About 25% of cancer cases globally are due to excess weight and a sedentary lifestyle. These results are alarming, as the world knows a pandemic of obesity and, in consequence, insulin resistance. ...Obesity may increase risk for various cancers by several mechanisms, including increasing sex and metabolic hormones, and inflammation. Here, we present a review of epidemiological and molecular evidences linking obesity and cancer--particularly colorectal, post-menopausal breast, endometrial, pancreatic, high grade prostate, hepatocellular, gallbladder, kidney and esophageal adenocarcinoma. The expected striking increase in the incidence of cancer in the near future related to obesity turns the knowledge of this field of great impact as it is needed to the development of strategies to prevent and treat this disease.
São Paulo state (Brazil) has one of the most overpopulated coastal zones in South America, where previous studies have already detected sediment and water contamination. However, biological-based ...monitoring considering signals of xenobiotic exposure and effects are scarce. The present study employed a battery of biomarkers under field conditions to assess the environmental quality of this coastal zone. For this purpose, the activity of CYP 450, antioxidant enzymes, DNA damage, lipid peroxidation and lysosomal membrane were analysed in caged mussels and integrated using Factorial Analysis. A representation of estimated factor scores was performed in order to confirm the factor descriptions characterizing the studied areas. Biomarker responses indicated signals of mussels' impaired health during the monitoring, which pointed to the impact of different sources of contaminants in the water quality and identified critical areas. This integrated approach produced a rapid, sensitive and cost-effective assessment, which could be incorporated as a descriptor of environmental status in future coastal zones biomonitoring.
IntroductionCri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to ...confirm deletions in the short arm of chromosome 5 (5p-) greater than 10 Mb. In cases of smaller deletions, it is necessary to resort to other molecular techniques such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA) or genomic array. Case PresentationWe report a family with an atypical deletion in 5p (mother and 2 children) and variable phenotypes compared with the literature. We applied a P064 MLPA kit to evaluate 5p- in the mother and the 2 children, and we used the Infinium CytoSNP-850K BeadChip genomic array to evaluate the siblings, an 11-year-old boy and a 13-year-old girl, to better define the 5p breakpoints. Both children presented a high-pitched cry at birth, but they did not present any of the typical physical features of 5p- syndrome. The MLPA technique with 5 probes for the 5p region revealed that the patients and their mother presented an atypical deletion with only 4 probes deleted (TERT_ex2, TERT_ex13, CLPTM1L, and IRX4). The genomic array performed in the siblings' samples revealed a 6.2-Mb terminal deletion in 5p15.33p15.32, which was likely inherited from their mother, who presented similar molecular features, seen in MLPA. DiscussionThe sparing of the CTNND2 gene, which is associated with cerebral development, in both siblings may explain why these 2 patients had features such as better communication skills which most patients with larger 5p deletions usually do not present. In addition, both patients had smaller deletions than those found in patients with a typical 5p- phenotype. This report demonstrates the utility of genomic arrays as a diagnostic tool to better characterize atypical deletions in known syndromes such as 5p- syndrome, which will allow a better understanding of the genotype-phenotype correlations.
Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally ...associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.
This Open Access book presents the current state of the art knowledge on social and affective neuroscience based on empirical findings. This volume is divided into several sections first guiding the ...reader through important theoretical topics within affective neuroscience, social neuroscience and moral emotions, and clinical neuroscience. Each chapter addresses everyday social interactions and various aspects of social interactions from a different angle taking the reader on a diverse journey. The last section of the book is of methodological nature. Basic information is presented for the reader to learn about common methodologies used in neuroscience alongside advanced input to deepen the understanding and usability of these methods in social and affective neuroscience for more experienced readers.
Genomic rearrangements encompass deletions, duplications, inversions, insertions and translocations and may be the cause of several genetic diseases. One of the most frequent mechanisms that generate ...these rearrangements is the Non-Allelic Homologous Recombination (NAHR). They are caused by a misalignment between regions of high level of similarity, like Low Copy Repeats (LCRs) and Alu sequences. We aimed to sequence the breakpoint of a patient with a single deletion on chromosome 22q13.2 in order to understand the genomic structure of the region involved as well as elucidate the mechanism behind this rearrangement. Investigating breakpoints are of the utmost importance in the understanding the influence of the genomic architecture in clinical assays. We flanked the breakpoint detected by array and then we captured the regions using Illumina Nextera Rapid Capture Custom to sequence with Illumina MiSeq. We found a chimeric read on Chr22:41,026,090, setting a 624,688 bp deletion on Chr22:41,026,112-41,650,780 (hg19). This deletion merges the intronic region of MKL1 and RANGAP1 genes, on two different Alu sequences (AluSx and AluY, respectively). The sequence of the breakpoint reveals that Alu elements are an important characteristic of the human genome on generating rearrangements.
•We investigated the breakpoint on chromosome 22q13.2 in order to understand the genomic structure of the region involved as well as elucidate the mechanism behind this rearrangement.•Our results showed that the breakpoint is inserted in two different Alu regions and the absence of micro-homology inside the breakpoint, lead us to consider NAHR mechanism driven by Alu. It is the first time that a fusion between MKL1 and RANGAP1 genes are sequenced.•Delineate breakpoints is important to understanding the influence of the genomic architecture in clinical assays.
Although
Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of ...daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon.
Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group,
= 20) or placebo (unfermented milk,
= 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon.
Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group.
For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.
Introduction COVID-19 pandemic posed major challenges in obstetric health care services. Preparedness, development, and implementation of new protocols were part of the needed response. This study ...aims to describe the strategies implemented and the perspectives of health managers on the challenges to face the pandemic in 16 different maternity hospitals that comprise a multicenter study in Brazil, called REBRACO (Brazilian network of COVID-19 during pregnancy). Methods Mixed-method study, with quantitative and qualitative approaches. Quantitative data on the infrastructure of the units, maternal and perinatal health indicators, modifications on staff and human resources, from January to July/2020. Also, information on total number of cases, and availability for COVID-19 testing. A qualitative study by purposeful and saturation sampling was undertaken with healthcare managers, to understand perspectives on local challenges in facing the pandemic. Results Most maternities early implemented their contingency plan. REBRACO centers reported 338 confirmed COVID-19 cases among pregnant and post-partum women up to July 2020. There were 29 maternal deaths and 15 (51.8%) attributed to COVID-19. All maternities performed relocation of beds designated to labor ward, most (75%) acquired mechanical ventilators, only the minority (25%) installed new negative air pressure rooms. Considering human resources, around 40% hired extra health professionals and increased weekly workload and the majority (68.7%) also suspended annual leaves. Only one center implemented universal screening for childbirth and 6 (37.5%) implemented COVID-19 testing for all suspected cases, while around 60% of the centers only tested moderate/severe cases with hospital admission. Qualitative results showed that main challenges experienced were related to the fear of the virus, concerns about reliability of evidence and lack of resources, with a clear need for mental health support among health professionals. Conclusion Study findings suggest that maternities of the REBRACO initiative underwent major changes in facing the pandemic, with limitations on testing, difficulties in infrastructure and human resources. Leadership, continuous training, implementation of evidence-based protocols and collaborative initiatives are key to transpose the fear of the virus and ascertain adequate healthcare inside maternities, especially in low and middle-income settings. Policy makers need to address the specificities in considering reproductive health and childbirth during the COVID-19 pandemic and prioritize research and timely testing availability.
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