Biofunctionalization of titanium surfaces for dental implants: osteogenic, anti-microbial and tribocorrosion resistant surfaces

PhD thesis in Biomedical Engineering

Neural correlates of face familiarity in institutionally reared children with distinctive, atypical social behavior

Although the impact of early adverse experience on neural processing of face familiarity has been studied, research has not taken into account disordered child behavior. This work compared the neural processing of familiar versus strangers' faces in 47 institutionalized children with a mean age of 54 months to determine the effects of (a) the presence versus absence of atypical social behavior and (b) inhibited versus indiscriminant atypical behavior. Results revealed a pattern of cortical hypoactivation in institutionalized children manifesting atypical social behavior and that inhibited children displayed larger neural response to a caregiver's face than to the stranger's, while indiscriminant children did not discriminate between stimuli. These findings suggest that neural correlates of face familiarity are associated with social functioning in institutionalized children.

Spousal support and satisfaction with healthcare services as moderators between psychological morbidity and adherence to diet in Type 2 Diabetes patients

Objectives: This study analyzed the moderating role of partners’ support and satisfaction with healthcare services in the relationship between psychological morbidity and adherence to diet in patients with type 2 diabetes (T2DM). Methods: Participants were 387 recently diagnosed T2DM patients that answered the following instruments: Revised Summary of Diabetes Self- Care Activities Measure, Hospital Anxiety and Depression Scales, Multidimensional Diabetes Questionnaire and Patient Satisfaction Questionnaire. Results: Partners’ positive and negative support moderated the relationship between psychological morbidity and adherence to diet. Satisfaction with healthcare services also moderated the relationship between psychological morbidity and adherence to diet. Conclusions: Intervention programs to promote adherence to diet in patients with type 2 diabetes should focus on partners’ support and patient satisfaction with healthcare services.

The choroid plexus transcriptome reveals changes in type I and II interferon responses in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a marked decline in cognition and memory function. Increasing evidence highlights the essential role of neuroinflammatory and immune-related molecules, including those produced at the brain barriers, on brain immune surveillance, cellular dysfunction and amyloid beta (Aß) pathology in AD. Therefore, understanding the response at the brain barriers may unravel novel pathways of relevance for the pathophysiology of AD. Herein, we focused on the study of the choroid plexus (CP), which constitutes the blood-cerebrospinal fluid barrier, in aging and in AD. Specifically, we used the PDGFB-APPSwInd (J20) transgenic mouse model of AD, which presents early memory decline and progressive Aß accumulation, and littermate age-matched wild-type (WT) mice, to characterize the CP transcriptome at 3, 5-6 and 11-12months of age. The most striking observation was that the CP of J20 mice displayed an overall overexpression of type I interferon (IFN) response genes at all ages. Moreover, J20 mice presented a high expression of type II IFN genes in the CP at 3months, which became lower than WT at 5-6 and 11-12months. Importantly, along with a marked memory impairment and increased glial activation, J20 mice also presented a similar overexpression of type I IFN genes in the dorsal hippocampus at 3months. Altogether, these findings provide new insights on a possible interplay between type I and II IFN responses in AD and point to IFNs as targets for modulation in cognitive decline.

Evaluating balance, stability and gait symmetry of stroke patients using kinematic and dynamic gait lab data

Dissertação de mestrado integrado em Engenharia Biomédica

Binge eating prevalence according to obesity degrees and associated factors in women

Objective Investigate binge eating (BE) prevalence in women according to the obesity degree and assess the associated factors. Methods Cross-sectional study with female adults presenting body mass index (BMI) ≥ 35 kg/m2. The analyzed variables were: sociodemographics, health status, obesity history, lifestyle, eating behavior and obesity degree. In order to analyse BE it was used the Binge Eating Scale (BES), which is considered positive when BES ≥ 18 points. Prevalence and prevalence ratios (PR) were calculated with confidence intervals (CI) of 95%. Multivariate analysis was carried out using Poisson regression. Results BE prevalence was 53.2%, and the prevalence in super superobese women (BMI ≥ 60 kg/m2) was 75%. After multivariate analysis, associations were observed between the age group 40-49 years old (PR = 2.0; 95% CI = 1.2-3.4) and the “snacking habit” (PR = 1.9; 95% CI = 1.2-2.9). Conclusion The prevalence of BE in severe obese women was high. Association with the “snacking habit” can be a BE marker that should be monitored in the severely obese individuals that fit this profile.

Fundamental studies on natural deep eutectic solvents: physico-chemical, thermal and rheological properties

When combined at particular molar fractions, sugars, aminoacids or organic acids a present a high melting point depression, becoming liquids at room temperature. These are called Natural Deep Eutectic Solvents – NADES and are envisaged to play a major role on the chemical engineering processes of the future. Nonetheless, there is a significant lack of knowledge of its fundamental and basic properties, which is hindering their industrial applications. For this reason it is important to extend the knowledge on these systems, boosting their application development [1]. In this work, we have developed and characterized NADES based on choline chloride, organic acids, amino acids and sugars. Their density, thermal behavior, conductivity and polarity were assessed for different compositions. The conductivity was measured from 0 to 40 °C and the temperature effect was well described by the Vogel-Fulcher-Tammann equation. The morphological characterization of the crystallizable materials was done by polarized optical microscopy that provided also evidence of homogeneity/phase separation. Additionally, the rheological and thermodynamic properties of the NADES and the effect of water content were also studied. The results show these systems have Newtonian behavior and present significant viscosity decrease with temperature and water content, due to increase on the molecular mobility. The anhydrous systems present viscosities that range from higher than 1000Pa.s at 20°C to less than 1Pa.s at 70°C. DSC characterization confirms that for water content as high as 1:1:1 molar ratio, the mixture retains its single phase behavior. The results obtained demonstrate that the NADES properties can be finely tunned by careful selection of its constituents. NADES present the necessary properties for use as extraction solvents. They can be prepared from inexpensive raw materials and tailored for the selective extraction of target molecules. The data produced in this work is hereafter importance for the selection of the most promising candidates avoiding a time consuming and expensive trial and error phase providing also data for the development of models able to predict their properties and the mechanisms that allow the formation of the deep eutectic mixtures.

Morphology and oxygen incorporation effect on antimicrobial activity of silver thin films

Ag and AgxO thin films were deposited by non-reactive and reactive pulsed DC magnetron sputtering, respectively, with the final propose of functionalizing the SS316L substrate with antibacterial properties. The coatings were characterized chemically, physically and structurally. The coatings nanostructure was assessed by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), while the coatings morphology was determined by scanning electron microscopy (SEM). The XRD and XPS analyses suggested that Ag thin film is composed by metallic Ag, which crystallizes in fcc-Ag phase, while the AgxO thin film showed both metallic Ag and Ag-O bonds, which crystalize in fcc-Ag and silver oxide phases. The SEM results revealed that Ag thin film formed a continuous layer, while AgxO layer was composed of islands with hundreds of nanometers surrounded by small nanoparticles with tens of nanometers. The surface wettability and surface tension parameters were determined by contact angle measurements, being found that Ag and AgxO surfaces showed very similar behavior, with all the surfaces showing a hydrophobic character. In order to verify the antibacterial behavior of the coatings, halo inhibition zone tests were realized for Staphylococcus epidermidis and Staphylococcus aureus. Ag coatings did not show antibacterial behavior, contrarily to AgxO coating, which presented antibacterial properties against the studied bacteria. The presence of silver oxide phase along with the development of different morphology were pointed as the main factors in the origin of the antibacterial effect found in AgxO thin film. The present study demonstrated that AgxO coating presented antibacterial behavior and its application in cardiovascular stents is promising.

Screening for depression and anxiety disorders from pregnancy to postpartum with the EPDS and STAI

The Edinburgh Postnatal Depression Scale (EPDS) and the State Anxiety Inventory (STAI-S) are widely used self-report measures that still need to be further validated for the perinatal period. The aim of this study was to examine the screening performance of the EPDS and the STAI-S in detecting depressive and anxiety disorders at pregnancy and postpartum. Women screening positive on EPDS (EPDS ≥ 9) or STAI-S (STAI-S ≥ 45) during pregnancy (n = 90), as well as matched controls (n = 58) were selected from a larger study. At 3 months postpartum, 99 of these women were reassessed. At a second stage, women were administered a clinical interview to establish a DSM-IV-TR diagnosis. Receiver operator characteristics (ROC) analysis yielded areas under the curve higher than .80 and .70 for EPDS and STAI-S, respectively. EPDS and STAI-S optimal cut-offs were found to be lower at postpartum (EDPS = 7; STAI-S = 34) than during pregnancy (EPDS = 9; STAI-S = 40). EPDS and STAI-S are reasonably valid screening tools during pregnancy and the postpartum.

Infants’ behavioral and physiological profile and mother–infant interaction

This study aims to (a) identify and profile groups of infants according to their behavioral and physiological characteristics, considering their neurobehavioral organization, social withdrawal behavior, and endocrine reactivity to stress, and to (b) analyze group differences in the quality of mother–infant interaction. Ninety seven 8-week-old infants were examined using the Neonatal Behavioral Assessment Scale and the Alarm Distress Baby Scale. Cortisol levels were measured both before and after routine inoculation between 8 and 12 weeks. At 12 to 16 weeks mother–infant interaction was assessed using the Global Rating Scales of Mother–Infant Interaction. Three groups of infants were identified: (a) ‘‘withdrawn’’; (b) ‘‘extroverted’’; (c) ‘‘underaroused.’’ Differences between them were found regarding both infant and mother behaviors in the interaction and the overall quality of mother–infant interaction. The identification of behavioral and physiological profiles in infants is an important step in the study of developmental pathways.

Anxiety and depression symptoms in women and men from early pregnancy to 3-months postpartum: parity differences and effects

This study aimed to investigate both anxiety and depression symptoms from early pregnancy to 3-months postpartum, comparing women and men and first and second-time parents. Methods: A sample of 260 Portuguese couples (N=520), first or second-time parents, recruited in an Obstetrics Out-patients Unit, filled in the State-Anxiety Inventory (STAI-S) and the Edinburgh Post-Natal Depression Scale (EPDS) at the 1st, 2nd and 3rd pregnancy trimesters, childbirth, and 3-months postpartum. Results: A decrease in anxiety and depression symptoms from early pregnancy to 3-months postpartum was found in both women and men, as well as in first and second-time parents. Men presented less anxiety and depression symptoms than women, but the same pattern of symptoms over time. Second-time parents showed more anxiety and depression symptoms than first-time parents and a different pattern of symptoms over time: an increase in anxiety and depression symptoms from the 3rd trimester to childbirth was observed in first-time parents versus a decrease in second-time parents. Limitations: The voluntary nature of the participation may have lead to a selection bias; women and men who agreed to participate could be those who presented fewer anxiety and depression symptoms. Moreover, the use of self-report symptom measures does not give us the level of possible disorder in participants. Conclusions: Anxiety and depression symptoms diminish from pregnancy to the postpartum period in all parents. Patterns of anxiety and depression symptoms from early pregnancy to 3-months postpartum are similar in women and men, but somewhat different in first and second time parents. Second-time parents should also be considered while studying and intervening during pregnancy and the postpartum.

Mother's anxiety and depression during the third pregnancy trimester and neonate's mother versus stranger's face/voice visual preference

Background: Neonates show visual preference for their mother's face/voice and shift their attention from their mother to a stranger's face/voice after habituation. Aim: To assess neonate's mother versus stranger's face/voice visual preference, namely mother's anxiety and depression during the third pregnancy trimester and neonate's: 1) visual preference for the mother versus the stranger's face/voice (pretest visual preference), 2) habituation to the mother's face/voice and 3) visual preference for the stranger versus the mother's face/voice (posttest visual preference). Method: Mothers (N=100) filled out the Edinburgh Postnatal Depression Scale (EPDS) and the State Anxiety Inventory (STAI) both at the third pregnancy trimester and childbirth, and the “preference and habituation to the mother's face/voice versus stranger” paradigm was administered to their newborn 1 to 5 days after childbirth. Results: Neonates of anxious/depressed mothers during the third pregnancy trimester contrarily to neonates of non-anxious/non-depressed mothers did not look 1) longer at their mother's than at the stranger's face/voice at the pretest visual preference (showing no visual preference for the mother), nor 2) longer at the stranger's face/voice in the posttest than in the pretest visual preference (not improving their attention to the stranger's after habituation). Conclusion: Infants exposed to mother's anxiety/depression at the third gestational trimester exhibit less perceptual/social competencies at birth.

Postpartum Depression: Is it a condition affecting the mother-infant interaction and the development of the child across the first year of life?

Noting that maternal depression is common during a baby's first year, this study examined the interaction of depressed and non-depressed mother-child dyads. A sample of 26 first-time mothers with postpartum depression at the third month after birth and their 3-month-old infants was compared to a sample of 25 first-time mothers with no postpartum depression at the third month after birth and their 3-month-old infants. The observations were repeated at 6 months and again at 12 months postpartum. The samples were compared for differences in mother interaction behavior, mother's infant care, mother's concern with the baby, infant behavioral difficulties, infant mental and motor development, and infant behavior with the observer. Among the findings are the following: (1) depressed mothers' interaction behavior and care of their infants are less adequate than the non-depressed mothers' interaction behavior and care of their infants at 3, 6, and 12 months postpartum; (2) infants' interaction behaviors during feeding and face-to-face interaction with depressed mothers are less adequate than infants' interactions with non-depressed mothers at 3, 6, and 12 months postpartum; (3) mother-infant interactions are less adequate in the depressed mother dyads than the non-depressed dyads at 3, 6, and 12 months postpartum; (4) depressed mothers are less concerned about their infants than non-depressed mothers at 3, 6, and 12 months postpartum; (5) infants of depressed mothers have more behavioral difficulties at 3, 6, and 12 months postpartum than infants of non-depressed mothers; (6) infants of depressed mothers had lower mental and motor development rates at 6 and 12 months postpartum than infants of non-depressed mothers; and (7) infants of non-depressed mothers behaved in a more positive way with the observer than the infants of depressed mothers. (AS)

Química y actividad biológica en Huperzia saururus. Chemistry and biological activity in Huperzia saururus.

El presente proyecto apunta a buscar una posible solución a dos problemáticas de salud que afectan a un importante grupo de la población mundial y son los asociados a la enfermedad de Alzheimer (EA) y a la disfunción eréctil. La EA es una enfermedad neurodegenerativa progresiva caracterizada por la pérdida de memoria a corto plazo, entre otras manifestaciones. En la actualidad la terapia más utilizada son los inhibidores de la acetilcolinesterasa (AChE), ya que acetilcolina es el principal neurotransmisor afectado. No obstante, los agentes terapéuticos utilizados presentan efectos no deseados a nivel gastrointestinal, lo que motiva la búsqueda de nuevos agentes. A partir del estudio de la especie autóctona Huperzia saururus aislamos hasta el presente 10 alcaloides, algunos de los cuales resultaron activos sobre la retención de memoria, investigación realizada mediante ensayos tanto in vitro como in vivo. A partir de los promisorios resultados obtenidos se continuarán profundizando estos estudios y también se buscará el farmacóforo, la parte de la estructura responsable de la actividad. Para ello, se realizarán modificaciones químicas de los grupos funcionales y los productos obtenidos serán igualmente evaluados por su actividad sobre memoria. Los que resulten activos serán investigados en relación a su toxicidad, en la búsqueda de potenciales agentes terapéuticos. Paralelamente se estudiarán las diferentes familias de compuestos presentes en la especie, dado que el uso popular proclama su efecto afrodisíaco. La búsqueda de un afrodisíaco perfecto que incremente el deseo sexual, el placer y el desempeño, ha sido una constante desde los tiempos remotos. En todos los casos, se ha buscado mejorar el rendimiento sexual o combatir la disfunción eréctil (DE). Este término se describe como “la incapacidad constante para alcanzar o mantener una erección que es satisfactoria para el rendimiento sexual”. Para investigar la actividad biológica de H. saururus, los extractos y compuestos aislados serán evaluados por la generación de NO que produzcan, la que será estimada mediante la acumulación de nitrito, metabolito estable del NO, en sobrenadantes de cultivo de células endoteliales (HUVEC). Los que resulten efectivos serán evaluados mediante ensayos in vivo tales como, el de conducta sexual en machos y de comportamiento de monta. Del mismo modo que para los alcaloides, se estudiará la toxicidad de los compuestos que resulten activos a los fines de proseguir la metodología en la investigación preclínica de potenciales medicamentos. The present Project aims to look for a possible solution for two health problems that affect an important group of world population and they are those associated to Alzheimer Disease (AD) and Erectile Dysfunction. AD is a neurodegenerative progressive disease characterized by short term memory loss, among other signs. Nowadays the most used therapy are the acethylcholinesterase inhibitors (AChE), in view that the acethylcholine is the main neurotransmitter affected. Nevertheless, the therapeutic agents used present collateral effects at gastrointestinal level, so it motivates the search for new agents. From the autochthonous species Huperzia saururus we have isolated 10 alkaloids until the present, some of which were active on memory retention, investigation developed in vitro and in vivo. After these promising results, these studies will be continued, as well as the search for the pharmacophore. For this reason, chemical modifications on functional groups will be done and the obtained products will be evaluated on their activity on memory as well. In line with this, the different families of compounds present in H. saururus will be studied in view that the popular use claims its aphrodisiac effect. The search for a perfect aphrodisiac that increase the sexual desire, the pleasure and performance was a constant since the old times. In all the cases it was looked a better sexual performance or fight against the erectile dysfunction (DE). For investigate the biological activity of H. saururus, the extracts and the isolated compounds will be evaluated on the NO generation, which will be estimated by means of nitrite accumulation, stable metabolite of NO, in supernatants of endothelial cell cultures (HUVEC). The compounds that appear effectives will be evaluated by in vivo assays such as sexual male behavior, and mount behavior. As for alkaloids, toxicity of active compounds will be studied to follow the pre-clinic methodology research of potential medicines.

Ambulatory Blood Pressure Monitoring: Five Decades of More Light and Less Shadows

Abstract Casual blood pressure measurements have been extensively questioned over the last five decades. A significant percentage of patients have different blood pressure readings when examined in the office or outside it. For this reason, a change in the paradigm of the best manner to assess blood pressure has been observed. The method that has been most widely used is the Ambulatory Blood Pressure Monitoring - ABPM. The method allows recording blood pressure measures in 24 hours and evaluating various parameters such as mean BP, pressure loads, areas under the curve, variations between daytime and nighttime, pulse pressure variability etc. Blood pressure measurements obtained by ABPM are better correlated, for example, with the risks of hypertension. The main indications for ABPM are: suspected white coat hypertension and masked hypertension, evaluation of the efficacy of the antihypertensive therapy in 24 hours, and evaluation of symptoms. There is increasing evidence that the use of ABPM has contributed to the assessment of blood pressure behaviors, establishment of diagnoses, prognosis and the efficacy of antihypertensive therapy. There is no doubt that the study of 24-hour blood pressure behavior and its variations by ABPM has brought more light and less darkness to the field, which justifies the title of this review.