Biomimetic supramolecular designs for the controlled release of growth factors in bone regeneration

The extracellular matrix (ECM) of tissues is an assembly of insoluble macromolecules that specifically interact with soluble bioactive molecules and regulate their distribution and availability to cells. Recapitulating this ability has been an important target in controlled growth factor delivery strategies for tissue regeneration and requires the design of multifunctional carriers. This review describes the integration of supramolecular interactions on the design of delivery strategies that encompass self-assembling and engineered affinity components to construct advanced biomimetic carriers for growth factor delivery. Several glycan- and peptide-based self-assemblies reported in the literature are highlighted and commented upon. These examples demonstrate how molecular design and chemistry are successfully employed to create versatile multifunctional molecules which self-assemble/disassemble in a precisely predicted manner, thus controlling compartmentalization, transport and delivery. Finally, we discuss whether recent advances in the design and preparation of supramolecular delivery systems have been sufficient to drive real translation towards a clinical impact. 

Targeting lactate transport suppresses in vivo breast tumour growth.

BACKGROUND Most cancers, including breast cancer, have high rates of glucose consumption, associated with lactate production, a process referred as "Warburg effect". Acidification of the tumour microenvironment by lactate extrusion, performed by lactate transporters (MCTs), is associated with higher cell proliferation, migration, invasion, angiogenesis and increased cell survival. Previously, we have described MCT1 up-regulation in breast carcinoma samples and demonstrated the importance of in vitro MCT inhibition. In this study, we performed siRNA knockdown of MCT1 and MCT4 in basal-like breast cancer cells in both normoxia and hypoxia conditions to validate the potential of lactate transport inhibition in breast cancer treatment. RESULTS The effect of MCT knockdown was evaluated on lactate efflux, proliferation, cell biomass, migration and invasion and induction of tumour xenografts in nude mice. MCT knockdown led to a decrease in in vitro tumour cell aggressiveness, with decreased lactate transport, cell proliferation, migration and invasion and, importantly, to an inhibition of in vivo tumour formation and growth. CONCLUSIONS This work supports MCTs as promising targets in cancer therapy, demonstrates the contribution of MCTs to cancer cell aggressiveness and, more importantly, shows, for the first time, the disruption of in vivo breast tumour growth by targeting lactate transport.

Validity of the Brazilian Portuguese version of the bipolar spectrum diagnostic scale

OBJECTIVE: Bipolar spectrum disorders (BSDs) are prevalent and frequently unrecognized and undertreated. This report describes the development and validation of the Brazilian version of the bipolar spectrum diagnostic scale (B-BSDS), a screening instrument for bipolar disorders, in an adult psychiatric population. METHOD: 114 consecutive patients attending an outpatient psychiatric clinic completed the B-BSDS. A research psychiatrist, blind to the B-BSDS scores, interviewed patients by means of a modified version of the mood module of the Structured Clinical Interview for DSM-IV ("gold standard"). Subthreshold bipolar disorders were defined as recurrent hypomania without a major depressive episode or with fewer symptoms than those required for threshold hypomania. RESULTS: The internal consistency of the B-BSDS evaluated with Cronbach's alpha coefficient was 0.89 (95% CI; 0.86-0.91). On the basis of the modified SCID, 70 patients (61.4%) of the sample received a diagnosis of BSDs. A B-BSDS screening score of 16 or more items yielded: sensitivity of 0.79 (95% CI; 0.72-0.85), specificity of 0.77 (95% CI; 0.70-0.83), a positive predictive value of 0.85 (95% CI; 0.78-0.91) and a negative predictive value of 0.70 (95% CI; 0.63-0.75). CONCLUSION: The present data demonstrate that the B-BSDS is a valid instrument for the screening of BSDs.

Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

Development of procedures for the design, optimization and manufacturing of customized orthopaedic and trauma implants: Geometrical/anatomical modelling from 3D medical imaging

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

Reliability and convergent validity of the Childhood Anxiety Sensitivity Index in children and adolescents

OBJECTIVE: The purpose of this study was to examine the reliability and the convergent validity of the Children Anxiety Sensitivity Index (CASI) with DSM-IV anxiety disorder symptoms, by comparison with the Screen for Child Anxiety Related Emotional Disorders (SCARED), in a community sample of Brazilian children and adolescents. METHODS: Children and adolescents from five schools were selected from a larger study that aimed to assess different aspects of childhood anxiety disorders. All participants completed the CASI and the SCARED. RESULTS: This study supported the reliability of the CASI total score. Girls reported higher total anxiety sensitivity scores than boys and there were no differences in total anxiety sensitivity scores between children and adolescents. This study showed moderate to high correlations between the CASI scores with SCARED scores, all correlations coefficients being positive and significant. CONCLUSIONS: Our findings demonstrate an appropriate reliability and evidence of convergent validity in the CASI in a sample of Brazilian children and adolescents.

Exposição a trauma e transtorno de estresse pós-traumático em usuárias de crack

OBJETIVO: Verificar a ocorrência de trauma e transtorno de estresse pós-traumático (TEPT) em uma amostra de mulheres dependentes de cocaína tipo crack. MÉTODO: A amostra foi composta por 99 mulheres, entre 18 e 52 anos, internadas em uma unidade de desintoxicação e extensamente avaliadas por meio da SCID-I e a ASI-6. RESULTADOS: Verificou-se uma taxa de exposição a trauma de 86,9% entre mulheres dependentes de cocaína tipo crack. A taxa de TEPT na amostra foi de 15,1%. Os clusters de revivescência e hiperexcitabilidade foram os mais frequentes - 24,4% e 20,9% respectivamente. Entre os tipos de eventos relatados, os mais frequentes foram sofrer agressão/abuso físico e ser testemunha de violência a outros. CONCLUSÃO: Os resultados sugerem uma frequente exposição a eventos traumáticos. Com relação à idade da experiência traumática, sugere-se que as usuárias expostas a trauma durante a infância e adolescência apresentam um início do uso de drogas em idades mais precoces que aquelas cujo trauma ocorreu na vida adulta.

Conflito e trauma: XVI Colóquio de Outono

It has been the main concern of CEHUM, as a Research Centre within the Humanities which operates in an inter and transdisciplinary structure to listen attentively to the “noise of the world” and attempt a global interpretation of the signs of the times issuing from the world around us, as vibrant echoes of many social and cultural pressing issues. Every year each new Colóquio de Outono attempts to give evidence of that concern through the topic chosen for debate, ample enough and challenging enough to trigger a lively multidisciplinary dialogue amongst the diff erent research groups that compose this centre, the participants and our invited guest speakers. Throughout the three days of this 16th Colóquio de Outono we had the privilege to debate the propositions of a vast number of national and international specialists in the manifold fi elds of inquiry here represented, engaging keynote speakers, project advisors, members of research teams and external researchers attached to the various research projects currently running in CEHUM, in the fi elds of literature, linguistics, philosophy, ethics, visual arts, cultural studies, music and performance. Each specifi c fi eld of studies was however never seen isolated, but always embodied in a geo-cultural context and within the scope of a wide variety of critical debates and current theories of knowledge, as a signal of our understanding of the Humanities as a rich and plural territory which engages us all, scholars, researchers, students.

Growth of sulfate reducing bacteria on the methanogenic inhibitor BES

The metabolism of methanogenic archaea is inhibited by 2-bromoethanesulfonate (BES). Methane production is blocked because BES is an analog of methyl-coenzyme M and competes with this key molecule in the last step of methanogenesis. For this reason, BES is commonly used in several studies to avoid growth of acetoclastic and hydrogenotrophic methanogens [1]. Despite its effectiveness as methanogenic inhibitor, BES was found to alter microbial communities’ structure, to inhibit the metabolism of non-methanogenic microorganisms and to stimulate homoacetogenic metabolism [2,3]. Even though sulfonates have been reported as electron acceptors for sulfate- and sulfite-reducing bacteria (SRB), only one study described the reduction of BES by complex microbial communities [4]. In this work, a sulfate-reducing bacterium belonging to Desulfovibrio genus (98 % identity at the 16S rRNA gene level with Desulfovibrio aminophilus) was isolated from anaerobic sludge after several successive transfers in anaerobic medium containing BES as sole substrate. Sulfate was not supplemented to the anaerobic growth medium. This microorganism was able to grow under the following conditions: on BES plus H2/CO2 in bicarbonate buffered medium; on BES without H2/CO2 in bicarbonate buffered medium; and on BES in phosphate buffered medium. The main products of BES utilization were sulfide and acetate, the former was produced by the reduction of sulfur from the sulfonate moiety of BES and the latter likely originated from the carbon backbone of the BES molecule. BES was found, in this study, to represent not only an alternative electron acceptor but also to serve as electron donor, and sole carbon and energy source, supporting growth of a Desulfovibrio sp. obtained in pure culture. This is the first study that reports growth of SRB with BES as electron donor and electron acceptor, showing that the methanogenic inhibitor is a substrate for anaerobic growth.

The effect of hydrodynamic conditions in Corynebacterium glutamicum growth

[Excerpt] Corynebacterium glutamicum is a facultative anaerobic, gram-positive bacterium with a GRAS status that grows fast and achieves high cell densities. C. glutamicum is commonly used in amino acids production, and is also able to convert sugars in organic acids (OA) and alcohols in specific conditions: anaerobic and limited-oxygen environments. In these conditions, the carbon metabolism is modified, namely the flux shifts from the pentose phosphate pathway to glycolysis and the TCA cycle flux decreases and consequently bacterial growth is strongly affected [1,2]. (...)

Growth hormone for optimization of refractory heart failure treatment

It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine) and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day) for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 mg/l) and serum IGF-1 levels (from 130 to 300ng/ml) was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA) increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later). The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.

Study of the retinoic acid regulated genes in the rodent hypothalamus controlling growth and appetite and the potential for the epigenetic control

Dissertação de mestrado em Bioquímica (área de especialização em Biomedicina)

The Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A): a study with recently and non-recently divorced adults

Past research has demonstrated that divorced adults show more health problems and psychological distress than married adults. Considering the high prevalence rates of divorce among Western countries, new and robust measures should be developed to measure psychological distress after this specific transition in adulthood. The aim of this study was to adapt and validate a Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A; Sweeper and Halford in J Family Psychol 20(4):632–640, 2006). PAST-A is a self-report measure that assesses two key dimensions of separation adjustment problems: lonely-negativity and former partner attachment. Psychometric properties of the Portuguese version of PAST-A were assessed in terms of factor structure, internal consistency, and convergent and divergent validity, in an online convenience sample with divorced adults (N = 460). The PAST-A two-factor structure was confirmed by exploratory and confirmatory factor analyses, with each factor demonstrating very satisfactory internal consistency and good convergence. In terms of discriminant validity, the Portuguese PAST-A reveals a distinct factor from psychological growth after divorce. The results provided support for the use of the Portuguese PAST-A with divorced adults and also suggested that the explicative factors of the psychological adjustment to divorce may be cross-cultural stable. The non-existence of validated divorce-related well-being measures and its implications for divorce research are also discussed.

Mother’s anxiety and depression and associated risk factors during early pregnancy: effects on fetal growth and activity at 20–22 weeks of gestation

To examine effects of mother's anxiety and depression and associated risk factors during early pregnancy on fetal growth and activity. Repeated measures of mother's anxiety (State-Anxiety Inventory (STAI-S)) and depression (Edinburgh Postnatal Depression Scale (EPDS)) and related socio demographics and substance consumption were obtained at the 1st and 2nd pregnancy trimesters, and fetus' (N = 147) biometric data and behavior was recorded during ultrasound examination at 20-22 weeks of gestation. Higher anxiety symptoms were associated to both lower fetal growth and higher fetal activity. While lower education, primiparity, adolescent motherhood, and tobacco consumption predicted lower fetal growth, coffee intake predicted lower fetal activity. Vulnerability of fetal development to mother's psychological symptoms as well as to other sociodemographic and substance consumption risk factors during early and mid pregnancy is suggested.

Prenatal dysthymia versus major depression effects on maternal cortisol and fetal growth

To determine differences between pregnant women diagnosed with Dysthymia versus Major Depression, depressed pregnant women (N=102) were divided by their diagnosis into Dysthymic (N=48) and Major Depression (N=54) groups and compared on self-report measures (depression, anxiety, anger, daily hassles and behavioral inhibition), on stress hormone levels (cortisol and norepinephrine), and on fetal measurements. The Major Depression group had more self-reported symptoms. However, the Dysthymic group had higher prenatal cortisol levels and lower fetal growth measurements (estimated weight, femur length, abdominal circumference) as measured at their first ultrasound (M=18 weeks gestation). Thus, depressed pregnant women with Dysthymia and Major Depression appeared to have different prenatal symptoms.