Currently available recording methods limit the study of fast neuronal signaling by forcing a tradeoff between spatial and temporal resolution. Fortunately, advanced optical imaging techniques can be used to overcome this limitation. Specifically, we are developing confocal microscopy schemes that allow multisite recordings of neuron function in live brain tissue with high spatial and temporal resolution. The first scheme that is currently being investigated involves the use of a digital micromirror device (DMD) to implement the light paths necessary for high-speed confocal imaging: addressable point illumination and spatial filtering via addressable point detection. The second scheme involves the use of acousto-optic deflectors (AODs) in the illumination path to increase the excitation intensity, along with the DMD or an addressable CMOS imager as the spatial filter in the detection path. Calculations of the signal-to-noise ratios and operating parameters of the three devices indicate that we will be able to study both calcium concentration and fast membrane potential changes at several sites within the dendritic tree of a neuron.
Neurons are known to possess active computational properties. To investigate these properties, it is desirable to study the electrical and chemical properties not only at a living neuron's cell body, but also at many sites within its dendritic arborization. However, currently available recording techniques force a tradeoff between spatial and temporal resolution. To overcome these limitations, we have developed a confocal microscope that can make multisite optical recordings at an effective frame rate that is sufficient to measure fast neuronal events, such as action potentials, that occur on a timescale of milliseconds. We accomplished this by combining acousto-optic deflectors for addressable point illumination with a digital micromirror device for addressable point detection. After developing a registration algorithm to ensure synchronicity between point illumination and point detection, we used light-scattering test preparations to demonstrate that our system is capable of optical sectioning and therefore capable of imaging in living brain tissue. Furthermore, we have shown that fluorescence changes can be monitored at an effective frame rate of 25 kHz.
We compared the cost-effectiveness of two inpatient diabetes care models: one offered by a specialized diabetes team (SDT) versus a primary service team (PST).We retrospectively evaluated 756 hospital admissions of patients with diabetes to non-critical care units over 6 months. Out of 392 patients who met the eligibility criteria, 262 were matched 1:1 based on the mean of the initial four blood glucose (BG) values after admission. Primary outcomes were 30-day readmission rate and frequency, hospital length of stay (LOS) and estimated hospital cost. Secondary outcomes included glycemic control and BG variability.Diabetes complexity and in-hospital complications were significantly higher among patients treated by SDT versus PST. Thirty-day readmission rate to medical services was lower by 30.5% in the SDT group versus the PST group (P<0.001), while 30-day readmission rate to surgical services was 5% higher in the SDT group versus the PST group (P<0.05), but frequency of 30-day readmissions was lower (1.1 vs 1.6 times, P<0.05). LOS in medical services was not different between the two groups, but it was significantly longer in surgical services in SDT (P<0.05). However, LOS was significantly lower in patients who were seen by SDT during the first 24 hours of admission compared with those who were seen after that (4.7 vs 6.1 days, P<0.001). Compliance to follow-up was higher in the SDT group. These changes were translated into considerable cost saving.Inpatient diabetes management by an SDT significantly reduces 30-day readmission rate to medical services, reduces inpatient diabetes cost, and improves transition of care and adherence to follow-up. SDT consultation during the first 24 hours of admission was associated with a significantly shorter hospital LOS.
Abstract Locoregional recurrence (LRR) or second primary malignancy in the previously treated area continues to be a major cause of treatment failure with significant morbidity and mortality in head and neck cancer. Prognosis of recurrent disease is dismal. To manage LRR is a therapeutic challenge for multidisciplinary head and neck team and more so if it is in a previously irradiated area. Though surgery is the mainstay of treatment but curative resection is feasible in only minority of patients. Systemic therapy alone has no long-term response rate or survival advantage in the management of inoperable recurrences. Full dose reradiation (RERT) with or without concurrent systemic therapy (CRERT) remains the only viable treatment option offering long-term survival in carefully selected patients. RERT is not a new concept but traditionally been avoided because of concern regarding toxicity due to limitations of conventional radiotherapy techniques. Initial studies were restricted to brachytherapy with its limitations. During the past two decades with the revolution in radiation therapy treatment delivery, more precise treatment techniques such as intensity-modulated radiation therapy, image-guided radiation therapy (IGRT), adaptive radiation therapy, stereotactic body radiotherapy, stereotactic radiosurgery, tomotherapy, intensity modulated proton therapy, image-guided brachytherapy in combination with better imaging modalities to define the target with the concept of biological target volume, offer various options for RERT with improved survival and limited toxicity. Pattern of failure even after full dose RERT is mainly infield, inside recurrent gross tumor volume (r GTV); radioresistance and tumor hypoxia may be the probable explanation. Though RERT has been established as a mainstream treatment option, there is a lack of prospective multi-institutional studies and absence of phase III randomized trial except one in adjuvant setting. Optimum treatment is yet to be defined. We have reviewed the literature and attempt has been made to provide guidance to the priorities on which future investigation should focus. There is a need to reevaluate prognostic factors for survival, selection criteria for patients undergoing RERT, measures to reduce the infield recurrence and morbidity, reradiation tolerance of normal tissue in IGRT era, toxicity antagonist and molecular marker as a diagnostic and prognostic tool. There is a need of multi-institutional prospective randomize trial with uniform data reporting.
At present choice of adjuvants for human vaccination reflects a compromise between a requirement for adjuvanticity and an acceptable level of side-effects. To overcome the side effects, encapsulation of antigen in the biodegradable polymeric nanoparticles (NPs) may be a promising approach, which may be developed as adjuvants. Moreover, small size of these nano-formulations may help to project the antigen directly to the antigen presenting cells (APCs) for stimulating cell mediate immunity. The present study was directed towards the evaluation of PLA and PCL based nanoformulations as potential adjuvants by using tetanus toxoid as model antigen. The particles size was observed in the range from 92.9 ± 2.6 to 124.6 ± 3.7 nm having zeta potential of -12.4 ± 1.2 to -3.4 ± 1.5. The loading efficiency of different formulations ranges from 46.3 - 56.8 %. Highest loading of 56.8% and burst release (82 % in 48 days) was observed in PLA-PEG based nanoformulation. In terms of anti-tetanus antibodies (determined by ELISA) titer of > 0.5 IU/ml was observed upto 70 days in all the survived mice. Efficacy of nanoformulations was studied in mice by challenge method over different time intervals wherein tetanus loaded PLA, PLA-PEG and PCL NPs shows maximum efficacy at 28, 56 and 21 days respectively. The study shows that the biodegradable nanoparticle based formulations has no toxicity, comparable efficacy and therefore has a strong potential as vaccine adjuvant and delivery system.
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