Dual immunoadsorption for ABO-incompatible heart transplantation in a 35 kg child.

Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible (ABOi) heart transplantation. Here we report the first case of a patient transplanted with ABO-IA, that was of an age and weight that required two ABO-IA columns run in parallel, to enable the reduction in antibody titres to a sufficiently low level in the time available during implantation of the donor organ.

Constitutional mismatch repair deficiency: a case on a commonly misinterpreted mutation in colon cancer.

It is estimated that 153,020 cases of CRC per year, with an increase in diagnoses in younger patients. We present a case of a female with an early presentation of Lynch Syndrome and CRC, who, on her third malignant presentation, was re-diagnosed as a constitutional mismatch repair deficiency.

Multicenter validation of synthetic FLAIR as a substitute for FLAIR sequence in acute ischemic stroke.

PURPOSE: To evaluate performance of synthetic and real FLAIR for identifying early stroke in a multicenter cohort. METHODS: This retrospective study was conducted using DWI and FLAIR extracted from the Endovascular Treatment in Ischemic Stroke image registry (2017-2021). The database was partitioned into subsets according to MRI field strength and manufacturer, and randomly divided into training set (70%) used for model fine-tuning, validation set (15%), and test set (15%). In test set, five readers, blinded to FLAIR sequence type, assessed DWI-FLAIR mismatch using real and synthetic FLAIR. Interobserver agreement for DWI-FLAIR rating and concordance between synthetic and real FLAIR were evaluated with kappa statistics. Sensitivity and specificity for identification of ⩽4.5 h AIS were compared in patients with known onset-to-MRI delay using McNemar's test. RESULTS: 1454 complete MRI sets (1172 patients, median (IQR) age: 73 years (62-82); 762 women) acquired on 125 MRI units were analyzed. In test set (207 MRI), interobserver reproducibility for DWI-FLAIR mismatch labeling was substantial for real and synthetic FLAIR (Fleiss κ = 0.79 (95%CI: 0.73-0.84) and 0.77 (95%CI: 0.71-0.82), respectively). After consensus, concordance between real and synthetic FLAIR was excellent (κ = 0.85 (95%CI: 0.78-0.92)). In 141 MRI sets with known onset-to-MRI delay, diagnostic performances for ⩽4.5 h AIS identification did not differ between real and synthetic FLAIR (sensitivity: 60/71 (85%) vs 59/71 (83%), p = .56; specificity: 65/70 (93%) vs 65/70 (93%), p > 0.99). CONCLUSION: A deep-learning-based FLAIR fine-tuned on multicenter data can provide comparable performances to real FLAIR for early AIS identification. This approach may help reducing MR protocol duration and motion artifacts.

The Complex Pattern Mismatch Negativity as a Potential Indicator of Psychosis Across all Phases of Illness: A Meta-Analysis.

Over the past decade, there has been extensive research on the mismatch negativity (MMN) and its promise as a biomarker of illness in people with schizophrenia (SZ). Nevertheless, when attempting to assess the early stages of illness progression, the utility of MMN has been inconsistent. Recently, researchers have been investigating a more advanced MMN paradigm (the complex MMN [cMMN]) which is believed to index higher-order cognitive processing and has been suggested to be a more effective indicator of the early phases of SZ. The cMMN is defined as a paradigm that relies on alterations within a pre-established pattern of stimuli. In this meta-analysis, we investigated cMMN deficits in individuals with SZ, including an analysis involving those in the first 5 years of illness. Our search also included individuals with bipolar disorder who experience psychosis; however, no related papers were found and thus, no findings are reported. Our findings indicate a small/moderate effect (d = 0.47), suggesting that individuals with SZ exhibit reduced cMMN amplitudes compared to individuals without SZ. Interestingly, this effect seems to be more pronounced in individuals within the first 5 years of their illness (d = 0.58), suggesting that cMMN might be a more sensitive biomarker in the early phases of SZ compared to traditional paradigms.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Efficacy and safety of PD-1/L1 inhibitors as first-line therapy for metastatic colorectal cancer: a meta-analysis.

Objective: To evaluate the efficacy and safety of PD-1/L1 inhibitors as first-line therapy in metastatic colorectal cancer(mCRC). Method: Articles evaluating first-line PD-1/L1 inhibitors for mCRC were sought in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) from the inception of the databases until 11 November 2023. Meta-analyses were conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 treatment-related adverse events (trAEs). Results: Totally nine studies were included for meta-analysis. A subgroup analysis was performed based on mismatch repair(MMR) status and regimens. In patients diagnosed with mismatch repair-deficient(dMMR) mCRC who received PD-1/L1 inhibitors as their first-line treatment, the ORR was 0.54 (95% CI, 0.39 to 0.68), the median PFS was 53.2 months, the Grade≥ 3 TRAEs rate was 0.33(95% CI, 0.12 to 0.60) and the median OS was not determined. For patients with proficient mismatch repair (pMMR) mCRC who underwent a combined treatment of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody and chemotherapy as their first-line therapy, the ORR was 0.62 (95% CI, 0.56 to 0.68), the median PFS was 10.1 months, the median OS was 26.7 months, and the Grade≥ 3 TRAEs rate was 0.59(95% CI, 0.39 to 0.77). Conclusion: Our results revealed that the utilization of PD-1/L1 inhibitors as first-line therapy for dMMR mCRC yielded highly favorable outcomes, while maintaining an acceptable level of safety. Administering a combination of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody, and chemotherapy as first-line treatment in patients with pMMR mCRC led to an improved ORR. However, there was no significant improvement in the long-term prognosis of the tumor. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196, identifier CRD42024506196.

DNA mismatch repair defect and intratumor heterogeneous deficiency differently impact immune responses in diffuse large B-cell lymphoma.

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression profiling. The results showed that genetic dMMR was infrequent in DLBCL and was significantly associated with increased cancer gene mutations and favorable immune microenvironment, but not prognostic impact. Phenotypic dMMR was also infrequent, and MMR proteins were commonly expressed in DLBCL. However, intratumor heterogeneity existed, and increased DLBCL cells with phenotypic dMMR correlated with significantly increased T cells and PD-1+ T cells, higher average nearest neighbor distance between T cells and PAX5+ cells, upregulated immune gene signatures, LE4 and LE7 ecotypes and their underlying Ecotyper-defined cell states, suggesting the possibility that increased T cells targeted only tumor cell subsets with dMMR. Only in patients with MYC¯ DLBCL, high MSH6/PMS2 expression showed significant adverse prognostic effects. This study shows the immunologic and prognostic effects of genetic/phenotypic dMMR in DLBCL, and raises a question on whether DLBCL-infiltrating PD-1+ T cells target only tumor subclones, relevant for the efficacy of PD-1 blockade immunotherapy in DLBCL.

Unveiling Opportunities for Intervention: A Prospective Cohort Study Investigating the Clinical Significance of Diffusion-Weighted Imaging (DWI)-Fluid-Attenuated Inversion Recovery (FLAIR) Mismatch Beyond the Window Period in Acute Ischemic Stroke.

INTRODUCTION: Acute ischemic stroke causes irreversible damage to the brain parenchyma surrounded by salvageable tissue known as the ischemic penumbra. Magnetic resonance imaging (MRI), particularly the mismatch between abnormal diffusion-weighted imaging (DWI) signals and normal fluid-attenuated inversion recovery (FLAIR) signals, plays a critical role in detecting ischemic penumbra. It also allows for the identification of patients who may benefit from reperfusion therapy. Hence, this prospective cohort study aimed to explore the correlation between DWI-FLAIR mismatch and clinical outcomes in acute ischemic stroke patients, specifically those with delayed or uncertain symptom onset, offering potential insights into reperfusion therapy. METHODOLOGY: A total of 38 thrombotic stroke patients aged above 18 were included in this prospective cohort study. Baseline data, including demographics, lifestyle factors, and medical history, were recorded. DWI-FLAIR mismatch was evaluated through brain MRI within 4.5 hours to 12 hours of symptom onset. RESULTS:  Of the cohort, 63.2% were males, predominantly in the 61-70 age group. Smoking and alcohol consumption were reported by 15.79% each. DWI-FLAIR mismatch was present in 20 out of 38 subjects. No statistically significant differences were noted in the mean National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (MRS) scores between subjects with and without DWI-FLAIR mismatch. Thrombolysis in wake-up stroke subjects demonstrated a substantial reduction in mean MRS at discharge (1.29±0.95) and at six to eight weeks (1.71±1.11), suggesting potential benefits on functional outcomes. CONCLUSION:  The prevalence of DWI-FLAIR mismatch was seen in the majority of patients beyond their window period and also showed beneficiary outcomes with a mean reduction in NHISS and MRS scores following thrombolysis.

Evidence for a metal disease refuge: The amphibian-killing fungus (Batrachochytrium dendrobatidis) is inhibited by environmentally-relevant concentrations of metals tolerated by amphibians.

The amphibian-killing fungus Batrachochytrium dendrobatidis (Bd) has caused substantial declines in Bd-susceptible amphibian species worldwide. However, some populations of Bd-susceptible frogs have managed to survive at existing metal-polluted sites, giving rise to the hypothesis that frogs might persist in the presence of Bd if Bd is inhibited by metals at concentrations that frogs can tolerate. We tested this hypothesis by measuring the survival of Bd zoospores, the life stage that infects amphibians, and calculated the LC50 after exposure to environmentally-relevant elevated concentrations of copper (Cu), zinc (Zn), and their combination (Cu + Zn) in two repeated 4-day acute exposure runs. We also measured the chronic sensitivity of Bd to these metals over three generations by measuring the number of colonies and live zoospores and calculating EC50 concentrations after 42 days of exposure. We then compared acute and chronic sensitivity of Bd with amphibian sensitivities by constructing species sensitivity distributions (SSDs) using LC50 and EC50 data obtained from the literature. Acute sensitivity data showed that Bd zoospore survival decreased with increasing metal concentrations and exposure durations relative to the control, with the highest LC50 values for Cu and Zn being 2.5 µg/L and 250 µg/L, respectively. Chronic exposures to metals resulted in decreased numbers of Bd colonies and live zoospores after 42 days, with EC50 values of 0.75 µg/L and 1.19 µg/L for Cu and Zn, respectively. Bd zoospore survival was 10 and 8 times more sensitive to Cu and Zn, respectively in acute, and 2 and 5 times more sensitive to Cu and Zn in chronic exposure experiments than the most sensitive amphibian species recorded. Our findings are consistent with the hypothesis that metals in existing metal-polluted sites may have a greater impact on Bd relative to amphibians' performance, potentially enabling Bd-susceptible amphibians to persist with Bd at these sites.

Microsatellite instability at U2AF-binding polypyrimidic tract sites perturbs alternative splicing during colorectal cancer initiation.

BACKGROUND: Microsatellite instability (MSI) due to mismatch repair deficiency (dMMR) is common in colorectal cancer (CRC). These cancers are associated with somatic coding events, but the noncoding pathophysiological impact of this genomic instability is yet poorly understood. Here, we perform an analysis of coding and noncoding MSI events at the different steps of colorectal tumorigenesis using whole exome sequencing and search for associated splicing events via RNA sequencing at the bulk-tumor and single-cell levels. RESULTS: Our results demonstrate that MSI leads to hundreds of noncoding DNA mutations, notably at polypyrimidine U2AF RNA-binding sites which are endowed with cis-activity in splicing, while higher frequency of exon skipping events are observed in the mRNAs of MSI compared to non-MSI CRC. At the DNA level, these noncoding MSI mutations occur very early prior to cell transformation in the dMMR colonic crypt, accounting for only a fraction of the exon skipping in MSI CRC. At the RNA level, the aberrant exon skipping signature is likely to impair colonic cell differentiation in MSI CRC affecting the expression of alternative exons encoding protein isoforms governing cell fate, while also targeting constitutive exons, making dMMR cells immunogenic in early stage before the onset of coding mutations. This signature is characterized by its similarity to the oncogenic U2AF1-S34F splicing mutation observed in several other non-MSI cancer. CONCLUSIONS: Overall, these findings provide evidence that a very early RNA splicing signature partly driven by MSI impairs cell differentiation and promotes MSI CRC initiation, far before coding mutations which accumulate later during MSI tumorigenesis.

Examining the Complex Mismatch Negativity in Early Phase Psychosis Using the Dual Rule Paradigm.

Using electroencephalography (EEG) to examine the simple mismatch negativity (MMN), a marker of auditory cortex function, has been of great interest in the exploration of biomarkers for psychotic illness. Despite many studies reporting MMN deficits in chronic schizophrenia, there are inconsistent reports of MMN reductions in the early phases of psychotic illness, suggesting the MMN elicited by traditional paradigms may not be a sensitive enough measure of vulnerability to be used as a biomarker. Recently, a more computationally complex measure of auditory cortex function (the complex mismatch negativity; cMMN) has been hypothesized to provide a more sensitive marker of illness vulnerability. The current study employed a novel dual rule paradigm, in which two pattern rules are established and violated, to examine the cMMN in 14 individuals with early phase psychosis (EPP, < 5 years illness) and 15 healthy controls (HC). Relationships between cMMN waveforms, symptom severity, and measures of functioning were explored. We found reductions of cMMN amplitudes at the site of maximal amplitude in EPP (p = .017) with large effect sizes (Hedges' g = 0.96). This study is an early step in the exploration of the cMMN as a biomarker for psychosis. Our results provide evidence that the dual rule cMMN paradigm shows promise as a method for cMMN elicitation that captures more subtle neurofunctional changes in the early stages of illness.

Retrospective study of the changes in dynamic compliance and ventilation/perfusion mismatch following salbutamol inhalation in hypoxaemic mechanically ventilated anaesthetized horses.

OBJECTIVE: To study the changes in dynamic compliance (Cdyn), ventilation/perfusion (V˙/ Q˙) mismatch and haemodynamic variables in hypoxaemic anaesthetized horses whose PaO2 increased following salbutamol inhalation. STUDY DESIGN: Retrospective, clinical, cohort study. ANIMALS: A group of 73 client-owned horses treated with salbutamol when PaO2 <100 mmHg (13.3 kPa) during anaesthesia. METHODS: Horses were divided into two groups: responders (R), where PaO2 after salbutamol ≥1.2 PaO2 before treatment (i.e. ≥20% increase), and non-responders (NR), where PaO2 after salbutamol <1.2 PaO2 before treatment. Demographic data and intraoperative variables before treatment were compared between R and NR. Cdyn, arterial to end-tidal carbon dioxide difference [P(a-E´)CO2], estimated ratio of dead space to tidal volume (est.VD/VT), estimated shunt fraction (F-shunt), heart rate, systolic, mean and diastolic arterial pressure and dobutamine requirements were compared before and after treatment within R and NR. For each variable, the difference (Δ) between values pre- and posttreatment was calculated and compared between groups R and NR. Numerical data were compared using univariate or bivariate analysis and categorical data were compared using chi-square test; p < 0.05. RESULTS: Of the 73 horses 50 were classified as R while 23 horses were classified as NR. There was no statistical difference between R and NR for demographic data or initial intraoperative variables except for body weight [R: 531 (170-715) kg, NR: 540 (420-914) kg]. While salbutamol did not alter Cdyn in either group, it significantly decreased P(a-E´)CO2, est.VD/VT and F-shunt in R only. ΔP(a-E´)CO2, Δest.VD/VT and ΔF-shunt were significantly greater in R (-17.8%, -19.0% and -24.1%, respectively) than in NR (11.5%, 6.6% and -0.3%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: In hypoxaemic anaesthetized horses responding to inhaled salbutamol by a ≥1.2 increase in PaO2 no change in Cdyn was detected, but indicators of V˙/ Q˙ mismatch improved.

Mucin-Rich Brain Metastasis May Show the T2-FLAIR Mismatch Sign: A Case Report and Literature Review.

This study describes a unique case of single mucin-rich brain metastasis in a patient with breast cancer, mimicking the T2-fluid attenuation inversion recovery (FLAIR) mismatch sign and masquerading as an isocitrate dehydrogenase-mutant astrocytoma. This case highlights the importance of considering mucin-rich lesions in the differential diagnosis of intracranial tumors exhibiting T2-FLAIR mismatch. Clinicians must recognize the potential convergence in imaging characteristics between these metastases and gliomas to guarantee prompt and accurate patient care.

Comparison between MRI FLAIR vascular hyperintensity-DWI mismatch and perfusion based triage for thrombectomy in the late time window.

Background: The clinical impact of patient selection using FLAIR vascular hyperintensity (FVH)-diffusion-weighted imaging (DWI) mismatch for endovascular thrombectomy (EVT) in patients who have been symptomatic for over 6 h remains unclear. Herein, a retrospective study was conducted to compare the inter-rater reliability and clinical outcomes of patients selected for thrombectomy based on FVH-DWI mismatch with perfusion. Methods: Patients with anterior-circulation large-vessel occlusion selected simultaneously with MRI and perfusion imaging in the late time window from a single-center retrospective study were categorized into EVT-applicable (FVH-DWI mismatch on MRI or perfusion imaging meeting the DEFUSE3 standards) and EVT-inapplicable groups based on MRI and perfusion imaging. The primary outcome was the 90-day functional independence rate. Safety outcomes encompassed symptomatic intracranial hemorrhage and mortality in 90 days. We assessed the consistency of the two profiles and compared the differences in functional independence rates of EVT patients among the EVT-applicable groups determined by MRI and perfusion. Results: A total of 130 patients were enrolled, of which 114 were classified into the EVT-applicable group after triaging using MRI images. In this group, 96 patients underwent EVT, with 53 of them (55.2%) achieving functional independence. A total of 110 patients were divided into EVT-applicable group based on perfusion, among which 92 underwent EVT, with 49 of them (53.2%) achieving functional independence. The consistency of identifying EVT indication was moderate between two groups (κ = 0.42, 95% CI, 0.17-0.67). The functional independence rate was comparable between patients in the two EVT-applicable groups based on the two methods (55.2% vs. 53.2%, p = 0.789). Conclusion: MRI triaging based on FVH-DWI mismatch showed moderate inter-rater reliability compared with perfusion-based triage and comparable efficacy in predicting clinical outcomes after EVT.

Spinopelvic Parameters in the Elderly: Does Inadequate Correction Portend Worse Outcomes?

Introduction: This study aimed to compare the outcomes of corrective fusion for adult spinal deformity (ASD) in older people using two different sagittal correction goals: the conventional formula of "pelvic incidence (PI)-lumbar lordosis (LL) mismatch <10°" and an undercorrection strategy based on the range of 10°≤PI-LL≤20°. Methods: A total of 102 consecutive patients (11 male and 91 female patients; mean age, 72.0 years) aged above 65 years with scoliosis >20° or LL<20° who had undergone long-segment fusion from the lower thoracic spine to the pelvis for ASD and had been followed-up for a minimum of two years at our institution since March 2013 were included in this retrospective study. After excluding patients with PI-LL≤-10° on postoperative standing radiographs, the remaining patients were divided into two groups: 31 patients with 10°≤PI-LL≤20° (U group) and 63 patients with -10°

Ergonomic design of computer laboratory furniture: Mismatch analysis utilizing anthropometric data of university students.

Many studies have shown that ergonomically designed furniture improves productivity and well-being. As computers have become a part of students' academic lives, they will continue to grow in the future. We propose anthropometric-based furniture dimensions that are suitable for university students to improve computer laboratory ergonomics. We collected data from 380 participants and analyzed 11 anthropometric measurements, correlating them with 11 furniture dimensions. Two types of furniture were found and studied in different university computer laboratories: (1) a non-adjustable chair with a non-adjustable table and (2) an adjustable chair with a non-adjustable table. The mismatch calculation showed a significant difference between existing furniture dimensions and anthropometric measurements, indicating that 7 of the 11 existing furniture dimensions need improvement. The one-way ANOVA test with a significance level of 5% also showed a significant difference between the anthropometric data and existing furniture dimensions. All 11 dimensions were determined to match students' anthropometric data. The proposed dimensions were found to be more compatible and showed reduced mismatch percentages for nine furniture dimensions and nearly zero mismatches for seat width, backrest height, and under the hood for both males and females compared to the existing furniture dimensions. The proposed dimensions of the furniture set with adjustable seat height showed slightly improved match results for seat height and seat-to-table clearance, which showed zero mismatches compared with the non-adjustable furniture set. The table width and table depth dimensions were suggested according to Barnes and Squires' ergonomic work envelope model, considering hand reach. The positions of the keyboard and mouse are also suggested according to the work envelope. The monitor position and viewing angle were proposed according to OSHA guidelines. This study suggests that the proposed dimensions can improve comfort levels, reducing the risk of musculoskeletal disorders among students. Further studies on the implementation and long-term effects of the proposed dimensions in real-world computer laboratory settings are recommended.

Investment and financing maturity mismatch: Moderating role of financialization in regulatory context for A-share listed Chinese companies.

As the financialization issue is getting more and more attention, the behavioral motives and effects behind this appearance should not be ignored, and it is of great practical significance for the high-quality development of China's real economy to explore the impact and mechanism of the financialization trend on the investment and financing maturity mismatch of China's real enterprises. Using sample data of Chinese A-share listed companies from 2013 to 2020, this article empirically examines the impact of financialization on the investment and financing maturity structure from a new perspective of asset classification by using a fixed-effect model, and explores the mechanism of the financial regulatory environment's moderating effect on the relationship between the two mentioned above. The study shows that: there is an inverted U-shaped nonlinear relationship between the financialization of investment income and fixed income and "maturity mismatch ". The term mismatch of investment and financing increases with the degree of financialization, after reaching the critical point, it eases with the deepening of financialization. However, the specific point of view is different. In the sample interval, the investment income financialization exacerbates the investment and financing maturity mismatch more obviously; the fixed income financialization inhibits the investment and financing maturity mismatch more obviously. Under the different perspectives of the firms' ownership nature, financing constraints, and principal-agent problems, there are differences in the impact of firms' allocation of different types of financial assets on the investment and financing term structure. In addition, the regulatory effect of financial supervision weakens the inverted U-shaped relationship of investment income financialization with investment and financing maturity mismatch; it enhances the inverted U-shaped relationship between fixed income financialization and investment and financing maturity mismatch. In general, financial supervision has had a significant positive effect on investment and financing maturity mismatches. The findings have important policy implications in terms of corporate real investment, financial market development, and financial regulation, which can help promote China's economic development and stability.

Work-related socioeconomic determinants of health: evidence from educational mismatch in Italy.

Introduction: An educational mismatch is defined as the situation where the education qualifications of an employee do not match the qualifications required for the job they do. A mismatch can be vertical where the level of the employee's qualification is not the one required by the job. This study contributes to the literature on work-related social determinants of health, by carrying out the first assessment of the relationship between educational mismatch and health in Italy. Methods: Data come from PLUS, a national survey of labor supply. The risk of suffering from bad or very bad health associated with educational mismatch is investigated through a logistic regression model accounting for the socioeconomic context and occupation. Results: Our findings show women are at greater risk of suffering from bad or very bad health than men, especially if under-educated. Discussion: Our results show the need to address more research on work-related social determinants of health, which can represent a barrier to achieving health equity.

Lower frequency range of auditory input facilitates stream segregation in older adults.

The current study investigated the effect of lower frequency input on stream segregation acuity in older, normal hearing adults. Using event-related brain potentials (ERPs) and perceptual performance measures, we previously showed that stream segregation abilities were less proficient in older compared to younger adults. However, in that study we used frequency ranges greater than 1500 Hz. In the current study, we lowered the target frequency range below 1500 Hz and found similar stream segregation abilities in younger and older adults. These results indicate that the perception of complex auditory scenes is influenced by the spectral content of the auditory input and suggest that lower frequency ranges of input in older adults may facilitate listening ability in complex auditory environments. These results also have implications for the advancement of prosthetic devices.

Effectiveness of bimodal stimulation of the auditory-somatosensory system in the treatment of tonal tinnitus.

BACKGROUND AND OBJECTIVES: The dorsal cochlear nucleus (DCN) is the interaction site of auditory and somatosensory system inputs. According to the stochastic resonance theory, hearing loss increases the neural activity of the somatosensory system in the DCN and causes tinnitus. it is possible to modulate this neural hyperactivity by applying random noise through the auditory and somatosensory systems (bimodal stimulation). Therefore, this study aimed to investigate the effectiveness of the bimodal intervention based on the theory of stochastic resonance. METHODS: The study divided 34 participants into unimodal and bimodal groups with 17 subjects in each. The bimodal group received customized acoustic stimulation along with transcutaneous auricular vagus nerve stimulation (tAVNS) and the unimodal group received customized acoustic stimulation along with tAVNS as a sham. The treatment sessions in both groups were 6 sessions and each session lasted for 20 min. The participants were evaluated before, immediately after, and one month after the completion of the intervention sessions, using the Tinnitus Handicap Inventory (THI) questionnaire and the mismatch negativity (MMN) test. RESULTS: After the intervention sessions, the results indicated a statistically significant decrease in THI scores and a significant increase in the MMN amplitude in the bimodal group compared to the unimodal group. No significant changes in MMN latency were observed between the two groups. These changes were stable in the one-month follow-up visit. CONCLUSIONS: Our study showed that bimodal stimulation is a better intervention option compared to unimodal stimulation. Bimodal stimulation may be an effective intervention method for some subjects with tinnitus, especially people with hearing loss who have tonal tinnitus.