"There has to be more caring": patient and care partner experiences of the disclosure of amyloid-ß PET scan results.

OBJECTIVES: To explore patient and care partner experiences of receiving an amyloid scan result, with a focus on how clinician disclosure practices influenced patient and care partner emotional responses to the scan result and/or diagnosis. METHODS: Semi-structured interviews with 38 people with mild cognitive impairment or dementia and 62 care partners who experienced the disclosure of results from an amyloid PET scan as part of the CARE-IDEAS study. We used thematic analysis to analyze interview transcripts. RESULTS: We identified four aspects of the disclosure process that could influence patient and care partner emotional experiences of the scan result/diagnosis: (1) mode of delivery, (2) presence of a care partner, (3) clarity of the scan result explanation, and (4) discussion of post-scan treatment and support options. CONCLUSIONS: Emotional experiences of an amyloid scan result can vary depending on how results are communicated. These findings support previous efforts to develop standard disclosure protocols. Scan results should be delivered in person with the care partner present. Clinicians should give a clear explanation of the result and its implications in an empathetic manner. Options for treatment and support should be discussed for all patients.

Electrically tuned active metasurface towards metasurface-integrated liquid crystal on silicon (meta-LCoS) devices.

Active metasurfaces add a new dimension to static metasurfaces by introducing tunability, and this has received enormous attention from industry. Although various mechanisms have been proposed over the past few years in literature, solutions with good practicality are limited. Liquid crystal (LC)-based active metasurface is one of the most promising approaches due to the well-established LC industry. In this paper, an electrically tunable active metasurface was proposed and experimentally demonstrated using photoaligned nematic LC. The good quality of the LC photoalignment on the metasurface was demonstrated. Tunable transmission was obtained for telecommunication C band and the modulation depth in transmission amplitude of 94% was realized for 1530 nm. Sub-millisecond response time was achieved at operating a temperature of 60°C. The progress made here presents the potential of LC-based active metasurfaces for fast-switching photonic devices at optical communication wavelengths. More importantly, this work lays the foundations for the next-generation liquid crystal on silicon (LCoS) devices that are integrated with metasurfaces (meta-LCoS).

Psychosocial and Behavioral Outcomes for Persons With Cognitive Impairment and Caregivers Following Amyloid-ß PET Scan Disclosure: A Systematic Review.

BACKGROUND: Positron emission tomography (PET) scans for amyloid-ß can aid in the early and accurate detection of Alzheimer disease. The results of amyloid PET scans could help people with cognitive impairment and caregivers better understand their diagnosis; however, there are concerns that they could also cause psychological harm. METHODS: A systematic review of psychosocial and behavioral quantitative outcomes following the disclosure of an amyloid PET scan for persons living with cognitive impairment (subjective cognitive decline, mild cognitive impairment, Alzheimer's Disease, and other dementias) and caregivers. FINDINGS: Ten papers were identified from 7 studies. There was little evidence of an association between disclosure and depression. However, persons with mild cognitive impairment and their caregivers with elevated levels of amyloid had an increased risk of distress or anxiety compared with those without elevated amyloid. Participants correctly recalled the scan results; however, it is unclear whether this led to an increased understanding of their diagnosis. We did not identify any studies measuring behavioral outcomes. CONCLUSIONS: We found mixed evidence on the relationship between amyloid scans and psychosocial and behavioral outcomes in people with cognitive impairment and caregivers. These findings highlight the need for more methodologically rigorous research on this topic.

Ratiometric fluorescent aptasensor for convenient detection of ochratoxin A in beer and orange juice.

Based on the principle of fluorescence resonance energy transfer (FRET), a simple ratiometric fluorescent aptasensor for convenient detection of ochratoxin A (OTA), a Group IIB carcinogen secreted by some fungi, was established. Initially, the anti-OTA aptamer with a quadruplex structure was flanked with FAM and BHQ1, and its partially complementary DNA (cDNA) was tagged with Cy3. In the absence of OTA, this aptamer hybridized with the cDNA strand forming a DNA duplex structure, in which BHQ1 was adjacent to Cy3 and distant from FAM. Due to the FRET principle, the fluorescence intensity emitted by Cy3 (FCy3) was quenched by BHQ1, and the fluorescence intensity emitted by FAM (FFAM) recovered. In the presence of OTA, the prepared aptamer preferred to bind with OTA instead of cDNA, forming an aptamer-OTA complex structure in which BHQ1 was adjacent to FAM and distant from Cy3. As a result, FFAM was quenched and FCy3 was restored. OTA can be accurately detected via the determination of the FCy3/FFAM ratio value. Under optimal conditions, this ratiometric fluorescent aptasensor offers excellent OTA detection in the range of 0.6 nmol L-1-5 µmol L-1, with a limit of detection (LOD) of 0.3 nmol L-1. This ratiometric aptasensor showed the advantages of easy operation, accuracy and sensitive analysis. Good specificity of this aptasensor was demonstrated. This ratiometric aptasensor could be used for the detection of OTA in real samples, e.g. beer and orange juice, showing its promising application potential.

"I know that my role is going to change": a mixed-methods study of the relationship between amyloid-ß PET scan results and caregiver burden.

BACKGROUND: Caregiver burden consists of disease specific and perceived stressors, respectively referred to as objective and subjective indicators of burden, and is associated with negative outcomes. Previous research has found that care partners to persons living with cognitive impairment and elevated levels of amyloid-ß, as measured by a positron emission tomography (PET) scan, may experience caregiver burden. AIMS: To elucidate the relationship between amyloid scan results and subjective and objective indicators of burden. METHODS: A parallel mixed-methods design using survey data from 1338 care partners to persons with mild cognitive impairment (MCI) and dementia who received an amyloid scan from the CARE-IDEAS study; and semi-structured interviews with a subsample of 62 care partners. Logistic regression models were used to investigate objective factors associated with caregiver burden. A thematic analysis of semi-structured interviews was used to investigate subjective indicators by exploring care partners' perceptions of their role following an amyloid scan. RESULTS: Elevated amyloid was not associated with burden. However, the scan result influenced participants perceptions of their caregiving role and coping strategies. Care partners to persons with elevated amyloid expected increasing responsibility, whereas partners to persons without elevated amyloid and mild cognitive impairment did not anticipate changes to their role. Care partners to persons with elevated amyloid reported using knowledge gained from the scan to develop coping strategies. All care partners described needing practical and emotional support. CONCLUSIONS: Amyloid scans can influence subjective indicators of burden and present the opportunity to identify and address care partners' support needs.

Research Letter: Characterization of Older Adults Hospitalized With Traumatic Brain Injury Admitted to Long-Term Acute Care Hospitals.

OBJECTIVE: To describe patient, hospital, and geographic characteristics of older adult Medicare beneficiaries hospitalized with traumatic brain injury (TBI) and admitted to long-term acute care hospitals (LTACHs). SETTING: Acute hospital and LTACH facilities. PARTICIPANTS: In total, 15 148 Medicare beneficiaries 65 years and older with an acute TBI hospitalization who were discharged to an LTACH. DESIGN: This retrospective cohort study used data from Centers for Medicare & Medicaid Services' Medicare Enrollment and Provider Analysis and Review data files from 2011 to 2016. MAIN MEASURES: Patient variables (age, sex, premorbid health burden, medical complications and procedures), hospital variables (for-profit status, bed size), and state/regional geographic variation associated with LTACH TBI admission. RESULTS: Older adult Medicare beneficiaries admitted to LTACH facilities following TBI hospitalization were on average 77.1 years old and predominantly White males. In total, 94.6% of the sample had 2+ multimorbidities present during acute hospitalization. Average acute hospital length of stay of the sample was 19.4 days, and rates of acute mechanical ventilation of any duration and tracheostomy procedures were 56.6% and 40%, respectively. Only 4.1% of patients seen in LTACHs were discharged home after LTACH stay; the primary discharge disposition was skilled nursing facilities (41.3%). Geographic analyses indicated that selected Southern and Midwestern states had the greatest number of LTACH facilities and proportion of LTACH admissions. CONCLUSIONS: There has been limited characterization of the hospitalized TBI population admitted to LTACHs. Our findings among older adult Medicare beneficiaries suggest this population is highly medically complex and are seldom discharged home after their LTACH stay. There are also notable geographic variations in LTACH TBI admissions across the United States. More research is warranted to understand long-term functional outcomes among this population.

Memory care reduces nursing home admissions among assisted-living residents with dementia.

INTRODUCTION: We compare nursing-home and hospital admissions among residents with Alzheimer's disease and related dementias (ADRD) in memory-care assisted living to those in general assisted living. METHODS: Retrospective study of Medicare beneficiaries with ADRD in large (>25 bed) assisted-living communities. We compared admission to a hospital, to a nursing home, and long-term (>90 day) admission to a nursing home between the two groups, using risk differences and survival analysis. RESULTS: Residents in memory-care assisted living had a lower adjusted risk of hospitalization (risk difference = -1.8 percentage points [P = .014], hazard ratio = 0.93 [0.87-1.00]), a lower risk of nursing-home admission (risk difference = -2.2 percentage points [P < .001], hazard ratio = 0.87 [-.79-0.95]), and a lower risk of a long-term nursing home admission (risk difference = -1.1 percentage points [P < .001], hazard ratio = 0.71 [0.57-0.88]). DISCUSSION: Memory care is associated with reduced rates of nursing-home placement, particularly long-term stays, compared to general assisted living.

Developing a Peak Extraction and Retention (PEER) Algorithm for Improving the Temporal Resolution of Raman Spectroscopy.

In spectroscopic analysis, push-to-the-limit sensitivity is one of the important topics, particularly when facing the qualitative and quantitative analyses of the trace target. Normally, the effective recognition and extraction of weak signals are the first key steps, for which there has been considerable effort in developing various denoising algorithms for decades. Nevertheless, the lower the signal-to-noise ratio (SNR), the greater the deviation of the peak height and shape during the denoising process. Therefore, we propose a denoising algorithm along with peak extraction and retention (PEER). First, both the first and second derivatives of the Raman spectrum are used to determine Raman peaks with a high SNR whose peak information is kept away from the denoising process. Second, an optimized window smoothing algorithm is applied to the left part of the Raman spectrum, which is combined with the untreated Raman peaks to obtain the denoised Raman spectrum. The PEER algorithm is demonstrated with much better signal extraction and retention and successfully improves the temporal resolution of Raman imaging of a living cell by at least 1 order of magnitude higher than those by traditional algorithms.

Overview of chest involvement at computed tomography in children with coronavirus disease 2019 (COVID-19).

BACKGROUND: Chest computed tomography (CT) findings in children with coronavirus disease 2019 (COVID-19) have been rarely reported in a comprehensive and systematic manner. OBJECTIVE: We investigated the chest CT findings in children with COVID-19, and explored the differences in these findings between symptomatic patients and asymptomatic patients. MATERIALS AND METHODS: Demographic findings, clinical characteristics, duration of hospital stay and viral shedding, and chest CT findings in 201 children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were retrospectively analyzed from January 15 to March 20, 2020, and divided into two groups: symptomatic group (n=136) and asymptomatic group (n=65). Chi-square test and Student's t-test were used for statistical analysis. RESULTS: Symptomatic patients were mainly young children ≤3 years old (54/63, 86%),while asymptomatic patients were mainly children ≥ 6 years old (51/111, 46%). Fever (41%) and cough (41%) were the most common symptoms. Overall, 119/201 (59%) patients had chest CT findings, and symptomatic patients accounted for 82% (98/119). The CT findings presented as bilateral multiple lesions (60/119, 50.4%), ground-glass opacities (83/119, 70%) and/or consolidation (44/119, 37%) with a peripheral and subpleural distribution (62/83, 75%). Fifteen of 87 (7.2%) patients with lung lesions showed complete lesion absorption, and 42/87 (48%) improved within a mean of 9.1 (standard deviation [SD] 3.2) days. The mean duration of viral shedding was 8.7 (SD 4.9) days. Pleural effusion was very rare. No lymphadenopathy was found in either group. CONCLUSION: Symptoms associated with pulmonary involvement were most common in infants and young children. The lung lesions of most patients were absorbed and improved in about 9 days.

Hydroxycinnamic Acid Amide Dimers from Goji Berry and Their Potential Anti-AD Activity.

Three undescribed hydroxycinnamic acid amide dimers 1-3 were isolated and identified from an extract of Goji berry. Their molecular structures were elucidated based on NMR, MS, and IR spectra analysis. Compounds 1-3 were hydroxycinnamic acid amide dimers, which possess a cyclic butane moiety formed by head-to-head connection. These compounds at 25 µM showed the disaggregation potency on the copper-mediated Aß1-42 aggregation ranging from 27.3±3.2 to 31.0±2.9 %. This study provides new information on the antiaging traditional usage of goji berry.

Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors.

Rocaglates are a family of natural products isolated from the genus Aglaia which possess a highly substituted cyclopenta[b]benzofuran skeleton and inhibit cap-dependent protein synthesis. Rocaglates are attractive compounds due to their potential for inhibiting tumor cell maintenance in vivo by specifically targeting eukaryotic initiation factor 4A (eIF4A) and interfering with recruitment of ribosomes to mRNA. In this paper, we describe an intercepted retro-Nazarov reaction utilizing intramolecular tosyl migration to generate a reactive oxyallyl cation on the rocaglate skeleton. Trapping of the oxyallyl cation with a diverse range of nucleophiles has been used to generate over 50 novel amidino-rocaglate (ADR) and amino-rocaglate derivatives. Subsequently, these derivatives were evaluated for their ability to inhibit cap-dependent protein synthesis where they were found to outperform previous lead compounds including the rocaglate hydroxamate CR-1-31-B.

Chemical Synthesis Enables Structural Reengineering of Aglaroxin C Leading to Inhibition Bias for Hepatitis C Viral Infection.

As a unique rocaglate (flavagline) natural product, aglaroxin C displays intriguing biological activity by inhibiting hepatitis C viral entry. To further elucidate structure-activity relationships and diversify the pyrimidinone scaffold, we report a concise synthesis of aglaroxin C utilizing a highly regioselective pyrimidinone condensation. We have prepared more than 40 aglaroxin C analogues utilizing various amidine condensation partners. Through biological evaluation of analogues, we have discovered two lead compounds, CMLD012043 and CMLD012044, which show preferential bias for the inhibition of hepatitis C viral entry vs translation inhibition. Overall, the study demonstrates the power of chemical synthesis to produce natural product variants with both target inhibition bias and improved therapeutic indexes.

Effects of a Mobile Health Intervention to Promote HIV Self-testing with MSM in China: A Randomized Controlled Trial.

This study tested a mobile health (mHealth) intervention program entitled WeTest, delivered via the WeChat mobile app, to promote oral HIV self-testing (HIVST) among MSM in Hefei, China. A total of 100 MSM participants enrolled, completed baseline assessment, were randomly assigned to intervention or control, and completed 6-month follow-up surveys. Intervention participants (n = 50) received two oral HIVST kits and access to WeTest, a private WeChat group which provided app-based messages and referrals to health services related to HIV. Control participants (n = 50) received two oral HIVST kits only. All participants received instructions to upload photographic results of their oral HIVST, which were sent to the project counselor via a secure WeChat online portal; immediate contact and referrals were made to any participants who tested HIV-positive. In GEE analyses adjusting for time effects and baseline confounders, intervention participants had significantly higher rates of HIV testing (adjusted rate ratio RR = 1.99, 95% confidence interval (CI) 1.07-3.84) and, in particular, higher rates of testing via oral HIVST (adjusted RR = 2.17, 95% CI 1.08-4.37) compared with the control group. Significant time effects were also found such that all participants, regardless of group allocation, had significantly higher rates of reporting consistent condom use with main partners (adjusted RR = 18.13, 95% CI 5.19-63.31) and with non-main partners (adjusted RR = 5.33, 95% CI 2.35-12.08). Findings from this study provide evidence for the feasibility, acceptability and preliminary effects of this mHealth approach to promoting oral HIVST among MSM in China.

Solution to the Hole-Doping Problem and Tunable Quantum Hall Effect in Bi2Se3 Thin Films.

Bi2Se3, one of the most widely studied topological insulators (TIs), is naturally electron-doped due to n-type native defects. However, many years of efforts to achieve p-type Bi2Se3 thin films have failed so far. Here, we provide a solution to this long-standing problem, showing that the main culprit has been the high density of interfacial defects. By suppressing these defects through an interfacial engineering scheme, we have successfully implemented p-type Bi2Se3 thin films down to the thinnest topological regime. On this platform, we present the first tunable quantum Hall effect (QHE) study in Bi2Se3 thin films and reveal not only significantly asymmetric QHE signatures across the Dirac point but also the presence of competing anomalous states near the zeroth Landau level. The availability of doping tunable Bi2Se3 thin films will now make it possible to implement various topological quantum devices, previously inaccessible.

Topological Phase Transition with Nanoscale Inhomogeneity in (Bi1- xIn x)2Se3.

Topological insulators are a class of band insulators with nontrivial topology, a result of band inversion due to the strong spin-orbit coupling. The transition between topological and normal insulator can be realized by tuning the spin-orbit coupling strength and has been observed experimentally. However, the impact of chemical disorders on the topological phase transition was not addressed in previous studies. Herein, we report a systematic scanning tunneling microscopy/spectroscopy and first-principles study of the topological phase transition in single crystals of In-doped Bi2Se3. Surprisingly, no band gap closure was observed across the transition. Furthermore, our spectroscopic-imaging results reveal that In defects are extremely effective "suppressors" of the band inversion, which leads to microscopic phase separation of topological-insulator-like and normal-insulator-like nano regions across the "transition". The observed topological electronic inhomogeneity demonstrates the significant impact of chemical disorders in topological materials, shedding new light on the fundamental understanding of topological phase transition.

New acrylamide-substituted quinazoline derivatives with enhanced potency for the treatment of EGFR T790M-mutant non-small-cell lung cancers.

A new class of acrylamide-substituted quinazoline derivatives with enhanced inhibitory activity against mutant EGFR T790M enzyme were synthesized. Among them, compound 10b displayed the strongest inhibitory potency to block the phosphorylation of the EGFR T790M enzyme, with an IC50 value of 4.3 nM. Compared with the lead compound gefitinib, compound 10b significantly strengthened the activity against EGFR T790M (194 times higher). Furthermore, compound 10b only exhibited moderate activity against wild type EGFR, with an IC50 of 105.0 nM, suggesting its improved selectivity over the T790M-mutated EGFR. In addition, compound 10b also showed stronger activity against H1975 cells harboring the EGFR T790M mutation than gefitinib. Moreover, compound 10b has low inhibitory activity toward the normal HBE cells (IC50 > 34.04 µM), indicating its low cell cytotoxicity. Overall, this modification provided a new insight to design covalent binding EGFRT790M inhibitors to prevent NSCLC resistance.

MHealth approach to promote Oral HIV self-testing among men who have sex with men in China: a qualitative description.

BACKGROUND: HIV self-testing (HIVST) has demonstrated potential to expand HIV testing among key populations, including men who have sex with men (MSM) in China who have low testing rates. However, due to the autonomous nature of self-testing, people who undergo HIVST may lack access to relevant information and counseling support typically provided by in-person HIV testing counselors. WeChat, a popular smartphone application in China, offers a potential source of mobile health (mHealth) information and support for individuals using HIVST. This paper aimed to explore the opinions of MSM in China about the feasibility and potential concerns of using WeChat to support HIVST and reduce risk for HIV infection. METHODS: We conducted in-depth interviews with 36 MSM about their mobile smartphone usage and the use of WeChat for helping MSM self-administer HIVST kits in Hefei, China. Each interview was digitally recorded and transcribed. Transcripts were analyzed used content analysis method according to Elo and Kyngas. RESULTS: MSM described their use of WeChat and expressed cautious endorsement about using this platform to promote HIVST and disseminate HIV-related information. They described their preferences about the implementation features of an mHealth intervention to promote HIVST, including the delivery source of intervention messages, as well as message timing, frequency, form, tone, and content. Participants also described privacy-related concerns about receiving messages via WeChat and offered potential solutions. CONCLUSIONS: Findings from this study show the potential utility of WeChat app-based messaging for engaging MSM in HIV self-testing and prevention. Future research is needed to integrate the concerns expressed in this analysis and evaluate a WeChat-based intervention to promote oral HIV self-testing, risk reduction, and health promotion among MSM in China.

Isolation and Total Structure Determination of an All-Alkynyl-Protected Gold Nanocluster Au144.

Total structure determination of a ligand-protected gold nanocluster, Au144 , has been successfully carried out. The composition of title nanocluster is Au144 (C≡CAr)60 (1; Ar=2-FC6 H4 -). The cluster 1 exhibits a quasi-spherical Russian doll-like architecture, comprising a Au54 two-shelled Mackay icosahedron (Au12 @Au42 ), which is further enclosed by a Au60 anti-Mackay icosahedral shell. The Au114 kernel is enwrapped by thirty linear ArC≡C-Au-C≡CAr staple motifs. The absorption spectrum of 1 shows two bands at 560 and 620 nm. This spectrum is distinctly different from that of thiolated Au144 , which was predicted to have an almost identical metal kernel and very similar ligands arrangement in 1. These facts indicate the molecule-like behavior of 1 and significant involvement of ligands in the electronic structure of 1. The cluster 1 is hitherto the largest coinage metal nanocluster with atomically precise molecular structure in the alkynyl family. The work not only addresses the concern of structural information of Au144 , which had been long-pursued, but also provides an interesting example showing ligand effects on the optical properties of ligand protected metal nanoclusters.

Total synthesis of the dictyodendrins as an arena to highlight emerging synthetic technologies.

Covering: 1993-2017This review discusses the isolation, biological activity, and syntheses of the dictyodendrin class of natural products, covering the years 1993-2017. The dictyodendrins are a family of alkaloids isolated from marine sponges, Dictyodendrilla verongiformis and Ianthella sp., which possess a highly substituted pyrrolo[2,3-c]carbazole core at the phenol or quinone oxidation states. Dictyodendrins exhibit a wide range of biological activities, such as telomerase inhibition, BACE1 enzyme inhibition, and cytotoxicity against several cancer cell lines. The unique structure and interesting biological activities of dictyodendrins provided a platform for the application of novel synthetic methods including C-H insertion, C-H arylation, and electrocyclization cascades.

A Concise Total Synthesis of Dictyodendrins F, H, and I Using Aryl Ynol Ethers as Key Building Blocks.

We report a concise total synthesis of dictyodendrin F and the first total syntheses of dictyodendrins H and I in six steps. In these syntheses, aryl ynol ethers were employed as the key building blocks to introduce aryl and heteroaryl rings in the dictyodendrins. This rapid synthesis utilized a novel hetero-[2 + 2]-cycloaddition reaction between two aryl ynol ethers to yield a cyclobutenone ring. The cyclobutenone was sequentially converted into a highly substituted carbazole via a retro-4π/6π-electrocyclization-N-acylation cascade reaction to provide the dictyodendrin core. Consecutive intramolecular oxidative coupling and deprotection gave dictyodendrins F, H, and I.