Spatially-Dense, Multi-Spectral, Frequency-Domain Diffuse Optical Tomography of Breast Cancer

Diffuse optical tomography (DOT) employs near-infrared light to image the concentration of chromophores and cell organelles in tissue and thereby providing access to functional parameters that can differentiate cancerous from normal tissues. This thesis describes research at the bench and in the clinic that explores and identifies the potential of DOT breast cancer imaging. The bench and clinic instrumentation differ but share important features: they utilize a very large, spatially dense, set of source-detector pairs (10E7) for imaging in the parallel-plate geometry. The bench experiments explored three-dimensional (3D) image resolution and fidelity as a function of numerous parameters and also ascertained the effects of a chest wall phantom. The chest wall is always present but is typically ignored in breast DOT. My experiments clarified chest wall influences and developed schemes to mitigate these effects. Mostly, these schemes involved selective data exclusion, but their efficacy also depended on reconstruction approach. Reconstruction algorithms based on analytic (fast) Fourier inversion and linear algebraic techniques were explored. The clinical experiments centered around a DOT instrument that I designed, constructed, and have begun to test (in-vitro and in-vivo). This instrumentation offers many features new to the field. Specifically, the imager employs spatially-dense, multi-spectral, frequency-domain data; it possesses the world\u27s largest optical source-detector density yet reported, facilitated by highly-parallel CCD-based frequency-domain imaging based on gain-modulation heterodyne detection. The instrument thus measures both phase and amplitude of the diffusive light waves. Other features include both frontal and sagittal breast imaging capabilities, ancillary cameras for measurement of breast boundary profiles, real-time data normalization, and mechanical improvements for patient comfort. The instrument design and construction is my most significant contribution, but first imaging experiments with tissue phantoms and of cancer bearing breasts were also carried out. A parallel effort with simulated data has yielded important information about new reconstruction regularization issues that arise when phase and amplitude are measured. With these gains in device implementation and DOT reconstruction, my research takes valuable steps towards bringing this novel imaging technique closer to clinical utilization

Curative Effects of Thiacremonone against Acetaminophen-Induced Acute Hepatic Failure via Inhibition of Proinflammatory Cytokines Production and Infiltration of Cytotoxic Immune Cells and Kupffer Cells

High doses of acetaminophen (APAP; N-acetyl-p-aminophenol) cause severe hepatotoxicity after metabolic activation by cytochrome P450 2E1. This study was undertaken to examine the preventive effects of thiacremonone, a compound extracted from garlic, on APAP-induced acute hepatic failure in male C57BL/6J. Mice received with 500 mg/kg APAP after a 7-day pretreatment with thiacremonone (10–50 mg/kg). Thiacremonone inhibited the APAP-induced serum ALT and AST levels in a dose-dependent manner, and markedly reduced the restricted area of necrosis and inflammation by administration of APAP. Thiacremonone also inhibited the APAP-induced depletion of intracellular GSH, induction of nitric oxide, and lipid peroxidation as well as expression of P450 2E1. After APAP injection, the numbers of Kupffer cells, natural killer cells, and cytotoxic T cells were elevated, but the elevated cell numbers in the liver were reduced in thiacremonone pretreated mice. The expression levels of I-309, M-CSF, MIG, MIP-1α, MIP-1β, IL-7, and IL-17 were increased by APAP treatment, which were inhibited in thiacremonone pretreated mice. These data indicate that thiacremonone could be a useful agent for the treatment of drug-induced hepatic failure and that the reduction of cytotoxic immune cells as well as proinflammatory cytokine production may be critical for the prevention of APAP-induced acute liver toxicity

Sleep Disorders and Genes

Versão preprintThe sleep-wake cycle is a neurobiological phenomenon that shows intervals of activity alternating with restfulness that appears with a periodicity approximating the 24h day-night cycle. The sleep-wake cycle is under the control of diverse neuroanatomical and neurochemical systems, including monoaminergic, cholinergic, adenosinergic among many other systems. In addition, neuroanatomical centers linked to sleep promotion, such as hypothalamus, project to the cerebral cortex, subcortical relays and brainstem. In addition, the sleep-wake cycle has been associated to aberrant features known as sleep disorders. Here, we will discuss the role of specific gene expression on sleep disturbances. Given the expansion of the knowledge in the sleep-wake cycle area, it is indeed ambitious to describe all the genetics involved in the sleep modulation. However, in this chapter we reviewed the current understanding of the sleep disorders and gene expression.info:eu-repo/semantics/publishedVersio

Precision measurement of the branching fractions of J/psi -> pi+pi-pi0 and psi' -> pi+pi-pi0

We study the decays of the J/psi and psi' mesons to pi+pi-pi0 using data samples at both resonances collected with the BES III detector in 2009. We measure the corresponding branching fractions with unprecedented precision and provide mass spectra and Dalitz plots. The branching fraction for J/psi -> pi+pi-pi0 is determined to be (2.137 +- 0.004 (stat.) +0.058-0.056 (syst.) +0.027-0.026 (norm.))*10-2, and the branching fraction for psi' -> pi+pi-pi0 is measured as (2.14 +- 0.03 (stat.) +0.08-0.07 (syst.) +0.09-0.08 (norm.))*10-4. The J/psi decay is found to be dominated by an intermediate rho(770) state, whereas the psi' decay is dominated by di-pion masses around 2.2 GeV/c2, leading to strikingly different Dalitz distributions.Comment: 15 pages, 2 figure

Higher-order multipole amplitude measurement in ψ(2S)→γχc2\psi(2S)\to\gamma\chi_{c2}

Using $106\times10^6$ $\psi(2S)$ events collected with the BESIII detector at the BEPCII storage ring, the higher-order multipole amplitudes in the radiative transition $\psi(2S)\to\gamma\chi_{c2}\to\gamma\pi\pi/\gamma KK$ are measured. A fit to the $\chi_{c2}$ production and decay angular distributions yields $M2=0.046\pm0.010\pm0.013$ and $E3=0.015\pm0.008\pm0.018$, where the first errors are statistical and the second systematic. Here $M2$ denotes the normalized magnetic quadrupole amplitude and $E3$ the normalized electric octupole amplitude. This measurement shows evidence for the existence of the $M2$ signal with $4.4\sigma$ statistical significance and is consistent with the charm quark having no anomalous magnetic moment.Comment: 14 pages, 4 figure

Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin

Measurements of h_c(^1P_1) in psi' Decays

We present measurements of the charmonium state $h_c(^1P_1)$ made with 106M $\psi'$ events collected by BESIII at BEPCII. Clear signals are observed for $\psi'\to\pi^0 h_c$ with and without the subsequent radiative decay $h_c\to\gamma\eta_c$. First measurements of the absolute branching ratios $\mathcal{B}(\psi' \to\pi^0 h_c) = (8.4 \pm 1.3 \pm 1.0) \times 10^{-4}$ and $\mathcal{B}(h_c \to \gamma \eta_c) = (54.3 \pm 6.7 \pm5.2)$ are presented. A statistics-limited determination of the previously unmeasured $h_c$ width leads to an upper limit $\Gamma(h_c)<1.44$MeV (90% confidence). Measurements of $M(h_c) = 3525.40 \pm 0.13 \pm 0.18$MeV/$c^2$ and $\mathcal{B}(\psi'\to \pi^0 h_c) \times \mathcal{B}(h_c \to \gamma\eta_c) = (4.58 \pm 0.40 \pm 0.50) \times 10^{-4}$ are consistent with previous results.Comment: 5 pages, 1 figure, accepted for publication in Physical Review Letter

First observation of η(1405)\eta(1405) decays into f0(980)π0f_{0}(980)\pi^0

The decays $J/\psi \rightarrow \gamma \pi^+\pi^-\pi^0$ and $J/\psi \rightarrow \gamma \pi^0\pi^0\pi^0$ are analyzed using a sample of 225 million \jpsi events collected with the BESIII detector. The decay of \eta(1405)\ar f_{0}(980)\pi^0 with a large isospin violation is observed for the first time. The width of the $f_{0}(980)$ observed in the dipion mass spectra is anomalously narrower than the world average. Decay rates for three-pion decays of the $\eta'$ are also measured precisely.Comment: Revtex, 6 pages, 4 eps figures, version accepted by Phys. Rev. Letter

Study of resonant structure around 1.8 GeV/c2c^2 and η(1405)\eta(1405) in J/ψ→ωηπ+π−J/\psi\rightarrow\omega\eta\pi^+\pi^-

We present results of a study of the decay $J/\psi\rightarrow\omega\eta\pi^+\pi^-$ using a sample of $(225.2\pm2.8)\times10^6$ $J/\psi$ events collected by the BESIII detector, and report the observation of a new process of $J/\psi\rightarrow \omega X(1870)$ in which X(1870) decays to $a_0(980)\pi$. The statistical significance of this process is larger than $7.2\sigma$. Signals for $J/\psi\rightarrow \omega f_1(1285)$ and $J/\psi\rightarrow \omega\eta(1405)$ are also observed in $\eta\pi^+\pi^-$ spectrum, with statistical significances much larger than $10\sigma$.Comment: 6 pages, 7 figure