The Diagnosis of Granulomatosis With Polyangiitis When Serology and Biopsies are Negative.

Objective: Granulomatosis with polyangiitis (GPA) is a potentially fatal condition which often manifests in the head and neck. Currently, diagnosis relies on antineutrophil cytoplasmic autoantibody (c-ANCA) serology and mucosal or renal biopsy. However, a significant proportion of patients with GPA limited to the head and neck are seronegative and biopsy negative. This study evaluates the role of clinical diagnosis of GPA in the absence of positive laboratory findings. Study Design: Case series with chart review. Setting: Academic Tertiary Medical Center. Methods: This was a retrospective review of 143 patients treated in an outpatient otolaryngology clinic at a tertiary care hospital for known or suspected GPA from 1998 to 2021. Presenting symptoms, C-ANCA status at initial presentation, biopsy results, long-term serology results, and time to initiation of treatment were analyzed. Results: Twenty-six of 143 (18.2%) patients were seronegative; only 3 of these patients (12%) had positive biopsies. Seventeen (73.9%) of these patients presented with nasal and sinus disease and 12 (52.2%) presented with airway involvement. Only 4 (17.4%) patients had renal involvement. Delay in treatment of patients with negative laboratory workup ranged from 0 months to 11 years. All patients who were seronegative and/or biopsy negative at presentation responded clinically to immunosuppressive therapy. Conclusion: GPA cases are often limited to the upper respiratory tract, making diagnosis difficult, particularly in seronegative patients. These results suggest that, when GPA is suspected, despite negative serology, the diagnosis of GPA should be made on clinical grounds, and empiric therapy encouraged to prevent delay in treatment.

The Effect of Cognitive Fusion on Change in PTSD and Depression Symptom Severity in Veterans Engaged in Group Psychotherapy.

Cognitive fusion occurs when people experience their thoughts as literally true and allow them to dictate behavior. Fusion has been shown to be associated with increased symptoms of post-traumatic stress disorder (PTSD) and depression; however, the association between change in cognitive fusion, PTSD, and depression symptoms has been relatively uninvestigated. Our study aims to examine the associations between PTSD, depression symptoms, and cognitive fusion in Canadian veterans from pre- to post-treatment. Clients (N = 287) completed measures of PTSD symptom severity, depression symptom severity, and cognitive fusion at pre- and post-treatment. Our results supported that pretreatment PTSD and depression symptom severity were found to be negatively associated with changes in pre- to post-treatment cognitive fusion, while pretreatment cognitive fusion was not associated with changes in depression or PTSD symptoms. Furthermore, pretreatment depression symptoms predicted pre- to post-treatment changes in PTSD symptoms. However, pretreatment PTSD symptoms did not predict changes in depression symptoms. These findings highlight the importance of understanding the bidirectional associations between PTSD, depression, and cognitive fusion. Furthermore, our results are indicative of PTSD and depression symptoms playing a role in the change in cognitive fusion (e.g., defusion) and of depression playing a larger role in the maintenance of PTSD symptoms. Theoretical and practical implications are discussed.

Four-dimensional quantitative analysis of cell plate development in Arabidopsis using lattice light sheet microscopy identifies robust transition points between growth phases.

Cell plate formation during cytokinesis entails multiple stages occurring concurrently and requiring orchestrated vesicle delivery, membrane remodelling, and timely deposition of polysaccharides, such as callose. Understanding such a dynamic process requires dissection in time and space; this has been a major hurdle in studying cytokinesis. Using lattice light sheet microscopy (LLSM), we studied cell plate development in four dimensions, through the behavior of yellow fluorescent protein (YFP)-tagged cytokinesis-specific GTPase RABA2a vesicles. We monitored the entire duration of cell plate development, from its first emergence, with the aid of YFP-RABA2a, in both the presence and absence of cytokinetic callose. By developing a robust cytokinetic vesicle volume analysis pipeline, we identified distinct behavioral patterns, allowing the identification of three easily trackable cell plate developmental phases. Notably, the phase transition between phase I and phase II is striking, indicating a switch from membrane accumulation to the recycling of excess membrane material. We interrogated the role of callose using pharmacological inhibition with LLSM and electron microscopy. Loss of callose inhibited the phase transitions, establishing the critical role and timing of the polysaccharide deposition in cell plate expansion and maturation. This study exemplifies the power of combining LLSM with quantitative analysis to decode and untangle such a complex process.

A Randomized, Phase 3, Double-Blind, Crossover Comparison of Multilayer, Extended-Release Methylphenidate (PRC-063), and Lisdexamfetamine in the Driving Performance of Young Adults With ADHD.

OBJECTIVE: To compare PRC-063 (multilayer-release methylphenidate) and lisdexamfetamine dimesylate (LDX) on the driving performance of young adults with attention deficit hyperactivity disorder (ADHD) in a randomized, double-blind, crossover study. METHOD: Following up to 21 days of each treatment in each treatment course (PRC-063/LDX or LDX/PRC-063), subjects completed a 15-hour driving simulator laboratory assessment. The primary outcome measure was the Tactical Driving Quotient (TDQ) and the Clinical Global Impressions-Improvement (CGI-I) scale was a secondary outcome measure. RESULTS: Forty-four subjects completed the study. PRC-063 and LDX had equivalent effects on driving performance through a 15-hour time period (least square mean difference -0.3 [standard error 1.08], 95% confidence interval [-2.4, 1.8], p = .793). Consistent improvement in CGI-I was observed. The incidence of treatment-emergent adverse events was similar for each treatment sequence. CONCLUSIONS: PRC-063 and LDX had comparable effects on driving performance, from 1 through 15 hours, the last time point measured.

Developing the Ready Military Medical Force: military-specific training in Graduate Medical Education.

Introduction: Graduate Medical Education plays a critical role in training the next generation of military physicians, ensuring they are ready to uphold the dual professional requirements inherent to being both a military officer and a military physician. This involves executing the operational duties as a commissioned leader while also providing exceptional medical care in austere environments and in harm's way. The purpose of this study is to review prior efforts at developing and implementing military unique curricula (MUC) in residency training programs. Methods: We performed a literature search in PubMed (MEDLINE), Embase, Web of Science, and the Defense Technical Information Center through August 8, 2023, including terms "graduate medical education" and "military." We included articles if they specifically addressed military curricula in residency with terms including "residency and operational" or "readiness training", "military program", or "military curriculum". Results: We identified 1455 articles based on title and abstract initially and fully reviewed 111. We determined that 64 articles met our inclusion criteria by describing the history or context of MUC, surveys supporting MUC, or military programs or curricula incorporated into residency training or military-specific residency programs. Conclusion: We found that although there have been multiple attempts at establishing MUC across training programs, it is difficult to create a uniform curriculum that can be implemented to train residents to a single standard across services and specialties.

The role of the therapeutic bond when working with clients in suicidal crisis.

The desire to die by suicide has been linked with interpersonal difficulties and impeded clinical outcomes. Despite the emphasis on the therapeutic relationship in clinical guidelines for working with suicidal clients, little is known about how suicidal clients' interpersonal difficulties manifest in clinical contexts. Additionally, there is limited understanding of the therapeutic relationship in single-session suicidal crisis contexts. Our aim was to examine the trajectory of the therapeutic bond in mediating clients' suicidal desire and outcome in single-session suicidal crisis intervention. Single-session online text-based crisis intervention sessions (N = 354; Mage = 29.43, SD = 9.15; 64.5% women) were coded for suicidal desire, therapeutic bond (each quarter), and outcome. We examined the proposed sequential mediating model (suicidal desire to early bond to bond change to outcome) using structural equation modeling. The proposed sequential mediation model fits the data well, χ2(11) = 22.030, p = .0241, root-mean-square error of approximation = .053, 90% CI [.019, .085], comparative fit index = .983, Tucker-Lewis index = .977, and was a better fit than several alternative models. Further, the indirect effect from suicidal desire to outcome through early bond and bond change was significant (b = -0.474, 99% CI [-0.782, -0.203]). Our findings indicate that therapeutic bonds were beneficial for clients with elevated suicidal desire-and-elevated suicidal desire was negatively associated with therapeutic bonds. These findings highlight the importance of training clinicians to navigate the unique challenges of developing therapeutic bonds with acutely suicidal clients. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Bridging the multicultural orientation framework with sexual and gender minority psychotherapy: A mixed studies systematic review.

Sexual and gender minorities (SGM) experience higher rates of psychological distress and seek psychotherapy at higher rates compared to their heterosexual and cisgender counterparts. However, few therapists are trained on how to provide effective psychotherapy with SGM clients. The multicultural orientation (MCO) framework, which has been linked to improved therapeutic processes and outcomes, may be a valuable tool for working with SGM clients. The primary aim of this systematic review was to link the MCO framework to existing empirical psychotherapy research with SGM clients. A secondary aim was to examine how MCO constructs that we identified within the SGM literature have been associated with therapeutic processes and outcomes with SGM clients. A systematic search of five databases yielded 61 studies that were included in the review. Framework analysis was used to extract data and identify themes and subthemes related to MCO constructs from included studies. Results of the review demonstrate how the MCO framework can be used to conceptualize psychotherapy with SGM clients and-using the MCO framework-highlight potential beneficial and harmful therapist qualities and actions when working with SGM clients. Implications for future research and psychotherapy practice with SGM clients are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cathemerality: a key temporal niche.

Given the marked variation in abiotic and biotic conditions between day and night, many species specialise their physical activity to being diurnal or nocturnal, and it was long thought that these strategies were commonly fairly fixed and invariant. The term 'cathemeral', was coined in 1987, when Tattersall noted activity in a Madagascan primate during the hours of both daylight and darkness. Initially thought to be rare, cathemerality is now known to be a quite widespread form of time partitioning amongst arthropods, fish, birds, and mammals. Herein we provide a synthesis of present understanding of cathemeral behaviour, arguing that it should routinely be included alongside diurnal and nocturnal strategies in schemes that distinguish and categorise species across taxa according to temporal niche. This synthesis is particularly timely because (i) the study of animal activity patterns is being revolutionised by new and improved technologies; (ii) it is becoming apparent that cathemerality covers a diverse range of obligate to facultative forms, each with their own common sets of functional traits, geographic ranges and evolutionary history; (iii) daytime and nighttime activity likely plays an important but currently neglected role in temporal niche partitioning and ecosystem functioning; and (iv) cathemerality may have an important role in the ability of species to adapt to human-mediated pressures.

A Distress-Processing Model for Clients in Suicidal Crisis.

Background: While crisis intervention frameworks have indicated the importance of clients in suicidal crisis better understanding their distress to decrease suicidality, it is unclear how clients in suicidal crisis process their distress. Aims: To develop (Study 1) and validate (Study 2) a sequential distress-processing model for clients in suicidal crisis. Methods: Applying task analysis, Study 1 consisted of three phases, which resulted in a theoretically and empirically informed model. In Study 2, we examined the distress-processing model's validity using a longitudinal design. In both studies, data were online crisis chats with adults in suicidal crisis. Results: In Study 1, we developed a sequential five-stage distress-processing model: (Stage 1) unengaged with distress, (Stage 2) distress awareness, (Stage 3) distress clarity, (Stage 4) distress insight, and (Stage 5) applying distress insight. In Study 2, the model's validity was supported via evidence that (H1) progression through the processing stages was sequential and (H2) clients with good outcomes had greater progression in their processing than clients with poor outcomes. Limitation: Clients who were suicidal but did not disclose their suicidality were not included. Conclusion: Our findings provide a framework for conceptualizing and operationalizing how clients move through suicidal crises, which can facilitate intervention and research developments.

Ecosystem functioning across the diel cycle in the Anthropocene.

Given the marked differences in environmental conditions and active biota between daytime and nighttime, it is almost inevitable that ecosystem functioning will also differ. However, understanding of these differences has been hampered due to the challenges of conducting research at night. At the same time, many anthropogenic pressures are most forcefully exerted or have greatest effect during either daytime (e.g., high temperatures, disturbance) or nighttime (e.g., artificial lighting, nights warming faster than days). Here, we explore current understanding of diel (daily) variation in five key ecosystem functions and when during the diel cycle they primarily occur [predation (unclear), herbivory (nighttime), pollination (daytime), seed dispersal (unclear), carbon assimilation (daytime)] and how diel asymmetry in anthropogenic pressures impacts these functions.

Graft-derived cfDNA Monitoring in Plasma and Bile During Normothermic Machine Perfusion in Liver Transplantation Is Feasible and a Potential Tool for Assessing Graft Viability.

BACKGROUND: Ex vivo normothermic machine perfusion (NMP) is an organ preservation technique that enables an extended assessment of graft suitability before liver transplantation (LT). Established monitoring protocols used during NMP vary significantly in their assessment of transplant suitability when applied to the same grafts. Graft-derived cell-free DNA (gdcfDNA) analysis is an emerging tool for monitoring graft health post-transplantation. We investigated the feasibility of monitoring gdcfDNA during NMP for LT in a proof-of-concept, observational study. METHODS: Serial plasma and bile samples were collected during NMP for 10 consecutive grafts, at 15 min post-machine reperfusion and then 2-h intervals. Digital polymerase chain reaction was used to quantify gdcfDNA at each time point. RESULTS: Five grafts were suitable for LT, there were no cases of primary nonfunction or death in the recipients. gdcfDNA was quantified in all bile and plasma samples (n > 100). In plasma, gdcfDNA concentrations climbed post-machine reperfusion until 4.25 h (median 2.25 h = 15.98 × 10 6 copies/mL, 4.25 h = 40.21 × 10 6 copies/mL). gdcfDNA levels then diverged significantly when comparing the viable and non-viable graft groups (6.25 h, median viable: 117.15 × 10 6 copies/mL versus non-viable: 16.72 × 10 6 copies/mL, P = 0.01). These opposing trends correlated in each graft and in all cases with the viable/non-viable outcome. There was a trend of gradual decline in bile gdcfDNA from viable grafts post-machine reperfusion; discarded grafts showed more variable patterns of release. CONCLUSIONS: gdcfDNA analysis during NMP is a feasible and potential tool to inform viability assessment during NMP for LT. Bile gdcfDNA monitoring offers the prospect of an objective means to assess the degree of biliary injury associated with organ procurement.

Changes in neuropeptide large dense core vesicle trafficking dynamics contribute to adaptive responses to a systemic homeostatic challenge.

Neuropeptides are packed into large dense core vesicles (LDCVs) that are transported from the soma out into their processes. Limited information exists regarding mechanisms regulating LDCV trafficking, particularly during challenges to bodily homeostasis. Addressing this gap, we used 2-photon imaging in an ex vivo preparation to study LDCVs trafficking dynamics in vasopressin (VP) neurons, which traffic and release neuropeptide from their dendrites and axons. We report a dynamic bidirectional trafficking of VP-LDCVs with important differences in speed and directionality between axons and dendrites. Acute, short-lasting stimuli known to alter VP firing activity and axonal/dendritic release caused modest changes in VP-LDCVs trafficking dynamics. Conversely, chronic/sustained systemic osmotic challenges upregulated VP-LDCVs trafficking dynamic, with a larger effect in dendrites. These results support differential regulation of dendritic and axonal LDCV trafficking, and that changes in trafficking dynamics constitute a novel mechanism by which peptidergic neurons can efficiently adapt to conditions of increased hormonal demand.

Cold-Temperature Coding with Bursting and Spiking Based on TRP Channel Dynamics in Drosophila Larva Sensory Neurons.

Temperature sensation involves thermosensitive TRP (thermoTRP) and non-TRP channels. Drosophila larval Class III (CIII) neurons serve as the primary cold nociceptors and express a suite of thermoTRP channels implicated in noxious cold sensation. How CIII neurons code temperature remains unclear. We combined computational and electrophysiological methods to address this question. In electrophysiological experiments, we identified two basic cold-evoked patterns of CIII neurons: bursting and spiking. In response to a fast temperature drop to noxious cold, CIII neurons distinctly mark different phases of the stimulus. Bursts frequently occurred along with the fast temperature drop, forming a peak in the spiking rate and likely coding the high rate of the temperature change. Single spikes dominated at a steady temperature and exhibited frequency adaptation following the peak. When temperature decreased slowly to the same value, mainly spiking activity was observed, with bursts occurring sporadically throughout the stimulation. The spike and the burst frequencies positively correlated with the rate of the temperature drop. Using a computational model, we explain the distinction in the occurrence of the two CIII cold-evoked patterns bursting and spiking using the dynamics of a thermoTRP current. A two-parameter activity map (Temperature, constant TRP current conductance) marks parameters that support silent, spiking, and bursting regimes. Projecting on the map the instantaneous TRP conductance, governed by activation and inactivation processes, reflects temperature coding responses as a path across silent, spiking, or bursting domains on the map. The map sheds light on how various parameter sets for TRP kinetics represent various types of cold-evoked responses. Together, our results indicate that bursting detects the high rate of temperature change, whereas tonic spiking could reflect both the rate of change and magnitude of steady cold temperature.

Optimizing a Drone Network to Respond to Opioid Overdoses.

Introduction:Effective out-of-hospital administration of naloxone in opioid overdoses is dependent on timely arrival of naloxone. Delays in emergency medical services (EMS) response time could potentially be overcome with drones to deliver naloxone efficiently to the scene for bystander use. Our objective was to evaluate a mathematical optimization simulation for geographical placement of drone bases in reducing response time to opioid overdose. Methods: Using retrospective data from a single EMS system from January 2016-February 2019, we created a geospatial drone-network model based on current technological specifications and potential base locations. Genetic optimization was then used to maximize county coverage by drones and the number of overdoses covered per drone base. From this model, we identified base locations that minimize response time and the number of drone bases required. Results: In a drone network model with 2,327 opioid overdoses, as the number of modeled drone bases increased the calculated response time decreased. In a geospatially optimized drone network with four drone bases, response time compared to ambulance arrival was reduced by 4 minutes 38 seconds and covered 64.2% of the county. Conclusion: In our analysis we found that in a mathematical model for geospatial optimization, implementing four drone bases could reduce response time of 9-1-1 calls for opioid overdoses. Therefore, drones could theoretically improve time to naloxone delivery.

Elucidating the nature of the proton radioactivity and branching ratio on the first proton emitter discovered 53mCo.

The observation of a weak proton-emission branch in the decay of the 3174-keV 53mCo isomeric state marked the discovery of proton radioactivity in atomic nuclei in 1970. Here we show, based on the partial half-lives and the decay energies of the possible proton-emission branches, that the exceptionally high angular momentum barriers, [Formula: see text] and [Formula: see text], play a key role in hindering the proton radioactivity from 53mCo, making them very challenging to observe and calculate. Indeed, experiments had to wait decades for significant advances in accelerator facilities and multi-faceted state-of-the-art decay stations to gain full access to all observables. Combining data taken with the TASISpec decay station at the Accelerator Laboratory of the University of Jyväskylä, Finland, and the ACTAR TPC device on LISE3 at GANIL, France, we measured their branching ratios as bp1 = 1.3(1)% and bp2 = 0.025(4)%. These results were compared to cutting-edge shell-model and barrier penetration calculations. This description reproduces the order of magnitude of the branching ratios and partial half-lives, despite their very small spectroscopic factors.

Multimodal intrathecal analgesia (MITA) with morphine for reducing postoperative opioid use and acute pain following hepato-pancreato-biliary surgery: A multicenter retrospective study.

INTRODUCTION: The optimal analgesic modality for patients undergoing hepato-pancreato-biliary (HPB) surgery remains unknown. The analgesic effects of a multimodal intrathecal analgesia (MITA) technique of intrathecal morphine (ITM) in combination with clonidine and bupivacaine compared to ITM alone have not been investigated in these patients. METHODS: We performed a multicenter retrospective study of patients undergoing complex HPB surgery who received ITM, bupivacaine, and clonidine (MITA group) or ITM-only (ITM group) as part of their perioperative analgesia strategy. The primary outcome was the unadjusted oral morphine equivalent daily dose (oMEDD) in milligrams on postoperative day 1. After adjusting for age, body mass index, hospital allocation, type of surgery, operation length, and intraoperative opioid use, postoperative oMEDD use was investigated using a bootstrapped quantile regression model. Other prespecified outcomes included postoperative pain scores, opioid-related adverse events, major complications, and length of hospital stay. RESULTS: In total, 118 patients received MITA and 155 patients received ITM-only. The median (IQR) cumulative oMEDD use on postoperative day 1 was 20.5 mg (8.6:31.0) in the MITA group and 52.1 mg (18.0:107.0) in the ITM group (P < 0.001). There was a variation in the magnitude of the difference in oMEDD use between the groups for different quartiles. For the MITA group, on postoperative day 1, patients in the 25th percentile required 14.0 mg less oMEDD (95% CI: -25.9 to -2.2; P = 0.025), patients in the 50th percentile required 27.8 mg less oMEDD (95% CI: -49.7 to -6.0; P = 0.005), and patients in the 75th percentile required 38.7 mg less oMEDD (95% CI: -72.2 to -5.1; P = 0.041) compared to patients in the same percentile of the ITM group. Patients in the MITA group had significantly lower pain scores in the postoperative recovery unit and on postoperative days 1 to 3. The incidence of postoperative respiratory depression was low (<1.5%) and similar between groups. Patients in the MITA group had a significantly higher incidence of postoperative hypotension requiring vasopressor support. However, no significant differences were observed in major postoperative complications, or the length of hospital stay. CONCLUSION: In patients undergoing complex HPB surgery, the use of MITA, consisting of ITM in combination with intrathecal clonidine and bupivacaine, was associated with reduced postoperative opioid use and resulted in superior postoperative analgesia without risk of respiratory depression when compared to patients who received ITM alone. A randomized prospective clinical trial investigating these two intrathecal analgesic techniques is justified.

Neural substrates of cold nociception in Drosophila larva.

Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus specific behaviors to either navigate away from injury-causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Recent studies in Drosophila larvae have revealed that somatosensory class III multidendritic (CIII md) neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Recent advances in circuit bases of behavior have identified and functionally validated Drosophila larval somatosensory circuitry involved in innocuous (mechanical) and noxious (heat and mechanical) cues. However, central processing of cold nociceptive cues remained unexplored. We implicate multisensory integrators (Basins), premotor (Down-and-Back) and projection (A09e and TePns) neurons as neural substrates required for cold-evoked behavioral and calcium responses. Neural silencing of cell types downstream of CIII md neurons led to significant reductions in cold-evoked behaviors and neural co-activation of CIII md neurons plus additional cell types facilitated larval contraction (CT) responses. We further demonstrate that optogenetic activation of CIII md neurons evokes calcium increases in these neurons. Collectively, we demonstrate how Drosophila larvae process cold stimuli through functionally diverse somatosensory circuitry responsible for generating stimulus specific behaviors.

CCT and Cullin1 regulate the TORC1 pathway to promote dendritic arborization in health and disease.

The development of cell-type-specific dendritic arbors is integral to the proper functioning of neurons within their circuit networks. In this study, we examine the regulatory relationship between the cytosolic chaperonin CCT, key insulin pathway genes, and an E3 ubiquitin ligase (Cullin1) in homeostatic dendritic development. CCT loss of function (LOF) results in dendritic hypotrophy in Drosophila Class IV (CIV) multidendritic larval sensory neurons, and CCT has recently been shown to fold components of the TOR (Target of Rapamycin) complex 1 (TORC1), in vitro. Through targeted genetic manipulations, we have confirmed that LOF of CCT and the TORC1 pathway reduces dendritic complexity, while overexpression of key TORC1 pathway genes increases dendritic complexity in CIV neurons. Both CCT and TORC1 LOF significantly reduce microtubule (MT) stability. CCT has been previously implicated in regulating proteinopathic aggregation, thus we examined CIV dendritic development in disease conditions as well. Expression of mutant Huntingtin leads to dendritic hypotrophy in a repeat-length-dependent manner, which can be rescued by TORC1 disinhibition via Cullin1 LOF. Together, our data suggest that Cullin1 and CCT influence dendritic arborization through regulation of TORC1 in both health and disease.

SARS-CoV-2 omicron spike simulations: broad antibody escape, weakened ACE2 binding, and modest furin cleavage.

The recent emergence of the omicron variant of the SARS-CoV-2 virus with large numbers of mutations has raised concern about a potential new surge in infections. Here we use molecular dynamics to study the biophysics of the interface of the BA1 and BA2 omicron spike protein binding to (i) the ACE2 receptor protein, (ii) antibodies from all known binding regions, and (iii) the furin binding domain. Our simulations suggest that while there is a significant reduction of antibody (Ab) binding strength corresponding to escape, the omicron spikes pay a cost in terms of weaker receptor binding as measured by interfacial hydrogen bonds (H-bond). The furin cleavage domain (FCD) is the same or weaker binding than the delta variant, suggesting lower fusogenicity resulting in less viral load and disease intensity than the delta variant. IMPORTANCE The BA1 and BA2 and closely related BA2.12.2 and BA.5 omicron variants of SARS-CoV-2 dominate the current global infection landscape. Given the high number of mutations, particularly those which will lead to antibody escape, it is important to establish accurate methods that can guide developing health policy responses that identify at a fundamental level whether omicron and its variants are more threatening than its predecessors, especially delta. The importance of our work is to demonstrate that simple in silico simulations can predict biochemical binding details of the omicron spike protein that have epidemiological consequences, especially for binding to the cells and for fusing the viral membrane with the cells. In each case, we predicted weaker binding of the omicron spike, which agreed with subsequent experimental results. Future virology experiments will be needed to test these predictions further.