Assessment of the impact of race and proxies of socioeconomic status on the prevalence and health outcome of peripartum cardiomyopathy (PPCM) using the “All of Us” Databank

Background: Peripartum Cardiomyopathy (PPCM) is a form of cardiomyopathy occurring during the last month of pregnancy or within months after giving birth in women with previously normal hearts. PPCM is an idiopathic systolic dysfunction that causes a reduced left ventricle ejection fraction. The estimated incidence of PPCM worldwide is 1 diagnosis out of 2,000 live births, and the causes of PPCM remain unknown. A retrospective cohort study conducted at the University of Pennsylvania Health System by Getz et al. showed that black race and socioeconomic proxies (like neighborhood disadvantage index (NDI)) were independently associated with sustained cardiac dysfunction (Getz et al., Am Heart J 2021). This study also showed that from all the components of NDI (education, high rental occupied housing, annual income below poverty line, female headed household, adults unemployed, adults on public assistance), low education and high rental occupied housing were significantly associated with sustained cardiac dysfunction. The central aim of the present project is to assess the effect of socioeconomic proxies (including NDI, lack of access to health care and food insecurity) on the prevalence of sustained cardiac dysfunction from PPCM across the US using the “All of Us” databank. A secondary aim is to test the compliance of the All of Us database capacity to interrogate this potential association. Lastly, we aim to compare the results obtained from the All of Us database with the UK Biobank. Methods: The All of Us databank (Ramirez et al., Patterns 2022; The All of US Research Program, NEJM 2019) will be used to conduct a retrospective cohort study to assess how proxies of socioeconomic status may affect the incidence and prevalence of sustained cardiac dysfunction from PPCM across different ethnicities in the US. The All of Us database focuses on enrolling people in the US from diverse groups that have historically been underrepresented in medical research. Therefore, it includes a more diverse population than the population targeted in the retrospective study conducted at the University of Pennsylvania in which only black women from Philadelphia, PA, were included. To further interrogate the impact that geographic location and population ethnicity may have on the prevalence of sustained cardiac dysfunction from PPCM, the results obtained from the “All of Us” database will be compared against data obtained from the UK Biobank. Expected Results: We expect that the socioeconomic proxies interrogated in this study will have a significant impact on the prevalence of sustained cardiac dysfunction from PPCM. Current knowledge is limited on how socioeconomic status affects sustained cardiac dysfunction resulting from PPCM. Previous studies have been done on populations restricted to small geographic areas and did not analyze factors such as food security, access to care, or disability status. Understanding how these factors affect the incidence and prevalence of sustained cardiac dysfunction from PPCM may be used to improve prevention, early diagnosis, and management of PPCM

QCD-like Theories at Finite Baryon and Isospin Density

We use 2-color QCD as a model to study the effects of simultaneous presence of chemical potentials for isospin charge, $\mu_I$, and for baryon number, $\mu_B$. We determine the phase diagrams for 2 and 4 flavor theories using the method of effective chiral Lagrangians at low densities and weak coupling perturbation theory at high densities. We determine the values of various condensates and densities as well as the spectrum of excitations as functions of $\mu_I$ and $\mu_B$. A similar analysis of QCD with quarks in the adjoint representation is also presented. Our results can be of relevance for lattice simulations of these theories. We predict a phase of inhomogeneous condensation (Fulde-Ferrel-Larkin-Ovchinnikov phase) in the 2 colour 2 flavor theory, while we do not expect it the 4 flavor case or in other realizations of QCD with a positive measure.Comment: 17 pages, 14 figure

Analysis of autophagy and inflammasome regulation in neuronal cells and monocytes infected with Chlamydia pneumoniae: Implications for Alzheimer’s disease

Objectives: Our laboratory has been studying the role of infection with the obligate intracellular bacterium Chlamydia pneumoniae in sporadic late-onset Alzheimer disease (LOAD). This infection may be a trigger for the pathology observed in LOAD as a function of initiating changes in gene regulation following entry of the organism into the brain. As such, we are analyzing how this infection can promote changes in autophagy and inflammasome gene regulation as both have been shown to be altered in LOAD. Methods: Human SKNMC neuronal cells and THP1 monocytes were infected in vitro for 24-72 hrs with a laboratory strain of Chlamydia pneumoniae followed by RNA extraction, cDNA synthesis and analysis using Real-Time PCR microarrays for autophagy and inflammasome genes. Results: Gene expression for autophagy and inflammasome pathways was altered dramatically following infection. Genes encoding for co-regulation of autophagy, apoptosis, and the cell cycle that were significantly changed included: BCL2L1, FAS, PIK3CG, APP, and TP53. In addition, ATG3, and GABARAP, genes encoding for protein transport & ubiquitination and autophagic vacuole formation were significantly deregulated. Of the inflammasome genes, 4 NOD-like receptor genes were significantly up-regulated. IL-1beta, AIM2, CCL2, and CCL7 genes were all dramatically up-regulated in monocytes during the 72 hrs of infection. Conclusions: Our data suggest that Chlamydia pneumoniae-infected human SKNMC neuronal cells and THP1 monocytes exhibit specific changes in gene regulation for both autophagy and inflammasome pathways. These gene changes appear to correlate with pathologic changes previously reported in AD and further support the contention that infection with Chlamydia pneumoniae plays a role in LOAD pathogenesis.https://digitalcommons.pcom.edu/posters/1001/thumbnail.jp

Search for the Radiative Capture d+d->^4He+\gamma Reaction from the dd\mu Muonic Molecule State

A search for the muon catalyzed fusion reaction dd --> ^4He +\gamma in the dd\mu muonic molecule was performed using the experimental \mu CF installation TRITON and NaI(Tl) detectors for \gamma-quanta. The high pressure target filled with deuterium at temperatures from 85 K to 800 K was exposed to the negative muon beam of the JINR phasotron to detect \gamma-quanta with energy 23.8 MeV. The first experimental estimation for the yield of the radiative deuteron capture from the dd\mu state J=1 was obtained at the level n_{\gamma}\leq 2\times 10^{-5} per one fusion.Comment: 9 pages, 3 Postscript figures, submitted to Phys. At. Nuc

The Spectrum of Goldstini and Modulini

When supersymmetry is broken in multiple sectors via independent dynamics, the theory furnishes a corresponding multiplicity of "goldstini" degrees of freedom which may play a substantial role in collider phenomenology and cosmology. In this paper, we explore the tree-level mass spectrum of goldstini arising from a general admixture of F-term, D-term, and almost no-scale supersymmetry breaking, employing non-linear superfields and a novel gauge fixing for supergravity discussed in a companion paper. In theories of F-term and D-term breaking, goldstini acquire a mass which is precisely twice the gravitino mass, while the inclusion of no-scale breaking renders one of these modes, the modulino, massless. We argue that the vanishing modulino mass can be explained in terms of an accidental and spontaneously broken "global" supersymmetry.Comment: 10 pages, 2 figures; v2: typo corrected, references updated; v3: version to appear in JHE

A Precision Measurement of Nuclear Muon Capture on 3He

The muon capture rate in the reaction mu- 3He -> nu + 3H has been measured at PSI using a modular high pressure ionization chamber. The rate corresponding to statistical hyperfine population of the mu-3He atom is (1496.0 +- 4.0) s^-1. This result confirms the PCAC prediction for the pseudoscalar form factors of the 3He-3H system and the nucleon.Comment: 13 pages, 6 PostScript figure

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer\u27s disease: Research outline and call for collaboration.

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer\u27s disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer\u27s Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients

Cetuximab potentiates oxaliplatin cytotoxic effect through a defect in NER and DNA replication initiation

Preclinical studies have demonstrated that the chemotherapeutic action of oxaliplatin, a third generation platinum derivative, is improved when combined with cetuximab, a monoclonal antibody inhibitor of epidermal growth factor receptors. To explore the mechanism of this synergistic benefit, we used HCT-8 and HCT-116, two human colon cancer cell lines, respectively, responsive and non-responsive to the oxaliplatin/cetuximab combination. We examined the effect of drug exposure on glutathione-S-transferase-mediated oxaliplatin detoxification, DNA–platinum adducts formation, cell cycle distribution, apoptosis, and the expression of multiple targets involved in DNA replication, recombination, and repair. The major changes we found in HCT-8 were a stimulation of oxaliplatin–DNA adduct formation associated with reduced expression of the key enzyme (excision repair cross complementation group1: ERCC1) in the key repair process of oxaliplatin–DNA platinum adduct, the nucleotide excision repair (NER), both at the mRNA and protein levels. We also observed a reduced expression of factors involved in DNA replication initiation, which correlates with an enrichment of cells in the G1 phase of the cell cycle as well as an acceleration of apoptosis. None of these changes occurred in the non-responsive HCT-116 cell that we used as a negative control. These findings support the fact that cetuximab potentiates the oxaliplatin-mediated cytotoxic effect as the result of inhibition of NER and also DNA replication initiation

Muon capture by 3He nuclei followed by proton and deuteron production

The paper describes an experiment aimed at studying muon capture by ${}^{3}\mathrm{He}$ nuclei in pure ${}^{3}\mathrm{He}$ and $\mathrm{D}_2 + {}^{3}\mathrm{He}$ mixtures at various densities. Energy distributions of protons and deuterons produced via $\mu^-+{}^{3}\mathrm{He}\to p+n+n + \nu_{\mu }$ and $\mu^-+{}^{3} \mathrm{He} \to d+n + \nu_{\mu}$ are measured for the energy intervals $10 - 49$ MeV and $13 - 31$ MeV, respectively. Muon capture rates, $\lambda_\mathrm{cap}^p (\Delta E_p)$ and $\lambda_\mathrm{cap}^d (\Delta E_d)$ are obtained using two different analysis methods. The least--squares methods gives $\lambda_\mathrm{cap}^p = (36.7\pm 1.2) {s}^{- 1}$, $\lambda_\mathrm{cap}^d = (21.3 \pm 1.6) {s}^{- 1}$. The Bayes theorem gives $\lambda_\mathrm{cap}^p = (36.8 \pm 0.8) {s}^{- 1}$, $\lambda_\mathrm{cap}^d = (21.9 \pm 0.6) {s}^{- 1}$. The experimental differential capture rates, $d\lambda_\mathrm{cap}^p (E_p) / dE_p$ and $d\lambda_\mathrm{cap}^d (E_d) / dE_d$, are compared with theoretical calculations performed using the plane--wave impulse approximation (PWIA) with the realistic NN interaction Bonn B potential. Extrapolation to the full energy range yields total proton and deuteron capture rates in good agreement with former results.Comment: 17 pages, 13 figures, accepted for publication in PR

First Measurement of the Tensor Structure Function b1b_1 of the Deuteron

The \Hermes experiment has investigated the tensor spin structure of the deuteron using the 27.6 GeV/c positron beam of \Hera. The use of a tensor polarized deuteron gas target with only a negligible residual vector polarization enabled the first measurement of the tensor asymmetry \At and the tensor structure function \bd for average values of the Bj{\o}rken variable $0.01<0.45$ and of the squared four-momentum transfer $0.5 {\rm GeV^2} <5 {\rm GeV^2}$. The quantities \At and \bd are found to be non-zero. The rise of \bd for decreasing values of $x$ can be interpreted to originate from the same mechanism that leads to nuclear shadowing in unpolarized scattering