TbCu7-type Sm-Fe(-N) powder synthesized by low-temperature reduction-diffusion process using the Li-Ca reductant.

It was predicted that TbCu7-type Sm-Fe powder prepared by the low-temperature reduction-diffusion (LTRD) process using a Li-Ca reductant would contain no residual ɑ-Fe because this reductant would not produce the absorbed water that hinders the reaction between Sm and Fe by forming oxychlorides when molten salt is used as the reductant. Contrary to this expectation, a detailed microstructure analysis revealed that a residual phase of unreacted ɑ-Fe existed in some TbCu7-type Sm-Fe particles rather than as separate Fe particles. This residual ɑ-Fe phase was not located in the center of the Sm-Fe particles and was not detected in some Sm-Fe particles, suggesting that the reason for the residual ɑ-Fe phase is inhomogeneous diffusion of Sm into the Fe due to slow diffusion at low temperatures. Although this TbCu7-type Sm-Fe powder contained a small amount of unreacted ɑ-Fe phase, the magnetic properties of the nitride TbCu7-type Sm-Fe were also estimated.

Parental education and income are linked to offspring cortical brain structure and psychopathology at 9-11 years.

Background: A child's socioeconomic environment can shape central aspects of their life, including vulnerability to mental disorders. Negative environmental influences in youth may interfere with the extensive and dynamic brain development occurring at this time. Indeed, there are numerous yet diverging reports of associations between parental socioeconomic status (SES) and child cortical brain morphometry. Most of these studies have used single metric- or unimodal analyses of standard cortical morphometry that downplay the probable scenario where numerous biological pathways in sum account for SES-related cortical differences in youth. Methods: To comprehensively capture such variability, using data from 9758 children aged 8.9-11.1 years from the ABCD Study®, we employed linked independent component analysis (LICA) and fused vertex-wise cortical thickness, surface area, curvature and grey-/white-matter contrast (GWC). LICA revealed 70 uni- and multimodal components. We then assessed the linear relationships between parental education, parental income and each of the cortical components, controlling for age, sex, genetic ancestry, and family relatedness. We also assessed whether cortical structure moderated the negative relationships between parental SES and child general psychopathology. Results: Parental education and income were both associated with larger surface area and higher GWC globally, in addition to local increases in surface area and to a lesser extent bidirectional GWC and cortical thickness patterns. The negative relation between parental income and child psychopathology were attenuated in children with a multimodal pattern of larger frontal- and smaller occipital surface area, and lower medial occipital thickness and GWC. Conclusion: Structural brain MRI is sensitive to SES diversity in childhood, with GWC emerging as a particularly relevant marker together with surface area. In low-income families, having a more developed cortex across MRI metrics, appears beneficial for mental health.

A new double-antigen sandwich test based on the light-initiated chemiluminescent assay for detecting anti-hepatitis C virus antibodies with high sensitivity and specificity.

Objectives: The aim of this study was to evaluate the performance of a new double-antigen sandwich test that is based on the light-initiated chemiluminescent assay (LiCA®) for detecting anti-hepatitis C virus antibodies (anti-HCV) in comparison to Architect®. Methods: Analytical characteristics and diagnostic performance were tested using seroconversion panels and large pools of clinical samples. Positive results were validated by the strip immunoblot assay (RIBA) and HCV RNA. Results: Repeatability and within-lab imprecision of LiCA® anti-HCV were 1.31%-3.27%. The C5-C95 interval was -5.44%-5.03% away from C50. LiCA® detected seroconversion in an average of 28.9 days and showed a mean of 3.7 (p = 0.0056) days earlier than Architect®. In a pool of 239 samples with known HCV genotypes 1 to 6, both assays correctly detected all subjects. In 16,305 clinical patient sera, LiCA® detected 4 false-negative (0.25‰) and 14 false-positive (0.86‰) anti-HCV cases, while Architect® recorded 6 false-negative (0.37‰) and 138 false-positive (8.46‰) subjects, respectively. Compared to Architect®, LiCA® presented a significantly better performance in specificity (99.91% vs. 99.14%, n = 16,018, p < 0.0001), positive predictive value (95.29% vs. 67.06%, n = 419, p < 0.0001), and overall accuracy (99.89% vs. 99.12%, n = 16,305, p < 0.0001), while no significant difference in sensitivity (98.61% vs. 97.91%, n = 287, p = 0.5217) and negative predictive value (99.98% vs. 99.96%, n = 15,886, p = 0.3021) was seen. An S/Co value of 3.28 was predicted to be the threshold with a positivity ≥95% for the LiCA® anti-HCV assay. Conclusion: LiCA® anti-HCV is a precise and fully automatic chemiluminescent assay with superior sensitivity and specificity. The assay can be used as a valuable tool to supplement the diagnosis of HCV infection.

Evaluation of a high-sensitivity SARS-CoV-2 antigen test on the fully automated light-initiated chemiluminescent immunoassay platform.

OBJECTIVES: To describe a high-sensitivity SARS-CoV-2 antigen test that is based on the fully automated light-initiated chemiluminescent immunoassay (LiCA®), and to validate its analytical characteristics and clinical agreement on detecting SARS-CoV-2 infection against the reference molecular test. METHODS: Analytical performance was validated and detection limits were determined using different types of nucleocapsid protein samples. 798-pair anterior nasal swab specimens were collected from hospitalized patients and asymptomatic screening individuals. Agreement between LiCA® antigen and real-time reverse transcription polymerase chain reaction (rRT-PCR) was evaluated. RESULTS: Repeatability and within-lab precision were 1.6-2.3%. The C5∼C95 interval was -5.1-4.6% away from C50. Detection limits in average (SD) were 325 (±141) U/mL on the national reference panel, 0.07 (±0.04) TCID50/mL on active viral cultures, 0.27 (±0.09) pg/mL on recombinant nucleocapsid proteins and 1.07 (±1.01) TCID50/mL on inactivated viral suspensions, respectively. LiCA detected a median of 374-fold (IQR 137-643) lower levels of the viral antigen than comparative rapid tests. As reference to the rRT-PCR method, overall sensitivity and specificity were determined to be 97.5% (91.4-99.7%) and 99.9% (99.2-100%), respectively. Total agreement between both methods was 99.6% (98.7-99.9%) with Cohen's kappa 0.98 (0.96-1). A positive detection rate of 100% (95.4-100%) was obtained as Ct≤37.8. CONCLUSIONS: The LiCA® system provides an exceptionally high-sensitivity and fully automated platform for the detection of the SARS-CoV-2 antigen in nasal swabs. The assay may have high potential use for large-scale population screening and surveillance of COVID-19 as an alternative to the rRT-PCR test.

Prevention of Recurrent Benign Paroxysmal Positional Vertigo: The Role of Combined Supplementation with Vitamin D and Antioxidants.

Benign paroxysmal positional vertigo (BPPV) usually has a favorable course, although it is possible to observe BPPV with a high recurrence rate. Previous studies suggested that vitamin D deficiency might affect BPPV recurrences, and oxidative stress might play a complementary role in BPPV pathogenesis. This multicentric trial aimed to evaluate the effectiveness of oral nutritional supplementation with a compound of alpha-lipoic acid, Carnosine, and Zinc (LICA® (Difass International, Coriano (RN), Italy)), vitamins of group B and vitamin D in preventing BPPV recurrences. A total of 128 patients with high recurrence-BPPV were randomized in three arms: Arm 1 consisted of subjects with "insufficient" or "deficient" vitamin D blood levels, treated with daily oral supplementation of LICA®, vitamins of group B and vitamin D3 (800 UI), Arm 2 included BPPV subjects with "sufficient" vitamin D who did not receive any nutritional support, and Arm 3 included subjects with a "sufficient" serum concentration of vitamin D who received supplementation with a compound of LICA® and Curcumin. After six months of follow-up, a significant reduction of BPPV relapses compared to the baseline was found only in Arm 1 (−2.32, 95% CI: 3.41−1.62, p-value < 0.0001). Study results suggested that oral nutritional supplementation with vitamin D3 plus antioxidants can prevent relapses in patients suffering from high recurrence-BPPV.

Analytical and clinical evaluation of the light-initiated chemiluminescent assays for measurement of human thyroid hormones.

BACKGROUND: Light-initiated chemiluminescent assay (LiCA) is a new homogeneous immunoassay. The aim of this study was to evaluate the analytical and clinical performance of the assays for the detection of thyroid hormones based on the fully automated LiCA 800 analyzer. METHODS: Analytical validations of the LiCA thyroid assays (TSH, FT3, FT4, T3, and T4) included precision, linearity, analytical sensitivity, interference, and method comparison applying the protocols of the Clinical and Laboratory Standards Institute (CLSI). The diagnostic performance was assessed by the receiver operating characteristic (ROC) curve analysis with different assay schemes for the diagnosis of hyperthyroidism and hypothyroidism. RESULTS: Within-run and within-lab precisions (%CV) of the five assays ranged from 1.06 to 6.40% at all concentrations evaluated. A satisfactory linearity was verified over the entire measuring range for TSH, T3, and T4 (R > 0.99, change in recovery <10%, p = 0.000 all). Paired-comparison measurements presented a comparable assay for each of the five assays (R > 0.96, median bias <5%, p < 0.0001 all) between LiCA and Cobas across three institutes. The diagnostic accuracy of the LiCA assays for hyperthyroidism or hypothyroidism was quantified by the areas under curves (AUC) as 0.925 or 0.832 with the five-assay panel (TSH, FT3, FT4, T3, and T4) and as 0.921 or 0.811 with the three-assay panel (TSH, FT3, and FT4), respectively. No significant difference was found between the AUC of LiCA and that of DxI, Cobas, or Centaur (p > 0.3 all). CONCLUSION: LiCA 800 provides a precise and high-throughput immunoassay platform for detection of thyroid hormones. It is acceptable for clinical use.

Performance characteristics of the light-initiated chemiluminescent assay for quantitative determination of progesterone.

BACKGROUND: To study the performance of quantitative determination of progesterone by light-initiated chemiluminescent assay (LICA). METHODS: Clinical samples of serum were used for detection of progesterone by LICA. The precision study was performed according to Clinical and Laboratory Standards Institute (CLSI) EP15-A3, the linear range validation was performed according to CLSI EP06-A, accuracy was evaluated according to CLSI EP9-A3, and the performance of detection capability was confirmed according to CLSI EP17-A2. All data were analyzed using SPSS software. Function regression analysis was performed by OriginPro software. RESULTS: The LICA-800 system exhibited low coefficients of variation (CVs) and high reproducibility, and the calculated synthetic CV was 2.16%. The access progesterone assay showed excellent linearity in the assay measuring range (0.37-40 ng/mL) using the polynomial regression method in accordance with CLSI EP06-A. Bias assessment was used to verify accuracy, and the percentage deviation met the quality requirements of the laboratory's allowable deviation of 10.00%. In terms of the detection capability of LICA, the calculated limit of blank (LoB) was 0.046 ng/mL, limit of detection (LoD) was 0.057 ng/mL, and the limit of quantitation (LoQ) value was 0.161 ng/mL. CONCLUSIONS: The competitive LICA provided a highly sensitive, accurate and precise method for measuring serum progesterone level.

A light-initiated chemiluminescent assay for the detection of children's milk protein-specific IgE with excellent ability to avoid interference of specific IgG.

The detection of allergen-specific IgE is of value for the diagnosis of children''s milk allergy. However, its accuracy will interfere with the presence of high levels of specific IgG in the serum of children with milk allergy. To solve this problem, we established a light-initiated chemiluminescent assay (LICA) based on nanomicrospheres, which neutralized the interference of specific IgG by increasing the amount of antigen coated on the microspheres. The ability of this method to resist IgG interference was confirmed by adding extra specific IgG to the serum of allergic patients. Finally, the positive rate of allergen-specific IgE was increased to 85%, which was better than the indirect ELISA (70%), indicating that this method has certain advantages for the detection of specific IgE in children with milk allergy.

Anomalous origin of right vertebral artery from right common carotid artery.

Anomalous origin of vertebral arteries is a rare vascular anomaly and mostly discovered as incidental findings during computed tomography angiogram , magnetic resonance angiography or digital subtracted angiogram of the aortic arch and cerebral vessels. Herein, we present an extremely rare case of a 31-year-old female who presented with headache after emotional trauma. A conventional cerebral angiogram showed anomalous origin of the right vertebral artery. This finding was incidentally discovered, and it is of utmost importance for future head and neck endovascular interventions to avoid inadvertent arterial injury.

Establishment of a homogeneous immunoassay-light-initiated chemiluminescence assay for detecting anti-Müllerian hormone in human serum.

Anti-Müllerian hormone (AMH) is known as a reliable marker of ovarian reserve (OR). The determination of AMH is of great importance and most existed AMH detection methods are heterogeneous immunoassay. In this study, a novel homogeneous sandwich immunoassay-light-initiated chemiluminescence assay (LICA) for detecting AMH serum level was developed. This AMH-LICA was performed by incubating serum samples with AMH mouse monoclonal antibody coated with chemibeads, streptavidin-coated sensibeads, and biotinylated AMH mouse monoclonal antibody. Sensitivity, precision, accuracy and cross-reactivity of this assay were evaluated. Besides, a regression analysis showed a high correlation between AMH-LICA and Roche Elecsys® AMH assay (y = 0.9851x + 0.07147, R2 = 0.9569). As a homogeneous immunoassay, this AMH-LICA could accurately and rapidly determine the serum level of AMH with high-throughput. Thus, this new developed assay may be a new useful analytical tool for the determination of AMH.

AICAR and compound C negatively modulate HCC-induced primary human hepatic stellate cell activation in vitro.

Tumor stroma and microenvironment have been shown to affect hepatocellular carcinoma (HCC) growth, with activated hepatic stellate cells (HSC) as a major contributor in this process. Recent evidence suggests that the energy sensor adenosine monophosphate-activated kinase (AMPK) may mediate a series of essential processes during carcinogenesis and HCC progression. Here, we investigated the effect of different HCC cell lines with known TP53 or CTNBB1 mutations on primary human HSC activation, proliferation, and AMPK activation. We show that conditioned media obtained from multiple HCC cell lines differently modulate human hepatic stellate cell (hHSC) proliferation and hHSC AMPK activity in a paracrine manner. Pharmacological treatment of hHSC with AICAR and Compound C inhibited the HCC-induced proliferation/activation of hHSC through AMPK-dependent and AMPK-independent mechanisms, which was further confirmed using mouse embryonic fibroblasts (MEFs) deficient of both catalytic AMPKα isoforms (AMPKα1/α2-/-) and wild type (wt) MEF. Both compounds induced S-phase cell-cycle arrest and, in addition, AICAR inhibited the mTORC1 pathway by inhibiting phosphorylation of 4E-BP1 and S6 in hHSC and wt MEF. Data mining of the Cancer Genome Atlas (TCGA) and the Liver Cancer (LICA-FR) showed that AMPKα1 (PRKAA1) and AMPKα2 (PRKAA2) expression differed depending on the mutation (TP53 or CTNNB1), tumor grading, and G1-G6 classification, reflecting the heterogeneity in human HCC. Overall, we provide evidence that AMPK modulating pharmacological agents negatively modulate HCC-induced hHSC activation and may therefore provide a novel approach to target the mutual, tumor-promoting interactions between hHSC and HCC.NEW & NOTEWORTHY HCC is marked by genetic heterogeneity and activated hepatic stellate cells (HSC) are considered key players during HCC development. The paracrine effect of different HCC cell lines on the activation of primary hHSC was accompanied by differential AMPK activation depending on the HCC line used. Pharmacological treatment inhibited the HCC-induced hHSC activation through AMPK-dependent and AMPK-independent mechanisms. This heterogenic effect on HCC-induced AMPK activation was confirmed by data mining TCGA and LICA-FR databases.

A hook-effect-free homogeneous light-initiated chemiluminescence assay: is it reliable for screening and the quantification of the hepatitis B surface antigen?

BACKGROUND: Hepatitis B virus (HBV) infection remains a threat to global public health. As a hallmark of HBV infection, hepatitis B surface antigen (HBsAg) has been used to screen for HBV infection for decades, and quantitative assays are also being clinically rejuvenated to predict the disease outcome and monitor the antiviral response. Herein, we developed and evaluated a hook-effect-free homogeneous quantitative HBsAg assay based on the light-initiated chemiluminescence immunoassay (LICA). METHODS: A hook-effect-free LICA algorithm was established by measuring the relative light units (RLUs) of two time points during the immunoreaction. The precision was assessed using low- and high-level controls. Consecutive clinical serum samples were tested using the LICA and Abbott Architect assay; samples producing inconsistent results were retested using supplementary assays including the HBsAg neutralization, HBV DNA, and Roche Elecsys HBsAg assays for further confirmation. The consistency, sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. For the quantitative results, the correlation was analyzed. The coverage of different genotypes and mutations by the LICA was evaluated. Moreover, serial on-treatment and follow-up samples from chronic hepatitis B patients were also measured using the two assays. RESULTS: The LICA had better within-run and within-laboratory precisions than the Architect assay. In total, 5,176 clinical samples were tested. The two assays showed a consistency of 99.63%. The LICA showed greater specificity (99.95% vs. 99.77%) and PPV (99.75% vs. 98.77%) than the Architect assay, whereas the Architect assay showed greater sensitivity (100.00% vs. 99.01%) and NPV (100.00% vs. 99.82%). The two assays displayed an excellent correlation independent of genotypes and mutations. The LICA hook-free algorithm recognized 100% of the underestimated results. Furthermore, similar HBsAg dynamics were demonstrated using the LICA and Architect HBsAg assay. CONCLUSIONS: The hook-free LICA provides a reliable tool for screening for HBV infection and quantifying HBsAg.

Licochalcone A-Induced Apoptosis Through the Activation of p38MAPK Pathway Mediated Mitochondrial Pathways of Apoptosis in Human Osteosarcoma Cells In Vitro and In Vivo.

BACKGROUND: Licochalcone A (LicA) is isolated from the roots of Glycyrrhiza glabra and possesses antitumor and anti-invasive activities against several tumor cells. However, the antitumor effects of LicA on human osteosarcoma cells have yet to be demonstrated either in vitro or in vivo. METHODS: Cell viability was measured by MTT assay. Apoptosis and mitochondrial dysfunction were detected with Annexin V/PI staining and JC-1 staining by flow cytometry. The expressions of caspase- or mitochondrial-related proteins were demonstrated by western blotting. Antitumor effect of LicA on 143B xenograft mice in vivo. RESULTS: LicA could inhibit cell proliferation and induce apoptosis in human osteosarcoma cells, as evidenced by a decrease in cell viability, loss of mitochondrial membrane potentials, and activation of caspases. LicA treatment substantially reduced the expression of Bcl-2 and Mcl-1 and increased the expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, and Bax in HOS and U2OS cells. Moreover, mitochondrial membrane potential and apoptosis suppression mediated by Z-VAD or tauroursodeoxycholic acid significantly reduced LicA-induced mitochondria-dependent apoptosis. The study also determined that LicA treatment induced p38MAPK phosphorylation, but siRNA-p38 or BIRB796 substantially reversed cell viability through the inhibition of mitochondria-dependent apoptosis pathways. Finally, an in vivo study revealed that LicA significantly inhibited 143B xenograft tumor growth. CONCLUSIONS: These findings demonstrate that LicA has antitumor activities against human osteosarcoma cells through p38MAPK regulation of mitochondria-mediated intrinsic apoptotic pathways in vitro and in vivo.

Clinical diagnostic performance of light-initiated chemiluminescent assay compared with the Architect chemiluminescence immunoassay for detection of HCV antibody.

BACKGROUND: Hepatitis C virus antibody (anti-HCV) test had been approved as a preliminary screening test for HCV infection. Light-initiated chemiluminescent assay (LiCA) was a homogenous method. We aimed to assess the clinical diagnostic performance of LiCA and compare it with that of chemiluminescence immunoassay (CLIA) which was widely used in clinical laboratories. METHODS: A total of 10 772 patients from the Peking University Third Hospital were enrolled. The serum samples were detected on the ChIVD LiCA500 and Abbott Architect i2000SR platforms. Recombinant immunoblot assay (RIBA) and HCV RNA assay were used for confirmation. RESULTS: The negative agreement rate between ChIVD LiCA anti-HCV assay and Abbott Architect anti-HCV assay was 99.91%, the positive agreement rate was 37.31%, the total agreement rate was 98.74%, and the kappa coefficient (κ) was 0.519. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ChIVD LiCA anti-HCV assay were 96.39%, 99.95%, 89.58%, and 99.97%, respectively, which were superior to those of Abbott Architect anti-HCV assay (93.98%, 99.25%, 51.90%, and 99.95%, respectively). CONCLUSION: ChIVD LiCA anti-HCV assay was a highly sensitive, specific homogenous method with good diagnostic performance, and was applicable for the routine screening of HCV infection in clinical laboratories.

Competitive light-initiated chemiluminescent assay: using 5-α-dihydrotestosterone-BSA as competitive antigen for quantitation of total testosterone in human sera.

This paper described a homogeneous method, light-initiated chemiluminescent assay (LICA), for quantitation of total testosterone in human sera. The assay was bead based and built on a competitive-binding reaction format, in which 5-α-dihydrotestosterone (5-α-DHT) competed with the testosterone in serum samples in binding with biotinylated anti-testosterone antibody. The more testosterone in the serum sample, the less 5-α-DHT that bonded with biotinylated anti-testosterone antibodies. 5-α-DHT was coupled with emission beads (doped with thioxene derivatives and Eu(III) as a chemiluminescence emitter) via bovine serum albumin as a linker. Once streptavidin-coated sensitizer beads (modified with phthalocyanine as a photosensitizer) were added, the streptavidin/biotin reaction between 5-α-DHT-bound anti-testosterone antibody and sensitizer beads could bring emission and sensitizer beads together, which allowed energy transfer from sensitizer bead to emission bead. As such, an exciting light (680 nm) impinging on the sensitizer beads led to light emission at 520-620 nm by emission beads. The strength of the emitted light was inversely proportional to the testosterone in serum sample. The detection range of this assay was from 13.3 to 1200 ng/dL. The coefficient variation for intra- and inter-assay was lower than 15%. The recovery of this method ranged from 95.5 to 105.9% for different samples. Moreover, the LICA assay was highly specific with low cross-reactivity and interference. The concentration of testosterone from 58 serum samples analyzed by the LICA method significantly correlated (y = 0.97x + 1.87, R2 = 0.970, p < 0.001) with those obtained with the SIEMENS Centaur Xp System. Graphical abstract ᅟ.

Development of a light-initiated chemiluminescent assay for the quantitation of sIgE against egg white allergens based on component-resolved diagnosis.

The determination of specific IgE (sIgE) level is of great importance in IgE-mediated food allergies. Our aim was to develop a homogeneous immunoassay-light-initiated chemiluminescent assay (LICA)-for measuring allergen sIgE of a single component in egg white, thus evaluating the LICA-sIgE assay as a useful tool in the diagnosis of food allergy. The LICA-sIgE assay was performed by incubating serum sample with anti-human IgE antibody coated with chemiluminescer beads, streptavidin-coated sensitizer beads, and biotinylated antigens, which consist of four components in egg white. Serum samples from egg allergic patients (n = 70) and healthy volunteers (n = 30) were collected. For calibration, purified human IgE was used as the calibrator. Working conditions of this homogeneous immunoassay were optimized, analytical performance was determined, and correlation of the results between LICA and ImmunoCAP was evaluated. The assays were performed in 8-well plates with a sample volume diluted to 1:10 of 25 µl. Intra-assay precision (% coefficient of variation) ranged from 1.83 to 4.13%, and inter-assay precision ranged from 2.70 to 8.70%. It exhibited excellent sensitivity, which could distinguish between positive samples and negative samples even at a large dilution level. The sIgE-LICA and ImmunoCAP correlated well in patients allergic to single component (r 2 = 0.929). Also, the components ovomucoid and ovalbumin were best at predicting ImmunoCAP results, with the same area under the ROC curve (AUC) of 0.81, and a specificity of 90.0 and 93.3%, respectively. Our data show effective performance characteristics of LICA to detect sIgE in human serum based on component-resolved diagnostic tests (CRD). The homogeneous sIgE-LICA assay has the following key advantages: requires no washing, simplicity and rapidity, reproducibility, high-throughput, good performance in a liquid phase assay, and good suitability for sIgE diagnosis in food allergy based on CRD. Graphical abstract A light-initiated chemiluminescent assay was developed for the quantitation of sIgE against egg white allergens based on component-resolved diagnosis. Components Gal d 1 and Gal d 2 with the highest AUC values of 0.81 were considered the best at predicting egg allergy.

Distinct multivariate brain morphological patterns and their added predictive value with cognitive and polygenic risk scores in mental disorders.

The brain underpinnings of schizophrenia and bipolar disorders are multidimensional, reflecting complex pathological processes and causal pathways, requiring multivariate techniques to disentangle. Furthermore, little is known about the complementary clinical value of brain structural phenotypes when combined with data on cognitive performance and genetic risk. Using data-driven fusion of cortical thickness, surface area, and gray matter density maps (GMD), we found six biologically meaningful patterns showing strong group effects, including four statistically independent multimodal patterns reflecting co-occurring alterations in thickness and GMD in patients, over and above two other independent patterns of widespread thickness and area reduction. Case-control classification using cognitive scores alone revealed high accuracy, and adding imaging features or polygenic risk scores increased performance, suggesting their complementary predictive value with cognitive scores being the most sensitive features. Multivariate pattern analyses reveal distinct patterns of brain morphology in mental disorders, provide insights on the relative importance between brain structure, cognitive and polygenetic risk score in classification of patients, and demonstrate the importance of multivariate approaches in studying the pathophysiological substrate of these complex disorders.

Elemental variability in the coralline alga Lithophyllum yemenense as an archive of past climate in the Gulf of Aden (NW Indian Ocean).

This study presents the first algal thallus (skeleton) archive of Asian monsoon strength and Red Sea influence in the Gulf of Aden. Mg/Ca, Li/Ca, and Ba/Ca were measured in Lithophyllum yemenense from Balhaf (Gulf of Aden) using laser ablation inductively coupled plasma mass spectrometry, and Mg/Ca ratio oscillation was used to reconstruct the chronology (34 y). Oscillations of element rates corresponding to the algal growth between 1974 and 2008 were compared with recorded climate and oceanographic variability. During this period, sea surface temperatures (SST) in Balhaf recorded a warming trend of 0.55°C, corresponding to an increase in Mg and Li content in the algal thallus of 2.1 mol-% and 1.87 µmol-%, respectively. Lithophyllum yemenense recorded decadal SST variability by Li/Ca, and the influence of the Pacific El-Niño Southern Oscillation on the NW Indian Ocean climate system by Ba/Ca. Additionally, algal Mg/Ca, Li/Ca, and Ba/Ca showed strong and significant correlations with All Indian Rainfall in the decadal range indicating that these proxies can be useful for tracking variability in the Indian monsoon system, possibly due to changes of the surface wind system, with deep water upwelling in summer, and a distinct seasonality.

Identification of residues that control Li+ versus Na+ dependent Ca2+ exchange at the transport site of the mitochondrial NCLX.

BACKGROUND: The Na+/Ca2+/Li+ exchanger (NCLX) is a member of the Na+/Ca2+ exchanger family. NCLX is unique in its capacity to transport both Na+ and Li+, unlike other members, which are Na+ selective. The major aim of this study was twofold, i.e., to identify NCLX residues that confer Li+ or Na+ selective Ca2+ transport and map their putative location on NCLX cation transport site. METHOD: We combined molecular modeling to map transport site of NCLX with euryarchaeal H+/Ca2+ exchanger, CAX_Af, and fluorescence analysis to monitor Li+ versus Na+ dependent mitochondrial Ca2+ efflux of transport site mutants of NCLX in permeabilized cells. RESULT: Mutation of Asn149, Pro152, Asp153, Gly176, Asn467, Ser468, Gly494 and Asn498 partially or strongly abolished mitochondrial Ca2+ exchange activity in intact cells. In permeabilized cells, N149A, P152A, D153A, N467Q, S468T and G494S demonstrated normal Li+/Ca2+ exchange activity but a reduced Na+/Ca2+ exchange activity. On the other hand, D471A showed dramatically reduced Li+/Ca2+ exchange, but Na+/Ca2+ exchange activity was unaffected. Finally, simultaneous mutation of four putative Ca2+ binding residues was required to completely abolish both Na+/Ca2+ and Li+/Ca2+ exchange activities. CONCLUSIONS: We identified distinct Na+ and Li+ selective residues in the NCLX transport site. We propose that functional segregation in Li+ and Na+ sites reflects the functional properties of NCLX required for Ca2+ exchange under the unique membrane potential and ion gradient across the inner mitochondrial membrane. GENERAL SIGNIFICANCE: The results of this study provide functional insights into the unique Li+ and Na+ selectivity of the mitochondrial exchanger. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.

Normative Study of the Literacy Independent Cognitive Assessment in Illiterate and Literate Elderly Koreans.

OBJECTIVE: The aim of this study was to provide normative data on the Literacy Independent Cognitive Assessment (LICA) and to explore the effects of age, education/literacy, and gender on the performance of this test. METHODS: Eight hundred and eighty-eight healthy elderly subjects, including 164 healthy illiterate subjects, participated in this study. None of the participants had serious medical, psychiatric, or neurological disorders including dementia. Bivariate linear regression analyses were performed to examine the effects of age, education/literacy, and sex on the score in each of the LICA cognitive tests. The normative scores for each age and education/literacy groups are presented. RESULTS: Bivariate linear regression analyses revealed that total score and all cognitive tests of the LICA were significantly influenced by both age and education/literacy. Younger and more-educated subjects outperformed older and illiterate or less-educated subjects, respectively, in all of the tests. The normative scores of LICA total score and subset score were presented according to age (60-64, 65-69, 70-74, 75-80, and ≥80 years) and educational levels (illiterate, and 0-3, 4-6, and ≥7 years of education). CONCLUSION: These results on demographic variables suggest that age and education should be taken into account when attempting to accurately interpret the results of the LICA cognitive subtests. These normative data will be useful for clinical interpretations of the LICA neuropsychological battery in illiterate and literate elderly Koreans. Similar normative studies and validations of the LICA involving different ethnic groups will help to enhance the dementia diagnosis of illiterate people of different ethnicities.