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Background Plasmodium falciparum (Pf) is the leading protozoan causing malaria, the most devastating parasitic dis‑ ease. To ensure transmission, a small subset of Pf parasites diferentiate into the sexual forms (gametocytes). Since the abundance of these essential parasitic forms is extremely low within the human host, little is currently known about the molecular regulation of their sexual diferentiation, highlighting the need to develop tools to investigate Pf gene expression during this fundamental mechanism. Methods We developed a high-throughput quantitative Reverse-Transcription PCR (RT-qPCR) platform to robustly monitor Pf transcriptional patterns, in particular, systematically profling the transcriptional pattern of a large panel of gametocyte-related genes (GRG). Initially, we evaluated the technical performance of the systematic RT-qPCR platform to ensure it complies with the accepted quality standards for: (i) RNA extraction, (ii) cDNA synthesis and (iii) evaluation of gene expression through RT-qPCR. We then used this approach to monitor alterations in gene expres‑ sion of a panel of GRG upon treatment with gametocytogenesis regulators. Results We thoroughly elucidated GRG expression profles under treatment with the antimalarial drug dihydroar‑ temisinin (DHA) or the metabolite choline over the course of a Pf blood cycle (48 h). We demonstrate that both signifcantly alter the expression pattern of PfAP2-G, the gametocytogenesis master regulator. However, they also markedly modify the developmental rate of the parasites and thus might bias the mRNA expression. Additionally, we screened the efect of the metabolites lactate and kynurenic acid, abundant in severe malaria, as potential regulators of gametocytogenesis. Conclusions Our data demonstrate that the high-throughput RT-qPCR method enables studying the immediate transcriptional response initiating gametocytogenesis of the parasites from a very low volume of malaria-infected RBC samples. The obtained data expand the current knowledge of the initial alterations in mRNA profles of GRG upon treatment with reported regulators. In addition, using this method emphasizes that asexual parasite stage composi‑ tion is a crucial element that must be considered when interpreting changes in GRG expression by RT-qPCR, specif‑ cally when screening for novel compounds that could regulate Pf sexual diferentiation. [ABSTRACT FROM AUTHOR]

Introduction: Rate smoothing algorithms, while known to help prevent ventricular tachyarrhythmias in some patients, have been shown to result in underdetection of ventricular tachycardia (VT) due to interaction between bradycardia pacing and tachycardia detection parameters. A new algorithm named Bradycardia Tachycardia Response (BTR) has been developed in order to prevent rate smoothing-induced underdetection. The efficacy of BTR is not known. The aim of this study was to assess the effectiveness of BTR in preventing VT underdetection due to rate smoothing. Methods and Results: Two ICD models (TELIGEN and VITALITY AVT, Boston Scientific, St. Paul, MN, USA) bearing identical rate smoothing algorithms were connected to a VT simulator. Devices were programmed similarly except for the BTR feature that exists in TELIGEN only. The detection performance of both devices was tested using varying combinations of AV delay, rate smoothing down, and upper rate limit and compared between the two models. VT underdetection (delay or nondetection) occurred during pacing in 62% of the VT episodes with VITALITY AVT. In TELIGEN, all simulated VT episodes were detected appropriately as soon as their rates exceeded the programmed VT detection rate. Detection tended to be affected by higher upper rate, longer AV delays, and more aggressive rate smoothing. Conclusion: The BTR algorithm effectively counteracts VT detection delay caused by the interaction of rate smoothing with VT detection parameters, thus enabling safe use of the rate smoothing feature. (PACE 2012; 1-6) [ABSTRACT FROM AUTHOR]

LURIA, D., et al.: Use of Automatic Threshold Tracking Function with Non-Low Polarization Leads: Risk for Algorithm Malfunction. The AutoCapture (AC) function of new pacemakers (PM) from St Jude Medical (SJM) was originally recommended for use with low polarization (LP) ventricular leads only. However, recent reports have encouraged the use of the AC function with various leads, including those lacking a special LP design. The objective of this study was to analyze the reliability and safety of the AC algorithm application with different types of pacing leads. The study group comprised 30 consecutive patients with AC PMs connected to three different types of non-LP leads. Ten patients with SJM LP leads served as the control group. The study protocol included a complete AC function test using four different pulse widths (PW). The pacing threshold was independently assessed by a manual/semiautomatic check. Erratic behavior of polarization measurements with increasing PWs was demonstrated in 43% (n = 13) of the study group. Invalid polarization measurements resulted in erroneous algorithm recommendation to apply AC function in 17% (n = 5) of the study patients. Subsequent AC function activation lead to incorrect threshold determination due to missed noncapture in three patients. AC function should be applied with caution with non-LP leads. “Off label” use of these leads may cause erroneous polarization signal measurements which, in some cases, may result in incorrect pacing threshold determination, rendering a potential risk to dependent patients. (PACE 2004; 27:453–459) [ABSTRACT FROM AUTHOR]