On the existence of supersolid helium-4 monolayer films

Extensive Monte Carlo simulations of helium-4 monolayer films adsorbed on weak substrates have been carried out, aimed at ascertaining the possible occurrence of a quasi-two-dimensional supersolid phase. Only crystalline films not registered with underlying substrates are considered. Numerical results yield strong evidence that helium-4 will not form a supersolid film on {any} substrate strong enough to stabilize a crystalline layer. On weaker substrates, continuous growth of a liquid film takes place

Influencia de la inclinación acetabular en la luxación de la artroplastia parcial de cadera

La luxación de la prótesis parcial de cadera, representa en la actualidad un grave problema de incapacidad para el paciente, debido no solo, a la complicación de la marcha en sí, sino a todas aquellas derivadas de la estancia hospitalaria de estos pacientes en nuestros centros. Respecto a la vía de abordaje, se ha sentado una mayor incidencia de luxaciones en la vía posterolateral, frente a las anteriores o laterales transtrocantéreas en decúbito supino. Objetivo: evaluar la influencia del ángulo de inclinación anatómico del acetábulo, techo y cobertura en la luxación de la artroplastia parcial de cadera. Material y método: el estudio incluyó un total de 718 pacientes intervenidos por fractura cervical de fémur, durante los años de 1992 a 2005. Las prótesis parciales implantadas fueron del modelo Thompson; los tipos de vías de abordaje quirúrgico utilizados fueron; la anterior de Smith Petersen, y la posterior de Gibson Moore. Se realizaron las mediciones radiográficas del ángulo formado entre las línea trazada en el borde externo del acetábulo y la línea biisquiática. Resultados: Del total de pacientes incluidos en el estudio el número de luxaciones fue de 24 prótesis, lo que representa el 3,3 %. La edad media fue de 84 años, y un intervalo de 76 a 92 años. El sexo predominante fue el femenino con un 83%. La vía más utilizada fue la anterior con un 67 %. El mayor porcentaje de luxación fue para aquellas pacientes con un ángulo de inclinación anatómico del acetábulo de > 55º. El tiempo medio seguimiento hasta producirse la luxación fue de 35 días y un intervalo entre 1 a 89 días. El tratamiento más frecuente fue el conservador 88%. Conclusión: El presente estudio demuestra que la luxación temprana de una prótesis parcial de cadera está directamente relacionado con un ángulo de inclinación anatómico del acetábulo mayor de 55º.The dislocation of partial hip replacements represents an important postoperative complication. Apart from the most important problem which is patient mobility, another aspect is the prolonged hospital stay detrimental to patient health and the evonawy of hospital. With respect to the incidence of pos- toperative dislocations and the type of surgical approach, it seated that there is a greater incidence using the lateroposterior hip sur- gical approach, in comparision to the anterior or lateral access. Objective: To evidence the influence of acetabular inclination in postoperative dislocations of partial hip arthroplasty. Methods: A study involuing 718 cases of intervened femoral neck fractures using Thompson endoprosthesis during the period including 1992 to 2005.With respect to type of surgical approaches, these included the Smith-Petersen anterior and the Gibson-Moore posterior access. The acetabular inclination was measurements radiologi- cally, obtaining the angle between the bi-ischial line and the exter- nal border of the acetabulum. Results: A total of twentyfour (24) prosthesis suffered dislocation, with respect to the total of seven hundred and eighteen (718) patients intervened for partial hip arth- roplasty, representing 3,3% of the total. The average age for dislocated arthroplasties was 84 years, with a range between 76-92 years, and the predominant sex was female. Concerning surgical access, the anterior was the most frecuently used (67%). There was found to be a greater percentage of dislo- cated arthroplasties when the angle of acetabular inclination exce- eded fifty five (55º) degrees. The average time elapsed before dis- location was diagnosed included a 35 days time period, with a range between to 89 days. The most frequent management of pos- toperative dislocations was conservative treatment. Conclusion: This study demonstrates that when the acetabular inclination is greater than 55º, there is a greater incidence of early dislocation of partial hip replacements

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy

Biobased polymers derived from itaconic acid bearing clickable groups with potent antibacterial activity and negligible hemolytic activity.

Herein, we report, for the first time, the synthesis of clickable polymers derived from biobased itaconic acid, which was then used for the preparation of novel cationic polymers with antibacterial properties and low hemotoxicity via click chemistry. Itaconic acid (IA) was subjected to chemical modification by incorporating clickable alkyne groups on the carboxylic acids. The resulting monomer with pendant alkyne groups was easily polymerized and copolymerized with dimethyl itaconate (DMI) by radical polymerization. The feed molar ratio of comonomers was varied to precisely tune the content of alkyne groups in the copolymers and the amphiphilic balance. Subsequently, an azide with a thiazole group, which is a component of the vitamin thiamine (B1), was attached onto the polymers by copper-catalyzed azidealkyne cycloaddition (CuAAC) click chemistry leading to triazole linkages. N-Alkylation reactions of the thiazole and triazole groups with methyl and butyl iodides provide the corresponding itaconate derivatives with pendant azolium groups. The copolymers with variable cationic charge densities and hydrophobic/ hydrophilic balances, depending on the comonomer feed ratio, display potent antibacterial activity against Gram-positive bacteria, whereas the activity was almost null against Gram-negative bacteria. Hemotoxicity assays demonstrated that the copolymers exhibited negligible hemolysis and excellent selectivity, more than 1000-fold, for Gram-positive bacteria over human red blood cells.post-print1945 K

Solidification of small para-H2 clusters at zero temperature

We have determined the ground-state energies of para-H$_2$ clusters at zero temperature using the diffusion Monte Carlo method. The liquid or solid character of each cluster is investigated by restricting the phase through the use of proper importance sampling. Our results show inhomogeneous crystallization of clusters, with alternating behavior between liquid and solid phases up to N=55. From there on, all clusters are solid. The ground-state energies in the range N=13--75 are established and the stable phase of each cluster is determined. In spite of the small differences observed between the energy of liquid and solid clusters, the corresponding density profiles are significantly different, feature that can help to solve ambiguities in the determination of the specific phase of H$_2$ clusters.Comment: 17 pages, accepted for publication in J. Phys. Chem.

IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies

Antifúngic; Candidèmia; DesescaladaAntifúngico; Candidemia; DesescaladaAntifungal; Candidemia; De-escalationBackground There are no clear criteria for antifungal de-escalation after initial empirical treatments. We hypothesized that early de-escalation (ED) (within 5 days) to fluconazole is safe in fluconazole-susceptible candidemia with controlled source of infection. Methods This is a multicenter post hoc study that included consecutive patients from 3 prospective candidemia cohorts (2007–2016). The impact of ED and factors associated with mortality were assessed. Results Of 1023 candidemia episodes, 235 met inclusion criteria. Of these, 54 (23%) were classified as the ED group and 181 (77%) were classified as the non-ED group. ED was more common in catheter-related candidemia (51.9% vs 31.5%; P = .006) and episodes caused by Candida parapsilosis, yet it was less frequent in patients in the intensive care unit (24.1% vs 39.2%; P = .043), infections caused by Nakaseomyces glabrata (0% vs 9.9%; P = .016), and candidemia from an unknown source (24.1% vs 47%; P = .003). In the ED and non-ED groups, 30-day mortality was 11.1% and 29.8% (P = .006), respectively. Chronic obstructive pulmonary disease (odds ratio [OR], 3.97; 95% confidence interval [CI], 1.48–10.61), Pitt score > 2 (OR, 4.39; 95% CI, 1.94–9.20), unknown source of candidemia (OR, 2.59; 95% CI, 1.14–5.86), candidemia caused by Candida albicans (OR, 3.92; 95% CI, 1.48–10.61), and prior surgery (OR, 0.29; 95% CI, 0.08–0.97) were independent predictors of mortality. Similar results were found when a propensity score for receiving ED was incorporated into the model. ED had no significant impact on mortality (OR, 0.50; 95% CI, 0.16–1.53). Conclusions Early de-escalation is a safe strategy in patients with candidemia caused by fluconazole-susceptible strains with controlled source of bloodstream infection and hemodynamic stability. These results are important to apply antifungal stewardship strategies.This research forms part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union that receives support from the European Union´s Horizon 2020 Research and Innovation Program. This study has been cofunded by the European Regional Development Fund. E. M.-G. (PI18/01061), P. P.-A. (“Rio Hortega” contract CM18/00132), M. F.-R. (“Miguel Servet” contract CP18/00073), and C. G.-V. (FIS PI18/01061) have received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III

Dietary and health profiles of spanish women in preconception, pregnancy and lactation

Abstract: The nutritional status and lifestyle of women in preconception, pregnancy and lactation determine maternal, fetal and child health. The aim of this cross-sectional study was to evaluate dietary patterns and lifestyles according the perinatal physiological status in a large sample of Spanish women. Community pharmacists that were previously trained to collect the data recruited 13,845 women. General information, anthropometric measurements, physical activity, unhealthy habits and dietary data were assessed using a validated questionnaire. Mean values and percentages were used as descriptive statistics. The t-test, ANOVA or chi-squared test were used to compare groups. A score that included dietary and behavioral characteristics was generated to compare lifestyles in the three physiological situations. The analysis revealed that diet quality should be improved in the three stages, but in a different manner. While women seeking a pregnancy only met dairy recommendations, those who were pregnant only fulfilled fresh fruits servings and lactating women only covered protein group requirements. In all cases, the consumption allowances of sausages, buns and pastries were exceeded. Food patterns and unhealthy behaviors of Spanish women in preconception, pregnancy and lactation should be improved, particularly in preconception. This information might be useful in order to implement educational programs for each population group

Encuesta seroepidemiológica de pian en la Costa Pacífica colombiana

Yaws has been endemic in the Pacific Coast of Colombia, but the actual prevalence is not known. For this reason we carried out a survey in the communities of this part of the countty where cases had been observed. The active search for cases was based on clinical observations of patients with dermatological disorders, to whom VDRL and FA-ABS tests were administered. The epidemiological survey included 4 intradomiciliary cases for each of the clinical patients detected and also 42 extradomiciliary cases. From a total of 1,830 persons examined, only 6 presented positive results for the VDRL and FTA-ABS tests, which represents a treponema infection prevalence of 0.3%. None of the clinically suspected yaw cases reacted positively to the mentioned tests. These findings permit us to conclude that yaws is not a public health problem in the Pacific Coast of Colombia, and that the sole use of clinical parameters induces to mistaken diagnosis.El pian ha sido endémico en la Costa Pacífica colombiana, pero actualmente su frecuencia real es desconocida, razón por la cual se realizó un estudio en las comunidades de esta zona del país donde se habían conocido casos de pian. Se hizo búsqueda activa de casos clínicos sospechosos a través de examen físico de personas con problemas dermatológicos; a todos ellos se les practicaron exámenes serológicos de VDRL y FTA-ABS. Por cada caso clínico sospechoso de pian, se estudiaron - por clínica y serologia - 4 contactos intradomiciliarios y 42 contactos extradomiciliarios. De las 1.830 personas examinadas, sólo 6 fueron reactivas a las pruebas de VDRL y FTA-ABS, lo cual representa una prevalencia de treponematosis de 0,3%. Ninguna de las pruebas serológicas fue reactiva en los casos clínicos sospechosos de pian. Esto nos lleva a concluir que, en la Costa Pacífica colombiana, el pian no es un problema de salud pública y que se registran como pian otras enfermedades cuando el diagnóstico tiene sólo bases clínicas