Synergistic activity of gold nanoparticles with amphotericin B on persister cells of Candida tropicalis biofilms.

AIM: The antifungal activity was studied on sessile and persister cells (PCs) of Candida tropicalis biofilms of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB). MATERIALS/METHODS: The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy. RESULTS/CONCLUSIONS: After the combination of both AuNPs and AmB the biofilm biomass was reduced, with significant differences in architecture being observed with a reduced biofilm matrix. In addition, the CTAB-AuNPs-AmB combination significantly reduced PCs. Understanding how these AuNPs aid in the fight against biofilms and the development of new approaches to eradicate PCs has relevance for chronic infection treatment.

Lexicon for classifying ear-canal shapes.

The ear canal is usually described as an S-shaped funnel. In attempting to classify ear-canal shapes obtained from point clouds digitized from molds of 300 ears, the problem of designing criteria for distinguishing and organizing the canal shapes arose. In this work, we extracted features inspired by the S-shape characteristic (critical point, maximum, minimum, twist, writhe, translation, rotation) and, through them, introduced 14 types of ear-canal shapes. This classification allowed comparison of ears within a type and of ears between different types. It expanded our range of descriptors of canal shapes and unlocked perspectives for applications.

Estudio sobre el empleo de sistemas personalizados de reacondicionamiento para mejorar los valores de tensión arterial en pacientes hipertensos / Study on the use of multi-compartment compliance aids to improve blood pressure values in hypertensive patients

Objetivos: analizar la mejora de la adherencia en pacientes no adherentes con HTA no controlada, polimedicados y mayores de 55 años tras el empleo de sistemas personalizados de reacondicionamiento (SPD). Diseño: estudio longitudinal (6 meses). Se analizaron los niveles de adherencia al tratamiento mediante una adaptación del test de Morisky-Green, contaje de medicación devuelta (en el grupo SPD) y valores de presión arterial. Emplazamiento: estudio multicéntrico en 35 farmacias comunitarias de toda España. Participantes: 195 participantes (88 grupo SPD y 107 grupo control) mayores de 55 años, polimedicados, no adherentes a la medicación, con HTA no controlada y que empleaban receta médica electrónica. Intervenciones: el grupo SPD recibió su medicación en SPD mientras el grupo control recibía su medicación de manera rutinaria. Mediciones principales: a ambos grupos se les realizaron tomas periódicas de sus valores de PAS/PAD mediante tensiómetro digital.Resultados: el grupo SPD obtuvo un descenso significativo de los valores de PA frente al grupo control (la PAS disminuyó en 18,3 mmHg en el grupo SPD vs. 9,9 mmHg en el grupo control y la PAD en 9,9 mmHg vs. 8,9 mmHg). Ambos grupos aumentaron su adherencia hasta superar el 90 %.Conclusiones: el empleo de SPD permitió controlar los niveles de PA a casi un 50 % de los pacientes por lo que se postula como una buena herramienta (costo-efectiva, bien tolerada por los usuarios, de fácil uso…) para mejorar la adherencia de los pacientes y controlar la HTA de estos, aunque son necesarios más estudios. (AU)

[Asymptomatic celiac disease: the importance of neuroimaging]. / Enfermedad celíaca asintomática: importancia de la neuroimagen.

TITLE: Enfermedad celíaca asintomática: importancia de la neuroimagen.

Síndrome del hombre rojo en pediatría: a propósito de 2 casos / Syndrome of the red man in pediatrics: a report of 2 cases

Describimos dos casos de aparición de síndrome de hombre rojo o cuello rojo (SHR) en población pediátrica, una lactante de 3 meses y un niño de 12 años. En ambos pacientes se sustituyó vancomicina por otro glucopéptido, teicoplanina, sin haberse presentado este síndrome en ninguna de sus administraciones a pesar de la semejanza estructural existente entre ambos fármacos. (AU)

We describe two cases of red man or red neck syndrome (RRS) appearance in paediatric population, an infant of 3 months and a child of 12 years. In both patients vancomycin was replaced by another glycopeptide, teicoplanin, without this syndrome having occurred in any of their administrations despite the structural similarity between two drugs. (AU)

[Megalencephalic leukoencephalopathy with cysts -the clinical importance in the genetic era]. / Leucoencefalopatía megalencefálica con quistes: importancia de la descripción clínica en la era genética.

INTRODUCTION: Megalencephalic leukoencephalopathy with cysts is a leukodystrophy of genetic origin that produces an alteration in the water and ion homeostasis in the brain, generating vacuolar forms and chronic oedema in the white matter with progressive neurological deterioration. It should be suspected in infants who present progressive macrocephaly during the first year of life, motor retardation and characteristic findings in magnetic resonance brain scans. CASE REPORT: We report the case of a girl who was followed up from the age of 9 months due to progressive macrocephaly and delayed psychomotor development and brain MRI findings consistent with megalencephalic leukoencephalopathy with cysts, and the appearance of epilepsy during its development. The usual genetic studies (new generation sequencing and array) were negative, but as the diagnostic criteria were met, a complementary messenger RNA and DNA study was conducted, which confirmed the presence of two pathogenic variants in MLC1. CONCLUSIONS: Megalencephalic leukoencephalopathy with cysts is a rare condition. Progressive macrocephaly in the first year of life, the absence of deterioration or slow deterioration, and the possibility of developing epilepsy, spasticity and ataxia are characteristic signs in its course. It is important for these patients to undergo an imaging test that shows findings that characterise this condition, which, together with the clinical features, makes it possible to differentiate it from other leukodystrophies and to establish a confirmatory diagnosis. Genetic studies can confirm the associated mutation that makes it possible to predict the clinicoradiological phenotype.

TITLE: Leucoencefalopatía megalencefálica con quistes: importancia de la descripción clínica en la era genética.Introducción. La leucoencefalopatía megalencefálica con quistes es una leucodistrofia de origen genético que produce una alteración de la homeostasis del agua e iones en el cerebro, generando formas vacuolares y edema crónico en la sustancia blanca con deterioro neurológico progresivo. Debe sospecharse en los lactantes que presentan macrocefalia progresiva durante el primer año de vida, retraso motor y hallazgos característicos en la resonancia magnética cerebral. Caso clínico. Niña en seguimiento desde los 9 meses por macrocefalia progresiva y retraso del desarrollo psicomotor con presencia en la resonancia magnética cerebral de hallazgos compatibles con leucoencefalopatía megalencefálica con quistes, y aparición de epilepsia en su evolución. Los estudios genéticos habituales (secuenciación de nueva generación y array) fueron negativos, pero, al cumplir los criterios diagnósticos, se procedió al estudio del ARN mensajero y el ADN complementario, que confirmó la presencia de dos variantes patogénicas en MLC1. Conclusiones. La leucoencefalopatía megalencefálica con quistes es una entidad infrecuente. Es característica la macrocefalia progresiva en el primer año de vida, la ausencia de deterioro o deterioro lento, y la posibilidad de desarrollar epilepsia, espasticidad y ataxia en su evolución. Cobra importancia en dichos pacientes la realización de una prueba de imagen que muestre hallazgos propios de la entidad, lo que, junto con la clínica, permite diferenciarla de otras leucodistrofias y establecer un diagnóstico confirmatorio. Los estudios genéticos pueden constatar la mutación asociada que posibilita predecir el fenotipo clinicorradiológico.

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

PURPOSE: Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. MATERIALS AND METHODS: Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). RESULTS: At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). CONCLUSION: Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

Energy yield analysis of textured perovskite silicon tandem solar cells and modules.

Perovskite silicon tandem solar cells combine potentially low production costs with the ability to surpass the efficiency limit of silicon single junction solar cells. Optical modeling and optimization are crucial to achieve this ambitious goal in the near future. The optimization should seek to maximize the energy yield based on realistic environmental conditions. This work analyzes the energy yield of perovskite silicon tandem solar cells and modules based on realistic experimental data, with a special focus on the investigation of surface textures at the front and rear side of the solar cell and its implication for reflection as well as parasitic absorption properties. The investigation reveals a 7.3%rel higher energy yield for an encapsulated tandem cell with a textured front side compared with an encapsulated high efficiency single junction solar cell with 24.3% harvesting efficiency for irradiance data of the year 2014 in Freiburg/Germany.

Efficacy of Lysinibacillus sphaericus against mixed-cultures of field-collected and laboratory larvae of Aedes aegypti and Culex quinquefasciatus.

Lysinibacillus sphaericus (Bacillales: Planococcaceae) is a spore-forming bacillus used for the biological control of mosquitoes (Diptera: Culicidae) due to its larvicidal activity determined by various toxins and S-layer protein produced either during sporulation or by the vegetative cell. Aedes aegypti and Culex quinquefasciatus are the vectors of arboviruses that cause tropical diseases representing a current public health problem. Both species may coexist in the same larval development sites and are susceptible to the larvicidal activity of L. sphaericus. In this study, we compared the larvicidal effects of L. sphaericus 2362 (WHO Reference strain) and native strains III(3)7 and OT4b.25 against Cx. quinquefasciatus and Ae. aegypti in single-species and mixed-culture bioassays. Findings showed that L. sphaericus spores, vegetative cells and a combination thereof possessed high larvicidal activity against Cx. quinquefasciatus larvae, whereas only the formulation of L. sphaericus vegetative cells was effective against Ae. aegypti larvae. Similar results were obtained for field-collected larvae. We propose that a formulation of vegetative cells of L. sphaericus 2362 or III(3)7 could be a good alternative to chemical insecticides for the in situ control of mixed populations of Ae. aegypti and Cx. quinquefasciatus.

Small-sized follicles could contribute to high-order multiple pregnancies: outcomes of 6552 intrauterine insemination cycles.

RESEARCH QUESTION: Can predictors of twin and high-order multiple pregnancy among women with multiple cycles of ovarian stimulation intrauterine insemination (IUI) be identified? DESIGN: Retrospective cohort study of IUI cycles carried out between January 2014 and December 2015 in a private clinic in Spain. The 4879 women and 6552 cycles analysed in this study include single IUI with ovarian stimulation using recombinant FSH. RESULTS: Number of follicles and follicle size were the only factors with a significant effect (P < 0.001) on the likelihood of achieving a twin or multifetal pregnancy. Follicles 12 mm or wider greatly increase the chances of achieving a twin or multifetal pregnancy. A total of 73 out of 127 (57.5%) twin pregnancies occurred in cycles with at least one additional follicle measuring 12 mm or wider, and 102 out of 127 twin pregnancies (80.3%) occurred in cycles with at least one additional follicle measuring 14 mm or wider. Cancellation criteria should consider the presence of follicles 12 mm or wider. CONCLUSION: Follicles measuring 12 mm or wider increase the risk of having a twin or a high-order multiple pregnancy rate. These data may help clinicians balance decision-making between cancelling and performing the cycle within an IUI procedure.

Evaluation of the effect of live LaSota Newcastle disease virus vaccine as primary immunization on immune development in broilers.

Newcastle disease remains a major concern to the poultry industry; however, it can be managed with effective vaccination programs. The main objective of this study was to evaluate the effect of 2 1× doses of live LaSota strain Newcastle disease virus (NDV) vaccine administered oculo-nasally on d one and 21 on development of humoral and cell-mediated immune response in broilers, and to compare different immunization schedules. Two experiments were conducted. In Experiment I (n = 320), Ross 308 birds were randomly assigned to an unvaccinated control group or vaccinated treatment. [Both treatments consisted of 4 pens per treatment and 40 birds per pen]. At d one, live NDV LaSota strain vaccine was used as a primary immunization to evaluate its impact on adaptive immunity. No substantial NDV-specific humoral immune response was established. Body weights were significantly higher (P < 0.05) in the vaccinated birds on d 4 and 7. Spleen index of the vaccinated birds was significantly (P < 0.05) lower at d 28 and 35. Flow cytometry showed reduced levels of peripheral and splenic B and T lymphocytes. Interferon gamma secreted by splenocytes and in circulation was measured; the results showed a reduced expression post-secondary immunization. In Experiment II (n = 180), the role of maternal antibodies and primary vaccination at d one was evaluated using 3 vaccination protocols. Protocol 1 used live B1 strain as primary immunization, whereas protocol 2 used live LaSota strain. Protocol 3 used live LaSota strain after maternal antibodies had decayed. Protocol 3 resulted in the highest NDV-titer level during the trial. Protocol 2 had the lowest NDV titer. Feed conversion was significantly higher (P < 0.05) in protocol 3 compared to 1 and 2. Overall, the results indicate that the use of live LaSota strain NDV vaccine as primary immunization at d one has a detrimental effect on the development of adaptive immunity in broilers; however, its use after the level of maternal antibodies decays results in a robust antigen-specific humoral immune response.

Efficient skyrmion transport mediated by a voltage controlled magnetic anisotropy gradient.

Despite the inefficiencies associated with current-induced spin torques, they remain the predominant mode of skyrmion propulsion. In this work, we demonstrate numerically that skyrmions can be transported much more efficiently with a voltage-controlled magnetic anisotropy (VCMA) gradient. An analytical model was developed to understand the underlying skyrmion dynamics on a track under the VCMA conditions. Our calculations reveal that the repulsive skyrmion-edge interaction not only prevents the skyrmion from annihilating but also generates most of the skyrmion propulsion. A multiplexed array of gate electrodes can be used to create discrete anisotropy gradients over a long distance, leading to the formation of a series of translatable skyrmion potential wells. Due to the strong confining potentials, skyrmions are transported at a 70% higher packing density. Finally, we demonstrated that this form of skyrmion propulsion can also be implemented on almost any 2D geometry, providing improved versatility over current-induced methods.

Impact assessment of the rational selection of training and test sets on the predictive ability of QSAR models.

This study performed an analysis of the influence of the training and test set rational selection on the quality and predictively of the quantitative structure-activity relationship (QSAR) model. The study was carried out on three different datasets of Influenza Neuraminidase (H1N1) inhibitors. The three datasets were divided into training and test sets using three rational selection methods: based on k-means, Kennard-Stone algorithm and Activity and the results were compared with Random selection. Then, a total of 31,490 mathematical models were developed and those models that presented a determination coefficient higher than: r2train > 0.8, r2loo > 0.7, r2test > 0.5 and minimum standard deviation (SD) and minimum root-mean square error (RMS) were selected. The selected models were validated using the internal leave-one-out method and the predictive capacity was evaluated by the external test set. The results indicate that random selection could lead to erroneous results. In return, a rational selection allows for obtaining more reliable conclusions. The QSAR models with major predictive power were found using the k-means algorithm and selection by activity.

[Short-term results of Weils osteotomy in patients with propulsive metatarsalgia]. / Resultados funcionales a corto plazo de la osteotomía de Weil en pacientes con metatarsalgia propulsiva.

INTRODUCTION: Metatarsalgia is the most common reason for consultation in orthopedic pathology of the foot. The key to its treatment lies in the correct determination of the symptoms, which are biological, morphological and mechanical alterations responsible for pain. Weil´s osteotomy is commonly used for multiple forefoot pathologies, including metatarsalgias. MATERIAL AND METHODS: We included patients with first-line failure syndrome and associated mechanical metatarsalgia-producing deformities. The minimum follow-up was six months. All individuals were interviewed with a standardized questionnaire based on the AOFAS, a survey to know their degree of satisfaction about the surgery. RESULTS: Twelve female subjects with a mean age of 51 years were recruited between March and September of 2013. Seven right feet, five left. The AOFAS values improved only in six, in which an excellent result was obtained; five rated them as good and six as unsatisfactory. CONCLUSIONS: In a very small series, postoperative complications were observed when the shortening of the metatarsal was greater than four millimeters, with the appearance of stiffness (floating finger).

INTRODUCCIÓN: La metatarsalgia es el motivo de consulta más frecuente en patología ortopédica del pie. La clave de su tratamiento radica en la correcta determinación del síntoma, que son alteraciones biológicas, morfológicas y mecánicas responsables del dolor. La osteotomía de Weil es comúnmente utilizada para múltiples patologías del antepié, incluyendo las metatarsalgias. MATERIAL Y MÉTODOS: Se estudiaron pacientes intervenidos por síndrome de insuficiencia del primer rayo y deformidades asociadas productoras de metatarsalgia mecánica. El seguimiento mínimo fue de seis meses. Se entrevistó a todos los individuos con un cuestionario estandarizado basado en la AOFAS, una encuesta para saber su grado de satisfacción acerca de la cirugía. RESULTADOS: Se obtuvieron 12 sujetos femeninos con un promedio de 51 años de edad en el período entre Marzo y Septiembre de 2013. Siete pies derechos, cinco izquierdos. Los valores de AOFAS mejoraron sólo en seis, se obtuvo un resultado excelente; cinco los calificaron como buenos y seis como no satisfactorio. CONCLUSIONES: En una serie muy pequeña, se identificaron complicaciones postquirúrgicas cuando el acortamiento del metatarsiano es mayor a cuatro milímetros, con la aparición de rigidez (dedo flotante).

[Obstetric brachial plexus palsy: incidence, monitoring of progress and prognostic factors]. / Paralisis braquial obstetrica: incidencia, seguimiento evolutivo y factores pronosticos.

INTRODUCTION: Obstetric brachial plexus palsy is related with shoulder dystocia, and its main risk factor is macrosomia. Its incidence is estimated to be between 0.1 and 6.3 cases per 1,000 live newborn infants. Most cases are resolved but can give rise to permanent functional deficiency, which means that there is an interest to identify possible prognostic factors. PATIENTS AND METHODS: We conducted a descriptive study of newborn infants with obstetric brachial plexus palsy born in our hospital between the years 2011 and 2015. Maternal, perinatal and obstetric variables, as well as the type of lesion, were collected and were related with the possibility of recovery at six months. RESULTS: Altogether 32 cases were diagnosed, which represents an incidence of 1.44‰ of live newborn infants. 59% were males and 37.5% of them were macrosomic. The most frequent disorder was injury to the plexus at the proximal level (94%). 44% suffered from shoulder dystocia, and 47% still had sequelae at the sixth month. The antecedent of shoulder dystocia was related with a poor prognosis for recovery. CONCLUSIONS: The incidence of obstetric brachial plexus palsy has remained stable in recent years. The percentage of children who present sequelae at six months is significant. Prospective studies are needed to be able to establish the long-term prognostic factors of this pathology.

TITLE: Paralisis braquial obstetrica: incidencia, seguimiento evolutivo y factores pronosticos.Introduccion. La paralisis braquial obstetrica se relaciona con la distocia de hombros, y su principal factor de riesgo es la macrosomia. Su incidencia se estima entre 0,1 y 6,3 casos por 1.000 recien nacidos vivos. La mayoria de los casos se resuelve, pero puede provocar deficit funcional permanente, por lo que es de interes identificar posibles factores pronosticos. Pacientes y metodos. Estudio descriptivo de los recien nacidos con paralisis del plexo braquial obstetrica nacidos en el hospital entre los años 2011 y 2015. Se han recogido variables maternas, perinatales, obstetricas y del tipo de lesion, y se han relacionado con la posibilidad de la recuperacion a los seis meses. Resultados. Se diagnosticaron 32 casos, lo que supone una incidencia del 1,44‰ de recien nacidos vivos. El 59% fueron varones, y el 37,5%, macrosomicos. La afectacion mas frecuente fue la lesion del plexo a nivel proximal (94%). El 44% sufrio distocia de hombros, y el 47% permanecio con secuelas al sexto mes. El antecedente de distocia de hombros se relaciono con mal pronostico de recuperacion. Conclusiones. La incidencia de paralisis braquial obstetrica se mantiene estable en los ultimos años. El porcentaje de niños que presentan secuelas a los seis meses es relevante. Son necesarios estudios prospectivos para poder establecer los factores pronosticos a largo plazo de esta patologia.

IPM Use With the Deployment of a Non-High Dose Bt Pyramid and Mitigation of Resistance for Western Corn Rootworm (Diabrotica virgifera virgifera).

Recent detection of western corn rootworm resistance to Bt (Bacillus thuringiensis) corn prompted recommendations for the use of integrated pest management (IPM) with planting refuges to prolong the durability of Bt technologies. We conducted a simulation experiment exploring the effectiveness of various IPM tools at extending durability of pyramided Bt traits. Results indicate that some IPM practices have greater merits than others. Crop rotation was the most effective strategy, followed by increasing the non-Bt refuge size from 5 to 20%. Soil-applied insecticide use for Bt corn did not increase the durability compared with planting Bt with refuges alone, and both projected lower durabilities. When IPM participation with randomly selected management tools was increased at the time of Bt commercialization, durability of pyramided traits increased as well. When non-corn rootworm expressing corn was incorporated as an IPM option, the durability further increased. For corn rootworm, a local resistance phenomenon appeared immediately surrounding the resistant field (hotspot) and spread throughout the local neighborhood in six generations in absence of mitigation. Hotspot mitigation with random selection of strategies was ineffective at slowing resistance, unless crop rotation occurred immediately; regional mitigation was superior to random mitigation in the hotspot and reduced observed resistance allele frequencies in the neighborhood. As resistance alleles of mobile pests can escape hotspots, the scope of mitigation should extend beyond resistant sites. In the case of widespread resistance, regional mitigation was less effective at prolonging the life of the pyramid than IPM with Bt deployment at the time of commercialization.

Presence of a thapsigargin-sensitive calcium pump in Trypanosoma evansi: Immunological, physiological, molecular and structural evidences.

In higher eukaryotes, the sarco-endoplasmic reticulum (ER) Ca(2+)-ATPase (SERCA) is characterized for its high sensitivity to low concentrations of thapsigargin (TG), a very specific inhibitor. In contrast, SERCA-like enzymes with different sensitivities to TG have been reported in trypanosomatids. Here, we characterized a SERCA-like enzyme from Trypanosoma evansi and evaluated its interaction with TG. Confocal fluorescence microscopy using BODIPY FL TG and specific anti-SERCA antibodies localized the T. evansi SERCA-like enzyme in the ER and confirmed its direct interaction with TG. Moreover, the use of either 1 µM TG or 25 µM 2',5'-di (tert-butyl)-1,4-benzohydroquinone prevented the reuptake of Ca(2+) and consequently produced a small increase in the parasite cytosolic calcium concentration in a calcium-free medium, which was released from the ER pool. A 3035 bp-sequence coding for a protein with an estimated molecular mass of 110.2 kDa was cloned from T. evansi. The corresponding gene product contained all the invariant residues and conserved motifs found in other P-type ATPases but lacked the calmodulin binding site. Modeling of the three-dimensional structure of the parasite enzyme revealed that the amino acid changes found in the TG-SERCA binding pocket do not compromise the interaction between the enzyme and the inhibitor. Therefore, we concluded that T. evansi possesses a SERCA-like protein that is inhibited by TG.