Hybrid approach to complex thoracic aortic aneurysms in high-risk patients: Surgical challenges and clinical outcomes

BackgroundEndovascular therapy is a less invasive alternative treatment for high-risk patients with thoracic aortic aneurysms. However, this technology alone is often not applicable to complex aneurysmal morphology. The purpose of this study was to evaluate the utility of hybrid strategies in high-risk patients who are otherwise unsuitable for endovascular therapy alone.MethodsDuring an 18-month period, 31 high-risk patients (mean age, 69 years; range, 52-89 years) underwent combined open and endovascular approaches for complex aneurysms, including 16 patients with ascending and arch aneurysms and 15 patients with aneurysms involving visceral vessels. Among them, 11 patients had histories of aneurysm repairs. To overcome the anatomic limitations of endovascular repairs, various adjunctive surgical maneuvers were used, including aortic arch reconstruction in 3 patients, supra-aortic trunk debranching in 13 patients (including 8 patients who required aortas as inflow sources), and visceral vessel bypasses in 15 patients (including 10 patients who required bypasses to all 3 visceral branches). Additionally, carotid artery access was obtained in 1 patient, and iliac artery conduits were created in 12 patients.ResultsTechnical success was achieved in all patients. There was one perioperative death (3.2%) due to postoperative bleeding. Two patients (6.4%) had immediate type II endoleaks, which were resolved by the 1-month follow-up. Other procedure-related complications occurred in three patients (9.6%), including renal bypass thromboses in two patients and retroperitoneal hematoma, which was successfully managed conservatively, in one patient. During a mean follow-up of 16 months, two patients died of unrelated causes, whereas the remainder of patients were asymptomatic, without aneurysm enlargement.ConclusionsOur study highlights how hybrid strategies incorporating surgical and endovascular approaches can be used successfully in treating patients with complex thoracic aortic aneurysms. This combined approach potentially expands the field of endovascular stent grafting and is an attractive solution for patients with poor cardiopulmonary reserves

Transgenerational sperm DMRs escape DNA methylation erasure during embryonic development and epigenetic inheritance

Germline transmission of epigenetic information is a critical component of epigenetic inheritance. Previous studies have suggested that an erasure of DNA methylation is required to develop stem cells in the morula embryo. An exception involves imprinted genes that escape this DNA methylation erasure. Transgenerational differential DNA methylation regions (DMRs) have been speculated to be imprinted-like and escape this erasure. The current study was designed to assess if morula embryos escape the erasure of dichlorodiphenyltrichloroethane-induced transgenerational sperm DMR methylation. Observations demonstrate that the majority (98%) of transgenerational sperm DMR sites retain DNA methylation and are not erased, so appearing similar to imprinted-like sites. Interestingly, observations also demonstrate that the majority of low-density CpG genomic sites had a significant increase in DNA methylation in the morula embryo compared to sperm. This is in contrast to the previously observed DNA methylation erasure of higher-density CpG sites. The general erasure of DNA methylation during embryogenesis appears applicable to high-density DNA methylation sites (e.g. CpG islands) but neither to transgenerational DMR methylation sites nor to low-density CpG deserts, which constitute the vast majority of the genome's DNA methylation sites. The role of epigenetics during embryogenesis appears more dynamic than the simple erasure of DNA methylation

Epigenetic transgenerational inheritance of testis pathology and Sertoli cell epimutations: generational origins of male infertility

Male reproductive health has been in decline for decades with dropping sperm counts and increasing infertility, which has created a significant societal and economic burden. Between the 1970s and now, a general decline of over 50% in sperm concentration has been observed in the population. Environmental toxicant-induced epigenetic transgenerational inheritance has been shown to affect testis pathology and sperm count. Sertoli cells have an essential role in spermatogenesis by providing physical and nutritional support for developing germ cells. The current study was designed to further investigate the transgenerational epigenetic changes in the rat Sertoli cell epigenome and transcriptome that are associated with the onset of testis disease. Gestating female F0 generation rats were transiently exposed during the period of fetal gonadal sex determination to the environmental toxicants, such as dichlorodiphenyltrichloroethane (DDT) or vinclozolin. The F1 generation offspring were bred (i.e. intercross within the lineage) to produce the F2 generation grand-offspring that were then bred to produce the transgenerational F3 generation (i.e. great-grand-offspring) with no sibling or cousin breeding used. The focus of the current study was to investigate the transgenerational testis disease etiology, so F3 generation rats were utilized. The DNA and RNA were obtained from purified Sertoli cells isolated from postnatal 20-day-old male testis of F3 generation rats. Transgenerational alterations in DNA methylation, noncoding RNA, and gene expression were observed in the Sertoli cells from vinclozolin and DDT lineages when compared to the control (vehicle exposed) lineage. Genes associated with abnormal Sertoli cell function and testis pathology were identified, and the transgenerational impacts of vinclozolin and DDT were determined. Alterations in critical gene pathways, such as the pyruvate metabolism pathway, were identified. Observations suggest that ancestral exposures to environmental toxicants promote the epigenetic transgenerational inheritance of Sertoli cell epigenetic and transcriptome alterations that associate with testis abnormalities. These epigenetic alterations appear to be critical factors in the developmental and generational origins of testis pathologies and male infertility

Anticipatory pleasure predicts effective connectivity in the mesolimbic system

Convergent evidence suggests the important role of the mesolimbic pathway in anticipating monetary rewards. However, the underlying mechanism of how the sub-regions interact with each other is still not clearly understood. Using dynamic causal modeling, we constructed a reward-related network for anticipating monetary reward using the Monetary Incentive Delay Task. Twenty-six healthy adolescents (Female/Male = 11/15; age = 18.69 +/- 1.35 years; education = 12 +/- 1.58 years) participated in the present study. The best-fit network involved the right substantia nigra/ventral tegmental area (SN/VTA), the right nucleus accumbens (NAcc) and the right thalamus, which were all activated during anticipation of monetary gain and loss. The SN/VTA directly activates the NAcc and the thalamus. More importantly, monetary gain modulated the connectivity from the SN/VTA to the NAcc and this was significantly correlated with subjective anticipatory pleasure (r = 0.649, p < 0.001). Our findings suggest that activity in the mesolimbic pathway during the anticipation of monetary reward could to some extent be predicted by subjective anticipatory pleasure

Evaluation of simulated soil carbon dynamics in Arctic-Boreal ecosystems

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Huntzinger, D. N., Schaefer, K., Schwalm, C., Fisher, J. B., Hayes, D., Stofferahn, E., Carey, J., Michalak, A. M., Wei, Y., Jain, A. K., Kolus, H., Mao, J., Poulter, B., Shi, X., Tang, J., & Tian, H. Evaluation of simulated soil carbon dynamics in Arctic-Boreal ecosystems. Environmental Research Letters, 15(2), (2020): 025005, doi:10.1088/1748-9326/ab6784.Given the magnitude of soil carbon stocks in northern ecosystems, and the vulnerability of these stocks to climate warming, land surface models must accurately represent soil carbon dynamics in these regions. We evaluate soil carbon stocks and turnover rates, and the relationship between soil carbon loss with soil temperature and moisture, from an ensemble of eleven global land surface models. We focus on the region of NASA's Arctic-Boreal vulnerability experiment (ABoVE) in North America to inform data collection and model development efforts. Models exhibit an order of magnitude difference in estimates of current total soil carbon stocks, generally under- or overestimating the size of current soil carbon stocks by greater than 50 PgC. We find that a model's soil carbon stock at steady-state in 1901 is the prime driver of its soil carbon stock a hundred years later—overwhelming the effect of environmental forcing factors like climate. The greatest divergence between modeled and observed soil carbon stocks is in regions dominated by peat and permafrost soils, suggesting that models are failing to capture the frozen soil carbon dynamics of permafrost regions. Using a set of functional benchmarks to test the simulated relationship of soil respiration to both soil temperature and moisture, we find that although models capture the observed shape of the soil moisture response of respiration, almost half of the models examined show temperature sensitivities, or Q10 values, that are half of observed. Significantly, models that perform better against observational constraints of respiration or carbon stock size do not necessarily perform well in terms of their functional response to key climatic factors like changing temperature. This suggests that models may be arriving at the right result, but for the wrong reason. The results of this work can help to bridge the gap between data and models by both pointing to the need to constrain initial carbon pool sizes, as well as highlighting the importance of incorporating functional benchmarks into ongoing, mechanistic modeling activities such as those included in ABoVE.This work was supported by NASA'S Arctic Boreal Vulnerability Experiment (ABoVE; https://above.nasa.gov); NNN13D504T. Funding for the Multi-scale synthesis and Terrestrial Model Intercomparison Project (MsTMIP; https://nacp.ornl.gov/MsTMIP.shtml) activity was provided through NASA ROSES Grant #NNX10AG01A. Data management support for preparing, documenting, and distributing model driver and output data was performed by the Modeling and Synthesis Thematic Data Center at Oak Ridge National Laboratory (MAST-DC; https://nacp.ornl.gov), with funding through NASA ROSES Grant #NNH10AN681. Finalized MsTMIP data products are archived at the ORNL DAAC (https://daac.ornl.gov). We also acknowledge the modeling groups that provided results to MsTMIP. The synthesis of site-level soil respiration, temperature, and moisture data reported in Carey et al 2016a, 2016b) was funded by the US Geological Survey (USGS) John Wesley Powell Center for Analysis and Synthesis Award G13AC00193. Additional support for that work was also provided by the USGS Land Carbon Program. JBF carried out the research at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. California Institute of Technology. Government sponsorship acknowledged

Coulomb interactions at quantum Hall critical points of systems in a periodic potential

We study the consequences of long-range Coulomb interactions at the critical points between integer/fractional quantum Hall states and an insulator. We use low energy theories for such transitions in anyon gases in the presence of an external periodic potential. We find that Coulomb interactions are marginally irrelevant for the integer quantum Hall case. For the fractional case, depending upon the anyon statistics parameter, we find behavior similar to the integer case, or flow to a novel line of fixed points with exponents $z=1$, $\nu > 1$ stable against weak disorder in the position of the critical point, or run-away flow to strong coupling.Comment: 12 pages, REVTEX, 1 figur

Spin-flip scattering in the quantum Hall regime

We present a microscopic theory of spin-orbit coupling in the integer quantum Hall regime. The spin-orbit scattering length is evaluated in the limit of long-range random potential. The spin-flip rate is shown to be determined by rare fluctuations of anomalously high electric field. A mechanism of strong spin-orbit scattering associated with exchange-induced spontaneous spin-polarization is suggested. Scaling of the spin-splitting of the delocalization transition with the strength of spin-orbit and exchange interactions is also discussed.Comment: References added, small additional comments, to appear in Phys. Rev. B; 23 pages, RevTeX 3.

Characterization and determinant factors of critical illness and in-hospital mortality of COVID-19 patients: A retrospective cohort of 1,792 patients in Kenya

Limited data is available on the coronavirus disease 2019 (COVID-19), critical illness rate, and in-hospital mortality in the African setting. This study investigates determinants of critical illness and in-hospital mortality among COVID-19 patients in Kenya. We conducted a retrospective cohort study at Kenyatta National Hospital (KNH) in Kenya. Multivariate logistic regression and Cox proportional hazard regression were employed to determine predictor factors for intensive care unit (ICU) admission and in-hospital mortality, respectively. In addition, the Kaplan-Meier model was used to compare the survival times using log-rank tests. As a result, 346 (19.3 %) COVID-19 patients were admitted to ICU, and 271 (15.1 %) died. The majority of those admitted to the hospital were male, 1,137 (63.4 %) and asymptomatic, 1,357 (75.7 %). The most prevalent clinical features were shortness of breath, fever, and dry cough. In addition, older age, male, health status, patient on oxygen (O2), oxygen saturation levels (SPO2), headache, dry cough, comorbidities, obesity, cardiovascular diseases (CVDs), diabetes, chronic lung disease (CLD), and malignancy/cancer can predicate the risk of ICU admission, with an area under the receiver operating characteristic curve (AUC-ROC) of 0.90 (95 % confidence interval [CI]: 0.88 – 0.92). Survival analysis indicated 271 (15.1 %) patients died and identified older age, male, headache, shortness of breath, health status, patient on oxygen, SPO2, headache, comorbidity, CVDs, diabetes, CLD, malignancy/cancer, and smoking as risk factors for mortality (AUC-ROC: 0.90, 95 % CI: 0.89 – 0.91). This is the first attempt to explore predictors for ICU admission and hospital mortality among COVID-19 patients in Kenya