Development of affinity polymeric particles for the removal of 4-dimethylaminopyridine (DMAP) from active pharmaceutical ingredient crude streams using a green technology

Funding Information: The financial support projects from PTDC/QEQ-PRS/2757/2012 , and PTDC/EQU-EQU/32473/2017 (by national funds through FCT/MCTES, PIDDAC) through Fundaç ão para a Ciência e a Tecnologia , Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES), Portugal, is acknowledged by the authors. The Associate Laboratory for Green Chemistry for Green Chemistry - Clean Technologies and Processes - LAQV is financed by national funds from FCT/MCTES ( UIDB/50006/2020 and UIDP/50006/2020 ) and co-financed by the ERDF under the PT2020 Partnership Agreement ( POCI-01–0145-FEDER – 007265 ). R.V. would like to thank FCT/MCTES and HOVIONE for her doctoral grant SFRH/BDE/51907/2012 and Individual Scientific Employment Stimulus (CEEC-IND), reference 2020.00377.CEECIND from the FCT/MCTES. N.C. is a PhD candidate from Doctoral Programme in Chemistry at NOVA School of Science and Technology | FCT NOVA. Publisher Copyright: © 2023Polymeric particles with affinity for 4-dimethylaminipyridine (DMAP) were developed by molecular imprinting using supercritical carbon dioxide (scCO2) technology, for cleanup of this potentially genotoxic impurity from crude mixtures of Active Pharmaceutical Ingredients (APIs). DMAP-molecularly imprinted polymer (DMAP-MIP) and the respective control, the non-molecularly imprinted polymer (NIP) were produced by free radical polymerization using methacrylic acid as monomer, ethylene glycol dimethacrylate as crosslinker and AIBN as free-radical initiator in scCO2. The materials were obtained in high yield and were characterized chemically, physically and morphologically. Their extraction efficiency was evaluated by dynamic binding experiments using two solutions: i) a solution containing 104 ppm DMAP solution; ii) model pharmaceutical mixture containing 104 ppm of DMAP and 1018 ppm of Mometasone furoate (API). Particles were able to remove 18.3 µmol DMAP/g polymer from a 104 ppm DMAP solution (i) and 1004.6 µmol DMAP/g API (ii). In addition, high recoveries of both DMAP and API were obtained, above 99%.publishersversionpublishe

Enzyme-inspired dry-powder polymeric catalyst for green and fast pharmaceutical manufacturing processes

Funding Information: The authors thank financial support from Fundação para a Ciência e a Tecnologia , Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES Portugal), through project PTDC/EQU-EQU/32473/2017 , a Principal Investigator contract IF/00915/2014 (T.C.), and a doctoral grant SFRH/BDE/51907/2012 , a partnership from FCT/MCTES and the pharmaceutical company HOVIONE (R.V.). L.B.M. would like to acknowledge for FCT/MCTES funding with reference CEECIND/03810/2017. The NMR spectrometers in LabNMR@Cenimat are part of the National NMR Facility, supported by FCT (ROTEIRO/0031/2013 - PINFRA/22161/2016 ), co-financed by FEDER through COMPETE 2020, POCI, and PORL and FCT through PIDDAC ( POCI-01-0145-FEDER-007688 ; UID/CTM/50025/2020-2023 ). The Associate Laboratory Research Unit for Green Chemistry - Clean Technologies and Processes - LAQV is financed by national funds from FCT/MCTES ( UIDB/QUI/50006/2020 ) and cofunded by the ERDF under the PT2020 Partnership Agreement ( POCI-01-0145-FEDER-007265 ). We also acknowledge Dr. Luz Fernandes, REQUIMTE analytical services, for GC analysis. Publisher Copyright: © 2022Catalysis in pharma manufacturing processes is typically homogeneous, expensive and with hard catalyst recovery/regeneration. Herein an enzyme-inspired dry-powder molecularly imprinted polymeric (MIP) system was designed for fast, selective oxidation of a cholesterol derivative and easy catalyst regeneration. The strategy involved the synthesis of a template-monomer (T:M) complex followed by the crosslinked polymerization in supercritical carbon dioxide (scCO2). A 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)-MIP catalyst is obtained after the template cleavage from the matrix, and the oxidation of the N[sbnd]H groups turns available TEMPO moieties within the MIP. The oxidation of benzyl alcohol, 5α-cholestan-3β-ol and cholic acid was fast, in high yield and with selective oxidation capacity.publishersversionpublishe

Princípios gerais de tratamento da dor músculo-esquelética

The many dimentions of pain should be evaluated and treated. The treatment of pain is based in the elimination ofits causes, and in the use of pharmacological agents, physical medicine, psychotherapy, anesthetic blocks and functional neurosurgical procedures. The methods should be safe, low cost and efficacious. The pharmachological treatment is based in the use of antiinflammatory drugs, opioids, psychotropics, miorrelaxants, anticonvulsants or noradrenergic and serotoninergic modulators. Physical medicine is necessary in almost all cases of muscle skeletal pain patienrts. Trigger points infiltration is an important adjuvant procedure for physical medicine treatment. The coagulation of the recurrent branches of spinal roots by radiofrequency and of the intervertebral disks are efficient in the treatment of low back pain and the implantation of pumps for spinal infusion ofanalgesics is efficient in the treatment of many muscle skeletal pains.A dor apresenta várias dimensões que devem ser avaliadas e normalizadas quando se objetiva seu controle. O tratamento da dor deve ser fundamentado na eliminação dos fatores causais e, quando necessário, no uso de procedimentos analgésicos farmacológicos, medicina física, procedimentos psicocomportamentais, procedimentos neuroanestésicos e ou neurocirúrgicos funcionais. As medidas devem ser simples, seguras, de baixo custo operacional e accessíveis. O tratamento farmacológico consiste no uso de analgésicos antiinflamatórios não hormonais, analgésicos opióides e medicação adjuvantes representada por antidepressivos tricíclicos, neurolépticos, anticonvulsivantes, corticosteróides, moduladores da atividade adrenérgica e serotoninérgica, miorrelaxantes etc. Dentre esses, os agentes analgésicos antiinflamatórios e os opióides associados aos psicotrópicos e miorrelaxantes são os mais empregados no tratamento da dor músculo-esquelética. Procedimentos de medicina física são necessários no tratamento da grande maioria das afecções álgicas músculo-esqueléticas. As infiltrações dos pontos gatilhos são procedimentos bastante úteis no tratamento da síndrome dolorosa miofascial. A descompressão de estruturas neurais, o implante de sistemas para a infusão de medicação analgésica no sistema nervoso central, a lesão por radiofreqüência, dos nervos recorrentes posteriores e a coagulação do disco intervertebral são indicados em casos rebeldes

Character, Incidence, and Predictors of Knee Pain and Activity after Infrapatellar Intramedullary Nailing of an Isolated Tibia Fracture

© Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved. Objective: To study the activity and incidence of knee pain after sustaining an isolated tibia fracture treated with an infrapatellar intramedullary nail at 1 year. Design: Retrospective review of prospective cohort. Setting: Multicenter Academic and Community hospitals. Patients: Four hundred thirty-seven patients with an isolated tibia fracture completed a 12-month assessment on pain and self-reported activity. Intervention: Infrapatellar intramedullary nail. Outcomes: Demographic information, comorbid conditions, injury characteristics, and surgical technique were recorded. Knee pain was defined on a 1-7 scale with 1 being no pain and 7 being a very great deal of pain. Knee pain \u3e4 was considered clinically significant. Patients reported if they were able, able with difficulty, or unable to perform the following activities: kneel, run, climb stairs, and walk prolonged. Variables were tested in multilevel multivariable regression analyses. Results: In knee pain, 11% of patients reported a good deal to a very great deal of pain (\u3e4), and 52% of patients reported no or very little pain at 12 months. In activity at 12 months, 26% and 29% of patients were unable to kneel or run, respectively, and 31% and 35% of patients, respectively, stated they were able with difficulty or unable to use stairs or walk. Conclusions: Clinically significant knee pain (\u3e4/7) was present in 11% of patients 1 year after a tibia fracture. Of note, 31%-71% of patients had difficulty performing or were unable to perform routine daily activities of kneeling, running, and stair climbing, or walking prolonged distances

Effects of Brazil's political crisis on the science needed for biodiversity conservation

The effects of Brazil’s political crisis on science funding necessary for biodiversity conservation are likely to be global. Brazil is not only the world’s most biodiverse nation, it is responsible for the greater part of the Amazon forest, which regulates the climate and provides rain to much of southern South America. Brazil was a world leader in satellite monitoring of land-use change, in-situ biodiversity monitoring, reduction in tropical-forest deforestation, protection of indigenous lands, and a model for other developing nations. Coordinated public responses will be necessary to prevent special-interest groups from using the political crisis to weaken science funding, environmental legislation and law enforcement. Keywords: Brazil, biodiversity, climate change, governance, fundin

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe