An RNA virus hijacks an incognito function of a DNA repair enzyme

A previously described mammalian cell activity, called VPg unlinkase, specifically cleaves a unique protein-RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection. For over three decades, the identity of this cellular activity and its normal role in the uninfected cell had remained elusive. Here we report the purification and identification of VPg unlinkase as the DNA repair enzyme, 5'-tyrosyl-DNA phosphodiesterase-2 (TDP2). Our data show that VPg unlinkase activity in different mammalian cell lines correlates with their differential expression of TDP2. Furthermore, we show that recombinant TDP2 can cleave the protein-RNA linkage generated by different picornaviruses without impairing the integrity of viral RNA. Our results reveal a unique RNA repair-like function for TDP2 and suggest an unusual role in host-pathogen interactions for this cellular enzyme. On the basis of the identification of TDP2 as a potential antiviral target, our findings may lead to the development of universal therapeutics to treat the millions of individuals afflicted annually with diseases caused by picornaviruses, including myocarditis, aseptic meningitis, encephalitis, hepatitis, and the common cold.     

Characteristics of individuals meeting criteria for new onset panic attacks following exposure to a typhoon

The association between trauma exposure and panic attacks has received increased attention over the past decade, with mounting evidence suggesting an overlapping etiologic pathway. This study examined the incidence of new onset panic attacks in 775 Vietnamese individuals in the 2–3 months following Typhoon Xangsane. Pre-typhoon (Wave 1) and post-typhoon (Wave 2) assessments were conducted, allowing for consideration of factors occurring prior to the typhoon in addition to typhoon-relevant responding. Of the 775 participants, 11.6% (n=90) met criteria for lifetime panic attack pre-typhoon and 2.8% (n=22) met post-typhoon panic attack criteria. Individuals with pre-typhoon panic were significantly older and reported less education compared to the no-panic group. Individuals in both panic groups were more likely to screen positive on a Wave1 psychiatric screening measure, endorse greater typhoon exposure and prior traumatic event exposure and were significantly more likely to meet DSM-IV criteria for posttraumatic stress disorder (PTSD) and major depression (MDD) post-typhoon compared with persons reporting no history of panic attacks. Pre and post-typhoon panic exhibited similar patterns across variables and both panic conditions were associated with the development of PTSD and MDD, suggesting that persons experiencing panic attacks may represent a vulnerable population in need of early intervention services.     

Binge-like ethanol exposure during the early postnatal period impairs eyeblink conditioning at short and long CS-US intervals in rats

Binge-like ethanol exposure on postnatal days (PD) 4-9 in rodents causes cerebellar cell loss and impaired acquisition of conditioned responses (CRs) during "short-delay" eyeblink classical conditioning (ECC), using optimal (280-350 ms) interstimulus intervals (ISIs). We extended those earlier findings by comparing acquisition of delay ECC under two different ISIs. From PD 4 to 9, rats were intubated with either 5.25 g/kg of ethanol (2/day), sham intubated, or were not intubated. They were then trained either as periadolescents (about PD 35) or as adults (>PD 90) with either the optimal short-delay (280-ms) ISI, a long-delay (880-ms) ISI, or explicitly unpaired CS and US presentations. Neonatal binge ethanol treatment significantly impaired acquisition of conditioning at both ages regardless of ISI, and deficits in the acquisition and expression of CRs were comparable across ISIs. These deficits are consistent with the previously documented ethanol-induced damage to the cerebellar-brainstem circuit essential for Pavlovian ECC.     

WHO's Service Availability and Readiness Assessment of primary health care services of commune health centers in a rural district of Northern Vietnam

The objective of this study was to assess the availability and readiness of the primary health care (PHC) services of commune health centers (CHCs) in Quoc Oai, a rural district of Northern Vietnam based on the World Health Organization's Service Availability and Readiness Assessment (SARA) tool. The study was done in 2 steps. First, the heads of the 21 CHCs of Quoc Oai district were interviewed using SARA, a quantitative survey, and the responses were then validated by direct observations of each facility. The results showed that although the average number of health staffs in each CHC met the national standards (at least 5 staffs per CHC), its allocation within each CHC was not properly met because some CHCs had only 2 health staffs. Several health equipment and facilities were not fully available in many CHCs, and although the majority of the PHC services were available at the CHCs, their readiness remained limited. Several significant correlates between the availability of health care workers and the availability of the facilities and the PHC services were observed, suggesting that they depend upon and affect one another in the health system. Using the SARA‐based inventory, the study helps health managers and policy makers to prioritize efforts and allocate resources more appropriately. To be effective, attention should be given to how to make facilities, services, and human resources for health ready for PHC activities—more investment and support from the system (from higher to lower level) and the government.     

Does the Age Affect the Fluoroscopy‐Guided Transseptal Puncture in Catheter Ablation of Atrial Fibrillation?

BACKGROUND: The anatomical differences with age may raise difficulty in determining the proper positioning of the transseptal puncture site in the therapeutic left heart catheterization. This study investigated whether age affects the fluoroscopy-guided transseptal puncture in the catheter ablation of atrial fibrillation. METHODS AND RESULTS: Fifty patients (52 +/- 12 years, 35 men) who underwent ablation for paroxysmal/persistent atrial fibrillation were included. The patients were divided into two groups according to their age (cut-point 50 y/o): young group (n = 20) and old group (n = 30). In the 30 degrees right anterior oblique view (RAO), the width between the transseptal puncture site and coronary sinus ostium (H (N-CSO)) was longer in old-age group (14.4 +/- 9.4 vs 10.9 +/- 10.4 mm, P = 0.034). In the 60 degrees left anterior oblique view (LAO) view, the angle of the direction of the transseptal needle (N-angle) was less in the old-age group (56.0 +/- 10.0 degrees vs 58.4 +/- 9.8 degrees , P = 0.041). The ratio of the transseptal puncture site-coronary sinus ostium (CSO) distance over the distance between the superior vena cava-right atrial junction and CSO (V(N-CSO)/V(J-CSO)) was significantly higher in the old-age group (0.73 +/- 0.12 vs 0.63 +/- 0.2, P = 0.009). CONCLUSION: The transseptal puncture site in the RAO view moved higher and more posterior and the transseptal puncture angle in the LAO view decreased with age. These findings highlight the influence of age on the atrial anatomy and transseptal puncture site.