A Computational Approach for the Understanding of Stochastic Resonance Phenomena in the Human Auditory System

Stochastic resonance (SR) is a nonlinear phenomenon by which the introduction of noise in a system causes a counterintuitive increase in levels of detection performance of a signal. SR has been extensively studied in different physical and biological systems, including the human auditory system (HAS), where a positive role for noise has been recognized both at the level of peripheral auditory system (PAS) and central nervous system (CNS). This dualism regarding the mechanistic underpinnings of the RS phenomenon in the HAS is confirmed by discrepancies among different experimental studies and reflects on a disagreement about how this phenomenon can be exploited for the improvement of prosthesis and aids devoted to hypoacusic people. HAS is one of the human body’s most complex sensory system. On the other hand, SR involves system nonlinearities. Then, the characterization of SR in the HAS is very challenging and many efforts are being made to characterize this mechanism as a whole. Current computational modelling tools make possible to investigate the phenomena separately in the CNS and in the PAS, then simplifying the analysis of the involved mechanisms. In this work we present a computational model of PAS supporting SR, that shows improved detection of sounds when input noise is added. As preparatory step, we provided a test signal to the system, at the edge of the hearing threshold. As next step, we repeated the experiment adding background noise at different intensities. We found an increase of relative spike count in the frequency bands of the test signal when input noise is added, confirming that the maximum value is obtained under a specific range of added noise, whereas further increase in noise intensity only degrades signal detection or information content

Anti-tumor activity of the methanolic extracts of Salvia menthifolia

In the present research we investigated the anti-proliferative activity of Salvia menthifolia Ten. (formerly Salvia menthaefolia), Lamiaceae, on a glioblastoma cell line, since up to date poor therapeutic results have been reported for treatment of malignant glioblastoma. Methanol extracts from different anatomical parts of S. menthifolia were tested on DBTRG-05MG cell line by MTT assay. The most active primary stems extract was also evaluated for apoptosis induction. Results confirmed the anti-tumor property of all the organs and demonstrated that the primary stems extract induced apoptosis after 4 h with the highest values of DNA fragmentation after 6 to 24 h. Some extracts were also HPLC analyzed for polyphenols, althought activities could be due also to other constituents and to synergistic interactions. Rosmarinic acid, caffeic acid, luteolin-7-O-glucosyde and quercitrin were found in all the extracts. The good performance revealed for S. menthifolia towards this extremely aggressive human glioblastoma cell line confirms that the genus Salvia is a natural source of anti-tumor agents though there are great differences among the various species

a computational approach for the understanding of stochastic resonance phenomena in the human auditory system

Stochastic resonance (SR) is a nonlinear phenomenon by which the introduction of noise in a system causes a counterintuitive increase in levels of detection performance of a signal. SR has been extensively studied in different physical and biological systems, including the human auditory system (HAS), where a positive role for noise has been recognized both at the level of peripheral auditory system (PAS) and central nervous system (CNS). This dualism regarding the mechanistic underpinnings of the RS phenomenon in the HAS is confirmed by discrepancies among different experimental studies and reflects on a disagreement about how this phenomenon can be exploited for the improvement of prosthesis and aids devoted to hypoacusic people. HAS is one of the human body's most complex sensory system. On the other hand, SR involves system nonlinearities. Then, the characterization of SR in the HAS is very challenging and many efforts are being made to characterize this mechanism as a whole. Current computational modelling tools make possible to investigate the phenomena separately in the CNS and in the PAS, then simplifying the analysis of the involved mechanisms. In this work we present a computational model of PAS supporting SR, that shows improved detection of sounds when input noise is added. As preparatory step, we provided a test signal to the system, at the edge of the hearing threshold. As next step, we repeated the experiment adding background noise at different intensities. We found an increase of relative spike count in the frequency bands of the test signal when input noise is added, confirming that the maximum value is obtained under a specific range of added noise, whereas further increase in noise intensity only degrades signal detection or information content

Clinical manifestations of intermediate allele carriers in Huntington disease

Objective: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. Methods: We assessed a cohort of participants at risk with <36 CAG repeats of the huntingtin (HTT) gene. Outcome measures were the Unified Huntington's Disease Rating Scale (UHDRS) motor, cognitive, and behavior domains, Total Functional Capacity (TFC), and quality of life (Short Form-36 [SF-36]). This cohort was subdivided into IA carriers (27-35 CAG) and controls (<27 CAG) and younger vs older participants. IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. Results: Of 12,190 participants, 657 (5.38%) with <36 CAG repeats were identified: 76 IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores. However, older participants with IAs had higher chorea scores compared to controls (p 0.001). Linear regression analysis showed that aging was the most contributing factor to increased UHDRS motor scores (p 0.002). On the other hand, 1-year follow-up data analysis showed IA carriers had greater cognitive decline compared to controls (p 0.002). Conclusions: Although aging worsened the UHDRS scores independently of the genetic status, IAs might confer a late-onset abnormal motor and cognitive phenotype. These results might have important implications for genetic counseling. ClinicalTrials.gov identifier: NCT01590589

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis