Graphene Oxide-Based Nanocomposites for Stereolithography (SLA) 3D Printing: Comprehensive Mechanical Characterization under Combined Loading Modes.

Additive manufacturing, particularly Stereolithography (SLA), has gained widespread attention thanks to its ability to produce intricate parts with high precision and customization capacity. Nevertheless, the inherent low mechanical properties of SLA-printed parts limit their use in high-value applications. One approach to enhance these properties involves the incorporation of nanomaterials, with graphene oxide (GO) being a widely studied option. However, the characterization of SLA-printed GO nanocomposites under various stress loadings remains underexplored in the literature, despite being essential for evaluating their mechanical performance in applications. This study aimed to address this gap by synthesizing GO and incorporating it into a commercial SLA resin at different concentrations (0.2, 0.5, and 1 wt.%). Printed specimens were subjected to pure tension, combined stresses, and pure shear stress modes for comprehensive mechanical characterization. Additionally, failure criteria were provided using the Drucker--Prager model.

Impact of posture and CPAP on nasal airflow.

Obstructive sleep apnea (OSA) patients who use continuous positive airway pressure (CPAP) often complain of nasal dryness and nasal obstruction as side effects of CPAP. The physiological mechanisms by which CPAP may cause nasal dryness and nasal obstruction remain poorly understood. It has been hypothesized that CPAP interferes with the nasal cycle, abolishing the resting phase of the cycle and leading to nasal dryness. We performed rhinomanometry measurements in 31 OSA patients sitting, laid supine, and supine after 10 min of CPAP at 10 cmH2O. A posture change from sitting to supine led to more symmetric airflow partitioning between the left and right nostrils in the supine position. CPAP did not have a significant impact on nasal resistance, unilateral airflows, or airflow partitioning. Our results suggest that airflow partitioning becomes more symmetric immediately after changing to a supine position, while CPAP had no effect on nasal airflow, thus preserving the nearly symmetric airflow partitioning achieved after the posture change.

Effects of Mucosal Decongestion on Nasal Aerodynamics: A Pilot Study.

OBJECTIVE: Mucosal decongestion with nasal sprays is a common treatment for nasal airway obstruction. However, the impact of mucosal decongestion on nasal aerodynamics and the physiological mechanism of nasal airflow sensation are incompletely understood. The objective of this study is to compare nasal airflow patterns in nasal airway obstruction (NAO) patients with and without mucosal decongestion and nondecongested healthy subjects. STUDY DESIGN: Cross-sectional study of a convenience sample. SETTING: Academic tertiary medical center. METHODS: Forty-five subjects were studied (15 nondecongested healthy subjects, 15 nondecongested NAO patients, and 15 decongested NAO patients). Three-dimensional models of the nasal anatomy were created from computed tomography scans. Steady-state simulations of airflow and heat transfer were conducted at 15 L/min inhalation rate using computational fluid dynamics. RESULTS: In the narrow side of the nose, unilateral nasal resistance was similar in decongested NAO patients and nondecongested healthy subjects, but substantially higher in nondecongested NAO patients. The vertical airflow distribution within the nasal cavity (inferior vs middle vs superior) was also similar in decongested NAO patients and nondecongested healthy subjects, but nondecongested NAO patients had substantially less middle airflow. Mucosal cooling, quantified by the surface area where heat flux exceeds 50 W/m2, was significantly higher in decongested NAO patients than in nondecongested NAO patients. CONCLUSION: This pilot study suggests that mucosal decongestion improves objective measures of nasal airflow, which is consistent with improved subjective sensation of nasal patency after decongestion.

Estimation of Nasal Airway Cross-sectional Area From Endoscopy Using Depth Maps: A Proof-of-Concept Study.

OBJECTIVE: Endoscopy is routinely used to diagnose obstructive airway diseases. Currently, endoscopy is only a visualization technique and does not allow quantification of airspace cross-sectional areas (CSAs). This pilot study tested the hypothesis that CSAs can be accurately estimated from depth maps created from virtual endoscopy videos. STUDY DESIGN: Cross-sectional. SETTING: Academic tertiary medical center. METHODS: Virtual endoscopy and depth map videos of the nasal cavity were digitally created based on anatomically accurate three-dimensional (3D) models built from computed tomography scans of 30 subjects. A software tool was developed to outline the airway perimeter and estimate the airspace CSA from the depth maps. Two otolaryngologists used the software tool to estimate the nasopharynx CSA and the nasal valve minimal CSA (mCSA) in the left and right nasal cavities. Model validation statistics were performed. RESULTS: Nasopharynx CSA had a median percent error of 3.7% to 4.6% when compared to the true values measured in the 3D models. Nasal valve mCSA had a median percent error of 22.7% to 33.6% relative to the true values. Raters successfully used the software tool to identify subjects with nasal valve stenosis (ie, mCSA < 0.20 cm2) with a sensitivity of 83.3%, specificity ≥ 90.7%, and classification accuracy ≥ 90.0%. Interrater and intrarater agreements were high. CONCLUSION: This study demonstrates that airway CSAs in 3D models can be accurately estimated from depth maps. The development of artificial intelligence algorithms to compute depth maps may soon allow the quantification of airspace CSAs from clinical endoscopies.

Sterile inflammation induces vasculopathy and chronic lung injury in murine sickle cell disease.

Murine sickle cell disease (SCD) results in damage to multiple organs, likely mediated first by vasculopathy. While the mechanisms inducing vascular damage remain to be determined, nitric oxide bioavailability and sterile inflammation are both considered to play major roles in vasculopathy. Here, we investigate the effects of high mobility group box-1 (HMGB1), a pro-inflammatory damage-associated molecular pattern (DAMP) molecule on endothelial-dependent vasodilation and lung morphometrics, a structural index of damage in sickle (SS) mice. SS mice were treated with either phosphate-buffered saline (PBS), hE-HMGB1-BP, an hE dual-domain peptide that binds and removes HMGB1 from the circulation via the liver, 1-[4-(aminocarbonyl)-2-methylphenyl]-5-[4-(1H-imidazol-1-yl)phenyl]-1H-pyrrole-2-propanoic acid (N6022) or N-acetyl-lysyltyrosylcysteine amide (KYC) for three weeks. Human umbilical vein endothelial cells (HUVEC) were treated with recombinant HMGB1 (r-HMGB1), which increases S-nitrosoglutathione reductase (GSNOR) expression by ∼80%, demonstrating a direct effect of HMGB1 to increase GSNOR. Treatment of SS mice with hE-HMGB1-BP reduced plasma HMGB1 in SS mice to control levels and reduced GSNOR expression in facialis arteries isolated from SS mice by ∼20%. These changes were associated with improved endothelial-dependent vasodilation. Treatment of SS mice with N6022 also improved vasodilation in SS mice suggesting that targeting GSNOR also improves vasodilation. SCD decreased protein nitrosothiols (SNOs) and radial alveolar counts (RAC) and increased GSNOR expression and mean linear intercepts (MLI) in lungs from SS mice. The marked changes in pulmonary morphometrics and GSNOR expression throughout the lung parenchyma in SS mice were improved by treating with either hE-HMGB1-BP or KYC. These data demonstrate that murine SCD induces vasculopathy and chronic lung disease by an HMGB1- and GSNOR-dependent mechanism and suggest that HMGB1 and GSNOR might be effective therapeutic targets for reducing vasculopathy and chronic lung disease in humans with SCD.

Inhaled fosamprenavir for laryngopharyngeal reflux: Toxicology and fluid dynamics modeling.

Objectives: Approximately 25% of Americans suffer from laryngopharyngeal reflux (LPR), a disease for which no effective medical therapy exists. Pepsin is a predominant source of damage during LPR and a key therapeutic target. Fosamprenavir (FOS) inhibits pepsin and prevents damage in an LPR mouse model. Inhaled FOS protects at a lower dose than oral; however, the safety of inhaled FOS is unknown and there are no inhalers for laryngopharyngeal delivery. A pre-Good Lab Practice (GLP) study of inhaled FOS was performed to assess safety and computational fluid dynamics (CFD) modeling used to predict the optimal particle size for a laryngopharyngeal dry powder inhaler (DPI). Methods: Aerosolized FOS, amprenavir (APR), or air (control) were provided 5 days/week for 4 weeks (n = 6) in an LPR mouse model. Organs (nasal cavity, larynx, esophagus, trachea, lung, liver, heart, and kidney) were assessed by a pathologist and bronchoalveolar lavage cytokines and plasma cardiotoxicity markers were assessed by Luminex assay. CFD simulations were conducted in a model of a healthy 49-year-old female. Results: No significant increase was observed in histologic lesions, cytokines, or cardiotoxicity markers in FOS or APR groups relative to the control. CFD predicted that laryngopharyngeal deposition was maximized with aerodynamic diameters of 8.1-11.5 µm for inhalation rates of 30-60 L/min. Conclusions: A 4-week pre-GLP study supports the safety of inhaled FOS. A formal GLP assessment is underway to support a phase I clinical trial of an FOS DPI for LPR. Level of Evidence: NA.

Prenatal Findings in Postnatal Cases of Disorders of Sex Development: Experience from a Tertiary-Specialized Center in Brazil.

INTRODUCTION AND OBJECTIVE: Prenatal suspicion of disorders/differences of sex development (DSDs) is a relatively new phenomenon. The aim of this study was to review the prenatal findings of DSD cases postnatally diagnosed in our tertiary referral center. METHODS: We evaluated 57 DSD cases with sex ambiguity who had undergone prenatal ultrasound with phenotypic sex assessment and/or cell-free fetal DNA (cffDNA) for genotypic sex assessment. RESULTS: Prenatal cffDNA had been performed in 32 cases, being positive (suggestive of male genotypic sex) in 26 and negative (suggestive of female genotypic sex) in 6. Five with cffDNA negative had a prenatal ultrasound indicating female external genitalia, in turn, in those with cffDNA positive, only two had a prenatal ultrasound indicating male external genitalia. Our postnatal data showed that when external genitalia were female or poorly virilized, prenatal ultrasound indicated female sex, but in cases of higher degree of virilization, ultrasound showed similar rates of male, female, or undetermined sex. Regarding the karyotype, our data showed those with XY karyotype had positive cffDNA, those with XX karyotype had negative cffDNA, and all five with sex chromosome anomalies had positive cffDNA because they were 45,X/46,XY. We suggested an algorithm to investigate these cases during gestation, including evaluation of uterus, fetal growth, and malformations. CONCLUSION: We suggest that the parents should be counseled prenatally by a dedicated multidisciplinary team with experience in DSD management and evaluated as soon as possible after birth.

The association of myocardial strain with cardiac magnetic resonance and clinical outcomes in patients with acute myocarditis.

Introduction: The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients. Material and methods: This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction. Results: The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858-0.982, p = 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046-1.325, p = 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031-1.334, p = 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022-1.524, p = 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed. Conclusion: Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients.

Quantifying strategies to minimize aerosol dispersion in dental clinics.

Many dental procedures are aerosol-generating and pose a risk for the spread of airborne diseases, including COVID-19. Several aerosol mitigation strategies are available to reduce aerosol dispersion in dental clinics, such as increasing room ventilation and using extra-oral suction devices and high-efficiency particulate air (HEPA) filtration units. However, many questions remain unanswered, including what the optimal device flow rate is and how long after a patient exits the room it is safe to start treatment of the next patient. This study used computational fluid dynamics (CFD) to quantify the effectiveness of room ventilation, an HEPA filtration unit, and two extra-oral suction devices to reduce aerosols in a dental clinic. Aerosol concentration was quantified as the particulate matter under 10 µm (PM10) using the particle size distribution generated during dental drilling. The simulations considered a 15 min procedure followed by a 30 min resting period. The efficiency of aerosol mitigation strategies was quantified by the scrubbing time, defined as the amount of time required to remove 95% of the aerosol released during the dental procedure. When no aerosol mitigation strategy was applied, PM10 reached 30 µg/m3 after 15 min of dental drilling, and then declined gradually to 0.2 µg/m3 at the end of the resting period. The scrubbing time decreased from 20 to 5 min when the room ventilation increased from 6.3 to 18 air changes per hour (ACH), and decreased from 10 to 1 min when the flow rate of the HEPA filtration unit increased from 8 to 20 ACH. The CFD simulations also predicted that the extra-oral suction devices would capture 100% of the particles emanating from the patient's mouth for device flow rates above 400 L/min. In summary, this study demonstrates that aerosol mitigation strategies can effectively reduce aerosol concentrations in dental clinics, which is expected to reduce the risk of spreading COVID-19 and other airborne diseases.

A workflow for viewing biomedical computational fluid dynamics results and corresponding data within virtual and augmented reality environments.

Researchers conducting computational fluid dynamics (CFD) modeling can spend weeks obtaining imaging data, determining boundary conditions, running simulations and post-processing files. However, results are typically viewed on a 2D display and often at one point in time thus reducing the dynamic and inherently three-dimensional data to a static image. Results from different pathologic states or cases are rarely compared in real-time, and supplementary data are seldom included. Therefore, only a fraction of CFD results are typically studied in detail, and associations between mechanical stimuli and biological response may be overlooked. Virtual and augmented reality facilitate stereoscopic viewing that may foster extraction of more information from CFD results by taking advantage of improved depth cues, as well as custom content development and interactivity, all within an immersive approach. Our objective was to develop a straightforward, semi-automated workflow for enhanced viewing of CFD results and associated data in an immersive virtual environment (IVE). The workflow supports common CFD software and has been successfully completed by novice users in about an hour, demonstrating its ease of use. Moreover, its utility is demonstrated across clinical research areas and IVE platforms spanning a range of cost and development considerations. We are optimistic that this advancement, which decreases and simplifies the steps to facilitate more widespread use of immersive CFD viewing, will foster more efficient collaboration between engineers and clinicians. Initial clinical feedback is presented, and instructional videos, manuals, templates and sample data are provided online to facilitate adoption by the community.

Mandibular advancement reduces pharyngeal collapsibility by enlarging the airway rather than affecting velopharyngeal compliance.

Mandibular advancement devices (MADs) are frequently prescribed for obstructive sleep apnea (OSA) patients, but approximately one third of patients experience no therapeutic benefit. Understanding the mechanisms by which MADs prevent pharyngeal collapse may help optimize MAD therapy. This study quantified the relative contributions of changes in airspace cross-sectional area (CSA) versus changes in velopharyngeal compliance in determining MAD efficacy. Sixteen patients with moderate to severe OSA (mean apnea-hypopnea index of 32 ± 15 events/h) underwent measurements of the velopharyngeal closing pressure (PCLOSE ) during drug induced sedated endoscopy (DISE) via stepwise reductions in nasal mask pressure and recording of the intraluminal pressure with a catheter. Airspace CSA was estimated from video endoscopy. Pharyngeal compliance was defined as the slope of the area-pressure relationship of the velopharyngeal airspace. MAD therapy reduced PCLOSE from a median of 0.5 cmH2 O pre-advancement to a median of -2.6 cmH2 O post-advancement (p = 0.0009), increased the minimal CSA at the velopharynx by approximately 20 mm2 (p = 0.0067), but did not have a statistically significant effect on velopharyngeal compliance (p = 0.23). PCLOSE had a strong correlation with CSA but did not correlate with velopharyngeal compliance. Our results suggest that MADs reduce velopharyngeal collapsibility by increasing airway size as opposed to affecting velopharyngeal compliance. This contradicts the speculation of previous literature that the effectiveness of MADs is partially due to a reduction in velopharyngeal compliance resulting from stretching of the soft palate. These findings suggest that quantification of velopharyngeal CSA pre- and post-MAD advancement has potential as a biomarker to predict the success of MAD therapy.

Anatomical determinants of upper airway collapsibility in obstructive sleep apnea: A systematic review and meta-analysis.

Upper airway (UA) collapsibility is one of the key factors that determine the severity of obstructive sleep apnea (OSA). Interventions for OSA are aimed at reducing UA collapsibility, but selecting the optimal alternative intervention for patients who fail CPAP is challenging because currently no validated method predicts how anatomical changes affect UA collapsibility. The gold standard objective measure of UA collapsibility is the pharyngeal critical pressure (Pcrit). A systematic literature review and meta-analysis were performed to identify the anatomical factors with the strongest correlation with Pcrit. A search using the PRISMA methodology was performed on PubMed for English language scientific papers that correlated Pcrit to anatomic variables and OSA severity as measured by the apnea-hypopnea index (AHI). A total of 29 papers that matched eligibility criteria were included in the quantitative synthesis. The meta-analysis suggested that AHI has only a moderate correlation with Pcrit (estimated Pearson correlation coefficient r = 0.46). The meta-analysis identified four key anatomical variables associated with UA collapsibility, namely hyoid position (r = 0.53), tongue volume (r = 0.51), pharyngeal length (r = 0.50), and waist circumference (r = 0.49). In the future, biomechanical models that quantify the relative importance of these anatomical factors in determining UA collapsibility may help identify the optimal intervention for each patient. Many anatomical and structural factors such as airspace cross-sectional areas, epiglottic collapse, and palatal prolapse have inadequate data and require further research.

Morphological integration during postnatal ontogeny: implications for evolutionary biology.

How covariance patterns of phenotypes change during development is fundamental for a broader understanding of evolution. There is compelling evidence that mammalian cranium covariance patterns change during ontogeny. However, it is unclear to what extent variation in covariance patterns during ontogeny can impact the response to selection. To tackle this question, we explored: (a) the extent to which covariance patterns change during postnatal ontogeny; (b) in which ontogenetic stages covariance patterns differ the most; and (c) the extent to which the phenotypic covariance pattern at different ontogenetic stages can be explained by the same processes determining additive genetic covariance. We sampled the postnatal ontogenetic series for both marsupials and placentals. Within each ontogenetic series, we compared covariance matrices (P-matrices) at different ontogenetic stages. Furthermore, we compared these P-matrices to two target matrices [adult P-matrix and an additive genetic covariance matrix (G-matrix)]. Our results show that for all ontogenetic series, covariance patterns from weaning onward are conserved and probably shaped by the same processes determining the G-matrix. We conclude that irrespective of eventual differences in how selection operates during most of the postnatal ontogeny, the net response to such pressures will probably not be affected by ontogenetic differences in the covariance pattern.

Remotely piloted aircraft-based automated vertical surface survey.

Remotely Piloted Aircrafts (RPAs) are commonly used as a platform for collecting images which can be processed with Structure from Motion-Multi View Stereo (SfM-MVS) to generate 3D models. However, mobile applications for mapping planning are not designed for image acquisition of vertical surfaces, such as quarry walls or large cliffs, leaving the user to a manual flight operation, which does not ensure optimal overlap between images. Here we describe a workflow, based on the Litchi App, for automated RPA missions designed to acquire images of vertical surfaces or structures.•An easy-to-follow 8 steps method to survey vertical surfaces using a Remotely Piloted Aircraft.•It can be applied to outcrops, quarry walls, high cliffs and virtually any other type of vertical surface.•The workflow is flexible and can be adapted to a variety of target configurations and user-defined parameters.

Methods Applied to the Diagnosis of Cattle Trypanosoma vivax Infection: An Overview of the Current State of the Art.

Bovine trypanosomiasis caused by Trypanosoma vivax is a relevant disease in domestic ungulates in Latin America, causing different types of livestock losses, particularly in African and South American countries, leading to loss of millions of dollars/year related to dairy and meat production. In addition, T. vivax trypanosomiasis requires intensive veterinary care. While vector control is a feasible measure to manage disease spreading, the search for accurate diagnostic tools still represents a gap in routine veterinary practices and a challenge for the scientific community. The parasite is mechanically transmitted by fomites or by the saliva of haematophagous flies, such as Stomoxys sp. and Tabanus sp., infecting cattle as well as a number of animal hosts. The main symptoms of T. vivax bovine trypanosomiasis are apathy, fever, restricted growth, miscarriage, progressive weakness, neurological signs, pale mucous, loss of appetite, lethargy, and substantial weight loss. In most cases, the presence of animals with subclinical infections, nonspecific symptoms and without apparent parasitaemia presents a challenge when making a diagnosis, which requires accurate methods. Herein, we review state of the art concerning current methods available for the diagnosis of T. vivax bovine trypanosomiasis, focusing on clinical, parasitological, immunological and molecular approaches, highlighting the main features of each method, including "pros and cons". Overall, combining several diagnostic techniques is a better choice since it leads to fewer false negative results and contributes to better disease control.

Early emotional memories and bonding as predictors of short-term and long-term outcome in adults with generalized anxiety disorder.

The impact of childhood experiences on the development of psychopathology is well established in the literature. Few studies, however, have assessed parental bonding during childhood as a predictor of response to anxiety disorders treatment. The aim of the study was to examine whether emotional memories of childhood parenting could predict short-term and long-term outcome in three different interventions for patients with generalized anxiety disorder (GAD): mindfulness-based intervention (Body in Mind Training [BMT]), fluoxetine (FLX), and an active control group (quality of life [QoL]). A total of 124 participants from a randomized controlled trial for GAD treatment were evaluated pre- and post-treatment and after 18 months. Patients were assessed for the severity of GAD symptoms (GAD-7, PSWQ, and DERS), early memories of warmth and safeness (EMWSS), and recall of perceived threat and subordination/submission in childhood (ELES). Negative childhood memories predicted a greater reduction in anxiety symptoms on BMT treatment compared to FLX and QoL, whereas positive childhood memories predicted more symptomatic improvement in the QoL group. Our findings suggest that individuals with GAD who have early memories of subordination and threat appear to benefit more from interventions that focus on developing emotion-regulation strategies and enhancing self-compassion, such as mindfulness-based interventions.