Cardiac Repolarization Abnormalities and Potential Evidence for Loss of Cardiac Sodium Currents on ECGs of Patients with Chagas' Heart Disease

Some individuals with Chagas disease develop right precordial lead ST segment elevation in response to an ajmaline challenge test, and the prevalence of right bundle branch block (RBBB) is also high in Chagas disease. Because these same electrocardiographic abnormalities occur in the Brugada syndrome, which involves genetically defective cardiac sodium channels, acquired damage to cardiac sodium channels may also occur in Chagas disease. We studied several conventional and advanced resting 12-lead/derived Frank-lead ECG parameters in 34 patients with Chagas -related heart disease (mean age 39 14 years) and in 34 age-/gender-matched healthy controls. All ECG recordings were of 5-10 min duration, obtained in the supine position using high fidelity hardware/software (CardioSoft, Houston, TX). Even after excluding those Chagas patients who had resting BBBs, tachycardia and/or pathologic arrhythmia (n=8), significant differences remained in multiple conventional and advanced ECG parameters between the Chagas and control groups (n=26/group), especially in their respective QT interval variability indices, maximal spatial QRS-T angles and low frequency HRV powers (p=0.0006, p=0.0015 and p=0.0314 respectively). In relation to the issue of potential damage to cardiac sodium channels, the Chagas patients had: 1) greater than or equal to twice the incidence of resting ST segment elevation in leads V1-V3 (n=10/26 vs. n=5/26) and of both leftward (n=5/26 versus n=0/26) and rightward (n=7/26 versus n=3/26) QRS axis deviation than controls; 2) significantly increased filtered (40-250 Hz) QRS interval durations (92.1 8.5 versus 85.3 plus or minus 9.0 ms, p=0.022) versus controls; and 3) significantly decreased QT and especially JT interval durations versus controls (QT interval: 387.5 plus or minus 26.4 versus 408.9 plus or minus 34.6 ms, p=0.013; JT interval: 290.5 plus or minus 26.3 versus 314.8 plus or minus 31.3 ms; p=0.0029). Heart rates and Bazett-corrected QTc/JTc intervals were not significantly different between groups. Patients with Chagas heart disease have increased cardiac repolarization abnormalities, especially by advanced ECG. Moreover, as a group, they have decreased uncorrected JT and QT interval durations and increased filtered QRS interval durations (versus age/gender-matched controls), all suggesting a potential loss of cardiac sodium channel function that might be mediated, in part, by cardiac autonomic damage. Overall findings support Brugada et al's recent hypothesis that the pathway leading to sudden death may often be similar in Chagas' disease and Brugada syndrome i.e., damage to the sodium channel (infectious/immunologic/autonomic in Chagas' genetic in Brugada) with consequent loss of sodium currents may facilitate a phase II-reentry based arrhythmic substrate for ventricular fibrillation in both conditions. In general, JT interval-related results have been underreported in the Chagas literature

Identification and quantification of particle growth channels during new particle formation

Atmospheric new particle formation (NPF) is a key source of ambient ultrafine particles that may contribute substantially to the global production of cloud condensation nuclei (CCN). While NPF is driven by atmospheric nucleation, its impact on CCN concentration depends strongly on atmospheric growth mechanisms since the growth rate must exceed the loss rate due to scavenging in order for the particles to reach the CCN size range. In this work, chemical composition measurements of 20 nm diameter particles during NPF in Hyytiälä, Finland, in March–April 2011 permit identification and quantitative assessment of important growth channels. In this work we show the following: (A) sulfuric acid, a key species associated with atmospheric nucleation, accounts for less than half of particle mass growth during this time period; (B) the sulfate content of a growing particle during NPF is quantitatively explained by condensation of gas-phase sulfuric acid molecules (i.e., sulfuric acid uptake is collision-limited); (C) sulfuric acid condensation substantially impacts the chemical composition of preexisting nanoparticles before new particles have grown to a size sufficient to be measured; (D) ammonium and sulfate concentrations are highly correlated, indicating that ammonia uptake is driven by sulfuric acid uptake; (E) sulfate neutralization by ammonium does not reach the predicted thermodynamic end point, suggesting that a barrier exists for ammonia uptake; (F) carbonaceous matter accounts for more than half of the particle mass growth, and its oxygen-to-carbon ratio (~ 0.5) is characteristic of freshly formed secondary organic aerosol; and (G) differences in the overall growth rate from one formation event to another are caused by variations in the growth rates of all major chemical species, not just one individual species

Advanced Electrocardiographic Predictors of Sudden Death in Familial Dysautonomia

To identify accurate predictors for the risk of sudden death in patients with familial dysautonomia (FD). Ten-minute resting high-fidelity 12-lead ECGs were obtained from 14 FD patients and 14 age/gender-matched healthy subjects. Multiple conventional and advanced ECG parameters were studied for their ability to predict sudden death in FD over a subsequent 4.5-year period, including multiple indices of linear and non-linear heart rate variability (HRV); QT variability; waveform complexity; high frequency QRS; and derived Frank-lead parameters. Four of the 14 FD patients died suddenly during the follow-up period, usually with concomitant pulmonary disorder. The presence of low vagally-mediated HRV was the ECG finding most predictive of sudden death. Concomitant left ventricular hypertrophy and other ECG abnormalities such as increased QTc and JTc intervals, spatial QRS-T angles, T-wave complexity, and QT variability were also present in FD patients, suggesting that structural heart disease is fairly common in FD. Although excessive or unopposed cardiac vagal (relative to sympathetic) activity has been postulated as a contributor to sudden death in FD, the presence of low vagally-mediated HRV was paradoxically the best predictor of sudden death. However, we suggest that low vagally-mediated HRV be construed not as a direct cause of sudden death in FD, but rather as an effect of concurrent pathological processes, especially hypoxia due to pulmonary disorders and sleep apnea, that themselves increase the risk of sudden death in FD and simultaneously diminish HRV. We speculate that adenosine may play a role in sudden death in FD, possibly independently of vagal activity, and that adenosine inhibitors such as theophylline might therefore be useful as prophylaxis in this disorder

Seasonal calibration of the end-cretaceous Chicxulub impact event

The end-Cretaceous Chicxulub impact triggered Earth’s last mass-extinction, extinguishing ~ 75% of species diversity and facilitating a global ecological shift to mammal-dominated biomes. Temporal details of the impact event on a fine scale (hour-to-day), important to understanding the early trajectory of mass-extinction, have largely eluded previous studies. This study employs histological and histo-isotopic analyses of fossil fish that were coeval with a unique impact-triggered mass-death assemblage from the Cretaceous-Paleogene (KPg) boundary in North Dakota (USA). Patterns of growth history, including periodicity of ẟ18O and ẟ13C and growth band morphology, plus corroborating data from fish ontogeny and seasonal insect behavior, reveal that the impact occurred during boreal Spring/Summer, shortly after the spawning season for fish and most continental taxa. The severity and taxonomic symmetry of response to global natural hazards are influenced by the season during which they occur, suggesting that post-impact perturbations could have exerted a selective force that was exacerbated by seasonal timing. Data from this study can also provide vital hindsight into patterns of extant biotic response to global-scale hazards that are relevant to both current and future biomes

A seismically induced onshore surge deposit at the KPg boundary, North Dakota

This work is licensed under a Creative Commons Attribution 4.0 International License.The most immediate effects of the terminal-Cretaceous Chicxulub impact, essential to understanding the global-scale environmental and biotic collapses that mark the Cretaceous–Paleogene extinction, are poorly resolved despite extensive previous work. Here, we help to resolve this by describing a rapidly emplaced, high-energy onshore surge deposit from the terrestrial Hell Creek Formation in Montana. Associated ejecta and a cap of iridium-rich impactite reveal that its emplacement coincided with the Chicxulub event. Acipenseriform fish, densely packed in the deposit, contain ejecta spherules in their gills and were buried by an inland-directed surge that inundated a deeply incised river channel before accretion of the fine-grained impactite. Although this deposit displays all of the physical characteristics of a tsunami runup, the timing (<1 hour postimpact) is instead consistent with the arrival of strong seismic waves from the magnitude Mw ∼10 to 11 earthquake generated by the Chicxulub impact, identifying a seismically coupled seiche inundation as the likely cause. Our findings present high-resolution chronology of the immediate aftereffects of the Chicxulub impact event in the Western Interior, and report an impact-triggered onshore mix of marine and terrestrial sedimentation—potentially a significant advancement for eventually resolving both the complex dynamics of debris ejection and the full nature and extent of biotic disruptions that took place in the first moments postimpact.Netherlands Organization for Scientific Research Grant 864.12.005United Kingdom Science and Technology Facilities Council (Grant STFC:ST/M001814/1

Damaging variants in FOXI3 cause microtia and craniofacial microsomia

Q1Q1Pacientes con Microtia y Microsomía craneofacialPurpose: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. Methods: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. Results: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. Conclusion: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.https://orcid.org/0000-0003-3822-7780https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N

Burden of Rare Sarcomere Gene Variants in the Framingham and Jackson Heart Study Cohorts

Rare sarcomere protein variants cause dominant hypertrophic and dilated cardiomyopathies. To evaluate whether allelic variants in eight sarcomere genes are associated with cardiac morphology and function in the community, we sequenced 3,600 individuals from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS) cohorts. Out of the total, 11.2% of individuals had one or more rare nonsynonymous sarcomere variants. The prevalence of likely pathogenic sarcomere variants was 0.6%, twice the previous estimates; however, only four of the 22 individuals had clinical manifestations of hypertrophic cardiomyopathy. Rare sarcomere variants were associated with an increased risk for adverse cardiovascular events (hazard ratio: 2.3) in the FHS cohort, suggesting that cardiovascular risk assessment in the general population can benefit from rare variant analysis

Seasonal calibration of the end-cretaceous Chicxulub impact event

From Springer Nature via Jisc Publications RouterHistory: received 2021-08-29, accepted 2021-11-29, collection 2021-12, registration 2021-12-01, pub-electronic 2021-12-08, online 2021-12-08Publication status: PublishedAbstract: The end-Cretaceous Chicxulub impact triggered Earth’s last mass-extinction, extinguishing ~ 75% of species diversity and facilitating a global ecological shift to mammal-dominated biomes. Temporal details of the impact event on a fine scale (hour-to-day), important to understanding the early trajectory of mass-extinction, have largely eluded previous studies. This study employs histological and histo-isotopic analyses of fossil fish that were coeval with a unique impact-triggered mass-death assemblage from the Cretaceous-Paleogene (KPg) boundary in North Dakota (USA). Patterns of growth history, including periodicity of ẟ18O and ẟ13C and growth band morphology, plus corroborating data from fish ontogeny and seasonal insect behavior, reveal that the impact occurred during boreal Spring/Summer, shortly after the spawning season for fish and most continental taxa. The severity and taxonomic symmetry of response to global natural hazards are influenced by the season during which they occur, suggesting that post-impact perturbations could have exerted a selective force that was exacerbated by seasonal timing. Data from this study can also provide vital hindsight into patterns of extant biotic response to global-scale hazards that are relevant to both current and future biomes