Sudden hearing loss as an early detector of multiple sclerosis: a systematic review

To evaluate whether Sudden Sensorineural Hearing Loss (S-SNHL) may be an early symptom of Multiple Sclerosis (MS). A systematic review was conducted using the following keywords: "Multiple sclerosis, hearing loss, sudden hearing loss, vertigo, tinnitus, magnetic resonance imaging, otoacoustic emission, auditory brainstem responses, white matter lesions, sensorineural hearing loss, symptoms of MS and otolaryngology, nerve disease and MS". Only the articles that included results of at least one auditory test and MRI were considered. We evaluated the prevalence of SNHL in patients with MS, the presence of different forms of SNHL (S-SNHL and Progressive SNHL (P-SNHL)) and their correlation with the stage of MS, the results of electrophysiological tests, and the location (if any) of MS lesions as detected by white matter hyperintensities in the MRI. We reviewed a total of 47 articles, which included 29 case reports, 6 prospective studies, 6 cohort studies, 4 case-control studies, and 2 retrospective studies. 25% of patients suffered from SNHL. S-SNHL typically occurred in the early stage of the disease (92% of patients) and was the only presenting symptom in 43% of female subjects. Instead, P-SNHL occurred in the late stage of MS (88% of patients). Auditory Brainstem Responses (ABR) were abnormal in all MS patients with S-SNHL. When S-SNHL appeared during the early stage of the disease, MS lesions were found in the brain in 60% of patients and in the Internal Auditory Canal in 40% of patients. ABR remained abnormal after recovery. S-SNHL can be an early manifestation of MS and should always be considered in the differential diagnosis of this condition, especially in women. The pathophysiology can be explained by the involvement of microglia attacking the central and/or peripheral auditory pathways as indicated by WMHs

Aberrant brain network connectivity in pre-symptomatic and manifest Huntington's disease: a systematic review

Resting-state functional magnetic resonance imaging (rs-fMRI) has the potential to shed light on the pathophysiological mechanisms of Huntington's disease (HD), paving the way to new therapeutic interventions. A systematic review of the literature was conducted in three online databases according to PRISMA guidelines, using keywords for HD, functional connectivity, and rs-fMRI. We included studies investigating connectivity in pre-symptomatic (pre-HD) and manifest HD gene carriers compared to healthy controls, implementing seed-based connectivity, independent component analysis, regional property and graph analysis approaches. Visual network showed reduced connectivity in manifest HD, while network/areas underpinning motor functions were consistently altered in both manifest HD and pre-HD, showing disease stage-dependent changes. Cognitive networks underlying executive and attentional functions showed divergent anterior-posterior alterations, reflecting possible compensatory mechanisms. The involvement of these networks in pre-HD is still unclear. In conclusion, aberrant connectivity of the sensory-motor network is observed in the early stage of HD while, as pathology spreads, other networks might be affected, such as the visual and executive/attentional networks. Moreover, sensory-motor and executive networks exhibit hyper- and hypo-connectivity patterns following different spatiotemporal trajectories. These findings could help to implement future huntingtin-lowering interventions

Human NDE1 splicing and mammalian brain development.

Exploring genetic and molecular differences between humans and other close species may be the key to explain the uniqueness of our brain and the selective pressures under which it evolves. Recent discoveries unveiled the involvement of Nuclear distribution factor E-homolog 1 (NDE1) in human cerebral cortical neurogenesis and suggested a role in brain evolution; however the evolutionary changes involved have not been investigated. NDE1 has a different gene structure in human and mouse resulting in the production of diverse splicing isoforms. In particular, mouse uses the terminal exon 8 T, while Human uses terminal exon 9, which is absent in rodents. Through chimeric minigenes splicing assay we investigated the unique elements regulating NDE1 terminal exon choice. We found that selection of the terminal exon is regulated in a cell dependent manner and relies on gain/loss of splicing regulatory sequences across the exons. Our results show how evolutionary changes in cis as well as trans acting signals have played a fundamental role in determining NDE1 species specific splicing isoforms supporting the notion that alternative splicing plays a central role in human genome evolution, and possibly human cognitive predominance

Cognitive stimulation of the default-mode network modulates functional connectivity in healthy aging

A cognitive-stimulation tool was created to regulate functional connectivity within the brain Default-Mode Network (DMN). Computerized exercises were designed based on the hypothesis that repeated task-dependent coactivation of multiple DMN regions would translate into regulation of resting-state network connectivity. Forty seniors (mean age: 65.90 years; SD: 8.53) were recruited and assigned either to an experimental group (n = 21) who received one month of intensive cognitive stimulation, or to a control group (n = 19) who maintained a regime of daily-life activities explicitly focused on social interactions. An MRI protocol and a battery of neuropsychological tests were administered at baseline and at the end of the study. Changes in the DMN (measured via functional connectivity of posterior-cingulate seeds), in brain volumes, and in cognitive performance were measured with mixed models assessing group-by-timepoint interactions. Moreover, regression models were run to test gray-matter correlates of the various stimulation tasks. Significant associations were found between task performance and gray-matter volume of multiple DMN core regions. Training-dependent up-regulation of functional connectivity was found in the posterior DMN component. This interaction was driven by a pattern of increased connectivity in the training group, while little or no up-regulation was seen in the control group. Minimal changes in brain volumes were found, but there was no change in cognitive performance. The training-dependent regulation of functional connectivity within the posterior DMN component suggests that this stimulation program might exert a beneficial impact in the prevention and treatment of early AD neurodegeneration, in which this neurofunctional pathway is progressively affected by the disease

Ultra-small dye-doped silica nanoparticles via modified sol-gel technique

In modern biosensing and imaging, fluorescence-based methods constitute the most diffused approach to achieve optimal detection of analytes, both in solution and on the single-particle level. Despite the huge progresses made in recent decades in the development of plasmonic biosensors and label-free sensing techniques, fluorescent molecules remain the most commonly used contrast agents to date for commercial imaging and detection methods. However, they exhibit low stability, can be difficult to functionalise, and often result in a low signal-to-noise ratio. Thus, embedding fluorescent probes into robust and bio-compatible materials, such as silica nanoparticles, can substantially enhance the detection limit and dramatically increase the sensitivity. In this work, ultra-small fluorescent silica nanoparticles (NPs) for optical biosensing applications were doped with a fluorescent dye, using simple water-based sol-gel approaches based on the classical Stober procedure. By systematically modulating reaction parameters, controllable size tuning of particle diameters as low as 10 nm was achieved. Particles morphology and optical response were evaluated showing a possible single-molecule behaviour, without employing microemulsion methods to achieve similar results

ELISA assay employing epitope-specific monoclonal antibodies to quantify circulating HER2 with potential application in monitoring cancer patients undergoing therapy with trastuzumab

Circulating HER2 extracellular domain (HER2 ECD) levels were proposed as a surrogate for HER2 tissue expression to monitor breast cancer patients for early relapse or responses to standard or HER2-targeted therapies, such as the monoclonal antibody (mAb) trastuzumab. Currently, available commercial ELISA assays for HER2 ECD rely on antibodies recognizing undisclosed or unknown epitopes. In this work, two ELISA assays employing MGR2 and MGR3 epitope-specific mAbs for HER2 ECD were developed and validated, showing good assay precision and linearity of the dose-response signal within the dynamic range of 0.19–12.50 ng mL−1 and detection limits of 0.76 and 0.75 ng mL−1 for the MGR2 and MGR3 assays, respectively. The developed assay showed a good agreement with two widely used commercial kits for HER2 ECD quantification in serum samples from breast cancer patients. A complete characterization of mAb-HER2 ECD interaction was performed by means of surface plasmon resonance using trastuzumab as control for both epitope mapping and kinetics analysis. The epitopes recognized by the two mAbs showed no overlap with trastuzumab, which was confirmed by trastuzumab interference analysis in serum samples. The method showed to be a practical approach to determine HER2 ECD with a high degree of sensitivity, reliability and recovery in samples containing mAbs-based therapies

Analysis of the trueness and precision of complete denture bases manufactured using digital and analog technologies

PURPOSE. Digital technology has enabled improvements in the fitting accuracy of denture bases via milling techniques. The aim of this study was to evaluate the trueness and precision of digital and analog techniques for manufacturing complete dentures (CDs). MATERIALS AND METHODS. Sixty identical CDs were manufactured using different production protocols. Digital and analog technologies were compared using the reference geometric approach, and the Delta-error values of eight areas of interest (AOI) were calculated. For each AOI, a precise number of measurement points was selected according to sensitivity analyses to compare the Delta-error of trueness and precision between the original model and manufactured prosthesis. Three types of statistical analysis were performed: to calculate the intergroup cumulative difference among the three protocols, the intergroup among the AOIs, and the intragroup difference among AOIs. RESULTS. There was a statistically significant difference between the dentures made using the oversize process and injection molding process (P < .001), but no significant difference between the other two manufacturing methods (P = .1227). There was also a statistically significant difference between the dentures made using the monolithic process and the other two processes for all AOIs (P = .0061), but there was no significant difference between the other two processes (P = 1). Within each group, significant differences among the AOIs were observed. CONCLUSION. The monolithic process yielded better results, in terms of accuracy (trueness and precision), than the other groups, although all three processes led to dentures with Delta-error values well within the clinical tolerance limit. [J Adv Prosthodont 2023;15:22-32

Evaluation of trueness and precision of removable partial denture metal frameworks manufactured with digital technology and different materials

PURPOSE. The aim of this study is to evaluate the accuracy of removable partial denture (RPD) frameworks produced using different digital protocols. MATERIALS AND METHODS. 80 frameworks for RPDs were produced using CAD-CAM technology and divided into four groups of twenty (n = 20): Group 1, Titanium frameworks manufactured by digital metal laser sintering (DMLS); Group 2, Co-Cr frameworks manufactured by DMLS; Group 3, Polyamide PA12 castable resin manufactured by multi-jet fusion (MJF); and Group 4, Metal (Co-Cr) casting by using lost-wax technique. After the digital acquisition, eight specific areas were selected in order to measure the Δ-error value at the intaglio surface of RPD. The minimum value required for point sampling density (0.4 mm) was derived from the sensitivity analysis. The obtained Δ-error mean value was used for comparisons: 1. between different manufacturing processes; 2. between different manufacturing techniques in the same area of interest (AOI); and 3. between different AOI of the same group. RESULTS. The Δ-error mean value of each group ranged between -0.002 (Ti) and 0.041 (Co-Cr) mm. The Pearson’s Chi-squared test revealed significant differences considering all groups paired two by two, except for group 3 and 4. The multiple comparison test documented a significant difference for each AOI among group 1, 3, and 4. The multiple comparison test showed significant differences among almost all different AOIs of each group. CONCLUSION. All Δ-mean error values of all digital protocols for manufacturing RPD frameworks optimally fit within the clinical tolerance limit of trueness and precision

Improving water use efficiency in vertical farming: Effects of growing systems, far-red radiation and planting density on lettuce cultivation

Vertical farms (VFs) are innovative urban production facilities consisting of multi-level indoor systems equipped with artificial lighting in which all the environmental conditions are controlled independently from the external climate. VFs are generally provided with a closed loop fertigation system to optimize the use of water and nu-trients. The objective of this study, performed within an experimental VF at the University of Bologna, was to quantify the water use efficiency (WUE, ratio between plant fresh weight and the volume of water used) for a lettuce (Lactuca sativa L.) growth cycle obtained in two different growing systems: an ebb-and-flow substrate culture and a high pressure aeroponic system. Considering the total water consumed (water used for irrigation and climate management), WUE of ebb-and-flow and aeroponics was 28.1 and 52.9 g L-1 H2O, respectively. During the growing cycle, the contribution generated by the recovery of internal air moisture from the heating, ventilation and air conditioning (HVAC) system, was quantified. Indeed, by recovering water from the dehu-midifier, water use decreases dramatically (by 67 %), while WUE increased by 206 %. Further improvement of WUE in the ebb-and-flow system was obtained through ameliorated crop management strategies, in particular, by increasing planting densities (e.g., 153, 270 and 733 plants m-2) and by optimizing the light spectrum used for plant growth (e.g., adjusting the amount of far-red radiation in the spectrum). Strategies for efficient use of water in high-tech urban indoor growing systems are therefore proposed

Assessment of the different types of failure on anterior cantilever resin-bonded fixed dental prostheses fabricated with three different materials: An in vitro study

background: resin-bonded fixed dental prosthesis (RBFDP) represents a highly aesthetic and conservative treatment option to replace a single tooth in a younger patient. The purpose of this in vitro study was to compare the fracture strength and the different types of failure on anterior cantilever RBFDPs fabricated using zirconia (ZR), lithium disilicate (LD), and PMMA-based material with ceramic fillers (PM) by the same standard tessellation language (STL) file. Methods: sixty extracted bovine mandibular incisives were embedded resin block; scanned to design one master model of RBFDP with a cantilevered single-retainer. Twenty cantilevered single-retainer RBFDPs were fabricated using ZR; LD; and PM. Static loading was performed using a universal testing machine. Results: the mean fracture strength for the RBFDPs was: 292.5 Newton (Standard Deviation (SD) 36.6) for ZR; 210 N (SD 37.6) for LD; and 133 N (SD 16.3) for PM. All the failures of RBFDPs in ZR were a fracture of the abutment tooth; instead; the 80% of failures of RBFDPs in LD and PM were a fracture of the connector. Conclusion: within the limitations of this in vitro study, we can conclude that the zirconia RBFDPs presented load resistance higher than the maximum anterior bite force reported in literature (270 N) and failure type analysis showed some trends among the groups