Evaluation of a Fully Digital, In-House Virtual Surgical Planning Workflow for Bimaxillary Orthognathic Surgery.

BACKGROUND: The advantages of virtual surgical planning (VSP) for orthognathic surgery are clear. Previous studies have evaluated in-house VSP; however, few fully digital, in-house protocols for orthognathic surgery have been studied. PURPOSE: The purpose of this study was to evaluate the difference between the virtual surgical plan and actual surgical outcome for orthognathic surgery using a fully digital, in-house VSP workflow. STUDY DESIGN, SETTING, SAMPLE: This is a prospective cohort study from September 2020 to November 2022 of patients at the Victoria General Hospital in Halifax, NS, Canada who underwent bimaxillary orthognathic surgery. Patients were excluded if they had previously undergone orthognathic surgery or were diagnosed with a craniofacial syndrome. MAIN OUTCOME VARIABLES: The primary outcome variables were the mean 3-dimensional (3D) (Euclidean) distance error, as well as mean error and mean absolute error in the transverse (x axis), vertical (y axis), and anterior-posterior (z axis) dimensions. COVARIATES: Covariates included age, sex, and surgical sequence (mandible-first or maxilla-first). ANALYSES: The primary outcome was tested using Z and t critical value confidence intervals. The P value was set at .05. The 3D distance error for mandible-first and maxilla-first groups was compared using a 2-sample t-test as well as analysis of variance. RESULTS: The study sample included 52 subjects (24 males and 28 females) with a mean age of 27.7 (± 12.1) years. Forty three subjects underwent mandible-first surgery and 9 maxilla-first surgery. The mean absolute distance error was largest in the anterior-posterior dimension for all landmarks (except posterior nasal spine, left condyle, and gonion) and exceeded the threshold for clinical acceptability (2 mm) in 16 of 23 landmarks. Additionally, mean distance error in the anterior-posterior dimension was negative for all landmarks, indicating deficient movement in that direction. The effect of surgical sequence on 3D distance error was not statistically significant (P = .37). CONCLUSION AND RELEVANCE: In general, the largest contributor to mean 3D distance error was deficient movement in the anterior-posterior direction. Otherwise, mean absolute distance error in the vertical and transverse dimensions was clinically acceptable (< 2 mm). These findings were felt to be valuable for treatment planning purposes when using a fully digital, in-house VSP workflow.

Does Sub-Anesthetic Ketamine Provide Postoperative Analgesia for Third Molar Surgery?

PURPOSE: Despite ketamine's effectiveness as an anesthetic and its known analgesic properties, the role of ketamine in postoperative pain after third molar surgery remains unclear. Therefore, this study aimed to investigate whether patients undergoing third molar surgery who received a sub-anesthetic preoperative dose of intravenous ketamine would experience less postoperative pain. MATERIALS AND METHODS: We implemented a randomized, double-blinded, placebo-controlled trial. The study sample consisted of participants undergoing third molar surgery with procedural sedation anesthesia. Participants were randomized to receive a preoperative intravenous dose of ketamine or placebo, as predictor variables. The primary outcome variable was postoperative pain intensity determined by a 10-point visual analog scale at 6-hour intervals over a period of 48 hours. The secondary outcome variable was the quantity of postoperative non-opioid and opioid consumption. Other variables included the extent and difficulty of surgery performed, patient satisfaction, gender, and age. Data analysis involved descriptive statistics, multivariate analysis, and regression analysis. The P value was set at .05. RESULTS: A total of 134 participants were randomly enrolled into either the ketamine group (n = 74, 55.2%) or placebo group (n = 60, 44.8%). No statistically significant differences in the distribution of study variables were found between the groups. A small yet statistically significant (P < .05) difference was noted in the median pain score at 6 hours postoperatively, with the ketamine group experiencing more pain. However, no further differences were detected at any postoperative time between the 2 groups. Similar results were obtained after adjusting for age, gender, and surgical difficulty. No difference in the amount of postoperative non-opioid or opioid medication use was found between the 2 groups. CONCLUSIONS: This study did not find evidence that a preoperative sub-anesthetic dose of ketamine could reduce pain after third molar surgery or have any effects on non-opioid or opioid analgesic consumption. Nevertheless, ketamine remains a valuable option among sedation medications for oral and maxillofacial surgeons.

Characterization of a Quadrotor Unmanned Aircraft System for Aerosol-Particle-Concentration Measurements.

High-spatial-resolution, near-surface vertical profiling of atmospheric chemical composition is currently limited by the availability of experimental platforms that can sample in constrained environments. As a result, measurements of near-surface gradients in trace gas and aerosol particle concentrations have been limited to studies conducted from fixed location towers or tethered balloons. Here, we explore the utility of a quadrotor unmanned aircraft system (UAS) as a sampling platform to measure vertical and horizontal concentration gradients of trace gases and aerosol particles at high spatial resolution (1 m) within the mixed layer (0-100 m). A 3D Robotics Iris+ autonomous quadrotor UAS was outfitted with a sensor package consisting of a two-channel aerosol optical particle counter and a CO2 sensor. The UAS demonstrated high precision in both vertical (±0.5 m) and horizontal positions (±1 m), highlighting the potential utility of quadrotor UAS drones for aerosol- and trace-gas measurements within complex terrain, such as the urban environment, forest canopies, and above difficult-to-access areas such as breaking surf. Vertical profiles of aerosol particle number concentrations, acquired from flights conducted along the California coastline, were used to constrain sea-spray aerosol-emission rates from coastal wave breaking.

Volatility of primary organic aerosol emitted from light duty gasoline vehicles.

Primary organic aerosol (POA) emitted from light duty gasoline vehicles (LDGVs) exhibits a semivolatile behavior in which heating the aerosol and/or diluting the aerosol leads to partial evaporation of the POA. A single volatility distribution can explain the median evaporation behavior of POA emitted from LDGVs but this approach is unable to capture the full range of measured POA volatility during thermodenuder (TD) experiments conducted at atmospherically relevant concentrations (2-5 µg m(-3)). Reanalysis of published TD data combined with analysis of new measurements suggest that POA emitted from gasoline vehicles is composed of two types of POA that have distinctly different volatility distributions: one low-volatility distribution and one medium-volatility distribution. These correspond to fuel combustion-derived POA and motor oil POA, respectively. Models that simultaneously incorporate both of these distributions are able to reproduce experimental results much better (R(2) = 0.94) than models that use a single average or median distribution (R(2) = 0.52). These results indicate that some fraction of POA emitted from LDGVs is essentially nonvolatile under typical atmospheric dilution levels. Roughly 50% of the vehicles tested in the current study had POA emissions dominated by fuel combustion products (essentially nonvolatile). Further testing is required to determine appropriate fleet-average emissions rates of the two POA types from LDGVs.

Development of a hybrid pollution index for heavy metals in marine and estuarine sediments.

Heavy metal pollution of sediments is a growing concern in most parts of the world, and numerous studies focussed on identifying contaminated sediments by using a range of digestion methods and pollution indices to estimate sediment contamination have been described in the literature. The current work provides a critical review of the more commonly used sediment digestion methods and identifies that weak acid digestion is more likely to provide guidance on elements that are likely to be bioavailable than other traditional methods of digestion. This work also reviews common pollution indices and identifies the Nemerow Pollution Index as the most appropriate method for establishing overall sediment quality. Consequently, a modified Pollution Index that can lead to a more reliable understanding of whole sediment quality is proposed. This modified pollution index is then tested against a number of existing studies and demonstrated to give a reliable and rapid estimate of sediment contamination and quality.

Real-time emission factor measurements of isocyanic acid from light duty gasoline vehicles.

Exposure to gas-phase isocyanic acid (HNCO) has been previously shown to be associated with the development of atherosclerosis, cataracts and rheumatoid arthritis. As such, accurate emission inventories for HNCO are critical for modeling the spatial and temporal distribution of HNCO on a regional and global scale. To date, HNCO emission rates from light duty gasoline vehicles, operated under driving conditions, have not been determined. Here, we present the first measurements of real-time emission factors of isocyanic acid from a fleet of eight light duty gasoline-powered vehicles (LDGVs) tested on a chassis dynamometer using the Unified Driving Cycle (UC) at the California Air Resources Board (CARB) Haagen-Smit test facility, all of which were equipped with three-way catalytic converters. HNCO emissions were observed from all vehicles, in contrast to the idealized laboratory measurements. We report the tested fleet averaged HNCO emission factors, which depend strongly on the phase of the drive cycle; ranging from 0.46 ± 0.13 mg kg fuel(-1) during engine start to 1.70 ± 1.77 mg kg fuel(-1) during hard acceleration after the engine and catalytic converter were warm. The tested eight-car fleet average fuel based HNCO emission factor was 0.91 ± 0.58 mg kg fuel(-1), within the range previously estimated for light duty diesel-powered vehicles (0.21-3.96 mg kg fuel(-1)). Our results suggest that HNCO emissions from LDGVs represent a significant emission source in urban areas that should be accounted for in global and regional models.

A calvarial osteolytic lesion of probable vascular origin in a Maya juvenile from the Classic Period ( 250-900 CE).

OBJECTIVE: This case study evaluates a focal osteolytic lesion in the right sulcus sinus transversi of an isolated os occipitale. MATERIALS: The os occipitale is from a juvenile from the Cueva de Sangre at the Classic Period (250-900 CE) site of Dos Pilas, Guatemala METHODS: The lesion was examined macroscopically, microscopically, and radiographically. RESULTS: The oval lesion has a well-circumscribed margin, endocranial origin, and involves cortical destruction of the inner and outer tables. Subperiosteal bone reaction around the lesion is present on the ectocranial surface. Skeletal evidence of increased vascularity, diploë expansion, and perimortem fracture near the lesion are not observed. CONCLUSIONS: The lesion appears to reflect a response to the presence of an expansile process that has caused pressure erosion. The anatomical location of the lesion and the endocranial origin suggest a probable vascular anomaly, such as a vascular malformation. SIGNIFICANCE: This case study represents one of the few bioarchaeological evaluations of probable vascular anomaly in a juvenile. As such, it expands our knowledge about vascular anomalies in the past and provides a comparative and core reference for guiding future paleopathological investigations on cranial osteolytic lesions. LIMITATIONS: The skeletal assemblage is commingled and fragmentary preventing the assessment of the distribution of lesions across the skeleton. SUGGESTIONS FOR FUTURE RESEARCH: Further scrutiny of bioarchaeological collections is needed to better understand the distribution of vascular anomalies in the past.

Long-term potentiation-dependent spine enlargement requires synaptic Ca2+-permeable AMPA receptors recruited by CaM-kinase I.

It is well established that long-term potentiation (LTP), a paradigm for learning and memory, results in a stable enlargement of potentiated spines associated with recruitment of additional GluA1-containing AMPA receptors (AMPARs). Although regulation of the actin cytoskeleton is involved, the detailed signaling mechanisms responsible for this spine expansion are unclear. Here, we used cultured mature hippocampal neurons stimulated with a glycine-induced, synapse-specific form of chemical LTP (GI-LTP). We report that the stable structural plasticity (i.e., spine head enlargement and spine length shortening) that accompanies GI-LTP was blocked by inhibitors of NMDA receptors (NMDARs; APV) or CaM-kinase kinase (STO-609), the upstream activator of CaM-kinase I (CaMKI), as well as by transfection with dominant-negative (dn) CaMKI but not dnCaMKIV. Recruitment of GluA1 to the spine surface occurred after GI-LTP and was mimicked by transfection with constitutively active CaMKI. Spine enlargement induced by transfection of GluA1 was associated with synaptic recruitment of Ca(2+)-permeable AMPARs (CP-AMPARs) as assessed by an increase in the rectification index of miniature EPSCs (mEPSCs) and their sensitivity to IEM-1460, a selective antagonist of CP-AMPARs. Furthermore, the increase in spine size and mEPSC amplitude resulting from GI-LTP itself was blocked by IEM-1460, demonstrating involvement of CP-AMPARs. Downstream signaling effectors of CP-AMPARs, identified by suppression of their activation by IEM-1460, included the Rac/PAK/LIM-kinase pathway that regulates spine actin dynamics. Together, our results suggest that synaptic recruitment of CP-AMPARs via CaMKI may provide a mechanistic link between NMDAR activation in LTP and regulation of a signaling pathway that drives spine enlargement via actin polymerization.

Astrocyte metabolism and signaling during brain ischemia.

Brain ischemia results from cardiac arrest, stroke or head trauma. These conditions can cause severe brain damage and are a leading cause of death and long-term disability. Neurons are far more susceptible to ischemic damage than neighboring astrocytes, but astrocytes have diverse and important functions in many aspects of ischemic brain damage. Here we review three main roles of astrocytes in ischemic brain damage. First, we consider astrocyte glycogen stores, which can defend the brain against hypoglycemic brain damage but may aggravate brain damage during ischemia due to enhanced lactic acidosis. Second, we review recent breakthroughs in understanding astrocytic mechanisms of transmitter release, particularly for those transmitters with known roles in ischemic brain damage: glutamate, D-serine, ATP and adenosine. Third, we discuss the role of gap-junctionally connected networks of astrocytes in mediating the spread of damaging molecules to healthy 'bystanders' during infarct expansion in stroke.

Change in modifiable dementia risk factors during COVID-19 lockdown: The experience of over 50s in Tasmania, Australia.

INTRODUCTION: Containment measures implemented to minimize the spread of coronavirus disease 2019 (COVID-19) are reported to be negatively affecting mental health, diet, and alcohol consumption. These factors, as well as poor cardiometabolic health and insufficient physical and cognitive activity, are known to increase the risk of developing dementia. COVID-19 "lockdown" measures may have exacerbated these dementia risk factors among people in mid-to-later life. METHODS: We compared longitudinal data from before (October 2019) and during (April-June 2020) the first COVID-19 lockdown period in Tasmania, Australia. Participants (n = 1671) were 50+ years of age and engaged in a public health program targeting dementia risk reduction, with one-third participating in the Preventing Dementia Massive Open Online Course (PD-MOOC). Regression models were used to assess changes in smoking, alcohol use, body mass index (BMI), diet, physical exercise, cognitive and social activity, anxiety and depression, and management of cholesterol, diabetes, and blood pressure. Where significant changes were noted, the moderating influence of being in current employment, living with others, and completing the PD-MOOC was tested. RESULTS: Although friend networks contracted marginally during lockdown, no detrimental effects on modifiable dementia risk factors were noted. Anxiety levels and alcohol consumption decreased, there was no change in depression scores, and small but significant improvements were observed in cognitive and physical activity, smoking, diet, and BMI. Stronger improvements in cognitive activity were observed among people who were cohabiting (not living alone) and both cognitive activity and adherence to the MIND diet (Mediterranean-DASH diet Intervention for Neurological Delay) improved more for people who participated in the PD-MOOC. DISCUSSION: Longitudinal data did not show widespread negative effects of COVID-19 lockdown on modifiable dementia risk factors in this sample. The results counter the dominant narratives of universal pandemic-related distress and suggest that engaging at-risk populations in proactive health promotion and education campaigns during lockdown events could be a protective public health strategy.

MxB Restricts HIV-1 by Targeting the Tri-hexamer Interface of the Viral Capsid.

The human antiviral protein MxB is a restriction factor that fights HIV infection. Previous experiments have demonstrated that MxB targets the HIV capsid, a protein shell that protects the viral genome. To make the conical-shaped capsid, HIV CA proteins are organized into a lattice composed of hexamer and pentamer building blocks, providing many interfaces for host proteins to recognize. Through extensive biochemical and biophysical studies and molecular dynamics simulations, we show that MxB is targeting the HIV capsid by recognizing the region created at the intersection of three CA hexamers. We are further able to map this interaction to a few CA residues, located in a negatively charged well at the interface between the three CA hexamers. This work provides detailed residue-level mapping of the targeted capsid interface and how MxB interacts. This information could inspire the development of capsid-targeting therapies for HIV.

FEZ1 Is Recruited to a Conserved Cofactor Site on Capsid to Promote HIV-1 Trafficking.

HIV-1 uses the microtubule network to traffic the viral capsid core toward the nucleus. Viral nuclear trafficking and infectivity require the kinesin-1 adaptor protein FEZ1. Here, we demonstrate that FEZ1 directly interacts with the HIV-1 capsid and specifically binds capsid protein (CA) hexamers. FEZ1 contains multiple acidic, poly-glutamate stretches that interact with the positively charged central pore of CA hexamers. The FEZ1-capsid interaction directly competes with nucleotides and inositol hexaphosphate (IP6) that bind at the same location. In addition, all-atom molecular dynamic (MD) simulations establish the molecular details of FEZ1-capsid interactions. Functionally, mutation of the FEZ1 capsid-interacting residues significantly reduces trafficking of HIV-1 particles toward the nucleus and early infection. These findings support a model in which the central capsid hexamer pore is a general HIV-1 cofactor-binding hub and FEZ1 serves as a unique CA hexamer pattern sensor to recognize this site and promote capsid trafficking in the cell.

Comparison of partial extraction reagents for assessing potential bioavailability of heavy metals in sediments.

Assessment of heavy metal bioavailability in sediments is complex because of the number of partial extraction methods available for the assessment and the general lack of certified reference materials. This study evaluates five different extraction methodologies to ascertain the relative strengths and weaknesses of each method. The results are then compared to previously published work to ascertain the most effective partial extraction technique, which was established to dilute (0.75-1M) nitric acid solutions. These results imply that single reagent; weak acid extractions provide a better assessment of potentially bioavailable metals than the chelating agents used in sequential extraction methods.

Weak acid extractable metals in Bramble Bay, Queensland, Australia: temporal behaviour, enrichment and source apportionment.

Sediment samples were taken from six sampling sites in Bramble Bay, Queensland, Australia between February and November in 2012. They were analysed for a range of heavy metals including Al, Fe, Mn, Ti, Ce, Th, U, V, Cr, Co, Ni, Cu, Zn, As, Cd, Sb, Te, Hg, Tl and Pb. Fraction analysis, Enrichment Factors and Principal Component Analysis-Absolute Principal Component Scores (PCA-APCS) were carried out in order to assess metal pollution, potential bioavailability and source apportionment. Cr and Ni exceeded the Australian Interim Sediment Quality Guidelines at some sampling sites, while Hg was found to be the most enriched metal. Fraction analysis identified increased weak acid soluble Hg and Cd during the sampling period. Source apportionment via PCA-APCS found four sources of metals pollution, namely, marine sediments, shipping, antifouling coatings and a mixed source. These sources need to be considered in any metal pollution control measure within Bramble Bay.

CHO-S antibody titers >1 gram/liter using flow electroporation-mediated transient gene expression followed by rapid migration to high-yield stable cell lines.

In recent years, researchers have turned to transient gene expression (TGE) as an alternative to CHO stable cell line generation for early-stage antibody development. Despite advances in transfection methods and culture optimization, the majority of CHO-based TGE systems produce insufficient antibody titers for extensive use within biotherapeutic development pipelines. Flow electroporation using the MaxCyte STX Scalable Transfection System is a highly efficient, scalable means of CHO-based TGE for gram-level production of antibodies without the need for specialized expression vectors or genetically engineered CHO cell lines. CHO cell flow electroporation is easily scaled from milligram to multigram quantities without protocol reoptimization while maintaining transfection performance and antibody productivity. In this article, data are presented that demonstrate the reproducibility, scalability, and antibody production capabilities of CHO-based TGE using the MaxCyte STX. Data show optimization of posttransfection parameters such as cell density, media composition, and feed strategy that result in secreted antibody titers >1 g/L and production of multiple grams of antibody within 2 weeks of a single CHO-S cell transfection. In addition, data are presented to demonstrate the application of scalable electroporation for the rapid generation of high-yield stable CHO cell lines to bridge the gap between early- and late-stage antibody development activities.

A synthetic Rev-independent bovine immunodeficiency virus-based packaging construct.

Replication competent lentivirus (RCL) has been the major safety concern associated with applications of lentivirus-based gene transfer systems for human gene therapy. Minimization and elimination of overlaps between the packaging and the transfer vector constructs are expected to reduce the potential to generate RCL. We previously developed second- and third-generation bovine immunodeficiency virus (BIV)-based gene transfer systems. However, some sequence homologies between the vector and gag/pol packaging constructs remained. In order to minimize the sequence homologies, we recoded gag/pol with codon usage optimized for expression in human cells in this report. Expression of the recoded gag/pol was Rev/RRE independent. Thus, RRE was eliminated from the packaging construct, thereby removing a 312 bp block of homology. In addition, recoding gag/pol minimized overall homologies between the packaging and transfer vector constructs. Vectors generated by the recoded packaging construct with a four plasmid system had titers greater than 1 x 10(6) transducing units per milliliter, equivalent to those of the earlier generation systems. The vectors were functional in vitro and efficiently transduced rat pigment epithelial cells in vivo. Generation of the synthetic packaging construct provides further advances to the safety of lentiviral vectors for clinical applications.

Immunotolerance toward native alphaA-crystallin in knockout mice deficient in the functional protein.

Immune response against self antigens is normally prevented by an elaborate immunotolerance mechanism. A potential problem for recipients of gene therapy is, therefore, an immune response against the newly introduced gene product. To examine this issue we tested the immune response to the native proteins in knockout (KO) mice in which the genes for alphaA- or alphaB-crystallin were disrupted by partial or complete gene deletion, respectively. alphaA- and alphaB-crystallins are two immunologically distinct polypeptides which form the large ( approximately 800 kDa) complex in the lens referred to as alpha-crystallin. When immunized with murine alpha-crystallin, alphaB-crystallin KO mice, in which the corresponding gene was completely deleted, responded well to the absent self antigen. In contrast, alphaA-crystallin KO mice, with the partial gene deletion, resembled wild type (WT) mice in being immunotolerant toward the native crystallin. Although no functional alphaA-crystallin could be detected in the lens of alphaA-crystallin KO mice, mRNA transcript coding for a truncated alphaA-crystallin gene was found in thymi of these mice, suggesting that thymic expression of a residual fragment of the protein is responsible for the tolerance induction. These data suggest that nonfunctional proteins may induce immunotolerance and protect recipients of gene therapy from immunity against the native proteins.