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1.
J Cancer Surviv ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38839694

RESUMO

PURPOSE: The purpose of this study is to evaluate the associations between neighborhood income, education, and neighborhood racial composition (measured as a low percentage of white residents) and risk of developing cardiovascular diseases (CVD), diabetes (DM), and severe depression among survivors of AYA cancer and matched non-cancer peers. METHODS: Two-year survivors of AYA cancers diagnosed at age 15-39 yrs at Kaiser Permanente Southern California (diagnosed 2000-2012) and individually matched (1:13) non-cancer subjects were included. The development of CVD, DM, and severe depression was ascertained via electronic health records. Neighborhood characteristics were obtained from census-based geocoded data. Cox regression evaluated associations between neighborhood characteristics and the health outcomes of interest among both the cancer survivors and the non-cancer comparison cohort and effect modification by cancer survivor status on these relationships. RESULTS: Among cancer survivors (n = 6774), living in mostly non-white neighborhoods, was associated with risk of CVD (hazard ratio (HR) = 1.54 (95% CI 1.00-2.36)), while lower education level (HR = 1.41 (95% CI 1.02-1.94)) was associated with risk of severe depression. None of the neighborhood characteristics were associated with risk of DM. Effect modification was found for neighborhood education and risk of DM and severe depression. CONCLUSION: When jointly considered, cancer survivors who resided in the most disadvantaged neighborhoods were at the highest risk of developing these health outcomes compared to other subgroups. IMPLICATIONS FOR CANCER SURVIVORS: Our findings may inform screening strategy and addressing social determinants of health among AYA cancer survivors.

2.
Heliyon ; 10(11): e31628, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38845905

RESUMO

Mercury poisoning is a rare yet critical toxicological emergency, typically associated with chronic exposure. This case report details the unusual presentation of acute parkinsonism in a 66-year-old woman who had been ingesting black pills, an unidentified kind of traditional Chinese medicine, obtained from a pirate radio source. The patient displayed symptoms such as acute onset frequent falls, unsteady gait, and slow movements, prompting a detailed medical examination. The patient's neurological assessment revealed classic parkinsonian features, including mask face, cogwheel rigidity, and bradykinesia. Subsequent laboratory investigations disclosed an elevated blood mercury level (47 µg/L), and imaging studies, including 99mTc-TRODAT-1 SPECT, confirmed bilateral putamina dysfunction consistent with secondary parkinsonism. Traditional medications of Parkinsonism provided minimal relief, leading to the introduction of chelation therapy with dimercaptosuccinic acid (DMSA), resulting in a significant improvement in symptoms following a 20-day course. The discussion emphasizes the distinctive clinical manifestations of organic and inorganic mercury poisoning, underscoring the delayed onset and central nervous system involvement in organic mercury toxicity. The unidentified black pills, known to exceed mercury standards, were identified as the likely source of mercury poisoning in this case. This report acknowledges the potential reversibility of certain causes of acute parkinsonism and highlights the importance of a thorough drug history and toxicology assessment in patients presenting with acute parkinsonism. This report also contributes to the existing understanding of mercury-induced parkinsonism and emphasizes the significance of timely intervention in managing similar cases.

3.
Cureus ; 16(4): e57911, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38725774

RESUMO

Binasal quadrantanopia is a rare type of visual field defect characteristic of vision loss in either the upper or lower quadrants of both nasal visual fields. The affected individuals often exhibit impairments in peripheral vision, leading to difficulties in various daily activities such as navigation, object recognition, and hazard avoidance. The consequences of binasal quadrantanopia can be profound, affecting the individual's quality of life and functional independence. However, due to its atypical presentation and overlapping clinical features with other visual field defects, accurately pinpointing the lesion's precise location for further management becomes a complex task. Here, we present an unusual case of binasal quadrantanopia caused by bilateral anterior ischemic optic neuropathy (AION) and aim to explore the unique characteristics, etiology, and diagnostic approaches associated with binasal quadrantanopia, shedding light on the challenges encountered in lesion localization.

6.
Acta Neurol Taiwan ; 32(4): 202-206, 2023 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-37723912

RESUMO

PURPOSE: While the gustatory pathway of animals has been well-researched, that of humans is still a mystery. Several theories have been established, and some earlier reports hypothesized the relation to laterality. However, some cases could not be fully explained by the laterality theory (1). To clarify the gustatory pathway, we reported a case with bilateral hypogeusia after right thalamic infarction. CASE: This 55-year-old, right-handed man suffered from sudden decreased sensitivity of taste. He was unable to differentiate sweetness and saltiness at bilateral anterior parts of tongue. Additionally, there was numbness at the upper palate and the lips. Neurological examination revealed decreased taste sense at both sides of his anterior tongue and decreased pin-prick sensation of the left part of his lips. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke at the right ventral posteromedial nucleus (VPM). Thus, single antiplatelet therapy was administered. Two weeks later, the symptoms improved significantly and completely recovered without sequelae. CONCLUSION: The exact gustatory pathway in humans remains uncertain nowadays. First, there were few reports about dysgeusia, which might be related to clinical neglect of taste deficits. Second, our knowledge of the human gustatory pathway depends solely on sporadic cases of taste-involved brain lesions. We reported a case of bilateral hypogeusia after right thalamic infarction. This finding indicates that, although there might be laterality of gustatory fibers to the left hemisphere, anatomical variations may exist in the human gustatory system. More research is needed to elucidate the understanding of the gustatory pathway in humans.


Assuntos
Ageusia , AVC Isquêmico , Acidente Vascular Cerebral Lacunar , Animais , Masculino , Humanos , Pessoa de Meia-Idade , Ageusia/etiologia , Tálamo/diagnóstico por imagem , Núcleos Ventrais do Tálamo , Infarto Cerebral/complicações , Infarto Cerebral/diagnóstico por imagem
7.
Eur Arch Otorhinolaryngol ; 280(10): 4561-4567, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37428229

RESUMO

PURPOSE: Post-stroke dysphagia (PSD) is the most common type of dysphagia. Stroke patients with sustained dysphagia have poorer outcomes. The severity of PSD is assessed using miscellaneous scales with unknown consistencies. We aim to investigate the consistencies among miscellaneous scales, which could aid in the assessment of PSD. METHODS: A total of 49 PSD patients were enrolled. Functional Oral Intake Scale (FOIS), Dysphagia Severity Scale (DSS), Ohkuma Questionnaire, Eating Assessment Tool-10, and Repetitive Saliva Swallowing Test were performed. FOIS was performed by physicians, and DSS was conducted by both the physicians and nurses; the physicians used either videofluoroscopy (VF) or videoendoscopy (VE) for evaluation; while, the nurses assessed PSD by observation and subjective judgment. RESULTS: When using VF (VF-DSS and VF-FOIS) as the gold standard for the evaluation, VE-FOIS (κ = 0.625, 95% CI 0.300-0.950, p < 0.001) has a substantial agreement with VF-FOIS, and VE-DSS (κ = 0.381, 95% CI 0.127-0.636, p = 0.007) has a fair agreement with VF-DSS. The weighted kappa of FOIS to DSS in VE (weighted κ = 0.577, 95% CI 0.414-0.740, p < 0.001) is not lower than that in VF (weighted kappa = 0.249, 95% CI 0.136-0.362, p < 0.001). CONCLUSION: For both DSS and FOIS, only VE has a statistically significant agreement with VF. Though VF has been viewed as the traditional gold standard of dysphagia screening, it has the limitations of being invasive and equipment dependent. For PSD, VE could be considered as a substitution when VF is not available or suitable.


Assuntos
Transtornos de Deglutição , Acidente Vascular Cerebral , Humanos , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Deglutição , Programas de Rastreamento
8.
Int J Med Sci ; 20(6): 725-736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213669

RESUMO

High serum phosphate levels in chronic kidney disease (CKD) are linked to adverse health outcomes, including cardiovascular disease, kidney disease progression, and all-cause mortality. This study is aimed to find out which microorganisms or microbial functions have a significant impact on higher calcium-phosphorus product (Ca x P) after they undergo hemodialysis (HD) treatment. Feces samples from 30 healthy controls, 15 dialysis patients with controlled Ca xP (HD), and 16 dialysis patients with higher Ca xP (HDHCP) were collected to perform in 16S amplicon sequencing. We found gut microbial composition was significantly different between hemodialysis patients and healthy controls. Three phyla including Firmicutes, Actinobacteria, and Proteobacteria were significantly enriched in hemodialysis patients. Although only one genus, Lachnospiraceae_FCS020_group, was significantly increased in higher Ca xP group, there were four metabolic pathways predicted by PICRUSt significantly increased in higher Ca xP group and associated with causing VC, including the pentose phosphate pathway, steroid biosynthesis, terpenoid backbone biosynthesis, and fatty acid elongation pathway. Characterizing dysbiosis of gut microbiome played the important role in hemodialysis patients.


Assuntos
Microbioma Gastrointestinal , Insuficiência Renal Crônica , Humanos , Microbioma Gastrointestinal/genética , Rim , Fezes , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/microbiologia , Diálise Renal
9.
Int J Med Sci ; 20(3): 429-436, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860676

RESUMO

Introduction: Dysphagia-associated pneumonia is a critical health issue especially in the elders and stroke patients which carries a poorer prognosis. Therefore, we aim to identify methods with the potentials to predict subsequent pneumonia in dysphagia patients, which will be of great value in the prevention and early management of pneumonia. Methods: One-hundred dysphagia patients were enrolled and measurements including Dysphagia Severity Scale (DSS), Functional Oral Intake Scale (FOIS), Ohkuma Questionnaire, and Eating Assessment Tool-10 (EAT-10) were assessed by either videofluoroscopy (VF), videoendoscopy (VE), or the study nurse. The patients were categorized into mild or severe groups based on each screening method. All the patients were assessed for pneumonia at 1, 3, 6, and 20 months after the examinations. Results: VF-DSS (p=0.001) is the only measurement being significantly associated with subsequent pneumonia with sensitivity and specificity of 0.857 and 0.486. The Kaplan-Meier curves revealed that significant differences between the mild/severe groups start to emerge 3 months after VF-DSS (p=0.013). Cox regression models used for adjusted hazard ratio of severe VF-DSS in association with subsequent pneumonia of different timepoints after controlling the important covariates showed the following results: 3 months, p=0.026, HR=5.341, 95%CI=1.219-23.405; 6 months, p=0.015, HR=4.557, 95%CI=1.338-15.522; 20 months, p=0.004, HR=4.832, 95%CI=1.670-13.984. Conclusions: Dysphagia severity evaluated by VE-DSS, VE-FOIS, VF-FOIS, Ohkuma Questionnaire, and EAT-10 is not associated with subsequent pneumonia. Only VF-DSS is associated with both short-term and long-term subsequent pneumonia. In patients with dysphagia, VF-DSS is predictive of subsequent pneumonia.


Assuntos
Transtornos de Deglutição , Pneumonia , Acidente Vascular Cerebral , Humanos , Idoso , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Pneumonia/diagnóstico , Pneumonia/diagnóstico por imagem , Grupo Social , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
11.
Curr Alzheimer Res ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36453507

RESUMO

Alzheimer's disease (AD) and dysphagia are important health and socioeconomic problems in the aging population. Currently, the medical treatment of dysphagia in AD patients remains insufficient, and there are significant gaps in the management and clinical needs to postpone tube feeding. Literatures published over the last 30 years were searched in the PubMed and Embase databases. All relevant and promising pharmacological management studies were included. Because of the heterogeneity in design and methodology, only narrative reports were mentioned. Nine studies were included with two case reports, two case series, and two observational and three randomized controlled trials. The key approaches and clinical problems related to dysphagia include onset pattern, dementia stage, review of offending drugs and polypharmacy, and comorbidities (cerebrovascular disease, hypertension, parkinsonism, depression, and anorexia). The corresponding strategies of pharmacological treatments are further proposed and discussed comprehensively, with transient receptor potential channel modulators as promising treatment. With the integration of adequate and potential pharmacomanagement, AD patients with dysphagia can achieve a good prognosis and postpone tube feeding to maintain a better quality of life. More rigorous studies are needed to verify the effectiveness of innovative strategies and develop targets for neurostimulation.

12.
J Clin Neurol ; 18(6): 653-662, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36367063

RESUMO

BACKGROUND AND PURPOSE: Thoroughly acquainting physicians with the effects of antiseizure medications (ASMs) is essential for developing appropriate therapeutic regimens for seizure management. This review summarizes the available evidence regarding patients receiving the antiseizure agent perampanel (PER) and its effects on the cognition, behavior, and psychological status of patients. METHODS: The PubMed and Google Scholar databases were searched for all relevant articles published during 2015-2021 and without any other publication limitations, and also manually searched the reference lists in the identified articles. Outcomes of interest were changes in seizure frequency relative to baseline, 50% responder rate, seizure-free rate, and retention rate (proportion of participants continuing PER at study endpoints). Safety outcomes included adverse effects and the percentage of patients experiencing effects on cognitive, psychiatric, and behavioral symptoms. RESULTS: We identified 139 studies, of which 28 were included after screening. Most studies found reduced seizure frequencies and satisfactory responder and retention rates, demonstrating the effectiveness and tolerability of PER. No negative effects were found for cognitive function, but a nonnegligible impact on aggressive behavior was noted when compared with other ASMs. Patients with previous psychiatric comorbidities had a greater risk of psychiatric side effects under PER treatment. PER induces an overall improvement in quality of life. CONCLUSIONS: After synthesizing the study results, PER was a safe and effective choice as an additional therapy for patients with refractory epilepsy. A comprehensive evaluation of behavior and psychiatric risk is suggested before implementing PER.

13.
Acta Neurol Taiwan ; 31(2): 80-83, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35266135

RESUMO

PURPOSE: Vertebrobasilar insufficiency (VBI) is a common transient neurological condition related to posterior circulation hemodynamic insufficiency. However, it is rarely seen as an initial presentation in basilar artery (BA) fenestration or hypoglycemia. We present this case to further clarify the association between BA fenestration and hypoglycemia-induced VBI, as well as the difficulty in diagnosis, especially in acute clinical settings. CASE REPORT: Herein, we report a case with BA fenestration, in which the patient suffered from transient episodes of focal neurological deficits, including dysarthria, focal limbs weakness, and ataxia with subsequent total recovery. Apart from hypoglycemia, no other abnormal laboratory surveys were found. This concurrent finding of hypoglycemia with transient focal neurological deficit poses a difficulty in differentiating between hypoglycemia-induced VBI and true acute ischemic stroke in the clinical setting. Subsequent brain imaging studies revealed no evidence of acute infarction and no evidence of atherosclerosis changes in vessels but BA fenestration was observed. We prescribed antiplatelets for the prevention of future strokes. However, currently, no consensus exists regarding the prevention of cerebral ischemia with BA fenestration. CONCLUSION: BA fenestration-induced VBI and hypoglycemia-induced VBI are rarely reported and their mechanisms of action remain uncertain and controversial. However, BA fenestration-induced VBI may pose a risk for future cerebral ischemic events and warrants further investigations.


Assuntos
Hipoglicemia , AVC Isquêmico , Insuficiência Vertebrobasilar , Artéria Basilar , Infarto Cerebral/complicações , Humanos , Hipoglicemia/complicações , Insuficiência Vertebrobasilar/complicações , Insuficiência Vertebrobasilar/diagnóstico
14.
Gerontology ; 68(1): 53-61, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33882496

RESUMO

INTRODUCTION: Dementia is one of the major causes of disability and dependency among older people worldwide. Alz-heimer's disease (AD), the most common cause of dementia among the elderly, has great impact on the health-care system of developed nations. Several risk factors are suggestive of an increased risk of AD, including APOE-ε4, male, age, diabetes mellitus, hypertension, and low social engagement. However, data on risk factors of AD progression are limited. Air pollution is revealed to be associated with increasing dementia incidence, but the relationship between air pollution and clinical AD cognitive deterioration is unclear. METHODS: We conducted a case-control and city-to-city study to compare the progression of AD patients in different level of air-polluted cities. Clinical data of a total of 704 AD patients were retrospectively collected, 584 residences in Kaohsiung and 120 residences in Pingtung between 2002 and 2018. An annual interview was performed with each patient, and the Clinical Dementia Rating score (0 [normal] to 3 [severe stage]) was used to evaluate their cognitive deterioration. Air pollution data of Kaohsiung and Pingtung city for 2002-2018 were retrieved from Taiwan Environmental Protection Administration. Annual Pollutant Standards Index (PSI) and concentrations of particulate matter (PM10), sulfur dioxide (SO2), ozone (O3), nitrogen dioxide (NO2), and carbon monoxide (CO) were obtained. RESULTS: The PSI was higher in Kaohsiung and compared with Pingtung patients, Kaohsiung patients were exposed to higher average annual concentrations of CO, NO2, PM10, and SO2. AD patients living in Kaohsiung suffered from faster cognitive deterioration in comparison with Pingtung patients (log-rank test: p = 0.016). When using multivariate Cox proportional hazards regression analysis, higher levels of CO, NO2, PM10, and SO2 exposure were associated with increased risk of AD cognitive deterioration. Among all these air pollutants, high SO2 exposure has the greatest impact while O3 has a neutral effect on AD cognitive deterioration. CONCLUSIONS: Air pollution is an environment-related risk factor that can be controlled and is associated with cognitive deterioration of AD. This finding could contribute to the implementation of public intervention strategies of AD.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença de Alzheimer , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Poluição do Ar/estatística & dados numéricos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/etiologia , Cognição , Humanos , Masculino , Estudos Retrospectivos
15.
Aging (Albany NY) ; 13(15): 19878-19893, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34375303

RESUMO

To date, different experimental strategies have been developed for the ex vivo expansion of human hematopoietic stem cells (HSCs) for clinical applications. However, differences in the genomic function of expanded HSCs under different culture systems remain unclear. In this study, we compared the gene expression profiles of HSCs in ex vivo expanded serum (10% FBS, fetal bovine serum) and serum-free culture systems and analyzed the molecular functions of differentially expressed genes using microarray chips. We identified 839 differentially expressed genes between the two culture systems. These genes were enriched in the TNF -regulated inflammatory pathway in an FBS culture system. In addition, the mRNA expression of CCL2 (C-C motif chemokine ligand 2), TNF (tumor necrosis factor) and FOS (FBJ murine osteosarcoma viral oncogene homolog) was validated by RT-qPCR. Our data revealed that ex vivo expansion of HSCs using the FBS culture system induces an inflammatory response and high CD38 expression, indicating that this system might activate an inflammatory pathway and induce expression of the cancer marker CD38 during ex vivo expansion of HSCs. This study provides a transcriptional profile and new insights into the genomic functions of HSCs under different expanded cultures.


Assuntos
Antígenos CD34/metabolismo , Quimiocina CCL2/metabolismo , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/fisiologia , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Células Cultivadas , Quimiocina CCL2/genética , Perfilação da Expressão Gênica , Genes fos/genética , Humanos , Recém-Nascido , Fator de Necrose Tumoral alfa/genética
16.
J Int Med Res ; 49(4): 3000605211008292, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33906530

RESUMO

Trochlear palsy often results from traumatic, congenital and microvascular disorders. An intra-axial lesion as a cause of trochlear palsy is uncommon. Moreover, it usually accompanies other neurological deficits. Isolated trochlear palsy as the only presentation of brainstem stroke is unexpected. This current case report describes a 74-year-old male that presented with trochlear palsy without other neurological signs. Brain magnetic resonance imaging (MRI) revealed an acute midbrain infarction. The case report also reviews recent literature and provides a stepwise algorithm for clinicians to approach patients with trochlear palsy. Despite its rarity, clinicians are advised to consider ischaemic stroke as a cause of trochlear palsy even without other neurological deficits. Early MRI should be performed for prompt and proper management.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Doenças do Nervo Troclear , Idoso , Humanos , Imageamento por Ressonância Magnética , Masculino , Mesencéfalo/diagnóstico por imagem , Paralisia , Acidente Vascular Cerebral/diagnóstico por imagem , Doenças do Nervo Troclear/complicações , Doenças do Nervo Troclear/diagnóstico por imagem
18.
J Clin Oncol ; 38(27): 3161-3174, 2020 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-32673152

RESUMO

PURPOSE: To describe the incidence, relative risk, and risk factors for chronic comorbidities in survivors of adolescent and young adult (AYA) cancer. METHODS: This retrospective cohort study included 2-year survivors of AYA cancer diagnosed between age 15 and 39 years at Kaiser Permanente Southern California from 2000 to 2012. A comparison cohort without cancer was individually matched (13:1) to survivors of cancer on age, sex, and calendar year. Using electronic medical records, all participants were followed through December 31, 2014, for chronic comorbidity diagnoses. Poisson regression was used to evaluate the association between cancer survivor status and risk of developing each comorbidity. The associations between cumulative exposure to chemotherapy and radiation therapy and selected comorbidities were examined for survivors of cancer. RESULTS: The cohort included 6,778 survivors of AYA cancer and 87,737 persons without a history of cancer. The incidence rate ratio (IRR) for survivors of cancer was significantly increased for nearly all comorbidities examined. IRR ranged from 1.3 (95% CI, 1.2 to 1.4) for dyslipidemia to 8.3 (95% CI, 4.6 to 14.9) for avascular necrosis. Survivors of AYA cancer had a 2- to 3-fold increased risk for cardiomyopathy, stroke, premature ovarian failure, chronic liver disease, and renal failure. Among survivors of cancer, significant associations between chemotherapy and radiation therapy exposures and late effects of cardiomyopathy, hearing loss, stroke, thyroid disorders, and diabetes were observed from the multivariable analyses. Forty percent of survivors of AYA cancer had multiple (≥ 2) comorbidities at 10 years after index date, compared with 20% of those without cancer. CONCLUSION: Risk of developing comorbidities is increased in survivors of AYA cancer compared with the general population. Specific cancer treatment exposures were associated with risk of developing different comorbidities. These findings have important implications for survivorship care planning and patient education.


Assuntos
Antineoplásicos/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças do Sistema Endócrino/epidemiologia , Neoplasias/epidemiologia , Radioterapia/estatística & dados numéricos , Adolescente , Adulto , California/epidemiologia , Sobreviventes de Câncer , Estudos de Casos e Controles , Doença Crônica/epidemiologia , Comorbidade , Dislipidemias/epidemiologia , Feminino , Perda Auditiva/epidemiologia , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Hepatopatias/epidemiologia , Masculino , Neoplasias/terapia , Osteonecrose/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
19.
Transl Psychiatry ; 10(1): 146, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398703

RESUMO

Self-antigen presentation outside the central nervous system has crucial role regarding self-proteins tolerance and autoimmunity, leading to neuroinflammation. Self-antigen with strong-binding affinity is considered to be pathogenic. We aim to investigate whether strong-binding affinity self-antigen load is associated with early/late-onset Alzheimer's disease (AD). A total of 54 AD samples (22 early-onset, 32 late-onset) underwent next-generation sequencing (NGS) for whole-exome sequencing. Genotypes of HLA class I genes and germline mutations were obtained for estimation of the binding affinity and number of self-antigens. For each patient, self-antigen load was estimated by adding up the number of self-antigens with strong-binding affinity. Self-antigen load of early-onset AD was significantly higher than late-onset AD (mean ± SD: 6115 ± 2430 vs 4373 ± 2492; p = 0.011). An appropriate cutoff value 2503 for dichotomizing self-antigen load was obtained by receiver operating characteristic (ROC) curve analysis. Patients were then dichotomized into high or low self-antigen load groups in the binary multivariate logistic regression analysis. Adjusted odds ratio of the high self-antigen load (>2503) was 14.22 (95% CI, 1.22-165.70; p = 0.034) after controlling other covariates including gender, education, ApoE status, and baseline CDR score. This is the first study using NGS to investigate germline mutations generated self-antigen load in AD. As strong-binding affinity self-antigen is considered to be pathogenic in neuroinflammation, our finding indicated that self-antigen load did have a role in the pathogenesis of AD owing to its association with neuroinflammation. This finding may also contribute to further research regarding disease mechanism and development of novel biomarkers or treatment.


Assuntos
Doença de Alzheimer , Idade de Início , Doença de Alzheimer/genética , Apolipoproteínas E , Autoantígenos , Predisposição Genética para Doença , Células Germinativas , Humanos , Sequenciamento do Exoma
20.
Clin Med (Lond) ; 20(3): e18-e19, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32414734

RESUMO

Piriformis syndrome refers to sciatica symptoms that do not originate from spinal root compression, but involve the overlying piriformis muscle. Diagnosis is clinical since there are no definitive tests to confirm the diagnosis. Piriformis syndrome is often misinterpreted as sciatica or other pains. Rarely, it could be one of the manifestations of pelvic osteomyelitis. Pelvic osteomyelitis is rare in adults, but it is associated with high morbidity and mortality. One of the severe complications is bacteraemia, which is life-threatening and may be associated with poor outcome. Acute pelvic osteomyelitis is often not initially diagnosed owing to its non-specific symptoms, including fever and severe but poorly localised pain, which may result in a delay of appropriate treatment. Thus, prompt diagnosis is crucial to the prognosis. Here, we report a patient suffering from acute pelvic osteomyelitis with piriformis syndrome as the only initial manifestation without fever. This unusual manifestation rendered prompt and correct diagnosis difficult.


Assuntos
Osteomielite , Síndrome do Músculo Piriforme , Ciática , Adulto , Humanos , Imageamento por Ressonância Magnética , Músculo Esquelético , Osteomielite/diagnóstico , Síndrome do Músculo Piriforme/diagnóstico
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