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BACKGROUND: The recent increase in opioid misuse and overdose among the Hispanic population signifies the need for an initiative to increase efforts in pain management in the Hispanic population. Yoga is an evidence-based therapeutic intervention that is effective for several pain-associated disorders. However, in the United States, it is primarily taught in English and not always accessible. This quality improvement (QI) project aimed to assess the outcome of implementing a yoga program on pain and quality of life in the Hispanic population. METHODS: Twenty Spanish-speaking community center members participated in a linguistically-tailored yoga program over the course of 10 weeks that included educational, demonstration, and practice videos. Outcome measures of the QI program included changes in pain interference, physical function, opioid medication use, the overall impression of change in pain, satisfaction with the program, and the likelihood of continuation of yoga practice. RESULTS: Data collected from participants (n = 16) after the 10-week period indicated that nearly 60% experienced an improvement in their overall impression of change in pain; their reported likelihood of continuation of yoga practice at home or another location were 6.8 and 7.4, respectively, on a 10-point scale. While pain interference was unaffected, there was an improvement in markers of physical function, including a two-fold improvement in general activity without limitations. The mean average intensity of pain decreased by 33%. CONCLUSION: The use of a linguistically-tailored yoga program improved self-reported overall pain, physical function, average intensity of pain, and initiated an interest in participants in utilizing yoga practice for self-management of pain. This QI project provides results that can be used for further implementation initiatives at other sites and consideration of use in diverse populations.
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Dor Crônica , Hispânico ou Latino , Manejo da Dor , Melhoria de Qualidade , Yoga , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Dor Crônica/terapia , Hispânico ou Latino/estatística & dados numéricos , Hispânico ou Latino/psicologia , Adulto , Manejo da Dor/métodos , Manejo da Dor/normas , Manejo da Dor/estatística & dados numéricos , Idoso , Qualidade de Vida/psicologiaRESUMO
BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults. METHODS: Pioglitazone has been shown to improve liver histology in adult patients with MASLD, and in some studies, it attenuated liver fibrosis. Despite its perceived efficacy, pioglitazone is not widely used, likely due to its side effect profile, specifically increased weight gain. Topiramate lowers body weight in adolescents and in combination with phentermine, is one of the few FDA-approved medications for the management of obesity in children over 12 years of age. We performed a retrospective review of the outcomes in pediatric patients with severe MASLD, treated with the combined pioglitazone and topiramate therapy. RESULTS: Here, we report a case series of seven adolescents with severe MASLD and ≥F2 liver fibrosis treated with the combined pioglitazone and topiramate therapy. The combined therapy improved mean serum ALT from 165 ± 80 U/L to 89 ± 62 U/L after 12 months mean duration of treatment. One patient who completed 24 months of the combined therapy demonstrated a decrease in liver stiffness from 8.9 kPa to 5.6 kPa, as assessed by FibroScan elastography. There was a significant increase in body weight during this time, however, body mass index as a percentage of the 95 th percentile adjusted for age and gender did not increase significantly, 151 ± 29% vs. 152 ± 28%. Moreover, waist circumference, mid-upper arm circumference, percent body fat, and muscle mass were not significantly different before and after treatment. Serum lipid levels and hemoglobin A1c also did not change with the treatment. CONCLUSION: In summary, this case series provides encouraging results about the efficacy of the combined pioglitazone and topiramate therapy for the management of adolescents with severe MASLD, which should be further explored in clinical studies.
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Quimioterapia Combinada , Pioglitazona , Topiramato , Humanos , Topiramato/uso terapêutico , Topiramato/administração & dosagem , Pioglitazona/uso terapêutico , Pioglitazona/administração & dosagem , Adolescente , Masculino , Feminino , Estudos Retrospectivos , Resultado do Tratamento , Criança , Fígado Gorduroso/tratamento farmacológico , Frutose/análogos & derivados , Frutose/uso terapêutico , Frutose/administração & dosagem , Hipoglicemiantes/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Índice de Gravidade de Doença , Índice de Massa CorporalRESUMO
PURPOSE: Although many integrative therapies exist, studies increasingly demonstrate yoga can help change the negative neuroplastic effects experienced by people living with chronic pain. Despite encouraging findings, a gap exists in accessible yoga programs designed to meet the individual needs of those experiencing limitations from chronic pain. This study evaluated a yoga program designed for people living with chronic pain delivered in a health care setting. Although yoga began as a spiritual practice thousands of years ago, it is now widely practiced for its physical and mental well-being aspects achieved through movement and breathing techniques. DESIGN: This was a piolt study that did not include a control group. METHODS: Twenty-one people with chronic pain participated in an in-person group yoga program for 8 weeks that included an educational program and yoga practice. A prepost design was used to measure effectiveness of the program on pain interference (Brief Pain Inventory), physical function, opioid medication use, overall impression of change in pain, satisfaction with the program, and likelihood of continuation of yoga practice. RESULTS: Data collected from participants demonstrated a decrease in pain interference as measured by the Brief Pain Inventory subscale between pre- and postintervention (5.6 ± 2.2 to 4.0 ± 2.3). In addition, the proportion of respondents with a pain interference rating of severe decreased by 15.4% (38.1% to 22.7%) between the pre- and postintervention time point. On follow-up from a survey 3 months after the completion of the study, more than 25% (Nâ¯=â¯5) of participants were still practicing yoga daily. CONCLUSIONS: Despite yoga being practiced for thousands of years, studies evaluating the neural effects of yoga show possible reversal of persistent patterns leading to chronic pain, leading to new interest in an ancient practice. This study helps fill the gap in research findings addressing the benefits of yoga programs designed to meet the needs of people living in chronic pain and provides an accessible option. This program provides pain management nurses an innovative nonpharmacological intervention to consider for people living with chronic pain. CLINICAL IMPLICATIONS: Evidence supporting the use of yoga in the treatment of chronic pain is growing, yet it remains an underutilized approach in a comprehensive treatment plan. Yoga can not only improve self-agency, but also reduces social isolation. Pain management nurses can play an important role in promoting the application of yoga for chronic pain and advocating for yoga programs that are focused on accessibility for people living with pain.
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Dor Crônica , Manejo da Dor , Yoga , Humanos , Yoga/psicologia , Dor Crônica/terapia , Dor Crônica/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Manejo da Dor/métodos , Manejo da Dor/normas , Idoso , Medição da Dor/métodosRESUMO
INTRODUCTION: Differentiating Parkinson's disease (PD) from progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) is a common clinical problem. We aimed to apply the T1-/T2-weighted ratio imaging technique, based on standard clinical MRI, to reveal differences in neurodegeneration in three large cohorts. METHODS: Three cohorts, with a total of 405 participants (269 PD, 44 PSP, 38 MSA, 54 controls), were combined and T1/T2-weighted ratio image analyses were carried out. A combination of automatic segmentation and atlas-based ROI were used in this study. The cohorts were combined using the ComBat batch correction procedure. RESULTS: Group differences were found in the putamen (p = 0.040), with higher T1/T2-weighted ratio in this region in PSP compared to PD and healthy controls (p-values 0.010 and 0.007 respectively). Using putaminal T1/T2-weighted ratio for diagnostic separation, a fair performance was found in separating PSP from healthy controls, with an area under the receiver operating characteristic curve of 0.701. CONCLUSION: Different patterns of T1/T2-weighted ratio, reflecting differences in underlying pathophysiology, were found between the groups. Since T1/T2-weighted ratio can be applied to standard clinical MRI sequences to allow more quantitative analyses, this seems to be a promising biomarker for diagnostics and treatment evaluation of parkinsonian disorders for clinical trials.
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Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Humanos , Doença de Parkinson/diagnóstico por imagem , Estudos de Coortes , Transtornos Parkinsonianos/diagnóstico , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Atrofia de Múltiplos Sistemas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Diagnóstico DiferencialRESUMO
A positron emission tomography (PET) tracer detecting α-synuclein pathology will improve the diagnosis, and ultimately the treatment of α-synuclein-related diseases. Here we show that the PET ligand, [18F]ACI-12589, displays good in vitro affinity and specificity for pathological α-synuclein in tissues from patients with different α-synuclein-related disorders including Parkinson's disease (PD) and Multiple-System Atrophy (MSA) using autoradiography and radiobinding techniques. In the initial clinical evaluation we include 23 participants with α-synuclein related disorders, 11 with other neurodegenerative disorders and eight controls. In vivo [18F]ACI-12589 demonstrates clear binding in the cerebellar white matter and middle cerebellar peduncles of MSA patients, regions known to be highly affected by α-synuclein pathology, but shows limited binding in PD. The binding statistically separates MSA patients from healthy controls and subjects with other neurodegenerative disorders, including other synucleinopathies. Our results indicate that α-synuclein pathology in MSA can be identified using [18F]ACI-12589 PET imaging, potentially improving the diagnostic work-up of MSA and allowing for detection of drug target engagement in vivo of novel α-synuclein targeting therapies.
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Atrofia de Múltiplos Sistemas , Doença de Parkinson , Humanos , alfa-Sinucleína/metabolismo , Atrofia de Múltiplos Sistemas/metabolismo , Doença de Parkinson/metabolismo , Tomografia por Emissão de PósitronsRESUMO
The diagnosis of Parkinsonian disorders is currently based on clinical criteria, which have limited sensitivity until most dopaminergic neurons are lost. Here we show that cerebrospinal fluid levels of DOPA decarboxylase (DDC) (also known as aromatic L-amino acid decarboxylase) can accurately identify patients with Lewy body disease (LBD) (area under the curve (AUC) = 0.89; PFDR = 2.6 × 10-13) and are associated with worse cognitive performance (P < 0.05). We also found that DDC can detect preclinical LBD stages in clinically unimpaired individuals with a positive seed amplification α-synuclein assay (AUC = 0.81, P = 1.0 × 10-5) and that this biomarker could predict progression to clinical LBD over a 3-year period in preclinical cases (hazard ratio = 3.7 per s.d. change, confidence interval = 1.1-12.7). Moreover, DDC levels were also increased in atypical Parkinsonian disorders but not in non-Parkinsonian neurodegenerative disorders. These cerebrospinal fluid results were replicated in an independent cohort, where we also found that DDC levels in plasma could identify both LBD and atypical Parkinsonian disorders (AUC = 0.92, P = 1.3 × 10-14). Our results show that DDC might have a future role in clinical practice as a biomarker of dopaminergic dysfunction to detect Parkinsonian disorders even during the preclinical disease stages and predict their progression to clinical LBD.
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Doença por Corpos de Lewy , Doenças Neurodegenerativas , Transtornos Parkinsonianos , Humanos , Doença por Corpos de Lewy/diagnóstico , Dopa Descarboxilase , Transtornos Parkinsonianos/diagnóstico , Biomarcadores/líquido cefalorraquidianoRESUMO
There is poor knowledge about the clinical effects of Lewy body (LB) pathology in patients with cognitive impairment, especially when coexisting with Alzheimer's disease (AD) pathology (amyloid-ß and tau). Using a seed amplification assay, we analyzed cerebrospinal fluid for misfolded LB-associated α-synuclein in 883 memory clinic patients with mild cognitive impairment or dementia from the BioFINDER study. Twenty-three percent had LB pathology, of which only 21% fulfilled clinical criteria of Parkinson's disease or dementia with Lewy bodies at baseline. Among these LB-positive patients, 48% had AD pathology. Fifty-four percent had AD pathology in the whole sample (17% of mild cognitive impairment and 24% of patients with dementia were also LB-positive). When examining independent cross-sectional effects, LB pathology but not amyloid-ß or tau, was associated with hallucinations and worse attention/executive, visuospatial and motor function. LB pathology was also associated with faster longitudinal decline in all examined cognitive functions, independent of amyloid-ß, tau, cognitive stage and a baseline diagnosis of dementia with Lewy bodies/Parkinson's disease. LB status provides a better precision-medicine approach to predict clinical trajectories independent of AD biomarkers and a clinical diagnosis, which could have implications for the clinical management of cognitive impairment and the design of AD and LB drug trials.
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Doença de Alzheimer , Disfunção Cognitiva , Doença por Corpos de Lewy , Doença de Parkinson , Humanos , Corpos de Lewy/patologia , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/patologia , Doença de Parkinson/patologia , Estudos Transversais , Doença de Alzheimer/patologia , Disfunção Cognitiva/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidianoRESUMO
α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer's disease (AD) pathology (ß-amyloid (Aß) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182 cognitively and neurologically unimpaired participants from the BioFINDER study: 8% were LB positive, 26% Aß positive (13% of those were LB positive) and 16% tau positive. LB positivity occurred more often in the presence of Aß positivity but not tau positivity. LB pathology had independently negative effects on cross-sectional and longitudinal global cognition and memory and on longitudinal attention/executive function. Tau had cognitive effects of a similar magnitude, but these were less pronounced for Aß. Participants with both LB and AD (Aß and tau) pathology exhibited faster cognitive decline than those with only LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell. Only LB-positive participants progressed to clinical LB disease over 10 years. These results are important for individualized prognosis, recruitment and choice of outcome measures in preclinical LB disease trials, but also for the design of early AD trials because >10% of individuals with preclinical AD have coexisting LB pathology.
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Doença de Alzheimer , Disfunção Cognitiva , Doença por Corpos de Lewy , Humanos , alfa-Sinucleína , Corpos de Lewy/patologia , Proteínas tau/líquido cefalorraquidiano , Estudos Transversais , Doença de Alzheimer/patologia , Doença por Corpos de Lewy/líquido cefalorraquidiano , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/patologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Cognição , Disfunção Cognitiva/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Tomografia por Emissão de PósitronsRESUMO
INTRODUCTION: The diagnosis of progressive supranuclear palsy (PSP) is often challenging since PSP may clinically resemble other neurodegenerative disorders. Recently, the tau PET tracer [18F]RO948, a potential new biomarker for PSP, was developed. The aim of this study was to determine the ability of three different biomarkers, including [18F]RO948 PET, to distinguish PSP patients from healthy controls and from patients with α-synucleinopathies. METHODS: Patients with PSP (n = 23), α-synucleinopathies (n = 47) and healthy controls (n = 61) were included from the BioFINDER-2 study. [18F]RO948 standardized uptake value ratios (SUVR), magnetic resonance imaging midbrain/pons ratio, and cerebrospinal fluid neurofilament light (NfL) levels were compared between diagnostic groups individually and in combination. RESULTS: [18F]RO948 PET SUVR in the globus pallidus, NfL, and midbrain/pons area ratios were all able to differentiate PSP patients from controls and from patients with α-synucleinopathies ([18F]RO948 [mean ± SD]: controls 1.24 ± 0.22; PSP 1.47 ± 0.4; PD 1.18 ± 0.2; DLB 1.25 ± 0.24, p < 0.05), (NfL pg/mL [mean ± SD]: controls 1055 ± 569; PSP 2197 ± 1010; PD 1038 ± 416; DLB 1548 ± 687, p < 0.001) and (midbrain/pons ratio [mean ± SD]: controls 0.46 ± 0.07; PSP 0.34 ± 0.09; PD 0.43 ± 0.06; DLB 0.40 ± 0.07, p < 0.01). Receiver operating characteristic (ROC) analyses indicated that combining the three biomarkers resulted in the highest area under the ROC values (0.94 [0.88-1.00]) for separating controls from PSP and (0.92 [0.85-0.99]) for separating PSP from α-synucleinopathies. CONCLUSIONS: All studied biomarkers could individually separate PSP from controls and α-synucleinopathies patients at a group level. The optimal prediction models included NfL and midbrain/pons ratio for separating controls from PSP and all three biomarkers for separating PSP from α-synucleinopathies.
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Doença de Parkinson , Paralisia Supranuclear Progressiva , Sinucleinopatias , Humanos , Paralisia Supranuclear Progressiva/diagnóstico , Doença de Parkinson/diagnóstico , Diagnóstico Diferencial , Filamentos Intermediários/patologia , Imageamento por Ressonância Magnética/métodos , Biomarcadores/líquido cefalorraquidianoRESUMO
Genetic analysis of intra-host viral populations provides unique insight into pre-emergent mutations that may contribute to the genotype of future variants. Clinical samples positive for SARS-CoV-2 collected in California during the first months of the pandemic were sequenced to define the dynamics of mutation emergence as the virus became established in the state. Deep sequencing of 90 nasopharyngeal samples showed that many mutations associated with the establishment of SARS-CoV-2 globally were present at varying frequencies in a majority of the samples, even those collected as the virus was first detected in the US. A subset of mutations that emerged months later in consensus sequences were detected as subconsensus members of intra-host populations. Spike mutations P681H, H655Y, and V1104L were detected prior to emergence in variant genotypes, mutations were detected at multiple positions within the furin cleavage site, and pre-emergent mutations were identified in the nucleocapsid and the envelope genes. Because many of the samples had a very high depth of coverage, a bioinformatics pipeline, "Mappgene", was established that uses both iVar and LoFreq variant calling to enable identification of very low-frequency variants. This enabled detection of a spike protein deletion present in many samples at low frequency and associated with a variant of concern.
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COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2/genética , Mutação , Biologia Computacional , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Currently, there is a need for diagnostic markers in Lewy body disorders (LBD). α-synuclein (αSyn) RT-QuIC has emerged as a promising assay to detect misfolded αSyn in clinically or neuropathologically established patients with various synucleinopathies. In this study, αSyn RT-QuIC was used to analyze lumbar CSF in a clinical cohort from the Swedish BioFINDER study and postmortem ventricular CSF in a neuropathological cohort from the Arizona Study of Aging and Neurodegenerative Disorders/Brain and Body Donation Program (AZSAND/BBDP). The BioFINDER cohort included 64 PD/PDD, 15 MSA, 15 PSP, 47 controls and two controls who later converted to PD/DLB. The neuropathological cohort included 101 cases with different brain disorders, including LBD and controls. In the BioFINDER cohort αSyn RT-QuIC identified LBD (i.e. PD, PDD and converters) vs. controls with a sensitivity of 95% and a specificity of 83%. The two controls that converted to LBD were αSyn RT-QuIC positive. Within the AZSAND/BBDP cohort, αSyn RT-QuIC identified neuropathologically verified "standard LBD" (i.e. PD, PD with AD and DLB; n = 25) vs. no LB pathology (n = 53) with high sensitivity (100%) and specificity (94%). Only 57% were αSyn RT-QuIC positive in the subgroup with "non-standard" LBD (i.e., AD with Lewy Bodies not meeting criteria for DLB or PD, and incidental LBD, n = 23). Furthermore, αSyn RT-QuIC reliably identified cases with LB pathology in the cortex (97% sensitivity) vs. cases with no LBs or LBs present only in the olfactory bulb (93% specificity). However, the sensitivity was low, only 50%, for cases with LB pathology restricted to the brainstem or amygdala, not affecting the allocortex or neocortex. In conclusion, αSyn RT-QuIC of CSF samples is highly sensitive and specific for identifying cases with clinicopathologically-defined Lewy body disorders and shows a lower sensitivity for non-standard LBD or asymptomatic LBD or in cases with modest LB pathology not affecting the cortex.
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Doença por Corpos de Lewy , Sinucleinopatias , Encéfalo/patologia , Química Encefálica , Humanos , Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/patologia , alfa-Sinucleína/metabolismoRESUMO
People diagnosed with Parkinson's disease (PD) can experience significant neuropsychiatric symptoms, including cognitive impairment and dementia, the neuroanatomical substrates of which are not fully characterised. Symptoms associated with cognitive impairment and dementia in PD may relate to direct structural changes to the corpus callosum via primary white matter pathology or as a secondary outcome due to the degeneration of cortical regions. Using magnetic resonance imaging, the corpus callosum can be investigated at the midsagittal plane, where it converges to a contiguous mass and is not intertwined with other tracts. The objective of this project was thus twofold: First, we investigated possible changes in the thickness of the midsagittal callosum and cortex in patients with PD with varying levels of cognitive impairment; and secondly, we investigated the relationship between the thickness of the midsagittal corpus callosum and the thickness of the cortex. Study participants included cognitively unimpaired PD participants (n = 35), PD participants with mild cognitive impairment (n = 22), PD participants with dementia (n = 17) and healthy controls (n = 27). We found thinning of the callosum in PD-related dementia compared with PD-related mild cognitive impairment and cognitively unimpaired PD participants. Regression analyses found thickness of the left medial orbitofrontal cortex to be positively correlated with thickness of the anterior callosum in PD-related mild cognitive impairment. This study suggests that a midsagittal thickness model can uncover changes to the corpus callosum in PD-related dementia, which occur in line with changes to the cortex in this advanced disease stage.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Parkinson , Doença de Alzheimer/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologiaRESUMO
BACKGROUND: Neuroinflammation is implicated in the pathophysiology of Parkinson's disease (PD) and related conditions, yet prior clinical biomarker data report mixed findings. OBJECTIVES: The aim was to measure a panel of neuroinflammatory acute phase response (APR) proteins in the cerebrospinal fluid (CSF) of participants with PD and related disorders. METHODS: Eleven APR proteins were measured in the CSF of 867 participants from the BioFINDER cohort who were healthy (612) or had a diagnosis of PD (155), multiple system atrophy (MSA) (26), progressive supranuclear palsy (PSP) (22), dementia with Lewy bodies (DLB) (23), or Parkinson's disease with dementia (PDD) (29). RESULTS: CSF APR proteins were mostly unchanged in PD, with only haptoglobin and α1-antitrypsin significantly elevated compared to controls. These proteins were variably increased in the other disorders. Certain protein components yielded unique signatures according to diagnosis: ferritin and transthyretin were selectively elevated in MSA and discriminated these patients from all others. Haptoglobin was selectively increased in PSP, discriminating this disease from MSA when used in combination with ferritin and transthyretin. This panel of proteins did not correlate well with severity of motor impairment in any disease category, but several (particularly ceruloplasmin and ferritin) were associated with memory performance (Mini-Mental State Examination) in patients with DLB and PDD. CONCLUSIONS: These findings provide new insights into inflammatory changes in PD and related disorders while also introducing biomarkers of potential clinical diagnostic utility. © 2022 International Parkinson and Movement Disorder Society.
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Doença de Alzheimer , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Transtornos Parkinsonianos , Paralisia Supranuclear Progressiva , Reação de Fase Aguda/complicações , Reação de Fase Aguda/diagnóstico , Doença de Alzheimer/complicações , Biomarcadores/líquido cefalorraquidiano , Diagnóstico Diferencial , Ferritinas , Haptoglobinas/metabolismo , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico , Doença de Parkinson/diagnóstico , Transtornos Parkinsonianos/complicações , Pré-Albumina/metabolismo , Paralisia Supranuclear Progressiva/diagnósticoRESUMO
INTRODUCTION: Monoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans. OBJECTIVES: The main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA). METHODS: Patients with OA (n = 52) and pain-free controls (n = 30) provided CSF samples for measurement of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), noradrenaline (3-methoxy-4-hydroxyphenylglycol [HMPG]), and dopamine (homovanillic acid [HVA]) monoamine metabolites. Patients with OA completed longitudinal evaluation of pain using clinical measures and quantitative sensory testing. RESULTS: Patients with OA had higher HMPG levels when compared with controls (P = 0.036). Within patients with OA undergoing THA, higher 5-HIAA and HVA levels were consistently associated with higher preoperative pain severity. Higher concentrations of 5-HIAA and HVA were also associated with lower conditioned pain modulation levels, whereas higher HMPG levels were linked to more efficient conditioned pain modulation. Patients with higher levels of CSF HVA exhibited increased pressure pain sensitivity (arm pressure pain detection threshold < 250 kPa vs ≥ 250 kPa, P = 0.042). Higher preoperative levels of CSF 5-HIAA predicted poorer pain control 6 months postoperatively (brief pain inventory pain severity; adjusted ß = 0.010, 95% CI 0.001-0.019). CONCLUSIONS: In OA patients with disabling pain, higher CSF levels of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization. Increased noradrenergic activity may be associated with more efficient pain inhibitory capacity.
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Translational Relevance: Subclinical or clinical inflammation often arises during ocular gene therapy with viral vectors. Understanding the biological bases and impacts on efficacy are important for clinical management and the improvement of future therapies.
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Terapia Genética , Vetores Genéticos , Cegueira/genética , Vetores Genéticos/genética , Humanos , Inflamação/genética , Visão OcularRESUMO
This study seeks a better understanding of possible pathophysiological mechanisms associated with cognitive impairment and dementia in Parkinson's disease using structural and functional MRI. We investigated resting-state functional connectivity of important subdivisions of the caudate nucleus, putamen and thalamus, and also how the morphology of these structures are impacted in the disorder. We found cognitively unimpaired Parkinson's disease subjects (n = 33), compared to controls (n = 26), display increased functional connectivity of the dorsal caudate, anterior putamen and mediodorsal thalamic subdivisions with areas across the frontal lobe, as well as reduced functional connectivity of the dorsal caudate with posterior cortical and cerebellar regions. Compared to cognitively unimpaired subjects, those with mild cognitive impairment (n = 22) demonstrated reduced functional connectivity of the mediodorsal thalamus with the paracingulate cortex, while also demonstrating increased functional connectivity of the mediodorsal thalamus with the posterior cingulate cortex, compared to subjects with dementia (n = 17). Extensive volumetric and surface-based deflation was found in subjects with dementia compared to cognitively unimpaired Parkinson's disease participants and controls. Our research suggests that structures within basal ganglia-thalamocortical circuits are implicated in cognitive impairment and dementia in Parkinson's disease, with cognitive impairment and dementia associated with a breakdown in functional connectivity of the mediodorsal thalamus with para- and posterior cingulate regions of the brain respectively.
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Disfunção Cognitiva , Demência , Doença de Parkinson , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Demência/diagnóstico por imagem , Neuroimagem Funcional , Humanos , Neuroimagem , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagemRESUMO
CONTEXT.: Helicobacter pylori-associated and autoimmune gastritis may coexist in a subset of patients who require treatment for both disorders. OBJECTIVE.: To delineate findings that identify autoimmune gastritis in the background of H pylori infection. DESIGN.: We examined cases of (1) patients with H pylori-associated gastritis who had successful eradication therapy and subsequent biopsies diagnostic of autoimmune gastritis and (2) H pylori-associated gastritis wherein pathologists noted features of autoimmune gastritis during original interpretation. Control patients underwent H pylori eradication but lacked evidence of autoimmune gastritis or H pylori infection after 10 years of follow-up. RESULTS.: Eight subjects had H pylori-associated gastritis followed by H pylori-negative sampling that showed autoimmune gastritis. Review of original samples showed full-thickness inflammation of oxyntic mucosa in 8 of 8 and oxyntic gland loss in 7 of 8 cases. Enterochromaffin-like (ECL) cell hyperplasia, pyloric metaplasia, and intestinal metaplasia were present in 4 of 8 (80% of 5 tested cases), 4 of 8, and 3 of 8 cases, respectively. Features of autoimmune gastritis were noted at the time of their original H pylori diagnosis in 11 study subjects. Ten of 11 samples displayed full-thickness inflammation of oxyntic mucosa and/or partial loss of oxyntic glands, 8 of 11 had ECL cell hyperplasia (all tested cases), 6 of 11 showed pyloric metaplasia, and 4 of 11 harbored intestinal metaplasia. Except for full-thickness oxyntic mucosa inflammation, these features were absent in control cases. CONCLUSIONS.: Full-thickness inflammation combined with oxyntic gland loss and ECL cell hyperplasia may help to identify autoimmune gastritis in patients with concomitant H pylori infection.
Assuntos
Gastrite , Infecções por Helicobacter , Helicobacter pylori , Mucosa Gástrica , Gastrite/diagnóstico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Humanos , MetaplasiaRESUMO
BACKGROUND: Alzheimer's disease co-pathology is common in dementia with Lewy bodies and Parkinson's disease with dementia (Lewy body disease) and can reliably be detected with positron emission tomography (PET) or cerebrospinal fluid (CSF) biomarkers. Recently developed blood biomarkers are more accessible and less expensive alternatives. OBJECTIVE: To investigate if plasma phospho-tau217 and phospho-tau181 can detect Alzheimer's pathology in Lewy body disease with dementia. METHODS: In this cross-sectional study we investigated plasma phospho-tau217 and phospho-tau181 in 35 patients with Lewy body disease with dementia. Patients underwent tau-PET imaging (18 F-RO948). RESULTS: Plasma phospho-tau217 correlated with plasma phospho-tau181, CSF phospho-tau217 (rs = 0.68, P < 0.001), and negatively with CSF ß-amyloid42/40 (rs = -0.52, P = 0.001). Plasma phospho-tau217 and phospho-tau181 correlated with tau-PET signal in the temporal cortex (rs > 0.56, P < 0.001) and predicted abnormal tau-PET status and ß-amyloid status (area under the curve > 0.78 and > 0.81, respectively). CONCLUSION: Plasma phospho-tau might be a useful marker for Alzheimer's co-pathology in Lewy body disease with dementia. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Assuntos
Doença de Alzheimer , Doença por Corpos de Lewy , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides , Biomarcadores , Estudos Transversais , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Plasma , Proteínas tauRESUMO
ABSTRACT: Neuroinflammation is implicated in the development and maintenance of persistent pain states, but there are limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans. In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplasty due to disabling pain symptoms (n = 52) and pain-free comparison controls (n = 30). In OA patients only, detailed clinical examination and quantitative sensory testing were completed. Cerebrospinal fluid samples were analyzed for 10 proinflammatory mediators using Meso Scale Discovery platform. Compared to controls, OA patients had higher CSF levels of interleukin 8 (IL-8) (P = 0.002), intercellular adhesion molecule 1 (P = 0.007), and vascular cell adhesion molecule 1 (P = 0.006). Osteoarthritis patients with central sensitization possibly indicated by arm pressure pain detection threshold <250 kPa showed significantly higher CSF levels of Fms-related tyrosine kinase 1 (Flt-1) (P = 0.044) and interferon gamma-induced protein 10 (IP-10) (P = 0.024), as compared to subjects with PPDT above that threshold. In patients reporting pain numerical rating scale score ≥3/10 during peripheral venous cannulation, Flt-1 was elevated (P = 0.025), and in patients with punctate stimulus wind-up ratio ≥2, CSF monocyte chemoattractant protein 1 was higher (P = 0.011). Multiple logistic regression models showed that increased Flt-1 was associated with central sensitization, assessed by remote-site PPDT and peripheral venous cannulation pain, and monocyte chemoattractant protein-1 with temporal summation in the area of maximum pain. Multiple proinflammatory mediators measured in CSF are associated with persistent hip OA-related pain. Pain phenotype may be influenced by specific CSF neuroinflammatory profiles.
Assuntos
Osteoartrite do Quadril , Dor , Artralgia , Humanos , Osteoartrite do Quadril/complicações , Dor/etiologia , Limiar da Dor , FenótipoRESUMO
OBJECTIVES: Cholinergic dysfunction plays a prominent role in cognitive impairment in Parkinson's disease (PD). The aim of this study was to assess the relationship of baseline and longitudinal basal forebrain atrophy with cognitive decline and dementia in PD. METHODS: We included 106 non-demented PD patients, 19 PD dementia (PDD) patients and 42 controls with longitudinal structural MRI and cognitive testing. After 4.2 ± 1.8 years, 20 non-demented PD patients were diagnosed with dementia (PD-dementia converters), whereas the rest of PD patients remained non-demented (stable-PD). We compared MRI volumes of the medial septum/diagonal band (Ch1/Ch2) and nucleus basalis of Meynert (Ch4) between groups. Cox regression analyses were applied to test whether Ch1/Ch2 or Ch4 atrophy could predict future dementia and linear mixed models assessed their association with cognitive decline. RESULTS: Compared to controls, we found reduced Ch4 baseline volumes in PD-dementia converters (p = .003) and those who already had PDD (p < .001) but not in stable-PD. Over time, there was a greater loss in Ch1/Ch2 volumes in PD-dementia converters and PDD compared to the other groups (p = .004). Baseline and longitudinal Ch4 volumes were associated with cognition (p < .002) and longitudinal Ch4 atrophy predicted future dementia (p = .009). CONCLUSIONS: Atrophy of Ch4 precedes and predicts future dementia in PD and is followed by changes in Ch1/Ch2, reflecting a posterior-anterior pattern of basal forebrain atrophy. This pattern could be used to track the spread of cholinergic degeneration and identify patients at risk of developing dementia.