Task-dependent spatial processing in the visual cortex.

To solve spatial tasks, the human brain asks for support from the visual cortices. Nonetheless, representing spatial information is not fixed but depends on the reference frames in which the spatial inputs are involved. The present study investigates how the kind of spatial representations influences the recruitment of visual areas during multisensory spatial tasks. Our study tested participants in an electroencephalography experiment involving two audio-visual (AV) spatial tasks: a spatial bisection, in which participants estimated the relative position in space of an AV stimulus in relation to the position of two other stimuli, and a spatial localization, in which participants localized one AV stimulus in relation to themselves. Results revealed that spatial tasks specifically modulated the occipital event-related potentials (ERPs) after the onset of the stimuli. We observed a greater contralateral early occipital component (50-90 ms) when participants solved the spatial bisection, and a more robust later occipital response (110-160 ms) when they processed the spatial localization. This observation suggests that different spatial representations elicited by multisensory stimuli are sustained by separate neurophysiological mechanisms.

The impact of waiting time for orthopaedic consultation on pain levels in individuals with osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: Time spent waiting for access to orthopaedic specialist health services has been suggested to result in increased pain in individuals with osteoarthritis (OA). We assessed whether time spent on an orthopaedic waiting list resulted in a detrimental effect on pain levels in patients with knee or hip OA. METHODS: We searched Ovid MEDLINE, EMBASE and EBSCOhost databases from inception until September 2021. Eligible articles included individuals with OA on an orthopaedic waitlist and not receiving active treatment, and reported pain measures at two or more time points. Random-effects meta-analysis was used to estimate the pooled effect of waiting time on pain levels. Meta-regression was used to determine predictors of effect size. RESULTS: Thirty-three articles were included (n = 2,490 participants, 67 ± 3 years and 62% female). The range of waiting time was 2 weeks to 2 years (20.8 ± 18.8 weeks). There was no significant change in pain over time (effect size = 0.082, 95% CI = -0.009, 0.172), nor was the length of time associated with longitudinal changes in pain over time (ß = 0.004, 95% CI = -0.005, 0.012). Body mass index was a significant predictor of pain (ß = -0.043, 95% CI = -0.079, 0.006), whereas age and sex were not. CONCLUSIONS: Pain remained stable for up to 1 year in patients with OA on an orthopaedic waitlist. Future research is required to understand whether pain increases in patients waiting longer than 1 year.

Mortality and prognostic factors in patients with bullous pemphigoid: a retrospective multicenter Italian study.

INTRODUCTION: Bullous pemphigoid is the most common autoimmune bullous dermatosis. In recent years several studies have tried to identify the main factors of the disease related with an increased risk of death. The aim of this multicenter Italian study was to assess the risk score of death considering epidemiologic, clinical, immunological, and therapeutic factors in a cohort of patients affected by bullous pemphigoid and try to identify the cumulative survival up to 120 months. METHODS: We retrospectively reviewed the medical records of patients with bullous pemphigoid who were diagnosed between 2005 and 2020 in the 12 Italian centers. Data collected included sex, age at the time of diagnosis, laboratory findings, severity of disease, time at death/censoring, treatment, and multimorbidity. RESULTS: A total of 572 patients were included in the study. The crude mortality rate was 20.6%, with an incidence mortality rate of 5.9 × 100 person/year. The mortality rate at 1, 3, 5, and 10 years was 3.2%, 18.2%, 27.4% and 51.9%, respectively. Multivariate model results showed that the risk of death was significantly higher in patients older than 78 years, in presence of multimorbidity, anti-BP180 autoantibodies >72 U/mL, or anti-BP230 > 3 U/mL at diagnosis. The variables jointly included provided an accuracy (Harrel's Index) of 77% for predicting mortality. CONCLUSION: This study represents the first nationwide Italian study to have retrospectively investigated the mortality rates and prognostic factors in patients with bullous pemphigoid. A novel finding emerged in our study is that a risk prediction rule based on simple risk factors (age, multimorbidity, steroid-sparing drugs, prednisone use, and disease severity) jointly considered with two biomarkers routinely measured in clinical practice (anti-BP230 and anti-BP180 autoantibodies) provided about 80% accuracy for predicting mortality in large series of patients with this disease.

Beneficial effects of adaptive servo-ventilation on natriuretic peptides and diastolic function in acute heart failure patients with preserved ejection fraction and sleep-disordered breathing.

PURPOSE: Adaptive servo-ventilation (ASV) is a ventilator algorithm able to correct breathing through anticyclic support of breathing in patients with central sleep apnea (CSA). So far, very few data exist regarding the role of ASV on acute heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a single-center prospective, randomized, case-control study in consecutive acute HFpEF (left ventricle ejection fraction, LVEF ≥ 45%) patients with sleep-disordered breathing (SDB, apnea-hypopnea index, AHI > 15/h) and prevalence of CSA. RESULTS: We included ten consecutive patients randomized for ASV on top of standard therapy for acute heart failure (group 1) versus standard care alone (group 2). ASV therapy significantly reduced AHI and CSA. An improvement in cardiac diastolic function was seen in group 1 compared to group 2 (E/E' 17.5 to 9.6, p < 0.02 vs 18.5 to 14.5, p = 0.4). Brain natriuretic peptide (BNP) markedly decreased in cases, but not in controls (298 to 84 pg/ml, p < 0.02 vs 280 to 120 pg/ml, p = 0.06). Right ventricle (RV) function significantly improved in group 1, differently from group 2. CONCLUSIONS: An acute use of ASV seems effective in reducing BNP and improving diastolic and RV function in acute HFpEF patients with SDB and CSA, compared to standard treatment.

Tantalum monoblock cups in total hip arthroplasty: clinical results and outcome predictors.

This study aims to report the minimum 2-year follow-up results of the tantalum monoblock cup in primary THA and to identify possible outcome predictors. Eighty-eight porous tantalum monoblock acetabular cup in primary THA were reviewed. The Harris Hip Score (HHS) and the Short Form-36 Health Survey (SF-36) were used for the evaluation of outcomes. Radiographic evaluation included acetabular component orientation, presence of bone gaps, radiolucent lines, new bone formation and heterotopic ossifications. After a mean follow-up of 55.4±19.5 months, no component revision was noted. The HHS improved from 43.6±14.6 to 88.3±8.4 (P less than 0.001). The mean physical domain of the SF-36 did not significantly differ from that of age-matched, healthy subjects (P=0.072); the mean mental component of the SF-36 was significantly higher than that of age-matched, healthy subjects (P less than 0.001). Negative determinants of postoperative HHS (total adjusted R2=0.328) using tantalum monoblock cups were age at surgery (R2=0.164, P less than 0.001), female sex (R2=0.103, P less than 0.001), and acetabular inclination (R2=0.084, P equals 0.003).

Reinfusion-drains reduce blood transfusions in total joint arthroplasty.

This study aims to evaluate the effect of postoperative blood recovery with reinfusion drains on hematologic parameters and blood transfusion rate in patients undergoing total joint arthroplasty. Three-hundred-and-forty-four patient records were reviewed and 271 patients were included in the study; 56.8% of patients were treated with postoperative cell salvage procedure using reinfusion drains (PCS) and 43.2% had closed-suction drain (CSD) postoperatively. In comparison to the CSD group, the PCS group showed higher hemoglobin (Hb) levels on the first and second days postoperatively but no statistical differences were noted at the day of discharge. 75.2% and 37.7% of patients required blood transfusions in the CSD and PCS groups, respectively. The PCS group had a lower number of blood transfusions than the CSD group. At multivariate analysis, Hb loss rate was related to preoperative Hb values, total amount of drained blood and chronic antiplatelet therapy. The number of blood transfusions was related to preoperative Hb values, closed-suction drains, preoperative platelet count, TKA surgery and BMI. This study supports the use of PCS with reinfusion drains after THA and TKA at least for the short-term.

Estimating the real incidence of invasive listeriosis through an integrated surveillance model in use in Lombardy (Italy, 2006-2014).

The annual incidence of listeriosis in Italy is lower (0·19-0·27 per 100 000 inhabitants per year) than in Europe (0·34-0·52 per 100 000 inhabitants per year). Since the observed incidence of listeriosis may be biased downward for underdiagnosis or under-reporting, this work aims to estimate the real incidence of listeriosis during a 9-year period in the Lombardy region, Italy. Data on listeriosis cases were collected from national mandatory notification system (MAINF) and Laboratory-based Surveillance System (LabSS). The two sources were cross-matched and capture-recapture method was applied to estimate the number of undetected cases and the real incidence of invasive listeriosis. Five hundred and eighty invasive listeriosis cases were detected by the two sources between 2006 and 2014: 50·2% were identified only via MAINF, 16·7% were recorded only via LabSS, overlaps occurred in 192 cases (33·1%). The mean annual incidence detected only by MAINF was 0·56 per 100 000 inhabitants, which rose to 0·67 per 100 000 considering also the cases detected by LabSS. The capture-recapture method allowed to estimate an incidence of 0·84 per 100 000. The high incidence of listeriosis may be due to improved sensitivity of the surveillance system, but also reflect a real increase, associated with an increased population at risk.

Hyaluronan: an overview.

Hyaluronic acid (HA) is a polyanionic natural polymer occurring as a linear polysaccharide composed of glucuronic acid and N-acetylglucosamine repeats. Hyaluronic acid has a wide range of applications with its excellent physicochemical properties such as biodegradability, biocompatibility, non-toxicity, non-immunogenicity and serves as an excellent tool in biomedical applications such as osteoarthritis surgery, ocular surgery, plastic surgery, tissue engineering and drug delivery. This work provides an overview on hyaluronic acid, its chemistry and biochemistry and its medical applications.

C3f is a potential tool for the staging of osteoarthritis.

An attractive method for osteoarthritis (OA) staging is the measurement of biochemical markers in biological fluids, which could reflect dynamic and quantitative changes in joint remodeling and therefore disease progression. Proteome analysis has been recognized as one of the most effective tools to explore biomarkers as it can furnish a wealth of information in both diagnosis and prognosis of diseases. We have recently described an innovative tool for peptidome and lipidome profiling of fluids based on mesoporous aluminosilicate (MPAS) and Matrix-Assisted Laser Desorption/Ionization time-of-flight Mass Spectrometry (MALDI-TOF MS). The aim of this study was to analyze peptide profiles of human synovial fluid in patients with different grade of OA using MALDI-TOF-MS technique in order to identify potential markers of disease progression. Twenty-five patients older than 50 years and affected by primary knee OA diagnosed according to clinical and radiological criteria were enrolled. For each patient a synovial fluid sample was aspirated from the affected knee and analyzed using MALDI-TOF-MS technique. A statistically significant difference in the normalized area of two peaks (m/z=1865 and m/z=2021) was detected among different stages of OA. The 2 peaks were identified as Complement C3 peptide fragments: C3f and C3f Des-Arg. The expression levels of these two peptides (m/z=1865 and 2021) decreased with the progression of OA degrees severity (ρs=-0.434, p=0.03, and ρs=-0.532, p=0.006, respectively). This marker may be a useful tool for assessing the severity of knee OA and it may be a novel target for drug discovery, specifically for the development of disease modifying OA drugs. However further studies are required to clarify the role of C3f in OA pathogenesis.

Complications and survival of megaprostheses after resection of bone metastases.

Treatment of bone metastases is often palliative, aiming at pain control and stabilization or prevention of pathological fractures. However, a complete resection with healing purposes can be performed in selected cases. The aim of our work was to evaluate the survival of megaprostheses used for reconstruction after bone metastases. Between January 2001 and March 2015, we implanted 169 Megasystem-C® (Waldemar LINK® GmbH & Co. KG, Hamburg, Germany) after bone metastasis resection. Patients, 95 females and 74 males, were operated at an average age of 61 (12-87) years for proximal femoral resection in 135 (79.9%) cases, distal femur in 24 (14.2%), proximal tibia in 6 (3.6%), total femur in 3 (1.8%) and intercalary femur in 1 (0.6%). Mostly, breast cancer metastases (30.8%), kidney (17.8%) and lung (14.2%) were treated. At an average follow-up of 21 (1-150) months, we found a 99.4% overall limb salvage and a 96.1% overall survival rate at 1 year, 92.8% at 2 years, and 86.8% at 5 and 10 years. We found 9 (5.3%) mobilization cases of the proximal femoral implant, 3 needed surgical reduction; 2 (1.2%) cases of aseptic loosening of the prosthetic stem; 2 (1.2%) periprotetic infection cases, one requiring a 2-stage revision. Few literature studies have evaluated the survival of megaprosthetic implant in the treatment of bone metastases. Our data show how in this specific context the rate of complications is significantly lower than expected in general orthopedic orthopedic surgery. The use of modular prostheses is a valid reconstructive strategy after bone metastasis resection in selected patients. The rate of short-term complications is exceptionally low; further studies will have to confirm this in the longer term.

Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds.

This study investigated chromosomal aneuploidies and DNA damage in spermatozoa from male patients contaminated by perfluorinated compounds (PFCs) in whole blood and seminal plasma. Sperm aneuploidy and diploidy rate for chromosomes 18, X and Y were evaluated by FISH; sperm DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling technique coupled to flow cytometry. Our results indicated that PFC contamination was present in 58% of subjects included in the study. A significant increase in alterations of sperm parameters was observed in PFC-positive subjects compared to PFC-negative subjects. As regards the sperm aneuploidy, both disomy and diploidy rates resulted significantly increased in subjects positive for PFC contamination compared to PFC-negative samples. In addition, sperm DNA fragmentation index resulted significantly increased in PFC-contaminated subjects compared to PFC-non-contaminated subjects, with a significant increased level of dimmer DNA fragmentation index. Our results clearly indicate that PFC contamination may detrimentally affect spermatogenesis, disturbing both meiotic segregation and DNA integrity. We could therefore suggest cautions to reduce or eliminate any contact with these compounds because the long-term effects of PFC accumulation in the body are not predictable.

Dr-MUSIC: An Effective Device for Investigating Multisensory Mechanisms during Development with EEG recordings.

From birth, we are continuously exposed to multisensory stimuli that we learn to select and integrate during development to perceive a coherent world. To date, there are no optimal solutions to investigate how auditory, visual and tactile signals are integrated during EEG recording in infants and children. The present work aims to introduce Dr-MUSIC, a novel multisensory device with EEG-compatible timing and an attractive design for children. It is composed of audio, visual, and tactile stimulators arranged in the form of a couple of chubby dragons that can simultaneously provide selectable uni-, bi-, or tri-modal information. We first validated the system's EEG compatibility in 8 adults by implementing an audio-tactile oddball task during a high-density EEG recording. Then, we replicated the same task in a couple of toddlers to validate the device's usability for young children. The results suggest that the system can be effectively used for setting new experimental protocols to understand the neural basis of multisensory integration in the first years of life.Clinical Relevance- The amusing design and the possibility of changing the stimulation's characteristics (i.e., light, sound, and vibrotactile features) make it attractive in children with and without sensory impairments. Therefore, Dr-MUSIC could be used to investigate multisensory development and related neural correlates in typical and atypical children to design new early rehabilitation protocols.

MultiTab: A Novel Portable Device to Evaluate Multisensory Skills.

To infer spatial-temporal features of an external event we are guided by multisensory cues, with intensive research showing an enhancement in the perception when information coming from different sensory modalities are integrated. In this scenario, the motor system seems to also have an important role in boosting perception. With the present work, we introduce and validate a novel portable technology, named MultiTab, which is able to provide auditory and visual stimulation, as well as to measure the user's manual responses. Our preliminary results indicate that MultiTab reliably induces multisensory integration in a spatial localization task, shown by significantly reduced manual response times in the localization of audiovisual stimuli compared to unisensory stimuliClinical relevance- The current work presents a novel portable device that could contribute to the clinical evaluation of multisensory processing as well as spatial perception. In addition, by promoting and recording manual actions, MultiTab could be especially suitable for the design of rehabilitative protocols using multisensory motor training.

A novel multisensory device for the assessment and rehabilitation of perceptual and attentional competencies.

The present study aims to assess a novel technological device suitable for investigating perceptual and attentional competencies in people with or without sensory impairment. The TechPAD is a cabled system including embedded sensors and actuators to enable visual, auditory, and tactile interactions and a capacitive surface receiving inputs from the user. The system is conceived to create multisensory environments, using multiple units controlled separately and simultaneously. We assessed the device by adapting a spatial attention task comparing performances in different cognitive load conditions (high or low) and stimulation (unimodal, bimodal, or trimodal). 28 sighted adults were asked to monitor both the central and peripheral parts of the device and to tap a target stimulus (either visual, auditory, haptic, or multimodal) as fast as they could. Our results suggest that this new device can provide congruent and incongruent multimodal stimuli and quantitatively measure parameters such as reaction time and accuracy, allowing to investigate perceptual mechanisms in multisensory environments.Clinical Relevance-The TechPad is a reliable tool for the assessment of spatial attention during interactive tasks. its application in clinical trials will pave the way to its role in multisensory rehabilitation.

Clinical variables associated with late-onset thrombotic and cardiovascular events, after SARS-CoV-2 infection, in a cohort of patients from the first epidemic wave: an 18-month analysis on the "Surviving-COVID" cohort from Bergamo, Italy.

Importance: Population studies have recorded an increased, unexplained risk of post-acute cardiovascular and thrombotic events, up to 1 year after acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives: To search for clinical variables and biomarkers associated with late post-acute thrombotic and cardiovascular events after SARS-CoV-2 infection. Design: Retrospective cohort study. Setting: Third-level referral hospital in Bergamo (Italy). Participants: Analysis of an existing database of adult patients, who received care for SARS-CoV-2 infection at our institution between 20 February and 30 September 2020, followed up on a single date ("entry date") at 3-6 months. Exposure: Initial infection by SARS-CoV-2. Main outcomes and measures: Primary outcome: occurrence, in the 18 months after entry date, of a composite endpoint, defined by the International Classification of Diseases-9th edition (ICD-9) codes for at least one of: cerebral/cardiac ischemia, venous/arterial thrombosis (any site), pulmonary embolism, cardiac arrhythmia, heart failure. Measures (as recorded on entry date): history of initial infection, symptoms, current medications, pulmonary function test, blood tests results, and semi-quantitative radiographic lung damage (BRIXIA score). Individual clinical data were matched to hospitalizations, voluntary vaccination against SARS-CoV-2 (according to regulations and product availability), and documented reinfections in the following 18 months, as recorded in the provincial Health Authority database. A multivariable Cox proportional hazard model (including vaccine doses as a time-dependent variable) was fitted, adjusting for potential confounders. We report associations as hazard ratios (HR) and 95% confidence intervals (CI). Results: Among 1,515 patients (948 men, 62.6%, median age 59; interquartile range: 50-69), we identified 84 endpoint events, occurring to 75 patients (5%): 30 arterial thromboses, 11 venous thromboses, 28 arrhythmic and 24 heart failure events. From a multivariable Cox model, we found the following significant associations with the outcome: previous occurrence of any outcome event, in the 18 months before infection (HR: 2.38; 95% CI: 1.23-4.62); BRIXIA score ≥ 3 (HR: 2.43; 95% CI: 1.30-4.55); neutrophils-to-lymphocytes ratio ≥ 3.3 (HR: 2.60; 95% CI: 1.43-4.72), and estimated glomerular filtration rate < 45 ml/min/1.73 m2 (HR: 3.84; 95% CI: 1.49-9.91). Conclusions and relevance: We identified four clinical variables, associated with the occurrence of post-acute thrombotic and cardiovascular events, after SARS-CoV-2 infection. Further research is needed, to confirm these results.

Audio drawing and working memory in blindness: design, development and validation of a multi-sensory system.

Working memory (WM) plays a crucial role in helping individuals perform everyday activities and interact with the external environment. However, despite valuable insights into visual memory mechanisms, the multi-sensory aspects of WM have not been thoroughly investigated, especially in congenitally blind individuals, primarily due to a lack of proper technologies. This work presents an audio-haptic system to study the generation and recall of multi-sensory spatial representations in visually impaired and sighted individuals. Precisely, we developed an audio-tactile tablet composed of a set of spatialized speakers covered by tactile sensors and tri-modal stimulations units providing acoustic, visual, and haptic feedback. Furthermore, we integrated these two systems among each other. Interestingly, visually impaired and sighted adults could easily interact with these devices. Technologies like the ones we developed might be suitable in experimental and clinical settings to study the influence of the different sensory modalities on high-level cognitive skills and the impact of early visual deprivation on such abilities for rehabilitative intervention since the first period of life.

Early visual deprivation disrupts the mental representation of numbers in visually impaired children.

Several shreds of evidence indicate that visual deprivation does not alter numerical competence neither in adults nor in children. However, studies reporting non-impaired numerical abilities in the visually impaired population present some limitations: (a) they mainly assessed the ability to process numbers (e.g. mathematical competence) rather than represent numbers (e.g. mental number line); (b) they principally focused on positive rather than negative number estimates; (c) they investigated numerical abilities in adult individuals except one focusing on children (Crollen et al. in Cognition 210:104586, 2021). Overall, this could limit a comprehensive explanation of the role exerted by vision on numerical processing when vision is compromised. Here we investigated how congenital visual deprivation affects the ability to represent positive and negative numbers in horizontal and sagittal planes in visually impaired children (thirteen children with low vision, eight children with complete blindness, age range 6-15 years old). We adapted the number-to-position paradigm adopted by Crollen et al. (Cognition 210:104586, 2021), asking children to indicate the spatial position of positive and negative numbers on a graduated rule positioned horizontally or sagittally in the frontal plane. Results suggest that long-term visual deprivation alters the ability to identify the spatial position of numbers independently of the spatial plane and the number polarity. Moreover, results indicate that relying on poor visual acuity is detrimental for low vision children when asked to localize both positive and negative numbers in space, suggesting that visual experience might have a differential role in numerical processing depending on number polarity. Such findings add knowledge related to the impact of visual experience on numerical processing. Since both positive and negative numbers are fundamental aspects of learning mathematical principles, the outcomes of the present study inform about the need to implement early rehabilitation strategies to prevent the risk of numerical difficulties in visually impaired children.

Phenotyping congestion in patients with acutely decompensated heart failure with preserved and reduced ejection fraction: The Decongestion duRing therapY for acute decOmpensated heart failure in HFpEF vs HFrEF- DRY-OFF study.

AIMS: To evaluate pulmonary and intravascular congestion at admission and repeatedly during hospitalization for acute decompensated heart failure (ADHF) in HFrEF and HFpEF patients using lung (LUS) and inferior vena cava (IVC) ultrasound. METHODS AND RESULTS: Three-hundred-fourteen patients (82±9 years; HFpEF =172; HFrEF=142) admitted to Internal Medicine wards for ADHF were enrolled in a multi-center prospective study. At admission HFrEF presented higher indexes of pulmonary and intravascular congestion (LUS-score: 0.9 ±â€¯0.4 vs 0.7 ±â€¯0.4; p<0.01; IVC end-expiratory diameter: 21.6 ±â€¯5.1 mm vs 20±5.5 mm, p<0.01; IVC collapsibility index 24.4 ±â€¯17.4% vs 30.9 ±â€¯21.1% p<0.01) and higher Nt-proBNP values (8010 vs 3900 ng/l; p<0.001). At discharge, HFrEF still presented higher B-scores (0.4 ±â€¯4 vs 0.3 ±â€¯0.4; p = 0.023), while intravascular congestion improved to a greater extent, thus IVC measurements were similar in the two groups. No differences in diuretic doses, urine output, hemoconcentration, worsening renal function were found. At 90-days follow up HF readmission/death did not differ in HFpEF and HFrEF (28% vs 31%, p = 0,48). Residual congestion was associated with HF readmission/death considering the whole population; while intravascular congestion predicted readmission/death in the HFrEF, no association between sonographic indexes and the outcome was found in HFpEF. CONCLUSIONS: Serial assessment of pulmonary and intravascular congestion revealed a higher burden of fluid overload in HFrEF and, conversely, a greater reduction in intravascular venous congestion with diuretic treatment. Although other factors beyond EF could play a role in congestion/decongestion patterns, our data may be relevant for further phenotyping HF patients, considering the importance of decongestion optimization in the clinical approach.

Regulatory functions of insulin-like growth factor binding proteins in osteoarthritis.

Insulin-like growth factor binding proteins (IGFBPs) are a group of secreted proteins, which bind to IGF-I (and IGF-II) with high affinity and modulate the biological actions of IGFs. Abundant evidence points the importance of the IGF-I/IGFBP system on both cell growth and differentiation. A role for the IGF-I/IGFBP system in the regulation of normal human cartilage has been previously reported. In this context, recent studies suggest an emerging role for IGFBPs in the failure of cartilage during osteoarthritis (OA). Indeed, increased IGFBP levels have been reported in both the articular cartilage and synovial fluid from patients with OA. Overexpression of IGFBPs, by altering the bioavailability and function of IGFs, is likely to deliver IGFs-independent signals for chondrocyte survival. This, at least in part, might explain the degenerative changes of the cartilage in OA. Further studies are necessary to clarify the mechanisms that cause the overexpression of IGFBPs in patients with OA. Advances in our understanding of the relationship between osteoarthritis and the IGF-I/IGFBP system may lead to new treatment strategies for this degenerative disease.

A novel Android app to evaluate and enhance auditory and tactile temporal thresholds.

With this work, we introduce a novel Android app designed to monitor and enhance auditory and tactile temporal sensitivity. To assess the app's reliability, we tested its technical performance evaluating stimuli production's accuracy (i.e., onset, offset, and duration of stimulation). To validate the app with participants we generated temporal intervals, using either sounds or vibratory stimuli, by implementing two versions of a Two-Alternative Forced-Choice (2AFC) task. Auditory and tactile temporal sensitivity of 12 participants was evaluated using this procedure. To investigate whether temporal abilities could be enhanced using the app, participants were then divided into two groups: one group was trained for four days on the auditory temporal task, while the other was trained for four days on the tactile temporal task. Results suggest that the app can i) effectively measure auditory and tactile temporal thresholds and ii) be used to enhance temporal abilities through perceptual learning. The accessibility of the experimental protocols, combined with our findings, fosters the app's involvement in rehabilitation programs, for example, with a specific focus on sensory disabilities that are associated with temporal deficits (e.g., deafness and Parkinson).Clinical Relevance- The current work introduces a novel app that can be used to monitor and improve temporal abilities, in both the auditory and the tactile modalities.