A conserved motif in the immune-subdominant RAP-1 related antigen of Babesia bovis contains a B-cell epitope recognized by antibodies from protected cattle.

Introduction: Babesia bovis, a tick-borne apicomplexan parasite causing bovine babesiosis, remains a significant threat worldwide, and improved and practical vaccines are needed. Previous studies defined the members of the rhoptry associated protein-1 (RAP-1), and the neutralization-sensitive rhoptry associated protein-1 related antigen (RRA) superfamily in B. bovis, as strong candidates for the development of subunit vaccines. Both RAP-1 and RRA share conservation of a group of 4 cysteines and amino acids motifs at the amino terminal end (NT) of these proteins. Methods and results: Sequence comparisons among the RRA sequences of several B. bovis strains and other Babesia spp parasites indicate a high level of conservation of a 15-amino acid (15-mer) motif located at the NT of the protein. BlastP searches indicate that the 15-mer motif is also present in adenylate cyclase, dynein, and other ATP binding proteins. AlphaFold2 structure predictions suggest partial exposure of the 15-mer on the surface of RRA of three distinct Babesia species. Antibodies in protected cattle recognize a synthetic peptide representing the 15-mer motif sequence in iELISA, and rabbit antibodies against the 15-mer react with the surface of free merozoites in immunofluorescence. Discussion and conclusion: The presence of the 15-mer-like regions in dynein and ATP-binding proteins provides a rationale for investigating possible functional roles for RRA. The demonstrated presence of a surface exposed B-cell epitope in the 15-mer motif of the B. bovis RRA, which is recognized by sera from protected bovines, supports its inclusion in future subunit epitope-based vaccines against B. bovis.

A transaminase-mediated aldol reaction and applications in cascades to styryl pyridines.

Transaminase enzymes are well established biocatalysts that are used in chemical synthesis due to their beneficial sustainability profile, regio- and stereoselectivity and substrate specificity. Here, the use of a wild-type Chromobacterium violaceum transaminase (CvTAm) in enzyme cascades revealed the formation of a novel hydroxystyryl pyridine product. Subsequent studies established it was a transaminase mediated reaction where it was exhibiting apparent aldolase reactivity. This promiscuous enzyme reaction mechanism was then explored using other wild-type transaminases and via the formation of CvTAm mutants. Application of one pot multi-step enzyme cascades was subsequently developed to produce a range of hydroxystyryl pyridines.

Top Ten Tips Palliative Care Clinicians Should Know About the Physical Manifestations of Psychiatric Illness and Treatment.

Addressing the psychiatric aspects of serious illness in palliative care (PC) is crucial to both care delivery and outcomes. Psychiatric comorbidities are common among patients with PC needs and can significantly impact their total burden of symptomatic distress, overall quality of life, functional independence, and healthcare utilization. Yet, these aspects of care are often deferred to mental health consultant teams in the context of busy PC services and often limited human resources. To provide comprehensive and person-centered care, PC clinicians must understand the interplay between medical conditions and psychiatric presentations within a biopsychosocial framework to respond empathically, efficiently, and effectively. This article is the first of a two-part series developed in collaboration with a group of psychiatric-palliative care specialists. This article explores ten common physical manifestations of psychiatric illness and treatment among patients facing serious illnesses. The second article will provide pragmatic tips PC clinicians should know about the psychiatric manifestations of nonpsychiatric serious illness and treatment. Combined, these two articles support a holistic approach that PC clinicians can use to prioritize and integrate both mental and emotional well-being throughout the continuum of serious illness.

Bystander effects, pharmacokinetics, and linker-payload stability of EGFR-targeting antibody-drug conjugates Losatuxizumab vedotin and Depatux-M in glioblastoma models.

PURPOSE: Antibody-drug conjugates (ADCs) are targeted therapies with robust efficacy in solid cancers, and there is intense interest in using EGFR-specific ADCs to target EGFR-amplified glioblastoma (GBM). Given the molecular heterogeneity of GBM, bystander activity of ADCs may be important for determining treatment efficacy. In this study, the activity and toxicity of two EGFR-targeted ADCs, Losatuxizumab vedotin (ABBV-221) and Depatuxizumab mafodotin (Depatux-M), with similar auristatin toxins, were compared in GBM patient-derived xenografts (PDXs) and normal murine brain following direct infusion by convection enhanced delivery (CED). METHODS: EGFRviii-amplified and non-amplified GBM PDXs were used to determine in vitro cytotoxicity, in vivo efficacy, and bystander activities of ABBV-221 and Depatux-M. Non-tumor bearing mice were used to evaluate pharmacokinetics and toxicity of ADCs using LC-MS/MS and immunohistochemistry. RESULTS: CED improved intracranial efficacy of Depatux-M and ABBV-221 in three EGFRviii-amplified GBM PDX models (Median survival: 125 to >300 days vs 20-49 days with isotype-control AB095). Both ADCs had comparable in vitro and in vivo efficacy. However, neuronal toxicity and CD68+ microglia/macrophage infiltration were significantly higher in brains infused with ABBV-221, with the cell-permeable MMAE, as compared to Depatux-M, with the cell-impermeant MMAF. CED infusion of ABBV-221 into brain or incubation of ABBV-221 with normal brain homogenate resulted in significant release of MMAE, which is consistent with linker instability in the brain microenvironment. CONCLUSION: EGFR-targeting ADCs are promising therapeutic options for GBM when delivered intra-tumorally by CED. However, the linker and payload for the ADC must be carefully considered to maximize the therapeutic window.

Synergistic clinical application of synthetic electrospun fiber wound matrix in the management of a complex traumatic wound: degloving left groin and thigh auger injury.

BACKGROUND: Managing complex traumatic soft tissue wounds involving a large surface area while attempting to optimize healing, avoid infection, and promote favorable cosmetic outcomes is challenging. Regenerative materials such as ECMs are typically used in wound care to enhance the wound healing response and proliferative phase of tissue formation. CASE REPORT: The case reported herein is an example of the efficacious use of an SEFM in the surgical management of a large complex traumatic wound involving the left lower extremity and lower abdominal region. The wound bed was successfully prepared for skin grafting over an area of 1200 cm2, making this among the largest applications of the SEFM reported in the literature. CONCLUSION: This case report demonstrates the clinical versatility of the SEFM and a synergistic approach to complex traumatic wound care. The SEFM was successfully used to achieve tissue granulation for a successful skin graft across a large surface in an anatomic region with complex topography.

Enhanced recovery program in ambulatory pediatric urology: A quality improvement initiative.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) was established in 2001 for adult patients undergoing complex procedures. ERAS in adult ambulatory surgery later followed with similar positive outcomes. For the pediatric population, ERAS implementation has shown promising results in complex surgeries such as bladder reconstruction. Its application in pediatric ambulatory surgery has only recently been reported. We hereby report a Quality Improvement initiative in implementing an Enhanced Recovery Protocol (ERP) for pediatric urology in an ambulatory surgery center. METHODS: A project was launched to evaluate and implement enhanced recovery elements into an institutional Enhanced Recovery Protocol (ERP). These included reliance on peripheral nerve blocks for all inguinal and genital cases and reduction of opioids intraoperatively and postoperatively. Improvements were placed into a project plan broken into one preparation phase to collect baseline data and three implementation phases to enhance existing and implement new elements. The implementation phase went through iterative Plan-Do-Study-Act (PDSA) cycles for all sub-projects. Team countermeasures were based on available evidence. A consensus process was used to resolve disagreement. Monthly meetings were held to share real-time data, gather new feedback, and modify plans as needed. The primary outcome measures selected were percent intraoperative opioid use, percent opioid prescribing, mean PACU length of stay, and average number of opioid doses prescribed. Secondary outcome measures were mean maximum pain score in PACU, PACU rescue rate for PONV, and patient/family satisfaction scores. Post-implementation data for 18 months was included for evaluation. Statistical process control methodology was used. RESULTS: The total number of participants was 3306: 561 (baseline), 220 (Phase 1) 356 (Phase 2) and 527 (Phase 3), 1642 (post-implementation). Intraoperative opioid use was eliminated in >99% of cases. Post-operative opioid prescribing was reduced from 30% to 15% of patients. The number of opioid doses was also reduced from an average of 7.6 to 6.1 doses. There was no change for the mean maximum pain score in the recovery room despite elimination of opioids. Patient/family satisfaction scores were high and sustained throughout the period of study (9.8/10). Balancing measures such as return to the operating room within 30 days and return to the emergency department within 7 days were unchanged. CONCLUSIONS: This QI project demonstrated the feasibility of a pediatric enhanced recovery protocol in a urology ambulatory surgery setting. With implementation of this protocol, intraoperative opioid use was virtually eliminated, and opioid prescribing was reduced without affecting pain scores or post-operative complications.

Topical application of a P2X2/P2X3 purine receptor inhibitor suppresses the bitter taste of medicines and other taste qualities.

BACKGROUND AND PURPOSE: Many medications taste intensely bitter. The innate aversion to bitterness affects medical compliance, especially in children. There is a clear need to develop bitter blockers to suppress the bitterness of vital medications. Bitter taste is mediated by TAS2R receptors. Because different pharmaceutical compounds activate distinct sets of TAS2Rs, targeting specific receptors may only suppress bitterness for certain, but not all, bitter-tasting compounds. Alternative strategies are needed to identify universal bitter blockers that will improve the acceptance of every medication. Taste cells in the mouth transmit signals to afferent gustatory nerve fibres through the release of ATP, which activates the gustatory nerve-expressed purine receptors P2X2/P2X3. We hypothesized that blocking gustatory nerve transmission with P2X2/P2X3 inhibitors (e.g. 5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidine-2,4-diamine [AF-353]) would reduce bitterness for all medications and bitter compounds. EXPERIMENTAL APPROACH: Human sensory taste testing and mouse behavioural analyses were performed to determine if oral application of AF-353 blocks perception of bitter taste and other taste qualities but not non-gustatory oral sensations (e.g. tingle). KEY RESULTS: Rinsing the mouth with AF-353 in humans or oral swabbing it in mice suppressed the bitter taste and avoidance behaviours of all compounds tested. We further showed that AF-353 suppressed other taste qualities (i.e. salt, sweet, sour and savoury) but had no effects on other oral or nasal sensations (e.g, astringency and oral tingle). CONCLUSION AND IMPLICATIONS: This is the first time a universal, reversible taste blocker in humans has been reported. Topical application of P2X2/P2X3 inhibitor to suppress bitterness may improve medical compliance.

Metabolic immaturity of newborns and breast milk bile acid metabolites are the central determinants of heightened neonatal vulnerability to norovirus diarrhea.

Noroviruses are the leading global cause of acute gastroenteritis, responsible for 685 million annual cases. While all age groups are susceptible to noroviruses, children are vulnerable to more severe infections than adults, underscored by 200 million pediatric cases and up to 200,000 deaths in children annually. Understanding the basis for the increased vulnerability of young hosts is critical to developing effective treatments. The pathogenic outcome of any enteric virus infection is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors. A central mediator in these complex relationships are host- and microbiota-derived metabolites. Noroviruses bind a specific class of metabolites, bile acids, which are produced by the host and then modified by commensal bacterial enzymes. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Considering these opposing effects, the microbiota-regulated balance of the bile acid pool may be a key determinant of the pathogenic outcome of a norovirus infection. The bile acid pool in newborns is unique due to immaturity of host metabolic pathways and developing gut microbiota, which could underlie the vulnerability of these hosts to severe norovirus infections. Supporting this concept, we demonstrate herein that microbiota and their bile acid metabolites protect from severe norovirus diarrhea whereas host-derived bile acids promote disease. Remarkably, we also report that maternal bile acid metabolism determines neonatal susceptibility to norovirus diarrhea during breastfeeding by delivering proviral bile acids to the newborn. Finally, directed targeting of maternal and neonatal bile acid metabolism can protect the neonatal host from norovirus disease. Altogether, these data support the conclusion that metabolic immaturity in newborns and ingestion of proviral maternal metabolites in breast milk are the central determinants of heightened neonatal vulnerability to norovirus disease.

Potent neutralization by a receptor binding domain monoclonal antibody with broad specificity for SARS-CoV-2 JN.1 and other variants.

SARS-CoV-2 continues to be a public health burden, driven in-part by its continued antigenic diversification and resulting emergence of new variants. While increasing herd immunity, current vaccines, and therapeutics have improved outcomes for some; prophylactic and treatment interventions that are not compromised by viral evolution of the Spike protein are still needed. Using a rationally designed SARS-CoV-2 Receptor Binding Domain (RBD) - ACE2 fusion protein and differential selection process with native Omicron RBD protein, we developed a recombinant human monoclonal antibody (hmAb) from a convalescent individual following SARS-CoV-2 Omicron infection. The resulting hmAb, 1301B7 potently neutralized a wide range of SARS-CoV-2 variants including the original Wuhan and more recent Omicron JN.1 strain, as well as SARS-CoV. Structure determination of the SARS-CoV-2 EG5.1 Spike/1301B7 Fab complex by cryo-electron microscopy at 3.1Å resolution demonstrates 1301B7 contacts the ACE2 binding site of RBD exclusively through its VH1-69 heavy chain, making contacts using CDRs1-3, as well as framework region 3 (FR3). Broad specificity is achieved through 1301B7 binding to many conserved residues of Omicron variants including Y501 and H505. Consistent with its extensive binding epitope, 1301B7 is able to potently diminish viral burden in the upper and lower respiratory tract and protect mice from challenge with Omicron XBB1.5 and Omicron JN.1 viruses. These results suggest 1301B7 has broad potential to prevent or treat clinical SARS-CoV-2 infections and to guide development of RBD-based universal SARS-CoV-2 prophylactic vaccines and therapeutic approaches.

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Sagittal Full-Spine vs. Sectional Cervical Lateral Radiographs: Are the Measurements of Cervical Alignment Interchangeable?

(1) Background: This study assessed the relationship between cervical spine parameters taken on standing full-spine lateral radiographic images compared to sectional lateral cervical radiographs. (2) Methods: Full-spine (FS) and sectional lateral cervical (LC) radiographs from four spine treatment facilities across the USA retrospectively provided data collected on 220 persons to assess the comparison of three sagittal cervical radiographic measurements between the two views. The measures included cervical lordosis using the absolute rotation angle from C2-C7, sagittal cervical translation of C2-C7, and atlas plane angle to horizontal. Linear correlation and R2 models were used for statistical comparison of the measures for the two views. (3) Results: The mean values of the three measurements were statistically different from each other: C2-C7 translation (FS = 19.84 ± 11.98 vs. LC = 21.18 ± 11.8), C2-C7 lordosis (FS = -15.3 ± 14.63 vs. LC = -18.32 ± 13.16), and atlas plane (FS = -19.99 ± 8.88 vs. LC = -22.56 ± 8.93), where all values were p < 0.001. Weak-to-moderate-to-strong correlations existed between the full-spine and sectional lateral cervical radiographic variables. The R2 values varied based on the measurement were R2 = 0.768 (p < 0.001) for sagittal cervical translation of C2-C7 (strong), R2 = 0.613 (p < 0.001) for the absolute rotation angle C2-C7 (moderate), and R2 = 0.406 (p < 0.001) for the atlas plane line (weak). Though a linear correlation was identified, there were consistent intra-person differences between the measurements on the full spine versus sectional lateral cervical radiographic views, where the full-spine view consistently underestimated the magnitude of the variables. (4) Conclusion: Key sagittal cervical radiographic measurements on the full spine versus sectional lateral cervical radiographic views show striking intra-person differences. The findings of this study confirm that full spine versus sectional lateral cervical radiographic views provide different biomechanical magnitudes of cervical sagittal alignment, and caution should be exercised by health care providers as these are not interchangeable. We recommend the LC view for measurement of cervical sagittal alignment variables.

Abnormal Static Sagittal Cervical Curvatures following Motor Vehicle Collisions: A Retrospective Case Series of 41 Patients before and after a Crash Exposure.

Previous investigations have found a correlation between abnormal curvatures and a variety of patient complaints such as cervical pain and disability. However, no study has shown that loss of the cervical curve is a direct result of exposure to a motor vehicle collision (MVC). This investigation presents a retrospective consecutive case series of patients with both a pre-injury cervical lateral radiograph (CLR) and a post-injury CLR after exposure to an MVC. Computer analysis of digitized vertebral body corners on CLRs was performed to investigate the possible alterations in the geometric alignment of the sagittal cervical curve. METHODS: Three spine clinic records were reviewed over a 2-year period, looking for patients where both an initial lateral cervical X-ray and an examination were performed prior to the patient being exposed to a MVC; afterwards, an additional exam and radiographic analysis were obtained. A total of 41 patients met the inclusion criteria. Examination records of pain intensity on numerical pain rating scores (NPRS) and neck disability index (NDI), if available, were analyzed. The CLRs were digitized and modeled in the sagittal plane using curve fitting and the least squares error approach. Radiographic variables included total cervical curve (ARA C2-C7), Chamberlain's line to horizontal (skull flexion), horizontal translation of C2 relative to C7, segmental translations (retrolisthesis and anterolisthesis), and circular modelling radii. RESULTS: There were 15 males and 26 females with an age range of 8-65 years. Most participants were drivers (28) involved in rear-end impacts (30). The pre-injury NPRS was 2.7 while the post injury was 5.0; p < 0.001. The NDI was available on 24/41 (58.5%) patients and increased after the MVC from 15.7% to 32.8%, p < 0.001. An altered cervical curvature was identified following exposure to MVC, characterized by an increase in the mean radius of curvature (265.5 vs. 555.5, p < 0.001) and an approximate 8° reduction of lordosis from C2-C7; p < 0.001. The mid-cervical spine (C3-C5) showed the greatest curve reduction with an averaged localized mild kyphosis at these levels. Four participants (10%) developed segmental translations that were just below the threshold of instability, segmental translations < 3.5 mm. CONCLUSIONS: The post-exposure MVC cervical curvature was characterized by an increase in radius of curvature, an approximate 8° reduction in C2-C7 lordosis, a mild kyphosis of the mid-cervical spine, and a slight increase in anterior translation of C2-C7 sagittal balance. The modelling result indicates that the post-MVC cervical sagittal alignment approximates a second-order buckling alignment, indicating a significant alteration in curve geometry. Future biomechanics experiments and clinical investigations are needed to confirm these findings.

Determination of change of direction deficit thresholds across a spectrum of angles in basketball players.

Change of direction deficit (CODD) offers valuable insights into a player's balance between linear and multidirectional speed. However, there are still no established reference values for CODD. The objectives of this study were to determine CODD thresholds for various change of direction angles in basketball players according to gender and analyse the relationships between CODD and execution time in speed tests. One hundred and thirty basketball players (46% female; age: 23.7 ± 5.29 years; height: 189.1 ± 11.1 cm; body mass: 84.3 ± 15.7 kg) undertook 10-m linear and change of direction speed test at 45º, 90º and 180º. A k-means cluster analysis was conducted to standardise CODD thresholds and a one-way analysis of variance to identify the differences between clusters. The results revealed angulation-specific CODD thresholds, ranging from 3% to 8%, 17% to 25% and 43% to 51% for 45º, 90º and 180º cutting angles, respectively for the pooled sample. Furthermore, differences inter-clusters (p < 0.05) were observed for execution time at all cutting angles for both genders. Therefore, strength and conditioning coaches are encouraged to assess CODD as a highly valid variable for evaluating change of direction performance and to use current CODD thresholds to tailor training programmes according to each athlete's needs.

A level playing field? Evaluation of the virtual Objective Structured Clinical Examination in Psychiatry and Addiction Medicine: A mixed methods study.

OBJECTIVE: The Objective Structured Clinical Examination (OSCE) has been used for clinical assessment of a broad range of medical student competencies in Psychiatry and Addiction Medicine. However, there has been little research into online assessments. We investigated the virtual OSCE (v-OSCE) from the user perspective to better understand its acceptability, usefulness, benefits, challenges and potential improvements. METHODS: At the conclusion of the v-OSCE, all participants (medical students, examiners and simulated patients) were invited to participate in a brief online survey, based on the Technology and Acceptance Model. Freeform qualitative feedback was also obtained to explore participants' experiences and attitudes. RESULTS: Participants reported the v-OSCE was acceptable, efficient, convenient and easy to use. It was perceived as useful for demonstrating students' interviewing skills and interacting with the simulated patient. Benefits included greater convenience, reduced stress and travel time. Challenges were similar to those experienced in 'real world' telepsychiatry, primarily related to assessment of non-verbal cues and emotional prosody. CONCLUSIONS: Our findings inform recommendations for improving online examinations. These include increased preparation, practice and professionalism, to better simulate the in-person experience. Study credibility was strengthened by the triangulation of qualitative, quantitative and psychometric data.

Clostridium tanneri sp. nov., isolated from the faecal material of an alpaca.

A strictly anaerobic, Gram-stain-negative rod-shaped bacterium, designated A1-XYC3T, was isolated from the faeces of an alpaca (Lama pacos). On the basis of the results of a comparative 16S rRNA gene sequence analysis, the isolate was assigned to the genus Clostridium with the highest sequence similarities to Clostridium magnum DSM 2767T (96.8 %), Clostridium carboxidivorans P7T (96.3 %) and Clostridium aciditolerans JW/YJL-B3T (96.1 %). The average nucleotide identity between A1-XYC3T, C. magnum, C. carboxidivorans and C. aciditolerans was 77.4, 76.1 and 76.6  %, respectively. The predominant components of the cellular fatty acids of A1-XYC3T were C14 : 0, C16 : 0 and summed feature 10, containing C18:0/C17:0 cyclo. The DNA G+C content was 32.4 mol%. On the basis of biochemical, phylogenetic, genotypic and chemotaxonomic criteria, this isolate represents a novel species within Clostridium sensu stricto for which the name Clostridium tanneri sp. nov. is proposed. The type strain of this species is strain A1-XYC3T (=CCM 9376T=NRRL B-65691T).

Landau Theory of Altermagnetism.

We formulate a Landau theory for altermagnets, a class of collinear compensated magnets with spin-split bands. Starting from the nonrelativistic limit, this Landau theory goes beyond a conventional analysis by including spin-space symmetries, providing a simple framework for understanding the key features of this family of materials. We find a set of multipolar secondary order parameters connecting existing ideas about the spin symmetries of these systems, their order parameters, and the effect of nonzero spin-orbit coupling. We account for several features of canonical altermagnets such as RuO_{2}, MnTe, and CuF_{2} that go beyond symmetry alone, relating the order parameter to key observables such as magnetization, anomalous Hall conductivity, and magnetoelastic and magneto-optical probes. Finally, we comment on generalizations of our framework to a wider family of exotic magnetic systems derived from the zero spin-orbit coupled limit.

Evaluation of clinical predictors of postoperative outcomes in tegmen defect patients with and without concurrent superior semicircular canal dehiscence and cerebrospinal fluid leak.

OBJECTIVES: Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical utility of intraoperative intracranial pressure measurements has yet to be tested. This report aims to use intraoperative opening pressure and concurrent superior semicircular canal dehiscence (SSCD) to analyze factors influencing disease course and clinical outcomes in patients with tegmen dehiscence. METHODS: A retrospective analysis of 61 patients who underwent tegmen defect repair was performed. Multiple variables of interest including body mass index (BMI), presence of SSCD, presence of dural venous sinus stenosis, opening pressure, and acetazolamide therapy use were recorded. The cohort was divided into those with or without concurrent SSCD and those presenting with or without cerebrospinal fluid (CSF) leak for analysis. RESULTS: A linear relationship between opening pressure and BMI (p = 0.009) was noted; however, intraoperative opening pressure was not associated with disease outcome. Concurrent SSCD was present in 25 % of patients, while 62 % presented with CSF leak. The concurrent SSCD group exhibited higher opening pressure, higher likelihood of having dural sinus stenosis, and higher likelihood of being discharged on acetazolamide. The CSF leak group had higher likelihood of obstructive sleep apnea and persistent symptoms. CONCLUSIONS: In patients undergoing tegmen defect repair, concurrent SSCD suggests increased disease severity. The presence of preoperative CSF leak predicts persistent symptoms following repair. BMI is linearly correlated with intracranial pressure in these patients.

Comparing novel smartphone pose estimation frameworks with the Kinect V2 for knee tracking during athletic stress tests.

PURPOSE: To compare the accuracy of the Microsoft Kinect V2 with novel pose estimation frameworks, in assessing knee kinematics during athletic stress tests, for fast and portable risk assessment of anterior cruciate ligament (ACL) injury. METHODS: We captured 254 varsity athletes, using the Kinect V2 and a smartphone application utilizing Google's MediaPipe framework. The devices were placed as close as possible and used to capture a person, facing the cameras, performing one of three athletic stress tests at a distance of 2.5 ms. Custom software translated the results from both frameworks to the same format. We then extracted relevant knee angles at key moments of the jump and compared them, using the Kinect V2 as the ground truth. RESULTS: The results show relatively small angle differences between the two solutions in the coronal plane and moderate angle differences on the sagittal plane. Overall, the MediaPipe framework results seem to underestimate both knee valgus angles and knee sagittal angles compared to the Kinect V2. CONCLUSION: This preliminary study demonstrates the potential for Google's MediaPipe framework to be used for calculating lower limb kinematics during athletic stress test motions, which can run on most modern smartphones, as it produces similar results to the Kinect V2. A smartphone application similar to the one developed could potentially be used for low cost and widespread ACL injury prevention.

Acute toxicity effects of pesticides on predatory snout mites (Trombidiformes: Bdellidae).

Predatory mites biologically control a range of arthropod crop pests and are often central to agricultural IPM strategies globally. Conflict between chemical and biological pest control has prompted increasing interest in selective pesticides with fewer off-target impacts on beneficial invertebrates, including predatory mites. However, the range of predatory mite species included in standardized pesticide toxicity assessments does not match the diversity of naturally occurring species contributing to biocontrol, with most testing carried out on species from the family Phytoseiidae (Mesostigmata). Here, we aim to bridge this knowledge gap by investigating the impacts of 22 agricultural pesticides on the predatory snout mite, Odontoscirus lapidaria (Kramer) (Trombidiformes: Bdellidae). Using internationally standardized testing methodologies, we identified several active ingredients with minimal impact on O. lapidaria mortality, including Bacillus thuringiensis, nuclear polyhedrosis virus, flonicamid, afidopyropen, chlorantraniliprole, and cyantraniliprole, which may therefore be good candidates for IPM strategies utilizing both chemical and biological control. Comparison of our findings with previous studies on Phytoseiid mites reveals important differences in responses to a number of chemicals between predatory mite families, including the miticides diafenthiuron and abamectin, highlighting the risk of making family-level generalizations from acute toxicity assessments. We also tested the impacts of several pesticides on a second Bdellidae species (Trombidiformes: Bdellidae) and found differences in the response to chlorpyrifos compared with O. lapidaria, further highlighting the taxon-specific nature of nontarget toxicity effects.

P2Y12 Inhibitor Monotherapy after Short Term Dual Antiplatelet Therapy in Acute Coronary Syndrome.

Recent studies have shown similar safety and efficacy of short-term dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor (P2Y12i) monotherapy when compared with standard DAPT. However, the optimal DAPT duration and regimen in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) is still unclear. Online databases were searched for randomized controlled trials (RCTs) evaluating P2Y12i monotherapy after short DAPT (≤3 months) vs standard DAPT (≥12 months) in ACS patients. The outcomes of interest were all cause death, cardiovascular (CV) death, myocardial infarction (MI), stent thrombosis (ST), target-vessel revascularization (TVR) and major bleeding. Random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI). Six RCTs with a total of 23,884 patients (n=11,904 P2Y12i monotherapy, n=11,980 standard DAPT) were included. Compared with standard DAPT, P2Y12i monotherapy after short DAPT was associated with similar odds of all cause death (OR 0.86, 0.65-1.12, p = 0.26) and CV death (OR 0.75, 0.43-1.29, p = 0.29) at 1 year. Similarly, there were no significant differences in rates of MI (OR 1.09, 0.83-1.43, p = 0.53), ST (OR 1.09, 0.71-1.67, p = 0.70) and TVR (OR 0.81, 0.65-1.01, p = 0.07) between the P2Y12i monotherapy and standard DAPT arms. The P2Y12i monotherapy group had significantly lower major bleeding (OR 0.49, 0.38-0.64, p<0.001) when compared to standard DAPT. In conclusion, among patients with ACS undergoing PCI, P2Y12i monotherapy after short DAPT significantly reduces bleeding without increasing ischemic risk when compared to standard DAPT therapy.