Association of Polymorphisms in Cytokine genes with susceptibility to Precancerous Lesions and Cervical Cancer: A systematic review with meta-analysis.

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools.Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case-control studies.Results: A total of 35 relevant case-control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA -308 G > A and IL-10 - 1082A>G) and ZNF263 (TNFA -238 G > A) transcription factors binding.Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.

Daily variations in the expression of miR-16 and miR-181a in human leukocytes.

Circadian rhythms are controlled by a molecular mechanism that is organized in transcriptional and translational feedback loops of gene expression. Recent studies have been demonstrating the involvement of microRNAs (miRs) in post-transcriptional/translational control of circadian rhythms. In the present study we aimed to analyze the daily variations of miR-16 and miR-181a expression in human leukocytes. These miRs were independently associated with hematopoiesis and circadian rhythms in previous studies using experimental models. Peripheral blood from 6 subjects was sampled in a 24 hour period for expression analysis using quantitative real-time PCR (RT-qPCR). Initially, we evaluated the expression stability of RNU6-2, RNU1A-1, RNU5A-1, SNORD-25, SCARNA-17 and SNORA-73A as candidate genes for normalization of RT-qPCR data. The combination of the four most stable genes (SNORA-73A/SCARNA-17/SNORD-25/RNU6-2) was indicated to provide a better normalization of miRs expressions. The results show a daily variation of miR-181a and miR-16 expression in human leukocytes, suggesting a potential participation of these genes in the modulation of the circadian rhythms present in blood cells.

Building a National Pediatric Cancer Center and Network in Paraguay: Lessons for Addressing Challenges in a Low-income Country.

In Paraguay, cancer is among the leading causes of death among children. We report challenges and solutions for building the country's first pediatric cancer center at the National University School of Medicine (PCC-SM) and describe the outcomes of the National Network for Pediatric Cancer. We found that children with acute lymphoblastic leukemia treated between 2008 and 2012 had higher 3-year survival rates and lower treatment abandonment rates than did children treated between 2000 and 2007 before the network was established. This improvement directly coincided with the increased treatment capacity of the PCC-SM. Herein, we describe the role of local, national, and international contributors in improving the health care at Paraguay's PCC-SM and discuss how expediting access to specialized cancer diagnosis and care and implementing a system for referral and follow-up visits can improve cancer outcomes in other low-resource countries.

Molecular epidemiology of hepatitis B virus in Paraguay.

Hepatitis B virus (HBV) infection is a leading cause of severe chronic liver disease worldwide. The HBV epidemiology in Latin American countries is complex and the data is still scanty and fragmentary. The aim of this study was to investigate the distribution of HBV genotypes in Paraguay and to estimate the viral population dynamic and spread pattern of the main phylogenetic group. To this end, partial and complete genome sequences were obtained from 60 blood donor candidates and analysed by phylogenetic and Bayesian phylodynamic approaches. The phylogenetic analysis based on sequences of partial Polymerase/Pre-S1 overlapping region showed a predominance of the Native American subgenotype F4 (81.7%), the presence of the European subgenotypes A2 (1.7%) and D3 (8.3%), the African subgenotype A1 (3, 5%) and the Asian subgenotypes B2 (1.7%) and C2 (1.7%). The distribution of HBV genotypes was in accordance with the ethnic composition of the population. The phylogeographic analysis of subgenotype F4 complete genomes suggests that this lineage emerged and spread in the last 300 years. Paraguay was the most probable location of the common ancestor. The lineage diverged into two main clades and spread to neighbor regions, mainly Bolivia and Northwest Argentina, and Buenos Aires. The phylogeny showed a scanty geographical structure and a complex migratory pattern. In conclusion, the HBV genotypes circulating in Paraguay reflect the ethnic origin of the population. The distribution of genotypes and the phylogeographic reconstruction showed the impact of both global and local migrations in shaping the HBV molecular epidemiology in the region.

Characterization and Structural Performance in Bending of CLT Panels Made from Small-Diameter Logs of Loblolly/Slash Pine.

The main objective of this work was to study the structural viability of using small-diameter logs of Uruguayan Loblolly/Slash pine, mainly from thinning operations, to design cross-laminated timber (CLT) panels. A visual grade named "CTH" (coniferous thinning) was proposed, and 45 specimens of sawn timber boards were tested, resulting in 51% lower bending strength than that of the minimum strength class C14. Subsequently, 20 CLT panels were manufactured and experimentally tested, the results showed that the bending strength of the CLT panels was 43% above that of the individual layers. Additionally, the structural performance of the CLT panels for use in floors was calculated, and the thickness-span relationship depending on strength class and imposed load are presented. Results showed than the use of CTH timber to design CLT floors implies a volume (m³/m²) 17% higher than that using C24 timber.

Usual normalization strategies for gene expression studies impair the detection and analysis of circadian patterns.

Recent studies have shown that transcriptomes from different tissues present circadian oscillations. Therefore, the endogenous variation of total RNA should be considered as a potential bias in circadian studies of gene expression. However, normalization strategies generally include the equalization of total RNA concentration between samples prior to cDNA synthesis. Moreover, endogenous housekeeping genes (HKGs) frequently used for data normalization may exhibit circadian variation and distort experimental results if not detected or considered. In this study, we controlled experimental conditions from the amount of initial brain tissue samples through extraction steps, cDNA synthesis, and quantitative real time PCR (qPCR) to demonstrate a circadian oscillation of total RNA concentration. We also identified that the normalization of the RNA's yield affected the rhythmic profiles of different genes, including Per1-2 and Bmal1. Five widely used HKGs (Actb, Eif2a, Gapdh, Hprt1, and B2m) also presented rhythmic variations not detected by geNorm algorithm. In addition, the analysis of exogenous microRNAs (Cel-miR-54 and Cel-miR-39) spiked during RNA extraction suggests that the yield was affected by total RNA concentration, which may impact circadian studies of small RNAs. The results indicate that the approach of tissue normalization without total RNA equalization prior to cDNA synthesis can avoid bias from endogenous broad variations in transcript levels. Also, the circadian analysis of 2-Cycle threshold (Ct) data, without HKGs, may be an alternative for chronobiological studies under controlled experimental conditions.

Variants in SNCA Gene Are Associated with Parkinson's Disease Risk and Cognitive Symptoms in a Brazilian Sample.

Genetic susceptibility contributes to the etiology of sporadic Parkinson's Disease (PD) and worldwide studies have found positive associations of polymorphisms in the alpha-synuclein gene (SNCA) with the risk for PD. However, little is known about the influence of variants of SNCA in individual traits or phenotypical aspects of PD. Further, there is a lack of studies with Latin-American samples. We evaluated the association between SNCA single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs - rs2583988, rs356219, rs2736990, and rs11931074) and PD risk in a Brazilians sample. In addition, we investigated their potential interactions with environmental factors and specific clinical outcomes (motor and cognitive impairments, depression, and anxiety). A total of 105 PD patients and 101 controls participated in the study. Single locus analysis showed that the risk allele of all SNPs were more frequent in PD patients (p < 0.05), and the associations of SNPs rs2583988, rs356219, and rs2736990 with increased PD risk were confirmed. Further, the G-rs356219 and C-rs2736990 alleles were associated with early onset PD. T-rs2583988, G-rs356219 and C-2736990 alleles were significantly more frequent in PD patients with cognitive impairments than controls in this condition. In addition, in a logistic regression model, we found an association of cognitive impairment with PD, and the practice of cognitive activity and smoking habits had a protective effect. This study shows for the first time an association of SNCA polymorphism and PD in a South-American sample. In addition, we found an interaction between SNP rs356219 and a specific clinical outcome, i.e., the increased risk for cognitive impairment in PD patients.

Do suicide attempts occur more frequently in the spring too? A systematic review and rhythmic analysis.

BACKGROUND: Seasonal variations in suicides have been reported worldwide, however, there may be a different seasonal pattern in suicide attempts. The aim of this study was to perform a systematic review on seasonality of suicide attempts considering potential interfering variables, and a statistical analysis for seasonality with the collected data. METHOD: Observational epidemiological studies about seasonality in suicide attempts were searched in PubMed, Web of Science, LILACS and Cochrane Library databases with terms attempted suicide, attempt and season. Monthly or seasonal data available were evaluated by rhythmic analysis softwares. RESULTS: Twenty-nine articles from 16 different countries were included in the final review. It was observed different patterns of seasonality, however, suicide attempts in spring and summer were the most frequent seasons reported. Eight studies indicated differences in sex and three in the method used for suicide attempts. Three articles did not find a seasonal pattern in suicide attempts. Cosinor analysis identified an overall pattern of seasonal variation with a suggested peak in spring, considering articles individually or grouped and independent of sex and method used. A restricted analysis with self-poisoning in hospital samples demonstrated the same profile. LIMITATIONS: Grouping diverse populations and potential analytical bias due to lack of information are the main limitations. CONCLUSIONS: The identification of a seasonal profile suggests the influence of an important environmental modulator that can reverberate to suicide prevention strategies. Further studies controlling interfering variables and investigating the biological substrate for this phenomenon would be helpful to confirm our conclusion.

Predicted microRNAs for mammalian circadian rhythms.

There is little evidence for the involvement of microRNAs (miRs) in the regulation of circadian rhythms, despite the potential relevance of these elements in the posttranscriptional regulation of the clock machinery. The present work aimed to identify miRs targeting circadian genes through a predictive analysis of conserved miRs in mammals. Besides 23 miRs previously associated with circadian rhythms, we found a number of interesting candidate genes, equally predicted by the 3 software programs used, including miR-9, miR-24, miR25, miR-26, miR-27, miR-29, miR-93, miR-211, miR-302, and miR-346. Moreover, several miRs are predicted to be regulated by circadian transcription factors, such as CLOCK/BMAL, DEC2, and REV-ERBalpha. Using real-time PCR we demonstrated that the selected candidate miR-27b showed a daily variation in human leukocytes. This study presents predicted feedback loops for mammalian molecular clock and the first description of an miR with in vivo daily variation in humans.

Management of children with brain tumors in Paraguay.

BACKGROUND: Cure rates among children with brain tumors differ between low-income and high-income countries. To evaluate causes of these differences, we analyzed aspects of care provided to pediatric neuro-oncology patients in a low middle-income South American country. METHODS: Three methods were used to evaluate treatment of children with brain tumors in Paraguay: (1) a quantitative needs assessment questionnaire for local treating physicians, (2) site visits to assess 3 tertiary care centers in Asunción and a satellite clinic in an underdeveloped area, and (3) interviews with health care workers from relevant disciplines to determine their perceptions of available resources. Treatment failure was defined as abandonment of therapy, relapse, or death. RESULTS: All 3 tertiary care facilities have access to chemotherapy and pediatric oncologists but lack training and tools for neuropathology and optimal neurosurgery. The 2 public hospitals also lack access to appropriate radiological tests and timely radiotherapy. These results demonstrate disparities in Paraguay, with rates of treatment failure ranging from 37% to 83% among the 3 facilities. CONCLUSIONS: National and center-specific deficiencies in resources to manage pediatric brain tumors contribute to poor outcomes in Paraguay and suggest that both national and center-specific interventions are warranted to improve care. Disparities in Paraguay reflect different levels of governmental and philanthropic support, program development, and socio-economic status of patients and families, which must be considered when developing targeted strategies to improve management. Effective targeted interventions can serve as a model to develop pediatric brain tumor programs in other low- and middle-income countries.

Intususcepción intestinal debido a un pólipo fibroide inflamatorio (tumor de vanek) / Intestinal intussusception due to an inflammatory fibroid polyp (vanek tumor)

La intususcepción en un adulto debe hacer sospechar un tumor (benigno o potencialmente riesgoso); el diagnóstico certero es crucial para el tratamiento adecuado del paciente1. Alrededor del 90% de estos casos se dan en el intestino delgado y colon, el 10% restante se originan en el estómago y en estomas creados quirúrgicamente2. En los adultos, aproximadamente 90% de los casos de intususcepción son secundarios a una lesión definible3. El tumor de Vanek o pólipo fibroide inflamatorio, se conoce como una lesión benigna, rara, de localización submucosa, no encapsulada, cuya ubicación puede darse a lo largo del tracto digestivo, siendo más común en el antro gástrico (80 %), aunque también se ha descrito en la unión gastroesofágica, duodeno, yeyuno, íleon y colon4.

Intussusception in an adult must make us suspect the presence of a tumor (benign or potentially dangerous) as the most frequent cause. Accurate diagnosis is of great importance in order to provide appropriate treatment and improve patient prognosis1. About 90% of these cases occur in the small intestine and colon, and the remaining 10% originate in the stomach and surgically created ostomas2. In adults, approximately 90% of cases of intussusception are secondary to a definable lesión3. The Vanek's tumor or inflammatory fibroid polyp (IFP) is a rare benign lesion of submucosal location, not encapsulated, that may be located throughout the digestive tract, being more common in the gastric antrum (80%), although it has also been described in the gastroesophageal junction, duodenum, jejunum, ileum and colon4.