Selective inhibition of CDK7 reveals high-confidence targets and new models for TFIIH function in transcription.

CDK7 associates with the 10-subunit TFIIH complex and regulates transcription by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). Few additional CDK7 substrates are known. Here, using the covalent inhibitor SY-351 and quantitative phosphoproteomics, we identified CDK7 kinase substrates in human cells. Among hundreds of high-confidence targets, the vast majority are unique to CDK7 (i.e., distinct from other transcription-associated kinases), with a subset that suggest novel cellular functions. Transcription-associated factors were predominant CDK7 substrates, including SF3B1, U2AF2, and other splicing components. Accordingly, widespread and diverse splicing defects, such as alternative exon inclusion and intron retention, were characterized in CDK7-inhibited cells. Combined with biochemical assays, we establish that CDK7 directly activates other transcription-associated kinases CDK9, CDK12, and CDK13, invoking a "master regulator" role in transcription. We further demonstrate that TFIIH restricts CDK7 kinase function to the RNAPII CTD, whereas other substrates (e.g., SPT5 and SF3B1) are phosphorylated by the three-subunit CDK-activating kinase (CAK; CCNH, MAT1, and CDK7). These results suggest new models for CDK7 function in transcription and implicate CAK dissociation from TFIIH as essential for kinase activation. This straightforward regulatory strategy ensures CDK7 activation is spatially and temporally linked to transcription, and may apply toward other transcription-associated kinases.

This land is your land, this could be marsh land: Property parcel characteristics of marsh migration corridors in Rhode Island, USA.

Salt marshes, critical habitats offering many ecosystem services, are threatened by development, accelerated sea level rise (SLR) and other anthropogenic stressors that are projected to worsen. As seas rise, some salt marshes can migrate inland if there is adjacent, permeable, undeveloped land available. Facilitating marsh migration is necessary for coastal resilience efforts, but extensive coastal development can make finding suitable migration corridors challenging. This work seeks to characterize changes in land use, ownership, and economic value at the property parcel level within current versus future marsh areas for the state of Rhode Island, USA. We find that most parcels currently containing salt marsh are publicly owned, whereas most adjacent parcels projected to contain new salt marsh in 2050 are privately owned. Additionally, parcels containing new marsh in 2050 have 47% higher per-hectare assessed values than parcels containing current marsh. We describe the locations and characteristics of parcels within migration corridors with the lowest per-hectare values that may be the most cost-effective for marsh conservation practitioners to protect. This study highlights the expanding land use types and landowner sets that will be involved in marsh conservation decisions, and the economic value of potential migration corridors where costly tradeoffs may be necessary to promote coastal resilience.

Medication Deprescribing Among Patients With Type 2 Diabetes: A Qualitative Case Series of Lifestyle Medicine Practitioner Protocols.

This study is a qualitative case series of lifestyle medicine practitioners' protocols for medication de-escalation in the context of reduced need for glucose-lowering medications due to lifestyle modifications. Increasing numbers of lifestyle medicine practitioners report achieving reductions in medications among patients with type 2 diabetes, and in some cases remission, but limited data exist on the clinical decision-making process used to determine when and how medications are deprescribed. Practitioners interviewed here provide accounts of their deprescribing protocols. This information can serve as pilot data for other practitioners seeking examples of how deprescribing in the context of lifestyle medicine treatment is conducted.

Hazardous and contaminated sites within salt marsh migration corridors in Rhode Island, USA.

As salt marshes attempt to migrate upland due to sea level rise, they will encounter many kinds of land development and infrastructure in highly populated, urbanized coastal communities. Hazardous and contaminated sites (HCSs) -- facilities and infrastructure that store, use, or release harmful substances -- are particularly concerning obstacles to salt marsh migration because of their potential to release contaminants if their structural integrity is compromised. Inventorying HCSs within migration pathways can inform coastal resilience planning. To understand what kinds of HCSs migrating marsh may encounter in Rhode Island, USA, we inventoried sites from federal and state sources, assigned contaminant hazard rankings to most sites, and overlayed them with projected marsh migration corridors. We found that HCSs are extensive across marsh migration corridors in the state, especially in urban areas. Among the most common HCSs in and around Rhode Island salt marshes are stormwater outfalls, underground storage tanks, and facilities registered with EPA's Resource Conservation and Recovery Act (RCRA) or EPA's National Pollutant Discharge Elimination System (NPDES). These sites pose varying hazards to human and aquatic life if breached, with some sites representing little or no threat but most posing some degree of hazard to their surroundings. This coastal HCSs inventory can inform prioritization and management of coastal salt marshes subject to accelerated sea level rise. Management decisions such as allowing marsh migration, implementing adaptation actions to build salt marsh elevation, or erecting physical barriers at marsh sites will influence future salt marsh extent, marshes' ability to provide ecosystem services, and public health exposures to toxic releases. In addition, as Rhode Island and other coastal states work to promote coastal resiliency, this type of inventory can inform decisions about which HCSs to prioritize for remediation and other climate adaptation actions. Marsh migration is just one potential consequence of sea level rise, so many of the considerations outlined here are widely applicable to the broader goal of preparing coastal communities for rising seas.

Determining the heat of desorption for cassava products based on data measured by an automated gravimetric moisture sorption system.

BACKGROUND: The isosteric heat of desorption is vital in evaluating the energy performance of food dryers. The isosteric heat of desorption was investigated for different cassava (Manihot esculenta Crantz) products prepared as flour or starch, with and without fermentation. An automated moisture sorption gravimetric analyser was used to measure the desorption isotherms over 10-90% relative humidity of the drying air at temperatures ranging from 25 to 65 °C. RESULTS: Analysis of variance showed an imperceptible contribution of the preparation method in the measured desorption data. This finding also agreed with microscopical images, which revealed the lack of compelling structural differences among different products. A set of empirical sorption equations suggested by the ASAE standard was examined over the measured desorption isotherms. The standard error of estimation was found to be in the acceptable range of 2.36-3.71%. Furthermore, the fulfilment of the enthalpy-entropy compensation theory was considered as an additional criterion in the thermodynamic results of different sorption equations, besides their fitting adequacy. The modified Chung-Pfost equation has proved to be the most suitable equation for cassava products, as it is capable of reflecting the temperature dependency of the isosteric heat of desorption. The net isosteric heat of desorption obtained was in the range of 540-1110 kJ kg-1 for 0.10 kg kg-1 dry-basis moisture content and 52-108 kJ kg-1 for 0.25 kg kg-1 dry-basis moisture content. CONCLUSION: These findings are technologically relevant for optimising common drying technologies such as flash and flatbed dryers. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Prehospital Mechanical Ventilation: An NAEMSP Position Statement and Resource Document.

Airway emergencies and respiratory failure frequently occur in the prehospital setting. Patients undergoing advanced airway management customarily receive manual ventilations. However, manual ventilation is associated with hypo- and hyperventilation, variable tidal volumes, and barotrauma, among other potential complications. Portable mechanical ventilators offer an important strategy for optimizing ventilation and mitigating ventilatory complications.EMS clinicians, including those performing emergency response as well as interfacility transports, should consider using mechanical ventilation after advanced airway insertion.Prehospital mechanical ventilation techniques, strategies, and parameters should be disease-specific and should mirror in-hospital best practices.EMS clinicians must receive training in the general principles of mechanical ventilation as well as detailed training in the operation of the specific system(s) used by the EMS agency.Patients undergoing mechanical ventilation must receive appropriate sedation and analgesia.

Evaluation of alfaxalone total intravenous anesthesia in rabbits (Oryctolagus cuniculus) premedicated with dexmedetomidine or dexmedetomidine and buprenorphine.

OBJECTIVE: To evaluate alfaxalone for total intravenous anesthesia (TIVA) in rabbits premedicated with dexmedetomidine or dexmedetomidine and buprenorphine. STUDY DESIGN: Crossover study (part 1) with observational study (part 2). ANIMALS: A total of eight New Zealand White rabbits (Oryctolagus cuniculus), four female and four male, aged 12-16 weeks and weighing 2.8-3.5 kg in part 1. Separately, four additional rabbits in part 2. METHODS: Crossover study design with eight rabbits per treatment. Rabbits were administered treatment D, dexmedetomidine (0.2 mg kg-1), or treatment DB, dexmedetomidine (0.1 mg kg-1) and buprenorphine (0.05 mg kg-1) intramuscularly. Anesthesia was induced with alfaxalone intravenously until a supraglottic airway device was placed to deliver 100% oxygen. Anesthesia was maintained with alfaxalone (TIVA). Infusion rates were adjusted to achieve an absent pedal withdrawal reflex. Heart rate, respiratory rate, noninvasive blood pressure, end-tidal carbon dioxide partial pressure and peripheral hemoglobin oxygen saturation (SpO2) were recorded every 5 minutes. Subsequently, four rabbits underwent ovariohysterectomy using treatment DB and alfaxalone TIVA. RESULTS: The mean ± standard deviation alfaxalone infusion rate was 9.6 ± 2.6 and 4.5 ± 1.3 mg kg-1 hour-1 for treatments D and DB, respectively. In both treatments, blood pressure remained within acceptable range and SpO2 was > 95%. Postinduction apnea and respiratory depression were observed in both treatments and managed with manual positive pressure ventilation. Four separate rabbits underwent successful ovariohysterectomy with treatment DB and alfaxalone TIVA. One rabbit required supplementation with inhalant anesthesia; three rabbits were successfully maintained using alfaxalone TIVA alone. CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with dexmedetomidine-buprenorphine combined with alfaxalone TIVA may be a viable alternative for performing abdominal surgery in the rabbit. The use of supplemental oxygen and ability to provide respiratory support are advised.

Charged particle radiation induced changes to optical properties of acousto-optic materials.

We report on the measurement of the transmittance and reflectance of unpolarized light (425-700 nm) in three birefringent, acousto-optic materials, including quartz, lithium niobate, and tellurium dioxide, after exposure to varying fluences of proton radiation ($ {10^{14}} {-} {10^{18}}\;{\rm protons}/{{\rm cm}^2} $1014-1018protons/cm2) delivered by a 10 keV hydrogen ion beamline. We observe a general monotonic decrease in transmittance with increasing fluence for all three materials, but with varying rates of change and critical points of change. Reflectance measurements also exhibit a general monotonic trend with fluence, but increases in quartz are observed versus decreases in both lithium niobate and tellurium dioxide. These observations are used to assess the suitability of the materials for acousto-optic applications in the space environment where charged particles from the solar wind are dominant and pose a threat to device operation. Our measurements agree with previously reported work concluding that tellurium dioxide is suitable for space applications at low fluences (below $ {{10}^{16}}\;{\rm ions}/{{\rm cm}^2} $1016ions/cm2), but our findings also raise previously unreported concerns for higher accumulated fluences observed for longer mission lifetimes of greater than five to 10 years in space in an unshielded configuration.

Effects of subcutaneous alfaxalone alone and in combination with dexmedetomidine and buprenorphine in guinea pigs (Cavia porcellus).

OBJECTIVE: To characterize alfaxalone administered subcutaneously (SC) in guinea pigs, both alone and in combination with dexmedetomidine and buprenorphine. STUDY DESIGN: Prospective, blinded, crossover study. ANIMALS: A total of 15 healthy female guinea pigs weighing 400-600 g. METHODS: Alfaxalone (10, 20 and 40 mg kg-1) was administered SC to three guinea pigs as a pilot dose-finding study. Alfaxalone (20 mg kg-1; A20) was selected for comparison against combination protocols of alfaxalone (15 and 20 mg kg-1) with dexmedetomidine (0.25 mg kg-1) and buprenorphine (0.05 mg kg-1; A15DB, A20DB). Each protocol was randomly administered to 12 guinea pigs separated by ≥7 days. Time and quality of induction and recovery, heart rate, respiratory rate, peripheral hemoglobin oxygen saturation, rectal temperature, pedal withdrawal reflex and adverse effects were recorded. RESULTS: The median time to induction for A20, A15DB and A20DB was 6.8-8.0 minutes with no significant difference between treatments. Mean duration of recumbency for A20 was 73.6 ± 19.6 minutes. Recumbency duration for A15DB and A20DB extended to 90 minutes, at which time dexmedetomidine was antagonized using atipamezole (0.025 mg kg-1 SC). Physiological variables were within normal limits with the exception of one animal that died 45 minutes following treatment with A20DB. Pedal withdrawal reflex remained intact with all treatments. Minor side effects such as twitching or bruxism occurred sporadically with treatment A20 but not with A15DB and A20DB. CONCLUSIONS AND CLINICAL RELEVANCE: SC alfaxalone produced uncomplicated sedation that may be recommended for nonpainful procedures that do not require complete immobility. The addition of dexmedetomidine and buprenorphine increased the duration of sedation and immobility, but did not result in general anesthesia. This combination sedation protocol may be useful for nonpainful procedures requiring extended immobility.

Site-specific cation release drives actin filament severing by vertebrate cofilin.

Actin polymerization powers the directed motility of eukaryotic cells. Sustained motility requires rapid filament turnover and subunit recycling. The essential regulatory protein cofilin accelerates network remodeling by severing actin filaments and increasing the concentration of ends available for elongation and subunit exchange. Although cofilin effects on actin filament assembly dynamics have been extensively studied, the molecular mechanism of cofilin-induced filament severing is not understood. Here we demonstrate that actin filament severing by vertebrate cofilin is driven by the linked dissociation of a single cation that controls filament structure and mechanical properties. Vertebrate cofilin only weakly severs Saccharomyces cerevisiae actin filaments lacking this "stiffness cation" unless a stiffness cation-binding site is engineered into the actin molecule. Moreover, vertebrate cofilin rescues the viability of a S. cerevisiae cofilin deletion mutant only when the stiffness cation site is simultaneously introduced into actin, demonstrating that filament severing is the essential function of cofilin in cells. This work reveals that site-specific interactions with cations serve a key regulatory function in actin filament fragmentation and dynamics.

Intra-rater and inter-rater reliability of ultrasonographic measurements of acromion-greater tuberosity distance in patients with post-stroke hemiplegia.

BACKGROUND: Glenohumeral subluxation (GHS) is reported in up to 81% of patients with stroke. Ultrasonographic measurements of GHS by measuring the acromion-greater tuberosity (AGT) have been found to be reliable for experienced raters. OBJECTIVES: The primary aim was to assess the intra-rater reliability of measurements of AGT distance in people with stroke following a short course of rater training. A secondary aim was to compare the inter-rater reliability of these measurements between novice and experienced raters. METHODS: Patients with stroke (n = 16; 5 men, 11 women; 74 ± 10 years) with 1-sided weakness who gave informed consent were recruited. Ultrasonographic measurements were recorded at the bedside by two physiotherapists with patients seated upright in a hospital chair. Reliability was assessed by intra-class correlation coefficients (ICCs) and the standard error of measurements (SEM). Minimum detectable change (MDC90) scores were used to estimate the magnitude of change that is likely to exceed measurement error. RESULTS: Mean ± SD AGT distances on the affected and unaffected sides for rater 1 were 2.2 ± 0.7 and 1.7 ± 0.4 cm, respectively. Corresponding values for rater 2 were 2.5 ± 0.6 and 2.0 ± 0.4 cm. Intra-class correlation coefficient values for the affected and unaffected shoulders for rater 1 were 0.96 and 0.91, respectively. Corresponding values for rater 2 were 0.95 and 0.90.SEM and MDC90 for both affected and unaffected shoulders were ≤ 0.2 cm. Inter-rater reliability coefficients were 0.86 (affected) and 0.76 (unaffected) shoulders. CONCLUSION: Ultrasonographic measurement of AGT distance demonstrates excellent intra-rater reliability for a novice rater. Inter-rater reliability of ultrasonographic measurement of AGT also demonstrates good reliability between novice and experienced raters.

Increased dissolution rates of carbamazepine--gluconolactone binary blends processed by hot melt extrusion.

Carbamazepine (CBZ) shows a poor dissolution, therefore, it is important to enhance its dissolution in GI tract to improve its bioavailability. In the present study, a new hydrophilic carrier, d-gluconolactone (GNL), was extruded with CBZ at various molar ratios to produce granules by using hot melt extrusion (HME) processing. The granular extrudates were characterised by X-ray powder diffraction, differential scanning calorimetry and hot stage microscopy to determine the solid state of CBZ. It was found that bulk CBZ (Form-III) transformed to the polymorphic Form-I during the HME processing. GNL was proved to be an efficient carrier for CBZ to enhance the dissolution rate. The increase in the dissolution rate was observed for both physical mixtures and the extrudates of CBZ-GNL. However, the extrudates showed faster dissolution rates compared to physical mixtures in an ascending order of 2:1 < 1:1 < 1.5:1 (CBZ:GNL). The increase in the dissolution rates was attributed to the transformation of CBZ III to Form-I and also to the increased drug wettability/solubilisation in the presence of the carrier.

Alteration in the cavity size adjacent to the active site of RB69 DNA polymerase changes its conformational dynamics.

Internal cavities are a common feature of many proteins, often having profound effects on the dynamics of their interactions with substrate and binding partners. RB69 DNA polymerase (pol) has a hydrophobic cavity right below the nucleotide binding pocket at the tip of highly conserved L415 side chain. Replacement of this residue with Gly or Met in other B family pols resulted in higher mutation rates. When similar substitutions for L415 were introduced into RB69pol, only L415A and L415G had dramatic effects on pre-steady-state kinetic parameters, reducing base selectivity by several hundred fold. On the other hand, the L415M variant behaved like the wild-type. Using a novel tC(o)-tCnitro Förster Resonance Energy Transfer (FRET) assay, we were able to show that the partition of the primer terminus between pol and exonuclease (exo) domains was compromised with the L415A and L415G mutants, but not with the L415M variant. These results could be rationalized by changes in their structures as determined by high resolution X-ray crystallography.

Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness.

The assembly of actin monomers into filaments and networks plays vital roles throughout eukaryotic biology, including intracellular transport, cell motility, cell division, determining cellular shape, and providing cells with mechanical strength. The regulation of actin assembly and modulation of filament mechanical properties are critical for proper actin function. It is well established that physiological salt concentrations promote actin assembly and alter the overall bending mechanics of assembled filaments and networks. However, the molecular origins of these salt-dependent effects, particularly if they involve nonspecific ionic strength effects or specific ion-binding interactions, are unknown. Here, we demonstrate that specific cation binding at two discrete sites situated between adjacent subunits along the long-pitch helix drive actin polymerization and determine the filament bending rigidity. We classify the two sites as "polymerization" and "stiffness" sites based on the effects that mutations at the sites have on salt-dependent filament assembly and bending mechanics, respectively. These results establish the existence and location of the cation-binding sites that confer salt dependence to the assembly and mechanics of actin filaments.

Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate.

Rab GTPases are key regulators of membrane traffic pathways within eukaryotic cells. They are specifically activated by guanine nucleotide exchange factors (GEFs), which convert them from their "inactive" GDP-bound form to the "active" GTP-bound form. In higher eukaryotes, proteins containing DENN-domains comprise a major GEF family. Here we describe at 2.1-Å resolution the first structure of a DENN-domain protein, DENND1B-S, complexed with its substrate Rab35, providing novel insights as to how DENN-domain GEFs interact with and activate Rabs. DENND1B-S is bi-lobed, and interactions with Rab35 are through conserved surfaces in both lobes. Rab35 binds via switch regions I and II, around the nucleotide-binding pocket. Positional shifts in Rab residues required for nucleotide binding may lower its affinity for bound GDP, and a conformational change in switch I, which makes the nucleotide-binding pocket more solvent accessible, likely also facilitates exchange.

Regulation of actin by ion-linked equilibria.

Actin assembly, filament mechanical properties, and interactions with regulatory proteins depend on the types and concentrations of salts in solution. Salts modulate actin through both nonspecific electrostatic effects and specific binding to discrete sites. Multiple cation-binding site classes spanning a broad range of affinities (nanomolar to millimolar) have been identified on actin monomers and filaments. This review focuses on discrete, low-affinity cation-binding interactions that drive polymerization, regulate filament-bending mechanics, and modulate interactions with regulatory proteins. Cation binding may be perturbed by actin post-translational modifications and linked equilibria. Partial cation occupancy under physiological and commonly used in vitro solution conditions likely contribute to filament mechanical heterogeneity and structural polymorphism. Site-specific cation-binding residues are conserved in Arp2 and Arp3, and may play a role in Arp2/3 complex activation and actin-filament branching activity. Actin-salt interactions demonstrate the relevance of ion-linked equilibria in the operation and regulation of complex biological systems.

Computer-Assisted Navigation Accurately Delivers Preoperative Targets for Acetabular Component Orientation During Direct Anterior Approach Total Hip Arthroplasty.

Despite its success, total hip arthroplasty (THA) remains associated with potentially significant complications associated with component malposition. Preoperative planning can mitigate some of these potential concerns; however, the accurate intraoperative delivery of preoperative targets can be challenging. Computer-assisted navigation may assist with intraoperative target delivery, although the integration of these two technologies is relatively uncommon. We retrospectively reviewed cases of THA planned with a computed tomography-based preoperative planning software and performed with the use of an imageless, computer-assisted navigation system. Postoperative acetabular component orientation from radiographs was compared with preoperative targets and intraoperative navigation measurements. A total of 76 patients were included in the analysis. The mean anteversion target (20.0°±3.1°) did not differ significantly from the mean intraoperative navigation measurement (20.5°±3.3°; P=.30; mean difference, 2.2°±2.3°). The mean radiographic measurement (26.6°±6.5°) differed from the target by a mean of 7.5°±6.1° (P<.001). The mean inclination target (38.4°±1.9°) did not differ significantly from the mean intra-operative measurement (38.0°±1.5°; P=.20; mean difference, 1.3°±1.7°) but differed from the radiographic measurement by a mean of 5.2°±4.2° (41.8°±5.6°; P<.001). No adverse events were reported in the 90-day period following the index procedure. Our study demonstrated that an imageless navigation system can accurately deliver computed tomography-derived preoperative targets for acetabular component orientation. Differences noted on radiographs may be due to the difference in patient positioning for the postoperative imaging (standing) as compared with preoperative imaging or surgery itself (supine). [Orthopedics. 2023;46(4):218-223.].

Segregation of formulated powders in direct compression process and evaluations by small bench-scale testers.

Powder segregation can cause severe issues in processes of pharmaceutical drugs for control of content uniformity if the powder is likely to be free or easy flowing. Assessing segregation intensity of formulated powders in a process is challenging at the formulation stage because of the limited availability of samples. An advanced segregation evaluation using small bench-scale testers can be useful for formulation decisions and suggestions of operation conditions in the process, which has not been practically investigated before. In this study, eight formulations (two co-processed excipients blended with one active pharmaceutical ingredient at different ratios) were used for the segregation study on two types of bench-scale testers (air-induced and surface rolling segregation tester), and a pilot simulation process rig as a comparative study. The results show that segregation measured on the bench-scale testers can give a good indication of the segregation intensity of a blend if the segregation intensity is not more than 20%. The comparison also shows that both the bench-scale testers have a good correlation to the process rig, respectively, which means either segregation tester can be used independently for the evaluation. A linear regression model was explored for prediction of segregation in the process.

Evaluating the Functional Equivalency of Test Organism Performance in Negative and Solvent Controls During Chronic Sediment Ecotoxicity Studies Based on US Environmental Protection Agency Guidance.

The US Environmental Protection Agency (USEPA) considers sediment toxicity tests as conditional registration requirements for pesticides with soil Kd ≥50 L/kg-solid, Koc ≥1000 L/kg-organic carbon, or log Kow ≥3. The hydrophobicity of these compounds often necessitates use of solvents to ensure accurate and homogeneous dosing of spiked-sediment studies. For sediment tests, a volatile solvent (e.g., acetone) is generally used as a transient carrier. Due to low water solubility, test material is dissolved in a volatile solvent to create stock solutions. A measured aliquot of stock solution is then mixed with sand substrate, after which the solvent is evaporated. This spiking process results in negligible solvent exposure to organisms. In 2016, USEPA released final ecotoxicity test guidelines for subchronic freshwater (850.1735) and marine (850.1740) sediment test. These methods provide an option for conducting experiments with only a solvent control and no negative control. To adopt this testing strategy, functional equivalency between the negative and solvent control must be demonstrated. These test guidelines describe specific factors that should be considered for evaluating functional equivalency, including (a) the concentration of solvent in the test sediment after evaporation, (b) the levels of solvent that are known to affect organism health, (c) the known impurities in the solvent and their potential impact on organism health, and (d) the historical organism performance of solvent versus negative controls. Our analysis considers these factors and overall supports the elimination of the negative control requirement because this change is unlikely to impact the robustness or interpretability of spiked-sediment toxicity tests. Environ Toxicol Chem 2023;00:1-7. © 2023 CropLife America. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Improving alignment in total knee arthroplasty: a cadaveric assessment of a surgical navigation tool with computed tomography imaging.

PURPOSE: To investigate the accuracy of an imageless, optical surgical navigation tool to assist with femoral and tibial bone cuts performed during TKA. PATIENTS AND METHODS: Six board-certified orthopedic surgeons participated in a laboratory cadaver investigation, performing femoral and tibial bone cuts with the assistance of a computer navigation tool. Femoral and tibial varus/valgus, tibial slope, femoral flexion, and both femoral and tibial rotation measurements from the device were compared with angular measurements calculated from computed tomography (CT) images of the knees. RESULTS: Measurements with the navigation tool were highly correlated with those obtained from CT scans in all three axes. For the distal femoral cut, the absolute mean difference in varus/valgus was 0.83° (SD 0.46°, r = 0.76), femoral flexion was 1.91° (SD 1.16°, r = 0.85), and femoral rotation was 1.29° (SD 1.01°, r = 0.88) relative to Whiteside's line and 0.97° (SD 0.56°, r = 0.81) relative to the posterior condylar axis. For the tibia, the absolute mean difference in varus/valgus was 1.08° (SD 0.64°, r = 0.85), posterior slope was 2.78° (SD 1.40°, r = 0.60), and rotation relative to the anteroposterior axis (posterior cruciate ligament to the medial third of the tibial tuberosity) was 2.98° (SD 2.54°, r = 0.79). CONCLUSION: Utilization of an imageless navigation tool may aid surgeons in accurately performing and monitoring femoral and tibial bone cuts, and implant rotation in TKA and thus, more accurately align TKA components.