Ronaldo Abraham - Academia.edu (original) (raw)
Papers by Ronaldo Abraham
Expert Review of Neurotherapeutics
Expert review of neurotherapeutics, 2018
Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological mor... more Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high-income countries due to migration. Many advances have been made in understanding NC, but unanswered questions remain Areas covered: This review discusses the epidemiology, pathophysiology, immunology, diagnosis, treatment, and eradication of NC. Expert commentary: The global NC prevalence remains unknown and needs proper ascertainment. Further understanding of the pathophysiology of extraparenchymally located cysts is needed to improve management. The role of inflammation, which is required for parasite death and reabsorption, but may lead to severe complications, must be better understood. Valid screening tools including immunological and molecular tests need to be developed to reduce the reliance on neuroimaging which is not usually accessible in endemic areas. Prognosis for people with parenchymal NC is generally g...
Boletim Neuro Atual, Mar 18, 2012
Arquivos de Neuro-Psiquiatria, 2013
Arquivos de neuro-psiquiatria, 2013
The consequences of inflammatory response are primarily responsible for morbimortality in bacteri... more The consequences of inflammatory response are primarily responsible for morbimortality in bacterial meningitis. Early use of steroids in these cases can reduce mortality and hearing loss and improve functional outcome without causing significant side effects. The formal recommendation towards pneumoccocal meningitis is being extended to other forms of Bacterial Meningitis. The same thought can be applied to tuberculous meningitis. In neurocysticercosis and neuroschistosomiasis steroids are more useful than parasiticides in most cases. Despite the evidence favoring the use of steroids in herpes simplex encephalitis, it is not sufficient to definitely support such indication. Among the opportunistic infections that affect AIDS patients, neurotoxoplasmosis and progressive multifocal leukoencephalopaty are those most often considered for the use of steroids; steroids are safe to use, but no definite benefit could be demonstrated in both conditions.
Expert review of neurotherapeutics, 2018
Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological mor... more Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high-income countries due to migration. Many advances have been made in understanding NC, but unanswered questions remain Areas covered: This review discusses the epidemiology, pathophysiology, immunology, diagnosis, treatment, and eradication of NC. Expert commentary: The global NC prevalence remains unknown and needs proper ascertainment. Further understanding of the pathophysiology of extraparenchymally located cysts is needed to improve management. The role of inflammation, which is required for parasite death and reabsorption, but may lead to severe complications, must be better understood. Valid screening tools including immunological and molecular tests need to be developed to reduce the reliance on neuroimaging which is not usually accessible in endemic areas. Prognosis for people with parenchymal NC is generally g...
Objective: The diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogen... more Objective: The diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogeneity of its clinical, immunological, and imaging characteristics. Our aim was to develop and assess a new set of diagnostic criteria for NCC, which might allow for the accurate detection of, and differentiation between, parenchymal and extraparenchymal disease. Methods: A group of Latin American NCC experts developed by consensus a new set of diagnostic criteria for NCC. A multicenter, retrospective study was then conducted to validate it. The reference standard for diagnosis of active NCC was the disappearance or reduction of cysts after anthelmintic treatment. In total, three pairs of independent neurologists blinded to the diagnosis evaluated 93 cases (with NCC) and 93 controls (without NCC) using the new diagnostic criteria. Mixed-effects logistic regression models were used to estimate sensitivity and specificity. Results: Inter-rater reliability (kappa) of diagnosis among evaluators was 0.60. For diagnosis of NCC versus no NCC, the new criteria had a sensitivity of 93.2% and specificity of 81.4%. For parenchymal NCC, the new criteria had a sensitivity of 89.8% and specificity of 80.7% and for extraparenchymal NCC, the new criteria had a sensitivity of 65.9% and specific-ity of 94.9%. Interpretation: These criteria have acceptable reliability and validity and could be a new tool for clinicians and researchers. An advantage of the new criteria is that they consider parasite location (ie, parenchymal or extraparenchymal), which is an important factor determining the clinical, immunological, and radiological presentation of the disease, and importantly, its treatment and prognosis.
Arquivos De Neuro Psiquiatria, Jun 1, 2001
Brain vascular disease as the first presentation of temporal arteritis is unusual. We present two... more Brain vascular disease as the first presentation of temporal arteritis is unusual. We present two cases in which the diagnosis emerged from the anamnesis. A 54 years old woman has had a left cerebral infarct 3 months ago. She was getting better when severe visual loss occurred and the family decided to get a second opinion. The patient have had right hemiparesis, aphasia and a left visual disturbance in the first episode; now she had severe bilateral visual disturbance. We suspected temporal arteritis was the etiology. HSR was 97 mm and fundoscopy disclosed severe ischemic optic neuritis. A 75 years old man presented Wallenberg syndrome. The history disclosed temporal headache and the examination showed inflammation in temporal artery. HSR was 70 mm and biopsy confirmed the diagnosis. "Tecnolatry" is affecting medical practice; it's necessary to put back in the center the clinical sovereignty.
![Research paper thumbnail of [Metopic suture craniosynostosis: sodium valproate teratogenic effect. Case report]](https://attachments.academia-assets.com/42671025/thumbnails/1.jpg)
](Arquivos de neuro-psiquiatria, 2001
the aim of this report is to warn that sodium valproate used during pregnancy can produce cranios... more the aim of this report is to warn that sodium valproate used during pregnancy can produce craniosynostosis in the newborn, particularly trigonocephaly. we describe a case of trigonocephaly in a six month-old girl, daughter of a young non-smoker couple, whose mother had used phenobarbital 100 mg daily and sodium valproate 500 mg twice daily during the whole pregnancy. We also review current literature about this topic. bone sclerosis over the metopic suture was confirmed during surgery. Bibliographical review yields previous reports on valproate teratogenicity, mainly determining metopic suture craniosynostosis. sodium valproate used during pregnancy can produce craniosynostosis by teratogenic effect, specially trigonocephaly (premature fusion of metopic suture).
Arquivos De Neuro-psiquiatria, 2001
RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cran... more RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cranioestenose no recém-nascido, em especial a trigonocefalia. Método: relato de um caso de trigonocefalia em menina de 6 meses, filha de pais jovens, não fumantes e cuja mãe fez uso de fenobarbital 100 mg/dia e valproato de sódio 500 mg duas vezes/dia durante toda a gravidez. Foi realizada revisão bibliográfica sobre o assunto. Resultado: no ato cirúrgico pôde-se confirmar a presença de esclerose óssea sobre a sutura metópica. A revisão bibliográfica permitiu o encontro de relatos prévios sobre a teratogenicidade do valproato de sódio, que determina principalmente cranioestenose da sutura metópica. Conclusão: o uso de valproato de sódio durante a gravidez pode determinar como ação teratogênica a cranioestenose, especialmente a trigonocefalia (fechamento precoce da sutura metópica).
Novel Aspects on Cysticercosis and Neurocysticercosis, 2013
European Archives of Psychiatry and Clinical Neuroscience, 2006
■ Abstract Neurocysticercosis is the most frequent parasitic infection of the CNS and the main ca... more ■ Abstract Neurocysticercosis is the most frequent parasitic infection of the CNS and the main cause of acquired epilepsy worldwide. Seizures are the most common symptoms of the disease, together with headache, involuntary movements, psychosis and a global mental deterioration. Absolute diagnostic criteria include the identification of cysticerci, with scolex, in the brain by MRI imaging. We demonstrate here, for the first time, that T. solium DNA is present in the cerebrospinal fluid of patients. The PCR amplification of the parasite DNA in the CSF enabled the correct identification of 29/30 cases (96.7 %). The PCR diagnosis of parasite DNA in the CSF may be a strong support for the diagnosis of neurocysticercosis.
Arquivos de Neuro- …, 1986
A síndrome de Aicardi, descrita inicialmente me 1965 3 , é caracterizada por alguns achados const... more A síndrome de Aicardi, descrita inicialmente me 1965 3 , é caracterizada por alguns achados constantes 2.4.5,9,10 : ocorrência no sexo feminino; crises convulsivas, principalmente do tipo espasmo em flexão generalizado; agenesia do corpo caloso; múltiplas lacunas coriorretinianas; alterações características do eletrencefalograma (EEG); retardo mental. Outros achados menos constantes incluem anormalidades oculares, do sistema nervoso central (SNC), além de displasias ósseas. Acredita-se que seja determinada por gen ligado ao cromossoma X, letal para os portadores do sexo masculino. Apresentamos dois casos que mostram o quadro clínico completo dessa entidade de que até hoje poucas centenas de casos foram registrados na literatura, discutindo posteriormente alguns aspectos da síndrome julgados importantes.
Arquivos de Neuro-Psiquiatria, 2001
Arquivos de Neuro-Psiquiatria, 2001
RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cran... more RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cranioestenose no recém-nascido, em especial a trigonocefalia. Método: relato de um caso de trigonocefalia em menina de 6 meses, filha de pais jovens, não fumantes e cuja mãe fez uso de fenobarbital 100 mg/dia e valproato de sódio 500 mg duas vezes/dia durante toda a gravidez. Foi realizada revisão bibliográfica sobre o assunto. Resultado: no ato cirúrgico pôde-se confirmar a presença de esclerose óssea sobre a sutura metópica. A revisão bibliográfica permitiu o encontro de relatos prévios sobre a teratogenicidade do valproato de sódio, que determina principalmente cranioestenose da sutura metópica. Conclusão: o uso de valproato de sódio durante a gravidez pode determinar como ação teratogênica a cranioestenose, especialmente a trigonocefalia (fechamento precoce da sutura metópica).
Arquivos de Neuro-Psiquiatria, 2004
(1) To determine the concentration of Taenia antigens in the cerebrospinal fluid (CSF) of patient... more (1) To determine the concentration of Taenia antigens in the cerebrospinal fluid (CSF) of patients with neurocysticercosis (NC); (2) to establish its relationship with clinical activity of the disease and with classical variables of CSF. A CSF examination was performed in one sample from 36 patients with definitive diagnosis of NC, including: quantitative and cytomorphological study, biochemical tests, immunological reactions for cysticercosis and Taenia antigens. The antibodies for antigens detection were obtained from the larval form of Taenia crassiceps, ORF strain. After intraperitoneal passage through female mice, a group of rabbits was immunized with vesicular fluid antigens. The Taenia antigen was detected in CSF from 17 patients (47.2%), especially in those patients with epileptic symptoms in the last 12 months. Taenia antigens presence in CSF have significant relationship with clinically active forms of NC, being a more sensitive marker than the classic eosinophil presence.
Arquivos de Neuro-Psiquiatria, 2010
To determine the relationship between Taenia antigen (TA) detection in cerebrospinal fluid (CSF) ... more To determine the relationship between Taenia antigen (TA) detection in cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings in patients with definite diagnosis of neurocysticercosis (NC). Sixty-three patients with definite diagnosis of NC were submitted to a MRI of the brain, and to a CSF examination, with a meticulous search for TA by ELISA. TA detection was positive in 36 patients (57.1%). A total of 836 lesions were analyzed, greatly within the cerebral parenchyma (98.7 of the lesions). Intact or non-degenerating cysts were the most common evolutive phase observed (50.4% of all lesions), 22.1% were degenerating cysts and 19.5% calcified cysts. We observed a significant relationship between TA levels detected and the total number of lesions and the number of non-degenerating cysts, but not with calcified lesions. According to our results, we propose at least four important types of contribution: (1) TA detection may allow etiologic diagnosis in transitional phases of NC, with non-characteristic images; (2) in final stages of evolution of cysticercoids in the CNS, lesions may not appear on CT or MRI, and TA detection may contribute to a definite etiologic diagnosis; (3) TA detection may permit diagnosis of NC in some patients with previous negative tests for antibody detection in CSF; (4) TA detection may represent an accurate marker of disease activity in the epileptic form of NC.
Expert Review of Neurotherapeutics
Expert review of neurotherapeutics, 2018
Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological mor... more Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high-income countries due to migration. Many advances have been made in understanding NC, but unanswered questions remain Areas covered: This review discusses the epidemiology, pathophysiology, immunology, diagnosis, treatment, and eradication of NC. Expert commentary: The global NC prevalence remains unknown and needs proper ascertainment. Further understanding of the pathophysiology of extraparenchymally located cysts is needed to improve management. The role of inflammation, which is required for parasite death and reabsorption, but may lead to severe complications, must be better understood. Valid screening tools including immunological and molecular tests need to be developed to reduce the reliance on neuroimaging which is not usually accessible in endemic areas. Prognosis for people with parenchymal NC is generally g...
Boletim Neuro Atual, Mar 18, 2012
Arquivos de Neuro-Psiquiatria, 2013
Arquivos de neuro-psiquiatria, 2013
The consequences of inflammatory response are primarily responsible for morbimortality in bacteri... more The consequences of inflammatory response are primarily responsible for morbimortality in bacterial meningitis. Early use of steroids in these cases can reduce mortality and hearing loss and improve functional outcome without causing significant side effects. The formal recommendation towards pneumoccocal meningitis is being extended to other forms of Bacterial Meningitis. The same thought can be applied to tuberculous meningitis. In neurocysticercosis and neuroschistosomiasis steroids are more useful than parasiticides in most cases. Despite the evidence favoring the use of steroids in herpes simplex encephalitis, it is not sufficient to definitely support such indication. Among the opportunistic infections that affect AIDS patients, neurotoxoplasmosis and progressive multifocal leukoencephalopaty are those most often considered for the use of steroids; steroids are safe to use, but no definite benefit could be demonstrated in both conditions.
Expert review of neurotherapeutics, 2018
Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological mor... more Neurocysticercosis (NC) is a neglected disease that contributes substantially to neurological morbidity/mortality in lower-income countries and increasingly among high-income countries due to migration. Many advances have been made in understanding NC, but unanswered questions remain Areas covered: This review discusses the epidemiology, pathophysiology, immunology, diagnosis, treatment, and eradication of NC. Expert commentary: The global NC prevalence remains unknown and needs proper ascertainment. Further understanding of the pathophysiology of extraparenchymally located cysts is needed to improve management. The role of inflammation, which is required for parasite death and reabsorption, but may lead to severe complications, must be better understood. Valid screening tools including immunological and molecular tests need to be developed to reduce the reliance on neuroimaging which is not usually accessible in endemic areas. Prognosis for people with parenchymal NC is generally g...
Objective: The diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogen... more Objective: The diagnosis of neurocysticercosis (NCC) remains problematic because of the heterogeneity of its clinical, immunological, and imaging characteristics. Our aim was to develop and assess a new set of diagnostic criteria for NCC, which might allow for the accurate detection of, and differentiation between, parenchymal and extraparenchymal disease. Methods: A group of Latin American NCC experts developed by consensus a new set of diagnostic criteria for NCC. A multicenter, retrospective study was then conducted to validate it. The reference standard for diagnosis of active NCC was the disappearance or reduction of cysts after anthelmintic treatment. In total, three pairs of independent neurologists blinded to the diagnosis evaluated 93 cases (with NCC) and 93 controls (without NCC) using the new diagnostic criteria. Mixed-effects logistic regression models were used to estimate sensitivity and specificity. Results: Inter-rater reliability (kappa) of diagnosis among evaluators was 0.60. For diagnosis of NCC versus no NCC, the new criteria had a sensitivity of 93.2% and specificity of 81.4%. For parenchymal NCC, the new criteria had a sensitivity of 89.8% and specificity of 80.7% and for extraparenchymal NCC, the new criteria had a sensitivity of 65.9% and specific-ity of 94.9%. Interpretation: These criteria have acceptable reliability and validity and could be a new tool for clinicians and researchers. An advantage of the new criteria is that they consider parasite location (ie, parenchymal or extraparenchymal), which is an important factor determining the clinical, immunological, and radiological presentation of the disease, and importantly, its treatment and prognosis.
Arquivos De Neuro Psiquiatria, Jun 1, 2001
Brain vascular disease as the first presentation of temporal arteritis is unusual. We present two... more Brain vascular disease as the first presentation of temporal arteritis is unusual. We present two cases in which the diagnosis emerged from the anamnesis. A 54 years old woman has had a left cerebral infarct 3 months ago. She was getting better when severe visual loss occurred and the family decided to get a second opinion. The patient have had right hemiparesis, aphasia and a left visual disturbance in the first episode; now she had severe bilateral visual disturbance. We suspected temporal arteritis was the etiology. HSR was 97 mm and fundoscopy disclosed severe ischemic optic neuritis. A 75 years old man presented Wallenberg syndrome. The history disclosed temporal headache and the examination showed inflammation in temporal artery. HSR was 70 mm and biopsy confirmed the diagnosis. "Tecnolatry" is affecting medical practice; it's necessary to put back in the center the clinical sovereignty.
Arquivos de neuro-psiquiatria, 2001
the aim of this report is to warn that sodium valproate used during pregnancy can produce cranios... more the aim of this report is to warn that sodium valproate used during pregnancy can produce craniosynostosis in the newborn, particularly trigonocephaly. we describe a case of trigonocephaly in a six month-old girl, daughter of a young non-smoker couple, whose mother had used phenobarbital 100 mg daily and sodium valproate 500 mg twice daily during the whole pregnancy. We also review current literature about this topic. bone sclerosis over the metopic suture was confirmed during surgery. Bibliographical review yields previous reports on valproate teratogenicity, mainly determining metopic suture craniosynostosis. sodium valproate used during pregnancy can produce craniosynostosis by teratogenic effect, specially trigonocephaly (premature fusion of metopic suture).
Arquivos De Neuro-psiquiatria, 2001
RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cran... more RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cranioestenose no recém-nascido, em especial a trigonocefalia. Método: relato de um caso de trigonocefalia em menina de 6 meses, filha de pais jovens, não fumantes e cuja mãe fez uso de fenobarbital 100 mg/dia e valproato de sódio 500 mg duas vezes/dia durante toda a gravidez. Foi realizada revisão bibliográfica sobre o assunto. Resultado: no ato cirúrgico pôde-se confirmar a presença de esclerose óssea sobre a sutura metópica. A revisão bibliográfica permitiu o encontro de relatos prévios sobre a teratogenicidade do valproato de sódio, que determina principalmente cranioestenose da sutura metópica. Conclusão: o uso de valproato de sódio durante a gravidez pode determinar como ação teratogênica a cranioestenose, especialmente a trigonocefalia (fechamento precoce da sutura metópica).
Novel Aspects on Cysticercosis and Neurocysticercosis, 2013
European Archives of Psychiatry and Clinical Neuroscience, 2006
■ Abstract Neurocysticercosis is the most frequent parasitic infection of the CNS and the main ca... more ■ Abstract Neurocysticercosis is the most frequent parasitic infection of the CNS and the main cause of acquired epilepsy worldwide. Seizures are the most common symptoms of the disease, together with headache, involuntary movements, psychosis and a global mental deterioration. Absolute diagnostic criteria include the identification of cysticerci, with scolex, in the brain by MRI imaging. We demonstrate here, for the first time, that T. solium DNA is present in the cerebrospinal fluid of patients. The PCR amplification of the parasite DNA in the CSF enabled the correct identification of 29/30 cases (96.7 %). The PCR diagnosis of parasite DNA in the CSF may be a strong support for the diagnosis of neurocysticercosis.
Arquivos de Neuro- …, 1986
A síndrome de Aicardi, descrita inicialmente me 1965 3 , é caracterizada por alguns achados const... more A síndrome de Aicardi, descrita inicialmente me 1965 3 , é caracterizada por alguns achados constantes 2.4.5,9,10 : ocorrência no sexo feminino; crises convulsivas, principalmente do tipo espasmo em flexão generalizado; agenesia do corpo caloso; múltiplas lacunas coriorretinianas; alterações características do eletrencefalograma (EEG); retardo mental. Outros achados menos constantes incluem anormalidades oculares, do sistema nervoso central (SNC), além de displasias ósseas. Acredita-se que seja determinada por gen ligado ao cromossoma X, letal para os portadores do sexo masculino. Apresentamos dois casos que mostram o quadro clínico completo dessa entidade de que até hoje poucas centenas de casos foram registrados na literatura, discutindo posteriormente alguns aspectos da síndrome julgados importantes.
Arquivos de Neuro-Psiquiatria, 2001
Arquivos de Neuro-Psiquiatria, 2001
RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cran... more RESUMO -Objetivo: alertar que o uso de valproato de sódio durante a gravidez pode determinar cranioestenose no recém-nascido, em especial a trigonocefalia. Método: relato de um caso de trigonocefalia em menina de 6 meses, filha de pais jovens, não fumantes e cuja mãe fez uso de fenobarbital 100 mg/dia e valproato de sódio 500 mg duas vezes/dia durante toda a gravidez. Foi realizada revisão bibliográfica sobre o assunto. Resultado: no ato cirúrgico pôde-se confirmar a presença de esclerose óssea sobre a sutura metópica. A revisão bibliográfica permitiu o encontro de relatos prévios sobre a teratogenicidade do valproato de sódio, que determina principalmente cranioestenose da sutura metópica. Conclusão: o uso de valproato de sódio durante a gravidez pode determinar como ação teratogênica a cranioestenose, especialmente a trigonocefalia (fechamento precoce da sutura metópica).
Arquivos de Neuro-Psiquiatria, 2004
(1) To determine the concentration of Taenia antigens in the cerebrospinal fluid (CSF) of patient... more (1) To determine the concentration of Taenia antigens in the cerebrospinal fluid (CSF) of patients with neurocysticercosis (NC); (2) to establish its relationship with clinical activity of the disease and with classical variables of CSF. A CSF examination was performed in one sample from 36 patients with definitive diagnosis of NC, including: quantitative and cytomorphological study, biochemical tests, immunological reactions for cysticercosis and Taenia antigens. The antibodies for antigens detection were obtained from the larval form of Taenia crassiceps, ORF strain. After intraperitoneal passage through female mice, a group of rabbits was immunized with vesicular fluid antigens. The Taenia antigen was detected in CSF from 17 patients (47.2%), especially in those patients with epileptic symptoms in the last 12 months. Taenia antigens presence in CSF have significant relationship with clinically active forms of NC, being a more sensitive marker than the classic eosinophil presence.
Arquivos de Neuro-Psiquiatria, 2010
To determine the relationship between Taenia antigen (TA) detection in cerebrospinal fluid (CSF) ... more To determine the relationship between Taenia antigen (TA) detection in cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) findings in patients with definite diagnosis of neurocysticercosis (NC). Sixty-three patients with definite diagnosis of NC were submitted to a MRI of the brain, and to a CSF examination, with a meticulous search for TA by ELISA. TA detection was positive in 36 patients (57.1%). A total of 836 lesions were analyzed, greatly within the cerebral parenchyma (98.7 of the lesions). Intact or non-degenerating cysts were the most common evolutive phase observed (50.4% of all lesions), 22.1% were degenerating cysts and 19.5% calcified cysts. We observed a significant relationship between TA levels detected and the total number of lesions and the number of non-degenerating cysts, but not with calcified lesions. According to our results, we propose at least four important types of contribution: (1) TA detection may allow etiologic diagnosis in transitional phases of NC, with non-characteristic images; (2) in final stages of evolution of cysticercoids in the CNS, lesions may not appear on CT or MRI, and TA detection may contribute to a definite etiologic diagnosis; (3) TA detection may permit diagnosis of NC in some patients with previous negative tests for antibody detection in CSF; (4) TA detection may represent an accurate marker of disease activity in the epileptic form of NC.