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Brain : a Journal of Neurology Sep 2023Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid...
Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses found the families were related, and ANO1 p.Met658Val segregated with moyamoya disease in the family with an LOD score of 3.3. Six additional ANO1 rare variants were identified in moyamoya disease families. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harbouring these gain-of-function ANO1 variants had classic features of moyamoya disease, but also had aneurysm, stenosis and/or occlusion in the posterior circulation. Our studies support that ANO1 gain-of-function pathogenic variants predispose to moyamoya disease and are associated with unique involvement of the posterior circulation.
Topics: Child; Humans; Young Adult; Anoctamin-1; Chloride Channels; Moyamoya Disease; Neoplasm Proteins
PubMed: 37253099
DOI: 10.1093/brain/awad172 -
Annals of Emergency Medicine Oct 2023We examined the diagnostic performance of a recalibrated History, Electrocardiogram, Age, Risk factors, Troponin (HEART), and Thrombolysis in Myocardial Infarction...
STUDY OBJECTIVE
We examined the diagnostic performance of a recalibrated History, Electrocardiogram, Age, Risk factors, Troponin (HEART), and Thrombolysis in Myocardial Infarction (TIMI) score in patients with suspected acute cardiac syndrome (ACS). Recalibration of troponin thresholds was performed, including shifting from the 99th percentile to the limit of detection (LOD) or to the limit of quantification (LOQ) We compared the discharge potential and safety of the recalibrated composite scores using a single presentation high-sensitivity cardiac troponin (hs-cTn) T to the conventional scores and with a LOD/LOQ troponin strategy alone.
METHODS
We undertook a 2-center prospective cohort study in the United Kingdom (UK) (2018) (Clinicaltrials.gov NCT03619733) to specifically assess recalibrated risk scores (shifting the troponin subset scoring from 99th percentile to LOD [UK]) and combined the results of this with secondary analyses of 2 prospective cohort studies in the UK (2011) and the United States (2018, using LOQ rather than LOD). The primary outcome was major adverse cardiovascular events (MACE), defined as adjudicated type 1 myocardial infarction (MI), urgent coronary revascularization, and all-cause death, at 30 days. We evaluated the original scores using hs-cTn below the 99th percentile and recalibrated scores using hs-cTn <LOD/LOQ and compared these composite scores with a single hs-cTnT less than LOD/LOQ combined with a nonischemic ECG. For each discharge strategy, an assessment of clinical effectiveness was also made, defined as the proportion of patients eligible for discharge from the emergency department without the need for further inpatient testing.
RESULTS
We studied 3,752 patients (3,003 in the UK and 749 in the United States). Median age was 58 years, and 48% were female. At 30 days, 330/3,752 (8.8%) experienced MACE. The sensitivities of the original HEART less or equal to 3 and recalibrated HEART less or equal to 3 scores for rule-out were 96.1% (95% confidence interval [CI], 93.4 to 97.9) and 98.6% (95% CI, 96.5 to 99.5) respectively; the original TIMI less or equal to 1 and recalibrated TIMI less or equal to 1 scores' sensitivities were 79.7% (95% CI, 74.9 to 83.9) and 96.1% (95% CI, 93.4 to 97.9) respectively; and nonischemic ECG with hs-cTn T below the 99th percentile and hs-cTn T less than LOD/LOQ was 79.7% (95%CI, 0.749 to 0.839) and 99.1% (95% CI, 0.974 to 0.998), respectively. Recalibrated HEART less or equal to 3 was projected to discharge 14% more patients than hs-cTn T less than LOD/LOQ. The improved sensitivity of rule-out for recalibrated HEART less than or equal to 3 came at the cost of reduced specificity (50.8% versus 53.8% for recalibrated HEART and conventional HEART respectively).
CONCLUSION
This study indicates that recalibrated HEART score of less or equal to 3 is a feasible and safe early discharge strategy using a single presentation hs-cTnT. This finding should be further tested using competitor hs-cTn assays in independent prospective cohorts before implementation.
Topics: Humans; Female; Middle Aged; Male; Troponin T; Prospective Studies; Troponin; Myocardial Infarction; Acute Coronary Syndrome; Biomarkers; Emergency Service, Hospital
PubMed: 37306637
DOI: 10.1016/j.annemergmed.2023.04.024 -
BMC Chemistry Aug 2023This study aims to develop an effective and sensitive HPLC (High Performance Liquid Chromatography) method to determine the nitrate concentration in fruits and...
This study aims to develop an effective and sensitive HPLC (High Performance Liquid Chromatography) method to determine the nitrate concentration in fruits and vegetables (F & V) using a C column (ZORBAX Eclipse XDB-C, 80Å, 250 × 4.6 mm, 5 μm (Agilent Technologies)) maintained at 40 C, a mobile phase made up of methanol and buffer (pentane sulfonic acid sodium salt solution), and a Photo Diode Array Detector (PDA) at 225 nm. The developed method is validated in terms of selectivity, linearity, accuracy, precision, suitability, the limit of detection (LOD), and the limit of quantification (LOQ) according to the European Union Decision 2002/657/EC. The result revealed that a ratio of 30: 70 of the organic modifier methanol and buffer with pH 2.8 shows the highest efficiency. The calibration curve shows linearity with a correlation coefficient (r) of 0.9985. The LOD and LOQ were found to be 2.26 mg/kg and 7.46 mg/kg. The recovery was in the range of 98.96-100.21%. Moreover, the greenness assessment scores of different approaches (eco-scale score of 76, AGREE score of 0.71, and few red shades in GAPI portray) were at a very excellent level. Thus, our developed method is fully validated and can determine the nitrate content in F & V.
PubMed: 37620944
DOI: 10.1186/s13065-023-01008-y -
Alzheimer Disease and Associated...Executive function (EF) involves a general cognitive process linked to strategic organization and control of complex goal-oriented tasks. In young-onset dementia (YOD),...
INTRODUCTION
Executive function (EF) involves a general cognitive process linked to strategic organization and control of complex goal-oriented tasks. In young-onset dementia (YOD), especially Alzheimer's disease, the symptoms that stand out in the initial stage are deficits in attention, visual-spatial function, praxis, and language. The present study aims to investigate what components of EF differ in young and late-onset dementia (LOD) and its impact on awareness and its domains.
METHODS
Using a cross-sectional design, we included 44 people with YOD and 70 with LOD. We assessed awareness and its domains, cognition, dementia severity, EF, functionality, and neuropsychiatric symptoms.
RESULTS
The YOD group was more impaired in general cognition ( P =0.017) and had a worse performance in Wechsler Digit Span Backward (DSB) ( P =0.007) and Phonemic fluency task (FAS) ( P =0.046) tests. In the LOD group, deficits in EF had a greater impact on awareness and on most domains (awareness total score, cognitive functioning and health condition, functional activity impairments and social function).
CONCLUSIONS
Our study findings support the heterogeneity of awareness, not only with regard to the difference between the domains and the measures of EF, but also to the groups studied.
Topics: Humans; Dementia; Executive Function; Cross-Sectional Studies; Age of Onset; Alzheimer Disease
PubMed: 37561987
DOI: 10.1097/WAD.0000000000000561 -
Clinica Chimica Acta; International... Aug 2023The Enhanced Liver Fibrosis (ELF) Test comprises 3 direct serum markers of fibrosis-hyaluronic acid (HA), amino-terminal pro-peptide of type III procollagen (PIIINP),...
BACKGROUND
The Enhanced Liver Fibrosis (ELF) Test comprises 3 direct serum markers of fibrosis-hyaluronic acid (HA), amino-terminal pro-peptide of type III procollagen (PIIINP), and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)-whose results are combined in an algorithm to generate the ELF score. Outside the U.S., the ELF Test and score are CE marked for assessment of liver fibrosis severity in patients with signs, symptoms, or risk factors of chronic liver disease to support diagnosis of fibrosis staging or prognosis for likelihood of progression to cirrhosis and liver-related clinical events. In the U.S., the FDA granted de novo marketing authorization to aid prognostic evaluation of disease progression (to cirrhosis and liver-related clinical events) in nonalcoholic steatohepatitis patients with advanced liver fibrosis. We describe the analytical performance of the ELF analytes and score on the Atellica® IM Analyzer.
METHODS
Clinical and Laboratory Standards Institute protocols were followed for detection capability (limits of blank [LoB], detection [LoD], and quantitation [LoQ]), precision, interference, linearity, hook effect, and ELF reference interval.
RESULTS
All parameters met predetermined requirements: HA (LoB 1.00 ng/mL, LoD 2.00 ng/mL, LoQ 3.00 ng/mL); PIIINP (LoB 0.50 ng/mL, LoD 0.75 ng/mL, LoQ 1.00 ng/mL); TIMP-1 (LoB 3.0 ng/mL, LoD 4.0 ng/mL, LoQ 5.0 ng/mL). Across the 3 assays, repeatability was ≤5.4% CV; within-lab precision was ≤8.5% CV. ELF score repeatability was ≤0.6% CV, within-lab precision ≤1.3% CV, and reproducibility ≤1.1% CV. Good correlation was obtained between the Atellica IM ELF and ADVIA Centaur ELF Tests (y = 1.01x - 0.22, r = 0.997). Assays were linear across analytical measuring ranges.
CONCLUSIONS
Analytical performance validation results for the ELF Test and ELF score were excellent making the test acceptable for routine clinical use.
Topics: Humans; Tissue Inhibitor of Metalloproteinase-1; Reproducibility of Results; Liver Cirrhosis; Fibrosis; Liver; Biomarkers; Hyaluronic Acid
PubMed: 37390944
DOI: 10.1016/j.cca.2023.117461 -
International Journal of Molecular... Nov 2023Rice plant height is an agricultural trait closely related to biomass, lodging tolerance, and yield. Identifying quantitative trait loci (QTL) regions related to plant...
Rice plant height is an agricultural trait closely related to biomass, lodging tolerance, and yield. Identifying quantitative trait loci (QTL) regions related to plant height regulation and developing strategies to screen potential candidate genes can improve agricultural traits in rice. In this study, a double haploid population (CNDH), derived by crossing 'Cheongcheong' and 'Nagdong' individuals, was used, and a genetic map was constructed with 222 single-sequence repeat markers. In the RM3482-RM212 region on chromosome 1, , , , , and were identified for five consecutive years. The phenotypic variance explained ranged from 9.3% to 13.1%, and the LOD score ranged between 3.6 and 17.6. , a candidate gene related to plant height regulation, was screened in RM3482-RM212. is an ortholog of gibberellin 20 oxidase 2, and its haplotype was distinguished by nine SNPs. Plants were divided into two groups based on their height, and tall and short plants were distinguished and clustered according to the expression level of . QTLs and candidate genes related to plant height regulation, and thus, biomass regulation, were screened and identified in this study, but the molecular mechanism of the regulation remains poorly known. The information obtained in this study will help develop molecular markers for marker-assisted selection and breeding through rice plant height control.
Topics: Humans; Quantitative Trait Loci; Chromosome Mapping; Oryza; Plant Breeding; Phenotype
PubMed: 38069217
DOI: 10.3390/ijms242316895 -
Analytical Sciences : the International... Sep 2023The sensitive, non-destructive constant wavelength (CW) and constant energy (CE) SFS techniques have been used for the simultaneous determination of 1-amino pyrene (AP)...
The sensitive, non-destructive constant wavelength (CW) and constant energy (CE) SFS techniques have been used for the simultaneous determination of 1-amino pyrene (AP) and 1-napthyl amine (NA) in their mixtures without prior separation via optimization of different experimental conditions (Δλ 70.0 nm, Δν 4000.0 cm, scan rate 240.0 nm/min, 25.0 °C, methanol). Amplitude-concentration plots have been linear for 1-amino pyrene, AP (0.01-0.1 mg/L) and 1-napthyl amine, NA (0.1-1.0 mg/L). In aqueous methanolic binary mixtures, the mean recoveries (RSD, LOD and LOQ) of AP were found to be 100.09% (0.053, 0.008 mg/L and 0.034 mg/L) for emission, 100.11% (0.141, 0.008 mg/L, 0.034 mg/L) for CWSFS, 100.05% (0.109, 0.007 mg/L and 0.032 mg/L) for first derivative CWSFS, 100.00% (0.148, 0.007 mg/L and 0.031 mg/L) for CESFS, 99.99% (0.109, 0.008 mg/L and 0.035 mg/L) for first derivative CESFS modes respectively. Additionally, for NA the mean recoveries (RSD, LOD and LOQ) were 100.29% (0.360, 0.046 mg/L and 0.204 mg/L) for emission, 100.06% (0.089, 0.098 mg/L, 0.436 mg/L) for CWSFS, 100.09% (0.144, 0.065 mg/L and 0.288 mg/L) for first derivative CWSFS, 100.05% (0.178, 0.077 mg/L and 0.339 mg/L) for CESFS, 100.03% (0.181, 0.082 mg/L and 0.364 mg/L) for first derivative CESFS modes respectively. Considering their safety and greenness, these methods might be considered as green tools using analytical eco-scale approaches (eco-scale score 88.0).
PubMed: 37244980
DOI: 10.1007/s44211-023-00368-8 -
The American Journal of Geriatric... Mar 2024Understanding experiences and challenges faced by persons living with Early-Onset Dementia (EOD) compared to individuals diagnosed with Late-Onset Dementia (LOD) is...
BACKGROUND
Understanding experiences and challenges faced by persons living with Early-Onset Dementia (EOD) compared to individuals diagnosed with Late-Onset Dementia (LOD) is important for the development of targeted interventions.
OBJECTIVE
Describe differences in sociodemographic, neuropsychiatric behavioral symptoms, caregiver characteristics, and psychotropic use.
DESIGN, SETTING, PARTICIPANTS
Cross-sectional, retrospective study including 908 UCLA Alzheimer's Dementia Care Program participants (177 with EOD and 731 with LOD).
MEASUREMENTS
Onset of dementia was determined using age at program enrollment, with EOD defined as age <65 years and LOD defined as age >80 years. Sociodemographic and clinical characteristics were measured once at enrollment. Behavioral symptoms were measured using the Neuropsychiatric Inventory Questionnaire (NPI-Q) severity score and caregiver distress was measured using the NPI-Q distress score. Medications included antipsychotic, antidepressant, benzodiazepines and other hypnotics, antiepileptics, and dementia medications.
RESULTS
EOD compared to LOD participants were more likely men, college graduates, married, live alone, and have fewer comorbidities. EOD caregivers were more often spouses (56% vs 26%, p <0.01), whereas LOD caregivers were more often children (57% vs 10%, p <0.01). EOD was associated with lower odds of being above the median (worse) NPI-Q severity (adjusted odds ratio [aOR], 0.58; 95% CI 0.35-0.96) and NPI-Q distress scores (aOR, 0.53; 95% CI 0.31-0.88). Psychotropic use did not differ between groups though symptoms were greater for LOD compared to EOD.
CONCLUSION
Persons with EOD compared to LOD had sociodemographic differences, less health conditions, and fewer neuropsychiatric symptoms. Future policies could prioritize counseling for EOD patients and families, along with programs to support spousal caregivers of persons with EOD.
PubMed: 38600005
DOI: 10.1016/j.jagp.2024.03.009 -
Psychology Research and Behavior... 2023Late-onset depression (LOD) with poor treatment response has high incidence and mortality in the China's aged people, this study aims to explore the correlation between...
PURPOSE
Late-onset depression (LOD) with poor treatment response has high incidence and mortality in the China's aged people, this study aims to explore the correlation between health-promoting lifestyle, meaning in life, interleukin-6 (IL-6) and LOD for providing scientific basis of LOD prevention and rehabilitation.
PATIENTS AND METHODS
A total of 496 LOD patients (study group) and healthy older adults (control group) were enrolled and investigated by using the Health-promoting lifestyle Profile-II, revised (HPLP-IIR), Meaning in Life Questionnaire-Chinese Version (MLQ-C), and Hamilton Depression Scale (HAMD). The interleukin-6 (IL-6) in the circulating blood was detected by utilizing ELISA kit.
RESULTS
The results showed that the scores of all factors in HPLP-IIR and MLQ were significantly lower and IL-6 level was higher in the study group than the control group. Scores of most factors in HPLP-IIR and MLQ negatively and IL-6 positively correlated with scores of subscales and total HAMD score. Meaning in life and IL-6 partially mediated the relationship between health-promoting lifestyles and depression severity in the study group, with the mediating effect explains 15.76% and 22.64% of the total effect, respectively.
CONCLUSION
Health-promoting lifestyles, meaning in life, and IL-6 are predictors of LOD, and an unhealthy lifestyle could induce LOD through the mediating effect of meaning in life and IL-6 in older adults.
PubMed: 38146389
DOI: 10.2147/PRBM.S441277