Measuring mental ill-health in the veterinary industry: A systematic review.

Many instruments have been developed to examine and quantify symptoms of psychopathology. The main objective of this systematic review was to examine the instrument choice employed to measure mental ill-health in professionals working in the veterinary industry and reporting of psychometric testing of these instruments by researchers. 78 papers were reviewed. A total of 73 different instruments used to measure 19 symptoms of mental ill-health were identified. Quality assessment of included papers indicated 9 were low, 63 were moderate, and 6 were high quality. Reliability testing was conducted and reported in 36 papers and validity testing was reported in 23 papers. There is considerable heterogeneity in instrument choice measuring symptoms of mental ill-health in this population and inconsistency in conducting and reporting psychometric testing of instruments across studies. Adopting commonly employed instruments that yield high quality data in psychometric testing of instruments would be beneficial at advancing understanding in this field.

Barriers to mental health help-seeking in veterinary professionals working in Australia and New Zealand: A preliminary cross-sectional analysis.

Despite higher reported rates of mental ill-health than the general population, professionals working in the animal care industry have low reported rates of help-seeking behavior. Potential factors involved in veterinary professionals' reluctance to seek help include stigma toward mental ill-health, practical barriers to accessing supports, and a cultural normalization of symptoms in the industry. This preliminary study sought to explore these factors in a sample of veterinarians, veterinary nurses, and veterinary technicians and examine effects of gender, years' experience, and practice location. A total of 408 veterinary professionals working in Australia and New Zealand completed an online survey between June and December 2021 measuring perceived stigma, practical barriers to mental health help-seeking, perceptions of normalized psychopathology and sickness presenteeism. Results indicated moderate levels of both perceived stigma and barriers to mental health help-seeking. Interestingly, psycho/pathology (e.g., burnout, fatigue, and sickness presenteeism) was perceived to be a normalized aspect of the profession by majority of respondents. Although no effect of gender or geographic location were observed, stage of career did have an effect on findings. Early career veterinary professionals were identified as more vulnerable to perceived stigma and barriers to care. The practical and research implications of the findings are discussed and include the need for mental health to be more centrally incorporated into the veterinary curriculum and professional development. Also discussed is an agenda for future research aimed at improving the mental health and wellbeing of professionals working in the animal care industry.

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication.

The organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold-attachment factor A (SAF-A), also known as heterogeneous nuclear ribonucleoprotein U (HNRNPU), contributes to the formation of open chromatin structure. Here, we demonstrate that SAF-A promotes the normal progression of DNA replication and enables resumption of replication after inhibition. We report that cells depleted of SAF-A show reduced origin licensing in G1 phase and, consequently, reduced origin activation frequency in S phase. Replication forks also progress less consistently in cells depleted of SAF-A, contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed two distinct effects of SAF-A depletion: first, the boundaries between early- and late-replicating domains become more blurred; and second, SAF-A depletion causes replication timing changes that tend to bring regions of discordant domain compartmentalisation and replication timing into concordance. Associated with these defects, SAF-A-depleted cells show elevated formation of phosphorylated histone H2AX (γ-H2AX) and tend to enter quiescence. Overall, we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.

Digital anthropomorphic phantoms of non-rigid human respiratory and voluntary body motion for investigating motion correction in emission imaging.

The development of methods for correcting patient motion in emission tomography has been receiving increased attention. Often the performance of these methods is evaluated through simulations using digital anthropomorphic phantoms, such as the commonly used extended cardiac torso (XCAT) phantom, which models both respiratory and cardiac motion based on human studies. However, non-rigid body motion, which is frequently seen in clinical studies, is not present in the standard XCAT phantom. In addition, respiratory motion in the standard phantom is limited to a single generic trend. In this work, to obtain a more realistic representation of motion, we developed a series of individual-specific XCAT phantoms, modeling non-rigid respiratory and non-rigid body motions derived from the magnetic resonance imaging (MRI) acquisitions of volunteers. Acquisitions were performed in the sagittal orientation using the Navigator methodology. Baseline (no motion) acquisitions at end-expiration were obtained at the beginning of each imaging session for each volunteer. For the body motion studies, MRI was again acquired only at end-expiration for five body motion poses (shoulder stretch, shoulder twist, lateral bend, side roll, and axial slide). For the respiratory motion studies, an MRI was acquired during free/regular breathing. The magnetic resonance slices were then retrospectively sorted into 14 amplitude-binned respiratory states, end-expiration, end-inspiration, six intermediary states during inspiration, and six during expiration using the recorded Navigator signal. XCAT phantoms were then generated based on these MRI data by interactive alignment of the organ contours of the XCAT with the MRI slices using a graphical user interface. Thus far we have created five body motion and five respiratory motion XCAT phantoms from the MRI acquisitions of six healthy volunteers (three males and three females). Non-rigid motion exhibited by the volunteers was reflected in both respiratory and body motion phantoms with a varying extent and character for each individual. In addition to these phantoms, we recorded the position of markers placed on the chest of the volunteers for the body motion studies, which could be used as external motion measurement. Using these phantoms and external motion data, investigators will be able to test their motion correction approaches for realistic motion obtained from different individuals. The non-uniform rational B-spline data and the parameter files for these phantoms are freely available for downloading and can be used with the XCAT license.

Alcohol sclerosis of a giant liver cyst following failed deroofings.

Percutaneous alcohol sclerotherapy for simple liver cysts is an established and safe procedure. We report alcohol ablation of a very large (5.5 liters) liver cyst that had failed laparoscopic deroofing procedures twice. The cyst responded to multisession alcohol sclerotherapy.

The effect of thrombospondin-1 on breast cancer metastasis.

Thrombospondin-1 (TSP-1) has been proposed to have both pro-metastatic and anti-metastatic properties. To elucidate its role in breast cancer metastasis, we compared tumor progression in the polyomavirus middle T antigen (Pyt) transgenic mouse and the TSP-1-null Pyt transgenic mouse. We characterized the tumors in these mice at 45, 60 and 90 days of age. Tumor size, areas of necrosis, macrophage infiltration, levels of active and total TGF-beta, vessel morphology, and lung and blood metastasis were measured in these mice. Mammary tumors were larger in the TSP-1-null mouse, and vessels were larger, but fewer in number in these tumors. The level of total TGF-beta was significantly higher in the Pyt tumors at 90 days of age. Importantly, significantly fewer metastases were observed in the lungs of the TSP-1-null/Pyt mouse. Primary Pyt tumor cells were more migratory than TSP-1-null Pyt tumor cells on collagen. Treatment of Pyt mice with recombinant proteins that contain the type-1 repeats of TSP-1 resulted in decreased primary tumor growth and metastasis. Sequences that are involved in CD36 binding and those required for TGF-beta activation mediated the inhibition of primary tumor growth. Thus, TSP-1 in the mammary tumor microenvironment inhibits angiogenesis and tumor growth, but promotes metastasis to the lung in the Pyt transgenic mouse. The ability of TSP-1 to support metastasis correlates with its ability to promote tumor cell migration.

Continuous administration of the three thrombospondin-1 type 1 repeats recombinant protein improves the potency of therapy in an orthotopic human pancreatic cancer model.

Thrombospondin-1 is one of most important natural angiogenic inhibitors. The three thrombospondin-1 type 1 repeats (3TSR), an anti-angiogenic domain of thrombospondin-1, is a promising novel agent for anti-angiogenic treatment. In the present study, we showed 3TSR was biologically stable at least for 7 days in mini-osmotic pumps in vivo, and continuous administration of 3TSR decreased the dosage and improved the potency of therapy in an orthotopic pancreatic cancer model. By using different dosage and delivery routes, we proved that the anti-tumor efficacy of 3TSR was correlated with its anti-angiogenic efficacy. 3TSR treatment also decreased tumor vessel patency and blood flow. The results indicate the advantage of continuous administration of angiogenic inhibitors and provide rationale for using such delivery methods for cancer treatment.

Halofuginone inhibits tumor growth in the polyoma middle T antigen mouse via a thrombospondin-1 independent mechanism.

Halofuginone inhibits fibrosis by decreasing type I collagen synthesis and tumor growth through an anti-angiogenic mechanism. In vitro data suggested that halofuginone inhibits angiogenesis through upregulating thrombospondin-1 (TSP-1) expression and by inhibiting cell proliferation. To determine whether thrombospondin-1 (TSP-1) is necessary for inhibition of tumor growth and angiogenesis by halofuginone, we tested the effect of halofuginone on mammary tumor growth in polyoma middle T antigen, TSP-1 null (TSP-1-/-PyT) transgenic mice. After 30 days of treatment, we found a significant decrease in tumor weight in these mice and the extent of tumor growth inhibition was comparable to that found in TSP-1 expressing PyT mice (TSP-1+/+PyT). However, no significant difference in tumor weight was observed after 60 days of halofuginone treatment between control and treated mice in both genotypes. Interestingly, type I collagen level was lower in the halofuginone treated TSP-1+/+PyT tumors at 30 days, but this was not observed in the TSP-1-/-PyT mice. Levels of type I collagen did not correlate with blood vessel number as a decrease in the number of vessels was observed in the halofuginone treated tumors from both the TSP-1+/+PyT and TSP-1-/-PyT mice as compared to control tumors. Because halofuginone has been shown to inhibit type I collagen synthesis by inhibiting the TGF-beta signaling pathway, we measured Smad 2/3 phosphorylation levels and found that halofuginone inhibited Smad 2/3 phosphorylation in cells derived from TSP-1+/+PyT tumors. We also found that it inhibited Smad 2/3 phosphorylation in cells treated with the TGF-beta activating sequence of TSP-1, TSR2+RFK. Our data demonstrate that halofuginone inhibits mammary tumor growth in a transgenic mouse model via a TSP-1 independent pathway, by decreasing tumor angiogenesis and by inhibiting TGF-beta signaling.