Executive functions in preschool and school-age cochlear implant users: do they differ from their hearing peers? A systematic review and meta-analysis.

PURPOSE: Executive functions (EF) play a fundamental role in planning and executing goal-driven behaviours. The purpose of this systematic review and meta-analysis was to investigate EF skills mastered by preschool/school-age cochlear implanted children (CIC) without morpho-functional abnormalities and to compare their outcomes with typically hearing children (THC). METHODS: Bibliographic search for observational studies of any language/date up to 16 December 2022 was performed with the following electronic databases: PubMed, Scopus, and Web of Science. After removal of duplicates, 2442 records were subjected to a three-stage screening process and 83 potentially eligible articles were identified. A total of 15 studies was included in the final analysis: 9 articles directly meeting the eligibility criteria plus 6 more studies thanks to the authors sharing their data set, specifically for participants who met present inclusion criteria. RESULTS: Meta-analysis showed a statistically significant difference only for verbal short-term memory, whereas group differences for visuospatial short-term memory and verbal/visuospatial working memory were not significant. For fluency skills, meta-analysis revealed statistical significance for the semantic fluency task but not for the rapid naming test. Qualitative analysis reflected group similarities in flexibility but CIC's difficulties in auditory attention/planning skills. Controversial findings for inhibitory control skills were observed. CONCLUSIONS: EF performance comparisons between CIC and THC show inter-skill and inter-test variances. Due to the paucity of existing studies, present findings should be interpreted with caution. Future research in this domain is strongly recommended.

Low-frequency pitch coding: relationships with speech-in-noise and music perception by pediatric populations with typical hearing and cochlear implants.

PURPOSE: This study aimed to investigate the effects of low frequency (LF) pitch perception on speech-in-noise and music perception performance by children with cochlear implants (CIC) and typical hearing (THC). Moreover, the relationships between speech-in-noise and music perception as well as the effects of demographic and audiological factors on present research outcomes were studied. METHODS: The sample consisted of 22 CIC and 20 THC (7-10 years). Harmonic intonation (HI) and disharmonic intonation (DI) tests were used to assess LF pitch perception. Speech perception in quiet (WRSq)/noise (WRSn + 10) were tested with the Italian bisyllabic words for pediatric populations. The Gordon test was used to evaluate music perception (rhythm, melody, harmony, and overall). RESULTS: CIC/THC performance comparisons for LF pitch, speech-in-noise, and all music measures except harmony revealed statistically significant differences with large effect sizes. For the CI group, HI showed statistically significant correlations with melody discrimination. Melody/total Gordon scores were significantly correlated with WRSn + 10. For the overall group, HI/DI showed significant correlations with all music perception measures and WRSn + 10. Hearing thresholds showed significant effects on HI/DI scores. Hearing thresholds and WRSn + 10 scores were significantly correlated; both revealed significant effects on all music perception scores. CI age had significant effects on WRSn + 10, harmony, and total Gordon scores (p < 0.05). CONCLUSION: Such findings confirmed the significant effects of LF pitch perception on complex listening performance. Significant speech-in-noise and music perception correlations were as promising as results from recent studies indicating significant positive effects of music training on speech-in-noise recognition in CIC.

PANC-1 Cell Line as an Experimental Model for Characterizing PIVKA-II Production, Distribution, and Molecular Mechanisms Leading to Protein Release in PDAC.

Pancreatic ductal adenocarcinoma (PDAC) represents a highly aggressive malignancy with a lack of reliable diagnostic biomarkers. Protein induced by vitamin K absence (PIVKA-II) is a protein increased in various cancers (particularly in hepatocellular carcinoma), and it has recently exhibited superior diagnostic performance in PDAC detection compared to other biomarkers. The aim of our research was to identify an in vitro model to study PIVKA-II production, distribution, and release in PDAC. We examined the presence of PIVKA-II protein in a panel of stabilized pancreatic cancer cell lines by Western blot analysis and indirect immunofluorescence (IFA). After quantitative evaluation of PIVKA-II in PaCa 44, H-Paf II, Capan-1, and PANC-1, we adopted the latter as a reference model. Subsequently, we analyzed the effect of glucose addiction on PIVKA-II production in a PANC-1 cell line in vitro; PIVKA-II production seems to be directly related to an increase in glucose concentration in the culture medium. Finally, we evaluated if PIVKA-II released in the presence of increasing doses of glucose is concomitant with the expression of two well-acknowledged epithelial-mesenchymal transition (EMT) markers (Vimentin and Snail). According to our experimental model, we can speculate that PIVKA-II release by PANC-1 cells is glucose-dependent and occurs jointly with EMT activation.

Bisphenol-A in Drinking Water Accelerates Mammary Cancerogenesis and Favors an Immunosuppressive Tumor Microenvironment in BALB-neuT Mice.

Bisphenol-A (BPA), a synthetic compound ubiquitously present in the environment, can act as an endocrine disruptor by binding to both canonical and non-canonical estrogen receptors (ERs). Exposure to BPA has been linked to various cancers, in particular, those arising in hormone-targeted tissues such as the breast. In this study, we evaluated the effect of BPA intake through drinking water on ErbB2/neu-driven cancerogenesis in BALB-neuT mice, transgenic for a mutated ErbB2/neu receptor gene, which reproducibly develop carcinomas in all mammary glands. In this model, BPA accelerated mammary cancerogenesis with an increase in the number of tumors per mouse and a concurrent decrease in tumor-free and overall survival. As assessed by immunohistochemistry, BALB-neuT tumors were ER-negative but expressed high levels of the alternative estrogen receptor GPR30, regardless of BPA exposure. On the other hand, BPA exposure resulted in a marked upregulation of progesterone receptors in preinvasive tumors and of Ki67, CD31, and phosphorylated Akt in invasive tumors. Moreover, based on several infiltration markers of immune cells, BPA favored an immunosuppressive tumor microenvironment. Finally, in vitro cell survival studies performed on a cell line established from a BALB-neuT breast carcinoma confirmed that BPA's impact on cancer progression can be particularly relevant after chronic, low-dose exposure.

The influence of auditory selective attention on linguistic outcomes in deaf and hard of hearing children with cochlear implants.

PURPOSE: Auditory selective attention (ASA) is crucial to focus on significant auditory stimuli without being distracted by irrelevant auditory signals and plays an important role in language development. The present study aimed to investigate the unique contribution of ASA to the linguistic levels achieved by a group of cochlear implanted (CI) children. METHODS: Thirty-four CI children with a median age of 10.05 years were tested using both the "Batteria per la Valutazione dell'Attenzione Uditiva e della Memoria di Lavoro Fonologica nell'età evolutiva-VAUM-ELF" to assess their ASA skills, and two Italian standardized tests to measure lexical and morphosyntactic skills. A regression analysis, including demographic and audiological variables, was conducted to assess the unique contribution of ASA to language skills. RESULTS: The percentages of CI children with adequate ASA performances ranged from 50 to 29.4%. Bilateral CI children performed better than their monolateral peers. ASA skills contributed significantly to linguistic skills, accounting alone for the 25% of the observed variance. CONCLUSIONS: The present findings are clinically relevant as they highlight the importance to assess ASA skills as early as possible, reflecting their important role in language development. Using simple clinical tools, ASA skills could be studied at early developmental stages. This may provide additional information to outcomes from traditional auditory tests and may allow us to implement specific training programs that could positively contribute to the development of neural mechanisms of ASA and, consequently, induce improvements in language skills.

Curcumin potentiates the ErbB receptors inhibitor Afatinib for enhanced antitumor activity in malignant mesothelioma.

Several attempts have been made to develop targeted therapies for malignant mesothelioma (MM), an aggressive tumour with a poor prognosis. In this study we evaluated whether Curcumin (CUR) potentiated the antitumor activity of the ErbB receptors inhibitor Afatinib (AFA) on MM, employing cell lines cultured in vitro and mice bearing intraperitoneally transplanted, syngeneic MM cells. The rationale behind this hypothesis was that CUR could counteract mechanisms of acquired resistance to AFA. We analysed CUR and AFA effects on MM cell growth, cell cycle, autophagy, and on the modulation of tumour-supporting signalling pathways.This study demonstrated that, as compared to the individual compounds, the combination of AFA + CUR had a stronger effect on MM progression which can be ascribed either to increased tumour cell growth inhibition or to an enhanced pro-apoptotic effect. These results warrant future studies aimed at further exploring the therapeutic potential of AFA + CUR-based combination regimens for MM treatment.

The Spectrum of Neurological and Sensory Abnormalities in Gaucher Disease Patients: A Multidisciplinary Study (SENOPRO).

Gaucher disease (GD) has been increasingly recognized as a continuum of phenotypes with variable neurological and sensory involvement. No study has yet specifically explored the spectrum of neuropsychiatric and sensory abnormalities in GD patients through a multidisciplinary approach. Abnormalities involving the nervous system, including sensory abnormalities, cognitive disturbances, and psychiatric comorbidities, have been identified in GD1 and GD3 patients. In this prospective study, named SENOPRO, we performed neurological, neuroradiological, neuropsychological, ophthalmological, and hearing assessments in 22 GD patients: 19 GD1 and 3 GD3. First, we highlighted a high rate of parkinsonian motor and non-motor symptoms (including high rates of excessive daytime sleepiness), especially in GD1 patients harboring severe glucocerebrosidase variants. Secondly, neuropsychological evaluations revealed a high prevalence of cognitive impairment and psychiatric disturbances, both in patients initially classified as GD1 and GD3. Thirdly, hippocampal brain volume reduction was associated with impaired short- and long-term performance in an episodic memory test. Fourthly, audiometric assessment showed an impaired speech perception in noise in the majority of patients, indicative of an impaired central processing of hearing, associated with high rates of slight hearing loss both in GD1 and GD3 patients. Finally, relevant structural and functional abnormalities along the visual system were found both in GD1 and GD3 patients by means of visual evoked potentials and optical coherence tomography. Overall, our findings support the concept of GD as a spectrum of disease subtypes, and support the importance of in-depth periodic monitoring of cognitive and motor performances, mood, sleep patterns, and sensory abnormalities in all patients with GD, independently from the patient's initial classification.

ZnO Nanorods Create a Hypoxic State with Induction of HIF-1 and EPAS1, Autophagy, and Mitophagy in Cancer and Non-Cancer Cells.

Nanomaterials are gaining increasing attention as innovative materials in medicine. Among nanomaterials, zinc oxide (ZnO) nanostructures are particularly appealing because of their opto-electrical, antimicrobial, and photochemical properties. Although ZnO is recognized as a safe material and the Zn ion (Zn2+) concentration is strictly regulated at a cellular and systemic level, different studies have demonstrated cellular toxicity of ZnO nanoparticles (ZnO-NPs) and ZnO nanorods (ZnO-NRs). Recently, ZnO-NP toxicity has been shown to depend on the intracellular accumulation of ROS, activation of autophagy and mitophagy, as well as stabilization and accumulation of hypoxia-inducible factor-1α (HIF-1α) protein. However, if the same pathway is also activated by ZnO-NRs and how non-cancer cells respond to ZnO-NR treatment, are still unknown. To answer to these questions, we treated epithelial HaCaT and breast cancer MCF-7 cells with different ZnO-NR concentrations. Our results showed that ZnO-NR treatments increased cell death through ROS accumulation, HIF-1α and endothelial PAS domain protein 1 (EPAS1) activation, and induction of autophagy and mitophagy in both cell lines. These results, while on one side, confirmed that ZnO-NRs can be used to reduce cancer growth, on the other side, raised some concerns on the activation of a hypoxic response in normal cells that, in the long run, could induce cellular transformation.

ERp57 chaperon protein protects neuronal cells from Aß-induced toxicity.

Alzheimer's disease (AD) is a neurodegenerative disorder whose main pathological hallmark is the accumulation of Amyloid-ß peptide (Aß) in the form of senile plaques. Aß can cause neurodegeneration and disrupt cognitive functions by several mechanisms, including oxidative stress. ERp57 is a protein disulfide isomerase involved in the cellular stress response and known to be present in the cerebrospinal fluid of normal individuals as a complex with Aß peptides, suggesting that it may be a carrier protein which prevents aggregation of Aß. Although several studies show ERp57 involvement in neurodegenerative diseases, no clear mechanism of action has been identified thus far. In this work, we gain insights into the interaction of Aß with ERp57, with a special focus on the contribution of ERp57 to the defense system of the cell. Here, we show that recombinant ERp57 directly interacts with the Aß25-35 fragment in vitro with high affinity via two in silico-predicted main sites of interaction. Furthermore, we used human neuroblastoma cells to show that short-term Aß25-35 treatment induces ERp57 decrease in intracellular protein levels, different intracellular localization, and ERp57 secretion in the cultured medium. Finally, we demonstrate that recombinant ERp57 counteracts the toxic effects of Aß25-35 and restores cellular viability, by preventing Aß25-35 aggregation. Overall, the present study shows that extracellular ERp57 can exert a protective effect from Aß toxicity and highlights it as a possible therapeutic tool in the treatment of AD.

Accuracy of Dysphagia Standard Assessment (DSA®) bedside screening test: a flowchart for patient eligibility.

BACKGROUND: Oropharyngeal dysphagia (OD) screening tests have improved patient management; however, the complex applicability and high percentage of false negatives do not allow these tests to be considered completely reliable if not supported by an instrumental investigation. The aim of the present study is to evaluate an OD screening test, the Dysphagia Standard Assessment (DSA®) with different volumes and viscosities. MATERIALS AND METHODS: Prospective study of 72 patients evaluated for suspected OD through a double-blind methodology conducted by two operators. All patients underwent fiberoptic endoscopic evaluation of swallowing (FEES) as a reference test and a separate DSA® test. DSA® was performed by administering boluses with different viscosities, with the signal of interruption of the test being: onset of the cough reflex, wet voice after swallowing, and/or desaturation of O2 ≥ 5%. The Penetration-Aspiration Scale (PAS) was evaluated by FEES. The cut-off identified to diagnose OD was PAS ≥ 3. RESULTS: The test showed an accuracy of 82%, a sensitivity of 0.93 (95% C.I. 0.84-0.97), and a specificity of 0.78 (95% C.I. 0.67-0.87); positive predictive value 0.55 (95% C.I. 0.43-0.67); negative predictive value 0.97 (95% C.I. 0.90-0.99), positive likelihood ratio 4.37 (95% C.I. 3.6-5.2); likelihood negative ratio 0.08 (95% C.I. 0.06-0.09). CONCLUSIONS: According to the preliminary results, the test showed good outcomes in determining the presence or absence of OD with a wide spectrum of applicability with some limitations that could be overcome by the selection of a target population. For this reason, a flowchart to address patient eligibility was developed.

Music perception and speech intelligibility in noise performance by Italian-speaking cochlear implant users.

OBJECTIVE: The goal of this study was to investigate the performance correlations between music perception and speech intelligibility in noise by Italian-speaking cochlear implant (CI) users. MATERIALS AND METHODS: Twenty postlingually deafened adults with unilateral CIs (mean age 65 years, range 46-92 years) were tested with a music quality questionnaire using three passages of music from Classical Music, Jazz, and Soul. Speech recognition in noise was assessed using two newly developed adaptive tests in Italian: The Sentence Test with Adaptive Randomized Roving levels (STARR) and Matrix tests. RESULTS: Median quality ratings for Classical, Jazz and Soul music were 63%, 58% and 58%, respectively. Median SRTs for the STARR and Matrix tests were 14.3 dB and 7.6 dB, respectively. STARR performance was significantly correlated with Classical music ratings (rs = - 0.49, p = 0.029), whereas Matrix performance was significantly correlated with both Classical (rs = - 0.48, p = 0.031) and Jazz music ratings (rs = - 0.56, p = 0.011). CONCLUSION: Speech with competitive noise and music are naturally present in everyday listening environments. Recent speech perception tests based on an adaptive paradigm and sentence materials in relation with music quality measures might be representative of everyday performance in CI users. The present data contribute to cross-language studies and suggest that improving music perception in CI users may yield everyday benefit in speech perception in noise and may hence enhance the quality of listening for CI users.

Listening comprehension in profoundly deaf children with cochlear implants: the role of auditory perception and foundational linguistic and cognitive skills.

PURPOSE: The aim of the study was to investigate the listening comprehension (LC) skills in deaf and hard of hearing children (DHH) using cochlear implants (CI). Besides, personal and audiological variables that could influence the levels of competence reached were analyzed. METHODS: Thirty-four children using CI were enrolled. LC skills were assessed through the standardized Italian test "Comprensione Orale-Test e Trattamento" (CO-TT). A univariate analysis was conducted to compare LC with gender, listening mode (unilateral or bilateral), maternal level of education and family income. A bivariate analysis was performed to search possible connections between children's performances and their individual characteristics, audiological conditions, and language levels. Finally, a multivariate analysis was performed using a stepwise hierarchical linear regression model which included all variables whose p value resulted ≤ 0.05. RESULTS: Twenty-one children using CI (61.8%) showed adequate performances in terms of chronological age, while 13 (38.2%) showed difficulties in LC. Maternal level of education, age at diagnosis and non-verbal cognitive level accounted for 43% of the observed variance. Auditory attention skills explained an additional 15% of variance. Morphosyntactic comprehension added a further 12% of variance. CONCLUSION: CI can really help many DHH children to reach adequate LC skills, but in some cases difficulties remain. Factors influencing LC need to be early investigated and considered when planning an appropriate rehabilitative intervention.

Cellular Redox Metabolism Is Modulated by the Distinct Localization of Cyclic Nucleotide Phosphodiesterase 5A Isoforms.

3'-5' cyclic nucleotide phosphodiesterases (PDEs) are a family of evolutionarily conserved cAMP and/or cGMP hydrolyzing enzymes, components of transduction pathways regulating crucial aspects of cell life. Among them, cGMP-specific PDE5-being a regulator of vascular smooth muscle contraction-is the molecular target of several drugs used to treat erectile dysfunction and pulmonary hypertension. Production of full-length murine PDE5A isoforms in the milk-yeast Kluyveromyces lactis showed that the quaternary assembly of MmPDE5A1 is a mixture of dimers and tetramers, while MmPDE5A2 and MmPDE5A3 only assembled as dimers. We showed that the N-terminal peptide is responsible for the tetramer assembly of MmPDE5A1, while that of the MmPDE5A2 is responsible for its mitochondrial localization. Overexpression of the three isoforms alters at different levels the cAMP/cGMP equilibrium as well as the NAD(P)+/NAD(P)H balance and induces a metabolic switch from oxidative to fermentative. In particular, the mitochondrial localization of MmPDE5A2 unveiled the existence of a cAMP-cGMP signaling cascade in this organelle, for which we propose a metabolic model that could explain the role of PDE5 in some cardiomyopathies and some of the side effects of its inhibitors.

Variables influencing executive functioning in preschool hearing-impaired children implanted within 24 months of age: an observational cohort study.

PURPOSE: Executive Functions (EFs) are fundamental to every aspect of life. The present study was implemented to evaluate factors influencing their development in a group of preschools orally educated profoundly deaf children of hearing parents, who received CI within 2 years of age. METHODS: Twenty-five preschool CI children were tested using the Battery for Assessment of Executive Functions (BAFE) to assess their flexibility, inhibition, and non-verbal visuo-spatial working memory skills. The percentage of children performing in normal range was reported for each of the EF subtests. Mann-Whitney and Kruskal-Wallis were performed to assess differences between gender, listening mode, and degree of parents' education subgroups. The Spearman Rank Correlation Coefficient was calculated to investigate the relationship between EF scores of audiological and linguistic variables. RESULTS: Percentages ranging from 76 to 92% of the children reached adequate EF scores at BAFE. Significant relations (p < 0.05) were found between EFs and early intervention, listening, and linguistic skills. Furthermore, CI children from families with higher education level performed better at the response shifting, inhibitory control, and attention flexibility tasks. Economic income correlated significantly with flexibility and inhibitory skills. Females performed better than males only in the attention flexibility task. CONCLUSIONS: The present study is one of the first to focus attention on the development of EFs in preschool CI children, providing an initial understanding of the characteristics of EFs at the age when these skills emerge. Clinical practice must pay increasing attention to these aspects which are becoming the new emerging challenge of rehabilitation programs.

Bimodal cochlear implantation in elderly patients.

OBJECTIVE: Bimodal stimulation is a standard option for asymmetric hearing loss in adults. Questions have been raised whether receiving two stimulations may conflict in elderly listeners where the central integration of an acoustic/electrical signal may be very important to obtain benefit in terms of speech perception. DESIGN: Clinical retrospective study. STUDY SAMPLE: The outcomes from 17 bimodal cochlear implant (CI) users were analysed. The test material consisted of speech audiometry in quiet and in noise (STARR and Matrix). RESULTS: Bimodal PTA and speech perception both in quiet and in noise were significantly better than CI or HA alone. Age showed a significant effect on bimodal STARR outcomes. Similarly, bimodal STARR scores improved significantly in comparison to Better Ear. CONCLUSION: Both Matrix and STARR tests were very difficult for many elderly CI listeners from the present study group, especially in unilateral listening condition. The performance improved significantly, emphasising a good integration of acoustic and electric hearing in this group of elderly bimodal listeners. Overall results highlighted how a specific study, based on speech perception in noise in the elderly listeners, might shed light on the effect of speech test modality on bimodal outcomes.

Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization.

The ability of endocannabinoid (eCB) to change functional microglial phenotype can be explored as a possible target for therapeutic intervention. Since the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of anandamide (AEA), may provide beneficial effects in mice model of Alzheimer's disease (AD)-like pathology, we aimed at determining whether the FAAH inhibitor URB597 might target microglia polarization and alter the cytoskeleton reorganization induced by the amyloid-ß peptide (Aß). The morphological evaluation showed that Aß treatment increased the surface area of BV-2 cells, which acquired a flat and polygonal morphology. URB597 treatment partially rescued the control phenotype of BV-2 cells when co-incubated with Aß. Moreover, URB597 reduced both the increase of Rho protein activation in Aß-treated BV-2 cells and the Aß-induced migration of BV-2 cells, while an increase of Cdc42 protein activation was observed in all samples. URB597 also increased the number of BV-2 cells involved in phagocytosis. URB597 treatment induced the polarization of microglial cells towards an anti-inflammatory phenotype, as demonstrated by the decreased expression of iNOS and pro-inflammatory cytokines along with the parallel increase of Arg-1 and anti-inflammatory cytokines. Taken together, these data suggest that FAAH inhibition promotes cytoskeleton reorganization, regulates phagocytosis and cell migration processes, thus driving microglial polarization towards an anti-inflammatory phenotype.

Production of third-person direct object clitics in children with cochlear implants speaking Italian.

Previous research has shown that the production of third-person singular accusative object clitics (3DO clitics) might be taxing in Italian-speaking pre-school children with cochlear implants (CIs). We investigated this topic by assessing 3DO clitic production in 14 children with an average age of 8 years, who had received CI between age 1 and 4. The first goal of the study was to analyze whether school-aged children with CIs exhibit atypical behavior in 3DO clitic production. The second goal was to analyze whether children with CIs are prone to agreement errors in case of gender mismatch between the subject and the 3DO clitic, as has been shown for normal-hearing, typically developing children. To achieve this, we used two tasks in which subject and object clitic grammatical genders were manipulated so that they would or would not match. As for the first goal, the majority of children with CIs had good performance on the clitic tasks. However, some participants' performance was poor. The pattern of deviant responses differed among the poor performers. We believe that children with CIs showing impairments in 3DO clitic production need careful individual analysis in order to plan effective speech therapy. As for the second goal, children with CIs were more prone to agreement errors in the mismatch condition compared to the match condition; this dimension needs to be considered when assessing and eventually rehabilitating clitic production.

Intonational cues for speech perception in noise by cochlear implant listeners.

PURPOSE: The objectives of this study are to evaluate cochlear implant (CI) listeners' ability to infer low frequency (LF) pitch information from temporal fine structure (TFS) cues and to gain insight into its effects on speech perception, especially in the presence of a fluctuating background noise. Pitch perception assessment using linguistic stimuli is believed to better reflect the role of pitch in communicatively realistic situations. METHODS: The low-pass-filtered sentence intonation (SI-LPF) test based on linguistic stimuli marked by intonation changes is used to estimate a difference limen for discrimination of LF pitch changes in adult CI listeners (N = 17 ears). Speech perception in the presence of noise is assessed using the sentence test with adaptive randomized roving level (STARR), where everyday sentences are presented at low, medium, and high levels in a fluctuating background noise. SI-LPF correlations with STARR are compared to those with sentence recognition tests presented in quiet (SRQ) and in noise, using fixed signal-to-noise ratio (SNRs at +10 and +5 dB). RESULTS: SI-LPF findings show significant positive correlations with STARR performance (rs = 0.63, p = 0.007), whilst the associations with SRQ (rs = - 0.37, p = 0.149), SNR + 10 (rs = - 0.24, p = 0.345), and SNR + 5 (rs = - 0.14, p = 0.587) are not statistically significant. CONCLUSIONS: Present findings reflecting considerably stronger correlations than previous studies using non-linguistic stimuli, in particular for speech perception with roving-level adaptive test method (STARR) highlight the effects of LF pitch perception and TFS sensitivity on challenging everyday situations, where CI users listen to speakers with varying levels in a fluctuating background.

Perception of lexical stress cued by low-frequency pitch and insights into speech perception in noise for cochlear implant users and normal hearing adults.

PURPOSE: Cochlear implant (CI) users show great difficulty for understanding speech in noise and this fact may partly stem from their poor low-frequency (LF) pitch perception and temporal fine structure (TFS) processing. Clinical assessment of pitch perception is usually based on non-speech tasks. However, linguistically relevant contexts such as lexical stress may better reflect the role of pitch in speech perception, especially for everyday speech where background noise is inevitable. Hence, the study aimed to assess perception of lexical stress cued by LF pitch and TFS cues for CI and normal hearing (NH) listeners, and to investigate relationships with speech perception in noise. METHODS: The low-pass-filtered Word Stress Pattern (WSP-LPF) test was used to evaluate perception of lexical stress cued by LF pitch. Speech perception was assessed with the sentence test with adaptive randomized roving level (STARR) test which presented everyday sentences at low, medium, and high levels in a fluctuating noise to estimate a Speech Reception Threshold. This new test intended to give a realistic estimate for real-world listening. RESULTS: Median WSP-LPF scores in NH (N = 18) and CI listeners (N = 18) were 12.0 Hz and 67.0 Hz, respectively. The corresponding STARR scores were - 9.1 dB and 17.3 dB. Group differences were statistically significant (p < 0.001). Analysis showed significant positive correlations for NH (rs = 0.50) and CI listeners (rs = 0.60). CONCLUSIONS: Present findings reveal stronger correlations than previous studies using non-speech materials, supporting that CI listeners' poor speech perception in noise might be strongly associated with their inability for LF pitch perception and TFS processing.

Anti-Inflammatory Activity of A Polyphenolic Extract from Arabidopsis thaliana in In Vitro and In Vivo Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. One of the main features of AD is the increase in amyloid-beta (Aß) peptide production and aggregation, leading to oxidative stress, neuroinflammation and neurodegeneration. Polyphenols are well known for their antioxidant, anti-inflammatory and neuroprotective effects and have been proposed as possible therapeutic agents against AD. Here, we investigated the effects of a polyphenolic extract of Arabidopsis thaliana (a plant belonging to the Brassicaceae family) on inflammatory response induced by Aß. BV2 murine microglia cells treated with both Aß25⁻35 peptide and extract showed a lower pro-inflammatory (IL-6, IL-1ß, TNF-α) and a higher anti-inflammatory (IL-4, IL-10, IL-13) cytokine production compared to cells treated with Aß only. The activation of the Nrf2-antioxidant response element signaling pathway in treated cells resulted in the upregulation of heme oxygenase-1 mRNA and in an increase of NAD(P)H:quinone oxidoreductase 1 activity. To establish whether the extract is also effective against Aß-induced neurotoxicity in vivo, we evaluated its effect on the impaired climbing ability of AD Drosophila flies expressing human Aß1⁻42. Arabidopsis extract significantly restored the locomotor activity of these flies, thus confirming its neuroprotective effects also in vivo. These results point to a protective effect of the Arabidopsis extract in AD, and prompt its use as a model in studying the impact of complex mixtures derived from plant-based food on neurodegenerative diseases.