How to establish an arrhythmia unit in the 21st century

Arrhythmia and cardiac electrophysiology services are an innovative and fast-growing branch of clinical cardiology. Initiating an arrhythmia unit involves proper selection of personnel, as well as technical, structural, and organizational requirements. Proper selection of personnel includes specialized and well-trained physicians, nurses, and medical technicians in the electrophysiology laboratories and on the hospital wards. Standard electrophysiology laboratories must support the full spectrum of catheter-based diagnosis and therapies of cardiac arrhythmias. This includes state-of-the-art fluoroscopy and 3-dimensional mapping systems used during complex procedures such as catheter ablation of atrial fibrillation or ventricular tachycardia. Furthermore, technical requirements need to support pacemaker and defibrillator implantation as one of the core tasks of a specialized arrhythmia unit. Outpatient clinics should fulfill technical capabilities to perform a diverse spectrum of pre-and postinterventional diagnostics, guaranteeing proper patient follow-up. Structural requirements should focus on close physical integration of individual functional units allowing for an effective and safe workflow. Finally, organizational requirements such as networking between arrhythmia specialists and referring physicians and hospitals are essential for patient recruitment and high-quality postdischarge patient care. Regular educational programs for physicians, nurses, and technicians are essential in such an innovative and fast-growing field of cardiology.     

Medizinischer Kinderschutz während des Corona-Lockdowns

Monatsschrift Kinderheilkunde - Es gibt Anhaltspunkte dafür, dass die Gefahr von Kindesmisshandlung, sexuellem Kindesmissbrauch und Vernachlässigung während der strengen...     

In-depth analysis of G-to-A hypermutation rate in HIV-1 env DNA induced by endogenous APOBEC3 proteins using massively parallel sequencing

Some APOBEC3 proteins cause G-to-A hypermutation in HIV-1 DNA when the accessory viral protein Vif is absent or non-functional. So far, cloning and sequencing has been performed to study G-to-A hypermutation. This is time-consuming and labour-intensive especially in the context of in vivo investigations where the number of hypermutated sequences can be very low. Thus, a massively parallel sequencing protocol has been developed for in-depth analysis of G-to-A hypermutation using the 454 pyrosequencing FLX system. Part of HIV-1 env was amplified and pyrosequenced after two rounds of infection in T cell lines and PBMCs using HIV-1 NL4-3Δvif. Specific criteria were applied to cope with major technical challenges: (1) the inclusion of hypermutated sequences, (2) the high genome diversity of HIV-1 env, and (3) the exclusion of sequences containing frameshift errors caused by pyrosequencing. In total, more than 140,000 sequences were obtained. 1.3-6.5% of guanines were mutated to adenine, most frequently in the GG dinucleotide context, the preferred deamination site of APOBEC3G. Non-G-to-A mutations occurred only in low frequencies (<0.6%). Single hypermutated sequences contained up to 24 G-to-A mutations. Overall, massively parallel sequencing is a very useful tool for in-depth analysis of G-to-A hypermutation in HIV-1 DNA induced by APOBEC3 proteins.     

Simian immunodeficiency virus-specific cytotoxic T lymphocytes and protection against challenge in rhesus macaques immunized with a live attenuated simian immunodeficiency virus vaccine

In this study, we examined the role of simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocytes (CTLs) in macaques immunized with an attenuated strain of simian immunodeficiency virus (SIVmac239Deltanef) in protection against pathogenic challenge with SIVmac251. Our results indicate that attenuated SIVmac239Deltanef can elicit specific CTL precursor cells (CTLp), but no correlation was observed between breadth or strength of CTLp response to structural proteins SIV-Env, -Gamg or -Pol (as measured by limiting dilution assay) and protection against infection. In one animal, we longitudinally followed the SIV-Gag-specific response to an MHC class I Mamu-A*01-restricted epitope p11C, C-M using a tetrameric MHC/peptide complex reagent. A low frequency of SIV p11C, C-M peptide-specific tetramer-reactive cells was present at the time of challenge but could be expanded in vitro. Surprisingly, the low level of Mamu-A*01/p11C, C-M-specific CTLs induced through attenuated SIVmac239Deltanef vaccination increased in the absence of detectable SIVmac251 or SIVmac239Deltanef proviral DNA. Overall, our results suggest that protection against infection in this model can be achieved through more than one mechanism, with SIV-specific CTLs being important in controlling SIVmac239Deltanef viral replication postchallenge.