesiones , Demencia/diagnóstico , Demencia/etiología , Humanos , Dolor de Cuello/diagnóstico , Dolor de Cuello/etiología , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Heridas no Penetrantes/diagnóstico
2.
Cancers (Basel) ; 13(1)2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33466329

RESUMEN

Targeting a tumor's metabolic dependencies is a clinically actionable therapeutic approach; however, identifying subtypes of tumors likely to respond remains difficult. The use of lipids as a nutrient source is of particular importance, especially in breast cancer. Imaging techniques offer the opportunity to quantify nutrient use in preclinical tumor models to guide development of new drugs that restrict uptake or utilization of these nutrients. We describe a fast and dynamic approach to image fatty acid uptake in vivo and demonstrate its relevance to study both tumor metabolic reprogramming directly, as well as the effectiveness of drugs targeting lipid metabolism. Specifically, we developed a quantitative optical approach to spatially and longitudinally map the kinetics of long-chain fatty acid uptake in in vivo murine models of breast cancer using a fluorescently labeled palmitate molecule, Bodipy FL c16. We chose intra-vital microscopy of mammary tumor windows to validate our approach in two orthotopic breast cancer models: a MYC-overexpressing, transgenic, triple-negative breast cancer (TNBC) model and a murine model of the 4T1 family. Following injection, Bodipy FL c16 fluorescence increased and reached its maximum after approximately 30 min, with the signal remaining stable during the 30-80 min post-injection period. We used the fluorescence at 60 min (Bodipy60), the mid-point in the plateau region, as a summary parameter to quantify Bodipy FL c16 fluorescence in subsequent experiments. Using our imaging platform, we observed a two- to four-fold decrease in fatty acid uptake in response to the downregulation of the MYC oncogene, consistent with findings from in vitro metabolic assays. In contrast, our imaging studies report an increase in fatty acid uptake with tumor aggressiveness (6NR, 4T07, and 4T1), and uptake was significantly decreased after treatment with a fatty acid transport inhibitor, perphenazine, in both normal mammary pads and in the most aggressive 4T1 tumor model. Our approach fills an important gap between in vitro assays providing rich metabolic information at static time points and imaging approaches visualizing metabolism in whole organs at a reduced resolution.

3.
Cell Rep ; 30(10): 3368-3382.e7, 2020 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-32160543

RESUMEN

Tumors that overexpress the MYC oncogene are frequently aneuploid, a state associated with highly aggressive cancers and tumor evolution. However, how MYC causes aneuploidy is not well understood. Here, we show that MYC overexpression induces mitotic spindle assembly defects and chromosomal instability (CIN) through effects on microtubule nucleation and organization. Attenuating MYC expression reverses mitotic defects, even in established tumor cell lines, indicating an ongoing role for MYC in CIN. MYC reprograms mitotic gene expression, and we identify TPX2 to be permissive for spindle assembly in MYC-high cells. TPX2 depletion blocks mitotic progression, induces cell death, and prevents tumor growth. Further elevating TPX2 expression reduces mitotic defects in MYC-high cells. MYC and TPX2 expression may be useful biomarkers to stratify patients for anti-mitotic therapies. Our studies implicate MYC as a regulator of mitosis and suggest that blocking MYC activity can attenuate the emergence of CIN and tumor evolution.


Asunto(s)
Mitosis , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Proto-Oncogénicas c-myc/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Muerte Celular , Línea Celular Tumoral , Inestabilidad Cromosómica , Citoprotección , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Huso Acromático/metabolismo , Mutaciones Letales Sintéticas
4.
Invest Ophthalmol Vis Sci ; 61(2): 17, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-32053727

RESUMEN

Purpose: Vigabatrin (VGB) is an effective antiepileptic that increases concentrations of inhibitory γ-aminobutyric acid (GABA) by inhibiting GABA transaminase. Reports of VGB-associated visual field loss limit its clinical usefulness, and retinal toxicity studies in laboratory animals have yielded conflicting results. Methods: We examined the functional and morphologic effects of VGB in C57BL/6J mice that received either VGB or saline IP from 10 to 18 weeks of age. Retinal structure and function were assessed in vivo by optical coherence tomography (OCT), ERG, and optomotor response. After euthanasia, retinas were processed for immunohistochemistry, and retinal GABA, and VGB quantified by mass spectrometry. Results: No significant differences in visual acuity or total retinal thickness were identified between groups by optomotor response or optical coherence tomography, respectively. After 4 weeks of VGB treatment, ERG b-wave amplitude was enhanced, and amplitudes of oscillatory potentials were reduced. Dramatic rod and cone bipolar and horizontal cell remodeling, with extension of dendrites into the outer nuclear layer, was observed in retinas of VGB-treated mice. VGB treatment resulted in a mean 3.3-fold increase in retinal GABA concentration relative to controls and retinal VGB concentrations that were 20-fold greater than brain. Conclusions: No evidence of significant retinal thinning or ERG a- or b-wave deficits were apparent, although we describe significant alterations in ERG b-wave and oscillatory potentials and in retinal cell morphology in VGB-treated C57BL/6J mice. The dramatic concentration of VGB in retina relative to the target tissue (brain), with a corresponding increase in retinal GABA, offers insight into the pathophysiology of VGB-associated visual field loss.


Asunto(s)
Anticonvulsivantes/farmacología , GABAérgicos/farmacología , Plasticidad Neuronal/efectos de los fármacos , Retina/efectos de los fármacos , Vigabatrin/farmacología , Animales , Masculino , Ratones Endogámicos C57BL , Plasticidad Neuronal/fisiología , Músculos Oculomotores/efectos de los fármacos , Distribución Aleatoria , Retina/fisiopatología , Enfermedades de la Retina/tratamiento farmacológico , Enfermedades de la Retina/fisiopatología , Tomografía de Coherencia Óptica , Campos Visuales/fisiología
5.
Transl Vis Sci Technol ; 8(5): 22, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31616579

RESUMEN

PURPOSE: To validate the use of aqueous angiography (AA) in characterizing distal aqueous outflow pathways in normal and glaucomatous cats. METHODS: Ex vivo AA and optical coherence tomography (OCT) were performed in nine adult cat eyes (5 feline congenital glaucoma [FCG] and 4 normal), following intracameral infusion of 2.5% fluorescein and/or 0.4% indocyanine green (ICG) at physiologic intraocular pressure (IOP). Scleral OCT line scans were acquired in areas of high- and low-angiographic signal. Tissues dissected in regions of high- and low-AA signal, were sectioned and hematoxylin and eosin (H&E)-stained or immunolabeled (IF) for vascular endothelial and perivascular cell markers. Outflow vessel numbers and locations were compared between groups by Student's t-test. RESULTS: AA yielded circumferential, high-quality images of distal aqueous outflow pathways in normal and FCG eyes. No AA signal or scleral lumens were appreciated in one buphthalmic FCG eye, though collapsed vascular profiles were identified on IF. The remaining eight of nine eyes all showed segmental AA signal, distinguished by differences in time of signal onset. AA signal always corresponded with lumens seen on OCT. Numbers of intrascleral vessels were not significantly different between groups, but scleral vessels were significantly more posteriorly located relative to the limbus in FCG. CONCLUSIONS: A capacity for distal aqueous humor outflow was confirmed by AA in FCG eyes ex vivo but with significant posterior displacement of intrascleral vessels relative to the limbus in FCG compared with normal eyes. TRANSLATIONAL RELEVANCE: This report provides histopathologic correlates of advanced diagnostic imaging findings in a spontaneous model of congenital glaucoma.

6.
PLoS One ; 14(1): e0207785, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30601825

RESUMEN

Traumatic brain injury (TBI) is a major cause of death and disability worldwide, with mild TBI (mTBI) accounting for 85% of cases. mTBI is also implicated in serious long-term sequelae including second impact syndrome and chronic traumatic encephalopathy. mTBI often goes undiagnosed due to delayed symptom onset and limited sensitivity of conventional assessment measures compared with severe TBI. Current efforts seek to identify accurate and reliable non-invasive biomarkers associated with functional measures relevant to long-term outcomes. Here we evaluated the utility of serum and salivary microRNAs (miRNAs) to serve as sensitive and specific peripheral biomarkers of possible mTBI. Our primary objectives were to establish the relationship between peripheral measures of miRNA, objective quantification of head impacts, and sensitive indices of balance and cognitive function in healthy young adult athletes. A secondary objective was to compare the sensitivity of miRNA versus commonly used blood-based protein biomarkers. 50 amateur mixed martial arts (MMA) fighters participated. 216 saliva and serum samples were collected at multiple time points, both pre- and post-fight. Levels of 10 serum proteins were compared in a subset of the fighters (n = 24). Levels of miRNAs were obtained by next generation sequencing. Functional outcomes were evaluated using a computerized assessment system that measured cognitive performance, body sway, and combined cognitive performance and body sway during dual task completion. Data were analyzed using multivariate logistic regression for predictive classification, analysis of variance, correlation analysis and principal component analysis. We identified a subset of salivary and serum miRNAs that showed robust utility at predicting TBI likelihood and demonstrated quantitative associations with head impacts as well as cognitive and balance measures. In contrast, serum proteins demonstrated far less utility. We also found that the timing of the responses varies in saliva and serum, which is a critical observation for biomarker studies to consider.


Asunto(s)
Conmoción Encefálica/sangre , Artes Marciales , MicroARNs/sangre , Saliva/metabolismo , Adulto , Biomarcadores/sangre , Proteínas Sanguíneas/metabolismo , Conmoción Encefálica/genética , Femenino , Cabeza , Humanos , Modelos Logísticos , Masculino , Postura , Análisis de Componente Principal , Factores de Tiempo
7.
Autism Res ; 11(9): 1286-1299, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30107083

RESUMEN

Autism spectrum disorder (ASD) is associated with several oropharyngeal abnormalities, including buccal sensory sensitivity, taste and texture aversions, speech apraxia, and salivary transcriptome alterations. Furthermore, the oropharynx represents the sole entry point to the gastrointestinal (GI) tract. GI disturbances and alterations in the GI microbiome are established features of ASD, and may impact behavior through the "microbial-gut-brain axis." Most studies of the ASD microbiome have used fecal samples. Here, we identified changes in the salivary microbiome of children aged 2-6 years across three developmental profiles: ASD (n = 180), nonautistic developmental delay (DD; n = 60), and typically developing (TD; n = 106) children. After RNA extraction and shotgun sequencing, actively transcribing taxa were quantified and tested for differences between groups and within ASD endophenotypes. A total of 12 taxa were altered between the developmental groups and 28 taxa were identified that distinguished ASD patients with and without GI disturbance, providing further evidence for the role of the gut-brain axis in ASD. Group classification accuracy was visualized with receiver operating characteristic curves and validated using a 50/50 hold-out procedure. Five microbial ratios distinguished ASD from TD participants (79.5% accuracy), three distinguished ASD from DD (76.5%), and three distinguished ASD children with/without GI disturbance (85.7%). Taxonomic pathways were assessed using the Kyoto Encyclopedia of Genes and Genomes microbial database and compared with one-way analysis of variance, revealing significant differences within energy metabolism and lysine degradation. Together, these results indicate that GI microbiome disruption in ASD extends to the oropharynx, and suggests oral microbiome profiling as a potential tool to evaluate ASD status. Autism Res 2018, 11: 1286-1299. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Previous research suggests that the bacteria living in the human gut may influence autistic behavior. This study examined genetic activity of microbes living in the mouth of over 300 children. The microbes with differences in children with autism were involved in energy processing and showed potential for identifying autism status.


Asunto(s)
Trastorno del Espectro Autista/microbiología , Microbioma Gastrointestinal/fisiología , Boca/microbiología , Saliva/microbiología , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino
8.
PLoS One ; 13(7): e0198288, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30020932

RESUMEN

The microbiome plays a vital role in human health and disease. Interaction between human hosts and the microbiome occurs through a number of mechanisms, including transcriptomic regulation by microRNA (miRNA). In animal models, circadian variations in miRNA and microbiome elements have been described, but patterns of co-expression and potential diurnal interaction in humans have not. We investigated daily oscillations in salivary miRNA and microbial RNA to explore relationships between these components of the gut-brain-axis and their implications in human health. Nine subjects provided 120 saliva samples at designated times, on repeated days. Samples were divided into three sets for exploration and cross-validation. Identification and quantification of host miRNA and microbial RNA was performed using next generation sequencing. Three stages of statistical analyses were used to identify circadian oscillators: 1) a two-way analysis of variance in the first two sample sets identified host miRNAs and microbial RNAs whose abundance varied with collection time (but not day); 2) multivariate modeling identified subsets of these miRNAs and microbial RNAs strongly-associated with collection time, and evaluated their predictive ability in an independent hold-out sample set; 3) regulation of circadian miRNAs and microbial RNAs was explored in data from autistic children with disordered sleep (n = 77), relative to autistic peers with typical sleep (n = 63). Eleven miRNAs and 11 microbial RNAs demonstrated consistent diurnal oscillation across sample sets and accurately predicted collection time in the hold-out set. Associations among five circadian miRNAs and four circadian microbial RNAs were observed. We termed the 11 miRNAs CircaMiRs. These CircaMiRs had 1,127 predicted gene targets, with enrichment for both circadian gene targets and metabolic signaling processes. Four CircaMiRs had "altered" expression patterns among children with disordered sleep. Thus, novel and correlated circadian oscillations in human miRNA and microbial RNA exist and may have distinct implications in human health and disease.


Asunto(s)
Trastorno Autístico/genética , MicroARNs/genética , Saliva/química , Trastornos del Sueño-Vigilia/genética , Adolescente , Adulto , Trastorno Autístico/microbiología , Trastorno Autístico/fisiopatología , Niño , Preescolar , Relojes Circadianos/genética , Femenino , Regulación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Interacciones Huésped-Patógeno/genética , Humanos , Masculino , MicroARNs/química , MicroARNs/aislamiento & purificación , Microbiota/genética , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , ARN Bacteriano/química , ARN Bacteriano/genética , ARN Bacteriano/aislamiento & purificación , Saliva/microbiología , Trastornos del Sueño-Vigilia/microbiología , Trastornos del Sueño-Vigilia/fisiopatología , Transcriptoma/genética , Adulto Joven
9.
Artículo en Inglés | MEDLINE | ID: mdl-28725215

RESUMEN

Obesity leads to a loss of muscle mass and impaired muscle regeneration. In obese individuals, pathologically elevated levels of prolyl hydroxylase domain enzyme 2 (PHD2) limit skeletal muscle hypoxia-inducible factor-1 alpha and vascular endothelial growth factor (VEGF) expression. Loss of local VEGF may further impair skeletal muscle regeneration. We hypothesized that PHD2 inhibition would restore vigorous muscle regeneration in a murine model of obesity. Adult (22-week-old) male mice were fed either a high-fat diet (HFD), with 60% of calories derived from fat, or a regular diet (RD), with 10% of calories derived from fat, for 16 weeks. On day 5 following cryoinjury to the tibialis anterior muscle, newly regenerated muscle fiber cross-sectional areas were significantly smaller in mice fed an HFD as compared to RD, indicating an impaired regenerative response. Cryoinjured gastrocnemius muscles of HFD mice also showed elevated PHD2 levels (twofold higher) and reduced VEGF levels (twofold lower) as compared to RD. Dimethyloxalylglycine, a cell permeable competitive inhibitor of PHD2, restored VEGF levels and significantly improved regenerating myofiber size in cryoinjured mice fed an HFD. We conclude that pathologically increased PHD2 in the obese state drives impairments in muscle regeneration, in part by blunting VEGF production. Inhibition of PHD2 over activity in the obese state normalizes VEGF levels and restores muscle regenerative potential.

10.
Front Cell Dev Biol ; 5: 35, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28443280

RESUMEN

The past few decades have welcomed tremendous advancements toward understanding the functional significance of altered metabolism during tumorigenesis. However, many conclusions drawn from studies of cancer cells in a dish (i.e., in vitro) have been put into question as multiple lines of evidence have demonstrated that the metabolism of cells can differ significantly from that of primary tumors (in vivo). This realization, along with the need to identify tissue-specific vulnerabilities of driver oncogenes, has led to an increased focus on oncogene-dependent metabolic programming in vivo. The oncogene c-MYC (MYC) is overexpressed in a wide variety of human cancers, and while its ability to alter cellular metabolism is well-established, translating the metabolic requirements, and vulnerabilities of MYC-driven cancers to the clinic has been hindered by disparate findings from in vitro and in vivo models. This review will provide an overview of the in vivo strategies, mechanisms, and conclusions generated thus far by studying MYC's regulation of metabolism in various cancer models.

11.
Proc Natl Acad Sci U S A ; 113(44): 12556-12561, 2016 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-27791115

RESUMEN

Human vision is surprisingly malleable. A static stimulus can seem to move after prolonged exposure to movement (the motion aftereffect), and exposure to tilted lines can make vertical lines seem oppositely tilted (the tilt aftereffect). The paradigm used to induce such distortions (adaptation) can provide powerful insights into the computations underlying human visual experience. Previously spatial form and stimulus dynamics were thought to be encoded independently, but here we show that adaptation to stimulus dynamics can sharpen form perception. We find that fast flicker adaptation (FFAd) shifts the tuning of face perception to higher spatial frequencies, enhances the acuity of spatial vision-allowing people to localize inputs with greater precision and to read finer scaled text, and it selectively reduces sensitivity to coarse-scale form signals. These findings are consistent with two interrelated influences: FFAd reduces the responsiveness of magnocellular neurons (which are important for encoding dynamics, but can have poor spatial resolution), and magnocellular responses contribute coarse spatial scale information when the visual system synthesizes form signals. Consequently, when magnocellular responses are mitigated via FFAd, human form perception is transiently sharpened because "blur" signals are mitigated.


Asunto(s)
Adaptación Fisiológica/fisiología , Percepción de Forma/fisiología , Percepción de Movimiento/fisiología , Visión Ocular/fisiología , Adulto , Femenino , Humanos , Masculino , Estimulación Luminosa , Agudeza Visual/fisiología , Percepción Visual/fisiología
12.
Plast Reconstr Surg Glob Open ; 4(8): e832, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27622100

RESUMEN

BACKGROUND: Nipple reconstruction is the last stage in cosmetic reconstruction of the breast after mastectomy, but no method produces reliable and consistent aesthetic results. This study examined the use of the Biodesign Nipple Reconstruction Cylinder (NRC) during reconstruction of the nipple after mastectomy. METHODS: Patients with a history of breast cancer and mastectomy desiring nipple reconstruction were invited to participate. After obtaining consent, unilateral or bilateral nipple reconstruction was performed. Skin flaps were raised, the NRC was placed beneath the flaps as a stent, and the site was protected for up to 4 weeks with a nipple shield. Nipple projection was measured for 12 months after surgery. Patient satisfaction was measured and adverse events were recorded. Follow-up examinations were performed at 1 week, and then at 1, 3, 6, and 12 months after surgery. RESULTS: Eighty-two nipple reconstructions were performed in 50 patients. Related postoperative adverse events were minor, but reported in 8 reconstructions (9.8%) representing 7 patients (14.0%). Average projection at 6 and 12 months was 4.1 ± 1.6 mm and 3.8 ± 1.5 mm, respectively, compared with 10.5 ± 2.2 mm 1 week after surgery. Of patients completing the satisfaction questionnaire at 12 months, 70/75 (93.3%) of reconstructions were rated "pleased" or "very pleased" with the overall outcome. Overall, 45/46 (97.8%) patients would recommend nipple reconstruction to other women. CONCLUSIONS: The Biodesign NRC offers a safe alternative to nipple reconstruction, resulting in stable projection and a high level of patient satisfaction for 12 months after placement.

14.
Cell ; 164(5): 884-95, 2016 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-26919427

RESUMEN

Ischemic preconditioning is the phenomenon whereby brief periods of sublethal ischemia protect against a subsequent, more prolonged, ischemic insult. In remote ischemic preconditioning (RIPC), ischemia to one organ protects others organs at a distance. We created mouse models to ask if inhibition of the alpha-ketoglutarate (αKG)-dependent dioxygenase Egln1, which senses oxygen and regulates the hypoxia-inducible factor (HIF) transcription factor, could suffice to mediate local and remote ischemic preconditioning. Using somatic gene deletion and a pharmacological inhibitor, we found that inhibiting Egln1 systemically or in skeletal muscles protects mice against myocardial ischemia-reperfusion (I/R) injury. Parabiosis experiments confirmed that RIPC in this latter model was mediated by a secreted factor. Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting.


Asunto(s)
Prolina Dioxigenasas del Factor Inducible por Hipoxia/antagonistas & inhibidores , Precondicionamiento Isquémico , Ácidos Cetoglutáricos/metabolismo , Animales , Isquemia/prevención & control , Ácido Quinurénico/metabolismo , Hígado/metabolismo , Ratones , Modelos Animales , Daño por Reperfusión Miocárdica/prevención & control , Parabiosis
15.
Brain Res ; 1615: 116-128, 2015 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-25957790

RESUMEN

STUDY OBJECTIVE: To examine the differential effects of acute and chronic sleep fragmentation (SF) on spatial learning and memory, and hippocampal long-term potentiation (LTP) in pubertal mice. METHODS: Two studies were performed during which adolescent C57/Bl6 mice were subjected to acute-SF 24h a day × 3 days or chronic-SF for 12h a day × 2 weeks using a programmable rotating lever that provides tactile stimulus with controls housed in similar cages. Spatial learning and memory was examined using the Morris water maze, and long-term potentiation (LTP) was evaluated after stimulation of Schaffer collaterals in CA1 hippocampus post SF. Actigraphy was used during the period of SF to monitor rest-activity patterns. Electroencephalographic (EEG) recordings were acquired for analysis of vigilance state patterns and delta-power. Serum corticosterone was measured to assess stress levels. RESULTS: Acute-SF via tactile stimulation negatively impacted spatial learning, as well as LTP maintenance, compared to controls with no tactile stimulation. While actigraphy showed significantly increased motor activity during SF in both groups, EEG data indicated that overall sleep efficiency did not differ between baseline and SF days, but significant increases in number of wakeful bouts and decreases in average NREM and REM bout lengths were seen during lights-on. Acute sleep fragmentation did not impact corticosterone levels. CONCLUSIONS: The current results indicate that, during development in pubertal mice, acute-SF for 24h a day × 3 days negatively impacted spatial learning and synaptic plasticity. Further studies are needed to determine if any inherent long-term homeostatic mechanisms in the adolescent brain afford greater resistance to the deleterious effects of chronic-SF.


Asunto(s)
Potenciación a Largo Plazo , Privación de Sueño/fisiopatología , Privación de Sueño/psicología , Aprendizaje Espacial/fisiología , Animales , Corteza Cerebral/fisiopatología , Corticosterona/sangre , Estimulación Eléctrica , Electroencefalografía , Electromiografía , Crecimiento , Hipocampo/fisiopatología , Masculino , Memoria/fisiología , Ratones , Ratones Endogámicos C57BL , Actividad Motora
16.
Crit Care ; 18(3): R98, 2014 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-24887537

RESUMEN

INTRODUCTION: Blunt chest wall trauma accounts for over 15% of all trauma admissions to Emergency Departments worldwide. Reported mortality rates vary between 4 and 60%. Management of this patient group is challenging as a result of the delayed on-set of complications. The aim of this study was to develop and validate a prognostic model that can be used to assist in the management of blunt chest wall trauma. METHODS: There were two distinct phases to the overall study; the development and the validation phases. In the first study phase, the prognostic model was developed through the retrospective analysis of all blunt chest wall trauma patients (n = 274) presenting to the Emergency Department of a regional trauma centre in Wales (2009 to 2011). Multivariable logistic regression was used to develop the model and identify the significant predictors for the development of complications. The model's accuracy and predictive capabilities were assessed. In the second study phase, external validation of the model was completed in a multi-centre prospective study (n = 237) in 2012. The model's accuracy and predictive capabilities were re-assessed for the validation sample. A risk score was developed for use in the clinical setting. RESULTS: Significant predictors of the development of complications were age, number of rib fractures, chronic lung disease, use of pre-injury anticoagulants and oxygen saturation levels. The final model demonstrated an excellent c-index of 0.96 (95% confidence intervals: 0.93 to 0.98). CONCLUSIONS: In our two phase study, we have developed and validated a prognostic model that can be used to assist in the management of blunt chest wall trauma patients. The final risk score provides the clinician with the probability of the development of complications for each individual patient.


Asunto(s)
Modelos Teóricos , Traumatismos Torácicos/diagnóstico , Heridas no Penetrantes/diagnóstico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Traumatismos Torácicos/terapia , Resultado del Tratamiento , Heridas no Penetrantes/terapia
17.
Int J Sports Physiol Perform ; 9(3): 503-10, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24434117

RESUMEN

PURPOSE: To determine the effects of acute short-term creatine (Cr) supplementation on physical performance during a 90-min soccer-specific performance test. METHODS: A double-blind, placebo-controlled experimental design was adopted during which 16 male amateur soccer players were required to consume 20 g/d Cr for 7 d or a placebo. A Ball-Sport Endurance and Speed Test (BEAST) comprising measures of aerobic (circuit time), speed (12- and 20-m sprint), and explosive-power (vertical jump) abilities performed over 90 min was performed presupplementation and postsupplementation. RESULTS: Performance measures during the BEAST deteriorated during the second half relative to the first for both Cr (1.2-2.3%) and placebo (1.0-2.2%) groups, indicating a fatigue effect associated with the BEAST. However, no significant differences existed between groups, suggesting that Cr had no performance-enhancing effect or ability to offset fatigue. When effect sizes were considered, some measures (12-m sprint, -0.53 ± 0.69; 20-m sprint, -0.39 ± 0.59) showed a negative tendency, indicating chances of harm were greater than chances of benefit. CONCLUSIONS: Acute short-term Cr supplementation has no beneficial effect on physical measures obtained during a 90-min soccer-simulation test, thus bringing into question its potential as an effective ergogenic aid for soccer players.


Asunto(s)
Creatina/administración & dosificación , Suplementos Dietéticos , Sustancias para Mejorar el Rendimiento/administración & dosificación , Resistencia Física/efectos de los fármacos , Carrera , Fútbol , Aceleración , Adulto , Creatina/efectos adversos , Método Doble Ciego , Prueba de Esfuerzo , Humanos , Masculino , Fatiga Muscular/efectos de los fármacos , Sustancias para Mejorar el Rendimiento/efectos adversos , Análisis y Desempeño de Tareas , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
19.
J Hazard Mater ; 244-245: 570-81, 2013 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-23177273

RESUMEN

On January 2, 2010 the Nyamuragira volcano erupted lava fountains extending up to 300 m vertically along an ~1.5 km segment of its southern flank cascading ash and gas on nearby villages and cities along the western side of the rift valley. Because rain water is the only available potable water resource within this region, volcanic impacts on drinking water constitutes a major potential hazard to public health within the region. During the 2010 eruption, concerns were expressed by local inhabitants about water quality and feelings of physical discomfort (e.g. nausea, bloating, indigestion, etc.) after consuming rain water collected after the eruption began. We present the elemental and ionic chemistry of drinking water samples collected within the region on the third day of the eruption (January 5, 2010). We identify a significant impact on water quality associated with the eruption including lower pH (i.e. acidification) and increases in acidic halogens (e.g. F(-) and Cl(-)), major ions (e.g. SO(4)(2-), NH(4)(+), Na(+), Ca(2+)), potentially toxic metals (e.g. Al(3+), Mn(2+), Cd(2+), Pb(2+), Hf(4+)), and particulate load. In many cases, the water's composition significantly exceeds World Health Organization (WHO) drinking water standards. The degree of pollution depends upon: (1) ash plume direction and (2) ash plume density. The potential negative health impacts are a function of the water's pH, which regulates the elements and their chemical form that are released into drinking water.


Asunto(s)
Agua Potable/análisis , Lluvia/química , Erupciones Volcánicas , Contaminantes Químicos del Agua/análisis , Arsénico/análisis , República Democrática del Congo , Conductividad Eléctrica , Monitoreo del Ambiente , Concentración de Iones de Hidrógeno , Metales/análisis , Calidad del Agua
20.
Artículo en Inglés | MEDLINE | ID: mdl-26464877

RESUMEN

The goal of this investigation was to determine if playing or training on third-generation artificial turf (AT) surfaces increases the incidence rate of injuries compared to natural grass (NG) surfaces. This was accomplished by a meta-analysis performed on previously published research. Eight studies met the criteria of competitive soccer players, participation on both surfaces, and presentation of both exposure time and injury occurrence. Exposure time and injury incidence values were used to generate injury rate ratios (IRRs, AT/NG) for all injuries as well as specific injuries. Subgroup analyses were also performed by condition (match or training), gender, and age (youth or adult). The overall IRR was 0.86 (P < 0.05) suggesting a lower injury risk on AT than NG. However, there was considerable heterogeneity between studies. Analyses of individual injuries and subgroups found that in many cases IRR values were significantly less than 1.0. In no case was the IRR significantly greater than 1.0. Based on this, it appears that the risk of sustaining an injury on AT under some conditions might be lowered compared to NG. However, until more is known about how issues such as altered playing styles affect injury incidence, it is difficult to make firm conclusions regarding the influence of AT on player safety.

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