Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex

Cortical dynamics can be imaged at high spatiotemporal resolution with voltage-sensitive dyes (VSDs) and calcium-sensitive dyes (CaSDs). We combined these two imaging techniques using epifluorescence optics together with whole cell recordings to measure the spatiotemporal dynamics of activity in the mouse somatosensory barrel cortex in vitro and in the supragranular layers in vivo. The two optical signals reported distinct aspects of cortical function. VSD fluorescence varied linearly with membrane potential and was dominated by subthreshold postsynaptic potentials, whereas the CaSD signal predominantly reflected local action potential firing. Combining VSDs and CaSDs allowed us to monitor the synaptic drive and the spiking activity of a given area at the same time in the same preparation. The spatial extent of the two dye signals was different, with VSD signals spreading further than CaSD signals, reflecting broad subthreshold and narrow suprathreshold receptive fields. Importantly, the signals from the dyes were differentially affected by pharmacological manipulations, stimulation strength, and depth of isoflurane anesthesia. Combined VSD and CaSD measurements can therefore be used to specify the temporal and spatial relationships between subthreshold and suprathreshold activity of the neocortex.

Fibula free flap reconstruction of the mandible in cancer patients: Evaluation of a combined surgical and prosthodontic treatment concept

The final goal of mandibular reconstruction following ablative surgery for oral cancer is often considered to be dental implant-supported oral rehabilitation, for which bone grafts should ideally be placed in a suitable position taking subsequent prosthetic restoration into account. The aim of this study was to evaluate the efficacy of a standardized treatment strategy for mandibular reconstruction according to the size of the bony defect and planned subsequent dental prosthetic rehabilitation. Data of 56 patients, who had undergone such a systematic mandibular fibula free flap reconstruction, were retrospectively analyzed. Early complications were observed in 41.5% of the patients but only in those who had been irradiated. Late complications were found in 38.2%. Dental implant survival rate was 92%, and dental prosthetic treatment has been completed in all classes of bony defects with an overall success rate of 42.9%. The main reasons for failure of the complete dental reconstruction were patients' poor cooperation (30.4%) and tumour recurrence (14.3%) followed by surgery-related factors (10.8%) such as implant failure and an unfavourable intermaxillary relationship between the maxilla and the mandible. A comparison of our results with the literature findings revealed no marked differences in the complication rates and implant survival rates. However, a systematic concept for the reconstructive treatment like the method presented here, plays an important role in the successful completion of dental reconstruction. The success rate could still be improved by some technical progress in implant and bone graft positioning.

Micro combined heat and power laboratory development

Micro Combined Heat and Power (Micro-CHP) system produces both electricity and heat required for residential or small business applications. Use of Micro-CHP in a residential application not only creates energy and economic savings but also reduces the carbon foot print of the house or small business. Additionally, micro-CHP can subsidize its cost of operation by selling excess electricity produced back to the grid. Even though Micro-CHP remains attractive on paper, high initial cost and optimization issues in residential scale heat and electrical requirement has kept this technology from becoming a success. To understand and overcome all disadvantages posed my Micro-CHP system, a laboratory is developed to test different scenarios of Micro-CHP applications so that we can learn and improve the current technology. This report focuses on the development of this Micro-CHP laboratory including installation of Ecopower micro-CHP unit, developing fuel line and exhaust line for Ecopower unit, design of electrical and thermal loop, installing all the instrumentation required for data collection on the Ecopower unit and developing controls for heat load simulation using thermal loop. Also a simulation of Micro-CHP running on Syngas is done in Matlab. This work was supported through the donation of ‘Ecopower’ a Micro-CHP unit by Marathon Engine and through the support of Michigan Tech REF-IF grand.

Biomechanical analysis of torsion and shear forces in lumbar and lumbosacral spine segments of nonchondrodystrophic dogs

OBJECTIVE: To determine stiffness and load-displacement curves as a biomechanical response to applied torsion and shear forces in cadaveric canine lumbar and lumbosacral specimens. STUDY DESIGN: Biomechanical study. ANIMALS: Caudal lumbar and lumbosacral functional spine units (FSU) of nonchondrodystrophic large-breed dogs (n=31) with radiographically normal spines. METHODS: FSU from dogs without musculoskeletal disease were tested in torsion in a custom-built spine loading simulator with 6 degrees of freedom, which uses orthogonally mounted electric motors to apply pure axial rotation. For shear tests, specimens were mounted to a custom-made shear-testing device, driven by a servo hydraulic testing machine. Load-displacement curves were recorded for torsion and shear. RESULTS: Left and right torsion stiffness was not different within each FSU level; however, torsional stiffness of L7-S1 was significantly smaller compared with lumbar FSU (L4-5-L6-7). Ventral/dorsal stiffness was significantly different from lateral stiffness within an individual FSU level for L5-6, L6-7, and L7-S1 but not for L4-5. When the data from 4 tested shear directions from the same specimen were pooled, level L5-6 was significantly stiffer than L7-S1. CONCLUSIONS: Increased range of motion of the lumbosacral joint is reflected by an overall decreased shear and rotational stiffness at the lumbosacral FSU. CLINICAL RELEVANCE: Data from dogs with disc degeneration have to be collected, analyzed, and compared with results from our chondrodystrophic large-breed dogs with radiographically normal spines.

Combined cardiac and lung volume reduction surgery

Coronary artery disease is prevalent in patients who have severe emphysema and who are being considered for lung volume reduction surgery (LVRS). Significant valvular heart diseases may also coexist in these patients. Few thoracic surgeons have performed LVRS in patients who have severe cardiac diseases. Conversely, few cardiac surgeons have been willing to undertake major cardiac surgery in patients who have severe emphysema. This report reviews the evidence regarding combined cardiac surgery and LVRS to determine the optimal management strategy for patients who have severe emphysema and who are suitable for LVRS, but who also have coexisting significant cardiac diseases that are operable.

Lions-type compactness and Rubik actions on the Heisenberg group

In this paper we prove a Lions-type compactness embedding result for symmetric unbounded domains of the Heisenberg group. The natural group action on the Heisenberg group TeX is provided by the unitary group U(n) × {1} and its appropriate subgroups, which will be used to construct subspaces with specific symmetry and compactness properties in the Folland-Stein’s horizontal Sobolev space TeX. As an application, we study the multiplicity of solutions for a singular subelliptic problem by exploiting a technique of solving the Rubik-cube applied to subgroups of U(n) × {1}. In our approach we employ concentration compactness, group-theoretical arguments, and variational methods.

Effects of Combined Bevacizumab and Paclitaxel on Tumor Interstitial Fluid Pressure in a Preclinical Breast Cancer Model

Effects of Combined Bevacizumab and Paclitaxel on Tumor Interstitial Fluid Pressure in a Preclinical Breast Cancer Model by Ricardo H. Alvarez Several mechanisms of cell resistance are often accountable for unsuccessful chemotherapy against cancer. Another reason, which has received increased attention, is the inefficient transport of anticancer drugs into tumor tissue. These impaired transports of chemotherapy into the tumor have been attributed to abnormal microvasculature and to pathologically increased tumor hypertension also called: interstitial fluid pressure (IFP). The pathophysiological processes leading to elevated tumor IFP are poorly understood. Here, in a preclinical breast cancer model, it is argued that a condition of raised IFP is a major factor in preventing optimal access of systemically administered chemotherapy agents. In our experimental model, we used a GILM2 human breast cancer in xenografts; mice were treated with different doses of paclitaxel –a widely used antimicrotubular agent, and bevacizumab –monoclonal antibody against vascular endothelial growth factor (VEGF). The proposed research project is designed to test the hypothesis that paclitaxel in combination with bevacizumab decreases the tumor IPF by restoring tumor permeability and increasing chemotherapy delivery. We demonstrated that the combination of paclitaxel and bevacizumab produced greater tumor control than either agent given alone and this combination reduced the IFP, producing an increment of 75% of apoptosis compared with the control arm. In addition, the intra-tumor paclitaxel quantification by liquid chromatography/Mass Spectrometry (LC/MS) demonstrated that lower dose of both agents showed a synergistic effect compared with high dose of treatment, where there is no significantly increase of paclitaxel into the tumor. These preclinical results are likely to have broad implications for the utility of anti-angiogenic therapies alone and in combination with chemotherapeutic agents.

Effect of combined drought and heat stress on heat shock proteins in wheat varieties

Introduction: The re sponse of crop plants ex posed on drought or heat shock is related to de crease in the synthesis of normal proteins, accompanied by increased translation of heat shock proteins (HSPs). Though drought and heat stress have been studied individually, little is known about their combined effect on plants. Methods: The wheat (Triticum aestivum L.) varieties (Katya-tolerant, Sadovo or Mladka-susceptible) were potted in soil. Eight-day-old plants were ex posed to with drawing water for seven days. Heat shock was realized in growth chamber at 40 °C for 6h. A combination of drought and heat shock was per formed by subjecting drought-stressed plants to heat shock treatment. Expression of HSPs in the first leaf of wheat varieties was analyzed by SDS electrophoresis and immunoblotting. Polyclonal antibodies against HSP20, HSP60, HSP110 and mononclonal antibodies against HSP70 were used to distinguish the mentioned HSPs. Results: The leaf relative water content (RWC), which indicated the level of plant dehydration decreased significantly (34 %) under drought stressed conditions The electrolyte leakage of ions (EL), representing the level of the cell membrane stability in creased mark edly (68 %), especially under combination of drought and heat. Maximum EL was ob served in drought susceptible varieties Sadovo and Mladka. Drought and heat shock combination in the wheat plants resulted in the induction of specific HSPs. Conclusions: Our results demonstrate that the response of the wheat plants to a combination of drought and heat stress is different from the response of plants to each of these stresses applied separately. Induction of synergetic effect on HSP expression in case of combination between drought and heat was discussed in the case of two contrasting wheat varieties.

Combined systemic and local morpholino treatment rescues the phenotype of the SMA Delta 7 mouse model

Spinal muscular atrophy (SMA) is a childhood fatal motor neuron disease caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, currently without effective treatment. One possible therapeutic approach is the use of antisense oligonucleotides (ASOs) to redirect the splicing of a paralogous gene, SMN2, to increase the production of functional SMN protein. A range of ASOs with different chemical properties is suitable for these applications, including a morpholino (MO) variant, which has a particularly excellent safety, and efficacy profile. We used a 25- nt MO oligomer sequence against the ISS-N1 region of SMN2 (HSMN2Ex7D(-10-34)) with superior efficacy to previously described sequences also in transgenic SMA Δ7 mice. The combined local and systemic administration of MO (bare or conjugated to octa-guanidine) is necessary to increase full-length SMN expression, leading to robust neuropathological features improvement and survival rescue. Additionally, several snRNA levels that are dysregulated in SMA mice could be restored by MO treatment. These results demonstrate that MO therapy is efficacious and can result in phenotypic rescue. These data provide important insights for the development of therapeutic strategies in SMA patients.

Clinical and radiographic outcomes of a combined resective and regenerative approach in the treatment of peri-implantitis: a prospective case series

AIM To assess the clinical and radiographic outcomes applying a combined resective and regenerative approach in the treatment of peri-implantitis. MATERIALS AND METHODS Subjects with implants diagnosed with peri-implantitis (i.e., pocket probing depth (PPD) ≥5 mm with concomitant bleeding on probing (BoP) and ≥2 mm of marginal bone loss or exposure of ≥1 implant thread) were treated by means of a combined approach including the application of a deproteinized bovine bone mineral and a collagen membrane in the intrabony and implantoplasty in the suprabony component of the peri-implant lesion, respectively. The soft tissues were apically repositioned allowing for a non-submerged healing. Clinical and radiographic parameters were evaluated at baseline and 12 months after treatment. RESULTS Eleven subjects with 11 implants were treated and completed the 12-month follow-up. No implant was lost yielding a 100% survival rate. At baseline, the mean PPD and mean clinical attachment level (CAL) were 8.1 ± 1.8 mm and 9.7 ± 2.5 mm, respectively. After 1 year, a mean PPD of 4.0 ± 1.3 mm and a mean CAL of 6.7 ± 2.5 mm were assessed. The differences between the baseline and the follow-up examinations were statistically significant (P = 0.001). The mucosal recession increased from 1.7 ± 1.5 at baseline to 3.0 ± 1.8 mm at the 12-month follow-up (P = 0.003). The mean% of sites with BoP+ around the selected implants decreased from 19.7 ± 40.1 at baseline to 6.1 ± 24.0 after 12 months (P = 0.032). The radiographic marginal bone level decreased from 8.0 ± 3.7 mm at baseline to 5.2 ± 2.2 mm at the 12-month follow-up (P = 0.000001). The radiographic fill of the intrabony component of the defect amounted to 93.3 ± 13.0%. CONCLUSION Within the limits of this study, a combined regenerative and resective approach for the treatment of peri-implant defects yielded positive outcomes in terms of PPD reduction and radiographic defect fill after 12 months.