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Wild boars or feral pigs are classified by the Brazilian Institute for the Environment and Renewable Resources (IBAMA) in "Category I of invasive exotic species". They cause economic losses, harm the environment, serve as hosts and reservoirs for several zoonotic disease agents, and provide a blood meal for tick species that act as vectors for zoonotic diseases. The objective of this study was to identify tick species on wild boars, assess host-seeking ticks in the related environment, and identify other potential tick hosts coexisting with wild boars on a farm located in the state of Minas Gerais, southeastern Brazil. Additionally, the study aimed to determine the presence of rickettsiae in these arthropods and assess the exposure of wild boars to rickettsiae species from the Spotted Fever Group and Rickettsia bellii through serology. A total of 3585 host-seeking ticks from three species (Amblyomma sculptum - 41.58%; Amblyomma dubitatum - 0.39% and Rhipicephalus microplus - 0.05%) were collected in the environment and A. sculptum was the most abundant species. Thirty-one wild boars were evaluated, resulting in the collection of 415 ticks, all of which were A. sculptum. Rickettsia DNA was not detected in samples of A. sculptum and R. microplus from the environment or in A. sculptum ticks from wild boars. However, all A. dubitatum ticks (n = 14) had Rickettsia bellii DNA confirmed by the species-specific PCR protocol. Out of the 31 serum samples from wild boars, 24 reacted with at least one Rickettsia antigen. Among these, seven individuals exhibited a reaction to a probable homologous antigen (PHA) of three rickettsiae species: R. rickettsii (n = 3), R. amblyommatis (n = 3) and R. rhipicephali (n = 1). Despite the high prevalence of seroreactivity, titers were low, indicating limited exposure to Rickettsia spp. Camera traps generated 874 animal records, capturing a total of 1688 individuals. At least 11 species of birds and 14 species of mammals (12 wild and two domestic) shared the environment with wild boars and potentially shared ticks with them. These findings provide baseline information for understanding the sharing of ticks and tick-borne pathogens between wild boars and other animals within the Cerrado biome. Further studies are necessary to monitor the potential and actual risk of wild boars to harbor infected ticks and their role in the transmission and maintenance cycle of Rickettsia spp., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest in the research work submitted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In several urban and peri‑urban areas of Brazil, populations of Amblyomma sculptum and Amblyomma dubitatum ticks are maintained by capybaras (Hydrochoerus hydrochaeris). In some of these areas, this host and these tick species are associated with Brazilian spotted fever (BSF), a lethal human disease caused by the bacterium Rickettsia rickettsii. In this work, we evaluated the risk of human exposure to these tick species using four collection techniques to discern host-seeking behavior. The study was carried out in 10 urban sites inhabited by capybaras in Uberlândia, a BSF-free municipality in southeastern Brazil. Ticks were collected in areas of 400 m 2 at each site and at three seasons. Within the same municipality, the distance and speed of A. sculptum nymphs moving towards the CO 2 traps were evaluated. In a sample of ticks Rickettsia DNA was investigated. During the study period, 52,953 ticks were collected. Among these, 83.4 % were A. sculptum (1,523 adults, 10,545 nymphs and 32,104 larvae) and 16.6 % were A. dubitatum (464 adults, 2,153 nymphs and 6,164 larvae). An average annual questing tick density of 4.4/m² was observed, with the highest density recorded at one site in autumn (31.8/m²) and the lowest in summer at another site (0.03/m²). The visual search yielded the highest proportion of A. sculptum larvae, constituting 47 % of the total and 63.6 % of all A. sculptum larvae. In contrast, CO 2 traps collected a greater proportion of nymphs and adults of A. sculptum ticks. In the case of A. dubitatum, the CO 2 trap was the most efficient technique with 57.7 % of captures of this species, especially of nymphs (94.5 % of captures) and adults (97.8 % of captures). Ticks' ambush height on vegetation (9 to 77 cm), observed by visual search 30 times, yielded a total of 20,771 ticks. Of these, 28 (93 %) were A. sculptum ticks, with only two (7 %) identified as A. dubitatum ticks. Among A. sculptum ticks, the nymph was the most attracted stage to humans and larva in the case of A. dubitatum. Amblyomma sculptum adults and nymphs were significantly more attracted to humans than those of A. dubitatum, but A. dubitatum larvae were significantly more attracted than the same stage of A. sculptum. The maximum distance and speed of horizontal displacement for A. sculptum nymphs were five meters and 2.0 m/h, respectively. The only species of Rickettsia detected in ticks, exclusively in A. dubitatum, was R. bellii. Importantly, it was observed that the higher the proportion of A. sculptum in the community of ticks, the lower the rate of infection of A. dubitatum by R. bellii. In conclusion, host-seeking behavior differed between the two tick species, as well as between stages of the same species. A greater restriction of A. dubitatum ticks to the soil was observed, while larvae and nymphs of A. sculptum dispersed higher in the vegetation. The behavior presented by A. sculptum provides greater opportunities for contact with the hosts, while A. dubitatum depends more on an active search for a host, the hunter behavior. Taken together, these observations show that a human being crossing an area infested with A. sculptum and A. dubitatum ticks will have almost exclusive contact with A. sculptum larvae and/or nymphs. Humans in a stationary position (sitting, lying or immobile) are exposed to both tick species, but they are more attractive to adults and mainly nymphs of A. sculptum compared to the corresponding stages of the tick A. dubitatum. The negative effect of A. sculptum on A. dubitatum infection by R. bellii deserves further studies., Competing Interests: Declaration of competing interest The authors declared that no competing interests exist., (Copyright © 2024. Published by Elsevier GmbH.)

Ticks are obligate hematophagous parasites that can transmit to vertebrate hosts several pathogens, including viruses, bacteria, protozoa and helminths. Among these agents, some Borrelia species some Borrelia species cause disease in humans and other vertebrate hosts; therefore, they have medical and veterinary health importance. To gather additional information on Borrelia species in Brazil, the current study aimed to detect the presence of these species in Ornithodoros cavernicolous ticks collected in September 2019 from cement pipes that are used by bats as shelter in a farm located in the midwestern region of Brazil. DNA samples obtained from 18 specimens of O. cavernicolous were subjected of two polymerase chain reactions, targeting a segment of the Borrelia fla B gene. Of the samples tested, only one (6 %, 1/18) showed amplification. The nucleotide sequence of the amplified DNA showed more than 97 % (293/300) identity with a sequence of a Borrelia sp. detected in blood collected from a bat from Macaregua Cave, Colombia, and more than 97 % (292/300) detected in lungs from vampire bats from northeastern Brazil. The deduced amino acid sequences were identical to each other. Phylogenetic analysis indicated that these sequences formed a group of Borrelia species (putatively associated with bats) that is closely related to sequences of Borrelia species of the Lyme borreliosis group. Further investigations should be carried out in order to determine whether the sequence of the Borrelia sp. we found belongs to a new taxon. It will also be of great importance to determine which vertebrate hosts, besides bats, O. cavernicolous ticks can parasitize in order to investigate whether the Borrelia sp. we found may be transmitted and cause disease to the other vertebrate hosts., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023. Published by Elsevier GmbH.)

We report Rickettsia species from 2,334 ticks collected from environment (1,939 ticks) and animals (395 ticks) in the largest inland fragment of the Atlantic rainforest of southern Brazil and its fragments. Additionally, the DNA infection rates of Amblyomma ovale tick populations in the Neotropics with Rickettsia bellii and Rickettsia parkeri strain Atlantic rainforest were calculated using data from scientific publications, and their correlation was evaluated. From 11 tick species Rickettsia DNA was detected in seven (Amblyomma brasiliense, Amblyomma coelebs, Amblyomma incisum, Amblyomma longirostre, A. ovale, Haemaphysalis juxtakochi, Ixodes fuscipes) and was not detected in four species (Amblyomma dubitatum, Ixodes loricatus, Rhipicephalus microplus and Rhipicephalus sanguineus sensu lato). DNA of five Rickettsia species was detected (R. bellii, Rickettsia amblyommatis, Rickettsia rhipicephali, Rickettsia felis and Rickettsia sp. Aragaoi). To determine the prevalence of Rickettsia DNA positivity according to vector species, ticks were processed individually or in pools of 2-10 individuals (samples). The most prevalent Rickettsia species was R. bellii, found in 112 samples, followed by R. amblyommatis, R. rhipicephali, R. felis and Rickettsia sp. Aragaoi, found in 16, five, two and one sample, respectively. Rickettsia bellii DNA was found in five tick species with the highest infection rate in A. ovale and A. brasiliense. Absence of R. parkeri strain Atlantic rainforest in A. ovale ticks was an unexpected result. Furthermore, a negative correlation was identified between the infection rates (DNA) of R. bellii and/or R. parkeri strain Atlantic rainforest within A. ovale tick populations in the Neotropics. Putting together current knowledge, it can be proposed that, within natural settings, the diversity of rickettsiae and ticks creates a buffering effect on the overgrowth of rickettsiae and episodes of bacteremia in the hosts., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Research concerning leptospirosis in donkeys and mules has been neglected around the world. Therefore, the aim of this study was to investigate the epidemiological situation of the prevalence of anti-Leptospira spp. antibodies in donkeys and mules from the state of Minas Gerais, Brazil. Blood serum samples were collected from 180 animals (109 donkeys and 71 mules) in two rural properties from the state of Minas Gerais, Brazil, and then submitted to a microscopic agglutination test (MAT). Urea and creatinine values were also quantified. Epidemiological variables such as age, breeding system, contact with other animal species, source of water and food, vaccination against leptospirosis, presence of reproductive alterations, and rodent control were also investigated. From 180 samples collected, 39 (21.67%) showed positive results in the MAT, at a dilution ≥ 1:100. Some animals were reactive for more than one serovar. The serovar Tarassovi was the most frequent (14.07%), followed by Hardjo (11.85%) and Wolffi (11.11%). There was a statistically significant difference between animals from 0 to 3 years of age reactive in the MAT in comparison to the other age groups. Most of the animals had urea and creatinine concentrations within the acceptable reference limit; however, there was a significant increase in creatinine levels in some of the test animals. The studied properties showed differences in some epidemiological aspects such as vaccination of the animals, presence of reproductive problems in the herd, and rodent control. Such aspects pointed as risk factors that may influence the frequency of positive serological results in property 1. The present study demonstrated that the prevalence of leptospirosis in donkeys and mules is high and several serovars are being maintained by these animals, representing a potential public health risk., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Persistent organic pollutants (POPs) are highly lipophilic and can accumulate and biomagnify in food chains. Characterized as a public health problem, exposure to these compounds enables the development of diseases like cancer, cardiovascular disease, diabetes, and obesity. The objective of this study was to estimate the plasma levels of organochlorine pesticides and PCBs in 151 samples (97 women; 54 men) in hospitalized individuals in Petropolis, Brazil. Individuals over 18 years of age and residing for at least 2 years in the mountainous region of the State of Rio de Janeiro, Brazil, participated in a cross-sectional study. Interviews using a structured questionnaire and blood samples to estimate plasma levels of persistent organic pollutants provided data. Gas chromatography coupled with triple quadrupole mass spectrometry provided the levels of organochlorine pesticides and PCBs. Compared to data present in the literature, the concentration of POPs was lower, and individuals from 55 to 64 years of age (3.28 ng mL -1 ) and women (2.52 ng mL -1 ) presented a higher average concentration of organochlorine pesticides; men (0.05 ng mL -1 ) also presented a high concentration of PCBs. This is the first Brazilian study to estimate the concentration of several POPs in a hospital-based sample that includes men and women, thus contributing to the characterization of our population regarding environmental exposures relevant to health., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To investigate the association between pesticide use and breast cancer. A hospital-based case-control study was conducted in Petrópolis city, Brazil. The study data were obtained through interviews, and the magnitude of the association between self-reported pesticide exposure and breast cancer was determined using unconditional logistic regression. A higher estimated risk for breast cancer was found in women exposed to pesticides for 10 or more years, where this association was not statistically significant after adjusting for potential confounders (OR = 1.40; 95% CI 0.85-2.49). A positive statistically significant association was found between breast cancer and higher educational level or previous use of hormone replacement therapy (HRT), whereas having had 2 or more pregnancies to term proved a protective factor. Further studies elucidating the contribution of pesticide exposure to the development of breast cancer are needed, given that current findings in the literature are conflicting., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The synthesis, physico-chemical characterization and in vitro antiproliferative activity against the promastigote form of Leishmania amazonensis of two new cobalt(II) coordination compounds (i.e. [Co(HL1)Cl 2 ]0.4,2H 2 O (1) and [Co(HL2)(Cl)(CH 3 OH)](ClO 4 ).2H 2 O (2)) are reported, where HL1 = 4-{3-[bis(pyridin-2-ylmethyl)amino]-2-hydroxypropoxy}-2H-chromen-2-one and HL2 = 7-{3-[bis(pyridin-2-ylmethyl)amino]-2-hydroxypropoxy}-2H-chromen-2-one. X-ray diffraction studies were performed for complex (2) and the structure of complex (1) was built through Density Functional Theory (DFT) calculations. Complex (1) presented no cytotoxicity to LLC-MK2, but complex (2) was toxic. IC 50 against promastigotes of L. amazonensis for complex (1) were 4.90 (24 h), 3.50 (48 h) and 3. 80 μmol L -1 (72 h), and for complex (2) were 2.09, 4.20 and 2.80 μmol L -1 , respectively. Due to the high toxicity presented by complex (2) against LLC-MK2 host cells, mechanistic studies, to shed light on the probable mode of leishmanicidal activity, were carried out only for the non-cytotoxic complex. Complex (1) was able to elevate mitochondrial membrane potential of the parasites after treatment. Transmission electron microscopy revealed typical apoptotic condensation of chromatin, altered kinetoplast and mitochondria structures, suggesting that apoptosis-like cell death of the protozoa is probably mediated by an apoptotic mechanism associated with mitochondrial dysfunction (intrinsic pathway). Molecular docking studies with complex (1) upon protein tyrosine phosphatase (LmPRL-1) suggests a plausible positive complex anchoring mainly by hydrophobic and hydrogen bond forces close to the enzyme's catalytic site. These promising results for complex 1 will prompt future investigations against amastigote form of L. amazonensis., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2022. Published by Elsevier Inc.)

Neoadjuvant chemotherapy (NACT) is offered to patients with operable or inoperable breast cancer (BC) to downstage the disease. Clinical responses to NACT may vary depending on a few known clinical and biological features, but the diversity of responses to NACT is not fully understood. In this study, 80 women had their metabolite profiles of pre-treatment sera analyzed for potential NACT response biomarker candidates in combination with immunohistochemical parameters using Nuclear Magnetic Resonance (NMR). Sixty-four percent of the patients were resistant to chemotherapy. NMR, hormonal receptors (HR), human epidermal growth factor receptor 2 (HER2), and the nuclear protein Ki67 were combined through machine learning (ML) to predict the response to NACT. Metabolites such as leucine, formate, valine, and proline, along with hormone receptor status, were discriminants of response to NACT. The glyoxylate and dicarboxylate metabolism was found to be involved in the resistance to NACT. We obtained an accuracy in excess of 80% for the prediction of response to NACT combining metabolomic and tumor profile data. Our results suggest that NMR data can substantially enhance the prediction of response to NACT when used in combination with already known response prediction factors.

The aim of this study was to verify the effects of moderate-intensity continuous (MICT) and high-intensity interval (HIIT) aerobic training on cardiac morphology and function and the mechanical properties of single cardiomyocytes in spontaneously hypertensive rats (SHR) in the compensated phase of hypertension. Sixteen-week-old male SHR and normotensive Wistar (WIS) rats were allocated to six groups of six animals each: SHR CONT or WIS CONT (control); SHR MICT or WIS MICT (underwent MICT, 30 min/day, five days per week for eight weeks); and SHR HIIT or WIS HIIT (underwent HIIT, 30 min/day, five days per week for eight weeks). Total exercise time until fatigue and maximum running speed were determined using a maximal running test before and after the experimental period. Systolic (SAP), diastolic (DAP), and mean (MAP) blood pressures were measured using tail plethysmography before and after the experimental period. Echocardiographic evaluations were performed at the end of the experimental period. The rats were euthanized after in vivo assessments, and left ventricular myocytes were isolated to evaluate global intracellular Ca 2+ transient ([Ca 2+ ] i ) and contractile function. Cellular measurements were performed at basal temperature (~37°C) at 3, 5, and 7 Hz. The results showed that both training programs increased total exercise time until fatigue and, consequently, maximum running speed. In hypertensive rats, MICT decreased SAP, DAP, MAP, interventricular septal thickness during systole and diastole, and the contraction amplitude at 5 Hz. HIIT increased heart weight and left ventricular wall thickness during systole and diastole and reduced SAP, MAP, and the time to peak [Ca 2+ ] i at all pacing frequencies. In conclusion, both aerobic training protocols promoted beneficial adaptations to cardiac morphology, function, and mechanical properties of single cardiomyocytes in SHR.

Back pain is common in adolescents as a result of their typical daily activities. There is a critical need for developing instruments that can assess the adolescents' knowledge of proper posture, because adequate postural habits are essential for preventing back pain and facilitating physical well-being. Unfortunately, there is insufficient understanding about appropriate back health in the general public, even though this knowledge is decisive in the development of physical skills and attainment of health literacy. Furthermore, relevant substantive literature is scarce. Therefore, the proposed systematic review aims to identify instruments that are used for assessing knowledge of back health in adolescents. Relevant search terms and descriptors will be combined, and searches will be carried out in a uniform sequence within the PubMed, Embase, CINAHL, and Cochrane Library databases. Eligible articles must present data on the assessment of the adolescents' knowledge of back health and describe the applied instrumentation. Articles will be selected by two reviewers independently; all disagreements will be resolved by a third reviewer. Mendeley and the Rayyan software will be used for the systematic review, and the checklist proposed by Brink and Louw will be used to verify the methodological quality of the included studies. Our findings may confirm the relevance of constructing and validating back health instruments for use in Brazil and other countries.

Background: The social isolation (quarantine) caused by COVID-19 has generated several consequences for the physical and mental health of the general population; however, little is known about the effects of this disease on elite athletes. We seek to assess the effect of social isolation on anxiety, sleep quality and quality of life for elite athletes., Methods: 206 athletes from collective and individual sports (116 men and 90 women) participated in the present study, with an average age of 24.61±8.73 years. Time devoted to physical training before and during the pandemic was assessed. Assessment of anxiety symptoms, sleep quality and mood were assessed using semistructured questionnaires., Results: There was a reduction in hours dedicated to training, as well as in training sessions for both groups evaluated. There is a high prevalence (>90%) of anxiety symptoms (medium and high) in both groups. There were no major losses in the sleep quality of the athletes (>75% presented regular to very good sleep)., Conclusions: There are no differences regarding the traits and state of anxiety between athletes of collective and individual modalities. However, both groups showed traces of anxiety, which, from the point of view of health, becomes worrying.

The objective of this work was to evaluate the relationship between the populations of the ticks Amblyomma triste Koch, 1844, Rhipicephalus microplus (Canestrini, 1888), Amblyomma sculptum Berlese, 1888, the pathogenic bacteria Rickettsia parkeri and a marsh deer (Blastocerus dichotomus) population after its removal from a pristine environment. For this purpose, ticks were collected from the cervical region of deer at the Marsh Deer Conservation Center in Promissão, São Paulo State, Brazil for nine consecutive years (2000 - 2008). Deer in captivity at the Center were kept in 2,000 m² paddocks surrounded by two-meter-high fences in the Tiete-river marsh. In total, 1,012 ticks of 26 deer were collected. Prevalence of the species A. triste among tick-infested hosts was the highest in the first triennium but decreased to the second and further to the third triennium. In contrast, the R. microplus prevalence amidst infested host population, increased from the first to the third triennium and was the species that attained the highest infestation intensity. Amblyomma sculptum was the tick with the lowest infestation prevalence and intensity throughout the period. The change in the proportion between the two most prevalent species was attributed to the new environment, specifically its restricted size and within it a dry area more suitable for R. microplus. DNA of 424 ticks processed in 276 pools was tested for Rickettsia genetic material by polymerase chain reactions (PCR). Twenty samples of the study were positive for the rickettsial gltA gene. Of these, 18 were from A. triste ticks and revealed the presence of the ompA spotted fever group gene as well. Eleven samples were sequenced and showed 100% identity with R. parkeri sensu stricto. Two samples from R. microplus did not amplify ompA gene neither yielded product in a PCR specific for Rickettsia bellii. Sequencing of the gltA gene in the DNA of these two ticks was also 100% identical with R. parkeri s.s. In conclusion, the changes in the deer environment modified the tick populations but maintained, at least temporary, R. parkeri bacteria in A. triste ticks. Rhipicephalus microplus was refractory to the R. parkeri infection and bacterial DNA in this tick species indicated DNA spill over from other tick species. It was demonstrated that captive marsh deer may sustain cattle tick populations on its own. This would hardly occur under pristine conditions because of the inadequacy the marsh deer´s naturally humid habitat for the cattle tick. However, deer transportations of R. microplus ticks from one farm to another may occur whenever habitat loss pushes this wild animal towards farms., (Copyright © 2021. Published by Elsevier GmbH.)

Plasma and tissue from breast cancer patients are valuable for diagnostic/prognostic purposes and are accessible by multiple mass spectrometry (MS) tools. Liquid chromatography-mass spectrometry (LC-MS) and ambient mass spectrometry imaging (MSI) were shown to be robust and reproducible technologies for breast cancer diagnosis. Here, we investigated whether there is a correspondence between lipid cancer features observed by desorption electrospray ionization (DESI)-MSI in tissue and those detected by LC-MS in plasma samples. The study included 28 tissues and 20 plasma samples from 24 women with ductal breast carcinomas of both special and no special type (NST) along with 22 plasma samples from healthy women. The comparison of plasma and tissue lipid signatures revealed that each one of the studied matrices (i.e., blood or tumor) has its own specific molecular signature and the full interposition of their discriminant ions is not possible. This comparison also revealed that the molecular indicators of tissue injury, characteristic of the breast cancer tissue profile obtained by DESI-MSI, do not persist as cancer discriminators in peripheral blood even though some of them could be found in plasma samples.

The giant anteater (Myrmecophaga tridactyla) and the collared anteater (Tamandua tetradactyla) are widespread in Brazil and found in all Brazilian biomes. These hosts frequently use domestic animal environments such as pastures, where tick and related microorganism interchange may occur between hosts. Reports of tick infestations of these animals are scattered and refer to small samples and/or are geographically restricted. We herein present data on a wide geographic distribution of ticks and their Rickettsia collected from 72 giant and 30 collared anteaters, mostly road killed, over a period of 18 years, from Southeast and Central-West Brazil encompassing four States and 46 Municipalities. Overall nine tick species (Amblyomma auricularium, A. calcaratum, A. nodosum, A. ovale, A. parvum, A. sculptum, A. triste, Rhipicephalus microplus and R. sanguineus sensu lato) were collected from anteaters. Amblyomma sculptum, A. nodosum, and A. calcaratum were the most prevalent corresponding to, respectively, 48.8%, 39.3% and 2.7% of all ticks (n = 1775). However, A. nodosum tick numbers on collared anteaters were significantly higher (P < 0.001) than those on giant anteaters. At the same time, an abundance of A. sculptum adults on giant anteaters was significantly higher (Z = 2.875; P = 0.004) than that of A. nodosum and only eight A. sculptum nymphs were found on collared anteaters. DNA samples from 20 ticks from nine different animals yielded a visible amplicon in PCR targeting gltA. The PCR products targeting spotted-fever Rickettsia gene (ompA) from five adults of A. nodosum were sequenced and were shown to be 100% identical to Rickettsia parkeri strain NOD (MF737635.1). The product of one nymph and one adult of A. sculptum yielded a sequence 99% identical to R. parkeri strain NOD. Further, Rickettsia bellii genes were found in three A. nodosum adults. Ecological, behavioral and anatomical traits of anteaters are discussed to explain reported tick infestations and Rickettsia DNA found., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Introduction: Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) modify the risk and severity of sporadic breast cancer (BC). In this context, the MTHFR C677T and A1298C polymorphisms have been associated with risk and severity of sporadic BC., Patients and Methods: In total, 253 women with BC and 257 controls were enrolled in this study. Polymorphisms were analyzed using restriction fragment length polymorphism - polymerase chain reaction. Epidemiology, tumor characteristics, and reproductive factors were considered in the analysis. Statistical tests included the χ 2 test, the Fisher exact test, and the Mann-Whitney and Kruskal-Wallis tests, or parametric equivalents., Results: MTHFR polymorphisms were not a risk factor for BC. The 677CC genotype was associated with distant metastasis (odds ratio [OR] = 5.311; 95% confidence interval [CI] = 1.124-25.09) and lower estrogen receptor expression, whereas the 1298AA genotype was associated with stage 0 (OR = 0.244; 95% CI = 0.077-0.771) and increased estrogen receptor expression. In haplotype analysis, 677CC/1298AA was associated with hypertension (OR = 1.979; 95% CI = 1.036-3.782), and 677CT/1298AC was associated with invasive carcinoma of no special type (OR = 0.472; 95% CI = 0.243-0.918) and stage 0 (OR = 3.476; 95% CI = 1.341-10.47)., Conclusion: The MTHFR C677T and A1298C polymorphisms do not alter the risk of BC, but are associated with the clinical severity of BC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Reproductive factors pose a risk for sporadic breast cancer (BC) development owing to the lifetime exposure to estrogen, a hormone responsible for cell proliferation in the breast. Because variants of the estrogen receptor (ER) alpha and beta genes have been associated with BC risk in numerous populations, the objective of the study was to determine whether the risk and severity of sporadic BC was associated with the rs2228480 (ESR1) and rs4986938 (ESR2) variants in a Brazilian population., Methods: A total of 253 DNA samples from sporadic BC patients and 257 DNA samples from healthy controls were studied. The samples were genotyped by PCR-RFLP. Epidemiological, clinical, and reproductive factors were analyzed. Statistical tests conducted included the χ 2 test, Fisher's exact test, and Mann-Whitney and Kruskal-Wallis tests or their parametric equivalents., Results: There was a high frequency of the rs2228480*GG genotype among the ER-positive tumors (OR=2.13; 95% CI=1.189-3.816) and it showed minor association with clinical stage 0 (OR=0.324; 95% CI=0.116-0.904). The rs2228480*GA genotype was associated with minor ER expression, whereas rs2228480*GG was associated with high expression of the progesterone receptor (PR). The frequency of rs4986938*GA was high among women who breastfed (OR=2.11; 95% CI=1.203-3.702), and it showed high association with clinical stage 0 (OR=4.383; 95% CI=1.606-11.96) whereas it had minor association with systemic arterial hypertension (OR=0.53; 95% CI=0.319-0.880). The rs2228480*GG/rs4986938*GG haplotype occurred at a low frequency among women who breastfed (OR=0.525; 95% CI=0.298-0.924) but it was associated with a high expression of PR., Conclusion: The rs2228480 and rs4986938 variants did not alter sporadic BC risk, but they did modulate the BC severity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Burkitt lymphoma (BL) is an aggressive B cell lymphoma characterized by the reciprocal translocation of the c-Myc gene with immunoglobulin genes. Recently, MYC has been shown to maintain the neoplastic state via the miR-17-92 microRNA cluster that suppresses chromatin regulatory genes and the apoptosis regulator Bim. However, the expression and prognostic impact of miR-17-92 members in pediatric BL (pBL) are unknown. Therefore, we investigated miR-17, miR-19a, miR-19b, miR-20, and miR-92a expression and prognostic impact in a series of 41 pBL samples. In addition, Bim protein expression was evaluated and compared to miR-17, miR-19a, miR-19b, miR-20, and miR-92a levels and patient outcomes. The expression of miR-17-92 members was evaluated by qPCR and Bim protein by immunohistochemistry. Log-rank test was employed to assess prognostic impact. We found that upregulated expression of miR-17 and miR-20a correlates with lack of pro-apoptotic Bim expression. Patients bearing tumors with upregulated miR-17 displayed decreased overall survival (OS), and multivariate analysis revealed that miR-17 was a significant predictor of shortened OS. Using hairpin inhibitors, we showed that inhibition of miR-17 resulted in enhanced Bim expression in a BL cell line overexpressing the miR-17-92 cluster. Our results describe for the first time miR-17, miR-19a, miR-19b, miR-20a, and miR-92a expression profiles in pBL. The prognostic impact of miR-17 should be validated in a larger series, and may provide new therapeutic avenues in the era of anti-miRNA therapy research. Additional functional studies are further required to understand the specific role of miR-17-92 cluster members in BL.

The present study aims at establishing whether the diversity in pathogenesis within a genetically diverse host population infected with a single polyclonal strain of Trypanosoma cruzi is due to selection of specific subpopulations within the strain. For this purpose we infected Swiss mice, a genetically diverse population, with the polyclonal strain of Trypanosoma cruzi Berenice-78 and characterized via LSSP-PCR the kinetoplast DNA of subpopulations isolated from blood samples collected from the animals at various times after inoculation (3, 6 and 12 months after inoculation). We examined the biological behavior of the isolates in acellular medium and in vitro profiles of infectivity in Vero cell medium. We compared the characteristics of the isolates with the inoculating strain and with another strain, Berenice 62, isolated from the same patient 16 years earlier. We found that one of the isolates had intermediate behavior in comparison with Berenice-78 and Berenice-62 and a significantly different genetic profile by LSSP-PCR in comparison with the inoculating strain. We hereby demonstrate that genetically distinct Trypanosoma cruzi isolates may be obtained upon experimental murine infection with a single polyclonal Trypanosoma cruzi strain.

Phospholamban (PLN) is an effective inhibitor of the sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA). Here, we examined PLN stability and degradation in primary cultured mouse neonatal cardiomyocytes (CMNCs) and mouse hearts using immunoblotting, molecular imaging, and [(35)S]methionine pulse-chase experiments, together with lysosome (chloroquine and bafilomycin A1) and autophagic (3-methyladenine and Atg5 siRNA) antagonists. Inhibiting lysosomal and autophagic activities promoted endogenous PLN accumulation, whereas accelerating autophagy with metformin enhanced PLN degradation in CMNCs. This reduction in PLN levels was functionally correlated with an increased rate of SERCA2a activity, accounting for an inotropic effect of metformin. Metabolic labeling reaffirmed that metformin promoted wild-type and R9C PLN degradation. Immunofluorescence showed that PLN and the autophagy marker, microtubule light chain 3, became increasingly colocalized in response to chloroquine and bafilomycin treatments. Mechanistically, pentameric PLN was polyubiquitinylated at the K3 residue and this modification was required for p62-mediated selective autophagy trafficking. Consistently, attenuated autophagic flux in HECT domain and ankyrin repeat-containing E3 ubiquitin protein ligase 1-null mouse hearts was associated with increased PLN levels determined by immunoblots and immunofluorescence. Our study identifies a biological mechanism that traffics PLN to the lysosomes for degradation in mouse hearts.

Methylation of CpG islands in promoter gene regions is frequently observed in lymphomas. DNA methylation is established by DNA methyltransferases (DNMTs). DNMT1 maintains methylation patterns, while DNMT3A and DNMT3B are critical for de novo DNA methylation. Little is known about the expression of DNMTs in lymphomas. DNMT3A and 3B genes can be regulated post-transcriptionally by miR-29 family. Here, we demonstrated for the first time the overexpression of DNMT1 and DNMT3B in Burkitt lymphoma (BL) tumor samples (69% and 86%, respectively). Specifically, the treatment of two BL cell lines with the DNMT inhibitor 5-aza-dC decreased DNMT1 and DNMT3B protein levels and inhibited cell growth. Additionally, miR-29a, miR-29b and miR-29c levels were significantly decreased in the BL tumor samples. Besides, the ectopic expression of miR-29a, miR-29b and miR-29c reduced the DNMT3B expression and miR-29a and miR-29b lead to increase of p16(INK4a) mRNA expression. Altogether, our data suggest that deregulation of DNMT1, DNMT3B and miR29 may be involved in BL pathogenesis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: This study determined the frequency of clinical features, reactivations, sequelae, mortality, and overall survival (OS) and compared paediatric with adult Langerhans cell histiocytosis (LCH) patients., Materials and Methods: Ninety patients (60 paediatric and 30 adults) with LCH treated during 28 years were analysed retrospectively., Results: Craniofacial lesion was the most frequent lesion at LCH presentation in children and adults. However, some differences were found. Orbital lesions were more frequent in paediatric than adult patients (P = 0.001). There was a tendency for mandible lesions to be more common in adults than the paediatric group (P = 0.0710). Mucocutaneous lesions were observed in a higher proportion in adults compared to paediatric patients (P = 0.0395). Reactivation episodes (36.8 versus 62.5%) and deaths (10.7 versus 24.0%) occurred in lower proportions in paediatric than adult patients, respectively. The probability of OS in 10 years for both groups was similar (P = 0.137)., Conclusion: The OS was similar in both groups despite clinical differences between paediatric and adult patients, and higher reactivation and death rates in adults.

CDKN2A is a tumor suppressor gene critical in the cell cycle regulation. Little is known regarding the role of CDKN2A methylation in the pathogenesis of Burkitt lymphoma (BL). CDKN2A methylation was investigated using pyrosequencing in 51 tumor samples. p16(INK4a) mRNA and protein levels were measured using real-time PCR and immunohistochemistry, respectively. CDKN2A methylation was detectable in 72% cases. Nuclear expression of p16(INK4a) was not detected in 41% cases. There was an association between methylation and absence of CDKN2A mRNA (P=0.003). In conclusion, CDKN2A methylation occurs at a high frequency suggesting a role in BL pathogenesis and potential therapeutic implications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma more common in children comprising one third of pediatric non-Hodgkin lymphoma cases. The recent discovery in BL pathogenesis highlighted the activation of PI3K pathway in cooperation with Myc in the development of BL. In this study, we demonstrated that PI3K/Akt pathway is a target to histone deacetylase inhibitor (HDACi) in BL cells. The combination of HDACi (sodium butyrate, NaB) and chemotherapy (VP-16) inhibited 51 % of the proliferation and enhanced the blockage of the cell cycle progression at G2/M with a concurrent decrease in the S phase. Microarray profiling showed a synergistic action of NaB/VP-16 combination through the differential regulation of 1,413 genes. Comparing VP-16 treatment with the NaB/VP-16 combination, 318 genes were deregulated: 250 genes were downregulated, and 68 were upregulated when compared with untreated cells. Among these genes, six (CDKN1A, CCND1, FAS, CHEK2, MDM4, and SESN2) belong to the p53-signaling pathway. The activation of this signaling pathway is usually induced by stress signals and ultimately leads to cell cycle arrest. Besides, the inhibition of the cell growth was related to reduced Akt phosphorylation, and decrease of c-Myc protein expression by about 60 % (p ≤ 0.005). Moreover, HDACi enhanced miR-101, miR-143, and miR-145 levels in BL cell line, which were inversely associated with the levels of miR-101, miR-143, and miR-145 found to be extremely downregulated in the sample of BL patients. We highlight the fact that effective combinations of HDACis with other target drugs could improve BL therapy in the future.

Centroblastic diffuse large B cell lymphoma (DLBCL) samples were analyzed by immunohistochemistry to evaluate the expression of p53, Bcl-2, Survivin, XIAP, and Ki-67. Survivin was the only protein which expression exhibited a trend for impact in progression-free (p = .077) and overall survival (p = .054). In the Mann-Whitney test, Survivin expression correlated with a negative overall survival (p = .045). These results appeared to be intimately related to Survivin cytoplasmic localization. Moreover, the anti-apoptotic proteins Bcl-2 and Survivin were less frequent in centroblastic DLBCL. Our results indicate that centroblastic DLBCL may be a disease with characteristic biology and clinical course and, therefore, specific prognostic factors.

The aim of the current study was to verify if cattle vaccinated against leptospirosis may react in diagnostic tests for brucellosis. Sixty cows were divided into 5 groups, each comprising 12 animals. Four groups were given different vaccines against leptospirosis, while the control group received only saline. Two doses of vaccine were given, as recommended by the manufacturers. Serum samples were collected on the first day of immunization (day 0) and on postvaccination days 7, 14, 21, 28, 35, 42, 49, 56, 96, and 126. All the serum samples were tested for brucellosis and leptospirosis. Twenty animals were reactive at least once to the Rose Bengal test, but by day 96, no further reactions were elicited by this test. Twenty-six samples were reactive to the Rose Bengal test, but only 7 remained positive in confirmatory tests: 1 to the 2-mercaptoethanol test, 2 to the fluorescence polarization assay, and 6 to indirect enzyme-linked immunosorbent assays. None of the samples was reactive in the complement fixation test. None of the animals in the control group was reactive. A significant difference was found between the control group and the groups vaccinated against leptospirosis, according to Fisher exact test. However, the groups were found to respond independently of the vaccine brand. The results indicate that cattle vaccinated against leptospirosis may show reactivity on screening tests for brucellosis.

Various dietary carbohydrates have been linked to obesity and altered adipose metabolism; however, the influences of honey vs common sweeteners have not been fully explored. We hypothesized that in comparison with sucrose, a honey-based diet would promote lower weight gain, adiposity, and related biomarkers (leptin, insulin, and adiponectin) as well as a better blood lipid profile. Thirty-six male Sprague-Dawley rats (228.1 ± 12.5 g) were equally divided by weight into 2 groups (n = 18) and provided free access to 1 of 2 diets of equal energy densities differing only in a portion of the carbohydrate. Diets contained 20% carbohydrate (by weight of total diet) from either clover honey or sucrose. After 33 days, epididymal fat pads were excised and weighed, and blood was collected for analyses of serum concentrations of lipids, glucose, and markers of adiposity and inflammation. Body weight gain was 14.7% lower (P ≤ .05) for rats fed honey, corresponding to a 13.3% lower (P ≤ .05) consumption of food/energy, whereas food efficiency ratios were nearly identical. Epididymal fat weight was 20.1% lower (P ≤ .05) for rats fed honey. Serum concentrations of triglycerides and leptin were lower (P ≤ .05) by 29.6% and 21.6%, respectively, and non-high-density lipoprotein cholesterol was higher (P ≤ .05) by 16.8% for honey-fed rats. No significant differences in serum total cholesterol, high-density lipoprotein cholesterol, adiponectin, C-reactive protein, monocyte chemoattractant protein-1, glucose, or insulin were detected. These results suggest that in comparison with sucrose, honey may reduce weight gain and adiposity, presumably due to lower food intake, and promote lower serum triglycerides but higher non-high-density lipoprotein cholesterol concentrations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Tumor-derived DNA is elevated in the plasma of patients with cancer. The analysis of circulating DNA may be useful for diagnosis, prognosis evaluation, and early detection of disease recurrence. In order to investigate cf-DNA as a marker during treatment, we serially quantified total cell-free (cf) and EBV plasma DNA in 30 cases of pediatric B-non-Hodgkin lymphoma by real-time PCR. The cf-DNA levels were significantly increased in patient samples at diagnosis as compared with the healthy controls (p < 0.001). At the end of treatment, a significant decrease in plasma DNA concentration was observed as compared with values observed at diagnosis (median: 94.0 copies/mL, p = 0.001). EBV was detected by ISH in 7/30 patients. Plasma EBV DNA levels were obtained from seven EBV-positive patients (median: 1278 copies/mL), while EBV DNA was not detected in 23 EBV-negative patients and 10 healthy controls. The association between the two methods of detection was statistically significant, with 100% correlation (Kappa coefficient, p = 1). In addition, the decrease of EBV viral load was associated with therapy response. Quantification of plasma EBV DNA may become a valuable source for disease detection of pediatric EBV-associated lymphomas and for monitoring treatment response.

Transplant patients are particularly at risk of developing B post-transplant lymphoproliferative disease (PTLD) related to intensive immunosuppressive treatment to prevent graft rejection. In EBV-positive PTLDs, EBV-DNA can be found in the patients' peripheral blood. Several methods have been described to assess peripheral blood EBV viral load. We report a case of a 13-year-old child who developed EBV-positive PTLD after renal transplantation. We assessed EBV plasma viral load by quantitative PCR and we found that the clearance of EBV-DNA correlated well with response to treatment.

It has been suggested that alterations of cell cycle genes probably contribute to the pathogenesis of endemic Burkitt's lymphoma (BL) in addition to c-MYC translocation. Mutations disrupting the normal nuclear localization signal of the retinoblastoma-related gene Rb2/p130 have been documented in BL cell lines and primary tumors from endemic areas. The aim of this study was to investigate the involvement of Rb2/p130 gene in the pathogenesis of sporadic BL in Brazil. DNA samples from 26 pediatric BL tumors and two healthy blood donors were screened by PCR amplification followed by single strand conformation polymorphism analysis of exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus), where most of the point mutations in the Rb2/p130 gene were identified. No abnormal band shifts were present in the samples analyzed. We concluded that mutations in exons 19-22 of the Rb2/p130 are unlikely to be involved directly in the pathogenesis of sporadic Brazilian BL., (Copyright (c) 2006 Wiley-Liss, Inc.)