Trabecular bone score and its association with Cobb angle kyphosis in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) Study.

Hyperkyphosis (HK), or accentuated forward spinal curvature, commonly affects older people, although its causes are not completely understood. We tested whether a measure of bone quality, trabecular bone score (TBS), is associated with HK in 1997 older men, and determined that men with degraded TBS were more likely to have HK. INTRODUCTION: While vertebral fractures and low bone mineral density (BMD) contribute to kyphosis progression, it is unknown whether the trabecular bone score (TBS) may provide additional information on bone quality that could influence the degree of kyphosis. We hypothesized that degraded TBS would be associated with hyperkyphosis (HK) defined as a Cobb angle > 50°. METHODS: Using data from 1997 participants of the Osteoporotic Fractures in Men (MrOS) Study who had baseline TBS and Cobb angle kyphosis measured, we investigated whether men with degraded TBS were more likely to be hyperkyphotic, even after adjustment for BMD and prevalent vertebral fractures. RESULTS: Men were an average age of 74 ± 6 (mean ± SD) years with a mean kyphosis angle of 38.6 ± 11.5°, 295 (15%) were classified as hyperkyphotic, and 416 (21%) had degraded TBS. Compared with men with TBS > 1.2, men with degraded TBS were more likely to have HK (OR: 1.47, 95% CI: 1.06-2.06, p = 0.02) after adjusting for age, clinic, race, BMI, hip BMD, and prevalent vertebral fracture. If spine instead of hip BMD was included in the model, the odds ratio decreased to 1.35 (95% CI: 0.97-1.89, p = 0.08). CONCLUSIONS: Older men with degraded TBS are more likely to have HK not explained by underlying vertebral fractures.

The effect of obesity and subsequent weight reduction on cardiac structure and function in dogs.

BACKGROUND: In people, the cardiovascular effects of obesity include systemic hypertension, cardiac remodelling and both systolic and diastolic dysfunction, whilst weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. To date, variable results are reported in studies of the effect of obesity and controlled weight reduction on cardiovascular morphology and function in dogs. This prospective study aimed to assess cardiac function, heart rate variability, cardiac biomarkers and body composition before and after weight reduction in pet dogs with obesity. Twenty-four client-owned dogs referred for weight management due to obesity were recruited. To assess the cardiac effects of obesity, body composition analysis (by dual energy X-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, Doppler blood pressure, electrocardiography, cardiac biomarkers) were performed prior to weight management. Twelve dogs completed the study and reached target weight, receiving a further cardiovascular assessment and DEXA. A Wilcoxon-signed rank test was used to compare each variable pre- and post- weight reduction. RESULTS: Median (interquartile range) duration of weight loss was 224 days (124-245 days), percentage weight loss was 23% (18-31%) of starting weight. Median change in body fat mass was -50% (-44% to -55%; P = 0.004), whilst median change in lean mass was -7% (+ 1% to -18%, P = 0.083). Before weight reduction, diastolic dysfunction (evidence of impaired relaxation in all dogs), increased left ventricular wall thickness and mildly elevated systolic blood pressure (14/24 ≥ 160 mmHg, median 165 mmHg (140-183)) were common features in dogs with obesity. However, systolic left ventricular wall dimensions were the only variables that changed after weight reduction, with a decrease in both the systolic interventricular septum (P = 0.029) and systolic left ventricular free wall (P = 0.017). There was no evidence of decreased heart rate variability in dogs with obesity (P = 0.367), and no change in cardiac biomarker concentrations with weight reduction (N-terminal proBNP, P = 0.262; cardiac troponin I P = 0.657). CONCLUSIONS: Canine obesity results in diastolic dysfunction and left ventricular hypertrophy, the latter of which improves with significant weight and fat mass reduction. Further studies are required to clarify the clinical consequences of these findings.

SURPRISINGLY FEW WOMEN WITH SEVERE OSTEOPOROSIS BY BONE DENSITOMETRY UNDERGO WORKUP FOR SECONDARY CAUSES - A RETROSPECTIVE EVALUATION.

We describe clinical features of women with extremely low bone density, and investigate secondary causes of osteoporosis. Our hypothesis was that this population would be enriched in identifiable causes of osteoporosis. We performed a retrospective review of medical records of all women seen at our university over 4 years with T-score on bone densitometry at/below -4 at any site. Historical and fracture details were abstracted. We considered a thorough work up to include Vitamin D, PTH, CBC, chemistry panel, cortisol, transglutaminase, myeloma screen, tryptase and 24-hour urine calcium. Results: 137 women were identified with T-score at/below -4. Percent identified as Asian was 26% (higher than local prevalence of 8%). Average BMI was 21.6 kg/m2. Clearly identifiable causes of osteoporosis were noted in 57% (inflammatory disorder, glucocorticoid or antacid exposure, prolonged immobilization and alcoholism were most prevalent). Of the remainder, full work up was performed only in 8%. Endocrine consultation and white race predicted thoroughness of secondary work-up. Conclusion: Fragility fractures, leanness and Asian race were common in women with very low T-score. However, few new causes were identified. Underlying etiology was either immediately evident or inadequately studied, especially in minorities.

Midface toddler excoriation syndrome (MiTES) can be caused by autosomal recessive biallelic mutations in a gene for congenital insensitivity to pain, PRDM12.

BACKGROUND: Midface toddler excoriation syndrome (MiTES) is a condition recently reported in three unrelated children. Habitual scratching from the first year of life inflicted deep, chronic, scarring wounds around the nose and eyes. One child had a mild neurological deficit but there was no other evidence of insensitivity to pain. Bilateral distribution and localization to the midface distinguish MiTES from other causes of self-inflicted skin damage such as trigeminal trophic syndrome. An earlier study of five siblings from a consanguineous Irish family, with lesions corresponding to MiTES plus other sensory deficits, showed homozygous mutations in a gene for hereditary sensory and autonomic neuropathy type VIII (HSAN8), PRDM12. OBJECTIVES: To study further cases of MiTES, including analysis of PRDM12. METHODS: We describe five further children, from four families, with facial lesions typical of MiTES, in whom mutation analysis of PRDM12 was carried out. RESULTS: Homozygous or compound heterozygous pathogenic expansions of the PRDM12 polyalanine tract were found in four of five affected individuals, in three families. CONCLUSIONS: Our finding of autosomal recessive mutations in PRDM12 in four of five patients with MiTES extends the phenotypic spectrum of PRDM12 mutations, which usually cause HSAN8, characterized by mutilating self-inflicted wounds of the extremities, lips and tongue. By contrast, MiTES shows severe midfacial lesions with little if any evidence of generalized pain insensitivity. The condition is probably genetically heterogeneous, and other congenital insensitivity to pain and HSAN genes such as SCN11A may be implicated. This new understanding of the nature of MiTES, which can masquerade as factitious disease, will facilitate appropriate management.

Devil Facial Tumor Disease.

Devil facial tumor disease (DFTD) is an emergent transmissible cancer exclusive to Tasmanian devils (Sarcophilus harrisii) and threatening the species with extinction in the wild. Research on DFTD began 10 years ago, when nothing was known about the tumor and little about the devils. The depth of knowledge gained since then is impressive, with research having addressed significant aspects of the disease and the devils' responses to it. These include the cause and pathogenesis of DFTD, the immune response of the devils and the immune evasion mechanisms of the tumor, the transmission patterns of DFTD, and the impacts of DFTD on the ecosystem. This review aims to collate this information and put it into the context of conservation strategies designed to mitigate the impacts of DFTD on the devil and the Tasmanian ecosystem.

Diagnostic yield of percutaneous, ultrasound-guided, fine needle aspirates of the gastrointestinal wall: a retrospective analysis of 152 samples.

OBJECTIVES: The aim was to assess the technical success of percutaneous ultrasound-guided fine needle aspirates of gastrointestinal wall lesions and evaluate predictors of success. Secondary aims included comparing the cytological diagnosis with histopathology, evaluating the utility of concurrent locoregional lymph node cytology and assessing the procedure's complication rate. MATERIAL AND METHODS: Gastrointestinal wall cytology from 75 dogs and 70 cats obtained between 2018 and 2023 were reviewed and categorised as successful (resulting in a diagnostic cytology report) and accurate (resulting in the correct diagnosis when compared to histopathology). Unsuccessful fine needle aspirates, not submitted for cytology, were not recorded. Variables recorded included animal signalment, lesion and lymph node's appearance on ultrasound, size, location, number of smears submitted and experience of the ultrasonographer. RESULTS: One hundred and fifty-two reports were analysed. Eighty-eight (58%) were successful: three normal epithelium, 21 inflammatory processes and 64 neoplasms. Variables associated with increased technical success included description of a mass, higher number of slides submitted and thickness of gastrointestinal lesion on ultrasound. Comparison with histopathology, performed for 17 lesions, showed discrepancies in eight, complete agreement in seven and partial in two. Eighty-four loco-regional lymph nodes were sampled, of which, 67 were successful (80%) and 52 brought additional clinical information (supporting GI wall cytology or diagnosing neoplasia not identified on GI wall cytology). No complication strictly attributable to gastrointestinal wall sampling was reported but when possibly related, death of the patient occurred in 2.5% of cases. CLINICAL SIGNIFICANCE: Ultrasound-guided fine needle aspirate of gastrointestinal wall had moderate accuracy and was unsuccessful in 42% of cases, but technical success increased when sampling mass lesions, thicker intestinal layers and submitting more slides.

Dietary vitamin D alters the response of the skin to UVB-irradiation depending on the genetic background of the mice.

Ultraviolet B (UVB) irradiation of the skin has the benefit of causing the local production of previtamin D3 but also results in cutaneous DNA damage and suppression of the skin immune system (SIS). Strains of mice differ in their ability to be suppressed by UVB irradiation: BALB/c mice are considered "resistant" and C57BL/6 "sensitive". This study evaluated whether vitamin D-replete (D+) and deficient (D-) BALB/c and C57BL/6 mice differed in their cutaneous response to UVB irradiation. Immunosuppression was assessed by measuring the contact hypersensitivity (CHS) response, DNA damage and repair determined by counting thymine dimer positive keratinocyte nuclei, and cutaneous inflammation and epidermal hyperplasia evaluated by light microscopy. The suppression in the CHS response induced by the UVB irradiation was reduced in the D+ C57BL/6 mice compared with the D- C57BL/6 mice. Similarly there was a reduction in DNA damage and promotion of its repair in the D+ C57BL/6 mice compared with the D- C57BL/6 mice. A reduction in inflammation in female D+ C57BL/6 mice compared with D- C57BL/6 females also occurred. In contrast, the suppression in the CHS response, DNA damage and its repair, and inflammation induced by UVB irradiation were similar in the D+ and D- BALB/c mice. These results indicate that dietary vitamin D3 can reduce UVB-induced suppression of the CHS response depending on the genetic background of the mice, an effect that may relate to the reduction in DNA damage and an increase in its rate of repair.

Functional characterization of the TSC2 c.3598C>T (p.R1200W) missense mutation that co-segregates with tuberous sclerosis complex in mildly affected kindreds.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a combination of neurological symptoms and hamartomatous growths, and caused by mutations in the TSC1 and TSC2 genes. Overall, TSC2 mutations are associated with a more severe disease phenotype. We identified the c.3598C>T (R1200W) change in the TSC2 gene in seven different families. The clinical phenotypes in the families were mild, characterized by mild skin lesions, remitting epilepsy and a lack of severe mental retardation or major organ involvement. Functional analysis of the TSC2 R1200W variant, and four other TSC2 missense variants associated with a mild TSC phenotype, confirmed that the changes disrupted the TSC1-TSC2 function. Interestingly however, in each case, the TSC1-TSC2 interaction was not affected by the amino acid substitution.

A murine xenograft model for a transmissible cancer in Tasmanian devils.

The number of Tasmanian devils in the wild is rapidly declining owing to a transmissible cancer, devil facial tumor disease (DFTD). Although progress has been made to understand the spread of this disease, crucial research on the pathogenesis of DFTD has been limited because of the threatened status of the host species. Here, the authors describe the development of a NOD/SCID (nonobese diabetic / severe combined immunodeficiency) mouse model that reproduces DFTD and provides a much-needed model to undertake studies into this intriguing transmissible cancer. Histologically, the DFTD produced in NOD/SCID mice (xenografted DFTD) was indistinguishable from the DFTD identified in Tasmanian devils. At the protein level, all xenografted DFTD tumors expressed periaxin, a marker that confirmed the diagnosis of DFTD. The karyotype of DFTD in NOD/SCID mice reproduced similar chromosomal alterations as seen in diseased devils. Furthermore, each NOD/SCID mouse inoculated with cultured DFTD tumor cells developed tumors, whereas DFTD did not develop in any of the inoculated immune-competent BALB/c mice.

Tumor-specific diagnostic marker for transmissible facial tumors of Tasmanian devils: immunohistochemistry studies.

Devil facial tumor disease (DFTD) is a transmissible neoplasm that is threatening the survival of the Tasmanian devil. Genetic analyses have indicated that the disease is a peripheral nerve sheath neoplasm of Schwann cell origin. DFTD cells express genes characteristic of myelinating Schwann cells, and periaxin, a Schwann cell protein, has been proposed as a marker for the disease. Diagnosis of DFTD is currently based on histopathology, cytogenetics, and clinical appearance of the disease in affected animals. As devils are susceptible to a variety of neoplastic processes, a specific diagnostic test is required to differentiate DFTD from cancers of similar morphological appearance. This study presents a thorough examination of the expression of a set of Schwann cell and other neural crest markers in DFTD tumors and normal devil tissues. Samples from 20 primary DFTD tumors and 10 DFTD metastases were evaluated by immunohistochemistry for the expression of periaxin, S100 protein, peripheral myelin protein 22, nerve growth factor receptor, nestin, neuron specific enolase, chromogranin A, and myelin basic protein. Of these, periaxin was confirmed as the most sensitive and specific marker, labeling the majority of DFTD cells in 100% of primary DFTD tumors and DFTD metastases. In normal tissues, periaxin showed specificity for Schwann cells in peripheral nerve bundles. This marker was then evaluated in cultured devil Schwann cells, DFTD cell lines, and xenografted DFTD tumors. Periaxin expression was maintained in all these models, validating its utility as a diagnostic marker for the disease.

Maintenance energy requirements in cats following controlled weight loss: An observational study.

There is a paucity of information regarding the phenomenon of weight regain after successful weight reduction in cats. This study aimed to estimate post-weight reduction maintenance energy requirements (MER) required to maintain stable weight in a group of pet cats. Nineteen cats that had successfully completed a controlled weight reduction programme were enrolled. For inclusion, at least 2 months of follow-up had to be available for review, and the maximum change in weight during maintenance was ±2%. Post-weight-reduction MER was estimated by determining dietary energy consumption from owner diary records. The Friedman test was used to compare bodyweight and energy intake at different stages of weight management. Simple and multiple linear regression were used to identify factors associated with post-weight-reduction MER. The median (interquartile range) duration of weight maintenance was 179 days (119-408 days) and, during this time, MER was 273 ± 56.7 kJ per kg0.67 ideal bodyweight (IBW) per day. Post-weight-reduction MER was greater than metabolisable energy intake at the end (233 ± 29.5 kJ IBW per kg0.67 per day; P < 0.001) but not the start (255 ± 38.6 kJ per kg0.67 IBW per day; P = 0.148) of the weight reduction period. Using simple and multiple linear regression, the only variable that was associated with post-weight reduction MER was the mean ME intake during weight reduction (r2 = 0.349, P = 0.008). Post-weight-reduction MER at the lower limits of MER recommendations for pet cats might predispose to weight regain during the weight maintenance phase.

Complications associated with bone marrow sampling in dogs and cats.

OBJECTIVES: To evaluate the prevalence of complications during bone marrow sampling and associated patient and procedural factors in dogs and cats. MATERIALS AND METHODS: Retrospective cohort study, records were evaluated to identify dogs and cats that had bone marrow sampling between 2012 and 2019. Data including signalment, the presence of specific clinicopathological findings, anatomical site of bone marrow sampling, number of attempts, diagnostic quality of sampling, analgesia protocol and complications postprocedure were recorded. RESULTS: A total of 131 dogs and 29 cats were included in the study. Complications were recorded in 22 of 160 (14%) of cases. Pain was the most common complication of bone marrow sampling in 20 of 22 (91%) of cases with bruising reported in the remaining patients. A local anaesthetic block was used in 98 of 160 (61%) of patients. CLINICAL SIGNIFICANCE: Excluding pain, complications associated with bone marrow sampling were rare and no clear association were detected between patient or procedural variables. Haemorrhage and infection are rare complications in dogs and cats when thrombocytopenia and neutropenia are present. Peri-procedure analgesia is strongly recommended to minimise complications.

Common mental disorders among Irish jockeys: prevalence and risk factors.

OBJECTIVE: Jockeys compete in a sport, horseracing, renowned for its physical and psychological demands. Previous research has identified that common mental disorders (CMDs) may be prevalent among this unique population of athletes. The aim of the present study was to further explore the prevalence of CMDs among jockeys and to test for associations with potential risk factors. METHODS: An anonymous survey was distributed to professional jockey online. Self-report screening tools for four CMDs (psychological distress, depression, generalized anxiety, and adverse alcohol use) were included alongside predictor variables from questionnaires assessing for burnout, career satisfaction, social support, and the contemplation of retirement. Binary logistic regression was used to explore associations between CMDs (present versus not present) and risk factors. Eighty-four professional jockeys completed the questionnaire (response rate = 52%). RESULTS: In total, 79% of jockeys met the threshold for at least one CMD. Prevalence (%) of CMD varied as follows: adverse alcohol (61%), depression (35%), generalized anxiety (27%), and psychological distress (19%). Burnout, career (dis)satisfaction, lower levels of social support, and the contemplation of retirement increased the odds of meeting the criteria for CMDs. CONCLUSION: The findings indicate that jockeys report CMD symptoms at comparable rates to athletes in other sports. The study was the first to highlight potential risk factors as predictors of CMDs among jockeys, including burnout, career satisfaction, and the current contemplation of retirement. Screening tools for the risk factors demonstrated may, therefore, provide useful in the early identification of CMDs among jockeys. The development of jockey-specific assessment tools, education programmes, and interventions may help better understand and support the mental health of jockeys.

Eosinophilic pericardial effusion in a cat with complex systemic disease and associated peripheral eosinophilia.

An 11-year-old domestic shorthair cat was referred for investigation of dry cough of 1-week duration and cardiomegaly. Echocardiography revealed pericardial effusion, and eosinophils were identified as the predominant cell type in fluid collected by pericardiocentesis. Thoracic computed tomography imaging and bronchoscopy were supportive of mild lower airway disease, while bronchoalveolar lavage confirmed eosinophilic inflammation and concurrent Mycoplasma felis infection. A few months after the initial presentation, there was clinical deterioration, and further investigation suggested intestinal lymphoma. It was hypothesized that pericardial effusion and lower airway inflammation were an early manifestation of hypereosinophilic syndrome, possibly as a paraneoplastic consequence of lymphoma.

Vitamin D3 deficiency enhances contact hypersensitivity in male but not in female mice.

To ascertain the influence of vitamin D3 and its metabolites on the function of the skin immune system and the induction of the contact hypersensitivity (CHS) response, a population of vitamin D3-deficient BALB/c mice was established, through dietary vitamin D3 restriction and limitation of exposure to UVB irradiation. Vitamin D3 normal female mice had higher CHS responses than their male counterparts, and dietary vitamin D3 deficiency significantly increased the CHS responses in male, but not in female, mice. This change in the vitamin D3-deficient male mice was not due to an alteration in skin dendritic cell function including antigen carriage, migration or costimulatory molecule expression. In addition, 18 h after sensitisation, the lymph node populations in the vitamin D3-deficient and normal male mice showed similar proliferation and IFN-gamma production. However, during the sensitisation phase of CHS, there was lower lymphocyte recruitment to the skin draining lymph nodes of the vitamin D3-deficient and normal male mice compared with their female counterparts which could account for the difference between the sexes in the extent of the CHS response. These results indicate the vitamin D system can influence cutaneous immune responses in male mice, but this did not occur through the modulation of the dendritic cell functions analysed.

An open-label randomised clinical trial to compare the efficacy of dietary caloric restriction and physical activity for weight loss in overweight pet dogs.

Canine obesity is usually managed with a combination of dietary caloric restriction and increasing physical activity, but no previous study has compared both of these strategies in a prospective randomised controlled trial. Thirteen overweight dogs (body condition score 6-9/9) were randomised to one of two interventions: dietary caloric restriction or physical activity. The dietary caloric restriction intervention comprised feeding a therapeutic weight loss diet, while the physical activity intervention comprised increasing the dog's current physical activity pattern by at least a third. The primary outcome measure was change in body weight, while secondary outcome measures included change in neck, thorax and abdominal circumference and change in physical activity measured by triaxial accelerometer. Bodyweight decreased significantly with the dietary caloric restriction (median -10% of starting body weight [SBW], 5 to -12%; P=0.028) but not with the physical activity intervention (-2% SBW, +3% to -6%; P=0.107). Abdominal circumference (dietary caloric restriction: median -12.0%; physical activity: median -7.8%, P=0.016) and thoracic circumference (dietary caloric restriction: median -7.5%, P=0.031; physical activity: median -3.6%, P=0.031) changed significantly in both groups. There was no change in activity levels within the dietary caloric restriction group, but vigorous activity increased significantly in the physical activity group (P=0.016). Dietary caloric restriction was more effective than physical activity for controlled weight loss in overweight pet dogs. Although advising owners to increase their dog's activity by a third led to a modest increase in measured vigorous physical activity, this was insufficient to promote weight loss on its own.

Efforts of the United States' National Marrow Donor Program and Registry to improve utilization and representation of minority donors.

SUMMARY: Haematopoietic stem cell transplantation is often used as a therapy for patients with certain blood, metabolic or immune system disorders. The United States' National Marrow Donor Program (NMDP) works to facilitate such life-saving transplants by coordinating the donor search and match process. However, concern exists that the NMDP Registry is underutilized and under-representative of racial and ethnic minorities. African-Americans and Hispanics are somewhat under-represented within the total number of donors, and it is estimated that the Registry is used by only approximately one-third of patients needing transplants. The NMDP has instituted programmes that address such concerns, resulting in an increase in both the total number of donors and the minority representation on the Registry. It has also increased efforts to recruit donors of umbilical cord blood, often a viable alternative source of haematopoietic stem cells. Over the past 8 years, the Registry has grown by more than 30% to contain over seven million donors, and the proportional distribution of racial and ethnic groups on the Registry has steadily approached their proportional distribution in the US population. Continued efforts on the part of the NMDP to maintain a Registry that is large in number and ethnically diverse should help ensure access to haematopoietic stem cell transplants for all patients who need them. The procedures and experience of the NMDP and its Registry may have implications for registries elsewhere in the world as they confront similar issues of number and diversity.

Mitogen-induced responses in lymphocytes from platypus, the Tasmanian devil and the eastern barred bandicoot.

OBJECTIVE: As the platypus (Ornithorhynchus anatinus), the Tasmanian devil (Sarcophilus harrisi) and the eastern barred bandicoot (Perameles gunni) are currently at risk of serious population decline or extinction from fatal diseases in Tasmania, the goal of the present study was to describe the normal immune response of these species to challenge using the lymphocyte proliferation assay, to give a solid basis for further studies. METHODS: For this preliminary study, we performed lymphocyte proliferation assays on peripheral blood mononuclear cells (PBMC) from the three species. We used the common mitogens phytohaemagglutinin (PHA), concanavalin A (ConA), lipopolysaccharide (LPS) and pokeweed mitogen (PWM). RESULTS: All three species recorded the highest stimulation index (SI) with the T-cell mitogens PHA and ConA. Tasmanian devils and bandicoots had greater responses than platypuses, although variability between individual animals was high. CONCLUSION: For the first time, we report the normal cellular response of the platypus, the Tasmanian devil and the eastern barred bandicoot to a range of commonly used mitogens.