Freeze-Dried Therapeutic Microbubbles: Stability and Gas Exchange

Microbubbles (MBs) are widely used as contrast enhancement agents for ultrasound imaging and have the potential to enhance therapeutic delivery to diseases such as cancer. Yet, they are only stable in solution for a few hours to days after production, which limits their potential application. Freeze-drying provides long-term storage, ease of transport, and consistency in structure and composition, thereby facilitating their use in clinical settings. Therapeutic microbubbles (thMBs) consisting of MBs with attached therapeutic payload potentially face even greater issues for production, stability, and well-defined drug delivery. The ability to freeze-dry thMBs represents an important step for their translation to the clinic. Here, we show that it is possible to freeze-dry and reconstitute thMBs that consist of lipid-coated MBs with an attached liposomal payload. The thMBs were produced microfluidically, and the liposomes contained either calcein, as a model drug, or gemcitabine. The results show that drug-loaded thMBs can be freeze-dried and stored for at least 6 months. Upon reconstitution, they maintain their structural integrity and drug loading. Furthermore, we show that their in vivo echogenicity is maintained post-freeze-drying. Depending on the gas used in the original bubbles, we also demonstrate that the approach provides a method to exchange the gas core to allow the formulation of thMBs with different gases for combination therapies or improved drug efficacy. Importantly, this work provides an important route for the facile off-site production of thMBs that can be reformulated at the point of care

Effect of MWCNTs on Gastric Emptying in Mice

After making model of gastric functional disorder (FD), part of model mice were injected intravenously (i.v.) with oxide multi-walled carbon nanotubes (oMWCNTs) to investigate effect of carbon nanotubes on gastric emptying. The results showed that NO content in stomach, compared with model group, was decreased significantly and close to normal level post-injection with oMWCNTs (500 and 800 μg/mouse). In contrast to FD or normal groups, the content of acetylcholine (Ach) in stomach was increased obviously in injection group with 500 or 800 μg/mouse of oMWCNTs. The kinetic curve of emptying was fitted to calculate gastric motility factor k; the results showed that the k of injection group was much higher than FD and normal. In other words, the gastric motility of FD mice was enhanced via injection with oMWCNTs. In certain dosage, oMWCNTs could improve gastric emptying and motility

Effectiveness and costs of implementation strategies to reduce acid suppressive drug prescriptions: a systematic review

<p>Abstract</p> <p>Background</p> <p>Evaluation of evidence for the effectiveness of implementation strategies aimed at reducing prescriptions for the use of acid suppressive drugs (ASD).</p> <p>Methods</p> <p>A systematic review of intervention studies with a design according to research quality criteria and outcomes related to the effect of reduction of ASD medication retrieved from Medline, Embase and the Cochrane Library. Outcome measures were the strategy of intervention, quality of methodology and results of treatment to differences of ASD prescriptions and costs.</p> <p>Results</p> <p>The intervention varied from a single passive method to multiple active interactions with GPs. Reports of study quality had shortcomings on subjects of data-analysis. Not all outcomes were calculated but if so rction of prescriptions varied from 8% up to 40% and the cost effectiveness was in some cases negative and in others positive. Few studies demonstrated good effects from the interventions to reduce ASD.</p> <p>Conclusion</p> <p>Poor quality of some studies is limiting the evidence for effective interventions. Also it is difficult to compare cost-effectiveness between studies. However, RCT studies demonstrate that active interventions are required to reduce ASD volume. Larger multi-intervention studies are necessary to evaluate the most successful intervention instruments.</p

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure

Effectiveness of an evidence-based chiropractic continuing education workshop on participant knowledge of evidence-based health care

BACKGROUND: Chiropractors must continue to learn, develop themselves professionally throughout their careers, and become self-directed and lifelong learners. Using an evidence-based approach increases the probability of optimal patient outcomes. But most chiropractors lack knowledge and interest in evidence-based approaches. The purpose of this study was to develop and measure the effectiveness of evidence-based training for chiropractic practitioners in a continuing education setting. METHODS: We developed and evaluated a continuing education workshop on evidence-based principles and methods for chiropractic practitioners. Forty-seven chiropractors participated in the training and testing. The course consisted of 12.5 hours of training in which practitioners learned to develop focused questions, search electronic data bases, critically review articles and apply information from the literature to specific clinical questions. Following the workshop, we assessed the program performance through the use of knowledge testing and anonymous presentation quality surveys. RESULTS: Eighty-five percent of the participants completed all of the test, survey and data collection items. Pretest knowledge scores (15-item test) were low (47%). Post intervention scores (15-item test) improved with an effect size of 2.0. A 59-item knowledge posttest yielded very good results (mean score 88%). The quality of presentation was rated very good, and most participants (90%) would "definitely recommend" or "recommend" the workshop to a colleague. CONCLUSION: The results of the study suggest that the continuing education course was effective in enhancing knowledge in the evidence-based approach and that the presentation was well accepted

Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN

Variation in MSRA Modifies Risk of Neonatal Intestinal Obstruction in Cystic Fibrosis

Meconium ileus (MI), a life-threatening intestinal obstruction due to meconium with abnormal protein content, occurs in approximately 15 percent of neonates with cystic fibrosis (CF). Analysis of twins with CF demonstrates that MI is a highly heritable trait, indicating that genetic modifiers are largely responsible for this complication. Here, we performed regional family-based association analysis of a locus that had previously been linked to MI and found that SNP haplotypes 5′ to and within the MSRA gene were associated with MI (P = 1.99×10−5 to 1.08×10−6; Bonferroni P = 0.057 to 3.1×10−3). The haplotype with the lowest P value showed association with MI in an independent sample of 1,335 unrelated CF patients (OR = 0.72, 95% CI [0.53–0.98], P = 0.04). Intestinal obstruction at the time of weaning was decreased in CF mice with Msra null alleles compared to those with wild-type Msra resulting in significant improvement in survival (P = 1.2×10−4). Similar levels of goblet cell hyperplasia were observed in the ilea of the Cftr−/− and Cftr−/−Msra−/− mice. Modulation of MSRA, an antioxidant shown to preserve the activity of enzymes, may influence proteolysis in the developing intestine of the CF fetus, thereby altering the incidence of obstruction in the newborn period. Identification of MSRA as a modifier of MI provides new insight into the biologic mechanism of neonatal intestinal obstruction caused by loss of CFTR function

Reducing depression in older home care clients: design of a prospective study of a nurse-led interprofessional mental health promotion intervention

Abstract Background Very little research has been conducted in the area of depression among older home care clients using personal support services. These older adults are particularly vulnerable to depression because of decreased cognition, comorbid chronic conditions, functional limitations, lack of social support, and reduced access to health services. To date, research has focused on collaborative, nurse-led depression care programs among older adults in primary care settings. Optimal management of depression among older home care clients is not currently known. The objective of this study is to evaluate the feasibility, acceptability and effectiveness of a 6-month nurse-led, interprofessional mental health promotion intervention aimed at older home care clients with depressive symptoms using personal support services. Methods/Design This one-group pre-test post-test study aims to recruit a total of 250 long-stay (> 60 days) home care clients, 70 years or older, with depressive symptoms who are receiving personal support services through a home care program in Ontario, Canada. The nurse-led intervention is a multi-faceted 6-month program led by a Registered Nurse that involves regular home visits, monthly case conferences, and evidence-based assessment and management of depression using an interprofessional approach. The primary outcome is the change in severity of depressive symptoms from baseline to 6 months using the Centre for Epidemiological Studies in Depression Scale. Secondary outcomes include changes in the prevalence of depressive symptoms and anxiety, health-related quality of life, cognitive function, and the rate and appropriateness of depression treatment from baseline to 12 months. Changes in the costs of use of health services will be assessed from a societal perspective. Descriptive and qualitative data will be collected to examine the feasibility and acceptability of the intervention and identify barriers and facilitators to implementation. Discussion Data collection began in May 2010 and is expected to be completed by July 2012. A collaborative nurse-led strategy may provide a feasible, acceptable and effective means for improving the health of older home care clients by improving the prevention, recognition, and management of depression in this vulnerable population. The challenges involved in designing a practical, transferable and sustainable nurse-led intervention in home care are also discussed. Trial Registration ClinicalTrials.gov: NCT0140792

Supernova remnants: the X-ray perspective

Supernova remnants are beautiful astronomical objects that are also of high scientific interest, because they provide insights into supernova explosion mechanisms, and because they are the likely sources of Galactic cosmic rays. X-ray observations are an important means to study these objects.And in particular the advances made in X-ray imaging spectroscopy over the last two decades has greatly increased our knowledge about supernova remnants. It has made it possible to map the products of fresh nucleosynthesis, and resulted in the identification of regions near shock fronts that emit X-ray synchrotron radiation. In this text all the relevant aspects of X-ray emission from supernova remnants are reviewed and put into the context of supernova explosion properties and the physics and evolution of supernova remnants. The first half of this review has a more tutorial style and discusses the basics of supernova remnant physics and thermal and non-thermal X-ray emission. The second half offers a review of the recent advances.The topics addressed there are core collapse and thermonuclear supernova remnants, SN 1987A, mature supernova remnants, mixed-morphology remnants, including a discussion of the recent finding of overionization in some of them, and finally X-ray synchrotron radiation and its consequences for particle acceleration and magnetic fields.Comment: Published in Astronomy and Astrophysics Reviews. This version has 2 column-layout. 78 pages, 42 figures. This replaced version has some minor language edits and several references have been correcte