Chromosome-Y haplogroups in Asturias (Northern Spain) and their association with severe COVID-19.

The main objective of this study was to determine whether the common Y-haplogroups were be associated with the risk of developing severe COVID-19 in Spanish male. We studied 479 patients who required hospitalization due to COVID-19 and 285 population controls from the region of Asturias (northern Spain), They were genotyped for several polymorphisms that define the common European Y-haplogroups. We compared the frequencies between patients and controls aged ≤ 65 and >65 years. There were no different haplogroup frequencies between the two age groups of controls. Haplogroup R1b was less common in patients aged ≤65 years. Haplogroup I was more common in the two patient´s groups compared to controls (p = 0.02). Haplogroup R1b was significantly more frequent among hypertensive patients, without difference between the hypertensive and normotensive controls. This suggested that R1b could increase the risk for severe COVID-19 among male with pre-existing hypertension. In conclusion, we described the Y-haplogroup structure among Asturians. We found an increased risk of severe COVID-19 among haplogroup I carriers, and a significantly higher frequency of R1b among hypertensive patients. These results indicate that Y-chromosome variants could serve as markers to define the risk of developing a severe form of COVID-19.

Feasibility of allogeneic hematopoietic stem cell transplantation in advanced age.

Although it is known that increasing age is associated with increased morbidity and mortality in allogeneic transplantation (allo-HSCT), individualization of the process may allow to perform it in progressively older patients.This study analyzed the outcome of 97 patients older than 60 years with a first allo-HSCT performed at our institution between 2011 and 2019.Median age was 66 years (range 60-79) and 15.4% were older than 70 years. The most frequent diagnosis was acute leukemia (50.5%), and 58.8% received a myeloablative conditioning. With a median follow-up of 33.9 months (range 7.9-111.5), at 3-years overall survival (OS) was 50%; progression-free survival (PFS), 46%; cumulative incidence of relapse, 22%; and non-relapse mortality (NRM), 32%. There were no significant differences in OS (p = 0.415), PFS (p = 0.691), cumulative incidence of relapse (p = 0.357) or NRM (p = 0.658) between patients of 60-64 years (n = 37), 65-69 (n = 45) and ≥ 70 years (n = 15). No differences were observed either depending on the intensity of the conditioning regimen in terms of OS (p = 0.858), PFS (p = 0.729), cumulative incidence of relapse (p = 0.416) or NRM (p = 0.270).In conclusion, older adults can safely and effectively undergo allo-HSCT with proper patient selection and individualized transplantation procedures.

Ultrasound and Anatomical Study of Accessing the Nerves in the Knee by Fascial Planes.

The fascia is an undifferentiated mesenchymal tissue related to the peripheral nerves. Both can be identified by ultrasound, which is useful when performing peripheral nerve blocks. However, there is no unanimity about the approaching point of each nerve, nor is there a consensus on how to name the appropriate infiltration zone, although the paraneural zone is frequently mentioned. The aims of this study were to determine if ultrasound is accurate for identifying the fascial planes and the paraneural space of the nerves in the knee, infiltrating them, and achieving a correct anatomical diffusion, as well as for establishing access routes to avoid intraneural infiltration. The study was performed in 16 cryopreserved lower extremities of the dissection room of the Faculty of Medicine and Health Sciences, University of Barcelona. Nerves of the knee were injected with colorant guided by ultrasound after they were visualized. Correct location of the nerves by ultrasound was achieved in 98.75% of the cases, correct visualization of the needle by ultrasound in 82.5%, the hypoechogenic image around the nerve after infiltration in 82.5%, and a correct paraneural infiltration in 76.25% of cases. With these results, we can conclude that high-definition ultrasound enables location of the peripheral nerves and adjacent structures as well as the fasciae that surround them, and therefore allows performance of infiltrations in the paraneural spaces.

Mitochondrial Heteroplasmy as a Marker for Premature Coronary Artery Disease: Analysis of the Poly-C Tract of the Control Region Sequence.

Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production and involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs. 21.21%, p < 0.01) and dyslipidemia (38.83% vs. 28.41%, p = 0.02) were significantly more frequent among STEMI patients. Moreover, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI male patients than in controls. The OR associated C16223T mtDNA with the increased presence of cardiovascular risk factors. Our data suggest that mtDNA 16223T and heteroplasmy may be associated with unstable premature atherosclerosis disease in men. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated with C16223T mtDNA, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Preventing exposure to the damaging mechanisms associated with CVRFs is of utmost importance.

Anatomical Changes of Full-Thickness Macular Hole Documented by Microscope-Integrated Spectral-Domain Optical Coherence Tomography.

BACKGROUND AND OBJECTIVE: To evaluate anatomical changes of idiopathic macular hole (MH) after internal limiting membrane removal and after passive suction at the hole's borders using microscope-integrated intraoperative optical coherence tomography (iOCT). PATIENTS AND METHODS: Five eyes of five subjects with full-thickness idiopathic MH underwent phacoemulsification, intraocular lens implantation, pars plana vitrectomy, and internal limiting membrane (ILM) removal. iOCT was performed after ILM removal and after passive suction at the hole's borders. RESULTS: iOCT showed decreased MH diameter after ILM removal in all cases. Passive suction achieved complete apposition of borders. All cases presented successful postsurgical closure. CONCLUSIONS: iOCT provides anatomical information during MH surgery that may impact surgical decision-making by allowing a real-time evaluation of structures. iOCT with preservative-free triamcinolone acetonide enhanced ILM visualization. Its use is superior to iOCT alone for the identification of vitreomacular interface structures. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e105-e111.].

Preparation of acrylic bone cements for vertebroplasty with bismuth salicylate as radiopaque agent.

One of the problems of percutaneous vertebroplasty attributed to the use of acrylic cements is related to the radiopacity of the formulation. The use of bismuth salicylate as the radiopaque agent is proposed in this work, taking into account the high radiopacity of organobismuth compounds used in dental applications and the possible analgesic effect of salicylic acid. Various cements formulated with this compound (some of them modified with polyethylene oxide) were examined. Setting parameters, mechanical properties, rheological behaviour, injectability, radiopacity and biocompatibility were studied for a variety of formulations, showing that the cement formulations containing bismuth salicylate have a higher radiopacity and better injection properties than commercial bone cement preparations and present good mechanical properties.

Mitochondrially Targeted Nanoparticles Based on α-TOS for the Selective Cancer Treatment.

The aim of this work is the preparation of an active nanovehicle for the effective administration of α-tocopheryl succinate (α-TOS). α-TOS is loaded in the core of nanoparticles (NPs) based on amphiphilic pseudo-block copolymers of N-vinyl pyrrolidone and a methacrylic derivative of α-TOS. These well-defined spherical NPs have sizes below 165 nm and high encapsulation efficiencies. In vitro activity of NPs is tested in hypopharynx squamous carcinoma (FaDu) cells and nonmalignant epithelial cells, demonstrating that the presence of additional α-TOS significantly enhances its antiproliferative activity; however, a range of selective concentrations is observed. These NPs induce apoptosis of FaDu cells by activating the mitochondria death pathway (via caspase-9). Both loaded and unloaded NPs act via complex II and produce high levels of reactive oxygen species that trigger apoptosis. Additionally, these NPs effectively suppress the vascular endothelial growth factor (VEGF) expression of human umbilical vein endothelial cells (HUVECs). These results open the possibility to use this promising nanoformulation as an α-TOS delivery system for the effective cancer treatment, effectively resolving the current limitations of free α-TOS administration.

Self-curing controlled release systems for steroids. Application of prednisolone-based polymeric systems to ear diseases.

An injectable delivery system for prednisolone has been prepared based on a self-curing formulation comprised of poly(methyl methacrylate) particles and hydroxyethyl methacrylate as monomer. The polymerisation reaction was initiated by the redox system 4,4'-bis (dimethylaminobenzydrol)/benzoyl peroxide (BZN/BPO) and followed at 25 degrees C by measuring the time-temperature profile. A maximum temperature of 53 degrees C and a setting time of 15 min were obtained, calculated according to standard specifications. The swelling of the cured system was studied in phosphate-buffered saline (PBS) at 37 degrees C giving a hydration degree at equilibrium of 20%. The swelling kinetics fitted a fickian behaviour at the initial stages of the experiments, with a diffusion coefficient of 0.72 x 10(-7) cm2/s. The release of the drug was sustained from the beginning without an initial drug burst. The study of the wettability showed a rather hydrophilic character of the surface of the loaded system, and the biocompatibility evaluated through MTT assay revealed the absence of cytotoxicity due to the release of toxic substances.

Evaluation of drug delivery characteristics of microspheres of PMMA-PCL-cholesterol obtained by supercritical-CO2 impregnation and by dissolution-evaporation techniques.

Poly(methyl methacrylate), PMMA, and of PMMA/Poly(epsilon-caprolactone), PCL, microspheres were loaded with different amounts of cholesterol by using a supercritical carbon dioxide (SC-CO2) impregnation process in order to use a clean technique with the absence of organic solvents, and to provide information for the infusion of additives into nonporous polymeric substrates. A conventional dissolution-evaporation method was also used to obtain PMMA and PMMA-PCL microparticles loaded with cholesterol. The obtained microspheres were characterized by environmental scanning electronic microscope, ESEM, nuclear magnetic resonance spectroscopy, NMR, and differential scanning calorimetry, DSC, thermal analysis. A comparison of drug release from particles obtained using both methods, the supercritical and the conventional, is presented.

Hydrophilic polymer drug from a derivative of salicylic acid: synthesis, controlled release studies and biological behavior.

Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The reactivity ratios of both monomers have been determined by 1H NMR spectra by applying non-linear least square treatments to the copolymerization equation (terminal model), and the kinetic parameters obtained indicated that the microstructure of copolymer chains is homogeneous, with a random distribution of the active HTRF units along the copolymer chains. That means that for the copolymer system THDMA22 used in this work, HTRF units are mainly isolated in relatively long DMA sequences. Therefore, in this structure the intramolecular interactions between adjacent HTRF units are negligible. Release of Triflusal from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4 and 10 and 37 degrees C. The system showed an interesting pseudo-zero order release profile at pH = 7.4 during several months. It has been also evaluated the pharmacological activity and the behavior of the system in contact with biological media. In this sense, we have carried out some in vitro studies about the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate that this copolymer inhibits platelet aggregation in its macromolecular form and presents a good biocompatibility with Human Osteoblastic Cells (HOS).

Validity of the cognitive factor of the Positive and Negative Syndrome Scale as a measure of cognitive functioning in schizophrenia.

INTRODUCTION: The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument for measuring symptomatology in patients with schizophrenia. Numerous studies have analyzed the factorial structure of this scale and have suggested a fivefactor model, namely: negative, positive, excited, anxiety/depression, and disorganized (or cognitive). The latter factor has been related to neuropsychological tests, with a view to analyzing its utility as a measure of cognitive functioning in schizophrenia, but data are inconclusive. The aim of the present study was to analyze the factorial structure of the PANSS and to assess the relationships between factors and neurocognitive tests. MATERIAL AND METHODS: The sample comprised 235 outpatients diagnosed with schizophrenia. To investigate the factorial structure of the PANSS, a principal component factor analysis was performed. Cognitive functioning was measured with a shortened version of the Barcelona Test. RESULTS: Unlike previous studies, our study obtained a six-factor model, with disorganized and cognitive symptoms separated in two different factors. The cognitive factor obtained in this study was related to all subtests of the Barcelona Test. The disorganized factor, however, was only related to two of these subtests. CONCLUSIONS: Our results support the use of a six-factor model and suggest that the cognitive factor could be a valid measure of cognitive deficits in schizophrenia, although the use of a standard neuropsychological battery is advisable.

Self-curing acrylic formulations with applications in intervertebral disk restoration: drug release and biological behaviour.

New injectable acrylic formulations have been prepared to be applied in restoration processes for intervertebral disks (IVDs). The solid phase of the formulations is composed of poly(methyl methacrylate) (PMMA), incorporating in some cases chondroitin sulphate (CS) as a regenerative bioactive molecule, whereas the liquid phase is constituted by an amphiphilic macromonomer (MT), 2-hydroxyethyl methacrylate (HEMA) and, in some formulations, acrylic acid (AA). The curing parameters and the mechanical properties of the IVD formulations make them excellent candidates for intervertebral application. In vitro and in vivo evaluation of the prepared IVD formulations is described in terms of CS release, surface analysis after immersion in SBF solutions, and biocompatibility studies based on MTT assay and Alamar blue test, as well as in vivo implantation in female Wistar rats, by injection of the IVD formulations followed by histological evaluations to assess tissue response.

Cell supports of chitosan/hyaluronic acid and chondroitin sulphate systems. Morphology and biological behaviour.

Films and sponges of chitosan (CHI), chitosan/hyaluronic acid (CHI-HA) and chitosan/chondroitin sulphate (CHI-CHOS), were prepared by film deposition or lyophilization (sponges), avoiding the formation of interpolyelectrolyte complexes. The biological behaviour of the systems was analysed by studying the cell behaviour using a fibroblast cell line and standard biological MTT and Alamar Blue tests. The morphology of films, sponges and cell seeded samples was analysed by ESEM. The results obtained indicate that all the systems can be considered as good supports for cell adhesion and proliferation, but there is specific activation of the proliferative process in the presence of hyaluronic acid and chondroitin sulphate.

Polymeric drugs with prolonged sustained delivery of specific anti-aggregant agents for platelets: kinetic analysis of the release mechanism.

The in vitro aqueous behaviour of a metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate (THEMA)/N,N'-dimethylacrylamide (DMA) copolymer with a THEMA molar content of 39% (labeled THDMA39) has been investigated. This composition has been selected to achieve a system able to keep both the non-water solubility during the release and the resorbability (and the water solubility) after the completion of the drug release. This copolymer exhibited, at pH 7.4, a constant release during several months, very interesting for a long term treatments required for the application of some cardiovascular devices. A kinetic model has been developed to explain the pseudo-zero-order kinetics of the release process. This model, which considers (from the aqueous studies) a linear increase with time of the amount of water present in the polymeric matrix, has been able to fit adequately the experimental data.

Polymeric active coatings with functionality in vascular applications.

Copolymers containing functional groups with activity as antiaggregating agents for platelets, based on random chains of metacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)]benzoate, TH, and 2-acrylamido-2-metylpropanesulfonic acid, AMPS, with AMPS molar fractions ranging from 0.1 to 0.4, have been prepared. The spectroscopical characterization and the in vitro swelling behavior have been studied, as well as the surface free energy, showing the copolymers an appropriate surface properties from a haemocompatible point of view. Preliminary in vitro tests using human blood have shown a promising antiaggregating behavior.