Bioactive Coatings on Titanium: A Review on Hydroxylation, Self-Assembled Monolayers (SAMs) and Surface Modification Strategies

Titanium (Ti) and its alloys have been demonstrated over the last decades to play an important role as inert materials in the field of orthopedic and dental implants. Nevertheless, with the widespread use of Ti, implant-associated rejection issues have arisen. To overcome these problems, antibacterial properties, fast and adequate osseointegration and long-term stability are essential features. Indeed, surface modification is currently presented as a versatile strategy for developing Ti coatings with all these challenging requirements and achieve a successful performance of the implant. Numerous approaches have been investigated to obtain stable and well-organized Ti coatings that promote the tailoring of surface chemical functionalization regardless of the geometry and shape of the implant. However, among all the approaches available in the literature to functionalize the Ti surface, a promising strategy is the combination of surface pre-activation treatments typically followed by the development of intermediate anchoring layers (self-assembled monolayers, SAMs) that serve as the supporting linkage of a final active layer. Therefore, this paper aims to review the latest approaches in the biomedical area to obtain bioactive coatings onto Ti surfaces with a special focus on (i) the most employed methods for Ti surface hydroxylation, (ii) SAMs-mediated active coatings development, and (iii) the latest advances in active agent immobilization and polymeric coatings for controlled release on Ti surfaces.This research was funding by Basque Government (ELKARTEK program, HAZITEK program–IMABI exp number ZE-2019/00012), Department of Development and Infrastructures of the Basque Country, University of the Basque Country UPV/EHU (GIU 207075), Ministry of Economy, Industry and Competitiveness (grant MAT2017-89553-P) and i+Med S. Coop

Myocardial injury determination improves risk stratification and predicts mortality in COVID-19 patients

Background: Despite being associated with worse prognosis in patients with COVID-19, systematic determination of myocardial injury is not recommended. The aim of the study was to study the effect of myocardial injury assessment on risk stratification of COVID-19 patients.Methods: Seven hundred seven consecutive adult patients admitted to a large tertiary hospital with confirmed COVID-19 were included. Demographic data, comorbidities, laboratory results and clinical outcomes were recorded. Charlson comorbidity index (CCI) was calculated in order to quantify the degree of comorbidities. Independent association of cardiac troponin I (cTnI) increase with outcomes was evaluated by multivariate regression analyses and area under curve. In addition, propensity-score matching was performed to assemble a cohort of patients with similar baseline characteristics.Results: In the matched cohort (mean age 66.76 ± 15.7 years, 37.3% females), cTnI increase above the upper limit was present in 20.9% of the population and was associated with worse clinical outcomes, including all-cause mortality within 30 days (45.1% vs. 23.2%; p = 0.005). The addition of cTnI to a multivariate prediction model showed a significant improvement in the area under the time-dependent receiver operating characteristic curve (0.775 vs. 0.756, DC-statistic = 0.019; 95% confidence interval 0.001–0.037). Use of renin–angiotensin–aldosterone system inhibitors was not associated with mortality after adjusting by baseline risk factors.Conclusions: Myocardial injury is independently associated with adverse outcomes irrespective of baseline comorbidities and its addition to multivariate regression models significantly improves their performance in predicting mortality. The determination of myocardial injury biomarkers on hospital admission and its combination with CCI can classify patients in three risk groups (high, intermediate and low) with a clearly distinct 30-day mortality

Efficacy of Manual Therapy on Facilitatory Nociception and Endogenous Pain Modulation in Older Adults with Knee Osteoarthritis: A Case Series.

Background: manual therapy (MT) has been shown to have positive effects in patients with osteoarthritis (OA)-related pain, and its use in clinical settings is recommended. However, the mechanisms of action for how these positive effects occur are not yet well understood. The aim of the present study was to investigate the influence of MT treatment on facilitatory nociception and endogenous pain modulation in patients with knee OA related pain. Methods: Twenty-eight patients with knee OA were included in this study. Pain intensity using the numerical pain rating scale (NPRS), temporal summation (TS), conditioned pain modulation (CPM), and local (knee) and distant (elbow) hyperalgesia through the pressure pain threshold (PPT), were assessed to evaluate the pain modulatory system. Patients underwent four sessions of MT treatments within 3 weeks and were evaluated at the baseline, after the first session and after the fourth session. Results: the MT treatment reduced knee pain after the first session (p = 0.03) and after the fourth session (p = 0.04). TS decreased significantly after the fourth session of MT (p = 0.02), while a significant increase in the CPM assessment was detected after the fourth session (p = 0.05). No significant changes in the PPT over the knee and elbow were found in the follow-ups. Conclusions: The results from our study suggest that MT might be an effective and safe method for improving pain and for decreasing temporal summation.post-print502 K

Encapsulation of folic acid in different silica porous supports: A comparative study

Although folic acid is essential to numerous bodily functions, recent research indicates that a massive exposition to the vitamin could be a double-edged sword. In this study, the capacity of different caped mesoporous silica particles (i.e. Hollow Silica Shells, MCM-41, SBA-15 and UVM-7) to dose FA during its passage through the gastrointestinal tract has been evaluated. Results confirmed that the four capped materials were capable to hinder the delivery of FA at low pH (i.e. stomach) as well as able to deliver great amounts of the vitamin at neutral pH (i.e. intestine). Nevertheless, the encapsulation efficiency and the deliver kinetics differed among supports. While supports with large pore entrance exhibited an initial fast release, MCM-41, showed a sustained release along the time. This correlation between textural properties and release kinetics for each of the supports reveals the importance of a proper support selection as a strategy to control the delivery of active molecules.Authors gratefully acknowledge the financial support from the Ministerio de Economia y Competitividad (Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02 and MAT2012-38429-C04-01) and the Generalitat Valenciana (project PROMETEO/2009/016). E.P. and M.R. are grateful to the Ministerio de Ciencia e Innovacion for their Grants (AP2008-00620, AP2010-4369). Electron Microscopy Service of the UPV is also acknowledged.Pérez-Esteve, É.; Ruiz Rico, M.; De La Torre Paredes, C.; Villaescusa Alonso, LA.; Sancenón Galarza, F.; Marcos Martínez, MD.; Amoros Del Toro, PJ.... (2016). Encapsulation of folic acid in different silica porous supports: A comparative study. Food Chemistry. 196:66-75. https://doi.org/10.1016/j.foodchem.2015.09.017S667519

Comparação de pH e matéria seca em três processos de silagem com forragem de gergelim (Sesamum indicum) nos trópicos secos.

El objetivo de este estudio fue comparar el pH y la materia seca (MS) en tres procesos de ensilaje con planta de ajonjolí en climas secos. Los experimentos se realizaron en la Facultad de Medicina Veterinaria y Zootecnia No. 1 de la Universidad Autónoma de Guerrero. En el experimento 1, se ensiló forraje de maíz combinado con forraje de ajonjolí (T1: 100:00, T2: 75:25, T3: 50:50, T4: 25:75 y T5: 00:100% respectivamente). En el experimento 2 se ensiló forraje de ajonjolí mezclado con melaza (T1:0, T2:4, T3:8 y T4:12% respectivamente) En el experimento 3 se ensiló planta de ajonjolí sola (T1), con melaza 8% (T2), planta presecada sola (T3) y planta presecada con melaza 8% (T4). Se realizaron síes microsilos por tratamiento (6 réplicas). Los diseños experimentales fueron completamente al azar. En el experimento 1, el pH más bajo fue para el T1 con un valor de 3.83, en el experimento 2 fue para el T4 con un valor de 3.94 y en el experimento 3 fue para el T2 con un valor de 4.00. Para la MS, el contenido fue mayor para el T1 con 28.55%, en el experimento 2 fue para el T4 con 27.63% y en el experimento 3 fue para el T3 con 36.00%. Todos los experimentos mostraron diferencia estadística (p< 0.0001) entre tratamientos. Sin embargo, los valores para pH y MS son aceptables para prácticamente todos los tratamientos, en acuerdo con otras investigaciones. Por lo tanto, se concluye que al ensilar forraje de ajonjolí mezclado con forraje de maíz, melaza o planta presercada se logra mejorar la fermentación ácida y se incrementa el contenido de materia seca. Sin embargo, es necesario realizar evaluaciones posteriores de las propiedades físico-químicas y determinar su valor nutritivo.The objective of this study was to compare the pH and dry matter (DM) in three silage processes with sesame plants in dry climates. The experiments were carried out at the Faculty of Veterinary Medicine and Zootechnics No. 1 of the Autonomous University of Guerrero. In experiment 1, corn forage combined with sesame forage was ensiled (T1: 100:00, T2: 75:25, T3: 50:50, T4: 25:75 and T5: 00:100% respectively). In experiment 2 sesame forage mixed with molasses (T1:0, T2:4, T3:8 and T4:12% respectively) was ensiled. In experiment 3 sesame plant alone (T1) was ensiled with 8% molasses ( T2), pre-dried plant alone (T3) and pre-dried plant with 8% molasses (T4). Six microsilos per treatment (6 replicates) were made. The experimental designs were completely randomized. In experiment 1, the lowest pH was for T1 with a value of 3.83, in experiment 2 it was for T4 with a value of 3.94 and in experiment 3 it was for T2 with a value of 4.00. For DM, the content was higher for T1 with 28.55%, in experiment 2 it was for T4 with 27.63% and in experiment 3 it was for T3 with 36.00%. All the experiments showed statistical difference (p< 0.0001) between treatments. However, the values for pH and DM are acceptable for practically all treatments, in agreement with other investigations. Therefore, it is concluded that ensiling sesame forage mixed with corn forage, molasses or presercated plant improves acid fermentation and increases the dry matter content. However, it is necessary to carry out further evaluations of the physical-chemical properties and determine its nutritive value.O objetivo deste estudo foi comparar o pH e a matéria seca (MS) em três processos de silagem com plantas de gergelim em climas secos. Os experimentos foram realizados na Faculdade de Medicina Veterinária e Zootecnia nº 1 da Universidade Autônoma de Guerrero. No experimento 1, a forragem de milho combinada com a forragem de gergelim foi ensilada (T1: 100:00, T2: 75:25, T3: 50:50, T4: 25:75 e T5: 00:100% respectivamente). No experimento 2 a forragem de gergelim foi ensilada misturada com melaço (T1:0, T2:4, T3:8 e T4:12% respectivamente) - planta seca sozinha (T3) e planta pré-seca com 8% de melaço (T4). Seis microsilos por tratamento (6 réplicas) foram feitos. Os delineamentos experimentais foram inteiramente casualizados. No experimento 1, o menor pH foi para T1 com valor de 3,83, no experimento 2 foi para T4 com valor de 3,94 e no experimento 3 foi para T2 com valor de 4,00. Para MS o teor foi maior para T1 com 28,55%, no experimento 2 foi para T4 com 27,63% e no experimento 3 foi para T3 com 36,00%. Todos os experimentos apresentaram diferença estatística (p< 0,0001) entre os tratamentos. No entanto, os valores de pH e MS são aceitáveis ​​para praticamente todos os tratamentos, concordando com outras investigações. Portanto, conclui-se que a ensilagem de forragem de gergelim misturada com forragem de milho, melaço ou planta preservada melhora a fermentação ácida e aumenta o teor de matéria seca. No entanto, é necessário realizar mais avaliações das propriedades físico-químicas e determinar seu valor nutritivo

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed

Inhaled Methoxyflurane Provides Greater Analgesia and Faster Onset of Action Versus Standard Analgesia in Patients With Trauma Pain: InMEDIATE: A Randomized Controlled Trial in Emergency Departments

Study objective: The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe. Methods: This was a randomized, controlled study that enrolled adult patients with acute moderate to severe (score >= 4 on the 11-point Numeric Rating Scale) trauma-associated pain in 14 Spanish emergency departments. Patients were randomized 1:1 to methoxyflurane (up to 2x3 mL) or standard analgesic treatment. Coprimary endpoints were the change from baseline in Numeric Rating Scale pain intensity score during the first 20 minutes of treatment and time to first pain relief. Results: Three hundred five patients were randomized (methoxyflurane 156; standard analgesic treatment 149). Most patients in the standard analgesic treatment group (70%) received intravenous first-step analgesics and 9.4% of patients were treated with opioids. Mean decrease from baseline in Numeric Rating Scale pain intensity score was greater for methoxyflurane than standard analgesic treatment at all points, with a significant treatment difference overall up to 20 minutes (repeated-measures model 2.47 versus 1.39; treatment difference 1.00; 95% confidence interval 0.84 to 1.32). Median time to first pain relief was significantly shorter for methoxyflurane than standard analgesic treatment (3 versus 10 minutes). Methoxyflurane achieved better patient and clinician ratings for pain control and comfort of treatment than standard analgesic treatment and exceeded patient and clinician expectations of treatment in, respectively, 77% and 72% of cases compared with 38% and 19% for standard analgesic treatment. Conclusion: These results support consideration of methoxyflurane as a nonnarcotic, easy-to-administer, rapid-acting, first-line alternative to currently available analgesic treatments for trauma pain

Dystrophinopathy Phenotypes and Modifying Factors in Exon 45-55 Deletion

Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset. This cross-sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies. The series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index-case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45-57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors. We confirmed that del45-55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793-80

Estudio histórico del poblamiento, la evolución del paisaje y los usos en la sierra de Aralar

El uso y la gestión de la montaña en la sierra de Aralar han podido ser documentados desde el Neolítico hasta nuestros días en restos antrópicos que van desde megalitos hasta minas, pasando por el aprovechamiento de cuevas y diversos tipos de asentamientos en forma de cabañas. Estas evidencias han podido ser inventariadas, estudiadas y datadas en muchos casos. La ganadería, estacional, es la principal actividad relacionada con estas estructuras, y las condiciones ambientales, culturales y económicas han ido determinando sus características. Ha sido necesaria una metodología multidisciplinaria que apoyara a la arqueología para ir estudiando desde 1993 los a veces esquivos restos dejados por las personas que han gestionado los recursos de la zona