Evaluation of three acetabular measurement methods for total hip replacement in dogs.

Objective: To compare three measurement methods for acetabular sizing and evaluate the influence of osteoarthritis (OA) on the accuracy of measurements.

Study Design: Observational study.

Sample: Radiographic images of 73 hip joints from 60 dogs with cementless cups.

Genome-scale clustered regularly interspaced short palindromic repeats screen identifies nucleotide metabolism as an actionable therapeutic vulnerability in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common malignancy that develops in patients with ataxia-telangiectasia, a cancer-predisposing inherited syndrome characterized by inactivating germline ATM mutations. ATM is also frequently mutated in sporadic DLBCL. To investigate lymphomagenic mechanisms and lymphoma-specific dependencies underlying defective ATM, we applied RNA sequencing and genome-scale loss-of-function clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens to systematically interrogate B-cell lymphomas arising in a novel murine model (Atm-/-nu-/-) with constitutional Atm loss, thymic aplasia but residual T-cell populations.

Synthesis and characterisation of a nucleotide based pro-drug formulated with a peptide into a nano-chemotherapy for colorectal cancer.

Recent studies in colorectal cancer patients (CRC) have shown that increased resistance to thymidylate synthase (TS) inhibitors such as 5-fluorouracil (5-FU), reduce the efficacy of standard of care (SoC) treatment regimens. The nucleotide pool cleanser dUTPase is highly expressed in CRC and is an attractive target for potentiating anticancer activity of chemotherapy. The purpose of the current work was to investigate the activity of P, P-di(2',5'-dideoxy-5'-selenouridinyl)-tetraphosphate (P-SedU), a selenium-modified symmetrically capped dinucleoside with prodrug capabilities that is specifically activated by dUTPase.

Compromised health: Examining growth and health in a late antique Roman infant and child cemetery.

Objectives: Combining research from infant and child development, public health, anthropology, and history, this research examines the relationship between growth, growth disruption, and skeletal indicators of chronic and/or episodic physiological stress (stress) among juvenile individuals (n = 60) interred at the late antique infant and child cemetery at Poggio Gramignano (PG) (ca. 5th century CE), associated with a rural agricultural community.

Materials And Methods: Growth disruption-evidenced by decreased long bone length compared to dental age-and stress experience-evidenced by skeletal stress indicators-within these individuals are compared to those within juveniles from a comparative sample (n = 66) from two urban Roman-era cemeteries, Villa Rustica (VR) (0-250 CE) and Tragurium City Necropolis (TCN) (0-700 CE).

The osteogenic and angiogenic potential of microRNA-26a delivered via a non-viral delivery peptide for bone repair.

Bone-related injuries and diseases are among the most common causes of morbidity worldwide. Current bone-regenerative strategies such as auto- and allografts are invasive by nature, with adverse effects such as pain, infection and donor site morbidity. MicroRNA (miRNA) gene therapy has emerged as a promising area of research, with miRNAs capable of regulating multiple gene pathways simultaneously through the repression of post-transcriptional mRNAs.

Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine.

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed.

POLθ processes ssDNA gaps and promotes replication fork progression in BRCA1-deficient cells.

Polymerase theta (POLθ) is an error-prone DNA polymerase whose loss is synthetically lethal in cancer cells bearing breast cancer susceptibility proteins 1 and 2 (BRCA1/2) mutations. To investigate the basis of this genetic interaction, we utilized a small-molecule inhibitor targeting the POLθ polymerase domain. We found that POLθ processes single-stranded DNA (ssDNA) gaps that emerge in the absence of BRCA1, thus promoting unperturbed replication fork progression and survival of BRCA1 mutant cells.

Exploring the genetic space of the DNA damage response for cancer therapy through CRISPR-based screens.

The concepts of synthetic lethality and viability have emerged as powerful approaches to identify vulnerabilities and resistances within the DNA damage response for the treatment of cancer. Historically, interactions between two genes have had a longstanding presence in genetics and have been identified through forward genetic screens that rely on the molecular basis of the characterized phenotypes, typically caused by mutations in single genes. While such complex genetic interactions between genes have been studied extensively in model organisms, they have only recently been prioritized as therapeutic strategies due to technological advancements in genetic screens.

Analysis of risk factors associated with complications following mandibulectomy and maxillectomy in dogs.

Objective: To provide information about complication rates and the risk factors for complications with mandibulectomy and maxillectomy procedures in dogs.

Animals: 459 client-owned dogs that underwent a mandibulectomy or maxillectomy between January 1, 2007, and January 1, 2018.

Procedures: Inclusion criteria included a complete medical record that contained an anesthesia record, surgical report, available histopathology results, and results of CBC and serum biochemical analysis before surgery.

Geospatial and Temporal Associations between Increases in Opioid Deaths, Socioeconomics, and Rates of Sexually Transmitted Infections in the Northeast United States 2012-2017.

With the introduction of fentanyl to illegal markets in 2013 and an overall rise in rates of synthetic opioid use, opioid-related deaths have increased significantly. A similar trend has been observed for sexually transmitted infections, homicides, and poor mental health outcomes. In this paper, we explore the spatiotemporal relationship between opioid death rates and sexually transmitted infection (STI) rates in counties from the Northeast region of the United States between the years 2012-2017.

A Cautionary Tale of Etanercept Use in Patients With Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis (TEN) is a severe cutaneous reaction that can be life-threatening. In the United States, there are no established guidelines for the treatment of TEN. Supportive care including fluids and supportive therapies are the current recommendations.

Risk Factors of Recurrent Falls Among Older Adults Admitted to the Trauma Surgery Department.

Falls affect more than 29 million American adults ages ≥65 years annually. Many older adults experience recurrent falls requiring medical attention. These recurrent falls may be prevented through screening and intervention.

A single cell transcriptional atlas of early synovial joint development.

Synovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage-tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents.

Changes of the end plate cartilage are associated with intervertebral disc degeneration: A quantitative magnetic resonance imaging study in rhesus monkeys and humans.

Background: The end plate plays an important role in intervertebral disc degeneration progression. The aim of the study was to examine the compositional and structural changes of the end plate with age and to investigate the correlation between end plate and disc degeneration by T1ρ and T2 map magnetic resonance imaging.

Methods: There were 12 young monkeys (6-7 years old), 20 aged monkeys (14-17 years old) and 12 human participants (30-50 years old) in this study.

Synthesis and Evaluation of a Thermoresponsive Degradable Chitosan-Grafted PNIPAAm Hydrogel as a "Smart" Gene Delivery System.

Thermoresponsive hydrogels demonstrate tremendous potential as sustained drug delivery systems. However, progress has been limited as formulation of a stable biodegradable thermosensitive hydrogel remains a significant challenge. In this study, free radical polymerization was exploited to formulate a biodegradable thermosensitive hydrogel characterized by sustained drug release.

Solid-phase synthesis and structural characterisation of phosphoroselenolate-modified DNA: a backbone analogue which does not impose conformational bias and facilitates SAD X-ray crystallography.

Oligodeoxynucleotides incorporating internucleotide phosphoroselenolate linkages have been prepared under solid-phase synthesis conditions using dimer phosphoramidites. These dimers were constructed following the high yielding Michaelis-Arbuzov (M-A) reaction of nucleoside -phosphonate derivatives with 5'-deoxythymidine-5'-selenocyanate and subsequent phosphitylation. Efficient coupling of the dimer phosphoramidites to solid-supported substrates was observed under both manual and automated conditions and required only minor modifications to the standard DNA synthesis cycle.

Altered gait mechanics are associated with severity of chondropathy after hip arthroscopy for femoroacetabular impingement syndrome.

Background: Suboptimal patient-reported function and movement impairments often persist after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Individuals with FAIS with preoperative cartilage pathology (ie. chondropathy) demonstrate distinct movement patterns and have worse post-operative outcomes.

Phytoremediation removal rates of benzene, toluene, and chlorobenzene.

Phytoremediation is a sustainable remedial approach, although performance efficacy is rarely reported. In this study, we assessed a phytoremediation plot treating benzene, toluene, and chlorobenzene. A comparison of the calculated phytoremediation removal rate with estimates of onsite contaminant mass was used to forecast cleanup periods.

Phytoforensics: Trees as bioindicators of potential indoor exposure via vapor intrusion.

Human exposure to volatile organic compounds (VOCs) via vapor intrusion (VI) is an emerging public health concern with notable detrimental impacts on public health. Phytoforensics, plant sampling to semi-quantitatively delineate subsurface contamination, provides a potential non-invasive screening approach to detect VI potential, and plant sampling is effective and also time- and cost-efficient. Existing VI assessment methods are time- and resource-intensive, invasive, and require access into residential and commercial buildings to drill holes through basement slabs to install sampling ports or require substantial equipment to install groundwater or soil vapor sampling outside the home.

Contaminant Gradients in Trees: Directional Tree Coring Reveals Boundaries of Soil and Soil-Gas Contamination with Potential Applications in Vapor Intrusion Assessment.

Contaminated sites pose ecological and human-health risks through exposure to contaminated soil and groundwater. Whereas we can readily locate, monitor, and track contaminants in groundwater, it is harder to perform these tasks in the vadose zone. In this study, tree-core samples were collected at a Superfund site to determine if the sample-collection location around a particular tree could reveal the subsurface location, or direction, of soil and soil-gas contaminant plumes.

Tree Sampling as a Method to Assess Vapor Intrusion Potential at a Site Characterized by VOC-Contaminated Groundwater and Soil.

Vapor intrusion (VI) by volatile organic compounds (VOCs) in the built environment presents a threat to human health. Traditional VI assessments are often time-, cost-, and labor-intensive; whereas traditional subsurface methods sample a relatively small volume in the subsurface and are difficult to collect within and near structures. Trees could provide a similar subsurface sample where roots act as the "sampler' and are already onsite.

Plants as bio-indicators of subsurface conditions: impact of groundwater level on BTEX concentrations in trees.

Numerous studies have demonstrated trees' ability to extract and translocate moderately hydrophobic contaminants, and sampling trees for compounds such as BTEX can help delineate plumes in the field. However, when BTEX is detected in the groundwater, detection in nearby trees is not as reliable an indicator of subsurface contamination as other compounds such as chlorinated solvents. Aerobic rhizospheric and bulk soil degradation is a potential explanation for the observed variability of BTEX in trees as compared to groundwater concentrations.