HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status

BACKGROUND: Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. METHODS: Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. RESULTS: A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). CONCLUSIONS: A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. Cancer (Cancer Cytopathol) 2015. (c) 2015 American Cancer Society.

Cost-effective and lightweight mobile units for MixAR: A comparative trial among different setups

Cultural heritage has arousing the interest of the general public (e.g. tourists), resulting in the increasing number of visitations to archaeological sites. However, many buildings and monuments are severely damaged or completely destroyed, which doesn’t allow to get a full experience of “travelling in time”. Over the years, several Augmented Reality (AR) approaches were proposed to overcome these issues by providing three-dimensional visualization of reconstructed ancient structures in situ. However, most of these systems were made available through heavy and expensive technological bundles. Alternatively, MixAR intends to be a lightweight and cost-effective Mixed Reality system which aims to provide the visualization of virtual ancient buildings reconstructions in situ, properly superimposed and aligned with real-world ruins. This paper proposes and compares different AR mobile units setups to be used in the MixAR system, with low-cost and lightweight requirements in mind, providing different levels of immersion. It was propounded four different mobile units, based on: a laptop computer, a single-board computer (SBC), a tablet and a smartphone, which underwent a set of tests to evaluate their performances. The results show that mobile units based on laptop computer and SBC reached a good overall performance while mobile units based on tablet and smartphone did not meet such a satisfactory result even though they are acceptable for the intended use.

Thrombophilia screening: An artificial neural network approach

Thrombotic disorders have severe consequences for the patients and for the society in general, being one of the main causes of death. These facts reveal that it is extremely important to be preventive; being aware of how probable is to have that kind of syndrome. Indeed, this work will focus on the development of a decision support system that will cater for an individual risk evaluation with respect to the surge of thrombotic complaints. The Knowledge Representation and Reasoning procedures used will be based on an extension to the Logic Programming language, allowing the handling of incomplete and/or default data. The computational framework in place will be centered on Artificial Neural Networks.

Predictors of dropout in a controlled clinical trial of psychotherapy for moderate depression

A significant number of psychotherapy clients remain untreated, and dropping out is one of the main reasons. Still, the literature around this subject is incoherent. The present study explores potential pre-treatment predictors of dropout in a sample of clients who took part in a clinical trial designed to test the efficacy of narrative therapy for major depressive disorder compared to cognitive-behavioral therapy. Logistic regression analysis showed that: (1) treatment assignment did not predict dropout, (2) clients taking psychiatric medication at intake were 80% less likely to drop out from therapy, compared to clients who were not taking medication, and (3) clients presenting anxious comorbidity at intake were 82% less likely to dropout compared to those clients not presenting anxious comorbidity. Results suggest that clinicians should pay attention to depressed clients who are not taking psychiatric medication or have no comorbid anxiety. More research is needed in order to understand this relationship.

Myopia control with a novel peripheral gradient soft lens and orthokeratology: a 2-year clinical trial

Objective. To evaluate the degree of axial elongation with soft radial refractive gradient (SRRG) contact lenses, orthokeratology (OK), and single vision (SV) spectacle lenses (control) during a period of 1 year before treatment and 2 years after treatment. Methods. This was a prospective, longitudinal, nonrandomized study. The study groups consisted of 30, 29, and 41 children, respectively. The axial length (AL) was measured during 2 years after recruitment and lens fitting. Results. The baseline refractive sphere was correlated significantly (r 2 = 0.542; P < 0.0001) with the amount of myopia progression before baseline. After 2 years, the mean myopia progression values for the SRRG, OK, and SV groups were −0.56 ± 0.51, −0.32 ± 0.53, and −0.98 ± 0.58 diopter, respectively. The results represent reductions in myopic progression of 43% and 67% for the SRRG and OK groups, respectively, compared to the SV group. The AL increased more in the SV group compared to the SRRG and OK groups, with 27% and 38% lower axial elongation, respectively, compared to the SV group at the 2-year visit (P < 0.05). SRRG and OK showed no differences (P = 0.430). Conclusion. The SRRG lens significantly decreased AL elongation compared to the SV control group. The SRRG lens was similarly effective to OK in preventing myopia progression in myopic children and adolescent.

Cognitive stimulation for portuguese older adults with cognitive impairment: a randomized controlled trial of efficacy, comparative duration, feasibility and experiential relevance

Although some studies point to cognitive stimulation as a beneficial therapy for older adults with cognitive impairments, this area of research and practice is still lacking dissemination and is underrepresented in many countries. Moreover, the comparative effects of different intervention durations remain to be established and, besides cognitive effects, pragmatic parameters, such as cost-effectiveness and experiential relevance to participants, are seldom explored. In this work, we present a randomized con- trolled wait-list trial evaluating 2 different intervention durations (standard 1⁄4 17 vs brief 1⁄4 11 sessions) of a cognitive stimulation program developed for older adults with cognitive impairments with or without dementia. 20 participants were randomly assigned to the standard duration intervention program (17 sessions, 1.5 months) or to a wait-list group. At postintervention of the standard intervention group, the wait-list group crossed over to receive the brief intervention program (11 sessions, 1 month). Changes in neuropsychological, functionality, quality of life, and caregiver outcomes were evaluated. Experience during intervention and costs and feasibility were also evaluated. The current cognitive stimulation programs (ie, standard and brief) showed high values of experiential relevance for both intervention durations. High adherence, completion rates, and reasonable costs were found for both formats. Further studies are needed to definitively establish the potential efficacy, optimal duration, cost-effectiveness, and experiential relevance for participants of cognitive intervention approaches.

The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds. The identified molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their glucuronated and methylated derivatives obtained by chemical synthesis were also evaluated for the same bioactivity, in order to establish structure-activity relationships and to comprehend the effects of in vivo metabolism reactions in the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential (EC50 values 96 ± 1 to 190 ± 6 µg/mL, and also the highest concentration of cinnamic acid (656 to 156 µg/g), which was also the individual compound with the highest anti-inflammatory activity. The derivatives of p-coumaric acid revealed the strongest properties, specially the derivative methylated in the carboxylic group (CoA-M1) that exhibited similar activity to the one showed by dexamethaxone used as anti-inflammatory standard; by contrast, the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO production. All in all, whereas the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

Historical analysis of the Brazilian cervical cancer screening program from 2006 to 2013: a time for reflection

BACKGROUND: The Cervical Cancer Database of the Brazilian National Health Service (SISCOLO) contains information regarding all cervical cytological tests and, if properly explored, can be used as a tool for monitoring and managing the cervical cancer screening program. The aim of this study was to perform a historical analysis of the cervical cancer screening program in Brazil from 2006 to 2013. MATERIAL AND METHODS: The data necessary to calculate quality indicators were obtained from the SISCOLO, a Brazilian health system tool. Joinpoint analysis was used to calculate the annual percentage change. RESULTS: We observed important trends showing decreased rates of low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) and an increased rate of rejected exams from 2009 to 2013. The index of positivity was maintained at levels below those indicated by international standards; very low frequencies of unsatisfactory cases were observed over the study period, which partially contradicts the low rate of positive cases. The number of positive cytological diagnoses was below that expected, considering that developed countries with low frequencies of cervical cancer detect more lesions annually. CONCLUSIONS: The evolution of indicators from 2006 to 2013 suggests that actions must be taken to improve the effectiveness of cervical cancer control in Brazil.

A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

Zebrafish embryos as in vivo model for toxicity evaluation: screening of nanoparticle formulations DODAB:MO and DODAC:MO

Dissertação de mestrado em Molecular Genetics

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.

Pre-clinical trials for Machado-Joseph Disease: Hypothesis-based and hypothesis-free therapeutic approaches

Tese de Doutoramento em Ciências da Saúde