Metastable-solid phase diagrams derived from polymorphic solidification kinetics.

Nonequilibrium processes during solidification can lead to kinetic stabilization of metastable crystal phases. A general framework for predicting the solidification conditions that lead to metastable-phase growth is developed and applied to a model face-centered cubic (fcc) metal that undergoes phase transitions to the body-centered cubic (bcc) as well as the hexagonal close-packed phases at high temperatures and pressures. Large-scale molecular dynamics simulations of ultrarapid freezing show that bcc nucleates and grows well outside of the region of its thermodynamic stability. An extensive study of crystal-liquid equilibria confirms that at any given pressure, there is a multitude of metastable solid phases that can coexist with the liquid phase. We define for every crystal phase, a solid cluster in liquid (SCL) basin, which contains all solid clusters of that phase coexisting with the liquid. A rigorous methodology is developed that allows for practical calculations of nucleation rates into arbitrary SCL basins from the undercooled melt. It is demonstrated that at large undercoolings, phase selections made during the nucleation stage can be undone by kinetic instabilities amid the growth stage. On these bases, a solidification-kinetic phase diagram is drawn for the model fcc system that delimits the conditions for macroscopic grains of metastable bcc phase to grow from the melt. We conclude with a study of unconventional interfacial kinetics at special interfaces, which can bring about heterogeneous multiphase crystal growth. A first-order interfacial phase transformation accompanied by a growth-mode transition is examined.

Consensus on the preoperative management of patients with chronic moderate to severe shoulder pain to improve postoperative outcomes: Delphi results.

BACKGROUND: Appropriate preoperative management of patients with chronic moderate to severe shoulder pain who are candidates for surgery owing to rotator cuff disease or glenohumeral osteoarthritis may improve surgery and patient outcomes, but published evidence in this regard is scarce. Therefore, the availability of recommendations on preoperative interventions based on expert consensus may serve as guidance. METHODS: A Delphi study was conducted to develop a preoperative management algorithm based on a national expert consensus. A Delphi questionnaire was developed by a scientific committee following a systematic review of the relevant literature published during the past 10 years using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) criteria. It consisted of 48 statements divided into 5 blocks (block I, assessment and diagnosis of preoperative pain; block II, preoperative function and psychosocial aspects; block III, therapeutic objectives; block IV, treatment; and block V, follow-up and referral), and 28 experienced shoulder surgeons from across the country were invited to answer. RESULTS: All participants responded to the Delphi questionnaire in the first round, and 25 responded in the second round (89.3% of those invited). Overall, 46 of 49 final statements reached a consensus, on the basis of which a final preoperative management algorithm was defined by the scientific committee. First, surgeons should assess shoulder pain intensity and characteristics, shoulder functionality, and psychosocial aspects using specific validated questionnaires. Preoperative therapeutic objectives should include shoulder pain control, depression and/or nocturnal sleep improvement, opioid consumption adjustment, and substance abuse cessation. Postoperative objectives regarding the degree of shoulder pain reduction or improvement in functionality and/or quality of life should be established in agreement with the patient. Treatment of preoperative chronic moderate to severe shoulder pain should comprise nonpharmacologic as well as pharmacologic interventions. Follow-up of the shoulder pain levels, treatment adherence, and mental health status of these patients may be carried out by the surgical team (surgeon and anesthesiologist) together with the primary care team. Patients with very intense shoulder pain levels may be referred to a pain unit following specific protocols. CONCLUSION: A preoperative management algorithm for patients with chronic moderate to severe shoulder pain who are candidates for surgery owing to rotator cuff disease or glenohumeral osteoarthritis was defined based on a national expert consensus. Main points include comprehensive patient management starting with an objective assessment of shoulder pain and function, as well as quality of life; establishment of preoperative and postoperative therapeutic targets; prescription of individualized therapeutic interventions; and multidisciplinary patient follow-up. Implementation of these recommendations into clinical practice may result in better preoperative shoulder pain management and more successful surgical outcomes and patient satisfaction.

Artificial Intelligence in Facial Plastic and Reconstructive Surgery: A Systematic Review.

Artificial intelligence (AI) is a technology that is evolving rapidly and is changing the world and medicine as we know it. After reviewing the PROSPERO database of systematic reviews, there is no article related to this topic in facial plastic and reconstructive surgery. The objective of this article was to review the literature regarding AI applications in facial plastic and reconstructive surgery.A systematic review of the literature about AI in facial plastic and reconstructive surgery using the following keywords: Artificial Intelligence, robotics, plastic surgery procedures, and surgery plastic and the following databases: PubMed, SCOPUS, Embase, BVS, and LILACS. The inclusion criteria were articles about AI in facial plastic and reconstructive surgery. Articles written in a language other than English and Spanish were excluded. In total, 17 articles about AI in facial plastic met the inclusion criteria; after eliminating the duplicated papers and applying the exclusion criteria, these articles were reviewed thoroughly. The leading type of AI used in these articles was computer vision, explicitly using models of convolutional neural networks to objectively compare the preoperative with the postoperative state in multiple interventions such as facial lifting and facial transgender surgery.In conclusion, AI is a rapidly evolving technology, and it could significantly impact the treatment of patients in facial plastic and reconstructive surgery. Legislation and regulations are developing slower than this technology. It is imperative to learn about this topic as soon as possible and that all stakeholders proactively promote discussions about ethical and regulatory dilemmas.

Cooperative Binding of SRSF3 to Structured 3'ss-α Exon RNA during α Exon Inclusion in the ZO-1 mRNA.

ZO-1α+ and ZO-1α- proteins are expressed in hermetic and leaky tight junctions, respectively. Two cis-acting distant exonic elements partly activate the 240 nucleotide-long α exon producing the ZO-1α+ isoform. However, the elements within and around the α exon and their respective factors involved in its splicing are unknown. To study the dynamic interaction between SRSF3 and its bioinformatically predicted target sites around the 3'ss upstream of the α exon during its activation, we performed EMSA, crosslinking, and in vivo splicing assays by ZO-1 minigene expression and siRNA-mediated silencing in transfected cells. Using V1 RNase, we probed the possible formation of a hairpin RNA structure between the intronic and proximal exonic SRSF3 binding sites. The hairpin sufficed for complex formations in the EMSA. The interaction of SRSF3 with the intronic site promoted the cooperative binding of SRSF3 to the exonic site. Finally, SRSF3 restored α exon activation in SRSF3 knockdown transfectants. Altogether, our results show that SRSF3-hairpin RNA interaction is crucial in the early recognition of 3'ss for α exon activation. It remains to be explored whether SRSF3 recruits or stabilizes the binding of other factors or brings separate splice sites into proximity.

Impact of severe lymphopenia on the early prediction of clinical outcome in hospitalized patients with pneumococcal community-acquired pneumonia.

PURPOSE: To evaluate the impact of an optimal and reproducible cutoff value set according to a predefined lymphopenia scale as an early predictor of in-hospital mortality and other outcomes in patients hospitalized with pneumococcal pneumonia and positive urinary antigen at admission to the emergency department. METHODS: An observational cohort study was conducted based on analysis of a prospective registry of consecutive immunocompetent adults hospitalized for pneumococcal pneumonia in two tertiary hospitals. Generalized additive models were constructed to assess the smooth relationship between in-hospital mortality and lymphopenia. RESULTS: We included 1173 patients. Lymphopenia on admission was documented in 686 (58.4%). No significant differences were observed between groups regarding the presence of comorbidities. Overall, 299 (25.5%) patients were admitted to intensive care and 90 (7.6%) required invasive mechanical ventilation. Fifty-nine (5%) patients died, among them 23 (38.9%) in the first 72 h after admission. A lymphocyte count < 500/µL, documented in 282 (24%) patients, was the predefined cutoff point that best predicted in-hospital mortality. After adjustment, these patients had higher rates of intensive care admission (OR 2.9; 95% CI 1.9-4.3), invasive mechanical ventilation (OR 2.2; 95% CI 1.2-3.9), septic shock (OR 1.8; 95% CI 1.1-2.9), treatment failure (OR 2.1; 95% CI 1.2-3.5), and in-hospital mortality (OR 2.2; 95% 1.1-4.9). Severe lymphopenia outperformed PSI score in predicting early and 30-day mortality in patients classified in the higher-risk classes. CONCLUSION: Lymphocyte count < 500/µL could be used as a reproducible predictor of complicated clinical course in patients with an early diagnosis of pneumococcal pneumonia.

Probing the limits of metal plasticity with molecular dynamics simulations.

Ordinarily, the strength and plasticity properties of a metal are defined by dislocations-line defects in the crystal lattice whose motion results in material slippage along lattice planes. Dislocation dynamics models are usually used as mesoscale proxies for true atomistic dynamics, which are computationally expensive to perform routinely. However, atomistic simulations accurately capture every possible mechanism of material response, resolving every "jiggle and wiggle" of atomic motion, whereas dislocation dynamics models do not. Here we present fully dynamic atomistic simulations of bulk single-crystal plasticity in the body-centred-cubic metal tantalum. Our goal is to quantify the conditions under which the limits of dislocation-mediated plasticity are reached and to understand what happens to the metal beyond any such limit. In our simulations, the metal is compressed at ultrahigh strain rates along its [001] crystal axis under conditions of constant pressure, temperature and strain rate. To address the complexity of crystal plasticity processes on the length scales (85-340 nm) and timescales (1 ns-1µs) that we examine, we use recently developed methods of in situ computational microscopy to recast the enormous amount of transient trajectory data generated in our simulations into a form that can be analysed by a human. Our simulations predict that, on reaching certain limiting conditions of strain, dislocations alone can no longer relieve mechanical loads; instead, another mechanism, known as deformation twinning (the sudden re-orientation of the crystal lattice), takes over as the dominant mode of dynamic response. Below this limit, the metal assumes a strain-path-independent steady state of plastic flow in which the flow stress and the dislocation density remain constant as long as the conditions of straining thereafter remain unchanged. In this distinct state, tantalum flows like a viscous fluid while retaining its crystal lattice and remaining a strong and stiff metal.

Human Bone Marrow Mesenchymal Stem Cells Promote the M2 Phenotype in Macrophages Derived from STEMI Patients.

Acute ST-elevation myocardial infarction (STEMI) leads to myocardial injury or necrosis, and M1 macrophages play an important role in the inflammatory response. Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are capable of modulating macrophage plasticity, principally due to their immunoregulatory capacity. In the present study, we analyzed the capacity of MSCs to modulate macrophages derived from monocytes from patients with STEMI. We analyzed the circulating levels of cytokines associated with M1 and M2 macrophages in patients with STEMI, and the levels of cytokines associated with M1 macrophages were significantly higher in patients with STEMI than in controls. BM-MSCs facilitate the generation of M1 and M2 macrophages. M1 macrophages cocultured with MSCs did not have decreased M1 marker expression, but these macrophages had an increased expression of markers of the M2 macrophage phenotype (CD14, CD163 and CD206) and IL-10 and IL-1Ra signaling-induced regulatory T cells (Tregs). M2 macrophages from patients with STEMI had an increased expression of M2 phenotypic markers in coculture with BM-MSCs, as well as an increased secretion of anti-inflammatory cytokines and an increased generation of Tregs. The findings in this study indicate that BM-MSCs have the ability to modulate the M1 macrophage response, which could improve cardiac tissue damage in patients with STEMI.

Atomistic insights into metal hardening.

For millennia, humans have exploited the natural property of metals to get stronger or harden when mechanically deformed. Ultimately rooted in the motion of dislocations, mechanisms of metal hardening have remained in the cross-hairs of physical metallurgists for over a century. Here, we performed atomistic simulations at the limits of supercomputing that are sufficiently large to be statistically representative of macroscopic crystal plasticity yet fully resolved to examine the origins of metal hardening at its most fundamental level of atomic motion. We demonstrate that the notorious staged (inflection) hardening of metals is a direct consequence of crystal rotation under uniaxial straining. At odds with widely divergent and contradictory views in the literature, we observe that basic mechanisms of dislocation behaviour are the same across all stages of metal hardening.

Surface-enhanced Raman spectroscopy and ultrastructural analysis of penicillin-producing Penicillium rubens strains.

Raman spectroscopy, transmission electron microscopy (TEM) and atomic force microscopy (AFM) techniques can perform chemical analyses and acquire high-resolution images of cell samples. For this reason, in this study, semi-thin sections of a single Penicillium rubens cell were analysed by Raman enhanced surface spectroscopy. The spectra showed peaks corresponding to the macromolecules that make up the cellular components. In addition, the various organelles were analysed by TEM and AFM to observe the cellular nanostructures. With the use of these techniques, it is possible to identify molecules in semi-thin sections, which provides a wide potential for biomedical applications and for the analysis of cell dynamics. The observation of the most detailed possible structure of cells is used as a starting point in numerous studies to identify and localise some biochemical processes. Given that the function of eukaryotic cells depends on the location, shape, structure and function of the subcellular organelles (and on the interaction between them), the sum of the data obtained allows a complete analysis of what happens in the cell. This article addresses, from a multidisciplinary point of view, what happens in a single cell of a filamentous fungus (Penicillium rubens) while it is in a physiological moment (secondary metabolism) that allows the biosynthesis of an antibiotic (penicillin). For this purpose, different types of microscopies were used (TEM: transmission electron microscopy, and AFM: atomic force microscopy, which allow visualising small details in the cell) and a spectroscopy method (Raman, which allows detecting certain characteristics of the macromolecules and some stretching bonds). Regarding the results, during the synthesis of penicillin, the antibiotic-producing Penicillium rubens cells showed significant changes compared to the non-producing cells: the cell wall is observed to be significantly thickened in the production phase, organelles such as peroxisomes grow in number and size since it is known that the final route of metabolite synthesis takes place in them. When penicillin is released from peroxisomes, they must be degraded to release the load from the cell; this is done by vacuoles, which are active and engulf peroxisomes. The newly synthesised penicillin is found within secretory vesicles that travel towards the cell membrane and both membranes fuse creating ripples. On the other hand, and given that a single cell is being studied, it is essential to increase the signal to detect biomolecules employing the Raman-SERS technique, using a silver substrate to obtain the increased signal.

COVID-19 in young and middle-aged adults: predictors of poor outcome and clinical differences.

INTRODUCTION: Young and middle-aged adults are the largest group of patients infected with SARS-CoV-2 and some of them develop severe disease. OBJECTIVE: To investigate clinical manifestations in adults aged 18-65 years hospitalized for COVID-19 and identify predictors of poor outcome. Secondary objectives: to explore differences compared to the disease in elderly patients and the suitability of the commonly used community-acquired pneumonia prognostic scales in younger populations. METHODS: Multicenter prospective registry of consecutive patients hospitalized for COVID-19 pneumonia aged 18-65 years between March and May 2020. We considered a composite outcome of "poor outcome" including intensive care unit admission and/or use of noninvasive ventilation, continuous positive airway pressure or high flow nasal cannula oxygen and/or death. RESULTS: We identified 513 patients < 65 years of age, from a cohort of 993 patients. 102 had poor outcomes (19.8%) and 3.9% died. 78% and 55% of patients with poor outcomes were classified as low risk based on CURB and PSI scores, respectively. A multivariate Cox regression model identified six independent factors associated with poor outcome: heart disease, absence of chest pain or anosmia, low oxygen saturation, high LDH and lymphocyte count < 800/mL. CONCLUSIONS: COVID-19 in younger patients carries significant morbidity and differs in some respects from this disease in the elderly. Baseline heart disease is a relevant risk factor, while anosmia and pleuritic pain are associated to better prognosis. Hypoxemia, LDH and lymphocyte count are predictors of poor outcome. We consider that CURB and PSI scores are not suitable criteria for deciding admission in this population.

The efficacy of combining topiramate and 4-aminopyridine to reduce relapses and interictal progression in two cases of episodic ataxia type 2.

BACKGROUND: Episodic ataxia type 2 is an autosomal dominant channelopathy, caused by genetic variants in the voltage-dependent calcium channel a-1 subunit (CACNA1A), which is characterized by intermittent episodes of vertigo and ataxia. A slow progression of cerebellar signs is commonly observed in the course of the disease. Treatment with the carbonic anhydrase inhibitor acetazolamide is recommended. METHODS: We report the cases of two patients with EA-2 and migraine, linked to a novel CACNA1A mutation associated with disabling ictal and interictal disease, which did not respond to acetazolamide. RESULTS: A 30-year-old woman and a 50-year-old man, who was a ski instructor, reported disabling episodes of rotatory vertigo and progressive interictal ataxia. In both cases, the disease progressed despite treatment with acetazolamide. The concomitant use of topiramate and 4-aminopyridine significantly reduced the frequency and severity of relapses and migraine and improved the interictal cerebellar progression in both cases. CONCLUSIONS: We propose combined applications of topiramate and 4-aminopyridine in refractory cases and those with poor tolerance to acetazolamide and also in those with frequent associated migraine. The effectiveness of this combination of drugs for treating intermittent ataxic episodes and interictal signs in EA-2 has not been previously reported.

Aflatoxin levels and prevalence of TP53 aflatoxin-mutations in hepatocellular carcinomas in Mexico.

OBJECTIVE: To determine the exposure to aflatoxin B1 (AFB1) in southern Mexico and the presence of the aflatoxin signature mutation in hepatocellular carcinoma (HCC) tissue from patients from a cancer referral center. MATERIALS AND METHODS: We estimated the prevalence and distribution of AFB1 in a representative sample of 100 women and men from Chiapas using the National Health and Nutrition Survey 2018-19. We also examined the presence of the aflatoxin signature mutation in codon 249 (R249S), and other relevant mutations of the TP53 gene in HCC tissue blocks from 24 women and 26 men treated in a national cancer referral center. RESULTS: The prevalence of AFB1 in serum samples was 85.5% (95%CI 72.1-93.1) and the median AFB1 was 0.117 pg/µL (IQR, 0.050-0.350). We detected TP53 R249S in three of the 50 HCCs (6.0%) and observed four other G>T transversions potentially induced by AFB1. CONCLUSION: Our analysis provides evidence that AFB1 may have a relevant role on HCC etiology in Mexico.

Use of Coffee Bean Bagasse Extracts in the Brewing of Craft Beers: Optimization and Antioxidant Capacity.

Coffee bean bagasse is one of the main by-products generated by industrial coffee production. This by-product is rich in bioactive compounds such as caffeine, caffeic and chlorogenic acid, and other phenols. The aims of this work are to optimize the extraction conditions of phenolic compounds present in coffee bean bagasse and incorporate them into stout-style craft beers, as well as to determine their effect on the phenol content and antioxidant capacity. The optimal conditions for extraction were 30% ethanol, 30 °C temperature, 17.5 mL of solvent per gram of dry sample, and 30 min of sonication time. These conditions presented a total phenol content of 115.42 ± 1.04 mg GAE/g dry weight (DW), in addition to an antioxidant capacity of 39.64 ± 2.65 µMol TE/g DW in DPPH• and 55.51 ± 6.66 µMol TE/g DW for FRAP. Caffeine, caffeic and chlorogenic acids, and other minor compounds were quantified using HPLC-DAD. The coffee bean bagasse extracts were added to the stout craft beer and increased the concentration of phenolic compounds and antioxidant capacity of the beer. This work is the first report of the use of this by-product added to beers.

Preventive treatment can reverse cognitive impairment in chronic migraine.

OBJECTIVE: To study the impact of chronic migraine (CM) on the cognition and quality of life (QoL) of patients in the interictal period, and to analyse the degree of reversibility of any observed alterations following the use of preventive treatment. BACKGROUND: CM is a highly disabling disease, and migraineurs often have associated comorbidities, such as subjective memory problems, that are involved in the development of cognitive impairment. Our hypotheses are that patients suffering from chronic migraine experience objective cognitive alterations that are not only due to the pain that they suffer or their current emotional state. Furthermore, preventive treatment should be capable of reversing, or at least reducing, the impact of CM on the cognition and QoL of migraineurs. METHODS: The cognition and QoL of 50 control subjects and 46 patients with CM were assessed using a battery of tests, prior to the use of preventive treatment based on botulinum toxin or oral drugs and after 3 months of this treatment. RESULTS: Compared with controls, patients with CM had lower scores on the assessment of cognitive performance (Rey-Osterrieth Complex Figure test [ROCF] (p<0.05), Trail Making Test [TMT] B) (p < 0.05) and QoL (p < 0.05). Three months after the use of preventive treatment, improvement was observed in all cognitive parameters (p < 0.05) and QoL (p < 0.05), except the ROCF copy task (p = 0.79). No statistically significant differences were observed when these outcomes were compared based on treatment. CONCLUSIONS: This study confirms poor cognitive performance that is not explained by migraine pain itself, as it occurs in the interictal period, irrespective of the patient's emotional status. Our findings show that these effects are reversible in some cases with preventive treatment of CM, reaffirming the important impact of this condition on the QoL of these patients, and the need to establish preventive treatment guidelines.

Evaluation of the toxicology, anti-lipase, and antioxidant effects of Callistemon citrinus in rats fed with a high fat-fructose diet.

CONTEXT: Callistemon citrinus Skeels (Myrtaceae) exhibits many biological activities. OBJECTIVE: This study analyzes for the first time, the toxicity, obesogenic, and antioxidant effects of C. citrinus in rats fed with a high fat-fructose diet (HFFD). MATERIALS AND METHODS: Four studies using male Wistar rats were conducted: (a) 7 groups (n = 3): control (corn oil) and ethanol extract of C. citrinus leaf (single oral dose at 100-4000 mg/kg) for acute toxicity; (b) 2 groups (n = 8): control (corn oil) and C. citrinus (1000 mg/kg/day) for 28 days for subacute toxicity; (c) 3 groups (n = 4) with single oral dose of lipid emulsion: control (lipid emulsion), C. citrinus and orlistat (250 and 50 mg/kg, respectively) for lipid absorption; (d) 4 groups (n = 6): control (normal diet) and 3 groups fed with HFFD: HFFD only, C. citrinus and simvastatin (oral dose 250 and 3 mg/kg, respectively) for 13 weeks. Antioxidant enzymes and biomarkers were evaluated and inhibition of pancreatic lipase was determined in vitro. RESULTS: Toxicological studies of C. citrinus showed no differences in biochemical parameters and lethal dose (LD50) was higher than 4000 mg/kg. C. citrinus inhibited pancreatic lipase activity, with IC50 of 392.00 µg/mL, and decreased lipid absorption by 70%. Additionally, it reduced the body weight 22%, restored the activities of antioxidant enzymes, and reduced the biomarkers of oxidative stress. CONCLUSIONS: Callistemon citrinus showed an effect against oxidative stress by reducing biomarkers and induced antioxidant system, without toxic effects.

Efficacy and safety of dulaglutide 3.0 and 4.5 mg in patients aged younger than 65 and 65 years or older: Post hoc analysis of the AWARD-11 trial.

AIM: To evaluate the efficacy and safety of dulaglutide 3.0 and 4.5 mg versus 1.5 mg when used as an add-on to metformin in subgroups defined by age (<65 and ≥65 years). MATERIALS AND METHODS: Of 1842 patients included in this post hoc analysis, 438 were aged 65 years or older and 1404 were younger than 65 years. The intent-to-treat (ITT) population, while on treatment without rescue medication, was used for all efficacy analyses; the ITT population without rescue medication was used for hypoglycaemia analyses; all other safety analyses used the ITT population. RESULTS: Patients aged 65 years or older and those younger than 65 years had a mean age of 69.5 and 53.2 years, respectively. In each age subgroup, the reduction from baseline in HbA1c and body weight (BW), and the proportion of patients achieving a composite endpoint of HbA1c of less than 7% (<53 mmol/mol) with no weight gain and no documented symptomatic or severe hypoglycaemia, were larger for dulaglutide 3.0 and 4.5 mg compared with dulaglutide 1.5 mg, but the treatment-by-age interactions were not significant. The safety profile for the additional dulaglutide doses was consistent with that of dulaglutide 1.5 mg and was similar between the age subgroups. CONCLUSION: Dulaglutide doses of 3.0 or 4.5 mg provided clinically relevant, dose-related improvements in HbA1c and BW with no significant treatment-by-age interactions, and with a similar safety profile across age subgroups.

Synthesis, Characterization, and Preliminary In Vitro Cytotoxic Evaluation of a Series of 2-Substituted Benzo [d] [1,3] Azoles.

A series of benzo [d] [1,3] azoles 2-substituted with benzyl- and allyl-sulfanyl groups were synthesized, and their cytotoxic activities were in vitro evaluated against a panel of six human cancer cell lines. The results showed that compounds BTA-1 and BMZ-2 have the best inhibitory effects, compound BMZ-2 being comparable in some cases with the reference drug tamoxifen and exhibiting a low cytotoxic effect against healthy cells. In silico molecular coupling studies at the tamoxifen binding site of ERα and GPER receptors revealed affinity and the possible mode of interaction of both compounds BTA-1 and BMZ-2.

Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico.

INTRODUCTION: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. OBJECTIVE: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. METHODS: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. RESULTS: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. CONCLUSIONS: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

INTRODUCCIÓN: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. OBJETIVO: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. MÉTODOS: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. RESULTADOS: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. CONCLUSIONES: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

A major genetic determinant of autoimmune diseases is associated with the presence of autoantibodies in hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with hypersensitivity pneumonitis develops autoantibodies with or without clinical manifestations of autoimmune disease. However, the mechanisms involved in this process and the effect of the autoantibodies on clinical course in hypersensitivity pneumonitis is unknown. We evaluated the association between human leukocyte antigen (HLA) class II alleles and hypersensitivity pneumonitis patients with and without autoantibodies. METHODS: 170 hypersensitivity pneumonitis patients were included. We analysed the presence of antinuclear antibodies, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-CCP at the time of diagnosis. In addition, in a subset of patients we evaluated anti-Scl-70, anti-neutrophil cytoplasmic antibody, and anti-DNA. HLA typing was performed using PCR sequence-specific primers in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing Epi-Info v7 and SPSS v20. RESULTS: 60 hypersensitivity pneumonitis patients showed sera autoantibodies (HPAbs+), and 110 hypersensitivity pneumonitis patients did not (HPAbs-). The frequency of the allele HLA-DRB1*03:01 was remarkably increased in the HPAbs+ group (10.8% versus 0.45%; OR 30.14, 95% CI 3.83-237.1; p=1.65×10-4 after Bonferroni's correction). Likewise, we found that the haplotype DRB1*03:01-DQB1*02:01, which is part of the 8.1 ancestral haplotype, a major genetic determinant of autoimmune diseases, confers significant risk to develop autoantibodies (OR 19.23, 95% CI 2.37-155.9; p=0.0088 after Bonferroni's correction). In addition, the HLA-DRB1*03:01 allele was associated with higher mortality in patients with hypersensitivity pneumonitis (adjusted OR 5.9, 95% CI 1.05-33.05; p=0.043). CONCLUSIONS: A subset of hypersensitivity pneumonitis patients presents circulating autoantibodies and higher mortality that are associated with some alleles of 8.1 ancestral haplotype.

Photochemical and electrochemical reduction of graphene oxide thin films: tuning the nature of surface defects.

Individual and combined photo(electro)chemical reduction treatments of graphene oxide thin films have been performed to modulate the type of defects introduced into the graphene sheets during the reduction. These were characterized by X-ray photoelectron and Raman spectroscopies, nuclear reaction analysis and electrochemical methods. Illumination of the graphene oxide thin film electrodes with low irradiance simulated solar light provoked the photoassisted reduction of the material with negligible photothermal effects. The photoreduced graphene oxide displayed a fragmented sp2 network due to the formation of a high density of defects (carbon vacancies) and the selective removal of epoxides and hydroxyl groups. In contrast, the electrochemical reduction under mild polarization conditions favored the formation of sp3 defects over vacancies, with a preferential removal of carbonyl and carboxyl groups over hydroxyl/epoxides. Used in conjunction, mild photochemical and electrochemical treatments allowed the obtainment of reduced graphene oxides with varied reduction degrees (ca. C/O ratio ranging from 4.9 to 2.2), and surface defects. Furthermore, the electrochemical reduction prevented the formation of vacancies during the subsequent illumination step. In contrast, both types of defects were accumulated when the GO electrode was first exposed to illumination and then polarized.