Variational Quantum Simulators Based on Waveguide QED.

Waveguide QED simulators are analog quantum simulators made by quantum emitters interacting with one-dimensional photonic band gap materials. One of their remarkable features is that they can be used to engineer tunable-range emitter interactions. Here, we demonstrate how these interactions can be a resource to develop more efficient variational quantum algorithms for certain problems. In particular, we illustrate their power in creating wave function Ansätze that capture accurately the ground state of quantum critical spin models (XXZ and Ising) with fewer gates and optimization parameters than other variational Ansätze based on nearest-neighbor or infinite-range entangling gates. Finally, we study the potential advantages of these waveguide Ansätze in the presence of noise. Overall, these results evidence the potential of using the interaction range as a variational parameter and place waveguide QED simulators as a promising platform for variational quantum algorithms.

Evaluation of chitosan salt properties in the production of AgNPs materials with antibacterial activity.

In this study, water-soluble chitosan salts (chitosan amine sulfopropyl salts) were prepared from chitosan samples with different molecular weights and deacetylation degrees. These soluble-in-water polymer salts allowed us to produce, in an eco-friendly and facile method, silver nanoparticles (AgNPs) with better control on size and polydispersity, even at large silver concentrations than their corresponding chitosan sample. Chitosan salt-based materials (films and scaffolds) were analyzed in terms of antibacterial properties against Staphylococcus aureus ATCC23915 or Pseudomonas aeruginosa ATCC 27853. 3D scaffolds enhanced the effect of the chitosan-AgNPs combination compared to the equivalent films.

Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Spain: Clinical and Genetic Characterization.

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is a very rare hereditary disorder characterized by cutaneous leiomyomas (CLMs), uterine leiomyomas (ULMs), renal cysts (RCys) and renal cell cancers (RCCs). We aimed to describe the genetics, clinical features and potential genotype-phenotype associations in the largest cohort of fumarate hydratase enzyme mutation carriers known from Spain using a multicentre, retrospective study of individuals with a genetic or clinical diagnosis of HLRCC. We collected clinical information from medical records, analysed genetic variants and looked for genotype-phenotype associations. Analyses were performed using R 3.6.0. software. We included 197 individuals: 74 index cases and 123 relatives. CLMs were diagnosed in 65% of patients, ULMs in 90% of women, RCys in 37% and RCC in 10.9%. Twenty-seven different pathogenic variants were detected, 12 (44%) of them not reported previously. Patients with missense pathogenic variants showed higher frequencies of CLMs, ULMs and RCys, than those with loss-of-function variants (p = 0.0380, p = 0.0015 and p = 0.024, respectively). This is the first report of patients with HLRCC from Spain. The frequency of RCCs was lower than those reported in the previously published series. Individuals with missense pathogenic variants had higher frequencies of CLMs, ULMs and RCys.

SEOM clinical guideline on hereditary colorectal cancer (2019).

In the last 2 decades, clinical genetics on hereditary colorectal syndromes has shifted from just a molecular characterization of the different syndromes to the estimation of the individual risk of cancer and appropriate risk reduction strategies. In the last years, new specific therapies for some subgroups of patients have emerged as very effective alternatives. At the same time, germline multigene panel testing by next-generation sequencing (NGS) technology has become the new gold standard for molecular genetics.

Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

Determination of halides using Ag nanoparticles-modified disposable electrodes. A first approach to a wearable sensor for quantification of chloride ions.

This work reports a simple voltammetric method for the determination of chloride, bromide, and iodide ions using screen-printed carbon electrodes modified with silver nanoparticles electrochemically deposited on the working electrode surface. UV/Vis absorption spectroelectrochemistry was used to study the electrodeposition of silver nanoparticles on the working carbon electrode on PET or Gore-Tex® supports, and their subsequent oxidation in the presence of halide ions. The main figures of merit of the developed sensors, such as reproducibility and detection limit, have been calculated. Reproducibility values of 2.22%, 2.83% and 3.23% were obtained for chloride, bromide and iodide determinations, respectively. Additionally, the lowest detected amount of chloride, bromide and iodide ions were 3.0·10-6 M, 5.0·10-6 M and 5.0·10-6 M, respectively. Taking into account the relevance of the determination of chloride ion concentration in sweat, the voltammetric method for the determination of halides has been successfully transferred to a Gore-Tex® support to build a first approach to a wearable sensor that facilitates the quantification of this ion in sweat samples. The Gore-Tex® sensor provides a good reproducibility (RSD = 1.61%).

The effect of preparation processes on the physicochemical characteristics and antibacterial activity of chitooligosaccharides.

The bioactivities of chitooligosaccharides are markedly influenced by the degree of acetylation, degree of polymerization or molecular weight and pattern of acetylation. Thus, it is crucial to identify reproducible processes that will give rise to well-defined chitooligosaccharides and establish methods for their posterior physicochemical characterization in order to advance in the knowledge of their bioactivity. Chitooligosaccharides were prepared by two different processes. The first used chitosanase enzymatic hydrolysis and the second consisted of a two-step procedure based on chemical hydrolysis followed by chitosanase hydrolysis. Chitooligosaccharides produced in the second process were composed of 63 % of fully deacetylated sequences and inhibited the growth of Escherichia coli and Listeria monocytogenes. Better antibacterial activity was found for those obtained in the first process composed of 27 % of fully deacetylated sequences. Therefore, a low percentage of free amino groups and the presence of acetylated sequences are necessary in these molecules to exert good antibacterial capacity.

Clinical guideline seom: hereditary colorectal cancer.

Genetic mutations have been identified as the cause of inherited cancer risk in some colon cancer; these mutations are estimated to account for only 5-6 % of colorectal cancer (CRC) cases overall. Up to 25-30 % of patients have a family history of CRC that suggests a hereditary component, common exposures among family members, or a combination of both. Cancers in people with a hereditary predisposition typically occur at an earlier age than in sporadic cases. A predisposition to CRC may include a predisposition to other cancers, such as endometrial cancer. We describe genetics, current diagnosis and management of CRC hereditary syndromes pointing to a multidisciplinary approach to achieve the best results in patients and family outcomes.

Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice.

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥ 7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004-2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2-11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1-8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7-5.4) and higher response rate (OR: 2.1, 95%CI: 1.2-3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.

Antiviral activity of casein and αs2 casein hydrolysates against the infectious haematopoietic necrosis virus, a rhabdovirus from salmonid fish.

Salmonid fish viruses, such as infectious haematopoietic necrosis virus (IHNV), are responsible for serious losses in the rainbow trout and salmon-farming industries, and they have been the subject of intense research in the field of aquaculture. Thus, the aim of this work is to study the antiviral effect of milk-derived proteins as bovine caseins or casein-derived peptides at different stages during the course of IHNV infection. The results indicate that the 3-h fraction of casein and α(S2) -casein hydrolysates reduced the yield of infectious IHNV in a dose-dependent manner and impaired the production of IHNV-specific antigens. Hydrolysates of total casein and α(S2) -casein target the initial and later stages of viral infection, as demonstrated by the reduction in the infective titre observed throughout multiple stages and cycles. In vivo, more than 50% protection was observed in the casein-treated fish, and the kidney sections exhibited none of the histopathological characteristics of IHNV infection. The active fractions from casein were identified, as well as one of the individual IHNV-inhibiting peptides. Further studies will be required to determine which other peptides possess this activity. These findings provide a basis for future investigations on the efficacy of these compounds in treating other viral diseases in farmed fish and to elucidate the underlying molecular mechanisms of action. However, the present results provide convincing evidence in support of a role for several milk casein fractions as suitable candidates to prevent and treat some fish viral infections.

Development and evaluation of a SYBR Green real-time RT-PCR assay for evaluation of cytokine gene expression in horse.

Cytokine secretion is one of the main mechanisms by which the immune system is regulated in response to pathogens. Therefore, the measurement of cytokine expression is fundamental to characterizing the immune response to infections. Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) is widely used to measure cytokine mRNA levels, but assay conditions should be properly evaluated before analyzing important equine infections through relative quantification of gene expression. The aim of this study was to develop and evaluate a set of RT-qPCR assays for a panel of the most common cytokines in horses involved in innate and adaptive immune responses. Eight cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-10, IL-12, TNFα, IFNß and IFNγ) and a housekeeping gene (ß-actin) were detected and amplified with the same annealing temperature in a SYBR Green RT-qPCR assay of samples of mitogen-stimulated peripheral blood mononuclear cells from a healthy horse and whole blood from a horse infected with African horse sickness virus. The method gave good efficiency for all genes tested, allowing quantification of relative expression levels. These SYBR Green RT-qPCR assays may be useful for examining cytokine gene expression in horses in response to exposure to economically important pathogens.

Nano and microparticulate chitosan-based systems for antiviral topical delivery.

Acyclovir (ACV) is one of the drugs of choice for the treatment of epidermal, ocular or systemic herpetic infections. Nevertheless, its trans-mucosal limited absorption and the scarce contact time of the formulation with the mucosal surface - especially in the ocular mucosa - constitute a big limitation of the antiviral efficiency. The most effective way to solve these problems is to increase the quantity and the residence time of the drug over the ocular surface. In order to cope with all these requirements, micro-particles (MPs) and nano-particles (NPs) containing ACV have been developed using cross-linked chitosan with tripolyphosphate (TPP) due to the biocompatibility, bio-adhesion ability and the potential power as penetration enhancer of this polymer. Particles were characterized by Fourier-transformed infrared (FTIR) spectroscopy, X-ray diffraction, SEM, Zeta potential and particle size. Encapsulation efficiency and release profiles in flow through diffusion cells were also determined. Besides the Slug Mucosal Irritation (SMI) assay has been applied as an alternative to the Draize test to predict the mucosal irritation of the selected formulation. FTIR and X-ray results suggested an electrostatic interaction ACV-Chitosan that made ACV be molecularly dispersed within the polymer matrix. Encapsulation efficiency was 75% for MP and 16% for NP. Release profiles in flow through diffusion cells were also determined. From the diffusion profiles, it was found that the amounts of ACV effectively diffused in 24h were 30, 430 and 80 µg for the ACV solution, MP and NP respectively. SMI results showed that chitosan-based particles induced moderate irritation and mild tissue damage, what supposes that ACV-MP constitute a promising alternative for further development of an antiviral formulation.

Schwannoma melanótico: reporte de un caso y revisión de la literatura / Melanotic schwannoma: a case report and literature review

Schwannomas are benign neoplastic lesions which originate from Schwann cells. A rare variant is the melanotic schwannoma. Accurate discrimination of this entity may be difficult due to differential diagnosis with malignant tumors, especially with metastatic melanoma, which has a potential ominous prognosis and a radically different treatment. We report the case of a 60-year-old woman with neurological sensorimotor involvement, presenting progressive caudo-cranial involvement more pronounced on the right side. MRI showed an intradural extramedullary mass with hyperintense signal intensity on T1 and T2 images, whereas no significant increase in signal intensity of the spinal cord was observed. Tumor was resected and sent for anatomopathological analysis which revealed a non-psammomatous melanotic schwannoma.

Los schwannomas son lesiones neoplásicas benignas derivadas de las células de Schwann. Una variante poco frecuente es el schwannoma melanótico. El diagnóstico de esta entidad reviste complejidad debido al diagnóstico diferencial con tumores malignos, especialmente el melanoma metastásico, teniendo este último un potencial pronóstico ominoso y un tratamiento radicalmente distinto. Se realizó una revisión de literatura en relación a un caso clínico de una mujer de 60 años con compromiso neurológico de tipo sensitivo-motor, progresivo caudo-craneal mayor a derecha. La RM demostró una masa intradural extramedular, con hiperintensidad en secuencias T1 e hiposeñal en T2, sin aumento de señal significativo de la médula espinal. El tumor fue resecado revelando en el estudio anatomopatológico un schwannoma melanótico, no psammomatoso. En relación al caso clínico, pudimos observar la importancia del estudio imaginológico con RM y su confirmación anatomopatológica. Recalcamos además, la necesidad del seguimiento a largo plazo.

Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers.

BACKGROUND AND AIMS: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. METHODS AND RESULTS: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance. CONCLUSION: The results confirm the cholesterol lowering properties of nut-enriched diets. They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content, which clearly deserves further study.

Diagnostic performance of PCR and ELISA on blood and milk samples and serological survey for small ruminant lentiviruses in central Spain.

The diagnostic performance of an ELISA for the detection of antibodies to the small ruminant lentiviruses (SRLVs) maedi-visna virus and caprine arthritis-encephalitis virus in milk and corresponding blood samples was evaluated in 50 sheep. The agreement between ELISA results in blood and milk was 90 per cent, and the κ value was 0.79. In addition, a serological survey in the central zone of Spain was performed using milk samples from 413 animals (250 sheep and 163 goats) from 12 flocks/herds. All flocks/herds had some animals that were positive for SRLV. Among the animals, 60.0 per cent of the sheep and 8.0 per cent of the goats tested were seropositive. Each sample was also tested using a PCR technique, which increased the percentage of positive animals detected. Using a combination of ELISA and PCR gave a total of 72.2 per cent of sheep and 28.8 per cent of goats positive for SRLV.

An active DNA vaccine against infectious pancreatic necrosis virus (IPNV) with a different mode of action than fish rhabdovirus DNA vaccines.

Although there are some commercial vaccines available against infectious pancreatic necrosis virus (IPNV), the disease still continues to be a major problem for aquaculture development worldwide. In the current work, we constructed a DNA vaccine against IPNV (pIPNV-PP) by cloning the long open reading frame of the polyprotein encoded by the viral RNA segment A. In vitro, the vaccine is properly translated giving the functional IPNV polyprotein since preVP2, VP2 and VP3 proteins were detected because of the VP4-protease cleavage. EPC cells transfected with the vaccine plasmid expressed the viral proteins and induced the expression of type I interferon (IFN)-induced Mx genes. Furthermore, IPNV synthesized proteins seemed to assemble in virus-like particles as evidenced by electron microscopy. In vivo, rainbow trout specimens were intramuscularly injected with the vaccine and expression of immune-relevant genes, the presence of neutralizing antibodies and effect on viral load was determined. The pIPNV-PP vaccine was expressed at the injection site and up-regulated MHC Ialpha, MHC IIalpha, type-I interferon (IFN), Mx, CD4 and CD8alpha gene expression in the muscle, head kidney or spleen, although to a much lower extent than the up-regulations observed in response to an effective DNA vaccine against viral hemorrhagic septicaemia virus (VHSV). However, the IPNV vaccine was also very effective in terms of acquired immunity since it elicited neutralizing antibodies (in 6 out of 8 trout fingerlings) and decreased 665-fold the viral load after IPNV infection. The effectiveness of this new IPNV DNA vaccine and its possible mechanism of action are discussed and compared to other viral vaccines.

Gastric residual volume during enteral nutrition in ICU patients: the REGANE study.

OBJECTIVE: To compare the effects of increasing the limit for gastric residual volume (GRV) in the adequacy of enteral nutrition. Frequency of gastrointestinal complications and outcome variables were secondary goals. DESIGN: An open, prospective, randomized study. SETTING: Twenty-eight intensive care units in Spain. PATIENTS: Three hundred twenty-nine intubated and mechanically ventilated adult patients with enteral nutrition (EN). INTERVENTIONS: EN was administered by nasogastric tube. A protocol for management of EN-related gastrointestinal complications was used. Patients were randomized to be included in a control (GRV = 200 ml) or in study group (GRV = 500 ml). MEASUREMENTS AND RESULTS: Diet volume ratio (diet received/diet prescribed), incidence of gastrointestinal complications, ICU-acquired pneumonia, days on mechanical ventilation and ICU length of stay were the study variables. Gastrointestinal complications were higher in the control group (63.6 vs. 47.8%, P = 0.004), but the only difference was in the frequency of high GRV (42.4 vs. 26.8%, P = 0.003). The diet volume ratio was higher for the study group only during the 1st week (84.48 vs. 88.20%) (P = 0.0002). Volume ratio was similar for both groups in weeks 3 and 4. Duration of mechanical ventilation, ICU length of stay or frequency of pneumonia were similar. CONCLUSIONS: Diet volume ratio of mechanically ventilated patients treated with enteral nutrition is not affected by increasing the limit in GRV. A limit of 500 ml is not associated with adverse effects in gastrointestinal complications or in outcome variables. A value of 500 ml can be equally recommended as a normal limit for GRV.

Salmonid fish viruses and cell interactions at early steps of the infective cycle.

A flow cytometric virus-binding assay that directly visualizes the binding and entry of infectious pancreatic necrosis virus (IPNV), infectious haematopoietic necrosis virus (IHNV) and virus haemorrhagic septicaemia virus (VHSV) to several cell lines was established. The highest efficiency of binding was shown by the BF-2 cell line and this was used to study, at the attachment level, the interactions of these cells with salmonid fish viruses in coinfections, and to further determine if the earliest stage of the viral growth cycle could explain the previously described loss of infectivity of IHNV when IPNV is present. Our results demonstrated that IPNV binds to around 88% of cells either in single or dual infections, whereas IHNV attachment always decreased in the presence of any of the other viruses. VHSV binding was not affected by IPNV, but coinfection with IHNV reduced the percentage of virus-binding cells, which suggests competition for viral receptors or co-receptors. Internalization of the adsorbed IHNV was not decreased by coinfection with IPNV, so the hypothetical competence could be restricted to the binding step. Treatment of the cells with antiviral agents, such as amantadine or chloroquine, did not affect the binding of IPNV and VHSV, but reduced IHNV binding by more than 30%. Tributylamine affected viral binding of the three viruses to different degrees and inhibited IPNV or IHNV entry in a large percentage of cells treated for 30 min. Tributylamine also inhibited IHNV cytopathic effects in a dose-dependent manner, decreasing the virus yield by 4 log of the 50% endpoint titre, at 10 mm concentration. IPNV was also inhibited, but at a lower level. The results of this study support the hypothesis that IHNV, in contrast to VHSV or IPNV, is less efficient at completing its growth cycle in cells with a simultaneous infection with IPNV. It can be affected at several stages of viral infection and is more sensitive to the action of antiviral compounds.

Comparative expression analysis of the renin-angiotensin system components between white and brown perivascular adipose tissue.

Recent studies have demonstrated that the rat adipose tissue expresses some of the components necessary for the production of angiotensin II (Ang II) and the receptors mediating its actions. The aim of this work is to characterize the expression of the renin-angiotensin system (RAS) components in perivascular adipose tissue and to assess differences in the expression pattern depending on the vascular bed and type of adipose tissue. We analyzed Ang I and Ang II levels as well as mRNA levels of RAS components by a quantitative RT-PCR method in periaortic (PAT) and mesenteric adipose tissue (MAT) of 3-month-old male Wistar-Kyoto rats. PAT was identified as brown adipose tissue expressing uncoupling protein-1 (UCP-1). It had smaller adipocytes than those from MAT, which was identified as white adipose tissue. All RAS components, except renin, were detected in both PAT and MAT. Levels of expression of angiotensinogen, Ang-converting enzyme (ACE), and ACE2 were similar between PAT and MAT. Renin receptor expression was five times higher, whereas expression of chymase, AT(1a), and AT(2) receptors were significantly lower in PAT compared with MAT respectively. In addition, three isoforms of the AT(1a) receptor were found in perivascular adipose tissue. The AT(1b) receptor was found at very a low expression level. Ang II levels were higher in MAT with no differences between tissues in Ang I. The results show that the RAS is differentially expressed in white and brown perivascular adipose tissues implicating a different role for the system depending on the vascular bed and the type of adipose tissue.