t(2;11)(q37;q23) in AML

Review on t(2;11)(q37;q23) in AML, with data on clinics, and the genes involved

Benchmarking a Mobile Implementation of the Social Engineering Prevention Training Tool

As the nature of information stored digitally be- comes more important and confidential, the security of the systems put in place to protect this information needs to be increased. The human element, however, remains a vulnerability of the system and it is this vulnerability that social engineers attempt to exploit. The Social Engineering Attack Detection Model version 2 (SEADMv2) has been proposed to help people identify malicious social engineering attacks. Prior to this study, the SEADMv2 had not been implemented as a user friendly application or tested with real subjects. This paper describes how the SEADMv2 was implemented as an Android application. This Android application was tested on 20 subjects, to determine whether it reduces the probability of a subject falling victim to a social engineering attack or not. The results indicated that the Android implementation of the SEADMv2 significantly reduced the number of subjects that fell victim to social engineering attacks. The Android application also significantly reduced the number of subjects that fell victim to malicious social engineering attacks, bidirectional communication social engineering attacks and indirect communication social engineering attacks. The Android application did not have a statistically significant effect on harmless scenarios and unidirectional communication social engineering attacks

Intraepidermal Epidermotropic Metastatic Melanoma: a Clinical and Histopathological Mimicker of Melanoma in Situ Occurring in Multiplicity

The distinction between primary melanoma and melanoma metastatic to the skin has major prognostic implications. We report a case of a 67-year-old male with a diagnosis of a superficial spreading melanoma (stage IB) rendered 6 years earlier who presented clinically with an atypical nevus on his left thigh. Histopathological examination showed an intraepidermal melanocytic proliferation that was interpreted as melanoma in situ. Subsequently, 45 additional pigmented macules appeared in crops over a 9-month period. Clinically and dermoscopically, these lesions were extremely polymorphic. Histopathological findings were compatible with melanoma in situ, as each lesion consisted of a wholly intraepidermal proliferation of markedly atypical melanocytes arranged singly and in nests. A complete gastrointestinal study showed multiple pigmented metastatic lesions throughout the stomach and small bowel, which supported a diagnosis of metastatic melanoma with gastrointestinal and epidermotropic skin involvement. Monosomy of chromosome 9 and a BRAF V600E mutation were detected in the primary tumor sample and in macro-dissected secondary lesions. No CDKN2A or CDK4 germline mutations were found. Intraepidermal epidermotropic metastases of melanoma have been rarely described in literature. In this case, histopathology alone was insufficient to distinguish metastatic melanoma from multiple in situ melanomas. The recognition of epidermotropic metastases should be based on the correlation between clinical, dermoscopic, histopathological and molecular findings

o caso do estudo da mutilação genital feminina em Portugal, de 2015

UID/SOC/04647/2013publishersversionpublishe

a quantitative study for Lisbon Region, Portugal

The role of migration as a determinant in child mental health has been demonstrated in a number of studies. However, results are not always consistent, and the research continues to be scarce, especially in Portugal. We examined the association between sociodemographic profiles and the chance for the development of emotional and behavioral difficulties in a group of 420 children, immigrant (n = 217) and born in Portugal to Portuguese born parents (n = 203). We used a structured questionnaire to obtain sociodemographic information and the Strength and Difficulties Questionnaire (SDQ). Descriptive statistics were used to characterize children and their families; variables were compared between groups using the Chi-squared, Fisher’s Exact Test, or the Mann–Whitney U test and logistic regression was used to analyze the association between socio-demographic factors and emotional and behavioral difficulties. Results showed a pattern of social and mental health inequalities with immigrant children at a disadvantage: they are more often part of families with low income and where parents had low skilled jobs. Internalizing behaviors are more frequent in immigrants than in children born in Portugal to Portuguese-born parents (p = 0.001) whereas a high total SDQ difficulties score (p = 0.039) and externalizing behaviors were more frequent in 1st generation immigrant children (p = 0.009). A low family income (aOR 4.5; 95% CI: 1.43–13.95), low parental education level (aOR 2.5; 95% CI: 1.11–5.16), and being a first-generation immigrant child (aOR 2.2; 95% CI: 1.06–4.76) increased significantly the chance of developing emotional and behavioral difficulties. This study contributes to the identification of children vulnerable to mental health problems who can benefit from monitoring, early detection and preventive interventions in order to mitigate possible negative outcomes in the futurepublishersversionpublishe

Clinicopathological features as prognostic predictors of poor outcome in papillary thyroid carcinoma

Papillary thyroid cancer (PTC) has an indolent nature and usually excellent prognosis. Some PTC clinicopathological features may contribute to the development of aggressive metastatic disease. In this work, we want to evaluate PTC clinicopathological features that are presurgical prognostic predictors of patients’ outcomes and find which indicators are more adequate for tailoring surgical procedures and follow-up. We studied a series of 241 PTC patients submitted to surgery. All patients’ files and histological tumor samples were reviewed. The 8th edition AJCC/UICC (American Joint Committee on Cancer/Union for International Cancer) Controlstaging system and the 2015 American Thyroid Association risk stratification system were used. Total thyroidectomy was performed in 228 patients, lymphadenectomy in 28 patients. Gross extrathyroidal extension (ETE) was present in 10 patients and 31 tumor resection margins were incomplete. Cervical lymph node metastases (LNMs) were present in 34 patients and distant metastases at diagnosis in four patients. In multivariate analysis, male gender (OR = 15.4, p = 0.015), venous invasion (OR = 16.7, p = 0.022), and lateral compartment LNM (OR = 26.7, p = 0.004) were predictors of mortality; psammoma bodies (PBs) (OR = 4.5, p = 0.008), lymph vessel invasion (OR = 6.9, p < 0.001), and gross ETE (OR = 16.1, p = 0.001) were predictors of structural disease status; male gender (OR = 2.9, p = 0.011), lymph vessel invasion (OR = 2.8, p = 0.006), and incomplete resection margins (OR = 4.6, p < 0.001) were predictors of recurrent/persistent disease. Our study supports that the factors helping to tailor patient’s surgery are male gender, presence of PBs, gross ETE, and lateral compartment LNM. Together with pathological factors, lymph vessel invasion, venous invasion, necrosis, and incomplete surgical resection, should be taken into consideration regarding treatment and follow-up of patients.This study was supported by FCT, the Portuguese Foundation for Science and Technology through a PhD grant to E.T. SFRH/BD/143458/2019. This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020. Additional funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalization— COMPETE2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390: CANCEL STEM and from the FCT under the project POCI-01-0145-FEDER-031438: The other faces of telomerase: Looking beyond tumor immortalization (PDTC/MED_ONC/31438/2017). Additional funding through the Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo-BOLSA SPEDM PARA PROJECTO DE INVESTIGAÇÃO-2017

Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant

Introduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals. Case presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene. Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk

Identification of candidate genes for yeast engineering to improve bioethanol production in very high gravity and lignocellulosic biomass industrial fermentations

<p>Abstract</p> <p>Background</p> <p>The optimization of industrial bioethanol production will depend on the rational design and manipulation of industrial strains to improve their robustness against the many stress factors affecting their performance during very high gravity (VHG) or lignocellulosic fermentations. In this study, a set of <it>Saccharomyces cerevisiae </it>genes found, through genome-wide screenings, to confer resistance to the simultaneous presence of different relevant stresses were identified as required for maximal fermentation performance under industrial conditions.</p> <p>Results</p> <p>Chemogenomics data were used to identify eight genes whose expression confers simultaneous resistance to high concentrations of glucose, acetic acid and ethanol, chemical stresses relevant for VHG fermentations; and eleven genes conferring simultaneous resistance to stresses relevant during lignocellulosic fermentations. These eleven genes were identified based on two different sets: one with five genes granting simultaneous resistance to ethanol, acetic acid and furfural, and the other with six genes providing simultaneous resistance to ethanol, acetic acid and vanillin. The expression of <it>Bud31 </it>and <it>Hpr1 </it>was found to lead to the increase of both ethanol yield and fermentation rate, while <it>Pho85</it>, <it>Vrp1 </it>and <it>Ygl024w </it>expression is required for maximal ethanol production in VHG fermentations. Five genes, <it>Erg2</it>, <it>Prs3</it>, <it>Rav1</it>, <it>Rpb4 </it>and <it>Vma8</it>, were found to contribute to the maintenance of cell viability in wheat straw hydrolysate and/or the maximal fermentation rate of this substrate.</p> <p>Conclusions</p> <p>The identified genes stand as preferential targets for genetic engineering manipulation in order to generate more robust industrial strains, able to cope with the most significant fermentation stresses and, thus, to increase ethanol production rate and final ethanol titers.</p

Genetic transformation of novel isolates of chicken Lactobacillus bearing probiotic features for expression of heterologous proteins: a tool to develop live oral vaccines

BACKGROUND: The use of lactic acid bacteria as vehicles to delivery antigens to immunize animals is a promising issue. When genetically modified, these bacteria can induce a specific local and systemic immune response against selected pathogens. Gastric acid and bile salts tolerance, production of antagonistic substances against pathogenic microorganisms, and adhesive ability to gut epithelium are other important characteristics that make these bacteria useful for oral immunization. RESULTS: Bacteria isolated on de Man, Rogosa and Sharpe medium (MRS) from different gastrointestinal portions of broiler chicks were evaluated for their resistance to artificial gastric acid and bile salts, production of hydrogen peroxide, and cell surface hydrophobicity. Thirty-eight isolates were first typed at species level by PCR amplification of 16S-23S rRNA intergenic spacers using universal primers that anneal within 16S and 23S genes, followed by restriction digestion analyses of PCR amplicons (PCR-ARDRA). An expression cassette was assembled onto the pCR2.1-Topo vector by cloning the promoter, leader peptide, cell wall anchor and terminator sequences derived from the laminin binding S-layer protein gene of L. crispatus strain F5.7 (lbs gene). A sequence encoding the green fluorescent protein (GFP) was inserted as reporter gene, and an erythromycin resistance gene was added as selective marker. All constructs were able to express GFP in the cloning host E. coli XL1-Blue and different Lactobacillus strains as verified by FACS and laser scanning confocal microscopy. CONCLUSION: Lactobacillus isolated from gastrointestinal tract of broiler chickens and selected for probiotic characteristics can be genetically modified by introducing an expression cassette into the lbs locus. The transformed bacteria expressed on its cell wall surface different fluorescent proteins used as reporters of promoter function. It is possible then that similar bacterial model expressing pathogen antigens can be used as live oral vaccines to immunize broilers against infectious diseases