Nuclear localization of epidermal growth factor receptor (EGFR) in ameloblastomas

Background: Ameloblastoma is a locally invasive neoplasm often associated with morbidity and facial deformities, showing increased Epidermal Growth Factor Receptor (EGFR) expression. Inhibition of EGFR was suggested as a treatment option for a subset of ameloblastomas. However, there are resistance mechanisms that impair anti-EGFR therapies. One important resistance mechanism for EGFR-inhibition is the EGFR nuclear localization, which activates genes responsible for its mitogenic effects, such as Cyclin D1.Methods: We assessed EGFR nuclear localization in encapsulated (unicystic, n = 3) and infiltrative (multicystic, n = 11) ameloblastomas and its colocalization with Cyclin D1 by using anti-EGFR and anti-lamin B1 double labeling immunofluorescence analyzed by confocal microscopy. Oral inflammatory fibrous hyperplasia and oral squamous cell carcinoma samples were used for comparison.Results: Twelve cases of ameloblastoma exhibited nuclear EGFR colocalization with lamin B1. This positive staining was mainly observed in the ameloblast-like cells. The EGFR nuclear localization was also observed in control samples. In addition, nuclear EGFR colocalized with Cyclin D1 in ameloblastomas.Conclusions: Nuclear EGFR occurs in ameloblastomas in association with Cyclin D1 expression, which is important in terms of tumor biology clarification and raises a concern about anti-EGFR treatment resistance in ameloblastomas.     

Monocyte and Lymphocyte Activation in Bipolar Disorder: A New Piece in the Puzzle of Immune Dysfunction in Mood Disorders

Background:

This study tested the hypothesis that the low-grade inflammation presented in patients with bipolar disorder (BD) is associated with expansion of activated T cells, and this activated state may be due to a lack of peripheral regulatory cells.

Methods:

Specifically, we investigated the distribution of monocytes and lymphocyte subsets, and investigated Th1/Th2/Th17 cytokines in plasma by flow cytometry. Twenty-one BD type I patients and 21 age- and sex-matched controls were recruited for this study.

Results:

BD patients had increased proportions of monocytes (CD14+). Regarding lymphocyte populations, BD patients presented reduced proportions of T cells (CD3+) and cytotoxic T cells (CD3+CD8+). BD patients also exhibited a higher percentage of activated T CD4+CD25+ cells, and a lower percentage of IL-10 expressing Treg cells.

Conclusions:

Our data shed some light into the underlying mechanisms involved with the chronic low-grade inflammatory profile described in BD patients.     

The Brazilian Back Complaints in the Elders (Brazilian BACE) study: characteristics of Brazilian older adults with a new episode of low back pain

Objective

Low back pain (LBP) is little explored in the aging population especially when considering age-relevant and culturally dependent outcomes. We aimed to describe socio-demographic and clinical characteristics of Brazilian older people with a new episode of LBP presenting to primary care.

The Valsalva maneuver in Chagas disease patients without cardiopathy.

BACKGROUND: The Valsalva maneuver is a simple and reliable test of parasympathetic heart control that can also be used as a trigger of cardiac arrhythmia. Few studies are available about the Valsalva maneuver in Chagas disease patients without cardiac involvement and their results are contradictory. In a cross-sectional study, we compared Chagas disease patients without cardiac involvement and normal individuals using the Valsalva maneuver in order to study the vagal cardiac control and the occurrence of cardiac arrhythmia in the early phase of Chagas disease. METHODS: Fifty-nine patients with Chagas disease without cardiac involvement and 37 controls were submitted to a carefully standardized Valsalva maneuver. Cardiac vagal control was assessed by the Valsalva ratio and the occurrence of cardiac arrhythmia was recorded and coded. RESULTS: The two groups were comparable in terms of left ventricular ejection fraction and left ventricular end-diastolic dimension. When compared to the control group, patients with Chagas disease had significantly lower Valsalva ratios (1.81+/-0.41 versus 2.01+/-0.41, P=0.017) which were not significantly correlated with age, left ventricular function or the presence of radiological esophageal abnormalities. Atrioventricular block (mainly 2nd degree Mobitz type I) occurred exclusively in Chagas disease patients (15,6%, P=0.021) and may indicate an early involvement of the AV node. Premature ventricular contraction was more frequent in Chagas disease patients (16.9% versus 8.1%, P=0.217), although the difference was not statistically significant. CONCLUSION: The Valsalva maneuver is a useful test to detect early vagal dysfunction in Chagas disease patients without cardiac involvement.