António Paiva

The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case–control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E−9) and Italian (OR, 1.84; P=6.0E−5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.

Perioperative tumor cell dissemination in patients with primary or metastatic colorectal cancer

INTRODUCTION Although there is general correlation between the TNM stage of colorectal cancer (CRC) and its prognosis, there is often significant variability of tumor behaviour and individual patient outcome, which is unaccounted for by pathologic factors alone. Our aim was to estimate perioperative tumor cell dissemination in patients with primary or CRC liver metastases as a possible factor influencing the outcome. METHODS Forty patients were prospectively enrolled in the study from the year 2007 to 2008. Eighteen patients had histologically proven CRC (50% rectal, 44% colonic, 6% colonic and rectal). Sixteen patients (47%) had CRC liver metastases only. The remaining six patients who underwent colon or liver resection for benign conditions, acted as the control group. All patients with malignant pathologies had R0 resections. Blood samples were taken before the surgical incision (T0), immediately after tumor resection (T1) and at the end of the surgical intervention (T2). Data acquisition was performed using a dual-laser FACSCalibur flow cytometer. Circulating malignant cells were identified as being CD45-/cytokeratin+. RESULTS The analysis of patients overall (CRC resection subgroup and hepatectomy subgroup) revealed that there was no statistically significant difference of the tumoral cell count in the blood per million of hematopoietic cells at T0, T1 and T2. CONCLUSIONS This study demonstrates no differences in the detected circulating numbers of tumor cells at different stages of surgical intervention.

Cultural Adaptation of the Portuguese Version of the "Sniffin' Sticks" Smell Test: Reliability, Validity, and Normative Data.

The cross-cultural adaptation and validation of the Sniffin`Sticks test for the Portuguese population is described. Over 270 people participated in four experiments. In Experiment 1, 67 participants rated the familiarity of presented odors and seven descriptors of the original test were adapted to a Portuguese context. In Experiment 2, the Portuguese version of Sniffin`Sticks test was administered to 203 healthy participants. Older age, male gender and active smoking status were confirmed as confounding factors. The third experiment showed the validity of the Portuguese version of Sniffin`Sticks test in discriminating healthy controls from patients with olfactory dysfunction. In Experiment 4, the test-retest reliability for both the composite score (r71 = 0.86) and the identification test (r71 = 0.62) was established (p<0.001). Normative data for the Portuguese version of Sniffin`Sticks test is provided, showing good validity and reliability and effectively distinguishing patients from healthy controls with high sensitivity and specificity. The Portuguese version of Sniffin`Sticks test identification test is a clinically suitable screening tool in routine outpatient Portuguese settings.

The Portuguese version of Mini-Tinnitus Questionnaire: brief screening test for assessment of tinnitus-induced stress.

Hypothesis: The Portuguese version of Mini-Tinnitus Questionnaire (Mini-TQ) is as valid as the English version to assess tinnitus-associated distress in the Portuguese-speaking population. Background: Tinnitus is a major symptom in ENT practice affecting subjects in all demographic groups. Our objective is to validate a Portuguese version of Mini-TQ (Mini-TQ-pv) to be used in clinical practice and research. Methods: Mini-TQ-pv was administered to 51 patients with chronic tinnitus. Statistical analysis was done to determine the psychometric properties of the instrument. Results: After double translation, face and content validity were confirmed by high internal consistency (Cronbach &agr; = 0.861) and significant correlation between individual items and total score. The questionnaire was easy and quick to administer (2.57 min). Conclusion: We provide a suitable Mini-TQ-pv to be used in the assessment of Portuguese-speaking patients with tinnitus.

Vértigo posicional paroxístico benigno: revisión de 101 casos

INTRODUCTION AND OBJECTIVE Benign paroxysmal positional vertigo is one of the most common vestibular disorders, with a lifetime prevalence of 2.4%. This study aimed to assess age, gender, lesion type and site, association with other vestibular diseases, progression and recurrence in a Portuguese population. METHODS This was a retrospective observational study of 101 patients diagnosed with benign paroxysmal positional vertigo by the same senior doctor, in a tertiary academic hospital, between January 2009 and May 2011. RESULTS A total of 101 cases were pooled, with a mean age of 56.57±15.33 years (15-90 years). From these, 72.3% were women. The posterior canal was affected in 72.3%, the lateral in 24.7%, the anterior in 2% and multiple canals in 1%. Unilateral canal and left labyrinth involvement were more frequent. The therapeutic maneuver used most was Epleys. Recurrence was observed in 10.9% of the cases. It was idiopathic in 83.2% of cases. No association was found between the number of maneuvers necessary to treat benign paroxysmal positional vertigo and etiology. CONCLUSION Benign paroxysmal positional vertigo is more frequent in female subjects, in the 6th decade and involves preferably the posterior semicircular canal of the right labyrinth. In most cases it is idiopathic and treatment with repositioning maneuvers has a mean success of 90%. Our results were in accordance with the literature; nevertheless, in this study the left labyrinth was most affected and the follow-up period was variable.

Oxidative Stress, DNA, Cell Cycle/Cell Cycle Associated Proteins and Multidrug Resistance Proteins: Targets of Human Amniotic Membrane in Hepatocellular Carcinoma

The anticancer effects of human amniotic membrane (hAM) have been studied over the last decade. However, the action mechanisms responsible for these effects are not fully understood until now. Previously results reported by our team proved that hAM is able to induce cytotoxicity and cell death in hepatocellular carcinoma (HCC), a worldwide high incident and mortal cancer. Therefore, this experimental study aimed to investigate the cellular targets of hAM protein extracts (hAMPE) in HCC through in vitro studies. Our results showed that hAMPE is able to modify oxidative stress environment in all HCC cell lines, as well as its cell cycle. hAMPE differently targets deoxyribonucleic acid (DNA), P21, P53, β-catenin and multidrug resistance (MDR) proteins in HCC cell lines. In conclusion, hAMPE has several targets in HCC, being clear that the success of this treatment depends of a personalized therapy based on the biological and genetic characteristics of the tumor.

Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation

Chromatin structure is a major regulator of transcription and gene expression. Herein we explore the use of osmotic modulation to modify the chromatin structure and reprogram gene expression. In this study we use the extracellular osmotic pressure as a chromatin structure and transcriptional modulator. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. The chromatin decondensation opens space for higher amounts of DNA engaged RNA Pol II. Hyposmotic modulation constitutes an alternative route to manipulate cell fate decisions. This technology was tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34+ umbilical-cord-blood (UCB), fibroblasts and B-cells. The efficiency and kinetics of these cell fate modulation processes were improved by transient hyposmotic modulation of the cell environment.

Translation of the international outcome inventory for hearing aids into Portuguese from Portugal

Objective To translate the International Outcome Inventory for Hearing Aids (IOI-HA) Questionnaire from English to Portuguese (from Portugal) and to validate this instrument of study on the Portuguese population. Design In this prospective study, a translation from English into Portuguese of the IOI-HA was performed, and linguistic adaptation and counter translation were also accomplished. The data were analysed for internal consistency testing for correlations between each individual item and the total score of the IOI-HA, assessing the Cronbach α and performing test–retest analysis. Setting and participants 80 hearing aid users aged 18 years or older were recruited from an ear, nose and throat (ENT) appointment in Coimbras hospital, Portugal. 84% of the participants were unilateral hearing aid users, whereas 16% were bilateral users. Interventions The patients volunteered to answer the questionnaire during an ENT appointment. All of the patients had been using the hearing aids for more than 3 years. After the first application of the questionnaire, a new appointment was planned for retesting, within at least 7 days to no more than 60 days. 29 participants answered the questionnaire again according to the same procedure. Results The mean IOI-HA total score in the study population was 27.33±4.93 (9–35). The mean values obtained for each item of the questionnaire ranged from 3.19 to 4.54. The Cronbach α was 0.838 and the Cronbach α values when the item was removed, were also significantly strong. The test–retest analysis revealed no differences between the paired groups. Conclusions In the present study a valid and reliable translation and adaptation of the IOI-HA into Portuguese from Portugal is proposed. This tool will be available for clinical assessment of hearing aid users.

Accelerated age-related olfactory decline among type 1 Usher patients

Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome.

Author Correction: Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.