Tone-in-noise detection deficits in elderly patients with clinically normal hearing

One of the most common complaints among the elderly is the inability to understand speech in noisy environments. In many cases, these deficits are due to age-related hearing loss; however, some of the elderly that have difficulty hearing in noise have clinically normal pure-tone thresholds. While speech in noise testing is informative, it fails to identify specific frequencies responsible for the speech processing deficit. Auditory neuropathy patients and animal models of hidden hearing loss suggest that tone-in-noise thresholds may provide frequency specific information for those patients who express difficulty, but have normal thresholds in quiet. Therefore, we aimed to determine if tone-in-noise thresholds could be a useful measure in detecting age-related hearing deficits, despite having normal audiometric thresholds

The Biological Role and Translational Implications of the Long Non-Coding RNA GAS5 in Breast Cancer

: The lncRNA GAS5 plays a significant role in tumorigenicity and progression of breast cancer (BC). In this review, we first summarize the role of GAS5 in cell biology, focusing on its expression data in human normal tissues. We present data on GAS5 expression in human BC tissues, highlighting its downregulation in all major BC classes. The main findings regarding the molecular mechanisms underlying GAS5 dysregulation are discussed, including DNA hypermethylation of the CpG island located in the promoter region of the gene. We focused on the action of GAS5 as a miRNA sponge, which is able to sequester microRNAs and modulate the expression levels of their mRNA targets, particularly those involved in cell invasion, apoptosis, and drug response. In the second part, we highlight the translational implications of GAS5 in BC. We discuss the current knowledge on the role of GAS5 as candidate prognostic factor, a responsive molecular therapeutic target, and a circulating biomarker in liquid biopsies with clinical importance in BC. The findings position GAS5 as a promising druggable biomolecule and stimulate the development of strategies to restore its expression levels for novel therapeutic approaches that could benefit BC patients in the future

Results of COVID-19 screening in a dermatologic clinic in northern Italy

Introduction The COVID-19 pandemic has been a social, economic and sanitary challenge, which caused a great slowdown in most clinical activities. At the beginning of 2021, the gradual reopening of outpatient services was threatened by the risk of COVID-19 outbreaks in healthcare facilities. Methods Between January and March 2021, our dermatologic clinic promoted a screening campaign based on rapid antigen-testing: adhering patients were tested for COVID-19 and were visited only after getting a negative result. Results Among 635 recruited subjects, 514 agreed to be enrolled in the study, while 121 refused and were not tested. Only 1 of the 514 tests was positive for COVID-19, thus the incidence of COVID-19 infections was very low (0,002%). A significant percentage of patients (19,1%) refused to be tested. Among those who did not give consent for COVID-19 testing, 52,9% were male, although the total recruited population was prevalently female (56,1%). Discussion and conclusions Screening for COVID-19 in outpatient clinics is a promising tool to prevent virus outbreaks, despite the limitations posed by testing hesitancy. Moreover, the very low incidence of COVID-19 infection we detected could be seen as a sign of hope for the resumption of non-essential clinical activities

Arrhythmic risk in elderly patients candidates to transcatheter aortic valve replacement. predicative role of repolarization temporal dispersion

Degenerative aortic valve stenosis (AS) is associated to ventricular arrhythmias and sudden cardiac death, as well as mental stress in specific patients. In such a context, substrate, autonomic imbalance as well as repolarization dispersion abnormalities play an undoubted role. Aim of the study was to evaluate the increase of premature ventricular contractions (PVC) and complex ventricular arrhythmias during mental stress in elderly patients candidate to the transcatheter aortic valve replacement (TAVR). In eighty-one elderly patients with AS we calculated several short-period RRand QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE). All the myocardial repolarization dispersion markers worsened during mental stress (p < 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p < 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p < 0.05). Eventually, twenty-four (30%) and twelve (15%) patients increased significantly PVC and, respectively, complex ventricular arrhythmias during the MMSE administration. At multivariate logistic regression analysis, the standard deviation of QTend (QTesd), obtained at rest, was predictive of increased PVC (odd ratio: 1.54, 95% CI 1.14–2.08; p = 0.005) and complex ventricular arrhythmias (odd ratio: 2.31, 95% CI 1.40–3.83; p = 0.001) during MMSE. The QTesd showed the widest sensitive-specificity area under the curve for the increase of PVC (AUC: 0.699, 95% CI: 0.576–0.822, p < 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p < 0.05). In elderly with AS ventricular arrhythmias worsened during a simple cognitive assessment, this events being a possible further burden on the outcome of TAVR. QTesd might be useful to identify those patients with the highest risk of ventricular arrhythmias. Whether the TAVR could led to a QTesd reduction and, hence, to a reductionof thearrhythmicburdenin thissettingofpatients isworthytobe investigated

Cardiac amyloidosis: the great pretender

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition

Determination of plasmatic microRNA levels by ddPCR as peripheral biomarkers for IDH-wild type glioblastomas: a pilot study

BACKGROUND: Glioblastoma (GBM) is the most frequent malignant brain tumour in adults with a dismal prognosis. Peripheral biomarkers may be useful and effective in managing patients affected by GBM. The aim of our study was to analyse the plasmatic levels of three miRNAs as possible GBM-specific biomarkers. We focused on miR-21-5p – an onco-miR overexpressed in blood, tumour tissue and cell cultures derived from patients affected by GBM – miR-23b-3p – overexpressed in GBM, especially under hypoxic conditions – and miR-34a-5p – a tumour suppressor miR downregulated in tumour tissue and serum of patients with GBM. MATERIALS AND METHODS: Eight patients presenting with firstly-diagnosed IDH-wild type GBM and 10 age- and gender-matched healthy volunteers (hV) have been enrolled in the study. Peripheral blood samples were collected at diagnosis and one month after surgery. Total RNA was isolated from plasma by means of miRNeasy Serum/Plasma Kit (Qiagen), according to the manufacturer’s instructions. Digital droplet PCR (ddPCR) was performed for each miRNA according to the QX200 EvaGreen ddPCR protocol. RESULTS: The circulating concentrations of miR-21-5p were in mean 24.00 (28.44) and 72.40 (147.88) copies/L in patients with GBM at diagnosis and one month after surgery (p=0.38), respectively, compared with 98.74 copies/L ( 123.60) quantified in hV (p=0.09; p=0.69). The mean peripheral levels of miR-23b-3p were 0.49 copies/L (0.49) at diagnosis and 3.02 copies/L (6.88) one month after surgery (p=0.32) in patients with GBM, and 2.56 copies/L (5.57) in hV (p=0.31; p=0.88). Analysing plasmatic expression of miR-34a-5p, 1.11 (1.55) and 1.85 copies/L (1.87) were measured on average at diagnosis and one month after surgery in patients with GBM (p=0.41), while 0.73 copies/L (0.85) in hV (p=0.52; p=0.11). CONCLUSIONS: We preliminarily reported higher concentrations of circulating miR-21-5p, miR-23b-3p and miR-34a-5p in plasma of patients affected by IDH-wild type GBM one month after surgery compared to the levels at diagnosis

Plasmatic microRNA levels by ddPCR as peripheral biomarkers for IDH-wild type glioblastomas: a pilot study

BACKGROUND: Glioblastoma (GBM) is the most frequent malignant brain tumour in adults with a dismal prognosis and peripheral biomarkers may be useful and effective in managing patients with GBM. The main aim of our study was the use of ddPCR to assess the absolute quantification of the plasmatic levels of three miRNAs as possible GBM-specific biomarkers. We focused on: miR-21-5p, an onco-miR overexpressed in blood, tumour tissue and cell cultures derived from patients affected by GBM, miR-23b-3p and miR-34a-5p, tumour suppressor miRs dysregulated in GMB. MATERIALS AND METHODS: Eight patients presenting with firstly-diagnosed IDH-wild type GBM and 10 age- and gender-matched healthy control donors (hC) have been enrolled in the study. Peripheral blood samples were collected at diagnosis and one month after surgery. Total RNA was isolated from plasma by means of miRNeasy Serum/Plasma Kit (Qiagen), according to the manufacturer’s instructions. Digital droplet PCR (ddPCR) was performed to assess the absolute quantification of each miRNA level according to the QX200 ddPCR protocol. RESULTS: The expression analysis revealed: i) different levels of each miRNA in hC: 98.74 copies/L (±123.60), 2.56 copies/L (±5.57), 0.73 copies/L (±0.85) for miR-21-5p, miR-23b-3p and miR-34a-5p, respectively; ii) a trend of downregulation of miR-21-5p and miR-23b-3p in GMB patients at diagnosis compared to hC; iii) a trend of upregulation of each miRNA in GMB patients one month after surgery compared with the levels measured at diagnosis, in particular 3.02, 6.2 and 1.7 fold increase for miR-21-5p, miR-23b-3p and miR-34a-5p, respectively. CONCLUSIONS: In this pilot study we reported higher amounts of circulating miR-21-5p, miR-23b-3p and miR-34a-5p in plasma of patients affected by IDH-wild type GBM one month after surgery compared to the levels at diagnosis

Expression of Cellular and Extracellular TERRA, TERC and TERT in Hepatocellular Carcinoma

Non-coding RNAs are transcribed from telomeres and the telomeric repeat-containing RNAs (TERRA) are implicated in telomere homeostasis and in cancer. In this study, we aimed to assess in hepatocellular carcinoma (HCC) the cellular and extracellular expression of TERRA, the telomerase RNA subunit (TERC) and the telomerase catalytic subunit (TERT). We determined by qPCR the expression level of TERRA 1_2_10_13q, TERRA 15q, TERRA XpYp, TERC and of TERT mRNA in HCC tissues and in the plasma of HCC patients. Further, we profiled the same transcripts in the HCC cell lines, HA22T/VGH and SKHep1C3, and in the extracellular vesicles (EVs) derived from their secretomes. We found that the expression of TERRA and TERT mRNA was significantly deregulated in HCC, being TERRA downregulated and TERT mRNA upregulated in HCC tissues vs. the peritumoral (PT) ones, and the receiver operating characteristic (ROC) curve analyses revealed a significant ability in discriminating HCC from PT tissue. Further, the determinations of circulating TERRA and TERC showed higher amounts of these transcripts in the plasma of HCC patients vs. controls and ROC analyses gave significant results. The expression characterization of the cultured HCC cells showed their ability to produce and secrete TERRA and TERC into the EVs; the ability to produce TERT mRNA that was not detectable in the EVs; and the ability to respond to sorafenib treatment increasing TERRA expression. Our results highlight that: (i) both cellular and extracellular expressions of TERRA and TERC are dysregulated in HCC as well as the cellular expression of TERT mRNA and (ii) the combined detection of TERRA and TERC in plasma may represent a promising approach for non-invasive diagnostic molecular indicators of HCC