Heavy ion irradiation and unloading effects on mouse lumbar vertebral microarchitecture,mechanical properties and tissue stresses

Astronauts are exposed to both musculoskeletal disuse and heavy ion radiation in space. Disuse alters the magnitude and direction of forces placed upon the skeleton causing bone remodeling, while energy deposited by ionizing radiation causes free radical formation and can lead to DNA strand breaks and oxidative damage to tissues. Radiation and disuse each result in a net loss of mineralized tissue in the adult, although the combined effects, subsequent consequences for mechanical properties and potential for recovery may differ. First, we examined how a high dose (2 Gy) of heavy ion radiation (⁵⁶Fe) causes loss of mineralized tissue in the lumbar vertebrae of skeletally mature (4 months old), male, C57BL/6 mice using microcomputed tomography and determined the influence of structural changes on mechanical properties using whole bone compression tests and finite element analyses. Next, we tested if a low dose (0.5 Gy) of heavy particle radiation prevents skeletal recovery from a 14-day period of hindlimb unloading. Irradiation with a high dose of ⁵⁶Fe (2 Gy) caused bone loss (?14%) in the cancellous-rich centrum of the fourth lumbar vertebra (L4) 1 month later, increased trabecular stresses (+ 27%), increased the propensity for trabecular buckling and shifted stresses to the cortex. As expected, hindlimb unloading (14 days) alone adversely affected microarchitectural and mechanical stiffness of lumbar vertebrae, although the reduction in yield force was not statistically significant (?17%). Irradiation with a low dose of ⁵⁶Fe (0.5 Gy) did not affect vertebrae in normally loaded mice, but significantly reduced compressive yield force in vertebrae of unloaded mice relative to sham-irradiated controls (?24%). Irradiation did not impair the recovery of trabecular bone volume fraction that occurs after hindlimb unloaded mice are released to ambulate normally, although microarchitectural differences persisted 28 days later (96% increase in ratio of rod- to plate-like trabeculae). In summary, ⁵⁶Fe irradiation (0.5 Gy) of unloaded mice contributed to a reduction in compressive strength and partially prevented recovery of cancellous microarchitecture from adaptive responses of lumbar vertebrae to skeletal unloading. Thus, irradiation with heavy ions may accelerate or worsen the loss of skeletal integrity triggered by musculoskeletal disuse.     

Rising incidence of type 1 diabetes in Scottish children, 1984-93. The Scottish Study Group for the Care of Young Diabetics

OBJECTIVES: To calculate the incidence of type 1 diabetes in Scottish children aged less than 15 years between 1984 and 1993; to examine changes in incidence; and to calculate the prevalence of diabetes at the end of this period. DESIGN: Three data sources were used to construct the Scottish Study Group for the Care of Young Diabetics register: active reporting of all new cases; reports from the Scottish Morbidity Register 1; and local registers. SUBJECTS: All children resident in Scotland diagnosed with primary insulin dependent diabetes mellitus when less than 15 years of age between 1984 and 1993. MAIN OUTCOME MEASURES: Annual incidence and prevalence rate for Scotland; time trend in incidence over the 10 years; differences in incidence between the three different age groups; and completeness of the register. RESULTS: The average annual incidence for Scotland was 23.9/100,000 children. The prevalence rate was 1.5/1000 in 1993. A total of 2326 cases was identified from the three sources. Capture-recapture analysis suggests a case ascertainment of 98.6%. The annual incidence rates increased at a rate of 2% each year (rate ratio = 1.02, 95% confidence interval (CI) 1.01 to 1.03). The incidence was higher in boys than girls (rate ratio = 1.08, 95% CI 1.00 to 1.18), and the incidence rates increased with age: 15.3/100,000/year for age 0-4 years, 24.4/ 100,000/year for age 5-9 years, and 31.9/ 100,000/year for age 10-14 years. CONCLUSIONS: The incidence of type 1 diabetes in Scotland is increasing and the prevalence is relatively high. These findings have important implications for health service resource allocation. The Scottish Study Group for the Care of Young Diabetics' register provides a base for monitoring and research.     

Pulp revascularization for immature replanted teeth: a case report

Immature avulsed teeth are not usually treated with pulp revascularization because of the possibility of complications. However, this therapy has shown success in the treatment of immature teeth with periapical lesions. This report describes the case of an immature replanted tooth that was successfully treated by pulp revascularization. An 8‐year‐old boy suffered avulsion on his maxillary left lateral incisor. The tooth showed incomplete root development and was replanted after 30 minutes. After diagnosis, revascularization therapy was performed by irrigating the root canal and applying a calcium hydroxide paste and 2% chlorhexidine gel for 21 days. In the second session, the intracanal dressing was removed and a blood clot was stimulated up to the cervical third of the root canal. Mineral trioxide aggregate was placed as a cervical barrier at the entrance of the root canal and the crown was restored. During the follow‐up period, periapical repair, apical closure and calcification in the apical 4 mm of the root canal was observed. An avulsed immature tooth replanted after a brief extra‐alveolar period and maintained in a viable storage medium may be treated with revascularization.     

Reduction of ER stress via a chemical chaperone prevents disease phenotypes in a mouse model of primary open angle glaucoma

Mutations in myocilin (MYOC) are the most common genetic cause of primary open angle glaucoma (POAG), but the mechanisms underlying MYOC-associated glaucoma are not fully understood. Here, we report the development of a transgenic mouse model of POAG caused by the Y437H MYOC mutation; the mice are referred to herein as Tg-MYOC(Y437H) mice. Analysis of adult Tg-MYOC(Y437H) mice, which we showed express human MYOC containing the Y437H mutation within relevant eye tissues, revealed that they display glaucoma phenotypes (i.e., elevated intraocular pressure [IOP], retinal ganglion cell death, and axonal degeneration) closely resembling those seen in patients with POAG caused by the Y437H MYOC mutation. Mutant myocilin was not secreted into the aqueous humor but accumulated in the ER of the trabecular meshwork (TM), thereby inducing ER stress in the TM of Tg-MYOC(Y437H) mice. Furthermore, chronic and persistent ER stress was found to be associated with TM cell death and elevation of IOP in Tg-MYOC(Y437H) mice. Reduction of ER stress with a chemical chaperone, phenylbutyric acid (PBA), prevented glaucoma phenotypes in Tg-MYOC(Y437H) mice by promoting the secretion of mutant myocilin in the aqueous humor and by decreasing intracellular accumulation of myocilin in the ER, thus preventing TM cell death. These results demonstrate that ER stress is linked to the pathogenesis of POAG and may be a target for treatment in human patients.     

Experimental acute alcohol pancreatitis‐related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect

OBJECTIVE: The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. METHODS: Sprague–Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full‐blown, rats were fed an alcohol‐rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. RESULTS: Synbiotics but not metronidazole improved the acute pancreatitis‐induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic‐treated group, while metronidazole had a negative effect on liver damage. CONCLUSIONS: Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.     

Retention of "safe" blood donors. The Retrovirus Epidemiology Donor Study

BACKGROUND: There are obvious advantages to increasing donor retention. However, for reasons of blood safety, certain donors may, in fact, be more desirable to retain than others. “Safe” donors are defined as those who provided a blood donation that was negative on all laboratory screening tests and who subsequently reported no behavioral risks in response to an anonymous survey. This study identifies the most important factors affecting the intention of “safe” donors to provide another donation. STUDY DESIGN AND METHODS: An anonymous survey asking about donation history, sexual history, injecting drug use, and recent donation experience was mailed to 50,162 randomly selected allogeneic donors (including directed donors) who gave blood from April through July or from October through December 1993 at one of the five United States blood centers participating in the Retrovirus Epidemiology Donor Study. Before mailing, questionnaires were coded to designate donors with nonreactive laboratory screening tests at their most recent donation. RESULTS: A total of 34,726 donors (69%) responded, with substantially higher response among repeat donors. According to reported intentions only, the vast majority of “safe” donors indicated a high likelihood of donating again within the next 12 months. Only 3.4 percent reported a low likelihood of donating again. A comparison of those likely to return and those unlikely to return reveals significant differences in demographics and in ratings of the donation experience. A higher proportion of those unlikely to return were first-time donors, minority-group donors, and donors with less education. The highest projected loss among “safe” donors was seen for those who gave a fair to poor assessment of their treatment by blood center staff or of their physical well-being during or after donating. CONCLUSION: These data suggest that efforts to improve donors' perceptions of their donation experience, as well as attention to the physical effects of blood donation, may aid in the retention of both repeat and first-time donors.     

Effect of freezing on the in vivo recovery of irradiated red cells

BACKGROUND: Transfusion-associated graft-versus-host disease can be prevented by gamma radiation of blood components. The increased use of blood components donated for patients by their family members has resulted in an increased demand for the storage and handling of irradiated units, and the ability to freeze the cells would allow storage beyond their current expiration date. STUDY DESIGN AND METHODS: To assess the effect of freezing and deglycerolization on irradiated red cells, studies of autologous radiolabeled red cell recovery were performed using normal volunteers. Each unit of CPDA-1 red cells was immediately divided into two equal volumes. Further handling of each half was identical except that one was irradiated (3500 cGy). The units were grouped under three protocols: I, irradiated on Day 0 and frozen on Day 5 (n = 4); II, irradiated on Day 7, rejuvenated, and frozen on Day 14 (n = 5); and III, irradiated on Day 14, rejuvenated, and frozen on Day 18 (n = 3). All cells were frozen for 3 to 10 months at -80 degrees C. RESULTS: Irradiated and control units showed no significant differences in supernatant potassium or hemoglobin. Autologous 24-hour posttransfusion recoveries (mean +/− SD) for the three groups were: I, 89.7 +/− 5.6 percent (control, 90.6 +/− 3.2%); II, 85.3 +/− 5.7 percent (control, 83.7 +/− 3.0%); and III, 79.5 +/− 1.4 percent (control, 82.6 +/− 5.2%). CONCLUSION: Irradiated red cells can be frozen after being stored under various conditions and can still meet established guidelines requiring 75-percent recovery 24 hours after transfusion.     

Dual Diagnosis in Older Adults: A Review

Dual diagnosis is associated with frequent relapse, poor treatment engagement and overall unsatisfactory treatment outcomes. A comprehensive review of the contemporary literature examining this issue was conducted, finding a paucity of literature concerning dual diagnosis in older adults. Of the literature appraised for this review, a number of studies examined US Veteran's Affairs populations, which were largely male. Studies concerning older mental health populations were scarce. During the literature search, a number of background studies that influenced contemporary research regarding dual diagnosis in older adults were found; these studies were examined regarding their contribution to contemporary paradigms concerning older adults with co-occurring mental illness and substance use disorders. This review presents the results of the contemporary literature concerning dual diagnosis in older adults. Several recurring themes emerge from the literature, including the notion of a statistically small population that, in absolute terms, represents a sizeable number of individuals coming to the attention of aged mental health services in the future. Additionally, the potential for under-diagnosis in this cohort is highlighted, potentially creating a hidden population of older adults with dual diagnosis.     

The Experiences of Clinicians Caring for Older Adults with Dual Diagnosis: An Exploratory Study

Dual diagnosis has been identified as a significant challenge to mental health services, resulting in higher rates of psychiatric relapse and greater illness severity. Much research explores dual diagnosis in the adult mental health cohort, however little research attention has been paid to older adults with dual diagnosis. Far from being a trivial issue, preliminary studies have shown that dual diagnosis in older adults is under diagnosed and poorly identified by clinicians with few specific treatment options available. In addition, studies of the ageing baby boomer cohort demonstrate a potential for dual diagnosis presentations to increase in the coming years. This article explores the experiences of a clinical team providing care to older adults with dual diagnosis in Melbourne, Australia, through a semi-structured interview process. The participants described a number of systemic barriers to providing care to the older adults with dual diagnosis presenting to the mental health service, in addition to feeling poorly prepared and expressing a degree of clinical helplessness. Additionally, the participants described service improvement, which included a strong dual diagnosis culture in the leadership team of the mental health service and role modelling dual diagnosis competent practice among clinicians.