Blue biotechnology: enhancement of bioremediation using bacterial biofilms on biodegradable scaffolds

Petroleum hydrocarbons are still the most threatening environmental pollutants. A promising non invasive and low-cost technology for the treatment of contaminated sites is based on bioremediation by biodegrading microorganism endowed with catabolic ability towards oil and derivatives. New methods are needed to enhance and optimize natural biodegradation, such as the immobilization of hydrocarbons degraders in many types of supports. We developed a scaffold-bacteria bioremediation system to clean up oil contamination based on degradable 3D scaffolds. The polycaprolactone component is biodegradable, produced in the melt, i.e. at low cost and without the use of toxic solvents. The biofilm is made of highly performing HC-degrading bacteria such as the marine hydrocarbonoclastic bacteria (HCB) (1) or solid n-alkane degrading Actinobacteria (2, 3). The bacterial biofilm is observed within the whole structure of scaffold using scanning electron microscopy. The bioremediation efficiency of such systems was tested on crude oil by GC-FID analysis and compared whit planktonic cells. The biofilms formation was a promoting factor for biodegradation showing hydrocarbon removal up to 70% and 15% more in respect to the planktonic cells. Increasing availability of the contaminants and a better interaction between the hydrophobic substrate and the bacterial cells resulted in developing the degradation rate. Biofilm-mediated bioremediation is a new tool to be developed for bioremediation of acquatic system

Radiographic evaluation of calcaneal fractures: To measure or not to measure

Objective: The aim of this study was to correlate the functional outcome after treatment for displaced intra-articular calcaneal fracture with plain radiography. Design: The design was a prognostic study of a retrospective cohort with concurrent follow-up. Patients: A total of 33 patients with a unilateral calcaneal fracture and a minimum follow-up of 13 months participated. Patients filled in three disease-specific questionnaires, graded their satisfaction and the indication for an arthrodesis was noted. Standardised radiographs were made of the previously injured side and the normal (control) side. Different angles and distances were measured on these radiographs and compared with values described in the literature. The differences in values in angles and distances between the injured and uninjured (control) foot were correlated with the outcome of the questionnaires, and the indication for an arthrodesis. Results: None of the angles correlated with the disease-specific outcome scores. Of the angles only the tibiotalar angle correlated with the VAS (r=0.35, p=0.045) and only the absolute foot height correlated with the indication for an arthrodesis (odds=0.70, CI=0.50-0.99). Conclusion: In this study the radiographic evaluation correlated poorly with the final outcome. Measurements on plain radiographs seem not to be useful in determining outcome after intra-articular calcaneal fractures

Evidence of destabilization of the human thymidylate synthase (hTS) dimeric structure induced by the interface mutation Q62R

In human cells, thymidylate synthase (TS) provides the only source of 2\u2019-deoxythymidyne-5\u2019-monophosphate (dTMP), which is required for DNA biosynthesis. Because of its pivotal role, human TS (hTS) represents a validated target for anticancer chemotherapy. Nonetheless, the efficacy of drugs blocking the hTS active site has limitations due to the onset of resistance in cancer cells, requiring the identification of new strategies to effectively inhibit this enzyme. Human TS works as an obligate homodimer, making the inter-subunit interface an attractive targetable area. Here, we report the design and investigation of a new hTS variant, in which Gln62, located at the dimer interface, has been replaced by arginine in order to destabilize the enzyme quaternary assembly. The hTS Q62R variant has been characterized though kinetic assay, thermal denaturation analysis and X-ray crystallography. Our results provide evidence that hTS Q62R has a reduced melting temperature. The effective destabilization of the TS quaternary structure is also confirmed by structural analysis, showing that the introduced mutation induces a slight aperture of the hTS dimer. The generation of hTS variants having a more accessible interface area can facilitate the screening of interface-targeting molecules, providing key information for the rational design of innovative hTS interface inhibitors

The fate of Böhler's angle in conservatively-treated displaced intra-articular calcaneal fractures

Purpose: Although the predictive value of Böhler's angle on outcome remains subject of debate, the initial angle at the time of trauma still guides treatment. Changes in Böhler's angle during follow-up are frequently reported following surgical treatment of displaced intra-articular calcaneal fractures (DIACF). The aim of the present study was to determine the changes in Böhler's angle as a measure of secondary fracture displacement following conservative management of DIACF. Methods: Thirty-eight patients with a total of 44 displaced intra-articular calcaneal fractures treated conservatively with a minimum of two lateral radiographs during follow-up were analysed. Böhler's angle at different follow-up times was measured by three observers. The change in angle was compared with the angle at trauma, and influence of trauma mechanism and common calcaneal fracture classifications were determined. Results: The results showed a significant decline over time of the Böhler's angle in conservatively-treated patients of more than 11° on average at a mean follow-up of 29.2 weeks. This decrease was not related to gender, the initial angle, or the Essex-Lopresti or Sanders classification. A statistically significantly higher decrease was detected in high energetic trauma compared with low energetic trauma. Conclusion: The conservative treatment of displaced intra-articular calcaneal fractures is still a viable option, yet a significant secondary displacement in time should be taken into account, as reflected in a decrease of Böhler's angle of 11° up to one year following trauma

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

High Rate of Hypothyroidism in Multidrug-Resistant Tuberculosis Patients Co-Infected with HIV in Mumbai, India.

Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients

RAFT aqueous dispersion polymerization yields poly(ethylene glycol)-based diblock copolymer nano-objects with predictable single phase morphologies

A poly(ethylene glycol) (PEG) macromolecular chain transfer agent (macro-CTA) is prepared in high yield (>95%) with 97% dithiobenzoate chain-end functionality in a three-step synthesis starting from a monohydroxy PEG113 precursor. This PEG113-dithiobenzoate is then used for the reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Polymerizations conducted under optimized conditions at 50 °C led to high conversions as judged by 1H NMR spectroscopy and relatively low diblock copolymer polydispersities (Mw/Mn < 1.25) as judged by GPC. The latter technique also indicated good blocking efficiencies, since there was minimal PEG113 macro-CTA contamination. Systematic variation of the mean degree of polymerization of the core-forming PHPMA block allowed PEG113-PHPMAx diblock copolymer spheres, worms, or vesicles to be prepared at up to 17.5% w/w solids, as judged by dynamic light scattering and transmission electron microscopy studies. Small-angle X-ray scattering (SAXS) analysis revealed that more exotic oligolamellar vesicles were observed at 20% w/w solids when targeting highly asymmetric diblock compositions. Detailed analysis of SAXS curves indicated that the mean number of membranes per oligolamellar vesicle is approximately three. A PEG 113-PHPMAx phase diagram was constructed to enable the reproducible targeting of pure phases, as opposed to mixed morphologies (e.g., spheres plus worms or worms plus vesicles). This new RAFT PISA formulation is expected to be important for the rational and efficient synthesis of a wide range of biocompatible, thermo-responsive PEGylated diblock copolymer nano-objects for various biomedical applications

Text Mining the History of Medicine

Historical text archives constitute a rich and diverse source of information, which is becoming increasingly readily accessible, due to large-scale digitisation efforts. However, it can be difficult for researchers to explore and search such large volumes of data in an efficient manner. Text mining (TM) methods can help, through their ability to recognise various types of semantic information automatically, e.g., instances of concepts (places, medical conditions, drugs, etc.), synonyms/variant forms of concepts, and relationships holding between concepts (which drugs are used to treat which medical conditions, etc.). TM analysis allows search systems to incorporate functionality such as automatic suggestions of synonyms of user-entered query terms, exploration of different concepts mentioned within search results or isolation of documents in which concepts are related in specific ways. However, applying TM methods to historical text can be challenging, according to differences and evolutions in vocabulary, terminology, language structure and style, compared to more modern text. In this article, we present our efforts to overcome the various challenges faced in the semantic analysis of published historical medical text dating back to the mid 19th century. Firstly, we used evidence from diverse historical medical documents from different periods to develop new resources that provide accounts of the multiple, evolving ways in which concepts, their variants and relationships amongst them may be expressed. These resources were employed to support the development of a modular processing pipeline of TM tools for the robust detection of semantic information in historical medical documents with varying characteristics. We applied the pipeline to two large-scale medical document archives covering wide temporal ranges as the basis for the development of a publicly accessible semantically-oriented search system. The novel resources are available for research purposes, while the processing pipeline and its modules may be used and configured within the Argo TM platform

Polymersome-Mediated Delivery of Combination Anticancer Therapy to Head and Neck Cancer Cells: 2D and 3D in Vitro Evaluation

Polymersomes have the potential to encapsulate and deliver chemotherapeutic drugs into tumor cells, reducing off-target toxicity that often compromises anticancer treatment. Here, we assess the ability of the pH-sensitive poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)- poly 2-(diisopropylamino)ethyl methacrylate (PDPA) polymersomes to encapsulate chemotherapeutic agents for effective combinational anticancer therapy. Polymersome uptake and ability to deliver encapsulated drugs into healthy normal oral cells and oral head and neck squamous cell carcinoma (HNSCC) cells was measured in two and three-dimensional culture systems. PMPC-PDPA polymersomes were more rapidly internalized by HNSCC cells compared to normal oral cells. Polymersome cellular uptake was found to be mediated by class B scavenger receptors. We also observed that these receptors are more highly expressed by cancer cells compared to normal oral cells, enabling polymersome-mediated targeting. Doxorubicin and paclitaxel were encapsulated into pH-sensitive PMPC-PDPA polymersomes with high efficiencies either in isolation or as a dual-load for both singular and combinational delivery. In monolayer culture, only a short exposure to drug-loaded polymersomes was required to elicit a strong cytotoxic effect. When delivered to three-dimensional tumor models, PMPC-PDPA polymersomes were able to penetrate deep into the center of the spheroid resulting in extensive cell damage when loaded with both singular and dual-loaded chemotherapeutics. PMPC-PDPA polymersomes offer a novel system for the effective delivery of chemotherapeutics for the treatment of HNSCC. Moreover, the preferential internalization of PMPC polymersomes by exploiting elevated scavenger receptor expression on cancer cells opens up the opportunity to target polymersomes to tumors

Use of biochar as filler for biocomposite blown films: Structure-processing-properties relationships

In this work, biocomposite blown films based on poly(butylene adipate-co-terephthalate) (PBAT) as biopolymeric matrix and biochar (BC) as filler were successfully fabricated. The materials were subjected to a film-blowing process after being compounded in a twin-screw extruder. The preliminary investigations conducted on melt-mixed PBAT/BC composites allowed PBAT/BC 5% and PBAT/BC 10% to be identified as the most appropriate formulations to be processed via film blowing. The blown films exhibited mechanical performances adequate for possible application as film for packaging, agricultural, and compost bags. The addition of BC led to an improvement of the elastic modulus, still maintaining high values of deformation. Water contact angle measurements revealed an increase in the hydrophobic behavior of the biocomposite films compared to PBAT. Additionally, accelerated degradative tests monitored by tensile tests and spectroscopic analysis revealed that the filler induced a photo-oxidative resistance on PBAT by delaying the degradation phenomena