Cognitive Effects of Three ß-Adrenoceptor Acting Drugs in Healthy Volunteers and Patients with Parkinson's Disease.

Background: Noradrenergic signaling declines in Parkinson's disease (PD) following locus coeruleus neurodegeneration. Epidemiologic studies demonstrate that ß-acting drugs slow PD progression. Objective: The primary objective was to compare the safety and effects of 3 ß-adrenoceptor (ß-AR) acting drugs on central nervous system (CNS) function after a single dose in healthy volunteers (HVs) and evaluate the effects of multiple doses of ß-AR acting drugs in HVs and PD-patients. Methods: In Part A, HVs received single doses of 32 mg salbutamol, 160µg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. In Part B (randomized cross-over) and Part C (parallel, 2:1 randomized), placebo and/or clenbuterol (20µg on Day 1, 40µg on Day 2, 80µg on Days 3-7) were administered. CNS functions were assessed using the NeuroCart test battery, including pupillometry, adaptive tracking and recall tests. Results: Twenty-seven HVs and 12 PD-patients completed the study. Clenbuterol improved and pindolol reduced the adaptive tracking and immediate verbal recall performance. Clenbuterol and salbutamol increased and pindolol decreased pupil-to-iris ratios. Clenbuterol was selected for Parts B and C. In Part B, clenbuterol significantly increased performance in adaptive tracking with a tendency toward improved performance in immediate and delayed verbal recall. In Part C trends toward improved performance in immediate and delayed verbal recall were observed in PD-patients. Typical cardiovascular peripheral ß2-AR effects were observed with clenbuterol. Conclusions: This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of ß2-ARs in the CNS.

Aims and Purpose of the Research:This research aimed to explore how three different drugs affect brain function. These drugs are salbutamol, clenbuterol, and pindolol and work in the brain by stimulating specific brain cells that can improve aspects like memory and coordination. The main question was to see how safe these drugs were and how they impact the brain function after one dose in healthy people, and after multiple doses in both healthy people and those with Parkinson's disease.Background of the Research:Parkinson's disease is a condition where brain cells start to die, which affects different areas of the brain, including movement function, as well as memory and attention. This research matters because finding drugs that affect the brain function could improve the lives of people with Parkinson's disease.Methods and Research Design:The study was conducted in three parts. In the first part, healthy volunteers took one dose of each of the three drugs­ salbutamol, clenbuterol, and pindolol­ as well as a placebo (a harmless pill that has no effect). The researchers tested the participants' brain functions using various tasks including memory tests and eye response measurements. In the second and third part, healthy people and people with Parkinson's disease took the drug that performed best in healthy volunteers for seven days.Results and Importance:In the first part, a single dose of clenbuterol was safe and improved memory and attentions tasks in healthy people, and therefore was chosen for further testing in the second and third part. In these parts, multiple doses of clenbuterol were safe and helped improve memory and attention tasks in healthy people, with similar positive trends seen in people with Parkinson's disease. The study suggests that clenbuterol might help improve brain function by activating specific receptors in the brain.These results are important because they suggest that clenbuterol could be a potential treatment to help improve brain function in people with Parkinson's disease. However, more research is needed to fully understand its effects and to confirm these findings.

Effects on cerebral blood flow after single doses of the ß2 agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease.

AIMS: Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, ß-adrenoceptor (ß-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant ß2-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD). METHODS: This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, ß2-AR agonist clenbuterol (20-160 µg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5 mg), a ß-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral ß2-AR responses. RESULTS: Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3 h after 20, 40, 80 and 160 µg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 µg clenbuterol were observed both without and with 5 mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of ß2-agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol. CONCLUSIONS: The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful ß2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.

Comparison and Influence of a Multicomponent Educational Program on the Patient-Reported Outcomes of a Group of Patients With Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease that affects different areas of the patient's body. Patient education and health literacy is essential for them to participate actively in follow-up. OBJECTIVES: The aim of this study was to assess differences between clinimetric measurements done by a medical team and patient-reported outcome measures (PROMs) in RA and understand the impact of patient education strategies in order to identify differences between RA assessment methods. METHODS: This is a longitudinal cohort study. It included adult patients with RA and access to digital tools. These were divided into 3 groups by type of education. Group 1 included patients who participated in a multicomponent RA educational program. Group 2 did not have this multicomponent RA education. Group 3 did not receive any education. The 3 groups performed PROMs. Disease activity scales, functional class, and quality of life were measured. Univariate and bivariate analysis (χ 2 and Wilcoxon for paired data) were done. RESULTS: Twenty-eight patients were included in group 1, 26 in group 2, and 37 in group 3. All were women. In group 1, there were no significant differences in clinimetrics between the medical team and patient's PROMs except for fatigue. In group 2 and group 3, significant differences were found. The RAPID3 and PAS variables did not show significant differences when analyzed by intervention subgroups. CONCLUSIONS: This study shows no differences between clinimetrics/PROMs for patients with a high-level education on RA and physicians. On the other hand, when patient did not have any RA education, the clinimetric results differed from physician measurement.

Single- and Multiple-Dose Pharmacokinetics of Gefapixant (MK-7264), a P2X3 Receptor Antagonist, in Healthy Adults.

Gefapixant (MK-7264, RO4926219, AF-219) is a first-in-class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single- and multiple-dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single-dose administration of 10-450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter-subject variability and a dose-proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose-proportional at doses ranging from 7.5 to 50 mg and less than dose-proportional at doses ranging from 100 to 1800 mg. The time to mean peak drug concentration ranged from 2 to 3 h post-dose, and steady state was achieved by 7 days after dosing, with an accumulation ratio of approximately 2, comparing data from day 1 to steady state. The mean apparent terminal half-life ranged from 8.2 to 9.6 h. Gefapixant was primarily excreted unmodified in urine. Gefapixant was well tolerated following single-dose administration up to 1800 mg and multiple doses up to 1800 mg twice daily; there were no serious adverse events (AEs) reported. The most common AE reported was dysgeusia. The PK profile supports a twice-daily dosing regimen.

Advances in the Development of Biofertilizers and Biostimulants from Microalgae.

Microalgae have commercial potential in different sectors of the industry. Specifically in modern agriculture, they can be used because they have the ability to supply nutrients to the soil and produce plant growth hormones, polysaccharides, antimicrobial compounds, and other metabolites that improve agricultural productivity. Therefore, products formulated from microalgae as biofertilizers and biostimulants turn out to be beneficial for agriculture and are positioned as a novel and environmentally friendly strategy. However, these bioproducts present challenges in preparation that affect their shelf life due to the rapid degradation of bioformulated products. Therefore, this work aimed to provide a comprehensive review of biofertilizers and biostimulants from microalgae, for which a bibliometric analysis was carried out to establish trends using scientometric indicators, technological advances were identified in terms of formulation methods, and the global market for these bioproducts was analyzed.

Usefulness of Lung Ultrasound as a Method for Early Diagnosis of Interstitial Lung Disease in Patients with Rheumatoid Arthritis.

Purpose: To determine the value of lung ultrasound (LUS) compared to high-resolution computed tomography (HRCT) in the early diagnosis of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Patients and Methods: An observational prospective study was performed. Were included patients with respiratory symptoms or/and, patients with crackles in auscultation during medical consultation. All patients underwent to chest X-rays, LUS, HRCT,and respiratory function tests. Results: A total of 192 patients with RA were included. Mean disease duration was 16.8 ± 11.1 years. 72% were positive for rheumatoid factor or anti-citrullinated antibodies. Of the total number of subjects, 54.7% had respiratory symptoms. The other patients did not have respiratory symptoms, but they did have had crackles on pulmonary auscultation. B lines > 11.5 on the ROC curve predicted ILD (AUC 0.63; CI 95%: 0.55-0.71; p < 0.003). A DLCO value of <7.13 significantly predicted the presence of ILD (AUC 0.61; 95% CI: 0.52-0.70; p < 0.028). Conclusion: The findings of this study suggest that LUS is a valuable tool for the early diagnosis of ILD in patients with RA, and together with DLCO, can adequately predict the presence of ILD in this population. LUS also helps to determine which patients with respiratory symptoms and signs suggestive for ILD are undergo to HRCT.

Tolerance Evaluation of Celery Commercial Cultivars and Genetic Variability of Fusarium oxysporum f. sp. apii.

Celery (Apium graveolens var. dulce) is affected by several plant diseases, such as Fusarium oxysporum f. sp. apii (Foa). Four Foa races have been found in the US. The goals of this study were to determine which races are present in Costa Rica and to quantify the tolerance of the imported commercial cultivars of celery produced in the country. Isolates from 125 symptomatic celery plants from three different geographical locations were analyzed, 65 of which were selected for phylogenetic analysis. All isolates presented a short sequence of five nucleotides that differentiates Foa race 3 in the IGS rDNA region. Three different haplotypes closely related to race 3 were found, which were highly virulent, produced great losses, and affected all cultivars (resistant to races 2 and 4) of imported commercial celery. Additionally, five different cultivars of celery were evaluated against seven pathogen isolates identified as race 3 in greenhouse conditions. Two of the cultivars showed significantly less chlorosis, wilting, mortality, and higher fresh weight. Most of the Foa isolates significantly increased chlorosis, wilting, and mortality compared to non-inoculated control. Celery producers in Costa Rica lack access to seeds resistant to the Foa race 3 present in the country.

CO2 adsorption on carbonaceous materials obtained from forestry and urban waste materials: a comparative study.

The increasing emissions of gaseous pollutants of anthropogenic origin, such as carbon dioxide (CO2), which causes global warming, have raised great interest in developing and improving processes that allow their mitigation. Among them, adsorption on porous materials has been proposed as a sustainable alternative. This work presents a study of CO2 equilibrium adsorption at low temperatures (0, 10, and 20 °C) over a wide range of low pressures, on activated carbon derived from Eucalyptus (ES) and Patula pine (PP) forest waste, and carbonaceous material derived from waste tires (WT). The precursors of these materials were previously prepared, and their physicochemical properties were characterized. ES and PP were thermochemically treated with phosphoric acid, and WT was oxidized with nitric acid. Additionally, these materials were used to obtain monoliths using uniaxial compaction techniques and different binding agents, with better results obtained with montmorillonite. A total of six adsorbent solids had their textural and chemical properties characterized and were tested for CO2 adsorption. The highest specific surface area (1405 m2 g-1), and micropore properties were found for activated carbon derived from Eucalyptus whose highest adsorption capacity ranged from 2.27 mmol g-1 (at 0 °C and 100 kPa) to 1.60 mmol g-1 (at 20 °C and 100 kPa). The activated carbon monoliths presented the lowest CO2 adsorption capacities; however, the studied materials showed high potential for CO2 capture and storage applications at high pressures. The isosteric heats of adsorption were also estimated for all the materials and ranged from 16 to 45 kJ mol-1 at very low coverage explained by the energetic heterogeneity and weak repulsive interactions among adsorbed CO2 molecules.

Neutralization, by a polyspecific antivenom, of the coagulopathy induced by the venom of Bothrops asper: Assessment by standard coagulation tests and rotational thromboelastometry in a murine model.

Venom-induced consumption coagulopathy and thrombocytopenia are common and potentially severe manifestations of viperid snakebite envenoming since they contribute to local and systemic hemorrhage. Therefore, the assessment of the efficacy of antivenoms to neutralize coagulopathic and thrombocytopenic toxins should be part of the preclinical evaluation of these drugs. To evaluate the efficacy of the polyvalent (Crotalinae) antivenom produced in Costa Rica, in this study we have used a mouse model of coagulopathy and thrombocytopenia induced by the venom of Bothrops asper, based on the bolus intravenous (i.v.) injection of venom. When venom and antivenom were incubated before injection, or when antivenom was administered i.v. immediately after venom injection, venom-induced hemostatic alterations were largely abrogated. We also studied the recovery rate of clotting parameters in conditions where antivenom was administered when mice were coagulopathic. Some parameters recovered more rapidly in antivenom-treated mice than in control envenomed animals, but others showed a spontaneous recovery without antivenom. This is due to a rapid clearance of plasma venom levels in these experimental conditions. This implies that models based on the bolus i.v. injection of venom have limitations for assessing the effect of antivenom in the recovery of clotting alterations once coagulopathy has developed. It is suggested that alternative models should be developed based on a slower systemic absorption of venom. Overall, our findings provide a protocol for the preclinical evaluation of antivenoms and demonstrate that the polyvalent antivenom is effective in neutralizing the toxins of B. asper venom responsible for coagulopathy and thrombocytopenia.

Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.

Adrenoceptors (ARs) throughout the brain are stimulated by noradrenaline originating mostly from neurons of the locus coeruleus, a brainstem nucleus that is ostensibly the earliest to show detectable pathology in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The α1-AR, α2-AR, and ß-AR subtypes expressed in target brain regions and on a range of cell populations define the physiological responses to noradrenaline, which includes activation of cognitive function in addition to modulation of neurometabolism, cerebral blood flow, and neuroinflammation. As these heterocellular functions are critical for maintaining brain homeostasis and neuronal health, combating the loss of noradrenergic tone from locus coeruleus degeneration may therefore be an effective treatment for both cognitive symptoms and disease modification in neurodegenerative indications. Two pharmacologic approaches are receiving attention in recent clinical studies: preserving noradrenaline levels (e.g., via reuptake inhibition) and direct activation of target adrenoceptors. Here, we review the expression and role of adrenoceptors in the brain, the preclinical studies which demonstrate that adrenergic stimulation can support cognitive function and cerebral health by reversing the effects of noradrenaline depletion, and the human data provided by pharmacoepidemiologic analyses and clinical trials which together identify adrenoceptors as promising targets for the treatment of neurodegenerative disease.

Comparative Exergy and Environmental Assessment of the Residual Biomass Gasification Routes for Hydrogen and Ammonia Production.

The need to reduce the dependency of chemicals on fossil fuels has recently motivated the adoption of renewable energies in those sectors. In addition, due to a growing population, the treatment and disposition of residual biomass from agricultural processes, such as sugar cane and orange bagasse, or even from human waste, such as sewage sludge, will be a challenge for the next generation. These residual biomasses can be an attractive alternative for the production of environmentally friendly fuels and make the economy more circular and efficient. However, these raw materials have been hitherto widely used as fuel for boilers or disposed of in sanitary landfills, losing their capacity to generate other by-products in addition to contributing to the emissions of gases that promote global warming. For this reason, this work analyzes and optimizes the biomass-based routes of biochemical production (namely, hydrogen and ammonia) using the gasification of residual biomasses. Moreover, the capture of biogenic CO2 aims to reduce the environmental burden, leading to negative emissions in the overall energy system. In this context, the chemical plants were designed, modeled, and simulated using Aspen plus™ software. The energy integration and optimization were performed using the OSMOSE Lua Platform. The exergy destruction, exergy efficiency, and general balance of the CO2 emissions were evaluated. As a result, the irreversibility generated by the gasification unit has a relevant influence on the exergy efficiency of the entire plant. On the other hand, an overall negative emission balance of -5.95 kgCO2/kgH2 in the hydrogen production route and -1.615 kgCO2/kgNH3 in the ammonia production route can be achieved, thus removing from the atmosphere 0.901 tCO2/tbiomass and 1.096 tCO2/tbiomass, respectively.

Polyautoimmunity in systemic lupus erythematosus patients: New insights from a cross-sectional study.

Objective: To assess the frequency of polyautoimmunity (PolyA) in a cohort of Colombian patients with systemic lupus erythematosus (SLE) and to identify associated factors. Methods: This is an analytical cross-sectional study in a specialized center., a comprehensive review of the medical records of SLE patients was performed from 2015 to 2020 in order to obtain demographic, clinical data, laboratory, and treatment information. Associations between PolyA, demographic, and characteristics of the disease were explored. Results: A total of 463 patients were included in the analysis. The average age was 47.3 ± 15 years. Most of this population were female (87.4%), whom were diagnosed with SLE in a long-term SLE (10.6 ± 10.1 years). Out of the total patients, 34.7% were diagnosed with PolyA. Among the most frequent clinical criteria for SLICC, arthritis (65%), kidney impairment (39.5%), and alopecia (34.8%) were found. The most frequent SLE-associated PolyA were antiphospholipid syndrome (APS) and Sjögren's syndrome (SS) (16.63% and 10.58%, respectively). PolyA-associated factors were age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis (DVT). In contrast, renal impairment was significantly less frequent in PolyA patients after multivariate analysis. Conclusion: The results have showed associated factors with PolyA like age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis in this cohort. On the other hand, lupus nephritis was less frequent in patients with PolyA. This study provides a spotlight of a specific SLE population as real-life evidence for a better characterization of PolyA in the future.

Unilateral Cervical Facet Fractures: Relevance of Acute Disc Injury in Conservative Treatment Failure.

STUDY DESIGN: Case-control study. PURPOSE: Analyze association between imaging factors related to the failure of conservative treatment in isolated subaxial cervical facet fractures. OVERVIEW OF LITERATURE: Facet fracture (F1, F2, and F3 AOSpine) may be stable or unstable depending on clinical and imaging variables, which are not well established. As a result, differences in fracture management lead to differences in surgical or conservative indications, and there is no evidence to predict conservative treatment failure. METHODS: Patients were categorized into two groups: six patients (16.2%) with conservative treatment failure (defined as the appearance of neurological symptoms, listhesis >3.5 mm, kyphotic deformation >11°, and/or non-union), and 31 patients (83.7%) with successful conservative management (defined as complete consolidation confirmed by computed tomography [CT] at the 6-month followup). All participants were fitted with rigid collars of the Miami type, and standardized follow-up was performed until consolidation or failure. CT and magnetic resonance imaging (MRI) was used to examine imaging characteristics. Sagittal balance parameters were assessed using CT, and signs of acute disc injury, prevertebral edema, facet synovitis, and interspinous hyperintense signal were assessed using MRI. RESULTS: Thirty-seven patients were diagnosed with unilateral cervical facet fractures between 2009 and 2020. In this sample, acute disc injury had a significative association to failure of conservative treatment in F2 and F3 AOSpine facet fractures, 100% of the failure group presented with traumatic disc injury compared to 9.7% of the successful group, for the other variables: prevertebral edema, 83.7% vs. 41.9%; facet synovitis, 100% vs. 77.4%; and interspinous hyperintensity, 71.4% vs. 38.7%, respectively. With conservative management, all F1 fractures healed successfully. Conservative treatment failed in 20% of F2 fractures and 50% of F3 fractures, respectively. In terms of cervical sagittal balance parameters, there were no significant differences between groups. CONCLUSIONS: Conservative management was successful in all F1 fractures. In F2 and F3 types, there was a significant association between acute disc injury and conservative treatment failure.

Modifications in self-care, quality of life and therapeutic adherence in patients with rheumatoid arthritis during the SARS-CoV-2 pandemic treated by telehealth

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, causing pain and stiffness in the joints. SARS-CoV-2 increases the clinical vulnerability of the population with RA and has led to the implementation and/or development of telemedicine. Objective: To describe changes in level of therapeutic adherence, quality of life and capacity for self-care agency, during the follow-up period of a group of patients linked to a non-face-to-face multidisciplinary consultation model during the SARS-CoV-2 pandemic. Methodology: Descriptive cohort study (July to October 2020). Description of the level of therapeutic adherence (Morisky Green Test), quality of life (EuroQOL-5-Dimensions-3-Level-version) and self-care capacity (ASA-R Scale) in the context of a telehealth model. A univariate and bivariate analysis was performed (Stata Software, Considered p-value <0.05). Results: Of 71 patients treated under the telehealth model, 85.9% were women, the age range was between 33 and 86 years with a median of 63. The most prevalent comorbidity was arterial hypertension (35.2%). Quality of life did not change during follow-up nor did adherence to treatment, apart from in one item [the patients did not stop taking the medication when they were well (p = 0.029)]. In self-care capacity, there were significant improvements in five dimensions (p < 0.05), without significant differences in the global score. Conclusion: Patients with RA evaluated in the context of telehealth in a period of pandemic did not present significant changes in quality of life, adherence to treatment, or capacity for self-care, and remained close to baseline values when they attended a traditional face-to-face assessment.

INTRODUCCIÓN: La artritis reumatoide (AR) es una enfermedad autoinmune caracterizada por una inflamación crónica que produce dolor y rigidez articular. El SARS-CoV-2 aumenta la vulnerabilidad clínica en pacientes con AR, lo que ha conllevado la implementación o el desarrollo de la telesalud. OBJETIVO: Describir los cambios en el nivel de adherencia terapéutica, la calidad de vida y la capacidad de autocuidado durante el periodo de seguimiento, en un grupo de pacientes con AR vinculados con un modelo de consulta multidisciplinar no presencial, en el curso de la pandemia por SARS-CoV-2. METODOLOGÍA: Estudio de cohorte descriptiva (julio a octubre del 2020). Descripción del nivel de adherencia terapéutica (TEST MORISKY GREEN), calidad de vida (EUROQOL-5-DIMENSIONS-3-LEVEL-VERSION) y capacidad de autocuidado (Escala ASA-R) en el contexto de un modelo de telesalud. Se realizó análisis univariado y bivariado (SOFTWARE Stata®, valor de p considerado <0,05). RESULTADOS: De 71 pacientes atendidos en modalidad de telesalud, el 85,9% fueron mujeres, la mediana de la edad fue de 63 (33-86) anos. La comorbilidad más prevalente fue la hipertensión (35,2%). La calidad de vida no tuvo cambios durante el seguimiento, al igual que la adherencia al tratamiento, excepto en uno de los ítems (los pacientes no dejaron de tomar la medicación cuando se encontraban bien; p = 0,029). En la capacidad de autocuidado hubo mejoras significativas en 5 dimensiones (p < 0,05), sin diferencias significativas en el puntaje global. CONCLUSIÓN: Los pacientes con AR evaluados en el contexto de la telesalud, en un periodo de pandemia, no presentaron cambios significativos en la calidad de vida, la adherencia al tratamiento y la capacidad de autocuidado; se mantuvieron en niveles similares a los valores basales cuando asistían a valoración tradicional presencial.

Metabolic Abnormalities, Cardiovascular Disease, and Metabolic Syndrome in Adult Rheumatoid Arthritis Patients: Current Perspectives and Clinical Implications.

Aim: Rheumatoid arthritis is a prevalent worldwide disease, associated with an increased risk of multiple metabolic abnormalities that generate a higher disease burden. Objective: To gather the available evidence on the epidemiology, pathophysiology, current perspectives, clinical implications and prognosis of metabolic abnormalities in patients with rheumatoid arthritis. Methods: This is a narrative literature review. Search was conducted in PubMed, OVID, and Taylor & Francis databases, using the following MeSH terms: "Arthritis Rheumatoid", "Metabolic Diseases", and "Metabolic Syndrome". Results: This study describes the main metabolic manifestations of rheumatoid arthritis. Research has recognized that rheumatoid arthritis and metabolic abnormalities share pathophysiological mechanisms with an additive effect that increases cardiovascular risk. In that context, appropriate antirheumatic treatment can also impact on cardiovascular risk. Conclusion: There are metabolic abnormalities in rheumatoid arthritis patients that increase cardiovascular risk. Therefore, it is crucial to evaluate cardiovascular risk to provide appropriate comprehensive management to reduce morbidity and mortality in patients with this disease.

Adherence to Subcutaneous Anti-Tumour Necrosis Factor Treatment in a Cohort of Patients with Rheumatoid Arthritis Before and After the Implementation of a Comprehensive Care Model.

Purpose: To assess, in a cohort of patients with rheumatoid arthritis (RA) treated with subcutaneous antitumor necrosis factor drugs (anti-TNFs), the levels of treatment adherence before and after implementing a comprehensive care model (CCM). Patients and Methods: An observational study including RA patients under treatment with subcutaneous anti-TNFs (adalimumab, etanercept, and golimumab) selected at convenience was performed; a sample size of 125 patients was calculated. The outcome variable was adherence assessed with the Compliance Questionnaire on Rheumatology (CQR19), measured before and after implementing a CCM. Descriptive and bivariate analyses were performed comparing adherence before and after applying the model (Wilcoxon and McNemar's Chi2 test). For multivariate analysis, a generalized linear model adjusted for covariates was performed, where the difference in the proportion of adherence was the outcome measure. Results: A total of 131 RA patients were followed-up for 24 months; average age was 62 years, and 83.9% were women. The median of DAS28 at the beginning of the follow-up was 2.32, and the HAQ was 0.25. At baseline, 87.8% were adherent; after 24 months, 96.2% were adherent according to CQR19. At the end of follow-up, adherence increased with the three types of anti-TNFs treatment. In a matched model adjusted for clinical variables, the CCM was estimated to produce a 9.4% increase in the total percentage of adherent patients. Additionally, a statistically significant increase of 4.5% in the percentage of adherent patients treated with golimumab compared with etanercept and adalimumab was found. Conclusion: A CCM produced an important increase in the percentage of patients with rheumatoid arthritis adherent to treatment after 24 months of follow-up. It is noteworthy that Golimumab patients were more adherent when compared with other current anti-TNFs treatments.

Better Clinical Results in Rheumatoid Arthritis Patients Treated Under a Multidisciplinary Care Model When Compared with a National Rheumatoid Arthritis Registry.

Purpose: To describe clinical characteristics and effectiveness of health care in patients with rheumatoid arthritis (RA) as part of a multidisciplinary care model (MCM) in a specialized rheumatology center, compared with the results of a national registry of RA (NARRA) as evidence of real-world management. Patients and Methods: We conducted a real-world study (July 1, 2018 to June 30, 2019) based on an analysis of electronic health records of a cohort of RA patients managed with the "Treat-to-Target" strategy in a specialized rheumatology center in Colombia with an MCM, compared with the NARRA that includes different models of usual care. Results: We have analyzed 7053 subjects with RA treated at a specialized rheumatology center and 81,492 patients from the NARRA. Cohorts were similar in their baseline characteristics, with women in predominance and diagnosis age close to 50 years. At the time of diagnosis, a higher proportion of clinical diagnostic test use and rheumatology consultation access was observed in the specialized rheumatology center than in the national registry (4-6 per year versus three or less). In addition, higher proportions of patients in remission and low disease activity were reported for the specialized rheumatology center, with a >40% amount of data lost in the national registry. Pharmacological management was similar regarding the analgesic use. In the specialized center, Certolizumab was more frequently used than in the NARRA registry; also, there were significant differences in methotrexate, leflunomide, and sulfasalazine use, being higher in the specialized rheumatology center. Conclusion: The MCM of a specialized center in RA can guarantee comprehensive care, with better access to all the services required to manage the disease. It ensures specialist management and evidence-based care that facilitates the achievement of therapeutic objectives. In addition, better patient records and follow-ups are available to evaluate health outcomes.

Vascular Age, Metabolic Panel, Cardiovascular Risk and Inflammaging in Patients With Rheumatoid Arthritis Compared With Patients With Osteoarthritis.

Introduction: The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is 1.5-2 times higher than the general population. The fundamental risk factor for CVD is age, related to alterations at the arterial level. The aim of the study was to compare vascular age (VA) in RA patients under a strict treat-to-target (T2T) strategy with Osteoarthritis (OA) patients without strict follow up and to assess the influence of inflammaging (chronic, sterile, low-grade inflammation related to aging) and metabolic markers on VA. Materials and Methods: This was an analytical cross-sectional study. Patients with RA (under a strict a T2T strategy) and OA patients without strict clinical follow-up were included. Patients with a history of uncontrolled hypertension, CVD, and/or current smoking were excluded. Sociodemographic, physical activity, and toxic exposure data were obtained. Waist-hip ratio and body mass index (BMI) were measured. DAS-28 (RA) and inflammatory markers, lipid profile, and glycaemia were analyzed. Pulse wave velocity (PWV) was measured (oscillometric method, Arteriograph-TensioMed®). VA was calculated based on PWV. Eleven components of inflammaging [six interleukins, three metalloproteinases (MMP), and two tissue inhibitors of metalloproteinases (TIMP)] were evaluated (Luminex® system). Univariate and bivariate analyzes (Mann Whitney U and chi-square) and correlations (Spearmans Rho) were done to compare the two groups. Results: A total of 106 patients (74% women) were included, 52/RA and 54/OA. The mean age was 57 (Interquartile range - IQR 9 years). The BMI, waist circumference, and weight were higher in patients with OA (p < 0.001). RA patients had low disease activity (DAS-28-CRP). There were no differences in VA, inflammaging nor in PWV between the two groups. VA had a positive, but weak correlation, with age and LDL. In group of RA, VA was higher in those who did not receive methotrexate (p = 0.013). LDL levels correlated with MMP1, TIMP1, and TIMP2. Conclusions: When comparing RA patients with low levels of disease activity with OA patients with poor metabolic control, there are no differences in VA. Furthermore, methotrexate also influences VA in RA patients. This shows that implemented therapies may have an impact on not only the inflammatory state of the joint but also CVD risk.

Trends on CO2 Capture with Microalgae: A Bibliometric Analysis.

The alarming levels of carbon dioxide (CO2) are an environmental problem that affects the economic growth of the world. CO2 emissions represent penalties and restrictions due to the high carbon footprint. Therefore, sustainable strategies are required to reduce the negative impact that occurs. Among the potential systems for CO2 capture are microalgae. These are defined as photosynthetic microorganisms that use CO2 and sunlight to obtain oxygen (O2) and generate value-added products such as biofuels, among others. Despite the advantages that microalgae may present, there are still technical-economic challenges that limit industrial-scale commercialization and the use of biomass in the production of added-value compounds. Therefore, this study reviews the current state of research on CO2 capture with microalgae, for which bibliometric analysis was used to establish the trends of the subject in terms of scientometric parameters. Technological advances in the use of microalgal biomass were also identified. Additionally, it was possible to establish the different cooperation networks between countries, which showed interactions in the search to reduce CO2 concentrations through microalgae.

First-in-human development of a pharmacodynamic biomarker for PAC1 receptor antagonists using intradermal injections of maxadilan.

Maxadilan, a potent vasodilator peptide, selectively activates the PAC1 receptor, a promising target for migraine therapy. Therefore, maxadilan has been suggested as a tool to study the pharmacodynamics (PDs) of PAC1 receptor antagonists. The objectives of this first-in-human study were to: (1) determine the safety, tolerability, dose response, and time course of the dermal blood flow (DBF) changes after intradermal (i.d.) injections of maxadilan in the human forearm, and (2) assess the inter-arm and inter-period reproducibility of this response. This was a single-center, open-label study in healthy subjects, comprising three parts: (1) dose-response (n = 25), (2) response duration (n = 10), and (3) reproducibility (n = 15). DBF measurements were performed using laser Doppler imaging (LDI) up to 60 min postinjection, or up to 5 days for the response duration assessments. To assess reproducibility, the intraclass correlation coefficient (ICC) and sample sizes were calculated. The i.d. maxadilan (0.001, 0.01, 0.1, 0.9, 3, and 10 ng) produced a well-tolerated, dose-dependent increase in DBF, with a half-maximal effective concentration fitted at 0.0098 ng. The DBF response to 0.9 ng maxadilan was quantifiable with LDI up to 72 h postinjection. The inter-period reproducibility of the DBF response was better upon 0.9 ng (ICC > 0.6) compared to 0.01 ng (ICC < 0.4) maxadilan. However, irrespective of the study design or maxadilan dose, a sample size of 11 subjects is sufficient to detect a 30% difference in DBF response with 80% power. In conclusion, intradermal maxadilan provides a safe, well-tolerated, and reproducible PD biomarker for PAC1 receptor antagonists in vivo in humans.