Inferencing Abilities of Deaf College Students: Foundations and Implications for Metaphor Comprehension and Theory of Mind

Understanding nonliteral language requires inferencing ability and is an important but complex aspect of social interaction, involving cognitive (e.g., theory of mind, executive function) as well as language skill, areas in which many deaf individuals struggle. This study examined comprehension of metaphor and sarcasm, assessing the contributions of hearing status, inferencing ability, executive function (verbal short-term/working memory capacity), and deaf individuals’ communication skills (spoken versus signed language, cochlear implant use). Deaf and hearing college students completed a multiple-choice metaphor comprehension task and inferencing tasks that included both social-emotional (i.e., theory of mind) and neutral inferences, as well as short-term memory span and working memory tasks. Results indicated the hearing students to have better comprehension of nonliteral language and the ability to make social-emotional inferences, as well as greater memory capacity. Deaf students evidenced strong relationships among inferential comprehension, communication skills, and memory capacity, with substantial proportions of the variance in understanding of metaphor and sarcasm accounted for by these variables. The results of this study enhance understanding of the language and cognitive skills underlying figurative language comprehension and theory of mind and have implications for the social functioning of deaf individuals

Soluble Serum CD81 Is Elevated in Patients with Chronic Hepatitis C and Correlates with Alanine Aminotransferase Serum Activity

Aim: Cellular CD81 is a well characterized hepatitis C virus (HCV) entry factor, while the relevance of soluble exosomal CD81 in HCV pathogenesis is poorly defined. We performed a case-control study to investigate whether soluble CD81 in the exosomal serum fraction is associated with HCV replication and inflammatory activity. Patients and Methods: Four cohorts were investigated, patients with chronic hepatitis C (n = 37), patients with chronic HCV infection and persistently normal ALT levels (n = 24), patients with long term sustained virologic response (SVR, n = 7), and healthy volunteers (n = 23). Concentration of soluble CD81 was assessed semi-quantitatively after differential centrifugation ranging from 200 g to 100,000 g in the fifth centrifugation fraction by immunoblotting and densitometry. Results: Soluble CD81 was increased in patients with chronic hepatitis C compared to healthy subjects (p = 0.03) and cured patients (p = 0.017). Patients with chronic HCV infection and persistently normal ALT levels and patients with long term SVR had similar soluble CD81 levels as healthy controls (p>0.2). Overall, soluble CD81 levels were associated with ALT levels (r = 0.334, p = 0.016) and severe liver fibrosis (p = 0.027). Conclusion: CD81 is increased in the exosomal serum fraction in patients with chronic hepatitis C and appears to be associated with inflammatory activity and severity of fibrosis

Neuro-ophthalmologic and blood biomarker responses in ADHD following subconcussive head impacts: a case–control trial

IntroductionThis clinical trial aimed to determine the influence of attention-deficit/hyperactivity disorder (ADHD) on neuro-ophthalmologic function and brain-derived blood biomarkers following acute subconcussive head impacts.MethodsThe present trial consisted of age- and sex-matched samples with a ratio of 1:1 between two groups with a total sample size of 60 adults (age ± SD; 20.0 ± 1.8 years). Soccer players diagnosed with and medicated daily for ADHD were assigned into an ADHD group (n = 30). Soccer players without ADHD were assigned into a non-ADHD group (n = 30). Participants performed 10 soccer headers with a soccer ball projected at a velocity of 25mph. King-Devick test (KDT), near point of convergence (NPC), and serum levels of NF-L, tau, GFAP, and UCH-L1 were assessed at baseline (pre-heading) and at 2 h and 24 h post-heading.ResultsThere were no statistically significant group-by-time interactions in outcome measures. However, at baseline, the ADHD group exhibited lower neuro-ophthalmologic functions compared to the non-ADHD group (NPC: p = 0.019; KDT: p = 0.018), and persisted at 2 h-post (NPC: p = 0.007; KDT: p = 0.014) and 24 h-post heading (NPC: p = 0.001). NPC significantly worsened over time in both groups compared to baseline [ADHD: 2 h-post, 1.23 cm, 95%CI:(0.77, 1.69), p < 0.001; 24 h-post, 1.68 cm, 95%CI:(1.22, 2.13), p = 0.001; Non-ADHD: 2 h-post, 0.96 cm, 95%CI:(0.50, 1.42), p < 0.001; 24 h-post, 1.09 cm, 95%CI:(0.63, 1.55), p < 0.001]. Conversely, improvements in KDT time compared to baseline occurred at 2 h-post in the non-ADHD group [−1.32 s, 95%CI:(−2.55, −0.09), p = 0.04] and at 24 h-post in both groups [ADHD: −4.66 s, 95%CI:(−5.89, −3.43), p < 0.001; Non-ADHD: −3.46 s, 95%CI:(−4.69, −2.23), p < 0.001)]. There were no group-by-time interactions for GFAP as both groups exhibited increased levels at 2 h-post [ADHD: 7.75 pg./mL, 95%CI:(1.41, 14.10), p = 0.019; Non-ADHD: 7.91 pg./mL, 95%CI:(1.71, 14.14), p = 0.015)] that returned to baseline at 24 h-post. NF-L levels increased at 2 h-post heading in the ADHD group [0.45 pg./mL, 95%CI:(0.05, 0.86), p = 0.032], but no significant NF-L changes were observed in the non-ADHD group over time.DiscussionTen soccer headers elevated GFAP levels and NPC impairment in both groups. However, persisting group difference in NPC, blunted KDT performance, and increased NF-L levels in the ADHD group suggest that ADHD may reduce neuro-ophthalmologic function and heighten axonal response to soccer headers.Clinical trial registrationClinicalTrials.gov, identifier ID: (NCT04880304)

Was ist "Populäre Musik"? : Überlegungen in eigener Sache

Many common disorders across the lifespan feature impaired working memory (WM). Reported benefits of a WM training program include improving inattention in daily life, but this has not been evaluated in a meta-analysis. This study aimed to evaluate whether one WM training method has benefits for inattention in daily life by conducting a systematic review and meta-analysis.We searched Medline and PsycINFO, relevant journals and contacted authors for studies with an intervention and control group reporting post-training estimates of inattention in daily life. To reduce the influence of different WM training methods on the findings, the review was restricted to trials evaluating the Cogmed method. A meta-analysis calculated the pooled standardised difference in means (SMD) between intervention and control groups.A total of 622 studies were identified and 12 studies with 13 group comparisons met inclusion criteria. The meta-analysis showed a significant training effect on inattention in daily life, SMD=-0.47, 95% CI -0.65, -0.29, p<.00001. Subgroup analyses showed this significant effect was observed in groups of children and adults as well as users with and without ADHD, and in studies using control groups that were active and non-adaptive, wait-list and passive as well as studies using specific or general measures. Seven of the studies reported follow-up assessment and a meta-analysis showed persisting training benefits for inattention in daily life, SMD=-0.33, 95% CI -0.57 -0.09, p=.006. Additional meta-analyses confirmed improvements after training on visuospatial WM, SMD=0.66, 95% CI 0.43, 0.89, p<.00001, and verbal WM tasks, SMD=0.40, 95% CI 0.18, 0.62, p=.0004.Benefits of a WM training program generalise to improvements in everyday functioning. Initial evidence shows that the Cogmed method has significant benefits for inattention in daily life with a clinically relevant effect size

Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response

BACKGROUND: Plasma biomarkers may be particularly useful as a predictor or early marker of clinical response to treatment in addition to radiological imaging. Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18-Asp396) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a simple, non-invasive way to monitor or predict responses to treatment. METHODS: Soluble plasma CK18-Asp396 and CK18 were measured by ELISA from 73 patients with advanced gastrointestinal adenocarcinomas before treatment and during chemotherapy, as well as 100 healthy volunteers. RESULTS: Both CK18-Asp396 and total CK18 plasma levels were significantly higher in patients compared with the healthy volunteers (P = 0.015, P &lt; 0.001). The total CK18 baseline plasma levels before treatment were significantly higher (P = 0.009) in patients who develop progressive disease than those who achieve partial response or stable disease and this correlation was confirmed in an independent validation set. The peak plasma levels of CK18 occurring in any cycle following treatment were also found to be associated with tumour response, but peak levels of CK18-Asp396 did not reach significance (P = 0.01, and P = 0.07, respectively). CONCLUSION: Plasma levels CK18 are a potential marker of tumour response in patients with advanced gastrointestinal malignancy

Serum MicroRNA-21 as Marker for Necroinflammation in Hepatitis C Patients with and without Hepatocellular Carcinoma

Background: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC. Methodology/Principal Findings: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = −0.494, P = 0.00002), alanine aminotransferase (ALT) (r = −0.309, P = 0.007), aspartate aminotransferase (r = −0.495, P = 0.000007), bilirubin (r = −0.362, P = 0.002), international normalized ratio (r = −0.338, P = 0.034) and γ-glutamyltransferase (r = −0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dCT of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%. Conclusions/Significance: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC

EBV-gp350 Confers B-Cell Tropism to Tailored Exosomes and Is a Neo-Antigen in Normal and Malignant B Cells—A New Option for the Treatment of B-CLL

gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies

Insulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes–Associated Variants

International audienceObjective. Zinc ions are essential for the formation of hexameric insulin and hormone crystallisation. Correspondingly, a non-synonymous single nucleotide polymorphism rs13266634 in the SLC30A8 gene, encoding the secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. Here, we describe the effects of deleting the ZnT8 gene in mice and explore the action of the at-risk allele. Research Design and Methods. Slc30a8 null mice were generated and backcrossed at least twice onto a C57BL/6J background. Glucose and insulin tolerance were measured by intraperitoneal injection, or euglycemic clamp, respectively. Insulin secretion, electrophysiology, imaging, and the generation of adenoviruses encoding the low- (W325) or elevated- (R325) risk ZnT8 alleles, were undertaken using standard protocols. Results. ZnT8(-/-) mice displayed age, sex and diet-dependent abnormalities in glucose tolerance, insulin secretion and body weight. Islets isolated from null mice had reduced granule zinc content, and showed age-dependent changes in granule morphology, with markedly fewer dense cores but more rod-like crystals. Glucose-stimulated insulin secretion, granule fusion and insulin crystal dissolution, as assessed by total internal reflection fluorescence microscopy, were unchanged or enhanced in ZnT8(-/-) islets. Insulin processing was normal. Molecular modelling revealed that residue-325 was located at the interface between ZnT8 monomers. Correspondingly, the R325 variant displayed lower apparent Zn(2+) transport activity than W325 ZnT8 by fluorescence-based assay. Discussion and conclusions. ZnT8 is required for normal insulin crystallisation and insulin release in vivo but not, remarkably, in vitro. Defects in the former processes in carriers of the R allele may increase type 2 diabetes risk

Method validation and preliminary qualification of pharmacodynamic biomarkers employed to evaluate the clinical efficacy of an antisense compound (AEG35156) targeted to the X-linked inhibitor of apoptosis protein XIAP

Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates different forms of circulating cytokeratin 18 (CK18) as putative surrogate markers of both apoptotic and nonapoptotic tumour cell death, was shown to be highly reproducible: calibration curve linearity r2=0.996, mean accuracy >91% and mean precision <3%, n=27. Employing recombinant (r) CK18 and caspase cleaved CK18 (CK18 Asp396 neo-epitope) as external standards, kit to kit reproducibly was <6% (n=19). rCK18 was stable in plasma for 4 months at −20°C and −80°C, for 4 weeks at 4°C and had a half-life of 2.3 days at 37°C. Cytokeratin 18 Asp396 NE, the M30 Apoptosense Elisa assay antigen, was stable in plasma for 6 months at −20°C and −80°C, for 3 months at 4°C, while its half-life at 37°C was 3.8 days. Within-day variations in endogenous plasma concentrations of the M30 and M65 antigens were assessed in two predose blood samples collected from a cohort of 15 ovarian cancer patients receiving carboplatin chemotherapy and were shown to be no greater than the variability associated with methods themselves. Between-day fluctuations in circulating levels of the M30 and M65 antigens and in XIAP mRNA levels measured in peripheral blood mononuclear cells by quantitative (q) RT–PCR were evaluated in two predose blood samples collected with a 5- to 7-day gap from 23 patients with advanced cancer enrolled in a phase I trial. The mean variation between the two pretreatment values ranged from 13 to 14 to 25%, respectively, for M65, M30 and qRT–PCR. These data suggest that the M30 and M65 Elisa's and qRT–PCR as PD biomarker assays have favourable performance characteristics for further investigation in clinical trials of anticancer agents which induce tumour apoptosis/necrosis or knockdown of the anti-apoptotic protein XIAP