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Ear length (EL) is a key trait that contributes greatly to grain yield in maize (Zea mays). While numerous quantitative trait loci for EL have been identified, few causal genes have been studied in detail. Here we report the characterization of ear apical degeneration1 (ead1) exhibiting strikingly shorter ears and the map-based cloning of the casual gene EAD1. EAD1 is preferentially expressed in the xylem of immature ears and encodes an aluminum-activated malate transporter localizing to the plasma membrane. We show that EAD1 is a malate efflux transporter and loss of EAD1 leads to lower malate contents in the apical part of developing inflorescences. Exogenous injections of malate rescued the shortened ears of ead1. These results demonstrate that EAD1 plays essential roles in regulating maize ear development by delivering malate through xylem vessels to the apical part of the immature ear. Overexpression of EAD1 led to greater EL and kernel number per row and the EAD1 genotype showed a positive association with EL in two different genetic segregating populations. Our work elucidates the critical role of EAD1 in malate-mediated female inflorescence development and provides a promising genetic resource for enhancing maize grain yield.
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Inflorescencia , Zea mays , Mapeo Cromosómico/métodos , Grano Comestible/genética , Inflorescencia/genética , Malatos/metabolismo , Fenotipo , Sitios de Carácter Cuantitativo , Zea mays/metabolismoRESUMEN
OBJECTIVE: In Australia, 30% of newly diagnosed epilepsy patients were not immediately treated at diagnosis. We explored health outcomes between patients receiving immediate, deferred, or no treatment, and compared them to the general population. METHODS: Adults with newly diagnosed epilepsy in Western Australia between 1999 and 2016 were linked with statewide health care data collections. Health care utilization, comorbidity, and mortality at up to 10 years postdiagnosis were compared between patients receiving immediate, deferred, and no treatment, as well as with age- and sex-matched population controls. RESULTS: Of 603 epilepsy patients (61% male, median age = 40 years) were included, 422 (70%) were treated immediately at diagnosis, 110 (18%) received deferred treatment, and 71 (12%) were untreated at the end of follow-up (median = 6.8 years). Immediately treated patients had a higher 10-year rate of all-cause admissions or emergency department presentations than the untreated (incidence rate ratio [IRR] = 2.0, 95% confidence interval [CI] = 1.4-2.9) and deferred treatment groups (IRR = 1.7, 95% CI = 1.0-2.8). They had similar 10-year risks of mortality and developing new physical and psychiatric comorbidities compared with the deferred and untreated groups. Compared to population controls, epilepsy patients had higher 10-year mortality (hazard ratio = 2.6, 95% CI = 2.1-3.3), hospital admissions (IRR = 2.3, 95% CI = 1.6-3.3), and psychiatric outpatient visits (IRR = 3.2, 95% CI = 1.6-6.3). Patients with epilepsy were also 2.5 (95% CI = 2.1-3.1) and 3.9 (95% CI = 2.6-5.8) times more likely to develop a new physical and psychiatric comorbidity, respectively. SIGNIFICANCE: Newly diagnosed epilepsy patients with deferred or no treatment did not have worse outcomes than those immediately treated. Instead, immediately treated patients had greater health care utilization, likely reflecting more severe underlying epilepsy etiology. Our findings emphasize the importance of individualizing epilepsy treatment and recognition and management of the significant comorbidities, particularly psychiatric, that ensue following a diagnosis of epilepsy.
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Epilepsia , Adulto , Humanos , Masculino , Femenino , Epilepsia/epidemiología , Epilepsia/terapia , Epilepsia/diagnóstico , Comorbilidad , Hospitalización , Incidencia , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
OBJECTIVES: Amygdala enlargement is detected on magnetic resonance imaging (MRI) in some patients with drug-resistant temporal lobe epilepsy (TLE), but its clinical significance remains uncertain We aimed to assess if the presence of amygdala enlargement (1) predicted seizure outcome following anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) and (2) was associated with specific histopathological changes. METHODS: This was a case-control study. We included patients with drug-resistant TLE who underwent ATL-AH with and without amygdala enlargement detected on pre-operative MRI. Amygdala volumetry was done using FreeSurfer for patients who had high-resolution T1-weighted images. Mann-Whitney U test was used to compare pre-operative clinical characteristics between the two groups. The amygdala volume on the epileptogenic side was compared to the amygdala volume on the contralateral side among cases and controls. Then, we used a two-sample, independent t test to compare the means of amygdala volume differences between cases and controls. The chi-square test was used to assess the correlation of amygdala enlargement with (1) post-surgical seizure outcomes and (2) histopathological changes. RESULTS: Nineteen patients with and 19 patients without amygdala enlargement were studied. Their median age at surgery was 38 years for cases and 39 years for controls, and 52.6% were male. There were no statistically significant differences between the two groups in their pre-operative clinical characteristics. There were significant differences in the means of volume difference between cases and controls (Diff = 457.2 mm3, 95% confidence interval [CI] 289.6-624.8; p < .001) and in the means of percentage difference (p < .001). However, there was no significant association between amygdala enlargement and surgical outcome (p = .72) or histopathological changes (p = .63). SIGNIFICANCE: The presence of amygdala enlargement on the pre-operative brain MRI in patients with TLE does not affect the surgical outcome following ATL-AH, and it does not necessarily suggest abnormal histopathology. These findings suggest that amygdala enlargement might reflect a secondary reactive process to seizures in the epileptogenic temporal lobe.
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Amígdala del Cerebelo , Epilepsia del Lóbulo Temporal , Imagen por Resonancia Magnética , Humanos , Amígdala del Cerebelo/cirugía , Amígdala del Cerebelo/patología , Amígdala del Cerebelo/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/cirugía , Epilepsia del Lóbulo Temporal/diagnóstico por imagen , Epilepsia del Lóbulo Temporal/patología , Masculino , Femenino , Adulto , Estudios de Casos y Controles , Resultado del Tratamiento , Adulto Joven , Persona de Mediana Edad , Lobectomía Temporal Anterior/métodos , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/patología , Hipocampo/patología , Hipocampo/diagnóstico por imagen , Hipocampo/cirugía , AdolescenteRESUMEN
OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.
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Accidente Cerebrovascular Isquémico , Humanos , Estudios Retrospectivos , Constricción Patológica/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Angiografía por Tomografía Computarizada/métodos , Perfusión , Angiografía Cerebral/métodosRESUMEN
The effect of aqueous solution chemistry on the ionic hydration structure and its corresponding nanofiltration (NF) selectivity is a research gap concerning ion-selective transport. In this study, the hydration distribution of two typical monovalent anions (Cl- and NO3-) under different aqueous solution chemical conditions and the corresponding transmembrane selectivity during NF were investigated by using in situ liquid time-of-flight secondary ion mass spectrometry in combination with molecular dynamics simulations. We demonstrate the inextricable link between the ion hydration structure and the pore steric effect and further find that ionic transmembrane transport can be regulated by breaking the balance between the hydrogen bond network (i.e., water-water) and ion hydration (i.e., ion-water) interactions of hydrated ion. For strongly hydrated (H2O)nCl- with more intense ion-water interactions, a higher salt concentration and coexisting ion competition led to a larger hydrated size and, thus, a higher ion rejection by the NF membrane, whereas weakly hydrated (H2O)nNO3- takes the reverse under the same conditions. Stronger OH--anion hydration competition resulted in a smaller hydrated size of (H2O)nCl- and (H2O)nNO3-, showing a lower observed average hydration number at pH 10.5. This study deepens the long-overlooked understanding of NF separation mechanisms, concerning the hydration structure.
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Filtración , Agua/química , Iones , Simulación de Dinámica Molecular , Soluciones , Aniones/químicaRESUMEN
BACKGROUND: Physical activity may be associated with health benefits for people with epilepsy. It remains unclear how the prevalence of physical activity has changed at a national level over the years and whether this prevalence varies between subgroups. METHODS: The National Health and Interview Survey, which was conducted from 2010 to 2017 and again in 2022, was used for our nationally representative study. This study explored the trends and disparities in meeting physical activity guidelines among US individuals with epilepsy and non-epilepsy adults. RESULTS: The prevalence of adults with epilepsy meeting physical activity guidelines was consistently lower and remained unchanged compared to those without epilepsy. Among the population with epilepsy, the prevalence of aerobic physical activity was 38.1 % (95 % CI, 32.6 %-43.5 %) in 2010 and 39.0 % (95 % CI, 33.4 %-44.7 %) in 2017 (P for trend = 0.84), and remained unchanged in 2022 (39.1 %). For muscle-strength training, the prevalence was 17.5 % (95 % CI, 13.3 %-21.7 %) in 2010 and 18.8 % (95 % CI, 14.8 %-22.8 %) in 2017 (P for trend = 0.82). The prevalence for both activities combined was 12.4 % (95 % CI, 8.7 %-16.2 %) in 2010 and 16.6 % (95 % CI, 12.8 %-20.5 %) in 2017 (P for trend = 0.26). The prevalence of aerobic physical activity varied by educational attainment, body mass index, comorbid conditions, alcohol-drinking status, and epilepsy status. CONCLUSION: This study suggests that the adherence rate to meeting physical activity guidelines among US adults with epilepsy was at a low level and had not improved over time. This finding highlights the need for additional nationwide efforts to promote physical activity in the US population with epilepsy.
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Epilepsia , Ejercicio Físico , Humanos , Epilepsia/epidemiología , Ejercicio Físico/fisiología , Masculino , Adulto , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Prevalencia , Adulto Joven , Anciano , Adolescente , Encuestas EpidemiológicasRESUMEN
Identifying when recovery from a sports-related concussion (SRC) has occurred remains a challenge in clinical practice. This study investigated the utility of ocular motor (OM) assessment to monitor recovery post-SRC between sexes and compared to common clinical measures. From 139 preseason baseline assessments (i.e. before they sustained an SRC), 18 (12 males, 6 females) consequent SRCs were sustained and the longitudinal follow-ups were collected at 2, 6, and 13 days post-SRC. Participants completed visually guided, antisaccade (AS), and memory-guided saccade tasks requiring a saccade toward, away from, and to a remembered target, respectively. Changes in latency (processing speed), visual-spatial accuracy, and errors were measured. Clinical measures included The Sports Concussion Assessment Tool, King-Devick test, Stroop task, and Digit span. AS latency was significantly longer at 2 days and returned to baseline by 13-days post-SRC in females only (P < 0.001). Symptom numbers recovered from 2 to 6 days and 13 days (P < 0.05). Persistently poorer AS visual-spatial accuracy was identified at 2, 6 and 13 days post-SRC (P < 0.05) in both males and females but with differing trajectories. Clinical measures demonstrated consistent improvement reminiscent of practice effects. OM saccade assessment may have improved utility in tracking recovery compared to conventional measures and between sexes.
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Traumatismos en Atletas , Conmoción Encefálica , Masculino , Femenino , Humanos , Movimientos Sacádicos , Recuerdo Mental , CogniciónRESUMEN
INTRODUCTION: The C-reactive protein/albumin ratio is a reliable indicator of outcome risk in several diseases. This study aims to evaluate prognostic power of the C-reactive protein/albumin ratio for in-hospital mortality and the dose-response relationship between the two in the oldest-old patients with acute ischemic stroke. METHODS: A longitudinal observational study was conducted on patients with acute ischemic stroke (aged ≥80 years) from two tertiary hospitals between January 1, 2014, and January 31, 2020. Based on the tertiles of the C-reactive protein/albumin ratio, the patients were divided into three groups. Restrictive cubic spline and robust locally weighted regression analysis were performed on continuous variables to examine the dose-response relationship between the C-reactive protein/albumin ratio and in-hospital mortality risk. All-cause mortality during hospitalization was the outcome for this study. RESULTS: The study included 584 patients (mean age = 84.6 ± 3.1 years; 59.6% men). The C-reactive protein/albumin ratio was divided into three groups, namely, T1 of <0.73, T2 of 0.73-2.03, and T3: >2.03. After adjusting for demographic and clinical characteristics, a higher C-reactive protein/albumin ratio was independently associated with in-hospital mortality. The hazard ratio for this association was 2.01 (95% confidence interval: 1.12-3.60, p = 0.019). A dose-response relationship between the C-reactive protein/albumin ratio and in-hospital mortality risk was observed. Sensitivity analysis found no attenuation in the hazard ratio in uninfected individuals, whereas no difference in the hazard ratio was noted in individuals with infections. CONCLUSIONS: When predicting in-hospital mortality in the oldest-old patients with ischemic stroke, the C-reactive protein/albumin ratio might be a helpful and convenient metric.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Albúminas , Proteína C-Reactiva/análisis , Mortalidad Hospitalaria , Accidente Cerebrovascular Isquémico/complicaciones , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Sleep disturbance and fatigue are common in individuals undergoing inpatient rehabilitation following stroke. Understanding the relationships between sleep, fatigue, motor performance, and key biomarkers of inflammation and neuroplasticity could provide valuable insight into stroke recovery, possibly leading to personalized rehabilitation strategies. This study aimed to investigate the influence of sleep quality on motor function following stroke utilizing wearable technology to obtain objective sleep measurements. Additionally, we aimed to determine if there were relationships between sleep, fatigue, and motor function. Lastly, the study aimed to determine if salivary biomarkers of stress, inflammation, and neuroplasticity were associated with motor function or fatigue post-stroke. METHODS: Eighteen individuals who experienced a stroke and were undergoing inpatient rehabilitation participated in a cross-sectional observational study. Following consent, participants completed questionnaires to assess sleep patterns, fatigue, and quality of life. Objective sleep was measured throughout one night using the wearable Philips Actiwatch. Upper limb motor performance was assessed on the following day and saliva was collected for biomarker analysis. Correlation analyses were performed to assess the relationships between variables. RESULTS: Participants reported poor sleep quality, frequent awakenings, and difficulties falling asleep following stroke. We identified a significant negative relationship between fatigue severity and both sleep quality (r=-0.539, p = 0.021) and participants experience of awakening from sleep (r=-0.656, p = 0.003). A significant positive relationship was found between grip strength on the non-hemiplegic limb and salivary gene expression of Brain-derived Neurotrophic Factor (r = 0.606, p = 0.028), as well as a significant negative relationship between grip strength on the hemiplegic side and salivary gene expression of C-reactive Protein (r=-0.556, p = 0.048). CONCLUSION: The findings of this study emphasize the importance of considering sleep quality, fatigue, and biomarkers in stroke rehabilitation to optimize recovery and that interventions may need to be tailored to the individual. Future longitudinal studies are required to explore these relationships over time. Integrating wearable technology for sleep and biomarker analysis can enhance monitoring and prediction of outcomes following stroke, ultimately improving rehabilitation strategies and patient outcomes.
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Actigrafía , Biomarcadores , Fatiga , Saliva , Rehabilitación de Accidente Cerebrovascular , Dispositivos Electrónicos Vestibles , Humanos , Rehabilitación de Accidente Cerebrovascular/instrumentación , Rehabilitación de Accidente Cerebrovascular/métodos , Masculino , Femenino , Fatiga/etiología , Fatiga/diagnóstico , Persona de Mediana Edad , Biomarcadores/análisis , Estudios Transversales , Actigrafía/instrumentación , Anciano , Saliva/metabolismo , Saliva/química , Sueño/fisiología , Adulto , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología , Movimiento/fisiologíaRESUMEN
Abstractï¼Objective: To explore the relationship between risk factors of cognitive dysfunction and blood pressure variability after acute ischemic stroke in northwest Shanghai to establish a model for early identification of high-risk groups of cognitive dysfunction and formulation of more targeted prevention and treatment measures. Methods: Spearman test was used to evaluate the correlation between blood pressure variability and Montreal Cognitive Assessment (MoCA) score in patients with acute ischemic stroke and the partial regression coefficient model was constructed based on the above independent risk factors, and the receiver operating characteristic (ROC) curve was described to analyze the relevant independent risk factors. Results: ROC curve analysis results showed that the clinical prediction model was significantly more effective than a single factor in predicting the risk of cognitive impairment after acute ischemic stroke in northwest Shanghaiï¼P < 0.05ï¼. Conclusion: Cognitive dysfunction after acute ischemic stroke was closely related to high Homocysteine (Hcy) levels, high standard deviation of systolic blood pressure, previous infarction history and infarction of cognitive function area in northwest Shanghai. The prediction model based on the above factors showed satisfactory value in predicting of cognitive dysfunction risk after acute ischemic stroke and there was also the correlation between cognitive function and blood pressure variability.
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BACKGROUND: There are no robust population-based Australian data on prevalence and attributed burden of migraine and medication-overuse headache (MOH) data. In this pilot cross-sectional study, we aimed to capture the participation rate, preferred response method, and acceptability of self-report questionnaires to inform the conduct of a future nationwide migraine/MOH epidemiological study. METHODS: We developed a self-report questionnaire, available in hard-copy and online, including modules from the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) questionnaire, the Eq. 5D (quality of life), and enquiry into treatment gaps. Study invitations were mailed to 20,000 randomly selected households across Australia's two most populous states. The household member who most recently had a birthday and was aged ≥ 18 years was invited to participate, and could do so by returning a hard-copy questionnaire via reply-paid mail, or by entering responses directly into an online platform. RESULTS: The participation rate was 5.0% (N = 1,000). Participants' median age was 60 years (IQR 44-71 years), and 64.7% (n = 647) were female. Significantly more responses were received from areas with relatively older populations and middle-level socioeconomic status. Hard copy was the more commonly chosen response method (n = 736). Females and younger respondents were significantly more likely to respond online than via hard-copy. CONCLUSIONS: This pilot study indicates that alternative methodology is needed to achieve satisfactory engagement in a future nationwide migraine/MOH epidemiological study, for example through inclusion of migraine screening questions in well-resourced, interview-based national health surveys that are conducted regularly by government agencies. Meanwhile, additional future research directions include defining and addressing treatment gaps to improve migraine awareness, and minimise under-diagnosis and under-treatment.
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Autoinforme , Humanos , Proyectos Piloto , Femenino , Persona de Mediana Edad , Masculino , Australia/epidemiología , Adulto , Anciano , Estudios Transversales , Encuestas y Cuestionarios , Trastornos Migrañosos/epidemiología , Cefaleas Secundarias/epidemiología , Prevalencia , Encuestas Epidemiológicas/métodosRESUMEN
OBJECTIVES: To assess the temporal trends in the use of second antiseizure (ASM) regimens and compare the efficacy of substitution monotherapy and combination therapy after failure of initial monotherapy in people with epilepsy. METHODS: This was a longitudinal observational cohort study conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. We included patients who were newly treated for epilepsy with ASMs between July 1982, and October 2012. All patients were followed up for a minimum of 2 years. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow up. RESULTS: During the study period, 498 patients were treated with a second ASM regimen after failure of the initial ASM monotherapy, of whom 346 (69%) were prescribed combination therapy and 152 (31%) were given substitution monotherapy. The proportion of patients receiving second regimen as combination therapy increased during the study period from 46% in first epoch (1985-1994) to 78% in the last (2005-2015) (RR = 1.66, 95% CI: 1.17-2.36, corrected-p = .010). Overall, 21% (104/498) of the patients achieved seizure freedom on the second ASM regimen, which was less than half of the seizure-free rate on the initial ASM monotherapy (45%, p < .001). Patients who received substitution monotherapy had similar seizure-free rate compared with those who received combination therapy (RR = 1.17, 95% CI: 0.81-1.69, p = .41). Individual ASMs used, either alone or in combination, had similar efficacy. However, the subgroup analysis was limited by small sample sizes. SIGNIFICANCE: The choice of second regimen used based on clinical judgment was not associated with treatment outcome in patients whose initial monotherapy failed due to poor seizure control. Alternative approaches such as machine learning should be explored to aid individualized selection of the second ASM regimen.
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Anticonvulsivantes , Epilepsia , Humanos , Anticonvulsivantes/efectos adversos , Estudios de Cohortes , Epilepsia/tratamiento farmacológico , Epilepsia/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Resultado del TratamientoRESUMEN
Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug-resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes. We conducted a systematic review and meta-analysis using Medline, Embase, and Cochrane Central Register of Controlled Trials. All studies reporting pre- and post-epilepsy surgery QoL scores in adults with DRE via validated instruments were included. Meta-analysis assessed the postsurgery change in QoL. Meta-regression assessed the effect of postoperative seizure outcomes on postoperative QoL as well as change in pre- and postoperative QoL scores. A total of 3774 titles and abstracts were reviewed, and ultimately 16 studies, comprising 1182 unique patients, were included. Quality of Life in Epilepsy Inventory-31 item (QOLIE-31) meta-analysis included six studies, and QOLIE-89 meta-analysis included four studies. Postoperative change in raw score was 20.5 for QOLIE-31 (95% confidence interval [CI] = 10.9-30.1, I2 = 95.5) and 12.1 for QOLIE-89 (95% CI = 8.0-16.1, I2 = 55.0%). This corresponds to clinically meaningful QOL improvements. Meta-regression demonstrated a higher postoperative QOLIE-31 score as well as change in pre- and postoperative QOLIE-31 score among studies of cohorts with higher proportions of patients with favorable seizure outcomes. At an individual study level, preoperative absence of mood disorders, better preoperative cognition, fewer trials of antiseizure medications before surgery, high levels of conscientiousness and openness to experience at the baseline, engagement in paid employment before and after surgery, and not being on antidepressants following surgery were associated with improved postoperative QoL. This study demonstrates the potential for epilepsy surgery to provide clinically meaningful improvements in QoL, as well as identifies clinicodemographic factors associated with this outcome. Limitations include substantial heterogeneity between individual studies and high risk of bias.
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Epilepsia Refractaria , Epilepsia , Adulto , Humanos , Calidad de Vida , Epilepsia/cirugía , Convulsiones , AntidepresivosRESUMEN
We developed a phosphine-catalyzed ring-opening reaction of cyclopropenones with dicarbonyl compounds as C-nucleophiles, leading to 1,3,3'-tricarbonyl compounds. During this neutral procedure, C-acylation is more dominant than O-acylation. This transition-metal free procedure features mild and neutral reaction conditions with good atom economy. As such, it represents a facile pathway to access 1,3,3'-tricarbonyl derivatives.
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MHC class I (MHC-I)-restricted CD4+ T cells have long been discovered in the natural repertoire of healthy humans as well as patients with autoimmune diseases or cancer, but the exact origin of these cells remains to be fully characterized. In mouse models, mature peripheral CD8+ T cells have the potential to convert to CD4+ T cells in the mesenteric lymph nodes. This conversion can produce a unique population of MHC-I-restricted CD4+ T cells including Foxp3+ regulatory T cells termed MHC-I-restricted CD4+Foxp3+ T (CI-Treg) cells. In this study we examined the cellular and molecular elements that promote CD8-to-CD4 lineage conversion and the development of CI-Treg cells in mice. Using adoptive transfer and bone marrow chimera experiments, we found that the differentiation of CI-Treg cells was driven by lymph node stromal cell (LNSC)-intrinsic MHC-II expression as opposed to transcytosis of MHC-II from bone marrow-derived APCs. The lineage conversion was accompanied by Runx3 versus ThPOK transcriptional switch. This finding of a new role for LNSCs in vivo led us to develop an efficient tissue culture method using LNSCs to generate and expand CI-Treg cells in vitro. CI-Treg cells expanded in vitro with LNSCs effectively suppressed inflammatory tissue damage caused by pathogenic CD4+ T cells in mouse models of colitis. This study identified a novel role of MHC-II expressed by LNSCs in immune regulation and the potential utilization of LNSCs to generate novel subsets of immune regulatory cells for therapeutic applications.
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Linfocitos T CD8-positivos/inmunología , Linaje de la Célula/genética , Colitis/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Ganglios Linfáticos/inmunología , Transducción de Señal/genética , Células del Estroma/inmunología , Linfocitos T Reguladores/inmunología , Traslado Adoptivo/métodos , Animales , Células Presentadoras de Antígenos/inmunología , Linaje de la Célula/inmunología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Antígenos de Histocompatibilidad Clase II/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
People with epilepsy have variable and dynamic trajectories in response to antiseizure medications. Accurately modelling long-term treatment response will aid prognostication at the individual level and health resource planning at the societal level. Unfortunately, a robust model is lacking. We aimed to develop a Markov model to predict the probability of future seizure-freedom based on current seizure state and number of antiseizure medication regimens trialled. We included 1795 people with newly diagnosed epilepsy who attended a specialist clinic in Glasgow, Scotland, between July 1982 and October 2012. They were followed up until October 2014 or death. We developed a simple Markov model, based on current seizure state only, and a more detailed model, based on both current seizure state and number of antiseizure medication regimens trialled. Sensitivity analyses were performed for the regimen-based states model to examine the effect of regimen changes due to adverse effects. The model was externally validated in a separate cohort of 455 newly diagnosis epilepsy patients seen in Perth, Australia, between May 1999 and May 2016. Our models suggested that once seizure-freedom was achieved, it was likely to persist, regardless of the number of antiseizure medications trialled to reach that point. The likelihood of achieving long-term seizure-freedom was highest with the first antiseizure medication regimen, at approximately 50%. The chance of achieving seizure-freedom fell with subsequent regimens. Fluctuations between seizure-free and not seizure-free states were highest earlier on but decreased with chronicity of epilepsy. Seizure-freedom/recurrence risk tables were constructed with these probability data, similar to cardiovascular risk tables. Sensitivity analyses showed that the general trends and conclusions from the base model were maintained despite perturbing the model and input data with regimen changes due to adverse effects. Quantitative comparison with the external validation cohort showed excellent consistency at Year 1, good at Year 3 and moderate at Year 5. Quantitative models, as used in this study, can provide pertinent clinical insights that are not apparent from simple statistical analysis alone. Attaining seizure freedom at any time in a patient's epilepsy journey will confer durable benefit. Seizure-freedom risk tables may be used to individualize the prediction of future seizure control trajectory.
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Anticonvulsivantes , Epilepsia , Anticonvulsivantes/uso terapéutico , Estudios de Cohortes , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Humanos , Convulsiones/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVES: To compare survival and risk factors associated with mortality in common young-onset dementias (YOD) including Huntington's disease. METHODS: This retrospective cohort study included inpatients from an Australian specialist neuropsychiatry service, over 20 years. Dementia diagnoses were based on consensus criteria and Huntington's disease (HD) was confirmed genetically. Mortality and cause of death were determined using linkage to the Australian Institute of Health and Welfare National Death Index. RESULTS: There were 386 individuals with YOD included. The dementia types included frontotemporal dementia (FTD) (24.5%), HD (21.2%) and Alzheimer's disease (AD) (20.5%). 63% (n = 243) individuals had died. The longest median survival was for those who had HD, 18.8 years from symptom onset and with a reduced mortality risk compared to AD and FTD (hazard ratio 0.5). Overall, people with YOD had significantly increased mortality, of 5-8 times, compared to the general population. Females with a YOD had higher standardised mortality ratio compared to males (9.3 vs. 4.9) overall. The most frequent cause of death in those with HD was reported as HD, with other causes of death in the other YOD-subtypes related to dementia and mental/behavioural disorders. DISCUSSION: This is the first Australian study to investigate survival and risk factors of mortality in people with YOD. YOD has a significant risk of death compared to the general population. Our findings provide useful clinical information for people affected by YOD as well as future planning and service provision.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedad de Huntington , Masculino , Femenino , Humanos , Estudios Retrospectivos , Edad de Inicio , Australia/epidemiologíaRESUMEN
OBJECTIVE: This study characterized substance use (alcohol, illicit drugs, amphetamines) in patients with traumatic brain injury (TBI) receiving rehabilitation to determine potential benefit of rehabilitation and whether substance use influenced outcomes in moderate-severe TBI. DESIGN: Prospective, longitudinal study of adults with moderate or severe TBI receiving inpatient rehabilitation. SETTING: Specialist-staffed acquired brain injury rehabilitation center in Melbourne, Australia. PARTICIPANTS: A total of 153 consecutive inpatients with TBI admitted between January 2016 and December 2017 (24 months). INTERVENTIONS: All inpatients with TBI (n=153) received specialist-provided brain injury rehabilitation in accordance with evidence-based guideline care at one 42-bed rehabilitation center. MAIN OUTCOME MEASURES: Data were collected at time of TBI, upon rehabilitation admission, and discharge and 12 months' post-TBI. Recovery was measured by posttraumatic amnesia posttraumatic amnesia length-days and change in Glasgow Coma Scale (admission-discharge). Functional independence was measured on the FIM, Functional Assessment Measure, and Mayo Portland Adaptability Index. Quality of life (QOL) was measured on the EuroQOL-5D-5L and Quality of Life After Brain Injury (QOLIBRI) instruments. RESULTS: Inpatients with history of illicit drug use (n=54) reported lower QOL and adjustment at 12 months' post-TBI compared with those with no history (QOLIBRI social relationships: ratio of means=0.808, P=.028; Mayo Portland Adaptability Index adjustment: incidence rate ratio, 1.273; P=.032). Amphetamine use at time of injury (n=10) was associated with quicker recovery (posttraumatic amnesia length-days: incidence rate ratio, 0.173; P<.01); however, lower QOL at 12 months post-TBI was noted in those with a history of amphetamine use (n=34) compared with those without (QOLIBRI bothered feelings: ratio of means, 0.489, P=.036). CONCLUSIONS: All participants made improvements with rehabilitation post-TBI; however, a history of substance use was associated with lower reported 12-month QOL. These findings add insight to the associations between substance use and acute recovery, potentially suggestive of a short-term recovery-promoting effect of amphetamines but highlighting the importance of rehabilitation to address long-term sequalae.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Trastornos Relacionados con Sustancias , Adulto , Humanos , Calidad de Vida , Estudios Longitudinales , Estudios Prospectivos , Recuperación de la Función , Lesiones Traumáticas del Encéfalo/rehabilitación , Lesiones Encefálicas/rehabilitación , Trastornos Relacionados con Sustancias/epidemiología , Amnesia , AnfetaminaRESUMEN
OBJECTIVES: Vascular dementia (VD) is one of the more common types of dementia. Much is known about VD in older adults in terms of survival and associated risk factors, but comparatively less is known about VD in a younger population. This study aimed to investigate survival in people with young-onset VD (YO-VD) compared to those with late-onset VD (LO-VD) and to investigate predictors of mortality. DESIGN: Retrospective file review from 1992 to 2014. SETTING: The inpatient unit of a tertiary neuropsychiatry service in Victoria, Australia. PARTICIPANTS: Inpatients with a diagnosis of VD. MEASUREMENTS AND METHODS: Mortality information was obtained from the Australian Institute of Health and Welfare. Clinical variables included age of onset, sex, vascular risk factors, structural neuroimaging, and Hachinksi scores. Statistical analyses used were Kaplan-Meier curves for median survival and Cox regression for predictors of mortality. RESULTS: Eighty-four participants were included with few clinical differences between the LO-VD and YO-VD groups. Sixty-eight (81%) had died. Median survival was 9.9 years (95% confidence interval 7.9, 11.7), with those with LO-VD having significantly shorter survival compared to those with YO-VD (6.1 years and 12.8 years, respectively) and proportionally more with LO-VD had died (94.6%) compared to those with YO-VD (67.5%), χ2(1) = 9.16, p = 0.002. The only significant predictor of mortality was increasing age (p = 0.001). CONCLUSION: While there were few clinical differences, and older age was the only factor associated with survival, further research into the effects of managing cardiovascular risk factors and their impact on survival are recommended.
Asunto(s)
Enfermedad de Alzheimer , Demencia Vascular , Humanos , Anciano , Demencia Vascular/epidemiología , Estudios Retrospectivos , Australia , Factores de Riesgo , Enfermedad de Alzheimer/epidemiologíaRESUMEN
BACKGROUND: IgG4-related disease (IgG4-RD) is a newly discovered systemic disease that can affect any organ or tissue in the body. IgG4-related kidney disease (IgG4-RKD) is relatively rare but essential to IgG4-RD. However, there are few reports of IgG4-RD mimicking malignant ureteral tumors leading to hydronephrosis. We report here a rare case of IgG4-RD involving the ureter. CASE PRESENTATION: An 87-year-old man presented to our nephrology department with anorexia, nausea, and acute kidney injury in November 2020. Urinary computed tomography (CT) examination revealed a right lower ureter mass with right renal and ureter hydronephrosis. The serum level of IgG4 was 1890 mg/dL, and the concurrently renal biopsy revealed extensive infiltration of IgG4-positive plasma cells in renal interstitium, which was diagnosed as IgG4-associated tubule-interstitial nephritis(IgG4-TIN). The renal function improved significantly after double-J tube implantation of the right ureter and moderate-dose hormone therapy. The serum IgG4 decreased to the normal range, and the right lower ureter mass almost disappeared after one year of low-dose hormone maintenance therapy. CONCLUSION: IgG4-RD can present as a mass in the renal pelvis and (or) ureter, leading to hydronephrosis. Therefore, early recognition of this disease is significant. Most patients respond well to hormonal therapy to avoid surgical treatment due to misdiagnosis as malignant tumors, causing secondary harm to patients.