TP53 p.R337H prevalence in a series of Brazilian hereditary breast cancer families

Abstract\ud \ud Background\ud Approximately 5-10% of breast cancers are hereditary. Among hereditary syndromes, Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Li-Fraumeni Syndrome (LFS) have received the most attention. HBOC is due to mutations in the BRCA1 and BRCA2 genes and is characterized by breast adenocarcinoma and/or epithelial ovarian carcinoma. LFS is associated with germline mutations in TP53; the most frequent cancer types associated with this syndrome are sarcoma, breast cancer, leukemia, brain tumors and adrenocortical carcinomas. Other cancers related to LFS are found at lower frequencies. In Brazil, especially in the southern part of the country, a specific mutation in the TP53 gene, TP53 p.R337H, occurs at a high frequency in childhood adrenocortical tumors. It has been proposed that this mutation increases breast cancer risk in southern Brazilian women.\ud \ud \ud Methods\ud We carried out a case-control study to determine the prevalence of the TP53 p.R337H mutation in 28 female cancer patients attended at the Cancer Genetic Counseling Service of the General Hospital of the University of São Paulo Medical School of Ribeirão Preto who fulfilled Hereditary Breast and Ovary Cancer Syndrome genetic test criteria compared to healthy woman (controls). TP53 p.R337H mutation status was determined using the High Resolution Melting (HRM) method, followed by DNA sequencing. Fisher’s test was used to compare the prevalence of TP53 p.R337H in the patient and control groups.\ud \ud \ud Results\ud Two of the breast cancer cases (7.1%) and none of the controls carried the TP53 p.R337H mutation. At the time of the investigation, both cases fulfilled testing criteria for Hereditary Breast and Ovary Cancer Syndrome but not Li-Fraumeni or Li-Fraumeni-like Syndrome, based on genetic testing criteria of NCCN Clinical Practice Guidelines in Oncology (v.1.2010).\ud \ud \ud Conclusions\ud We suggest that genetic screening of Brazilian breast cancer patients who fulfill Hereditary Breast and Ovary Cancer Syndrome criteria and have a family history that includes other tumors of the LFS/LFL spectrum be tested for the TP53 p.R337H mutation.This work was supported by grant 1998/14247-6 of the São Paulo Research Foundation (FAPESP)CNPQ grant 573754/2008-0CAPE

Paratuberculosis control strategies in dairy cattle: A systematic review

Background: Mycobacterium avium subsp. paratuberculosis is the causative agent of paratuberculosis (PTB), incurable enterocolitis, affecting domestic and wild ruminants. Economic losses, impacts on animal health and welfare, and public health concerns justify its herd-level control.Aim: To systematically collect information to answer: What are the control and eradication strategies of PTB in dairy cattle worldwide?Methods: The search procedure was carried out on October 2nd, 2019, and updated on August 3rd, 2021, using OVID®, SciELO, and Redalyc databases, and the registers from the International Colloquium on Paratuberculosis (1991–2018). The inclusion criteria considered articles published in English, Portuguese, and Spanish and in peerreviewed journals. The exclusion criteria included irrelevant topics, species other-than bovines, and not original articles. Definitive studies were obtained through the consensus of the authors on eligibility and quality. Data extraction was performed, considering bibliographic information, control and outcome strategies, follow-up time, and results.Results: Twenty-six relevant studies were found, reporting the use of three grouped control strategies: hygiene and management strategy (HMS), test-and-cull strategy (TCS), and vaccination strategy (VS). The HMS was the most common one (20/26), followed by TCS (17/26) and VS (7/26). Combined control strategies such as TCS-HMS (12/26), TCS-VS (1/26), and HMS-VS (1/26) were also described, and the consideration of the three control strategies (TCSHMS-VS) was reported in two articles. The HMS included practices such as neonates/juvenile livestock hygiene, biosecurity, prevention of infection introduction into the herd, and environmental management. Within HMS, the most frequent practices were to remove calves from their dams as soon as possible after birth and to keep the minimal exposure of calves and heifers to adult cattle. As limitations, within the HMS, it is considered that some strategies cannot be included due to lack of compliance, or the application of the same strategy among one study and another may have a different degree of interpretation; publication bias was not controlled since the results of the control programs in endemic countries may be not available.Conclusion: The main PTB control strategies in dairy cattle worldwide are HMS, TCS, and VS. The use of one or several combined strategies has been found to succeed in controlling the disease at the herd-level

Spatio-Temporal Vegetation Pixel Classification by Using Convolutional Networks

Plant phenology studies rely on long-term monitoring of life cycles of plants. High-resolution unmanned aerial vehicles (UAVs) and near-surface technologies have been used for plant monitoring, demanding the creation of methods capable of locating, and identifying plant species through time and space. However, this is a challenging task given the high volume of data, the constant data missing from temporal dataset, the heterogeneity of temporal profiles, the variety of plant visual patterns, and the unclear definition of individuals' boundaries in plant communities. In this letter, we propose a novel method, suitable for phenological monitoring, based on convolutional networks (ConvNets) to perform spatio-temporal vegetation pixel classification on high-resolution images. We conducted a systematic evaluation using high-resolution vegetation image datasets associated with the Brazilian Cerrado biome. Experimental results show that the proposed approach is effective, overcoming other spatio-temporal pixel-classification strategies

Genetic analysis of enteropathogenic Escherichia coli (EPEC) adherence factor (EAF) plasmid reveals a new deletion within the EAF probe sequence among O119 typical EPEC strains

Enteropathogenic Escherichia coli (EPEC) are classified into typical and atypical strains based on the presence of the E. coli adherence factor (EAF) plasmid. The EAF plasmid contains the bfp (bundle-forming pilus) operon and the perABC (plasmid encoded regulator) gene cluster. A 1-kb cryptic region of EAF plasmid has been widely used as a genetic probe for EPEC detection. However, some EPEC strains may harbor an EAF plasmid lacking the EAF probe sequence, which makes the differentiation between typical and atypical a complex task. In this study, we report the genetic analysis of the EAF plasmid-encoded genes in a collection of EPEC clinical isolates. A total of 222 EPEC clinical isolates, which were previously classified as typical (n = 70) or atypical (n = 152) by EAF probe reactivity, were screened for the presence of different EAF sequences by PCR and DNA hybridization. All typical strains possessed intact bfpA and perA genes, and most of them were positive in the PCR for EAF probe sequence. However, a subset of 30 typical strains, 22 of which belonged to O119 serogroup, presented a 1652 pb deletion in the region between 1093-bp downstream perC and 616-bp of the EAF fragment. The bfpA, bfpG, and per genes were found in all typical strains. In addition, 32 (21 %) atypical strains presented the perA gene, and 20 (13.2 %) also presented the bfpA gene. Among the 32 strains, 16 belonged to the O119:H2, O119:HND, and ONT:HND serotypes. All 32 atypical strains contained perA mutation frameshifts and possessed an IS1294 element upstream of the per operon as detected by PCR followed by restriction fragment length polymorphism (RFLP) typing and multiplex PCR. Among the 20 bfpA probe-positive strains, eight O119 strains possessed deletion in the bfp operon at the 3'end of bfpA due to an IS66 element. Our data show that typical O119 strains may contain a deletion within the EAF probe sequence not previously reported. This new finding suggests that care should be taken when using the previously described EAF PCR assay in epidemiological studies for the detection of typical O119 strains. In addition, we were able to confirm that some atypical strains carry vestiges of the EAF plasmid.1520

Factors associated with Mycobacterium avium subsp. paratuberculosis in dairy cows from Northern Antioquia, Colombia

Background: Johne´s disease (JD) is a severe enteritis that affects ruminants and has been diagnosed in cattle and sheep in Colombia. However, epidemiological information on the disease in this country is scarce. Objective: to identify factors associated with the JD serum enzyme-linked immunosorbent assay (ELISA) status of dairy cows. Methods: a cross-sectional study was carried out in 307 asymptomatic adult Holstein dairy cows from 14 herds in nine districts of Belmira and San Pedro de los Milagros municipalities during November, 2007. Nineteen to 29 cows, ≥ 2 years of age were randomly selected and blood sampled from every herd. A commercial ELISA kit was used to analyze sera. Information regarding cow related factors (age, farm-born, parity, and daily milk yield) and herd management practices (i.e. herd size, herd average milk production, current presence of symptomatic animals, cattle purchase, own animals grazing in foreign pastures, feeding of calves before weaning, manure spread on pastures, and sighting of birds in feed storing areas) was collected using questionnaires. Descriptive statistics were computed for all variables and a multivariable logistic regression model was constructed (p 1 parity. The OR was 0.74 times lower (OR = 0.26; 95% CI: 0.096-0.70; p<0.01) in herds feeding calves with pooled colostrum from several cows, compared to herds feeding calves with colostrum from their own dams. Conclusion: JD seroprevalence was 10 and 70% at animal and herd-level, respectively. Cow and herd factors “parity” and “feeding of calves before weaning” showed weak and strong association with positive results, respectively

Prevalence of Mycobacterium avium subsp. paratuberculosis and associated risk factors in dairies under mechanical milking parlor-systems in Antioquia, Colombia

El presente estudio tuvo como objetivo determinar la prevalencia de Mycobacterium avium subsp. paratuberculosis (MAP) según muestras ambientales y explorar los factores de riesgo a nivel de hato asociados a la infección por MAP en hatos lecheros bajo sistemas de sala de ordeño mecánico y basados en pastoreo de prados. Los hatos de estudio (n= 94) se ubicaron en 60 distritos de cinco municipios de la región Norte de la Provincia de Antioquia, Colombia. Los hatos fueron visitados una vez en 2016 para recolectar dos muestras ambientales compuestas y completar un cuestionario de evaluación de riesgos. La identificación de MAP se llevó a cabo utilizando un método de PCR cuantitativo en tiempo real basado en la secuencia IS900. Un hato se consideró como MAP-positivo si una o ambas muestras ambientales resultaron positivas mediante la técnica molecular. La información sobre los factores de riesgo se analizó utilizando un modelo de regresión logística multivariable. La prevalencia aparente a nivel de hato encontrada fue de 14.9 % (14/94; IC 95 %: 7.7-22.1), oscilando entre 0 y 33.3 % a nivel municipal. Los hatos en los que predominaban razas distintas a la Holstein pura (estas son, Jersey, cruzas de Jersey) tenían más probabilidades de estar positivamente infectados con MAP-qPCR que aquellos en los que predominaba el ganado Holstein puro (OR= 3.7; IC 95 %: 1.1-15.2). El presente estudio reporta la prevalencia de MAP en hatos lecheros de la Provincia de Antioquia (Colombia), y la asociación entre la positividad ambiental de MAP con la raza predominante en el hato.The present study aimed to determine Mycobacterium avium subsp. paratuberculosis (MAP) prevalence according to environmental samples and to explore the herd-level risk factors associated to MAP infection in dairy herds under mechanical milking parlor and pasture grazing-based systems. The study herds (n= 94) were located in 60 districts from five municipalities in the Northern region of the province of Antioquia, Colombia. Herds were visited once in 2016 to collect two composite environmental samples and to complete a risk assessment questionnaire. MAP identification was carried out using a quantitative real-time PCR method based on the IS900 sequence. A herd was considered as MAP-positive if one or both of the environmental samples were found positive by the molecular technique. The information on risk factors was analyzed using a multivariable logistic regression model. The apparent herd-level prevalence found was 14.9 % (14/94; 95 % CI: 7.7-22.1), ranging from 0 to 33.3 % at municipality-level. Herds where other than Pure-Holstein breeds were predominant (i.e. Jersey, Jersey crossbreeds) were more likely to be MAP-qPCR positively infected than those on which where pure-Holstein cattle was predominant (OR=3.7; 95 % CI: 1.1-15.2). The present study reports MAP prevalence in dairy herds in the province of Antioquia (Colombia), and the association between MAP environmental positivity with the predominant breed in the herd

Fecal culture and two fecal-PCR methods for the diagnosis of Mycobacterium avium subsp. paratuberculosis in a seropositive herd

Background: paratuberculosis is a slow-developing infectious disease, characterized by chronic granulomatous enterocolitis. This disease has a variable incubation period from 6 months to over 15 years, and is caused by Mycobacterium avium subsp. paratuberculosis (MAP). Its detection by direct and indirect diagnostic techniques has been of special interest. Objective: to report the diagnosis and detection of MAP using several diagnostic tests in a herd of the Northern region of Antioquia, Colombia. Methods: serum samples from the study herd were analyzed, using a commercial ELISA (enzyme-linked immunosorbent assay) kit. Fecal samples were cultured by duplicate using Herrold´s egg yolk medium (HEYM), and analyzed by an endpoint IS900-specific nested PCR protocol, and a commercial F57-real-time PCR kit. Results: eight out of 27 serum samples in the study herd resulted ELISA-positive. None of fecal samples resulted positive to HEYM culture by duplicate and none were found to be positive by F57-real-time PCR. Seven of the 27 fecal samples were found to be positive by end-point IS900-specific nested PCR. Agreement was found between ELISA and end-point IS900-specific nested PCR in one of the animals. Conclusion: the present study gives information about the agreement between direct and indirect MAP-detection techniques, using different matrixes from animals under the same husbandry conditions

Activation of PPARγ reduces N-acetyl-cysteine -induced hypercorticoidism by down-regulating MC2R expression into adrenal glands

We previously demonstrated that oral supplementation with antioxidants induced hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis, attested by hypercorticoidism, through an up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal. This study analyzed the role of peroxisome proliferator-activated receptor (PPAR)-γ on HPA axis hyperactivity induced by N-acetyl-cysteine (NAC). Male Swiss-Webster mice were orally treated with NAC for 1, 3, 5, 10, 15, or 18 consecutive days. The PPAR-γ agonist rosiglitazone and/or antagonist GW9662 were daily-injected i.p. for 5 consecutive days, starting concomitantly with NAC treatment. Rosiglitazone treatment inhibited NAC-induced adrenal hypertrophy and hypercorticoidism. Rosiglitazone also significantly reversed the NAC-induced increase in the MC2R expression in adrenal, but not steroidogenic acute regulatory protein (StAR). NAC treatment reduces the expression of PPARγ in the adrenals, but rosiglitazone did not restore the expression of this cytoprotective gene. In addition, GW9662 blocked the ability of rosiglitazone to decrease plasma corticosterone levels in NAC-treated mice. In conclusion, our findings showed that antioxidant supplementation induced a state of hypercorticoidism through down-regulation of PPARγ expression in the adrenals, in a mechanism probably related to a down-regulation of ACTH receptor expression.Fil: Ventura, Raíssa D.. Fundación Oswaldo Cruz; BrasilFil: Chaves, Amanda S.. Fundación Oswaldo Cruz; BrasilFil: Magalhães, Nathalia S.. Fundación Oswaldo Cruz; BrasilFil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Pacini, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Pérez Ransanz, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Silva, Patrícia M.R.. Fundación Oswaldo Cruz; BrasilFil: Martins, Marco A.. Fundación Oswaldo Cruz; BrasilFil: Carvalho, Vinicius F.. Fundación Oswaldo Cruz; Brasi

[(2R,3S,6S)-3-Acet­yloxy-6-(1-phenyl-1H-1,2,3-triazol-4-yl)-3,6-dihydro-2H-pyran-2-yl]methyl acetate

In the title compound, C18H19N3O5, the 3,6-dihydro-2H-pyran ring adopts a half-chair, distorted towards a half-boat, conformation with Q T = 0.5276(14) Å. The benzene ring is twisted out of the place of the triazole ring [dihedral angle = 23.54 (8)°]. In the crystal, supra­molecular layers in the ac plane are formed through C—H⋯O and C—H⋯π(triazole) inter­actions. These stack along the b axis being connected by C—H⋯N contacts

Functional Properties of Brazilian Propolis: From Chemical Composition Until the Market

Propolis is a product obtained from resins and exudates of different plants from different regions in order to protect the comb, with peculiar organoleptic, chemicals and biological properties. Considering this, this chapter presents the types of Brazilian propolis as the types available nowadays, their chemical compositions, as well as, some of their important biological properties enabling employing them as important health food, such as antimicrobial, antioxidant, and immunomodulation action. Various “in vivo” and clinical trial studies, conducted in different regions, on the safety and dosage of propolis, technologies used to obtain propolis extract, and several innovative presentations of this promising bee product are also presented in this chapter. Finally, this chapter aims to present the regulatory affairs, potential market for propolis around the world, and perspectives for a near future