Search

© 2017 American Chemical Society.The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

Establishing the N-terminal sequence of intact proteins plays a critical role in biochemistry and potential drug development. N-terminal sequence analysis is necessary for quality control of protein biologics for determining sites of signal peptide cleavage events, as a first step in elucidating the sequences of genes from uncommon species an for the characterization of monoclonal antibodies. Automated Edman degradation has been the method of choice for these analyses. However, alternate methods for N-terminal sequence analysis have emerged. The recent PSRG studies have established that Edman sequencing and mass spectrometry based techniques have varied strengths and weaknesses depending on several experimental factors and both play an important role in terminal sequencing. With this complimentary role realized, the 2011 PSRG study attempts to evaluate the sensitivity limits of the various sequencing techniques. The PSRG distributed three sample sets of 3 tubes each, varying by sample format (lyophilized, gel slice or membrane piece). Each set of three samples contains the same recombinant protein with increasing amounts of material. The sequence of this protein is not listed in any database. Participants could request any one, two, or all three sample sets. Including PSRG committee, a total of 38 participants requested 74 sample sets. The participants were asked to determine as many amino acids from both termini by their method of choice, and were encouraged to try multiple methods for sequence elucidation. Study participants were directed to a website to anonymously upload sequences and supporting data. Our analysis focuses on the length and accuracy of the sequence calls reported by the participants, and how that compares with decreasing amounts o protein and the type of sample format analyzed. A comparison of the results obtained by Edman chemistry and by alternative technologies as well as information on the type of instruments and protocols is reported.

Establishing the N-terminal sequence of intact proteins plays a critical role in biochemistry and potential drug development. N-terminal sequence analysis is necessary for quality control of protein biologics, for determining sites of signal peptide cleavage events, as a first step in elucidating the sequences of genes from uncommon species and for the characterization of monoclonal antibodies. Automated Edman degradation has been the method of choice for these analyses. However, alternate methods for N-terminal sequence analysis have emerged. The recent PSRG studies have established that Edman sequencing and mass spectrometry based techniques have varied strengths and weaknesses depending on several experimental factors and both play an important role in terminal sequencing. With this complimentary role realized, the 2011 PSRG study attempts to evaluate the sensitivity limits of the various sequencing techniques. The PSRG distributed three sample sets of 3 tubes each, varying by sample format (lyophilized, gel slice or membrane piece). Each set of three samples contains the same recombinant protein with increasing amounts of material. The sequence of this protein is not listed in any database. Participants could request any one, two, or all three sample sets. Including PSRG committee, a total of 38 participants requested 74 sample sets. The participants were asked to determine as many amino acids from both termini by their method of choice, and were encouraged to try multiple methods for sequence elucidation. Study participants were directed to a website to anonymously upload sequences and supporting data. Our analysis focuses on the length and accuracy of the sequence calls reported by the participants, and how that compares with decreasing amounts of protein and the type of sample format analyzed. A comparison of the results obtained by Edman chemistry and by alternative technologies as well as information on the type of instruments and protocols is reported.

r9-1

Arguably the current era of “ one size fits all ” medical strategies is associated with suboptimal efficacy un necessary toxicity and wasting of resources in healthcare. Why ? The currently dominating paradigm of medical care named “ evidence based medicine ” claims that the ultimate truth for medicine is found in randomized multi center trials and meta analyses in particular those focusing on mortality. The assumption is that statistics describing the average efficacy of a therapy in a large cohort included in a clinical trial will be predictive for the benefit of this therapy in future individual patients and will therefore represent the best therapeutic choice. This will typically include a significant number of individuals at such low risk that harm/benefit and cost/benefit ratios are such that in these few events are avoided many side effects are induced and financial expense is substantial; likewise those patients with highest risk may not get sufficiently intense therapy to circumvent an adverse clinical course. This neglect of the huge variability in genetic and phenotypic setup in mankind (reflected in genomics epigenetics proteomics etc.) which is of major importance for disease course and therapeutic efficacy relegates knowledge about individual variations in the pathophysiology anatomic presentations and temporal course in a given disease ( “ the art of medicine ” ) to second class information. As the limitations of such a “ one size fits all ” approach are increasingly evident (1) we need to progress beyond “ evidence based medicine ” towards a “ knowledge based medicine ” that embraces a broader view on a patient by giving adequate weight to all knowledge about a patient and his/her disease integrating cohort information with molecular information about the individual.

The ABRF amino acid analysis study evaluated the general utility of amino acid analysis (AAA) for identification of proteins after denaturing gel electrophoresis and electroblotting to polyvinylidene difluoride (PVDF) membrane.Thirty-eight participating laboratories analyzed a known control (ovalbumin, 5 microg applied to the gel) and either lysozyme or bovine serum albumin as unknown samples (1-, 5-, and 10-microg amounts applied to the gel). Analyses of the unknowns yielded average compositional errors of approximately 30%, 19%, and 18%, respectively, from the low, intermediate, and higher sample amounts; the ovalbumin control exhibited an approximately 17% average error. Compositional data were submitted to the ExPASy and PROPSEARCH Internet sites for protein identification.Without search parameter adjustments or restrictions, both computer programs provided identification of about 20%, 66%, and 74% of the data from the 1-, 5-, and 10-microg gel samples, respectively. Deleting problematic data (Gly, Met, and Pro) did not always facilitate protein identification. Incorporating control results into the ExPASy search increased identifications 2% to 10%, and restricting search parameters by species, isoelectric pH, and molecular weight increased identifications by more than 80%. Average amounts analyzed for correct identifications were approximately 0.4 microg, 1.8 microg, and 2.9 microg for the 1-, 5-, and 10-microg gel samples, respectively.The results support the efficacy of AAA in the low microgram and nanogram range for the identification of PVDF-immobilized proteins from two-dimensional gels.

High resolution multidimensional image data yield huge datasets. For compression and analysis, 2D approaches are often used, neglecting the information coherence in higher dimensions, which can be exploited for improved compression. We designed a wavelet compression algorithm suited for data of arbitrary dimensions, and assessed its ability for compression of 4D medical images. Basically, separable wavelet transforms are done in each dimension, followed by quantization and standard coding. Results were compared with conventional 2D wavelet. We found that in 4D heart images, this algorithm allowed high compression ratios, preserving diagnostically important image features. For similar image quality, compression ratios using the 3D/4D approaches were typically much higher (2-4 times per added dimension) than with the 2D approach. For low-resolution images created with the requirement to keep predefined key diagnostic information (contractile function of the heart), compression ratios up to 2000 could be achieved. Thus, higher-dimensional wavelet compression is feasible, and by exploitation of data coherence in higher image dimensions allows much higher compression than comparable 2D approaches. The proven applicability of this approach to multidimensional medical imaging has important implications especially for the fields of image storage and transmission and, specifically, for the emerging field of telemedicine.

For patients with myocardial infarct-related cardiogenic shock (CS), urgent percutaneous coronary intervention is the recommended treatment strategy to limit cardiac and systemic ischemia. However, a specific therapeutic intervention is often missing in non-ischemic CS cases. Though drug treatment with inotropes and/or vasopressors may be required to stabilize the patient initially, their ongoing use is associated with excess mortality. Coronary intervention in unstable patients often leads to further hemodynamic compromise either during or shortly after revascularization. Support devices like the intra-aortic balloon pump failed to improve clinical outcomes in infarct-related CS. Currently, more powerful and active hemodynamic support devices unloading the left ventricle such as transvalvular microaxial pumps are available and are being increasingly used. However, as for other devices large randomized trials are not yet available, and device use is based on registry data and expert consensus. In this article, a multidisciplinary group of experienced users of transvalvular microaxial pumps outlines the pathophysiological background on hemodynamic changes in CS, the available mechanical support devices, and current guideline recommendations. Furthermore, different hemodynamic situations in several case-based scenarios are used to illustrate candidate settings and to provide the theoretic and scientific rationale for left-ventricular unloading in these scenarios. Finally, organization of shock networks, monitoring, weaning, and typical complications and their prevention are discussed.

BACKGROUND: Recently, it has been suggested that the type of stent used in primary percutaneous coronary interventions (pPCI) might impact upon the outcomes of patients with acute myocardial infarction (AMI). Indeed, drug-eluting stents (DES) reduce neointimal hyperplasia compared to bare-metal stents (BMS). Moreover, the later generation DES, due to its biocompatible polymer coatings and stent design, allows for greater deliverability, improved endothelial healing and therefore less restenosis and thrombus generation. However, data on the safety and performance of DES in large cohorts of AMI is still limited. AIM: To compare the early outcome of DES vs. BMS in AMI patients. METHODS: This was a prospective, multicentre analysis containing patients from 64 hospitals in Switzerland with AMI undergoing pPCI between 2005 and 2013. The primary endpoint was in-hospital all-cause death, whereas the secondary endpoint included a composite measure of major adverse cardiac and cerebrovascular events (MACCE) of death, reinfarction, and cerebrovascular event. RESULTS: Of 20,464 patients with a primary diagnosis of AMI and enrolled to the AMIS Plus registry, 15,026 were referred for pPCI and 13,442 received stent implantation. 10,094 patients were implanted with DES and 2,260 with BMS. The overall in-hospital mortality was significantly lower in patients with DES compared to those with BMS implantation (2.6% vs. 7.1%,p < 0.001). The overall in-hospital MACCE after DES was similarly lower compared to BMS (3.5% vs. 7.6%, p < 0.001). After adjusting for all confounding covariables, DES remained an independent predictor for lower in-hospital mortality (OR 0.51,95% CI 0.40-0.67, p < 0.001). Since groups differed as regards to baseline characteristics and pharmacological treatment, we performed a propensity score matching (PSM) to limit potential biases. Even after the PSM, DES implantation remained independently associated with a reduced risk of in-hospital mortality (adjusted OR 0.54, 95% CI 0.39-0.76, p < 0.001). CONCLUSIONS: In unselected patients from a nationwide, real-world cohort, we found DES, compared to BMS, was associated with lower in-hospital mortality and MACCE. The identification of optimal treatment strategies of patients with AMI needs further randomised evaluation; however, our findings suggest a potential benefit with DES.

BACKGROUND: Patients who have acute coronary syndromes with or without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy of early clopidogrel administration (300 mg) (

To assess the impact of admission to different hospital types on early and 1-year outcomes in patients with acute coronary syndrome (ACS). Between 1997 and 2009, 31 010 ACS patients from 76 Swiss hospitals were enrolled in the AMIS Plus registry. Large tertiary institutions with continuous (24 hour/7 day) cardiac catheterisation facilities were classified as type A hospitals, and all others as type B. For 1-year outcomes, a subgroup of patients admitted after 2005 were studied. Eleven type A hospitals admitted 15987 (52%) patients and 65 type B hospitals 15023 (48%) patients. Patients admitted into B hospitals were older, more frequently female, diabetic, hypertensive, had more severe comorbidities and more frequent non-ST segment elevation (NSTE)-ACS/unstable angina (UA). STE-ACS patients admitted into B hospitals received more thrombolysis, but less percutaneous coronary intervention (PCI). Crude in-hospital mortality and major adverse cardiac events (MACE) were higher in patients from B hospitals. Crude 1-year mortality of 3747 ACS patients followed up was higher in patients admitted into B hospitals, but no differences were found for MACE. After adjustment for age, risk factors, type of ACS and comorbidities, hospital type was not an independent predictor of in-hospital mortality, in-hospital MACE, 1-year MACE or mortality. Admission indicated a crude outcome in favour of hospitalisation during duty-hours while 1-year outcome could not document a significant effect. ACS patients admitted to smaller regional Swiss hospitals were older, had more severe comorbidities, more NSTE-ACS and received less intensive treatment compared with the patients initially admitted to large tertiary institutions. However, hospital type was not an independent predictor of early and mid-term outcomes in these patients. Furthermore, our data suggest that Swiss hospitals have been functioning as an efficient network for the past 12 years.