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1.
Chem Commun (Camb) ; 60(42): 5490-5493, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38699837

ABSTRACT

The immobilisation of artificial metalloenzymes (ArMs) holds promise for the implementation of new biocatalytic reactions. We present the synthesis of cross-linked artificial metalloenzyme aggregates (CLArMAs) with excellent recyclability, as an alternative to carrier-based immobilisation strategies. Furthermore, iron-siderophore supramolecular anchoring facilitates redox-triggered cofactor release, enabling CLArMAs to be recharged with alternative cofactors for diverse selectivity.


Subject(s)
Oxidation-Reduction , Siderophores , Siderophores/chemistry , Stereoisomerism , Metalloproteins/chemistry , Metalloproteins/metabolism , Catalysis , Biocatalysis , Cross-Linking Reagents/chemistry , Iron/chemistry
2.
EMBO J ; 42(19): e113880, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37602956

ABSTRACT

Dermal Fibroblast Progenitors (DFPs) differentiate into distinct fibroblast lineages during skin development. However, the epigenetic mechanisms that regulate DFP differentiation are not known. Our objective was to use multimodal single-cell approaches, epigenetic assays, and allografting techniques to define a DFP state and the mechanism that governs its differentiation potential. Our initial results indicated that the overall transcription profile of DFPs is repressed by H3K27me3 and has inaccessible chromatin at lineage-specific genes. Surprisingly, the repressive chromatin profile of DFPs renders them unable to reform the skin in allograft assays despite their multipotent potential. We hypothesized that chromatin derepression was modulated by the H3K27me3 demethylase, Kdm6b/Jmjd3. Dermal fibroblast-specific deletion of Kdm6b/Jmjd3 in mice resulted in adipocyte compartment ablation and inhibition of mature dermal papilla functions, confirmed by additional single-cell RNA-seq, ChIP-seq, and allografting assays. We conclude that DFPs are functionally derepressed during murine skin development by Kdm6b/Jmjd3. Our studies therefore reveal a multimodal understanding of how DFPs differentiate into distinct fibroblast lineages and provide a novel publicly available multiomics search tool.


Subject(s)
Chromatin , Histones , Animals , Mice , Chromatin/genetics , Histones/genetics , Histones/metabolism , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Cell Differentiation/genetics , Demethylation , Fibroblasts/metabolism
3.
J Pediatr ; 262: 113563, 2023 11.
Article in English | MEDLINE | ID: mdl-37329979

ABSTRACT

OBJECTIVE: To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. STUDY DESIGN: In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3 weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. RESULTS: All 2x taVNS treated infants significantly increased their feeding volumes compared with 10 days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5 days [1x], P < .05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. CONCLUSIONS: In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04643808).


Subject(s)
Transcutaneous Electric Nerve Stimulation , Vagus Nerve Stimulation , White Matter , Female , Humans , Infant , White Matter/diagnostic imaging , Vagus Nerve Stimulation/methods , Gastrostomy , Prospective Studies , Transcutaneous Electric Nerve Stimulation/methods , Vagus Nerve/physiology
4.
Pediatr Emerg Care ; 39(5): 360-363, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37079552

ABSTRACT

BACKGROUND/OBJECTIVE: Throughout the pandemic, febrile seizures have resulted from infection secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The objective of this study is to determine if there is an increased association between COVID-19 and febrile seizures as compared with other causes of febrile seizures. METHODS: This was a retrospective case control study. Data were collected from the National Institute of Health (NIH) supported National COVID Cohort Collaborative (N3C). Patients from 6 to 60 months who were tested for COVID-19 were included; cases were defined as COVID-19-positive patients whereas controls were defined as COVID-19-negative patients. Febrile seizures diagnosed within 48 hours of the COVID-19 test were considered to be associated with the test result. Patients were subjected to a stratified gender and date matching design followed by a logistic regression controlling for age and race. RESULTS: During the study period, 27,692 patients were included. Of those, 6923 patients were COVID-19-positive, among which 189 had febrile seizures (2.7%). After logistic regression, the likelihood of having febrile seizures concurrently with COVID-19 as compared with other causes was 0.96 ( P = 0.949; confidence interval, 0.81, 1.14). CONCLUSIONS: There were 2.7% of the patients with COVID-19 that were diagnosed with a febrile seizure. However, when subjected to a matched case control design with logistic regression controlling for confounding variables, there does not appear to be an increased risk of febrile seizures secondary to COVID-19 as compared with other causes.


Subject(s)
COVID-19 , Seizures, Febrile , Humans , Seizures, Febrile/epidemiology , Seizures, Febrile/etiology , Seizures, Febrile/diagnosis , COVID-19/complications , COVID-19/epidemiology , Case-Control Studies , Retrospective Studies , SARS-CoV-2
5.
Front Vet Sci ; 10: 1137078, 2023.
Article in English | MEDLINE | ID: mdl-37008349

ABSTRACT

Introduction: Stressors predisposing to bovine respiratory disease (BRD) upon arrival in the feedlot, include the ranch to feedlot transition and mixing cattle from multiple sources. Preconditioning (PC) reduces multiple stressors, but commingling PC and auction-derived (AD) calves in a feedlot may increase BRD risk. Our objective was to evaluate PC calf performance over the first 40 days in the feedlot and determine impacts of commingling with varying proportions of AD calves (25, 50, and 75%). Methods: Calves were either preconditioned at one ranch (n = 250) or mixed-source and bought from a local auction (n = 250). At arrival, calves were assigned into 1 of 5 pens: 100 PC, 75 PC, 50 PC, 25 PC, and 0 PC, reflecting the percentage of PC calves in a 100-head pen. Results: Over 40 days, morbidity in pen 100 PC was lower compared to 0 PC (24 vs. 50%, P < 0.001) and varied in commingled pens, being highest (63%) in 25 PC and least (21%) in 50 PC (P < 0.05). There were 3 AD deaths in 0 PC and 2 deaths in 25 PC. The AD calves in 0 PC were 3 times more likely to get BRD than PC calves in 100 PC; however, AD calves gained 0.49 kg/d more than PC calves (P < 0.0001). Ignoring pen placement, AD calves were 2.76 times more likely to get BRD but gained 0.27 kg/d more than PC calves (P < 0.0001). Commingling did not affect morbidity of PC (P = 0.5) or AD calves (P = 0.96), implying commingling did not affect health. Calves in 25 PC were 3.39 times more likely to get BRD than those in the 100 PC (P < 0.001). Furthermore, 25 PC calves gained the most (1.08 kg/d), followed by 50 PC (0.62 kg/d) and 75 PC (0.61 kg/d), compared to 100 PC (P < 0.05). Calf weight at arrival modified ADG (P < 0.05). Discussion: In conclusion, PC calves had lower morbidity over the first 40 days, irrespective of commingling. With larger variations in arrival weight, there was no advantage of PC for ADG in the first 40 days. The unknown weaning strategies and comparable arrival weights of AD calves may have contributed to greater ADG in AD calves.

6.
bioRxiv ; 2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36945417

ABSTRACT

Dermal Fibroblast Progenitors (DFPs) differentiate into distinct fibroblast lineages during skin development. However, the mechanisms that regulate lineage commitment of naive dermal progenitors to form niches around the hair follicle, dermis, and hypodermis, are unknown. In our study, we used multimodal single-cell approaches, epigenetic assays, and allografting techniques to define a DFP state and the mechanisms that govern its differentiation potential. Our results indicate that the overall chromatin profile of DFPs is repressed by H3K27me3 and has inaccessible chromatin at lineage specific genes. Surprisingly, the repressed chromatin profile of DFPs renders them unable to reform skin in allograft assays despite their multipotent potential. Distinct fibroblast lineages, such as the dermal papilla and adipocytes contained specific chromatin profiles that were de-repressed during late embryogenesis by the H3K27-me3 demethylase, Kdm6b/Jmjd3. Tissue-specific deletion of Kdm6b/Jmjd3 resulted in ablating the adipocyte compartment and inhibiting mature dermal papilla functions in single-cell-RNA-seq, ChIPseq, and allografting assays. Altogether our studies reveal a mechanistic multimodal understanding of how DFPs differentiate into distinct fibroblast lineages, and we provide a novel multiomic search-tool within skinregeneration.org.

7.
Cureus ; 14(9): e29569, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36312605

ABSTRACT

INTRODUCTION: Vaso-occlusive crises (VOCs) are the leading cause of emergency department (ED) visits and hospitalizations in patients with sickle cell disease (SCD). Timely administration of analgesia, within 60 minutes of patient registration, is the standard of care for SCD patients with VOCs. Patients with VOCs have longer times to initial analgesia compared to similar painful conditions. The primary aim of the project is to have 75% of patients with VOCs receive initial analgesia within 60 minutes of being registered, the current recommended time frame from the National Heart, Lung, and Blood Institute (NHLBI). METHODS: A multi-disciplinary team used quality improvement (QI) methodology to develop a plan involving multiple Plan-Do-Study-Act (PDSA) cycles. A rapid evaluation process was employed which included notification of a patient with a VOC being placed in a room, rapid evaluation by all team members and use of an electronic order set. RESULTS: The aim was met 72% of the time during our intervention period, compared to 17% pre-intervention. Average time to initial analgesia was decreased from 61 minutes to 42 minutes (p-value < 0.001), while time to disposition was also decreased when time goals were achieved. CONCLUSION: Using a rapid evaluation process we were able to decrease time to initial analgesia in a patient population that has previously experienced delays in care and decrease overall time to disposition.

8.
Neuromodulation ; 25(3): 309-315, 2022 04.
Article in English | MEDLINE | ID: mdl-35396067

ABSTRACT

OBJECTIVES: Vagus nerve stimulation (VNS) is reemerging as an exciting form of brain stimulation, due in part to the development of its noninvasive counterpart transcutaneous auricular VNS. As the field grows, it is important to understand where VNS emerged from, including its history and the studies that were conducted over the past four decades. Here, we offer a comprehensive review of the history of VNS in the treatment of major depression. MATERIALS AND METHODS: Using PubMed, we reviewed the history of VNS and aggregated the literature into a narrative review of four key VNS epochs: 1) early invention and development of VNS, 2) path to Food and Drug Administration (FDA) approval for depression, 3) refinement of VNS treatment parameters, and 4) neuroimaging of VNS. RESULTS: VNS was described in the literature in the early 1900s; however, gained traction in the 1980s as Zabara and colleagues developed an implantable neurocybernetic prosthesis to treat epilepsy. As epilepsy trials proceed in the 1990s, promising mood effects emerged and were studied, ultimately leading to the approval of VNS for depression in 2005. Since then, there have been advances in understanding the mechanism of action. Imaging techniques like functional magnetic resonance imaging and positron emission tomography further aid in understanding direct brain effects of VNS. CONCLUSIONS: The mood effects of VNS were discovered from clinical trials investigating the use of VNS for reducing seizures in epileptic patients. Since then, VNS has gone on to be FDA approved for depression. The field of VNS is growing, and as noninvasive VNS quickly advances, it is important to consider a historical perspective to develop future brain stimulation therapies.


Subject(s)
Epilepsy , Transcutaneous Electric Nerve Stimulation , Vagus Nerve Stimulation , Depression , Epilepsy/therapy , Humans , Vagus Nerve/physiology , Vagus Nerve Stimulation/methods
9.
J Invest Dermatol ; 142(7): 1812-1823.e3, 2022 07.
Article in English | MEDLINE | ID: mdl-34922949

ABSTRACT

One of the keys to achieving skin regeneration lies within understanding the heterogeneity of neonatal fibroblasts, which support skin regeneration. However, the molecular underpinnings regulating the cellular states and fates of these cells are not fully understood. To investigate this, we performed a parallel multiomics analysis by processing neonatal murine skin for single-cell Assay for Transposase-Accessible Chromatin sequencing and single-cell RNA sequencing separately. Our approach revealed that fibroblast clusters could be sorted into papillary and reticular lineages on the basis of transcriptome profiling, as previously reported. However, single-cell Assay for Transposase-Accessible Chromatin sequencing analysis of neonatal fibroblast lineage markers, such as Dpp4/Cd26, Corin, and Dlk1 along with markers of myofibroblasts, revealed accessible chromatin in all fibroblast populations despite their lineage-specific transcriptome profiles. These results suggest that accessible chromatin does not always translate to gene expression and that many fibroblast lineage markers reflect a fibroblast state, which includes neonatal papillary fibroblasts, reticular fibroblasts, and myofibroblasts. This analysis also provides a possible explanation as to why these marker genes can be promiscuously expressed in different fibroblast populations under different conditions. Our single-cell Assay for Transposase-Accessible Chromatin sequencing analysis also revealed that the functional lineage restriction between dermal papilla and adipocyte fates is regulated by distinct chromatin landscapes. Finally, we have developed a webtool for our multiomics analysis: https://skinregeneration.org/scatacseq-and-scrnaseq-data-from-thompson-et-al-2021-2/.


Subject(s)
Fibroblasts , Single-Cell Analysis , Animals , Chromatin/genetics , Chromatin/metabolism , Fibroblasts/metabolism , Mice , Skin , Transposases/metabolism
10.
JMIR Med Educ ; 7(4): e29486, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-34591779

ABSTRACT

BACKGROUND: Due to challenges related to the COVID-19 pandemic, residency programs in the United States conducted virtual interviews during the 2020-2021 application season. As a result, programs and applicants may have relied more heavily on social media-based communication and dissemination of information. OBJECTIVE: We sought to determine social media's impact on residency applicants during an entirely virtual application cycle. METHODS: An anonymous electronic survey was distributed to 465 eligible 2021 Match applicants at 4 University of California Schools of Medicine in the United States. RESULTS: A total of 72 participants (15.5% of eligible respondents), applying to 16 specialties, responded. Of those who responded, 53% (n=38) reported following prospective residency accounts on social media, and 89% (n=34) of those respondents were positively or negatively influenced by these accounts. The top three digital methods by which applicants sought information about residency programs included the program website, digital conversations with residents and fellows of that program, and Instagram. Among respondents, 53% (n=38) attended virtual information sessions for prospective programs. A minority of applicants (n=19, 26%) adjusted the number of programs they applied to based on information found on social media, with most (n=14, 74%) increasing the number of programs to which they applied. Survey respondents ranked social media's effectiveness in allowing applicants to learn about programs at 6.7 (SD 2.1) on a visual analogue scale from 1-10. Most applicants (n=61, 86%) felt that programs should use social media in future application cycles even if they are nonvirtual. CONCLUSIONS: Social media appears to be an important tool for resident recruitment. Future studies should seek more information on its effect on later parts of the application cycle and the Match.

11.
Front Neurosci ; 15: 709436, 2021.
Article in English | MEDLINE | ID: mdl-34326720

ABSTRACT

Vagus nerve stimulation (VNS) is an established form of neuromodulation with a long history of promising applications. Earliest reports of VNS in the literature date to the late 1800's in experiments conducted by Dr. James Corning. Over the past century, both invasive and non-invasive VNS have demonstrated promise in treating a variety of disorders, including epilepsy, depression, and post-stroke motor rehabilitation. As VNS continues to rapidly grow in popularity and application, the field generally lacks a consensus on optimum stimulation parameters. Stimulation parameters have a significant impact on the efficacy of neuromodulation, and here we will describe the longitudinal evolution of VNS parameters in the following categorical progression: (1) animal models, (2) epilepsy, (3) treatment resistant depression, (4) neuroplasticity and rehabilitation, and (5) transcutaneous auricular VNS (taVNS). We additionally offer a historical perspective of the various applications and summarize the range and most commonly used parameters in over 130 implanted and non-invasive VNS studies over five applications.

12.
Cell ; 184(15): 3852-3872, 2021 07 22.
Article in English | MEDLINE | ID: mdl-34297930

ABSTRACT

Fibroblasts are diverse mesenchymal cells that participate in tissue homeostasis and disease by producing complex extracellular matrix and creating signaling niches through biophysical and biochemical cues. Transcriptionally and functionally heterogeneous across and within organs, fibroblasts encode regional positional information and maintain distinct cellular progeny. We summarize their development, lineages, functions, and contributions to fibrosis in four fibroblast-rich organs: skin, lung, skeletal muscle, and heart. We propose that fibroblasts are uniquely poised for tissue repair by easily reentering the cell cycle and exhibiting a reversible plasticity in phenotype and cell fate. These properties, when activated aberrantly, drive fibrotic disorders in humans.


Subject(s)
Disease , Fibroblasts/metabolism , Health , Animals , Cell Lineage , Humans , Molecular Targeted Therapy , Signal Transduction
13.
Am Surg ; 87(10): 1616-1620, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34139895

ABSTRACT

BACKGROUND: Recent studies have revealed a high rate of burnout among general surgery (GS) residents. Efforts to design and implement interventions to mitigate fatigue in surgical trainees are critical. Our aim was to assess the educational and wellness impact of outpatient scribe utilization at an academic GS residency program. METHODS: Electronic surveys were sent to 38 GS residents and 15 faculties who used outpatient scribes for at least 12 months. Questions were scored on a 5-point Likert scale with answers of "Strongly agree" or "Agree" representing affirmative responses. RESULTS: Thirty residents and 14 faculty completed the survey, resulting in an 83% overall response rate. Twenty-eight (93%) residents and 12 (86%) faculty believed that scribes decrease the daily workload of trainees. Twenty-seven (90%) residents felt that scribes allow them more time to focus on patient care and improve the quality of their surgical education. Ninety-three percent of residents (n = 28) and faculty (n = 13) believed that scribes enhance resident well-being. Twenty-four (80%) residents reported that scribes help improve adherence to duty hour restrictions. Twenty-five (83%) residents believed that utilizing scribes is an effective fatigue mitigation strategy for surgical training programs. CONCLUSION: Our findings demonstrate that the implementation of an outpatient scribe program at an academic GS residency program may enhance resident education and wellness.


Subject(s)
Allied Health Personnel , Burnout, Professional/prevention & control , General Surgery/education , Health Promotion , Physicians/psychology , Adult , Education, Medical, Graduate , Educational Measurement , Faculty, Medical/psychology , Female , Humans , Internship and Residency , Male , Personnel Staffing and Scheduling , Surveys and Questionnaires , Workload
14.
Optom Vis Sci ; 98(3): 289-294, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33633020

ABSTRACT

SIGNIFICANCE: The SVOne may prove useful to quickly and easily assess refractive correction needs in community screenings and low-resource settings, but not all subjects were testable with the device. PURPOSE: This study aimed to compare the SVOne handheld, smartphone-based wavefront aberrometer with a tabletop autorefractor in identifying refractive errors in elderly subjects. METHODS: Participants 50 years or older at community eye screenings with visual acuity worse than 20/40 in either eye underwent autorefraction followed by two SVOne trials. Power vectors of right eye data were analyzed. RESULTS: Of 84 subjects who underwent autorefraction, 67 (79.8%) were successfully autorefracted with the SVOne, of whom 82.1% (55/67) had a successful repeat reading. Mean M (spherical equivalent) values from tabletop and handheld autorefraction were -0.21 D (95% confidence interval [CI], -0.71 to +0.29 D) and -0.29 D (95% CI, -0.79 to +0.21 D), respectively (P > .05). Mean astigmatism values from tabletop and handheld devices were +1.06 D (95% CI, 0.87 to 1.26 D) and +1.21 D (95% CI, 0.99 to 1.43 D), respectively (P > .05). Intraclass correlation coefficients between devices were 0.95 (95% CI, 0.93 to 0.97) for M, 0.78 (95% CI, 0.66 to 0.86) for J0, and 0.45 (95% CI, 0.24 to 0.63) for J45 (P < .05 for all). Excellent test-retest correlation between SVOne measurements was noted for M (Pearson correlation [r] = 0.96; P < .05), but a weaker correlation was noted for J0 and J45 (r = 0.67 and r = 0.63 [P < .05 for both], respectively). CONCLUSIONS: The SVOne provided strong agreement for M, with the majority of readings within ±1.00 D of each other, when compared with the tabletop autorefractor. A weaker but still good correlation was noted for astigmatism. Similar findings were noted when assessing repeatability.


Subject(s)
Aberrometry/instrumentation , Corneal Wavefront Aberration/diagnosis , Refraction, Ocular/physiology , Refractive Errors/diagnosis , Vision Screening/methods , Aged , Aged, 80 and over , Community Health Services/methods , Corneal Wavefront Aberration/physiopathology , Female , Humans , Male , Middle Aged , Refractive Errors/physiopathology , Reproducibility of Results , Visual Acuity/physiology
15.
J Educ Teach Emerg Med ; 6(1): V9-V11, 2021 Jan.
Article in English | MEDLINE | ID: mdl-37465542

ABSTRACT

Hemoptysis is a common presenting symptom of hereditary hemorrhagic telangiectasia (HHT), an often overlooked diagnosis in the emergency setting. Patient history often includes telangiectasias, epistaxis, visceral lesions, and a family history of similar findings. Here, we review a case of HHT in a young woman, presenting initially with hemoptysis. Imaging was significant for large left upper lobe arteriovenous malformation (AVM), requiring patient admission and interventional radiology embolization of the AVM. The purpose of this report is to highlight a diagnosis that is important not to miss in the emergency department. Topics: Pulmonary arteriovenous malformation, hereditary hemorrhagic telangiectasia, Osler-Weber-Rendu syndrome.

16.
J Pediatr Hematol Oncol ; 42(6): 375-380, 2020 08.
Article in English | MEDLINE | ID: mdl-32569034

ABSTRACT

Sickle cell disease (SCD) can lead to potentially devastating complications that occur secondary to vaso-occlusion. Current national clinical guidelines are largely based on expert opinion, resulting in significant variation of management. Provider awareness regarding emergency department (ED) management of vaso-occlusive crises (VOC) remains unknown. A 23-question assessment of VOC management was administered to all eligible ED providers at Riley Hospital for Children between September and November 2018. Univariate analyses were performed to evaluate responses between groups. Of 52 respondents comprised of ED staff attendings (27%), resident trainees (58%), and ED nurses (15%), the majority were not aware of SCD management guidelines being available. Approximately 54% of providers endorsed a high comfort level in managing VOC, with staff and nurses more likely to report this than trainees (P=0.02). Less than 10% of all providers knew the recommended timeframe from triage to initial medication administration. Prolonged time between pain assessments was reported by 25% of providers with a high comfort level in managing VOC, which was similar to providers with a lower comfort level (13%, P=0.217). Only one fourth of all respondents appropriately did not use vital signs as an indication of a patient's pain level, and >10% reported not utilizing patient-reported pain scores. This was not significantly different between provider comfort levels (P=0.285 and 0.412, relatively). Our results suggest education regarding recommended practices was inadequate regardless of reported provider comfort. Further provider education and/or standardized ED VOC management guidelines may serve as areas for improvement in SCD care.


Subject(s)
Anemia, Sickle Cell/complications , Emergency Service, Hospital/statistics & numerical data , Health Personnel/psychology , Pain Management/methods , Pain/prevention & control , Acute Disease , Adult , Child , Cross-Sectional Studies , Female , Humans , Male , Pain/etiology , Pain Measurement , Surveys and Questionnaires
17.
Brain Stimul ; 13(3): 800-803, 2020.
Article in English | MEDLINE | ID: mdl-32289710

ABSTRACT

BACKGROUND: Studies have found that pairing vagus nerve stimulation (VNS) with motor activity accelerates cortical reorganization. This synchronous pairing may enhance motor recovery. OBJECTIVE: To develop and validate a motor-activated auricular vagus nerve stimulation (MAAVNS) system as a potential neurorehabilitation tool. METHODS: We created MAAVNS and validated its function as part of an ongoing clinical trial investigating whether taVNS-paired rehabilitation enhances oromotor learning. We compared 3 different MAAVNS EMG electrode configurations in 3 neonates. The active lead was placed over the buccinator muscle. Reference lead placements were orbital, temporal or frontal. RESULTS: The frontal reference lead produced the highest sensitivity (0.87 ± 0.07 (n = 8)) and specificity (0.64 ± 0.13 (n = 8)). Oral sucking reliably triggers MAAVNS stimulation with high confidence. CONCLUSION: EMG electrodes placed on target orofacial muscles can effectively trigger taVNS stimuli in infants in a closed loop fashion.


Subject(s)
Motor Activity/physiology , Neurological Rehabilitation/methods , Neurological Rehabilitation/standards , Vagus Nerve Stimulation/methods , Vagus Nerve Stimulation/standards , Electromyography/methods , Electromyography/standards , Female , Humans , Infant, Newborn , Reproducibility of Results , Stroke Rehabilitation/methods , Stroke Rehabilitation/standards , Vagus Nerve/physiology
18.
Front Hum Neurosci ; 14: 77, 2020.
Article in English | MEDLINE | ID: mdl-32256328

ABSTRACT

Neonates born premature or who suffer brain injury at birth often have oral feeding dysfunction and do not meet oral intake requirements needed for discharge. Low oral intake volumes result in extended stays in the hospital (>2 months) and can lead to surgical implant and explant of a gastrostomy tube (G-tube). Prior work suggests pairing vagus nerve stimulation (VNS) with motor activity accelerates functional improvements after stroke, and transcutaneous auricular VNS (taVNS) has emerged as promising noninvasive form of VNS. Pairing taVNS with bottle-feeding rehabilitation may improve oromotor coordination and lead to improved oral intake volumes, ultimately avoiding the need for G-tube placement. We investigated whether taVNS paired with oromotor rehabilitation is tolerable and safe and facilitates motor learning in infants who have failed oral feeding. We enrolled 14 infants [11 premature and 3 hypoxic-ischemic encephalopathy (HIE)] who were slated for G-tube placement in a prospective, open-label study of taVNS-paired rehabilitation to increase feeding volumes. Once-daily taVNS was delivered to the left tragus during bottle feeding for 2 weeks, with optional extension. The primary outcome was attainment of oral feeding volumes and weight gain adequate for discharge without G-tube while also monitoring discomfort and heart rate (HR) as safety outcomes. We observed no adverse events related to stimulation, and stimulation-induced HR reductions were transient and safe and likely confirmed vagal engagement. Eight of 14 participants (57%) achieved adequate feeding volumes for discharge without G-tube (mean treatment length: 16 ± 6 days). We observed significant increases in feeding volume trajectories in responders compared with pre-stimulation (p < 0.05). taVNS-paired feeding rehabilitation appears safe and may improve oral feeding in infants with oromotor dyscoordination, increasing the rate of discharge without G-tube, warranting larger controlled trials.

19.
J Educ Teach Emerg Med ; 5(4): T1-T44, 2020 Oct.
Article in English | MEDLINE | ID: mdl-37465339

ABSTRACT

Audience: This classic team-based learning activity is specifically designed for emergency medicine bound medical students and junior residents; however, general pediatrics residents and general medical students may also benefit from this activity. Senior residents and fellows felt that the cases were too basic for them but enjoyed acting as facilitators. Introduction/Background: Vomiting is a common chief complaint in pediatric patients seen in the Emergency Department. 1-3 Presentations include acute, chronic, and cyclic vomiting, with underlying etiologies such as toxin injection, emotional disturbances, and movement disequilibrium. 1 By understanding these various pathways, it is helpful for physicians to distinguish between gastrointestinal and non-gastrointestinal causes of vomiting. 1 Most cases of vomiting in the pediatric population are self-limiting and require only supportive treatment; however, physicians must be able to recognize red flags associated with vomiting that warrant further evaluation. 1,3 This task may be challenging for medical students and residents in emergency medicine and those with infrequent exposure to pediatric patients. Therefore, this team-based learning activity was developed to help junior learners in differentiating non-emergent and emergent cases of pediatric vomiting. This activity aids learners in formulating a differential based on age, history, and characteristics of vomiting. We also review specific causes of pediatric vomiting that physicians cannot miss including intussusception, pyloric stenosis, malrotation, intestinal atresia, and intracranial pathology. Educational Objectives: By the end of this TBL session, learners should be able to:Identify red flag symptoms that should prompt referral for urgent intervention by GI or surgical specialists.Recognize how chronicity of the vomiting can alter the differential diagnosisDescribe the varying pathways that can cause nausea and vomiting.Determine the necessity of imaging tests to confirm and possibly treat various causes of vomiting.Interpret imaging studies associated with specific causes of vomiting. Educational Methods: Classic Team Based Learning (cTBL). Research Methods: Learners and instructors provided verbal feedback after the session in a large group format. Learners were specifically asked if they felt the session was education, relevant, high-yield and level appropriate. One instructor provided written feedback to the cases as well. Results: Overall learners and instructors found the session to be engaging, informative and educational. Learners felt that the session was level appropriate for medical students and junior residents. As a result of feedback from the session, several of the iRAT/gRAT questions were adjusted and the group application cases were re-written and implemented. Discussion: Overall, the educational content and delivery was effective. This session was presented to a group of emergency medicine students, interns and residents. Learners were divided into smaller groups, and each group had a variety of level of learners, including pediatric emergency medicine fellows, present. The fellows, while not necessary to the delivery of the TBL, were extremely helpful in aiding the residents during the session. The final debriefing and answer review were essential to ensure that learners met all educational objectives and fully understood the materials. Topics: Pediatric vomiting, intussusception, pyloric stenosis, intestinal atresia, malrotation, gastroesophageal reflux disease, superior mesenteric artery (SMA) syndrome, hyperemesis.

20.
ChemSusChem ; 11(23): 4007-4017, 2018 Dec 11.
Article in English | MEDLINE | ID: mdl-30291806

ABSTRACT

Reaction pathways for the conversion of cellulose into C2 -C6 monoalcohols by supercritical methanol depolymerization and hydrodeoxygenation (SCM-DHDO) over a CuMgAl oxide catalyst have been elucidated using a range of model compounds. SCM-DHDO of intermediate oxygenates including glycerol, methyl lactate, and 1,2-ethanediol produces similar products as those produced from the SCM-DHDO of cellulose. The pathway to C2 -C6 monoalcohols occurs through rapid C-C coupling reactions between methanol and diols followed by C-C scission between vicinal alcohol groups to produce two monoalcohols. Methyl-branched monoalcohols are produced through a methyl shift in a secondary diol followed by dehydration. Esters are produced by dehydrogenative coupling between an adsorbed methoxy and a primary alcohol. Both dehydrogenation to a ketone and esterification to a methyl ester are in equilibrium with the corresponding alcohol and were reversible. Dehydration of diols is the slowest observed reaction and not a main pathway to monoalcohols. SCM-DHDO of glucose, dihydroxyacetone, and cellulose all produced similar high molecular weight species indicating that condensation of intermediates can produce undesired side products.

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