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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

Is Sotolon Relevant to the Aroma of Madeira Wine Blends?

Madeira wine (MW) oxidative aging results in the formation of several key aromas. Little is still known about their odor relevance to the aroma of the most commercialized MWs. This report presents an in-depth study of the odor impact of sotolon in MW blends. First, its odor perception was estimated in MWs according to ASTM E679, testing different 3-year-old (3-yo) commercial blends. The odor relevance of sotolon in the aroma of 3-, 5-, and 10-yo commercial blends (89 MWs) was then appraised by calculating its Odor Activity Value (OAV), after determining its content by RP-HPLC-MS/MS. The sotolon odor perception in MW was as low as 23 µg/L, although it was found that little differences in the wine matrix influenced its perception. OAVs varied between 0.1 and 22, increasing with the blend age. Considering that 16% of the OAVs are higher than 10 (mostly ≥ 10-yo), sotolon was found to be a key contributor to the overall aroma MW blends.

Manipulation of Magnetic Beads with Thin Film Microelectromagnet Traps.

Integration of point-of-care assays can be facilitated with the use of actuated magnetic beads (MB) to perform testing in less expensive settings to enable the delivery of cost-effective care. In this paper we present six different designs of planar microelectromagnets traps (MEMT) with four external coils in series and one central coil connected for an opposite direction of manipulation of MB in microfluidic flows. The development of a simulation tool facilitated the rapid and efficient optimization of designs by presenting the influence of system variables on real time concentrations of MB. Real time experiments are in good agreement with the simulations and showed that the design enabled synchronous concentration and dispersion of MB on the same MEMT. The yield of local concentration is seen to be highly dependent on coil design. Additional coil turns between the central and external coils (inter-windings) doubled magnetic concentration and repulsion with no significant electrical resistance increase. The assemblage of a copper microchannel closed loop cooling system to the coils successfully eliminated the thermal drift promoted by joule heating generated by applied current.

Fast and efficient microfluidic cell filter for isolation of circulating tumor cells from unprocessed whole blood of colorectal cancer patients.

Liquid biopsy offers unique opportunities for low invasive diagnosis, real-time patient monitoring and treatment selection. The phenotypic and molecular profile of circulating tumor cells (CTCs) can provide key information about the biology of tumor cells, contributing to personalized therapy. CTC isolation is still challenging, mainly due to their heterogeneity and rarity. To overcome this limitation, a microfluidic chip for label-free isolation of CTCs from peripheral blood was developed. This device, the CROSS chip, captures CTCs based on their size and deformability with an efficiency of 70%. Using 2 chips, 7.5 ml of whole blood are processed in 47 minutes with high purity, as compared to similar technologies and assessed by in situ immunofluorescence. The CROSS chip performance was compared to the CellSearch system in a set of metastatic colorectal cancer patients, resulting in higher capture of DAPI+/CK+/CD45- CTCs in all individuals tested. Importantly, CTC enumeration by CROSS chip enabled stratification of patients with different prognosis. Lastly, cells isolated in the CROSS chip were lysed and further subjected to molecular characterization by droplet digital PCR, which revealed a mutation in the APC gene for most patient samples analyzed, confirming their colorectal origin and the versatility of the technology for downstream applications.

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.

Efficient light trapping and broadband absorption of the solar spectrum in nanopillar arrays decorated with deep-subwavelength sidewall features.

Silicon nanopillar (NP) arrays are known to exhibit efficient light trapping and broadband absorption of solar radiation. In this study, we consider the effect of deep subwavelength sidewall scalloping (DSSS) on the broadband absorption of the arrays. Practically, the formation of DSSS is a side effect of top-down dry etching of NP arrays of several microns height. We use finite-difference time-domain electromagnetic calculations to show that the presence of DSSS can result in efficient excitation of optical modes in both the arrays and the underlying substrates. We demonstrate a broadband absorption enhancement of >10% in a DSSS-NP array with an underlying substrate. Finally, we use device calculations to examine the effect of DSSS on the electrical performance of a photovoltaic cell, as the main concern is the degradation of the open-circuit voltage due to surface recombination (DSSS results in higher surface-to-volume ratio). We show that the effect of DSSS on open-circuit voltage is negligible. Finally, deep-subwavelength sidewall features offer a new, interesting photon management strategy towards absorption enhancement.

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.