Janice Massey - Academia.edu (original) (raw)
Papers by Janice Massey
Pathogenic Th17 Cells in Autoimmune Myasthenia Gravis Exhibit a Pro-inflammatory Transcriptomic Signature that Promotes Disease Pathogenesis (S41.008)
Neurology, May 2, 2022
Autoimmunity, Aug 11, 2016
An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, auto... more An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune diseases populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR+ MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age=72.9 years; baseline MG-Composite=21; median TPE treatments=6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (approximately 60-70% reduction). Three weeks post-TPE mean AChR autoantibody, total IgG, IgG1 and IgG2 titers were below the reference range and had not recovered to within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns
Neuromuscular Disorders and Pregnancy
Continuum, Feb 1, 2022
ABSTRACT PURPOSE OF REVIEW This article provides an overview of neuromuscular disorders in pregna... more ABSTRACT PURPOSE OF REVIEW This article provides an overview of neuromuscular disorders in pregnancy, with a focus on diagnosis and management. RECENT FINDINGS Neuromuscular disorders with issues that occur in pregnancy include conditions that are acquired (including autoimmune) or genetic; each requires a unique approach to management and treatment prepartum, peripartum, and postpartum. Guidance in the literature regarding management and treatment options is predominantly from case series and retrospective reviews. Treatment can be complex, particularly in autoimmune neuromuscular diseases, because of the risks of side effects of the treatments that may affect the patient and fetus. SUMMARY This article summarizes expectations, diagnosis, and management for a wide range of neuromuscular disorders in pregnancy.
Archives of Otolaryngology-head & Neck Surgery, Jul 1, 1989
To the Editor.\p=m-\In their article "Management of Facial Spasm With Clostridium botulinum Toxin... more To the Editor.\p=m-\In their article "Management of Facial Spasm With Clostridium botulinum Toxin, Type A (Oculinum),"1 the authors report the use of botulinum toxin in 105 patients with "no lasting complications or systemic effects." They conclude that botulinum A toxin appears to be a safe,
Pregnancy in MuSK‐positive myasthenia gravis: A single‐center case series
Muscle & Nerve
Introduction/AimsMyasthenia gravis (MG) with muscle‐specific tyrosine kinase (MuSK) antibodies (M... more Introduction/AimsMyasthenia gravis (MG) with muscle‐specific tyrosine kinase (MuSK) antibodies (MMG) is predominantly seen in women of childbearing age. Our objective in this study was to describe the course of MMG during pregnancy and within 6 months postpartum, and to document any effect on fetal health.MethodsA retrospective review was performed of medical records of patients with MMG seen in the Duke Myasthenia Gravis Clinic from 2003 to 2022. MMG patients with onset of MMG symptoms before or during pregnancy as well as within 6 months postpartum were reviewed.ResultsA total of 14 pregnancies in 10 patients were included in our study cohort. Initial MG symptoms developed during pregnancy or within 6 months postpartum in six patients. Four patients had two pregnancies, three of whom developed MG during their first pregnancy. In the patients diagnosed before pregnancy, MG symptoms increased in five of eight patients during pregnancy or postpartum. Four patients required rescue the...
Muscle & Nerve, 2020
BackgroundThe immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly unde... more BackgroundThe immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG.MethodsWe performed high‐dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery‐replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG.ResultsAn increase in CD19+CD20−CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P‐value = .0003, replication P‐value = .0021). Interleukin (IL) ‐21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P = .004).ConclusionsReduced plasmablast frequencies are strongly associated with a SN ...
Effects of Therapeutic Plasma Exchange on Myasthenic Outcome Measures (P3.172)
Neurology, 2016
Objective: To demonstrate correlations between the effects of therapeutic plasma exchange (TPE) a... more Objective: To demonstrate correlations between the effects of therapeutic plasma exchange (TPE) and commonly used outcome measures of myasthenic response. Background: The MG Activities of Daily Living (MG-ADL), Quality of Life (MG-QOL15, Manual Muscle Testing (MG-MMT) and Composite (MGC) Scores are validated measures of myasthenic response to treatment that have not been examined in a prospective trial of therapeutic plasma exchange. Methods: TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Immunosuppressive medications were kept as constant as possible. We quantitated MG-ADL, MG-QOL15, MG-MMT and MGC Scores at 8 visits; screening, initiation and end of TPE, and at weeks 1, 2, 3, 6, 12 post procedure. Results: Ten patients (mean age=68 years; baseline MG-ADL=8.7, MG-QOL15=28.8, MG-MMT=29.5, MG-Composite=20.7) received a median of 6 TPE treatments during their first course; all improved. Three patients received more than one course ...
Journal of Neuroimmunology, 2020
A detailed understanding of the role of Tfh cells in MuSK-antibody positive myasthenia gravis (Mu... more A detailed understanding of the role of Tfh cells in MuSK-antibody positive myasthenia gravis (MuSK-MG) is lacking. We characterized phenotype and function of Tfh cells in MuSK-MG patients and controls. We found similar overall Tfh and follicular regulatory (Tfr) T cell frequencies in MuSK-MG and healthy controls, but MuSK-MG patients exhibited higher frequencies of Tfh17 cells and a higher ratio of Tfh:Tfr cells. These results suggest imbalanced Tfh cell regulation, further supported by increased frequencies of CD4 T cells co-producing IL-21/IL-17 and IL-17/IFN-γ, and increased Tfh-supported IgG production. These results support a role for Tfh cell dysregulation in MuSK-MG immunopathology.
170. Median nerve ultrasound as a screening tool in carpal tunnel syndrome
Clinical Neurophysiology, 2012
tudes at the healthy side. The severity of the facial palsy was graded clinically with the House–... more tudes at the healthy side. The severity of the facial palsy was graded clinically with the House–Brackmann (H–B) grading scale. Results: The denervation ratio in TMS (71.54 ± 18.38%) was significantly greater than the denervation ratio in electrical stimulation (41.96 ± 21.59%). The difference of denervation ratio between electrical and TMS was significantly greater in patients with Bell’s palsy (33.19%) than in patients with Ramsay Hunt syndrome (14.43%). The denervation ratio of electrical or TMS did not correlate significantly with the H–B grading scale. Conclusions: In the electrophysiologic study for evaluation of patients with facial palsy within 7 days from symptom onset, not only electrical stimulation but also TMS is useful to gain additional information about the neurophysiologic status of the facial nerve and may help to evaluate prognosis and set a management plan.
Botulinum toxin therapy for neurologic disorders
Postgraduate Medicine, May 1, 1992
In the last 20 years, the therapeutic uses of botulinum toxin, a potent neurotoxin, have been inv... more In the last 20 years, the therapeutic uses of botulinum toxin, a potent neurotoxin, have been investigated. The agent produces chemical denervation of muscle, thereby causing atrophy and weakness. Studies have shown that injection of this agent is an effective therapy for focal dystonias, particularly blepharospasm, hemifacial spasm, and torticollis. Investigation continues into the role of botulinum toxin in the treatment of anismus, detrusor-sphincter dyssynergia, writers' cramp, and other disorders in which focal weakening of selected muscles could be useful.
Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study
The Lancet Neurology
The Duke Myasthenia Gravis Clinic Registry: II . Analysis of outcomes
Muscle & Nerve
Muscle specific tyrosine kinase positive, seronegative myasthenia gravis Clinical characteristics and response to therapy
Neurology 60(5 Suppl, Jan 8, 2003
Polymer electrolyte membrane fuel cells (PEMFCs) represent promising energy storage solutions, bu... more Polymer electrolyte membrane fuel cells (PEMFCs) represent promising energy storage solutions, but challenges remain to maximize their utility. Nafion is frequently employed as the PEMFC membrane material, but degradation of Nafion can limit the life of PEMFCs. Using hybrid density functional theory (DFT), we carry out reaction pathway analysis on a range of candidate degradation pathways on both pristine and defect-containing models of Nafion. Degradation of pristine Nafion initiated by hydrogen radicals involves moderate (ca. 20 kcal/mol) barriers lower than alternative pathways initiated by hydroxyl radicals. We propose a new pathway for continued Nafion degradation after initial H radical attack in the presence of H 2 O 2. This pathway has a modest barrier and provides a mechanistic basis for the production of experimentally observed trifluoroacetic acid and hydrogen fluoride. Our work suggests inherent limits to mechanistic studies that use hydroxyl radical as the sole radical source to model Nafion degradation under operating conditions. We observe that hydroxyl radical-only degradation mechanisms have barriers competitive with hydrogen radical species only for initiation at carboxylic acid defects on the main chain or sulfonic acid functional groups on the Nafion side chain. We confirm our observations with DFT by comparison to correlated wavefunction theory. Our study highlights the importance of thorough first-principles modeling to identify the most probable, low energy pathways for materials degradation.
Proceedings of the National Academy of Sciences, 2022
Significance Our study, involving 1,873 patients and 36,370 healthy individuals, is an extensive ... more Significance Our study, involving 1,873 patients and 36,370 healthy individuals, is an extensive genome-wide study of myasthenia gravis. Our genome-wide association and transcriptome-wide association analyses identified two signals, namely CHRNA1 and CHRNB1 , encoding acetylcholine receptor subunits, which were replicated in an independent cohort obtained from the UK Biobank. Identifying these genes confirms the potential utility of using genetics to identify proteins that are the antigenic targets of autoantibodies. We confirmed that the genetic abnormalities underlying early-onset and late-onset myasthenia gravis are different. Our data offer a broader insight into the genetic architecture underlying the pathophysiology of myasthenia gravis.
Knowledge and perceptions of the COVID ‐19 pandemic among patients with myasthenia gravis
Muscle & Nerve, 2020
Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respi... more Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic due to risk of worsening disease during infection, potential adverse impacts of coronavirus disease 2019 (COVID‐19) treatments on neuromuscular transmission, and a limited ability to fight off infection related to immunosuppressive treatments. Our goal is to understand how patients are experiencing the COVID‐19 pandemic, including where they receive relevant information, how it has affected medical care, and what measures they use to protect themselves.
Neurology, 2020
ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal... more ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).MethodsThis study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody–positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18–65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 month...
Experimental Neurology, 2020
IL-17 producing CD4 T cells (Th17) cells increase significantly with disease severity in myasthen... more IL-17 producing CD4 T cells (Th17) cells increase significantly with disease severity in myasthenia gravis (MG) patients. To suppress the generation of Th17 cells, we examined the effect of inhibiting retinoic acid receptor-related-orphan-receptor-C (RORγ), a Th17-specific transcription factor critical for differentiation. RORγ inhibition profoundly reduced Th17 cell frequencies, including IFN-γ and IL-17 co-producing pathogenic Th17 cells. Other T helper subsets were not affected. In parallel, CD8 T cell subsets producing IL-17 and IL-17/IFN-γ were increased in MG patients and inhibited by the RORγ inhibitor. These findings provide rationale for exploration of targeted Th17 therapies, including ROR-γ inhibitors, to treat MG patients.
Journal of graduate medical education, 2014
The Neurology Milestone Project T he Milestones are designed only for use in evaluation of reside... more The Neurology Milestone Project T he Milestones are designed only for use in evaluation of resident physicians in the context of their participation in Accreditation Council for Graduate Medical Education (ACGME)-accredited residency or fellowship programs. The Milestones provide a framework for assessment of the development of the resident physician in key dimensions of the elements of physician competency in a specialty or subspecialty. They neither represent the entirety of the dimensions of the 6 domains of physician competency, nor are they designed to be relevant in any other context. Milestone Reporting & selecting the level of Milestones that best describes that resident's performance in relation to the Milestones, or & for Patient Care and Medical Knowledge Milestones, selecting the option that says the resident has ''Not yet rotated,'' or & for Interpersonal and Communication Skills, Practice-Based Learning and Improvement, Professionalism, and Systems-Based Practice Milestones, selecting the option that says the resident has ''Not yet achieved Level 1.''
Pathogenic Th17 Cells in Autoimmune Myasthenia Gravis Exhibit a Pro-inflammatory Transcriptomic Signature that Promotes Disease Pathogenesis (S41.008)
Neurology, May 2, 2022
Autoimmunity, Aug 11, 2016
An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, auto... more An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune diseases populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR+ MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age=72.9 years; baseline MG-Composite=21; median TPE treatments=6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (approximately 60-70% reduction). Three weeks post-TPE mean AChR autoantibody, total IgG, IgG1 and IgG2 titers were below the reference range and had not recovered to within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns
Neuromuscular Disorders and Pregnancy
Continuum, Feb 1, 2022
ABSTRACT PURPOSE OF REVIEW This article provides an overview of neuromuscular disorders in pregna... more ABSTRACT PURPOSE OF REVIEW This article provides an overview of neuromuscular disorders in pregnancy, with a focus on diagnosis and management. RECENT FINDINGS Neuromuscular disorders with issues that occur in pregnancy include conditions that are acquired (including autoimmune) or genetic; each requires a unique approach to management and treatment prepartum, peripartum, and postpartum. Guidance in the literature regarding management and treatment options is predominantly from case series and retrospective reviews. Treatment can be complex, particularly in autoimmune neuromuscular diseases, because of the risks of side effects of the treatments that may affect the patient and fetus. SUMMARY This article summarizes expectations, diagnosis, and management for a wide range of neuromuscular disorders in pregnancy.
Archives of Otolaryngology-head & Neck Surgery, Jul 1, 1989
To the Editor.\p=m-\In their article "Management of Facial Spasm With Clostridium botulinum Toxin... more To the Editor.\p=m-\In their article "Management of Facial Spasm With Clostridium botulinum Toxin, Type A (Oculinum),"1 the authors report the use of botulinum toxin in 105 patients with "no lasting complications or systemic effects." They conclude that botulinum A toxin appears to be a safe,
Pregnancy in MuSK‐positive myasthenia gravis: A single‐center case series
Muscle & Nerve
Introduction/AimsMyasthenia gravis (MG) with muscle‐specific tyrosine kinase (MuSK) antibodies (M... more Introduction/AimsMyasthenia gravis (MG) with muscle‐specific tyrosine kinase (MuSK) antibodies (MMG) is predominantly seen in women of childbearing age. Our objective in this study was to describe the course of MMG during pregnancy and within 6 months postpartum, and to document any effect on fetal health.MethodsA retrospective review was performed of medical records of patients with MMG seen in the Duke Myasthenia Gravis Clinic from 2003 to 2022. MMG patients with onset of MMG symptoms before or during pregnancy as well as within 6 months postpartum were reviewed.ResultsA total of 14 pregnancies in 10 patients were included in our study cohort. Initial MG symptoms developed during pregnancy or within 6 months postpartum in six patients. Four patients had two pregnancies, three of whom developed MG during their first pregnancy. In the patients diagnosed before pregnancy, MG symptoms increased in five of eight patients during pregnancy or postpartum. Four patients required rescue the...
Muscle & Nerve, 2020
BackgroundThe immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly unde... more BackgroundThe immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG.MethodsWe performed high‐dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery‐replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG.ResultsAn increase in CD19+CD20−CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P‐value = .0003, replication P‐value = .0021). Interleukin (IL) ‐21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P = .004).ConclusionsReduced plasmablast frequencies are strongly associated with a SN ...
Effects of Therapeutic Plasma Exchange on Myasthenic Outcome Measures (P3.172)
Neurology, 2016
Objective: To demonstrate correlations between the effects of therapeutic plasma exchange (TPE) a... more Objective: To demonstrate correlations between the effects of therapeutic plasma exchange (TPE) and commonly used outcome measures of myasthenic response. Background: The MG Activities of Daily Living (MG-ADL), Quality of Life (MG-QOL15, Manual Muscle Testing (MG-MMT) and Composite (MGC) Scores are validated measures of myasthenic response to treatment that have not been examined in a prospective trial of therapeutic plasma exchange. Methods: TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Immunosuppressive medications were kept as constant as possible. We quantitated MG-ADL, MG-QOL15, MG-MMT and MGC Scores at 8 visits; screening, initiation and end of TPE, and at weeks 1, 2, 3, 6, 12 post procedure. Results: Ten patients (mean age=68 years; baseline MG-ADL=8.7, MG-QOL15=28.8, MG-MMT=29.5, MG-Composite=20.7) received a median of 6 TPE treatments during their first course; all improved. Three patients received more than one course ...
Journal of Neuroimmunology, 2020
A detailed understanding of the role of Tfh cells in MuSK-antibody positive myasthenia gravis (Mu... more A detailed understanding of the role of Tfh cells in MuSK-antibody positive myasthenia gravis (MuSK-MG) is lacking. We characterized phenotype and function of Tfh cells in MuSK-MG patients and controls. We found similar overall Tfh and follicular regulatory (Tfr) T cell frequencies in MuSK-MG and healthy controls, but MuSK-MG patients exhibited higher frequencies of Tfh17 cells and a higher ratio of Tfh:Tfr cells. These results suggest imbalanced Tfh cell regulation, further supported by increased frequencies of CD4 T cells co-producing IL-21/IL-17 and IL-17/IFN-γ, and increased Tfh-supported IgG production. These results support a role for Tfh cell dysregulation in MuSK-MG immunopathology.
170. Median nerve ultrasound as a screening tool in carpal tunnel syndrome
Clinical Neurophysiology, 2012
tudes at the healthy side. The severity of the facial palsy was graded clinically with the House–... more tudes at the healthy side. The severity of the facial palsy was graded clinically with the House–Brackmann (H–B) grading scale. Results: The denervation ratio in TMS (71.54 ± 18.38%) was significantly greater than the denervation ratio in electrical stimulation (41.96 ± 21.59%). The difference of denervation ratio between electrical and TMS was significantly greater in patients with Bell’s palsy (33.19%) than in patients with Ramsay Hunt syndrome (14.43%). The denervation ratio of electrical or TMS did not correlate significantly with the H–B grading scale. Conclusions: In the electrophysiologic study for evaluation of patients with facial palsy within 7 days from symptom onset, not only electrical stimulation but also TMS is useful to gain additional information about the neurophysiologic status of the facial nerve and may help to evaluate prognosis and set a management plan.
Botulinum toxin therapy for neurologic disorders
Postgraduate Medicine, May 1, 1992
In the last 20 years, the therapeutic uses of botulinum toxin, a potent neurotoxin, have been inv... more In the last 20 years, the therapeutic uses of botulinum toxin, a potent neurotoxin, have been investigated. The agent produces chemical denervation of muscle, thereby causing atrophy and weakness. Studies have shown that injection of this agent is an effective therapy for focal dystonias, particularly blepharospasm, hemifacial spasm, and torticollis. Investigation continues into the role of botulinum toxin in the treatment of anismus, detrusor-sphincter dyssynergia, writers' cramp, and other disorders in which focal weakening of selected muscles could be useful.
Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study
The Lancet Neurology
The Duke Myasthenia Gravis Clinic Registry: II . Analysis of outcomes
Muscle & Nerve
Muscle specific tyrosine kinase positive, seronegative myasthenia gravis Clinical characteristics and response to therapy
Neurology 60(5 Suppl, Jan 8, 2003
Polymer electrolyte membrane fuel cells (PEMFCs) represent promising energy storage solutions, bu... more Polymer electrolyte membrane fuel cells (PEMFCs) represent promising energy storage solutions, but challenges remain to maximize their utility. Nafion is frequently employed as the PEMFC membrane material, but degradation of Nafion can limit the life of PEMFCs. Using hybrid density functional theory (DFT), we carry out reaction pathway analysis on a range of candidate degradation pathways on both pristine and defect-containing models of Nafion. Degradation of pristine Nafion initiated by hydrogen radicals involves moderate (ca. 20 kcal/mol) barriers lower than alternative pathways initiated by hydroxyl radicals. We propose a new pathway for continued Nafion degradation after initial H radical attack in the presence of H 2 O 2. This pathway has a modest barrier and provides a mechanistic basis for the production of experimentally observed trifluoroacetic acid and hydrogen fluoride. Our work suggests inherent limits to mechanistic studies that use hydroxyl radical as the sole radical source to model Nafion degradation under operating conditions. We observe that hydroxyl radical-only degradation mechanisms have barriers competitive with hydrogen radical species only for initiation at carboxylic acid defects on the main chain or sulfonic acid functional groups on the Nafion side chain. We confirm our observations with DFT by comparison to correlated wavefunction theory. Our study highlights the importance of thorough first-principles modeling to identify the most probable, low energy pathways for materials degradation.
Proceedings of the National Academy of Sciences, 2022
Significance Our study, involving 1,873 patients and 36,370 healthy individuals, is an extensive ... more Significance Our study, involving 1,873 patients and 36,370 healthy individuals, is an extensive genome-wide study of myasthenia gravis. Our genome-wide association and transcriptome-wide association analyses identified two signals, namely CHRNA1 and CHRNB1 , encoding acetylcholine receptor subunits, which were replicated in an independent cohort obtained from the UK Biobank. Identifying these genes confirms the potential utility of using genetics to identify proteins that are the antigenic targets of autoantibodies. We confirmed that the genetic abnormalities underlying early-onset and late-onset myasthenia gravis are different. Our data offer a broader insight into the genetic architecture underlying the pathophysiology of myasthenia gravis.
Knowledge and perceptions of the COVID ‐19 pandemic among patients with myasthenia gravis
Muscle & Nerve, 2020
Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respi... more Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic due to risk of worsening disease during infection, potential adverse impacts of coronavirus disease 2019 (COVID‐19) treatments on neuromuscular transmission, and a limited ability to fight off infection related to immunosuppressive treatments. Our goal is to understand how patients are experiencing the COVID‐19 pandemic, including where they receive relevant information, how it has affected medical care, and what measures they use to protect themselves.
Neurology, 2020
ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal... more ObjectiveTo examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).MethodsThis study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody–positive MG without thymoma. Patients were randomized 1:1 to thymectomy plus prednisone vs prednisone alone. Participants were age 18–65 years at enrollment with disease duration less than 5 years. All patients received oral prednisone titrated up to 100 mg on alternate days until they achieved MMS, which prompted a standardized prednisone taper as long as MMS was maintained. The achievement rate of sustained MMS (no symptoms of MG for 6 month...
Experimental Neurology, 2020
IL-17 producing CD4 T cells (Th17) cells increase significantly with disease severity in myasthen... more IL-17 producing CD4 T cells (Th17) cells increase significantly with disease severity in myasthenia gravis (MG) patients. To suppress the generation of Th17 cells, we examined the effect of inhibiting retinoic acid receptor-related-orphan-receptor-C (RORγ), a Th17-specific transcription factor critical for differentiation. RORγ inhibition profoundly reduced Th17 cell frequencies, including IFN-γ and IL-17 co-producing pathogenic Th17 cells. Other T helper subsets were not affected. In parallel, CD8 T cell subsets producing IL-17 and IL-17/IFN-γ were increased in MG patients and inhibited by the RORγ inhibitor. These findings provide rationale for exploration of targeted Th17 therapies, including ROR-γ inhibitors, to treat MG patients.
Journal of graduate medical education, 2014
The Neurology Milestone Project T he Milestones are designed only for use in evaluation of reside... more The Neurology Milestone Project T he Milestones are designed only for use in evaluation of resident physicians in the context of their participation in Accreditation Council for Graduate Medical Education (ACGME)-accredited residency or fellowship programs. The Milestones provide a framework for assessment of the development of the resident physician in key dimensions of the elements of physician competency in a specialty or subspecialty. They neither represent the entirety of the dimensions of the 6 domains of physician competency, nor are they designed to be relevant in any other context. Milestone Reporting & selecting the level of Milestones that best describes that resident's performance in relation to the Milestones, or & for Patient Care and Medical Knowledge Milestones, selecting the option that says the resident has ''Not yet rotated,'' or & for Interpersonal and Communication Skills, Practice-Based Learning and Improvement, Professionalism, and Systems-Based Practice Milestones, selecting the option that says the resident has ''Not yet achieved Level 1.''