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1.
Ann Surg Oncol ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909116

RESUMEN

PURPOSE: DOTATATE PET/CT (DOTATATE) is superior to conventional imaging in detecting metastasis for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, limited availability, high-cost, and additive radiation exposure necessitate guidelines for its use. This study seeks to investigate the relationship between clinical characteristics and metastasis on DOTATATE. METHODS: This was a retrospective analysis of 815 patients who underwent DOTATATE at UCLA from 2014 to 2022. After applying inclusion and exclusion criteria, the study cohort consisted of 163 patients with pathologically diagnosed GEP-NETs, who either underwent primary tumor resection within 1-year prior, or had not undergone resection at the time of DOTATATE imaging. The presence of metastasis was determined using DOTATATE. Fisher's exact test, chi-squared test, and Mann-Whitney test were conducted to compare intergroup difference. Multivariate analysis was performed to identify clinical characteristics associated with metastasis on DOTATATE. RESULTS: Of patients with GEP-NETs, 40.5% (n = 66) were diagnosed with metastases by using DOTATATE. Those with metastatic disease were more likely to exhibit a larger primary tumor size (median 3.4 vs. 1.2, cm, P < 0.001), elevated serum chromogranin A level (CgA, median 208 vs. 97, mg/ml, P = 0.005), and higher tumor grade (P < 0.001). Primary tumor size ≥2 cm and serum CgA level ≥150 ng/mL for metastatic disease had a sensitivity and specificity of 64% and 89%, and 72% and 59%, respectively. Multivariate analysis demonstrated that primary tumor size (≥2/<2, cm, odds ratio [OR] 47.90, P < 0.001), tumor functionality (functional/nonfunctional, adjusted OR 10.17 P = 0.008), serum CgA level (≥150/<150, ng/ml, OR 6.25, P = 0.005), and tumor grade G2 (G2/G1, OR 9.6, P < 0.001) were independently associated with metastases on DOTATATE. CONCLUSIONS: Among patients with GEP-NETs, primary tumor size ≥2 cm, serum CgA level ≥150 ng/mL, and tumor grade G2 are associated with an increased risk of metastases on DOTATATE, and these predictors may be helpful to identify patients where DOTATATE is indicated for complete staging.

2.
Ann Surg Oncol ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39044106

RESUMEN

BACKGROUND: Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). METHODS: Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. RESULTS: Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p = 0.04), more than three suspicious nodes on initial US (30% vs 13%; p ≤ 0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p = 0.0004), and more positive TAD nodes (median, 2 vs 1; p ≤ 0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p ≤ 0.0001), more positive TAD nodes (OR, 1.1; p ≤ 0.0001), larger clipped node metastasis (OR, 1.1; p ≤ 0.0001), and larger residual tumor on pathology (OR, 1.1; p = 0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. CONCLUSION: Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

3.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33597293

RESUMEN

Emerging evidence suggests that intratumoral interferon (IFN) signaling can trigger targetable vulnerabilities. A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are critical cofactors. Here, we show that IFN signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, and PARP14. Their individual contributions to this mechanism in PDAC have not been previously delineated. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway, a dominant source of NAD in cancer cells. We found that IFN-induced NAD consumption increased dependence upon NAMPT for its role in recycling NAM to salvage NAD pools, thus sensitizing PDAC cells to pharmacologic NAMPT inhibition. Their combination decreased PDAC cell proliferation and invasion in vitro and suppressed orthotopic tumor growth and liver metastases in vivo.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/patología , Citocinas/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica , Interferón Tipo I/metabolismo , NAD/deficiencia , Nicotinamida Fosforribosiltransferasa/antagonistas & inhibidores , Neoplasias Pancreáticas/patología , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Proliferación Celular , Citocinas/genética , Citocinas/metabolismo , Humanos , Interferón Tipo I/genética , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Nicotinamida Fosforribosiltransferasa/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Poli(ADP-Ribosa) Polimerasas/genética , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Transducción de Señal , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Vet Dermatol ; 34(6): 532-542, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37395162

RESUMEN

BACKGROUND: Hymenoptera envenomation occurs frequently in people and dogs and can trigger anaphylaxis. Venom immunotherapy (VIT) is the only preventive treatment for Hymenoptera hypersensitivity and is indicated for people with severe adverse reactions to insect stings. Rush VIT is an accelerated VIT protocol in people. This has not been reported in dogs. OBJECTIVES: The objective of the study was to evaluate the safety of modified rush VIT. ANIMALS: Twenty client-owned dogs with Hymenoptera hypersensitivity based on a history of adverse reactions to Hymenoptera envenomation and a positive intradermal test to honey bee and/or paper wasp venom. MATERIALS AND METHODS: Dogs received incremental doses of venom via subcutaneous injection one day per week for three consecutive weeks until the maintenance dose was achieved. Vital signs were recorded every 30 min prior to venom administration. Adverse reactions were categorised as localised or grade I-IV systemic reactions. RESULTS: Nineteen of 20 dogs (95%) completed rush VIT. One dog experienced a grade III systemic adverse reaction and was withdrawn from the study. No adverse reactions occurred in 10 of 20 dogs (50%). Localised and grade I-II systemic reactions occurred in nine of 20 dogs (45%), including nausea (n = 5), injection site pruritus (n = 3) and diarrhoea and lethargy (n = 1). CONCLUSIONS AND CLINICAL RELEVANCE: Modified rush VIT in dogs was well-tolerated and should be considered for dogs with Hymenoptera hypersensitivity. Larger studies are needed to evaluate the efficacy of VIT in dogs for preventing hypersensitivity reactions to insect stings.


Asunto(s)
Anafilaxia , Venenos de Abeja , Desensibilización Inmunológica , Enfermedades de los Perros , Himenópteros , Hipersensibilidad , Mordeduras y Picaduras de Insectos , Humanos , Perros , Animales , Mordeduras y Picaduras de Insectos/terapia , Mordeduras y Picaduras de Insectos/veterinaria , Venenos de Abeja/uso terapéutico , Venenos de Abeja/efectos adversos , Hipersensibilidad/tratamiento farmacológico , Hipersensibilidad/veterinaria , Anafilaxia/inducido químicamente , Anafilaxia/prevención & control , Anafilaxia/veterinaria , Desensibilización Inmunológica/métodos , Desensibilización Inmunológica/veterinaria , Inmunoterapia/métodos , Inmunoterapia/veterinaria , Enfermedades de los Perros/tratamiento farmacológico
5.
BMC Neurol ; 22(1): 75, 2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35246068

RESUMEN

BACKGROUND: Vagal nerve stimulation (VNS) is approved therapy for the treatment of intractable epilepsy. The stimulation of either nerve, left or right, is effective. However, due to the anatomic and physiological effects of cardiac innervation, the right vagus nerve is typically avoided in order to minimize the risk of cardiac bradyarrhythmias. The location of the VNS lead contacts on the nerve can also have an effect, namely, more distally placed contacts have been associated with lower risk of cardiac arrhythmias, presumably by avoiding vagal cervical cardiac branches; however, our case demonstrates reproducible asystole despite left sided, distal VNS lead placement. CASE PRESENTATION: We report a 28-year-old male patient with pharmacoresistant generalized clonic-tonic seizures. The VNS therapy with 1.5 mA output and 16% duty cycle drastically reduced his seizure burden for several years. The breakthrough seizures along with stabbing pain episodes at the implantable pulse generator (IPG) site have prompted the VNS lead revision surgery with new lead contacts placed more caudally than the old contacts. However, the intraoperative device interrogation with 1 mA output resulted in immediate asystole for the duration of stimulation and it was reproducible until the output was decreased to 0.675 mA. CONCLUSIONS: Our case highlights the possibility of new severe cardiac bradyarrhythmias following surgical VNS lead replacements even in patients without preoperatively known clinical side effects. We suggest preoperative electrocardiography and cardiology consultation for detected abnormalities for all patients undergoing new VNS implantations, as well as revision surgeries for VNS malfunctions. Intraoperatively, the surgeon and anesthesia team should be vigilant of cardiac rhythms and prepared for the immediate management.


Asunto(s)
Epilepsia Refractaria , Paro Cardíaco , Estimulación del Nervio Vago , Adulto , Epilepsia Refractaria/terapia , Paro Cardíaco/etiología , Paro Cardíaco/terapia , Humanos , Masculino , Convulsiones/etiología , Resultado del Tratamiento , Nervio Vago , Estimulación del Nervio Vago/efectos adversos , Estimulación del Nervio Vago/métodos
6.
Proc Natl Acad Sci U S A ; 116(14): 6842-6847, 2019 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-30894490

RESUMEN

Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibition in PDAC have not been systematically explored. We performed a comprehensive pharmacological inhibition screen of the protein kinome and found that replication stress response (RSR) inhibitors were synthetically lethal with chloroquine (CQ) in PDAC cells. CQ treatment reduced de novo nucleotide biosynthesis and induced replication stress. We found that CQ treatment caused mitochondrial dysfunction and depletion of aspartate, an essential precursor for de novo nucleotide synthesis, as an underlying mechanism. Supplementation with aspartate partially rescued the phenotypes induced by CQ. The synergy of CQ and the RSR inhibitor VE-822 was comprehensively validated in both 2D and 3D cultures of PDAC cell lines, a heterotypic spheroid culture with cancer-associated fibroblasts, and in vivo xenograft and syngeneic PDAC mouse models. These results indicate a codependency on functional lysosomes and RSR in PDAC and support the translational potential of the combination of CQ and RSR inhibitors.


Asunto(s)
Ácido Aspártico/deficiencia , Carcinoma Ductal Pancreático , Cloroquina/farmacología , Lisosomas/metabolismo , Mitocondrias , Neoplasias Pancreáticas , Animales , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Femenino , Humanos , Lisosomas/patología , Masculino , Ratones , Mitocondrias/metabolismo , Mitocondrias/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Estrés Fisiológico , Ensayos Antitumor por Modelo de Xenoinjerto
7.
Vet Dermatol ; 33(5): 435-439, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35644925

RESUMEN

Toxoplasma gondii is a ubiquitous protozoan, for which felids are the definitive host. Immunocompromised individuals are susceptible to recrudescent toxoplasmosis. This case describes a 6-year-old, feline immunodeficiency virus-positive domestic short hair cat with feline atopic skin syndrome that developed fatal toxoplasmosis after treatment with oclacitinib for five months.


Toxoplasma gondii est un protozoaire ubiquitaire dont les félidés sont l'hôte définitif. Les personnes immunodéprimées sont sensibles à la toxoplasmose recrudescente. Ce cas décrit un chat domestique à poils courts de 6 ans, positif pour le virus de l'immunodéficience féline, atteint du syndrome atopique cutané félin, qui a développé une toxoplasmose mortelle après un traitement à l'oclacitinib pendant cinq mois.


Toxoplasma gondii es un protozoo ubicuo, cuyo huésped definitivo son los felinos. Las personas inmunocomprometidas son susceptibles a la toxoplasmosis recrudescente. Este caso describe un gato doméstico de pelo corto positivo para el virus de la inmunodeficiencia felina de 6 años de edad con síndrome de piel atópica felina, que desarrolló toxoplasmosis fatal después del tratamiento con oclacitinib durante cinco meses.


Toxoplasma gondii é um protozoário ubíquo para o qual os felídeos são o hospedeiro definitivo. Indivíduos imunocomprometidos são suscetíveis a toxoplasmose recrudescente. Este relato descreve um caso de um felino doméstico de pelo curto de seis anos de idade, positivo para o vírus da imunodeficiência felina, com síndrome atópica felina, que desenvolveu toxoplasmose fatal após tratamento com oclacitinib por cinco meses.


Asunto(s)
Enfermedades de los Gatos , Dermatitis Atópica , Virus de la Inmunodeficiencia Felina , Toxoplasma , Toxoplasmosis Animal , Animales , Enfermedades de los Gatos/tratamiento farmacológico , Gatos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/veterinaria , Pirimidinas , Sulfonamidas , Toxoplasmosis Animal/tratamiento farmacológico
10.
Surg Technol Int ; 30: 25-30, 2017 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-28695970

RESUMEN

INTRODUCTION: Performance-based feedback is critical to surgical skills acquisition. Barriers of geography and time limit trainees' access to expert mentorship. In this study, we hypothesized that telementoring using an asynchronous, web-based video interface would allow trainees to receive systematic feedback from expert mentors despite these barriers. MATERIALS AND METHODS: Between October 2014 and October 2016, 18 surgeons in Brazil, Dominican Republic, Haiti, and Paraguay underwent in-person training in Lichtenstein for hernioplasty or laparoscopic total extraperitoneal inguinal hernia repair. After initial training, surgeons submitted 6- to 12-month interval operative videos for expert review. Expert surgeons reviewed each video using the Surgus web platform with performance metrics adapted from the Operative Performance Rating Scale (OPRS). The time required to perform video review, number of freeform comments, mean OPRS scores, and variance of OPRS scores among telementors was assessed. RESULTS: A total of 18 surgeons submitted 20 operative videos, and three expert surgeons reviewed each video using the Surgus platform. The median time to perform video review was 20 minutes. Median number of freeform verbal comments was eight. Mean OPRS overall performance scores were 3.9 ± 0.9 (scale of five). Mean variance in scoring among telementors for overall performance was 0.25 (maximum 5.29), suggesting a high degree of concordance. CONCLUSIONS: Video-based assessments had a high degree of concordance among expert raters. Asynchronous performance reviews by telementors offer opportunities for longitudinal feedback that overcome geographical, material, and temporal disparities. This platform offers a means of sharing expertise in surgical training, continuing education, credentialing, and global health.


Asunto(s)
Evaluación Educacional/métodos , Internet , Tutoría/métodos , Cirujanos/educación , Telemedicina/métodos , Américas , Competencia Clínica , Educación a Distancia/métodos , Herniorrafia/educación , Humanos , Laparoscopía/educación , Grabación en Video
11.
Surg Technol Int ; 28: 133-8, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27175807

RESUMEN

There have been a variety of absorbable and permanent tacks, tack deployment systems, and fasteners developed for the fixation of mesh during laparoscopic ventral hernia repair. The manufacturer recommendation for all systems is for perpendicular deployment of these tacks into the tissue. Achieving this optimal angle with previously developed deployment systems is often challenging and can lead to tack failure, mesh migration, and recurrence, or may require the placement of additional ports. Additionally, current tack deployment systems lack the ability to reload, leading to increased cost when entire systems must be opened each time a reload is necessary. This article presents products designed to addresses both of these problems. These deployment instruments incorporate an articulating shaft or a hinge mechanism allowing for improved access to different parts of the abdominal cavity and delivering perpendicular placement of tacks with fewer port sites. Devices with the option of reloadable fixation decrease costs and reduce waste.


Asunto(s)
Equipo Reutilizado , Herniorrafia/instrumentación , Laparoscopios , Implantación de Prótesis/instrumentación , Engrapadoras Quirúrgicas , Suturas , Diseño de Equipo , Análisis de Falla de Equipo , Herniorrafia/métodos , Evaluación de la Tecnología Biomédica
12.
Surg Technol Int ; 29: 131-139, 2016 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-27728955

RESUMEN

INTRODUCTION: Minimally invasive laparoscopic and robotic techniques for ventral hernia repair have evolved to achieve the benefits and minimize the limitations of both the open Rives-Stoppa sublay mesh repair and laparoscopic intraperitoneal onlay mesh (IPOM) repair. By combining the principles of a retromuscular repair with the benefits of a minimally invasive approach, these techniques attempt to decrease recurrence, increase functionality, exclude mesh from the viscera, limit infection and wound complications, and minimize pain. The difficult ergonomics, challenging dissection, and extensive suturing make traditional laparoscopic sublay repair technically challenging and has led to increased robotic utilization to overcome these limitations. We describe a laparoscopic extraperitoneal sublay mesh repair technique using an endoscopic stapler to facilitate reapproximation of the linea alba and creation of the retromuscular space, and self-gripping mesh to position and fixate the prosthetic. MATERIALS AND METHODS: Between January and June 2016, 10 patients with midline ventral and incisional hernias underwent laparoscopic extraperitoneal stapled sublay mesh repair with self-gripping mesh. Three of these cases included a laparoscopic posterior component separation with myofascial release of the transversus abdominis muscle to facilitate midline closure. Intraoperative and perioperative complications, early recurrence, pain, and narcotic usage were measured. RESULTS: There were no significant intraoperative complications or conversions to open surgery. Patients were discharged at 1.2 days on average. Early postoperative complications included a hernia site seroma in one patient, which resolved without intervention. There were no early postoperative infections or recurrences. Compared with traditional laparoscopic IPOM repair, there was less acute postoperative pain and use of analgesics. CONCLUSIONS: Laparoscopic extraperitoneal stapled sublay mesh repair is a safe and effective method for the treatment of medium- to large-sized ventral and incisional hernias. This extraperitoneal stapled approach using self-gripping mesh facilitates a minimally invasive sublay repair and abdominal wall reconstruction using traditional laparoscopic tools.


Asunto(s)
Herniorrafia/métodos , Laparoscopía , Mallas Quirúrgicas , Hernia Ventral , Humanos , Hernia Incisional , Complicaciones Posoperatorias , Recurrencia
13.
J Neurosci ; 33(34): 13713-23, 2013 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-23966693

RESUMEN

In the auditory cortex, synaptic inhibition is known to be involved in shaping receptive fields, enhancing temporal precision, and regulating gain. Cortical inhibition is provided by local GABAergic interneurons, which comprise 10-20% of the cortical population and can be separated into numerous subclasses. The morphological and physiological diversity of interneurons suggests that these different subclasses have unique roles in sound processing; however, these roles are yet unknown. Understanding the receptive field properties of distinct inhibitory cell types will be critical to elucidating their computational function in cortical circuits. Here we characterized the tuning and response properties of parvalbumin-positive (PV+) interneurons, the largest inhibitory subclass. We used channelrhodopsin-2 (ChR2) as an optogenetic tag to identify PV+ and PV- neurons in vivo in transgenic mice. In contrast to PV+ neurons in mouse visual cortex, which are broadly tuned for orientation, we found that auditory cortical PV+ neurons were well tuned for frequency, although very tightly tuned PV+ cells were uncommon. This suggests that PV+ neurons play a minor role in shaping frequency tuning, and is consistent with the idea that PV+ neurons nonselectively pool input from the local network. PV+ interneurons had shallower response gain and were less intensity-tuned than PV- neurons, suggesting that PV+ neurons provide dynamic gain control and shape intensity tuning in auditory cortex. PV+ neurons also had markedly faster response latencies than PV- neurons, consistent with a computational role in enhancing the temporal precision of cortical responses.


Asunto(s)
Corteza Auditiva/citología , Percepción Auditiva/fisiología , Interneuronas/metabolismo , Inhibición Neural/fisiología , Parvalbúminas/metabolismo , Estimulación Acústica , Potenciales de Acción/genética , Potenciales de Acción/fisiología , Animales , Channelrhodopsins , Femenino , Proteínas Fluorescentes Verdes/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Optogenética , Parvalbúminas/genética , Técnicas de Placa-Clamp , Estimulación Luminosa , Tiempo de Reacción/fisiología , Estadísticas no Paramétricas
15.
J Child Adolesc Psychopharmacol ; 33(4): 143-148, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36913518

RESUMEN

Objective: Fidgeting is a common symptom in patients with attention-deficit hyperactivity disorder (ADHD). The current study investigated ADHD stimulant medication effects on fidgeting in adolescents with ADHD during a short research study session using wrist-worn accelerometers. Method: Adolescents with ADHD who had been taking stimulant medications (ADHD group) and adolescents without ADHD (control group) participated in the study. Accelerometer data were obtained from both wrists of each participant to track their hand movements during two hearing testing sessions. All subjects in the ADHD group abstained from their stimulant medications for at least 24 hours before their first session (off-med session). The second session (on-med session) was conducted about 60-90 minutes after medication intake. The control group participated in two sessions in a similar time frame. Results: The current study focuses on relationships between hand movements and stimulant medication in adolescents with ADHD. Both conditions were compared to evaluate the relationship of hand movements and stimulant medication. We hypothesized the ADHD group will exhibit less hand movements during the on-medication session in comparison to off-medication session. Conclusion: Wrist-worn accelerometer measures obtained during nonphysical tasks in a short duration may not provide hand movement differences between on-med and off-med conditions in adolescents with ADHD. ClinicalTrials.gov Identifier: NCT04577417.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Adolescente , Humanos , Ansiedad , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Estimulantes del Sistema Nervioso Central/uso terapéutico
16.
J Child Neurol ; 37(6): 471-490, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35254148

RESUMEN

PURPOSE: Quantitative tractography using diffusion-weighted magnetic resonance imaging data is widely used in characterizing white matter microstructure throughout childhood, but more studies are still needed to investigate comprehensive brain-behavior relationships between tract-specific white matter measures and multiple cognitive functions in children. METHODS: In this study, we analyzed diffusion-weighted MRI data of 71 healthy 8-year-old children utilizing white matter tract-specific quantitative measures derived from diffusion-weighted MRI tractography based on a novel track-weighted imaging approach. Track density imaging, average path length map and 4 track-weighted diffusion tensor imaging measures including: mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for 63 white matter tracts. The track-weighted imaging measures were then correlated with a comprehensive set of neuropsychological test scores in different cognitive domains including intelligence, language, memory, academic skills, and executive functions to identify tract-specific brain-behavior relationships. RESULTS: Significant correlations (P < .05, false discovery rate corrected; r = 0.27-0.57) were found in multiple white matter tracts, with a total of 40 correlations identified between various track-weighted imaging measures including average path length map, track-weighted imaging-fractional anisotropy, and neuropsychological test scores and subscales. Specifically, track-weighted imaging measures indicative of better white matter connectivity and/or microstructural development significantly correlated with higher IQ and better language abilities. CONCLUSION: Our findings demonstrate the ability of track-weighted imaging measures in establishing associations between white matter and cognitive functioning in healthy children and can serve as a reference for normal brain/cognition relationships in young school-age children and further aid in identifying imaging biomarkers predictive of adverse neurodevelopmental outcomes.


Asunto(s)
Sustancia Blanca , Anisotropía , Encéfalo/diagnóstico por imagen , Niño , Cognición , Imagen de Difusión por Resonancia Magnética/métodos , Imagen de Difusión Tensora/métodos , Humanos , Sustancia Blanca/diagnóstico por imagen
17.
Front Hum Neurosci ; 16: 943341, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36147297

RESUMEN

Background: Physical activity is known to improve mental health, and is regarded as safe and desirable for uncomplicated pregnancy. In this novel study, we aim to evaluate whether there are associations between maternal physical activity during pregnancy and neonatal brain cortical development. Methods: Forty-four mother/newborn dyads were included in this longitudinal study. Healthy pregnant women were recruited and their physical activity throughout pregnancy were documented using accelerometers worn for 3-7 days for each of the 6 time points at 4-10, ∼12, ∼18, ∼24, ∼30, and ∼36 weeks of pregnancy. Average daily total steps and daily total activity count as well as daily minutes spent in sedentary/light/moderate/vigorous activity modes were extracted from the accelerometers for each time point. At ∼2 weeks of postnatal age, their newborns underwent an MRI examination of the brain without sedation, and 3D T1-weighted brain structural images were post-processed by the iBEAT2.0 software utilizing advanced deep learning approaches. Cortical surface maps were reconstructed from the segmented brain images and parcellated to 34 regions in each brain hemisphere, and mean cortical thickness for each region was computed for partial correlation analyses with physical activity measures, with appropriate multiple comparison corrections and potential confounders controlled. Results: At 4-10 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left caudal middle frontal gyrus (rho = 0.48, P = 0.04), right medial orbital frontal gyrus (rho = 0.48, P = 0.04), and right transverse temporal gyrus (rho = 0.48, P = 0.04); mother's daily time in moderate activity mode positively correlated with newborn's cortical thickness in the right transverse temporal gyrus (rho = 0.53, P = 0.03). At ∼24 weeks of pregnancy, mother's daily total activity count positively correlated (FDR corrected P ≤ 0.05) with newborn's cortical thickness in the left (rho = 0.56, P = 0.02) and right isthmus cingulate gyrus (rho = 0.50, P = 0.05). Conclusion: We identified significant relationships between physical activity in healthy pregnant women during the 1st and 2nd trimester and brain cortical development in newborns. Higher maternal physical activity level is associated with greater neonatal brain cortical thickness, presumably indicating better cortical development.

18.
Surgery ; 171(5): 1379-1387, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34774289

RESUMEN

BACKGROUND: Pathological treatment effect of resected pancreatic adenocarcinoma after neoadjuvant therapy has prognostic implications. The impact for patients who received chemotherapy alone or chemoradiotherapy is not well defined. METHODS: Patients with localized pancreatic adenocarcinoma who had pancreatectomy after neoadjuvant therapy at 3 centers from 2011 to 2017 were retrospectively analyzed. The chemotherapy and chemoradiotherapy groups were evaluated separately. RESULTS: Of 525 patients, 148 received neoadjuvant chemotherapy and 377 received chemoradiotherapy. The chemoradiotherapy group had a better treatment effect (score 0: 10%, score 1: 30%, score 2: 42%, and score 3: 18%) than the chemotherapy group (score 0: 2%, score 1: 8%, score 2: 35%, and score 3: 55%) (P < .001). Median overall survival was similar between the 2 groups (25.8 vs 26.4 months). Median overall survival for score 0/1, 2, or 3 was 72.2, 38.5, and 20.0 months in the chemotherapy group and 37.9, 24.5, and 19.0 months in the chemoradiotherapy group. Score 2 in the chemotherapy group was associated with better overall survival compared to score 3 (adjusted hazard ratio: 0.49, P = .005), whereas only combined score 0/1 reached significance over score 2 for the chemoradiotherapy group (hazard ratio: 0.63, P = .006). CONCLUSION: The prognostic significance of pathological treatment effect for localized pancreatic adenocarcinoma differs for patients receiving neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia , Humanos , Terapia Neoadyuvante , Neoplasias Pancreáticas/patología , Pronóstico , Estudios Retrospectivos , Neoplasias Pancreáticas
19.
PLoS One ; 16(10): e0258815, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34669741

RESUMEN

Rigorous healthcare design research is critical to inform design decisions that improve human experience. Current limitations in the field include a lack of consistent and valid measures that provide feedback about the role of the built environment in producing desirable outcomes. Research findings about nurses' efficiency, quality of care, and satisfaction related to inpatient unit designs have been mixed, and there was previously no validated instrument available to quantitatively measure nurses' ability to work efficiently and effectively in their environment. The objective of this study was to develop, refine, and validate a survey instrument to measure affordance of the care environment to nurse practice, based on various aspects of their work in inpatient units. The HDR Clinical Activities Related to the Environment (CARE) Scale Inpatient Version was developed using item design, refinement, and reliability and validity testing. Psychometric methods from classical test theory and item response theory, along with statistical analyses involving correlations and factor analysis, and thematic summaries of qualitative data were conducted. The four-phase process included (1) an initial pilot study, (2) a content validation survey, (3) cognitive interviews, and (4) a final pilot study. Results from the first three phases of analysis were combined to inform survey scale revisions before the second pilot survey, such as a reduction in the number and rewording of response options, and refinement of scale items. The updated 9-item scale showed excellent internal consistency and improved response distribution and discrimination. The factor analysis revealed a unidimensional measure of nurse practice, as well as potential subscales related to integration, efficiency, and patient care. Within the healthcare design industry, this scale is much needed to generate quantitative and standardized data and will facilitate greater understanding about the aspects of an inpatient healthcare facility that best support nurses' ability to provide quality patient care.


Asunto(s)
Atención de Enfermería/normas , Satisfacción del Paciente/estadística & datos numéricos , Psicometría/métodos , Adulto , Análisis Factorial , Femenino , Instituciones de Salud , Investigación sobre Servicios de Salud , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Encuestas y Cuestionarios
20.
Ecol Evol ; 11(18): 12542-12553, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34594519

RESUMEN

Environmental adaptation and species divergence often involve suites of co-evolving traits. Pigmentation in insects presents a variable, adaptive, and well-characterized class of phenotypes for which correlations with multiple other traits have been demonstrated. In Drosophila, the pigmentation genes ebony and tan have pleiotropic effects on flies' response to light, creating the potential for correlated evolution of pigmentation and vision. Here, we investigate differences in light preference within and between two sister species, Drosophila americana and D. novamexicana, which differ in pigmentation in part because of evolution at ebony and tan and occupy environments that differ in many variables including solar radiation. We hypothesized that lighter pigmentation would be correlated with a greater preference for environmental light and tested this hypothesis using a habitat choice experiment. In a first set of experiments, using males of D. novamexicana line N14 and D. americana line A00, the light-bodied D. novamexicana was found slightly but significantly more often than D. americana in the light habitat. A second experiment, which included additional lines and females as well as males, failed to find any significant difference between D. novamexicana-N14 and D. americana-A00. Additionally, the other dark line of D. americana (A04) was found in the light habitat more often than the light-bodied D. novamexicana-N14, in contrast to our predictions. However, the lightest line of D. americana, A01, was found substantially and significantly more often in the light habitat than the two darker lines of D. americana, thus providing partial support for our hypothesis. Finally, across all four lines, females were found more often in the light habitat than their more darkly pigmented male counterparts. Additional replication is needed to corroborate these findings and evaluate conflicting results, with the consistent effect of sex within and between species providing an especially intriguing avenue for further research.

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