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1.
Mol Neurobiol ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989383

RESUMO

Mevalonate pathway inhibitors have been extensively studied for their roles in cholesterol depletion and for inhibiting the prenylation and activation of various proteins. Inhibition of protein prenylation has potential therapeutic uses against neurological disorders, like neural cancers, neurodegeneration, and neurotramatic lesions. Protection against neurodegeneration and promotion of neuronal regeneration is regulated in large part by Ras superfamily small guanosine triphosphatases (GTPases), particularly the Ras, Rho, and Rab subfamilies. These proteins are prenylated to target them to cellular membranes. Prenylation can be specifically inhibited through altering the function of enzymes of the mevalonate pathway necessary for isoprenoid production and attachment to target proteins to elicit a variety of effects on neural cells. However, this approach does not address how prenylation affects a specific protein. This review focuses on the regulation of small GTPase prenylation, the different techniques to inhibit prenylation, and how this inhibition has affected neural cell processes.

2.
J Steroid Biochem Mol Biol ; 197: 105519, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31715316

RESUMO

There is need for a single assay able to quantify the most biologically active metabolite, 1α,25-dihydroxy-vitamin-D3, and the recently discovered biologically distinct C3-epimers of 25OHD, in addition to traditional vitamin D metabolites. We developed a method of chromatographic separation and absolute quantification of the following ten forms of vitamin D: 3-epi-25OHD3, 25OHD3, 3-epi-25OHD2, 25OHD2, 1α,25(OH)2D3, 24R,25(OH)2D3, 23R,25(OH)2D3, 1a,25(OH)2D2, D3, and D2 by single extraction and injection. Chemical derivatization followed by liquid chromatography using a charged surface hybrid C18 column and subsequent tandem mass spectrometry was utilized to detect and quantify each metabolite. This method is remarkable as a cooled column was required to achieve chromatographic resolution of epimers. Validation of each metabolite was performed at four concentrations and revealed inter- and intra-day precision and accuracy below 15% across three consecutive days of analysis. After validation, this method was applied to analyze the blood plasma from 739 samples from 352 subjects (8mo to 20 yr), 79 pooled plasma samples, and 10 NIST SRM972a samples. Healthy control samples (n = 357) were used to investigate developmentally associated changes in vitamin D metabolite concentrations during early life. This method yields excellent linearity (R2 ≥ 0.99) across concentrations encompassing the biological range of many metabolites including 1α,25(OH)2D3. Concentrations of 25OHD2 and 24R,25(OH)2D3 were significantly (q ≤0.05) lower in infants compared to both children and adolescents. The percentage of 3-epi-25OHD3 in total 25OHD3 was significantly lower (q ≤ 0.009) in post-puberty subjects. Here we present a single assay capable of separating and quantifying ten vitamin D metabolites including C3-epimers of 25OHD, and quantifying 1α,25-dihydroxy-vitamin-D3 at and below concentrations observed in human plasma (LLOQ < 10 pM).

3.
Artigo em Inglês | MEDLINE | ID: mdl-31600025

RESUMO

OBJECTIVE: The aim of this study was to determine the association of perceived stress with incident inflammatory arthritis (IA) defined as having at least 1 joint consistent with rheumatoid arthritis (RA)-like synovitis based on exam. METHODS: We conducted a prospective cohort study in the Studies of the Etiologies of Rheumatoid Arthritis (SERA). Participants without IA were recruited if they were a first degree relative of a RA proband or screened positive for anti-cyclic citrullinated peptide autoantibody (ACPA). Perceived stress was measured using the Perceived Stress Scale-14 (PSS) in which scores can range from 0 to 56 and a higher score indicates greater perceived stress. The total PSS score as well as two sub-scores indicative of perceived distress and self-efficacy were averaged across all study visits until development of IA or last follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) of IA associated with average PSS scores were obtained using Cox proportional hazards models. RESULTS: The mean total PSS score was 20.4. We found that a one-point increase in the perceived distress score was significantly associated with a 10 percent increase in the risk of IA (adjusted HR: 1.10; 95%CI: 1.02, 1.19). Total PSS and self-efficacy were not associated with IA risk (adjusted HR: 1.05 (95%CI: 0.99, 1.10) and 1.04 (95%CI: 0.91, 1.18), respectively. CONCLUSIONS: An association between perceived distress and incident IA was observed in this at-risk cohort. Replication of this finding in other preclinical and at-risk RA populations is needed.

4.
Mol Immunol ; 112: 256-265, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31207549

RESUMO

Rheumatoid arthritis (RA) is a complex autoimmune disease with an etiology that is not yet well understood, disproportionally affects women and also varies in incidence and prevalence by population. The presence of anti-citrullinated protein antibodies (ACPA) is a highly specific biomarker for the diagnosis of clinically apparent RA. ACPA are also present in the serum for an average of 3-5 years prior to the onset of RA during an asymptomatic period characterized by mucosal inflammation and local ACPA production at these sites. We hypothesized that systemic complement activation products might be generated during the pre-clinical initiation of RA and/or provide a second hit that promotes subsequent arthritis development in the joints. In addition, we evaluated which demographic and genetic features and environmental exposures could influence the complement activation process. We analyzed plasma from healthy subjects, subjects at-risk for the development of RA based on serum ACPA positivity in absence of inflammatory arthritis (IA), and ACPA positive RA subjects by Multiplex Assay and ELISA for eighteen complement system components, factors and activation products belonging to the classical, lectin and alternative pathways. By using regression models, associations between complement proteins and various demographic, genetic, and environmental factors previously found to be associated with RA, including sex, smoking, shared epitope, and oral contraceptive use, were examined. We found no evidence of systemic complement activation in ACPA positive subjects without IA, but in contrast found evidence of systemic involvement of the both classical and alternative pathways during the stage of the disease where classified RA is present, (i.e. during joint inflammation and damage). With regard to the demographic, genetic, and environmental variables, females who reported current or past oral contraceptive use and subjects with current tobacco exposure demonstrated alterations of the alternative pathway of complement. Furthermore, RA subjects with established disease who have a body mass index categorized as obese demonstrated higher levels of C2 compared to RA subjects who are not considered obese. In sum, the complement system may be involved in the pathogenesis of RA, with only localized mucosal effects during the preclinical period in those at-risk for RA but in the joint as well as systemically in those who have developed clinically apparent arthritis.


Assuntos
Artrite Reumatoide/imunologia , Proteínas do Sistema Complemento/imunologia , Anticorpos Anti-Proteína Citrulinada/imunologia , Índice de Massa Corporal , Estudos de Casos e Controles , Ativação do Complemento/imunologia , Progressão da Doença , Epitopos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/imunologia , Tabaco/imunologia
5.
Am J Gastroenterol ; 114(8): 1307-1314, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31082869

RESUMO

OBJECTIVES: To determine the association between the amount of gluten intake in childhood and later celiac disease (CD), for which data are currently scarce. METHODS: The prospective Diabetes Autoimmunity Study in the Young cohort includes 1875 at-risk children with annual estimates of gluten intake (grams/d) from age 1 year. From 1993 through January 2017, 161 children, using repeated tissue transglutaminase (tTGA) screening, were identified with CD autoimmunity (CDA) and persistent tTGA positivity; of these children, 85 fulfilled CD criteria of biopsy-verified histopathology or persistently high tTGA levels. Cox regression, modeling gluten intake between ages 1 and 2 years (i.e., in 1-year-olds), and joint modeling of cumulative gluten intake throughout childhood were used to estimate hazard ratios adjusted for confounders (aHR). RESULTS: Children in the highest third of gluten intake between the ages of 1 and 2 years had a 2-fold greater hazard of CDA (aHR 2.17; 95% confidence interval [CI], 1.22-3.88; P value = 0.01) and CD (aHR 1.96; 95% CI, 0.90-4.24; P value = 0.09) than those in the lowest third. The risk of developing CDA increased by 5% per daily gram increase in gluten intake (aHR 1.05; 95% CI, 1.00-1.09; P value = 0.04) in 1-year-olds. The association between gluten intake in 1-year-olds and later CDA or CD did not differ by the child's human leukocyte antigen genotype. The incidence of CD increased with increased cumulative gluten intake throughout childhood (e.g., aHR 1.15 per SD increase in cumulative gluten intake at age 6; 95% CI, 1.00-1.32; P value = 0.04). DISCUSSION: Gluten intake in 1-year-olds is associated with the future onset of CDA and CD in children at risk for the disease.

6.
J Am Pharm Assoc (2003) ; 59(4S): S19-S24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080150

RESUMO

OBJECTIVES: The objectives of this study were to assess how a charitable pharmacy model affects patient perception of health care insecurity, physical and emotional functioning, and medication access in an underserved population. METHODS: New patients presenting for medication at their initial pharmacy visit at Charitable Pharmacy of Central Ohio were screened for eligibility during a 12-week enrollment period. Participants completed a baseline survey containing the Health Care Insecurity Measure (HCIM), Veterans RAND 12-Item Health Survey (VR-12), and medication access questions. The follow-up survey, which contained the HCIM and VR-12 only, was administered during a pharmacy visit at least 14 days after the patient's initial visit. Survey data were analyzed with the use of descriptive statistics. RESULTS: A total of 105 patients met eligibility criteria, and 17 patients declined to participate. Of the 88 remaining participants, 33 (38%) completed the study (both baseline and follow-up survey). Of the 33 participants who completed the study, there was a statistically significant decrease from the baseline health care insecurity score (23.2 ± 11.1) to the follow-up score (17.9 ± 8.5; P = 0.0031). CONCLUSION: This study demonstrated that pharmacists working in a charitable pharmacy can have a positive impact on the sense of security patients feel about their health care and can better understand their medication-related needs.

7.
EBioMedicine ; 42: 76-85, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952617

RESUMO

BACKGROUND: Autoimmune disease prevention requires tools to assess an individual's risk of developing a specific disease. One tool is disease-associated autoantibodies, which accumulate in an asymptomatic preclinical period. However, patients sometimes exhibit autoantibodies associated with a different disease classification. When and how these alternative autoantibodies first appear remain unknown. This cross-sectional study characterizes alternative autoimmunity, and associated genetic and environmental factors, in unaffected first-degree relatives (FDRs) of patients, who exhibit increased future risk for the same disease. METHODS: Samples (n = 1321) from disease-specific autoantibody-positive (aAb+) systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes (T1D) patients; and unaffected aAb+ and autoantibody-negative (aAb-) SLE and RA FDRs were tested for SLE, RA, and T1D aAbs, as well as anti-tissue transglutaminase, anti-cardiolipin and anti-thyroperoxidase. FDR SLE and RA genetic risk scores (GRS) were calculated. FINDINGS: Alternative autoimmunity occurred in SLE patients (56%) and FDRs (57·4%), RA patients (32·6%) and FDRs (34·8%), and T1D patients (43%). Expanded autoimmunity, defined as autoantibodies spanning at least two other diseases, occurred in 18·5% of SLE patients, 16·4% of SLE FDRs, 7·8% of RA patients, 5·3% of RA FDRs, and 10·8% of T1D patients. SLE FDRs were more likely to have alternative (odds ratio [OR] 2·44) and expanded (OR 3·27) autoimmunity than RA FDRs. Alternative and expanded autoimmunity were associated with several environmental exposures. Alternative autoimmunity was associated with a higher RA GRS in RA FDRs (OR 1·41), and a higher SLE GRS in aAb+ RA FDRs (OR 1·87), but not in SLE FDRs. INTERPRETATION: Autoimmunity commonly crosses disease-specific boundaries in systemic (RA, SLE) and organ-specific (T1D) autoimmune diseases. Alternative autoimmunity is more common in SLE FDRs than RA FDRs, and is influenced by genetic and environmental factors. These findings have substantial implications for preclinical disease pathogenesis and autoimmune disease prevention studies. FUND: NIH U01AI101981, R01AR051394, U19AI082714, P30AR053483, P30GM103510, U54GM104938, U01AI101934, R01AI024717, U01AI130830, I01BX001834, & U01HG008666.


Assuntos
Artrite Reumatoide/etiologia , Autoimunidade/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/etiologia , Núcleo Familiar , Adulto , Idoso , Alelos , Artrite Reumatoide/diagnóstico , Autoanticorpos/imunologia , Meio Ambiente , Feminino , Frequência do Gene , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos/imunologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco
8.
J Immunol ; 202(8): 2210-2219, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30824481

RESUMO

The aim of this study was to test whether autoantibodies against neurologic surface Ags are found in nonneurologic autoimmune diseases, indicating a broader loss of tolerance. Patient and matched healthy donor (HD) sera were derived from four large cohorts: 1) rheumatoid arthritis (RA) (n = 194, HD n = 64), 2) type 1 diabetes (T1D) (n = 200, HD n = 200), 3) systemic lupus erythematosus (SLE) (n = 200, HD n = 67; neuro-SLE n = 49, HD n = 33), and 4) a control cohort of neurologic autoimmunity (relapsing-remitting multiple sclerosis [MS] n = 110, HD n = 110; primary progressive MS n = 9; secondary progressive MS n = 10; neuromyelitis optica spectrum disorders n = 15; and other neurologic disorders n = 26). Screening of 1287 unique serum samples against four neurologic surface Ags (myelin oligodendrocyte glycoprotein, aquaporin 4, acetylcholine receptor, and muscle-specific kinase) was performed with live cell-based immunofluorescence assays using flow cytometry. Positive samples identified in the screening were further validated using autoantibody titer quantification by serial dilutions or radioimmunoassay. Autoantibodies against neurologic surface Ags were not observed in RA and T1D patients, whereas SLE patients harbored such autoantibodies in rare cases (2/200, 1%). Within the CNS autoimmunity control cohort, autoantibodies against aquaporin 4 and high-titer Abs against myelin oligodendrocyte glycoprotein were, as expected, specific for neuromyelitis optica spectrum disorders. We conclude that neurologic autoantibodies do not cross disease barriers in RA and T1D. The finding of mildly increased neurologic autoantibodies in SLE may be consistent with a broader loss of B cell tolerance in this form of systemic autoimmunity.


Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Proteínas do Tecido Nervoso/imunologia , Doenças Autoimunes/patologia , Linfócitos B/patologia , Feminino , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade
9.
J Am Pharm Assoc (2003) ; 59(2S): S110-S117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733152

RESUMO

OBJECTIVES: To describe the implementation of enhanced health information technology (HIT), specifically an electronic health record (EHR), into the workflow of a charitable community pharmacy and to highlight the impact of the EHR on clinical service advancement, student and resident learning, research, and grant support for the pharmacy. SETTING: The Charitable Pharmacy of Central Ohio (CPCO) is a nonprofit community pharmacy that provides medications and pharmacy services for uninsured and underinsured patients. PRACTICE DESCRIPTION: CPCO has adopted a practice model in which patients discuss their medications and health conditions in a private counseling area with a pharmacist or pharmacy student. Counseling sessions incorporate point-of-care testing, medication therapy management, and community program referrals, with documentation of the visit in the patient's chart. PRACTICE INNOVATION: This article describes the implementation of a cloud-based EHR in a charitable community pharmacy. EVALUATION: The decision-making process for converting from a paper-based chart to an EHR is described. Feedback from stakeholders, discussions at staff meetings, and a quality improvement project led by 2 pharmacy residents helped to inform and improve the process. RESULTS: Implementation of an EHR has allowed CPCO to improve documentation of patient encounters and communicate more effectively and efficiently with other health care professionals. Student and resident learning has been enhanced, and reporting tools have facilitated additional opportunities for successful funding and more robust research. CONCLUSION: The use of an EHR at CPCO has provided opportunities to enhance patient care and improve other areas of practice. Community pharmacies should consider the utilization of HIT and EHRs to demonstrate the impact on patient care, elevate the standard of practice, and offer support for provider status.

10.
Diabetes Care ; 42(5): 789-796, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30796108

RESUMO

OBJECTIVE: To study the association of gluten intake with development of islet autoimmunity and progression to type 1 diabetes. RESEARCH DESIGN AND METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) follows children with an increased risk of type 1 diabetes. Blood samples were collected at 9, 15, and 24 months of age, and annually thereafter. Islet autoimmunity was defined by the appearance of at least one autoantibody against insulin, IA2, GAD, or ZnT8 (zinc transporter 8) in at least two consecutive blood samples. Using food frequency questionnaires, we estimated the gluten intake (in grams per day) annually from 1 year of age. Cox regression modeling early gluten intake, and joint modeling of the cumulative gluten intake during follow-up, were used to estimate hazard ratios adjusted for confounders (aHR). RESULTS: By August 2017, 1,916 subjects were included (median age at end of follow-up 13.5 years), islet autoimmunity had developed in 178 participants, and 56 of these progressed to type 1 diabetes. We found no association between islet autoimmunity and gluten intake at 1-2 years of age or during follow-up (aHR per 4 g/day increase in gluten intake 1.00, 95% CI 0.85-1.17 and 1.01, 0.99-1.02, respectively). We found similar null results for progression from islet autoimmunity to type 1 diabetes. Introduction of gluten at <4 months of age was associated with an increased risk of progressing from islet autoimmunity to type 1 diabetes compared with introduction at 4-5.9 months (aHR 8.69, 95% CI 1.69-44.8). CONCLUSIONS: Our findings indicate no strong rationale to reduce the amount of gluten in high-risk children to prevent development of type 1 diabetes.


Assuntos
Autoimunidade , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Ingestão de Alimentos/fisiologia , Glutens/administração & dosagem , Ilhotas Pancreáticas/imunologia , Autoanticorpos/sangue , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Inquéritos sobre Dietas , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Ilhotas Pancreáticas/patologia , Estudos Longitudinais , Masculino , Fatores de Risco
11.
J Neurotrauma ; 35(12): 1319-1328, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29295647

RESUMO

Spinal cord injury (SCI) without radiographical abnormalities (SCIWORA) presents a significant challenge because of the loss of function despite an apparent normal anatomy. The cause of dysfunction is not understood, and specific treatment options are lacking. Some scoliosis corrective surgeries result in SCIWORA, where stretching of the spinal cord can lead to vascular compromise and hypoxia. The iatrogenic nature of this injury allows for the implantation of neuroprotective strategies that are designed to prevent damage. We utilized a model of atraumatic SCI to evaluate the efficacy of the sodium-channel blocker, riluzole, as a prophylactic neuroprotectant. As expected, the stretch injury caused a significant reduction in intraparenchymal oxygen in distraction (-53.09 ± 22.23%) and riluzole pre-treated distraction animals (-43.04 ± 22.86%). However, in contrast to the oxidative stress and metabolic impairments observed in vehicle-treated distraction animals, in which protein carbonylation increased significantly (5.88 ± 1.3 nmol/mL), riluzole kept these levels within the normal range (1.8 ± 1.0 nmol/mL). This neurprotection also prevented ventral motor neuron hypoplasia and pyknosis, characteristic features of this atraumatic SCI model, and maintained normal gait function (e.g., stride length and stance time). This study provides evidence for the use of prophylactic neuroprotective strategies in which thoracic or spine surgeries present the risk of causing atraumatic SCI.


Assuntos
Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Riluzol/farmacologia , Traumatismos da Medula Espinal/patologia , Animais , Feminino , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Ratos , Ratos Long-Evans , Traumatismos da Medula Espinal/metabolismo
12.
J Am Pharm Assoc (2003) ; 57(3S): S203-S210.e3, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28400250

RESUMO

OBJECTIVES: This descriptive study explored whether patients with mental health conditions engage in personal medicine (self-care activities) as part of their treatment regimen. Personal medicine is patient-identified and -initiated activities of self-care that can improve mental health through various means, including physical activity, social engagement, and spiritual connectedness. The purpose of this study was to explore patient engagement in personal medicine within an underserved population and to evaluate the impact self-care might have on self-reported medication use and adherence and patient perception of mental health control. DESIGN: Cross-sectional study design with a face-to-face verbally administered survey assessing medication adherence, engagement in self-care activities, perception of self-care, and mental health control. SETTING: The study site was a nonprofit charitable pharmacy in an urban setting. The pharmacy provides medications and pharmacy services at no charge, including disease state education, point-of-care testing, and medication therapy management. PARTICIPANTS: Study participants included those who fill medications for mental health conditions and who are age 18 years and older. MAIN OUTCOME MEASURES: Main outcomes included engagement in self-care and self-reported medication adherence. Additional measures included stratification of dimensions of self-care, perception of mental health control, and patient knowledge of community resources. RESULTS: Overall, 81.7% of participants engaged in activities of self-care, with 98.3% recognizing self-care as important to improving and maintaining their mental health. Greater self-reported adherence rates and mental health control were seen with patients who participate in self-care. CONCLUSION: Participants who identify and engage in personal medicine recognize its value and are willing to incorporate it into their treatment regimen. As accessible and trusted health care providers, pharmacists can encourage patients to identify and use personal medicine to aid in the improvement of their mental health condition.


Assuntos
Adesão à Medicação/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Autocuidado/estatística & dados numéricos , Serviços Comunitários de Farmácia/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Masculino , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Participação do Paciente/estatística & dados numéricos , Farmacêuticos/estatística & dados numéricos , Testes Imediatos/estatística & dados numéricos
13.
J Neurotrauma ; 34(12): 2034-2044, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28125935

RESUMO

Corrective forces during spine deformity surgery, including distraction, impart significant stresses to the spinal cord that may result in permanent injury. Intraoperative neuromonitoring is commonly used by surgeons to recognize possible damage to the spinal cord in cases of evident traumatic or vascular damage to the spinal cord. However, mild insult to the spinal cord that does not result in obvious trauma or electrophysiological changes present a major clinical challenge as the mechanisms of this type of spinal cord injury (SCI) remain largely unknown, and thus preventive strategies are lacking. We used a sustained bidirectional spinal distraction animal model to determine the role of stretch-induced hypoxia in mild SCI. Direct measurement of intraparenchymal oxygen revealed an immediate decrease in partial pressure (47.08 ± 5.79% pO2) distal to the injury site following a 5-mm distraction. This hypoxic insult induced mitochondrial dysfunction as evidenced by an acute increase (216%) in protein oxidation 30 min post-injury, as well as a 37% decrease in perikaryal size and a 42% decrease in nuclear area (pyknosis) in ventral motor neurons at the injury site. These results indicate that hypoxic events during mild spine distraction may lead to cellular metabolic impairments and permanent functional deficits. The development of strategies targeting the prevention of hypoxic injury during spine distraction may be useful in protecting the cellular metabolic damage that may occur during spine surgery in the absence of overt mechanical or vascular SCI.


Assuntos
Mitocôndrias/metabolismo , Neurônios Motores/metabolismo , Procedimentos Neurocirúrgicos/efeitos adversos , Traumatismos da Medula Espinal/cirurgia , Medula Espinal/metabolismo , Tração/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Ratos , Ratos Long-Evans
14.
Med Eng Phys ; 38(2): 87-96, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26678325

RESUMO

Intraoperative neurophysiological monitoring (IONM) is utilized to minimize neurological morbidity during spine surgery. Transcranial motor evoked potentials (TcMEPs) are principal IONM signals in which the motor cortex of the subject is stimulated with electrical pulses and the evoked potentials are recorded from the muscles of interest. Currently available monitoring systems require the connection of 40-60 lengthy lead wires to the patient. These wires contribute to a crowded and cluttered surgical environment, and limit the maneuverability of the surgical team. In this work, it was demonstrated that the cumbersome wired system is vulnerable to electromagnetic interference (EMI) produced by operating room (OR) equipment. It was hypothesized that eliminating the lengthy recording wires can remove the EMI induced in the IONM signals. Hence, a wireless system to acquire TcMEPs was developed and validated through bench-top and animal experiments. Side-by-side TcMEPs acquisition from the wired and wireless systems in animal experiments under controlled conditions (absence of EMI from OR equipment) showed comparable magnitudes and waveforms, thus demonstrating the fidelity in the signal acquisition of the wireless solution. The robustness of the wireless system to minimize EMI was compared with a wired-system under identical conditions. Unlike the wired-system, the wireless system was not influenced by the electromagnetic waves from the C-Arm X-ray machine and temperature management system in the OR.


Assuntos
Artefatos , Fenômenos Eletromagnéticos , Potencial Evocado Motor , Monitorização Intraoperatória/instrumentação , Tecnologia sem Fio , Animais , Feminino , Salas Cirúrgicas , Ratos , Processamento de Sinais Assistido por Computador , Razão Sinal-Ruído , Fatores de Tempo
15.
Pediatr Res ; 78(4): 451-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26083762

RESUMO

BACKGROUND: Timing of solid food introduction in infancy has been associated with several chronic diseases. To explore potential mechanisms, we investigated the relationship between timing of solid food introduction and F2-isoprostanes-a marker of oxidative stress. METHODS: Urinary F2-isoprostanes were assessed in 336 healthy children aged less than 11.5 y with 1,266 clinic visits (mean = 3.8 visits per child) in the Diabetes Autoimmunity Study in the Young. We analyzed the association between F2-isoprostane concentrations and infant diet exposures using linear mixed models adjusted for age, age(2), HLA-DR3/4,DQB1*0302 genotype, first-degree relative with type 1 diabetes, maternal age, maternal education, sex, and exposure to in utero cigarette smoke. RESULTS: Later solid food introduction was associated with lower F2-isoprostane concentrations in childhood (on average, 0.10 ng/mg per month of age at introduction; estimate: -0.10 (95% confidence interval (CI): -0.18, -0.02) P value = 0.02). Moreover, childhood F2-isoprostane concentrations were, on average, 0.24 ng/mg lower in individuals breastfed at solid food introduction (estimate: -0.24 (95% CI: -0.47, -0.01) P value = 0.04) compared with those who were not. Associations remained significant after limiting analyses to F2-isoprostanes after 2 y of age. CONCLUSION: Our results suggest a long-term protective effect of later solid food introduction and breastfeeding at solid food introduction against increased F2-isoprostane concentrations throughout childhood.


Assuntos
F2-Isoprostanos/urina , Métodos de Alimentação , Alimentos Infantis , Fatores Etários , Biomarcadores/urina , Aleitamento Materno , Criança , Pré-Escolar , Métodos de Alimentação/efeitos adversos , Feminino , Humanos , Lactente , Alimentos Infantis/efeitos adversos , Modelos Lineares , Estudos Longitudinais , Masculino , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Fatores de Tempo
16.
Diabetologia ; 58(9): 2027-34, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26048237

RESUMO

AIMS/HYPOTHESIS: Dietary sugar intake may increase insulin production, stress the beta cells and increase the risk for islet autoimmunity (IA) and subsequent type 1 diabetes. METHODS: Since 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has followed children at increased genetic risk for type 1 diabetes for the development of IA (autoantibodies to insulin, GAD or protein tyrosine phosphatase-like protein [IA2] twice or more in succession) and progression to type 1 diabetes. Information on intake of fructose, sucrose, total sugars, sugar-sweetened beverages, beverages with non-nutritive sweetener and juice was collected prospectively throughout childhood via food frequency questionnaires (FFQs). We examined diet records for 1,893 children (mean age at last follow-up 10.2 years); 142 developed IA and 42 progressed to type 1 diabetes. HLA genotype was dichotomised as high risk (HLA-DR3/4,DQB1*0302) or not. All Cox regression models were adjusted for total energy, FFQ type, type 1 diabetes family history, HLA genotype and ethnicity. RESULTS: In children with IA, progression to type 1 diabetes was significantly associated with intake of total sugars (HR 1.75, 95% CI 1.07-2.85). Progression to type 1 diabetes was also associated with increased intake of sugar-sweetened beverages in those with the high-risk HLA genotype (HR 1.84, 95% CI 1.25-2.71), but not in children without it (interaction p value = 0.02). No sugar variables were associated with IA risk. CONCLUSIONS/INTERPRETATION: Sugar intake may exacerbate the later stage of type 1 diabetes development; sugar-sweetened beverages may be especially detrimental to children with the highest genetic risk of developing type 1 diabetes.


Assuntos
Carboidratos/química , Diabetes Mellitus Tipo 1/fisiopatologia , Dieta , Carboidratos da Dieta/efeitos adversos , Progressão da Doença , Autoimunidade , Criança , Pré-Escolar , Saúde da Família , Feminino , Seguimentos , Genótipo , Cadeias beta de HLA-DQ/metabolismo , Antígeno HLA-DR3/metabolismo , Antígeno HLA-DR4/metabolismo , Humanos , Lactente , Recém-Nascido , Insulina/química , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
17.
J Am Pharm Assoc (2003) ; 55(1): 59-66, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25575150

RESUMO

OBJECTIVE: To evaluate the impact that Charitable Pharmacy of Central Ohio (CPCO), a pharmacy providing free pharmacy services and medications, had on an indigent patient population by determining the change in patient-reported hospital use, ability to access medications, and perception of health status after receiving CPCO services. DESIGN: Cross-sectional study with face-to-face interviews using a convenience sample. SETTING: Columbus, OH, in January to March 2013. PATIENTS: 206 English-speaking patients 18 years or older at CPCO. INTERVENTION: Free pharmacy services and medications provided by CPCO. MAIN OUTCOMES MEASURES: Number of patient-reported hospital visits before and after CPCO use. RESULTS: In the year before using CPCO, patients reported using the hospital a mean of 2.36 (median, 2.00) times per year versus 1.33 (median, 0.67) times per year after, a decrease of 1.03 hospital visits per year per patient. Before coming to CPCO, 41% of patients were able to have all of their prescribed medications filled; this rose to 85% after using CPCO. A total of 89% of patients reported that not only was their overall health was better, but they also had a better understanding of their medications and believed they were in more control of their own health since receiving CPCO services. CONCLUSION: A charitable pharmacy model has the potential to decrease health care costs and empower patients to be more in control of their health.


Assuntos
Instituições de Caridade , Serviços Comunitários de Farmácia/provisão & distribução , Acesso aos Serviços de Saúde , Nível de Saúde , Hospitalização , Preparações Farmacêuticas/provisão & distribução , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Caridade/economia , Instituições de Caridade/tendências , Serviços Comunitários de Farmácia/economia , Serviços Comunitários de Farmácia/tendências , Estudos Transversais , Custos de Medicamentos , Prescrições de Medicamentos , Feminino , Pesquisas sobre Serviços de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Acesso aos Serviços de Saúde/economia , Acesso aos Serviços de Saúde/tendências , Hospitalização/economia , Hospitalização/tendências , Humanos , Entrevistas como Assunto , Masculino , Indigência Médica , Pessoa de Meia-Idade , Ohio , Participação do Paciente , Percepção , Preparações Farmacêuticas/economia , Avaliação de Programas e Projetos de Saúde , Fatores de Tempo , Adulto Jovem
18.
Conf Proc IEEE Eng Med Biol Soc ; 2015: 1013-6, 2015 08.
Artigo em Inglês | MEDLINE | ID: mdl-26736436

RESUMO

Functional stability and in-vivo reliability are significant factors determining the longevity of a neural interface. In this ongoing study, we test the performance of a wireless floating microelectrode array (WFMA) over a period of 143 days. The topography of the microelectrodes has allowed for selective stimulation of different fascicles of the rat sciatic nerve. We confirmed that motor evoked thresholds remain stable over time and that the nerve stimulation charges were within tissue safety limits. Importantly, motor evoked responses were elicited at threshold currents in fully awake animals without causing pain or discomfort. These data validate the use of the WFMA system for intraneural interfacing of peripheral nerves for neuroprosthetic and bioelectronics medical applications.


Assuntos
Tecnologia sem Fio , Animais , Estimulação Elétrica , Injeções , Microeletrodos , Ratos , Reprodutibilidade dos Testes , Nervo Isquiático
19.
Pediatr Diabetes ; 16(1): 31-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24444005

RESUMO

BACKGROUND: Cow's milk intake has been inconsistently associated with islet autoimmunity (IA) and type 1 diabetes (T1D) development. Genetic and environmental factors may modify the effect of cow's milk on IA and T1D risk. METHODS: The Diabetes Autoimmunity Study in the Young (DAISY) follows children at increased T1D risk of IA (presence of autoantibodies to insulin, GAD65, or IA-2 twice in succession) and T1D development. We examined 1835 DAISY children with data on cow's milk intake: 143 developed IA, 40 subsequently developed T1D. Cow's milk protein and lactose intake were calculated from prospectively collected parent- and self-reported food frequency questionnaires (FFQ). High risk HLA-DR genotype: HLA-DR3/4,DQB1*0302; low/moderate risk: all other genotypes. We examined interactions between cow's milk intake, age at cow's milk introduction, and HLA-DR genotype in IA and T1D development. Interaction models contained the base terms (e.g., cow's milk protein and HLA-DR genotype) and an interaction term (e.g., cow's milk protein*HLA-DR genotype). RESULTS: In survival models adjusted for total calories, FFQ type, T1D family history, and ethnicity, greater cow's milk protein intake was associated with increased IA risk in children with low/moderate risk HLA-DR genotypes [hazard ratio (HR): 1.41, 95% confidence interval (CI): 1.08-1.84], but not in children with high risk HLA-DR genotypes. Cow's milk protein intake was associated with progression to T1D (HR: 1.59, CI: 1.13-2.25) in children with IA. CONCLUSIONS: Greater cow's milk intake may increase risk of IA and progression to T1D. Early in the T1D disease process, cow's milk intake may be more influential in children with low/moderate genetic T1D risk.


Assuntos
Autoimunidade , Fenômenos Fisiológicos da Nutrição Infantil , Diabetes Mellitus Tipo 1/etiologia , Ingestão de Alimentos/fisiologia , Antígenos HLA-DR/genética , Ilhotas Pancreáticas/imunologia , Leite , Animais , Bovinos , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Suscetibilidade a Doenças , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Inquéritos e Questionários
20.
Diabetologia ; 57(2): 295-304, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24240437

RESUMO

AIMS/HYPOTHESES: We previously reported that lower n-3 fatty acid intake and levels in erythrocyte membranes were associated with increased risk of islet autoimmunity (IA) but not progression to type 1 diabetes in children at increased risk for diabetes. We hypothesise that specific n-3 fatty acids and genetic markers contribute synergistically to this increased risk of IA in the Diabetes Autoimmunity Study in the Young (DAISY). METHODS: DAISY is following 2,547 children at increased risk for type 1 diabetes for the development of IA, defined as being positive for glutamic acid decarboxylase (GAD)65, IA-2 or insulin autoantibodies on two consecutive visits. Using a case-cohort design, erythrocyte membrane fatty acids and dietary intake were measured prospectively in 58 IA-positive children and 299 IA-negative children. RESULTS: Lower membrane levels of the n-3 fatty acid, docosapentaenoic acid (DPA), were predictive of IA (HR 0.23; 95% CI 0.09, 0.55), while α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not, adjusting for HLA and diabetes family history. We examined whether the effect of dietary intake of the n-3 fatty acid ALA on IA risk was modified by fatty acid elongation and desaturation genes. Adjusting for HLA, diabetes family history, ethnicity, energy intake and questionnaire type, ALA intake was significantly more protective for IA in the presence of an increasing number of minor alleles at FADS1 rs174556 (pinteraction = 0.017), at FADS2 rs174570 (pinteraction = 0.016) and at FADS2 rs174583 (pinteraction = 0.045). CONCLUSIONS/INTERPRETATION: The putative protective effect of n-3 fatty acids on IA may result from a complex interaction between intake and genetically controlled fatty acid desaturation.


Assuntos
Autoanticorpos/sangue , Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/imunologia , Membrana Eritrocítica/metabolismo , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Autoanticorpos/genética , Autoimunidade/genética , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/prevenção & controle , Dieta , Progressão da Doença , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/metabolismo , Ingestão de Energia , Ácidos Graxos Dessaturases/genética , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Ilhotas Pancreáticas/imunologia , Masculino , Estudos Prospectivos , Medição de Risco , Fatores de Risco
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