[Acute disseminated encephalomyelitis associated with SARS-CoV-2 infection without respiratory compromise]. / Encefalomielitis aguda diseminada asociada a infección por el SARS-CoV-2 sin afectación respiratoria.

INTRODUCTION: COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to grow all over the world since december of 2019. Although the main clinical manifestation is pulmonary disease, neurological manifestations are a prominent and increasingly recognized feature of the disease. The Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune disorder, most commonly triggered by a viral infection. There are a few case reports of ADEM associated with COVID-19, almost all of them associated pulmonary disease. We report the case of a young patient with diagnosis of ADEM with SARS-CoV-2 infection without clinical respiratory symptoms. CASE REPORT: A 20-year-old woman with no relevant medical history was brought to the emergency department with a progressive confusional state lasted for 7 days. Family reported the development of smell and taste deficit since two weeks before the onset of neurological symptoms. There were no complaints of pulmonary symptoms. At admission, she was drowsy and disoriented. Left homonymous hemianopsia and an ipsilateral Babinski sign was identified. A brain magnetic resonance image was done showing multiple hyperintense bilateral, asymmetric patchy and poorly marginated lesions with gadolinium enhancement. She was SARS-CoV-2 PCR positive on nasopharyngeal swab. Intravenous high-dose glucocorticoids were administered with marked clinical improvement. CONCLUSION: ADEM is an extremely uncommon complication of SARS-CoV-2infection. Acute disseminated encephalomyelitis should be considered a potentially treatable cause of encephalopathy or multifocal neurological deficits in COVID-19 patients, even in the absence of respiratory symptoms.

TITLE: Encefalomielitis aguda diseminada asociada a infección por el SARS-CoV-2 sin afectación respiratoria.Introducción. COVID-19 (coronavirus disease-2019) es la enfermedad secundaria a la infección por el coronavirus de tipo 2 o SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2), que se ha constituido como pandemia desde diciembre de 2019. Si bien la afectación más frecuente y grave es la pulmonar, las complicaciones neurológicas secundarias a la COVID-19 son cada vez más reconocidas. La encefalomielitis aguda diseminada (EMAD) es una enfermedad autoinmune poco frecuente, clásicamente secundaria a una infección viral previa o concomitante. Existen informes de EMAD asociada a la COVID-19, casi todos con afectación respiratoria asociada. Presentamos el caso de una mujer joven diagnosticada con EMAD secundaria a la infección por el SARS-CoV-2 sin afectación respiratoria. Caso clínico. Mujer de 20 años que consultó por cuadro de desorientación y alteración conductual de una semana de evolución. Destaca en la historia la presencia de anosmia y sensación febril dos semanas antes del inicio de los síntomas neurológicos. En el examen físico destacó somnolencia, desorientación, hemianopsia homónima izquierda y síndrome piramidal ipsilateral. Se realizó una resonancia magnética encefálica que mostró múltiples lesiones inflamatorias desmielinizantes bihemisféricas de la sustancia blanca sugerentes de EMAD. La reacción en cadena de la polimerasa del SARS-CoV-2 en aspirado nasofaríngeo resultó positiva. Se descartaron otras causas de lesiones inflamatorias. Recibió esteroides con excelente respuesta. Conclusión. La EMAD es una complicación extremadamente rara en pacientes con COVID-19 que debe considerarse como una causa tratable de encefalopatía y/o déficits neurológicos multifocales en pacientes con infección activa o reciente por SARS-CoV-2 con o sin manifestaciones respiratorias.

Encefalomielitis aguda diseminada asociada a infección por el SARS-CoV-2 sin afectación respiratoria / Acute disseminated encephalomyelitis associated with SARS-CoV-2 infection without respiratory compromise

Introducción: COVID-19 (coronavirus disease-2019) es la enfermedad secundaria a la infección por el coronavirus de tipo 2 o SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2), que se ha constituido como pandemia desde diciembre de 2019. Si bien la afectación más frecuente y grave es la pulmonar, las complicaciones neurológicas secundarias a la COVID-19 son cada vez más reconocidas. La encefalomielitis aguda diseminada (EMAD) es una enfermedad autoinmune poco frecuente, clásicamente secundaria a una infección viral previa o concomitante. Existen informes de EMAD asociada a la COVID-19, casi todos con afectación respiratoria asociada. Presentamos el caso de una mujer joven diagnosticada con EMAD secundaria a la infección por el SARS-CoV-2 sin afectación respiratoria. Caso clínico: Mujer de 20 años que consultó por cuadro de desorientación y alteración conductual de una semana de evolución. Destaca en la historia la presencia de anosmia y sensación febril dos semanas antes del inicio de los síntomas neurológicos. En el examen físico destacó somnolencia, desorientación, hemianopsia homónima izquierda y síndrome piramidal ipsilateral. Se realizó una resonancia magnética encefálica que mostró múltiples lesiones inflamatorias desmielinizantes bihemisféricas de la sustancia blanca sugerentes de EMAD. La reacción en cadena de la polimerasa del SARS-CoV-2 en aspirado nasofaríngeo resultó positiva. Se descartaron otras causas de lesiones inflamatorias. Recibió esteroides con excelente respuesta. Conclusión: La EMAD es una complicación extremadamente rara en pacientes con COVID-19 que debe considerarse como una causa tratable de encefalopatía y/o déficits neurológicos multifocales en pacientes con infección activa o reciente por SARS-CoV-2 con o sin manifestaciones respiratorias.(AU)

Introduction: COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to grow all over the world since december of 2019. Although the main clinical manifestation is pulmonary disease, neurological manifestations are a prominent and increasingly recognized feature of the disease. The Acute Disseminated Encephalomyelitis (ADEM) is a rare autoimmune disorder, most commonly triggered by a viral infection. There are a few case reports of ADEM associated with COVID-19, almost all of them associated pulmonary disease. We report the case of a young patient with diagnosis of ADEM with SARS-CoV-2 infection without clinical respiratory symptoms. Case report: A 20-year-old woman with no relevant medical history was brought to the emergency department with a progressive confusional state lasted for 7 days. Family reported the development of smell and taste deficit since two weeks before the onset of neurological symptoms. There were no complaints of pulmonary symptoms. At admission, she was drowsy and disoriented. Left homonymous hemianopsia and an ipsilateral Babinski sign was identified. A brain magnetic resonance image was done showing multiple hyperintense bilateral, asymmetric patchy and poorly marginated lesions with gadolinium enhancement. She was SARS-CoV-2 PCR positive on nasopharyngeal swab. Intravenous high-dose glucocorticoids were administered with marked clinical improvement. Conclusion: ADEM is an extremely uncommon complication of SARS-CoV-2infection. Acute disseminated encephalomyelitis should be considered a potentially treatable cause of encephalopathy or multifocal neurological deficits in COVID-19 patients, even in the absence of respiratory symptoms.(AU)

Ecografía de los troncos supraaórticos / Ultrasonography of supra-aortic trunks

La ecografía es un recurso del que disponemos de primera mano los médicos de familia y al que cada vez más frecuentemente recurrimos, hasta el punto de formar ya parte de nuestra exploración física. Es una técnica diagnóstica de fácil acceso, asequible, versátil y no invasiva que emplea los ultrasonidos para definir las estructuras anatómicas de nuestro cuerpo sin necesidad de radiación y que se realiza en tiempo real, pudiendo permitir una exploración dinámica. Pese a todo lo mencionado, la ecografía vascular y, en concreto, la de los troncos supraaórticos no está tan extendida en nuestro ámbito, pese a su importante papel en el ámbito de la prevención cardiovascular, fundamental en la atención primaria. Por este motivo en este artículo se pretende llevar a cabo una breve y clara descripción de la técnica con el objetivo de extender su uso en la práctica cotidiana (AU)

Ultrasound is a resource that family doctors have first-hand and that we use more and more frequently, to the point of becoming part of our physical examination. It is an easily accessible, affordable, versatile and non-invasive diagnostic technique that uses ultrasound to define the anatomical structures of our body without radiation and is performed in real time, allowing a dynamic exploration. Despite all the above, vascular ultrasound and, specifically, the supra-aortic trunks ultrasound is not as widespread in our setting, despite its important role in the field of cardiovascular prevention, which is essential in primary care. For this reason, this article aims to carry out a brief-and-clear description of the technique with the aim of extending its use in daily practice (AU)

[Ultrasonography of supra-aortic trunks]. / Ecografía de los troncos supraaórticos.

Ultrasound is a resource that family doctors have first-hand and that we use more and more frequently, to the point of becoming part of our physical examination. It is an easily accessible, affordable, versatile and non-invasive diagnostic technique that uses ultrasound to define the anatomical structures of our body without radiation and is performed in real time, allowing a dynamic exploration. Despite all the above, vascular ultrasound and, specifically, the supra-aortic trunks ultrasound is not as widespread in our setting, despite its important role in the field of cardiovascular prevention, which is essential in primary care. For this reason, this article aims to carry out a brief-and-clear description of the technique with the aim of extending its use in daily practice.

Analysis of serum and endometrial progesterone in determining endometrial receptivity.

STUDY QUESTION: Is there a relationship between serum and endometrial progesterone (P4) levels, including P4 and metabolites (oestrone, oestradiol and 17α-hydroxyprogesterone), and endometrial receptivity? SUMMARY ANSWER: Serum P4 levels were not correlated with endometrial P4, nor associated with endometrial receptivity as determined by the ERA® test; however, endometrial P4 and 17α-hydroxyprogesterone levels were positively correlated and related to endometrial receptivity by ERA. WHAT IS KNOWN ALREADY: Acquisition of endometrial receptivity is governed by P4, which induces secretory transformation. A close relationship between serum P4 and pregnancy outcome is reported for hormone replacement therapy (HRT) cycles. However, the relationship between serum and uterine P4 levels has not been described, and it is unknown whether uterine receptivity depends more on serum or uterine P4 levels. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was performed during March 2018-2019 in 85 IVF patients undergoing an evaluation-only HRT cycle with oestradiol valerate (6 mg/day) and micronised vaginal progesterone (400 mg/12 h). PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were under 50 years of age, had undergone at least one failed IVF cycle, had no uterine pathology, and had adequate endometrial thickness (> 6.5 mm). The study was conducted at IVI Valencia and IVI Foundation. An endometrial biopsy and a blood sample were collected after 5 days of P4 vaginal treatment. Measures included serum P4 levels, ERA®-based evaluation of endometrial receptivity, and endometrial P4 levels along with metabolites (oestrone, oestradiol and 17α-hydroxyprogesterone) measured by ultra-performance liquid chromatography-tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Seventy-nine women were included (mean age: 39.9 ± 4.6, BMI: 24.2 ± 3.9 kg/m2, endometrial thickness: 8.2 ± 1.4 mm). The percentage of endometria indicated as receptive by ERA® was 40.5%. When comparing receptive versus non-receptive groups, no differences were observed in baseline characteristics nor in steroid hormones levels in serum or endometrium. No association between serum P4 and endometrial steroid levels or ERA result was found (P < 0.05). When the population was stratified according to metabolite concentration levels, endometrial P4 and 17α-hydroxyprogesterone were significantly associated with endometrial receptivity (P < 0.05). A higher proportion of receptive endometria by ERA was observed when endometrial P4 levels were higher than 40.07 µg/ml (relative maximum) and a lower proportion of receptive endometria was associated with endometrial 17α-hydroxyprogesterone lower than 0.35 ng/ml (first quartile). A positive correlation R2 = 0.67, P < 0.001 was observed between endometrial P4 and 17α-hydroxyprogesterone levels. LIMITATIONS, REASONS FOR CAUTION: This study did not analyse pregnancy outcomes. Further, the findings can only be extrapolated to HRT cycles with micronised vaginal progesterone for luteal phase support. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that the combined benefits of different routes of progesterone administration for luteal phase support could be leveraged to ensure an adequate concentration of progesterone both in the uterus and in the bloodstream. Further studies will confirm whether this method can optimise both endometrial receptivity and live birth rate. Additionally, targeted treatment to increase P4 endometrial levels may normalise the timing of the window of implantation without needing to modify the progesterone administration day. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the IVI-RMA Valencia (1706-VLC-051-EL) and Consellería d'Educació, Investigació, Cultura, i esport Generalitat Valenciana (Valencian Government, Spain, GV/2018//151). Almudena Devesa-Peiro (FPU/15/01398) and Cristina Rodriguez-Varela (FPU18/01657) were supported by the FPU program fellowship from the Ministry of Science, Innovation and Universities (Spanish Government). P.D.-G. is co-inventor on the ERA patent, with non-economic benefits. The other authors have no competing interests. TRIAL REGISTRATION NUMBER: NCT03456375.

Non reducible inguinal hernias in Malawi: an occupational hazard.

PURPOSE: Inguinal hernias are one of the most common surgical conditions worldwide. Due to limited surgical access in low- and middle-income countries, many hernias present emergently; however, data on the resultant outcome disparities is limited. We, therefore, sought to describe the epidemiology, clinical features, and outcomes of incarcerated inguinal hernias at a tertiary center in Malawi. METHODS: This is a retrospective analysis of the acute care surgery registry at Kamuzu Central Hospital in Lilongwe, Malawi. All patients > 13 years admitted with a non-reducible inguinal hernia from 2013 to 2019 were included. The primary outcome was in-hospital mortality. A Poisson multivariable regression determined factors associated with increased risk of mortality. RESULTS: A total of 297 patients presented with non-reducible inguinal hernias, the majority of which were young (median age 38), male (93.6%), farmers (47.8%). Of the 81% who underwent surgery, 55% were delayed ≥ 24 h. 19.5% of hernias were strangulated. Overall mortality was 5.4%. Increased age (RR 1.06, 95% CI 1.01-1.12), shock index ≥ 1 (RR 4.82, 95% CI 1.45-16.09), and delay ≥ 24 h from presentation to operative intervention (RR 11.24, 95% CI 1.55-81.34) resulted in an increase in relative risk of mortality. CONCLUSION: Non-reducible inguinal hernias largely affect young male farmers in Malawi. Delays to care can limit economic productivity for this rural population, as well as, yield considerable risk of mortality. While specific patient and institutional factors must be further elucidated, increased awareness, public health prioritization, and surgical capacity building is needed to reduce further hernia-related morbidity and mortality.

Complete Genome Sequences of 17 Clinical Campylobacter jejuni Strains from Chile.

Campylobacter jejuni is the leading cause of bacterial foodborne disease worldwide. Here, we report the complete annotated genomes and plasmid sequences of 17 Campylobacter jejuni strains isolated from patients with gastroenteritis in Santiago, Chile.

[Intermittent theta-burst transcranial magnetic stimulation for the treatment of spasticity in patients with recurring multiple sclerosis: the results of a double-blind randomised clinical trial]. / Estimulacion magnetica transcraneal theta-burst intermitente para el tratamiento de la espasticidad en pacientes con esclerosis multiple recurrente: resultados de un ensayo clinico aleatorizado doble ciego.

AIM: It has been suggested that the repetitive transcranial magnetic stimulation could be useful as a non-pharmacological treatment for spasticity. The aim of this study was to evaluate the clinical and neurophysiological effects of high-frequency intermittent theta burst stimulation (iTBS) on lower limb spasticity in patients with relapsing multiple sclerosis in a randomized, double-blind placebo controlled trial. PATIENTS AND METHODS: Seventeen patients in the remitting phase of the disease were randomly allocated to sham or magnetic therapy group and underwent iTBS over contralateral motor cortex of the most affected leg once a day for two weeks. Each session consisted of 10 bursts containing three pulses at 50 Hz repeated at 200 ms intervals (5 Hz) every 10 s for a total of 600 stimuli. The iTBS effect was assessed by using clinical (such as the Modified Ashworth Scale) and neuro-physiological (H/M amplitude ratio and cortical silent period duration) parameters. RESULTS: Two-week iTBS over motor cortex of the most affected leg did not produce any significant clinical effect on spasticity. However, it decreases the H/M amplitude ratio and increases duration of cortical silent period but not significantly, in patients with relapsing multiple sclerosis. CONCLUSION: The stimulation protocol used in this study does not have significant therapeutic effect. Therefore, we do recommend further studies as neurophysiological changes were evident.

TITLE: Estimulacion magnetica transcraneal theta-burst intermitente para el tratamiento de la espasticidad en pacientes con esclerosis multiple recurrente: resultados de un ensayo clinico aleatorizado doble ciego.Objetivo. La estimulacion magnetica transcraneal repetitiva podria ser util como tratamiento no farmacologico para la espasticidad. El objetivo de este estudio es reevaluar el efecto clinico y los cambios neurofisiologicos que produce la estimulacion theta-burst intermitente (ETBi) sobre la espasticidad de las extremidades inferiores en pacientes con esclerosis multiple recurrente en un ensayo aleatorizado, doble ciego, controlado con placebo. Pacientes y metodos. Diecisiete pacientes en la fase remitente de la enfermedad fueron aleatoriamente asignados al grupo placebo o al grupo de tratamiento activo mediante estimulacion magnetica transcraneal repetitiva con protocolo ETBi sobre la corteza motora contralateral de la pierna mas afectada. El procedimiento consistio en 10 sesiones diarias durante dos semanas. Cada sesion consistio en 10 rafagas que contenian tres pulsos a 50 Hz repetidos a intervalos de 200 ms (5 Hz) cada 10 s para un total de 600 estimulos. El efecto de ETBi se evaluo mediante el uso de parametros clinicos (como la escala de Ashworth modificada) y neurofisiologicos (ratio de amplitud H/M y duracion del periodo cortical silente). Resultados. Dos semanas de ETBi sobre la corteza motora de la pierna mas afectada no produjeron ningun efecto clinico significativo sobre la espasticidad en pacientes con esclerosis multiple recurrente. Sin embargo, aunque de forma no significativa, se observo disminucion de la ratio de amplitud H/M y un aumento de la duracion del periodo cortical silente. Conclusion. El protocolo de estimulacion utilizado en este estudio no parece tener un efecto terapeutico significativo. Sin embargo, recomendamos estudios adicionales, ya que los cambios neurofisiologicos fueron evidentes.

Laboratory exposure to Coccidioides: lessons learnt in a non-endemic country.

Coccidioides is a primary pathogenic fungus, which infects humans through highly infectious arthroconidia, causing substantial morbidity including life-threatening disseminated infections. Due to the low infectious dose, laboratory personnel might become infected during diagnostic procedures. Accordingly, coccidioidomycosis is reported as the most frequent laboratory-acquired systemic mycosis worldwide. This risk is aggravated in non-endemic countries, where the diagnosis may not be suspected. We report on an inadvertent exposure of 44 persons to Coccidioides posadasii in a clinical microbiology laboratory in Chile, the measures of containment after rapid diagnosis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the lessons learnt in a non-endemic setting.

An actuatable soft reservoir modulates host foreign body response.

The performance of indwelling medical devices that depend on an interface with soft tissue is plagued by complex, unpredictable foreign body responses. Such devices-including breast implants, biosensors, and drug delivery devices-are often subject to a collection of biological host responses, including fibrosis, which can impair device functionality. This work describes a milliscale dynamic soft reservoir (DSR) that actively modulates the biomechanics of the biotic-abiotic interface by altering strain, fluid flow, and cellular activity in the peri-implant tissue. We performed cyclical actuation of the DSR in a preclinical rodent model. Evaluation of the resulting host response showed a significant reduction in fibrous capsule thickness (P = 0.0005) in the actuated DSR compared with non-actuated controls, whereas the collagen density and orientation were not changed. We also show a significant reduction in myofibroblasts (P = 0.0036) in the actuated group and propose that actuation-mediated strain reduces differentiation and proliferation of myofibroblasts and therefore extracellular matrix production. Computational models quantified the effect of actuation on the reservoir and surrounding fluid. By adding a porous membrane and a therapy reservoir to the DSR, we demonstrate that, with actuation, we could (i) increase transport of a therapy analog and (ii) enhance pharmacokinetics and time to functional effect of an inotropic agent. The dynamic reservoirs presented here may act as a versatile tool to further understand, and ultimately to ameliorate, the host response to implantable biomaterials.

Brettanomyces bruxellensis SSU1 Haplotypes Confer Different Levels of Sulfite Tolerance When Expressed in a Saccharomyces cerevisiae SSU1 Null Mutant.

The addition of SO2 is practiced in the wine industry to mitigate the risk of microbial spoilage and to extend wine shelf-life. Generally, this strategy does not interfere with primary alcoholic fermentation, as wine strains of Saccharomyces cerevisiae exhibit significant SO2 tolerance, largely driven by the efflux pump Ssu1p. One of the key yeast species responsible for wine spoilage is Brettanomyces bruxellensis, which also exhibits strain-dependent SO2 tolerance, although this occurs via unknown mechanisms. To evaluate the factors responsible for the differential sulfite tolerance observed in B. bruxellensis strains, we employed a multifaceted approach to examine both expression and allelic differences in the BbSSU1 gene. Transcriptomic analysis following exposure to SO2 highlighted different inducible responses in two B. bruxellensis strains. It also revealed disproportionate transcription of one putative BbSSU1 haplotype in both genetic backgrounds. Here, we confirm the functionality of BbSSU1 by complementation of a null mutant in a S. cerevisiae wine strain. The expression of four distinct BbSSU1 haplotypes in the S. cerevisiae ΔSSU1 mutant revealed up to a 3-fold difference in conferred SO2 tolerance. Substitution of key amino acids distinguishing the encoded proteins was performed to evaluate their relative contribution to SO2 tolerance. Protein modeling of two haplotypes which differed in two amino acid residues suggested that these substitutions affect the binding of Ssu1p ligands near the channel opening. Taken together, preferential transcription of a BbSSU1 allele that encodes a more efficient Ssu1p transporter may represent one mechanism that contributes to differences in sulfite tolerances between B. bruxellensis strains.IMPORTANCEBrettanomyces bruxellensis is one of the most important wine spoilage microorganisms, with the use of sulfite being the major method to control spoilage. However, this species displays a wide intraspecies distribution in sulfite tolerance, with some strains capable of tolerating high concentrations of SO2, with relatively high concentrations of this antimicrobial needed for their control. Although SO2 tolerance has been studied in several organisms and particularly in S. cerevisiae, little is known about the mechanisms that confer SO2 tolerance in B. bruxellensis Here, we confirmed the functionality of the sulfite efflux pump encoded by BbSSU1 and determined the efficiencies of four different BbSSU1 haplotypes. Gene expression analysis showed greater expression of the haplotype conferring greater SO2 tolerance. Our results suggest that a combination of BbSSU1 haplotype efficiency, copy number, and haplotype expression levels likely contributes to the diverse SO2 tolerances observed for different B. bruxellensis strains.

Acute Kidney Injury After Cardiac Transplantation: Foe or Common Innocent Bystander?

BACKGROUND: Heart transplantation (HT) is regarded as the treatment of choice for end-stage heart failure (ESHF) patients. Severe acute kidney injury (AKI) after HT is a frequent clinical problem with devastating consequences for HT recipients. METHODS: Data from 112 ESHF patients undergoing HT in 2010-2015 were retrospectively reviewed. The primary end point was the development of AKI stage III, and secondary outcomes were in-hospital and 1-year mortality according to Kidney Disease Improving Global Outcomes criteria. RESULTS: In total, 81 patients (72.3%) developed AKI, of which 33 (29.4%) developed AKI stage I, 18 (16%) stage II, and 30 (26.7%) stage III; within this group, 27 recipients (24%) required renal replacement therapy (RRT). Overall hospital mortality was 14%. However, when stratifying by AKI stage, hospital mortality increased from 0% to 46% comparing recipients without AKI and those with AKI stage III, respectively (P = .001). In the same way, 1-year mortality increased from 6% to 53% for recipients without AKI compared with those who developed AKI stage III (log-rank test for trend: P = .001). Recipients that required RRT had a 1-year mortality of 59.2% compared with 5.8% in those without RRT requirement. CONCLUSIONS: The findings indicate that AKI stage III is common after HT and adversely affects early and late mortality. Clinical variables together with perioperative hemodynamic assessment could add more powerful prognostic information to predict severe AKI before HT and therefore evaluate potential heart-kidney recipients.

Radiation characterisation and dosimetric measurements of a femtosecond pulsed laser ablation system.

This work describes the radiation characterisation and dosimetric measurements performed on the low-energy micromachining station of the femtosecond STELA (Santiago TErawatt LAser) at the University of Santiago de Compostela (Spain). For this aim, ionisation chambers, solid state detectors, and radiochromic films were used. The results show the emission of pulsed x-ray produced by laser-accelerated electrons from the ablated material exhibiting both bremsstrahlung and characteristic radiation. Although this radiation was produced unintentionally, a high superficial dose rate can be achieved. This radiation can be successfully stopped using small shielding to protect personnel from its effects. Based on the results of this work, the yearly dose equivalent after installing the shielding was negligible.

Laser technique for the fabrication of blood vessels-like models for preclinical studies of pathologies under flow conditions.

In this work a method for fabricating functionalized preclinical devices is presented. The manufacturing process combines a laser indirect writing technique to fabricate a soda-lime glass master and soft-lithography methods to obtain the final structure in polydimethylsiloxane (PDMS). The roughness of the device is modified in a controlled manner by applying a post-thermal treatment to the master, and thus devices with different roughness values are created. The PDMS devices are fully covered with human umbilical vein cells in a two-step process. In order to determine the most suitable device to perform bioassays, the cell attachment to the channel is evaluated with regards to the walls roughness when flow experiments are carried out.

Sensory profile and volatile aroma composition of reduced alcohol Merlot wines fermented with Metschnikowia pulcherrima and Saccharomyces uvarum.

Strategies for production of wines containing lower alcohol concentrations are in strong demand, for reasons of quality, health, and taxation. Development and application of wine yeasts that are less efficient at transforming grape sugars into ethanol has the potential to allow winemakers the freedom to make lower alcohol wines from grapes harvested at optimal ripeness, without the need for post-fermentation processes aimed at removing ethanol. We have recently shown that two non-conventional wine yeast species Metschnikowia pulcherrima and Saccharomyces uvarum were both able to produce wine with reduced alcohol concentration. Both species produced laboratory-scale wines with markedly different volatile aroma compound composition relative to Saccharomyces cerevisiae. This work describes the volatile composition and sensory profiles of reduced-alcohol pilot-scale Merlot wines produced with M. pulcherrima and S. uvarum. Wines fermented with M. pulcherrima contained 1.0% v/v less ethanol than S. cerevisiae fermented wines, while those fermented with S. uvarum showed a 1.7% v/v reduction in ethanol. Compared to S. cerevisiae ferments, wines produced with M. pulcherrima showed higher concentrations of ethyl acetate, total esters, total higher alcohols and total sulfur compounds, while wines fermented with S. uvarum were characterised by the highest total concentration of higher alcohols. Sensorially, M. pulcherrima wines received relatively high scores for sensory descriptors such as red fruit and fruit flavour and overall exhibited a sensory profile similar to that of wine made with S. cerevisiae, whereas the main sensory descriptors associated with wines fermented with S. uvarum were barnyard and meat. This work demonstrates the successful application of M. pulcherrima AWRI3050 for the production of pilot-scale red wines with reduced alcohol concentration and highlights the need for rigorous evaluation of non-conventional yeasts with regard to their sensory impacts.

Volatile flavour profile of reduced alcohol wines fermented with the non-conventional yeast species Metschnikowia pulcherrima and Saccharomyces uvarum.

Production of quality wines with decreased alcohol concentration continues to be one of the major challenges facing wine producers. Therefore, there is considerable interest in the isolation or generation of wine yeasts less efficient at transforming grape sugars into ethanol. We recently demonstrated that Metschnikowia pulcherrima AWRI1149 and Saccharomyces uvarum AWRI2846 were both able to produce reduced alcohol wine when used in sequential inoculation with Saccharomyces cerevisiae. This effect is additive when both strains are co-inoculated in grape must. Here we describe the volatile flavour profile of Chardonnay and Shiraz wines produced with these two strains. Wines fermented with M. pulcherrima showed concentrations of ethyl acetate likely to affect negatively wine aroma. Wines fermented with S. uvarum and with a combination of M. pulcherrima and S. uvarum were characterised by increased concentrations of 2-phenyl ethanol and 2-phenylethyl acetate, both associated with positive sensory attributes.

¿Son los nuevos anticoagulantes orales iguales a las antivitaminas K para la isquemia aguda de los miembros inferiores? Revisión sistemática de la evidencia / Are the new oral anticoagulants the same as vitamin K antagonists for acute lower limb ischaemia? A systematic review of the evidence

INTRODUCCIÓN: Los nuevos anticoagulantes orales (dabigatran, ribaroxaban y apixaban) se presentan como alternativas a los antagonistas de la vitamina K (AVK) en la prevención de eventos embólicos en pacientes con fibrilación auricular (FA). No existen ensayos clínicos que comparen directamente estos fármacos para la prevención de la isquemia aguda (IA) de miembros inferiores. MATERIAL Y MÉTODOS: Este estudio presenta los ensayos clínicos aleatorizados (RE-LY, ROCKET-AF, ARISTOTLE) que describen la capacidad de prevención de IA entre estos nuevos fármacos. RESULTADOS: Los nuevos anticoagulantes orales han demostrado en diversos ensayos clínicos y metaanálisis una eficacia similar a los AVK en la prevención de accidente cerebrovascular y embolismo sistémico con un menor número de complicaciones en pacientes con FA no valvular. CONCLUSIONES: Todavía no disponemos de evidencia de calidad sobre el efecto de estos fármacos para la prevención de la IA de miembros inferiores. Son necesarios futuros ensayos clínicos en esta dirección

INTRODUCTION: New oral anticoagulants (apixaban, dabigatran, and rivaroxaban) are alternatives to vitamin-K antagonist (VKA) for preventing embolic events in patients withauricular auricular fibrillation. So far, direct comparative studies between agents in prevention of acute limb ischaemia are unavailable. MATERIAL AND METHODS: The present study shows the outcome from the 3 randomised clinical trials (RE-LY, ROCKET-AF, ARISTOTLE) regarding acute limb ischaemia risk prevention. RESULTS: Novel oral anticoagulant therapies have shown a non-inferior efficacy compared with VKAs in lowering cerebrovascular ischaemic events and systemic embolism risk in several randomised clinical trials as well as in meta-analysis. Moreover, they have been shown to have a decreased complication rate in non-valvularauricular auricular fibrillation. CONCLUSIONS: There is no high quality evidence available on the effect of these treatments in preventing acute limb ischaemia

Meta-analysis and adjusted indirect comparison of direct oral anticoagulants in prevention of acute limb ischemia in patients with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants are being presented as alternatives to warfarin for preventing stroke in patients with atrial fibrillation. Yet direct comparative trials between these agents in prevention of acute limb ischemia (ALI) are unavailable so far. OBJECTIVE: To conduct an adjusted indirect comparison meta-analysis between direct oral agents for prevention of acute limb ischemia in atrial fibrillation. METHODS: We conducted a systematic literature review searching electronic databases (MEDLINE and Embase) and the Cochrane Library from January 1990 through November 2014. Two blinded investigators reviewed all potentially relevant articles in a parallel manner by using a priori defined criteria. To assess the long-term efficacy and safety of these agents, only randomized clinical trials (RCTs) with follow-up durations of >1 year were included. The primary efficacy outcome was the end point of acute limb ischemia and/or extremity embolism. RESULTS: A total of 44,563 patients from three RCTs met criteria for inclusion. Patients randomized to direct oral anticoagulants had a non-significant decreased risk for acute limb ischemia (risk ratio [RR]: 0.57, 95% confidence interval [CI]: 0.26-1.2). In the analysis between agents, however, rivaroxaban significantly lowered the risk of ALI compared to warfarin (RR: 0.23, 95% CI: 0.064-0.82), apixaban (RR: 0.26, 95% CI: 0.081-0.83), and dabigatran (RR: 0.24, 95% CI: 0.077-0.83). CONCLUSIONS: Significant differences in prevention of acute limb ischemia may exist between oral anticoagulant agents in patients with atrial fibrillation. Rivaroxaban lowers the risk of limb embolism versus warfarin, apixaban and dabigatran.

Nuevas terapias target y vías moleculares clínicamente relevantes en carcinoma hepatocelular avanzado / New targeted therapies and molecular routes clinically relevant in advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. Most cases occur in patients with chronic liver disease who are diagnosed at an advanced stage, and their prognosis is poor. Because HCC is resistant to conventional systemic therapies, molecular therapies have emerged and been established as the standard for advanced forms of the disease. Since the publication of phase III clinical studies on sorafenib, research has searched for new molecular targets. Thus, multiple clinical studies that inhibit relevant molecular pathways have been performed with numerous patients. Many of these trials have had unexpectedly negative results, not only due to patient complexity and the difficulty in evaluating a therapeutic response, quality of life and the survival rate but also because phase II clinical studies, without the selection of molecular targets, have continued on to poor results in phase III studies. This review article aims to evaluate different phase II and phase III clinical studies to understand the clinically relevant molecular pathways and to improve the future management of HCC patients.

El carcinoma hepatocelular (CHC) es uno de los tumores más comunes a nivel mundial. La mayoría de los casos ocurre en pacientes con enfermedad hepática crónica, quienes son diagnosticados en un estado avanzado con muy pobre pronóstico. Terapias moleculares orientadas al tratamiento del CHC han sido destacadas; estas pueden afectar la proliferación celular del tumor, diferenciación celular, angiogénesis, invasión y metástasis, entre otros procesos críticos al desarrollo del tumor. El estándar para el CHC avanzado es la terapia target usando Sorafenib, sin embargo, nuevas moléculas han sido testeadas en estudios fase III de primera línea, tales como sunitinib, brivanib, erlotinib y linifanib, sin superioridad sobre sorafenib. La investigación de nuevos tratamientos es un desafío para investigadores, hepatólogos y oncólogos. Las principales vías moleculares de CHC con relevancia en estudios clínicos fase II y III son: MAP-kinase (MAPK), PI3K/AKT/mTOR, (HGF)/c-Met, cromatina y regulación epigenética, mantenimiento de telómeros, Notch, Hedgehog, Hippo y vía señalizante Jak/STAT. Las terapias futuras en CHC pueden ser orientadas rutinariamente usando sólo objetivos adecuados para terapias moleculares y seleccionando subgrupos de pacientes sobre la base de la expresión de targets moleculares o basados en nuevas clasificaciones definidas por estudios genómicos.

Expresión proteica de metaloproteinasa-2 (MMP-2) y su inhibidor tisular (TIMP-2) en aorta, fascia y plasma de pacientes con aneurisma de aorta abdominal / Protein expression of metalloproteinases-2 (MMP-2) and its tissue inhibitor (TIMP-2) in aorta, fascia and plasma of patients with abdominal aortic aneurysm

INTRODUCCIÓN: Existen datos que asocian los aneurismas de aorta abdominal (AAA) con un incremento de la prevalencia de la enfermedad herniaria. Una posible alteración estructural de la matriz extracelular puede ser común en el proceso degenerativo de la pared aórtica y de la fascia abdominal. OBJETIVO: Conocer la expresión de metaloproteinasas de matriz-2 (MMP-2) y el inhibidor tisular de metaloproteinasas-2 (TIMP-2) en pared aórtica, fascia abdominal y plasma de pacientes intervenidos de AAA frente a pacientes con enfermedad aórtica oclusiva (EAO). MATERIAL Y MÉTODOS: Estudio piloto, observacional prospectivo. Se analizó la expresión proteica de MMP-2 y TIMP-2 en 10 pacientes con AAA y 10 con EAO. Recogimos datos epidemiológicos, antecedentes de hernias y diámetros del AAA. El análisis se realizó por técnica de ELISA. RESULTADOS: En el subgrupo de AAA de mediano tamaño con antecedentes de hernia, encontramos sobreexpresión de MMP-2 en fascia y de TIMP-2 en aorta y fascia, respecto a EAO sin hernia (MMP-2 fascia: AAA = 4,53 [3,11-6,90]; EAO = 1,87 [1,45-2,90]; p = 0,04; TIMP-2 en aorta: AAA = 72,62 [9,26-161,12], EAO = 9,79 [5,55-25,61]; p = 0,04 y TIMP-2 en fascia: AAA = 35,24 [13,15-61,08], EAO = 4,98 [1,42-18,01]; p = 0,02). La MMP-2 y el TIMP-2 estaban aumentados en fascia de AAA con enfermedad herniaria frente a EAO sin hernia (MMP-2: 4,31 [3,35-6,35] versus 1,87 [1,45-2,90]; p = 0,009 y TIMP-2: 18,73 [7,76-57,97] versus 4,98 [1,42-18,01]; p = 0,08). En pared aórtica hubo aumento de TIMP-2 en AAA (29,27 [14,05-140,30] frente a EAO, 9,79 [6,19-32,74]; p = 0,06). CONCLUSIONES: La MMP-2 y el TIMP-2 están aumentados, en aorta y fascia de pacientes con AAA, sobre todo, en los de mediano tamaño, lo que indica cierto papel en la etiología. El incremento de MMP-2 y TIMP-2 en presencia de hernia potencia la idea de un mecanismo patogénico común

INTRODUCTION: There are data that associates abdominal aortic aneurysms (AAA) with an increased prevalence of hernia disease. A possible structural alteration of extracellular matrix may be common in the degenerative process of the aortic wall and the abdominal fascia. OBJECTIVE: Determine the expression of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in aortic wall tissue, abdominal fascia, and plasma of patients undergoing AAA versus patients with aortic occlusive disease (EAO). MATERIAL AND METHODS: A pilot, prospective observational study was conducted, in which the protein expression of MMP-2 and TIMP-2 was analyzed in 10 patients with AAA, and in 10 with EAO, using an ELISA technique. Epidemiological data, history of hernias, and AAA diameters were collected. RESULTS: In the subgroup of medium sized AAA with a history of hernia, over-expression of MMP-2 was found in fascia, and of TIMP-2 in aorta and fascia. As regards EAO without hernia (MMP-2 fascia: AAA = 4.53 [3.11-6.90], EAO = 1.87 [1.45-2.90], P=.04; TIMP-2 in aorta: AAA = 72.62 [9.26-161.12], EAO = 9.79 [5.55-25.61], P=.04, and TIMP-2 in fascia: AAA = 35.24 [13.15-61.08], EAO =4.98 [1.42-18.01], P=.02).The MMP-2 and TIMP-2 was increased in AAA fascia hernia disease compared with EAO without hernia (MMP-2: 4.31 [3.35-6.35] versus 1.87 [1.45-2.90], P=.009, and TIMP-2: 18.73 [7.76-57.97] versus 4.98 [1.42-18.01], P=.08).There was an increased TIMP-2 in the aortic wall, AAA (29.27 [14.05-140.30] vs. EAO 9.79 [6.19-32.74], P=.06). CONCLUSIONS: The MMP-2 and TIMP-2 are increased in aorta and fascia of patients with AAA, especially in the medium size, suggesting a role in the etiology. The increase in MMP-2 and TIMP-2 in the presence of hernia, enhances the idea of a common pathogenic mechanism