Combinatorial Inhibition of Myostatin and Activin A Improves Femoral Bone Properties in the G610C Mouse Model of Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a collagen-related bone disorder characterized by fragile osteopenic bone and muscle weakness. We have previously shown that the soluble activin receptor type IIB decoy (sActRIIB) molecule increases muscle mass and improves bone strength in the mild to moderate G610C mouse model of OI. The sActRIIB molecule binds multiple transforming growth factor-β (TGF-β) ligands, including myostatin and activin A. Here, we investigate the musculoskeletal effects of inhibiting activin A alone, myostatin alone, or both myostatin and activin A in wild-type (Wt) and heterozygous G610C (+/G610C) mice using specific monoclonal antibodies. Male and female Wt and +/G610C mice were treated twice weekly with intraperitoneal injections of monoclonal control antibody (Ctrl-Ab, Regn1945), anti-activin A antibody (ActA-Ab, Regn2476), anti-myostatin antibody (Mstn-Ab, Regn647), or both ActA-Ab and Mstn-Ab (Combo, Regn2476, and Regn647) from 5 to 16 weeks of age. Prior to euthanasia, whole body composition, metabolism and muscle force generation assessments were performed. Post euthanasia, hindlimb muscles were evaluated for mass, and femurs were evaluated for changes in microarchitecture and biomechanical strength using micro–computed tomography (μCT) and three-point bend analyses. ActA-Ab treatment minimally impacted the +/G610C musculoskeleton, and was detrimental to bone strength in male +/G610C mice. Mstn-Ab treatment, as previously reported, resulted in substantial increases in hindlimb muscle weights and overall body weights in Wt and male +/G610C mice, but had minimal skeletal impact in +/G610C mice. Conversely, the Combo treatment outperformed ActA-Ab alone or Mstn-Ab alone, consistently increasing hindlimb muscle and body weights regardless of sex or genotype and improving bone microarchitecture and strength in both male and female +/G610C and Wt mice. Combinatorial inhibition of activin A and myostatin more potently increased muscle mass and bone microarchitecture and strength than either antibody alone, recapturing most of the observed benefits of sActRIIB treatment in +/G610C mice. © 2022 American Society for Bone and Mineral Research (ASBMR).     

McArdle's disease with myoadenylate deaminase deficiency: observations in a combined enzyme deficiency

Exercise and work potential of a patient with coexistent myophosphorylase and myoadenylate deaminase (AMPDA) deficiency was compared with that of three patients with myophosphorylase deficiency alone. The patient with the combined defect failed to produce an abnormal rise in serum ammonia or hypoxanthine as seen in the other patients after forearm exercise. Maximum oxygen consumption and work rates during cycle ergometer testing were similar in all patients, but well below controls. The occurrence of two defects involving short-term energy metabolism in muscle presents an opportunity to define further the metabolic role of AMPDA.     

The Usefulness of Magnetic Resonance Imaging in the Diagnosis of Anterolateral Impingement of the Ankle

The purpose of this study is to assess the sensitivity and specificity of magnetic resonance imaging (MRI) in the diagnosis of anterolateral impingement of the ankle and to assess the most helpful sequence in making the diagnosis. Twenty-four patients who had undergone ankle arthroscopy were chosen. Twelve patients had arthroscopically documented anterolateral impingement, and 12 patients with no impingement on arthroscopy served as controls. Two musculoskeletal radiologists and an orthopedic surgeon, blinded to the operative diagnosis, retrospectively reviewed selective MRI images in the sagittal, axial, and coronal planes. The sensitivities and specificities were calculated for all 3 reviewers. The Kendall coefficient of concordance was calculated for overall agreement among reviewers. Sensitivities varied from 0.75 to 0.83, whereas specificities varied from 0.75 to 1.00. Using the Fisher exact test of contingency, the sensitivities and specificities showed that all reviewers' interpretations were statistically significant with P = .039, .001, and .012, respectively. The axial images were felt to be most helpful in making the diagnosis. The physicians felt that the sagittal images were helpful in 67%, 83%, and 100%, respectively. MRI is a useful tool that can aid the clinician in the diagnosis of anterolateral impingement of the ankle. T1 sagittal images demonstrating displacement of the normal fat signal anterior to the fibula by scar can be useful and help to confirm the diagnosis.     

Oilseed rape and seasonal symptoms: epidemiological and environmental studies.

BACKGROUND--There is widespread concern that the cultivation of oilseed rape leads to seasonal epidemics of respiratory symptoms in populations living in the neighbourhood, and it has been suggested that the plant is a potent allergen. A study was therefore undertaken to determine the prevalence of seasonal symptoms in rural populations close to and far from areas of oilseed rape cultivation, and to measure the levels of allergen and other potentially harmful substances released by the crop. METHODS--Random samples of 1000 adults from the general practice populations of two villages surrounded by oilseed rape fields, and 1000 adults from one village far from such cultivation, were taken. The subjects completed a previously validated questionnaire on respiratory and other symptoms, including questions on symptom seasonality, occupation, and smoking habits. Pollen and fungal spore counts were made around fields of oilseed rape and in the villages. The chemicals released by oilseed rape were measured in the field. RESULTS--Overall, 86.8% of the subjects completed the questionnaires and the populations of the two samples were generally comparable. Spring and summer exacerbations of symptoms occurred equally in the two areas in approximately 25% of the population. There were small but significant excesses of cough, wheeze, and headaches in spring in the oilseed rape area (2.3% v 1.1%, 6.8% v 4.6%, and 4.8% v 2.8%, respectively), and cough, wheeze, and itchy skin were more prevalent in smokers. Counts of oilseed rape pollen were generally low except adjacent to fields, and counts of fungal spores were mostly higher in the rape than the non-rape areas. Oilseed rape was shown to give off terpenes and these were detected close to fields. CONCLUSIONS--While it is likely that a proportion of the spring symptoms occurring in people living in close proximity to oilseed rape is caused by the plant, the excess of such symptoms is small. This, together with the low levels of pollen in the area, suggests that allergy to oilseed rape pollen is uncommon. The general prevalence of seasonal symptoms in rural areas is of interest, and a proportion of these cases is likely to be caused by factors other than allergy. Release of chemicals by plants and natural rises in summer ozone levels may be contributors.     

142Effects of Low‐Frequency Ultrasound Applied In Vitro to Highly Antibiotic‐Resistant Acinetobacter Isolates Recovered From Soldiers Returning From Iraq

Abstract  Brooke Army Medical Center isolated 25 highly antibiotic‐resistant Acinetobacter ssp . (primarily A. baumannii ) from wounded soldiers returning from Iraq. Concern about effective treatment of these organisms led our institution to begin investigating low‐frequency ultrasound (LFU) as a method of increasing the effectiveness of antibiotics on A.baumannii in wound management. Studies have suggested that LFU applied in conjunction with antibiotics may increase their overall effectiveness. We hypothesize that combining antibiotics with LFU may be an effective method of wound management and that this combination may be synergistic in its overall effect. In this initial work, we wanted to determine if sonocation would have an effect on our organism of interest, A. baumannii . We selected several organisms, both gram positive and gram negative, that have been shown to be killed by sonocation ( E. coli, S. aureus , and S. pyogenes ) and added three highly resistant A. baumannii isolates. Bacterial death was measured by both colony counts after 24 hours of growth and acridine orange staining using a standard protocol.
Colony counts were significantly reduced by sonocation. Furthermore, A.'baumannii colony counts were also greatly reduced by sonocation. Actual cell destruction was also visualized using acridine orange staining. Our data support the assertion that sonocation has an antibacterial effect on some bacteria, including A. baumannii . Our next step is to add antimicrobial agents and determine if their effectiveness can be increased by sonocation.     

Australian Research on Ageing and Social Support

This paper draws on primary publications in Austalian gerontology to review knowledge on ageing and support While there is a well-established literature on family care, social networks studies of the 1980s provided more comprehensive views of expressive and instrumental support across a range of relationships. Notwithstanding stereotypes to the contrary, older people contribute as well as receive support. A new generation of qualitive, interpretative shudies are reporting on the meanings and processes of social support as experienced by older people themselves. Policy-related studies examine social support as a cornerstone for community services, and epidemiological investigations examine social influence on health and well-being. The field could be advanced considerably by longiturdinal surveys and qualitative enquiris exploring the diversity of older people in a variety of social settings.