The characteristics of depressive symptoms in medical students during medical education and training: a cross-sectional study

Background: Medical education and training can contribute to the development of depressive symptoms that might lead to possible academic and professional consequences. We aimed to investigate the characteristics of depressive symptoms among 481 medical students (79.8% of the total who matriculated). Methods: The Beck Depression Inventory (BDI) and cluster analyses were used in order to better describe the characteristics of depressive symptoms. Medical education and training in Brazil is divided into basic (1(st) and 2(nd) years), intermediate (3(rd) and 4(th) years), and internship (5(th) and 6(th) years) periods. The study organized each item from the BDI into the following three clusters: affective, cognitive, and somatic. Statistical analyses were performed using analysis of variance (ANOVA) with post-hoc Tukey corrected for multiple comparisons. Results: There were 184 (38.2%) students with depressive symptoms (BDI > 9). The internship period resulted in the highest BDI scores in comparison to both the basic (p < .001) and intermediate (p < .001) periods. Affective, cognitive, and somatic clusters were significantly higher in the internship period. An exploratory analysis of possible risk factors showed that females (p = .020) not having a parent who practiced medicine (p = .016), and the internship period (p = .001) were factors for the development of depressive symptoms. Conclusion: There is a high prevalence towards depressive symptoms among medical students, particularly females, in the internship level, mainly involving the somatic and affective clusters, and not having a parent who practiced medicine. The active assessment of these students in evaluating their depressive symptoms is important in order to prevent the development of co-morbidities and suicide risk.

Prognostic index expression of cyclin-D1, cerbB-2 and VEGF: metastases vs corresponding primary cancers and metastatic vs non-metastatic adenocarcinomas

The prognostic relevance of different molecular markers in lung cancer is a crucial issue still worth investigating, and the specimens collected and analyzed represent a valuable source of material. Cyclin-D1, c-erbB-2 and vascular endothelial growth factor (VEGF) have shown to be promising as prognosticators in human cancer. In this study, we sought to examine the importance of Cyclin-D1, c-erbB-2 and VEGF, and to study the quantitative relationship among these factors and disease progression in metastases vs corresponding primary cancer, and metastatic vs non metastatic cancers. Material and Methods: We used immunohistochemistry and morphometric analysis to evaluate the amount of tumour staining for Cyclin-D1, c-erbB-2 and VEGF in 52 patients with surgically excised ademocarcinoma of the lung, and the outcome for our study was survival time until death from hematogenic metastases. Results: Metastasis presented lower c-erbB-2 expression than corresponding primary cancers (p=0.02). Cyclin-D1 and VEGF expression were also lower in metastases than in corresponding primary cancers, but this difference did not achieve statistical significance. Non-metastatic cancers also presented significantly lower Cyclin-D1 and c-erbB-2 expression than metastatic cancers (p<0.01 and p<0.01, respectively). Equally significant was the difference between higher c-erbB-2 expression by metastatic cancers compared to non-metastatic cancers (p=0.02). Considering survival in Kaplan-Maier analysis, Cyclin-D1 (p=0.04), c-erbB-2 (p=0.04) and VEGF (p<0.01) were important predictors of survival in metastatic cancers.

Sensitization Prevalence, Antibody Cross-Reactivity and Immunogenic Peptide Profile of Api g 2, the Non-Specific Lipid Transfer Protein 1 of Celery

Background: Celery (Apium graveolens) represents a relevant allergen source that can elicit severe reactions in the adult population. To investigate the sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a Mediterranean population and in a mouse model. Methodology: 786 non-randomized subjects from Italy were screened for IgE reactivity to rApi g 2, rArt v 3 (mugwort pollen LTP) and nPru p 3 (peach LTP) using an allergen microarray. Clinical data of 32 selected patients with reactivity to LTP under investigation were evaluated. Specific IgE titers and cross-inhibitions were performed in ELISA and allergen microarray. Balb/c mice were immunized with purified LTPs; IgG titers were determined in ELISA and mediator release was examined using RBL-2H3 cells. Simulated endolysosomal digestion was performed using microsomes obtained from human DCs. Results: IgE testing showed a sensitization prevalence of 25.6% to Api g 2, 18.6% to Art v 3, and 28.6% to Pru p 3 and frequent co-sensitization and correlating IgE-reactivity was observed. 10/32 patients suffering from LTP-related allergy reported symptoms upon consumption of celery stalks which mainly presented as OAS. Considerable IgE cross-reactivity was observed between Api g 2, Art v 3, and Pru p 3 with varying inhibition degrees of individual patients' sera. Simulating LTP mono-sensitization in a mouse model showed development of more congruent antibody specificities between Api g 2 and Art v 3. Notably, biologically relevant murine IgE cross-reactivity was restricted to the latter and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed generation of similar clusters, which presumably represent T-cell peptides. Conclusions: Api g 2 represents a relevant celery stalk allergen in the LTP-sensitized population. The molecule displays common B cell epitopes and endolysosomal peptides that encompass T cell epitopes with pollen and plant-food derived LTP.

Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.

An insight into the sialotranscriptome of the brown dog tick, Rhipicephalus sanguineus

Background: Rhipicephalus sanguineus, known as the brown dog tick, is a common ectoparasite of domestic dogs and can be found worldwide. R. sanguineus is recognized as the primary vector of the etiological agent of canine monocytic ehrlichiosis and canine babesiosis. Here we present the first description of a R. sanguineus salivary gland transcriptome by the production and analysis of 2,034 expressed sequence tags (EST) from two cDNA libraries, one consctructed using mRNA from dissected salivary glands from female ticks fed for 3-5 days (early to mid library, RsSGL1) and the another from ticks fed for 5 days (mid library, RsSGL2), identifying 1,024 clusters of related sequences. Results: Based on sequence similarities to nine different databases, we identified transcripts of genes that were further categorized according to function. The category of putative housekeeping genes contained similar to 56% of the sequences and had on average 2.49 ESTs per cluster, the secreted protein category contained 26.6% of the ESTs and had 2.47 EST's/clusters, while 15.3% of the ESTs, mostly singletons, were not classifiable, and were annotated as ""unknown function"". The secreted category included genes that coded for lipocalins, proteases inhibitors, disintegrins, metalloproteases, immunomodulatory and antiinflammatory proteins, as Evasins and Da-p36, as well as basic-tail and 18.3 kDa proteins, cement proteins, mucins, defensins and antimicrobial peptides. Comparison of the abundance of ESTs from similar contigs of the two salivary gland cDNA libraries allowed the identification of differentially expressed genes, such as genes coding for Evasins and a thrombin inhibitor, which were over expressed in the RsSGL1 (early to mid library) versus RsSGL2 (mid library), indicating their role in inhibition of inflammation at the tick feeding site from the very beginning of the blood meal. Conversely, sequences related to cement (64P), which function has been correlated with tick attachment, was largely expressed in the mid library. Conclusions: Our survey provided an insight into the R. sanguineus sialotranscriptome, which can assist the discovery of new targets for anti-tick vaccines, as well as help to identify pharmacologically active proteins.

Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.

Predictive factors of non-deterioration of glucose tolerance following a 2-year behavioral intervention

Aim: To identify predictive factors associated with non-deterioration of glucose metabolism following a 2-year behavioral intervention in Japanese-Brazilians. Methods: 295 adults (59.7% women) without diabetes completed 2-year intervention program. Characteristics of those who maintained/improved glucose tolerance status (non-progressors) were compared with those who worsened (progressors) after the intervention. In logistic regression analysis, the condition of non-progressor was used as dependent variable. Results: Baseline characteristics of non-progressors (71.7%) and progressors were similar, except for the former being younger and having higher frequency of disturbed glucose tolerance and lower C-reactive protein (CRP). In logistic regression, non-deterioration of glucose metabolism was associated with disturbed glucose tolerance impaired fasting glucose or impaired glucose tolerance - (p < 0.001) and CRP levels <= 0.04 mg/dL (p = 0.01), adjusted for age and anthropometric variables. Changes in anthropometry and physical activity and achievement of weight and dietary goals after intervention were similar in subsets that worsened or not the glucose tolerance status. Conclusion: The whole sample presented a homogeneous behavior during the intervention. Lower CRP levels and diagnosis of glucose intolerance at baseline were predictors of non-deterioration of the glucose metabolism after a relatively simple intervention, independent of body adiposity.

Management of Bell's Palsy: A Report of 2 Cases

Bell's palsy is a neuropathy of the peripheral seventh cranial nerve, resulting from traumatic, compressive, infective, inflammatory or metabolic abnormalities or it can be idiopathic. HIV, Epstein-Barr virus and hepatitis B virus have been suspected as initiating organisms, but herpes simplex virus is the most frequently implicated. This report describes 2 cases of Bell's palsy in children that were managed with antiviral agents. Both patients experienced complete recovery within 28 days; after 1 year follow-up, no recurrence was observed and both patients have normal facial movement. Differential diagnosis is essential to guide the treatment plan in Bell's palsy. Special attention should be given to children with respect to prescription of medications that can cause important side effects.

Application of Low-Level Laser Irradiation (LLLI) and rhBMP-2 in Critical Bone Defect of Ovariectomized Rats: Histomorphometric Evaluation

Objectives: The aim of this study was to evaluate the osteogenic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) and low-level laser irradiation (LLLI), isolated or combined in critical bone defects (5mm) in parietal bone using ovariectomized female rats as an experimental animal model. Materials and Methods: Forty-nine female Wistar rats, bilaterally ovariectomized (OVX), were divided into seven treatment groups of seven animals each: (I) laser in a single application, (II) 7 mu g of pure rhBMP-2, (III) laser and 7 mu g of pure rhBMP-2, (IV) 7 mu g of rhBMP-2/monoolein gel, (V) laser and 7 mu g of rhBMP-2/monoolein gel, (VI) laser and pure monoolein gel, and (VII) critical bone defect controls. The low-level laser source used was a gallium aluminum arsenide semiconductor diode laser device (lambda = 780 nm, D = 120 J/cm(2)). Results: Groups II and III presented higher levels of newly formed bone than all other groups with levels of 40.57% and 40.39%, respectively (p < 0.05). The levels of newly formed bone of groups I, IV, V, and VI were similar with levels of 29.67%, 25.75%, 27.75%, and 30.64%, respectively (p > 0.05). The area of new bone formation in group VII was 20.96%, which is significantly lower than groups I, II, III, and VI. Conclusions: It was concluded that pure rhBMP-2 and a single dose of laser application stimulated new bone formation, but the new bone formation area was significantly increased when only rhBMP-2 was used. Additionally, the laser application in combination with other treatments did not influence the bone formation area.

Ultra-Structural Changes at the Apical Stop Irradiated with CO(2) Laser

Objective: This study evaluated ultra-structural dentine changes at the apical stop after CO(2) laser irradiation used during biomechanical preparation. Background: Most studies evaluating the sealing efficiency of CO(2) lasers have been carried out after apical root canal resections and retro-filling procedures. Methods: Sixty human canines were prepared with #1 to #6 Largo burs. The apical stops were established at 1 mm (n = 30) and 2 mm (n = 30) from the apex. Final irrigation was performed with 1% NaOCl and 15% EDTA followed by 20 ml of distilled and deionized water. Specimens were subdivided into three subgroups (n = 10 for each stop distance): GI-no radiation (n = 20); GII-3W potency (n = 20), GIII-5W potency (n = 20). After preparation, specimens were evaluated by scanning electron microscopy, with ultra-structural changes classified according to a scoring system based on six qualitatively different outcomes. Results: Statistical analysis using the Mann-Whitney test confirmed more intense results for the specimens irradiated at 5 W potency than at 3 W (p<0.0001). The Kruskal-Wallis test indicated that when using the same potencies (3 or 5 W) at 1 and 2 mm from the apex, there were no statistically significant differences in ultra-structural changes. Conclusions: Our results showed that ultra-structural changes ranged from smear layer removal to dentine fusion. As laser potency was increased from 3 to 5 W, ultra-structural changes included extensive fused lava-like areas sealing the apical foramen.

A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.

The structure and dynamics of Abell 1942

Aims. We present a dynamical analysis of the galaxy cluster Abell 1942 based on a set of 128 velocities obtained at the European Southern Observatory. Methods. Data on individual galaxies are presented and the accuracy of the determined velocities as some properties of the cluster are discussed. We have also made use of publicly available Chandra X-ray data. Results. We obtained an improved mean redshift value z = 0.22513 +/- 0.0008 and velocity dispersion sigma = 908(139)(+147) km s(-1). Our analysis indicates that inside a radius of similar to 1.5 h(70)(-1) Mpc (similar to 7 arcmin) the cluster is well relaxed, without any remarkable features and the X-ray emission traces the galaxy distribution fairly well. Two possible optical substructures are seen at similar to 5 arcmin from the centre in the northwest and the southwest directions, but are not confirmed by the velocity field. These clumps are, however, kinematically bound to the main structure of Abell 1942. X-ray spectroscopic analysis of Chandra data resulted in a temperature kT = 5.5+/-0.5 keV and metal abundance Z = 0.33 +/- 0.15 Z(circle dot). The velocity dispersion corresponding to this temperature using the T(X-sigma) scaling relation is in good agreement with the measured galaxy velocities. Our photometric redshift analysis suggests that the weak lensing signal observed to the south of the cluster and previously attributed to a ""dark clump"" is produced by background sources, possibly distributed as a filamentary structure.

The stellar content of obscured Galactic giant H II regions. VI. W51A

We present K-band spectra of newly born OB stars in the obscured Galactic giant H II region W51A and approximate to 0.8 '' angular resolution images in the J, H, and K(S)-bands. Four objects have been spectroscopically classified as O-type stars. The mean spectroscopic parallax of the four stars gives a distance of 2.0 +/- 0.3 kpc (error in the mean), significantly smaller than the radio recombination line kinematic value of 5.5 kpc or the values derived from maser proper motion observations (6-8 kpc). The number of Lyman continuum photons from the contribution of all massive stars (NLyc approximate to 1.5 x 10(50) s(-1)) is in good agreement with that inferred from radio recombination lines (NLyc = 1.3 x 10(50) s(-1)) after accounting for the smaller distance derived here. We present analysis of archival high angular resolution images (NAOS CONICA at VLT and T-ReCS at Gemini) of the compact region W51 IRS 2. The K(S)-band images resolve the infrared source IRS 2 indicating that it is a very young compact H II region. Sources IRS 2E was resolved into compact cluster (within 660 AU of projected distance) of three objects, but one of them is just bright extended emission. W51d1 and W51d2 were identified with compact clusters of three objects (maybe four in the case of W51d1) each one. Although IRS 2E is the brightest source in the K-band and at 12.6 mu m, it is not clearly associated with a radio continuum source. Our spectrum of IRS 2E shows, similar to previous work, strong emission in Br gamma and He I, as well as three forbidden emission lines of Fe III and emission lines of molecular hydrogen (H(2)) marking it as a massive young stellar object.

Origin of primordial magnetic fields

Magnetic fields of intensities similar to those in our galaxy are also observed in high redshift galaxies, where a mean field dynamo would not have had time to produce them. Therefore, a primordial origin is indicated. It has been suggested that magnetic fields were created at various primordial eras: during inflation, the electroweak phase transition, the quark-hadron phase transition (QHPT), during the formation of the first objects, and during reionization. We suggest here that the large-scale fields similar to mu G, observed in galaxies at both high and low redshifts by Faraday rotation measurements (FRMs), have their origin in the electromagnetic fluctuations that naturally occurred in the dense hot plasma that existed just after the QHPT. We evolve the predicted fields to the present time. The size of the region containing a coherent magnetic field increased due to the fusion of smaller regions. Magnetic fields (MFs) similar to 10 mu G over a comoving similar to 1 pc region are predicted at redshift z similar to 10. These fields are orders of magnitude greater than those predicted in previous scenarios for creating primordial magnetic fields. Line-of-sight average MFs similar to 10(-2) mu G, valid for FRMs, are obtained over a 1 Mpc comoving region at the redshift z similar to 10. In the collapse to a galaxy (comoving size similar to 30 kpc) at z similar to 10, the fields are amplified to similar to 10 mu G. This indicates that the MFs created immediately after the QHPT (10(-4) s), predicted by the fluctuation-dissipation theorem, could be the origin of the similar to mu G fields observed by FRMs in galaxies at both high and low redshifts. Our predicted MFs are shown to be consistent with present observations. We discuss the possibility that the predicted MFs could cause non-negligible deflections of ultrahigh energy cosmic rays and help create the observed isotropic distribution of their incoming directions. We also discuss the importance of the volume average magnetic field predicted by our model in producing the first stars and in reionizing the Universe.

Alpha element abundances and gradients in the Milky Way bulge from FLAMES-GIRAFFE spectra of 650 K giants

Aims. We present the analysis of the [alpha/Fe] abundance ratios for a large number of stars at several locations in the Milky Way bulge with the aim of constraining its formation scenario. Methods. We obtained FLAMES-GIRAFFE spectra (R = 22 500) at the ESO Very Large Telescope for 650 bulge red giant branch (RGB) stars and performed spectral synthesis to measure Mg, Ca, Ti, and Si abundances. This sample is composed of 474 giant stars observed in 3 fields along the minor axis of the Galactic bulge and at latitudes b = -4 degrees, b = -6 degrees, b = -12 degrees. Another 176 stars belong to a field containing the globular cluster NGC 6553, located at b = -3 degrees and 5 degrees away from the other three fields along the major axis. Stellar parameters and metallicities for these stars were presented in Zoccali et al. (2008, A&A, 486, 177). We have also re-derived stellar parameters and abundances for the sample of thick and thin disk red giants analyzed in Alves-Brito et al. (2010, A&A, 513, A35). Therefore using a homogeneous abundance database for the bulge, thick and thin disk, we have performed a differential analysis minimizing systematic errors, to compare the formation scenarios of these Galactic components. Results. Our results confirm, with large number statistics, the chemical similarity between the Galactic bulge and thick disk, which are both enhanced in alpha elements when compared to the thin disk. In the same context, we analyze [alpha/Fe] vs. [Fe/H] trends across different bulge regions. The most metal rich stars, showing low [alpha/Fe] ratios at b = -4 degrees disappear at higher Galactic latitudes in agreement with the observed metallicity gradient in the bulge. Metal-poor stars ([Fe/H] < -0.2) show a remarkable homogeneity at different bulge locations. Conclusions. We have obtained further constrains for the formation scenario of the Galactic bulge. A metal-poor component chemically indistinguishable from the thick disk hints for a fast and early formation for both the bulge and the thick disk. Such a component shows no variation, neither in abundances nor kinematics, among different bulge regions. A metal-rich component showing low [alpha/Fe] similar to those of the thin disk disappears at larger latitudes. This allows us to trace a component formed through fast early mergers (classical bulge) and a disk/bar component formed on a more extended timescale.