3D printing in the design of pharmaceutical dosage forms.

Three-dimensional (3D) printing technologies are manufacturing approaches with widespread use in industry (e.g. automotive, automobile, pharmaceutical industries). With regard to its use in pharmaceutical industry, 3D printing is demonstrating to be of added value attributed to the possibility of printing tailored pharmaceutical products, namely personalized medical devices, such as implants and other dosage forms. However, with the approval of the first 3D-printed drug-product in 2015, a new perspective has arisen, i.e. the use of this technology to produce solid oral dosage forms exhibiting complex drug release profiles and allowing for individual dosing. Technological hurdles and regulatory issues still have to be overcome before this technology can truly find its place in the healthcare sector, where it can certainly contribute to a personalized and patient-centered healthcare. This manuscript offers a comprehensive analysis of the most extensively used methods of 3D printing in the pharmaceutical field, with examples of solid oral dosage forms and other medical devices currently under development or already marketed.

Ecotoxicological effect of zinc pyrithione in the freshwater fish Gambusia holbrooki.

Currently diverse biocidal agents can be used for distinct applications, such as personal hygiene, disinfection, antiparasitic activity, and antifouling effects. Zinc pyrithione is an organometallic biocide, with bactericidal, algicidal and fungicidal activities. It has been recently incorporated in antifouling formulas, such as paints, which prevent the establishment of a biofilm on surfaces exposed to the aquatic environment. It has also been used in cosmetics, such as anti-dandruff shampoos and soaps. Previously reported data has shown the presence of this substance in the aquatic compartment, a factor contributing to the potential exertion of toxic effects, and there is also evidence that photodegradation products of zinc pyrithione were involved in neurotoxic effects, namely by inhibiting cholinesterases in fish species. Additional evidence points to the involvement of zinc pyrithione in alterations of metal homeostasis and oxidative stress, in both aquatic organisms and human cell models. The present work assesses the potential ecotoxicity elicited by zinc pyrithione in the freshwater fish Gambusia holbrooki after an acute (96 h) exposure. The oxidative stress was assessed by the quantification of the activities of specific enzymes from the antioxidant defense system, such as catalase, and glutathione-S-transferases; and the extent of peroxidative damage was quantified by measuring the thiobarbituric acid reactive substances levels. Neurotoxicity was assessed through measurement of acetylcholinesterase activity; and a standardized method for the description and assessment of histological changes in liver and gills of was also used. Zinc pyrithione caused non-specific and reversible tissue alterations, both in liver and gills of exposed organisms. However, histopathological indices were not significantly different from the control group. In terms of oxidative stress biomarkers, none of the tested biomarkers indicated the occurrence of pro-oxidative effects, suggesting that the oxidative pathway is not the major toxicological outcome of exposure to zinc pyrithione.

Acute effects of tetracycline exposure in the freshwater fish Gambusia holbrooki: antioxidant effects, neurotoxicity and histological alterations.

A large body of evidence was compiled in the recent decades showing a noteworthy increase in the detection of pharmaceutical drugs in aquatic ecosystems. Due to its ubiquitous presence, chemical nature, and practical purpose, this type of contaminant can exert toxic effects in nontarget organisms. Exposure to pharmaceutical drugs can result in adaptive alterations, such as changes in tissues, or in key homeostatic mechanisms, such as antioxidant mechanisms, biochemical/physiological pathways, and cellular damage. These alterations can be monitored to determine the impact of these compounds on exposed aquatic organisms. Among pharmaceutical drugs in the environment, antibiotics are particularly important because they include a variety of substances widely used in medical and veterinary practice, livestock production, and aquaculture. This wide use constitutes a decisive factor contributing for their frequent detection in the aquatic environment. Tetracyclines are the individual antibiotic subclass with the second highest frequency of detection in environmental matrices. The characterization of the potential ecotoxicological effects of tetracycline is a much-required task; to attain this objective, the present study assessed the acute toxic effects of tetracycline in the freshwater fish species Gambusia holbrooki by the determination of histological changes in the gills and liver, changes in antioxidant defense [glutathione S-transferase (GST), catalase (CAT), and lipoperoxidative damage] as well as potential neurotoxicity (acetylcholinesterase activity). The obtained results suggest the existence of a cause-and-effect relationship between the exposure to tetracycline and histological alterations (more specifically in gills) and enzymatic activity (particularly the enzyme CAT in liver and GST in gills) indicating that this compound can exert a pro-oxidative activity.

Ecotoxicological effects of salicylic acid in the freshwater fish Salmo trutta fario: antioxidant mechanisms and histological alterations.

The presence of pharmaceutical drugs in aquatic ecosystems has been widely reported during the past years. Salicylic acid (SA) is mainly used in human medicine as an analgesic and antipyretic drug, being also active in preventing platelet aggregation. To study the ecotoxicological effects potentially elicited by SA in freshwater fish, brown trout individuals (Salmo trutta fario) were chronically exposed (28 days) to this drug, in order to evaluate the enzymatic and histological effects, in both gills and liver. A qualitative and semi-qualitative evaluation of the gills and liver was performed, and also a quantitative evaluation of various lamellar structures. Oxidative stress was quantified trough the determination of glutathione S-transferases (GSTs), glutathione reductase (GRed), total and selenium-dependent glutathione peroxidase (GPx) and Catalase (Cat) activities. Lipid peroxidative damage was also assessed by the quantification of thiobarbituric acid reactive substances (TBARS) in the liver. The here-obtained data showed the occurrence of oxidative stress, reflected by an increased activity of GPx and GRed in the liver; additionally, it was possible to observe non-specific histological changes in gills. The global significance of the entire set of results is discussed, giving emphasis to the ecological relevance of the responses.

Removable partial denture education in Portugal following the Bologna Process.

The aim of this study was to investigate the current guidelines used for the undergraduate course subject Removable Partial Denture in Portuguese Dental Schools following the Bologna Process. All Dental Schools were sent a questionnaire, divided into the following areas: (I) organization and syllabus; (II) teaching methods; (III) materials and techniques; Answers about organization and syllabus of course subjects showed the most variability; teaching methods were identical regarding principal textbook and live demonstrations of laboratory/clinical procedures; the same techniques and materials are used in all the schools' dental clinics. The majority of Dental Schools present similar guidelines for removable partial dentures.

Prevalence of osteoporotic fracture risk factors and antiosteoporotic treatments in the Valencia region, Spain. The baseline characteristics of the ESOSVAL cohort.

UNLABELLED: This study provides information on the prevalence of the most important risk factors for osteoporosis and osteoporotic fracture in a large sample of women and men from the Valencia region and also provides the FRAX 10-year major and hip fracture risks for this population, as well as data about the use of diagnostic tests and antiosteoporotic treatments. INTRODUCTION: The purpose of this study was to describe demographic characteristics, osteoporosis risk factors, the 10-year risk of osteoporotic fracture, and the use of densitometry and antiosteoporotic treatments in the Valencia region, Spain. METHODS: A cross-sectional study using the ESOSVAL cohort baseline data was conducted. We analyze the data from 5,310 women and 5,725 men aged 50 and over who attended to 272 collaborating primary care centers in 2009-2010. We collected the demographic, anthropometric, clinical, and pharmacy data from the electronic medical record. RESULTS: The mean age of participants was 64.3 years old for women and 65.6 years old for men. The most frequent fracture risk factors were sedentary life (22.2 %) and previous fracture (15.8 %) in women and low calcium intake (21.4 %) and current smoker (20.9 %) in men. According to FRAX(®), the 10-year risk of presenting a major fracture was 5.5 % for the women and 2.8 % for the men. The 10-year risk for hip fracture was 1.9 and 1.1 % for the women and the men, respectively; 23.8 % of the women and 5.2 % of the men had a densitometry test, 27.7 % of the women and 3.5 % of the men were taking calcium and/or vitamin D supplements, and 28.2 % of the women (22.0 % in the 50-64 age group) and 2.3 % of the men were taking antiosteoporotic drugs. CONCLUSIONS: The prevalence of certain fracture risk factors not included in the FRAX tool (sedentary life, falls, low calcium intake) is high. In young women, their low risks estimated by FRAX contrast with the high figures for densitometry testing and treatment.

Modeling and controller performance assessment for a switched reluctance motor drive based on setpoint relay.

This paper considers the implementation of a current control method for switched reluctance motors (SRMs) and presents a novel approach to the accurate on-line modeling of an SRM drive. A simple autotuning technique for the SRM drives using a PWM controller is considered. Furthermore, conventional PI control and Internal Model Control (IMC) are considered to validate this method and present corresponding robust control analysis for the process. The control structures are comparatively analyzed using standard robustness measures for stability and performance. The proposed PWM controller is simulated and a hardware prototype is then implemented using digital signal processor control to evaluate the method using a 12/8, three-phase SRM. The experimental results of the SRM drive model validates the performance of the current loop.

Core document on erectile dysfunction: key aspects in the care of a patient with erectile dysfunction.

The aim of this Core Document of the Spanish Consensus on Erectile dysfunction (ED) is to offer guidance to the nonspecialist physician in the management of patients with ED. ED is one of the most frequent chronic health problems in men older than 40 y of age and may also act as a sentinel symptom for other important underlying diseases. Its etiology can be classified into organic, psychogenic, or mixed. In most cases, the underlying cause of ED is usually a chronic health problem (such as diabetes, hypertension, atherosclerosis, and so on) or an adverse drug effect. The initial step in the management is to assess erectile function in patients with risk factors for ED. Once ED has been established, a detailed sexual, medical, and social history, including a review of medications used, is the most important aspect of a patient's assessment. Generally, examination should be limited to the cardiovascular, neurological, and urogenital systems. Fasting glucose and blood lipid profile should be performed in every man with ED, and free testosterone levels in men older than 50 y or if hypogonadism is suspected; other diagnostic tests are optional and should be requested on an individualized basis. In many cases, the most likely cause of ED can be identified based on the above information. Therapeutic intervention should be patient-oriented and based on the expectations and wishes of the patient and his partner, who should be included in discussions whenever possible. Basic interventions common to any type of ED include sexual counseling, lifestyle modifications, treatment of associated medical conditions, and switching to alternative drugs with lower risk of ED. In certain cases, an etiologic treatment may be performed (sex therapy, revascularization surgery, and hormonal therapy). Most patients with ED will benefit from symptomatic treatments; first-line therapy may be prescribed by physicians who are not specialists in ED, and includes oral agents such as inhibitors of phosphodiesterase type 5, currently considered the drugs of choice for initial treatment of ED. Intracavernous drugs are the second-line therapy, and surgical treatments, such as implantation of penile prostheses, are reserved for urologists/andrologists who specialize in ED. Referral may be appropriate where indicated by age, clinical findings, or the patient's request.

Oilfield wastewater treatment by combined microfiltration and biological processes.

This work deals with the treatment of offshore oilfield wastewater from the Campos Basin (Rio de Janeiro State, Brazil). After coarse filtration, this high saline wastewater was microfiltrated through mixed cellulose ester (MCE) membranes, resulting in average removals of COD, TOC, O&G and phenols of 35%, 25%, 92% and 35%, respectively. The permeate effluent was fed into a 1-L air-lift reactor containing polystyrene particles of 2mm diameter, used as support material. This reactor was operated for 210 days, at three hydraulic retention times (HRT): 48, 24 and 12h. Even when operated at the lowest HRT (12 h), removal efficiencies of 65% COD, 80% TOC, 65% phenols and 40% ammonium were attained. The final effluent presented COD and TOC values of 230 and 55 mg/L, respectively. Results obtained by gas chromatography analyses and toxicity tests with Artemia salina showed that a significant improvement in the effluent's quality was achieved after treatment by the combined (microfiltration/biological) process.

Pathogenesis of the Segond fracture: anatomic and MR imaging evidence of an iliotibial tract or anterior oblique band avulsion.

PURPOSE: To demonstrate the normal anatomy of the stabilizing structures of the lateral aspect of the knee and to investigate pathogenesis of the Segond fracture, with emphasis on the iliotibial tract (ITT) and anterior oblique band (AOB) of the fibular collateral ligament. MATERIALS AND METHODS: Dissection of the region of the AOB, ITT, and lateral capsular ligament was performed in three cadaveric knees, with placement of gadopentetate dimeglumine-filled tubes along their course and tibial insertions. These knees, in addition to three nondissected knees, were studied with magnetic resonance (MR) imaging by using standard and specialized oblique planes. Specimen sectioning provided anatomic correlation. Retrospective review of radiographs and MR images in 17 patients with acute Segond fractures was performed, and the relationship between the fragment and the demonstrated lateral supporting structures of the knee was noted. RESULTS: Anatomic dissection and MR imaging of the cadaveric knees demonstrated a broad tibial insertion of the ITT, with fibers extending posterior to the Gerdy tubercle. A firm band of tissue, the AOB, extended from the fibular collateral ligament to the midportion of the lateral tibia, the typical site of a Segond fracture. The lateral capsular ligament proved to be a mere thickening of the capsule, inserting at the lateral tibia. Clinical analysis of acute Segond fractures confirmed the frequent attachment of the ITT and AOB to the avulsed fragment. CONCLUSION: Anatomic and clinical findings suggest that fibers of the ITT and AOB are important factors in the pathogenesis of the Segond fracture.

Tele-education: the virtual medical laboratory.

The virtual medical laboratory (VML) was conceived to provide an Internet-accessible resource, offering access for clinicians and scientists to an invaluable data archive at the institute of Laryngology and Otology, London. The Institute is home to the largest collection of temporal bone, laryngeal, skull and sinus sections in Europe. The skull and sinus collections include an extensive section consisting of animal material. These were contributions from zoos around the world. Over the last 50 years, samples have been carefully sectioned and stained by specialized technicians to produce histology slices of most regions of the head and neck. The aim of the project is to create a virtual medical laboratory, which will provide access to archived histological material as well as computerized tomography and magnetic resonance data. Central to this aim is the reconstruction of the internal anatomy of the temporal bone from two-dimensional histology slices, to create three-dimensional views that can be used for anatomical simulation and surgical training in otolaryngology. State-of-the-art three-dimensional reconstruction and rendering technology allows us to develop such a model. Computer-generated simulation could be made available to all hospitals in which otolaryngology is practised, via digital communication networks. We aim to develop core technology in our own specialty that is applicable to other fields of higher education, which have not been exposed to such modern teaching modalities. This has the potential to become an invaluable teaching resource for anatomists, surgeons and other scientists.

[Enteropathogenic agents isolated in persistent diarrhoea]. / Aislamiento de agentes enteropatogenos en la diarrea persistente.

Out of 45558 patients admited in our hospital, from January 1990 to December 1993, the clinical records of 4445 children with diarrhoea (4289 with acute diarrihoea and 156 with persistent diarrhoea) were reviewed. Those with positive bacteriological or parasitological results were taken as sample. Salmonella was the bacteria most frequently isolated in both groups of patients. ECEP and ECEH had a similar distribution while Shigella showed a higher frequency in cases of persistent diarrhoea, for a third pace of incidence. From the parasitological point of view, Cryptosporidium and Giardia had the same behavior.

The analysis of profiles using curvature analysis.

The difficulties of localizing landmarks using standardized lateral skull radiographs has been acknowledged. A method is described for producing an objective way of identifying landmarks on the facial profile leading to a useful segmentation and quantitative description of the contours and features of the face. The method uses scale space filtering techniques and curvature analysis, first employed in pattern recognition. The method has been used on two groups: a random sample of twelve-year-old females and a sample of 10 patients with a normal facial morphology who had cephalometric X-rays taken at 5, 9, 13, 16, and 20 years. It demonstrated that the shape of each of the curves is similar in the first group except in the mouth region. The growth study produced meaningful data on the growth of the face.

Quimio-radioterapia em carcinoma tipo "oat cell" do esôfago / Chemoradiotherapy in oat cell carcinoma of esophagus

É relatado um caso de um paciente com carcinoma indiferenciado de pequenas células originário no esôfago que foi tratado com quimio-radioterapia. Durante a quimioterapia de induçäo com Ciclofosfamida, Epirrubicina e Etoposide houve desaparecimento completo da neoplasia. A radioterapia foi utilizada para consolidaçäo da resposta. Dois anos e meio após diagnóstico o paciente foi a óbito após desenvolvimento de múltiplas metástases.

Sinovite vilonodular pigmentada no tornozelo: relato de um caso / Pigmented villonodular synovitis of the ankle: report of a case

Os autores relatam um caso de sinovite vilonodular pigmentada (SVP) do tornozelo em um paciente do sexo masculino, 19 anos, acometendo o lado esquerdo e invadindo a articulaçäo subastragalina e tíbio-társica. A sintomatologia iniciou-se após prática de esportes. O diagnóstico constituiu-se de achados clínicos e radiológicos, incluindo tomografia computadorizada, sendo confirmado pelos achados histopatológicos. O tratamento realizado constou de sinovectomia ampla, com ressecçäo de toda a massa tumoral, como também do músculo tibial posterior, que estava comprometido, seguido de radioterapia. Por se tratar de um caso raro, visto que a literatura apresenta poucos relatos desta entidade patológica, os autores chamam a atençäo para o melhor diagnóstico e conduta terapêutica

[Malacoplakia of the ascending colon and appendix in children. Report of a case with ultrastructural observations]. / Malacoplaquia do cólon ascendente e apêdice cecal na infância. Relato de caso com observações ultra-estruturais.

Description of a case of malacoplakia involving the ascending colon and appendix in a 11-year-old boy with history of severe diarrhea. The lesions were studied by light and electron microscopy. They were composed of proliferation of histiocytes with the typical cytoplasmic inclusions known as Michaelis-Gutmann bodies. The authors comment the pathogenesis of malakoplakia pointing out its rarity in infancy and in the intestine. They also review the literature and stress the importance of the development of malakoplakia in severe enterocolitis.

Malacoplaquia do colon ascendente e apendice cecal na infancia. Relato de caso com observacoes ultra-estruturais. / Malacoplakia of the ascendent colon and appendix in children. Report of a case with ultrastructural observations

Os autores relatam um caso raro de malacoplaquia do colon ascendente e apendice cecal em um menino de 11 anos de idade, destacando o fato da lesao ser raramente descrita nesta localizacao e faixa etaria. Sao apresentados os aspectos macroscopicos e histologicos da lesao histiocitaria alem da ultra-estrutura destas celulas com os corpusculos patognomonicos de Michaelis-Gutmann. Os autores discutem a patogenia e sugerem que se considere a possibilidade de malacoplaquia no diagnostico diferencial das enterocolites graves

Plasmocitoma extramedular de localizacao em trato gastrintestinal. / Extramedullary plasmacytoma located in gastrointestinal tract. Report of a case

O plasmocitoma extramedular e um tumor relativamente raro, localizando-se perfeitamente nas vias aereas superiores e cavidade oral, aparecendo em muito menor proporcao no tubo digestivo. O diagnostico de certeza e dificil mesmo histologicamente, discutindo-se inclusive a existencia desta patologia como entidade nosologica propria. Neste trabalho, os autores apresentam um caso de plasmocitoma extramedular recidivante, localizado na terceira porcao do duodeno, tratado por derivacao cirurgia do transito gastrintestinal e radioterapia com bom resultado