Virtual reality (VR) systems are becoming increasingly attractive as joint kinematics monitoring systems during rehabilitation. This study aimed to evaluate the accuracy of the Oculus Quest 2 in ...measuring translational and rotational displacements. As the Oculus Quest 2 was chosen for future applications in shoulder rehabilitation, the translation range (minimum: ~200 mm, maximum: ~700 mm) corresponded to the forearm length of the 5th percentile female and the upper limb length of the 95th percentile male. The controller was moved on two structures designed to allow different translational displacements and rotations in the range 0–180°, to cover the range of motion of the upper limb. The controller measures were compared with those of a Qualisys optical capture system. The results showed a mean absolute error of 13.52 ± 6.57 mm at a distance of 500 mm from the head-mounted display along the x-direction. The maximum mean absolute error for rotational displacements was found to be 1.11 ± 0.37° for a rotation of 40° around the z-axis. Oculus Quest 2 is a promising VR tool for monitoring shoulder kinematics during rehabilitation. The inside-out movement tracking makes Oculus Quest 2 a viable alternative to traditional motion analysis systems.
► MBR process is more effective than CASP in the removal of bacteriophages. ► SOMCPH proves to be more resistant to MBR treatment than FRNAPH. ► BFRAGPH are not always detectable in the pre-treated ...effluent. ► SOMCPH are the most suitable indicators to evaluate the MBR process performance. ► SOMCPH are the most suitable indicators to evaluate the safety of the MBR effluent.
The effectiveness of a full scale membrane bioreactor (MBR) in the removal of bacteriophages and bacterial fecal indicators from municipal wastewater was compared with that obtained by conventional activated sludge process (CASP). Somatic coliphages (SOMCPH) and F-RNA specific bacteriophages (FRNAPH) were always detected in the pre-treated effluent (mean: 6Log10), while phages infecting Bacteroides fragilis were not always present (mean: 3.9Log10). The MBR process was able to achieve respectively 2.7 and 1.7Log10 higher reductions of SOMCPH and FRNAPH compared to CASP (significant differences: P<0.05). SOMCPH were found to be the most suitable indicators for assessing MBR performance, since they showed greater resistance to biofiltration than FRNAPH and a more regular distribution in pre-treated effluent than BFRAGPH. Moreover, since the traditional bacterial indicators were almost totally removed by biofiltration, SOMCPH proved to be the best indicators to evaluate the microbiological risk when MBR effluent is discharged into natural waters or reused.
Bone tissue is a nanocomposite consisting of an organic and inorganic matrix, in which the collagen component and the mineral phase are organized into complex and porous structures. Hydroxyapatite ...(HA) is the most used ceramic biomaterial since it mimics the mineral composition of the bone in vertebrates. However, this biomimetic material has poor mechanical properties, such as low tensile and compressive strength, which make it not suitable for bone tissue engineering (BTE). For this reason, HA is often used in combination with different polymers and crosslinkers in the form of composites to improve their mechanical properties and the overall performance of the implantable biomaterials developed for orthopedic applications. This review summarizes recent advances in HA-based biocomposites for bone regeneration, addressing the most widely employed inorganic matrices, the natural and synthetic polymers used as reinforcing components, and the crosslinkers added to improve the mechanical properties of the scaffolds. Besides presenting the main physical and chemical methods in tissue engineering applications, this survey shows that HA biocomposites are generally biocompatible, as per most in vitro and in vivo studies involving animal models and that the results of clinical studies on humans sometimes remain controversial. We believe this review will be helpful as introductory information for scientists studying HA materials in the biomedical field.
Brain tumors are particularly aggressive and represent a significant cause of morbidity and mortality in adults and children, affecting the global population and being responsible for 2.6% of all ...cancer deaths (as well as 30% of those in children and 20% in young adults). The blood-brain barrier (BBB) excludes almost 100% of the drugs targeting brain neoplasms, representing one of the most significant challenges to current brain cancer therapy. In the last decades, carbon dots have increasingly played the role of drug delivery systems with theranostic applications against cancer, thanks to their bright photoluminescence, solubility in bodily fluids, chemical stability, and biocompatibility. After a summary outlining brain tumors and the current drug delivery strategies devised in their therapeutic management, this review explores the most recent literature about the advances and open challenges in the employment of carbon dots as both diagnostic and therapeutic agents in the treatment of brain cancers, together with the strategies devised to allow them to cross the BBB effectively.
The analysis of viral nucleic acids (NA), DNA or RNA, is a crucial issue in the diagnosis of infections and the treatment and prevention of related human diseases. Conventional nucleic acid tests ...(NATs) require multistep approaches starting from the purification of the pathogen genetic material in biological samples to the end of its detection, basically performed by the consolidated polymerase chain reaction (PCR), by the use of specialized instruments and dedicated laboratories. However, since the current NATs are too constraining and time and cost consuming, the research is evolving towards more integrated, decentralized, user-friendly, and low-cost methods. These will allow the implementation of massive diagnoses addressing the growing demand of fast and accurate viral analysis facing such global alerts as the pandemic of coronavirus disease of the recent period. Silicon-based technology and microfluidics, in this sense, brought an important step up, leading to the introduction of the genetic point-of-care (PoC) systems. This review goes through the evolution of the analytical methods for the viral NA diagnosis of infection diseases, highlighting both advantages and drawbacks of the innovative emerging technologies versus the conventional approaches.
Background and purpose
Longitudinally extensive transverse myelitis (LETM) associated with aquaporin‐4 autoantibodies (AQP4‐IgG) can cause severe disability. Early diagnosis and prompt treatment are ...critical to prevent relapses. A novel score is described based on clinical and neuroimaging characteristics that predicts AQP4‐IgG positivity in patients with LETM.
Methods
Patients were enrolled both retrospectively and prospectively from multiple Italian centers. Clinical and neuroimaging characteristics of AQP4‐IgG positive and negative patients were compared through univariate and multivariate analysis.
Results
Sixty‐six patients were included. Twenty‐seven (41%) were AQP4‐IgG positive and median age at onset was 45.5 years (range 19–81, interquartile range 24). Female sex (odds ratio OR 17.9, 95% confidence interval CI 2.6–381.9; p = 0.014), tonic spasms (OR 45.6, 95% CI 3.1–2197; p = 0.017) and lesion hypointensity on T1‐weighted images (OR 52.9, 95% CI 6.8–1375; p = 0.002) were independently associated with AQP4‐IgG positivity. The AQP4‐IgG positivity in myelitis (AIM) score predicted AQP4‐IgG positivity with 85% sensitivity and 95% specificity. Positive and negative likelihood ratios were 16.6 and 0.2 respectively. The inter‐rater and intra‐rater agreement in the score application were both excellent.
Conclusions
The AIM score predicts AQP4‐IgG positivity with good sensitivity and specificity in patients with a first episode of LETM. The score may assist clinicians in early diagnosis and treatment of AQP4‐IgG positive LETM.
In this multicenter study, a score is developed to predict aquaporin‐4 (AQP4) immunoglobulin G (IgG) positivity in patients with longitudinally extensive myelitis (LETM). The AQP‐4‐IgG positive myelitis (AIM) score was applied both retrospectively and prospectively for 66 LETM patients, and a score ≥5 predicted AQP4‐IgG positivity with 85% sensitivity and 95% specificity. The AIM score appears a reliable tool to aid in the early diagnosis and treatment of AQP4‐IgG positive LETM.
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder. Since acetylcholine (ACh) is known to participate in the inflammatory response, we investigated the ...possible relationship between pro-inflammatory cytokines and acetylcholine levels in relapsing-remitting multiple sclerosis (RR-MS) patients. Levels of ACh and pro-inflammatory cytokines IL1-β and IL-17 were measured both in cerebrospinal fluid (CSF) and sera of 22 RR-MS patients in the relapsing phase and in 17 control subjects affected by other non-neurological diseases (OND). We observed higher levels of pro-inflammatory cytokines such as IL-1β and IL-17 in both CSF and serum of RR-MS patients compared to control subjects. Moreover, ACh levels were lower in CSF and serum of RR-MS patients compared to levels of control subjects. Although the relationship between high inflammatory cytokine levels and low ACh levels need to be further investigated in the future, our data suggest that IL-1β, and cytokines induced by it, such as IL-17 and ACh, may be involved in the pathogenesis of MS.
Background:
Little is known about COVID-19 course and outcomes after a third booster dose of mRNA vaccine against SARS-CoV-2 (mRNA-Vax) in patients with multiple sclerosis (pwMS) treated with ...ocrelizumab (OCR) and fingolimod (FNG), which showed a weakened immune response to mRNA-vax.
Objectives:
The aim of this study was to evaluate COVID-19 course and outcomes in pwMS on OCR and FNG after receiving the third dose of mRNA-Vax and to compare it with pwMS on natalizumab (NTZ).
Methods:
Inclusion criteria: >18 years of age, being treated with OCR/FNG/NTZ since the first mRNA-Vax dose; COVID-19 after a third booster dose of mRNA-Vax; no steroids use.
Results:
Overall, 290 pwMS (79 NTZ, 126 OCR, and 85 FNG) from 17 Italian MS centers were included. Age, Expanded Disability Status Scale (EDSS) score, MS phenotype, disease, and treatment duration were significantly different across groups. PwMS who had COVID-19 on OCR and FNG compared with those on NTZ were slightly more symptomatic with higher hospitalization rates (11.1% vs 7.1% vs 1.3%, respectively). Regression models showed that the majority of the differences observed were not related to the disease-modifying treatments (DMTs) used. No fatal cases were observed.
Conclusion:
Our results support the effectiveness of the third booster dose of mRNA-Vax against severe forms of COVID-19 in pwMS treated with OCR and FNG.
Recent studies estimated an incidence of 4–25% of disease rebound after withdrawal of fingolimod (FTY) for any reason, but specific data on disease reactivation after FTY withdrawal due to pregnancy ...are limited. The aim of the study was to evaluate the frequency and predictors of disease reactivation in patients who stopped FTY for pregnancy. A multicentre retrospective cohort study was conducted in four Italian MS centres in 2013–2019. Both planned and unplanned pregnancies were included. The annualized relapse rate (ARR) was calculated before FTY treatment, during FTY treatment, during pregnancy and during the year after delivery. In total, 27 patients (mean age 29 years) were included. The ARR 1 year before FTY treatment was 1.3. Patients were exposed to FTY for a median of 2.9 years. The ARR was 0.04 during the last year before conception (
p
< 0.001 compared with the ARR before FTY treatment). Eleven patients became pregnant after a mean of 88 days following FTY discontinuation, whereas 16 patients stopped FTY after pregnancy confirmation. Relapses were observed in 22% of patients during pregnancy and in 44% in the postpartum period. ARR increased both during pregnancy (0.49; p = 0.027) and in the first year after delivery (0.67;
p
< 0.001) compared to the last year before pregnancy. Compared with radiological assessment before pregnancy, more patients showed new or enlarging T2 lesions (63% vs 30%;
p
= 0.02) and gadolinium-enhancing lesions (44% vs 0;
p
= 0.0001) on brain Magnetic Resonance Imaging. Relapses during pregnancy were the only significant predictor for postpartum relapses (OR 1.9, 95% CI 1.11–3.1). One case of spontaneous abortion and no cases of abnormal foetal development were observed. Despite adequate and prolonged control of disease activity, women who discontinue FTY because of pregnancy are at risk for disease reactivation. In patients who relapsed during pregnancy, the initiation of high-efficacy disease modifying drugs (DMDs) soon after delivery is advisable to prevent postpartum relapses.
Background:
No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available.
...Objective:
To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA).
Methods:
Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models.
Results:
SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0.
Conclusion:
A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
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