Neck pain but not neurologic disease occurs more frequently in horses with transposition of the ventral lamina from C6 to C7.

OBJECTIVE: To determine reasons for horses to have neck radiographs performed, the incidence of transposition of the ventral lamina of C6 onto C7 (TC67), and the final diagnoses for all horses. Our hypotheses were to find a similar incidence of TC67, as has been previously reported, and an increased incidence of neck pain and dysfunction in horses with TC67. ANIMALS: 135 horses. METHODS: Retrospective observational study. Medical records of 135 horses with cervical vertebral column radiographs between 2020 and 2022 were assessed. Patient signalment, reasons for radiographs, radiographic findings, and diagnoses were analyzed. The Shapiro-Wilk test was used for normality determination. Nonparametric tests were used to analyze data. RESULTS: 20% of horses were diagnosed with TC67. Significantly more horses with TC67 were warmblood horses (63%); TC67 was found in 28% of warmblood horses. There was no significant difference in signalment or whether horses were in work between the groups, although significantly more horses with TC67 performed in English disciplines (71%). No differences in reasons for examination or final diagnoses of neurologic disease, cervical orthopedic disease, or lameness were present between groups. In horses with neck pain, TC67 was significantly more common (31%) than in horses without (18%). CLINICAL RELEVANCE: Our results indicated that TC67 occurs more in warmblood horses. In the small group of horses with neck pain reported, TC67 was more commonly seen than in those without. Given the complexity of this region and the paucity of studies exploring neck pain and neck biomechanics, we suggest the need for standardized prospective studies.

Opinions of Health Care Personnel Regarding Disincentives and Incentives for Living Kidney Donation at a Single Center.

BACKGROUND: Transplant societies continue to actively concentrate on increasing rates of living kidney donation (LKD) to bridge the gap between individuals awaiting transplantation and the number of kidneys available. A widely discussed strategy to increase living donation rates is the provision of incentives and removal of disincentives. Though opinions of the public regarding this strategy have been studied, the opinions of health care providers, including younger professionals, are less clear. We studied the opinions of medical students and other health care providers on strategies to increase LKD to determine if opinions were different among those < 25 or ≥ 25 years of age. METHODS: A simple cross-sectional survey was conducted at an academic medical center. Participants included medical students and employees in Internal Medicine, General Surgery, and the Organ Transplantation Center. Pearson's χ2 and Fisher's exact test were conducted on the responses regarding disincentives and incentives to determine whether opinions differed based on age. RESULTS: Six hundred and twenty-four participants completed the survey. There was no statistical difference in opinions between groups on reimbursing transportation costs, loss of wages, or childcare costs, but those aged ≥ 25 were more agreeable with covering food/lodging costs compared to those < 25 (96.5% vs 90.7%, P = .009). Respondents < 25 years old were more willing to donate a kidney for a financial incentive (P = .0002) accepting a median amount of $25,000. CONCLUSIONS: Health care personnel broadly support removing financial disincentives for living kidney donation, and those ≥ 25 were more in favor of covering food/lodging costs compared to those < 25. Those < 25 years old were more likely to accept financial incentives towards donating their kidney compared to those ≥ 25 years.

Exposure to galactic cosmic radiation compromises DNA repair and increases the potential for oncogenic chromosomal rearrangement in bronchial epithelial cells.

Participants in deep space missions face protracted exposure to galactic cosmic radiation (GCR). In this setting, lung cancer is a significant component of the overall risk of radiation-exposure induced death. Here we investigate persistent effects of GCR exposure on DNA repair capacity in lung-derived epithelial cells, using an enzyme-stimulated chromosomal rearrangement as an endpoint. Replicate cell cultures were irradiated with energetic 48Ti ions (a GCR component) or reference γ-rays. After a six-day recovery, they were challenged by expression of a Cas9/sgRNA pair that creates double-strand breaks simultaneously in the EML4 and ALK loci, misjoining of which creates an EML4-ALK fusion oncogene. Misjoining was significantly elevated in 48Ti-irradiated populations, relative to the baseline rate in mock-irradiated controls. The effect was not seen in γ-ray irradiated populations exposed to equal or higher radiation doses. Sequence analysis of the EML4-ALK joints from 48Ti-irradiated cultures showed that they were far more likely to contain deletions, sometimes flanked by short microhomologies, than equivalent samples from mock-irradiated cultures, consistent with a shift toward error-prone alternative nonhomologous end joining repair. Results suggest a potential mechanism by which a persistent physiological effect of GCR exposure may increase lung cancer risk.

Diagnostic Utility of Cytokeratin-5 for the Identification of Proliferative Inflammatory Atrophy in the Canine Prostate.

Proliferative inflammatory atrophy (PIA), which is comprised of highly proliferative but atrophic prostate epithelial cells in association with chronic inflammation, is considered a risk lesion for prostate cancer in men, while its role in canine prostate carcinogenesis is still unknown. We evaluated the value of immunohistochemical labelling for the basal cell marker cytokeratin-5 (CK5) in identifying PIA lesions in 87 samples of formalin-fixed and paraffin wax-embedded canine prostate. Canine PIA showed cytological features identical to the human counterpart and in most cases was associated with chronic lymphoplasmacytic inflammation. PIA lesions were identified in a higher number of CK5-labelled slides (43 out of 87) compared with slides stained by haematoxylin and eosin (HE) (24 out of 87). This lesion was frequently present in normal, hyperplastic and neoplastic canine prostates, although it was underestimated on evaluation of HE-stained slides. Therefore, CK5 can be considered a useful basal cell marker with high sensitivity and specificity for PIA.

ICRP Publication 131: Stem cell biology with respect to carcinogenesis aspects of radiological protection.

Current knowledge of stem cell characteristics, maintenance and renewal, evolution with age, location in 'niches', and radiosensitivity to acute and protracted exposures is reviewed regarding haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. The identity of the target cells for carcinogenesis continues to point to the more primitive and mostly quiescent stem cell population (able to accumulate the protracted sequence of mutations necessary to result in malignancy), and, in a few tissues, to daughter progenitor cells. Several biological processes could contribute to the protection of stem cells from mutation accumulation: (1) accurate DNA repair; (2) rapid induced death of injured stem cells; (3) retention of the intact parental strand during divisions in some tissues so that mutations are passed to the daughter differentiating cells; and (4) stem cell competition, whereby undamaged stem cells outcompete damaged stem cells for residence in the vital niche. DNA repair mainly operates within a few days of irradiation, while stem cell replications and competition require weeks or many months depending on the tissue type. This foundation is used to provide a biological insight to protection issues including the linear-non-threshold and relative risk models, differences in cancer risk between tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age.

Spontaneous tumor development in bone marrow-rescued DNA-PKcs(3A/3A) mice due to dysfunction of telomere leading strand deprotection.

Phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at the Thr2609 cluster is essential for its complete function in DNA repair and tissue stem cell homeostasis. This phenomenon is demonstrated by congenital bone marrow failure occurring in DNA-PKcs(3A/3A) mutant mice, which require bone marrow transplantation (BMT) to prevent early mortality. Surprisingly, an increased incidence of spontaneous tumors, especially skin cancer, was observed in adult BMT-rescued DNA-PKcs(3A/3A) mice. Upon further investigation, we found that spontaneous γH2AX foci occurred in DNA-PKcs(3A/3A) skin biopsies and primary keratinocytes and that these foci overlapped with telomeres during mitosis, indicating impairment of telomere replication and maturation. Consistently, we observed significantly elevated frequencies of telomere fusion events in DNA-PKcs(3A/3A) cells as compared with wild-type and DNA-PKcs-knockout cells. In addition, a previously identified DNA-PKcs Thr2609Pro mutation, found in breast cancer, also induces a similar impairment of telomere leading-end maturation. Taken together, our current analyses indicate that the functional DNA-PKcs T2609 cluster is required to facilitate telomere leading strand maturation and prevention of genomic instability and cancer development.

ICRP Publication 131: Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection.

This report provides a review of stem cells/progenitor cells and their responses to ionising radiation in relation to issues relevant to stochastic effects of radiation that form a major part of the International Commission on Radiological Protection's system of radiological protection. Current information on stem cell characteristics, maintenance and renewal, evolution with age, location in stem cell 'niches', and radiosensitivity to acute and protracted exposures is presented in a series of substantial reviews as annexes concerning haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. This foundation of knowledge of stem cells is used in the main text of the report to provide a biological insight into issues such as the linear-no-threshold (LNT) model, cancer risk among tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age. Knowledge of the biology and associated radiation biology of stem cells and progenitor cells is more developed in tissues that renew fairly rapidly, such as haematopoietic tissue, intestinal mucosa, and epidermis, although all the tissues considered here possess stem cell populations. Important features of stem cell maintenance, renewal, and response are the microenvironmental signals operating in the niche residence, for which a well-defined spatial location has been identified in some tissues. The identity of the target cell for carcinogenesis continues to point to the more primitive stem cell population that is mostly quiescent, and hence able to accumulate the protracted sequence of mutations necessary to result in malignancy. In addition, there is some potential for daughter progenitor cells to be target cells in particular cases, such as in haematopoietic tissue and in skin. Several biological processes could contribute to protecting stem cells from mutation accumulation: (a) accurate DNA repair; (b) rapidly induced death of injured stem cells; (c) retention of the DNA parental template strand during divisions in some tissue systems, so that mutations are passed to the daughter differentiating cells and not retained in the parental cell; and (d) stem cell competition, whereby undamaged stem cells outcompete damaged stem cells for residence in the niche. DNA repair mainly occurs within a few days of irradiation, while stem cell competition requires weeks or many months depending on the tissue type. The aforementioned processes may contribute to the differences in carcinogenic radiation risk values between tissues, and may help to explain why a rapidly replicating tissue such as small intestine is less prone to such risk. The processes also provide a mechanistic insight relevant to the LNT model, and the relative and absolute risk models. The radiobiological knowledge also provides a scientific insight into discussions of the dose and dose-rate effectiveness factor currently used in radiological protection guidelines. In addition, the biological information contributes potential reasons for the age-dependent sensitivity to radiation carcinogenesis, including the effects of in-utero exposure.

An accountability evaluation for the industry's responsible use of brand mascots and licensed media characters to market a healthy diet to American children.

Corporate strategies that target children are controversial given the link between food marketing and childhood obesity. This case study explored diverse stakeholders' accountability expectations and actions for industry policies and practices that used popular cartoon brand mascots and media characters to promote food products to American children. We reviewed five electronic databases and Internet sources between January 2000 and January 2015. Evidence (n = 90) was selected based upon the Institute of Medicine's LEAD principles (i.e. locate, evaluate, assemble evidence to inform decisions) and organized into two tables: peer-reviewed articles, books and grey-literature reports (n = 34); and media stories, news releases and public testimony (n = 56). A four-step accountability framework was used to evaluate accountability structures. The results showed that moderate progress was achieved by stakeholders to take and share the account, limited progress to hold industry and government to account, and limited progress to strengthen accountability structures. Between 2006 and 2015, the U.S. Children's Food and Beverage Advertising Initiative lacked clear policies for companies to use brand mascots and media characters on food packages, in merchandising, and as toy giveaways and premiums. Government, industry and civil society can substantially strengthen their accountability for these food marketing practices to ensure healthy food environments for children.

Influence of food companies' brand mascots and entertainment companies' cartoon media characters on children's diet and health: a systematic review and research needs.

Reducing the extent and persuasive power of marketing unhealthy foods to children worldwide are important obesity prevention goals. Research is limited to understand how brand mascots and cartoon media characters influence children's diet. We conducted a systematic review of five electronic databases (2000-2014) to identify experimental studies that measured how food companies' mascots and entertainment companies' media characters influence up to 12 diet-related cognitive, behavioural and health outcomes for children under 12 years. Eleven studies met the inclusion criteria. Studies used 21 unique popular media characters, but no brand mascots. Results suggest that cartoon media character branding can positively increase children's fruit or vegetable intake compared with no character branding. However, familiar media character branding is a more powerful influence on children's food preferences, choices and intake, especially for energy-dense and nutrient-poor foods (e.g. cookies, candy or chocolate) compared with fruits or vegetables. Future research should use a theoretically grounded conceptual model and larger and more diverse samples across settings to produce stronger findings for mediating and moderating factors. Future research can be used to inform the deliberations of policymakers, practitioners and advocates regarding how media character marketing should be used to support healthy food environments for children.

DNA double-strand breaks cooperate with loss of Ink4 and Arf tumor suppressors to generate glioblastomas with frequent Met amplification.

Glioblastomas (GBM) are highly radioresistant and lethal brain tumors. Ionizing radiation (IR)-induced DNA double-strand breaks (DSBs) are a risk factor for the development of GBM. In this study, we systematically examined the contribution of IR-induced DSBs to GBM development using transgenic mouse models harboring brain-targeted deletions of key tumor suppressors frequently lost in GBM, namely Ink4a, Ink4b, Arf and/or PTEN. Using low linear energy transfer (LET) X-rays to generate simple breaks or high LET HZE particles (Fe ions) to generate complex breaks, we found that DSBs induce high-grade gliomas in these mice which, otherwise, do not develop gliomas spontaneously. Loss of Ink4a and Arf was sufficient to trigger IR-induced glioma development but additional loss of Ink4b significantly increased tumor incidence. We analyzed IR-induced tumors for copy number alterations to identify oncogenic changes that were generated and selected for as a consequence of stochastic DSB events. We found Met amplification to be the most significant oncogenic event in these radiation-induced gliomas. Importantly, Met activation resulted in the expression of Sox2, a GBM cancer stem cell marker, and was obligatory for tumor formation. In sum, these results indicate that radiation-induced DSBs cooperate with loss of Ink4 and Arf tumor suppressors to generate high-grade gliomas that are commonly driven by Met amplification and activation.

OCT4 as a target of miR-34a stimulates p63 but inhibits p53 to promote human cell transformation.

Human cell transformation is a key step for oncogenic development, which involves multiple pathways; however, the mechanism remains unclear. To test our hypothesis whether cell oncogenic transformation shares some mechanisms with the process of reprogramming non-stem cells to induced pluripotent stem cells (iPSC), we studied the relationship among the key factors for promoting or inhibiting iPSC in radiation-transformed human epithelial cell lines derived from different tissues (lung, breast and colon). We unexpectedly found that p63 and OCT4 were highly expressed (accompanied by low expressed p53 and miR-34a) in all transformed cell lines examined when compared with their non-transformed counterparts. We further elucidated the relationship of these factors: the 3p strand of miR-34a directly targeted OCT4 by binding to the 3' untranslated region (3'-UTR) of OCT4 and, OCT4, in turn, stimulated p63 but inhibited p53 expression by binding to a specific region of the p63 or p53 promoter. Moreover, we revealed that the effects of OCT4 on promoting cell oncogenic transformation were by affecting p63 and p53. These results support that a positive loop exists in human cells: OCT4 upregulation as a consequence of inhibition of miR-34a, promotes p63 but suppresses p53 expression, which further stimulates OCT4 upregulation by downregulating miR-34a. This functional loop contributes significantly to cell transformation and, most likely, also to the iPSC process.

Home/family, peer, school, and neighborhood correlates of obesity in adolescents.

OBJECTIVE: This study was designed to (1) identify the most important home/family, peer, school, and neighborhood environmental characteristics associated with weight status and (2) determine the overall contribution of these contexts to explaining weight status among an ethnically/racially diverse sample of adolescents. DESIGN AND METHODS: Surveys and anthropometric measures were completed in 2009-2010 by 2,793 adolescents (53.2% girls, mean age = 14.4 ± 2.0, 81.1% non-white) in Minneapolis/St. Paul, Minnesota schools. Data representing characteristics of adolescents' environments were collected from parents/caregivers, friends, school personnel, and Geographic Information System sources. Multiple regression models controlled for adolescent age, ethnicity/race, and socioeconomic status. RESULTS: The variance in body mass index (BMI) z-scores explained by 51 multicontextual characteristics was 24% for boys and 22% for girls. Across models, several characteristics of home/family (e.g., infrequent family meals) and peer environments (e.g., higher proportion of male friends who were overweight) were consistently associated with higher BMI z-scores among both boys and girls. Among girls, additional peer (e.g., lower physical activity among female friends) and neighborhood (e.g., perceived lack of safety) characteristics were consistently associated with higher BMI z-scores. CONCLUSIONS: Results underscore the importance of addressing the home/family and peer environments in future research and intervention efforts designed to reduce adolescent obesity.

Relationships between the family environment and school-based obesity prevention efforts: can school programs help adolescents who are most in need?

Identifying factors that contribute to students' behavior and weight improvements during school-based obesity prevention interventions is critical for the development of effective programs. The current study aims to determine whether the support and resources that adolescent girls received from their families were associated with improvements in physical activity (PA), television use, dietary intake, body mass index (BMI) and body composition during participation in New Moves, a school-based intervention to prevent obesity and other weight-related problems. Adolescent girls in the intervention condition of New Moves (n = 135), and one parent of each girl, were included in the current analysis. At baseline, parents completed surveys assessing the family environment. At baseline and follow-up, 9-12 months later, girls' behaviors were self-reported, height and weight were measured by study staff and body fat was assessed using dual-energy X-ray absorptiometry. Results showed few associations between family environment factors and girls' likelihood of improving behavior, BMI or body composition. These findings suggest that in general, school-based interventions offer similar opportunities for adolescent girls to improve their PA, dietary intake, and weight, regardless of family support.

Elimination of the differential chemoresistance between the murine B-cell lymphoma LY-ar and LY-as cell lines after arsenic (As2O3) exposure via the overexpression of gsto1 (p28).

PURPOSE: Arsenic, in the form of As(2)O(3), has gained therapeutic importance because it has been shown to be very effective clinically in the treatment of acute promyelocytic leukemia (APL). Via numerous pathways arsenic induces cellular alterations such as induction of apoptosis, inhibition of cellular proliferation, stimulation of differentiation, and inhibition of angiogenesis. Responses vary depending on cell type, dose and the form of arsenic. GSTO1, a member of the glutathione S-transferase superfamily omega, has recently been shown to be identical to the rate-limiting enzyme, monomethyl arsenous (MMA(V)) reductase which catalyzes methylarsonate (MMA(V)) to methylarsenous acid (MMA(III)) during arsenic biotransformation. In this study, we investigated whether arsenic trioxide (As(2)O(3)) induces apoptosis in both chemosensitive and chemoresistant cell lines that varied in their expression of p28 (gsto1), the mouse homolog of GSTO1. METHODS: The cytotoxicity of arsenic in the gsto1- and bcl-2-expressing chemoresistant and radioresistant LY-ar mouse lymphoma cell line, was compared with that of the LY-ar's parental cell line, LY-as. LY-as cells are radiosensitive, apoptotically permissive, and do not express gsto1 or bcl-2. Cell survival, glutathione (GSH) levels, mitochondrial membrane potential, and stress-activated kinase status after arsenic treatment were examined in these cell lines. RESULTS: As(2)O(3) induced an equivalent dose- and time-dependent increase in apoptosis in these cell lines. Cellular survival, as measured after a 24-h exposure, was also the same in each cell line. Reduced GSH was modulated in a similar time- and dose-dependent manner. Apoptosis was preceded by loss of mitochondrial membrane potential that triggered caspase-mediated pathways associated with apoptosis. With a prolonged exposure of As(2)O(3), both cell lines showed decreased activation of ERK family members, ERK1, ERK2 and ERK5. As(2)O(3) enhanced the death signals in LY-ar cells through a decrease in GSH, loss of mitochondrial membrane potential, and abatement of survival signals. This effect is similar to that seen when LY-ar cells are treated with thiol-depleting agents or by the removal of methionine and cysteine (GSH precursor) from the growth medium. This response is also completely contrary to that seen for radiation, actinomycin D, VP-16 and other agents, where LY-ar cells do not succumb to apoptosis. CONCLUSIONS: The overexpression of gsto1 in normally chemoresistant and radioresistant LY-ar cells renders them vulnerable to the cytotoxic effects of As(2)O(3), despite the 30-fold overexpression of the survival factor bcl-2. Gsto1 and its human homolog, GSTO1, may serve as a marker for arsenic sensitivity, particularly in cells that are resistant to other chemotherapeutic agents.

Fibrosarcoma over the tarsal groove of a 14-month-old Quarter horse.

A 14-month-old male Quarter horse was presented for evaluation of a grade 3 out of 5 (grade 0 = sound; grade 5 = non-weight bearing) right rear lameness. A firm, 8 x 16 cm mass was palpable at the caudal medial aspect of the distal tibia and proximal tarsal region of the right hind limb. A percutaneous needle aspirate contained mesenchymal cells that were moderate to large in size with single, oblong nuclei. Differential diagnoses included fibrous hyperplasia, fibroma, or well-differentiated fibrosarcoma. Excisional biopsy for both definitive diagnosis and treatment was offered and selected by the owner. A fibrosarcoma was confirmed by histological examination of the mass. One and a half years after resection signs of lameness or evidence of regrowth of the mass were not evident.

Arthroscopic debridement of subchondral bone cysts in the distal phalanx of 11 horses (1994-2000).

REASONS FOR PERFORMING STUDY: Historically, there has been a consensus that conservative management of subchondral cystic lesions of the distal phalanx carries a poor prognosis. Surgical management has been advocated; however, there are no reports documenting its routine use and successful surgical treatment. OBJECTIVES: To describe arthroscopically-guided curettage of distal phalangeal subchondral cystic lesions (SCLs) and report the qualitative and quantitative results in 11 affected horses age 16-33 months. METHODS: Medical records of horses with previously treated lameness resulting from SCLs of the third phalanx were reviewed. Arthroscopic debridement of the SCLs was described. Follow-up information was obtained from race records and telephone contact with owners and trainers. The sign-rank test was used to compare performance of operated racehorses to that of unoperated siblings. RESULTS: Ten of the 11 horses (91%) in the study returned to athletic soundness after surgical treatment and had performance records similar to their siblings. CONCLUSIONS: Data show that arthroscopic debridement of distal phalangeal SCLs is a viable treatment for affected horses age 16-33 months and can result in a successful return to intended athletic performance. No horses younger than 16 months or older than 33 months were treated and results in horses younger or older than this group may vary in success. POTENTIAL RELEVANCE: The description of treatment and approach used for arthroscopic curettage will increase awareness of this option and increase treatment options for this condition.

Analysis of radiation-induced DNA double-strand breaks misrepair is not compromized by broken DNA in human fibroblasts.

It has been suggested that the technique for measuring repair fidelity of radiation-induced DNA double-strand breaks (DSBs) using Southern blotting and hybridization to defined regions of the genome could be compromised by broken or poorly-digested DNA. Since misrepair of DNA DSBs is an important aspect of radiation-induced chromosome aberrations, mutations, and cell killing, we checked for such a supposition in non-transformed human fibroblasts. DSB misrepair was assessed in a NotI-cleavable DNA fragment of 3.2 Mbp located on the long arm of chromosome 21 and detected by D21S1 probe. We hypothesized that the suggested DNA degradation, whether spurious in nature or the results of irradiation-induced phenomena such as apoptosis and/or necrosis, should be detectable with or without NotI restriction enzyme treatment. When the DNA embedded in agarose plugs was separated by electrophoresis without prior NotI restriction, no significant difference was observed in the relative amount of migrating DNA between the control (no irradiation) and 24 h of repair following 80 Gy irradiation. Furthermore, only about 10% of the total signal was located below the 3.2 Mbp band. This suggests that the amount of DNA fragmentation due to biological (apoptosis or necrosis) or technical processes was negligible. The Tunel assay supported these results, as there was little to no apoptosis detectable in these fibroblasts up to 24 h after irradiation. We conclude that in primary human fibroblasts, the NotI method for measuring radiation-induced misrepair is not compromised by DNA degradation.