Fernando Total Control 2
Objective: To determine whether oral magnesium supplementation (as magnesium chloride [MgCl(2)] solution) improves both insulin sensitivity and metabolic control in type 2 diabetic subjects with decreased serum magnesium levels.
Fernando Total Control 2
Research design and methods: This study was a clinical randomized double-blind placebo-controlled trial. A total of 63 subjects with type 2 diabetes and decreased serum magnesium (serum magnesium levels
Results: At the end of the study, subjects who received magnesium supplementation showed significant higher serum magnesium concentration (0.74 +/- 0.10 vs. 0.65 +/- 0.07 mmol/l, P = 0.02) and lower HOMA-IR index (3.8 +/- 1.1 vs. 5.0 +/- 1.3, P = 0.005), fasting glucose levels (8.0 +/- 2.4 vs. 10.3 +/- 2.1 mmol/l, P = 0.01), and HbA(1c) (8.0 +/- 2.4 vs. 10.1 +/- 3.3%, P = 0.04) than control subjects.
Conclusions: Oral supplementation with MgCl(2) solution restores serum magnesium levels, improving insulin sensitivity and metabolic control in type 2 diabetic patients with decreased serum magnesium levels.
Background: Parathyroid glands are difficult to identify during total thyroidectomies, and accidental resection can lead to problematic postoperative hypocalcemia. Our main goals were to evaluate the effectiveness of using near-infrared light (NIRL) autofluorescence intraoperatively for parathyroid gland identification and to measure its impact on postoperative hypocalcemia incidence.
Study design: Total thyroidectomies were performed on 170 patients with different thyroid pathologies, block-randomized (1:1) into 2 equal groups. Among controls, traditional overhead white light (WL) was used throughout. In the experimental group, NIRL was used to enhance parathyroid gland recognition before thyroid dissection. The number of parathyroid glands identified was compared after thyroid dissection in controls using WL vs pre-dissection in the experimental using NIRL and with WL vs NIRL before thyroid dissection in the experimental group. Postoperative serum calcium levels and hypocalcemia rates were compared.
Rosita wants to throw a birthday party at her house, despite Sofía and Javier trying to convince her to call it off, fearing a possible attack from the Avenger, to no avail. Quintanilla is removed as principal of National School by decision of the school council, given how poorly he has been handling the situation with the Avenger, with Susana taking over as his permanent replacement. Nevertheless, Susana is also unable to expel Raúl for the same reasons as Quintanilla. Fed up with being locked up at will, Gerry breaks his self-imposed curfew by leaving Raúl's house and going to a gay bar where he meets a man named Pipe. During the party, Javier and Natalia take a romantic interest for each other, much to Sofía's jealousy, while Pablo's controlling attitude towards María meets no boundaries. Realizing that the Avenger has poisoned a vodka bottle, Sofía tries to save everyone by throwing off their drinks, just as another fight breaks out between Raúl and the still outraged Pablo which ends with María, who has drunk from said bottle, collapsing and overdosing uncontrollably, leaving her hospitalized.
We studied three independent cohorts (n=115 total): cohorts 1 and 2 included individuals with paired plasma and serum, while cohort 3 included paired serum and CSF. Blood-based p-tau231 and p-tau181 were measured using in-house or commercial single molecule array (Simoa) methods.
So far, only p-tau181 has been shown to be measurable in paired samples and in matrices other than EDTA plasma [1, 24, 26, 29]. Despite strong inter-matrix correlations, p-tau181 concentrations varied significantly between paired samples in different matrices [24, 26]. This was also true for total-tau, suggesting that variable matrix-dependent concentrations may be common to tau biomarkers and not just to p-tau [24, 26]. These results also point to a need for thorough verification of tau-based biomarkers in non-EDTA plasma matrices prior to clinical use.
Blood biomarker verification in serum is essential given its widespread use in clinical settings. However, direct comparison of the diagnostic performances of different p-tau forms in serum is limited. In this proof-of-concept study, we investigated if p-tau231 and p-tau181 can be reliably measured in serum versus paired plasma samples to distinguish biomarker-positive AD cases from biomarker-negative controls, as previously shown for plasma and CSF in multiple independent cohorts [1, 5, 6, 9, 10, 13, 30,31,32,33,34]. We then compared inter-matrix agreements between p-tau measures, and further validated the serum performance by evaluating associations with paired CSF samples.
We studied three independent cohorts of n = 33, 47, and 35 individuals respectively (n = 115 total). Participants in cohort 1 and cohort 3 were pre-classified as biomarker-positive AD or biomarker-negative controls according to their neurochemical CSF biomarker profiles. Cohorts 1 and 3 included 18 and 19 biomarker-positive AD participants respectively. There were 15 and 16 biomarker-negative controls from cohort 1 and cohort 3 respectively. Both cohorts were recruited from the Sahlgrenska University Hospital, Mölndal, Sweden. Cohort 2 included a set of paired plasma and serum samples collected from apparently healthy volunteers, ranging in age from 22 to 69, collected with informed consent and in accordance with the Declaration of Helsinki. EDTA-plasma and serum were collected in February and September 2021, according to state-of-the-art recommendations . Every blood draw was tested for infectious disease (HIV, HCV), and total protein, albumin, and hemoglobin concentrations were within the normal range for all individuals.
The AD participants in cohort 1 and cohort 3 were clinically assessed for suspected AD. The control participants had their core CSF biomarkers in normal ranges. CSF Aβ42, p-tau181, and total-tau were measured with the INNOTEST β-AMYLOID (1-42), PHOSPHO-TAU (181P), and hTAU Ag immunoassays as previously described , and the results were used to categorize participants into biomarker-negative controls and biomarker-positive AD. In both cohorts, biomarker positivity was established according to the following cut-offs: Aβ42 350 ng/ml, and p-tau181 >60 pg/ml.
Statistical analyses were performed with Prism version 9 (GraphPad, San Diego, CA, USA). Non-parametric tests were used for non-normally distributed data. Continuous and categorical variables were evaluated with Spearman correlation and χ2 test respectively. Mann-Whitney test was used for group comparisons, and area under the receiver operating characteristics curve (AUC) to estimate diagnostic performance. Fold changes were calculated by dividing p-tau concentrations by the mean data for the control group. Bland-Altman plots were made to assess agreement of the p-tau measurements in paired serum and plasma . The 95% limits of agreement (LOA) were estimated by calculating the mean 2 standard deviations. For all statistical analyses, significance was set at two-sided p
Cohort 1 included 15 females and 18 males, with a distribution of 33.3% and 55.5% females among the controls and AD groups, respectively. The mean age was 67.39.1 years for controls and 77.45.8 years for AD (Mann Whitney U=48, P=0.0011). Cohort 2 included 47 individuals (27 female, 20 male) between the ages of 20 and 69 years. In cohort 3, there were 20 females and 15 males with comparable distributions between groups. The mean age was 66.612.3 years, without inter-group differences; 65.515.3 years for controls and 67.78.6 years for AD (Mann Whitney U=199.5, P=0.9947). The demographic characteristics are summarized in Table 1.
Profile of serum vs. plasma p-tau in paired samples from neurochemically defined biomarker-positive AD vs. biomarker-negative controls in cohort 1. A, B Boxplots of the concentrations of p-tau231 and p-tau181 in serum and plasma respectively. C The diagnostic performance of p-tau231 and p-tau181 in the paired plasma and serum samples, estimated using area under the curve (AUC) calculations
We further validated the diagnostic performance of serum p-tau in an independent cohort by performing paired measurements of p-tau231 and p-tau181 in both serum and CSF collected at the same clinical visit for each participant in cohort 3 (Table 1). Serum p-tau231 in biomarker-positive AD (mean = 3.8 pg/ml) was three-times higher than in biomarker-negative controls (mean=1.1 pg/ml; P=0.0008; Fig. 2A). For p-tau181, a fold change of four was observed in this cohort: mean concentrations of 10.1 pg/ml for biomarker-positive AD and 2.5 pg/ml for biomarker-negative controls (P
Concentrations and diagnostic performance of serum p-tau231 and p-tau181 in biomarker-positive AD vs. biomarker-negative controls in cohort 3. A, B Serum p-tau231 and p-tau181 levels respectively in controls and AD, expressed in pg/ml. C Area under the curve (AUC) performances of serum p-tau231 and p-tau181 to separate AD from age-matched controls
To evaluate that the serum results reflect brain-derived p-tau, we compared the p-tau biomarkers in paired serum and CSF samples from identical participants in cohort 3 using the same assay definition on the Simoa technology used for both blood matrices, at the appropriate dilution factors. CSF p-tau231 concentrations in biomarker-positive AD (mean = 777.9 pg/ml) were fivefold higher compared with biomarker-negative controls (mean = 154.4 pg/ml, P
While there were strong correlations between paired serum and plasma p-tau levels and either modality accurately differentiated between AD and controls, Bland-Altman plots support a bias in serum vs. plasma concentrations in paired samples, with the disagreements being higher at lower average values. This is explained by the observed differences in absolute levels of p-tau measures in paired samples from the same individuals. For example, paired p-tau231 levels were twofold higher in plasma compared with serum in cohort 1. Similarly, p-tau181 levels were higher in plasma vs. serum in both cohorts 1 and 2, although these differences reached statistical significance only in cohort 2. These consistently lower p-tau concentrations in serum vs. in plasma are in agreement with recent reports for p-tau181 and total-tau [1, 24, 26]. Thus, we propose that the measured concentrations of plasma and serum p-tau biomarkers are not interchangeable despite values in either matrix showing strong correlations and excellent diagnostic performances. In effect, it is important to use either plasma or serum samples independently for an entire study, including longitudinal monitoring, without switching between matrix types.