BACKGROUND: Although device-based optimization has been developed to overcome the limitations of conventional optimization methods in cardiac resynchronization therapy (CRT), few real-world data supports the results of clinical trials that showed the efficacy of automatic optimization algorithms. We investigated whether CRT using the adaptive CRT algorithm is comparable to non-adaptive biventricular (BiV) pacing optimized with electrocardiogram or echocardiography-based methods. METHODS: Consecutive 155 CRT patients were categorized into 3 groups according to the optimization methods: non-adaptive BiV (n = 129), adaptive BiV (n = 11), and adaptive left ventricular (LV) pacing (n = 15) groups. Additionally, a subgroup of patients (n = 59) with normal PR interval and left bundle branch block (LBBB) was selected from the non-adaptive BiV group. The primary outcomes included cardiac death, heart transplantation, LV assist device implantation, and heart failure admission. Secondary outcomes were electromechanical reverse remodeling and responder rates at 6 months after CRT. RESULTS: During a median 27.5-month follow-up, there was no significant difference in primary outcomes among the 3 groups. However, there was a trend toward better outcomes in the adaptive LV group compared to the other groups. In a more rigorous comparisons among the patients with normal PR interval and LBBB, similar patterns were still observed. CONCLUSION: In our first Asian-Pacific real-world data, automated dynamic CRT optimization showed comparable efficacy to conventional methods regarding clinical outcomes and electromechanical remodeling.
Bundle-Branch Block ; Cardiac Resynchronization Therapy ; Death ; Electrocardiography ; Follow-Up Studies ; Heart Failure ; Heart Transplantation ; Humans ; Immunodeficiency Virus, Bovine

Integrase plays a critical role in the recombination of viral DNA into the host genome. Therefore, over the past decade, it has been a hot target of drug design in the fight against type 1 human immunodeficiency virus (HIV-1). Bovine immunodeficiency virus (BIV) integrase has the same function as HIV-1 integrase. We have determined crystal structures of the BIV integrase catalytic core domain (CCD) in two different crystal forms at a resolution of 2.45 Å and 2.2 Å, respectively. In crystal form I, BIV integrase CCD forms a back-to-back dimer, in which the two active sites are on opposite sides. This has also been seen in many of the CCD structures of HIV-1 integrase that were determined previously. However, in crystal form II, BIV integrase CCD forms a novel face-to-face dimer in which the two active sites are close to each other. Strikingly, the distance separating the two active sites is approximately 20 Å, a distance that perfectly matches a 5-base pair interval. Based on these data, we propose a model for the interaction of integrase with its target DNA, which is also supported by many published biochemical data. Our results provide important clues for designing new inhibitors against HIV-1.
Animals ; Catalytic Domain ; genetics ; Cattle ; DNA ; genetics ; DNA, Viral ; HIV-1 ; genetics ; metabolism ; Humans ; Immunodeficiency Virus, Bovine ; enzymology ; genetics ; Integrases ; chemistry ; genetics ; metabolism

OBJECTIVEChimeric human/bovine immunodeficiency virus (HBIV) cDNA was constructed by replacing HIV tat and LTR with bovine immunodeficiency virus (BIV) tat and LTR to study the activity of BIV tat and LTR in the chimerae.

METHODSThe target fragments of BIV tat, LTR and HIV gag, pol, env were respectively amplified by using PCR and sequentially inserted into pBluescript SK(+) vector. The chimeric clone was transfected into human MT4 cells. The transcript and gene expression of the HBIV chimeric virus were detected by using RT-PCR and a reverse transcriptase assay, respectively.

RESULTSBIV tat mRNA and HIV gag mRNA were detected. The reverse transcriptase activity of the chimeric virus was analyzed in the fluctuation curve.

CONCLUSIONSIn chimeric HBIV cDNA transfected MT?4 cells, BIV tat and HIV gag were transcripted. The reverse transcriptase of the chimeric virus had biological activity. These data suggest that in MT4 cells, BIV LTR had promoter activity and BIV tat had the function of transactivation in the chimeric virus. The study of the chimeric virus with infectivity is in progress.

AIDS Vaccines ; Animals ; Cattle ; Cloning, Molecular ; DNA, Complementary ; genetics ; DNA, Viral ; genetics ; Genes, gag ; genetics ; Genes, pol ; genetics ; Genes, tat ; genetics ; HIV-1 ; genetics ; Humans ; Immunodeficiency Virus, Bovine ; genetics ; Recombinant Fusion Proteins ; genetics ; metabolism ; Transcription, Genetic ; Transcriptional Activation ; Transfection ; Virus Replication