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Objective: to evaluate a membrane based on type B gelatin (G) and porcine urinary bladder extracellular matrix (PUB-EM), highlighting the potential effect of the combination evaluated by biocompatibility and regulation of the expression of transcription factors involved in tissue regeneration. G-PUB-EM membranes were prepared at 12.5, 25, and 50% w/v, and evaluated for biocompatibility with Fibroblast. Chemical characterization by FTIR-ATR showed complex spectra during crosslinking process with glutaraldehyde. Physical tests were performed in deionized water and PBS for 48 h. A significant increase in swelling was observed during the first 2 h. Biocompatibility testing (MTS) and evaluation of the expression profile of genes involved in the cell cycle (Cyclin-D1 VEGF, TNF and NF-κ-B) by PCR showed an increase in viability in a PUB-EM content-dependent way, except for 50% PUB-EM membrane which showed cytotoxic effects with a decrease in cell viability below 70%. The membranes showed an increase in the expression of some factors of cell cycle, as well as inflammatory processes that could promote tissue repair. 12.5 and 25% gelatin type B/porcine urinary bladder extracellular matrix (G/PUB-EM) based membranes have potential for tissue regeneration applications., Impact Statement: The use of membranes based on type B gelatin and porcine urinary bladder for tissue engineering represents a novel strategy. Biocompatibility and signaling pathways play a primary role in tissue repair and wound recovery. Transcription factors that mediate signaling, cell division and vascularization are part of molecules that intervene in the regenerative potential of cells. These techniques will have a significant impact on tissue repair and regeneration and thus stop depending on tissue donors or other surgical sites from the same patient, as is the case with burn patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Statement of Problem: Lack of conversion of resin cements for luting glass fiber posts in deeper levels of the root canal may compromise clinical performance., Purpose: The purpose of this in vitro study was to evaluate the effect of the degree of conversion on the surface properties of dual-polymerized resin cements used for cemented glass fiber posts according to the root level., Material and Methods: Fifty maxillary central incisor teeth were endodontically treated, and glass fiber posts were cemented using the following systems: self-adhesive dual-polymerized resin luting cement (RelyX U200) and dual-polymerizing flowable core and a post luting system (Rebilda DC) with a self-etching adhesive (Futurabond DC). The degree of conversion was determined via attenuated total reflectance and Fourier transform infrared spectroscopy, and surface microhardness and cement film thickness were measured. The intraradicular fit was evaluated with microscopy. All tests were performed in the coronal, middle, and apical third of the root canal. Statistical analysis was done with ANOVA and the multiple comparison Tukey test (α=.05)., Results: The degree of conversion was higher in the coronal third using Rebilda DC (65.3 ±4.8%) than RelyX U200 (38.7 ±5.3%) (P<.05); on both resin cements, these values decreased from the coronal to the apical third (30.9 ±3.7%, 61.9 ±8.7%, respectively). The cement film thickness was higher for RelyX U200 in the 3 thirds than for Rebilda DC; significant differences (P<.05) were recorded in both cementing systems in the coronal and apical thirds. In the middle third, no significant differences were observed (P>.05). The mean surface microhardness values increased in the coronal thirds and decreased with increasing root canal depth. The marginal seal in the coronal thirds and the intraradicular fit in the middle thirds showed closer adaptation; however, some tags were observed in the interface resin cement and radicular dentin. Gap and tag formations were observed in the apical third., Conclusions: Depending on the root canal third, the surface properties of dual-polymerized resin cements are influenced by the degree of conversion., (Copyright © 2023 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Naegleria fowleri is an etiological agent that generates primary amoebic meningoencephalitis; unfortunately, no effective treatment or vaccine is available. The objective of this work was to determine the immunoprotective response of two vaccine antigens, as follows: (i) the polypeptide band of 19 kDa or (ii) a predicted immunogenic peptide from the membrane protein MP2CL5 (Smp145). Both antigens were administered intranasally in mice using cholera toxin (CT) as an adjuvant. The survival rate and immune response of immunized mice with both antigens and challenged with N. fowleri trophozoites were measured in the nose-associated lymphoid tissue (NALT) and nasal passages (NPs) by flow cytometry and enzyme-linked immunosorbent assay (ELISA). We also determined the immunolocalization of both antigens in N. fowleri trophozoites by confocal microscopy. Immunization with the polypeptide band of 19 kDa alone or coadministered with CT was able to confer 80% and 100% of protection, respectively. The immunization with both antigens (alone or coadministered with CT) showed an increase in T and B lymphocytes. In addition, there was an increase in the expression of integrin α4β1 and IgA in the nasal cavity of protected mice, and the IgA, IgG, and IgM levels were increased in serum and nasal washes. The immunolocalization of both antigens in N. fowleri trophozoites was observed in the plasma membrane, specifically in pseudopod-like structures. The MP2CL5 antigens evaluated in this work were capable of conferring protection which would lead us to consider them as potential candidates for vaccines against meningitis caused by N. fowleri., Competing Interests: The authors declare no conflict of interest.

The Human Immunodeficiency Virus (HIV-1) causes Acquired Immunodeficiency Syndrome (AIDS) and a high percentage of deaths. Therefore, it is necessary to design vaccines against HIV-1 for the prevention of AIDS. Bioinformatic tools and theoretical algorisms allow us to understand the structural proteins of viruses to develop vaccines based on immunogenic peptides (epitopes). In this work, we identified the epitopes: P1, P2, P10, P27 and P30 from the gp120 protein of HIV-1. These peptides were administered intranasally alone or with cholera toxin (CT) to BALB/c mice. The population of CD4+, CD8+ T lymphocytes and B cells (CD19/CD138+, IgA+ and IgG+) from nasal-associated lymphoid tissue, nasal passages, cervical and inguinal nodes was determined by flow cytometry. In addition, anti-peptides IgG and IgA from serum, nasal and vaginal washings were measured by ELISA. The results show that peptides administered by i.n. can modulate the immune response of T and B lymphocyte populations, as well as IgA and IgG antibodies secretion in the different sites analyzed. In conclusion, bioinformatics tools help us to select peptides with physicochemical properties that allow the induction of the humoral and cellular responses that depend on the peptide sequence., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Purpose: This study evaluated the association of surface degradation and formation of Streptococcus mutans (S. mutans) biofilm in resin-based composites (RBCs) after storage in different acidic liquids., Methods: To evaluate microhardness and surface micromorphology, hybrid and nanohybrid RBC discs were stored in artificial gastric acid, cola drink, orange juice, artificial saliva, and distilled water for three intervals of 15 min per day for 7, 15, and 30 days. After 30 days of storage, surface roughness was analyzed, and the RBC discs were placed in a biofilm reactor inoculated with S. mutans to evaluate surface biofilm formation., Results: As compared with nanohybrid RBCs, roughness and surface microhardness values were significantly lower (P < 0.05) for hybrid RBCs stored in artificial gastric acid, followed by specimens stored in cola drink and orange juice. Artificial gastric acid caused greater surface degradation, which increased the biomass of S. mutans on the surface of both RBC types., Conclusion: Surface degradation of hybrid and nanohybrid RBCs correlated with the pH of the liquid, while S. mutans biofilm formation was associated with increased surface roughness in hybrid RBCs.

Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid ( C1 ), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn's disease.

Background: We aim to describe and compare patients and general practitioners' opinions about the different variables related to acute and preventive treatment for migraine., Patients and Methods: An observational descriptive study was performed. Patients with episodic migraine and general practitioners, from our healthcare area, were invited to answer a survey about the different variables related to migraine treatment. They were asked for their opinions on the different variables, and to consider the desired efficacy in percentage terms and the desired action times of treatment., Results: Fifty-five patients and fifty-five general practitioners were selected. Effectiveness was considered the most important variable for symptomatic and preventive treatment. Cost was considered the least important variable. Patients desired percentage of efficacy was 84.0% (±16.7%) for symptomatic treatment and 79.9% (±17.1%) for preventive treatment. General practitioners desired percentage of efficacy was 75.0% (±14.0) for symptomatic treatment and 70.4% (±14.3) for preventive treatment. For symptomatic treatment the desired action time for pain cessation was selected as 27.5 min (±13.8) for patients and 24.0 min (±18.3) for GPs. For preventive treatment the desired action time for effect was 7.1 days (±4.5) for patients and 13.9 days (±8.9) for general practitioners., Conclusion: The most important endpoints were, for acute: effectiveness, a short action time and a persistent effect. For prophylactic: effectiveness, sustained effect and tolerability. Both patients and general practitioners agreed on the most and least preferred endpoints. Desired percentage of efficacy was above 75% for both symptomatic and preventive treatment; and the desired action time was below 30 min for acute treatment and 2 weeks for preventive treatment., (© 2021. The Author(s).)

The aims of this in vitro study were to synthesize, characterize, and evaluate the efficacy of a Calcium Hydroxide/Iodoform nanoparticles (CHIN) paste compared with Ultrapex as intracanal filling medication using an experimental model of bovine primary teeth. CH nanoparticle synthesis was performed via the simple hydrolysis technique of reacting calcium nitrate with sodium hydroxide. SEM-EDS and FT-IR analyses were used to characterize the obtained product. 30% of CH nanoparticles were combined with 40% of iodoform and 30% silicone oil to prepare an intracanal filling paste (CHIN). All endodontic procedures were performed on 34 uniradicular primary bovine teeth. Every root canal was instrumented with K files (up to #35) and obturated with the nanoparticle paste (experimental) or Ultrapex ® (control). Three outcome variables were studied: penetration depth through the root dentinal tubules, Ca 2+ ion release, and filling paste dissolution rate. The obtained data were analyzed by Student's t test. The X-ray diffraction pattern of CH nanoparticles showed characteristic peaks at CH, as confirmed by FT-IR analyses in which an intense signal was observed at 3643 cm -1 , characteristic of CH. In the morphological characterization, CH particles could be detected at the nanosize scale. When applied as intracanal filling, the CHIN paste exhibited a higher level of penetration through the root dentin tubules. The global mean penetration measures were 500 µm for the experimental paste and 380 µm for the control paste (p < 0.05). The release of Ca 2+ ions (up to the seventh day) and the dissolution rate were significantly higher in the experimental paste group than in the control group. No significant differences were observed between the groups regarding pH levels. The findings of this study suggest the potential suitability of CHI nanoparticles as an alternative intracanal filling medication for infected or devitalized primary teeth.

Background: Coronavirus disease 2019 (Covid-19) might present neurological symptoms. We aimed to evaluate the frequency of them at the moment of emergency department (ED) visit and their impact in the prognosis., Methods: Retrospective cohort study including all consecutive hospitalized cases between March 8th and April 11th, 2020. Covid-19 diagnosis was confirmed by polymerase chain reaction test and/or serology. We compared, in patients with and without neurological symptoms on admission, demographic, clinical presentation, and frequency and type of abnormal laboratory values. We analyzed the variables that were associated with in-hospital all-cause mortality by Cox-regression log-rank test., Results: We included 576 hospitalized patients, 250 (43.3%) female, aged 67.2 years. At the moment of ED visit, 320 (55.6%) described neurological symptoms, including anosmia (146, 25.3%), myalgia (139, 24.1%), headache (137, 23.8%), and altered mental status (98, 17.0%). Neurological symptoms started the first symptomatic day in 198 (54.2%) cases. Patients with neurological symptoms presented later to the ED (7.9 versus. 6.6 days, p = .019). Only four (0.6%) cases had no typical Covid-19 general symptoms, and only six (1.9%) had a normal laboratory results, for a sensitivity of 98.7% (95% confidence interval (CI): 96.6%-99.6%) and 98.1% (95% CI: 95.7%-99.2%), respectively. In the multivariate Cox-regression of mortality predictors, anosmia (HR: 0.358, 95%CI: 0.140-0.916) and altered mental status (HR: 1.867, 95%CI: 1.162-3.001) were significant., Conclusion: Neurological symptoms were the most frequent extrapulmonary symptoms. They were present in half of the Covid-19 patients at the time of the ED visit. Anosmia on admission was an independent predictor of lower in-hospital mortality and altered mental status on admission predicted in-hospital mortality., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Anosmia is common in Coronavirus disease 2019, but its impact on prognosis is unknown. We analysed whether anosmia predicts in-hospital mortality; and if patients with anosmia have a different clinical presentation, inflammatory response, or disease severity., Methods: Retrospective cohort study including all consecutive hospitalized patients with confirmed Covid-19 from March 8th to April 11th, 2020. We determined all-cause mortality and need of intensive care unit (ICU) admission. We registered the first and worst laboratory parameters. Statistical analysis was done by multivariate logistic and linear regression., Results: We included 576 patients, 43.3% female, and aged 67.2 years in mean. Anosmia was present in 146 (25.3%) patients. Patients with anosmia were more frequently females, younger and less disabled and had less frequently hypertension, diabetes, smoking habit, cardiac and neurological comorbidities. Anosmia was independently associated with lower mortality (OR: 0.180, 95% CI: 0.069-0.472) and ICU admission (OR: 0.438, 95% CI: 0.229-0.838, p = 0.013). In the multivariate analysis, patients with anosmia had a higher frequency of cough (OR: 1.96, 95%CI: 1.18-3.28), headache (OR: 2.58, 95% CI: 1.66-4.03), and myalgia (OR: 1.74, 95% CI: 1.12-2.71). They had higher adjusted values of hemoglobin (+0.87, 95% CI: 0.40-1.34), lymphocytes (+849.24, 95% CI: 157.45-1541.04), glomerular filtration rate (+6.42, 95% CI: 2.14-10.71), and lower D-dimer (-4886.52, 95% CI: -8655.29-(-1117.75)), and C-reactive protein (-24.92, 95% CI: -47.35-(-2.48))., Conclusions: Hospitalized Covid-19 patients with anosmia had a lower adjusted mortality rate and less severe course of the disease. This could be related to a distinct clinical presentation and a different inflammatory response., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Epicrania fugax consists of brief paroxysms of pain, which radiate in a line or in zigzag trajectory across the surface of the scalp or the face., Methods: A prospective, descriptive study was performed in five patients presenting with an epicrania fugax-type pain with extracephalic irradiation., Results: All patients were women, and the mean age at onset was 59.8 (standard deviation, 10.9). They had unilateral paroxysms of electrical pain starting at a particular point in the head (parietal, n = 3; vertex, n = 1; frontal, n = 1) and rapidly radiating downwards in a lineal trajectory to reach extracephalic regions (ipsilateral limbs, n = 2; shoulder, n = 2; low neck, n = 1) in 1-3 seconds. Pain intensity was moderate or severe. Three patients had nummular headache at the point where the paroxysms originated. One patient had spontaneous remission, and four patients achieved complete or almost complete response with therapy (onabotulinumtoxinA, n = 2; indomethacin, n = 1; amitriptyline, n = 1; lamotrigine, n = 1)., Conclusion: The spectrum of epicrania fugax may include paroxysms with extracephalic irradiation. The propagation of pain beyond the head and the face supports the involvement of central mechanisms in the pathophysiology of this entity.

Introduction: Headache is one of the most frequent neurologic manifestations in COVID-19. We aimed to analyze which symptoms and laboratory abnormalities were associated with the presence of headache and to evaluate if patients with headache had a higher adjusted in-hospital risk of mortality., Methods: Retrospective cohort study. We included all consecutive patients admitted to the Hospital with confirmed SARS-CoV-2 infection between March 8th and April 11th, 2020. We collected demographic data, clinical variables and laboratory abnormalities. We used multivariate regression analysis., Results: During the study period, 576 patients were included, aged 67.2 (SD: 14.7), and 250/576 (43.3%) being female. Presence of headache was described by 137 (23.7%) patients. The all-cause in-hospital mortality rate was 127/576 (20.0%). In the multivariate analysis, patients with headache had a lower risk of mortality (OR: 0.39, 95% CI: 0.17-0.88, p = 0.007). After adjusting for multiple comparisons in a multivariate analysis, variables that were independently associated with a higher odds of having headache in COVID-19 patients were anosmia, myalgia, female sex and fever; variables that were associated with a lower odds of having headache were younger age, lower score on modified Rankin scale, and, regarding laboratory variables on admission, increased C-reactive protein, abnormal platelet values, lymphopenia and increased D-dimer., Conclusion: Headache is a frequent symptom in COVID-19 patients and its presence is an independent predictor of lower risk of mortality in COVID-19 hospitalized patients.

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND., (Copyright © 2020 García-Azorín, Martínez-Pías, Trigo, Hernández-Pérez, Valle-Peñacoba, Talavera, Simón-Campo, de Lera, Chavarría-Miranda, López-Sanz, Gutiérrez-Sánchez, Martínez-Velasco, Pedraza, Sierra, Gómez-Vicente, Guerrero, Ezpeleta, Peñarrubia, Gómez-Herreras, Bustamante-Munguira, Abad-Molina, Orduña-Domingo, Ruiz-Martin, Jiménez-Cuenca, Juarros, del Pozo-Vegas, Dueñas-Gutierrez, de Paula, Cantón-Álvarez, Vicente and Arenillas.)

The intranasal administration of Naegleria fowleri lysates plus cholera toxin (CT) increases protection against N. fowleri meningoencephalitis in mice, suggesting that humoral immune response mediated by antibodies is crucial to induce protection against the infection. In the present study, we applied a protein analysis to detect and identify immunogenic antigens from N. fowleri , which might be responsible for such protection. A Western blot assay of N. fowleri polypeptides was performed using the serum and nasal washes from mice immunized with N. fowleri lysates, either alone or with CT after one, two, three, or four weekly immunizations and challenged with trophozoites of N. fowleri. Immunized mice with N. fowleri plus CT, after four doses, had the highest survival rate (100%). Nasal or sera IgA and IgG antibody response was progressively stronger as the number of immunizations was increased, and that response was mainly directed to 250, 100, 70, 50, 37, and 19 kDa polypeptide bands, especially in the third and fourth immunization. Peptides present in these immunogenic bands were matched by nano-LC-ESI-MSMS with different proteins, which could serve as candidates for a vaccine against N. fowleri infection.

Many pathogenicity factors are involved in the development of primary amoebic meningoencephalitis (PAM) caused by N fowleri. However, most of them are not exclusive for N fowleri and they have not even been described in other nonpathogenic Naegleria species. Therefore, the objective of this work was to identify differential proteins and protein pattern recognition between Naegleria fowleri and Naegleria lovaniensis using antibodies anti-N fowleri as strategy to find vaccine candidates against meningoencephalitis. Electrophoresis and Western blots conventional and 2-DE were performed for the identification of antigenic proteins, and these were analysed by the mass spectrometry technique. The results obtained in 2-DE gels and Western blot showed very notable differences in spot intensity between these two species, specifically those with relative molecular weight of 100, 75, 50 and 19 kDa. Some spots corresponding to these molecular weights were identified as actin fragment, myosin II, heat shock protein, membrane protein Mp2CL5 among others, with differences in theoretical post-translational modifications. In this work, we found differences in antigenic proteins between both species, proteins that could be used for a further development of vaccines against N fowleri infection., (© 2020 John Wiley & Sons Ltd.)

Peptide epitopes have been widely used to develop synthetic vaccines and immunotherapies. However, peptide epitopes may exhibit poor absorption or immunogenicity due to their low molecular weights. Conversely, fourth-generation polyamidoamine (G4-PAMAM) dendrimers are nonimmunogenic and relatively nontoxic synthetic nanoparticles that have been used as adjuvants and nanocarriers of small peptides and to improve nasal absorption. Based on this information, we hypothesized that the combination of intranasal immunization and G4-PAMAM dendrimers would be useful for enhancing the antibody responses of HIV-1 gp120 peptide epitopes. Therefore, we first used structural data, peptide epitope predictors and docking and MD simulations on MHC-II to identify two peptide epitopes on the CD4 binding site of HIV-1 gp120. The formation of G4-PAMAM-peptide complexes was evaluated in silico (molecular docking studies using different G4-PAMAM conformations retrieved from MD simulations as well as the MMGBSA approach) and validated experimentally (electrophoresis, 1 H NMR and cryo-TEM). Next, the G4-PAMAM dendrimer-peptide complexes were administered intranasally to groups of female BALB/cJ mice. The results showed that both peptides were immunogenic at the systemic and mucosal levels (nasal and vaginal), and G4-PAMAM dendrimer-peptide complexes improved IgG and IgA responses in serum and nasal washes. Thus, G4-PAMAM dendrimers have potential for use as adjuvants and nanocarriers of peptides., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The engineering of bone tissues represents an area of opportunity for the development of new polymeric compounds. In this context, the objective of this work is the generation and evaluation in vitro of supports obtained from mixtures of starch with poly (lactic acid) (PLA), treated with arginine-glycine-aspartic acid peptides (RGD). For this, non-woven fibers of PLA with different starch content (0.0, 2.5, 5.0 and 10.0%wt) were obtained using the electrospinning technique. Then the physical absorption of RGD was carried out, with the aim of increasing the cellular adhesion of the polymeric material. Subsequently, in vitro biocompatibility tests were performed, and viability (LIFE/DEAD), proliferation (MTS assay) and cell adhesion were carried out with osteoblasts incubated for 48 h. Regarding biocompatibility results, only viable cells were found for all the compositions, and the biocompatibility of the materials was validated by the morphological analysis of the cultured cells, where extended cells were observed. Proliferation assays show that osteoblasts proliferate better on the surfaces of PLA and PLA with 5.0% starch scaffolds. Therefore, it is concluded that the scaffolds obtained by electrospinning of PLA with starch and functionalized with RGD are promising for its use in the regeneration of bone tissue., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Balamuthia mandrillaris is the causative agent of granulomatous amoebic encephalitis, a rare and often fatal infection affecting the central nervous system. The amoeba is isolated from diverse environmental sources and can cause severe infections in both immunocompromised and immunocompetent individuals. Given the limited understanding of B. mandrillaris, our research aimed to explore its protein profile, identifying potential immunogens crucial for early granulomatous amoebic encephalitis diagnosis. Cultures of B. mandrillaris and other amoebas were grown under axenic conditions, and total amoebic extracts were obtained. Proteomic analyses, including two-dimensional electrophoresis and mass spectrometry, were performed. A 50-kDa band showed a robust recognition of antibodies from immunized BALB/c mice; peptides contained in this band were matched with elongation factor-1 alpha, which emerged as a putative key immunogen. Besides, lectin blotting revealed the presence of glycoproteins in B. mandrillaris, and confocal microscopy demonstrated the focal distribution of the 50-kDa band throughout trophozoites. Cumulatively, these observations suggest the participation of the 50-kDa band in adhesion and recognition mechanisms. Thus, these collective findings demonstrate some protein characteristics of B. mandrillaris, opening avenues for understanding its pathogenicity and developing diagnostic and therapeutic strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

5-[(4-carboxybutanoyl)amino]-2-hydroxybenzoic acid (C2) is a novel synthetic derivative of 5-aminosalicylic acid (5-ASA), which is currently being evaluated ex vivo as an anti-inflammatory agent and has shown satisfactory results. This study aimed to obtain the pharmacokinetic profiles, tissue distribution and plasma protein binding of C2 in Wistar Rats. Additionally, an HPLC method was developed and validated to quantify C2 in rat plasma. The pharmacokinetic profiles of intragastric, intravenous and intraperitoneal administration routes at singles doses of 100, 50, and 100 mg/kg, respectively, were studied in Wistar rats. The elimination half-life of intravenously administered C2 was approximately 33 min. The maximum plasma level of C2 was reached approximately 24 min after intragastric administration, with a Cmax value of 2.5 g/mL and an AUCtot value of 157 μg min-1/mL; the oral bioavailability was approximately 13%. Following a single intragastric or oral dose (100 mg/kg), C2 was distributed and detected in all examined tissues (including the brain and colon). The results showed that C2 accumulates over time. The plasma protein binding results indicated that the unbound fraction of C2 at concentrations of 1 to 20 μg/mL ranged from 89.8% to 92.5%, meaning that this fraction of C2 is available to cross tissues. Finally, the blood-plasma partitioning (BP ratio) of C2 in rat plasma was 0.71 and 0.6 at concentrations of 5 and 10 μg/mL, respectively, which indicates that C2 is free in the plasmatic phase and not inside blood cells. The results of this study suggest that a fraction of the administered C2 dose is absorbed in the stomach, and the fraction that is not absorbed reaches the small intestine and colon. This distribution constitutes the main advantage of C2 compared with 5-ASA for the treatment of ulcerative colitis (UC) and Crohn's disease (CD).

A case study of a 33-year-old woman who suffered from haemolytic-uraemic syndrome (HUS) and given acute peritoneal dialysis which help in recovering renal functions. Later she was diagnosed with focal segmental hyalinosis by renal biopsy and treated with angiotensin converting enzyme inhibitors which help in reducing proteinuria and maintain glomerular filtration rate. The data from the case study shows that HUS in children may cause renal failure, high blood pressure (HBP) and proteinuria.

A case study of a 35-year-old Moroccan male is presented who has no previous illnesses, is diagnosed with focal segmental glomerulonephritis (FSGN). He was treated with angiotensin converting enzyme inhibitors (ACEI) and immunoglobulin Ig d which helps in decreasing proteinuria. Later he was diagnosed with sarcoidosis by computerized tomography (CT) when he experience abdominal pain, diarrhoea and vomiting showing close association of FSGN with sarcoidosis.

Regenerative therapy, a key area of tissue engineering, holds promise for restoring damaged organs, especially in bone regeneration. Bone healing is natural to the body but becomes complex under stress and disease. Large bone deformities pose significant challenges in tissue engineering. Among various methods, scaffolds are attractive as they provide structural support and essential nutrients for cell adhesion and growth. Collagen and hydroxyapatite (HA) are widely used due to their biocompatibility and biodegradability. Collagen and nano-scale HA enhance cell adhesion and development. Thus, nano HA/collagen scaffolds offer potential solutions for bone regeneration. This review focuses on the use and production of nano-sized HA/collagen composites in bone regeneration. Article Highlights Current treatment options for bone trauma The skeletal system's structure, consisting of cortical and trabecular bone, is vital for mobility, support, protection, blood cell distribution, nutrient regulation and endocrine function. High-impact incidents, such as vehicle collisions and falls, are primary causes of bone deformities and trauma, leading to significant economic, psychological and social burdens. Large segmental bone abnormalities are mainly treated through surgical procedures like vascularized bone transplantation and bone transfer, with treatment outcomes influenced by various patient-specific factors. Ideal bone transplants should be osteoinductive, osteoconductive, osteogenic, readily available and cost-effective, with autografts being the most superior option due to their high efficacy and low risk of immune reaction. Allografts, derived from the same species, are treated to mitigate immunogenic response and infection risks, available in forms such as intact segments, cortical-spongy segments, bone chips, powder and demineralized bone matrices. Xenografts, particularly from bovine sources, provide a porous hydroxyapatite-based structure that supports mechanical reinforcement, osteoconduction and angiogenesis, commonly used in maxillary sinus floor elevation treatments. Emergence of scaffolds in bone regeneration Scaffolds play a crucial role in supporting tissue repair and regeneration, facilitating cellular deposition and morphogenic signals essential for bone regeneration in conditions like osteoporosis and bone malignancies. Exploration of biomaterials such as bioactive glass and calcium phosphate cements reveals promising outcomes, with bioactive glass demonstrating superior remodeling capabilities over autogenous bone and injectable cements providing customizable defect filling in procedures like cranioplasty. Surface characteristics, including chemistry, topography and roughness, profoundly influence scaffold integration and cellular behavior, impacting bone-forming cell adhesion, proliferation and protein binding essential for effective bone regeneration. Pore size is a critical parameter in scaffold design, with larger pores (>300 μm) favored for bone ingrowth, although optimal bone regeneration may vary with pore size, highlighting the complex connection between pore size, bone growth and scaffold strength. Biomaterial diversity, ranging from natural polymers like chitosan and collagen to synthetic polymers such as PCL, PLA, or PLGA, offers a variety of biodegradable options tailored for bone tissue engineering applications. Role of collagen in bone regeneration Natural biopolymers, such as collagen, are gaining attention in bone regeneration due to their resemblance to native extracellular matrix (ECM) components, reducing the risk of immunological reactions and facilitating tissue regeneration. Collagen, a predominant structural protein in vertebrates, regulates crucial biological processes like cell attachment, migration and differentiation, making it a promising candidate for scaffolds in bone tissue engineering. Despite collagen's favorable biological properties, its mechanical weaknesses hinder widespread utilization, prompting research into enhancing its durability through crosslinking methods. Chemical and physical crosslinking agents, such as choline-based salts, have been explored to strengthen collagen scaffolds, improving their stability and mechanical properties. Incorporating bio-ceramics like HA into collagen matrices can further enhance scaffold strength while maintaining porosity, offering significant potential for advancing bone tissue engineering applications. Hydroxyapatite in bone regeneration Hydroxyapatite (HA), a key component of bone composition, exhibits a complex crystal arrangement with uniform orientation of hydroxyl groups, contributing to its structural integrity and biocompatibility. HA, comprising approximately 20% of bone composition, possesses chemical elements analogous to vertebrate hard tissues, making it a biodegradable biomaterial with significant potential in orthopedics and maxillofacial surgery. The mechanical properties of HA can be tailored through synthesis methods like sintering, influencing its durability and in vivo biodegradability, with lower sintering temperatures enhancing biodegradability while compromising mechanical strength. Recent advancements in artificial bone grafts have focused on HA-based materials, either pure or in composites, due to their biocompatibility, biomineralization capabilities and porous interlinked structure, essential for osteoconduction and osteointegration. Utilization of collagen/HA composites in bone related ailments Collagen/HA composites offer synergistic osteoconductive effects, making them ideal for bone regeneration applications, with potential enhancements through additional active ingredients. Various fabrication techniques such as gel casting, compacting and computer-assisted rapid prototyping enable precise control over the mechanical and biological properties of collagen/HA scaffolds, enhancing their suitability for tissue engineering. The mechanical properties of collagen scaffolds are augmented by HA incorporation, with factors like particle size influencing cellular adhesion and proliferation, demonstrating enhanced osteogenic potential compared with pure collagen scaffolds. Synthesis methods for HA/collagen composites, including co-precipitation and direct blending, yield hierarchical structures resembling natural bone, with potential enhancements through the incorporation of growth factors or biologically active substances. Porosity plays a significant role in the biological characteristics of HA/collagen composites, with increased porosity facilitating cell migration, vascularization and mechanical adaptability, despite potential reductions in mechanical strength. HA/collagen scaffolds can be utilized for drug delivery in bone-related disorders, enabling sustained release of therapeutic agents to target specific sites, with potential applications in tumor inhibition and antimicrobial treatment, offering a promising avenue for personalized medicine in bone therapeutics. Future perspective Collagen and HA ceramics offer strong biocompatibility, tailored mechanical strength and osteoconductivity for bone regeneration. Ongoing research integrates bioactive compounds into HA/collagen hybrids to enhance osteoinductivity and pharmacological intervention in bone pathologies. Nano-HA promotes osteoblast adhesion and bone regeneration, enhancing scaffold effectiveness. Collagen scaffolds, though prone to degradation, are being optimized for stability and controlled degradation, ensuring suitability for bone regeneration. Advanced fabrication techniques like 3D printing aim to improve scaffold mechanical properties and drug delivery capabilities, advancing treatment effectiveness. Multifunctional composites, combining growth stimulants and antibiotics in HA/collagen scaffolds, show promise for tailored therapeutic approaches, enhancing treatment outcomes in bone defects and pathologies. [ABSTRACT FROM AUTHOR]

The approach to the personal experiences and previous ideas about physical education of future primary education teachers is a starting point of great interest for the teaching of the subject of physical education didactics. The aim of the study is to investigate these prior beliefs and to verify to what extent this initial perception changes after taking the "Didactics of Physical Education" course. A concurrent mixed-methods study was conducted, which included two data collection procedures: (1) a pre-experimental design with a single group featuring a pre-test and post-test; (2) the analysis of students' autobiographical accounts of their experiences with physical education in school. The participants were students enrolled in the Bachelor's degree program in primary education at the University of Santiago de Compostela (USC) who undertook the course in 2022–2023. The results obtained reveal that after taking the Didactics of Physical Education course, students gave greater value to more positive concepts of learning, socializing, participating, and playing, among others. Similarly, in the post-test, the assessment of concepts such as competitiveness and physical fatigue diminished. In their autobiographical accounts, students associated good memories with relationships with classmates and the playful socializing nature of the subject; among the bad memories, they highlight the content related to physical performance, competitiveness, and lack of attention to the diversity of students and their individual characteristics. [ABSTRACT FROM AUTHOR]

Previous research extensively characterized PLA blends for various biomedical applications, especially in polymer-based biodegradable implant fixations, offering advantages over metallic counterparts. Nevertheless, achieving an optimal PLA mixture with both mechanical resistance and fast biodegradability remains a challenge. Currently, literature still lacks insights into the manufacturing parameter impact on sago starch/PLA in combination with PEG plasticizer. The objective of this study is to assess variations in injection molding temperatures and sago/PLA/PEG weight compositions to identify the optimal combination enhancing miniplate mechanical properties and biodegradation behavior. Mechanical tests reveal that incorporating PEG into pure PLA yields high mechanical performance, correlating linearly with increasing injection temperature. However, the interaction once the three materials are mixed decreases mechanical performance across tested temperatures. Higher biodegradation rates are observed with a larger weight composition of the hydrophilic behavior attributed to sago starch presence. The observed novelty in PLA mixed with 20% sago starch and 10% PEG at 170 °C indicates a better performance in elastic modulus and elongation at break also the degradation rate, emphasizing the role of injection temperature in molding miniplate implants. In conclusion, the interplay of injection molding parameters and material compositions is crucial for optimizing PLA-based miniplate implants, with potential contributions to tissue implants rather than bone implants due to their mechanical limitation. [ABSTRACT FROM AUTHOR]