Preparation, Supramolecular Organization, and On-Surface Reactivity of Enantiopure Subphthalocyanines: From Bulk to 2D-Polymerization.

The development of chiral materials is severely limited by the challenge to achieve enantiopure derivatives with both configurational stability and good optoelectronic properties. Herein we demonstrate that enantiopure subphthalocyanines (SubPcs) fulfill such demanding requirements and bear the prospect of becoming components of chiral technologies. Particularly, we describe the synthesis of enantiopure SubPcs and assess the impact of chirality on aspects as fundamental as the supramolecular organization, the behavior in contact with metallic surfaces, and the on-surface reactivity and polymerization. We find that enantiopure SubPcs remarkably tend to organize in columnar polar assemblies at the solid state and highly ordered chiral superstructures on Au(111) surfaces. At the metal interface, such SubPcs are singled out by scanning tunneling microscopy. DFT calculations suggest that SubPcs undergo a bowl-to-bowl inversion that was shown to be dependent on the axial substituent. Finally, we polymerize by means of on-surface synthesis a highly regular 2D, porous and chiral, π-extended polymer that paves the way to future nanodevice fabrication.

Discarding metal incorporation in pyrazole macrocycles and the role of the substrate on single-layer assemblies.

Pyrazole derivatives are key in crystal engineering and liquid crystal fields and thrive in agriculture, pharmaceutical, or biomedicine industries. Such versatility relies in their supramolecular bond adaptability when forming hydrogen bonds or metal-pyrazole complexes. Interestingly, the precise structure of pyrazole-based macrocycles forming widespread porous structures is still unsolved. We bring insight into such fundamental question by studying the self-assembled structures of a bis-pyrazole derivative sublimed in ultra-high-vacuum conditions (without solvents) onto the three (111) noble metal surfaces. By means of high-resolution scanning tunneling microscopy that is validated by gas phase density functional theory calculations, we find a common hexagonal nanoporous network condensed by triple hydrogen bonds at the molecule-metal interface. Such assembly is disrupted and divergent after annealing: (i) on copper, the molecular integrity is compromised leading to structural chaos, (ii) on silver, an incommensurate new oblique structure requiring molecular deprotonation is found and, (iii) on gold, metal-organic complexes are promoted yielding irregular chain structures. Our findings confirm the critical role of these metals on the different pyrazole nanoporous structure formation, discarding their preference for metal incorporation into the connecting nodes whenever there is no solvent involved.

Ferromagnetism on an atom-thick & extended 2D metal-organic coordination network.

Ferromagnetism is the collective alignment of atomic spins that retain a net magnetic moment below the Curie temperature, even in the absence of external magnetic fields. Reducing this fundamental property into strictly two-dimensions was proposed in metal-organic coordination networks, but thus far has eluded experimental realization. In this work, we demonstrate that extended, cooperative ferromagnetism is feasible in an atomically thin two-dimensional metal-organic coordination network, despite only ≈ 5% of the monolayer being composed of Fe atoms. The resulting ferromagnetic state exhibits an out-of-plane easy-axis square-like hysteresis loop with large coercive fields over 2 Tesla, significant magnetic anisotropy, and persists up to TC ≈ 35 K. These properties are driven by exchange interactions mainly mediated by the molecular linkers. Our findings resolve a two decade search for ferromagnetism in two-dimensional metal-organic coordination networks.

Searching for kagome multi-bands and edge states in a predicted organic topological insulator.

Recently, mixed honeycomb-kagome lattices featuring metal-organic networks have been theoretically proposed as topological insulator materials capable of hosting nontrivial edge states. This new family of so-called "organic topological insulators" are purely two-dimensional and combine polyaromatic-flat molecules with metal adatoms. However, their experimental validation is still pending given the generalized absence of edge states. Here, we generate one such proposed network on a Cu(111) substrate and study its morphology and electronic structure with the purpose of confirming its topological properties. The structural techniques reveal a practically flawless network that results in a kagome network multi-band observed by angle-resolved photoemission spectroscopy and scanning tunneling spectroscopy. However, at the network island borders we notice the absence of edge states. Bond-resolved imaging of the network exhibits an unexpected structural symmetry alteration that explains such disappearance. This collective lifting of the network symmetry could be more general than initially expected and provide a simple explanation for the recurrent experimental absence of edge states in predicted organic topological insulators.

Towards a unification of treatments and interventions for tinnitus patients: The EU research and innovation action UNITI.

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.

Unification of Treatments and Interventions for Tinnitus Patients (UNITI): a study protocol for a multi-center randomized clinical trial.

BACKGROUND: Tinnitus represents a relatively common condition in the global population accompanied by various comorbidities and severe burden in many cases. Nevertheless, there is currently no general treatment or cure, presumable due to the heterogeneity of tinnitus with its wide variety of etiologies and tinnitus phenotypes. Hence, most treatment studies merely demonstrated improvement in a subgroup of tinnitus patients. The majority of studies are characterized by small sample sizes, unstandardized treatments and assessments, or applications of interventions targeting only a single organ level. Combinatory treatment approaches, potentially targeting multiple systems as well as treatment personalization, might provide remedy and enhance treatment responses. The aim of the present study is to systematically examine established tinnitus therapies both alone and in combination in a large sample of tinnitus patients. Further, it wants to provide the basis for personalized treatment approaches by evaluating a specific decision support system developed as part of an EU-funded collaborative project (Unification of treatments and interventions for tinnitus patients; UNITI project). METHODS/STUDY DESIGN: This is a multi-center parallel-arm randomized clinical trial conducted at five different clinical sites over the EU. The effect of four different tinnitus therapy approaches (sound therapy, structured counseling, hearing aids, cognitive behavioral therapy) applied over a time period of 12 weeks as a single or rather a combinatory treatment in a total number of 500 chronic tinnitus patients will be investigated. Assessments and interventions are harmonized over the involved clinical sites. The primary outcome measure focuses on the domain tinnitus distress assessed via the Tinnitus Handicap Inventory. DISCUSSION: Results and conclusions from the current study might not only provide an essential contribution to combinatory and personalized treatment approaches in tinnitus but could also provide more profound insights in the heterogeneity of tinnitus, representing an important step towards a cure for tinnitus. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663828 . Registered on 11 December 2020.

Complicaciones infecciosas de la ventilación mecánica. Necesidad de estrategias de prevención / Mechanic ventilation complicated with infections: Need of preventive measures

Hemos leído con gran interés el artículo de Varón-Vega FA et al "Traqueobronquitis y neumonía asociada a ventilación mecánica en unidades de cuidado intensivo de Latinoamérica: epidemiología, curso clínico y desenlaces (estudio LATINAVE)" Es conocido que la neumonía asociada a ventilación mecánica (NAVM) se relaciona con un incremento de la estancia en las Unidades de Cuidados Intensivos (UCI) y en el hospital, mayor consumo de antibióticos, un alargamiento de la duración de la ventilación mecánica y un aumento de la mortalidad bruta y atribuida

We have read with great interest the article by Varón-Vega FA et al "Tracheobronchitis and ventilator-associated pneumonia in intensive care units in Latin America: epidemiology, clinical course and outcomes (LATINAVE study)" It is known that ventilator-associated pneumonia (VAP) is associated with an increase in intensive care unit (ICU) and hospital stay, higher antibiotic consumption, a lengthening of the duration of mechanical ventilation and an increase in crude and attributed mortality.

[Community-acquired pneumonia due to Legionella pneumophila serogroup 1. Study of 97 cases]. / Neumonía comunitaria por Legionella pneumophila serogrupo 1. Estudio de 97 casos.

INTRODUCTION: Legionella pneumophila is the causal agent of 5% to 12% of sporadic community-acquired pneumonia cases, though rates are changing with the use of new diagnostic methods. METHODS: This is a retrospective study of all patients admitted to our hospital with community-acquired pneumonia due to Legionella pneumophila between 1997 and 2001. Diagnostic criteria included either a positive Legionella serogroup 1 urinary antigen test or seroconversion and a chest radiograph consistent with pneumonia. RESULTS: A total of 97 patients were studied. Ninety cases (92.8%) were community-acquired and 7 (7.2%) were associated with travelling. In 82 cases (84.5%) the presentation was sporadic. Seventy-five patients were smokers (77.3%). The most common symptoms were fever in 91 patients (93.8%) and cough in 67 (68.1%). In five patients (5.2%) creatine phosphokinase concentrations were over 5 times their baseline values (in two over 100 times); four of these patients presented acute renal failure. Seroconversion was observed in 23/42 patients (54.8%). There were no statistically significant differences between the administration of erythromycin or clarithromycin in monotherapy, or in combination with rifampin. Nineteen patients (19.6%) presented acute renal failure and mechanical ventilation was necessary in 22 (22.7%). Twelve patients died (12.5%). Independent prognostic factors associated with death included respiratory rate > 30 breaths/min, urea > 60 mg/dL and PaO2 < 60 mmHg. A significant linear association was found between severity scale scores and the presence of complications or mortality. CONCLUSION: The Legionella urinary antigen test permits early diagnosis and treatment of this disease. The severity scale is an indicator of complications or death.

Listeriosis. Estudio de 16 años en un hospital terciario en España / Listeriosis. A 16-year survey in a tertiary hospital in Spain

Objetivo: Revisar los casos de listeriosis recogidos en nuestro hospital durante los últimos 16 años. Métodos: Se revisaron retrospectivamente los casos de listeriosis recogidos en el Hospital de Cruces (Vizcaya, España), desde enero de 1990 hasta enero de 2006. Los pacientes se dividieron en 3 grupos: adultos no gestantes (38 pacientes, 63.3%), infección perinatal (7 gestantes y 11 neonatos, 30%) e infección pediátrica no perinatal (4 niños, 6.6%). Resultados: En el grupo de adultos el 89.4% tenía algún factor predisponente, predominando la neoplasia y la hepatopatía. En 17/38 hubo afectación del SNC (13 meningitis y 4 encefalitis) y en 16/38 sepsis. Otras manifestaciones fueron: peritonitis bacteriana espontánea (4 casos) y pericarditis (1 caso). La mortalidad fue del 29%. En los pacientes oncológicos la sepsis fue más frecuente que la enfermedad neurológica (p = 0.05) y la mortalidad fue superior que en otros enfermos crónicos (p = 0.003). En las gestantes la evolución fue buena y 4/7 tuvieron recién nacidos a término sanos. En los neonatos la infección fue de comienzo precoz en 10 casos, con diagnóstico de sepsis en el 60% y de meningitis en 40%. Fallecieron 2 neonatos (18%), ambos prematuros y con sepsis de comienzo precoz. En el grupo de listeriosis pediátrica no perinatal hubo 3 casos con meningitis y uno con invaginación intestinal y aislamiento de Listeria en adenopatía mesentérica, todos con evolución favorable. La mortalidad global fue del 21.6%. El serotipo predominante fue el 4b. Conclusiones: Las infecciones por L. monocytogenes se asocian a una alta morbi-mortalidad. Los factores predisponentes han sido determinantes en la evolución de los pacientes.