Bi-directional and multi-modal effects of dexamphetamine on spatial binding windows in healthy individuals.

OBJECTIVES: Stimuli that are separated by a short window of space or time, known as spatial and temporal binding windows (SBW/TBWs), may be perceived as separate. Widened TBWs are evidenced in schizophrenia, although it is unclear if the SBW is similarly affected. The current study aimed to assess if dexamphetamine (DEX) may increase SBWs in a multimodal visuo-tactile illusion, potentially validating usefulness as an experimental model for multimodal visuo-tactile hallucinations in schizophrenia, and to examine a possible association between altered binding windows (BWs) and working memory (WM) suggested by previous research. METHODS: A placebo-controlled, double-blinded, and counter-balanced crossover design was employed. Permuted block randomisation was used for drug order. Healthy participants received DEX (0.45 mg/kg, PO, b.i.d.) or placebo (glucose powder) in capsules. The Rubber Hand Illusion (RHI) and Wechsler Adult Intelligence Scale Spatial Span was employed to determine whether DEX would alter SBWs and WM, respectively. Schizotypy was assessed with a variety of psychological scales. RESULTS: Most participants did not experience the RHI even under normal circumstances. Bi-directional and multimodal effects of DEX on individual SBWs and schizotypy were observed, but not on WM. CONCLUSIONS: Bidirectional multimodal effects of DEX on the RHI and SBWs were observed in individuals, although not associated with alterations in WM.

Harnessing extracellular vesicles-mediated signaling for enhanced bone regeneration: novel insights into scaffold design.

The increasing prevalence of bone replacements and complications associated with bone replacement procedures underscores the need for innovative tissue restoration approaches. Existing synthetic grafts cannot fully replicate bone vascularization and mechanical characteristics. This study introduces a novel strategy utilizing pectin, chitosan, and polyvinyl alcohol to create interpenetrating polymeric network (IPN) scaffolds incorporated with extracellular vesicles (EVs) isolated from human mesenchymal stem cells (hMSCs). We assess the osteointegration and osteoconduction abilities of these modelsin vitrousing hMSCs and MG-63 osteosarcoma cells. Additionally, we confirm exosome properties through Transmission Electron Microscopy (TEM), immunoblotting, and Dynamic Light Scattering (DLS).In vivo, chick allantoic membrane assay investigates vascularization characteristics. The study did not includein vivoanimal experiments. Our results demonstrate that the IPN scaffold is highly porous and interconnected, potentially suitable for bone implants. EVs, approximately 100 nm in size, enhance cell survival, proliferation, alkaline phosphatase activity, and the expression of osteogenic genes. EVs-mediated IPN scaffolds demonstrate promise as precise drug carriers, enabling customized treatments for bone-related conditions and regeneration efforts. Therefore, the EVs-mediated IPN scaffolds demonstrate promise as precise carriers for the transport of drugs, allowing for customized treatments for conditions connected to bone and efforts in regeneration.

Effects of hours of sleep on ImPACT concussion testing: comparing baseline with postinjury scores.

OBJECTIVE: The influence of sleep on baseline and postconcussion neurocognitive performance prior to Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is poorly understood. Since ImPACT is widely used in youth sport to assess neurocognitive performance before and after head injury, it is important to delineate factors that affect testing performance. While some have reported correlations between fewer hours of sleep and lower scores on baseline tests, others have not observed any such associations. Therefore, the authors sought to compare the relationship between sleep and neurocognitive performance on ImPACT at both baseline and postinjury. METHODS: The authors queried a database of 25,815 ImPACT tests taken from 2009 to 2019 by athletes aged 12-22 years. There were 11,564 baseline concussion tests and 7446 postinjury concussion ImPACT tests used in the analysis. Linear regression was used to model the effect of sleep on baseline and postconcussion ImPACT scores adjusting for sex, age, learning disability, attention-deficit/hyperactivity disorder, number of prior concussions, number of games missed, and strenuous exercise before testing. RESULTS: Mean composite scores expectedly were all significantly lower in the post-head injury group compared with the baseline group. In the multivariable analysis, at baseline, hours of sleep significantly affected symptom scores (ß = -1.050, 95% CI -1.187 to -0.9138; p < 0.0001). In the postinjury multivariable analysis, verbal memory (ß = 0.4595, 95% CI 0.2080-0.7110; p = 0.0003), visual memory (ß = 0.3111, 95% CI 0.04463-0.5777; p = 0.0221), impulse control (ß = -0.2321, 95% CI -0.3581 to -0.1062; p = 0.0003), and symptom scores (ß = -0.9168, 95% CI -1.259 to -0.5750; p < 0.0001) were all affected by hours of sleep. CONCLUSIONS: Hours of sleep did not alter neurocognitive metrics at baseline but did have an impact on post-head injury metrics. These findings suggest that individuals may be able to compensate for lack of sleep at baseline but not immediately after concussion. Concussions may reduce cognitive reserve or detract from the brain's resources, making sleep even more important for proper neurocognitive functioning postconcussion. Future work will analyze the effects of sleep on postconcussion test performance.

Intelligent salivary biosensors for periodontitis: in vitro simulation of oral oxidative stress conditions.

ASTRACT: One of the most common oral diseases affecting millions of people worldwide is periodontitis. Usually, proteins in body fluids are used as biomarkers of diseases. This study focused on hydrogen peroxide, lipopolysaccharide (LPS), and lactic acid as salivary non-protein biomarkers for oxidative stress conditions of periodontitis. Electrochemical analysis of artificial saliva was done using Gamry with increasing hydrogen peroxide, bLPS, and lactic acid concentrations. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were conducted. From EIS data, change in capacitance and CV plot area were calculated for each test condition. Hydrogen peroxide groups had a decrease in CV area and an increase in percentage change in capacitance, lipopolysaccharide groups had a decrease in CV area and a decrease in percentage change in capacitance, and lactic acid groups had an increase of CV area and an increase in percentage change in capacitance with increasing concentrations. These data showed a unique combination of electrochemical properties for the three biomarkers. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) employed to observe the change in the electrode surface and elemental composition data present on the sensor surface also showed a unique trend of elemental weight percentages. Machine learning models using hydrogen peroxide, LPS, and lactic acid electrochemical data were applied for the prediction of risk levels of periodontitis. The detection of hydrogen peroxide, LPS, and lactic acid by electrochemical biosensors indicates the potential to use these molecules as electrochemical biomarkers and use the data for ML-driven prediction tool for the periodontitis risk levels.

Evaluating the effects of splinting implant scan bodies intraorally on the trueness of complete arch digital scans: A clinical study.

STATEMENT OF PROBLEM: A predictable protocol for accurately scanning implants in a complete edentulous arch has not been established. PURPOSE: The purpose of this clinical study was to investigate the effect of splinting implant scan bodies intraorally on the accuracy and scan time for digital scans of edentulous arches. MATERIAL AND METHODS: This single center, nonrandomized, clinical trial included a total of 19 arches. Definitive casts with scan bodies were fabricated and scanned with a laboratory scanner as the reference (control) scan. Each participant received 2 intraoral scans, the first with unsplinted scan bodies and the second with resin-splinted scan bodies. The scan time was also recorded for each scan. To compare the accuracy of the scans, the standard tessellation language (STL) files of the 2 scans were superimposed on the control scan, and positional and angular deviations were analyzed by using a 3-dimensional (3D) metrology software program. The Mann-Whitney U test was used to compare the distance and angular deviations between the splinted group and the unsplinted group with the control. The ANOVA test was conducted to examine the effect of the scan technique on trueness (distance deviation and angular deviation) and scan time (α=.05 for all tests). RESULTS: Statistically significant differences were found in the overall 3D positional and angular deviations of the unsplinted and splinted digital scans when compared with the reference scans (P<.05). No statistically significant differences in overall 3-dimensional positional deviations (P=.644) and angular deviations (P=.665) were found between the splinted and unsplinted experimental groups. A faster scan time was found with the splinted group in the maxillary arch. CONCLUSIONS: Conventional complete arch implant impressions were more accurate than digital complete arch implant scans. Splinting implant scan bodies did not significantly affect the trueness of complete arch digital scans, but splinting appeared to reduce the scan time. However, fabricating the splint was not considered in the time measurement.

Incidence and risk factors of omicron variant SARS-CoV-2 breakthrough infection among vaccinated and boosted individuals.

Background: SARS-CoV-2 vaccines have been shown to be safe and effective against infection and severe COVID-19 disease worldwide. Certain co-morbid conditions cause immune dysfunction and may reduce immune response to vaccination. In contrast, those with co-morbidities may practice infection prevention strategies. Thus, the real-world clinical impact of co-morbidities on SARS-CoV-2 infection in the recent post-vaccination period is not well established. We performed this study to understand the epidemiology of Omicron breakthrough infection and evaluate associations with number of comorbidities in a vaccinated and boosted population. Methods and Findings: We performed a retrospective clinical cohort study utilizing the Northwestern Medicine Enterprise Data Warehouse. Our study population was identified as fully vaccinated adults with at least one booster. The primary risk factor of interest was the number of co-morbidities. Our primary outcome was incidence and time to first positive SARS-CoV-2 molecular test in the Omicron predominant era. We performed multivariable analyses stratified by calendar time using Cox modeling to determine hazard of SARS-CoV-2. In total, 133,191 patients were analyzed. Having 3+ comorbidities was associated with increased hazard for breakthrough (HR=1.2 CI 1.2-1.6). During the second half of the study, having 2 comorbidities (HR= 1.1 95% CI 1.02-1.2) and having 3+ comorbidities (HR 1.7, 95% CI 1.5-1.9) were associated with increased hazard for Omicron breakthrough. Older age was associated with decreased hazard in the first 6 months of follow-up. Interaction terms for calendar time indicated significant changes in hazard for many factors between the first and second halves of the follow-up period. Conclusions: Omicron breakthrough is common with significantly higher risk for our most vulnerable patients with multiple co-morbidities. Age related behavioral factors play an important role in breakthrough infection with the highest incidence among young adults. Our findings reflect real-world differences in immunity and exposure risk behaviors for populations vulnerable to COVID-19.

A novel digital workflow for fabricating artificial periodontal ligament using three-dimensional printing flexible resin: A dental technique.

The fabrication of periodontal ligament (PDL) models for in vitro dental studies has seen a wide range of techniques and materials being utilized. This paper introduces a novel dental technique that employs a digital workflow for the fabrication of artificial PDL using three-dimensional printing of flexible resin. This innovative approach offers several advantages, including enhanced accuracy and realism in simulating PDL. The digital workflow facilitates a streamlined fabrication process, ensuring efficiency and precision. By presenting this novel technique, this digital approach contributes to the advancement of in vitro dental research, providing researchers with a reliable and realistic model for studying various dental phenomena.

Dexamphetamine increased speech and visual unimodal illusions in healthy participants without affecting temporal binding window.

OBJECTIVE: Stimuli received beyond a very short timeframe, known as temporal binding windows (TBWs), are perceived as separate events. In previous audio-visual multisensory integration (McGurk effect) studies, widening of TBWs has been observed in people with schizophrenia. The present study aimed to determine if dexamphetamine could increase TBWs in unimodal auditory and unimodal visual illusions that may have some validity as experimental models for auditory and visual hallucinations in psychotic disorders. METHODS: A double-blind, placebo-controlled, counter-balanced crossover design with permuted block randomisation for drug order was followed. Dexamphetamine (0.45 mg/kg, PO, q.d.) was administered to healthy participants. Phantom word illusion (speech illusion) and visual-induced flash illusion/VIFI (visual illusion) tests were measured to determine if TBWs were altered as a function of delay between stimuli presentations. Word emotional content for phantom word illusions was also analysed. RESULTS: Dexamphetamine significantly increased the total number of phantom words/speech illusions (p < 0.01) for pooled 220-1100 ms ISIs in kernel density estimation and the number of positive valence words heard (beta = 2.20, 95% CI [1.86, 2.55], t = 12.46, p < 0.001) with a large effect size (std. beta = 1.05, 95% CI [0.89, 1.22]) relative to placebo without affecting the TBWs. For the VIFI test, kernel density estimation for pooled 0-801 ms ISIs showed a significant difference (p < 0.01) in the data distributions of number of target flash (es) perceived by participants after receiving dexamphetamine as compared with placebo. CONCLUSIONS: Overall, healthy participants who were administered dexamphetamine (0.45 mg/kg, PO, q.d.) experienced increases in auditory and visual illusions in both phantom word illusion and VIFI tests without affecting their TBWs.

The effect of three dental cement types on the corrosion of dental implant surfaces.

Statement of problem: One of the main challenges facing dental implant success is peri-implantitis. Recent evidence indicates that titanium (Ti) corrosion products and undetected-residual cement are potential risk factors for peri-implantitis. The literature on the impact of various types of dental cement on Ti corrosion is very limited. Purpose: This study aimed to determine the influence of dental cement on Ti corrosion as a function of cement amount and type. Materials and methods: Thirty commercially pure Ti grade 4 discs (19 × 7mm) were polished to mirror-shine (Ra ≈ 40 nm). Samples were divided into 10 groups (n = 3) as a cement type and amount function. The groups were no-cement as control, TempBond NE (TB3mm, TB5mm, and TB8mm), FujiCEM-II (FC3mm, FC5mm, and FC8mm), and Panavia-F-2.0 (PC3mm, PC5mm, and PC8mm). Tafel's method estimated corrosion rate (icorr) and corresponding potential (Ecorr) from potentiodynamic curves. Electrochemical Impedance Spectroscopy (EIS) data was utilized to obtain Nyquist and Bode plots. An equivalent electrical circuit estimated polarization resistance (Rp) and double-layer capacitance (Cdl). Inductively coupled plasma mass spectrometry (ICP-MS) analysis was conducted to analyze the electrolyte solution after corrosion. pH measurements of the electrolyte were recorded before and after corrosion tests. Finally, the corroded surface was characterized by a 3D white-light microscope and scanning electron microscope. Statistical analysis was conducted using either one-way ANOVA followed by Tukey's Post Hoc test or Kruskal-Wallis followed by Dunn's test based on data distribution. Results: Based on cement amount, FC and PC significantly increased icorr in higher amounts (FC8mm-icorr = 8.22 × 10-8A/cm2, PC8mm-icorr = 5.61 × 10-8A/cm2) compared to control (3.35 × 10-8A/cm2). In contrast, TB3mm decreased icorr significantly compared to the control. As a function of cement type, FC increased icorr the most. EIS data agrees with these observations. Finally, corroded surfaces had higher surface roughness (Ra) compared to non-corroded surfaces. Conclusion: The study indicated that cement types FC and PC led to increased Ti-corrosion as a function of a higher amount. Hence, the implant stability could be impacted by the selection, excessive cement, and a potentially increased risk of peri-implantitis.

Digital workflow for duplication of gold onlay anatomy to monolithic zirconia onlay for a complete denture: A technique paper.

Digital replication of an existing cast gold onlay anatomy to a more esthetic material for a new complete denture is challenging. A technique is presented that uses digital technology to fabricate a new maxillary complete denture with monolithic zirconia onlays that duplicate the anatomy of an existing complete denture with cast gold onlays.

Machine learning enabled multiplex detection of periodontal pathogens by surface-enhanced Raman spectroscopy.

Periodontitis is a chronic inflammation of the periodontium caused by a persistent bacterial infection, resulting in destruction of the supporting structures of teeth. Analysis of microbial composition in saliva can inform periodontal status. Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Streptococcus mutans (Sm) are among reported periodontal pathogens, and were used as model systems in this study. Our atomic force microscopic (AFM) study revealed that these pathogens are biological nanorods with dimensions of 0.6-1.1 µm in length and 500-700 nm in width. Current bacterial detection methods often involve complex preparation steps and require labeled reporting motifs. Employing surface-enhanced Raman spectroscopy (SERS), we revealed cell-type specific Raman signatures of these pathogens for label-free detection. It overcame the complexity associated with spectral overlaps among different bacterial species, relying on high signal-to-noise ratio (SNR) spectra carefully collected from pure species samples. To enable simple, rapid, and multiplexed detection, we harnessed advanced machine learning techniques to establish predictive models based on a large set of raw spectra of each bacterial species and their mixtures. Using these models, given a raw spectrum collected from a bacterial suspension, simultaneous identification of all three species in the test sample was achieved at 95.6 % accuracy. This sensing modality can be applied to multiplex detection of a broader range and a larger set of periodontal pathogens, paving the way for hassle-free detection of oral bacteria in saliva with little to no sample preparation.

DAYWAKE implicates novel roles for circulating lipid-binding proteins as extracerebral regulators of daytime wake-sleep behavior.

Sleep during the midday, commonly referred to as siesta, is a common trait of animals that mainly sleep during the night. Work using Drosophila led to the identification of the daywake (dyw) gene, found to have anti-siesta activity. Herein, we show that the DYW protein undergoes signal peptide-dependent secretion, is present in the circulatory system, and accumulates in multiple organs, but, surprisingly, it is not detected in the brain where wake-sleep centers are located. The abundance of DYW in adult flies is regulated by age, sex, temperature, and the splicing efficiency of a nearby thermosensitive intron. We suggest that DYW regulates daytime wake-sleep balance in an indirect, extracerebral manner, via a multi-organ network that interfaces with the circulatory system.

Fretting-corrosion Apparatus with Low Magnitude Micro-motion (≤5 µm): Development and Preliminary Outcome.

Fretting-corrosion is one of the failure processes in many applications, including biomedical implants. For example, the modern design of hip implants with multiple components offers better flexibility and inventory storage. However, it will trigger the fretting at the implant interfaces with a small displacement amplitude (< 5 µm) and usually in a partial slip region. Although many studies have been reported on the fretting, they have high displacement amplitude and are in the gross slip region. It is imperative to have an apparatus to overcome such limitations, specifically for hip implant applications. Therefore, this study describes the development of a fretting-corrosion apparatus with low micro-motion (≤ 5 µm) that can simultaneously monitor the corrosion process. Initial experiments with Ti6Al4V-Ti6Al4V in 0.9% saline, Ti6Al4V-Ti6Al4V in bovine calf serum (BCS), and ZrO2-Ti6Al4V in BCS were conducted to validate the system. As a result, the fretting regime of all groups remained partially slip region throughout the 3600 cycles, and the possible failure mechanisms are proposed in this manuscript.

Photofunctionalization of Dental Implant Surfaces - A Histomorphometric Animal Study.

Aims: To compare and evaluate the degree of osseointegration of UV-treated (photo functionalized) and non-treated dental implants surface coated with Calcium phosphate using the Resorbable Blast Media (RBM) technique in an animal model. Settings and Design: Evaluative-Animal study design. Materials and Methods: Six titanium dental implants of diameter 3.2 mm and length of 8 mm with Calcium phosphate coated surface using RBM or resorbable blast media technology (Implant Genesis: Genesis Normo Implant system) were placed epicrestally into the proximal femoral condyle of New Zealand white female rabbits such that each animal received two implants. Before implantation, one out of the two dental implants was photo functionalized with intense UV light for 15 minutes. After twelve weeks of healing, the animals were euthanized and the harvested specimens were analyzed using histomorphometric light microscopy to assess two parameters bone-implant contact and bone volume density. Statistical Analysis Used: SPSS version 23. P less than 0.05 is considered statistically significant. Tests used ANOVA followed by Tukey post hoc test. Results: All six dental implants were osseointegrated. The overall mean bone-implant contact area (BIC) was 57.76% for non-UV treated whereas 88.4367% for UV-treated dental implants. The overall mean bone volume density (BVD) was 32.2333% for non-UV treated whereas 67.7533% for UV-treated dental implants. Conclusion: Significant effects were observed on the osseointegration of dental titanium implants within twelve weeks after UV photo functionalization. The UV photo functionalization of dental titanium implants in the current study significantly altered the BIC and bone density on osseointegration when observed over twelve weeks.

Proteomic-based electrochemical non-invasive biosensor for early breast cancer diagnosis.

Breast cancer is the second highest cause of cancer-related mortality in women worldwide and in the United States, accounting for around 571,000 deaths per year. Early detection of breast cancer increases treatment results and the possibility of a cure. While existing diagnostic modalities such as mammography, ultrasound, and biopsy exist, some are prohibitively expensive, uncomfortable, time-consuming, and have limited sensitivity, necessitating the development of a cost-effective, rapid, and highly sensitive approach such as an electrochemical biosensor. Our research focuses on detecting breast cancer patients using the ECM1 biomarker, which has higher expression in synthetic urine. Our study has two primary objectives: (i) Diverse ECM1 protein concentrations are measured using electrochemical impedance spectroscopy and ELISA. Establishing a standard curve for the electrochemical biosensor by calibrating ECM-1 protein levels using electrochemical impedance spectroscopy. (ii) Validation of the effectiveness of the electrochemical biosensor. This aim entails testing the unknown concentration of ECM1 in the synthetic urine to ensure the efficiency of the biosensor to detect the biomarker in the early stages. The results show that the synthetic urine solution's ECM-1 detection range ranges from 1 pg/ml to 500 ng/ml. This shows that by detecting changes in ECM-1 protein levels in patient urine, the electrochemical biosensor can consistently diagnose breast cancer in its early stages or during increasing recurrence. Our findings highlight the electrochemical biosensor's efficacy in detecting early-stage breast cancer biomarkers (ECM-1) in patient urine. Further studies will be conducted with patient samples and develop handheld hardware for patient usage.

Care Delivery for Patients with Leiomyomas: Failures, Real-Life Experiences, Analysis of Barriers, and Proposed Restorative Remedies.

In this narrative review, we describe historical and contemporary influences that prevent patients with fibroids from getting appropriate medical care. Using patient stories as examples, we highlight how misogyny on all levels hurts patients and prevents medical teams from doing their best. Importantly, inequity and disparities result in massive gaps in care delivery. We suggest that we, as gynecologists and surgeons, must join public discourse on this topic to highlight the inadequacies of care delivery and the reasons behind it, suggest potential solutions, and join patients and communities in formulating and implementing remedies.

High-Sensitivity Cardiac Troponin for Risk Assessment in Patients With Chronic Coronary Artery Disease.

BACKGROUND: Cardiac troponin is used for risk stratification of patients with acute coronary syndromes; however, the role of testing in other settings remains unclear. OBJECTIVES: The aim of this study was to evaluate whether cardiac troponin testing could enhance risk stratification in patients with chronic coronary artery disease independent of disease severity and conventional risk measures. METHODS: In a prospective cohort of consecutive patients with symptoms suggestive of stable angina attending for outpatient coronary angiography, high-sensitivity cardiac troponin I was measured before angiography, and clinicians were blinded to the results. The primary outcome was myocardial infarction or cardiovascular death during follow-up. RESULTS: In 4,240 patients (age 66 years [IQR: 59-73 years], 33% female), coronary artery disease was identified in 3,888 (92%) who had 255 (6%) primary outcome events during a median follow-up of 2.4 years (IQR: 1.3-3.6 years). In patients with coronary artery disease, troponin concentrations were 2-fold higher in those with an event compared with those without (6.7 ng/L [IQR: 3.2-14.2 ng/L] vs 3.3 ng/L [IQR: 1.7-6.6 ng/L]; P < 0.001). Troponin concentrations were associated with the primary outcome after adjusting for cardiovascular risk factors and coronary artery disease severity (adjusted HR: 2.3; 95% CI: 1.7-3.0, log10 troponin; P < 0.001). A troponin concentration >10 ng/L identified patients with a 50% increase in the risk of myocardial infarction or cardiovascular death. CONCLUSIONS: In patients with chronic coronary artery disease, cardiac troponin predicts risk of myocardial infarction or cardiovascular death independent of cardiovascular risk factors and disease severity. Further studies are required to evaluate whether routine testing could inform the selection of high-risk patients for treatment intensification. (Myocardial Injury in Patients Referred for Coronary Angiography [MICA]; ISRCTN15620297).