RESUMEN
There is a scarcity of nutritional screening tools for use in infants (<1 year). The infant Nutrition Early Warning Score (iNEWS) has been developed to identify infants who need further dietetic review. We introduced the iNEWS into clinical practice and evaluated its performance in Scotland, Belgium, Athens and Bulgaria. Of the 352 infants screened, 72 (20%) were placed in the high iNEWS category, and of these, 70 (97%) were reviewed by a hospital dietitian. iNEWS produced a true positive rate of 80% which increased to 96% after accounting for anticipated misclassified cases due to prematurity. In Belgium, false positive screens had a shorter length of stay (p = 0.014). Otherwise, misclassification was not related to a specific iNEWS component. This study corroborates previous research, underscoring the validity of iNEWS as a dietetic referral tool and demonstrating that it can be integrated into "real-world" clinical practice across international settings with diverse healthcare resources.
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Puntuación de Alerta Temprana , Desnutrición , Lactante , Humanos , Estado Nutricional , Evaluación Nutricional , Opinión Pública , Desnutrición/diagnóstico , Europa (Continente)RESUMEN
Endosomal sorting plays a fundamental role in directing neural development. By altering the temporal and spatial distribution of membrane receptors, endosomes regulate signaling pathways that control the differentiation and function of neural cells. Several genes linked to inherited demyelinating peripheral neuropathies, known as Charcot-Marie-Tooth (CMT) disease, encode proteins that directly interact with components of the endosomal sorting complex required for transport (ESCRT). Our previous studies demonstrated that a point mutation in the ESCRT component hepatocyte growth-factor-regulated tyrosine kinase substrate (HGS), an endosomal scaffolding protein that identifies internalized cargo to be sorted by the endosome, causes a peripheral neuropathy in the neurodevelopmentally impaired teetering mice. Here, we constructed a Schwann cell-specific deletion of Hgs to determine the role of endosomal sorting during myelination. Inactivation of HGS in Schwann cells resulted in motor and sensory deficits, slowed nerve conduction velocities, delayed myelination and hypomyelinated axons, all of which occur in demyelinating forms of CMT. Consistent with a delay in Schwann cell maturation, HGS-deficient sciatic nerves displayed increased mRNA levels for several promyelinating genes and decreased mRNA levels for genes that serve as markers of myelinating Schwann cells. Loss of HGS also altered the abundance and activation of the ERBB2/3 receptors, which are essential for Schwann cell development. We therefore hypothesize that HGS plays a critical role in endosomal sorting of the ERBB2/3 receptors during Schwann cell maturation, which further implicates endosomal dysfunction in inherited peripheral neuropathies.SIGNIFICANCE STATEMENT Schwann cells myelinate peripheral axons, and defects in Schwann cell function cause inherited demyelinating peripheral neuropathies known as CMT. Although many CMT-linked mutations are in genes that encode putative endosomal proteins, little is known about the requirements of endosomal sorting during myelination. In this study, we demonstrate that loss of HGS disrupts the endosomal sorting pathway in Schwann cells, resulting in hypomyelination, aberrant myelin sheaths, and impairment of the ERBB2/3 receptor pathway. These findings suggest that defective endosomal trafficking of internalized cell surface receptors may be a common mechanism contributing to demyelinating CMT.
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Enfermedad de Charcot-Marie-Tooth , Animales , Enfermedad de Charcot-Marie-Tooth/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte , Endosomas/metabolismo , Ratones , Enfermedades del Sistema Nervioso Periférico , ARN Mensajero , Células de Schwann/metabolismoRESUMEN
Health professions programs lack sufficient exposure to geriatric education in curricula. The Seniors Assisting in Geriatric Education (SAGE) Program exposes interprofessional (IP) teams of health professions students to older adults. To determine the impact of an interprofessional geriatric educational experience on student perceptions of team collaboration and older adults. IP teams of three or four students (n = 662) representing eight disciplines from two institutions were paired with an older adult to promote person-centered care over three semesters. Students completed two online questionnaires (pre- and post-SAGE Program, ~10 min). 136 students completed both questionnaires. Three IP collaborative practice sub-competencies under the Roles & Responsibilities and Interprofessional Communication Core Competencies increased significantly from pre- to post-SAGE Program (p ≤ 0.002). Comparison of the means for attitudes toward geriatric patients revealed statistically significant improvement in one item, Compassion (p < .002). The SAGE Program had a positive impact on IP collaborative practice and attitudes toward older people in some, but not all, areas.
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Geriatría , Estudiantes del Área de la Salud , Humanos , Anciano , Anciano de 80 o más Años , Relaciones Interprofesionales , Geriatría/educación , Curriculum , Empleos en Salud/educación , Actitud del Personal de SaludRESUMEN
PURPOSE: In patients with low rectal cancer, the intraoperative assessment of sufficient distal resection margins can be challenging. The assessment determines whether reconstruction can be performed or whether permanent colostomy is required. The goal of the present study was to evaluate intraoperative assessment of the total mesorectal excision (TME) specimen during an interruption of the operation. METHODS: The intraoperative strategy of eight patients with low rectal cancer was evaluated. In all cases, intraoperative pathological assessment of the TME specimen by an expert pathologist together with the surgeon was performed. Assessment of the distance of the tumor to the resection margin was measured macroscopically as well as microscopically. RESULTS: All patients underwent neoadjuvant chemoradiation. The tumor was located at an average 4.8 ± 1.4 cm from the anal verge. In all cases, preoperative MRI revealed mrT3 tumors. The intraoperative assessment showed a median distal resection margin of 10 mm (2-15 mm). In six patients, sufficient margins allowed for reconstruction while in two patients APR was needed. In three patients (37.5%), the pathological assessment changed the operative strategy: In one patient APR could be avoided while two patients required APR instead of the anticipated TME. CONCLUSION: The intraoperative assessment of the TME specimen by an expert pathologist together with the surgeon is a valuable tool to avoid unnecessary APR or R1 resections. We therefore suggest routine intraoperative pathological assessment in all operations for borderline low rectal cancers.
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Abdomen/cirugía , Cuidados Intraoperatorios , Patólogos , Perineo/cirugía , Neoplasias del Recto/cirugía , Recto/cirugía , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Gabapentinoid drugs (gabapentin and pregabalin) are effective in neuropathic pain, which has a prevalence of â¼7%. Concerns about increased prescribing have implications for patient safety, misuse, and diversion. Drug-related deaths (DRDs) have increased and toxicology often implicates gabapentinoids. We studied national and regional prescribing rates (2006-2016) and identified associated sociodemographic factors, co-prescriptions and mortality, including DRDs. METHODS: National data from the Information Service Division, NHS Scotland were analysed for prescribing, sociodemographic, and mortality data from the Health Informatics Centre, University of Dundee. DRDs in which gabapentinoids were implicated were identified from National Records of Scotland and Tayside Drug Death Databases. RESULTS: From 2006 to 2016, the number of gabapentin prescriptions in Scotland increased 4-fold (164 630 to 694 293), and pregabalin 16-fold (27 094 to 435 490). In 2016 'recurrent users' (three or more prescriptions) had mean age 58.1 yr, were mostly females (62.5%), and were more likely to live in deprived areas. Of these, 60% were co-prescribed an opioid, benzodiazepine, or both (opioid 49.9%, benzodiazepine 26.8%, both 17.1%). The age-standardised death rate in those prescribed gabapentinoids was double that in the Scottish population (relative risk 2.16, 95% confidence interval 2.08-2.25). Increases in gabapentinoids contributing to cause of DRDs were reported regionally and nationally (gabapentin 23% vs 15%; pregabalin 21% vs 7%). In Tayside, gabapentinoids were implicated in 22 (39%) of DRDs, 17 (77%) of whom had not received a prescription. CONCLUSIONS: Gabapentinoid prescribing has increased dramatically since 2006, as have dangerous co-prescribing and death (including DRDs). Older people, women, and those living in deprived areas were particularly likely to receive prescriptions. Their contribution to DRDs may be more related to illegal use with diversion of prescribed medication.
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Analgésicos Opioides/efectos adversos , Benzodiazepinas/efectos adversos , Sobredosis de Droga/epidemiología , Gabapentina/efectos adversos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pregabalina/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Analgésicos/efectos adversos , Niño , Preescolar , Quimioterapia Combinada/estadística & datos numéricos , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Escocia/epidemiología , Factores Sexuales , Adulto JovenRESUMEN
Neurons are particularly vulnerable to perturbations in endo-lysosomal transport, as several neurological disorders are caused by a primary deficit in this pathway. In this report, we used positional cloning to show that the spontaneously occurring neurological mutation teetering (tn) is a single nucleotide substitution in hepatocyte growth factor-regulated tyrosine kinase substrate (Hgs/Hrs), a component of the endosomal sorting complex required for transport (ESCRT). The tn mice exhibit hypokenesis, muscle weakness, reduced muscle size and early perinatal lethality by 5-weeks of age. Although HGS has been suggested to be essential for the sorting of ubiquitinated membrane proteins to the lysosome, there were no alterations in receptor tyrosine kinase levels in the central nervous system, and only a modest decrease in tropomyosin receptor kinase B (TrkB) in the sciatic nerves of the tn mice. Instead, loss of HGS resulted in structural alterations at the neuromuscular junction (NMJ), including swellings and ultra-terminal sprouting at motor axon terminals and an increase in the number of endosomes and multivesicular bodies. These structural changes were accompanied by a reduction in spontaneous and evoked release of acetylcholine, indicating a deficit in neurotransmitter release at the NMJ. These deficits in synaptic transmission were associated with elevated levels of ubiquitinated proteins in the synaptosome fraction. In addition to the deficits in neuronal function, mutation of Hgs resulted in both hypermyelinated and dysmyelinated axons in the tn mice, which supports a growing body of evidence that ESCRTs are required for proper myelination of peripheral nerves. Our results indicate that HGS has multiple roles in the nervous system and demonstrate a previously unanticipated requirement for ESCRTs in the maintenance of synaptic transmission.
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Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Regulación del Desarrollo de la Expresión Génica , Mutación , Fosfoproteínas/genética , Secuencia de Aminoácidos , Animales , Conducta Animal/fisiología , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Femenino , Hipocampo/patología , Masculino , Ratones Endogámicos C57BL , Ratones Mutantes , Datos de Secuencia Molecular , Actividad Motora/genética , Vaina de Mielina/genética , Vaina de Mielina/metabolismo , Unión Neuromuscular/genética , Unión Neuromuscular/fisiopatología , Fosfoproteínas/metabolismo , Nervio Ciático/metabolismo , Nervio Ciático/fisiopatología , Transmisión Sináptica/genéticaRESUMEN
BACKGROUND: Infants <32 weeks' gestation should not be exposed to topical iodine and its avoidance is recommended during pregnancy and breast feeding. Exposure to contrast media and topical iodine is frequently used in many preterm neonates. AIM: To determine whether thyrotropin levels in preterm infants are affected by exposure to intrapartum/neonatal topical iodine and/or the use of iodinated contrast media. DESIGN: Infants <32 weeks' gestation were recruited. Maternal and neonatal exposures to iodinated contrast media and topical iodine were recorded; levels of thyrotropin and thyroxine were measured from blood-spot cards on postnatal days 7, 14, 28 and the equivalent of 36 weeks' gestation. RESULTS: One hundred and twenty-five infants were exposed to topical iodine/contrast media and 48 infants were unexposed. No infants were treated for hypothyroidism; three infants (exposed group) had transient hyperthyrotropinaemia. Mean thyrotropin levels were significantly higher on postnatal days 7, 14 and 28 in infants exposed to topical iodine prior to caesarean section compared to unexposed infants, a relationship which persisted after adjustment. CONCLUSIONS: In the context of this study, neonatal thyroid dysfunction was seen following exposure to iodine via caesarean section but not via exposure to contrast media.
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Antiinfecciosos Locales/efectos adversos , Medios de Contraste/efectos adversos , Yodo/efectos adversos , Enfermedades de la Tiroides/inducido químicamente , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , MasculinoRESUMEN
BACKGROUND: Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity. METHODS: In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti-inflammatory activity and activity against Gram-positive and Gram-negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined. RESULTS: The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5-fold, EC50â=â5-11 µM) of rhinovirus-induced type I IFNß, type III IFNλ1 and type III IFNλ2/3 mRNA and the IFN-stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram-positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram-negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus influenzae. Further non-toxic Mac5 derivatives were identified with various anti-inflammatory, antiviral and antibacterial activities. CONCLUSIONS: The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also provide evidence that macrolides can be developed with anti-inflammatory, antibacterial and antiviral activity and show surprising versatility depending on the clinical need.
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Antibacterianos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antivirales/química , Antivirales/farmacología , Descubrimiento de Drogas , Interferones/inmunología , Macrólidos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/uso terapéutico , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios no Esteroideos/uso terapéutico , Antivirales/aislamiento & purificación , Antivirales/uso terapéutico , Asma/tratamiento farmacológico , Bronquios/citología , Bronquios/efectos de los fármacos , Células Cultivadas , Evaluación Preclínica de Medicamentos , Células Epiteliales/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Haemophilus influenzae/efectos de los fármacos , Humanos , Interferón beta/inmunología , Interferones/biosíntesis , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-8/inmunología , Interleucina-8/metabolismo , Macrólidos/química , Macrólidos/uso terapéutico , Proteínas de Resistencia a Mixovirus/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Proteínas/genética , Pseudomonas aeruginosa/efectos de los fármacos , Rhinovirus/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
OBJECTIVE: To study the outcomes of three different types of arteriovenous fistula (AVF) transpositions (forearm cephalic vein transposition [FACVT], upper arm cephalic vein transposition [UACVT], and upper arm basilic vein transposition [UABVT]) for dialysis patients in a single center. METHODS: A 6-year retrospective review, from 2006 to 2012, was conducted at a single institution in which the surgical outcomes for three different types of AVF transposition were reviewed. Preoperative duplex vein mapping was obtained in all patients to choose the best vein for access. RESULTS: There were 165 patients identified with 77 FACVTs, 52 UACVTs, and 36 UABVTs. Primary access maturation rates for the FACVT, UACVT, and UABVT groups were 86%, 90%, and 97%, respectively (P = .19). All transposed, matured primary AVFs were used after a mean of 9.9 weeks, without additional intervention. Primary 1-year patency for the FACVT, UACVT, and UABVT groups were 63%, 61%, and 70%, respectively (P = .71). Primary assisted 1-year patency for the FACVT, UACVT, and UABVT groups were 93%, 93%, and 100%, respectively (P > .999). Mean operating room times and time to intervention were not significantly different between the groups. The postoperative hematoma rate was 2% and wound infection rate was 2%. Multivariate analysis indicated no significant predictors of time to failure (P > .05). CONCLUSIONS: With low primary failure rates, reduced need for secondary interventions before maturation, and 1-year primary assisted patency rates in excess of 93%, our study showed that the transposition technique, in our experience, is superior to previously published literature in hemodialysis access creation.
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Brazo/irrigación sanguínea , Derivación Arteriovenosa Quirúrgica/métodos , Antebrazo/irrigación sanguínea , Diálisis Renal , Anciano , Anciano de 80 o más Años , Derivación Arteriovenosa Quirúrgica/efectos adversos , Femenino , Humanos , Masculino , Michigan , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: Coronary artery disease and abdominal aortic aneurysmal disease can occur in a single patient, and a therapeutic conundrum presents when open surgical repair is indicated for both conditions. The traditional standard of care is to conduct coronary artery bypass grafting (CABG) followed by abdominal aortic aneurysm (AAA) repair 2-6 months later, but there is significant risk with staging these 2 major surgeries. An alternative method is to surgically repair both diseases in 1 combined operation. The aim of our study is to review our own experience with the combined procedure and to review the published literature to assess morbidity and mortality of combined CABG and AAA repair. METHODS: A systematic search for relevant studies was performed in the PubMed/Medline database. Short-term mortality (<30 days) and postoperative complications were assessed from relevant case series from 1993 to 2013. We also conducted a retrospective chart review of all patients undergoing the combined procedure at our institution. RESULTS: Thirty case series with a total of 369 patients averaged a 30-day mortality of 3.0%. Fourteen percent and 6% of patients experienced a cardiovascular or respiratory complication, respectively. Other postoperative events included acute renal failure (7%) and superficial wound complications (5%). In our own experience, 3 patients underwent combined CABG and AAA repair. The mean age was 71 years, the average AAA size was 8.9 cm, and average operative time was 328 min. None experienced any postoperative complications. Two are still alive at 9 and 10 years after surgery, and 1 died of unrelated causes 8 years postoperatively. CONCLUSIONS: The results of this systematic review suggest that combined CABG and AAA repair is a viable procedure with low operative mortality. Patients with preserved ejection fractions, large AAA, and limited comorbidities appear to receive the most benefit from a combined approach based on reported data from the literature. We have experienced promising results in our highly selected patient population. More research is warranted to devise criteria to determine which patients would be good surgical candidates for this combined procedure.
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Aneurisma de la Aorta Abdominal/cirugía , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/cirugía , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/complicaciones , Enfermedad de la Arteria Coronaria/complicaciones , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Norepinephrine (NE) and epinephrine (EPI) levels are higher in cord arterial blood relative to venous blood, consistent with active mechanisms of placental-maternal clearance. There are no contemporary studies of cord arteriovenous blood levels of sulfated and non-sulfated catechols. AIM: To assess the arteriovenous differences in cord blood levels of dopamine (DA), the sulfated catecholamines and their sulfated and non-sulfated metabolites. To correlate levels of oxygen, H+/CO2, and glucose with cord catecholamine levels. METHODS: Fifty-seven term infants, delivered by elective cesarean section, were recruited. Cord arterial and venous blood was sampled; levels of glucose, lactate, blood gases, six catechols and their sulfated conjugates were measured. RESULTS: With one exception (DOPA sulfate), mean cord arterial levels of sulfated and non-sulfated catechols were significantly higher than venous levels. Arterial lactate and glucose levels were independently associated with NE levels, but only lactate was associated with levels of EPI and DA. CONCLUSION: This study establishes that in vivo metabolic parameters of hypoxia, respiratory and metabolic acidosis are associated with catecholamine levels, a key relationship for perinatal adaptation and homeostasis, and findings that are consistent with in vitro studies of the regulators of catecholamine secretion.
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Glucemia/metabolismo , Catecolaminas/sangre , Sangre Fetal/metabolismo , Ácido Láctico/sangre , Arterias , Análisis de los Gases de la Sangre , Cesárea , Femenino , Humanos , Recién Nacido , Masculino , Análisis de Regresión , VenasRESUMEN
AIM: To assess factors contributing to cord venous glucose homeostasis in term infants delivered by elective cesarean section. METHODS: Observational study of women-infant pairs at delivery. Biochemical and clinical data were collected about factors which might affect the levels of glucose, lactate, norepinephrine, epinephrine, cortisol, human growth hormone, glucagon, and insulin. RESULTS: In the context of this data-set, three models explained a substantial amount regarding the variation: 79% of the variation in cord glucose levels is explained by levels of maternal glucose, cord venous pH, and cord lactate; 77% of the variation of cord lactate is explained by levels of cord venous pH, valine, maternal lactate and glucose, and cord norepinephrine; and 71% of the variation in cord norepinephrine is explained by levels of cord venous pO2, maternal lactate, cord insulin, cord GABA (gamma-aminobutyric acid), cord lactate, cord epinephrine, cord norepinephrine sulfate, and cord valine. CONCLUSIONS: Term infants delivered by cesarean section are relatively hyperinsulinemic (insulin:glucose ratio of 2.4) and glucose levels are strongly associated with maternal glucose levels, cord pO2, and lactate levels. There were no associations with levels of cord glucose and levels of cortisol, epinephrine and lactate, which have been shown to be important contributors to postnatal glucose homeostasis in some infant groups.
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Glucemia/metabolismo , Cesárea , Sangre Fetal/metabolismo , Homeostasis , Embarazo/sangre , Adulto , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
Background: Lower extremity trauma can have a significant impact on a patient's quality of life. The LIMB-Q is a recently developed and validated patient-reported outcome measure that assesses patient-specific outcomes and experience of health care. The aim of this study was to translate and linguistically validate the LIMB-Q from English to German. Methods: The translation was performed by combining World Health Organization and Professional Society for Health Economics and Outcomes Research guidelines. The process consisted of forward translations, a backward translation, expert panel meetings, cognitive debriefing interviews with patients, and several rounds of discussion and reconciliation with the creators of LIMB-Q. The goal was to obtain a culturally and conceptually accurate translation of LIMB-Q into German for use in Switzerland. Results: From the two forward translations, there was one primary discrepancy between the two translators that was discussed to determine the most conceptually accurate translation. From the backward translations, there were 63 items that required discussion and re-translation. Nine patients participated in the cognitive debriefing interviews, which led to three items being modified. The translation process led to a linguistically validated and conceptually equivalent German version of the LIMB-Q. Conclusions: The German (Switzerland) version of LIMB-Q is now available. This will offer a valuable tool for lower extremity trauma research and clinical care in German-speaking populations.
RESUMEN
Protease-activated receptor-1 (PAR1) is an unusual G-protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. Although previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. Here, we used PAR1-/- mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1-/- mice have deficits in hippocampus-dependent memory. We also show that while PAR1-/- mice have normal baseline synaptic transmission at Schaffer collateral-CA1 synapses, they exhibit severe deficits in N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR-mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR-dependent processes subserving memory formation and synaptic plasticity.
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Hipocampo/citología , Potenciación a Largo Plazo/genética , Memoria/fisiología , Receptor PAR-1/metabolismo , Sinapsis/genética , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Animales , Biofisica , Condicionamiento Psicológico/fisiología , Estimulación Eléctrica , Antagonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/genética , Miedo/fisiología , Técnicas In Vitro , Potenciación a Largo Plazo/efectos de los fármacos , Trastornos de la Memoria/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Mensajero/metabolismo , Receptor PAR-1/deficiencia , Sinapsis/efectos de los fármacos , Sinapsis/fisiologíaRESUMEN
OBJECTIVE: This study reviewed the natural history of blunt thoracic aortic trauma (BTAT) over a 14-year period at our level 1 trauma center and compared open vs endovascular treatment. METHODS: All patients with BTAT presenting to a level 1 trauma center from 1998 to 2011 were included in a retrospective analysis. Multiple data points and short-term and midterm outcomes were ascertained through a retrospective record review. RESULTS: We identified 129 patients with BTAT. Of these, 32 (25%) were dead on arrival, 38 (29%) underwent a resuscitative thoracotomy and died, 33 (26%) underwent open repair, 14 (11%) underwent endovascular repair, 9 (7%) underwent simultaneous procedures, and 3 (2%) were managed nonoperatively. Mean Injury Severity Scores and Revised Trauma Scores were similar (P = .484, P = .551) between the open repair group (n = 36) and the endovascular repair group (n = 14). In the open repair group, there were 14 deaths (42%) ≤ 30 days of injury, 3 strokes (9%), 2 patients (6%) with paralysis, 2 myocardial infarctions (MIs; 6%), and 3 patients (9%) who required hemodialysis. In the endovascular group, there was 1 death (7%) ≤ 30 days of injury, 1 (7%) stroke, and 1 (7%) stent collapse. No paralysis, MI, or renal failure requiring hemodialysis was noted in the endovascular group. The average length of stay was 15 days for patients treated with endovascular repair vs 24 days for those treated with open repair (P = .003). CONCLUSIONS: The incidence of BTAT is low but the mortality associated with it is significant. During the 14-year period studied, there was a clear change in management preference from open repair to endovascular repair at our level 1 trauma center. Outcomes, including stroke, MI, renal failure, paralysis, length of stay, and death, appear to be reduced in the endovascular group.
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Aorta Torácica/lesiones , Aorta Torácica/cirugía , Procedimientos Endovasculares , Procedimientos Quirúrgicos Vasculares , Lesiones del Sistema Vascular/cirugía , Heridas no Penetrantes/cirugía , Adulto , Aorta Torácica/diagnóstico por imagen , Aortografía/métodos , Distribución de Chi-Cuadrado , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Incidencia , Puntaje de Gravedad del Traumatismo , Tiempo de Internación , Masculino , Persona de Mediana Edad , Parálisis/mortalidad , Parálisis/terapia , Valor Predictivo de las Pruebas , Sistema de Registros , Diálisis Renal , Insuficiencia Renal/mortalidad , Insuficiencia Renal/terapia , Estudios Retrospectivos , Rhode Island/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapia , Toracotomía , Factores de Tiempo , Tomografía Computarizada por Rayos X , Centros Traumatológicos , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad , Lesiones del Sistema Vascular/diagnóstico , Lesiones del Sistema Vascular/mortalidad , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/mortalidadRESUMEN
BACKGROUND: Sequential compression devices (SCDs) are commonly used for thromboprophylaxis in postoperative patients but compliance is often poor. We investigated causes for noncompliance, examining both hospital and patient related factors. METHODS: 100 patients undergoing inpatient urologic surgery were enrolled. All patient had SCD sleeves placed preoperatively. Postoperative observations determined SCD compliance and reasons for non-compliance. Patient demographics, length of stay, inpatient unit type, and surgery type were recorded. At discharge, a patient survey gauged knowledge and attitudes regarding SCDs and bother with SCDs. Statistical analysis was performed to correlate SCD compliance with patient demographics; patient knowledge and attitudes regarding SCDs; and patient self-reported bother with SCDs. RESULTS: Observed overall compliance was 78.6%. The most commonly observed reasons for non-compliance were SCD machines not being initially available on the ward (71% of non-compliant observations on post-operative day 1) and SCD use not being restarted promptly after return to bed (50% of non-compliant observations for entire hospital stay). Mean self-reported bother scores related to SCDs were low, ranging from 1-3 out of 10 for all 12 categories of bother assessed. Patient demographics, knowledge, attitudes and bother with SCD devices were not significantly associated with non-compliance. CONCLUSIONS: Patient self-reported bother with SCD devices was low. Hospital factors, including SCD machine availability and timely restarting of devices by nursing staff when a patient returns to bed, played a greater role in SCD non-compliance than patient factors. Identifying and addressing hospital related causes for poor SCD compliance may improve postoperative urologic patient safety.
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Adhesión a Directriz/estadística & datos numéricos , Aparatos de Compresión Neumática Intermitente/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/prevención & control , Procedimientos Quirúrgicos Urológicos , Trombosis de la Vena/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Aparatos de Compresión Neumática Intermitente/provisión & distribución , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Cooperación del Paciente/psicología , Guías de Práctica Clínica como Asunto , Encuestas y CuestionariosRESUMEN
BACKGROUND AND OBJECTIVE: Ovarian cancer has an extremely high mortality rate resulting from poor understanding of the disease. In order to aid understanding of disease etiology and progression, we identify the endogenous fluorophores present in a mouse model of ovarian cancer and describe changes in fluorophore abundance and distribution with age and disease. STUDY DESIGN/MATERIALS AND METHODS: A mouse model of ovarian cancer was created by dosing with 4-vinylcyclohexene diepoxide, which induces follicular apoptosis (simulating menopause), and 7,12-dimethylbenz[a]anthracene, a known carcinogen. Imaging of ovarian tissue was completed ex vivo with a multiphoton microscope using excitation wavelength of 780 nm and emission collection from 405 to 505 nm. Two-photon excited fluorescence images and corresponding histologic sections with selective stains were used to identify endogenous fluorophores. RESULTS: The majority of collected fluorescence emission was attributed to NADH and lipofuscin, with additional contributions from collagen and elastin. Dim cellular fluorescence from NADH did not show observable changes with age. Changes in ovarian morphology with disease development frequently caused increased fluorescence contributions from collagen and adipose tissue-associated NADH. Lipofuscin fluorescence was much brighter than NADH fluorescence and increased as a function of both age and disease. CONCLUSIONS: Our finding of NADH fluorescence patterns similar to that seen previously in human ovary, combined with the observation of lipofuscin accumulation with age and disease also seen in human organs, suggests that the findings from this model may be relevant to human ovarian disease. Increased lipofuscin fluorescence might be used as an indicator of disease in the ovary and this finding warrants further study.
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Adenocarcinoma/patología , Microscopía de Fluorescencia por Excitación Multifotónica , Neoplasias Ováricas/patología , Ovario/patología , 9,10-Dimetil-1,2-benzantraceno , Adenocarcinoma/inducido químicamente , Adenocarcinoma/metabolismo , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Biomarcadores de Tumor/metabolismo , Colágeno/metabolismo , Ciclohexenos , Progresión de la Enfermedad , Elastina/metabolismo , Femenino , Interpretación de Imagen Asistida por Computador , Modelos Lineales , Lipofuscina/metabolismo , Ratones , NAD/metabolismo , Neoplasias Ováricas/inducido químicamente , Neoplasias Ováricas/metabolismo , Ovario/metabolismo , Compuestos de ViniloRESUMEN
LAY ABSTRACT: Recently, therapy has been delivered at a distance (i.e. remotely) to help control the spread of coronavirus. Clinicians have voiced concerns that remote delivery is unsuitable for certain individuals, including those who are autistic, but they have also highlighted potential benefits for autistic individuals. Benefits include some individuals feeling more comfortable receiving therapy at home. This is the first study to interview autistic individuals about their experience of remote therapy. Participants were six young people aged 15-18 years and eight clinicians. Participants described their experience of remote delivery, including challenges, benefits, and suggestions. Most of these supported previous research findings, but some were new or provided further insight into those already identified. A newly identified challenge was knowing online social etiquette. All participants found aspects of the experience challenging, but all identified benefits and most voiced that remote sessions should be offered to young people. Participants further identified individual characteristics that may make someone less suited to remote delivery (e.g. shyness). They also identified ways of making the experience of remote delivery easier (e.g. sitting with a pet). Young people's and clinicians' views were similar overall, with only subtle differences. For example, young people uniquely voiced that remote delivery was similar to in-person, that benefits were hard to identify, and provided distinct reasons for the social interaction feeling less intense remotely. Findings may be used to improve remote delivery, for guiding future research, and as a case for continuing to offer it to those who may most benefit.
Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , COVID-19 , Humanos , Adolescente , Intervención Psicosocial , EmocionesRESUMEN
OBJECTIVE: Pediatric hypertension affects 2% to 5% of children and adolescents in the United States and is frequently undertreated. The increasing prevalence of pediatric hypertension and worsening physician shortage create difficulties in closing this treatment gap. Physician-pharmacist collaborations have been shown to improve patient outcomes in adult patients. Our aim was to demonstrate a similar benefit for pediatric hypertension. METHODS: Pediatric patients whose hypertension was managed at a single pediatric cardiology clinic from January 2020 to December 2021 were enrolled in collaborative drug therapy management (CDTM). Patients whose hypertension was managed in the same clinic from January 2018 to December 2019 were used as a comparison group. The primary outcomes were achievement of at-goal blood pressure at 3, 6, and 12 months and time to control of hypertension. Secondary outcomes were appointment adherence and serious adverse events. RESULTS: A total of 151 patients were included in the CDTM group, and 115 patients were included in the traditional care group. Of those, 100 CDTM patients and 78 traditional care patients were assessed for the primary outcome. Fifty-four (54%) CDTM patients and 28 (36%) traditional care patients achieved at-goal blood pressure at 12 months (OR, 2.09; 95% CI, 1.14-3.85). Appointment non-adherence was 9.4% for CDTM and 16% for traditional care (OR, 0.54; 95% CI, 0.35-0.82). Adverse events were similar between groups. CONCLUSIONS: CDTM increased rates of at-goal blood pressure without increased adverse events. Physician-pharmacist collaboration may improve treatment of hypertension in pediatric patients.
RESUMEN
Background: Burn wounds pose significant challenges in medical treatment due to their devastating nature and resource-intensive requirements. Temporary coverage of burn wounds using synthetic or biological dressings allows for reepithelization before definitive skin grafting. Allogenic skin grafts have been widely used but come with drawbacks such as rejection and disease transmission. The use of amniotic membranes (AMs) offers a promising alternative for temporary coverage, as they possess biological properties that promote faster healing and improved scar quality. The various components of the amniotic membrane, including pluripotent stem cells, extracellular matrix proteins, and regenerative factors, contribute to cell growth, migration, and differentiation, as well as preservation of the original epithelial phenotype. Objective: Reliable information on the treatment of burn wounds with AM is needed. The knowledge gained in this project may help to include this advantageous modern concept of biological dressings in clinical practice. The purpose of this study is to use human amniotic membranes from our in hospital laboratory, as an allogenic biological dressing after enzymatic debridement in superficial partial thickness, deep partial thickness or full thickness burn wounds. Methods: We will include 30 patients in a randomized-controlled trial with each patient receiving the study intervention and the control intervention. Two 7 × 7 cm burn wound areas will be compared regarding percentage of skin graft take, healing time, healing percentage value and total healing time. Human amniotic membranes will be compared to allogenic skin grafts.