Maxillary nerve blocks (MNBs) commonly facilitate dental surgeries in standing horses. The goal of this prospective, blinded, cross-over design trial including 15 client-owned horses was to evaluate ...3 methods of sensory function testing for confirming a successful MNB. Testing was performed bilaterally before sedation, 5 min after sedation, and 15 and 30 min after MNB with 0.5% bupivacaine and involved a needle prick dorsal to each naris, hemostat clamping of each nostril, and gingival algometry (measuring sensitivity to pain). Responses to stimulation were numerically scored and scores were summed up to a total score. Total score increases on the blocked side by ≥ 2 between baseline and 30 min Post MNB recordings signified a successful MNB. Sedation in the preceding 6 h, presence of sino-nasal disease, side of dental pathology, age, butorphanol administration, and detomidine dosing (µg/kg/min) throughout the tooth extraction procedure were recorded. In 73% of horses, MNB was successful. Sedation in the preceding 6 h (P = .732), age (P = .936), side of pathology (P = .516), and sino-nasal disease (P = .769) were not associated with total scores. Detomidine dosage and butorphanol use did not differ between horses in which the MNB was considered successful and for those in which it was not (P = .967 and P = .538, respectively). Scores obtained with gingival algometry were less closely associated with total scores (rho = .649) than those obtained with needle prick and nostril clamping (rho = .819 and .892, respectively). Therefore, needle prick and nostril clamping are considered the more reliable methods for use in clinical practice to determine the success of an MNB.
Decommissioning of offshore oil and gas structures is either occurring, or imminent in most regions of the world. Most jurisdictions require that offshore structures be removed for onshore disposal. ...However, there is growing interest in understanding the ecological and socio-economic benefits of leaving structures in the water. Descriptions of how fish utilize the vertical structure created by wellhead platform jackets (platforms) will provide insights into possible outcomes of decommissioning alternatives, such as full removal, leave
in situ
, or translocation to a designated reefing site. We surveyed fish assemblages associated with seven platforms and five reference sites located ∼150 km offshore in the central Gulf of Thailand. The platforms spanned the entire water column (∼75 m) and were a mix of three and four legged structures. We used a Remotely Operated Vehicle (ROV) fitted with an underwater stereo video system to quantify the abundance, size, biomass, and economic value of fish associated with the platforms. We recorded 43 species of fish on the platforms and five reference sites with most fishes on platforms categorized as coral-reef or coral-reef-associated species. We observed a strong vertical zonation in the fish assemblage on the platforms. The Regal demoiselle (
Neopomacentrus cyanomos
) was numerically dominant (75% of all fish observed). We measured 3,933 kg of fish on the platforms with
Caranx sexfasciatus
accounting for 76.12% of that. We conservatively estimate each platform had a scaled mean biomass of ∼2,927 kg and the fished species had scaled mean economic value of 175,500 Thai Baht per platform. We estimated that the biomass of fish associated with the seven platforms was at least four times higher per unit area than some of the world’s most productive coral reefs.
Constitutive NF-κB signaling promotes survival in multiple myeloma (MM) and other cancers; however, current NF-κB-targeting strategies lack cancer cell specificity. Here, we identify the interaction ...between the NF-κB-regulated antiapoptotic factor GADD45β and the JNK kinase MKK7 as a therapeutic target in MM. Using a drug-discovery strategy, we developed DTP3, a D-tripeptide, which disrupts the GADD45β/MKK7 complex, kills MM cells effectively, and, importantly, lacks toxicity to normal cells. DTP3 has similar anticancer potency to the clinical standard, bortezomib, but more than 100-fold higher cancer cell specificity in vitro. Notably, DTP3 ablates myeloma xenografts in mice with no apparent side effects at the effective doses. Hence, cancer-selective targeting of the NF-κB pathway is possible and, at least for myeloma patients, promises a profound benefit.
•GADD45β is a critical mediator of the NF-κB antiapoptotic function in MM•GADD45β binds to MKK7 and promotes MM cell survival by blocking MKK7/JNK signaling•GADD45β/MKK7 inhibitors display potent activity against MM, in vitro and in vivo•GADD45β/MKK7 inhibitors are far more cancer selective than IKK/NF-κB inhibitors
NF-κB is implicated in MM and other malignancies, but it is challenging to block NF-κB only in diseased cells. Tornatore et al. identify an interaction between MKK7 and NF-κB-regulated GADD45β as a therapeutic target and develop a peptide that disrupts the complex and selectively kills MM cells.
Mechanical models have potential to guide the development and use of engineered blood vessels as well as other engineered tissues. This paper presents a microstructurally motivated, pseudoelastic, ...mechanical model of the biaxial mechanics of engineered vessels in the physiologic pressure range. The model incorporates experimentally measured densities and alignments of engineered collagen. Specifically, these microstructural and associated mechanical inputs were measured directly from engineered blood vessels that were cultured over periods of 5-7.5 weeks. To the best of our knowledge, this is the first successful application of either a phenomenological or a microstructurally motivated mechanical model to engineered vascular tissues. Model development revealed the need to use novel theoretical configurations to describe the strain history of engineered vessels. The constitutive equations developed herein suggested that collagen remodeled between 5 and 7.5 weeks during a 7.5-week culture period. This remodeling led to strain energies for collagen that differed with alignment, which likely resulted from undulations that varied with alignment. Finally, biaxial data emphasized that axial extensions increase stresses in engineered vessels in the physiologic pressure range, thereby providing a guideline for surgical use: engineered vessels should be implanted at appropriate axial extension to minimize adverse stress responses.
Undocumented migrants (UM) frequently report mental health problems. It is unknown to what extent these migrants seek help for these problems in general practice and how these issues are explored, ...discussed, registered and treated by GPs.
To gain insight in the registration and treatment of mental health problems in general practice of UM compared to documented migrants (DM).
A survey study of general practice patient records of UM and DM in nine general practices in the Netherlands. Consultation rates, registration of mental health problems, prescription of psychotropic medication and referrals to mental health care institutions of UM and DM patients were compared.
A total of 541 migrants were included (325 UM and 216 DM). UM consulted a GP significantly less than DM (3.1 versus 4.9 times per year). Only 20.6% of the UM had at least one mental health problem diagnosis registered compared to 44.0% of the DM. In both groups, ~10% mentioned at least one main mental health complaint during the consultation that was not coded in the record. No significant differences were found in the prescription of psychotropic medication between the two groups. UM were referred less to mental health care institutions but more often to psychiatrists than to psychologists.
UM had less consultations with their GP, and in these consultations, less mental health problems were registered. UM were referred less to psychologists but more often to psychiatrists. GPs are advised to explore and register mental health problems more actively in UM.
We investigated the composition and abundance of fish assemblages associated with seven offshore oil and gas platform jackets in the Gulf of Thailand before (pre-lift and pre-tow), and immediately ...after relocation (post-tow and reefed). Jackets were cut, lifted until partly out of the water, and attached to the rear of a heavy lift vessel. They were towed at speeds of 2.7 – 3.3 knots for between 133.9 and 205.4 km before being placed on the seafloor at an artificial reef site. Sixteen species of fish were observed both before and after jacket towing. We believe these species have sought refuge in the complex structures out of the current and have remained with the jackets. Ten species of fish were observed before towing, but not after. A further seven species of fish were only observed after the jackets were relocated onto the seafloor and were assumed to be early colonisers to the structures. The paper provides empirical evidence of a much-discussed paradigm that fish can swim great distances following moved structures, and further evidence of the ability of fish to rapidly colonise reefed structures.
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•Fish on oil and gas jackets were surveyed before, during and after towing.•16 species of fish remained with the jackets during relocation (followers).•10 species of fish did not follow the jackets (deserters).•7 new species of fish were observed (colonisers) within two days of placement of jackets on the seabed.•“Followers” likely sought refuge in the complex structures out of the current during towing.
Hematological cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies ...are needed. The Wiskott-Aldrich syndrome protein (WASp) family regulates actin assembly in conjunction with the Arp2/3 complex, a ubiquitous nucleation factor. WASp is expressed exclusively in hematopoietic cells and exists in two allosteric conformations: autoinhibited or activated. Here, we describe the development of EG-011, a first-in-class small molecule activator of the WASp auto-inhibited form. EG-011 possesses in vitro and in vivo anti-tumor activity as a single agent in lymphoma, leukemia, and multiple myeloma, including models of secondary resistance to PI3K, BTK, and proteasome inhibitors. The in vitro activity was confirmed in a lymphoma xenograft. Actin polymerization and WASp binding was demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs-inducing actin polymerization.
Immune checkpoint inhibitor-related pneumonitis is a serious autoimmune event affecting up to 20% of patients with non-small cell lung cancer, yet the factors underpinning its development in some ...patients and not others are poorly understood.
To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis.
The study cohort consisted of non-small cell lung cancer patients who gave blood samples before and during immune checkpoint inhibitor treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with non-small cell lung cancer and patients with melanoma.
Across both cohorts, patients who developed pneumonitis had higher pre-treatment levels of immunoglobulin G autoantibodies targeting surfactant protein-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4
interferon-gamma-positive surfactant protein B-specific T cells, and expanding T cell clonotypes recognizing this protein, accompanied by a pro-inflammatory serum proteomic profile.
Our data suggest that the co-occurrence of surfactant protein-B-specific immunoglobulin G autoantibodies and CD4
T cells is associated with the development of pneumonitis during ICI therapy. Pre-treatment levels of these antibodies may represent a potential biomarker for elevated risk of developing pneumonitis and on-treatment levels may provide a diagnostic aid. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
After 25 years of studies on methodologies for behavioral assessment of equine pain, the Unesp-Botucatu Horse Acute Pain Scale (UHAPS) and the Orthopedic Composite Pain Scale (CPS) were recently ...considered suboptimal instruments to assess pain in hospitalized horses. However, the combination of the two instruments has never been examined. The objective was to investigate whether the merging, mining, and weighting of UHAPS and CPS behavioral items in a single instrument using a predictive model could improve the capacity to diagnose pain in horses. A previously video-collected behavioral database of 42 horses admitted to three different hospitals for orthopedic or soft tissue surgery was used. Multilevel binomial logistic regression models were used to merge, mine, and weight the behaviors of both instruments. The classification quality between the model and the instruments was compared by the area under the curve (AUC) and its 95% confidence interval. The short model containing 25% of the behaviors of the two instruments showed a higher AUC (98.64 98.16 – 99.12; p < 0.0001) than the UHAPS (84.63 82.08 – 87.18) and CPS (88.62 86.56 – 90.66), independently. We conclude that merging, mining, and weighting the UHAPS and CPS behavior items into a single predictive model appears to be a promising strategy to improve pain diagnostic skill and promote equine welfare.
●Predictive model improves the diagnosis of pain in horses.●Merging, mining, and weighting two behavioral pain scales improved pain diagnosis.●Model showed different importance levels of pain behaviors.
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