Two are better than one: Differences in cortical EEG patterns during auditory and visual verbal working memory processing between Unilateral and Bilateral Cochlear Implanted children.

Despite the proven effectiveness of cochlear implant (CI) in the hearing restoration of deaf or hard-of-hearing (DHH) children, to date, extreme variability in verbal working memory (VWM) abilities is observed in both unilateral and bilateral CI user children (CIs). Although clinical experience has long observed deficits in this fundamental executive function in CIs, the cause to date is still unknown. Here, we have set out to investigate differences in brain functioning regarding the impact of monaural and binaural listening in CIs compared with normal hearing (NH) peers during a three-level difficulty n-back task undertaken in two sensory modalities (auditory and visual). The objective of this pioneering study was to identify electroencephalographic (EEG) marker pattern differences in visual and auditory VWM performances in CIs compared to NH peers and possible differences between unilateral cochlear implant (UCI) and bilateral cochlear implant (BCI) users. The main results revealed differences in theta and gamma EEG bands. Compared with hearing controls and BCIs, UCIs showed hypoactivation of theta in the frontal area during the most complex condition of the auditory task and a correlation of the same activation with VWM performance. Hypoactivation in theta was also observed, again for UCIs, in the left hemisphere when compared to BCIs and in the gamma band in UCIs compared to both BCIs and NHs. For the latter two, a correlation was found between left hemispheric gamma oscillation and performance in the audio task. These findings, discussed in the light of recent research, suggest that unilateral CI is deficient in supporting auditory VWM in DHH. At the same time, bilateral CI would allow the DHH child to approach the VWM benchmark for NH children. The present study suggests the possible effectiveness of EEG in supporting, through a targeted approach, the diagnosis and rehabilitation of VWM in DHH children.

Dietary Polyphenols Effects on Focal Adhesion Plaques and Metalloproteinases in Cancer Invasiveness.

Focal adhesion plaques (FAPs) play an important role in the communication between cells and the extracellular matrix (ECM) and in cells' migration. FAPs are macromolecular complexes made by different proteins which also interact with matrix metalloproteinases (MMPs). Because of these fundamental properties, FAPs and MMPs are also involved in cancer cells' invasion and in the metastatic cascade. The most important proteins involved in FAP formation and activity are (i) integrins, (ii) a complex of intracellular proteins and (iii) cytoskeleton proteins. The latter, together with MMPs, are involved in the formation of filopodia and invadopodia needed for cell movement and ECM degradation. Due to their key role in cancer cell migration and invasion, MMPs and components of FAPs are often upregulated in cancer and are thus potential targets for cancer therapy. Polyphenols, a large group of organic compounds found in plant-based food and beverages, are reported to have many beneficial healthy effects, including anticancer and anti-inflammatory effects. In this review, we discuss the growing evidence which demonstrates that polyphenols can interact with the different components of FAPs and MMPs, inhibit various pathways like PI3K/Akt, lower focal adhesion kinase (FAK) phosphorylation and decrease cancer cells' invasiveness, leading to an overall antitumoral effect. Finally, here we highlight that polyphenols could hold potential as adjunctive therapies to conventional cancer treatments due to their ability to target key mechanisms involved in cancer progression.

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.

Emotional abilities in preadolescents and adolescents with long-term cochlear implant use.

OBJECTIVES: Emotional abilities (EAs) are particularly important during preadolescence/adolescence, two challenging periods characterized by significant biological, physical, and cognitive changes. The present study attempted to a holistic EA approach in preadolescents/adolescents with cochlear implants (CI) and typical hearing (TH), considering various aspects such as perception, cognitive facilitation, comprehension, and management of emotions. A secondary aim was to identify significant demographic and audiological factors of EA development. METHODS: CI/TH groups were matched for chronological age, nonverbal IQ, gender, economic income, and maternal level of education. Each group consisted of 43 participants (age range 10-18 years). EAs were evaluated by using the multi-trait/method IE-ACCME test. Auditory-linguistic assessments included participants' lexical skills and Matrix performance as well. RESULTS: EA performance for perception and cognitive facilitation did not show any statistically significant CI/TH group differences (p > 0.05). Significant CI/TH differences emerged for emotion comprehension and management: CI group performed significantly worse in understanding emotional blends (t = 2.56, p = 0.014) but better in personal emotion management (t = -2.01, p = 0.048). For the CI group, gender showed statistically significant effects on cognitive facilitation in sensations, with males performing better than females (U = 129, p = 0.018). TH preadolescents showed significantly lower scores in understanding emotional changes in comparison to TH adolescents (U = 125.5, p = 0.01). Emotional blends understanding showed a weak negative correlation with Matrix performance (r = - 0.38, p = 0.013) and a moderate positive correlation with lexical skills (r = 0.40, p = 0.008). Relationships management showed various significant correlations: weak negative correlations with age at CI (r = - 0.38, p = 0.011) and Matrix performance (r = - 0.36, p = 0.016) as well as weak positive correlations with nonverbal-IQ (r = 0.38, p = 0.013) and positive moderate correlations with lexical skills (r = 0.49, p < 0.001). CONCLUSION: Cochlear implantation seems to show significant positive effects on emotional development in children, allowing them to achieve age appropriate EAs as they grow up and become preadolescents/adolescents. EA assessment in CI users may not only support monitorization of EA trajectory, but also early identification of any EA disorders, so that subjects with low EA profiles could be timely and properly intervened.

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.

M2 muscarinic receptors negatively modulate cell migration in human glioblastoma cells.

Glioblastoma (GB) is a very aggressive human brain tumor. The high growth potential and invasiveness make this tumor surgically and pharmacologically untreatable. Our previous work demonstrated that the activation of the M2 muscarinic acetylcholine receptors (M2 mAChRs) inhibited cell proliferation and survival in GB cell lines and in the cancer stem cells derived from human biopsies. The aim of the present study was to investigate the ability of M2 mAChR to modulate cell migration in two different GB cell lines: U87 and U251. By wound healing assay and single cell migration analysis performed by time-lapse microscopy, we demonstrated the ability of M2 mAChRs to negatively modulate cell migration in U251 but not in the U87 cell line. In order to explain the different effects observed in the two cell lines we have evaluated the possible involvement of the intermediate conductance calcium-activated potassium (IKCa) channel. IKCa channel is present in the GB cells, and it has been demonstrated to modulate cell migration. Using the perforated patch-clamp technique we have found that selective activation of M2 mAChR significantly reduced functional density of the IKCa current in U251 but not in U87 cells. To understand whether the M2 mAChR mediated reduction of ion channel density in the U251 cell line was relevant for the cell migration impairment, we tested the effects of TRAM-34, a selective inhibitor of the IKCa channel, in wound healing assay. We found that it was able to markedly reduce U251 cell migration and significantly decrease the number of invadopodia-like structure formations. These results suggest that only in U251 cells the reduced cell migration M2 mAChR-mediated might involve, at least in part, the IKCa channel.

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.

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.

Vocal singing skills by cochlear implanted children without formal musical training: Familiar versus unfamiliar songs.

OBJECTIVES: Vocal singing skills in pediatric CI users are not much known due to the limited number of studies. The principal aim of the present study was to evaluate vocal singing skills in Italian pediatric CI users. A further aim was to investigate factors that may significantly influence their performance. METHODS: The participants were twenty-two implanted children and twenty-two hearing peers. Their vocal singing skills for familiar ("Happy Birthday to You") and unfamiliar songs ("Baton Twirler" from Pam Pam 2- Tribute to Gordon) were evaluated in relation to their music perception (the Gordon test). Acoustic analysis was performed using Praat and MATLAB software. Nonparametric statistical tests and principal component analysis (PCA) were used to analyze the data. RESULTS: Hearing children outperformed implanted peers in both music perception and vocal singing tasks (all measures regarding intonation, vocal range, melody, and memory for the familiar song versus measures regarding intonation and overall melody production for the unfamiliar song). Music perception and vocal singing performances revealed strong correlations. For the familiar and unfamiliar songs, age-appropriate vocal singing was observed in 27.3% versus 45.4% of children, all implanted within 24 months of age. Age at implantation and duration of CI experience were moderately correlated with the total score obtained from the Gordon test. CONCLUSION: Implanted children show limited vocal singing skills in comparison to their hearing peers. However, some children implanted within 24 months of age seem to achieve vocal singing skills as good as their hearing peers. Future research could be useful to better understand the role of brain plasticity to implement specific training programs for both music perception and vocal singing.

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.

Neuropsychological Functions and Audiological Findings in Elderly Cochlear Implant Users: The Role of Attention in Postoperative Performance.

OBJECTIVES: The present study aimed to investigate in a group of elderly CI users working memory and attention, conventionally considered as predictors of better CI performance and to try to disentangle the effects of these cognitive domains on speech perception, finding potential markers of cognitive decline related to audiometric findings. Methods Thirty postlingually deafened CI users aged >60 underwent an audiological evaluation followed by a cognitive assessment of attention and verbal working memory. A correlation analysis was performed to evaluate the associations between cognitive variables while a simple regression investigated the relationships between cognitive and audiological variables. Comparative analysis was performed to compare variables on the basis of subjects' attention performance. RESULTS: Attention was found to play a significant role in sound field and speech perception. Univariate analysis found a significant difference between poor and high attention performers, while regression analysis showed that attention significantly predicted recognition of words presented at Signal/Noise +10. Further, the high attention performers showed significantly higher scores than low attentional performers for all working memory tasks. CONCLUSION: Overall findings confirmed that a better cognitive performance may positively contribute to better speech perception outcomes, especially in complex listening situations. WM may play a crucial role in storage and processing of auditory-verbal stimuli and a robust attention may lead to better performance for speech perception in noise. Implementation of cognitive training in auditory rehabilitation of CI users should be investigated in order to improve cognitive and audiological performance in elderly CI users.

Antitumoral effects of Bortezomib in malignant mesothelioma: evidence of mild endoplasmic reticulum stress in vitro and activation of T cell response in vivo.

BACKGROUND: Malignant mesothelioma (MM) is a rare tumor with a dismal prognosis. The low efficacy of current treatment options highlights the urge to identify more effective therapies aimed at improving MM patients' survival. Bortezomib (Bor) is a specific and reversible inhibitor of the chymotrypsin-like activity of the 20S core of the proteasome, currently approved for the treatment of multiple myeloma and mantle cell lymphoma. On the other hand, Bor appears to have limited clinical effects on solid tumors, because of its low penetration and accumulation into tumor tissues following intravenous administration. These limitations could be overcome in MM through intracavitary delivery, with the advantage of increasing local drug concentration and decreasing systemic toxicity. METHODS: In this study, we investigated the effects of Bor on cell survival, cell cycle distribution and modulation of apoptotic and pro-survival pathways in human MM cell lines of different histotypes cultured in vitro. Further, using a mouse MM cell line that reproducibly forms ascites when intraperitoneally injected in syngeneic C57BL/6 mice, we investigated the effects of intraperitoneal Bor administration in vivo on both tumor growth and the modulation of the tumor immune microenvironment. RESULTS: We demonstrate that Bor inhibited MM cell growth and induced apoptosis. Further, Bor activated the Unfolded Protein Response, which however appeared to participate in lowering cells' sensitivity to the drug's cytotoxic effects. Bor also affected the expression of EGFR and ErbB2 and the activation of downstream pro-survival signaling effectors, including ERK1/2 and AKT. In vivo, Bor was able to suppress MM growth and extend mice survival. The Bor-mediated delay of tumor progression was sustained by increased activation of T lymphocytes recruited to the tumor microenvironment. CONCLUSIONS: The results presented herein support the use of Bor in MM and advocate future studies aimed at defining the therapeutic potential of Bor and Bor-based combination regimens for this treatment-resistant, aggressive tumor.

Long-term speech perception and morphosyntactic outcomes in adolescents and young adults implanted in childhood.

BACKGROUND: Long-term assessments of children with cochlear implants (CI) are important inputs to help guide families and professionals in therapeutic and counselling processes. Based on these premises, the primary aim of the present study was to assess the long-term speech and language outcomes in a sample of prelingually deaf or hard of hearing (DHH) adolescents and young adults with unilateral or bilateral implantation in childhood. The secondary aim was to investigate the correlations of age at implantation with long-term speech and language outcomes. MATERIALS AND METHODS: Retrospective observational study on 54 long-term CI users, 33 unilateral and 21 bilateral (mean age at CI surgery 38.1 ± 24.6 months; mean age at last follow-up assessment 19.1 ± 4.3 years of age and mean follow-up time 16 ± 3.7 years). Means and standards were used to describe speech perception (in quiet, in fixed noise and in adaptive noise using It-Matrix) and morphosyntactic comprehension (TROG-2) outcomes. A univariate analysis was used to evaluate outcome differences between unilateral and bilateral patients. Bivariate analysis was performed to investigate the relationships between age at CI, audiological variables, and language outcomes. Finally, multivariate analysis was performed to quantify the relationship between It-Matrix, sentence recognition in quiet and at SNR+10 and TROG-2. RESULTS: The participants showed good speech recognition performance in quiet (94% for words and 89% for sentences) whilst their speech-in-noise scores decreased significantly. For the It-Matrix, only 9.2% of the participants showed scores within the normative range. This value was 60% for TROG-2 performance. For both auditory and language skills, group differences for unilateral versus bilateral CI users were not statistically significant (p > 0.05). Bivariate analysis showed that age at CI correlated significantly with overall results at TROG-2 (r = -0.6; p < 0.001) and with It-Matrix (r = 0.5; p < 0.001). TROG-2 was negatively correlated with results for It-Matrix (r = -0.5; p < 0.001). In the multivariate analysis with It-Matrix as a dependent variable, the model explained 63% of the variance, of which 60% was related to sentence recognition and 3% to morphosyntax. CONCLUSIONS: These data contribute to the definition of average long-term outcomes expected in subjects implanted during childhood whilst increasing our knowledge of the effects of variables such as age at CI and morphosyntactic comprehension on speech perception. Although the majority of this prelingually DHH cohort did not achieve scores within a normative range, remarkably better It-Matrix scores were observed when compared to those from postlingually deafened adult CI users.

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.

2-hydroxyisobutyric acid (2-HIBA) modulates ageing and fat deposition in Caenorhabditis elegans.

High levels of 2-hydroxyisobutyric acid (2-HIBA) were found in urines of patients with obesity and hepatic steatosis, suggesting a potential involvement of this metabolite in clinical conditions. The gut microbial origin of 2-HIBA was hypothesized, however its actual origin and role in biological processes are still not clear. We investigated how treatment with 2-HIBA affected the physiology of the model organism Caenorhabditis elegans, in both standard and high-glucose diet (HGD) growth conditions, by targeted transcriptomic and metabolomic analyses, Coherent Anti-Stokes Raman Scattering (CARS) and two-photon fluorescence microscopy. In standard conditions, 2-HIBA resulted particularly effective to extend the lifespan, delay ageing processes and stimulate the oxidative stress resistance in wild type nematodes through the activation of insulin/IGF-1 signaling (IIS) and p38 MAPK pathways and, consequently, through a reduction of ROS levels. Moreover, variations of lipid accumulation observed in treated worms correlated with transcriptional levels of fatty acid synthesis genes and with the involvement of peptide transporter PEP-2. In HGD conditions, the effect of 2-HIBA on C. elegans resulted in a reduction of the lipid droplets deposition, accordingly with an increase of acs-2 gene transcription, involved in ß-oxidation processes. In addition, the pro-longevity effect appeared to be correlated to higher levels of tryptophan, which may play a role in restoring the decreased viability observed in the HGD untreated nematodes.

Milmed Yeast Alters the LPS-Induced M1 Microglia Cells to Form M2 Anti-Inflammatory Phenotype.

Microglial cells polarized towards a proinflammatory phenotype are considered the main cellular players of neuroinflammation, underlying several neurodegenerative diseases. Many studies have suggested that imbalance of the gut microbial composition is associated with an increase in the pro-inflammatory cytokines and oxidative stress that underlie chronic neuroinflammatory diseases, and perturbations to the gut microbiota were detected in neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease. The importance of gut-brain axis has been uncovered and the relevance of an appropriate microbiota balance has been highlighted. Probiotic treatment, rebalancing the gut microbioma, may reduce inflammation. We show that Milmed yeast, obtained from S. cerevisiae after exposure to electromagnetic millimeter wavelengths, induces a reversal of LPS-M1 polarized microglia towards an anti-inflammatory phenotype, as demonstrated morphologically by the recovery of resting phenotype by microglia, by the decrease in the mRNAs of IL-1ß, IL-6, TNF-α and in the expression of iNOS. Moreover, Milmed stimulated the secretion of IL-10 and the expression of Arginase-1, cell markers of M2 anti-inflammatory polarized cells. The present findings data suggest that Milmed may be considered to be a probiotic with diversified anti-inflammatory activity, capable of directing the polarization of microglial cells.

Gamma-Band Modulation in Parietal Area as the Electroencephalographic Signature for Performance in Auditory-Verbal Working Memory: An Exploratory Pilot Study in Hearing and Unilateral Cochlear Implant Children.

This pilot study investigates the neurophysiological patterns of visual and auditory verbal working memory (VWM) in unilateral cochlear implant users (UCIs). We compared the task-related electroencephalogram (EEG) power spectral density of 7- to 13-year-old UCIs (n = 7) with a hearing control group (HC, n = 10) during the execution of a three-level n-back task with auditory and visual verbal (letters) stimuli. Performances improved as memory load decreased regardless of sensory modality (SM) and group factors. Theta EEG activation over the frontal area was proportionally influenced by task level; the left hemisphere (LH) showed greater activation in the gamma band, suggesting lateralization of VWM function regardless of SM. However, HCs showed stronger activation patterns in the LH than UCIs regardless of SM and in the parietal area (PA) during the most challenging audio condition. Linear regressions for gamma activation in the PA suggest the presence of a pattern-supporting auditory VWM only in HCs. Our findings seem to recognize gamma activation in the PA as the signature of effective auditory VWM. These results, although preliminary, highlight this EEG pattern as a possible cause of the variability found in VWM outcomes in deaf children, opening up new possibilities for interdisciplinary research and rehabilitation 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.

School wellbeing and psychological characteristics of online learning in families of children with and without hearing loss during the Covid-19 pandemic.

This study investigated the psychological characteristics of online learning on Italian students with and without hearing loss (HL) and on their parents, who were forced into isolation during the Covid-19 pandemic. An online survey collected information on socio-demographic data and opinions concerning online learning from 61 children (mean age 11; 25 males, 36 females), including 43 with HL and also from their parents; additionally, school wellbeing and anxiety were assessed. The results showed that, in both the student and parent groups, no significant effect of HL on school wellbeing and anxiety was found. Additionally, in parents, State Anxiety was significantly higher than Trait Anxiety, suggesting one possible impact of lockdown on psychological wellbeing. Differences due to HL were observed and discussed in correlation analyses. The Authors believe that this study is the first contribution to the psychological evaluation of the impact of online learning on families with hearing-impaired children, from the perspective of a successful, inclusive didactic.