Footprints of BK and JC polyomaviruses in specimens from females affected by spontaneous abortion.

STUDY QUESTION: Are JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) infections associated with spontaneous abortion (SA)? SUMMARY ANSWER: There is no association of JCPyV or BKPyV with SA. WHAT IS KNOWN ALREADY: A large number of risk factors have been associated with SA. The role of polyomaviruses, including JCPyV and BKPyV, in SA remains to be clarified. STUDY DESIGN, SIZE, DURATION: This is a case-control study including women affected by spontaneous abortion (SA, n = 100, the cases) and women who underwent voluntary interruption of pregnancy (VI, n = 100, the controls). PARTICIPANTS/MATERIALS, SETTING, METHODS: Viral DNAs were investigated by qualitative PCR and quantitative droplet-digital PCR (ddPCR) in matched chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from SA (n = 100) and VI (n = 100). Indirect ELISAs with mimotopes/synthetic peptides corresponding to JCPyV and BKPyV viral capsid protein 1 epitopes were then employed to investigate specific IgG antibodies against JCPyV and BKPyV in human sera from SA (n = 80) and VI (n = 80) cohorts. MAIN RESULTS AND THE ROLE OF CHANCE: JCPyV DNA was detected in 51% and 61% of SA and VI samples, respectively, with a mean viral DNA load of 7.92 copy/104 cells in SA and 5.91 copy/104 cells in VI (P > 0.05); BKPyV DNA was detected in 11% and 12% of SA and VI specimens, respectively, with a mean viral DNA load of 2.7 copy/104 cells in SA and 3.08 copy/104 cells in VI (P > 0.05). JCPyV was more prevalent than BKPyV in both SA and VI specimens (P < 0.0001). In PBMCs from the SA and VI cohorts, JCPyV DNA was detected with a prevalence of 8% and 12%, respectively, with a mean viral DNA load of 2.29 copy/104 cells in SA and 1.88 copy/104 cells in VI (P > 0.05). The overall prevalence of serum IgG antibodies against JCPyV detected by indirect ELISAs was 52.5% and 48.7% in SA and VI groups, respectively, whereas BKPyV-positive sera were found in 80% SA and 78.7% VI samples. LIMITATIONS, REASONS FOR CAUTION: This study did not investigate the presence of viral mRNA and/or proteins, which are indicative of an active viral infection, and these might be taken into consideration in future studies. WIDER IMPLICATIONS OF THE FINDINGS: JCPyV and BKPyV DNA sequences were detected and quantitatively analyzed for the first time by PCR/ddPCR in chorionic villi tissues and PBMCs from SA and VI specimens. Moreover specific immunological approaches detected serum IgG against JCPyV/BKPyV. Statistical analyses, however, do not indicate an association between these polyomaviruses and SA. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the University of Ferrara, FAR research grants and the University Hospital of Ferrara/University of Ferrara joint grant. No potential conflicts of interest were disclosed.

La epigenética en el tratamiento del dolor / Epigenetics in the treatment of pain

Introducción: La epigenética se refiere a los cambios en el ADN e histonas que no implican alteraciones en la secuencia de nucleótidos y modifican la estructura y condensación de la cromatina, afectando de esta manera la expresión génica y el fenotipo. Las modificaciones epigenéticas son metilación del ADN y modificaciones de histonas. Objetivo: Realizar una revisión de la literatura sobre la importancia de la epigenética en la fisiopatología y el tratamiento del dolor. Materiales y métodos: se hizo una revisión de la bibliografía sobre el concepto de epigenética, sus bases biológicas, impacto sobre el dolor y su relación con posibles tratamientos. Resultados: Los mecanismos epigenéticos han cobrado cada vez más importancia debido a la creciente asociación con enfermedades complejas y comunes, así como por su influencia en el dolor y sus posibles tratamientos. Conclusiones: La epigenética tiene una clara relación en el dolor, en sus bases fisiopatológicas y posibles tratamientos

Introduction: Epigenetics refers to changes in DNA and histones that do not involve alterations in the nucleotide sequence and modify the structure and condensation of the chromatin, thus affecting gene expression and phenotype. Epigenetic modifications are DNA methylation and histone modifications. Objective: To carry out a review of the literature on the importance of Epigenetics in the pathophysiology and treatment of pain. Materials and methods: A review of the literature on the concept of epigenetics, its biological bases, the impact on pain and its relation to possible treatments. Results: Epigenetic mechanisms have become increasingly important due to the growing association with complex and common diseases, as well as their influence on pain and its possible treatments. Conclusions: Epigenetics has a clear relationship in pain, its pathophysiological bases and possible treatments

The polio eradication endgame: Why immunization and continued surveillance is critical.

The poliovirus is very close to being eradicated from the world. To this end, the four main objectives of the World Health Organization's Polio Eradication & Endgame Strategic Plan 2013-2018 are to: detect and interrupt all poliovirus transmission; strengthen immunization systems and withdraw oral polio vaccine; contain poliovirus and certify interruption of transmission; and plan polio's legacy. There is a need to maintain vigilance for circulating vaccine-derived polioviruses as well as maintaining both epidemiological and laboratory surveillance for polio at this critical point in history. Despite the elimination of indigenous wild poliovirus transmission in Canada, the risk of wild poliovirus importation from endemic countries, and the risk of importation of circulating vaccine strains remains. Due to this ongoing risk, active surveillance of acute flaccid paralysis (AFP) in children less than 15 years of age remains important. At least one stool specimen from all suspect AFP cases should be sent to the National Microbiology Laboratory at the Public Health Agency of Canada for polio isolation and testing to support and verify Canada's polio-free status. An added benefit of this is that it may also help identify other non-polio enteroviruses, such as enterovirus D68.

Pertussis Surveillance in Canada: Trends to 2012.

OBJECTIVE: The purpose of this report is to provide a summary of the pertussis activity in Canada. METHODS: A descriptive analysis of pertussis incidence by year, age group, gender and province/territory was conducted using national surveillance data, clinical administrative data and vital statistics data. RESULTS: Pertussis is an endemic cyclical disease in Canada with peaks in activity occurring every 2 to 5 years. Canada has experienced a decline in pertussis activity following the introduction of routine pertussis immunization programs. The incidence of pertussis is highest in infants and children. Hospitalization and mortality are more common among infants, particularly those less than three months of age. Trends in pertussis vary by province and territory. Canada experienced a notable increase in incidence in 2012. Reasons for this increase are unknown. CONCLUSION: Our understanding of the epidemiology of pertussis in Canada could be enhanced by improved approaches for monitoring the disease. Although the peak in activity observed in 2012 could be an isolated event, further work to support outbreak response in provinces and territories, including rapid research tools and resources, should be considered.

Methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples of infertile couples correlates with recurrent spontaneous abortion.

STUDY QUESTION: Is the methylation status of the methylenetetrahydrofolate reductase (MTHFR) promoter region in semen samples associated with 'recurrent spontaneous abortion' (RSA)? SUMMARY ANSWER: MTHFR promoter hypermethylation is more frequent in semen samples from RSA couples than in semen samples from infertile couples with no history of RSA (NRSA) and affects the whole sperm population significantly more often. WHAT IS KNOWN ALREADY: Modifications to the MTHFR gene such as polymorphisms and promoter methylations are associated with male infertility. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of semen samples from 20 RSA couples, 147 NRSA couples and 20 fertile men between 2011 and 2012. MATERIALS, SETTING AND METHODS: DNA from the semen samples of RSA, NRSA and fertile men were analyzed by methylation-specific PCR amplification using primers which anneal to the methylated or unmethylated cytosine-phosphodiester bond guanine (CpG) islands within the promoter region of MTHFR. The specificity of the PCR products was assessed by DNA sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: The methylated MTHFR epigenotype (including samples where it co-existed with unmethylated MTHFR epigenotypes) was detected in 75% of RSA men, 54% of NRSA men and 15% of fertile men. MTHFR methylation was observed in the whole sperm population in semen samples from 55% of RSA men compared with 8% in NRSA men (P < 0.05) and 0% in fertile men (P < 0.05). DNA sequencing analysis was fully concordant with the PCR results and revealed that when MTHFR methylation occurred, CpG islands within the promoter region were 100% methylated (hypermethylation of MTHFR promoter). LIMITATIONS, REASONS FOR CAUTION: The relatively small sample size of RSA infertile couples. WIDER IMPLICATIONS OF THE FINDINGS: The hypermethylation of the MTHFR gene promoter should be taken into consideration as a novel putative risk factor in RSA etiology. STUDY FUNDING/COMPETING INTEREST(S): Our institution has received an FAR research grant from the University of Ferrara, Ferrara, Italy. No competing interests declared.