In vitro cytocompatibility evaluation of poly(DL-lactic acid) scaffolds loaded with minocycline and voriconazole addressing osteomyelitis

Osteomyelitis or bone infection is an acute or chronic inflammatory process involving the bone and its structures, secondary to infection with pyogenic organisms, such as bacteria and fungi. Considering the associated high patient economic burden, morbidity, and mortality, it is essential to develop novel strategies for osteomyelitis management. Porous scaffolds based on biomaterials may locally deliver high concentrations of antibiotics, an effective strategy in eradicating bone infection. When incorporating bioactive bioglasses and bioresorbable polymers like poly(DL-lactic acid) (PDLLA), these structures exhibit biosafety, biodegradability, and the expected global structure to promote cell expansion and cell differentiation, being critical to consider and evaluate their biocompatibility compliance. As the encapsulation of more than one active pharmaceutical ingredient is an attractive approach, the present study focuses on the cytocompatibility evaluation of an innovative system based on the dual delivery of two antimicrobials, an antibiotic that enhances bone formation, minocycline (MH), and an antifungal agent with a broad spectrum of activity, voriconazole (VCZ), aiming bone infection therapeutics. Scaffolds were prepared by solvent casting/particulate leaching techniques and functionalized with bioglass. The scaffolds produced were adsorbed with 0.5 or 0.1 mg/mL of minocycline and also with 0.1 mg/mL of voriconazole. To test the bio-functionality and the biological safety of scaffolds, in vitro cell assays were achieved employing the MG-63 cell line (ATCC® CRL-1427TM human osteoblast cell line). The AlamarBlue® assay was used to measure cell proliferation in the scaffold. As osteoblast differentiation markers, the following were determined: alkaline phosphatase activity and mineralization using Alizarin red assay, an indicator of in vitro bone formation. All scaffolds sustained the proliferation of metabolically active cells, nonetheless, scaffolds adsorbed with the highest concentration of MH (0.5 mg/mL) presented a significant (p<0.05) cytotoxic effect. Matrix maturation assays supported early osteoblasts differentiation and the osteoinductive role of minocycline described in the literature was also highlighted. Matrix mineralization analysis showed the highest value associated with scaffolds with both antimicrobials adsorbed. Once the described scaffolds enhanced osteoblasts' differentiation, and matrix mineralization and evidenced no cytotoxic effects, they come to light as an auspicious alternative for local antimicrobial therapy addressing osteomyelitis prevention and therapeutics.info:eu-repo/semantics/publishedVersio

In vitro cytocompatibility evaluation of poly(DL-lactic acid) scaffolds loaded with minocycline and voriconazole addressing osteomyelitis

Purpose: In this work is proposed the cytocompatibility evaluation of an innovative system based on the dual delivery of minocycline (Min) and voriconazole (Vor), aiming for bone infection therapeutics.info:eu-repo/semantics/publishedVersio

Williams syndrome hypersociability: a neuropsychological study of the amygdala and prefrontal cortex hypotheses

Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS hypersociability was explored using three behavioral tasks – facial emotional recognition task, a social approach task and a go no/go task. Thus, a group 15 individuals with Williams syndrome was compared to two groups of normal developing individuals – a group of 15 individuals matched for chronological age (CA) and 15 individualsmatched for mental age (MA), and sex. Individuals with WS present a specific impairment in recognizing negative facial expressions and do not display impairments in response inhibition when compared with typically developing groups. Although these findings partially support the amygdala contribution to WS hypersociability, we found that general cognitive functioning predicted this performance. Additionally, individuals with WS did not differ from both CA and MA groups in the recognition of angry facial expressions, a finding suggesting that they are actually able to identify stimuli associated with social threat. Overall, the results seem to indicate that this social profile must be understood within a developmental framework.Fundação para a Ciência e a Tecnologia (FCT) - bolsa PIC/IC/83290/200

Release kinetic model and antimicrobial activity of an innovative minocycline and voriconazole co-delivery system

Purpose and Strategy: Development of a new local drug-delivery system aiming at bone infection and the modulation of the polymicrobial activity; simultaneous delivery of minocycline and voriconazole, antibacterial and antifungal agents, respectively; polylactide (PDLLA) scaffolds functionalized with collagen and bioglass, osteogenic enhancers.info:eu-repo/semantics/publishedVersio

Poly(DL-lactic acid) scaffolds adsorbed with minocycline and voriconazole: a new pathway towards infection containment

Bone infection (osteomyelitis): burden as a clinical complication of orthopedic surgeries. Controlled antimicrobial release systems: treat and prevent osteomyelitis. Biomaterials based on porous scaffolds: local administration of high concentration of drugs; no systemic toxicity; extended time. Scaffolds in bone tissue engineering: a combination of bioresorbable polymers with bioactive bioglasses; present biodegradability and biosafety; suitable microenvironment and structure; favor osteogenic differentiation and cell growth. Co-encapsulation of drugs: advantageous means for administration of drugs; novel strategy directed to the co-delivery of two antimicrobials (voriconazole and minocycline).info:eu-repo/semantics/publishedVersio

MRI amygdala volume in Williams syndrome

One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched controls. Magnetic resonance imaging scans were obtained on a GE 1.5-T magnet with 1.5- mm contiguous slices and were used to measure whole gray matter, white matter and cerebrospinal fluid volumes, as well as amygdala volume (right and left). Results revealed significantly reduced intracranial volume in individuals with WS, compared with controls. There were no differences between groups in absolute amygdalae volume, although there was a relative increase in amygdalae volumes, when adjusted for total intracranial content. There were no inter-hemispheric differences in amygdalae volumes in both groups. These results suggest a relative increase in amygdala volume in WS compared with healthy controls that likely reflects abnormal neurodevelopmental processes of midline brain structures.This research was supported by the grants PIC/IC/83290/2007 from Fundac¸a˜o para a Cieˆncia e Tecnologia (Portugal) and Fundacio´n Alicia Koplowitz. (V convocatoria de 2009. Ayudas a la investigacio´n en psiquiatrı´a de la infancia y adolescencia enfermedades neurodegenerativas tempranas

Poly(D,L-lactic acid) scaffolds as an innovative approach to the treatment of mixed S. aureus-C. albicans biofilms

Problem - Bone infections associated with polymicrobial biofilm formation; mixed bacterial-fungal biofilm infection; Staphylococcus aureus and Candida albicans most described microbials. Strategy - Local drug delivery scaffolds; development of poly-DL-lactic acid (PDLLA) scaffolds; co-delivery of antibacterial and antifungal drugs; minocycline and voriconazole as model drugs.info:eu-repo/semantics/publishedVersio

Empatía por defecto: correlatos en el cerebro en reposo

Background: Empathy, defined as the ability to access and respond to the inner world of another person, is a multidimensional construct involving cognitive, emotional and self-regulatory mechanisms. Neuroimaging studies report that empathy recruits brain regions which are part of the social cognition network. Among the different resting state networks, the Default Mode Network (DMN) may be of particular interest for the study of empathy since it has been implicated in social cognition tasks. Method: The current study compared the cognitive and emotional empathy scores, as measured by the Interpersonal Reactivity Index, with the patterns of activation within the DMN, through the neuroimaging methodology of resting-state functional magnetic resonance. Results: Results suggest a significant positive correlation between cognitive empathy and activation of the bilateral superior medial frontal cortex nodes of the DMN. Contrastingly, a negative correlation was found between emotional empathy and the same brain region. Conclusions: Overall, this data highlights a critical role of the medial cortical regions of the DMN, specifically its anterior node, for both cognitive and emotional domains of the empathic process.Antecedentes: la empatía, defi nida como la capacidad de acceder y responder al mundo interior de otra persona, es un constructo multidimensional que implica mecanismos cognitivos, emocionales y autorreguladores. Los estudios de neuroimagen informan que la empatía recluta regiones cerebrales que forman parte de la red de cognición social. Entre las diferentes redes de estado de reposo, la Red Neuronal por Defecto (Default Mode Network; DMN) puede ser de particular interés para el estudio de la empatía, ya que ha sido implicada en tareas de cognición social. Método: el presente estudio comparó los valores de empatía cognitiva y emocional, medidos por medio del Índice de Reactividad Interpersonal, con los patrones de activación dentro de la DMN, a través de la metodología de neuroimagen por resonancia magnética funcional en estado de reposo. Resultados: los resultados sugieren una correlación positiva signifi cativa entre la empatía cognitiva y la activación bilateral de los nodos de la región frontomedial superior de la DMN. En contraste, se encontró una correlación negativa entre la empatía emocional y la misma región del cerebro. Conclusiones: en general, estos datos destacan un papel crítico de las regiones corticales mediales de la DMN, específi camente su nodo anterior, para los dominios cognitivo y emocional del proceso empático.This study was supported by the Bial Foundation, under the fellowship numbers 89/08 and 87/12 and by the PFST Ref. UID/CED/04872/2016, Ref. SFRH/BD/65892/2009, Ref. PTDC/PSIPCL/115316/2009, and FEDER funds. Ref. POCI-01-0145-FEDER-007653.info:eu-repo/semantics/publishedVersio

Nodes of the default mode network implicated in the quality of empathic responses: a clinical perspective of the empathic response

The ability to empathize with another person's inner experience is believed to be a central element of our social interactions. Previous research has focused on cognitive (e.g., theory of mind) and emotional (e.g., emotional contagion) empathy, and less on behavioral factors (i.e., the ability to respond empathically). Recent studies suggest that the Default Mode Network (DMN) mediates individual variability in distinct empathy-related behaviors. However, little is known about DMN activity during actual empathic responses, understood in this study as the ability to communicate our understanding of the others’ experience back to them. This study used an empathy response paradigm with 28 participants (22-37 years old) to analyze the relationship between the quality of empathic responses to 14 empathy-eliciting vignettes and patterns of attenuation in the DMN. Overall, the results suggest that high levels of empathic response, are associated with sustained activation of the DMN when compared with lower levels of empathy. Our results demonstrate that the DMN becomes increasingly involved in empathy-related behavior, as our level of commitment to the other's experience increases. This study represents a first attempt to understand the relation between the capacity for responding in a supportive way to others’ needs and the intra-individual variability of the pattern of the DMN attenuation. Here we underline the critical role that the DMN plays in high-level social cognitive processes and corroborate the DMN role in different psychiatric disorders associated with a lack of empathy.info:eu-repo/semantics/publishedVersio

Chemical Quality of Rainwater and Surface Runoff Water in the Proximity of the Abstractions That Supply the São Pedro do Sul Medical Spa (Portugal)

São Pedro do Sul medical spa provides health services using hot natural groundwater superiorly classified as natural mineral water. The main source of supply of that medical spa, has been over time, the Traditional Spring, which in recent decades has been systematically controlled, and shows spectacular constancy in its chemical quality, if there are no outside contaminations. Within the context presented, the detailed physical-chemical quality of rainwater and surface runoff water was studied, in the proximity of the Traditional Spring, as there is a potential for them to infiltrate at depth and evolve into the natural mineral water aquifer system. Thus, in the present chapter, after presenting the physical-chemical quality of the natural mineral water from the Traditional Spring, as well as some elements of the literature on the physical-chemical quality of rainwater, the methodology of work is followed, and then the results obtained from the physical-chemical composition of rainwater and surface run-off water are presented and discussed, comparing them with the quality of the water from the Traditional Spring. Finally, the main conclusions are presented, and some recommendations are made on research into potential sources of pollution, which justify the poor quality of the rainwater studied