In silico analysis and functional characterization of a leucine-rich repeat protein of Leptospira interrogans.

Pathogenic spirochetes of the genus Leptospira are the causative agent of leptospirosis, a widely disseminated zoonosis that affects humans and animals. The ability of leptospires to quickly cross host barriers causing infection is not yet fully understood. Thus, understanding the mechanisms of pathogenicity is important to combat leptospiral infection. Outer membrane proteins are interesting targets to study as they are able to interact with host molecules. Proteins containing leucine-rich repeat (LRR) domains are characterized by the presence of multiple regions containing leucine residues and they have putative functions related to host-pathogen interactions. Hence, the present study aimed to clone and express the recombinant protein encoded by the LIC11098 gene, an LRR protein of L. interrogans serovar Copenhageni. In silico analyses predicted that the target protein is conserved among pathogenic strains of Leptospira, having a signal peptide and multiple LRR domains. The DNA sequence encoding the LRR protein was cloned in frame into the pAE vector, expressed without mutations in Escherichia coli and purified by His-tag chromatography. Circular dichroism (CD) spectrum showed that the recombinant protein was predominantly composed of ß-sheets. A dose-dependent interaction was observed with cellular and plasma fibronectins, laminin and the complement system component C9, suggesting a possible role of the protein encoded by LIC11098 gene at the initial stages of infection.

A Software Defined Radio Based Anti-UAV Mobile System with Jamming and Spoofing Capabilities.

The number of incidents between unmanned aerial vehicles (UAVs) and aircrafts at airports and airfields has been increasing over the last years. To address the problem, in this paper we describe a portable system capable of protecting areas against unauthorized UAVs, which is based on the use of low-cost SDR (software defined radio) platforms. The proposed anti-UAV system supports target localization and integrates effective jamming techniques with the generation of global positioning system (GPS) spoofing signals aimed at the drone. Real-life tests of the implemented prototype have shown that the proposed approach is capable of stopping the reliable reception of radionavigation signals and can also divert or even take control of unauthorized UAVs, whose flight path depends on the information obtained by the GPS system.

Hybrid Multisite Silicon Neural Probe with Integrated Flexible Connector for Interchangeable Packaging.

Multisite neural probes are a fundamental tool to study brain function. Hybrid silicon/polymer neural probes combine rigid silicon and flexible polymer parts into one single device and allow, for example, the precise integration of complex probe geometries, such as multishank designs, with flexible biocompatible cabling. Despite these advantages and benefiting from highly reproducible fabrication methods on both silicon and polymer substrates, they have not been widely available. This paper presents the development, fabrication, characterization, and in vivo electrophysiological assessment of a hybrid multisite multishank silicon probe with a monolithically integrated polyimide flexible interconnect cable. The fabrication process was optimized at wafer level, and several neural probes with 64 gold electrode sites equally distributed along 8 shanks with an integrated 8 µm thick highly flexible polyimide interconnect cable were produced. The monolithic integration of the polyimide cable in the same fabrication process removed the necessity of the postfabrication bonding of the cable to the probe. This is the highest electrode site density and thinnest flexible cable ever reported for a hybrid silicon/polymer probe. Additionally, to avoid the time-consuming bonding of the probe to definitive packaging, the flexible cable was designed to terminate in a connector pad that can mate with commercial zero-insertion force (ZIF) connectors for electronics interfacing. This allows great experimental flexibility because interchangeable packaging can be used according to experimental demands. High-density distributed in vivo electrophysiological recordings were obtained from the hybrid neural probes with low intrinsic noise and high signal-to-noise ratio (SNR).

Organ-on-a-Chip: A Preclinical Microfluidic Platform for the Progress of Nanomedicine.

Despite the progress achieved in nanomedicine during the last decade, the translation of new nanotechnology-based therapeutic systems into clinical applications has been slow, especially due to the lack of robust preclinical tissue culture platforms able to mimic the in vivo conditions found in the human body and to predict the performance and biotoxicity of the developed nanomaterials. Organ-on-a-chip (OoC) platforms are novel microfluidic tools that mimic complex human organ functions at the microscale level. These integrated microfluidic networks, with 3D tissue engineered models, have been shown high potential to reduce the discrepancies between the results derived from preclinical and clinical trials. However, there are many challenges that still need to be addressed, such as the integration of biosensor modules for long-time monitoring of different physicochemical and biochemical parameters. In this review, recent advances on OoC platforms, particularly on the preclinical validation of nanomaterials designed for cancer, as well as the current challenges and possible future directions for an end-use perspective are discussed.

Efficient light extraction in subwavelength GaAs/AlGaAs nanopillars for nanoscale light-emitting devices.

This work reports on high extraction efficiency in subwavelength GaAs/AlGaAs semiconductor nanopillars. We achieve up to 37-fold enhancement of the photoluminescence (PL) intensity from sub-micrometer (sub-µm) pillars without requiring back reflectors, high-Q dielectric cavities, nor large 2D arrays or plasmonic effects. This is a result of a large extraction efficiency for nanopillars <500 nm width, estimated in the range of 33-57%, which is much larger than the typical low efficiency (∼2%) of micrometer pillars limited by total internal reflection. Time-resolved PL measurements allow us to estimate the nonradiative surface recombination of fabricated pillars. We conclusively show that vertical-emitting nanopillar-based LEDs, in the best case scenario of both reduced surface recombination and efficient light out-coupling, have the potential to achieve notable large external quantum efficiency (∼45%), whereas the efficiency of large µm-pillar planar LEDs, without further methods, saturates at ∼2%. These results offer a versatile method of light management in nanostructures with prospects to improve the performance of optoelectronic devices including nanoscale LEDs, nanolasers, single photon sources, photodetectors, and solar cells.

3D Magnetic Field Reconstruction Methodology Based on a Scanning Magnetoresistive Probe.

The present work provides a detailed description on quantitative 3D magnetic field reconstruction using a scanning magnetoresistance microscopy setup incorporating a 19.5 μm × 2.5 μm magnetoresistive sensor. Therefore, making use of a rotation stage, 11 nm thick ferromagnetic CoFe elements with 20 μm × 5 μm planar size were measured along different sensor axes and converted into cartesian coordinate magnetic field components by use of the analytical coordinate transform equations. The reconstruction steps were followed and validated by numerical simulations based on a field averaging model caused by a non-negligible sensor volume. Detailed in-plane magnetic component reconstruction with ability to reconstruct sub-micrometer features is achieved. A discussion on the limiting factors for optimal resolution is presented.

High-Resolution Seismocardiogram Acquisition and Analysis System.

Several devices and measurement approaches have recently been developed to perform ballistocardiogram (BCG) and seismocardiogram (SCG) measurements. The development of a wireless acquisition system (hardware and software), incorporating a novel high-resolution micro-electro-mechanical system (MEMS) accelerometer for SCG and BCG signals acquisition and data treatment is presented in this paper. A small accelerometer, with a sensitivity of up to 0.164 µs/µg and a noise density below 6.5 µg/ Hz is presented and used in a wireless acquisition system for BCG and SCG measurement applications. The wireless acquisition system also incorporates electrocardiogram (ECG) signals acquisition, and the developed software enables the real-time acquisition and visualization of SCG and ECG signals (sensor positioned on chest). It then calculates metrics related to cardiac performance as well as the correlation of data from previously performed sessions with echocardiogram (ECHO) parameters. A preliminarily clinical study of over 22 subjects (including healthy subjects and cardiovascular patients) was performed to test the capability of the developed system. Data correlation between this measurement system and echocardiogram exams is also performed. The high resolution of the MEMS accelerometer used provides a better signal for SCG wave recognition, enabling a more consistent study of the diagnostic capability of this technique in clinical analysis.

Digital Platform for Wafer-Level MEMS Testing and Characterization Using Electrical Response.

The uniqueness of microelectromechanical system (MEMS) devices, with their multiphysics characteristics, presents some limitations to the borrowed test methods from traditional integrated circuits (IC) manufacturing. Although some improvements have been performed, this specific area still lags behind when compared to the design and manufacturing competencies developed over the last decades by the IC industry. A complete digital solution for fast testing and characterization of inertial sensors with built-in actuation mechanisms is presented in this paper, with a fast, full-wafer test as a leading ambition. The full electrical approach and flexibility of modern hardware design technologies allow a fast adaptation for other physical domains with minimum effort. The digital system encloses a processor and the tailored signal acquisition, processing, control, and actuation hardware control modules, capable of the structure position and response analysis when subjected to controlled actuation signals in real time. The hardware performance, together with the simplicity of the sequential programming on a processor, results in a flexible and powerful tool to evaluate the newest and fastest control algorithms. The system enables measurement of resonant frequency (Fr), quality factor (Q), and pull-in voltage (Vpi) within 1.5 s with repeatability better than 5 ppt (parts per thousand). A full-wafer with 420 devices under test (DUTs) has been evaluated detecting the faulty devices and providing important design specification feedback to the designers.

Osseodensification technique in crestal maxillary sinus elevation-A narrative review.

Osseodensification is a novel approach that has significantly advanced the field of implant dentistry, particularly in the context of transcrestal maxillary sinus floor elevation. This technique involves the use of specially designed burs that compact and densify bone along the osteotomy walls, thereby enhancing implant primary stability and facilitating osseointegration in low-density bone. This article reviews the historical evolution of implant site preparation, and the biomechanical, histological, and clinical evidence of osseodensification with a special focus on its application in sinus floor augmentation. The integration of this technique into contemporary practice represents a paradigm shift, offering a minimally invasive and efficient solution for addressing the challenges of posterior maxilla, with improved patient-reported outcomes and low complication rate. Three different protocols for sinus lift and implant placement using osseodensification burs are proposed based on available literature, and risk factors for Schneiderian membrane perforation based on residual bone height are discussed, along with implant-related outcomes and patient-reported outcome measures. The potential for osseodensification to become a standard practice in sinus floor augmentation is emphasized, highlighting key aspects such as surgical protocol and patient selection.

Osseodensification versus lateral window technique for sinus floor elevation with simultaneous implant placement: A randomized clinical trial on patient-reported outcome measures.

OBJECTIVES: To compare patient-reported outcome measures and additional surgical outcomes after sinus floor elevation (SFE) with osseodensification (OD) versus lateral window (LW), both with simultaneous implant placement. MATERIALS AND METHODS: Twenty participants requiring single-implant rehabilitation with residual bone height (RBH) ≤4 mm were enrolled. Pain experience, quality of life (QoL) via the Oral Health Impact Profile-14 (OHIP-14), analgesics intake, and other symptoms were self-reported for a week on a daily basis. Surgery duration, complications, and implant stability quotient at baseline (ISQ T0 ) and after 6 months (ISQ T6 ) were registered. Participants were followed up for 1 year. RESULTS: From Day 0 (day of surgery) to Day 3, pain experience was significantly lower (p < 0.05) in the OD group. OHIP-14 score was significantly lower (p < 0.05) in the OD group on all postoperative days, except on Day 5. Average analgesics intake was significantly lower (p < 0.001) in the OD group. Surgery mean duration was significantly higher (p < 0.001) in LW compared to OD (71.1 ± 10.4 vs. 32.9 ± 5.3 min). After osseointegration period, all implants were successfully restored with screw-retained crowns. CONCLUSIONS: Within the limitations of this study, it can be concluded that OD and LW techniques were similarly effective in SFE with simultaneous implant placement when RBH ≤ 4 mm. However, OD significantly outperformed LW in pain experience, impact on self-perceived QoL, surgery duration, postoperative edema, and analgesics intake.

Maxillary sinus membrane perforation rate utilizing osseodensification-mediated transcrestal sinus floor elevation: A multicenter clinical study.

PURPOSE: This multicenter cross-sectional clinical study aimed to evaluate the membrane perforation rate during transcrestal sinus floor elevation (TSFE) using osseodensification (OD) burs and assess risk factors associated with the procedure. MATERIALS AND METHODS: This study was conducted in six centers, following ethical standards and approved by local committees. It included patients over 18 years old missing maxillary posterior teeth with crestal residual bone height (RBH) ≥2 and ≤6 mm. Preoperative evaluations were done, including CBCT scans, to assess bone dimensions and sinus health. All centers and surgeons followed a standardized surgical protocol for TSFE using OD burs. Surgical complications, particularly sinus membrane perforations, were recorded and analyzed. Factors such as implant site, premolars or molars, as well as, healed or fresh socket, along with initial RBH were evaluated for their impact on membrane perforation rate. Descriptive statistics, χ2, and logistic regression analysis were used to analyze the data. RESULTS: A total of 621 subjects with an average age of 57.9 years were included. Sinus lifting was performed at 670 sites, with 621 implants placed in the maxilla. The majority of sinus lifts were done in the molar region (76.87%) and in healed bone sites (74.33%). The average RBH was 5.1 mm (ranging from 2 to 7 mm). Sinus membrane perforation occurred in 49 cases (7.31%). RBH ≤3 mm posed a risk factor for sinus membrane perforations followed by RBH >3 and ≤5 mm. Tooth region and implant site were not associated as risk factors for sinus membrane perforation. CONCLUSION: OD drilling used for TSFE resulted in low membrane perforation rate. Challenging scenarios of severe posterior maxillary atrophy presented as risk factors for increased perforation rate.

Arterial thrombosis and acute myocardial infarction with angiographically normal coronary arteries in a woman heterozygous for both factor V Leiden and prothrombin mutation.

Thirteen years after her last thrombotic event, anticoagulation was discontinued in a patient with combined thrombophilia involving mutation in factor V and G20210A polymorphism of the prothrombin gene. The only history was of arterial thrombosis. Three months later she presented a transmural myocardial infarction caused by coronary thrombosis.

Implant Stability of Osseodensification Drilling Versus Conventional Surgical Technique: A Systematic Review.

PURPOSE: This systematic review aimed to appraise the available evidence on the clinical characteristics produced by osseodensification drilling compared with the conventional drilling technique. MATERIALS AND METHODS: Five databases (PubMed, Google Scholar, LILACS, EMBASE, and CENTRAL) were searched up to July 2020. Randomized clinical trials (RCTs) and nonrandomized studies of interventions (NRSIs) that compared osseodensification drilling with conventional drilling in humans were included. Random-effects meta-analyses of standardized mean difference (MD) with 95% confidence intervals (CI) and risk ratio were performed. RESULTS: Three NRSIs fulfilled the inclusion criteria, and all were scored as low risk of bias. Meta-analysis showed that the osseodensification drilling technique presented higher average implant stability quotient (ISQ) scores at baseline (MD: 13.1, 95% CI: 10.0 to 16.1, P < .0001) than conventional drilling, with complete homogeneity (I2 = 0.0%). Furthermore, osseodensification drilling presented higher average ISQ scores at follow-up (MD: 5.99, 95% CI: 1.3 to 10.6, P < .0001) than conventional drilling, with high homogeneity (I2 = 73.0%). CONCLUSION: This systematic review showed that osseodensification presented consistently higher ISQ at baseline and at 4 to 6 months after implant placement compared with conventional drilling. However, these results should be carefully interpreted since only three studies were selected in this meta-analysis. In the future, RCTs will be necessary to confirm the consistency of these results.

Molar Septum Expansion with Osseodensification for Immediate Implant Placement, Retrospective Multicenter Study with Up-to-5-Year Follow-Up, Introducing a New Molar Socket Classification.

The ideal positioning of immediate implants in molar extraction sockets often requires the osteotomy to be in the interradicular septum, which can be challenging in some cases, with traditional site preparation techniques. Patients who had undergone molar tooth extraction and immediate implant placement at five different centers, and followed up between August 2015 and September 2020, were evaluated. Inclusion criteria were use of the osseodensification technique for implant site preparation. The primary outcome was septum width measurement pre-instrumentation and osteotomy diameter post expansion. Clinical outcomes, such as implant insertion torque (ISQ) and implant survival rate, were also collected. A total of 131 patients, who received 145 immediate implants, were included. The mean overall septum width at baseline was 3.3 mm and the mean osteotomy diameter post instrumentation was 4.65 mm. A total of ten implants failed: seven within the healing period and three after loading; resulting in a cumulative implant survival rate of 93.1%. This retrospective study showed that osseodensification is a predictable method for immediate implant placement with interradicular septum expansion in molar extraction sockets. Furthermore, it allowed the introduction of a new molar socket classification. In the future, well-designed controlled clinical studies are needed to confirm these results and further explore the potential advantages of this technique.

Double-Layer Flexible Neural Probe With Closely Spaced Electrodes for High-Density in vivo Brain Recordings.

Flexible polymer neural probes are an attractive emerging approach for invasive brain recordings, given that they can minimize the risks of brain damage or glial scaring. However, densely packed electrode sites, which can facilitate neuronal data analysis, are not widely available in flexible probes. Here, we present a new flexible polyimide neural probe, based on standard and low-cost lithography processes, which has 32 closely spaced 10 µm diameter gold electrode sites at two different depths from the probe surface arranged in a matrix, with inter-site distances of only 5 µm. The double-layer design and fabrication approach implemented also provides additional stiffening just sufficient to prevent probe buckling during brain insertion. This approach avoids typical laborious augmentation strategies used to increase flexible probes' mechanical rigidity while allowing a small brain insertion footprint. Chemical composition analysis and metrology of structural, mechanical, and electrical properties demonstrated the viability of this fabrication approach. Finally, in vivo functional assessment tests in the mouse cortex were performed as well as histological assessment of the insertion footprint, validating the biological applicability of this flexible neural probe for acquiring high quality neuronal recordings with high signal to noise ratio (SNR) and reduced acute trauma.

Dissolving microneedles for the delivery of peptides - Towards tolerance-inducing vaccines.

Tolerance inducing vaccines have re-appeared in recent years as a mean to re-establish immunological tolerance in the context of autoimmune disease. In the case of multiple sclerosis, several myelin-related peptides have been identified. The use of microneedles (MNs) allows the painless administration of molecules to the epidermal and intradermal space. This approach has been considered particularly promising in the scope of vaccination as the skin represents an immunologically super-active organ. This work explores the preparation of a MN patch that can deliver immunologically active peptides foreseeing the establishment of tolerance in the context of multiple sclerosis. A new MN design was achieved by microfabrication. The patches are composed of a dense MN array containing 33 × 33 needles with 200 or 125 µm diameter and height around 600 µm. Polymeric MNs composed by poly(vinyl alcohol), poly(vinyl pyrrolidone) and chitosan were successfully obtained, replicating the silicon masters morphology. The polymer MN patches showed to perforate pig skin, reaching more than 400 µm depth of penetration when assessed using agarose as a model for the skin viscoelastic properties. The MNs with 200 µm diameter showed improved mechanical properties in comparison to 125 µm diameter MNs. The presence of chitosan in the MN structure was explored and found not to affect mechanical properties or significantly alter the drug loading or release profile. The immunomodulatory peptide associated with the proteolipid protein PLP139-151 was loaded in 200 µm diameter MN patch and it is released in physiological conditions at therapeutic doses of the peptide, putting forward this strategy to integrate a new tolerance-inducing therapy for multiple sclerosis successfully.

Engineering of 2D transition metal carbides and nitrides MXenes for cancer therapeutics and diagnostics.

The 2D layered structured material with unique surface terminations and properties have showed great potential in variety of biomedical research fields including drug delivery and cancer therapeutics which forms the major focus of this review. MXenes as a multifunctional two-dimensional (2D) nanomaterial, has also received momentous research interest in oncology resulting from its intriguing structure and fascinating properties of magnetism and photodynamic properties such as luminescent, conductivity, magnetism, non-toxicity and its bio compatibility. This reported review intends to cover exclusively the synthesis and utilization of MXenes in oncological applications, and subsequently its future outlook in cancer therapeutic, diagnostic and theranostics. The versatile and unique physio-chemistry of MXenes permits fine tuning of its properties towards oncological applications ranging from the cancer therapeutic (e.g., photothermal therapy, photodynamic therapy, radiation therapy, chemotherapy) to cancer imaging (e.g., CT/MRI/PA imaging) as well as cancer theranostic applications. We have started the discussion by portraying the broad picture of physio-chemical aspects of MXenes followed by its drug delivery functionalities. Subsequently, ROS mediated therapeutic strategies of photodynamic therapy and radiotherapy as well as light triggered functionalities of MXenes were detailed comprehensively. In the middle of the gallery, various imaging and sensing aspects of MXenes were elucidated. Finally, we have concluded by explaining the combined therapy and diagnostic functions (theranostics) of MXenes. To put it in perspective, the current challenges and new opportunities in MXenes also discussed will give great realistic insights to motivate further research in realizing MXene as an intelligent oncological tool.

Facile synthesis and defect optimization of 2D-layered MoS2 on TiO2 heterostructure for industrial effluent, wastewater treatments.

Current research is paying much attention to heterojunction nanostructures. Owing to its versatile characteristics such as stimulating morphology, affluent surface-oxygen-vacancies and chemical compositions for enhanced generation of reactive oxygen species. Herein, we report the hydrothermally synthesized TiO2@MoS2 heterojunction nanostructure for the effective production of photoinduced charge carriers to enhance the photocatalytic capability. XRD analysis illustrated the crystalline size of CTAB capped TiO2, MoS2@TiO2 and L-Cysteine capped MoS2@TiO2 as 12.6, 11.7 and 10.2 nm, respectively. The bandgap of the samples analyzed by UV-Visible spectroscopy are 3.57, 3.66 and 3.94 eV. PL spectra of anatase phase titania shows the peaks present at and above 400 nm are ascribed to the defects in the crystalline structure in the form of oxygen vacancies. HRTEM reveals the existence of hexagonal layered MoS2 formation on the spherical shaped TiO2 nanoparticles at the interface. X-ray photoelectron spectroscopy recommends the chemical interactions between MoS2 and TiO2, specifically, oxygen vacancies. In addition, the electrochemical impedance spectroscopy studies observed that L-MT sample performed low charge transfer resistance (336.7 Ω cm2) that promotes the migration of electrons and interfacial charge separation. The photocatalytic performance is evaluated by quantifying the rate of Congo red dye degradation under visible light irradiation, and the decomposition efficiency was found to be 97%. The electron trapping recombination and plausible photocatalytic mechanism are also explored, and the reported work could be an excellent complement for industrial wastewater treatment.

Meteorological factors controlling soil gases and indoor CO2 concentration: a permanent risk in degassing areas.

Furnas volcano is one of the three quiescent central volcanoes of São Miguel Island (Azores Archipelago, Portugal). Its present activity is marked by several degassing manifestations, including fumarolic fields, thermal and cold CO2 springs and soil diffuse degassing areas. One of the most important soil diffuse degassing areas extends below Furnas village, located inside the volcano caldera. A continuous gas geochemistry programme was started at Furnas volcano in October 2001 with the installation of a permanent soil CO2 efflux station that has coupled meteorological sensors to measure barometric pressure, rain, air and soil temperature, air humidity, soil water content and wind speed and direction. Spike-like oscillations are observed on the soil CO2 efflux time series and are correlated with low barometric pressure and heavy rainfall periods. Stepwise multiple regression analysis, applied to the time series obtained, verified that the meteorological variables explain 43.3% of the gas efflux variations. To assess the impact of these influences in inhabited zones a monitoring test was conducted in a Furnas village dwelling placed where soil CO2 concentration is higher than 25 vol.%. Indoor CO2 air concentration measurements at the floor level reached values as higher as 20.8 vol.% during stormy weather periods. A similar test was performed in another degassing area, Mosteiros village, located on the flank of Sete Cidades volcano (S. Miguel Island), showing the same kind of relation between indoor CO2 concentrations and barometric pressure. This work shows that meteorological conditions alone increase the gas exposure risk for populations living in degassing areas.

A Perspective on Microneedle-Based Drug Delivery and Diagnostics in Paediatrics.

Microneedles (MNs) have been extensively explored in the literature as a means to deliver drugs in the skin, surpassing the stratum corneum permeability barrier. MNs are potentially easy to produce and may allow the self-administration of drugs without causing pain or bleeding. More recently, MNs have been investigated to collect/assess the interstitial fluid in order to monitor or detect specific biomarkers. The integration of these two concepts in closed-loop devices holds the promise of automated and minimally invasive disease detection/monitoring and therapy. These assure low invasiveness and, importantly, open a window of opportunity for the application of population-specific and personalised therapies.