Radon decay product particle radioactivity and oxidative stress biomarkers in patients with COPD.

Radon decay products include α-radiation emitting radionuclides that attach to airborne particles that have potential to promote oxidative tissue damage after inhalation. To assess associations between α-particle radioactivity (α-PR) with urinary biomarkers of oxidative tissue damage, 140 patients with chronic obstructive pulmonary disease (COPD) had up to four 1-week seasonal assessments (N = 413) of indoor (home) and ambient (central site) PM2.5 and black carbon (BC). Following environmental sampling, urine samples were analyzed for total and free malondialdehyde (MDA), biomarkers of lipid oxidation, and 8-hydroxyl-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage. Particle radioactivity was measured as α-activity on PM2.5 filter samples. Linear mixed-effects regression models adjusted for urinary creatinine and other personal characteristics were used to assess associations. Indoor α-PR was associated with an increase in 8-OhdG (8.53%; 95% CI: 3.12, 14.23); total MDA (5.59%; 95% CI: 0.20, 11.71); and free MDA (2.17%; 95% CI: 2.75, 7.35) per interquartile range (IQR) of α-PR [median 1.25 mBq/m3; IQR 0.64], similar adjusting for PM2.5 or BC. The ratio of indoor/ambient α-PR was positively associated with each biomarker and associations with ambient α-PR were positive but weaker than with indoor concentrations. These findings are consistent with a contribution of radon decay products as measured by α-PR to oxidative stress in patients with COPD, with a greater contribution of indoor radon decay products.

Prediagnosis Smoking Cessation and Overall Survival Among Patients With Non-Small Cell Lung Cancer.

Importance: Lung cancer remains the leading cause of cancer-related death globally; non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases, and cigarette smoking is the factor most significantly associated with its risk. However, little is known about the association of years since prediagnosis smoking cessation and cumulative smoking with overall survival (OS) following a lung cancer diagnosis. Objective: To characterize the association of years since smoking cessation before diagnosis and cumulative smoking pack-years with OS in patients with NSCLC in a lung cancer survivor cohort. Design, Setting, and Participants: The cohort study involved patients with NSCLC who were recruited to the Boston Lung Cancer Survival Cohort at Massachusetts General Hospital (Boston, Massachusetts) between 1992 and 2022. Patients' smoking history and baseline clinicopathological characteristics were prospectively collected through questionnaires, and OS following lung cancer diagnosis was regularly updated. Exposures: Duration of smoking cessation before a lung cancer diagnosis. Main Outcomes and Measures: The primary outcome was the association of detailed smoking history with OS following a lung cancer diagnosis. Results: Of 5594 patients with NSCLC (mean [SD] age, 65.6 [10.8] years; 2987 men [53.4%]), 795 (14.2%) were never smokers, 3308 (59.1%) were former smokers, and 1491 (26.7%) were current smokers. Cox regression analysis suggested that former smokers had 26% higher mortality (hazard ratio [HR], 1.26; 95% CI, 1.13-1.40; P < .001) and current smokers had 68% higher mortality (HR, 1.68; 95% CI, 1.50-1.89; P < .001) compared with never smokers. Log2-transformed years since smoking cessation before diagnosis were associated with significantly lower mortality among ever smokers (HR, 0.96; 95% CI, 0.93-0.99; P = .003). Subgroup analysis, stratified by clinical stage at diagnosis, revealed that former and current smokers had even shorter OS among patients with early-stage disease. Conclusions and Relevance: In this cohort study of patients with NSCLC, quitting smoking early was associated with lower mortality following a lung cancer diagnosis, and the association of smoking history with OS may have varied depending on clinical stage at diagnosis, potentially owing to the differing treatment regimens and efficacy associated with smoking exposure following diagnosis. Detailed smoking history collection should be incorporated into future epidemiological and clinical studies to improve lung cancer prognosis and treatment selection.

Cobalt chloride postconditioning as myoprotective therapy in cardiac ischemia-reperfusion.

Since damage induced by ischemia-reperfusion (I/R) involves alterations in Ca2+ homeostasis and is reduced by ischemic postconditioning (IP) and that CoCl2 can trigger changes resembling the response to a hypoxic event in normoxia and its blockade on Ca2+ current in heart muscle, our aim was to evaluate CoCl2 as an IP therapeutic tool. Mechanic and energetic parameters of isolated and arterially perfused male Wistar rat heart ventricles were simultaneously analyzed in a model of I/R in which 0.23 mmol/L CoCl2 was introduced upon reperfusion and kept or withdrawn after 20 min or introduced after 20 min of reperfusion. The presence of CoCl2 did not affect diastolic pressure but increased post-ischemic contractile recovery, which peaked at 20 min and decreased at the end of reperfusion. This decrease was prevented when CoCl2 was removed at 20 min of reperfusion. Total heat release increased throughout reperfusion, while economy increased between 15 and 25 min. No effect was observed when CoCl2 was introduced at 20 min of reperfusion. In addition, both the area under the contracture curve evoked by 10 mmol/L caffeine-36 mmol/L Na+ and the contracture tension relaxation rate were higher with CoCl2.Furthermore, CoCl2 decreased the number of arrhythmias during reperfusion and the ventricular damaged area. The presence of CoCl2 in reperfusion induces cardioprotection consistent with the improvement in cellular calcium handling. The use of CoCl2 constitutes a potential cardioprotective tool of clinical relevance.

Restless legs syndrome severity in the National RLS Opioid Registry during the COVID-19 pandemic.

OBJECTIVE/BACKGROUND: No research has yet assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on restless legs syndrome (RLS). We hypothesized that RLS symptom severity would be increased during the COVID-19 pandemic in a sample of patients with diagnosed RLS. PATIENTS/METHODS: The National RLS Opioid Registry is a longitudinal observational study of patients using opioid medications for treatment of RLS. Questionnaires assessing RLS symptom severity, medication dosages, sleep disturbance, depression, and anxiety are administered at baseline and at recurring 6-month surveys. Survey responses from the outset of the pandemic in April/May 2020 were compared to responses completed by other participants in January/February 2020 (between-subjects analysis), as well as responses by the same participants at baseline, approximately six months later in September 2020 through February 2021, and approximately one year later in March through June 2021 (within-subjects analyses). RESULTS: These analyses provide evidence for higher RLS symptom severity scores at the outset of the COVID-19 pandemic in the US. Symptom severity scores were still elevated on subsequent questionnaires completed over six months into the pandemic but had returned towards baseline by the spring of 2021. Participants with increases in RLS severity were significantly more likely than others to see increases in sleep disturbance, depression, and anxiety. CONCLUSIONS: This is the first study demonstrating increased RLS symptom severity during the earliest stage of the COVID-19 pandemic. These findings warrant similar investigations in other patient populations and suggest that clinicians should attend to RLS symptoms during times of socioeconomic and/or political uncertainty.

Tuning single-electron charging and interactions between compressible Landau level islands in graphene.

Interacting and tunable quantum dots (QDs) have been extensively exploited in condensed matter physics and quantum information science. Using a low-temperature scanning tunneling microscope (STM), we both create and directly image a new type of coupled QD system in graphene, a highly interacting quantum relativistic system with tunable density. Using detailed scanning tunneling spectroscopy (STS) measurements, we show that Landau quantization inside a potential well enables novel electron confinement via the incompressible strips between partially filled Landau levels (LLs), forming isolated and concentric LL QDs. By changing the charge density and the magnetic field we can tune continuously between single- and double-concentric LL QD systems within the same potential well. In the concentric QD regime, single-electron charging peaks of the two dots intersect, displaying a characteristic avoidance pattern. At moderate fields, we observe an unconventional avoidance pattern that differs significantly from that observed in capacitively coupled double-QD systems. We find that we can reproduce in detail this anomalous avoidance pattern within the framework of the electrostatic double-QD model by replacing the capacitive interdot coupling with a phenomenological charge-counting system in which charges in the inner concentric dot are counted in the total charge of both islands. The emergence of such strange forms of interdot coupling in a single potential well, together with the ease of producing such charge pockets in graphene and other two-dimensional (2D) materials, reveals an intriguing testbed for the confinement of 2D electrons in customizable potentials.

Interaction-driven quantum Hall wedding cake-like structures in graphene quantum dots.

Quantum-relativistic matter is ubiquitous in nature; however, it is notoriously difficult to probe. The ease with which external electric and magnetic fields can be introduced in graphene opens a door to creating a tabletop prototype of strongly confined relativistic matter. Here, through a detailed spectroscopic mapping, we directly visualize the interplay between spatial and magnetic confinement in a circular graphene resonator as atomic-like shell states condense into Landau levels. We directly observe the development of a "wedding cake"-like structure of concentric regions of compressible-incompressible quantum Hall states, a signature of electron interactions in the system. Solid-state experiments can, therefore, yield insights into the behavior of quantum-relativistic matter under extreme conditions.

An on/off Berry phase switch in circular graphene resonators.

The phase of a quantum state may not return to its original value after the system's parameters cycle around a closed path; instead, the wave function may acquire a measurable phase difference called the Berry phase. Berry phases typically have been accessed through interference experiments. Here, we demonstrate an unusual Berry phase-induced spectroscopic feature: a sudden and large increase in the energy of angular-momentum states in circular graphene p-n junction resonators when a relatively small critical magnetic field is reached. This behavior results from turning on a π Berry phase associated with the topological properties of Dirac fermions in graphene. The Berry phase can be switched on and off with small magnetic field changes on the order of 10 millitesla, potentially enabling a variety of optoelectronic graphene device applications.

Local atomic and electronic structure of boron chemical doping in monolayer graphene.

We use scanning tunneling microscopy and X-ray spectroscopy to characterize the atomic and electronic structure of boron-doped and nitrogen-doped graphene created by chemical vapor deposition on copper substrates. Microscopic measurements show that boron, like nitrogen, incorporates into the carbon lattice primarily in the graphitic form and contributes ~0.5 carriers into the graphene sheet per dopant. Density functional theory calculations indicate that boron dopants interact strongly with the underlying copper substrate while nitrogen dopants do not. The local bonding differences between graphitic boron and nitrogen dopants lead to large scale differences in dopant distribution. The distribution of dopants is observed to be completely random in the case of boron, while nitrogen displays strong sublattice clustering. Structurally, nitrogen-doped graphene is relatively defect-free while boron-doped graphene films show a large number of Stone-Wales defects. These defects create local electronic resonances and cause electronic scattering, but do not electronically dope the graphene film.

Connecting dopant bond type with electronic structure in N-doped graphene.

Robust methods to tune the unique electronic properties of graphene by chemical modification are in great demand due to the potential of the two dimensional material to impact a range of device applications. Here we show that carbon and nitrogen core-level resonant X-ray spectroscopy is a sensitive probe of chemical bonding and electronic structure of chemical dopants introduced in single-sheet graphene films. In conjunction with density functional theory based calculations, we are able to obtain a detailed picture of bond types and electronic structure in graphene doped with nitrogen at the sub-percent level. We show that different N-bond types, including graphitic, pyridinic, and nitrilic, can exist in a single, dilutely N-doped graphene sheet. We show that these various bond types have profoundly different effects on the carrier concentration, indicating that control over the dopant bond type is a crucial requirement in advancing graphene electronics.

Visualizing individual nitrogen dopants in monolayer graphene.

In monolayer graphene, substitutional doping during growth can be used to alter its electronic properties. We used scanning tunneling microscopy, Raman spectroscopy, x-ray spectroscopy, and first principles calculations to characterize individual nitrogen dopants in monolayer graphene grown on a copper substrate. Individual nitrogen atoms were incorporated as graphitic dopants, and a fraction of the extra electron on each nitrogen atom was delocalized into the graphene lattice. The electronic structure of nitrogen-doped graphene was strongly modified only within a few lattice spacings of the site of the nitrogen dopant. These findings show that chemical doping is a promising route to achieving high-quality graphene films with a large carrier concentration.