Mechanical differences between lumbar and tail discs in the mouse.

The mouse lumbar and tail discs are both used as models to study disc degeneration; however, the mechanical behavior of these two levels has not been compared. The objective of this study was to compare the elastic and viscoelastic mechanical properties of lumbar and tail discs of the mouse under axial compression-tension loading. We hypothesized that tail discs would have a larger transition zone (e.g., neutral zone) and would be less stiff in compression. To test these hypotheses, lumbar and tail bone-disc-bone motion segments were loaded in axial compression and tension. The nonlinear elastic mechanical behavior was examined using a tri-linear curvefit. Elastic behavior of lumbar and tail discs was most different in the low-stiffness transition region (neutral zone), where lumbar discs were nearly twice as stiff over half the axial displacement. In addition, viscoelastic behavior, which was examined using a stretch-exponential curvefit, also showed large lumbar and tail differences, where lumbar discs compressed by 60% of their original height and tail discs by 98% after static creep compression. These results demonstrate that tail discs undergo far more axial displacement than lumbar discs under the same load. These findings are relevant to rodent tail models where chronic loads are applied in vivo to study mechanical pathways of degeneration. Furthermore, the tri-linear model, used here to curvefit the nonlinear compression-tension data, quantified stiffness in the transition zone for the first time, which may prove useful in future disc mechanical studies.     

Degree of Trauma Differs for Major Osteoporotic Fracture Events in Older Men Versus Older Women

To examine the degree of trauma in major osteoporotic fractures (MOF) in men versus women, we used data from 15,698 adults aged ≥65 years enrolled in the Osteoporotic Fractures in Men (MrOS) study (5994 men) and the Study of Osteoporotic Fractures (SOF) (9704 women). Participants were contacted tri‐annually to ascertain incident fractures, which were confirmed by radiographic reports and coded according to degree of self‐reported trauma. Trauma was classified as low (fall from ≤ standing height; fall on stairs, steps, or curb; minimal trauma other than fall [coughing, turning over]); moderate (collisions with objects during normal activity without associated fall); or high (fall from > standing height; severe trauma [motor vehicle accident, assault]). MOF included hip, clinical vertebral, wrist, and humerus fractures. Mean fracture follow‐up was 9.1 years in SOF and 8.7 years in MrOS. A total of 14.6% of the MOF in men versus 6.3% of the MOF in women were classified as high trauma (p < 0.001); men versus women more often experienced fractures resulting from severe trauma as well as from fall > standing height. High‐trauma fractures were more significantly common in men versus women at the hip (p = 0.002) and wrist (p < 0.001) but not at the spine or humerus. Among participants with MOF, the odds ratio of a fracture related to high‐trauma fracture among men versus women was 3.12 (95% confidence interval [CI] 1.70–5.71) after adjustment for traditional risk factors. Findings were similar in analyses limited to participants with hip fractures (odds ratio [OR] = 3.34, 95% CI 1.04–10.67) and those with wrist fracture (OR = 5.68, 95% CI 2.03–15.85). Among community‐dwelling older adults, MOF are more likely to be related to high trauma in men than in women. These findings are not explained by sex differences in conventional risk factors and may reflect a greater propensity among men to engage in risky behavior. © 2015 American Society for Bone and Mineral Research.     

Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and the International Knockout Mouse Consortium

The International Knockout Mouse Consortium (IKMC) introduces its targeted constructs into C57BL/6N embryonic stem cells. However, breeding with a Cre-recombinase and/or Flp-recombinase mouse is required for the generation of a null allele with the IKMC cassette. Many recombinase strains are in the C57BL/6J background, resulting in knockout animals on a mixed strain background. This can lead to variability in metabolic data and the use of improper control groups. While C57BL/6N and C57BL/6J are derived from the same parental C57BL/6 strain, there are key genotypic and phenotypic differences between these substrains. Many researchers may not even be aware of these differences, as the shorthand C57BL/6 is often used to describe both substrains. We found that 58% of articles involving genetically modified mouse models did not completely address background strain. This review will describe these two substrains and highlight the importance of separate consideration in mouse model development. Our aim is to increase awareness of this issue in the diabetes research community and to provide practical strategies to enable researchers to avoid mixed strain animals when using IKMC knockout mice.     

Safety and Efficacy of Reteplase for the Treatment of Acute Arterial Occlusion: Complexity of Underlying Lesion Predicts Outcome

We evaluated both the safety and efficacy of reteplase for treatment of acute arterial occlusion as well as outcomes based on treatment of the underlying lesion. From November 2000 to February 2004, reteplase was used to treat arterial occlusions in 81 patients. Catheter-directed intrathrombus thrombolysis was performed with reteplase (0.5 units/hr) continuous infusion. Percutaneous mechanical thrombectomy (Angiojet) was performed in 61% (n = 50) of patients prior to thrombolysis. Unmasking of significant lesions resulted in endovascular intervention (39.5%), open surgical repair (24.6%), or both endovascular and surgical repair (9.8%) of the lesion. No lesion was found in 25.9% of patients. Major and minor complication rates as well as restoration of patency, limb salvage, and amputation-free survival were evaluated. Eighty-one patients received reteplase therapy (median = 10.3 +/- 5.3 units, 19.5 +/- 7.4 hr) followed by next-day arteriogram to assess thrombus removal. Technical success was achieved in 96.2% (n = 78) of cases. Kaplan-Meier life table analysis revealed overall primary patency rates of 76.3%, 60.1%, and 51.6%, at 1, 6, and 12 months, respectively. Overall amputation-free survival rates were 86.4%, 76.4%, and 69.7% at 1, 6, and 12 months, respectively. When subdivided into postlysis intervention, the lysis-only group achieved increased patency (p = 0.0143) and increased limb salvage (p = 0.0219) at 1 year compared to the lysis and endovascular intervention and the lysis and surgical groups. The 30-day complication rate was 17.3% (n = 14), with a major complication rate of 4.9% (n = 4) and a minor complication rate of 12.3% (n = 10). There were no intracranial hemorrhagic complications. Intra-arterial catheter-directed infusion of reteplase for acute lower extremity ischemia is safe and efficacious, as shown by the low risk of bleeding complications, high limb salvage rates, and low mortality rates in this study. The complexity of the lesion that is unmasked through thrombolytic therapy is a predictor of patency and limb salvage.     

Transplant data: sources, collection and research considerations, 2004

The process of collecting and analyzing transplant data is complex. Familiarity with how these data are collected is crucial to a thorough understanding of the information. This article focuses on available OPTN-SRTR data and the continuing evolution of data collection mechanisms; how that data collection system is improving the data quality and reducing the data collection burden; how additional ascertainment of outcomes both completes and validates existing data; and caveats that remain for researchers. This year's article focuses further on research considerations related to cohort choice, timing of data submission, and potential biases in follow-up data. Ongoing improvements in data collection timeliness and scope are covered. The impact of extra ascertainment of outcomes, particularly for post-transplant kidney graft failure from Medicare data, are also examined. A section on graft failure reporting among different sources traces the steps by which the SRTR reconciles different data sources in its analyses. It is important that those reading and conducting transplant research understand the origin, structure, and scope of the available data. All of these issues should be carefully considered when choosing cohorts and data sources for analysis.     

Video-assisted thoracic surgery (VATS) for resection of metastatic adenocarcinoma as an acceptable alternative

Background  Adenocarcinomas commonly metastasize to the lungs and can be resected using open thoracotomy or video-assisted thoracic surgery (VATS). This study reviews metastatic resections in primary adenocarcinoma patients, using both thoracotomy and VATS. We aim to compare long-term prognoses to test the efficacy and viability of VATS. Methods  A retrospective review of primary adenocarcinoma patients who underwent resection of pulmonary metastases from 1990 to 2006 was carried out. Information was obtained by chart review. Endpoints analyzed were disease-free interval (DFI), survival time, and recurrence-free survival (RFS). Results  In a total of 42 (16 male, 26 female; median age 58.5 years) primary adenocarcinoma patients, 21 patients underwent first pulmonary metastatic resection using VATS (7 male, 14 female; median age 57 years) and 21 using thoracotomy (9 male, 12 female; median age 59 years). Primary adenocarcinomas were mainly 27 colorectal (64%) and 11 breast (26%). Two VATS (10%) and three open patients (14%) had local recurrences of the original cancer. Median postoperative follow was 13.3 months [interquartile range (IQR) 4.5–32.8 months] for VATS and 36.9 months (IQR 19.3–48.6 months) after thoracotomy. Median DFI–1 was 22.3 months (IQR 13.5–40.6 months) for VATS patients and 35.6 months (IQR 26.7–61.3 months) for open patients. Second thoracic occurrences were noted in six VATS patients (median DFI–2 9.2 months), and in seven open patients (median DFI-2 21.5 months). Third thoracic occurrences were noted in one VATS patient (DFI-3 18.7 months) and in one thoracotomy patient (DFI-3 21.8 months). Odds ratio of recurrence showed 12.5% less chance of developing recurrence in VATS patients. Five-year RFS was 53% in VATS and 57% in thoracotomy patients. Conclusions  VATS has become a viable alternative to open thoracotomy for resection of pulmonary metastases. In cases of primary adenocarcinoma, VATS showed no increase in number of thoracic recurrences, and comparable RFS. Short-term follow-up is encouraging; long-term follow-up will be needed to confirm these results.     

Traumatic brain injury in a county jail population: prevalence,neuropsychological functioning and psychiatric disorders

Primary objective : To determine the prevalence of traumatic brain injury (TBI) among inmates in a county jail population.

Research design : Cross-sectional, observational study.

Methods and procedures : A standardized interview was used to determine prevalence of TBI in 69 randomly selected inmates. To examine cognitive and emotional differences between subjects with and without recent TBI, neuropsychological tests and structured psychiatric diagnostic interviews were conducted with 50 subjects (the first 25 with TBI and the first 25 without TBI in the prior year).

Results : Sixty (87.0%) reported TBI over their lifetime; 25 (36.2%) reported TBI in the prior year. The latter group had significantly worse anger and aggression scores and had a trend towards poorer cognitive test results and a higher prevalence of psychiatric disorders than the group without TBI in the prior year.

Conclusion : This study suggests the need for increased attention to TBI and its cognitive, behavioural and psychiatric sequelae in jail populations.     

Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection

OBJECT: Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. METHODS: The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are > or = 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression. RESULTS: Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006). CONCLUSIONS: In the FIA study, among the affected patients' FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.     

A tailored therapy for the metabolic syndrome: the dual peroxisome proliferator-activated receptor-alpha/gamma agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in preclinical models

A novel nonthiazolidinedione dual peroxisome proliferator- activated receptor (PPAR)-alpha/gamma agonist, LY465608, was designed to address the major metabolic disturbances of type 2 diabetes. LY465608 altered PPAR-responsive genes in liver and fat of db/db mice and dose-dependently lowered plasma glucose in hyperglycemic male Zucker diabetic fatty (ZDF) rats, with an ED(50) for glucose normalization of 3.8 mg small middle dot kg(-1) small middle dot day(-1). Metabolic improvements were associated with enhanced insulin sensitivity, as demonstrated in female obese Zucker (fa/fa) rats using both oral glucose tolerance tests and hyperinsulinemic-euglycemic clamps. Further characterization of LY465608 revealed metabolic changes distinct from a selective PPAR-gamma agonist, which were presumably due to the concomitant PPAR-alpha agonism, lower respiratory quotient, and less fat accumulation, despite a similar impact on glycemia in male ZDF rats. In addition to these alterations in diabetic and insulin-resistant animals, LY465608 dose-dependently elevated HDL cholesterol and lowered plasma triglycerides in human apolipoprotein A-I transgenic mice, demonstrating that this compound significantly improves primary cardiovascular risk factors. Overall, these studies demonstrate that LY465608 beneficially impacts multiple facets of type 2 diabetes and associated cardiovascular risk, including those facets involved in the development of micro- and macrovascular complications, which are the major sources for morbidity and mortality in these patients.