Offloading memory leaves us vulnerable to memory manipulation.

We often offload memory demands onto external artefacts (e.g., smartphones). While this practice allows us to subvert the limitations of our biological memory, storing memories externally exposes them to manipulation. To examine the impact of such manipulation, we report three experiments, two of which were pre-registered. Individuals performed a memory task where they could offload to-be-recalled information to an external store and on a critical trial, we surreptitiously manipulated the information in that store. Results demonstrated that individuals rarely noticed this manipulation. In addition, when individuals had information inserted into their external memory stores, they often encoded it into their biological memory, thereby leading to the creation of a false memory. The reported results highlight one of the cognitive consequences of offloading our memory to external artefacts.

Associação entre o polimorfismo VKORC1: C. 174-136G>A (rs9934438) e a dose semanal de varfarina em pacientes idosos ­ estudo piloto / Association between VKORC1: C.174-136G> A (rs9934438) polymorphism and weekly warfarin dose in elderly patients - pilot study

A varfarina é um anticoagulante utilizado na prevenção e no tratamento de doenças tromboembólicas, com janela terapêutica estreita e, elevado risco de hemorragias. Nos idosos, a principal indicação para tratamento anticoagulante oral é fibrilação atrial, cuja prevalência aumenta com a idade, atingindo 8% após os 80 anos. O exame utilizado para controle da anticoagulação oral é o tempo de protrombina, através do cálculo da razão normalizada internacional (RNI), visando o ajuste de dose e manutenção da faixa terapêutica (RNI= 2 a 3). Os idosos requerem um monitoramento efetivo devido a fatores inerentes da idade. Embora seja conhecido que os fatores genéticos influenciam na resposta terapêutica à varfarina, na rotina da maioria dos hospitais a farmacogenética ainda não é considerada no ajuste de dose. Visando estabelecer uma conduta terapêutica personalizada, o presente estudo tem como objetivo avaliar a associação entre o polimorfismo rs9934438 do gene VKORC1, que codifica a enzima vitamina K epóxido redutase, e a dose semanal de varfarina necessária para atingir o RNI adequado. Até o momento, foram incluídos 52 pacientes com idade superior a 70 anos, de ambos os sexos e em uso de varfarina. A análise do polimorfismofoi realizada através da PCR em tempo real utilizando os reagentes TaqMan™ Sample-to-SNP™ e o sistema de detecção TaqMan® SNP Genotyping Assay. As análises estatísticas foram realizadas utilizando o pacote SPSS v. 16.0 e nível de significância adotado foi de 5%. Dos 52 pacientes incluídos até o momento, 37 (71%) permaneceram na faixa terapêutica (Time in Therapeutic Range, TTR) em pelo menos 50% do tempo de anticoagulação e, para eles a dose semanal de varfarina variou de 15mg a 62,5mg. Apesar de ser um estudo piloto, a distribuição dos genótipos está em equilíbrio gênico, segundo Hardy-Weinberg (AA=19,2%, AG=34,6%, GG= 46,2%, χ2= 3,34 e p=0,067). Para os idosos com TTR ≥50%, a frequência do alelo A foi significantemente maior entre os pacientes que utilizaram doses menores de varfarina (Exato de Fisher, p=0,005). Adicionalmente, os portadores do genótipo AA necessitaram, em média, de aproximadamente metade da dose para atingir a faixa terapêutica quando comparados aos portadores do genótipo GG, 20,5 versus 36,5 mg/semana, respectivamente (ANOVA, p=0,006/ Pós-teste Bonferroni, p=0,039). Os resultados permitem concluir que portadores de alelo A são mais responsivos ao tratamento com varfarina, sugerindo que o perfil genotípico pode ser de grande valor para o direcionamento da dose terapêutica em idosos. (AU)

Bacteriocin production of the probiotic Lactobacillus acidophilus KS400.

In the last years, the use of probiotics, including Lactobacillus species, has received much attention to prevent and treat vaginal disorders. These species have been described as having the ability to colonize the epithelial surface and produce antimicrobial metabolites that are able to control the remaining vaginal microflora. This study aimed to identify and characterize, for the first time, a bacteriocin natively produced by Lactobacillus acidophilus KS400 (probiotic strain from Gynoflor®-Medinova AG, Switzerland) and its antimicrobial activity against relevant urogenital pathogens. After organic acids and hydrogen peroxide neutralization in the fermented Lactobacillus acidophilus KS400 culture medium, bacteriocin activity was tested against the indicator microorganism Lactobacillus delbrueckii ATCC9649. The fermentation of Lactobacillus acidophilus KS400 for bacteriocin production was carried out in batch mode, and its antimicrobial activity, optical density and pH were monitored. After production and extraction, the bacteriocin molecular weight was estimated by electrophoresis and tested against vaginal pathogenic microorganisms. As described for other bacteriocins, batch fermentation profiles indicated that bacteriocin production occurs during the exponential growth phase of the lactobacilli, and declines during their stationary growth phase. The molecular weight of the bacteriocin is approximately 7.5 kDa. The bacteriocin containing protein extract was shown to inhibit the growth of Gardnerella vaginalis, Streptococcus agalactiae, Pseudomonas aeruginosa and the indicator strain Lactobacillus delbrueckii ATCC9649. We conclude that L. acidophilus KS400 produces bacteriocin with antimicrobial activity against relevant urogenital pathogens.

Outcomes of phacoemulsification in patients with uveitis at a tertiary center in São Paulo, Brazil: a review of cases from 2007 to 2012.

PURPOSE:: To evaluate the outcomes of phacoemulsification with intraocular lens (IOL) implantation in eyes with uveitis. METHODS:: Consecutive patients with uveitis and cataracts who had phacoemulsification and acrylic IOL implantation during 2007-2012 were evaluated for visual outcomes, etiology, and complications. Inflammation was controlled for at least 3 months before surgery, and oral prednisone (0.5 mg/kg/day) was administered to patients with non-infectious uveitis. RESULTS:: This study investigated 45 eyes in 38 patients with a mean age of 52 ± 12.5 years. The most common etiologies among non-infectious causes (n=32; 73.3%) were Vogt-Koyanagi-Harada disease (n=9), Fuchs heterochromic iridocyclitis (n=4), and sympathetic ophthalmia (n=3). Four cases were idiopathic. Among infectious cases (n=13; 28.9%), the most common causes were toxoplasmosis (n=6) and presumed ocular tuberculosis (n=4). An acrylic IOL was implanted in-the-bag in all cases. After 1-year follow-up, an improvement in visual acuity of two or more lines was observed in 38 eyes (84.4%), and 28 eyes (62.2%) achieved a postoperative visual acuity of ≥0.5. Posterior capsule opacification was observed in 10 eyes (22.2%). Persistent postoperative inflammation (of >6 months) was observed in seven eyes (15.5%) and recurrence occurred in four eyes (8.8%). IOL was explanted in one eye. Intraocular hypertension was observed in six eyes (13.3%). CONCLUSIONS:: Phacoemulsification with IOL implantation improved vision in most patients with coexisting cataracts and uveitis. Good preoperative and postoperative control of inflammation plays an important role in achieving favorable visual outcomes. Furthermore, the final visual outcome depends on the posterior segment status.

Outcomes of phacoemulsification in patients with uveitis at a tertiary center in São Paulo, Brazil: a review of cases from 2007 to 2012 / Resultado da facoemulsificação em pacientes com uveíte em um centro terciário em São Paulo, Brasil: revisão de casos de 2007 a 2012

ABSTRACT Purpose: To evaluate the outcomes of phacoemulsification with intraocular lens (IOL) implantation in eyes with uveitis. Methods: Consecutive patients with uveitis and cataracts who had phacoemulsification and acrylic IOL implantation during 2007-2012 were evaluated for visual outcomes, etiology, and complications. Inflammation was controlled for at least 3 months before surgery, and oral prednisone (0.5 mg/kg/day) was administered to patients with non-infectious uveitis. Results: This study investigated 45 eyes in 38 patients with a mean age of 52 ± 12.5 years. The most common etiologies among non-infectious causes (n=32; 73.3%) were Vogt-Koyanagi-Harada disease (n=9), Fuchs heterochromic iridocyclitis (n=4), and sympathetic ophthalmia (n=3). Four cases were idiopathic. Among infectious cases (n=13; 28.9%), the most common causes were toxoplasmosis (n=6) and presumed ocular tuberculosis (n=4). An acrylic IOL was implanted in-the-bag in all cases. After 1-year follow-up, an improvement in visual acuity of two or more lines was observed in 38 eyes (84.4%), and 28 eyes (62.2%) achieved a postoperative visual acuity of ≥0.5. Posterior capsule opacification was observed in 10 eyes (22.2%). Persistent postoperative inflammation (of >6 months) was observed in seven eyes (15.5%) and recurrence occurred in four eyes (8.8%). IOL was explanted in one eye. Intraocular hypertension was observed in six eyes (13.3%). Conclusions: Phacoemulsification with IOL implantation improved vision in most patients with coexisting cataracts and uveitis. Good preoperative and postoperative control of inflammation plays an important role in achieving favorable visual outcomes. Furthermore, the final visual outcome depends on the posterior segment status.

RESUMO Objetivos: Avaliar os resultados da facoemulsificação com implante de lente intraocular em olhos com uveíte. Métodos: Foram incluídos pacientes consecutivos com catarata e uveíte, submetidos a facoemulsificação com implante de lente intraocular acrílica no período de 2007 a 2012, onde avaliou-se resultados visuais, etiologia e complicações. A inflamação estava quiescente por pelo menos três meses e foi usado prednisona oral (0,5 mg/kg/dia) em pacientes com uveíte não infecciosa. Resultados: Este estudo incluiu 45 olhos de 38 pacientes com idade media de 52±12.5 anos. As etiologias mais frequentes, entre as causas não-infecciosas (n=32; 73,3%), foram doença de Vogt-Koyanagi-Harada (n=9), idiopáticas (n=4), iridociclite heterocrômica de Fuchs (n=4) e oftalmia simpática (n=3). Entre as causas infecciosas (n=13; 28,9%), as mais frequentes foram toxoplamose (n=6) e tuberculose ocular presumida (n=4). Uma lente de acrílico foi implantada no saco capsular em todos os casos. Com um ano de seguimento, 38 olhos (84,4%) melhoraram 2 ou mais linhas; 28 olhos (62,2%) atingiram uma acuidade visual pós-operatória de 0,5 ou melhor. Opacidade de cápsula posterior foi observada em 10 olhos (22,2%). Inflamação pós-operatória persistente (>6 meses) foi observada em 7 olhos (15,5%) e a recorrência ocorreu em 4 olhos (8,8%). Houve necessidade de explante da lente em um olho. Hipertensão intraocular foi observada em 6 olhos (13,3%). Conclusões: Facoemulsificação com implante de lente intraocular melhorou a visão na maioria dos pacientes com catarata e uveíte. O controle adequado pré e pós-operatório da inflamação desempenha um papel reconhecidamente importante para obtenção de bons resultados visuais. O resultado visual final depende de alterações prévias do segmento posterior.

Microbiological quality control of non-sterile compounded medicines prepared in a Portuguese hospital centre.

OBJECTIVES: This work aimed to evaluate the quality of non-sterile formulations compounded at Centro Hospitalar Cova da Beira (Covilhã, Portugal) immediately after preparation and up to the defined 'beyond-use date'. METHODS: Microbiological quality control tests were performed in accordance with monograph 5.1.4 of the European Pharmacopoeia 8.0. Samples of compounded products were collected from January to December 2014 after preparation and were analysed immediately and reanalysed after storage under the established conditions, for each preparation. RESULTS: In the test period, 392 preparations were analysed, corresponding to 24 different formulations (8 intermediate preparations, 11 oral solutions/suspensions and 5 topical preparations). All preparations were in accordance with the pharmacopoeia specifications immediately after preparation. However, for the formulations 'prednisolone oral solution (5 mg/mL)' and 'nitroglycerine and cinchocaine ointment (0.25%/0.5%)', the microbial counts of some batches exceeded the defined limits after storage up to the beyond-use date. CONCLUSIONS: These results show that the compounding practices implemented at this pharmacy department are able to ensure the microbiological quality of compounded products. This microbiological quality control methodology also allowed identification of the need to replace formulations shown not to be stable throughout the storage period. On the basis of these results, a monthly routine of microbiological control of a random sample of compounded medicines was established in order to ensure their quality and safety for use.

Estimation of the collective ionizing dose in the Portuguese population for the years 2011 and 2012, due to nuclear medicine exams / Estimación de la dosis colectiva en la población portuguesa de los años 2011 y 2012, debido a los exámenes de medicina nuclear

Objectives. In 2009-2010 a Portuguese consortium was created to implement the methodologies proposed by the Dose Datamed II (DDM2) project, aiming to collect data from diagnostic X-ray and nuclear medicine (NM) procedures, in order to determine the most frequently prescribed exams and the associated ionizing radiation doses for the Portuguese population. The current study is the continuation of this work, although it focuses only on NM exams for the years 2011 and 2012. Material and methods. The annual frequency of each of the 28 selected NM exams and the average administered activity per procedure was obtained by means of a nationwide survey sent to the 35 NM centres in Portugal. Results. The results show a reduction of the number of cardiac exams performed in the last two years compared with 2010, leading to a reduction of the annual average effective dose of Portuguese population due to NM exams from 0.08 mSv ± 0.017 mSv/caput to 0.059 ± 0.011 mSv/caput in 2011 and 0.054 ± 0.011 mSv/caput in 2012. Portuguese total annual average collective effective dose due to medical procedures was estimated to be 625.6 ± 110.9 manSv in 2011 and 565.1 ± 117.3 manSv in 2012, a reduction in comparison with 2010 (840.3 ± 183.8 manSv). Conclusions. The most frequent exams and the ones that contributed the most for total population dose were the cardiac and bone exams, although a decrease observed in 2011 and in 2012 was verified. The authors intend to perform this study periodically to identify trends in the annual Portuguese average effective dose and to help to raise awareness about the potential dose optimization (AU)

Objetivo. En 2009 y 2010 un consorcio portugués ha sido creado para implementar las metodologías propuestas por el proyecto europeo Datamed II (DDM2), con el objetivo de coleccionar datos de procedimientos de radiología de diagnóstico y medicina nuclear (MN) más frecuentes, así como la dosis asociada en la población portuguesa. Este estudio es una continuación del trabajo, que se centrará en los datos de MN para los años de 2011 y 2012. Material y Métodos. La frecuencia anual de cada uno de los 28 exámenes de MN seleccionados y la actividad media administrada por procedimiento se obtuvieron a través de una encuesta enviada a los 35 departamentos de MN en Portugal. Resultados. Los resultados muestran una reducción drástica en el número de procedimientos cardiacos en los últimos dos años, lo que tiene como consecuencia una reducción de la dosis efectiva anual en la población portuguesa derivado de procedimientos de MN de 0,08mSv±0,017 mSv/caput en 2010, a 0,059±0,011 mSv/caput in 2011 y 0,054±0,011 mSv/caput in 2012. La dosis efectiva colectiva media en la población portuguesa es estimada en 625.6 ± 110.9 manSv en 2011, y 565.1 ± 117.3 manSv en 2012. Conclusiones. Los exámenes cardiacos y óseos fueron más frecuentes y los que más contribuyeron para la dosis total de la población, aunque se verificó una disminución en 2011 y en 2012. Los autores de este trabajo pretenden realizar este tipo de estudios periódicamente para identificar tendencias en los diferentes procedimientos de MN y ayudar a aumentar la conciencia de los profesionales de MN sobre este asunto (AU)

Estimation of the collective ionizing dose in the Portuguese population for the years 2011 and 2012, due to nuclear medicine exams.

OBJECTIVES: In 2009-2010 a Portuguese consortium was created to implement the methodologies proposed by the Dose Datamed II (DDM2) project, aiming to collect data from diagnostic X-ray and nuclear medicine (NM) procedures, in order to determine the most frequently prescribed exams and the associated ionizing radiation doses for the Portuguese population. The current study is the continuation of this work, although it focuses only on NM exams for the years 2011 and 2012. MATERIAL AND METHODS: The annual frequency of each of the 28 selected NM exams and the average administered activity per procedure was obtained by means of a nationwide survey sent to the 35 NM centres in Portugal. RESULTS: The results show a reduction of the number of cardiac exams performed in the last two years compared with 2010, leading to a reduction of the annual average effective dose of Portuguese population due to NM exams from 0.08 mSv ± 0.017 mSv/caput to 0.059 ± 0.011 mSv/caput in 2011 and 0.054 ± 0.011 mSv/caput in 2012. Portuguese total annual average collective effective dose due to medical procedures was estimated to be 625.6 ± 110.9 manSv in 2011 and 565.1 ± 117.3 manSv in 2012, a reduction in comparison with 2010 (840.3 ± 183.8 manSv). CONCLUSIONS: The most frequent exams and the ones that contributed the most for total population dose were the cardiac and bone exams, although a decrease observed in 2011 and in 2012 was verified. The authors intend to perform this study periodically to identify trends in the annual Portuguese average effective dose and to help to raise awareness about the potential dose optimization.

La heterogeneidad del flujo sanguíneo en resonancia magnética, biomarcador para clasificar por grados los astrocitomas cerebrales / The heterogeneity of blood flow on magnetic resonance imaging: a biomarker for grading cerebral astrocytomas

Objetivos: Estudiar si los histogramas de los parámetros cuantitativos de perfusión por RM obtenidos a partir de los volúmenes tumoral y peritumoral permiten clasificar in vivo el grado de los astrocitomas. Material y métodos: Se incluyen 61 pacientes diagnosticados histológicamente de astrocitoma grado II, III o IV, estudiados mediante RM de perfusión T2* con contraste intravenoso, seleccionando manualmente los volúmenes tumoral y peritumoral, cuantificándose vóxel a vóxel diferentes parámetros de perfusión: volumen sanguíneo (VS), flujo sanguíneo (FS), tiempo de tránsito medio (TTM), constante de transferencia (Ktrans), coeficiente de lavado, volumen intersticial y volumen vascular. Para cada volumen se obtuvo el histograma correspondiente con su media, desviación típica y curtosis, estas últimas como medidas de heterogeneidad, comparándose las diferencias por parámetro y grado tumoral. También se calcularon la media y desviación del 10% de los valores máximos. Finalmente se realizó un análisis discriminante multiparamétrico para mejorar la clasificación. Resultados: En el volumen tumoral se obtuvieron diferencias estadísticamente significativas entre los 3 grados tumorales para la media y la desviación de VS, FS y Ktrans, tanto para la distribución completa, como para el 10% máximo. En la región peritumoral no se obtuvieron diferencias significativas para ningún parámetro. El análisis discriminante mejoró ligeramente la clasificación. Conclusiones: La cuantificación de parámetros del volumen total de la región tumoral con VS, FS y Ktrans es útil para establecer el grado de los astrocitomas. La heterogeneidad, representada por la desviación típica del FS, es el parámetro con mayor fiabilidad diagnóstica para separar los tumores de bajo y alto grado (AU)

Objectives: To study whether the histograms of quantitative parameters of perfusion in MRI obtained from tumor volume and peritumor volume make it possible to grade astrocytomas in vivo. Material and methods: We included 61 patients with histological diagnoses of grade II, III, or IV astrocytomas who underwent T2*-weighted perfusion MRI after intravenous contrast agent injection. We manually selected the tumor volume and peritumor volume and quantified the following perfusion parameters on a voxel-by-voxel basis: blood volume (BV), blood flow (BF), mean transit time (TTM), transfer constant (Ktrans), washout coefficient, interstitial volume, and vascular volume. For each volume, we obtained the corresponding histogram with its mean, standard deviation, and kurtosis (using the standard deviation and kurtosis as measures of heterogeneity) and we compared the differences in each parameter between different grades of tumor. We also calculated the mean and standard deviation of the highest 10% of values. Finally, we performed a multiparametric discriminant analysis to improve the classification. Results: For tumor volume, we found statistically significant differences among the three grades of tumor for the means and standard deviations of BV, BF, and Ktrans, both for the entire distribution and for the highest 10% of values. For the peritumor volume, we found no significant differences for any parameters. The discriminant analysis improved the classification slightly. Conclusions: The quantification of the volume parameters of the entire region of the tumor with BV, BF, and Ktrans is useful for grading astrocytomas. The heterogeneity represented by the standard deviation of BF is the most reliable diagnostic parameter for distinguishing between low grade and high grade lesions (AU)

End-of-life care in COPD: a survey carried out with Portuguese pulmonologists.

INTRODUCTION: End-of-life (EoL) care is a major component in the management of patients with advanced COPD. Patient-physician communication is essential in this process. AIM: To evaluate the practice of Portuguese Pulmonologists in EoL communication and palliative care in COPD. METHODS: An on-line survey was sent to physicians affiliated to the Portuguese Pneumology Society. RESULTS: We obtained 136 answers from 464 eligible participants (29.3%). About half of the physicians reported that they have rarely introduced EoL discussions with their COPD patients (48.5%). Most had never/rarely suggested decision-making on the use of invasive mechanical ventilation (68.4%). Discussions were described as occurring mostly during/after a major exacerbation (53.7%). Only 37.5% of participants reported treating dyspnoea with opioids frequently/always. Only 9.6% stated that they never/rarely treated anxiety/depression. Most participants perceive the discussion of EoL issues as being difficult/very difficult (89.0%). The reasons most frequently given were feeling that patients were not prepared for this discussion (70.0%), fear of taking away a patient's hope (58.0%) and lack of training (51.0%). CONCLUSION: Patient and medical staff EoL communication in COPD is still not good enough. Training in this area and the creation of formal protocols to initiate EoL have been identified as major factors for improvement.

[The heterogeneity of blood flow on magnetic resonance imaging: a biomarker for grading cerebral astrocytomas]. / La heterogeneidad del flujo sanguíneo en resonancia magnética, biomarcador para clasificar por grados los astrocitomas cerebrales.

OBJECTIVES: To study whether the histograms of quantitative parameters of perfusion in MRI obtained from tumor volume and peritumor volume make it possible to grade astrocytomas in vivo. MATERIAL AND METHODS: We included 61 patients with histological diagnoses of grade II, III, or IV astrocytomas who underwent T2*-weighted perfusion MRI after intravenous contrast agent injection. We manually selected the tumor volume and peritumor volume and quantified the following perfusion parameters on a voxel-by-voxel basis: blood volume (BV), blood flow (BF), mean transit time (TTM), transfer constant (K(trans)), washout coefficient, interstitial volume, and vascular volume. For each volume, we obtained the corresponding histogram with its mean, standard deviation, and kurtosis (using the standard deviation and kurtosis as measures of heterogeneity) and we compared the differences in each parameter between different grades of tumor. We also calculated the mean and standard deviation of the highest 10% of values. Finally, we performed a multiparametric discriminant analysis to improve the classification. RESULTS: For tumor volume, we found statistically significant differences among the three grades of tumor for the means and standard deviations of BV, BF, and K(trans), both for the entire distribution and for the highest 10% of values. For the peritumor volume, we found no significant differences for any parameters. The discriminant analysis improved the classification slightly. CONCLUSIONS: The quantification of the volume parameters of the entire region of the tumor with BV, BF, and K(trans) is useful for grading astrocytomas. The heterogeneity represented by the standard deviation of BF is the most reliable diagnostic parameter for distinguishing between low grade and high grade lesions.

In vitro assessment of gentian violet anti- candida activity.

BACKGROUND/AIM: Recurrent vulvovaginal candidosis (RVVC) needs alternative therapeutic approaches. Gentian violet (GeV) has been traditionally used to treat mucocutaneous candidosis. The aim of the present study was to evaluate the in vitro activity of GeV against Candida spp. and contribute to clarify the mechanism of action, supporting its clinical therapeutic use. METHODS: Seventeen clinical Candida isolates from RVVC and one C. albicans type collection (ATCC 10231) were studied; the antifungal activity of GeV was evaluated according to the CLSI M27-A3 protocol. To elucidate its mechanism of action, cells were stained with propidium iodide and afterwards analyzed by flow cytometer. RESULTS: GeV showed a fungicidal activity against most Candida spp. C. albicans and C. tropicalis were the most susceptible species. Minimal lethal concentrations were similar to minimal inhibitory concentrations for most tested strains. The fungicidal effect was not related to a primary lesion of the cytoplasmic membrane. CONCLUSION: In accordance with our findings, GeV is a valuable potent fungicidal drug to be used topically, isolated or in combination with oral antifungal drugs, particularly in RVVC cases.

Neumotórax de repetición como presentación de sarcoma sinovial pleuropulmonar / Pleuropulmonary synovial sarcoma presenting as recurrent pneumothorax

Los sarcomas sinoviales son neoplasias de tejidos blandos, afectan a adultos jóvenes y de mediana edad, no existen diferencias con respecto a la distribución por sexo. Se localizan en el 90% de los casos en las extremidades. El sarcoma sinovial pleuropulmonar primario (SSPP) es muy poco frecuente, constituye el 0,1% de los tumores pulmonares. Frecuentemente se manifiesta con tos y/o hemoptisis, el neumotórax es una forma poco común de presentación. Son tumores con mal pronóstico y presentan alto riesgo de recidivas locales. Las mejores supervivencias están relacionadas con el tratamiento quirúrgico, siendo la resección completa tumoral el principal factor pronóstico. El tratamiento de elección es quirúrgico, seguido de quimioterapia, radioterapia o ambas. Presentamos el caso clínico de un sarcoma pleuropulmonar primario que clínicamente se manifestó como neumotórax (AU)

Synovial sarcomas are a soft-tissue neoplasms which affects young and middle-aged people, with no difference in distribution between sexes. They are located in the extremities in the 90% of the cases. Pleuropulmonary primary synovial sarcoma SSPP is very unusual, constitutes 0.1% of pulmonary tumors. In most cases the SSPP present themselves with cough and / or hemoptysis whereas pneumothorax is an uncommon form of presentation. Prognosis is usually poor, they present high risk of local recurrence. The survival rate depends on the surgical treatment, being the complete tumor resection the main predicting factor. Surgery is the treatment of choice followed by chemotherapy, radiotherapy or both. We present a case report of a pleuropulmonary synovial sarcoma which presented with pneumothorax (AU)

The anti-Candida activity of Thymbra capitata essential oil: effect upon pre-formed biofilm.

ETHNOPHARMACOLOGICAL RELEVANCE: [corrected] Thymbra capitata essential oil is traditionally considered to exhibit powerful antiseptic properties, thus being used to treat cutaneous infections. The aim of the present study was to evaluate the effect of Thymbra capitata essential oil upon pre-formed biofilm of different Candida strains while comparing it with the activity against planktonic cells. MATERIALS AND METHODS: Fifteen Candida isolates were included, corresponding to clinical and collection type strains. Essential oil was obtained by hydrodistillation and its composition analysed by GC/MS. Activity upon planktonic cells was evaluated according to M27-A3 macromethod. Its effect upon 24h preformed biofilm biomass was determined using the crystal violet procedure and the metabolic activity was studied applying the XTT/menadione technique. RESULTS: Biofilm biomass and metabolic activity of all tested species were reduced up to 50% at MIC values. The effect was more pronounced at double MIC values, achieving >80% reduction, except for Candida albicans that presented a more resistant profile (62%). CONCLUSION: Thymbra capitata essential oil presented an important effect upon Candida biofilms. It is proposed as a valuable antifungal product to be used in an appropriate pharmaceutical formulation for the management of resistant mucocutaneous candidosis.

The relationship between Candida species charge density and chitosan activity evaluated by ion-exchange chromatography.

Chitosan, a natural biopolymer presents antifungal activity that seems to be dependent on the interaction of its cationic amino groups and yeast cell surface. In this work we used ion-exchange chromatography to assess the surface charge density of Candida species and subsequently to relate this with their sensitivity profile to chitosan. The ability of several strains from distinct Candida species to interact with strong anionic and cationic exchangers was tested and the yeasts charge surface was assessed by measuring the zeta potential. Our results showed that all the yeast cells tested presented no interaction with the cationic resin and a species-related pattern of interaction was observed with the anionic resin. Specifically, regarding the Q-Sepharose support, Candida glabrata showed the lower retention affinity, followed by Candida albicans, presenting Candida tropicalis an intermediate profile; Candida parapsilosis and Candida guilliermondii revealed a stronger ionic interaction. The yeasts retention synergy in the anionic resin corroborates with the zeta potential outcomes. The behavior observed fit with sensitivity patterns to chitosan as the most susceptible species to chitosan presented higher affinity to the anionic resin in contrast to the less sensitive ones (C. albicans and C. glabrata). This data confirms and reinforces that chitosan activity is probably mediated by an ionic reaction between its amino free groups and ionic charges at the cell surface.

Sodium Tripolyphosphate: an excipient with intrinsic in vitro anti-Candida activity.

Sodium Tripolyphosphate (STPP) is a food additive that is being used in the development of micro and nanoparticles as it induces ionic interactions with chitosan molecules. Although the ability of STPP to inhibit the growth of several food contaminants has been reported, studies on its activity against clinical isolates are scarce. Candida spp. are common causative agents of mucocutaneous infections including the vulvovaginal tegument and new therapeutic approaches are needed in order to treat resistant and recurrent cases. The aim of this study was to evaluate in vitro both antifungal (anti-Candida spp.) activity, and cytotoxicity, on human dermal fibroblasts, of STPP solutions. STPP showed an inhibitory species-dependent activity against several Candida spp. strains being particularly active on C. glabrata, followed by C. guilliermondii. In vitro, STPP showed a concentration dependent cytotoxicity. Therefore STPP use, in low concentrations, seems to be interesting in the development of drug delivery systems for the treatment of vulvovaginal candidosis.

Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia.

Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n = 142; 122 males and 20 females) or SCZ (n = 143; 95 males and 48 females). We identified >200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1).

Anti-Candida activity of a chitosan hydrogel: mechanism of action and cytotoxicity profile.

Candida spp. are common causative agents of mucocutaneous infections. New therapeutic antifungal drugs are needed to treat chronic disease as these are frequently clinically resistant to azols. Chitosan, among other possible vehicles for active compounds, shows an added value as it appears to have intrinsic antimicrobial properties. The aim of the present study was to evaluate the anti-Candida activity of a medium-molecular-weight chitosan hydrogel (CH), to clarify its possible mechanism of action and to evaluate its cytotoxicity on human fibroblasts. CH antifungal activity was assessed according to CLSI reference M27-A3 protocol; its mechanism of action was investigated by flow cytometry, and its cytotoxicity was studied by MTT assay. CH demonstrated a full inhibition of C. tropicalis, C. krusei, C. guilliermondii and C. parapsilosis growth while impairing C. albicans and C. glabrata viability. Flow cytometry tests showed that CH acts by inducing primary lesion of the cytoplasmic membrane. However, CH showed no cytotoxic effect upon human fibroblasts cells. Resistant strains will require new therapeutic approaches. Chitosan being a good carrier and having itself anti-Candida activity seems to be a promising vehicle to be used for the treatment of mucocutaneous candidosis.

[Lethal pulmonary involvement of neutrophilic dermatosis following erythropoietin therapy]. / Extension pulmonaire d'une dermatose neutrophilique rapidement létale dans les suites d'un traitement par érythropoïétine.

BACKGROUND: Neutrophilic disease is characterized by aseptic visceral infiltration by normal polymorphonuclear leukocytes that can occur in any organ. Association with an underlying systemic disease, particularly haematological malignancy or inflammatory bowel disease, is frequent. This may produce a multisystem disorder, but diagnosis is usually based on skin lesions because of their clinical and histological accessibility. Pulmonary manifestations are the most common extracutaneous symptoms but may be misdiagnosed, as in our case report. CASE REPORT: A 77-year-old woman with IgA myeloma presented with an inflammatory bullous plaque of the leg coupled with fever lasting one week. The clinical and histological examinations were evocative of a neutrophilic dermatosis such as Sweet's syndrome. Significant improvement was initially obtained with systemic corticosteroids and colchicine. The course became complicated by necrotic neutrophilic papulopustular lesions of the upper limbs and pulmonary manifestations, with fever and decline in overall condition occurring the day after administration of erythropoietin. A hypothesis of septic aetiology prompted antibiotic and antifungal therapy, which remained ineffective. The patient died the day after the second erythropoietin injection. DISCUSSION: This case involved late identification of the aseptic neutrophilic aetiology of pulmonary manifestations. Several factors favouring their appearance and the fatal outcome may be suggested: the existence of a myeloma, association with myelodysplastic syndrome and the possible iatrogenic action of erythropoietin. To the best of our knowledge, this is the first reported case of extracutaneous neutrophilic infiltrate occurring in a patient treated with this haematopoietic hormone.