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Cerebrospinal fluid alpha-synuclein, amyloid beta, total tau, and phosphorylated tau in tremor-dominant Parkinson’s disease

Acta Neurol Belg. 2023 Mar 31. doi: 10.1007/s13760-023-02251-9. Online ahead of print.

ABSTRACT

BACKGROUND: Protein misfolding within specific brain regions is a common characteristic of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease (PD). Therefore, a common term often used for these disorders is “proteinopathy”. Currently, there has been increasing attention toward the overlap of pathogenesis between proteinopathies.

AIMS: We aimed to explore the cross-sectional and longitudinal level of the CSF α-synuclein (α-syn), amyloid βeta (Aβ1-42), total tau (t-tau), and phosphorylated tau (p-tau) in PD subjects with tremor dominant (TD) and a non-tremor dominant (nonTD) subtype from the Parkinson Progression Markers Initiative (PPMI).

METHODS: We enrolled 411 early-stage PD patients and 187 healthy controls (HCs) from the PPMI. We compared the level of CSF biomarkers at four time points including baseline, 6 months, 1 year, and 2 years. To investigate longitudinal changes in CSF proteins within each group, we used linear mixed models.

RESULTS: The level of CSF biomarkers was significantly lower in PD patients compared to HCs at any visit. Moreover, there was no statistically significant difference in the level of CSF α-syn, Aβ1-42, t-tau, and p-tau between PD-TD and PD-nonTD. Longitudinal analysis showed significant CSF α-syn reduction after one year from baseline in PD-TD patients (P = 0.047). Also, there was a significant reduction in the level of CSF Aβ1-42 after two years in PD-nonTD patients but not HCs and PD-TD (P = 0.033).

CONCLUSION: Our results indicate that different patterns in longitudinal changes of CSF biomarkers could be due to different pathophysiological mechanisms involved in each PD motor subtype.

PMID:37000407 | DOI:10.1007/s13760-023-02251-9

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Hypoalbuminemia increases complications in elderly patients operated for hip fracture

Aging Clin Exp Res. 2023 Mar 31. doi: 10.1007/s40520-023-02385-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hip fracture is a major cause of morbidity and mortality in elderly people. A drop in serum albumin after hip surgery has been reported, but few data are available on the effect on complications. The aim of this study was to assess the role of two distinct orthopedic surgical procedures (fixation or prosthesis) and pre-surgery albumin serum level on the development of clinical complications.

METHODS: Of 176 subjects aged 65 and older with hip fracture hospitalized either in orthopedics or geriatrics ward in a 15-month period, the data of 152 patients were analyzed. Interventions were fixation or prosthesis. Measurements included gender, age, surgical procedure, medical complications, admission albumin level (g/L), and post-surgical albumin level (g/L).

RESULTS: All patients (n = 152), regardless of the surgical procedure, underwent a loss of albumin from (mean ± standard deviation) 32.6 ± 4.3 to 25.0 ± 3.8 g/L. Complications were associated with albumin level both at pre-surgery (no complications mean ± SD 33.9 ± 3.5 g/L; n = 80; complications mean ± SD 31.2 ± 4.7 g/L; n = 72; p < 0.001) and post-surgery (no complications mean ± SD 26.2 ± 3.5 g/L; n = 80; complications mean ± SD 23.7 ± 3.6 g/L; n = 72; p < 0.001). When considering a multivariable model, an increased risk in the incidence of complications was found in subjects with preoperative albumin below 30 g/L (reference albumin greater than or equal to 30 g/L; OR 3.74; CI 95% 1.43-9.80) and in subjects undergoing prosthesis procedure (reference: fixation; OR 1.97; CI 95% 1.00-3.88).

CONCLUSIONS: We observed that fixation and prosthesis were associated with a decrease in albumin level. Given a low pre-surgery level of albumin, the risk of complications was higher than in patient with pre-surgery normal level of albumin. This pilot study suggests further prospective research, considering whether albumin administration could be effective in preventing a fall in the albumin level after surgery, thus reducing the postoperative complication rate.

PMID:37000402 | DOI:10.1007/s40520-023-02385-z

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Characteristics of microbiome-derived metabolomics according to the progression of alcoholic liver disease

Hepatol Int. 2023 Mar 31. doi: 10.1007/s12072-023-10518-9. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: The prevalence and severity of alcoholic liver disease (ALD) are increasing. The incidence of alcohol-related cirrhosis has risen up to 2.5%. This study aimed to identify novel metabolite mechanisms involved in the development of ALD in patients. The use of gut microbiome-derived metabolites is increasing in targeted therapies. Identifying metabolic compounds is challenging due to the complex patterns that have long-term effects on ALD. We investigated the specific metabolite signatures in ALD patients.

METHODS: This study included 247 patients (heathy control, HC: n = 62, alcoholic fatty liver, AFL; n = 25, alcoholic hepatitis, AH; n = 80, and alcoholic cirrhosis, AC, n = 80) identified, and stool samples were collected. 16S rRNA sequencing and metabolomics were performed with MiSeq sequencer and liquid chromatography coupled to time-of-flight-mass spectrometry (LC-TOF-MS), respectively. The untargeted metabolites in AFL, AH, and AC samples were evaluated by multivariate statistical analysis and metabolic pathotypic expression. Metabolic network classifiers were used to predict the pathway expression of the AFL, AH, and AC stages.

RESULTS: The relative abundance of Proteobacteria was increased and the abundance of Bacteroides was decreased in ALD samples (p = 0.001) compared with that in HC samples. Fusobacteria levels were higher in AH samples (p = 0.0001) than in HC samples. Untargeted metabolomics was applied to quantitatively screen 103 metabolites from each stool sample. Indole-3-propionic acid levels are significantly lower in AH and AC (vs. HC, p = 0.001). Indole-3-lactic acid (ILA: p = 0.04) levels were increased in AC samples. AC group showed an increase in indole-3-lactic acid (vs. HC, p = 0.040) level. Compared with that in HC samples, the levels of short-chain fatty acids (SCFAs: acetic acid, butyric acid, propionic acid, iso-butyric acid, and iso-valeric acid) and bile acids (lithocholic acids) were significantly decreased in AC. The pathways of linoleic acid metabolism, indole compounds, histidine metabolism, fatty acid degradation, and glutamate metabolism were closely associated with ALD metabolism.

CONCLUSIONS: This study identified that microbial metabolic dysbiosis is associated with ALD-related metabolic dysfunction. The SCFAs, bile acids, and indole compounds were depleted during ALD progression.

CLINICAL TRIAL: Clinicaltrials.gov, number NCT04339725.

PMID:37000389 | DOI:10.1007/s12072-023-10518-9

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Estimation of Two Diuretics Using Fluorescent Nitrogen Doped Carbon Quantum Dots: Application to Spiked Human Plasma and Tablets

J Fluoresc. 2023 Mar 31. doi: 10.1007/s10895-023-03217-z. Online ahead of print.

ABSTRACT

Highly fluorescent nitrogen doped carbon quantum dots (N-CQDs) were prepared by a single-step method based on microwave heating of cane sugar and urea. The produced N-CQDs were applied as nano-sensors for the spectrofluorimetric determination of eplerenone and spironolactone. A strong emission band at 376 nm was obtained after excitation at 216 nm due to the produced N-CQDs. The native fluorescence of N-CQDs was obviously quenched upon adding increased concentrations of each drug. A strong correlation was found between the fluorescence quenching of N-CQDs and the concentration of each drug. The method was found to be linear over the range of 0.5 to 5.0 μg/mL for eplerenone and 0.5 to 6.0 μg/mL for spironolactone with LOQ of 0.383 μg/mL and 0.262 μg/mL. The developed method was further extended for determination of both drugs in their pharmaceutical tablets and spiked human plasma. The results obtained were statistically compared with those of reported methods. The mechanism of fluorescence quenching of N-CQDs by the two drugs was discussed.

PMID:37000365 | DOI:10.1007/s10895-023-03217-z

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Elevated body mass index in modified natural cycle frozen euploid embryo transfers is not associated with live birth rate

J Assist Reprod Genet. 2023 Mar 31. doi: 10.1007/s10815-023-02787-y. Online ahead of print.

ABSTRACT

PURPOSE: To assess the impact of elevated BMI on the success of modified natural cycle frozen embryo transfers (mNC-FET) of euploid embryos.

METHODS: This retrospective cohort study at a single academic institution reviewed mNC-FET involving single euploid blastocysts from 2016 to 2020. Comparison groups were divided by pre-pregnancy BMI (kg/m2) category: normal weight (18.5-24.9), overweight (25-29.9) or obese (≥ 30). Underweight BMI (< 18.5) was excluded from the analysis. The primary outcome was live birth rate (LBR) and secondary outcome was clinical pregnancy rate (CPR), defined as presence of fetal cardiac activity on ultrasound. Absolute standardized differences (ASD) were calculated to compare descriptive variables and p-values and multivariable logistic regressions with generalized estimating equations (GEE) were used to compare pregnancy outcomes.

RESULTS: 562 mNC-FET cycles were completed in 425 patients over the study period. Overall, there were 316 transfers performed in normal weight patients, 165 in overweight patients, and 81 in obese weight patients. There was no statistically significant difference in LBR across all BMI categories (55.4% normal weight, 61.2% overweight, and 64.2% obese). There was also no difference for the secondary outcome, CPR, across all categories (58.5%, 65.5%, and 66.7%, respectively). This was confirmed in GEE analysis when adjusting for confounders.

CONCLUSION: While increased weight has commonly been implicated in poor pregnancy outcomes, the effect of BMI on the success of mNC-FET remains debated. Across five years of data from a single institution using euploid embryos in mNC-FET cycles, elevated BMI was not associated with reduced LBR or CPR.

PMID:37000344 | DOI:10.1007/s10815-023-02787-y

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Is artificial endometrial preparation more associated with early-onset or late-onset preeclampsia after frozen embryo transfer?

J Assist Reprod Genet. 2023 Mar 31. doi: 10.1007/s10815-023-02785-0. Online ahead of print.

ABSTRACT

PURPOSE: To explore whether the risks of early- or late-onset preeclampsia vary among frozen embryo transfer (FET) with different regimens for endometrial preparation and fresh embryo transfer (FreET).

METHODS: We retrospectively included a total of 24129 women who achieved singleton delivery during their first cycles of in vitro fertilization (IVF) between January 2012 and March 2020. The risks of early- and late-onset preeclampsia after FET with endometrial preparation by natural ovulation cycles (FET-NC) or by artificial cycles (FET-AC) were compared to that after FreET.

RESULTS: After adjustment via multivariable logistic regression, the total risk of preeclampsia was higher in the FET-AC group compared to the FreET group [2.2% vs. 0.9%; adjusted odds ratio (aOR): 2.00; 95% confidence interval (CI): 1.45-2.76] and FET-NC group (2.2% vs. 0.9%; aOR: 2.17; 95% CI: 1.59-2.96).When stratified by the gestational age at delivery based on < 34 weeks or ≥ 34 weeks, the risk of late-onset preeclampsia remained higher in the FET-AC group than that in the and FreET group (1.8% vs. 0.6%; aOR: 2.56; 95% CI: 1.83-3.58) and the FET-NC group (1.8% vs. 0.6%; aOR: 2.63; 95% CI: 1.86-3.73). We did not find a statistically significant difference in the risk of early-onset preeclampsia among the three groups.

CONCLUSIONS: An artificial regimen for endometrial preparation was more associated with an increased risk of late-onset preeclampsia after FET. Given that FET-AC is widely used in clinical practice, the potential maternal risk factors for late-onset preeclampsia when using the FET-AC regimen should be further explored, considering the maternal origin of late-onset preeclampsia.

PMID:37000343 | DOI:10.1007/s10815-023-02785-0

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The effect of ultrasonic access cavity preparation on dentinal inner walls: a micro-CT study on cadaveric samples

Oral Radiol. 2023 Mar 31. doi: 10.1007/s11282-023-00680-z. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study is to evaluate the occurrence of coronal dentinal micro-cracks after access cavity refinement using high-speed burs and ultrasonic tips by means of micro-computed tomography (micro-CT) analysis.

METHODS: In this study, 18 mandibular cadaveric incisors were divided into two groups according to the protocol of the preparation of the conventional access cavity. The diamond bur 802 # 12 was used until the perforation of the pulp roof. Then, the Endo-Z bur was used for the group #1 and the ultrasonic tip Start-X # 1 for the group #2 to finish and refine the access cavity. The preparation time of each access cavity has been recorded. The teeth underwent a micro-CT scan before and after the preparation of the access cavity. Fisher’s exact test, the Chi-square test, the Kolmogorov-Smirnov test, the Mann-Whitney test, and the Student’s test were used for statistical evaluation.

RESULTS: The percentage of teeth with new micro-cracks is not significantly different between the two groups (-p-value < 0.5). The number of newly formed micro-cracks and extension size were not significantly different between the two groups. The direction of extension of the micro- cracks was occluso-apical. The average duration of the access cavity is significantly smaller with the Endo-Z system (-p- value < 0.001). The roughness of walls surfaces has no statistically difference between the two groups.

CONCLUSION: The use of ultrasound, although slower, is considered safe in the creation of dentinal micro-cracks, in the preparation of the access cavity.

PMID:37000330 | DOI:10.1007/s11282-023-00680-z

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Modeling and optimization of the coagulation/flocculation process in turbidity removal from water using poly aluminum chloride and rice starch as a natural coagulant aid

Environ Monit Assess. 2023 Mar 31;195(4):527. doi: 10.1007/s10661-023-11150-8.

ABSTRACT

The application of the coagulation/flocculation process is very important due to its simplicity in removing turbidity. Due to the disadvantages of using chemical coagulants in water and the lack of sufficient effect of natural materials alone in removing turbidity for proper performance, the simultaneous use of chemical and natural coagulants is the best way to reduce the harmful effects of chemical coagulants in water. In this study, the application of poly aluminum chloride (PAC) as a chemical coagulant and rice starch as a natural coagulant aid to remove turbidity from aqueous solutions was investigated. Effects of the above coagulants on the four main factors, coagulant dose (0-10 mg/L), coagulant adjuvant dose (0-0.1 mg/L), pH (5-9), turbidity (NTU 0-50), and each five levels were assessed using a central composite design (CCD). Under the optimized conditions, the maximum turbidity elimination efficiency was found to be 96.6%. The validity and adequacy of the proposed model (quadratic model) were confirmed by the corresponding statistics (i.e., F-value of 23.3, p-values of 0.0001, and lack of fit of 0.877 for the model, respectively, R2 = 0.88, R2adj. = 0.84, R2pred = 0.79, AP = 22.04).

PMID:37000307 | DOI:10.1007/s10661-023-11150-8

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ASLncR: a novel computational tool for prediction of abiotic stress-responsive long non-coding RNAs in plants

Funct Integr Genomics. 2023 Mar 31;23(2):113. doi: 10.1007/s10142-023-01040-0.

ABSTRACT

Abiotic stresses are detrimental to plant growth and development and have a major negative impact on crop yields. A growing body of evidence indicates that a large number of long non-coding RNAs (lncRNAs) are key to many abiotic stress responses. Thus, identifying abiotic stress-responsive lncRNAs is essential in crop breeding programs in order to develop crop cultivars resistant to abiotic stresses. In this study, we have developed the first machine learning-based computational model for predicting abiotic stress-responsive lncRNAs. The lncRNA sequences which were responsive and non-responsive to abiotic stresses served as the two classes of the dataset for binary classification using the machine learning algorithms. The training dataset was created using 263 stress-responsive and 263 non-stress-responsive sequences, whereas the independent test set consists of 101 sequences from both classes. As the machine learning model can adopt only the numeric data, the Kmer features ranging from sizes 1 to 6 were utilized to represent lncRNAs in numeric form. To select important features, four different feature selection strategies were utilized. Among the seven learning algorithms, the support vector machine (SVM) achieved the highest cross-validation accuracy with the selected feature sets. The observed 5-fold cross-validation accuracy, AU-ROC, and AU-PRC were found to be 68.84, 72.78, and 75.86%, respectively. Furthermore, the robustness of the developed model (SVM with the selected feature) was evaluated using an independent test dataset, where the overall accuracy, AU-ROC, and AU-PRC were found to be 76.23, 87.71, and 88.49%, respectively. The developed computational approach was also implemented in an online prediction tool ASLncR accessible at https://iasri-sg.icar.gov.in/aslncr/ . The proposed computational model and the developed prediction tool are believed to supplement the existing effort for the identification of abiotic stress-responsive lncRNAs in plants.

PMID:37000299 | DOI:10.1007/s10142-023-01040-0

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Semiparametric regression analysis of length-biased and partly interval-censored data with application to an AIDS cohort study

Stat Med. 2023 Mar 31. doi: 10.1002/sim.9724. Online ahead of print.

ABSTRACT

Length-biased data occur often in many scientific fields, including clinical trials, epidemiology surveys and genome-wide association studies, and many methods have been proposed for their analysis under various situations. In this article, we consider the situation where one faces length-biased and partly interval-censored failure time data under the proportional hazards model, for which it does not seem to exist an established method. For the estimation, we propose an efficient nonparametric maximum likelihood method by incorporating the distribution information of the observed truncation times. For the implementation of the method, a flexible and stable EM algorithm via two-stage data augmentation is developed. By employing the empirical process theory, we establish the asymptotic properties of the resulting estimators. A simulation study conducted to assess the finite-sample performance of the proposed method suggests that it works well and is more efficient than the conditional likelihood approach. An application to an AIDS cohort study is also provided.

PMID:36999548 | DOI:10.1002/sim.9724