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Lippia alba (erva-cidreira) is often mentioned in Brazilian ethnopharmacological studies. Although its leaves have been used to treat hypertension, few studies have evaluated its hypotensive effects. This work aimed to evaluate the haemodynamic effects of Lippia alba methanolic extract and to characterise its chemical composition. Normotensive rats received an intravenous injection of L. alba extract. Systolic, diastolic, mean arterial pressures, and electrocardiographic data were analysed. 1 H-qNMR and LC-MS were used to assess the chemical composition. L. alba extract had significant hypotensive effects on systolic, diastolic, and mean arterial pressure. Acteoside was identified as major compound (292.6 ± 2.7 mg/g). Sixty-one other compounds were tentatively identified, mainly phenylethanoids, flavonoids, and iridoids. L. alba extract reduces systolic, diastolic, mean arterial pressure, and appears to be associated with a reduction in heart rate. Acteoside, a known hypotensive compound, may be responsible for these effects, but other structurally similar minority compounds may also contribute.

In vitro tissue culture can be an alternative method for endangered species propagation, biodiversity conservation and secondary metabolite studies. Paratecoma peroba (Record) Kuhlm. (Bignoniaceae) is an endemic and endangered Brazilian species. This work aimed to establish in vitro morphogenesis and callus induction and to perform a phytochemical analysis of P. peroba callus extract. Higher seed germination (43%) was obtained in Wood Plant Medium culture without activated charcoal (AC). Combination of 5 µM benzyladenine + 10 µM gibberellic acid, without AC, resulted in a higher number of shoots (2 shoots/explant). A callus culture was stabilised from zygotic embryos using 2,4-dichlorophenoxyacetic acid. A callus methanolic extract was used for phytochemical analysis. The isolated substance was identified as tiliroside (kaempferol 3- O-β-D -(6''- O-E-p -coumaroyl)-glucopyranoside) by NMR and quantified in callus and leaf extracts by HPLC. This study adds to the chemical knowledge of this species and it is the first report of a flavonol in Paratecoma .

Background: Lymphomas affecting the submandibular glands are very uncommon and few reports are currently available in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic features of an original series of lymphomas affecting the submandibular glands., Material and Methods: The pathology files of two institutions were searched for lymphoma cases affecting the submandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by a pathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation, treatment, follow-up and status at last appointment were retrieved from the patients' medical charts., Results: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with a mean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma represented the most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patients died, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma., Conclusions: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other subtypes may also be rarely diagnosed in this salivary gland.

Background: Subgemmal neurogenous plaques (SNP) are composed of neural structures found in the posterolateral portion of the tongue, rarely biopsied as most of them are asymptomatic or eventually only clinically managed. We aimed to investigate a case series of possible correlation of symptomatic subgemmal neurogenous plaque (SNP) with coronavirus disease 2019 (COVID-19)., Methods: Eleven formalin-fixed paraffin-embedded cases from patients with previous confirmed COVID-19 (by RT-PCR) were retrieved from two pathology files. Histological sections were morphologically studied, and then submitted to immunohistochemical reactions against S-100 and neurofilament proteins, neuron-specific enolase, Glial fibrillary acidic protein (GFAP), synaptophysin, CD56, Ki67, cytokeratins (7, 8-18, 19, 20), nucleocapsid and spike proteins (SARS-CoV-1; and -2) and epithelial membrane antigen (EMA) antibodies. Clinical data were retrieved from the patients' medical files, including the symptoms and the complete history of the progression of the disease., Results: The patients who had COVID-19 included in this study experienced painful lesions in the tongue that corresponded to prominent or altered SNP. Microscopically, neural structures were positive for S-100, GFAP and neurofilament protein. And the cellular proliferative index (by Ki-67) was very low., Conclusion: Thus, based on the current results, we hypothesize that symptomatic SNP may be a late manifestation of COVID-19 infection., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

It is hard for medical students to recognize and understand the clinical presentation of systemic connective tissue diseases (SCTDs). In this study, we aimed to review the immune mechanisms of the main SCTDs and to propose a classification system focused on the student and based on each immune dysfunction's clinical phenotype. The search involved the MEDLINE database and included the terms "systemic lupus erythematosus," "antiphospholipid syndrome," "inflammatory myopathies," "rheumatoid arthritis," "Sjögren's syndrome" or "systemic sclerosis" and "pathogenesis," and "immunology" or "mechanism of disease." Systemic lupus erythematosus (SLE) is a prototypic immune-complex disease with a tendency toward vascular injury. Antiphospholipid syndrome (APS) is a diffuse immune-mediated thrombotic vasculopathy. In inflammatory myopathies (IMs), muscle inflammation leading to muscle weakness is the cardinal manifestation. Rheumatoid arthritis (RA) is a unique form of erosive and destructive polyarthritis. Sjögren's syndrome (SS) causes sicca symptoms due to infiltration of the exocrine glands. Disseminated fibrosis in systemic sclerosis (SSc) is caused by vascular injury with excessive fibroblast activation. After the review, we created a focus group involving all the authors to group the diseases according to their pathogenesis and clinical phenotype. Our group agreed that SCTDs can be divided in 3 groups based on the preferential clinical presentation and immune dysfunction: 1) vasculopathic features (SLE and APS), 2) tissue inflammation (IMs, RA, and SS), and 3) tissue fibrosis (SSc). In synthesis, we suggest that clustering SCTDs in groups based on clinical phenotype and presumptive immune dysfunction instead of ordering autoantibodies randomly can help students understand the diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

Background: Epilepsy represents an essential component of Parry Romberg syndrome (PRS). This study aimed to identify clinical factors that influence the development of epilepsy and drug-resistant epilepsy (DRE) in PRS., Methods: We retrospectively reviewed the medical records of eighty patients with PRS. Data including the age of onset for PRS, history of seizures, use and timing of immunotherapy, antiseizure medication use, and EEG and brain imaging findings were reviewed. For comparison with the patients with epilepsy (PRSe+) group, we selected 18 age and sex-matched controls from the patient without epilepsy (PRSe-) cohort using propensity score matching., Results: Eighteen (22.5%) had epilepsy: 12 were female, and the median age was 14.5 years (range = 6-48 years). Eleven patients developed DRE. The median latency between the onset of cutaneous manifestations and diagnosis and timing and use of immunotherapy was similar between the PRSe + and PRSe- groups. Intracranial abnormalities were commonly seen in the PRSe + group (16 vs. 2, p < 0.01). White matter disease and ipsilateral atrophy were common among the PRSe + group. Timing and use of immunotherapy, epileptiform discharges, and brain imaging abnormalities did not differ between those with DRE and without., Conclusions: The presence and degree of severity of ipsilateral brain abnormalities are risk factors for the development of epilepsy in PRS but not factors in predicting drug resistance. The timing of immunotherapy did not influence the development of PRSe + or DRE. Prospective studies are needed to identify biomarkers for epilepsy and assess the role of immunotherapy on seizure outcomes in PRSe + ., (Copyright © 2022. Published by Elsevier B.V.)

The aim of this study was to investigate the immunohistochemical expression of REGγ, p53, MDM-2, Bcl-2, and Bax in oral tongue squamous cell carcinoma (OTSCC), and to correlate the findings with clinicopathological parameters. Fifty-eight OTSCC cases were selected for the study. The percentages of nuclear (REGγ, p53, and MDM-2) and cytoplasmic (Bcl-2 and Bax) staining in epithelial cells were determined and correlated with clinicopathological parameters (regional lymph node metastasis, clinical stage, clinical outcome, and histopathological grade of malignancy). Expression of REGγ was observed in all cases studied. Significantly lower percentages were observed in tumours with lymph node metastasis (P = 0.036) and in high-grade tumours (P = 0.013). No significant differences in p53, MDM-2, or Bax expression were observed according to the clinicopathological parameters. Lower percentages of Bcl-2 staining were found in high-grade OTSCC (P = 0.040) and in cases of disease-related death (P = 0.032). The expression of REGγ showed a weak positive correlation with the expression of MDM-2 (P = 0.001) and Bcl-2 (P = 0.014). The results of this study suggest that lower expression of REGγ may contribute to the progression of OTSCC. The role of REGγ in the development of OTSCC does not appear to be primarily related to the modulation of apoptosis in neoplastic cells., (Copyright © 2021. Published by Elsevier Inc.)

Background/objectives: Experimental and clinical studies have shown that vitamins A and E can inhibit cancer formation and progression. The unfavourable status of these vitamins can represent risk factors for the disease. This study aimed to evaluate the associations between the nutritional status of vitamins A and E (serum levels and dietary intake) and histopathological outcomes in Papillary Thyroid Carcinoma (PTC) patients., Subjects/methods: We applied a cross-sectional study (2017-2018) and quantified retinol (ROH) and α-tocopherol (TOH) serum levels and vitamins dietary intake of 46 PTC patients. Serum vitamins were quantified by high efficiency liquid chromatography and vitamins dietary intake was analyzed by 24-hr dietary recalls., Results: Patients with lower ROH serum levels were more likely to present lymph node metastasis and/or angiolymphatic invasion (p = 0.025). In addition, higher vitamin A and vitamin E intake are related to the absence of extrathyroidal extension (p = 0.013) and lymph node metastasis (p = 0.007), respectively. Our findings suggest that a ROH serum level greater than 2.65 μmol/L in PTC patients may be a protective factor against the presence of lymph node metastasis and angiolymphatic invasion. In addition, vitamin A and E intake may protect against extrathyroidal extension and lymph node metastasis., Conclusions: A favourable nutritional status (higher serum levels and/or intake) of vitamin A and E may be associated with less aggressive tumours in PTC patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell-cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies.

Background: Increasing evidence shows that chronic inflammation plays an important role in thyroid tumorigenesis. Cytokines as central mediators in inflammatory microenvironment can present both pro-tumour and anti-tumour effects and cytokine release may be influenced by soluble HLA-G (sHLA-G), an immune checkpoint molecule whose expression can also be induced by certain cytokines., Aim: To understand the role of these soluble factors in papillary thyroid cancer (PTC)., Methods: We evaluated plasma levels of sHLA-G and of 13 cytokines using ELISA and flow cytometry, respectively, in PTC patients at two time points: pre- and post-thyroidectomy; and control subjects., Results: Compared with controls, IL-6 levels were increased, while IL-1β, IFN-α and TGF-β1 levels were decreased in pre-thyroidectomy PTC patients. IFN-α and TGF-β1 efficiently discriminated patients from controls and were associated with extrathyroidal extension and lymph node metastasis, respectively. In addition, TNF and IL-13 were associated with male gender, lymph node metastasis and Hashimoto thyroiditis, and sHLA-G with tumour invasion. Compared with pre-thyroidectomy, IL-4, IL-10, TNF, IFN-α and TGF-β1 levels were increased in post-thyroidectomy., Conclusion: There are significant changes in the cytokine profile after surgical removal of the thyroid tumour, and IFN-α e TGF-β1 showed to be promising cytokines for discriminating PTC patients from controls. We also found that different cytokines are associated with clinicohistopathological characteristics of PTC related to poor prognosis, suggesting that cytokines seem to play an important role in PTC development and management., (© 2020 John Wiley & Sons Ltd.)

Dientamoeba fragilis is a trichomonad parasite of the human intestine that is found worldwide. However, the biological cycle and transmission of this parasite have yet to be elucidated. Although its pathogenic capacity has been questioned, there is increasing evidence that clinical manifestations vary greatly. Different therapeutic options with antiparasitic drugs are currently available; however, very few studies have compared the effectiveness of these drugs. In the present longitudinal study, we evaluate 13,983 copro-parasitological studies using light microscopy of stools, during 2013-2015, in Terrassa, Barcelona (Spain). A total of 1150 (8.2%) presented D. fragilis. Of these, 739 episodes were finally analyzed: those that involved a follow-up parasitology test up to 3 months later, corresponding to 586 patients with gastrointestinal symptoms (53% under 15 years of age). Coinfection by Blastocystis hominis was present in 33.6% of the subjects. Our aim was to compare therapeutic responses to different antiparasitic drugs and the factors associated with the persistence of D. fragilis post-treatment. Gender, age, and other intestinal parasitic coinfections were not associated with parasite persistence following treatment. Metronidazole was the therapeutic option in most cases, followed by paromomycin: 65.4% and 17.5% respectively. Paromomycin was found to be more effective at eradicating parasitic infection than metronidazole (81.8% vs. 65.4%; p = 0.007), except in children under six years of age (p = 0.538). Although Dientamoeba fragilis mainly produces mild clinical manifestations, the high burden of infection means we require better understanding of its epidemiological cycle and pathogenicity, as well as adequate therapeutic guidelines in order to adapt medical care and policies to respond to this health problem., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To review current evidence on the relationship between obsessive-compulsive disorder and feeding difficulties., Methods: Review the Science Direct and PubMed databases between 2007 and 2017 in English, Portuguese and Spanish. The search terms, used in association, were "obsessive compulsive disorder" and "picky eating/feeding difficulty". Cohort, case control and cross sectional studies were included that analyzed children, adolescents and/or adults of any sample size from any country in the world. Opinion articles were excluded., Results: Around 245 articles were selected, and only 4 were included in this review, according to previous criteria. Results from the studies essentially described that there is indeed a difference in "picky" behaviors between subjects with and without obsessive-compulsive disorder. Patients with obsessive-compulsive disorder tend to have exacerbated symptoms of disgust, anxiety and a higher eating behavior inflexibility score., Conclusions: Obsessive-compulsive disorder and feeding difficulties patients share common symptoms. The present study alerts health professionals who follow patients with feeding difficulties as to the importance of investigating possible psychiatric comorbidities.

Accurate laboratory diagnosis of Lyme disease (Lyme borreliosis), caused by the spirochete Borrelia burgdorferi (BB), is difficult and yet important to prevent serious disease. The US Centers for Disease Control and Prevention (CDC) presently recommends a screening test for serum antibodies followed by confirmation with a more specific Western blot (WB) test to detect IgG and IgM antibodies against antigens in whole cell lysates of BB. Borrelia species related to BB cause tick-borne relapsing fever (TBRF). TBRF is increasingly recognized as a health problem in the US and occurs in areas where Lyme disease is prevalent. The two groups of Borrelia share related antigens. We have developed a modified WB procedure termed the Lyme immunoblots (IBs) using recombinant antigens from common strains and species of the BB sensu lato complex for serological diagnosis of Lyme disease. A reference collection of 178 sera from 26 with and 152 patients without Lyme disease were assessed by WB and IB in a blinded manner using either criteria for positive antibody reactions recommended by the CDC or criteria developed in-house. The sensitivity, specificity, positive and negative predictive values obtained with the reference sera suggest that the Lyme IB is superior to the Lyme WB for detection of specific antibodies in Lyme disease. The Lyme IB showed no significant reaction with rabbit antisera produced against two Borrelia species causing TBRF in the US, suggesting that the Lyme IB may be also useful for excluding TBRF.

Background: Given the positive influence of responsive caregiving on dietary habits in childhood, to raise awareness of caregivers regarding their behavior is crucial in multidisciplinary care on infant feeding., Objectives: To identify the most common responsive and non-responsive feeding practices in mothers of children with feeding complaints, as well as to seek associations between practices and caregivers' profile., Methods: Cross-sectional study with 77 children under 18 years old, with complaints of feeding difficulties. Data were collected during interviews with mothers: child age, gender, duration of exclusive breastfeeding, presence of organic disease, dynamics of bottle use, self-feeding practices and posture at meals, use of appropriate feeding equipment; basic information about the mothers (parity and level of education), caregiver feeding style, presence of coercive feeding, frequency and characteristics of family meals. Statistical analysis considered significance level at 5%., Results: The non-responsive profile predominated among mothers (76.2%, with the Authoritarian style being the most prevalent-39.7%). The responsive profile was characterized by absence of coercive feeding, stimulation of self-feeding practices, use of appropriate feeding equipment and meal environment, with interaction at meals. Non-responsive profile consisted of both inadequate environment and posture at meals, use of distraction and coercive feeding, lack of shared meals, and disregard for children's hunger signals. Only the habit of sharing meals with children was associated with mothers' profile, and considered a protection factor against non-responsive care (OR 0.23; 95% CI 0.06-0.88). Both Authoritarian ( p  = 0.000) and indulgent mothers ( p  = 0.007) breastfed exclusively for longer time than negligent ones. There was a higher level of interaction with children in "responsive" parental style (OR 0.056; p  = 0.01) compared to other feeding styles., Conclusion: Results highlight the need for educational interventions focused on caregivers' behaviors.

Background: Thyroid cancer is a common malignant disease of the endocrine system with increasing incidence rates over the last few decades. In this study, we sought to analyze the possible association of 45 single nucleotide polymorphisms (SNPs) with thyroid cancer in a population from Rio Grande do Norte, Brazil., Methods: Based on histological analysis by a pathologist, 80 normal thyroid specimens of tissue adjacent to thyroid tumors were obtained from the biobank at the Laboratory of Pathology of Liga Norte Riograndense Contra o Câncer, Natal, RN. Patient samples were then genotyped using the MassARRAY platform (Sequenon, Inc) followed by statistical analysis employing the SNPassoc package in R program. The genotypic frequencies of all 45 SNPs obtained from the International HapMap Project database and based on data from the ancestral populations of European and African origin were used to compose the control study group., Results: In our study, the following 9 SNPs showed significant differences in their frequency when comparing the study and control groups: rs3744962, rs258107, rs1461855, rs4075022, rs9943744, rs4075570, rs2356508, rs17485896, and rs2651339. Furthermore, the SNPs rs374492 C/T and rs258107 C/T were associated with a relative risk for thyroid carcinoma of 3.78 (p = 6.27 × 10e -5 ) and 2.91 (p = 8.27 × 10e -5 ), respectively, after Bonferroni's correction for multiple comparisons., Conclusions: These nine polymorphisms could be potential biomarkers of predisposition to thyroid carcinoma in the population from Rio Grande do Norte. However, complementary studies including a control group with samples obtained from healthy subjects in Rio Grande do Norte state, should be conducted to confirm these results.

Background: Delays in gross motor development, sensory processing issues, and organic and behavioral problems are known to interfere in the development of feeding skills (FS); and-therefore-in the success of the process of feeding a child. Children with feeding difficulties (FD) commonly present inadequacy of FS., Objectives: Assessment of five FS in Brazilian children with FD, and search of associations with types of FD., Methods: Cross-sectional study with 70 children below 10 years old. Data were obtained from medical records: age, gender, age at texture transitions, feeding phase (breastfeeding, weaning to solids or full solids) at first complaint; characteristics of the meal (duration, environment, and shared meals with adults), self-feeding practices, use of feeding equipment and bottle, mouthing, feeding position and FD diagnosis. Skills were categorized according to standards for age. Chi-Square, Anova Test (or non-parametric equivalent) and Multinomial logistic regression tests were used, with a significance level of 5%., Results: There was no difference in FS ( p  > 0.05) or in the number of FS inadequateness ( p  = 0.84) according to FD diagnosis. The majority (94%) of children presented at least one delayed development of FS; 1/3 presented delays in more than half of the FS. The most prevalent inadequacies in FS were inadequate feeding position (73.5%), prolonged bottle feeding (56.9%), and inadequate self-feeding practices (37.9%). Feeding complaints first appeared at 10.9 ± 11.4 months, and picky eating was the most prevalent type of FD (37.1%). Most children were fed in inadequate environments (55.2%), without the company of adults (78%). Transition to solid foods occurred at 16 ± 5.6 months. Multinomial logistic regression showed no difference in likelihood of presenting any type of FD compared to picky eating, according to FS. Age at texture transition both from breastfeeding to complementary feeding ( p  = 0.95), and from complementary feeding to solid foods ( p  = 0.43) did not vary according to FD diagnosis., Conclusion: FS development or number of FS inadequateness did not vary according to FD diagnosis. Identification of these inadequacies could help the discussion for multi-professional treatment of patients with FD.

Purpose: To evaluate tumor shrinking kinetics in order to implement image-guided brachytherapy (IGBT) for the treatment of patients with cervix cancer., Material and Methods: This study has prospectively evaluated tumor shrinking kinetics of thirteen patients with uterine cervix cancer treated with combined chemoradiation. Four high dose rate brachytherapy fractions were delivered during the course of pelvic external beam radiation therapy (EBRT). Magnetic resonance imaging (MRI) exams were acquired at diagnosis (D), first (B1), and third (B3) brachytherapy fractions. Target volumes (GTV and HR-CTV) were calculated by both the ellipsoid formula (VE) and MRI contouring (VC), which were defined by a consensus between at least two radiation oncologists and a pelvic expert radiologist., Results: Most enrolled patients had squamous cell carcinoma and FIGO stage IIB disease, and initiated brachytherapy after the third week of pelvic external beam radiation. Gross tumor volume volume reduction from diagnostic MRI to B1 represented 61.9% and 75.2% of the initial volume, when measured by VE and VC, respectively. Only a modest volume reduction (15-20%) was observed from B1 to B3., Conclusions: The most expressive tumor shrinking occurred in the first three weeks of oncological treatment and was in accordance with gynecological examination. These findings may help in IGBT implementation.

The objective of this study was to evaluate the effects of steroid anabolic androgenic hormones use on lean mass gain in elderly men through a systematic review with a meta-analysis of randomized controlled studies. We systematically searched PubMed database until 4th October 2013. We included randomized placebo-controlled trials (RCT) that studied testosterone replacement therapy in men over 60 years of age, with total testosterone levels ≤550 ng/dl, observing gains in weight, lean mass tissue and fat mass as outcome. We excluded duplicated studies, studies which mixed men and women, and studies using weak androgens such as dehydroepiandrosterone or androstenedione. The initial search yielded 2681 articles, of which 26 were selected for full text analysis. In the end, 11 studies were included. However, 3 studies were not included in the meta-analysis. Meta-analysis showed that mean weight increased (lean mass), ranging from 1.65 (95 % CI, 1.61-1.69) to 6.20 (95 % CI, 5.22-7.18) kg, although it was heterogeneous (I (2) = 98 %). Effect estimate was 3.59 [2.38-4.81]. Androgen therapy decreased fat mass; effect estimate was -1.78 [-2.57, -0.99] that analysis had also a high level of heterogeneity (I (2) = 81 %). The results suggest that testosterone replacement therapy is able to increase muscle mass in elderly men and that is affected by the time that the treatment is carried out and the method of administration of the drug.

Background: Male breast cancer (MBC) is an uncommon disease that has been the focus of limited research. It is estimated that approximately 10% of men with breast cancer have a genetic predisposition, with BRCA2 being the most prevalent genetic mutation. Here we describe the case of MBC in a 64-year-old man who presented on physical examination a nodule in his left breast and declared to have an extensive family history of cancer., Methods and Results: The patient was firstly diagnosed with an invasive ductal carcinoma (IDC) with histological grade III, nuclear grade 3, pT4N2Mx and positive for hormonal receptors and HER2. Exome sequencing was performed by massive parallel sequencing which had detected a novel BRCA2 germline mutation that is a large genomic deletion of 3,492 nucleotides including BRCA2 exon 14, and this deletion is out of frame and is predicted to lead to a stop codon in exon 15 at codon 2,496., Conclusion: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer. This is the first report of the mutation del3492 in BRCA2 exon 14, which leads to a truncated protein and therefore is clinically relevant. Mutation segregation analysis should be further done in the Brazilian population. Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

Purpose: Angiogenesis and tumor invasion are complex processes that are mediated by various proteins, such as vascular endothelial growth factor (VEGF-α) and the matrix-degrading enzymes metalloproteinase-2 and -9 (MMP-2, MMP-9). The aim of this study was to determine what roles MMP-2, MMP-9, and VEGF-α play in colorectal cancer (CRC) by correlating their expression levels with the cancer TNM stage, modified Dukes criteria, degree of cell differentiation, and long-term patient survival., Methods: The present series consisted of tissue samples obtained from 180 patients who had undergone large bowel resection during 1995 and 2005 at the Luis Antonio Hospital. Archival paraffin-embedded CRC tissue samples were used to generate tissue microarray blocks, which were immunohistochemically stained for MMP-2, MMP-9, and VEGF-α. Three different grading systems were applied to evaluate staining intensity. Chi-squared Person test and Kaplan-Meier survival curves were used, and values of p<0.05 were considered statistically significant., Results: MMP-2 expression showed a significant association with more invasive cancer stages (p<0.001) and death (p<0.041). VEGF-α expression correlated with a high TNM stage (p<0.009), the degree of cell differentiation (p<0.025) and patient death as a result of disease (p<0.035). The Kaplan-Meier survival estimated that patients with strong staining for MMP-2 (log-rank x(2)=34.09; p<0.0001), MMP-9 (log-rank x(2)=12.83; p<0.0003) and VEGF (log-rank x(2)=33.9; p<0.0001) showed a greater tendency towards death during 60 months of follow up., Conclusions: The quantification of VEGF-α, MMP-2 and MMP-9 expression in colorectal cancer may be related to survival. These data add to the growing epidemiological and experimental evidence that VEGF-α, MMP-2 and MMP-9 may play a role in colorectal tumorigenesis., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

The aim of this research was to study prognostic parameters of CRC by analyzing clinical and pathological variables associated with cancer patients at a northeastern Brazilian Hospital. This was a retrospective study evaluating CRC-diagnosed patients across a 10-year period (1995-2005) at Dr. Luiz Antônio Hospital in Natal, RN, Brazil. Data were collected from patients' medical files. A total of 358 patients were included over the 10-year period. The average age at diagnosis was 58.8 years (S.D.=15.26), 48.3% of the patients were males and 51.7% were females. Alcohol consumption significantly increased the chance of dying (p<0.023) from colorectal cancer; this increased risk of death was approximately 71%, compared to 52.2% of the non-alcoholics. In addition, tobacco increased the chance of developing high TNM stage tumors (level III, IV; p<0.001). Another risk factor for increased mortality was a family history for colorectal cancer (p<0.002). Our analysis found that patients with an unhealthy lifestyle and/or family history of colorectal cancer were more likely to develop advanced stage colorectal cancer and to have a poor disease prognosis compared to patients with healthy lifestyle and/or sporadic colorectal cancer. These data suggest that a mass screening program should be implemented in northeastern Brazil in order to better prevent and treat colorectal cancer., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Background: This study investigated factors related to ethnicity and educational level, their correlation with tumor stage at the time of diagnosis, and their influence on treatment outcomes in patients with prostate cancer., Methods: In this retrospective observational study, we analyzed the medical records of 1,349 male patients treated for prostatic adenocarcinoma. We collected information about sociodemographic variables, including educational level and self-reported skin color. We also classified the disease according whether it was to more likely to present with metastasis and measured the tumor response to treatment., Results: Less-educated (<8 years of education) individuals were 4.8 times more likely to develop metastasis than those with more education (>11 years of education; p < 0.001). Similarly, patients with a self-reported black skin color had a 300% increased risk of metastasis at diagnosis (p = 0.001). Distant metastasis was independently correlated with worse outcomes, such that individuals with distant metastasis were 10 times more likely to die than were those without distant metastasis., Conclusions: Patients with self-reported black skin color and <8 years of education were more likely to display advanced disease at the time of diagnosis compared with their counterparts. Only the presence of metastasis was independently associated with mortality or progressive disease.

Rio Grande do Norte (RN) shows the highest relative incidence of papillary carcinomas in Brazil. To analyze histological features that might be associated with this incidence, the authors compared thyroid glands from 463 autopsies performed in RN with 427 surgical and autopsy glands previously studied in Sao Paulo (SP). The authors found 41 papillary thyroid microcarcinomas (PTMs) in 35 glands (8.1%), an incidence similar to the one reported in SP (7.8%). However, PTMs were predominantly nonencapsulated nonsclerosing at microscopy (44.0%), in contrast with SP where these types of lesion represented only 4 out of 32 PTMs (12.5%; P = .0046). The authors suggest that these nonencapsulated lesions with no sign of inflammation may represent an early stage that may evolve to clinical cancers, contributing to the high incidence of clinically differentiated thyroid carcinomas observed in RN.

This research-action type study aimed to establish clinical evaluation parameters essential to the patient subject to hemodynamic monitoring by Pulmonary Artery Catheter (PAC) and to develop a Nursing Care Protocol to critical care patients using catheter with the nurses of an ICU in Santa Catarina State. The population consisted of a non-probabilistic intentional sample of five nurses, and the data were collected through group meetings and questionnaire. The study is presented with descriptive statistics and qualitative analyses of the subjective questions. In conclusion, the clinical evaluation criteria, essential to the patient subjected to hemodynamic monitoring, are constituted by invasive and non-invasive parameters and the protocol grounds making clinical decisions when caring for patient using PAC.

The aim of the present study was to clinically, morphologically, and immunohistochemically correlate the expression of cytokeratins (CKs) 7, 10, 13, 14, 16, and 19 in 30 cases of tongue squamous cell carcinoma (SCC) with disease outcome, metastases, clinical stage (tumor, node, metastasis [TNM]), and histological grade of malignancy proposed by Bryne. Statistical analysis (chi2 test) showed that only histological grading was not significantly correlated with the clinical variables. CK expression varied in the samples analyzed. CK 10 expression was significantly correlated with the presence of metastases, and the expression of CK 16 was related to disease outcome and also to TNM stages III and IV. These results indicate that metastases and TNM are effective prognostic indicators. The histological grading proposed by Bryne did not reflect the biological behavior of the tongue SCC cases studied. Analysis of some intermediate CK filaments can reflect the biological behavior and aggressiveness of some tongue SCCs.

Purpose: To evaluate the effect of utilization of a specific training program of respiratory muscles on pulmonary function in tobacco smokers., Methods: Fifty asymptomatic tobacco smokers with age superior to 30 years were studied, at the moments: A0 - initial evaluation followed by protocol of respiratory exercises; A1 - reevaluation after 10 minutes of protocol application; and A2 - final reevaluation after 2 weeks of training utilizing the same protocol 3 times per week. The evaluation was realized through measures of maximum respiratory pressures (PImax and PEmax), respiratory peak flow (IPF and EPF), maximum voluntary ventilation (MVV), forced vital capacity (FVC) and forced expiratory volume at the 1st second (FEV1)., Results: There was no improvement from initial to final evaluation in FVC and FEV1. But there were significant increases in the variables IPF, EPF, MVV and PImax at evaluations A1 and A2. The PEmax variable increased only at evaluation A2., Conclusion: The application of the protocol of respiratory exercises with and without additional load in tobacco smokers produced immediate improvement in the performance of respiratory muscles, but this gain was more accentuated after 2 weeks of exercise.

Unlabelled: Histological staging of deep invasive margin of oral squamous cell carcinoma has a significant influence on survival of patients since the tumor cells are more poorly differentiated in this area and have high prognostic value., Aim: The purpose of the present study is to correlate TNM clinical classification with histopathologic characteristics (degree of keratinization, nuclear pleomorphism, invasion pattern and lymphoplasmocytic infiltrate) and histologic malignancy scores in 38 cases of oral epidermoid carcinoma in the lesion's deepest areas. STUDY FORM: Retrospective clinical study., Material and Method: This is a retrospective study based on histological review of 38 cases of oral squamous cell carcinoma selected from the medical files of Hospital Dr. Luis Antonio, Natal--Rio Grande do Norte, Brazil. TNM clinical classification data were obtained from the analysis of the medical records. Two pathologists performed histological malignancy staging on routine 3 microm-thick sections of invasive tumor areas stained with hematoxylin and eosin. For statistical analysis, parametric (ANOVA) and non-parametric tests (Tukey; Pearson; Chi2) were employed., Results: We found significant correlation between TNM clinical staging and malignancy mean score (p= 0.001) and histopathologic parameters, such as nuclear pleomorphism (p= 0.016) and degree of keratinization (p= 0.025). Furthermore, there were also statistically significant correlations between lymphocytic infiltration (p= 0.016) and nuclear pleomorphism (p= 0.004) with TNM classification when grouped in two series: TNM I/II and III/IV., Conclusion: TNM classification, as well as malignancy mean score, had statistically significant correlation with degree of keratinization, nuclear pleomorphism and lymphocytic infiltration. These highly significant results indicated that histologically invasive areas may be primarily responsible for the clinical behavior of the tumor, and this may be important for the therapy of choice for oral squamous cell carcinoma.

Background: Due to the condition known as middle ear squeeze, scuba diving has become one of the main causes of barotrauma, and the acute form of this condition has been relatively well established. However, there are few reports available on clinical or laboratory findings in divers who practise repeated diving. The objective of the present study was to assess the otological effects of repeated dives., Method: This was an observational study conducted on 19 recreational scuba divers, considered to be experienced divers according to the criteria established by the Professional Association of Dive Instructors (PADI). These divers undertook four dives per day on five consecutive days, and their tympanic membranes were assessed using tympanometry and otoscopy. Data were analysed using the chi(2)-test for trend. The level of statistical significance was set at p<0.05 in all analyses., Results: The findings suggest that multiple scuba dives over a short period of time cause damage to the structures of the ear, as evidenced by the tympanometric and otoscopic findings, which revealed cumulative effects of pressure against the tympanic membrane and within the middle ear. This condition was not observed when surface intervals exceeded 11h., Conclusions: The results suggest that extending surface intervals may offer protection against middle ear barotrauma in recreational scuba diving.

The canalicular adenoma is an uncommon, benign salivary gland tumour that most frequently occurs in the upper lip. Although the incidence of multifocal epithelial tumours of the minor salivary is very low, canalicular adenoma sometimes present as a multifocal lesion. We present a case of multifocal canalicular adenomas of upper lip in a woman aged 68 years and discuss their features, emphasising diagnosis, clinical behaviour, treatment, histological and immunohistochemical aspects.

Intracranial schwannoma not related to cranial nerves are unusual and rarely found in the subfrontal region. We report a case of olfactory groove schwannoma in a 27-year-old male, who presented with anosmia and headache initiated one year ago. At admission, bilateral papilledema was noted with absense of motor deficits or cranial nerves abnormalities. Cranial computed tomography (CT) revealed a bifrontal multicystic isodense enhancing mass lesion causing a frontal ventricular horn compression. Radiological features resembled that of a cystic olfactory groove meningioma. Decompressive bifrontal craniotomy was done. One month later, CT demonstrated a homogeneously contrast-enhancing mass in the olfactory groove region who extended into the left nasal cavity. Magnetic resonance imaging did not add more informations. A second surgical procedure was done through a nasoethmoidal approach with incomplete resection of the lesion. The complete tumor resection was only possible in a third surgery through another bifrontal approach. The hystopathological diagnosis of schwannoma was performed by conventional methods and confirmed by immunohistoquemical staining for S-100 protein. The rarity of this tumor and his clinical, radiological and histological aspects justify this publication.

The correlation between TNM classification and histological scores of malignancy, and the correlation of these parameters with the prognosis was evaluated in 16 cases of squamous cell carcinoma of the tongue. The cases were selected from the files of "Dr. Luiz Antônio" Cancer Hospital, Natal, RN, Brazil. After analysis of the patients' records, the data concerning TNM classification and prognosis (in a 5-year-follow-up) were obtained. All cases were classified according to the histological malignancy grading system proposed by Anneroth et al. [Scand Dent Res 1987;95:229-249]. There was no correlation (r = 0.3083) between TNM classification and histological scores of malignancy. There was significant correlation (r = 0.7206) between TNM classification and prognosis, but there was no correlation between the histological scores of malignancy and the prognosis. It was concluded that TNM classification is an important prognostic indicator of squamous cell carcinoma of the tongue.

Background: It is controversial if urothelial carcinoma of the bladder with squamous and/or glandular differentiation is a more aggressive neoplasm than conventional urothelial carcinoma., Design: A total of 165 transurethral resections of the bladder were reviewed. A group with squamous and/or glandular differentiation was compared to a group without this finding. The chi-square test was used to assess the association of the groups with stage (TNM, 1997)., Results: Of the total of 165 transurethral resections of the bladder, 153 (92.72%) were conventional urothelial carcinomas and 12 (7.27%) showed squamous and/or glandular differentiation. The distribution according to stage was 84 (54.9%), 35 (22.9%) and 34 (22.2%) for the group without differentiation and 0 (0%), 3 (25%) and 9 (75%) for the group with squamous and/or glandular differentiation, respectively for stages pTa, pT1 and pT2. Tumors with squamous and/or glandular differentiation showed a significant statistical correlation to higher stage at clinical presentation (p < 0.0001). There was no significant statistical relation according to age (p = 0.8433), sex (p = 0.5672) or race (p = 0.3137)., Conclusions: The results suggest that urothelial bladder carcinomas with squamous and/or glandular differentiation are more aggressive neoplasms. There was a significant statistical correlation between tumors with this differentiation and higher stage at clinical presentation.

During 1997 a large dengue epidemic occurred in Rio Grande do Norte, a State in north-east Brazil. The co-circulation of dengue virus type 1 and dengue virus type 2 was demonstrated by virus isolation in Aedes albopictus clone C6/36 cell-line and by reverse transcriptase-polymerase chain reaction (RT-PCR). IgM capture enzyme-linked immunosorbent assay confirmed 52.3% of the 8105 studied cases and dengue antigen was demonstrated by immunohistochemical reaction on hepatocytes from 2 out of 5 fatal cases studied. Individual risk factors for development of dengue haemorrhagic fever/dengue shock syndrome, such as hypertension, diabetes mellitus and bronchial asthma, are discussed.

Eight cases of subcutaneous phaeohyphomycosis are presented. A lack or scarcity of fungal pigmentation was seen in six of these cases. The simple act of lowering the microscope condenser makes these uncolored fungi easily visible. The thick hyaline capsule becomes refringent, presenting single oval or round cells and septated hyphae, which can be short or elongated, branched or unbranched, and irregularly swollen. The dematiacious character of the fungi is confirmed by using the Fontana-Masson stain. The fungi are not visible under polarized light. Our studies point to the probability of subcutaneous phaeohyphomycosis being a widespread tropical disease in Brazil. However, it is rarely diagnosed because of the common practice of fixing tissue specimens without prior culturing and the difficulties of detecting the fungal forms using customary microscopic procedures, especially when the fungi have a lack of pigment and are hard to detect by hematoxylin and eosin stain.

A case of fatal visceral leishmaniasis associated with immunodeficiency syndrome in a 32 year-old male patient is reported. The protozoonosis was responsible for the patient's death. Visceral leishmaniasis showed itself in an atypical form, at necropsy, with an intense parasitation of the mononuclear phagocitic system and damaging organs not usually affected by the disease, such as the adrenals, the kidneys, the lungs and the brain. Parasitised cells were observed within small vessels in several tissues. An immunohistochemical study was done on samples from the spleen, lymph nodes and brain, showing strong reactivity with antibody directed against leishmania.

Pathologic study of an abdominal mass removed from a 16-month-old girl revealed a marked granulomatous and fibroblastic reaction surrounding eggs and adults of Ascaris lumbricoides. As often occurs in such cases, there was an increased eosinophilia in the lesion and in the peripheral leukocytes. Both the clinical and gross aspects of the lesion simulated a benign neoplasm; this similarity justifies the designation "pseudotumorous form of ascariasis".

An apparently hitherto undescribed noncongenital universal alopecia, due to an autosomal dominant gene with variable expressivity, is described.