Triple negative breast cancer: nanosolutions for a big challenge

Triple negative breast cancer (TNBC) is a particular immunopathological subtype of breast cancer that lacks expression of estrogen and progesterone receptors (ER/PR) and amplification of the human epidermal growth factor receptor 2 (HER2) gene. Characterized by aggressive and metastatic phenotypes and high rates of relapse, TNBC is the only breast cancer subgroup still lacking effective therapeutic options, thus presenting the worst prognosis. The development of targeted therapies, as well as early diagnosis methods, is vital to ensure an adequate and timely therapeutic intervention in patients with TNBC. This review intends to discuss potentially emerging approaches for the diagnosis and treatment of TNBC patients, with a special focus on nano-based solutions that actively target these particular tumors.

Evidence for inter- and intra-species biofilm formation variability among a small group of coagulase-negative staphylococci

Coagulase-negative staphylococci (CoNS) are common bacterial colonisers of the human skin. They are often involved in nosocomial infections due to biofilm formation in indwelling medical devices. While biofilm formation has been extensively studied in Staphylococcus epidermidis, little is known regarding other CoNS species. Here, biofilms from six different CoNS species were characterised in terms of biofilm composition and architecture. Interestingly, the ability to form a thick biofilm was not associated with any particular species, and high variability on biofilm accumulation was found within the same species. Cell viability assays also revealed different proportions of live and dead cells within biofilms formed by different species, although this parameter was particularly similar at the intra-species level. On the other hand, biofilm disruption assays demonstrated important inter- and intra-species differences regarding extracellular matrix composition. Lastly, confocal laser scanning microscopy (CLSM) experiments confirmed this variability, highlighting important differences and common features of CoNS biofilms. We hypothesised that the biofilm formation heterogeneity observed was rather associated with biofilm matrix composition than with cells themselves. Additionally, our results indicate that polysaccharides, DNA and proteins are fundamental pieces in the process of CoNS biofilm formation.

Attachment style impacts behavior and early oculomotor response to positive, but not negative, pictures

The present study investigated whether oculomotor behavior is influenced by attachment styles. The Relationship Scales Questionnaire was used to assess attachment styles of forty-eight voluntary university students and to classify them into attachment groups (secure, preoccupied, fearful, and dismissing). Eye-tracking was recorded while participants engaged in a 3-seconds free visual exploration of stimuli presenting either a positive or a negative picture together with a neutral picture, all depicting social interactions. The task consisted in identifying whether the two pictures depicted the same emotion. Results showed that the processing of negative pictures was impermeable to attachment style, while the processing of positive pictures was significantly influenced by individual differences in insecure attachment. The groups highly avoidant regarding to attachment (dismissing and fearful) showed reduced accuracy, suggesting a higher threshold for recognizing positive emotions compared to the secure group. The groups with higher attachment anxiety (preoccupied and fearful) showed differences in automatic capture of attention, in particular an increased delay preceding the first fixation to a picture of positive emotional valence. Despite lenient statistical thresholds induced by the limited sample size of some groups (p < 0.05 uncorrected for multiple comparisons), the current findings suggest that the processing of positive emotions is affected by attachment styles. These results are discussed within a broader evolutionary framework.

Symptoms and signs in rigid gas permeable lens wearers during adaptation period

Objectives: To evaluate neophyte contact lens wearers’ fitting to rigid gas permeable (RGP) contact lenses in terms of wearing time, tear volume, stability, corneal staining, and subjective ratings, over a 1-month period of time. Methods: Twenty-two young healthy subjects were enrolled for wearing RGP on a daily wear basis. The participants included in this study never wore contact lenses and showed a value under 10 in McMonnies Questionnaire. Contact Lens Dry Eye Questionnaire, Visual Analog Scales, Schirmer test, tear film break-up time (BUT), and corneal staining grading were performed. Follow-up visits were scheduled at 1, 7, 15, and 28 days. Results: Six subjects dropped out due to discomfort from the study before 1 month (27% of discontinuation rate). Successful RGP wearers (16 participants) achieved high levels of subjective vision and reported comfort scores of approximately 9 of 10 between 10 and 15 days. They reported wearing their lenses for an average of 10.1262.43 hr after 1 month of wear. Conversely, unsuccessful wearers discontinued wearing the lenses after the first 10 to 15 days, showing comfort scores and wearing time significantly lower compared with the first day of wear. Schirmer test showed a signifi- cant increase at 10 days (P,0.001), and the BUT trends decreased after the first week of wear in unsuccessful group. Conclusions: Symptomatology related with dryness and discomfort, detected during the first 10 days of the adaptation, may help the clinician to predict those participants who will potentially fail to adapt to RGP lens wear.

Local non-negative initial data scalar characterization of the Kerr solution

For any vacuum initial data set, we define a local, non-negative scalar quantity which vanishes at every point of the data hypersurface if and only if the data are Kerr initial data. Our scalar quantity only depends on the quantities used to construct the vacuum initial data set which are the Riemannian metric defined on the initial data hypersurface and a symmetric tensor which plays the role of the second fundamental form of the embedded initial data hypersurface. The dependency is algorithmic in the sense that given the initial data one can compute the scalar quantity by algebraic and differential manipulations, being thus suitable for an implementation in a numerical code. The scalar could also be useful in studies of the non-linear stability of the Kerr solution because it serves to measure the deviation of a vacuum initial data set from the Kerr initial data in a local and algorithmic way.

Common symptoms of Nepalese soft contact lens wearers: A pilot study

Aim: To determine the common symptoms in current soft contact lens (CL) wearers and theirassociation with other factors among Nepalese population.Methods: All the current CL wearers who started to wear soft CL in Nepal Eye Hospital between July 2007 and June 2012 were invited for the participation. Frequency of the ten most common symptoms, divided into never, occasionally, frequently and consistent were recorded. Association between degree of symptoms with other factors, e.g. age, gender, profession, cigarette smoking, ethnicity, level of education and duration and wearing modality of CL wear were analyzed.Results: Out of 129 subjects participated in this study, 67% were female; the mean age of the subjects was 23.9 ± 4.3 years. Ninety seven percent of them had at least one symptom occasionally or frequently or consistently. Discomfort was found in 88.4% of the total subjects.Other common symptoms were foreign body sensation in 73.6%, redness in 65.9%, reduced wearing time in 63.6% and dryness in 62.8%. Symptoms were found occasionally in the majority of subjects. Degree of symptoms was not associated with age, gender, profession, education status, ethnicity of subjects and duration or modality of lens wear (p > 0.05) but was positively associated with passive cigarette smoking (p < 0.001).Conclusion: Almost all of the Nepalese soft CL wearers had some types of symptoms at least occasionally. Discomfort was the most common symptom. Degree of symptoms was associated with the passive smoking but not with other factors like age, sex, profession and duration of lens wear.

Cotard syndrome without depressive symptoms in a schizophrenic patient

Cotard Syndrome without Depressive Symptoms in a Schizophrenic Patient

Structural and enzymatic characterization of ABgp46, a novel phage endolysin with broad anti-Gram-negative bacterial activity

The present study demonstrates the antibacterial potential of a phage endolysin against Gram-negative pathogens, particularly against multidrug resistant strains of Acinetobacter baumannii. We have cloned, heterologously expressed and characterized a novel endolysin (ABgp46) from Acinetobacter phage vb_AbaP_CEB1 and tested its antibacterial activity against several multidrug-resistant A. baumannii strains. LC-MS revealed that ABgp46 is an N-acetylmuramidase, that is also active over a broad pH range (4.0-10.0) and temperatures up to 50°C. Interestingly, ABgp46 has intrinsic and specific anti-A. baumannii activity, reducing multidrug resistant strains by up to 2 logs within 2 hours. By combining ABgp46 with several organic acids that act as outer membrane permeabilizing agents, it is possible to increase and broaden antibacterial activity to include other Gram-negative bacterial pathogens. In the presence of citric and malic acid, ABgp46 reduces A. baumannii below the detection limit (> 5 log) and more than 4 logs P. aeruginosa and Salmonella Typhimurium strains. Overall, this globular endolysin exhibits a broad and high activity against Gram-negative pathogens, that can be enhanced in presence of citric and malic acid, and be used in human and veterinary medicine.

Paternal Adjustment and Paternal Attitudes Questionnaire: Antenatal and postnatal portuguese versions

The Paternal Adjustment and Paternal Attitudes Questionnaire (PAPA) was designed to assess paternal adjustment and paternal attitudes during the transition to parenthood. This study aimed to examine the psychometric characteristics of the Portuguese versions of the PAPA-Antenatal (PAPA-AN) and -Postnatal (PAPA-PN) versions. A nonclinical sample of 128 fathers was recruited in the obstetrics outpatient unit, and they completed both versions of the PAPA and selfreport measures of depressive and anxiety symptoms during pregnancy and the postpartum period, respectively. Good internal consistency for both PAPA-AN and PAPA-PN was found. A three-factor model was found for both versions of the instrument. Longitudinal confirmatory factor analysis revealed a good model fit. The PAPA-AN and PAPA-PN subscales revealed good internal consistency. Significant associations were found between PAPA (PAPA-AN and PAPA-PN) and depressive and anxiety symptoms, suggesting good criterion validity. Both versions also showed good clinical validity, with optimal cutoffs found. The present study suggested that the Portuguese versions of the PAPA are reliable multidimensional self-report measures of paternal adjustment and paternal attitudes that could be used to identify fathers with adjustment problems and negative attitudes during the transition to parenthood.

Maternal adjustment and maternal attitudes in adolescent and adult pregnant women

Study Objective: This study analyzes differences between adolescent and adult pregnant women and the contribution of maternal age to maternal adjustment and maternal attitudes during pregnancy. Design, Setting, and Participants: A sample of 398 Portuguese pregnant women (111 younger than 19 years) was recruited in a Portuguese Maternity Hospital and completed the Maternal Adjustment and Maternal Attitudes Questionnaire between the 24th and 36th weeks of gestation. Main Outcome Measures: Maternal Adjustment and Maternal Attitudes Questionnaire. Results: Adolescent pregnant women show lower maternal adjustment (poorer body image and worse marital relationship) and poorer maternal attitudes (more negative attitudes to sex) than adult pregnant women. When controlling for socio-demographics, age at pregnancy predicts poorer body image and more negative attitudes to sex, but not a worse marital relationship, more somatic symptoms or negative attitudes to pregnancy and the baby. A worse marital relationship was better predicted by living without the partner, and more somatic symptoms and negative attitudes to pregnancy and the baby was predicted by higher education. Conclusion: Adolescent pregnant women show lower maternal adjustment and poorer maternal attitudes than adult pregnant women according to socio-demographics and unfavorable developmental circumstances.

Parents' physical victimization in childhood and current risk of child maltreatment: the mediator role of psychosomatic symptoms

Objective: To test the potential mediation effect of psychosomatic symptoms on the relationship between parents' history of childhood physical victimization and current risk for child physical maltreatment. Methods: Data from the Portuguese National Representative Study of Psychosocial Context of Child Abuse and Neglect were used. Nine-hundred and twenty-four parents completed the Childhood History Questionnaire, the Psychosomatic Scale of the Brief Symptom Inventory, and the Child Abuse Potential Inventory. Results: Mediation analysis revealed that the total effect of the childhood physical victimization on child maltreatment risk was significant. The results showed that the direct effect from the parents' history of childhood physical victimization to their current maltreatment risk was still significant once parents' psychosomatic symptoms were added to the model, indicating that the increase in psychosomatic symptomatology mediated in part the increase of parents' current child maltreatment risk. Discussion: The mediation analysis showed parents' psychosomatic symptomatology as a causal pathway through which parents' childhood history of physical victimization exerts its effect on increased of child maltreatment risk. Somatization-related alterations in stress and emotional regulation are discussed as potential theoretical explanation of our findings. A cumulative risk perspective is also discussed in order to elucidate about the mechanisms that contribute for the intergenerational continuity of child physical maltreatment.

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.

Prevalência e preditores de sintomatologia depressiva após o parto

Contexto: A depressão pós-parto é uma patologia que ocorre nas primeiras semanas após o parto com conseqüências negativas não só para a mãe, como também para o bebê e para a família. Objetivo: Examinar a prevalência de depressão após o parto, bem como as circunstâncias suscetíveis de predizer a sintomatologia depressiva 1 semana e 3 meses após o parto. Métodos: 197 grávidas preencheram o Questionário de Antecipação do Parto (QAP) (Costa et al., 2005a) no segundo trimestre de gestação. Na primeira semana após o parto, responderam ao Questionário de Experiência e Satisfação com o Parto (QESP) (Costa et al., 2005b) e à Edinburgh Postnatal Depression Scale (EPDS) (Augusto et al., 1996), esta última aplicada novamente no terceiro mês do puerpério. Resultados: Uma percentagem significativa de mulheres encontra-se clinicamente deprimida (EPDS ≥ 13) na primeira semana e 3 meses após o parto (12,4% e 13,7%, respectivamente). Das que têm EPDS ≥ 13 na primeira semana, 25% estão ainda deprimidas 3 meses após o parto. Circunstâncias relativas à saúde física, à experiência emocional de parto e ao primeiro contato com o bebê predizem a sintomatologia depressiva na primeira semana do puerpério. A sintomatologia depressiva na primeira semana após o parto e a experiência emocional negativa de parto predizem a sintomatologia depressiva 3 meses após o parto. Conclusões: Constata-se a importância da experiência emocional de parto e do primeiro contato com o bebê, enfatizando a necessidade de atender às necessidades psicológicas da mulher.

Novel strategies to combat gram-negative bacterial pathogens using bacteriophage proteins

Dissertação de mestrado em Bioengenharia

Activity of carvacrol against Coagulase-negative Staphylococci biofilm related infections

Dissertação de mestrado em Bioengenharia