Comparative Analysis of the Comfort of Children and Adolescents in Digital and Conventional Full-Arch Impression Methods: A Crossover Randomized Trial.

The aim of this study was to evaluate the comfort of children and adolescents with conventional full-arch dental impression methods compared to two intraoral scanners (iTeroTM and PrimescanTM). METHODS: A monocentric, analytical, controlled crossover study was designed to compare conventional impression and digital impression with two intraoral scanners (iTeroTM and PrimescanTM) in children and teenagers. Patient comfort was evaluated using a 100 mm VAS scale adapted to Spanish and for children. A descriptive and analytical statistical method was conducted with a confidence level of 95% (p ≤ 0.05) and asymptotic or bilateral significance. RESULTS: A total of 51 subjects were enrolled in the study (mean age = 12.35 years). Although the group of 10-14-year-olds was the most numerous, gender was equally distributed among the age groups. None of the variables on the VAS scale showed differences between the gender categories (p > 0.05). There were differences (p < 0.05) with respect to the age categories, as the middle adolescent group showed the worst general perception and total comfort during the conventional impression. Statistically significant differences were found between all VAS scale items and the three impression methods (p < 0.05). CONCLUSIONS: The digital impression technique is superior in terms of total comfort to the conventional alginate impression in children and adolescents.

In vitro induction of hair follicle signatures using human dermal papilla cells encapsulated in fibrin microgels.

Cellular spheroids have been described as an appropriate culture system to restore human follicle dermal papilla cells (hFDPc) intrinsic properties; however, they show a low and variable efficiency to promote complete hair follicle formation in in vivo experiments. In this work, a conscientious analysis revealed a 25% cell viability in the surface of the dermal papilla spheroid (DPS) for all culture conditions, questioning whether it is an appropriate culture system for hFDPc. To overcome this problem, we propose the use of human blood plasma for the generation of fibrin microgels (FM) with encapsulated hFDPc to restore its inductive signature, either in the presence or in the absence of blood platelets. FM showed a morphology and extracellular matrix composition similar to the native dermal papilla, including Versican and Collagen IV and increasing cell viability up to 85%. While both systems induce epidermal invaginations expressing hair-specific keratins K14, K15, K71, and K75 in in vitro skin cultures, the number of generated structures increases from 17% to 49% when DPS and FM were used, respectively. These data show the potential of our experimental setting for in vitro hair follicle neogenesis with wild adult hFDPc using FM, being a crucial step in the pursuit of human hair follicle regeneration therapies.

Association between early sexual initiation and sexually transmitted infections among Peruvian reproductive-age women.

Background: Sexually transmitted infections (STIs) are a serious public health problem worldwide, especially among reproductive-age women. The early sexual onset of sexual intercourse (EOSI) has been suggested as a risk factor, although there is no data at the national level. Objective: To evaluate the association between EOSI and STIs in Peruvian women of childbearing age. Methods: Analytical cross-sectional study with secondary data analyzes of the Peruvian Demographic and Family Health Survey 2018. The outcome was the presence of STIs in the last 12 months and the exposure variable was EOSI (age < 15 years at the time of their first sexual experience). To evaluate the association of interest, crude and adjusted prevalence ratios (aPRs) were calculated using generalized linear models with Poisson family and logarithmic link function. Results: We analyzed data from 31,028 women of childbearing age. The 11.3% reported having STIs in the last 12 months and 20.2% of the participants had an EOSI. After adjusting for potential confounders, we found that EOSI was associated with STIs (aPR: 1.27; 95% CI: 1.08-1.50; p = 0.005). When conducting stratified analysis by area of residence and number of sexual partners, this association was maintained in women living in urban areas (aPR: 1.36; 95% CI: 1.11-1.66; p = 0.003) those who did not report having a history of multiple sexual partners (aPR: 1.27; 95% CI: 1.08-1.51; p = 0.005), and those in the middle (aPR: 1.42; 95% CI: 1.03-1.97; p = 0.034) and highest (aPR: 2.12; 95% CI: 1.33-3.39; p = 0.002) wealth quintiles. Conclusion: Among reproductive-age women from Peru, EOSI was associated with STIs, especially in women living in urban areas, with no history of multiple sexual partners, and belonging to the middle to higher wealth index. The implementation of measures to prevent EOSI and fostering appropriate sexual health counseling for women with EOSI is advised.

Technological advances in fibrin for tissue engineering.

Fibrin is a promising natural polymer that is widely used for diverse applications, such as hemostatic glue, carrier for drug and cell delivery, and matrix for tissue engineering. Despite the significant advances in the use of fibrin for bioengineering and biomedical applications, some of its characteristics must be improved for suitability for general use. For example, fibrin hydrogels tend to shrink and degrade quickly after polymerization, particularly when they contain embedded cells. In addition, their poor mechanical properties and batch-to-batch variability affect their handling, long-term stability, standardization, and reliability. One of the most widely used approaches to improve their properties has been modification of the structure and composition of fibrin hydrogels. In this review, recent advances in composite fibrin scaffolds, chemically modified fibrin hydrogels, interpenetrated polymer network (IPN) hydrogels composed of fibrin and other synthetic or natural polymers are critically reviewed, focusing on their use for tissue engineering.

Intraoral scanners in children: evaluation of the patient perception, reliability and reproducibility, and chairside time-A systematic review.

Purpose: The aim of this systematic review is to evaluate the perception of the patient, the chairside time, and the reliability and/or reproducibility of intraoral scanners for full arch in pediatric patients. Methods: A data search was performed in four databases (Medline-Pubmed, Scopus, ProQuest and Web of Science) in accordance with the PRISMA 2020 statements. Studies were classified in three categories (patient perception, scanning or impression time and reliability and/or reproducibility). The resources, the data extraction and the quality assessment were carried out independently by two operators. The variables recorded were population characteristics, material and methods aspects and included country, study design and main conclusion. A quality assessment of the selected studies was performed with QUADAS-2 tool, and Kappa-Cohen Index was calculated to analyze examiner agreement. Results: The initial search obtained 681 publications, and finally four studies matching inclusion criteria were selected. The distribution of the studies in the categories was three for the analysis of the patient's perception and scanning or impression time; and two items to assess the reliability and/or reproducibility of intraoral scans. All included studies have a repeated measures-transversal design. The sample size ranged between 26 and 59 children with a mean age. The intraoral scanners evaluated were Lava C.O.S, Cerec Omnicam, TRIOS Classic, TRIOS 3-Cart and TRIOS Ortho. The quality assessment of the studies using QUADAS-2 tool revealed a low risk of bias while evaluating patient perception, but an unclear risk of bias in the analysis of accuracy or chairside time. In relation to the applicability concerns, the patient selection was of high risk of bias. All studies agreed that the patient perception and comfort is better with intraoral scanners in comparison with the conventional method. The accuracy or reliability of the digital procedure is not clear, being clinically acceptable. In relation with the chairside time, it depends on the intraoral scanner, with contradictory data in the different analyzed studies. Conclusion: The use of intraoral scanners in children is a favorable option, finding a significantly higher patient perception and comfort with intraoral scanners compared to the conventional impression method. The evidence for reliability or reproducibility is not strong to date, however, the differences between the intraoral measurements and the digital models would be clinically acceptable.

Diagnostic Ability and Capacity of Optical Coherence Tomography-Angiography to Detect Retinal and Vascular Changes in Patients with Fibromyalgia.

Background: To evaluate the neuroretina and retinal vasculature of fibromyalgia (FM) patients and calculate a linear discriminant function (LDF) to improve retinal parameters' contribution to FM diagnosis. Methods: Fifty FM patients and 232 healthy controls underwent retinal evaluation using swept-source optical coherence tomography (SS-OCT) angiography (Triton plus; Topcon) and spectral domain OCT (SD-OCT) (Spectralis; Heidelberg). The macular (m) and peripapillary (p) retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) were assessed, as was the macular vascular density. A logistic regression analysis was performed, and an LDF was calculated to evaluate OCT's contribution to FM diagnosis. Results: With Triton OCT, the patients presented pRNFL thinning in the temporal sector (p=0.006). Spectralis OCT measurements showed decreased pRNFL in patients in the following sectors: superonasal, p=0.001; nasal, p=0.001; inferonasal, p=0.006; temporal, p=0.001; and inferotemporal, p=0.001. No significant differences were observed in the macular vascular plexus between patients and controls. However, vascular density in the superior sector showed a strong inverse correlation with disease duration (r = -0.978, p=0.022). The LDF calculated for Spectralis OCT yielded an area under the ROC curve of 0.968. Conclusions: FM patients present RNFL thinning observable using SS- and SD-OCT. However, these patients show similar vascular density in the macular area to healthy controls. The LDF that combines several RNFL parameters obtained using Spectralis OCT gives this device a powerful ability to differentiate between healthy individuals and individuals with FM.

Evaluation of different methodologies for primary human dermal fibroblast spheroid formation: automation through 3D bioprinting technology.

Cell spheroids have recently emerged as an effective tool to recapitulate native microenvironments of living organisms in anin vitroscenario, increasing the reliability of the results obtained and broadening their applications in regenerative medicine, cancer research, disease modeling and drug screening. In this study the generation of spheroids containing primary human dermal fibroblasts was approached using the two-widely employed methods: hanging-drop and U-shape low adhesion plate (LA-plate). Moreover, extrusion-based three-dimensional (3D) bioprinting was introduced to achieve a standardized and scalable production of cell spheroids, decreasing considerably the possibilities of human error. This was ensured when U-shape LA-plates were used, showing an 85% formation efficiency, increasing up to a 98% when it was automatized using the 3D bioprinting technologies. However, sedimentation effect within the cartridge led to a reduction of 20% in size of the spheroid during the printing process. Hyaluronic acid (HA) was chosen as viscosity enhancer to supplement the bioink and overcome cell sedimentation within the cartridge due to the high viability values exhibited by the cells-around 80%-at the used conditions. Finally, (ANCOVA) of spheroid size over time for different printing conditions stand out HA 0.4% (w/v) 60 kDa as the viscosity-improved bioink that exhibit the highest cell viability and spheroid formation percentages. Besides, not only did it ensure cell spheroid homogeneity over time, reducing cell sedimentation effects, but also wider spheroid diameters over time with less variability, outperforming significantly manual loading.

Preparation and Characterization of Plasma-Derived Fibrin Hydrogels Modified by Alginate di-Aldehyde.

Fibrin hydrogels are one of the most popular scaffolds used in tissue engineering due to their excellent biological properties. Special attention should be paid to the use of human plasma-derived fibrin hydrogels as a 3D scaffold in the production of autologous skin grafts, skeletal muscle regeneration and bone tissue repair. However, mechanical weakness and rapid degradation, which causes plasma-derived fibrin matrices to shrink significantly, prompted us to improve their stability. In our study, plasma-derived fibrin was chemically bonded to oxidized alginate (alginate di-aldehyde, ADA) at 10%, 20%, 50% and 80% oxidation, by Schiff base formation, to produce natural hydrogels for tissue engineering applications. First, gelling time studies showed that the degree of ADA oxidation inhibits fibrin polymerization, which we associate with fiber increment and decreased fiber density; moreover, the storage modulus increased when increasing the final volume of CaCl2 (1% w/v) from 80 µL to 200 µL per milliliter of hydrogel. The contraction was similar in matrices with and without human primary fibroblasts (hFBs). In addition, proliferation studies with encapsulated hFBs showed an increment in cell viability in hydrogels with ADA at 10% oxidation at days 1 and 3 with 80 µL of CaCl2; by increasing this compound (CaCl2), the proliferation does not significantly increase until day 7. In the presence of 10% alginate oxidation, the proliferation results are similar to the control, in contrast to the sample with 20% oxidation whose proliferation decreases. Finally, the viability studies showed that the hFB morphology was maintained regardless of the degree of oxidation used; however, the quantity of CaCl2 influences the spread of the hFBs.

Cardiac Extracellular Matrix Hydrogel Enriched with Polyethylene Glycol Presents Improved Gelation Time and Increased On-Target Site Retention of Extracellular Vesicles.

Stem-cell-derived extracellular vesicles (EVs) have demonstrated multiple beneficial effects in preclinical models of cardiac diseases. However, poor retention at the target site may limit their therapeutic efficacy. Cardiac extracellular matrix hydrogels (cECMH) seem promising as drug-delivery materials and could improve the retention of EVs, but may be limited by their long gelation time and soft mechanical properties. Our objective was to develop and characterize an optimized product combining cECMH, polyethylene glycol (PEG), and EVs (EVs-PEG-cECMH) in an attempt to overcome their individual limitations: long gelation time of the cECMH and poor retention of the EVs. The new combined product presented improved physicochemical properties (60% reduction in half gelation time, p < 0.001, and threefold increase in storage modulus, p < 0.01, vs. cECMH alone), while preserving injectability and biodegradability. It also maintained in vitro bioactivity of its individual components (55% reduction in cellular senescence vs. serum-free medium, p < 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, p < 0.05). In conclusion, the combination of EVs-PEG-cECMH is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.

Hyaluronic acid-fibrin hydrogels show improved mechanical stability in dermo-epidermal skin substitutes.

Human plasma-derived bilayered skin substitutes have been successfully used by our group in different skin tissue engineering applications. However, several issues associated with their poor mechanical properties were observed, and they often resulted in rapid contraction and degradation. In this sense, hydrogels composed of plasma-derived fibrin and thiolated-hyaluronic acid (HA-SH, 0.05-0.2% w/v) crosslinked with poly(ethylene glycol) diacrylate (PEGDA, 2:1, 6:1, 10:1 and 14:1 mol of thiol to moles of acrylate) were developed to reduce the shrinking rates and enhance the mechanical properties of the plasma-derived matrices. Plasma/HA-SH-PEGDA hydrogels showed a decrease in the contraction behaviour ranging from 5% to 25% and an increase in Young's modulus. Furthermore, the results showed that a minimal amount of the added HA-SH was able to escape the plasma/HA-SH-PEGDA hydrogels after incubation in PBS. The results showed that the increase in rigidity of the matrices as well as the absence of adhesion cellular moieties in the second network of HA-SH/PEGDA, resulted in a decrease in contraction in the presence of the encapsulated primary human fibroblasts (hFBs), which may have been related to an overall decrease in proliferation of hFBs found for all hydrogels after 7 days with respect to the plasma control. The metabolic activity of hFB returned to the control levels at 14 days except for the 2:1 PEGDA crosslinking ratio. The metabolic activity of primary human keratinocytes (hKCs) seeded on the hydrogels showed a decrease when high amounts of HA-SH and PEGDA crosslinker were incorporated. Organotypic skins formed in vitro after 21 days with plasma/HA-SH-PEGDA hydrogels with an HA content of 0.05% w/v and a 2:1 crosslinking ratio were up to three times thicker than the plasma controls, evidencing a reduction in contraction, while they also showed better and more homogeneous keratin 10 (K10) expression in the supra-basal layer of the epidermis. Furthermore, filaggrin expression showed the formation of an enhanced stratum corneum for the constructs containing HA. These promising results indicate the potential of using these biomimetic hydrogels as in vitro skin models for pharmaceutical products and cosmetics and future work will elucidate their potential functionality for clinical treatment.

Effect of Fibrin Concentration on the In Vitro Production of Dermo-Epidermal Equivalents.

Human plasma-derived bilayered skin substitutes were successfully used by our group to produce human-based in vitro skin models for toxicity, cosmetic, and pharmaceutical testing. However, mechanical weakness, which causes the plasma-derived fibrin matrices to contract significantly, led us to attempt to improve their stability. In this work, we studied whether an increase in fibrin concentration from 1.2 to 2.4 mg/mL (which is the useful fibrinogen concentration range that can be obtained from plasma) improves the matrix and, hence, the performance of the in vitro skin cultures. The results show that this increase in fibrin concentration indeed affected the mechanical properties by doubling the elastic moduli and the maximum load. A structural analysis indicated a decreased porosity for the 2.4 mg/mL hydrogels, which can help explain this mechanical behavior. The contraction was clearly reduced for the 2.4 mg/mL matrices, which also allowed for the growth and proliferation of primary fibroblasts and keratinocytes, although at a somewhat reduced rate compared to the 1.2 mg/mL gels. Finally, both concentrations of fibrin gave rise to organotypic skin cultures with a fully differentiated epidermis, although their lifespans were longer (25-35%) in cultures with more concentrated matrices, which improves their usefulness. These systems will allow the generation of much better in vitro skin models for the testing of drugs, cosmetics and chemicals, or even to "personalized" skin for the diagnosis or determination of the most effective treatment possible.

Elastin-Plasma Hybrid Hydrogels for Skin Tissue Engineering.

Dermo-epidermal equivalents based on plasma-derived fibrin hydrogels have been extensively studied for skin engineering. However, they showed rapid degradation and contraction over time and low mechanical properties which limit their reproducibility and lifespan. In order to achieve better mechanical properties, elasticity and biological properties, we incorporated a elastin-like recombinamer (ELR) network, based on two types of ELR, one modified with azide (SKS-N3) and other with cyclooctyne (SKS-Cyclo) chemical groups at molar ratio 1:1 at three different SKS (serine-lysine-serine sequence) concentrations (1, 3, and 5 wt.%), into plasma-derived fibrin hydrogels. Our results showed a decrease in gelation time and contraction, both in the absence and presence of the encapsulated human primary fibroblasts (hFBs), higher mechanical properties and increase in elasticity when SKSs content is equal or higher than 3%. However, hFBs proliferation showed an improvement when the lowest SKS content (1 wt.%) was used but started decreasing when increasing SKS concentration at day 14 with respect to the plasma control. Proliferation of human primary keratinocytes (hKCs) seeded on top of the hybrid-plasma hydrogels containing 1 and 3% of SKS showed no differences to plasma control and an increase in hKCs proliferation was observed for hybrid-plasma hydrogels containing 5 wt.% of SKS. These promising results showed the need to achieve a balance between the reduced contraction, the better mechanical properties and biological properties and indicate the potential of using this type of hydrogel as a testing platform for pharmaceutical products and cosmetics, and future work will elucidate their potential.

Generation of a Simplified Three-Dimensional Skin-on-a-chip Model in a Micromachined Microfluidic Platform.

This work presents a new, cost-effective, and reliable microfluidic platform with the potential to generate complex multilayered tissues. As a proof of concept, a simplified and undifferentiated human skin containing a dermal (stromal) and an epidermal (epithelial) compartment has been modelled. To accomplish this, a versatile and robust, vinyl-based device divided into two chambers has been developed, overcoming some of the drawbacks present in microfluidic devices based on polydimethylsiloxane (PDMS) for biomedical applications, such as the use of expensive and specialized equipment or the absorption of small, hydrophobic molecules and proteins. Moreover, a new method based on parallel flow was developed, enabling the in situ deposition of both the dermal and epidermal compartments. The skin construct consists of a fibrin matrix containing human primary fibroblasts and a monolayer of immortalized keratinocytes seeded on top, which is subsequently maintained under dynamic culture conditions. This new microfluidic platform opens the possibility to model human skin diseases and extrapolate the method to generate other complex tissues.

Contraction of fibrin-derived matrices and its implications for in vitro human skin bioengineering.

It is well-known that fibroblasts play a fundamental role in the contraction of collagen and fibrin hydrogels when used in the production of in vitro bilayered skin substitutes. However, little is known about the contribution of other factors, such as the hydrogel matrix itself, on this contraction. In this work, we studied the contraction of plasma-derived fibrin hydrogels at different temperatures (4, 23, and 37°C) in an isotonic buffer (phosphate-buffered saline). These types of hydrogels presented a contraction of approximately 30% during the first 24 hr, following a similar kinetics irrespectively of the temperature. This kinetics continued in a slowed down manner to reach a plateau value of 40% contraction after 10-15 days. Contraction of commercial fibrinogen hydrogels was studied under similar conditions and the kinetics was completed after 8 hr, reaching values between 20 and 70% depending on the temperature. We attribute these substantial differences to a modulatory effect on the contraction due to plasma proteins which are initially embedded in, and progressively released from, the plasma-based hydrogels. The elastic modulus of hydrogels measured at a constant frequency decreased with increasing temperature in 7-day gels. Rheological measurements showed the absence of a strain-hardening behavior in the plasma-derived fibrin hydrogels. Finally, plasma-derived fibrin hydrogels with and without human primary fibroblast and keratinocytes were prepared in transwell inserts and their height measured over time. Both cellular and acellular gels showed a height reduction of 30% during the first 24 hr likely due to the above-mentioned intrinsic fibrin matrix contraction.

Lidocaine-Loaded Solid Lipid Microparticles (SLMPs) Produced from Gas-Saturated Solutions for Wound Applications.

The delivery of bioactive agents using active wound dressings for the management of pain and infections offers improved performances in the treatment of wound complications. In this work, solid lipid microparticles (SLMPs) loaded with lidocaine hydrochloride (LID) were processed and the formulation was evaluated regarding its ability to deliver the drug at the wound site and through the skin barrier. The SLMPs of glyceryl monostearate (GMS) were prepared with different LID contents (0, 1, 2, 4, and 10 wt.%) using the solvent-free and one-step PGSS (Particles from Gas-Saturated Solutions) technique. PGSS exploits the use of supercritical CO2 (scCO2) as a plasticizer for lipids and as pressurizing agent for the atomization of particles. The SLMPs were characterized in terms of shape, size, and morphology (SEM), physicochemical properties (ATR-IR, XRD), and drug content and release behavior. An in vitro test for the evaluation of the influence of the wound environment on the LID release rate from SLMPs was studied using different bioengineered human skin substitutes obtained by 3D-bioprinting. Finally, the antimicrobial activity of the SLMPs was evaluated against three relevant bacteria in wound infections (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). SLMPs processed with 10 wt.% of LID showed a remarkable performance to provide effective doses for pain relief and preventive infection effects.

Bioprinting for Skin.

We describe an extrusion-based method to print a human bilayered skin using bioinks containing human plasma and primary human fibroblasts and keratinocytes from skin biopsies. We generate 100 cm2 of printed skin in less than 35 min. We analyze its structure using histological and immunohistochemical methods, both in in vitro 3D cultures and upon transplantation to immunodeficient mice. We have demonstrated that the printed skin is similar to normal human skin and indistinguishable from bilayered dermo-epidermal equivalents, previously produced manually in our laboratory and successfully used in the clinic.

Effect of Coffee Cascara Dietary Fiber on the Physicochemical, Nutritional and Sensory Properties of a Gluten-Free Bread Formulation.

This study aimed to assess the physicochemical, nutritional and sensory properties of gluten-free breads containing isolated coffee cascara dietary fiber (ICCDF) as a food ingredient. ICCDF was obtained by aqueous extraction. The oil and water holding capacity and the nutritional profile of the novel ingredient were determined. Its safety was certificated by analysis of ochratoxin A, caffeine and gluten. Gluten-free bread formulations were prepared enriching a commercial bakery premix in rice protein (8%) and ICCDF (3% and 4.5%). Nutritional profile of the novel gluten-free breads (dietary fiber, protein, amino acids, lipids, fatty acid profile and resistant starch), as well as bread volume, crumb density, moisture, firmness, elasticity and color intensity were determined. A sensory quantitative descriptive analysis of the breads was conducted using eight trained panelists. New breads showed significantly higher (p < 0.05) content of dietary fiber and protein than the control bread. The addition of ICCDF allowed increasing dough yield, a less crumb firmness and a higher crumb elasticity. The nutrition claims "source of protein and high in dietary fiber" were assigned to the new formulations. In conclusion, a certificated gluten-free bread with improved nutritional and physicochemical properties and good sensorial profile was obtained.

Perfil hormonal, metabólico y hematológico en adultos con el Virus de Inmunodeficiencia Humana / Hormonal, metabolic and hematological profile in adults with the Human Immunodeficiency Virus

Resumen Introducción: Son escasos los datos del impacto de la infección por el virus de inmunodeficiencia humana (VIH) a nivel hormonal, metabólico y hematológico en pacientes hospitalizados en Colombia. Objetivo: Describir el perfil hormonal, metabólico y hematológico de los pacientes con VIH hospitalizados en una institución de tercer nivel. Material y método: Estudio observacional de corte transversal, donde se incluyeron variables sociodemográficas, clínicas, hormonales, metabólicas y hematológicas de pacientes con VIH entre el 2013 y 2014. Resultados: Se incluyeron 52 pacientes, 34 hombres, con media de edad 39,7 años (Ds 12,6, Min: 21 Max: 79). 23% habían cursado con tuberculosis, 13% con toxoplasmosis cerebral. 26 pacientes tenían historia de consumo de tóxicos: cigarrillo (58%), alcohol (27%) y sustancias alucinógenas (15%). 14% de los pacientes recibían terapia antirretroviral al ingreso, los esquemas contenían principalmente inhibidores de proteasa. Otros medicamentos usados fueron: trimetoprim-sulfametoxazol (27.2%) y antituberculosos (15%). Las principales causas de hospitalización fueron toxoplasmosis cerebral (31%) y tuberculosis (15%). 52% de la población presentó síndrome de desgaste. El tiempo de diagnóstico del VIH fue <1 de un año en el 48% de la población. 79% de los pacientes tenía recuento de CD4 <200cel/mm3 (Ds 199, Min: 3 Max: 641). En el perfil hormonal, 58% (29 pacientes) presentaron alteración del eje tiroideo, de los cuales 14 presentaron perfil de hipotiroidismo central. 55,8% de los hombres presentaron hiperprolactinemia. El perfil metabólico se caracterizó por hipertrigliceridemia (44%) y HDL bajas (81%). La alteración electrolítica de mayor frecuencia fue hiponatremia (37%). Conclusiones: En la población de pacientes hospitalizados con VIH, se encontraron alteraciones endocrinas que sugieren compromiso glandular primario hipofisiario y adrenal; alteraciones lipídicas y electrolíticas en gran medida relacionadas con enfermedad avanzada.

Abstract Introduction: Data on the impact of human immunodeficiency virus (HIV) infection on a hormonal, metabolic and haematological level in patients hospitalized in Colombia are scarce. Objective: To describe the hormonal, metabolic and haematological profile of HIV patients hospitalized in a third level institution. Material and method: Cross-sectional observational study, which included sociodemographic, clinical, hormonal, metabolic and hematological variables of patients with HIV between 2013 and 2014. Results: We included 52 patients, 34 men, with an average age of 40 years (SD 12.6, Min: 21 Max: 79). 23% had tuberculosis, 13% had cerebral toxoplasmosis. 26 patients had a history of toxic consumption: cigarette (58%), alcohol (27%) and hallucinogenic substances (15%). 14% of the patients received antiretroviral therapy at admission, mainly with protease inhibitors. Other medications used were: trimethoprim-sulfamethoxazole (27.2%) and antituberculous drugs (15%). The main causes of hospitalization were cerebral toxoplasmosis (31%) and tuberculosis (15%). 52% of the population had Wasting syndrome. The time of diagnosis of HIV was <1 year in 48% of the population. 79% of the patients had a CD4 count <200 cell/mm3 (SD 199, Min: 3 Max: 641). In the hormonal profile, 58% (29 patients) presented alteration of the thyroid axis, of which 14 session profile of central hypothyroidism. 55.8% of men had hyperprolactinemia. The metabolic profile was characterized by hypertriglyceridemia (44%) and low HDL (81%). The most frequent electrolyte alteration was hyponatremia (37%). Conclusions: In the population of patients hospitalized with HIV, endocrine alterations were found suggesting primary glandular, pituitary and adrenal involvement, with lipid and electrolyte alterations largely related to advanced disease.

Unexpected Resistance to Base-Catalyzed Hydrolysis of Nitrogen Pyramidal Amides Based on the 7-Azabicyclic[2.2.1]heptane Scaffold.

Non-planar amides are usually transitional structures, that are involved in amide bond rotation and inversion of the nitrogen atom, but some ground-minimum non-planar amides have been reported. Non-planar amides are generally sensitive to water or other nucleophiles, so that the amide bond is readily cleaved. In this article, we examine the reactivity profile of the base-catalyzed hydrolysis of 7-azabicyclo[2.2.1]heptane amides, which show pyramidalization of the amide nitrogen atom, and we compare the kinetics of the base-catalyzed hydrolysis of the benzamides of 7-azabicyclo[2.2.1]heptane and related monocyclic compounds. Unexpectedly, non-planar amides based on the 7-azabicyclo[2.2.1]heptane scaffold were found to be resistant to base-catalyzed hydrolysis. The calculated Gibbs free energies were consistent with this experimental finding. The contribution of thermal corrections (entropy term, ⁻TΔS‡) was large; the entropy term (ΔS‡) took a large negative value, indicating significant order in the transition structure, which includes solvating water molecules.

3D bioprinting of functional human skin: production and in vivo analysis.

Significant progress has been made over the past 25 years in the development of in vitro-engineered substitutes that mimic human skin, either to be used as grafts for the replacement of lost skin, or for the establishment of in vitro human skin models. In this sense, laboratory-grown skin substitutes containing dermal and epidermal components offer a promising approach to skin engineering. In particular, a human plasma-based bilayered skin generated by our group, has been applied successfully to treat burns as well as traumatic and surgical wounds in a large number of patients in Spain. There are some aspects requiring improvements in the production process of this skin; for example, the relatively long time (three weeks) needed to produce the surface required to cover an extensive burn or a large wound, and the necessity to automatize and standardize a process currently performed manually. 3D bioprinting has emerged as a flexible tool in regenerative medicine and it provides a platform to address these challenges. In the present study, we have used this technique to print a human bilayered skin using bioinks containing human plasma as well as primary human fibroblasts and keratinocytes that were obtained from skin biopsies. We were able to generate 100 cm2, a standard P100 tissue culture plate, of printed skin in less than 35 min (including the 30 min required for fibrin gelation). We have analysed the structure and function of the printed skin using histological and immunohistochemical methods, both in 3D in vitro cultures and after long-term transplantation to immunodeficient mice. In both cases, the generated skin was very similar to human skin and, furthermore, it was indistinguishable from bilayered dermo-epidermal equivalents, handmade in our laboratories. These results demonstrate that 3D bioprinting is a suitable technology to generate bioengineered skin for therapeutical and industrial applications in an automatized manner.