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Objective: To compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in anesthetized pigs and to describe a new mode of ventilation for anesthetized veterinary species. Study design: Randomized, crossover design without washout. Animals: Twelve healthy, female white Landrace pigs. Methods: Following ketamine-midazolam premedication and anesthetic induction with propofol, the trachea was intubated, and each pig was positioned in dorsal recumbency. Anesthesia was maintained with propofol and sufentanil infusions. Pigs were instrumented and their lungs were sequentially ventilated with each mode, in random order, for 1 h according to predefined criteria [fraction of inspired oxygen (FiO2) = 0.21, 10 mL kg-1 tidal volume (VT), and arterial carbon dioxide tension (PaCO2) within 40-45 mmHg]. Cardiopulmonary data were collected at baseline, 30 and 60 min. In 8 pigs, thoracic computed tomography (CT) was performed following the 60 min time point for each mode of ventilation and images were analyzed to quantify lung aeration. The effects of ventilation mode, time, and order were analyzed using repeated measures ANOVA. Paired t-tests were used to compare lung aeration between modes. Significance was defined as p < 0.05. Results: Data from 12 pigs were analyzed. A significant effect of mode was found for heart rate, mean arterial pressure (MAP), pulmonary artery occlusion pressure, cardiac index (CI), stroke volume index, systemic vascular resistance, pulmonary vascular resistance, oxygen delivery index (DO2I), oxygen extraction ratio (O2ER), VT, arterial oxygen tension, arterial hemoglobin saturation, PaCO2, end-tidal carbon dioxide tension, alveolar dead space (VDalv/VTalv), venous admixture ( Q . s / Q . t ), mean airway pressure, and dynamic compliance index (CRSI). Order effects were also observed for some cardiovascular and respiratory variables. For the eight pigs that underwent thoracic CT, AAV resulted in significantly larger proportions of normally and hyperaerated lung while CMV resulted in larger proportions of hypoaerated and atelectatic lung. Conclusions: In dorsally recumbent anesthetized pigs, ventilated with FiO2 = 0.21, both modes of ventilation supported adequate oxygenation while AAV resulted in higher CRSI, and lower VDalv/VTalv and Q . s / Q . t , compared with CMV. AAV was also associated with lower MAP, CI, and DO2I and higher O2ER compared with CMV. Further investigation of AAV in anesthetized animals is warranted.
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Introduction: Use of mechanical ventilation during general anesthesia is a necessary practice in the anesthetization of small cetaceans as spontaneous ventilation fails to provide adequate gas exchange. Currently available methods of ventilation do not account for the intermittent breathing strategy of representative species within this infraorder of fully aquatic mammals and may have a significant effect on cardiac and respiratory physiology. Methods: To understand the impact of mechanical ventilation on cardiopulmonary function in one small species of cetacean, the bottlenose dolphin (Tursiops truncatus), we compared controlled mechanical ventilation (CMV) to a novel ventilation method known as apneustic anesthesia ventilation (AAV). AAV simulates the normal inspiratory breath-hold pattern of dolphins. Ten anesthetic procedures (dental procedure, n = 9; bronchoscopy, n = 2) were performed on nine dolphins (age range: 10-42 years; mean = 32 years; median = 37 years; female = 3, 40%; male = 6, 60%). In a cross-over study design, dolphins were instrumented and randomly assigned to AAV or CMV as the initial mode of ventilation, then switched to the alternate mode. Baseline cardiopulmonary data were collected and again after 30 min on each mode of ventilation. Cardiac index, stroke volume index, systemic vascular resistance, alveolar dead space, alveolar-arterial oxygen tension gradient, arterial oxygen content, oxygen delivery index, and dynamic respiratory system compliance index were calculated at each of the four time points. Results: During AAV, dolphins had higher arterial oxygen tension, higher mean airway pressure, reduced alveolar dead space ventilation and lower alveolar-arterial oxygen difference. Cardiovascular performance was not statistically different between the two modes. Discussion: Our study suggests AAV, which more closely resembles the conscious intermittent respiratory pattern phenotype of dolphins, improves ventilation and pulmonary function in the anesthetized dolphin. Future studies should evaluate the cardiopulmonary effects of neutral buoyancy and cardiopulmonary sparing drug protocols to reduce the need for hemodynamic support of current protocols.
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Feline oral squamous cell carcinoma (FOSCC) is an aggressive cancer in domestic cats that has no effective treatment option when advanced. Preventative or early diagnostic measures are thus crucial. FOSCC is also a model for human head and neck SCC (HNSCC); strong risk factors in HNSCC include exposure to alcohol, tobacco, areca nut, and high-risk human papillomavirus. Previous studies have identified flea collar and tobacco smoke exposure, feeding canned tuna, canned cat food and cat foods with chemical additives, living in a rural environment, and having outdoor access as risk factors for FOSCC but there was no overlap in the risk factors between studies. In our study, risks for FOSCC were evaluated in an online epidemiologic survey study in 67 cats with FOSCC and 129 control cats. Clumping clay cat litter and flea collar use were significant risk factors for FOSCC on multiple logistic regression with odds ratios of 1.66 (95% CI 1.20-2.30) and 4.48 (95% CI 1.46-13.75) respectively. Crystalline silica is a carcinogen that may be present in all clay cat litters and tetrachlorvinphos is a carcinogen that is present in the most commonly used flea collars in our study. We recommend further investigation into the association between FOSCC and clay-based litter and/or flea collars containing tetrachlorvinphos.
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Carcinoma de Células Escamosas , Enfermedades de los Gatos , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Gatos , Animales , Carcinoma de Células Escamosas de Cabeza y Cuello/veterinaria , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/veterinaria , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/etiología , Neoplasias de la Boca/veterinaria , Tetraclorvinfos , Arcilla , Factores de Riesgo , Estudios Epidemiológicos , Neoplasias de Cabeza y Cuello/veterinaria , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/etiologíaRESUMEN
OBJECTIVE: To compare PaO2 and PaCO2 in horses recovering from general anesthesia maintained with either apneustic anesthesia ventilation (AAV) or conventional mechanical ventilation (CMV). STUDY DESIGN: Randomized, crossover design. ANIMALS: A total of 10 healthy adult horses from a university-owned herd. METHODS: Dorsally recumbent horses were anesthetized with isoflurane in oxygen [inspired oxygen fraction = 0.3 initially, with subsequent titration to maintain PaO2 ≥ 85 mmHg (11.3 kPa)] and ventilated with AAV or CMV according to predefined criteria [10 mL kg-1 tidal volume, PaCO2 40-45 mmHg (5.3-6.0 kPa) during CMV and < 60 mmHg (8.0 kPa) during AAV]. Horses were weaned from ventilation using a predefined protocol and transferred to a stall for unassisted recovery. Arterial blood samples were collected and analyzed at predefined time points. Tracheal oxygen insufflation at 15 L minute-1 was provided if PaO2 < 60 mmHg (8.0 kPa) on any analysis. Time to oxygen insufflation, first movement, sternal recumbency and standing were recorded. Data were analyzed using repeated measures anova, paired t tests and Fisher's exact test with significance defined as p < 0.05. RESULTS: Data from 10 horses were analyzed. Between modes, PaO2 was significantly higher immediately after weaning from ventilation and lower at sternal recumbency for AAV than for CMV. No PaCO2 differences were noted between ventilation modes. All horses ventilated with CMV required supplemental oxygen, whereas three horses ventilated with AAV did not. Time to first movement was shorter with AAV. Time to oxygen insufflation was not different between ventilation modes. CONCLUSIONS: Although horses ventilated with AAV entered the recovery period with higher PaO2, this advantage was not sustained during recovery. Whereas fewer horses required supplemental oxygen after AAV, the use of AAV does not preclude the need for routine supplemental oxygen administration in horses recovering from general anesthesia.
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Infecciones por Citomegalovirus , Enfermedades de los Caballos , Caballos , Animales , Respiración Artificial/veterinaria , Respiración Artificial/métodos , Estudios Prospectivos , Anestesia General/veterinaria , Oxígeno , Infecciones por Citomegalovirus/veterinariaRESUMEN
OBJECTIVE: To compare the efficacy of 4 cleaning protocols applied to endotracheal tubes (ETTs) collected from anesthetized dogs. SAMPLE: 100 ETTs (25 per protocol). PROCEDURES: A 10-question survey designed to determine ETT reuse and cleaning practices was distributed via email to a sample of veterinary anesthesiologists. Informed by survey results, 4 ETT cleaning protocols were selected for use in a prospective clinical study. Dogs were intubated with sterile polyvinyl chloride ETTs. At extubation, each ETT was cultured for bacterial growth, randomly assigned to 1 of 4 protocols [water scrub (P1), detergent scrub (P2), detergent scrub and chlorhexidine gluconate (CHG) soak (P3), or detergent scrub and bleach soak (P4)], and cultured again after drying. Bacterial genera were identified using mass spectrometry and 16s rRNA sequencing. Proportions of ETTs exhibiting no post-cleaning growth were compared between protocols using the Fisher exact test with Bonferroni correction. RESULTS: Half of survey respondents that reused ETTs did not sterilize them before reuse, cleaning methods varied widely, and no reported methods were evidence-based. After use, the number of ETTs exhibiting no post-cleaning bacterial growth were 15/25 (60%), 14/25 (56%), 20/25 (80%), and 17/25 (68%) for protocols P1, P2, P3, and P4, respectively. Pairwise comparisons did not reveal any statistically significant differences between protocols. CLINICAL RELEVANCE: In small animal patients, some veterinary anesthesiologists reuse ETTs without sterilization and cleaning protocols vary widely. No differences between the studied protocols were identified. Further research is necessary to identify a safe, efficacious ETT cleaning protocol for use in small animal practice.
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Detergentes , Intubación Intratraqueal , Animales , Perros , Intubación Intratraqueal/veterinaria , Estudios Prospectivos , ARN Ribosómico 16SRESUMEN
OBJECTIVE: To compare the cardiopulmonary effects of apneustic anesthesia ventilation (AAV) and conventional mechanical ventilation (CMV) in dorsally recumbent anesthetized horses. STUDY DESIGN: Randomized, crossover design. ANIMALS: A total of 10 healthy adult horses from a university-owned herd. METHODS: Following xylazine, midazolam and ketamine administration, horses were orotracheally intubated and positioned in dorsal recumbency. Anesthesia was maintained with isoflurane in oxygen [inspired oxygen fraction (FiO2) = 0.3 initially, with subsequent titration to maintain PaO2 ≥ 85 mmHg (11.3 kPa)]. Horses were instrumented and ventilated with AAV or CMV for 1 hour according to predefined criteria [10 mL kg-1 tidal volume (VT), PaCO2 of 40-45 mmHg (5.3-6.0 kPa) during CMV and <60 mmHg (8.0 kPa) during AAV]. Dobutamine was administered to maintain mean arterial pressure (MAP) >65 mmHg. Cardiopulmonary data were collected at baseline, 30 and 60 minutes. The effects of ventilation mode and time were analyzed using repeated-measures anova with significance defined as p < 0.05. RESULTS: Data from nine horses were analyzed. A significant effect of mode at one or more time points was found for respiratory rate, arterial and end-tidal CO2 tensions, arterial pH, mean airway pressure (Paw), respiratory system dynamic compliance index (CrsI), venous admixture (QËs/QËt), mean pulmonary artery pressure and systemic vascular resistance. No significant differences between modes were found for VT, FiO2, PaO2, arterial hemoglobin saturation, alveolar dead space, heart rate, MAP, cardiac index, stroke volume index, oxygen delivery index, oxygen extraction ratio and dobutamine administration. CONCLUSIONS AND CLINICAL RELEVANCE: In dorsally recumbent anesthetized horses, both ventilation modes supported adequate oxygenation with minimal supplemental oxygen. Compared with CMV, AAV resulted in higher CrsI and lower QËs/QËt. Despite higher mean Paw with AAV, the cardiovascular effects of each mode were not different. Further trials of AAV in anesthetized horses are warranted.
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Anestesia , Infecciones por Citomegalovirus , Enfermedades de los Caballos , Anestesia/veterinaria , Animales , Infecciones por Citomegalovirus/veterinaria , Dobutamina , Caballos/cirugía , Humanos , Oxígeno , Respiración Artificial/métodos , Respiración Artificial/veterinariaRESUMEN
CT (computerized tomography) is a necessary imaging modality for cancer staging and disease monitoring. Rodent models of cancer are commonly studied prior to human clinical trials, but CT in rodents can be difficult due to their small size and constant movement, which necessitates general anesthesia. Because microCT equipment is not always available, clinical CT may be a viable alternative. Limitations of microCT and clinical CT include biosecurity, anesthesia to limit image distortion due to motion, and cost. To address several of these constraints, we created a 3D-printed apparatus that accommodated simultaneous imaging of as many as 9 rats under gas anesthesia. Rats were anesthetized in series and placed in a 3 × 3 arrangement. To assess differences in attenuation between individual chambers and rows or columns in the device, we first imaged a standardized phantom plug as a control. We hypothesized that attenuation of specific rat organs would not be affected regardless of the location or position in the 3D-printed device. Four organs-liver, kidney, femur, and brain-were evaluated in 9 rats. For both the phantom and kidneys, statistically significant, but clinically negligible, effects on attenuation were noted between rows but not between columns. We attribute this finding to the absence of a top layer of the apparatus, which thus created asymmetric attenuation and beam hardening through the device. This apparatus allowed us to successfully image 9 rats simultaneously in a clinical CT machine, with negligible effects on attenuation. Planned improvements in this apparatus include completely enclosed versions for biosecure imaging.
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Impresión Tridimensional , Animales , Fantasmas de Imagen , Ratas , Microtomografía por Rayos XRESUMEN
OBJECTIVE: Dysphagia is common following facial nerve injury; however, research is sparse regarding swallowing-related outcomes and targeted treatments. Previous animal studies have used eye blink and vibrissae movement as measures of facial nerve impairment and recovery. The purpose of this study was to create a mouse model of facial nerve injury that results in dysphagia to enhance translational research outcomes. STUDY DESIGN: Prospective animal study. METHODS: Twenty C57BL/6J mice underwent surgical transection of the main trunk (MT) (n = 10) or marginal mandibular branch (MMB) (n = 10) of the left facial nerve. Videofluoroscopic swallow study (VFSS) assays for drinking and eating were performed at baseline and 14 days postsurgery to quantify several deglutition-related outcome measures. RESULTS: VFSS analysis revealed that MT transection resulted in significantly slower lick and swallow rates during drinking (P ≤ .05) and significantly slower swallow rates and longer inter-swallow intervals during eating (P ≤ .05), congruent with oral and pharyngeal dysphagia. After MMB transection, these same VFSS metrics were not statistically significant (P > .05). CONCLUSION: The main finding of this study was that transection of the facial nerve MT leads to oral and pharyngeal stage dysphagia in mice; MMB transection does not. These results from mice provide novel insight into specific VFSS metrics that may be used to characterize dysphagia in humans following facial nerve injury. We are currently using this surgical mouse model to explore promising treatment modalities such as electrical stimulation to hasten recovery and improve outcomes following various iatrogenic and idiopathic conditions affecting the facial nerve. LEVEL OF EVIDENCE: NA Laryngoscope, 131:17-24, 2021.
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Trastornos de Deglución/etiología , Traumatismos del Nervio Facial/complicaciones , Animales , Modelos Animales de Enfermedad , Fluoroscopía , Ratones , Ratones Endogámicos C57BL , Estudios Prospectivos , Grabación en VideoRESUMEN
OBJECTIVE: To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. ANIMALS: I0 healthy purpose-bred sexually intact female hounds. PROCEDURES: Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. RESULTS: 7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/veterinaria , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Lomustina , Alanina Transaminasa , Fosfatasa Alcalina , Animales , Perros , Femenino , Hígado , Lomustina/efectos adversosRESUMEN
OBJECTIVE: To compare results for initial body-mounted inertial sensor (BMIS) measurement of lameness in equids trotting in a straight line with definitive findings after full lameness evaluation. ANIMALS: 1,224 equids. PROCEDURES: Lameness measured with BMIS equipment while trotting in a straight line was classified into categories of none, forelimb only, hind limb only, and 8 patterns of combined forelimb and hind limb lameness (CFHL). Definitive findings after full lameness evaluation were established in most horses and classified into types (no lameness, forelimb- or hind limb-only lameness, CFHL, or lameness not localized to the limbs). Observed proportions of lameness type in equids with definitive findings for each initial BMIS-assessed category were compared with hypothetical expected proportions through χ2 goodness-of-fit analysis. RESULTS: The most common initial BMIS-assessed lameness category was CFHL (693/1,224 [56.6%]), but this was the least common definitive finding (94/ 862 [10.9%]). The observed frequency of no lameness after full lameness evaluation was greater than expected only when initial BMIS measurements indicated no lameness. The observed frequency of forelimb-only lameness was greater than expected when initially measured as forelimb-only lameness and for CFHL categories consistent with the diagonal movement principle of compensatory lameness. Observed frequency of hind limb-only lameness was greater than expected when initially measured as hind limb-only lameness and for CFHL categories consistent with the sagittal movement principle of compensatory lameness. Equids initially assessed as having no lameness had the highest (103/112 [92%]) and those assessed as CFHL pattern 7 (forelimb with contralateral hind limb impact-only lameness) had the lowest (36/66 [55%]) rates of definitive findings. CONCLUSIONS AND CLINICAL RELEVANCE: In equids, results of initial straight-line trotting evaluations with a BMIS system did not necessarily match definitive findings but may be useful in planning the remaining lameness evaluation.
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Enfermedades de los Caballos , Cojera Animal , Animales , Fenómenos Biomecánicos , Miembro Anterior , Marcha , Miembro Posterior , CaballosRESUMEN
This study has investigated the immediate effect of induced hindlimb length difference on hindlimb lameness measured as differences in minimum (Pmin) and maximum (Pmax) pelvic heights in 16 horses trotting in a straight line and lungeing on both hard and soft surfaces with body-mounted inertial sensors. Hindlimb length differences were induced by applying an Easyboot Glue-on shoe to one hindlimb. Changes in Pmin and Pmax with induced hindlimb length difference were assessed with a two-way repeated-measures ANOVA with trial (straight, lunge with inside limb elevation, lunge with outside limb elevation) and surface (hard, soft) as within-subject factors. Change in Pmin, indicating an impact-type lameness, in the hind limb with the elevation, was significant in both the straight line and while lunging on both hard and soft surfaces. Change in Pmax, indicating pushoff-type lameness, in the opposite, non-elevated hind limb, was significant when trotting in a straight line but not while lunging.
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Miembro Posterior/patología , Enfermedades de los Caballos/diagnóstico , Cojera Animal/diagnóstico , Animales , Fenómenos Biomecánicos , Femenino , Marcha/fisiología , Análisis de la Marcha/métodos , Análisis de la Marcha/veterinaria , Miembro Posterior/fisiopatología , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/fisiopatología , Caballos , Cojera Animal/patología , Cojera Animal/fisiopatología , Masculino , Movimiento/fisiología , Pelvis/fisiopatologíaRESUMEN
The intricate sensorimotor neural circuits that control swallowing are heavily reliant on serotonin (5-hydroxytryptamine [5-HT]); however, the impact of 5-HT deficiency on swallow function remains largely unexplored. We investigated this using mice deficient in tryptophan-hydroxylase-2 (TPH2), the enzyme catalyzing the rate-limiting step in 5-HT synthesis. Videofluoroscopy was utilized to characterize the swallowing function of TPH2 knockout (TPH2-/-) mice as compared with littermate controls (TPH2+/+). Results showed that 5-HT deficiency altered all 3 stages of swallowing. As compared with controls, TPH2-/- mice had significantly slower lick and swallow rates and faster esophageal transit times. Future studies with this model are necessary to determine if 5-HT replacement may rescue abnormal swallowing function. If so, supplemental 5-HT therapy may have vast applications for a large population of patients with a variety of neurologic disorders resulting in life-diminishing dysphagia, particularly amyotrophic lateral sclerosis and Parkinson's disease, for which 5-HT deficiency is implicated in the disease pathogenesis.
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Trastornos de Deglución/etiología , Serotonina/deficiencia , Animales , Química Encefálica , Femenino , Masculino , Ratones , Serotonina/aislamiento & purificaciónRESUMEN
BACKGROUND: The objective of this study was to determine survival outcomes in patients who underwent retreatment of recurrent cases of cutaneous melanoma of the head and neck (CMHN). METHODS: Retrospective review of all patients who were treated for primary clinical stage I or II CMHN between January 1, 2000 and December 31, 2015. RESULTS: Twenty percent (33/168) of the patients developed a recurrence. Sixty-six percent (4/6) of patients who developed local recurrence first and 50% (3/6) of patients who developed regional recurrence first were alive without evidence (NED) of disease at last follow-up, while 0% (0/21) of patients who developed distant or simultaneous recurrences first were NED at last follow-up. Among the 7 patients who were NED, the mean time from recurrence to last follow-up was 735 days. CONCLUSIONS: Of patients with isolated local or regional recurrences, 58% (7/12) obtained durable curative treatment for recurrent melanoma.
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Neoplasias de Cabeza y Cuello/patología , Melanoma/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Adulto , Anciano , Análisis de Varianza , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/mortalidad , Melanoma/terapia , Persona de Mediana Edad , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Retratamiento , Estudios Retrospectivos , Medición de Riesgo , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Análisis de Supervivencia , Resultado del Tratamiento , Estados Unidos , Melanoma Cutáneo MalignoRESUMEN
Derivation and stable maintenance of porcine induced pluripotent stem cells (piPSCs) is challenging. We herein systematically analyzed two piPSC lines, derived by lentiviral transduction and cultured under either leukemia inhibitory factor (LIF) or fibroblast growth factor (FGF) conditions, to shed more light on the underlying biological mechanisms of porcine pluripotency. LIF-derived piPSCs were more successful than their FGF-derived counterparts in the generation of in vitro chimeras and in teratoma formation. When LIF piPSCs chimeras were transferred into surrogate sows and allowed to develop, only their prescence within the embryonic membranes could be detected. Whole-transcriptome analysis of the piPSCs and porcine neonatal fibroblasts showed that they clustered together, but apart from the two pluripotent cell populations of early porcine embryos, indicating incomplete reprogramming. Indeed, bioinformatic analysis of the pluripotency-related gene network of the LIF- versus FGF-derived piPSCs revealed that ZFP42 (REX1) expression was absent in both piPSC-like cells, whereas it was expressed in the porcine inner cell mass at Day 7/8. A second striking difference was the expression of ATOH1 in piPSC-like cells, which was absent in the inner cell mass. Moreover, our gene expression analyses plus correlation analyses of known pluripotency genes identified unique relationships between pluripotency genes in the inner cell mass, which are to some extent, in the piPSC-like cells. This deficiency in downstream gene activation and divergent gene expression may be underlie the inability to derive germ line-transmitting piPSCs, and provides unique insight into which genes are necessary to achieve fully reprogrammed piPSCs. 84: 229-245, 2017. © 2016 Wiley Periodicals, Inc.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Crecimiento de Fibroblastos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Factor Inhibidor de Leucemia/farmacología , Animales , Células Madre Pluripotentes Inducidas/citología , PorcinosRESUMEN
This study sought to evaluate the impact of street crossing infrastructure modifications on park use and park-based physical activity in a low-income and African American community. A five-lane major highway created an access barrier between low-income housing units and the local neighborhood park in Columbia, Missouri. The installation of a signalized pedestrian crosswalk provided an opportunity to conduct a natural experiment to examine the effect of improved safe access upon community active living behaviors. Direct observation using SOPARC was collected prior to the crosswalk instillation in June 2012, after the crosswalk installation in June 2013 and again as a follow up in June 2014 during the same two-week period to assess changes in total park use and total energy expenditure by age, gender and race/ethnicity. Analysis of covariance models, controlling for temperature examined changes in total counts and total energy expenditure using pairwise Sidak post-hoc comparisons. Total park use increased from 2012 (n=2080) to 2013 (n=2275) and remained constant in 2014 (n=2276). However, despite increases in safe access and overall park use, there was a significant decrease in total energy expenditure following the installation of the crosswalk that was sustained in 2014. This study shows that increasing safe access to parks primarily positively influences park use but not park-based physical activity. While improved safe access is encouraging greater park use, there is a need for future research to examine additional factors such as social support, programming and environmental changes to engage community members in park-based physical activity.
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Etnicidad/estadística & datos numéricos , Ejercicio Físico/fisiología , Parques Recreativos , Recreación , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Planificación Ambiental , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Missouri , Pobreza , Características de la Residencia , Seguridad , Factores SexualesRESUMEN
Infrastructure improvements such as pedestrian crosswalks that calm traffic and increase access to physical activity opportunities could alleviate important barriers to active living in underserved communities with outdated built environments. The purpose of this study was to explore how the built environment influences street-crossing behaviors and traffic speeds in a low-income neighborhood with barriers to active living in Columbia, Missouri. In 2013, a signalized pedestrian crosswalk and 400-ft-long median was constructed along a busy 5-lane, high-speed arterial highway linking low-income housing with a park and downtown areas. Data collection occurred prior to June 2012, and after June 2013, completion of the project at the intervention site and control site. Direct observation of street-crossing behaviors was performed at designated intersections/crosswalks or non-designated crossing points. Traffic volume and speed were captured using embedded magnetic traffic detectors. At the intervention site, designated crossings increased at the new crosswalk (p < 0.001), but not at non-designated crossings (p = 0.52) or designated crossings at intersections (p = 0.41). At the control site, there was no change in designated crossings (p = 0.94) or non-designated crossings (p = 0.79). Motor vehicles traveling above the speed limit of 35 mph decreased from 62,056 (46 %) to 46,256 (35 %) (p < 0.001) at the intervention site and increased from 57,891 (49 %) to 65,725 (59 %) (p < 0.001) at the control site. The installation of a signalized crosswalk facilitated an increase in safe street crossings and calmed traffic volume and speed in an underserved neighborhood. We believe these findings have significant public health implications that could be critical to advocacy efforts to improve infrastructure projects in similar communities.
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Conducción de Automóvil/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Seguridad/estadística & datos numéricos , Poblaciones Vulnerables/estadística & datos numéricos , Adolescente , Adulto , Anciano , Conducción de Automóvil/psicología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Missouri , Poblaciones Vulnerables/psicologíaRESUMEN
OBJECTIVES: Evaluation of the laryngeal adductor reflex (LAR) entails delivering air through an endoscope positioned 1 to 2 mm from the arytenoid mucosa to elicit bilateral vocal fold (VF) closure. This short working distance limits visualization to only the ipsilateral arytenoid and results in quantification of a single LAR metric: threshold pressure that evokes the LAR. Our goal was to evolve the LAR procedure to optimize its utility in clinical practice and translational research. STUDY DESIGN: Prospective translational experiment. SETTING: Academic institution. SUBJECTS: Young healthy human adults (n = 13) and 3 groups of mice: healthy, primary aging mice (n = 5), a transgenic mouse model of amyotrophic lateral sclerosis (ALS; n = 4), and young healthy controls (n = 10). METHODS: The VFs were visualized bilaterally during supramaximal air stimulation through an endoscope. Responses were analyzed to quantify 4 novel metrics: VF adduction phase duration, complete glottic closure duration, VF abduction phase duration, and total LAR duration. RESULTS: The 4 LAR metrics are remarkably similar between healthy young humans and mice. Compared to control mice, aging mice have shorter glottic closure durations, whereas ALS-affected mice have shorter VF abduction phase durations. CONCLUSIONS: We have established a new LAR protocol that permits quantification of novel LAR metrics that are translatable between mice and humans. Using this protocol, we showed that VF adduction is impaired in primary aging mice, whereas VF abduction is impaired in ALS-affected mice. These preliminary findings highlight the enhanced diagnostic potential of LAR testing.
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Esclerosis Amiotrófica Lateral/fisiopatología , Músculos Laríngeos/fisiopatología , Reflejo/fisiología , Pliegues Vocales/fisiopatología , Adulto , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Laringoscopía , Masculino , Ratones , Ratones Transgénicos , Estimulación Física , Tiempo de Reacción/fisiología , Valores de Referencia , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Presbyphagia affects approximately 40% of otherwise healthy people over 60 years of age. Hence, it is a condition of primary aging rather than a consequence of primary disease. This distinction warrants systematic investigations to understand the causal mechanisms of aging versus disease specifically on the structure and function of the swallowing mechanism. Toward this goal, we have been studying healthy aging C57BL/6 mice (also called B6), the most popular laboratory rodent for biomedical research. The goal of this study was to validate this strain as a model of presbyphagia for translational research purposes. We tested two age groups of B6 mice: young (4-7 months; n = 16) and old (18-21 months; n = 11). Mice underwent a freely behaving videofluoroscopic swallow study (VFSS) protocol developed in our lab. VFSS videos (recorded at 30 frames per second) were analyzed frame-by-frame to quantify 15 swallow metrics. Six of the 15 swallow metrics were significantly different between young and old mice. Compared to young mice, old mice had significantly longer pharyngeal and esophageal transit times (p = 0.038 and p = 0.022, respectively), swallowed larger boluses (p = 0.032), and had a significantly higher percentage of ineffective primary esophageal swallows (p = 0.0405). In addition, lick rate was significantly slower for old mice, measured using tongue cycle rate (p = 0.0034) and jaw cycle rate (p = 0.0020). This study provides novel evidence that otherwise healthy aging B6 mice indeed develop age-related changes in swallow function resembling presbyphagia in humans. Specifically, aging B6 mice have a generally slow swallow that spans all stages of swallowing: oral, pharyngeal, and esophageal. The next step is to build upon this foundational work by exploring the responsible mechanisms of presbyphagia in B6 mice.
Asunto(s)
Trastornos de Deglución/fisiopatología , Fluoroscopía/métodos , Envejecimiento , Animales , Deglución , Modelos Animales de Enfermedad , Femenino , Fluoroscopía/instrumentación , Masculino , Ratones Endogámicos C57BL , Grabación en VideoRESUMEN
BACKGROUND: Health care-associated infections are serious complications impacting 2 million patients and accounting for approximately 100,000 deaths per year. In the present study, we evaluated the effectiveness of a new hand hygiene monitoring program (HHMP) and measured the sustainability of this effectiveness over a 1-year period. METHODS: The HHMP consisted of 4 key components: extensive education, conspicuous and visible monitors, immediate feedback concerning compliance to health care workers, and real-time data dissemination to leadership. The HHMP was implemented in 2 hospital care units. Two different, but similar, departments served as controls, and hand hygiene compliance was monitored via the "secret shopper" technique. All 4 departments were followed for 12 months. RESULTS: Both experimental departments showed statistically significant increases in hand hygiene compliance. Experimental department 1 increased compliance from 49% to an average of 90%, and experimental department 2 increased compliance from 60% to an average of 96%. Both experimental departments were able to sustain these results for at least 6 months. Compliance rates were significantly higher in the experimental departments compared with the control departments. No significant changes were seen in the control departments. CONCLUSIONS: These finding suggest that continuous monitoring by salient observers and immediate feedback are critical to the success of hand hygiene programs.
Asunto(s)
Monitoreo Epidemiológico , Retroalimentación , Adhesión a Directriz , Desinfección de las Manos/métodos , Higiene de las Manos , Control de Infecciones/métodos , Hospitales , HumanosRESUMEN
Because many cases of non-traumatic intracerebral hemorrhage (NTICH) do not require surgery, establishing the most appropriate referral and treatment algorithms to optimize patient outcome, including appropriate utilization of specialty physicians, such as neurosurgeons and neurologists, would be helpful. In this retrospective study based on census and billing records, the best referral model showed that medical therapy was the chosen treatment option if patients did not meet all of the following three criteria: GCS < or = 13, age < or = 70 and lesion volume > or = 40 cm3. These criteria may be helpful in predicting the need for surgery and improving referral practices for patients with NTICH.