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Abstract Background This study aims to evaluate the impact of the loss of permanent molars on the duration of orthodontic treatment for space closure and without skeletal anchorage. Methods Records at the beginning (T0) and the end (T1) of orthodontic treatment were selected retrospectively. Patients were divided into two groups: loss of molar (n = 19) and control, without loss (n = 24). The impact of loss on treatment time was assessed using multiple linear regression adjusted for the number of absences, bonding failures, age, sex, PAR index at T0 and T1 at p 0.05). Conclusion Loss of the first permanent molar has a negative impact on orthodontic treatment time in cases of space closure. The treatment time is longer when there are more tooth losses and arches involved. Treatment time also increases with greater numbers of missed clinical appointments.

Currently, tissue engineering has been dedicated to the development of 3D structures through bioprinting techniques that aim to obtain personalized, dynamic, and complex hydrogel 3D structures. Among the different materials used for the fabrication of such structures, proteins and polysaccharides are the main biological compounds (biopolymers) selected for the bioink formulation. These biomaterials obtained from natural sources are commonly compatible with tissues and cells (biocompatibility), friendly with biological digestion processes (biodegradability), and provide specific macromolecular structural and mechanical properties (biomimicry). However, the rheological behaviors of these natural-based bioinks constitute the main challenge of the cell-laden printing process (bioprinting). For this reason, bioprinting usually requires chemical modifications and/or inter-macromolecular crosslinking. In this sense, a comprehensive analysis describing these biopolymers (natural proteins and polysaccharides)-based bioinks, their modifications, and their stimuli-responsive nature is performed. This manuscript is organized into three sections: (1) tissue engineering application, (2) crosslinking, and (3) bioprinting techniques, analyzing the current challenges and strengths of biopolymers in bioprinting. In conclusion, all hydrogels try to resemble extracellular matrix properties for bioprinted structures while maintaining good printability and stability during the printing process.

Crude polysaccharides extracted from the Codium sp. and Osmundea sp. macroalgae collected in different seasons (winter, spring and summer) from the Galician and North Portugal coasts were characterised, aiming to support their biomedical application to wound healing. An increase in polysaccharides’ sulphate content was registered from winter to summer, and higher values were obtained for Osmundea sp. In turn, the monosaccharide composition constantly changed with a decrease in glucose in Osmundea sp. from spring to winter. For Codium sp., a higher increase was noticed regarding glucose content in the Galician and Portugal coasts. Galactose was the major monosaccharide in all the samples, remaining stable in all seasons and collection sites. These results corroborate the sulphate content and antioxidant activity, since the Osmundea sp.-derived polysaccharides collected in summer exhibited higher scavenging radical ability. The biocompatibility and wound scratch assays revealed that the Osmundea sp. polysaccharide extracted from the Portugal coast in summer possessed more potential for promoting fibroblast migration. This study on seasonal variations of polysaccharides, sulphate content, monosaccharide composition and, consequently, biological properties provides practical guidance for determining the optimal season for algae harvest to standardise preparations of polysaccharides for the biomedical field.

Este estudo tem por objetivo verificar as relações preditivas entre motivação, identificação organizacional e intenção de rotatividade na carreira de militares. Para a realização do estudo foi considerada a abordagem quantitativa, com coleta de dados através de questionários. Já para a análise dos dados foram feitas análise fatorial, teste de correlação, regressão linear múltipla e Teste t. A amostra final foi composta por 388 militares da área finalística e de apoio de uma instituição das Forças Armadas. Os resultados mostraram que a motivação não mostrou relação significativa com a intenção de rotatividade, tendo sido apenas a identificação organizacional confirmada como variável preditora.

Cancer is considered a major societal challenge for the next decade worldwide. Developing strategies for simultaneous diagnosis and treatment has been considered a promising tool for fighting cancer. For this, the development of nanomaterials incorporating prototypic near-infrared (NIR)-light responsive probes, such as heptamethine cyanines, has been showing very promising results. The heptamethine cyanine-incorporating nanomaterials can be used for a tumor’s visualization and, upon interaction with NIR light, can also produce a photothermal/photodynamic effect with a high spatio-temporal resolution and minimal side effects, leading to an improved therapeutic outcome. In this work, we studied the interaction of 12 NIR-light responsive probes with lipid membrane models by molecular dynamics simulations. We performed a detailed characterization of the location, orientation, and local perturbation effects of these molecules on the lipid bilayer. Based on this information, the probes were divided into two groups, predicting a lower and higher perturbation of the lipid bilayer. From each group, one molecule was selected for testing in a membrane leakage assay. The experimental data validate the hypothesis that molecules with charged substituents, which function as two polar anchors for the aqueous phase while spanning the membrane thickness, are more likely to disturb the membrane by the formation of defects and pores, increasing the membrane leakage. The obtained results are expected to contribute to the selection of the most suitable molecules for the desired application or eventually guiding the design of probe modifications for achieving an optimal interaction with tumor cell membranes.

Abstract Objectives To assess if there is any difference in pain levels between orthodontic treatment with clear aligners or fixed appliances. Materials and methods An electronic search was completed in PubMed, The Cochrane Database, Web of Science, Scopus, Lilacs, Google Scholar, Clinical Trials, and OpenGrey databases without any restrictions until February 2019. All comparative study types contrasting pain levels between clear aligners and fixed appliances were included. The risk of bias (RoB) was assessed using the Newcastle-Ottawa Scale, ROBINS-I-Tool, or ROB 2.0 according to the study design. The level of evidence was assessed through the GRADE tool. Results After removal of duplicates, exclusion by title and abstract, and reading the full text, only seven articles were included. Five were prospective non-randomized clinical trials (CCT), one was a cross-sectional study, and one was a randomized clinical trial (RCT). Two studies presented a high RoB, three a moderate RoB, and two a low RoB (including the RCT). A meta-analysis was not performed because of clinical, statistical, and methodological heterogeneity. Most of the studies found that pain levels in patients treated with Invisalign were lower than those treated with conventional fixed appliances during the first days of treatment. Differences disappeared thereafter. No evidence was identified for other brands of clear aligners. Conclusions Based on a moderate level of certainty, orthodontic patients treated with Invisalign appear to feel lower levels of pain than those treated with fixed appliances during the first few days of treatment. Thereafter (up to 3 months), differences were not noted. Malocclusion complexity level among included studies was mild. Pain is one of many considerations and predictability and technical outcome are more important, mainly considering that the difference does not seem to occur after the first months of the orthodontic treatment.

Helichrysum italicum essential oil (H. italicum EO) is recognized for its anti-inflammatory, antimicrobial and wound-healing properties. The main goal of the present work was the development and characterization of a gel formulation comprising H. italicum EO loaded in chitosan nanoparticles (NPs) for dermatological applications. H. italicum EO-loaded chitosan NPs presented hydrodynamic diameter and PdI of about 300 nm and 0.28, respectively, and a surface charge of +19 mV. The H. italicum EO-loaded chitosan NPs were prepared by means of ionic gelation and then incorporated into a thermal water gel formulation. The organoleptic and physicochemical properties of the developed gel were studied. The gel remained stable under accelerated test conditions, maintaining pH, viscosity and organoleptic properties. In addition, the formulation presented pH, viscosity and spreadability properties suitable for topical application. Finally, the performance of the gel in topical application was evaluated on the skin of volunteers using non-invasive methods, particularly, by means of biometric evaluation. These assays showed that the properties of the developed thermal water-based gel formulation with H. italicum EO-loaded chitosan NPs can improve skin hydration and maintain healthy skin conditions, demonstrating its putative role for distinct dermatological applications.

Animal studies have shown that the nutritional status of parents can predispose the offspring to obesity and obesity-related diseases. Here the authors show that cardiac dysfunction induced by a high-fat diet persists for two generations in Drosophila, and that targeted expression of ATGL/bmm in the offspring, as well as inhibition of H3K27 trimethylation, is cardioprotective.

Bacterial conjunctivitis is a worldwide problem that, if untreated, can lead to severe complications, such as visual impairment and blindness. Topical administration of ciprofloxacin is one of the most common treatments for this infection; however, topical therapeutic delivery to the eye is quite challenging. To tackle this, nanomedicine presents several advantages compared to conventional ophthalmic dosage forms. Herein, the flash nanoprecipitation technique was applied to produce zein and hyaluronic acid nanoparticles loaded with ciprofloxacin (ZeinCPX_HA NPs). ZeinCPX_HA NPs exhibited a hydrodynamic diameter of

A pharmaceutical vehicle based on lyophilized liposomes is proposed for the buccal administration of drugs aimed at systemic delivery through the sublingual mucosa. Liposomes made of egg phosphatidylcholine and cholesterol (7/3 molar ratio) were prepared and lyophilized in the presence of different additive mixtures with mucoadhesive and taste-masking properties. Palatability was assayed on healthy volunteers. The lyophilization cycle was optimized, and the lyophilized product was compressed to obtain round and capsule-shaped tables that were evaluated in healthy volunteers. Tablets were also assayed regarding weight and thickness uniformities, swelling index and liposome release. The results proved that lyophilized liposomes in unidirectional round tablets have palatability, small size, comfortability and buccal retention adequate for sublingual administration. In contact with water fluids, the tablets swelled, and rehydrated liposomes were released at a slower rate than permeation efficiency determined using a biomimetic membrane. Permeability efficiency values of 0.72 ± 0.34 µg/cm2/min and 4.18 ± 0.95 µg/cm2/min were obtained for the liposomes with and without additives, respectively. Altogether, the results point to the vehicle proposed as a liposomal formulation suitable for systemic drug delivery through the sublingual mucosa.

Introdução: Em 2015 foi publicada a lista EU(7)-PIM, que identifica medicamentos potencialmente inapropriados na população idosa e resultou de um consenso de peritos de sete países europeus. Portugal não fez parte deste grupo, pelo que na sua origem não foi adaptada para a realidade portuguesa. Com este trabalho pretendemos elaborar uma lista de medicamentos potencialmente inapropriados adaptada à realidade dos medicamentos comercializados em Portugal, através da operacionalização da lista EU(7)-PIM para a realidade nacional, avaliar a adequabilidade do seu uso na prática clínica. Material e Métodos: Pesquisa, na base de dados Infomed do INFARMED, dos medicamentos incluídos na lista EU(7)-PIM que apresentam autorização de introdução no mercado, e análise de possíveis novos medicamentos para inclusão na lista. A ferramenta adaptada para a realidade Portuguesa foi aplicada a uma amostra de 1089 idosos polimedicados não institucionalizados, utentes de 38 unidades de cuidados de saúde primários da região centro. Resultados: A lista final adaptada para a realidade portuguesa inclui 184 medicamentos potencialmente inapropriados (dos quais 178 são substâncias ativas, cinco são classes de medicamentos e um corresponde ao esquema terapêutico sliding scale usado nas insulinas). Dos 1089 idosos polimedicados, 83,7% tomavam pelo menos um fármaco incluído na lista final de medicamentos potencialmente inapropriados ou pertencente a um dos grupos incluídos na lista e, em média, cada doente tomava 1,74 (IQR 1 – 2). Discussão: Apesar da disponibilidade de fármacos no mercado ser bastante diversa, a lista EU(7)-PIM tem sido utilizada em vários países europeus. Com este estudo operacionalizamos a lista europeia para a realidade portuguesa, facilitando assim a sua aplicação na prática clínica. Conclusão: A lista elaborada apresenta-se como uma ferramenta útil para a identificação de medicamentos potencialmente inapropriados, de fácil utilização na prática clínica e em investigação.

Zein- and chitosan-based nanoparticles have been described as promising carrier systems for food, biomedical and pharmaceutical applications. However, the manufacture of size-controlled zein and chitosan particles is challenging. In this study, an adapted anti-solvent nanoprecipitation method was developed. The effects of the concentration of zein and chitosan and the pH of the collection solution on the properties of the zein–honey–chitosan nanoparticles were investigated. Flash nanoprecipitation was demonstrated as a rapid, scalable, single-step method to achieve the self-assembly of zein–honey–chitosan nanoparticles. The nanoparticles size was tuned by varying certain formulation parameters, including the total concentration and ratio of the polymers. The zein–honey–chitosan nanoparticles’ hydrodynamic diameter was below 200 nm and the particles were stable for 30 days. Vitamin C was used as a hydrophilic model substance and efficiently encapsulated into these nanoparticles. This study opens a promising pathway for one-step producing zein–honey–chitosan nanoparticles by flash nanoprecipitation for hydrophilic compounds’ encapsulation.

Bacterial resistance is a naturally occurring process. However, bacterial antibiotic resistance has emerged as a major public health problem in recent years. The accumulation of antibiotics in the environment, including in wastewaters and drinking water, has contributed to the development of antibiotic resistant bacteria and the dissemination of antibiotic resistance genes (ARGs). Such can be justified by the growing consumption of antibiotics and their inadequate elimination. The conventional water treatments are ineffective in promoting the complete elimination of antibiotics and bacteria, mainly in removing ARGs. Therefore, ARGs can be horizontally transferred to other microorganisms within the aquatic environment, thus promoting the dissemination of antibiotic resistance. In this review, we discuss the efficiency of conventional water treatment processes in removing agents that can spread/stimulate the development of antibiotic resistance and the promising strategies for water remediation, mainly those based on nanotechnology and microalgae. Despite the potential of some of these approaches, the elimination of ARGs remains a challenge that requires further research. Moreover, the development of new processes must avoid the release of new contaminants for the environment, such as the chemicals resulting from nanomaterials synthesis, and consider the utilization of green and eco-friendly alternatives such as biogenic nanomaterials and microalgae-based technologies.

Abstract: During the COVID-19 pandemic the use of cloth masks has increased dramatically due to the shortage of medical masks. However, the efficiency of this material is controversial. We aimed to investigate the efficiency of cloth masks in reducing transmission and contamination by droplets and aerosols for the general population and healthcare workers. Electronic databases were searched without year or language restrictions. Clinical and laboratorial studies were included. The risk of bias (RoB) was assessed using an adapted quality checklist for laboratory-based studies. ROBINS-I tool and Cochrane RoB 2.0 were used to evaluate non-randomized (n-RCT) and randomized clinical trials (RCT), respectively. The quality of the evidence was assessed through GRADE tool. From the eleven studies selected, eight were laboratory-based studies, one non-randomized and one RCT supported by laboratory data. Between the evaluated fabrics only three presented a filtration efficiency > 90%. Hybrid of cotton/chiffon (95%CI 95.2 to 98.8), hybrid of cotton/silk (95%CI 92.2 to 95.8) and cotton quilt (95%CI 94.2 to 97.8). However, cloth masks are not recommended for healthcare workers. A meta-analysis was not feasible due to a high methodological heterogeneity. The overall quality of evidence ranged from very low to moderate. Despite the lower efficiency compared to medical masks, laboratorial results may underestimate the efficiency of cloth masks in real life. Cloth mask efficiency is higher when made of hybrid fabrics (cotton/chiffon, cotton/silk) and cotton quilt, mainly with multiple layers.

Cardoon (Cynara cardunculus L.) is a Mediterranean plant and member of the Asteraceae family that includes three botanical taxa, the wild perennial cardoon (C. cardunculus L. var. sylvestris (Lamk) Fiori), globe artichoke (C. cardunculus L. var. scolymus L. Fiori), and domesticated cardoon (C. cardunculus L. var. altilis DC.). Cardoon has been widely used in the Mediterranean diet and folk medicine since ancient times. Today, cardoon is recognized as a plant with great industrial potential and is considered as a functional food, with important nutritional value, being an interesting source of bioactive compounds, such as phenolics, minerals, inulin, fiber, and sesquiterpene lactones. These bioactive compounds have been vastly described in the literature, exhibiting a wide range of beneficial effects, such as antimicrobial, anti-inflammatory, anticancer, antioxidant, lipid-lowering, cytotoxic, antidiabetic, antihemorrhoidal, cardiotonic, and choleretic activity. In this review, an overview of the cardoon nutritional and phytochemical composition, as well as its biological potential, is provided, highlighting the main therapeutic effects of the different parts of the cardoon plant on metabolic disorders, specifically associated with hepatoprotective, hypolipidemic, and antidiabetic activity.

Staphylococcus aureus is a nosocomial bacterium causing different infectious diseases, ranging from skin and soft-tissue infections to more serious and life-threatening infections such as sepsis, meningitis and endocarditis, which may be exacerbated by antibiotic resistance. Plant products may be seen as an alternative as antibacterial agents, namely, against S. aureus. Thus, the aim of this work was to characterize the chemical composition and evaluate the bioactive properties of the T. zygis essential oil (EO), with a focus on antimicrobial activity against S. aureus. Gas chromatography coupled with mass spectrometry was used to assess the chemical composition of the T. zygis EO, and the antioxidant activity was evaluated using the DPPH method and β-carotene-bleaching assay. The antimicrobial activity against S. aureus strains, the interaction with different antibiotics and the attenuation of this bacterium’s virulence were evaluated. The T. zygis EO showed antioxidant activity acting through two different mechanisms and antibacterial activity against S. aureus, with antibiofilm and antihaemolytic properties. This EO also demonstrated synergistic or additive interactions in combination with ampicillin, ciprofloxacin or vancomycin against S. aureus strains and, in some cases, changed the antibiotic-resistance phenotype from resistant to susceptible. Therefore, the present work demonstrates the good bioactive properties of the EO of T. zygis, mainly the antimicrobial activity against S. aureus, revealing its potential to be used as an antibacterial agent.

Digoxin is a hydrophobic drug used for the treatment of heart failure that possesses a narrow therapeutic index, which raises safety concerns for toxicity. This is of utmost relevance in specific populations, such as the elderly. This study aimed to demonstrate the potential of the sodium alginate films as buccal drug delivery system containing zein nanoparticles incorporated with digoxin to reduce the number of doses, facilitating the administration with a quick onset of action. The film was prepared using the solvent casting method, whereas nanoparticles by the nanoprecipitation method. The nanoparticles incorporated with digoxin (0.25 mg/mL) exhibited a mean size of 87.20 ± 0.88 nm, a polydispersity index of 0.23 ± 0.00, and a zeta potential of 21.23 ± 0.07 mV. Digoxin was successfully encapsulated into zein nanoparticles with an encapsulation efficiency of 91% (±0.00). Films with/without glycerol and with different concentrations of ethanol were produced. The sodium alginate (SA) films with 10% ethanol demonstrated good performance for swelling (maximum of 1474%) and mechanical properties, with a mean tensile strength of 0.40 ± 0.04 MPa and an elongation at break of 27.85% (±0.58), compatible with drug delivery application into the buccal mucosa. The current study suggests that SA films with digoxin-loaded zein nanoparticles can be an effective alternative to the dosage forms available on the market for digoxin administration.

Solvent-free microwave extraction (SFME) is a combination of microwave heating and dry distillation performed at atmospheric pressure without the addition of water or organic solvents that has been proposed as a green method for the extraction of essential oils from aromatic and medicinal herbs. In this work, SFME and the conventional techniques of steam distillation (SD) and hydrodistillation (HD) were compared with respect to the extraction and antioxidant and antimicrobial activities of Thymus mastichina essential oil. The main constituent of essential oils obtained using different methods was 1,8-cineole (eucalyptol). The results showed that the essential oils extracted by means of SFME in 30 min were quantitatively (yield) and qualitatively (aromatic profile) similar to those obtained using conventional HD over 120 min. In addition, SFME generates less waste and less solvent, consumes less energy, and provides a higher yield for a shorter extraction time, which is advantageous for the extraction of the T. mastichina essential oil compared to SD. The antioxidant and antimicrobial activities of the T. mastichina essential oil obtained from either SFME or conventional extraction methods (SD or HD) showed a similar pattern. Large-scale experiments using this SFME procedure showed a potential industrial application.

The lyoprotective effects of mannitol and lactose have been evaluated in the production of sildenafil citrate liposomes. Liposomes were prepared by mixing the components under ultrasonic agitation, followed by a transmembrane pH gradient for remote drug loading. Mannitol and lactose, as compared to sucrose and trehalose, were used as the stabilizing agents, and different freeze-drying cycles were assayed. The remaining moisture and the thermal characteristics of the lyophilized samples were analyzed. Size, entrapment efficiency, biocompatibility, and cell internalization of original and rehydrated liposomes were compared. The type of additive did not affect the biocompatibility or cell internalization, but did influence other liposome attributes, including the thermal characteristics and the remaining moisture of the lyophilized samples. A cut-off of 5% (w/w) remaining moisture was an indicator of primary drying completion—information useful for scaling up and transfer from laboratory to large-scale production. Lactose increased the glass transition temperature to over 70 °C, producing lyoprotective effects similar to those obtained with sucrose. Based on these results, formulations containing liposomes lyophilized with lactose meet the FDA’s requirements and can be used as a biocompatible and biodegradable vehicle for the pulmonary delivery of therapeutic doses of sildenafil citrate.

Thymus mastichina has the appearance of a semishrub and can be found in jungles and rocky lands of the Iberian Peninsula. This work aimed to review and gather available scientific information on the composition and biological properties of T. mastichina. The main constituents of T. mastichina essential oil are 1,8-cineole (or eucalyptol) and linalool, while the extracts are characterized by the presence of flavonoids, phenolic acids, and terpenes. The essential oil and extracts of T. mastichina have demonstrated a wide diversity of biological activities. They showed antibacterial activity against several bacteria such as Escherichia coli, Proteus mirabilis, Salmonella subsp., methicillin-resistant and methicillin-sensitive Staphylococcus aureus, Listeria monocytogenes EGD, Bacillus cereus, and Pseudomonas, among others, and antifungal activity against Candida spp. and Fusarium spp. Additionally, it has antioxidant activity, which has been evaluated through different methods. Furthermore, other activities have also been studied, such as anticancer, antiviral, insecticidal, repellent, anti-Alzheimer, and anti-inflammatory activity. In conclusion, considering the biological activities reported for the essential oil and extracts of T. mastichina, its potential as a preservative agent could be explored to be used in the food, cosmetic, or pharmaceutical industries.

The competitiveness of the agro-industrial sector depends not only on its specific performance but also on the character and degree of the innovation performance, vital to added value development and differentiation in the biobased value-chain. This work intends to show, how through research and development (R&D), collaboration is possible to improve agri-food companies’ competitiveness, helping them to integrate biotechnology and offer innovative products. The method used to support the R&D collaboration model developed involves a diagnosis of biotechnological tools use, for developing appropriate solutions from food safety to food quality, improving health, and achieving new ingredients and/or food products within an agri-food Association partners survey results were integrated into the study of R&D collaboration practice. Results show that the companies (wine culture, fruticulture, and olive culture subsectors) inquired do not develop biotechnology research. They were all micro-business with a low volume of commercial billing, and only 27.3% claimed to have developed research activities in partnership with external research centres, but were not associated with higher education institutions. The barriers to the implementation of biotechnology techniques considered more relevant by respondents were access to capital and specialized human resources, which led to reinforcing the R&D collaboration strategy design.

A rabdomiólise é caracterizada por destruição de tecido muscular esquelético, sendo as suas principais causas o trauma, os tóxicos e os distúrbios hidroeletrolíticos. Entre esses últimos, inclui-se a rabdomiólise induzida por hiponatremia, uma situação rara, que ocorre principalmente em doentes com polidipsia psicogênica. Esta acomete maioritariamente doentes com esquizofrenia, cursando com hiponatremia em quase 25% dos casos. É também nesse contexto que a rabdomiólise secundária a hiponatremia ocorre mais frequentemente. Neste artigo, descreveu-se o caso de um homem de 49 anos, com antecedentes de esquizofrenia, medicado com clozapina, trazido ao serviço de urgência por quadro de coma e convulsões. Foi objetivada hiponatremia hiposmolar grave, com edema cerebral em tomografia computorizada, sendo feito posteriormente o diagnóstico de hiponatremia secundária à polidipsia psicogênica. Foi iniciada terapêutica de correção de hiponatremia e internado em unidade de terapia intensiva. Feita correção de hiponatremia, contudo apresentou analiticamente marcada rabdomiólise, de agravamento crescente, com creatinofosfoquinase de 44.058UI/L no 3º dia de internação. Houve posterior redução progressiva com a terapêutica, sem ocorrência de lesão renal. Este caso alerta para a necessidade de monitorização dos marcadores de rabdomiólise na hiponatremia grave, ilustrando um quadro de rabdomiólise secundária à hiponatremia induzida por polidipsia psicogênica, situação a considerar em doentes sob terapêutica com neurolépticos.

Listeria monocytogenes infections may lead to a severe and potentially lethal disease. This occurs mainly in risk groups (elderly, immunocompromised and newborns). Severe infections in people without any of these factors are rare. Here is reported the case of a 24-year old previously healthy female patient, who presented with altered mental status (Glasgow Coma Scale score of 11, with worsening to 6 within a few hours), fever and meningeal signs. The cerebrospinal fluid analysis was compatible with lymphocytic meningitis. Empirical therapy with Ceftriaxone and Acyclovir had been started. There was clinical worsening, with rhombencephalitis viewed in MRI. Ampicilin was associated and Listeria was actively searched, turning out positive. Despite all measures, the patient died in the Intensive Care Unit. This report of a Listeria monocytogenes infection in a patient without risk factors reinforces the need of an early detection and effective treatment.

In 2002, Spring et al reported a family with an autosomal dominant form of hereditary sensory neuropathy; patients also presented adult onset of gastroesophageal reflux and cough. Since then, no further families have been described. Objective: To study a new Portuguese family with these characteristics. Method: To describe the clinical and neurophysiologic characteristics of one family with features of sensory neuropathy associated with cough and gastroesophageal erflux. Results: Three of five siblings presented a similar history of paroxysmal cough (5th decade). About a decade later they experienced numbness and paraesthesia in the feets and in all cases there was evidence of an axonal sensory neuropathy. A history of gastroesophageal reflux of variable severity and age of onset was also present. Discussion: Molecular genetic studies have demonstrated genetic heterogeneity between the hereditary sensory neuropathy type 1 subtypes. The identification of these families is of major importance because further work is required to identify the underlying genetic defect.

Direct generation of a homogeneous population of skeletal myoblasts from human embryonic stem cells (hESCs) and formation of three-dimensional contractile structures for disease modeling in vitro are current challenges in regenerative medicine. Previous studies reported on the generation of myoblasts from ESC-derived embryoid bodies (EB), but not from undifferentiated ESCs, indicating the requirement for mesodermal transition to promote skeletal myogenesis. Here, we show that selective absence of the SWI/SNF component BAF60C (encoded by SMARCD3) confers on hESCs resistance to MyoD-mediated activation of skeletal myogenesis. Forced expression of BAF60C enables MyoD to directly activate skeletal myogenesis in hESCs by instructing MyoD positioning and allowing chromatin remodeling at target genes. BAF60C/MyoD-expressing hESCs are epigenetically committed myogenic progenitors, which bypass the mesodermal requirement and, when cultured as floating clusters, give rise to contractile three-dimensional myospheres composed of skeletal myotubes. These results identify BAF60C as a key epigenetic determinant of hESC commitment to the myogenic lineage and establish the molecular basis for the generation of hESC-derived myospheres exploitable for “disease in a dish” models of muscular physiology and dysfunction.

Change in the identity of the components of the transcription pre-initiation complex is proposed to control cell type-specific gene expression. Replacement of the canonical TFIID-TBP complex with TRF3/TBP2 was reported to be required for activation of muscle-gene expression. The lack of a developmental phenotype in TBP2 null mice prompted further analysis to determine whether TBP2 deficiency can compromise adult myogenesis. We show here that TBP2 null mice have an intact regeneration potential upon injury and that TBP2 is not expressed in established C2C12 muscle cell or in primary mouse MuSCs. While TFIID subunits and TBP are downregulated during myoblast differentiation, reduced amounts of these proteins form a complex that is detectable on promoters of muscle genes and is essential for their expression. This evidence demonstrates that TBP2 does not replace TBP during muscle differentiation, as previously proposed, with limiting amounts of TFIID-TBP being required to promote muscle-specific gene expression.

OBJETIVOS: A elevação da lipase e amilase séricas são frequentemente encontradas em doentes internados em unidade de terapia intensiva sem que exista doença pancreática prévia, constituindo um desafio diagnóstico e terapêutico. Baseados nesta evidência os autores propuseram-se a determinar a incidência de hiperlipasemia assintomática nos doentes críticos, fatores desencadeantes e evolução clínica destes doentes. MÉTODOS: Estudo retrospectivo dos doentes internados na unidade de terapia intensiva de 1 de janeiro a 31 de dezembro de 2006, excluídas internações por pancreatite aguda, história de patologia pancreática, insuficiência renal ou falta de dados. Pacientes foram distribuídos em dois grupos (com e sem hiperlipasemia) e feita comparação considerando diversas variáveis clínicas, laboratoriais, imagiológicas. Análise estatística: SPSS 13; testes t de Student e qui² (IC 95%), com significância estatística se p38 ºC (pOBJECTIVES: Elevated lipase and amylase are commonly found in patients in intensive care unit without a previously recognized pancreatic illness, constituting a diagnostic and therapeutic challenge. The authors therefore proposed to determine the frequency of asymptomatic high serum lipase in critically ill patients, involved risk factors and outcome. METHODS: Retrospective study of patients admitted in an intensive care unit from January 1 to December 31, 2006, excluding admissions for acute pancreatitis, history of pancreatic disease, renal insufficiency or lacking of data. Patients were divided in two groups (with and without high serum lipase) that were compared for clinical, laboratory and radiological variables. Statistical analysis: SPSS 13; Student's t test and Chi-square test (CI 95%) with statistical significance if p< 0.05). RESULTS: 102 patients were included with high serum lipase was present in 39.2% of patients, mean lipase of 797U/L. Patients with high serum lipase had longer hospital stay (p< 0.001), parenteral nutrition (p< 0.001), ventilator support (p=0.04), fever (p< 0.001), hyperamylasemia (p

Co-culture models are currently bridging the gap between classical cultures and in vivo animal models. Exploring this novel approach unlocks the possibility to mimic the tumor microenvironment in vitro, through the establishment of cancer-stroma synergistic interactions. Notably, these organotypic models offer a perfect platform for the development and pre-clinical evaluation of candidate nanocarriers loaded with anti-tumoral drugs in a high throughput screening mode, with lower costs and absence of ethical issues. However, this evaluation was until now limited to co-culture systems established with precise cell ratios, not addressing the natural cell heterogeneity commonly found in different tumors. Therefore, herein the multifunctional nanocarriers efficiency was characterized in various fibroblast-MCF-7 co-culture systems containing different cell ratios, in order to unravel key design parameters that influence nanocarrier performance and the therapeutic outcome. The successful establishment of the co-culture models was confirmed by the tissue-like distribution of the different cells in culture. Nanoparticles incubation in the various co-culture systems reveals that these nanocarriers possess targeting specificity for cancer cells, indicating their suitability for being used in this illness therapy. Additionally, by using different co-culture ratios, different nanoparticle uptake profiles were obtained. These findings are of crucial importance for the future design and optimization of new drug delivery systems, since their real targeting capacity must be addressed in heterogenous cell populations, such as those found in tumors.

Superficial siderosis is a potentially manageable neurodegenerative disorder, caused by chronic subarachnoid haemorrhage and iron deposition along the central nervous system surfaces. Association with oral anticoagulant therapy is well known, but its definite role as a causative agent is yet to be clarified. Two Caucasian women, both under long-term oral anticoagulation: a 74 year old woman with slowly progressive hearing loss and mild cerebellar ataxia; a 72 year old woman suffering from behavioural changes, rapidly progressive cognitive decline and latter developing paraparesis. Magnetic resonance imaging showed striking hypointensities along the surfaces of cerebellum, brainstem, frontotemporal cortices, spinal cord, and lumbar arachnoid therefore suggesting superficial siderosis. No specific bleeding source was found in any of the patients. Anticoagulation could not be stopped in the first patient due to a mechanic valve and slowly progressive worsening occurred. In contrast, for the second patient anticoagulation withdrawal was feasible and marked motor and cognitive improvement ensued. Superficial siderosis is associated with unvarying progression, mostly when no direct source of bleeding is identified. Nonetheless, we verified striking motor and cognitive improvement after anticoagulants withdrawal in one of the patients. This may reinforce the need to consider such modifiable factor in future patient management.