High-volume FES-cycling partially reverses bone loss in people with chronic spinal cord injury

Spinal cord injury (SCI) leads to severe bone loss in the paralysed limbs and to a resulting increased fracture risk thereof. Since long bone fractures can lead to comorbidities and a reduction in quality of life, it is important to improve bone strength in people with chronic SCI. In this prospective longitudinal cohort study, we investigated whether functional electrical stimulation (FES) induced high-volume cycle training can partially reverse the loss of bone substance in the legs after chronic complete SCI. Eleven participants with motor-sensory complete SCI (mean age 41.9+/-7.5 years; 11.0+/-7.1 years post injury) were recruited. After an initial phase of 14+/-7 weeks of FES muscle conditioning, participants performed on average 3.7+/-0.6 FES-cycling sessions per week, of 58+/-5 min each, over 12 months at each individual's highest power output. Bone and muscle parameters were investigated in the legs by means of peripheral quantitative computed tomography before the muscle conditioning (t1), and after six (t2) and 12 months (t3) of high-volume FES-cycle training. After 12 months of FES-cycling, trabecular and total bone mineral density (BMD) as well as total cross-sectional area in the distal femoral epiphysis increased significantly by 14.4+/-21.1%, 7.0+/-10.8% and 1.2+/-1.5%, respectively. Bone parameters in the femoral shaft showed small but significant decreases, with a reduction of 0.4+/-0.4% in cortical BMD, 1.8+/-3.0% in bone mineral content, and 1.5+/-2.1% in cortical thickness. These decreases mainly occurred between t1 and t2. No significant changes were found in any of the measured bone parameters in the tibia. Muscle CSA at the thigh increased significantly by 35.5+/-18.3%, while fat CSA at the shank decreased by 16.7+/-12.3%. Our results indicate that high-volume FES-cycle training leads to site-specific skeletal changes in the paralysed limbs, with an increase in bone parameters at the actively loaded distal femur but not the passively loaded tibia. Thus, we conclude that high-volume FES-induced cycle training has clinical relevance as it can partially reverse bone loss and thus may reduce fracture risk at this fracture prone site.

Torque converter turbine noise and cavitation noise over varying speed ratio

These investigations will discuss the operational noise caused by automotive torque converters during speed ratio operation. Two specific cases of torque converter noise will be studied; cavitation, and a monotonic turbine induced noise. Cavitation occurs at or near stall, or zero turbine speed. The bubbles produced due to the extreme torques at low speed ratio operation, upon collapse, may cause a broadband noise that is unwanted by those who are occupying the vehicle as other portions of the vehicle drive train improve acoustically. Turbine induced noise, which occurs at high engine torque at around 0.5 speed ratio, is a narrow-band phenomenon that is audible to vehicle occupants currently. The solution to the turbine induced noise is known, however this study is to gain a better understanding of the mechanics behind this occurrence. The automated torque converter dynamometer test cell was utilized in these experiments to determine the effect of torque converter design parameters on the offset of cavitation and to employ the use a microwave telemetry system to directly measure pressures and structural motion on the turbine. Nearfield acoustics were used as a detection method for all phenomena while using a standardized speed ratio sweep test. Changes in filtered sound pressure levels enabled the ability to detect cavitation desinence. This, in turn, was utilized to determine the effects of various torque converter design parameters, including diameter, torus dimensions, and pump and stator blade designs on cavitation. The on turbine pressures and motion measured with the microwave telemetry were used to understand better the effects of a notched trailing edge turbine blade on the turbine induced noise.

Body contouring surgery following bariatric surgery and dietetically induced massive weight reduction: a risk analysis

BACKGROUND: This study analyzed the impact of weight reduction method, preoperative, and intraoperative variables on the outcome of reconstructive body contouring surgery following massive weight reduction. METHODS: All patients presenting with a maximal BMI >/=35 kg/m(2) before weight reduction who underwent body contouring surgery of the trunk following massive weight loss (excess body mass index loss (EBMIL) >/= 30%) between January 2002 and June 2007 were retrospectively analyzed. Incomplete records or follow-up led to exclusion. Statistical analysis focused on weight reduction method and pre-, intra-, and postoperative risk factors. The outcome was compared to current literature results. RESULTS: A total of 104 patients were included (87 female and 17 male; mean age 47.9 years). Massive weight reduction was achieved through bariatric surgery in 62 patients (59.6%) and dietetically in 42 patients (40.4%). Dietetically achieved excess body mass index loss (EBMIL) was 94.20% and in this cohort higher than surgically induced reduction EBMIL 80.80% (p < 0.01). Bariatric surgery did not present increased risks for complications for the secondary body contouring procedures. The observed complications (26.9%) were analyzed for risk factors. Total tissue resection weight was a significant risk factor (p < 0.05). Preoperative BMI had an impact on infections (p < 0.05). No impact on the postoperative outcome was detected in EBMIL, maximal BMI, smoking, hemoglobin, blood loss, body contouring technique or operation time. Corrective procedures were performed in 11 patients (10.6%). The results were compared to recent data. CONCLUSION: Bariatric surgery does not increase risks for complications in subsequent body contouring procedures when compared to massive dietetic weight reduction.

COMBUSTION INITIATION BY ELECTRICAL-DISCHARGE-INDUCED PLASMA IN LEAN AND DILUTE METHANE-AIR MIXTURE: EXPERIMENTAL AND MODELING INVESTIGATION

This dissertation represents experimental and numerical investigations of combustion initiation trigged by electrical-discharge-induced plasma within lean and dilute methane air mixture. This research topic is of interest due to its potential to further promote the understanding and prediction of spark ignition quality in high efficiency gasoline engines, which operate with lean and dilute fuel-air mixture. It is specified in this dissertation that the plasma to flame transition is the key process during the spark ignition event, yet it is also the most complicated and least understood procedure. Therefore the investigation is focused on the overlapped periods when plasma and flame both exists in the system. Experimental study is divided into two parts. Experiments in Part I focuses on the flame kernel resulting from the electrical discharge. A number of external factors are found to affect the growth of the flame kernel, resulting in complex correlations between discharge and flame kernel. Heat loss from the flame kernel to code ambient is found to be a dominant factor that quenches the flame kernel. Another experimental focus is on the plasma channel. Electrical discharges into gases induce intense and highly transient plasma. Detailed observation of the size and contents of the discharge-induced plasma channel is performed. Given the complex correlation and the multi-discipline physical/chemical processes involved in the plasma-flame transition, the modeling principle is taken to reproduce detailed transitions numerically with minimum analytical assumptions. Detailed measurement obtained from experimental work facilitates the more accurate description of initial reaction conditions. The novel and unique spark source considering both energy and species deposition is defined in a justified manner, which is the key feature of this Ignition by Plasma (IBP) model. The results of numerical simulation are intuitive and the potential of numerical simulation to better resolve the complex spark ignition mechanism is presented. Meanwhile, imperfections of the IBP model and numerical simulation have been specified and will address future attentions.

Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy

OBJECTIVE: The mechanism underlying pericyte loss during incipient diabetic retinopathy remains controversial. Hyperglycemia induces angiopoietin-2 (Ang-2) transcription, which modulates capillary pericyte coverage. In this study, we assessed loss of pericyte subgroups and the contribution of Ang-2 to pericyte migration. RESEARCH DESIGN AND METHODS: Numbers of total pericytes and their subgroups were quantified in retinal digest preparations of spontaneous diabetic XLacZ mice. Pericytes were divided into subgroups according to their localization, their position relative to adjacent endothelial cells, and the expression of LacZ. The contribution of Ang-2 to pericyte migration was assessed in Ang-2 overexpressing (mOpsinhAng2) and deficient (Ang2LacZ) mice. RESULTS: Pericyte numbers were reduced by 16% (P < 0.01) in XLacZ mice after 6 months of diabetes. Reduction of pericytes was restricted to pericytes on straight capillaries (relative reduction 27%, P < 0.05) and was predominantly observed in LacZ-positive pericytes (-20%, P < 0.01). Hyperglycemia increased the numbers of migrating pericytes (69%; P < 0.05), of which the relative increase due to diabetes was exclusively in LacZ-negative pericytes, indicating reduced adherence to the capillaries (176%; P < 0.01). Overexpression of Ang-2 in nondiabetic retinas mimicked diabetic pericyte migration of wild-type animals (78%; P < 0.01). Ang-2 deficient mice completely lacked hyperglycemia-induced increase in pericyte migration compared with wild-type littermates. CONCLUSIONS: Diabetic pericyte loss is the result of pericyte migration, and this process is modulated by the Ang-Tie system.

Treatment of branch retinal vein occlusion induced macular edema with bevacizumab

Branch retinal vein occlusion is a frequent cause of visual loss with currently insufficient treatment options. We evaluate the effect of Bevacizumab (Avastin) treatment in patients with macular edema induced by branch retinal vein occlusion.

XIAP discriminates between type I and type II FAS-induced apoptosis

FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions.

Corticospinal output and loss of force during motor fatigue

The objective of this study was to analyze central motor output changes in relation to contraction force during motor fatigue. The triple stimulation technique (TST, Magistris et al. in Brain 121(Pt 3):437-450, 1998) was used to quantify a central conduction index (CCI = amplitude ratio of central conduction response and peripheral nerve response, obtained simultaneously by the TST). The CCI removes effects of peripheral fatigue from the quantification. It allows a quantification of the percentage of the entire target muscle motor unit pool driven to discharge by a transcranial magnetic stimulus. Subjects (n = 23) performed repetitive maximal voluntary contractions (MVC) of abductor digiti minimi (duration 1 s, frequency 0.5 Hz) during 2 min. TST recordings were obtained every 15 s, using stimulation intensities sufficient to stimulate all cortical motor neurons (MNs) leading to the target muscle, and during voluntary contractions of 20% of the MVC to facilitate the responses. TST was also repetitively recorded during recovery. This basic exercise protocol was modified in a number of experiments to further characterize influences on CCI of motor fatigue (4 min exercise at 50% MVC; delayed fatigue recovery during local hemostasis, "stimulated exercise" by 20 Hz trains of 1 s duration at 0.5 Hz during 2 min). In addition, the cortical silent period was measured during the basic exercise protocol. Force fatigued to approximately 40% of MVC in all experiments and in all subjects. In all subjects, CCI decreased during exercise, but this decrease varied markedly between subjects. On average, CCI reductions preceded force reductions during exercise, and CCI recovery preceded force recovery. Exercising at 50% for 4 min reduced muscle force more markedly than CCI. Hemostasis induced by a cuff delayed muscle force recovery, but not CCI recovery. Stimulated exercise reduced force markedly, but CCI decreased only marginally. Summarized, force reduction and reduction of the CCI related poorly quantitatively and in time, and voluntary drive was particularly critical to reduce the CCI. The fatigue induced reduction of CCI may result from a central inhibitory phenomenon. Voluntary muscle activation is critical for the CCI reduction, suggesting a primarily supraspinal mechanism.

Loss of inhibition over master pathways of bone mass regulation results in osteosclerotic bone metastases in prostate cancer

Prostate cancer is the most common cancer among men in industrialised countries. Most patients with prostate cancer, however, will not die of it. As a result, many of them will experience symptomatic metastasis during the course of the disease. Prostate cancer has a high propensity to metastasize to bone. Unlike many other cancers prostate cancer cells induce a rather osteosclerotic than osteolytic reaction in the bone marrow by interfering with physiological bone remodelling. A proper understanding of the mechanisms of tumour cell-induced bone alterations and exaggerated bone deposition in prostate cancer may open new and urgently needed therapeutic approaches in the field of palliative care for affected patients. In this review we focus on the central role of two major regulators of bone mass, the wingless type integration site family members (WNTs) and the bone morphogenetic proteins (BMPs), in the development of osteosclerotic bone metastases.

Switching of vascular phenotypes within a murine breast cancer model induced by angiopoietin-2

Sustained growth of solid tumours can rely on both the formation of new and the co-option of existing blood vessels. Current models suggest that binding of angiopoietin-2 (Ang-2) to its endothelial Tie2 receptor prevents receptor phosphorylation, destabilizes blood vessels, and promotes vascular permeability. In contrast, binding of angiopoietin-1 (Ang-1) induces Tie2 receptor activation and supports the formation of mature blood vessels covered by pericytes. Despite the intense research to decipher the role of angiopoietins during physiological neovascularization and tumour angiogenesis, a mechanistic understanding of angiopoietin function on vascular integrity and remodelling is still incomplete. We therefore assessed the vascular morphology of two mouse mammary carcinoma xenotransplants (M6378 and M6363) which differ in their natural angiopoietin expression. M6378 displayed Ang-1 in tumour cells but no Ang-2 in tumour endothelial cells in vivo. In contrast, M6363 tumours expressed Ang-2 in the tumour vasculature, whereas no Ang-1 expression was present in tumour cells. We stably transfected M6378 mouse mammary carcinoma cells with human Ang-1 or Ang-2 and investigated the consequences on the host vasculature, including ultrastructural morphology. Interestingly, M6378/Ang-2 and M6363 tumours displayed a similar vascular morphology, with intratumoural haemorrhage and non-functional and abnormal blood vessels. Pericyte loss was prominent in these tumours and was accompanied by increased endothelial cell apoptosis. Thus, overexpression of Ang-2 converted the vascular phenotype of M6378 tumours into a phenotype similar to M6363 tumours. Our results support the hypothesis that Ang-1/Tie2 signalling is essential for vessel stabilization and endothelial cell/pericyte interaction, and suggest that Ang-2 is able to induce a switch of vascular phenotypes within tumours.

Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone

Postmenopausal bone loss can be prevented by continuous or intermittent estradiol (E2) administration. Concomitant progestogen therapy is mandatory in nonhysterectomized women to curtail the risk of endometrial hyperplasia or cancer. However, the recurrence of vaginal bleeding induced by sequential progestogen therapy in addition to continuous estrogen administration is one of the reasons for noncompliance to hormone replacement therapy (HRT). Tibolone, a synthetic steroid with simultaneous weak estrogenic, androgenic, and progestational activity, which does not stimulate endometrial proliferation, has recently been proposed for the treatment of climacteric symptoms. To compare the efficacy of conventional oral and transdermal HRT with that of tibolone in the prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6 years; median duration of menopause, 3 years) were enrolled in an open 2-year study. Volunteers had been offered a choice between HRT and no therapy (control group, CO). Patients selecting HRT were randomly allocated to one of the following three treatment groups: TIB, tibolone, 2.5 mg/day continuously, orally; PO, peroral E2, 2 mg/day continuously, plus sequential oral dydrogesterone (DYD), 10 mg/day, for 14 days of a 28-day cycle; TTS, transdermal E2 by patch releasing 50 microg/day, plus DYD as above. Bone densitometry of the lumbar spine, upper femur, and whole body was performed using dual-energy X-ray absorptiometry at baseline, and then 6, 12, 18, and 24 months after initiation of therapy. One hundred and fifteen women (82%) completed the 2 years of the study. The dropout rate was similar in each group. Over 2 years, bone preservation was observed in all three treatment groups as compared with controls, without significant differences among treatment regimens. In conclusion, tibolone can be regarded as an alternative to conventional HRT to prevent postmenopausal bone loss.