Actualización en infección por VIH/SIDA en niños

Hasta hace pocos años la infección por el virus de la inmunodeficiencia humana (VIH) era invariablemente una enfermedad progresiva y mortal y el médico se convertía en un espectador de su historia natural, interviniendo sin éxito en la mayoría de las ocasiones para tratar las infecciones oportunistas resultado de las fallas del sistema inmunológico y de las escasas herramientas disponibles. Lamentablemente la investigación en niños con infección por VIH no va al mismo ritmo que la desarrollada en adultos. Con el impacto de la epidemia del VIH/SIDA a nivel mundial los esfuerzos y avances para abordarla incluyen un mejoramiento en el acceso a los programas de diagnóstico, tratamiento y prevención, tanto a nivel del país como de la región, así como un mejoramiento metodológico en la recolección y el cálculo de los datos estadísticos que actualmente demuestran una tendencia en la reducción del número de nuevas infecciones que a su vez provienen de una disminución en los comportamientos de riesgo

Criptosporidiosis en niños colombianos con infección por VIH/SIDA

Introduction: Enteric cryptosporidiosis in children with HIV/AIDS is an important cause of morbidity and mortality. Objective: To determine the prevalence of Cryptosporidium spp. in feces, via the Ziehl Neelsen modified technique, among Colombian children with HIV/AIDS and to determine possible associations. Methodology: Prevalence study in 131 children with HIV/AIDS at the Hospital Universitario del Valle in Cali, Colombia. We evaluated clinical records, laboratory results, environmental factors, and socio-demographic variables. Statistical analysis included the estimation of prevalence of infection in children and the corresponding 95% confidence interval; estimation of other descriptive conditions of interest and the association analyses by multiple logistic regression. Results: In this group of children with a mean age of 57 months, we found a prevalence of infection of 29%, more frequently among male children and among those with vertical HIV transmission. The infection was also associated with abdominal pain, having pets inside the house and C stage for HIV, with >100,000 copies/ml of viral load and CD4 percentage >25%. Association analysis showed a larger risk of Cryptosporidium infection with older age, and among patients not living in Cali, with more severe status of HIV disease, previous hospitalizations, and dried oral mucosa. Factors found finally associated were older age, chronic undernutrition, living in day-care institutions and having previous hospitalizations. Conclusion: Almost a third of these children patients had Cryptosporidium infection, and it was found associated with age, previous hospitalizations, chronic undernutrition and living in day-care institutions. Introducción: La criptosporidiosis entérica en niños infectados por VIH es una causa importante de enfermedad y muerte. Objetivo: Determinar la prevalencia de Cryptosporidium spp. en heces por medio de la técnica de Ziehl Neelsen modificada, en niños colombianos con infección por VIH/SIDA y establecer posibles asociaciones. Metodología: Estudio de prevalencia en 131 niños con infección por VIH/SIDA. Fueron consideradas variables clínicas, paraclínicas, ambientales y sociodemográficas. El análisis estadístico incluyó estimación de la prevalencia de infección en los niños y su correspondiente intervalo de confianza al 95%, la estimación de otras medidas descriptivas de interés y el análisis de asociación por regresión logística múltiple. Resultados: En esta población de niños con una edad promedio de 57 meses se encontró una prevalencia de 29% de infección, predominio del sexo masculino y el modo de transmisión vertical en VIH. La infección se asoció además con dolor abdominal, tenencia de animales en el intradomicilio y a estadio C para VIH, con >100.000 copias/ml de carga viral y porcentaje de CD4 >25%. En el análisis de asociación se encontró mayor oportunidad de infección por Cryptosporidium a mayor edad, en los pacientes de fuera de Cali, con mayor severidad del estadío para VIH, con hospitalizaciones previas, y con mucosa oral seca. Los factores finalmente asociados fueron la mayor edad, la DNT crónica, la convivencia en guarderías y las hospitalizaciones previas. Conclusión: Casi una tercera parte de los pacientes presentaron infección y esta se encontró asociada con la edad del niño, con hospitalizaciones previas, con convivencia en guarderías y DNT crónica

Current Stage of Marine Ceramic Grafts for 3D Bone Tissue Regeneration

Bioceramic scaffolds are crucial in tissue engineering for bone regeneration. They usually provide hierarchical porosity, bioactivity, and mechanical support supplying osteoconductive properties and allowing for 3D cell culture. In the case of age-related diseases such as osteoarthritis and osteoporosis, or other bone alterations as alveolar bone resorption or spinal fractures, functional tissue recovery usually requires the use of grafts. These bone grafts or bone void fillers are usually based on porous calcium phosphate grains which, once disposed into the bone defect, act as scaffolds by incorporating, to their own porosity, the intergranular one. Despite their routine use in traumatology and dental applications, specific graft requirements such as osteoinductivity or balanced dissolution rate are still not completely fulfilled. Marine origin bioceramics research opens the possibility to find new sources of bone grafts given the wide diversity of marine materials still largely unexplored. The interest in this field has also been urged by the limitations of synthetic or mammalian-derived grafts already in use and broadly investigated. The present review covers the current stage of major marine origin bioceramic grafts for bone tissue regeneration and their promising properties. Both products already available on the market and those in preclinical phases are included. To understand their clear contribution to the field, the main clinical requirements and the current available biological-derived ceramic grafts with their advantages and limitations have been collected.This research was partially supported by the European Union projects 0245_IBEROS_1_E and 0302_CVMAR_I_1_P, both from Interreg V-A Spain-Portugal (POCTEP 2015) and BLUEHUMAN EAPA_151/2016 from INTERREG Atlantic Area, European Regional Development Fund. Moreover, regional funds from Competitive Reference Groups (GRC) ED431C 2016/008 and ED431C 2017_51 and Research networks ED431D 2017/13 both from Xunta de Galicia (Spain) are also acknowledged. P. Diaz-Rodriguez and M. López-Alvarez are thankful for the funding support provided by 0245_IBEROS_1_E from EU Interreg V-A Spain-Portugal (POCTEP) project 2017/13 both from Xunta de Galicia (Spain) are also acknowledged. P. Diaz-Rodriguez and M. López-Alvarez are thankful for the funding support provided by 0245_IBEROS_1_E from EU Interreg V-A Spain-Portugal (POCTEP) project.S

Review article laser-induced hyperthermia on graphene oxide composites

Background: Hyperthermia-based therapies have shown great potential for clinical applications such as for the antitumor and antipathogenic activities. Within all strategies, the so-called photothermal therapy proposes to induce the hyperthermia by the remote laser radiation on a photothermal conversion agent, in contact with the target tissue. Methods: This paper reviews the most relevant in vitro and in vivo studies focused on NIR laser-induced hyperthermia due to photoexcitation of graphene oxide (GO) and reduced graphene oxide (rGO). Relevant parameters such as the amount of GO/rGO, the influence of the laser wavelength and power density are considered. Moreover, the required temperature and exposure time for each antitumor/antipathogenic case are collected and unified in a thermal dose parameter: the CEM43. Results: The calculated CEM43 thermal doses revealed a great variability for the same type of tumor/strain. In order to detect potential tendencies, the values were classified into four ranges, varying from CEM4360ºC). Conclusions: The ability of GO/rGO as effective photothermal conversion agents to promote a controlled hyperthermia is proven. The variability found for the CEM43 thermal doses on the reviewed studies reveals the potentiality to evaluate, for each application, the use of lower temperatures, by modulating time and/or repetitions in the dosesMinisterio de Ciencia e Innovación del Gobierno de España | Ref. BIOHEAT (PID 2020- 115415RB-100)Xunta de Galicia | Ref. GRC (ED431C 2021/49

Impact of prevalence ratios of chondroitin sulfate (CS)- 4 and -6 isomers derived from marine sources in cell proliferation and chondrogenic differentiation processes

[Abstract] Osteoarthritis is the most prevalent rheumatic disease. During disease progression, differences have been described in the prevalence of chondroitin sulfate (CS) isomers. Marine derived-CS present a higher proportion of the 6S isomer, offering therapeutic potential. Accordingly, we evaluated the effect of exogenous supplementation of CS, derived from the small spotted catshark (Scyliorhinus canicula), blue shark (Prionace glauca), thornback skate (Raja clavata) and bovine CS (reference), on the proliferation of osteochondral cell lines (MG-63 and T/C-28a2) and the chondrogenic differentiation of mesenchymal stromal cells (MSCs). MG-G3 proliferation was comparable between R. clavata (CS-6 intermediate ratio) and bovine CS (CS-4 enrichment), for concentrations below 0.5 mg/mL, defined as a toxicity threshold. T/C-28a2 proliferation was significantly improved by intermediate ratios of CS-6 and -4 isomers (S. canicula and R. clavata). A dose-dependent response was observed for S. canicula (200 µg/mL vs 50 and 10 µg/mL) and bovine CS (200 and 100 µg/mL vs 10 µg/mL). CS sulfation patterns discretely affected MSCs chondrogenesis; even though S. canicula and R. clavata CS up-regulated chondrogenic markers expression (aggrecan and collagen type II) these were not statistically significant. We demonstrate that intermediate values of CS-4 and -6 isomers improve cell proliferation and offer potential for chondrogenic promotion, although more studies are needed to elucidate its mechanism of action.Xunta de Galicia; IN607A 2017/11Xunta de Galicia; IN607B 2018/19European Commission; 0245_IBEROS_1_

Physicochemical properties of 3D-printed polylactic acid/hydroxyapatite scaffolds

The reconstruction or regeneration of damaged bone tissue is one of the challenges of orthopedic surgery and tissue engineering. Among all strategies investigated, additive manufacturing by fused deposition modeling (3D-FDM printing) opens the possibility to obtain patient-specific scaffolds with controlled architectures. The present work evaluates in depth 3D direct printing, avoiding the need for a pre-fabricated filament, to obtain bone-related scaffolds from direct mixtures of polylactic acid (PLA) and hydroxyapatite (HA). For it, a systematic physicochemical characterization (SEM-EDS, FT-Raman, XRD, micro-CT and nanoindentation) was performed, using different PLA/HA ratios and percentages of infill. Results prove the versatility of this methodology with an efficient HA incorporation in the 3D-printed scaffolds up to 13 wt.% of the total mass and a uniform distribution of the HA particles in the scaffold at the macro level, both longitudinal and cross sections. Moreover, an exponential distribution of the HA particles from the surface toward the interior of the biocomposite cord (micro level), within the first 80 µm (10% of the entire cord diameter), is also confirmed, providing the scaffold with surface roughness and higher bioavailability. In relation to the pores, they can range in size from 250 to 850 µm and can represent a percentage, in relation to the total volume of the scaffold, from 24% up to 76%. The mechanical properties indicate an increase in Young’s modulus with the HA content of up to ~50%, compared to the scaffolds without HA. Finally, the in vitro evaluation confirms MG63 cell proliferation on the 3D-printed PLA/HA scaffolds after up to 21 days of incubation

3D-printed PLA medical devices: physicochemical changes and biological response after sterilisation treatments

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGPolylactic acid (PLA) has become one of the most commonly used polymers in medical devices given its biocompatible, biodegradable and bioabsorbable properties. In addition, due to PLA’s thermoplastic behaviour, these medical devices are now obtained using 3D printing technologies. Once obtained, the 3D-printed PLA devices undergo different sterilisation procedures, which are essential to prevent infections. This work was an in-depth study of the physicochemical changes caused by novel and conventional sterilisation techniques on 3D-printed PLA and their impact on the biological response in terms of toxicity. The 3D-printed PLA physicochemical (XPS, FTIR, DSC, XRD) and mechanical properties as well as the hydrophilic degree were evaluated after sterilisation using saturated steam (SS), low temperature steam with formaldehyde (LTSF), gamma irradiation (GR), hydrogen peroxide gas plasma (HPGP) and CO2 under critical conditions (SCCO). The biological response was tested in vitro (fibroblasts NCTC-929) and in vivo (embryos and larvae wild-type zebrafish Danio rerio). The results indicated that after GR sterilisation, PLA preserved the O:C ratio and the semi-crystalline structure. Significant changes in the polymer surface were found after HPGP, LTSF and SS sterilisations, with a decrease in the O:C ratio. Moreover, the FTIR, DSC and XRD analysis revealed PLA crystallisation after SS sterilisation, with a 52.9% increase in the crystallinity index. This structural change was also reflected in the mechanical properties and wettability. An increase in crystallinity was also observed after SCCO and LTSF sterilisations, although to a lesser extent. Despite these changes, the biological evaluation revealed that none of the techniques were shown to promote the release of toxic compounds or PLA modifications with toxicity effects. GR sterilisation was concluded as the least reactive technique with good perspectives in the biological response, not only at the level of toxicity but at all levels, since the 3D-printed PLA remained almost unaltered.POCTEP INTERREG España- Portugal | Ref. BLUEBIOLABInterreg Atlantic Area | Ref. BLUEHUMAN EAPA_151/2016Ministerio de Ciencia e Innovación | Ref. PID 2020-115415RB-100Xunta de Galicia | Ref. ED431C 2021/49Xunta de Galicia | Ref. ED481A 2019/314Xunta de Galicia | Ref. IN606A-2017/011Fundação para a Ciência e a Tecnologia | Ref. UIDB/50016/202

Vancomycin-loaded 3D-printed polylactic acid–hydroxyapatite scaffolds for bone tissue engineering

The regeneration of bone remains one of the main challenges in the biomedical field, with the need to provide more personalized and multifunctional solutions. The other persistent challenge is related to the local prevention of infections after implantation surgery. To fulfill the first one and provide customized scaffolds with complex geometries, 3D printing is being investigated, with polylactic acid (PLA) as the biomaterial mostly used, given its thermoplastic properties. The 3D printing of PLA in combination with hydroxyapatite (HA) is also under research, to mimic the native mechanical and biological properties, providing more functional scaffolds. Finally, to fulfill the second one, antibacterial drugs locally incorporated into biodegradable scaffolds are also under investigation. This work aims to develop vancomycin-loaded 3D-printed PLA–HA scaffolds offering a dual functionality: local prevention of infections and personalized biodegradable scaffolds with osseointegrative properties. For this, the antibacterial drug vancomycin was incorporated into 3D-printed PLA–HA scaffolds using three loading methodologies: (1) dip coating, (2) drop coating, and (3) direct incorporation in the 3D printing with PLA and HA. A systematic characterization was performed, including release kinetics, Staphylococcus aureus antibacterial/antibiofilm activities and cytocompatibility. The results demonstrated the feasibility of the vancomycin-loaded 3D-printed PLA–HA scaffolds as drug-releasing vehicles with significant antibacterial effects for the three methodologies. In relation to the drug release kinetics, the (1) dip- and (2) drop-coating methodologies achieved burst release (first 60 min) of around 80–90% of the loaded vancomycin, followed by a slower release of the remaining drug for up to 48 h, while the (3) 3D printing presented an extended release beyond 7 days as the polymer degraded. The cytocompatibility of the vancomycin-loaded scaffolds was also confirmed.Agencia Estatal de Investigación | Ref. PID2020-115415RB-I00Xunta de Galicia | Ref. ED431C 2021/49Xunta de Galicia | Ref. ED481A 2019/31