Continuous monitoring of blood pCO2 is critical during extracorporeal circulation (ECC) to support clinical decision-making. This study aims to describe and investigate a new, low-cost, disposable fluorescent pCO2 sensor, namely MS2. The performance of MS2 is analysed by comparison with a blood gas analyzer. A significant challenge in developing sensors for in vivo applications is ensuring biocompatibility. In the MS2 sensor, biocompatibility is ensured by using a medical-grade gas-permeable membrane that isolates the sensing chemistry from the patient’s blood. The study also investigates the performance of a commercial optical pCO2 sensor, the PreSens MCR-O1P1C1, which is not approved for use with blood. The aim is to assess the feasibility of employing the PreSens MCR-O1P1C1 for blood monitoring in scenarios where biocompatibility is not a prerequisite, such as in the development stages of biomedical devices that require ex vivo blood testing. The results obtained during a 6.5-hour test with bovine blood demonstrate that both measuring systems can provide valid support for monitoring pCO2 in blood. However, despite its excellent response times, the off-label application of the PreSens MCR-O1P1C1 necessitates an adjustment of the measuring system to prevent significant measurement errors. Thus, these results position MS2 as a promising solution for real-time, in-line blood gas monitoring in ECC procedures.

ObjectiveTo assess the feasibility and, preliminarily, the effectiveness of long-term, personalized gait training using a digital wearable system (Gait Tutor) that provides real-time audio biofeedback to correct or reinforce gait behaviour.DesignOpen-label and non-controlled, with assessments before and after intervention.SettingReal-world.ParticipantsTwenty persons with Parkinson's disease.InterventionParticipants performed home-based gait training in their ON medication state for 30 minutes, 3 times per week, for 9 months using a Gait Tutor.Main measuresWe evaluated adherence (% of expected sessions), usability, and, preliminarily, efficacy by assessing the motor performance of the participants before and after the intervention.ResultsSeventeen participants (85%) completed the study, performing an average of 83 sessions. Adherence was higher for persons with an intermediate disease stage (80.5% of expected training sessions), compared to those with a more advanced disease stage (46.2%). All participants reported extremely positive scores on the questionnaire about ease of use and effectiveness (4.37 ± 0.42). The Movement Disorders Unified Parkinson's Disease Rating Scale motor scores remained stable after the training (mean 9 months). In people with an intermediate disease stage, clinical scores and physical capacity tended to improve.ConclusionsFor the first time, this study shows the feasibility of long-term real-world gait training for people with Parkinson's disease, providing preliminary evidence that personalized, technology-driven rehabilitation strategies can be sustained over extended periods and can assist clinicians in objectively assessing gait performance in the real world.

In this study, we present a low-cost, disposable fluorescent pCO(2) sensor designed for real-time blood pCO(2) monitoring in extracorporeal circulation (ECC) treatments. The sensor consists of a sensitive element enclosed inside a disposable cuvette. The sensor is interrogated by an optical head that, not coming into contact with the blood, can be non-disposable. The heart of the sensor is a gas filter composed of gas-permeable fibers, specifically developed for this application, designed to be low-cost and disposable, ensuring both affordability and convenience for real-time blood-pCO(2) monitoring. The blood in extracorporeal circulation is made to flow through the fibers that, being gas permeable, allow the exchange of gas with the measuring chamber, i.e., the space inside the cuvette outside the fibers, while preventing the exchange of anything that is not gaseous. Inside the measuring chamber, CO2 exchanged with the blood reacts and modifies the pH of the measuring chamber; this variation is measured thanks to a ratiometric pH-sensitive fluorophore inside the chamber. The fibers used are custom-made polypropylene porous hollow fibers produced using the TIPS technique (thermally induced phase separation) and have a unique structure that allows blood to flow through them. Before being inserted into the cuvette to make the sensor, the produced fibers were fully characterized by optical and scanning electron microscopy (SEM) and their permeability and porosity were also verified. The measuring system thus obtained was verified by simulating a 7-hour extracorporeal circulation treatment using bovine blood and comparing the measurements obtained with those provided by a bench-top blood gas analyzer.

BackgroundCueing can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD), but using the same cues continuously in daily life may compromise effectiveness. Therefore, we developed the DeFOG-system to deliver personalized auditory cues on detection of a FOG episode.ObjectivesWe aimed to evaluate the effects of DeFOG during a FOG-provoking protocol: (1) after 4 weeks of DeFOG-use in daily life against an active control group; (2) after immediate DeFOG-use (within-group) in different medication states.MethodIn this randomized controlled trial, 63 people with PD and daily FOG were allocated to the DeFOG or active control group. Both groups received feedback on their daily living step counts using the device, but the DeFOG group also received on-demand cueing. Video-rated FOG severity was compared pre- and post-intervention through a FOG-provoking protocol administered at home off and on-medication, but without using DeFOG. Within-group effects were tested by comparing FOG during the protocol with and without DeFOG.ResultsDeFOG-use during the 4 weeks was similar between groups, but we found no between-group differences in FOG-severity. However, the within-group analysis showed that FOG was alleviated by DeFOG (effect size d = 0.57), regardless of medication state. Combining DeFOG and medication yielded an effect size of d = 0.67.ConclusionsDeFOG reduced FOG considerably in a population of severe freezers both off and on medication. Nonetheless, 4 weeks of DeFOG-use in daily life did not ameliorate FOG during the protocol unless DeFOG was worn. These findings suggest that on-demand cueing is only effective when used, similar to other walking aids. (c) 2024 International Parkinson and Movement Disorder Society. DeFOG is a wearable device that delivers on-demand auditory cueing. After 4-weeks of DeFOG-use in the home, freezing of gait (FOG) did not improve relative to a control group when tested without DeFOG. However, when DeFOG was used, FOG improved with a sizeable effect, especially when combined with medication. image

Current in vitro and in vivo tests applied to assess the safety of medical devices retain several limitations, such as an incomplete ability to faithfully recapitulate human features and to predict the response of human tissues together with non-trivial ethical aspects. We here challenged a new hybrid biofabrication technique that combines bioprinting and Fast Diffusion-induced Gelation strategy to generate a vessel-like structure with the attempt to spatially organize fibroblasts, smooth-muscle cells, and endothelial cells. The introduction of Fast Diffusion-induced Gelation minimizes the endothelial cell mortality during biofabrication and produce a thin endothelial layer with tunable thickness. Cell viability, Von Willebrand factor and CD31 expression were evaluated on biofabricated tissues showing how bioprinting and Fast Diffusion-induced Gelation can replicate human vessels architecture and complexity. We then applied biofabricated tissue to study the cytotoxicity of a carbothane catheter under static condition and, to better recapitulate the effect of blood flow, a novel bioreactor named CuBiBox (Customized Biological Box) was developed and introduced in a dynamic modality. Collectively, we propose a novel bioprinted platform for human in vitro biocompatibility testing predicting the impact of medical devices and their materials on vascular systems reducing animal experimentation and, ultimately, accelerating time to market.

This study explores the monitoring of uraemic toxins in haemodialysis treatments, beyond urea concentration, in the perspective of reducing complications stemming from the lack of personalized haemodialysis therapies. Absorption and fluorescence techniques were employed to analyse low-middle weight molecules employing laboratory prepared solutions combining p-cresol, bovine albumin and bisphenol-A molecules. These optical techniques offer the advantage of analysing the sample without physical contact, ensuring the potential for implementation in a real-world scenario for continuous treatment monitoring. Real-time monitoring of these toxins in spent dialysate could offer insights into blood concentrations, enhancing dialysis treatment optimization and complication management.The considered absorption spectra fell within the ultraviolet range (240, 400) nm, while fluorescence spectra were obtained at a selected excitation wavelength of 285 nm. Data analysis revealed a correlation between molecule concentrations and signal intensity in both absorption and fluorescence measurements.

Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen. After stimulation by Transforming Growth factor beta (TGFβ), embedded cells differentiated into myofibroblasts and enhanced the contractile activity, as confirmed by the high level of α - smooth muscle actin (αSMA) and F-actin expression. As functional assays, SEM analysis revealed that after TGFβ stimulus the 3D microarchitecture of the scaffold was dramatically remolded with an increased fibronectin deposition with an abnormal collagen fibrillar pattern. Picrius Sirius Red staining additionally revealed that TGFβ stimulation enhanced of two logarithm the collagen fibrils neoformation in comparison with control. These data indicate that by bioprinting technology, it is possible to generate a reproducible and functional 3D platform to mimic fibrosis as key tool for drug discovery and impacting on animal experimentation and reducing costs and time in addressing fibrosis.

Under physiological conditions, the human body maintains blood pH within [7.36, 7.44] pH. Small deviations from this range can reveal the onset of pathological states and worsen the patient’s condition. This article reports the performance analysis of a real-time, noninvasive pH-measuring system for extracorporeal circulation (ECC). In particular, this study focuses on the analysis of the effects that the measurand temperature may have on the error in estimating blood pH. Even if the blood temperature in ECC is often thermostated at 37 °C, there are treatments in which the blood temperature is varied by a few Celsius degrees, and the exploited measurement principle—fluorescence—is known to be affected by temperature. First, we verified that the temperature-induced error could exceed the maximum permissible measurement error of ±0.04 pH. Hence, a linear-correction factor for temperature compensation was proposed. The results obtained showed how the simple addition to the measuring system of a temperature sensor and the use of a linear-correction factor can effectively allow maintaining the measurement error within the ±0.04-pH range, even when the fluid—phosphate buffer saline (PBS) and blood—temperature is varied in the range [30 °C, 39 °C].

Populations with potential damage to somatosensory, vestibular, and visual systems or poor motor control are often studied during gait initiation. Aquatic activity has shown to benefit the functional capacity of incomplete spinal cord injury (iSCI) patients. The present study aimed to evaluate gait initiation in iSCI patients using an easy-to-use protocol employing four wearable inertial sensors. Temporal and acceleration-based anticipatory postural adjustment measures were computed and compared between dry-land and water immersion conditions in 10 iSCI patients. In the aquatic condition, an increased first step duration (median value of 1.44 s vs. 0.70 s in dry-land conditions) and decreased root mean squared accelerations for the upper trunk (0.39 m/s2 vs. 0.72 m/s2 in dry-land conditions) and lower trunk (0.41 m/s2 vs. 0.85 m/s2 in dry-land conditions) were found in the medio-lateral and antero-posterior direction, respectively. The estimation of these parameters, routinely during a therapy session, can provide important information regarding different control strategies adopted in different environments.

Six Italian non-accredited laboratories participated to an interlaboratory study aimed at measuring Differential Pressure (DP) and Bacterial Filtration Efficiency (BFE) of three face-mask models using methods in-line with EN 14683 standard. Methodological non-conformities were annotated. Repeatability and reproducibility on quintuplicate samples were calculated according to ISO 5725-2. Sample stability was also assessed. Laboratories were ranked according to the total standard deviation over all samples and proficiency was evaluated using z-score according to ISO 13528. Although some non-conformities were present, performances for the DP measurements were always acceptable. One laboratory had to revise the bacterial suspension preparation for the BFE test. Overall, non-accredited laboratories working during pandemic emergency performed satisfactorily. Sample-to-sample variability impacted measurement repeatability. BFE values above 98% showed good repeatability (<1.0%) and reproducibility (<6.1%), but high BFE uncertainty was associated to community masks. Our findings suggest that relevant face-mask conformity standards should consider uncertainty of BFE and DP measurements.

Under physiological conditions, the body maintains blood pH within the very narrow range [7.36, 7.44] pH. Small deviations from this range can reveal the onset of pathological states. In this work the performances of a real-time, non-invasive pH measuring sysem for extracorporeal circulation (ECC) are analyzed. In particular, this study focuses on the analysis of the effects that temperature of the measurand may have on the error in estimating blood pH. Indeed, the sensor is based on the analysis of the fluorescence produced by HPTS, which is known to vary with temperature. The extent of such a variation, however, depends on various factors, including the chemical environment. Blood temperature in ECC is often thermostated at 37 °C. Nevertheless, there are treatments in which the blood temperature is varied by a few Celsius degrees, generally reduced, from the physiological temperature of 37 °C. Therefore, the first objective of this study was to evaluate whether a modest reduction in temperature, that is a few Celsius degrees, introduce an error such as the measuring system no longer conforms to the maximum permissible measurement error of ±0.04 pH. Once verified that the temperature-induced error could exceed the limit of ±0.04 pH, a correction factor for temperature compensation was investigated and its robustness to unevenness in the sensor production was explored. The results obtained from this preliminary study performed using Phosphate Buffer Saline (PBS) showed how the addition to the measuring system of a temperature sensor can effectively allow to maintain the measurement error within the ±0.04 pH range, even when the temperature of the measurand decreases by a few degrees from the physiological temperature of 37 °C.

The first wave of the COVID-19 pandemic brought about a broader use of masks by both professionals and the general population. This resulted in a severe worldwide shortage of devices and the need to increase import and activate production of safe and effective surgical masks at the national level. In order to support the demand for testing surgical masks in the Italian context, Universities provided their contribution by setting up laboratories for testing mask performance before releasing products into the national market. This paper reports the effort of seven Italian university laboratories who set up facilities for testing face masks during the emergency period of the COVID-19 pandemic. Measurement set-ups were built, adapting the methods specified in the EN 14683:2019+AC. Data on differential pressure (DP) and bacterial filtration efficiency (BFE) of 120 masks, including different materials and designs, were collected over three months. More than 60% of the masks satisfied requirements for DP and BFE set by the standard. Masks made of nonwoven polypropylene with at least three layers (spunbonded–meltblown–spunbonded) showed the best results, ensuring both good breathability and high filtration efficiency. The majority of the masks created with alternative materials and designs did not comply with both standard requirements, resulting in suitability only as community masks. The effective partnering between universities and industries to meet a public need in an emergency context represented a fruitful example of the so-called university “third-mission”.

During the coronavirus disease 2019 (COVID-19) pandemic, scientific authorities strongly suggested the use of face masks (FMs). FM materials (FMMs) have to satisfy the medical device biocompatibility requirements as indicated in the technical standard EN ISO 10993-1:2018. The biologic evaluation must be confirmed by in vivo tests to verify cytotoxicity, sensitisation, and skin irritation. Some of these tests require an extensive period of time for their execution, which is incompatible with an emergency situation. In this study, we propose to verify the safety of FMMs combining the assessment of 3-[4,5-dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT) with quantification of nitric oxide (NO) and interleukin-6 (IL-6), as predictive markers of skin sensitisation or irritation based on human primary fibroblasts. Two hundred and forty-two FMMs were collected and classified according to spectrometer IR in polypropylene, paper, cotton, polyester, polyethylene terephthalate, 3-dimensional printing, and viscose. Of all FMMs tested, 50.8% passed all the assays, 48% failed at least one, and only 1.2% failed all. By a low cost, rapid and highly sensitive multi assays strategy tested on human skin fibroblasts against a large variety of FMMs, we propose a strategy to promptly evaluate biocompatibility in wearable materials.

The possibility to monitor blood-pH has long been acknowledged to provide significant information for the diagnosis, management and treatment of a variety of diseases and it would be of considerable support for the administration of several treatments such as, for example, extracorporeal (blood) circulation (ECC). During ECC, the patient’s blood flows outside the body in disposable bloodlines and devices for treatments such as blood purification or circulation/ventilation/oxygenation support. Although blood-pH can be measured since the early twentieth century by using ion-selective electrodes (ISEs) and, more recently, also by using point-of-care testing (POCT) instruments, nowadays no measurement method has fully succeeded in providing a cost-effective, reliable and accurate estimate of the blood-pH to be routinely used for its real-time monitoring. In a recent paper, we have proposed and demonstrated a measuring instrument for the in-line and real-time monitoring of blood-pH during ECC. Such a measuring system consists of a low-cost fluorescent disposable sensor that can be integrated into the bloodline and, of a non-disposable reading system that interrogates the sensor without contacting the patient’s blood. In this paper, we investigated the robustness of such a measuring system to variations of blood parameters such as blood flow and hematocrit. The obtained results demonstrate that, although during the tests the pH, flow, and hematocrit values were significantly varied — pH from ≈ 6.8 pH, to ≈ 7.4 pH; hematocrit from 32%, to 40%; flow from 250 ml/min, to 400 ml/min, — the measuring system continued to guarantee a measurement error inferior to ±0.04 pH, thus complying with the metrological requirements for in-line and real-time monitoring of blood-pH during ECC

Despite the considerable technological progress made in the last decades in the biomedical field, no measuring system has yet fully succeeded in providing a reliable, accurate, safe and, cost-effective measure of the critical care analytes (CCAs) in the blood to be used for the real-time monitoring of routine extracorporeal (blood) circulation (ECC). In our recent article, we described and demonstrated an innovative measuring instrument that could allow to overcome all current limitations preventing the real-time measurement of the blood- p CO 2 during routine ECC. In this article, we investigate the robustness of such a measuring system to the considerable inter- and intra-variability in blood flow and hematocrit that characterize the ECC treatments. The obtained results demonstrate that, although during the tests the flow and hematocrit values were significantly varied ( p CO 2 from ≈ 20 mmHg, to ≈ 110 mmHg; hematocrit from 32%, to 40%; flow from 250 ml/min, to 400 ml/min), the measuring system continued to guarantee a measurement error in the range [-4, 4] mmHg, thus fully complying with the metrological requirements for the in-line and real-time monitoring of blood - p CO 2 during ECC.

BACKGROUND:Freezing of gait (FOG) is a highly incapacitating symptom that affects many people with Parkinson's disease (PD). Cueing triggered upon real-time FOG detection (on-demand cueing) shows promise for FOG treatment. Yet, the feasibility of implementation and efficacy in daily life is still unknown. Therefore, this study aims to investigate the effectiveness of DeFOG: a smartphone and sensor-based on-demand cueing solution for FOG.METHODS:Sixty-two PD patients with FOG will be recruited for this single-blind, multi-center, randomized controlled phase II trial. Patients will be randomized into either the intervention group or the active control group. For four weeks, both groups will receive feedback about their physical activity using the wearable DeFOG system in daily life. In addition, the intervention group will also receive on-demand auditory cueing and instructions. Before and after the intervention, home-based assessments will be performed to evaluate the primary outcome, i.e., "percentage time frozen" during a FOG-provoking protocol. Secondary outcomes include the training effects on physical activity monitored over 7 days and the user-friendliness of the technology.DISCUSSION:The DeFOG trial will investigate the effectiveness of personalized on-demand cueing in a controlled design, delivered for 4 weeks in the patient's home environment. We anticipate that DeFOG will reduce FOG to a greater degree than in the control group and we will explore the impact of the intervention on physical activity levels. We expect to gain in-depth insight into whether and how patients control FOG using cueing methods in their daily lives.TRIAL REGISTRATION:Clinicaltrials.gov NCT03978507.

OBJECTIVE: Diagnosing idiopathic normal pressure hydrocephalus (iNPH) still remains a clinical challenge. The callosal angle (CA) is a widely used neuroradiologic marker for iNPH. However, the relationship of the CA to clinical features has not been well investigated. We hypothesize that iNPH symptoms might better correlate with a variant of the CA (anterior callosal angle [ACA]). We aim to establish the validity of the ACA measurement for the diagnosis of iNPH and compare it with current radiologic parameters. METHODS: The multidisciplinary BOLOGNA PRO-HYDRO Study Group performed a retrospective review of consecutive iNPH patients. Magnetic resonance imaging studies for these patients were collected, as well as magnetic resonance imaging studies from Alzheimer disease and healthy control patients. The CA, ACA, and Evans Index were measured by 2 blinded members of the study team based on magnetic resonance images for each of these populations. RESULTS: The ACA shows high accuracy, sensitivity, and specificity in distinguishing iNPH patients from healthy control and Alzheimer disease patients. The optimal pathologic diagnostic cut-off value for the ACA is 119 degrees. The diagnostic accuracy of the ACA is not significantly different from the CA. CONCLUSIONS: The ACA could be a valid radiologic parameter in the diagnostic armamentarium for iNPH.

Abstract Background Gait disturbances are typical of persons with idiopathic normal pressure hydrocephalus (iNPH) without signs distinctive from other neurodegenerative and vascular conditions. Cerebrospinal fluid tap-test (CSF-TT) is expected to improve the motor performance of iNPH patients and is a prognostic indicator in their surgical management. This observational prospective study aims to determine which spatio-temporal gait parameter(s), measured during instrumented motor tests, and clinical scale(s) may provide a relevant contribution in the evaluation of motor performance pre vs. post CSF-TT on iNPH patients with and without important vascular encephalopathy. Methods Seventy-six patients (20 with an associated vascular encephalopathy) were assessed before, and 24 and 72 h after the CSF-TT by a timed up and go test (TUG) and an 18 m walking test (18 mW) instrumented using inertial sensors. Tinetti Gait, Tinetti Balance, Gait Status Scale, and Grading Scale were fulfilled before and 72 h after the CSF-TT. Stride length, cadence and total time were selected as the outcome measures. Statistical models with mixed effects were implemented to determine the relevant contribution to response variables of each quantitative gait parameter and clinical scales. Results and conclusion From baseline to 72 h post CSF-TT patients improved significantly by increasing cadence in 18 mW and TUG (on average of 1.7 and 2.4 strides/min respectively) and stride length in 18 mW (on average of 3.1 cm). A significant reduction of gait apraxia was reflected by modifications in double support duration and in coordination index. Tinetti Gait, Tinetti Balance and Gait Status Scale were able to explain part of the variability of response variables not covered by instrumental data, especially in TUG. Grading Scale revealed the highest affinity with TUG total time and cadence when considering clinical scales alone. Patients with iNPH and an associated vascular encephalopathy showed worst performances compared to pure iNPH but without statistical significance. Gait improvement following CSF-TT was comparable in the two groups. Overall these results suggest that, in order to augment CSF-TT accuracy, is key to assess the gait pattern by analyzing the main spatio-temporal parameters and set post evaluation at 72 h. Trial registration Approved by ethics committee: CE 14131 23/02/2015.

Diplegia is a specific subcategory of the wide spectrum of motion disorders gathered under the name of cerebral palsy. Recent works proposed to use gait analysis for diplegia classification paving the way for automated analysis. A clinically established gait-based classification system divides diplegic patients into 4 main forms, each one associated with a peculiar walking pattern. In this work, we apply two different deep learning techniques, namely, multilayer perceptron and recurrent neural networks, to automatically classify children into the 4 clinical forms. For the analysis, we used a dataset comprising gait data of 174 patients collected by means of an optoelectronic system. The measurements describing walking patterns have been processed to extract 27 angular parameters and then used to train both kinds of neural networks. Classification results are comparable with those provided by experts in 3 out of 4 forms.

INTRODUCTION:Idiopathic Normal Pressure Hydrocephalus (iNPH) is a complex and often misdiagnosed syndrome, whose major challenge is to identify which patients will benefit from surgery. Previous studies reported a variability in positive surgery response. The role of tap test(TT) in screening patients suitable for shunting is controversial. The primary aim of this study was to describe the clinical/instrumental features and their longitudinal progression after surgery in iNPH patients. Secondarily, we aimed to investigate the response of the three iNPH domains and the best time of outcome assessment after TT.METHODS:Patients compatible with iNPH underwent a 3-T-MRI and an inpatients program with TT including standardized clinical evaluations, neuropsychological assessments and instrumental gait analysis pre- and after-(24-h and 72-h) TT. The multidisciplinary team selected candidates for surgery. Patients were evaluated 6- and 12-months after surgery.RESULTS:A total of 154 consecutive patients were included from 2015 to 2018, 76 with an iNPH diagnosis (43 underwent surgery, 35 were evaluated after 6-months). Clinical and instrumented quantitative gait measures and urinary symptoms improved over time along with some neuropsychological functions. Concerning pre- and post-TT analyses, the three iNPH domains showed a different response after TT, the delayed motor assessment was more appropriate than the early one and the instrumental measures highlighted the motor improvement.CONCLUSION:iNPH patients improved after surgery, when accurately selected. A multidisciplinary team focused on this disease and a standardized protocol helped in achieving a correct diagnosis and management of iNPH. Our results could impact the management of this disease.