Persistently Frequent Emergency Department Utilization Among Persons With Systemic Lupus Erythematosus

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152017/1/acr23777.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152017/2/acr23777_am.pd

Meal and food preferences of nutritionally at-risk inpatients admitted to two Australian tertiary teaching hospitals

Aim: To determine preferences for meals and snack of long-stay patients and hospitalised patients with increased energy and protein requirements.----- Methods: Using consistent methodology across two tertiary teaching hospitals, a convenience sample of adult public hospital inpatients with increased energy and protein requirements or longer stays (seven days or more) were interviewed regarding meal and snack preferences. Descriptive reporting of sample representativeness, preferred foods and frequency of meals and between meal snacks.----- Results: Of 134 respondents, 55% reported a decreased appetite and 28% rated their appetite as 'poor'. Most felt like eating either nothing (42%) or soup (15%) when unwell. The most desired foods were hot meal items, including eggs (31%), meat dishes (20%) and soup (69%). Of items not routinely available, soft drink (7.6%) and alcohol (6.7%) were most commonly desired during admission. Almost half (49%) reported difficulty opening packaged food and a majority (81%) indicated finger foods were easy to eat.----- Conclusion: Appetites during admission were frequently lower than usual. Responses encourage consideration of eggs, meat dishes and soups for long-stayers or those with high-energy, high-protein needs. Easy to consume but not routinely offered, between meal items, such as soup, juice, cake, soft drink or Milo could be explored further to enhance oral intakes

Photon Assisted Tunneling of Zero Modes in a Majorana Wire

Hybrid nanowires with proximity-induced superconductivity in the topological regime host Majorana zero modes (MZMs) at their ends, and networks of such structures can produce topologically protected qubits. In a double-island geometry where each segment hosts a pair of MZMs, inter-pair coupling mixes the charge parity of the islands and opens an energy gap between the even and odd charge states at the inter-island charge degeneracy. Here, we report on the spectroscopic measurement of such an energy gap in an InAs/Al double-island device by tracking the position of the microwave-induced quasiparticle (qp) transitions using a radio-frequency (rf) charge sensor. In zero magnetic field, photon assisted tunneling (PAT) of Cooper pairs gives rise to resonant lines in the 2e-2e periodic charge stability diagram. In the presence of a magnetic field aligned along the nanowire, resonance lines are observed parallel to the inter-island charge degeneracy of the 1e-1e periodic charge stability diagram, where the 1e periodicity results from a zero-energy sub-gap state that emerges in magnetic field. Resonant lines in the charge stability diagram indicate coherent photon assisted tunneling of single-electron states, changing the parity of the two islands. The dependence of resonant frequency on detuning indicates a sizable (GHz-scale) hybridization of zero modes across the junction separating islands

Radio-frequency methods for Majorana-based quantum devices: fast charge sensing and phase diagram mapping

Radio-frequency (RF) reflectometry is implemented in hybrid semiconductor-superconductor nanowire systems designed to probe Majorana zero modes. Two approaches are presented. In the first, hybrid nanowire-based devices are part of a resonant circuit, allowing conductance to be measured as a function of several gate voltages ~40 times faster than using conventional low-frequency lock-in methods. In the second, nanowire devices are capacitively coupled to a nearby RF single-electron transistor made from a separate nanowire, allowing RF detection of charge, including charge-only measurement of the crossover from 2e inter-island charge transitions at zero magnetic field to 1e transitions at axial magnetic fields above 0.6 T, where a topological state is expected. Single-electron sensing yields signal-to-noise exceeding 3 and visibility 99.8% for a measurement time of 1 {\mu}s

Dispersive sensing in hybrid InAs/Al nanowires

Dispersive charge sensing is realized in hybrid semiconductor-superconductor nanowires in gate-defined single- and double-island device geometries. Signal-to-noise ratios (SNRs) were measured both in the frequency and time domain. Frequency-domain measurements were carried out as a function of frequency and power and yield a charge sensitivity of $1 \times 10^{-3} e/\sqrt{\rm Hz}$ for an 11 MHz measurement bandwidth. Time-domain measurements yield SNR > 1 for 20 $\mu$s integration time. At zero magnetic field, photon-assisted tunneling was detected dispersively in a double-island geometry, indicating coherent hybridization of the two superconducting islands. At an axial magnetic field of 0.6 T, subgap states are detected dispersively, demonstrating the suitability of the method for sensing in the topological regime

Solid-state NMR evidence for inequivalent GvpA subunits in gas vesicles

Gas vesicles are organelles that provide buoyancy to the aquatic microorganisms that harbor them. The gas vesicle shell consists almost exclusively of the hydrophobic 70-residue gas vesicle protein A, arranged in an ordered array. Solid-state NMR spectra of intact collapsed gas vesicles from the cyanobacterium Anabaena flos-aquae show duplication of certain gas vesicle protein A resonances, indicating that specific sites experience at least two different local environments. Interpretation of these results in terms of an asymmetric dimer repeat unit can reconcile otherwise conflicting features of the primary, secondary, tertiary, and quaternary structures of the gas vesicle protein. In particular, the asymmetric dimer can explain how the hydrogen bonds in the β-sheet portion of the molecule can be oriented optimally for strength while promoting stabilizing aromatic and electrostatic side-chain interactions among highly conserved residues and creating a large hydrophobic surface suitable for preventing water condensation inside the vesicle.National Institutes of Health (U.S.) (Grant EB002175)National Institutes of Health (U.S.) (Grant EB003151)National Institutes of Health (U.S.) (Grant EB002026

Early onset MSI-H colon cancer with MLH1 promoter methylation, is there a genetic predisposition?

<p>Abstract</p> <p>Background</p> <p>To investigate the etiology of <it>MLH1 </it>promoter methylation in mismatch repair (MMR) mutation-negative early onset MSI-H colon cancer. As this type of colon cancer is associated with high ages, young patients bearing this type of malignancy are rare and could provide additional insight into the etiology of sporadic MSI-H colon cancer.</p> <p>Methods</p> <p>We studied a set of 46 MSI-H colon tumors cases with <it>MLH1 </it>promoter methylation which was enriched for patients with an age of onset below 50 years (n = 13). Tumors were tested for CIMP marker methylation and mutations linked to methylation: <it>BRAF, KRAS</it>, <it>GADD45A </it>and the <it>MLH1 </it>-93G>A polymorphism. When available, normal colon and leukocyte DNA was tested for <it>GADD45A </it>mutations and germline <it>MLH1 </it>methylation. SNP array analysis was performed on a subset of tumors.</p> <p>Results</p> <p>We identified two cases (33 and 60 years) with <it>MLH1 </it>germline promoter methylation. <it>BRAF </it>mutations were less frequent in colon cancer patients below 50 years relative to patients above 50 years (p-value: 0.044). CIMP-high was infrequent and related to <it>BRAF </it>mutations in patients below 50 years. In comparison with published controls the G>A polymorphism was associated with our cohort. Although similar distribution of the pathogenic A allele was observed in the patients with an age of onset above and below 50 years, the significance for the association was lost for the group under 50 years. <it>GADD45A </it>sequencing yielded an unclassified variant. Tumors from both age groups showed infrequent copy number changes and loss-of-heterozygosity.</p> <p>Conclusion</p> <p>Somatic or germline <it>GADD45A </it>mutations did not explain sporadic MSI-H colon cancer. Although germline <it>MLH1 </it>methylation was found in two individuals, locus-specific somatic <it>MLH1 </it>hypermethylation explained the majority of sporadic early onset MSI-H colon cancer cases. Our data do not suggest an intrinsic tendency for CpG island hypermethylation in these early onset MSI-H tumors other than through somatic mutation of <it>BRAF</it>.</p

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Acetaminophen-induced inhibition of mitochondrial dehydrogenases and changes in mitochondrial NAD/NADH

The covalent binding of acetaminophen (APAP) to mitochondrial proteins has been postulated to alter the function of the organelle and contribute to the development of hepatotoxicity upon APAP overdose. There were 5 mitochondrial APAP-bound proteins with approximate molecular weights of 75, 60, 54, 44, and 35 kDa on western blots of SDS-PAGE probed with an anti-APAP antibody. On 2D gels of mitochondrial fractions, the 54 kDa band resolved into 3 proteins with pls of 6.4, 6.6 and 7.1. The pl 7.1 protein was the most prominent, and protein sequencing identified it as mitochondrial aldehyde dehydrogenase (ALDH), a protein which oxidizes aldehydes to acids using NAD. ALDH was inhibited 40% 4 hr after a toxic dose of APAP, and the time course of inhibition correlated with covalent binding to the 54 kDa protein suggesting that covalent binding causes this inhibition. Since the endogenous substrates of ALDH are not known, effects of ALDH inhibition on mitochondrial NAD/NADH were studied. NAD/NADH decreased by 40% at 4 hr but increased to 1.2x control by 8 hr after APAP. Use of an ALDH inhibitor, cyanamide, did not support a major role for aldehyde dehydrogenase in the APAP-induced NAD/NADH changes. Total ketone bodies were increased between 1 and 4 hr after APAP which suggests $\beta$-oxidation of fatty acids may play a role in the decreased NAD/NADH seen during that time. This was also supported by a time study with a subtoxic dose of APAP in which total ketone bodies increased and NAD/NADH decreased only at 8 hr after APAP. Attempts to normalize NAD/NADH with $\beta$-hydroxybutyrate and acetoacetate in preparation for protection experiments were unsuccessful, but led to the finding that $\beta$-hydroxybutyrate dehydrogenase was inhibited 35% 4 hr after APAP. Because the functioning of this enzyme in vivo is critical to the determination of NAD/NADH in these studies, detectable changes in NAD/NADH were probably not representative of areas of the liver where this enzyme has been inhibited by APAP. These data suggest that early changes in mitochondrial NAD/NADH resulted from changes in metabolism in an attempt by the liver to overcome the toxic insult while late changes were due to the liver being overwhelmed by APAP.