Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine.

Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway. Finally, we capitalize on the ability of these cell factories to produce derivatives of these bioactive scaffolds to establish a proof-of-principle drug discovery pipeline in which the corynanthe-type MIAs are screened for bioactivity on human drug targets, expressed in yeast. In doing so, we identify antagonistic and agonistic behavior against the human adrenergic G protein-coupled receptors ADRA2A and ADRA2B, and the serotonergic receptor 5HT4b, respectively. This study thus demonstrates a proto-drug discovery pipeline for bioactive plant-inspired small molecules based on one-pot biocatalysis of natural and new-to-nature corynanthe-type MIAs in yeast.

Photobiomodulation as a treatment for dermatitis caused by chemoradiotherapy for squamous cell anal carcinoma: case report and literature review.

In-field dermatitis is a severe and common adverse effect of radiation therapy, that can cause significant pain and treatment interruptions in patients with squamous cell anal carcinoma (SCAC) being treated with radical chemoradiation protocols. There are no established therapies for the treatment of radiation induced dermatitis. Photobiomodulation (PBM) is an effective and low-cost treatment for radiation induced mucositis, but have recently been explored to treat in-field dermatitis. We present a case report of the successful use of PBM for the treatment of dermatitis in the anal area in a patient with SCAC treated with concomitant chemoradiation with curative intent and follow with a literature review of the recent advances and possibilities of the use of PBM as a promising strategy. PBM therapy proved to be efficient in the radiodermatitis treatment, both in relieving the symptoms and controlling dermatitis, in addition to improving the patient's quality of life.

Missed Tillaux Fracture and Syndesmosis Injury in Adult: Arthroscopic Assisted Reduction and Fixation / Fratura de Tillaux não percebida e lesão por sindesmose em adultos: Redução e fixação artroscópica assistida

Abstract Tillaux fractures are fractures of the lateral margin of the distal tibia, usually reported in children between 12 and 14 years old. As intraarticular fractures, they require anatomic reduction and fixation to avoid posttraumatic complications. Since the injury mechanism is external rotation of the foot on the leg, these injuries are commonly associated with other fractures or ligamentous lesions. Currently, arthroscopy is being increasingly used to assist and improve surgical treatment of ankle fractures. The authors describe a 12-month follow-up of a rare case of a missed Tillaux fracture associated with syndesmosis injury in a 76-year-old polytrauma patient, successfully treated by arthroscopically-assisted reduction and internal fixation.

Resumo As fraturas de Tillaux são fraturas da margem lateral da tíbia distal, geralmente relatadas em crianças entre 12 e 14 anos. Como fraturas intra-articulares, requerem redução e fixação anatômica para evitar complicações pós-traumáticas. Como o mecanismo de lesão é a rotação externa do pé na perna, essas lesões são comumente associadas a outras fraturas ou lesões ligamentares. Atualmente, a artroscopia está sendo cada vez mais utilizada para auxiliar e melhorar o tratamento cirúrgico das fraturas do tornozelo. Os autores descrevem um acompanhamento de 12 meses de um caso raro de uma fratura não percebida de Tillaux associada a lesão por sindesmose em um paciente de politrauma com 76 anos de idade, tratado com sucesso por redução e fixação interna assistida por artroscopia.

Mapping Exposure to Multi-Pollutants Using Environmental Biomonitors-A Multi-Exposure Index.

Atmosphere is a major pathway for transport and deposition of pollutants in the environment. In industrial areas, organic compounds are released or formed as by-products, such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F's). Inorganic chemical elements, including lead and arsenic, are also part of the pollutants mixture, and even in low concentrations may potentially be toxic and carcinogenic. However, assessing the spatial pattern of their deposition is difficult due to high spatial and temporal heterogeneity. Lichens have been used as biomonitors of atmospheric deposition, because these organisms encompass greater spatial detail than air monitoring stations and provide an integration of overall pollution. Based upon the ability of lichens to concentrate pollutants such as PCDD/F and chemical elements, the main objectives of this study were to develop a new semi-quantitative multi-pollutant toxicity exposure index (TEQ-like), derived from risk estimates, in an attempt to correlate several atmospheric pollutants to human exposure levels. The actual pollutant concentrations were measured in the environment, from biomonitors (organisms that integrate multi-pollutants), enabling interpolation and mapping of contaminant deposition within the region. Thus, the TEQ-like index provides a spatial representation not from absolute accumulation of the different pollutants, but from the accumulation weighted by their relative risk. The assessment of environmental human exposure to multi-pollutants through atmospheric deposition may be applied to industries to improve mitigation processes or to health stakeholders to target populations for a comprehensive risk assessment, epidemiological studies, and health recommendations.

Three-dimensional vs standard laparoscopy: comparative assessment using a validated program for laparoscopic urologic skills.

OBJECTIVE: To compare the last generation of 3-dimensional imaging (3D) vs standard 2-dimensional imaging (2D) laparoscopy. MATERIALS AND METHODS: A prospective observational study was conducted during the 4th Minimally Invasive Urological Surgical Week Course held in Braga (Portugal) in April 2013. The course participants and faculty were asked to perform standardized tasks in the dry laboratory setting and randomly assigned into 2 study groups; one starting with 3D, the other with 2D laparoscopy. The 5 tasks of the European Training in Basic Laparoscopic Urological Skills were performed. Time to complete each task and errors made were recorded and analyzed. An end-of-study questionnaire was filled by the participants. RESULTS: Ten laparoscopic experts and 23 laparoscopy-naïve residents were included. Overall, a significantly better performance was obtained using 3D in terms of time (1115 seconds, interquartile range [IQR] 596-1469 vs 1299 seconds, IQR 620-1723; P = .027) and number of errors (2, IQR 1-3 vs 3, IQR 2-5.5; P = .001). However, the experts were faster only in the "peg transfer" task when using the 3D, whereas naïves improved their performance in 3 of the 5 tasks. A linear correlation between level of experience and performance was found. Three-dimensional imaging was perceived as "easier" by a third of the laparoscopy-naïve participants (P = .027). CONCLUSION: Three-dimensional imaging seems to facilitate surgical performance of urologic surgeons without laparoscopic background in the dry laboratory setting. The advantage provided by 3D for those with previous laparoscopic experience remains to be demonstrated. Further studies are needed to determine the actual advantage of 3D over standard 2D laparoscopy in the clinical setting.