A qualitative investigation of the Montgomery-Åsberg depression rating scale: discrepancies in rater perceptions and data trends in remote assessments of rapid-acting antidepressants in treatment resistant depression.

Introduction: Despite the development of many successful pharmaceutical interventions, a significant subset of patients experience treatment-resistant depression (TRD). Ketamine and its derivatives constitute a novel therapeutic approach to treat TRD; however, standard tools, such as the Montgomery-Åsberg Depression Rating Scale (MADRS) are still being used to measure symptoms and track changes. Methods: The aim of this study was to review item-level differences between rate of data change (MADRS score) and rater-weighted perception of the most useful items for assessing change in symptoms while remotely conducting the 10-item version of the MADRS in TRD in a clinical trial of rapid-acting antidepressants. Two studies of rapid-acting antidepressants in the treatment of TRD were used to identify item-scoring trends when MADRS is administered remotely and repeatedly (733 subjects across 10 visits). Scoring trends were evaluated in tandem to a rater survey completed by 75 raters. This was completed to gain insight on MADRS items' perceived level of helpfulness when assessing change of symptoms in rapid-acting antidepressant trials. Results: MADRS items 'Reduced sleep', 'Apparent sadness', and 'Pessimistic thoughts' were found to have the greatest average data change by visit, while raters ranked 'Reported sadness', 'Lassitude' and 'Apparent sadness' as the most helpful items when assessing symptom change. Discussion: The diversion between rate of data-change ranking and rater perception of helpfulness could be related to difficulty in assessing specific items, to the novel treatment itself, and/or to the sensitivity to symptom change to which raters are accustomed in traditional antidepressant treatments.

Valoración de un nuevo apósito para úlceras por presión: a propósito de un caso / Assessment for a new dressing for pressure ulcers: regarding a case

El objetivo de este estudio fue valorar la aplicación de un nuevo apósito superabsorbente a propósito de un caso clínico de un paciente con una úlcera por presión (UPP) con alto nivel exudativo, maceración de la piel perilesional, molestias y dolor. El paciente presentaba múltiples comorbilidades, estaba institucionalizado, desorientado, y presentaba una UPP grado IV. Accedió a comenzar un tratamiento con un apósito superabsorbente de nueva implementación en la institución. Se realizó una valoración en conjunto con su enfermera de la residencia según las Necesidades de Virginia Henderson. Según los resultados de dicha valoración se enunció un plan de cuidados con Diagnósticos NANDA, Resultados NOC con sus indicadores e Intervenciones NIC con sus actividades. Se priorizaron cuatro diagnósticos enfermeros: [00032] Patrón respiratorio ineficaz, [00129] Confusión crónica, [00312] Lesión por presión en el adulto y [00132] Dolor agudo. Los resultados NOC enunciados fueron [0402] Estado respiratorio: intercambio gaseoso, [0912] Estado neurológico: consciencia, [1101] Integridad tisular: piel y membranas mucosas, [110123] Necrosis, [1103] Curación de la herida: por segunda intención, [1004] Estado nutricional y [2109] Nivel de malestar. El plan de cuidados fue eficaz en el alcance de la puntuación diana de todos los indicadores excepto el indicador [110115] Lesiones cutáneas, cuya puntuación al alta se mantuvo igual que al ingreso, en 1 “grave”. El nuevo apósito disminuyó el exudado de la úlcera, redujo el tejido necrotizado y mejoró los bordes perilesionales. Esto mejoró a su vez el malestar del paciente al disminuir la frecuencia de cura de tres veces al día a una.(AU)

The objective of this study was to assess the application of a new super absorbent dressing, regarding the clinical case of a patient with one pressure ulcer (PU) with high levels of exudate, maceration of the perilesional skin, discomfort and pain. The patient presented multiple comorbidities; he was institutionalized, disoriented, and presented a Grade IV PU. The patient agreed to initiate treatment with a super absorbent dressing newly implemented at the institution. There was joint assessment with his nurse at the elderly home, according to Virginia Henderson’s Needs. Based on the results of said assessment, a plan of care was stated with NANDA diagnoses, NOC outcomes with their indicators, and NIC interventions with their activities. Four nursing diagnoses were prioritized: [00032] Ineffective breathing pattern, [00129] Chronic confusion, [00312] Pressure lesion in adults, and [00132] Acute pain. The NOC outcomes stated were [0402] Respiratory Status: Gas Exchange, [0912] Neurological status: Consciousness; [1101] Tissue Integrity: Skin and mucous membranes, [110123] Necrosis, [1103] Wound healing: Second intention, [1004] Nutritional status, and [2109] Discomfort level. The plan of care was effective at reaching the target score in all indicators except for [110115] Skin lesions with high score that stays the same than at admission, at 1 “severe”. The new dressing reduced the ulcer exudate and the necrotic tissue, and improved the perilesional edges. At the same time, there was an improvement in discomfort for the patient by reducing the frequency of cures from three times to once a day.(AU)

Reverse engineering DNA origami nanostructure designs from raw scaffold and staple sequence lists.

Designs for scaffolded DNA origami nanostructures are commonly and minimally published as the list of DNA staple and scaffold sequences required. In nearly all cases, high-level editable design files (e.g. caDNAno) which generated the low-level sequences are not made available. This de facto 'raw sequence' exchange format allows published origami designs to be re-attempted in the laboratory by other groups, but effectively stops designs from being significantly modified or re-purposed for new future applications. To make the raw sequence exchange format more accessible to further design and engineering, in this work we propose the first algorithmic solution to the inverse problem of converting staple/scaffold sequences back to a 'guide schematic' resembling the original origami schematic. The guide schematic can be used to aid the manual re-input of an origami into a CAD tool like caDNAno, hence recovering a high-level editable design file. Creation of a guide schematic can also be used to double check that a list of staple strand sequences does not have errors and indeed does assemble into a desired origami nanostructure prior to costly laboratory experimentation. We tested our reverse algorithm on 36 diverse origami designs from the literature and found that 29 origamis (81 %) had a good quality guide schematic recovered from raw sequences. Our software is made available at https://revnano.readthedocs.io.

Light-Up Split Broccoli Aptamer as a Versatile Tool for RNA Assembly Monitoring in Cell-Free TX-TL Systems, Hybrid RNA/DNA Origami Tagging and DNA Biosensing.

Binary light-up aptamers are intriguing and emerging tools with potential in different fields. Herein, we demonstrate the versatility of a split Broccoli aptamer system able to turn on the fluorescence signal only in the presence of a complementary sequence. First, an RNA three-way junction harbouring the split system is assembled in an E. coli-based cell-free TX-TL system where the folding of the functional aptamer is demonstrated. Then, the same strategy is introduced into a 'bio-orthogonal' hybrid RNA/DNA rectangle origami characterized by atomic force microscopy: the activation of the split system through the origami self-assembly is demonstrated. Finally, our system is successfully used to detect the femtomoles of a Campylobacter spp. DNA target sequence. Potential applications of our system include the real-time monitoring of the self-assembly of nucleic-acid-based devices in vivo and of the intracellular delivery of therapeutic nanostructures, as well as the in vitro and in vivo detection of different DNA/RNA targets.

Lessons learnt from the implementation of a colorectal cancer screening programme for lynch syndrome in a tertiary public hospital.

BACKGROUND: Lynch syndrome (LS) is the first cause of inherited colorectal cancer (CRC), being responsible for 2-4% of all diagnoses. Identification of affected individuals is important as they have an increased lifetime risk of multiple CRC and other neoplasms, however, LS is consistently underdiagnosed at the population level. We aimed to evaluate the yield of LS screening in CRC in a single-referral centre and to identify the barriers to its effective implementation. METHODS: LS screening programme included individuals with CRC < 70 years, multiple CRC, or endometrial cancer at any age. Mismatch repair (MMR) protein immunohistochemistry (IHC) analysis was performed in routine practice on the surgical specimen and, if MLH1 IHC was altered, MLH1 gene promoter methylation was analysed. Results were collected in the CRC multidisciplinary board database. LS suspected individuals (altered MMR IHC without MLH1 promoter methylation) were referred to the Cancer Genetic Counselling Unit (CGCU). If accepted, a genetic study was performed. Two checkpoints were included: review of the pathology data and verification of patient referral by a genetic counsellor. RESULTS: Between 2016 and 2019, 381 individuals were included. MMR IHC analysis was performed in 374/381 (98.2 %) CRC cases and MLH1 promoter methylation in 18/21 (85.7 %). Seventeen of the 20 LS suspected individuals were invited for referral at the CGCU. Two cases were not invited and the remaining patient died of cancer before completion of tumour screening. Fifteen individuals attended and a genetic analysis was performed in 15/20 (75 %) LS suspected individuals. Ten individuals were diagnosed with LS, in concordance with the IHC profile (2.7 % of the total cohort). This led to cascade testing in 58/75 (77.3 %) of the available adult relatives at risk, identifying 26 individuals with LS. CONCLUSIONS: Establishing a standardized institutional LS screening programme with checkpoints in the workflow is key to increasing the yield of LS identification.

Widespread Gene Expression Divergence in Butterfly Sensory Tissues Plays a Fundamental Role During Reproductive Isolation and Speciation.

Neotropical Heliconius butterflies are well known for their intricate behaviors and multiple instances of incipient speciation. Chemosensing plays a fundamental role in the life history of these groups of butterflies and in the establishment of reproductive isolation. However, chemical communication involves synergistic sensory and accessory functions, and it remains challenging to investigate the molecular mechanisms underlying behavioral differences. Here, we examine the gene expression profiles and genomic divergence of three sensory tissues (antennae, legs, and mouthparts) between sexes (females and males) and life stages (different adult stages) in two hybridizing butterflies, Heliconius melpomene and Heliconius cydno. By integrating comparative transcriptomic and population genomic approaches, we found evidence of widespread gene expression divergence, supporting a crucial role of sensory tissues in the establishment of species barriers. We also show that sensory diversification increases in a manner consistent with evolutionary divergence based on comparison with the more distantly related species Heliconius charithonia. The findings of our study strongly support the unique chemosensory function of antennae in all three species, the importance of the Z chromosome in interspecific divergence, and the nonnegligible role of nonchemosensory genes in the divergence of chemosensory tissues. Collectively, our results provide a genome-wide illustration of diversification in the chemosensory system under incomplete reproductive isolation, revealing strong molecular separation in the early stage of speciation. Here, we provide a unique perspective and relevant view of the genetic architecture (sensory and accessory functions) of chemosensing beyond the classic chemosensory gene families, leading to a better understanding of the magnitude and complexity of molecular changes in sensory tissues that contribute to the establishment of reproductive isolation and speciation.

Natural Volcanic Material as a Sustainable Photocatalytic Material for Pollutant Degradation under Solar Irradiation.

Recently, photocatalysis has been demonstrated as a solid approach for efficient wastewater cleaning. Using natural materials as photocatalysts means a promising solution to develop green catalysts for environmental purposes. This work aimed to study the suitability of a natural volcanic material (La Gomera, Canary Islands, Spain) as a photocatalytic material for the degradation of pollutants in wastewater with solar energy. After analysing the properties of the natural material (BET surface 0.188 m2/g and band-gap of 3 eV), the photocatalytic activity was evaluated at laboratory and pilot plant scale for the degradation of methylene blue (MB) in water (50 mg L-1), at 20 °C, during a period of 4 h, under UV/Vis light and solar irradiation. Photolytic and adsorption studies were developed to distinguish the photocatalytic contribution to the wastewater decontamination process by photocatalysis. Our results enable us to determine the viability of black sand as a photocatalytic material activated by solar irradiation (photodegradation of MB up to 100% by using solar energy), developing a natural and green photocatalytic system with significantly high potential for application in a sustainable wastewater cleaning process.

Long-term analysis of antibodies elicited by SPUTNIK V: A prospective cohort study in Tucumán, Argentina.

BACKGROUND: Gam-COVID-Vac (SPUTNIK V) has been granted emergency use authorization in 70 nations and has been administered to millions worldwide. However, there are very few peer-reviewed studies describing its effects. Independent reports regarding safety and effectiveness could accelerate the final approval by the WHO. We aimed to study the long-term humoral immune response in naïve and previously infected volunteers who received SPUTNIK V. METHODS: Humoral immune responses, assayed by anti-SARS-CoV-2-spike-RBD IgG ELISA and neutralization assays, were measured in 602 healthcare workers at 0, 14, 28, 60 and 180 days after receiving SPUTNIK V between December 2020 and July 2021 in Tucumán, Argentina. FINDINGS: Seroconversion was detected in 97% of individuals after 28 days post-vaccination (dpv) (N = 405). Anti-RBD titers began to decrease after 60 dpv (N = 328), but remained detectable in 94% at 90 dpv (N = 224). At 180 dpv, anti-RDB titers persisted in 31% (N = 146). Previous infection triggered an increased immune response to the first dose and increased neutralization activity against variants of concern (VOC). Second doses in previously infected individuals further increased titers, even 90 dpv (N = 75). Basal antibody titers had more influence on post-vaccination anti-RBD responses than the time elapsed between diagnosis and vaccination (N = 274). INTERPRETATION: Data presented herein provides essential knowledge regarding the kinetics of antibodies induced by SPUTNIK V up to six months after immunization, and suggests that when considering one-dose vaccination policies for individuals with previous SARS-CoV-2 infection, serological studies to determine basal titers may be important, independent of when diagnosis occurred. FUNDING: Tucumán Public Health System (SIPROSA), Argentinean National Research Council (CONICET), National University of Tucumán (UNT).

Elevated Humoral Immune Response to SARS-CoV-2 at High Altitudes Revealed by an Anti-RBD "In-House" ELISA.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 (COVID-19) challenges health systems to quickly respond by developing new diagnostic strategies that contribute to identify infected individuals, monitor infections, perform contact-tracing, and limit the spread of the virus. In this brief report, we developed a highly sensitive, specific, and precise "In-House" ELISA to correctly discriminate previously SARS-CoV-2-infected and non-infected individuals and study population seroprevalence. Among 758 individuals evaluated for anti-SARS-CoV-2 serology in the province of Tucumán, Argentina, we found a weak correlation between antibodies elicited against the RBD, the receptor-binding domain of the Spike protein, and the nucleocapsid (N) antigens of this virus. Additionally, we detected mild levels of anti-RBD IgG antibodies in 33.6% of individuals diagnosed with COVID-19, while only 19% showed sufficient antibody titers to be considered as plasma donors. No differences in IgG anti-RBD titers were found between women and men, neither in between different age groups ranging from 18 to 60. Surprisingly, individuals from a high altitude village displayed elevated and longer lasting anti-RBD titers compared to those from a lower altitude city. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-CoV-2 infection.

Progresión y predictores de insuficiencia valvular neoaórtica y dilatación de la raíz neoaórtica en adultos jóvenes tras cirugía de switch arterial / Time course and predictors for neoaortic root dilatation and neoaortic valve regurgitation during adult life after arterial switch operation

Introducción y objetivos Hay pocos datos sobre la evolución en adultos de la dilatación de la raíz neoaórtica (RAO) y la insuficiencia valvular neoaórtica (IA) tras la cirugía de switch arterial (SA) en la transposición de grandes arterias. Métodos Análisis retrospectivo de 152 pacientes con transposición de grandes arterias, mayores de 15 años, intervenidos mediante SA y seguidos durante 4,9±3,3 años en 2 centros de referencia. Se analizaron los cambios de diámetro de la RAO ajustados a superficie corporal y la progresión a grado moderado/grave de la IA con ecocardiografías seriadas. Se realizó un modelo de regresión de Cox para identificar factores predictores de progresión de la IA. Resultados Inicialmente, 4 pacientes (2,6%) presentaban IA grave (3 habían precisado cirugía valvular) y 9 (5,9%) moderada. La RAO basal media era 20,05±2,4mm/m2, y al final del seguimiento, 20,73±2,8mm/m2 (p<0,001), con un crecimiento medio de 0,14 (IC95%, 0,07-0,2) mm/m2/año. La IA progresó en 20 (13,5%) y 6 (4%) fueron intervenidos. La progresión de IA se asoció con válvula bicúspide, IA inicial, dilatación de la RAO inicial y crecimiento de la RAO. La válvula bicúspide (HR=3,3; IC95%, 1,1-15,2; p=0,037), la IA inicial (HR=5,9; IC95%, 1,6-59,2; p=0,006) y el crecimiento de la RAO (HR=4,1; IC95%, 2-13,5; p=0,023) resultaron predictores independientes. Conclusiones La dilatación de la RAO y la IA progresan en el adulto joven intervenido mediante SA. La válvula bicúspide, la IA basal y el crecimiento de la RAO son predictores de progresión de IA. (AU)

Introduction and objectives There are limited data on the long-term development of neoaortic root dilatation (NRD) and neoaortic valve regurgitation (AR) after arterial switch operation (ASO) for transposition of the great arteries during adult life. Methods We performed a retrospective longitudinal analysis of 152 patients older than 15 years who underwent ASO for transposition of the great arteries and who were followed-up for 4.9±3.3 years in 2 referral centers. Sequential changes in body surface-adjusted aortic root dimensions and progression to moderate/severe AR were determined in patients with 2 or more echocardiographic examinations. Risk factors for dilatation were tested by Cox regression to identify predictors of AR progression. Results At baseline, moderate AR was present in 9 patients (5.9%) and severe AR in 4 (2.6%), of whom 3 had required aortic valve surgery. Initially, the median neoaortic root dimension was 20.05±2.4mm/m2, which increased significantly to 20.73±2.8mm/m2 (P <.001) at the end of follow-up. The mean change over time was 0.14mm/m2/y (95%CI, 0.07-0.2). Progressive AR was observed in 20 patients (13.5%) and 6 patients (4%) required aortic valve surgery. Progressive AR was associated with bicuspid valve, AR at baseline, NRD at baseline, and neoaortic root enlargement. Independent predictors were bicuspid valve (HR, 3.3; 95%CI, 1.1-15.2; P=.037), AR at baseline (HR, 5.9; 95%CI, 1.6-59.2; P=.006) and increase in NRD (HR, 4.1 95%CI, 2-13.5; P=.023). Conclusions In adult life, NRD and AR progress over time after ASO. Predictors of progressive AR are bicuspid valve, AR at baseline, and increase in NRD. (AU)

Biomarker-Based Risk Prediction of Alzheimer's Disease Dementia in Mild Cognitive Impairment: Psychosocial, Ethical, and Legal Aspects.

BACKGROUND: Today, a growing number of individuals with mild cognitive impairment (MCI) wish to assess their risk of developing Alzheimer's disease (AD) dementia. The expectations as well as the effects on quality of life (QoL) in MCI patients and their close others through biomarker-based dementia risk estimation are not well studied. OBJECTIVE: The PreDADQoL project aims at providing empirical data on effects of such prediction on QoL and at developing an ethical and legal framework of biomarker-based dementia risk estimation in MCI. METHODS: In the empirical study, 100 MCI-patients and their close others will be recruited from two sites (Germany and Spain). They receive standardized counselling on cerebrospinal fluid (CSF) biomarker-based prediction of AD dementia and a risk disclosure based on their AD biomarker status. A mixed methods approach will be applied to assess outcomes. RESULTS: The pilot-study yielded a specification of the research topics and newly developed questionnaires for the main assessment. Within this binational quantitative and qualitative study, data on attitudes and expectations toward AD risk prediction, QoL, risk communication, coping strategies, mental health, lifestyle changes, and healthcare resource utilization will be obtained. Together with the normative part of the project, an empirically informed ethical and legal framework for biomarker-based dementia risk estimation will be developed. CONCLUSION: The empirical research of the PreDADQoL study together with the ethical and legal considerations and implications will help to improve the process of counselling and risk disclosure and thereby positively affect QoL and health of MCI-patients and their close others in the context of biomarker-based dementia risk estimation.

Time course and predictors for neoaortic root dilatation and neoaortic valve regurgitation during adult life after arterial switch operation.

INTRODUCTION AND OBJECTIVES: There are limited data on the long-term development of neoaortic root dilatation (NRD) and neoaortic valve regurgitation (AR) after arterial switch operation (ASO) for transposition of the great arteries during adult life. METHODS: We performed a retrospective longitudinal analysis of 152 patients older than 15 years who underwent ASO for transposition of the great arteries and who were followed-up for 4.9±3.3 years in 2 referral centers. Sequential changes in body surface-adjusted aortic root dimensions and progression to moderate/severe AR were determined in patients with 2 or more echocardiographic examinations. Risk factors for dilatation were tested by Cox regression to identify predictors of AR progression. RESULTS: At baseline, moderate AR was present in 9 patients (5.9%) and severe AR in 4 (2.6%), of whom 3 had required aortic valve surgery. Initially, the median neoaortic root dimension was 20.05±2.4mm/m2, which increased significantly to 20.73±2.8mm/m2 (P <.001) at the end of follow-up. The mean change over time was 0.14mm/m2/y (95%CI, 0.07-0.2). Progressive AR was observed in 20 patients (13.5%) and 6 patients (4%) required aortic valve surgery. Progressive AR was associated with bicuspid valve, AR at baseline, NRD at baseline, and neoaortic root enlargement. Independent predictors were bicuspid valve (HR, 3.3; 95%CI, 1.1-15.2; P=.037), AR at baseline (HR, 5.9; 95%CI, 1.6-59.2; P=.006) and increase in NRD (HR, 4.1 95%CI, 2-13.5; P=.023). CONCLUSIONS: In adult life, NRD and AR progress over time after ASO. Predictors of progressive AR are bicuspid valve, AR at baseline, and increase in NRD.

Increase of Neutrophil Activation Markers in Venous Thrombosis-Contribution of Circulating Activated Protein C.

Upon activation, neutrophils release their content through different mechanisms like degranulation and NETosis, thus prompting thrombosis. The natural anticoagulant activated protein C (APC) inhibits neutrophil NETosis and, consequently, this may lower the levels of neutrophil activation markers in plasma, further diminishing the thrombotic risk exerted by this anticoagulant. We aimed to describe the status of markers of neutrophil activation in plasma of patients with venous thrombosis, their association with the thrombotic risk and the potential contribution of APC. We quantified three markers of neutrophil activation (cell-free DNA, calprotectin, and myeloperoxidase) in 253 patients with venous thromboembolism (VTE) in a stable phase (192 lower extremity VTE and 61 splanchnic vein thrombosis) and in 249 healthy controls. In them, we also quantified plasma APC, soluble endothelial protein C receptor (EPCR), and soluble thrombomodulin (TM), and we genotyped two genetic regulators of APC: the EPCR gene (PROCR) haplotypes (H) and the TM gene (THBD) c.1418C>T polymorphism. We found a significant increase in plasma cell-free DNA (p < 0.0001), calprotectin (p = 0.0001) and myeloperoxidase (p = 0.005) in VTE patients compared to controls. Furthermore, all three neutrophil activation markers were associated with an increase in the thrombotic risk. Cell-free DNA and calprotectin plasma levels were significantly correlated (Spearman r = 0.28; p < 0.0001). As expected, the natural anticoagulant APC was significantly decreased in VTE patients (p < 0.0001) compared to controls, what was mediated by its genetic regulators PROCR-H1, PROCR-H3, and THBD-c.1418T, and inversely correlated with cell-free DNA levels. This is the largest case-control study that demonstrates the increase in markers of neutrophil activation in vivo in VTE patients and their association with an increased thrombotic risk. This increase could be mediated by low APC levels and its genetic regulators, which could also increase NETosis, further enhancing thrombosis and inflammation.

Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients.

microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism.

microRNAs and Markers of Neutrophil Activation as Predictors of Early Incidental Post-Surgical Pulmonary Embolism in Patients with Intracranial Tumors.

Venous thromboembolism (VTE) is a common complication of cancer that severely increases morbidity and mortality. Patients with intracranial tumors are more likely to develop VTE than patients with cancers at other sites. Conversely, limited tools exist to identify patients with high thrombotic risk. Upon activation, neutrophils release their content through different mechanisms triggering thrombosis. We explored the ability of microRNAs (miRNAs) and plasma markers of neutrophil activation measured before surgery to predict the risk of early post-surgical pulmonary embolism (PE) in glioma and meningioma patients. We recruited and prospectively followed 50 patients with glioma and 50 with meningioma, 34% of whom in each group developed an early objectively-diagnosed post-surgical PE. We measured miRNA expression and neutrophil markers (cell-free DNA, nucleosomes, calprotectin and myeloperoxidase) before surgery. In glioma patients, we adjusted and validated a predictive model for post-surgical PE with 6 miRNAs: miR-363-3p, miR-93-3p, miR-22-5p, miR-451a, miR-222-3p and miR-140-3p (AUC = 0.78; 95% Confidence Interval (CI) [0.63, 0.94]) and another with cfDNA and myeloperoxidase as predictors (AUC = 0.71; 95%CI [0.52, 0.90]). Furthermore, we combined both types of markers and obtained a model with myeloperoxidase and miR-140-3p as predictors (AUC = 0.79; 95%CI [0.64, 0.94]). In meningioma patients we fitted and validated a predictive model with 6 miRNAs: miR-29a-3p, miR-660-5p, miR-331-3p, miR-126-5p, miR-23a-3p and miR-23b-3p (AUC = 0.69; 95%CI [0.52, 0.87]). All our models outperformed the Khorana score. This is the first study that analyzes the capability of plasma miRNAs and neutrophil activation markers to predict early post-surgical PE in glioma and meningioma patients. The estimation of the thrombotic risk before surgery may promote a tailored thromboprophylaxis in a selected group of high-risk patients, in order to minimize the incidence of PE and avoid bleedings.

The killer yeast Wickerhamomyces anomalus Cf20 exerts a broad anti-Candida activity through the production of killer toxins and volatile compounds.

Candidiasis is a group of opportunistic infections caused by yeast of the genus Candida. The appearance of drug resistance and the adverse effects of current antifungal therapies require the search for new, more efficient therapeutic alternatives. Killer yeasts have aroused as suitable candidates for mining new antifungal compounds. Killer strains secrete antimicrobial proteins named killer toxins, with promissory antifungal activity. Here we found that the killer yeast Wickerhamomyces anomalus Cf20 and its cell-free supernatant (CFS) inhibited six pathogenic strains and one collection strain of Candida spp. The inhibition is mainly mediated by secreted killer toxins and, to a lesser extent, by volatile compounds such as acetic acid and ethyl acetate. A new large killer toxin (>180 kDa) was purified, which exerted 70-74% of the total CFS anti-Candida activity, and the previously described glucanase KTCf20 was inhibitory in a lesser extent as well. In addition, we demonstrated that Cf20 possesses the genes encoding for the ß-1,3-glucanases WaExg1 and WaExg2, proteins with extensively studied antifungal activity, particularly WaExg2. Finally, the 10-fold concentrated CFS exerted a high candidacidal effect at 37°C, completely inhibiting the fungal growth, although the nonconcentrated CFS (RCF 1) had very limited fungistatic activity at this temperature. In conclusion, W. anomalus Cf20 produces different low and high molecular weight compounds with anti-Candida activity that could be used to design new therapies for candidiasis and as a source for novel antimicrobial compounds as well.

Urinary microRNAs: Looking for a New Tool in Diagnosis, Prognosis, and Monitoring of Renal Cancer.

PURPOSE OF REVIEW: Renal cell carcinoma (RCC) is the third most common urologic malignancy. First symptoms are usually unspecific and belated causing the stages to be high when diagnosed. As compensation, incidental detection of RCC by abdominal imaging techniques for other medical purposes is a reality that favours a decrease in the stage of new diagnosed tumours. Therefore, identifying novel predictive biomarkers for diagnosis, progression and prognosis of RCC is fundamental. RECENT FINDINGS: To date, several studies have demonstrated that microRNAs (miRNAs) play a role in the particular scenario of urologic tumors, and alterations at miRNA level are involved in the initiation, progression and metastases formation of renal cancer. In the present review, we have summarized the up­to­date preliminary clinical works on the role of urinary miRNA profiling in RCC, including an evaluation of its value as a potential biomarker for diagnosis, prognosis and follow up of RCC patients.

Urine metabolomic analysis in clear cell and papillary renal cell carcinoma: A pilot study.

Renal cell carcinoma (RCC) is one of the most lethal type of tumors and is twice more frequent in men than in women. Initial symptoms are unspecific and belated thus increasing mortality. Moreover, current diagnostic and monitoring tools are harmful for the patient and unspecific in low-grade tumors. Therefore, novel minimally-invasive markers are needed to diagnose and monitor RCC patients. Urine represents the ideal sample source of non-invasive biomarkers for RCC. In our study we aimed to identify a urine metabolomic profile characteristic of RCC patients with diagnostic purposes and also to identify a profile with prognostic value. By an UPLC-Q-ToF MS untargeted metabolomic analysis, we compared the metabolomic profile of 23 RCC patients (14 clear cell RCC and 9 papillary RCC) before surgery and that of 23 healthy controls. Additionally, for the first time, we compared the metabolomic profile of these RCC patients pre-nephrectomy and 3 months and one year post-nephrectomy. We identified the dysregulated metabolomic variables by querying their exact mass against those presented in the Metlin and Human Metabolome Database. Next, we experimentally confirmed their identity. Both RCC subtypes showed similar metabolomic patterns at all stages. 51 metabolomic variables were significantly increased in RCC compared to controls and, among them, 4 were selected as potential discriminant metabolites between groups. We could experimentally confirm the identity of p-cresol glucuronide thus describing for the first time an increase in this metabolite in urine of RCC patients (fold change = 2.922, P = .012). Additionally, we confirmed that no metabolomic differences occur 3 months post-nephrectomy in RRC, while 188 variables were significantly increased one year post-nephrectomy. Of the 15 most discriminant metabolomic variables, we could experimentally confirm the identity of isobutyryl-l-carnitine (fold change = 2.098, P = .004) and l-proline betaine (fold change = 3.328, P = .004), for the first time. In summary, we have identified urine p-cresol glucuronide as potential diagnostic marker for RCC and isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. When confirmed in an independent cohort of RCC patients, these markers may improve the diagnosis and monitoring of RCC patients thus reducing current harmful diagnostic procedures. SIGNIFICANCE: The high-radiation dose of current imaging techniques available to diagnose and monitor renal cell carcinoma (RCC) are harmful for the patient and unspecific in low-grade tumors. Our untargeted metabolomic analysis carried out in urine samples from RCC patients and healthy individual reveals p-cresol glucuronide as potential diagnostic marker for RCC. Additionally, the analysis of RCC urine samples one year post-nephrectomy reveals isobutyryl-l-carnitine and l-proline betaine as potential prognostic markers. These novel non-invasive urine biomarkers may improve RCC management thus reducing the use of current harmful diagnostic techniques.