Convolutional neural networks for segmentation of FIB-SEM nanotomography data from porous polymer films for controlled drug release

Phase-separated polymer films are commonly used as coatings around pharmaceutical oral dosage forms (tablets or pellets) to facilitate controlled drug release. A typical choice is to use ethyl cellulose and hydroxypropyl cellulose (EC/HPC) polymer blends. When an EC/HPC film is in contact with water, the leaching out of the water-soluble HPC phase produces an EC film with a porous network through which the drug is transported. The drug release can be tailored by controlling the structure of this porous network. Imaging and characterization of such EC porous films facilitates understanding of how to control and tailor film formation and ultimately drug release. Combined focused ion beam and scanning electron microscope (FIB-SEM) tomography is a well-established technique for high-resolution imaging, and suitable for this application. However, for segmenting image data, in this case to correctly identify the porous network, FIB-SEM is a challenging technique to work with. In this work, we implement convolutional neural networks for segmentation of FIB-SEM image data. The data are acquired from three EC porous films where the HPC phases have been leached out. The three data sets have varying porosities in a range of interest for controlled drug release applications. We demonstrate very good agreement with manual segmentations. In particular, we demonstrate an improvement in comparison to previous work on the same data sets that utilized a random forest classifier trained on Gaussian scale-space features. Finally, we facilitate further development of FIB-SEM segmentation methods by making the data and software used open\ua0access

Requirement of a Membrane Potential for the Posttranslational Transfer of Proteins into Mitochondsria

Posttranslational transfer of most precursor proteins into mitochondria is dependent on energization of the mitochondria. Experiments were carried out to determine whether the membrane potential or the intramitochondrial ATP is the immediate energy source. Transfer in vitro of precursors to the ADP/ATP carrier and to ATPase subunit 9 into isolated Neurospora mitochondria was investigated. Under conditions where the level of intramitochondrial ATP was high and the membrane potential was dissipated, import and processing of these precursor proteins did not take place. On the other hand, precursors were taken up and processed when the intramitochondrial ATP level was low, but the membrane potential was not dissipated. We conclude that a membrane potential is involved in the import of those mitochondrial precursor proteins which require energy for intracellular translocatio

Is new drug prescribing in primary care specialist induced?

<p>Abstract</p> <p>Background</p> <p>Medical specialists are often seen as the first prescribers of new drugs. However, the extent to which specialists influence new drug prescribing in primary care is largely unknown.</p> <p>Methods</p> <p>This study estimates the influence of medical specialists on new drug prescribing in primary care shortly after market introduction. The influence of medical specialists on prescribing of five new drugs was measured in a cohort of 103 GPs, working in 59 practices, over the period 1999 until 2003. The influence of medical specialists on new drug prescribing in primary care was assessed using three outcome measures. Firstly, the proportion of patients receiving their first prescription for a new or reference drug from a specialist. Secondly, the proportion of GPs prescribing new drugs before any specialist prescribes to their patients. Thirdly, we compared the time until the GP's first own prescribing between GPs who waited for prescriptions from specialists and those who did not.</p> <p>Results</p> <p>The influence of specialists showed considerable differences among the new drugs studied. The proportion of patients receiving their first prescription from a specialist was greatest for the combination salmeterol/fluticasone (60.2%), and lowest for rofecoxib (23.0%). The proportion of GPs prescribing new drugs before waiting for prescriptions from medical specialists ranged from 21.1% in the case of esomeprazole to 32.9% for rofecoxib. Prescribing new drugs by specialists did not shorten the GP's own time to prescribing.</p> <p>Conclusion</p> <p>This study shows that the influence of medical specialists is clearly visible for all new drugs and often greater than for the existing older drugs, but the rapid uptake of new drugs in primary care does not seem specialist induced in all cases. GPs are responsible for a substantial amount of all early prescriptions for new drugs and for a subpopulation specialist endorsement is not a requisite to initiate in new drug prescribing. This contradicts with the idea that the diffusion of newly marketed drugs always follows a two-step model, with medical specialists as the innovators and GPs as the followers.</p

Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns

BACKGROUND: Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs). These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. METHODS: A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. RESULTS: Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS), risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. CONCLUSIONS: Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some Mexican physicians to change their prescription pattern. It is necessary to reach a consensus, in order to establish and standardize the treatment of schizophrenia, based on the information reported in clinical trials and prevailing economic conditions in Mexico

Effects of Temperature, Salinity and Fish in Structuring the Macroinvertebrate Community in Shallow Lakes: Implications for Effects of Climate Change

Climate warming may lead to changes in the trophic structure and diversity of shallow lakes as a combined effect of increased temperature and salinity and likely increased strength of trophic interactions. We investigated the potential effects of temperature, salinity and fish on the plant-associated macroinvertebrate community by introducing artificial plants in eight comparable shallow brackish lakes located in two climatic regions of contrasting temperature: cold-temperate and Mediterranean. In both regions, lakes covered a salinity gradient from freshwater to oligohaline waters. We undertook day and night-time sampling of macroinvertebrates associated with the artificial plants and fish and free-swimming macroinvertebrate predators within artificial plants and in pelagic areas. Our results showed marked differences in the trophic structure between cold and warm shallow lakes. Plant-associated macroinvertebrates and free-swimming macroinvertebrate predators were more abundant and the communities richer in species in the cold compared to the warm climate, most probably as a result of differences in fish predation pressure. Submerged plants in warm brackish lakes did not seem to counteract the effect of fish predation on macroinvertebrates to the same extent as in temperate freshwater lakes, since small fish were abundant and tended to aggregate within the macrophytes. The richness and abundance of most plant-associated macroinvertebrate taxa decreased with salinity. Despite the lower densities of plant-associated macroinvertebrates in the Mediterranean lakes, periphyton biomass was lower than in cold temperate systems, a fact that was mainly attributed to grazing and disturbance by fish. Our results suggest that, if the current process of warming entails higher chances of shallow lakes becoming warmer and more saline, climatic change may result in a decrease in macroinvertebrate species richness and abundance in shallow lakes

Treatment of Infected Hip Arthroplasty

The clinical outcomes of a consecutive series of deep total joint infections treated with a prosthesis retaining protocol were reviewed. The treatment of deep periprosthetic joint infections is challenging. In recent years, two-stage exchange arthroplasty has emerged as the gold standard for successful elimination of infection. With success rates averaging 82% to 96%, this treatment method has both the highest and most consistent rate of infection eradication. Another alternative in the treatment of the deep periprosthetic infection is the single-stage exchange arthroplasty. Successful eradication of infection after single-stage exchange arthroplasty has been reported to average from 60% to 83% after total hip infections. While both the single and two-stage exchange arthroplasty are viable treatment options, they are associated with negative factors such as they are time consuming, expensive, and may entail a 6- to 12-week period with a minimally functioning extremity after prosthesis removal. This paper reports the general principles of management, the treatment of acute infection occurring in the postoperative period or later, and the treatment of chronic infection by exchange arthroplasty or resection arthroplasty