T-wave and its association with myocardial fibrosis on cardiovascular magnetic resonance examination.

BACKGROUND: Risk stratification in non-ischemic myocardial disease poses a challenge. While cardiovascular magnetic resonance (CMR) is a comprehensive tool, the electrocardiogram (ECG) provides quick impactful clinical information. Studying the relationships between CMR and ECG can provide much-needed risk stratification. We evaluated the electrocardiographic signature of myocardial fibrosis defined as presence of late gadolinium enhancement (LGE) or extracellular volume fraction (ECV) ≥29%. METHODS: We evaluated 240 consecutive patients (51% female, 47.1 ± 16.6 years) referred for a clinical CMR who underwent 12-lead ECGs within 90 days. ECG parameters studied to determine association with myocardial fibrosis included heart rate, QRS amplitude/duration, T-wave amplitude, corrected QT and QT peak, and Tpeak-Tend. Abnormal T-wave was defined as low T-wave amplitude ≤200 µV or a negative T wave, both in leads II and V5. RESULTS: Of the 147 (61.3%) patients with myocardial fibrosis, 67 (28.2%) had ECV ≥ 29%, and 132 (54.6%) had non-ischemic LGE. An abnormal T-wave was more prevalent in patients with versus without myocardial fibrosis (66% versus 42%, p < .001). Multivariable analysis demonstrated that abnormal T-wave (OR 1.95, 95% CI 1.09-3.49, p = .03) was associated with myocardial fibrosis (ECV ≥ 29% or LGE) after adjustment for clinical covariates (age, gender, history of hypertension, and heart failure). Dynamic nomogram for predicting myocardial fibrosis using clinical parameters and the T-wave was developed: https://normogram.shinyapps.io/CMR_Fibrosis/. CONCLUSION: Low T-wave amplitude ≤ 200 µV or negative T-waves are independently associated with myocardial fibrosis. Prospective evaluation of T-wave amplitude may identify patients with a high probability of myocardial fibrosis and guide further indication for CMR.

The Genome of Peronospora belbahrii Reveals High Heterozygosity, a Low Number of Canonical Effectors, and TC-Rich Promoters.

Along with Plasmopara destructor, Peronosopora belbahrii has arguably been the economically most important newly emerging downy mildew pathogen of the past two decades. Originating from Africa, it has started devastating basil production throughout the world, most likely due to the distribution of infested seed material. Here, we present the genome of this pathogen and results from comparisons of its genomic features to other oomycetes. The assembly of the nuclear genome was around 35.4 Mbp in length, with an N50 scaffold length of around 248 kbp and an L50 scaffold count of 46. The circular mitochondrial genome consisted of around 40.1 kbp. From the repeat-masked genome, 9,049 protein-coding genes were predicted, out of which 335 were predicted to have extracellular functions, representing the smallest secretome so far found in peronosporalean oomycetes. About 16% of the genome consists of repetitive sequences, and, based on simple sequence repeat regions, we provide a set of microsatellites that could be used for population genetic studies of P. belbahrii. P. belbahrii has undergone a high degree of convergent evolution with other obligate parasitic pathogen groups, reflecting its obligate biotrophic lifestyle. Features of its secretome, signaling networks, and promoters are presented, and some patterns are hypothesized to reflect the high degree of host specificity in Peronospora species. In addition, we suggest the presence of additional virulence factors apart from classical effector classes that are promising candidates for future functional studies.

Low lead one ratio predicts clinical outcomes in left bundle branch block.

INTRODUCTION: We evaluated the association between a novel electrocardiographic (ECG) marker of late, rightward electrocardiographic forces (termed the lead one ratio [LOR]), and left ventricular ejection fraction (LVEF), myocardial scar, and clinical outcomes in patients with left bundle branch block (LBBB). METHODS AND RESULTS: LOR was calculated in patients with LBBB from a derivation cohort (n = 240) and receiver operator characteristic curves identified optimal threshold values for predicting myocardial scar and LVEF less than 35%. An independent validation cohort of patients with LBBB (n = 196) was used to test the association of LOR with the myocardial scar, LVEF, and the likelihood of death, heart transplant or left ventricular assist device (LVAD) implantation. The optimal thresholds in the derivation cohort were LOR less than 13.7 for identification of scar (sensitivity 55%, specificity 80%), and LOR less than 12.1 for LVEF less than 35% (sensitivity 49%, specificity 80%). In the validation cohort, LOR less than 13.7 was not associated with scar size or presence (P > 0.05 for both). LOR less than 12.1 was associated with lower LVEF (30 [20-40] versus 40 [25-55]%; P = 0.002) and predicted LVEF less than 35% in univariable (odds ratio [OR], 2.2 [1.2-4.1]; P = 0.01) and multivariable analysis (OR, 2.2 [1.2-4.3]; P = 0.02). LOR less than 12.1 was associated with scar presence when patients with nonischemic cardiomyopathy were excluded (OR = 7.2 [1.5-33.2]; P = 0.002). LOR less than 12.1 had an adjusted hazard ratio of 1.53 ([1.05-2.21]; P = 0.03) for death, transplant or LVAD implantation. CONCLUSIONS: In conclusion, ECG LOR less than 12.1 predicts reduced-LV systolic function and poorer prognosis in patients with LBBB.

Baseline adverse electrical remodeling and the risk for ventricular arrhythmia in Cardiac Resynchronization Therapy Recipients (MADIT CRT).

INTRODUCTION: Adverse electrical remodeling (AER), represented here as the sum absolute QRST integral (SAI QRST), has previously been shown to be directly associated with the risk for ventricular arrhythmia (VA). Cardiac resynchronization therapy (CRT) is known to reduce the risk for VA through various mechanisms, including reverse remodeling, and we aimed to evaluate the association between baseline AER and the risk for VA in CRT recipients. METHODS AND RESULTS: The study population comprised 961 CRT-D implanted patients from the MADIT CRT study. The relationship between SAI QRST, VA risk, and VA risk/death was evaluated as a continuous and as a categorical variable-tertiles (T1 ≤ 0.527, T2 0.528-0.766, T3 > 0.766). In a multivariable model, AER was inversely associated with the risk of VA. Each unit increase in SAI QRST was associated with 64% (P  =  0.007) and 54% (P  =  0.003) decrease in the risk of VA and VA/death, respectively. Patients with high SAI QRST (T3) and medium SAI QRST (T2) had 52% (P < 0.001) and 32% (P  =  0.027) reduced risk for VA and 44% (P  =  0.002) and 26% (P  =  0.055) reduced risk for VA/death as compared with patients with low SAI QRST (T1), respectively. CONCLUSION: In CRT implanted patients with mild heart failure, baseline AER was inversely associated with the risk for VA and VA/death; this is a finding that contradicts the relationship previously reported in non-CRT implanted patients. We theorize that CRT may abate the process of AER; however, characterization of this mechanism requires further study.

The ability of the electrocardiogram in left bundle branch block to detect myocardial scar determined by cardiovascular magnetic resonance.

AIMS: We aimed to improve the electrocardiographic 2009 left bundle branch block (LBBB) Selvester QRS score (2009 LBSS) for scar assessment. METHODS: We retrospectively identified 325 LBBB patients with available ECG and cardiovascular magnetic resonance imaging (CMR) with late gadolinium enhancement from four centers (142 [44%] with CMR scar). Forty-four semi-automatically measured ECG variables pre-selected based on the 2009 LBSS yielded one multivariable model for scar detection and another for scar quantification. RESULTS: The 2009 LBSS achieved an area under the curve (AUC) of 0.60 (95% confidence interval 0.54-0.66) for scar detection, and R2 = 0.04, p < 0.001, for scar quantification. Multivariable modeling improved scar detection to AUC 0.72 (0.66-0.77) and scar quantification to R2 = 0.21, p < 0.001. CONCLUSIONS: The 2009 LBSS detects and quantifies myocardial scar with poor accuracy. Improved models with extensive comparison of ECG and CMR had modest performance, indicating limited room for improvement of the 2009 LBSS.

Increasing the yield of middle silk gland expression system through transgenic knock-down of endogenous sericin-1.

Various genetically modified bioreactor systems have been developed to meet the increasing demands of recombinant proteins. Silk gland of Bombyx mori holds great potential to be a cost-effective bioreactor for commercial-scale production of recombinant proteins. However, the actual yields of proteins obtained from the current silk gland expression systems are too low for the proteins to be dissolved and purified in a large scale. Here, we proposed a strategy that reducing endogenous sericin proteins would increase the expression yield of foreign proteins. Using transgenic RNA interference, we successfully reduced the expression of BmSer1 to 50%. A total 26 transgenic lines expressing Discosoma sp. red fluorescent protein (DsRed) in the middle silk gland (MSG) under the control of BmSer1 promoter were established to analyze the expression of recombinant. qRT-PCR and western blotting showed that in BmSer1 knock-down lines, the expression of DsRed had significantly increased both at mRNA and protein levels. We did an additional analysis of DsRed/BmSer1 distribution in cocoon and effect of DsRed protein accumulation on the silk fiber formation process. This study describes not only a novel method to enhance recombinant protein expression in MSG bioreactor, but also a strategy to optimize other bioreactor systems.

Validation of an automatic diagnosis of strict left bundle branch block criteria using 12-lead electrocardiograms.

AIMS: Strict left bundle branch block (LBBB) criteria were recently proposed to identify LBBB patients to benefit most from cardiac resynchronization therapy (CRT). The aim of our study was to automate identification of strict LBBB in order to facilitate its broader application. METHODS: We developed a series of algorithms to automatically detect and measure parameters required for strict LBBB criteria and proposed a definition of QRS notch detection. The algorithms were developed using training (n = 20) and validation (n = 592) sets consisting of signal-averaged 12-lead ECGs (1,000 Hz sampling) recorded from 612 LBBB patients from Multicenter Automatic Defibrillator Implantation Trial-CRT. Four trained clinicians independently performed adjudication on 148 different ECGs for comparing automatic and manually adjudicated results, in addition to 13 ECGs for evaluation of intraobserver variability and 32 ECGs for interobserver variability. We assessed the performance of the automated algorithms using manually adjudicated ECGs as references. RESULTS: Overall sensitivity and specificity for detecting strict LBBB were 95% and 86%, respectively. The mean absolute deviation (MAD) of QRS duration and notch/slur locations for the automated method versus the manual method was below 1 ms, and MAD values were lower than 2 ms for interobserver and intraobserver variability. Sensitivity and specificity for detecting notch and slur locations were 87% and 96% for notches and 78% and 90% for slurs using the automatic method. In addition 95% and 93% agreements for notches and 90% and 88% agreements for slurs were reached for intra- and interobserver. CONCLUSION: The proposed algorithms automatically measure QRS features for the diagnosis of strict LBBB. Our study shows good performance in reference to manual results.

Population-based beat-to-beat QT analysis from Holter recordings in the long QT syndrome.

The increasing dissemination of wearable ECG recorders (e.g. Holter, patches, and strap sensors) enables the acquisition of large amounts of data during long periods of time. However, the clinical value of these long-term continuous recordings is hindered by the lack of automatic tools to extract clinically relevant information (other than non-sinus and life-threatening rhythms) from such long-term data, particularly when targeting population-based research. In this work, we propose and test a new tool for analyzing beat-to-beat interval measurements and extracting features from Holter ECGs. Specifically, we assess the adaptation of the QT interval following sudden changes in heart rate in the primary long QT types (1 & 2). We find that in long QT syndrome type 2, certain QT adaptation patterns can indicate a higher risk for cardiac events.

The local environment determines the assembly of root endophytic fungi at a continental scale.

Root endophytic fungi are found in a great variety of plants and ecosystems, but the ecological drivers of their biogeographic distribution are poorly understood. Here, we investigate the occurrence of root endophytes in the non-mycorrhizal plant genus Microthlaspi, and the effect of environmental factors and geographic distance in structuring their communities at a continental scale. We sampled 52 plant populations across the northern Mediterranean and central Europe and used a cultivation approach to study their endophytic communities. Cultivation of roots yielded 2601 isolates, which were grouped into 296 operational taxonomic units (OTUs) by internal transcribed spacer sequencing of 1998 representative colonies. Climatic and spatial factors were the best descriptors of the structure of endophytic communities, outweighing soil characteristics, host genotype and geographical distance. OTU richness was negatively affected by precipitation, and the composition of communities followed latitudinal gradients of precipitation and temperature. Only six widespread OTUs belonging to the orders Pleosporales, Hypocreales and Helotiales represented about 50% of all isolates. Assessments of their individual distribution revealed particular ecological preferences or a cosmopolitan occurrence. Our findings support a strong influence of the local environment in determining root endophytic communities, and show a different niche occupancy by individual endophytes.

Automatic QRS Selvester scoring system in patients with left bundle branch block.

AIMS: The Selvester QRS scoring system uses quantitative criteria from the standard 12-lead electrocardiogram (ECG) to estimate the myocardial scar size of patients, including those with left bundle branch block (LBBB). Automation of the scoring system could facilitate the clinical use of this technique which requires a set of multiple QRS patterns to be identified and measured. METHODS AND RESULTS: We developed a series of algorithms to automatically detect and measure the QRS parameters required for Selvester scoring. The 'QUantitative and Automatic REport of Selvester Score' was designed specifically for the analysis of ECGs from patients meeting new strict criteria for complete LBBB. The algorithms were designed using a training (n = 36) and a validation (n = 180) set of ECGs, consisting of signal-averaged 12-lead ECGs (1000 Hz sampling) recorded from 216 LBBB patients from the MADIT-CRT. We assessed the performance of the methods using expert manually adjudicated ECGs. The average of absolute differences between automatic and adjudicated Selvester scoring was 1.2 ± 1.5 points. The range of average differences for continuous measurements of wave locations and interval durations varied between 0 and 6 ms. Erroneous detection of Q, R, S, R', and S' waves (oversensed or missed) were 3, 1, 1, 16, and 6%, respectively. Seven percent of notches detected in the first 40 ms were misdetected. CONCLUSION: We propose an efficient computerized method for the automatic measurement of the Selvester score in patients with the strict LBBB.

The genome of the basal agaricomycete Xanthophyllomyces dendrorhous provides insights into the organization of its acetyl-CoA derived pathways and the evolution of Agaricomycotina.

BACKGROUND: Xanthophyllomyces dendrorhous is a basal agaricomycete with uncertain taxonomic placement, known for its unique ability to produce astaxanthin, a carotenoid with antioxidant properties. It was the aim of this study to elucidate the organization of its CoA-derived pathways and to use the genomic information of X. dendrorhous for a phylogenomic investigation of the Basidiomycota. RESULTS: The genome assembly of a haploid strain of Xanthophyllomyces dendrorhous revealed a genome of 19.50 Megabases with 6385 protein coding genes. Phylogenetic analyses were conducted including 48 fungal genomes. These revealed Ustilaginomycotina and Agaricomycotina as sister groups. In the latter a well-supported sister-group relationship of two major orders, Polyporales and Russulales, was inferred. Wallemia occupies a basal position within the Agaricomycotina and X. dendrorhous represents the basal lineage of the Tremellomycetes, highlighting that the typical tremelloid parenthesomes have either convergently evolved in Wallemia and the Tremellomycetes, or were lost in the Cystofilobasidiales lineage. A detailed characterization of the CoA-related pathways was done and all genes for fatty acid, sterol and carotenoid synthesis have been assigned. CONCLUSIONS: The current study ascertains that Wallemia with tremelloid parenthesomes is the most basal agaricomycotinous lineage and that Cystofilobasidiales without tremelloid parenthesomes are deeply rooted within Tremellomycetes, suggesting that parenthesomes at septal pores might be the core synapomorphy for the Agaricomycotina. Apart from evolutionary insights the genome sequence of X. dendrorhous will facilitate genetic pathway engineering for optimized astaxanthin or oxidative alcohol production.

Genome analyses of the sunflower pathogen Plasmopara halstedii provide insights into effector evolution in downy mildews and Phytophthora.

BACKGROUND: Downy mildews are the most speciose group of oomycetes and affect crops of great economic importance. So far, there is only a single deeply-sequenced downy mildew genome available, from Hyaloperonospora arabidopsidis. Further genomic resources for downy mildews are required to study their evolution, including pathogenicity effector proteins, such as RxLR effectors. Plasmopara halstedii is a devastating pathogen of sunflower and a potential pathosystem model to study downy mildews, as several Avr-genes and R-genes have been predicted and unlike Arabidopsis downy mildew, large quantities of almost contamination-free material can be obtained easily. RESULTS: Here a high-quality draft genome of Plasmopara halstedii is reported and analysed with respect to various aspects, including genome organisation, secondary metabolism, effector proteins and comparative genomics with other sequenced oomycetes. Interestingly, the present analyses revealed further variation of the RxLR motif, suggesting an important role of the conservation of the dEER-motif. Orthology analyses revealed the conservation of 28 RxLR-like core effectors among Phytophthora species. Only six putative RxLR-like effectors were shared by the two sequenced downy mildews, highlighting the fast and largely independent evolution of two of the three major downy mildew lineages. This is seemingly supported by phylogenomic results, in which downy mildews did not appear to be monophyletic. CONCLUSIONS: The genome resource will be useful for developing markers for monitoring the pathogen population and might provide the basis for new approaches to fight Phytophthora and downy mildew pathogens by targeting core pathogenicity effectors.

Selvester scoring in patients with strict LBBB using the QUARESS software.

BACKGROUND: Estimation of the infarct size from body-surface ECGs in post-myocardial infarction patients has become possible using the Selvester scoring method. Automation of this scoring has been proposed in order to speed-up the measurement of the score and improving the inter-observer variability in computing a score that requires strong expertise in electrocardiography. In this work, we evaluated the quality of the QuAReSS software for delivering correct Selvester scoring in a set of standard 12-lead ECGs. METHOD: Standard 12-lead ECGs were recorded in 105 post-MI patients prescribed implantation of an implantable cardiodefibrillator (ICD). Amongst the 105 patients with standard clinical left bundle branch block (LBBB) patterns, 67 had a LBBB pattern meeting the strict criteria. The QuAReSS software was applied to these 67 tracings by two independent groups of cardiologists (from a clinical group and an ECG core laboratory) to measure the Selvester score semi-automatically. Using various level of agreement metrics, we compared the scores between groups and when automatically measured by the software. RESULTS: The average of the absolute difference in Selvester scores measured by the two independent groups was 1.4±1.5 score points, whereas the difference between automatic method and the two manual adjudications were 1.2±1.2 and 1.3±1.2 points. Eighty-two percent score agreement was observed between the two independent measurements when the difference of score was within two point ranges, while 90% and 84% score agreements were reached using the automatic method compared to the two manual adjudications. CONCLUSION: The study confirms that the QuAReSS software provides valid measurements of the Selvester score in patients with strict LBBB with minimal correction from cardiologists.

Flexible Humidity Sensor Based on a Graphene Oxide-Carbon Nanotube-Modified Co3O4 Nanoparticle-Embedded Laser-Induced Graphene Electrode.

To meet evolving humidity monitoring needs, the development of flexible, high-performance humidity sensors is crucial. This study introduces an innovative flexible humidity sensor using a single-step laser scribing technique to fabricate a flexible in situ Co3O4 nanoparticle-embedded laser-induced graphene (Co3O4-LIG) composite electrode. Compared to conventional LIG electrodes, the Co3O4-LIG electrode exhibits improved conductivity and hydrophilicity, enhancing charge transfer and water molecule affinity. The unique two-dimensional structure and exceptional water permeability of graphene oxide (GO) combine with the rapid water response and high specific surface area of carboxylated multiwalled carbon nanotubes (MWCNTs), thereby assuming a crucial function in the modification and optimization of the performance of humidity sensors. Through the application of a homogenously blended aqueous solution comprising GO and MWCNTs in precise proportions onto the Co3O4-LIG composite electrode, an excellent humidity-responsive layer is established, culminating in the realization of a cutting-edge GO-MWCNTs@Co3O4-LIG flexible humidity sensor. Noteworthy attributes of this sensor include a heightened sensitivity [959.1% (ΔR/R0)], rapid response and recovery times (within 5 and 26 s, respectively), and a noteworthy linearity (R2 = 0.994) across a relative humidity range of 14 to 95%. The findings presented herein offer valuable insights and a practical blueprint for the design and production of flexible humidity sensors.

Analysis of factors associated with family disease burden and correlation with social support among family caregivers of patients with severe mental illnesses.

BACKGROUND: Caregivers are responsible for the home care of family members with severe mental illnesses (SMIs) and their lives are often subject to changes that can create stress and burden. The purpose of this study was to explore the current state of family disease burden and its correlation with social support among family caregivers of SMIs patients. METHODS: Using a random sampling method, a total of 1,108 family caregivers of SMIs patients in community health service centers were selected. A general information questionnaire of family caregivers and patients, the Family Disease Burden Scale, and the Social Support Rating Scale were used. RESULTS: The score of the Family Disease Burden Scale of 1108 family caregivers was 16.57 ± 10.65. Family disease burden was negatively correlated with social support (p < .05). The main influencing factors of family disease burden were average annual family income, duration of illness, distance to medical care, risk of unpredictable behavior, social support, caregiver-patient relationship, gender, and comorbid chronic conditions (p < .05). CONCLUSION: Family caregivers of SMIs patients have a relatively low level of caregiver-perceived social support. Interventions to enhance perceived social support could help maintain the health of family caregivers and improve the quality of family care.

Monitoring Pulse Rate in the Background Using Front Facing Cameras of Mobile Devices.

We propose a novel framework to passively monitor pulse rate during the time spent by users on their personal mobile devices. Our framework is based on passively capturing the user's pulse signal using the front-facing camera. Signal capture is performed in the background, while the user is interacting with the device as he/she normally would, e.g., watch movies, read emails, text, and play games. The framework does not require subject participation with the monitoring procedure, thereby addressing the well-known problem of low adherence with such procedures. We investigate various techniques to suppress the impact of spontaneous user motion and fluctuations in ambient light conditions expected in non-participatory environments. Techniques include traditional signal processing, machine learning classifiers, and deep learning methods. Our performance evaluation is based on a clinical study encompassing 113 patients with a history of atrial fibrillation (Afib) who are passively monitored at home using a tablet for a period of two weeks. Our results show that the proposed framework accurately monitors pulse rate, thereby providing a gateway for long-term monitoring without relying on subject participation or the use of a dedicated wearable device.

Heart rate and autonomic biomarkers distinguish convulsive epileptic vs. functional or dissociative seizures.

OBJECTIVE: 20-40% of individuals whose seizures are not controlled by anti-seizure medications exhibit manifestations comparable to epileptic seizures (ES), but there are no EEG correlates. These events are called functional or dissociative seizures (FDS). Due to limited access to EEG-monitoring and inconclusive results, we aimed to develop an alternative diagnostic tool that distinguishes ES vs. FDS. We evaluated the temporal evolution of ECG-based measures of autonomic function (heart rate variability, HRV) to determine whether they distinguish ES vs. FDS. METHODS: The prospective study includes patients admitted to the University of Rochester Epilepsy Monitoring Unit. Participants are 18-65 years old, without therapies or co-morbidities associated with altered autonomics. A habitual ES or FDS is recorded during admission. HRV analysis is performed to evaluate the temporal changes in autonomic function during the peri­ictal period (150-minutes each pre-/post-ictal). We determined if autonomic measures distinguish ES vs. FDS. RESULTS: The study includes 53 ES and 46 FDS. Temporal evolution of HR and autonomics significantly differ surrounding ES vs. FDS. The pre-to-post-ictal change (delta) in HR differs surrounding ES vs. FDS, stratified for convulsive and non-convulsive events. Post-ictal HR, total autonomic (SDNN & Total Power), vagal (RMSSD & HF), and baroreflex (LF) function differ for convulsive ES vs. convulsive FDS. HR distinguishes non-convulsive ES vs. non-convulsive FDS with ROC>0.7, sensitivity>70%, but specificity<50%. HR-delta and post-ictal HR, SDNN, RMSSD, LF, HF, and Total Power each distinguish convulsive ES vs. convulsive FDS (ROC, 0.83-0.98). Models with HR-delta and post-ictal HR provide the highest diagnostic accuracy for convulsive ES vs. convulsive FDS: 92% sensitivity, 94% specificity, ROC 0.99). SIGNIFICANCE: HR and HRV measures accurately distinguish convulsive, but not non-convulsive, events (ES vs. FDS). Results establish the framework for future studies to apply this diagnostic tool to more heterogeneous populations, and on out-of-hospital recordings, particularly for populations without access to epilepsy monitoring units.

A seven-WD40 protein related to human RACK1 regulates mating and virulence in Ustilago maydis.

In mammalian cells RACK1 serves as a scaffold protein that has a role in integrating inputs from different signalling pathways and affects translation through association with ribosomes. Ustilago maydis contains a seven-WD40 repeat motif protein designated Rak1, which shows 68% identity to RACK1 and 51% identity to Asc1p of Saccharomyces cerevisiae. An asc1 mutant could be complemented by introduction of U. maydis rak1. The deletion of rak1 affected cell growth, cell wall integrity and specifically attenuated cell fusion. This latter defect was caused by reduced expression of prf1 encoding the regulator for pheromone (mfa) and pheromone-receptor genes. Rak1 interacts with a variety of ribosomal proteins and microarray analysis revealed that the deletion of rak1 led to severely reduced expression of rop1, a transcriptional activator of prf1. The constitutive expression of rop1 could rescue the defect of mfa1 expression as well as conjugation tube formation in response to pheromone induction in the rak1 mutant. Moreover, a solopathogenic rak1 mutant failed to respond to plant-derived stimuli, resulting in attenuated filamentation and pathogenicity. This could be partially rescued by constitutive expression of the b heterodimer. These data suggest that rak1 is a regulator of rop1 expression with additional roles after cell fusion.

Markers of ventricular repolarization and overall mortality in sleep disordered breathing.

INTRODUCTION: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality. METHODS: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each). Overnight electrocardiograms were analyzed for QTc duration and QT variability (standard deviation of QT intervals, normalized QT interval variance and the short-term interval beat-to-beat QT variability). Cox proportional hazards penalized regression modeling was used to identify predictors of mortality. RESULTS: Eight hundred of 5600 participants were randomly selected. The participants (68 ± 10 years; 56.8% male) were followed for an average of 8.2 years during which time 222 (28.4%) died. QTc, SDQT, and QTVN were associated with the presence of SDB (p = 0.002, p = 0.014, and p = 0.024, respectively). After adjusting for covariates, the presence of sleep-disordered breathing did not moderate the association between QTc length, QT variability and mortality (p > 0.05). CONCLUSION: Sleep-disordered breathing was associated with some measures of ventricular repolarization. However, sleep-disordered breathing was not an effect modifier for the relationship between QTc and QT variability and mortality.

Sex hormones and repolarization dynamics during the menstrual cycle in women with congenital long QT syndrome.

BACKGROUND: Women with congenital long QT syndrome (LQTS) experience increased cardiac event risk after the onset of adolescence, perhaps stemming from the known modulating effects of sex hormones on the cardiac potassium channels. OBJECTIVE: We hypothesized that the effect of sex hormones on cardiac ion channel function may modify electrocardiographic (ECG) parameters associated with the propensity for ventricular tachyarrhythmias during the menstrual cycle in women with LQTS. METHODS: We prospectively enrolled 65 women with congenital LQTS (type 1 LQTS [LQT1], n = 24 [36.9%]; type 2 LQTS [LQT2], n = 20 [30.8%]) and unaffected female relatives (n = 21 [32.3%]). Patients underwent three 7-day ECG recordings during their menstrual cycles. Simultaneous saliva testing of sex hormone levels was conducted on the first day of each 7-day ECG recording cycle. RESULTS: The mean age was 35 ± 8 years, without a significant difference among the groups. In women with LQT2, linear mixed effects models showed significant inverse correlations of the corrected QT interval with progesterone levels (P < .001) and with the progesterone to estradiol ratio (P < .001). Inverse relationships of the R-R interval with estradiol levels (P = .003) and of the T-wave duration with testosterone levels (P = .014) were also observed in women with LQT2. In contrast, no significant associations were observed between ECG parameters and sex hormone levels in women with LQT1 or unaffected relatives. CONCLUSION: This is the first study to prospectively assess correlations between repolarization dynamics and sex hormone levels during the menstrual cycle in women with congenital LQTS. Our findings show genotype-specific unique corrected QT dynamics during the menstrual cycle that may affect the propensity for ventricular tachyarrhythmia in women with LQTS, particularly women with LQT2.