Looking for an objective parameter to identify early vocal dysfunctions in healthy prceived singers

The finding of minimal laryngeal dysfunctions in professional voice users is essential to prevent the onset of organic vocal pathologies. The purpose of this study is to identify an objective parameter that supports the phoniatric evaluation in detecting minimal laryngeal dysfunctions in singers. 54 professional and non-professional singers have been evaluated with laryngostroboscopy, Multi-Dimensional Voice Program (MDVP), Dysphonia Severity Index (DSI), maximum phonation time (TMF), minimum intensity of sound emission (I-min), maximum frequency (F-max), voice handicap index (VHI), singing voice handicap index (SVHI), manual phonogram and audiometric examination. The SVHI of all the “healthy” singers was on average 23.7 ± 22.5, while that of the “dysfunctional” 20.9 ± 18. No statistically significant difference was found between the SVHI scores of the total of healthy singers compared to the scores of the dysfunctional ones on the VSL (p = 0.6). The between-group comparison of the means of individual parameter values of DSI, TMF, F-max, Jitter, Shimmer, NHR, and SPI was not statistically significant (respectively p = 0.315, 0.2, 0.18, 0.09, 0.2, 0.08, 0.3). The only parameter analyzed that was statistically significant was the I-min (p < 0.05). SVHI is a valid instrument for the evaluation after a therapy but in our experience, it is not useful in distinguishing healthy from dysfunctional patients. The minimum intensity of sound emission measured with the sound level meter (I-low2) resulted a reliable parameter to identify minimal laryngeal dysfunctions and a useful tool in supporting the phoniatric diagnostic-therapeutic process in singers

Exome Sequencing in 200 Intellectual Disability/Autistic Patients: New Candidates and Atypical Presentations

Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: CACNA2D1 and GPR14. In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that "reverse phenotyping" is fundamental to enlarge the phenotypic spectra associated with specific genes

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

PDA management in preterm infants: keep your hands off the ductus!

The current management of a patent ductus arteriosus (PDA) in preterm infants is fundamentally aimed at the closure of ductus through the cyclooxygenase (Cox)-inhibitors or surgical ligation in case of failure. Although the role of surgical approach to morbidity and mortality remains unclear, measures avoiding it appear entirely justified. During the last two years, 8 newborns were admitted to our intensive care unit for surgical ligation of a hemodynamic significant PDA, after a two ineffective Cox-inhibitor courses. The mean gestational age was 26 5/7 weeks (24 6/7 - 28 3/7 w.), the mean birth weight 1,000 g (800-1,300 g) and the mean age at admission 20 days (9-29 d.) at a mean post-conceptional age (PCA) of 29 3/7 weeks (27 5/7 - 31 5/7 w.). We have submitted these newborns to an approach consisting in a continuous monitoring of cerebral and renal oxygenations, time-scheduled ultrasound controls, monitoring of blood pressure and of urine output and continuous aEEG registration. All were treated with dopamine infusion. Under dopamine, ranging from 5 to 10 μg/kg/min, the stabilization criteria (see text) were reached in 7/8 infants. Afterwards a new cycle of Cox-inhibitors has been tried with the result of closing the ductus in 4/8 and obtaining a flow closing pattern in other three. None of the seven infants has shown in the following weeks a reapparence of ductal reopening signs. In this way we avoided the surgical intervention in 7/8 newborns. An attempt with Cox-inhibitors (ibuprofen) has also been proved in the single newborn who didn’t reach the stabilization but resulted ineffective. This newborn has been submitted to surgical ligation immediately thereafter. Moreover, the clinical conditions observed in all the newborns at admission testify that the duration of the exposure to left-to-right shunt is a crucial factor of the organ damage. This aspect is often not considered, waiting for the Cox-inhibitor effects. The contribution of the aEEG recordings is, in this context, considerable, having shown a background pattern of burst suppression in four subjects and a discontinuous pattern not in line with reached PCA in other three. On the basis of these results we think that the therapy of PDA in preterm infants must be mainly aimed at the containment of the ductal shunt and of its effects on pulmonary and systemic flow. In this way the objective of the ductal closure stops to be primary, being possible, under conditions of hemodynamic stability, waiting during the first week of life for the physiologic events of closure or resorting in selected cases to the Cox-inhibitors or to the surgical intervention. This limited experience requires more consistent proofs of effectiveness, while the impact of this approach on the outcomes needs to be evaluated.   Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy) · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgio

Correlation between hearing aid use and cognitive impairment in the elderly

Presbycusis is the most prevalent age-related, non-reversible, sensorineural hearing loss. Evidence supporting the relationship between auditory dysfunction and cognitive degeneration has grown over the years. Because of the aging of the world population, an early identification of the disease and an audiological recovery could mitigate the rate of cognitive decline with positive consequences for quality of elderly’ social life. A group of 50 patient (70–92 years) underwent audiometric tonal examination to evaluate hearing ability. Only 50% (active group) were equipped with a bilateral hearing aid. After three years, all patients were retested. Among the active group, the Mini-Mental State Examination was administered to 7 pathological patients to assess cognitive status at the begin and at the end of the research. The results show that the active group has achieved a significantly higher minimum audibility threshold than the control group (p < 0.01) and a cognitive benefit