bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Dexmedetomidine on Posttraumatic Stress Disorder in Patients Undergoing Emergency Trauma Surgery
Authors: Yu Youjia , Li Yan , Han Dan , Gong Chuhao , Wang Liwei , Li Beiping , Yao Rui , Zhu Yangzi
Published: June 2023

Importance

Posttraumatic stress disorder (PTSD) is common in people who have experienced trauma, especially those hospitalized for surgery. Dexmedetomidine may reduce or reverse the early consolidation and formation of conditioned fear memory and prevent the occurrence of postoperative PTSD.

Objective

To evaluate the effects of intraoperative and postoperative low-dose intravenous pumping dexmedetomidine on PTSD among patients with trauma undergoing emergency surgery.

Design, Setting, and Participants

This double-blind, randomized clinical trial was conducted from January 22 to October 20, 2022, with follow-up 1 month postoperatively, in patients with trauma undergoing emergency surgery at 4 hospital centers in Jiangsu Province, China. A total of 477 participants were screened. The observers were blinded to patient groupings, particularly for subjective measurements.

Interventions

Dexmedetomidine or placebo (normal saline) was administered at a maintenance dose of 0.1 μg/kg hourly from the start of anesthesia until the end of surgery and at the same rate after surgery from 9 pm to 7 am on days 1 to 3.

Main Outcomes and Measures

The primary outcome was the difference in the incidence of PTSD 1 month after surgery in the 2 groups. This outcome was assessed with the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (CAPS-5). The secondary outcomes were the pain score within 48 hours and 1 month postoperatively; incidence of postoperative delirium, nausea, and pruritus; subjective sleep quality; anxiety; and occurrence of adverse events.

Results

A total of 310 patients (154 in the normal saline group and 156 in the dexmedetomidine group) were included in the modified intention-to-treat analysis (mean [SD] age, 40.2 [10.3] years; 179 men [57.7%]). The incidence of PTSD was significantly lower in the dexmedetomidine group than in the control group 1 month postoperatively (14.1% vs 24.0%; P = .03). The participants in the dexmedetomidine group had a significantly lower CAPS-5 score than those in the control group (17.3 [5.3] vs 18.9 [6.6]; mean difference, 1.65; 95% CI, 0.31-2.99; P = .02). After adjusting for potential confounders, the patients in the dexmedetomidine group were less likely to develop PTSD than those in the control group 1 month postoperatively (adjusted odds ratio, 0.51; 95% CI, 0.27-0.94; P = .03).

Conclusions and Relevance

In this randomized clinical trial, the administration of intraoperative and postoperative dexmedetomidine reduced the incidence of PTSD among patients with trauma. The findings of this trial support the use of dexmedetomidine in emergency trauma surgery.

Trial Registration

Chinese Clinical Trial Register Identifier: ChiCTR2200056162
Association of Open Reduction and Internal Fixation With Volar Locking Plate for Distal Radius Fractures With Patient-Reported Outcomes in Older Adults
Authors: Jayaram Mayank , Wood Shannon M. , Kane Robert L. , Yang Lan-Yan , Chung Kevin C.
Published: June 2023

Importance

Randomized clinical trials (RCTs) and meta-analyses have reported inconsistent conclusions regarding optimal distal radius fracture (DRF) treatment in older adults and are limited due to the inclusion of cohort studies with small sample sizes. A network meta-analysis (NMA) addresses these limitations by only synthesizing direct and indirect evidence from RCTs and may clarify optimal DRF treatment in older adults.

Objective

To examine DRF treatment results in optimal short-term and intermediate-term patient-reported outcomes.

Data Sources

Searches of MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials were conducted for RCTs that investigated DRF treatment outcomes in older adults between January 1, 2000, and January 1, 2022.

Study Selection

Randomized clinical trials including patients with a mean age of 50 years or older that compared the following DRF treatments were eligible for inclusion: casting, open reduction and internal fixation with volar lock plating (ORIF), external fixation, percutaneous pinning, and nail fixation.

Data Extraction and Synthesis

Two reviewers independently completed all data extraction. An NMA aggregated all direct and indirect evidence among DRF treatments. Treatments were ranked by surface under the cumulative ranking curve score. Data are reported as standard mean differences (SMDs) and 95% CIs.

Main Outcomes and Measures

The primary outcome was short-term (≤3 months) and intermediate-term (>3 months to 1 year) Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores. Secondary outcomes included Patient-Rated Wrist Evaluation (PRWE) scores and 1-year complication rates.

Results

In this NMA, 23 RCTs consisting of 3054 participants (2495 women [81.7%]) with a mean (SD) age of 66 (7.8) years were included. At 3 months, DASH scores were significantly lower for nail fixation (SMD, −18.28; 95% CI, −29.93 to −6.63) and ORIF (SMD, −9.28; 95% CI, −13.90 to −4.66) compared with casting. The PRWE scores were also significantly lower for ORIF (SMD, −9.55; 95% CI, −15.31 to −3.79) at 3 months. In the intermediate term, ORIF was associated with lowered DASH (SMD, −3.35; 95% CI, −5.90 to −0.80) and PRWE (SMD, −2.90; 95% CI, −4.86 to −0.94) scores. One-year complication rates were comparable among all treatments.

Conclusions and Relevance

The findings of this NMA suggest that ORIF may be associated with clinically significant improvements in short-term recovery compared with casting for multiple patient-reported outcomes measures with no increase in 1-year complication rates. Shared decision-making with patients may be useful to identify patient preferences regarding recovery to determine optimal treatment.
Experiences of US Clinicians Contending With Health Care Resource Scarcity During the COVID-19 Pandemic, December 2020 to December 2021
Authors: Butler Catherine R. , Wightman Aaron G. , Taylor Janelle S. , Hick John L. , O’Hare Ann M.
Published: June 2023

Importance

The second year of the COVID-19 pandemic saw periods of dire health care resource limitations in the US, sometimes prompting official declarations of crisis, but little is known about how these conditions were experienced by frontline clinicians.

Objective

To describe the experiences of US clinicians practicing under conditions of extreme resource limitation during the second year of the pandemic.

Design, Setting, and Participants

This qualitative inductive thematic analysis was based on interviews with physicians and nurses providing direct patient care at US health care institutions during the COVID-19 pandemic. Interviews were conducted between December 28, 2020, and December 9, 2021.

Exposure

Crisis conditions as reflected by official state declarations and/or media reports.

Main Outcomes and Measures

Clinicians’ experiences as obtained through interviews.

Results

Interviews with 23 clinicians (21 physicians and 2 nurses) who were practicing in California, Idaho, Minnesota, or Texas were included. Of the 23 total participants, 21 responded to a background survey to assess participant demographics; among these individuals, the mean (SD) age was 49 (7.3) years, 12 (57.1%) were men, and 18 (85.7%) self-identified as White. Three themes emerged in qualitative analysis. The first theme describes isolation. Clinicians had a limited view on what was happening outside their immediate practice setting and perceived a disconnect between official messaging about crisis conditions and their own experience. In the absence of overarching system-level support, responsibility for making challenging decisions about how to adapt practices and allocate resources often fell to frontline clinicians. The second theme describes in-the-moment decision-making. Formal crisis declarations did little to guide how resources were allocated in clinical practice. Clinicians adapted practice by drawing on their clinical judgment but described feeling ill equipped to handle some of the operationally and ethically complex situations that fell to them. The third theme describes waning motivation. As the pandemic persisted, the strong sense of mission, duty, and purpose that had fueled extraordinary efforts earlier in the pandemic was eroded by unsatisfying clinical roles, misalignment between clinicians’ own values and institutional goals, more distant relationships with patients, and moral distress.

Conclusions and Relevance

The findings of this qualitative study suggest that institutional plans to protect frontline clinicians from the responsibility for allocating scarce resources may be unworkable, especially in a state of chronic crisis. Efforts are needed to directly integrate frontline clinicians into institutional emergency responses and support them in ways that reflect the complex and dynamic realities of health care resource limitation.
Report on the FEBS‐IUBMB‐ENABLE 1st International Molecular Biosciences PhD and Postdoc Conference
Authors: Reyes‐Corral Marta , Pfirrmann Maren
Published: June 2023

The FEBS‐IUBMB‐ENABLE 1st International Molecular Biosciences PhD and Postdoc Conference was held in Seville, Spain, from the 16–18th of November 2022. Nearly 300 participants from all over the globe were welcomed by the host institution, the Institute of Biomedicine of Seville (IBiS). Following the theme “The perfect tandem: How technology expands the frontiers of biomedicine”, the Scientific Symposium of the conference hosted eight world‐renowned keynote speakers who presented their work in one of the four sessions: Innovation, Basic Research, Translational and Clinical Research, and Computational Biology and Artificial Intelligence. Participants had the chance to present their research to their peers: more than 200 posters were presented during the dedicated poster sessions and 19 selected PhD students and postdocs presented their work as short talks. The Career Day featured a wide range of workshops fully devoted to trainees' professional development, as well as a job fair and career chats with professionals to discuss future perspectives. Besides, several outreach activities were organised before and during the conference to engage with the general public and bring science closer to society. The success of this conference will be followed by the next FEBS‐IUBMB‐ENABLE conferences in Cologne, Germany, in 2023 and Singapore in 2024.
DNA‐Based Materials Inspired by Natural Extracellular DNA
Authors: Qin Zi‐xuan , Wang Chen‐yu , Zhang Jiang‐shan , Wang Zhang‐yi , Wei Yu , Li Yu‐tao , Dai Shi‐qi , Tay Franklin R , Niu Li‐na
Published: June 2023

The advent of biotechnology has expedited the understanding of the biochemistry of deoxyribonucleic acids (DNA). In the past, DNA are thought to be present only in cell nucleus as bearers of the genetic code. With the identification of extracellular DNA in circulating body fluids, DNA are now utilized, at least experimentally, for diagnosis and treatment of diseases. Extracellular DNA of host origin trigger immune responses, and are closely linked to autoimmune disease, cancer‐related inflammation, bacteria adhesion and thrombosis. Recent advancements in DNA nanotechnology have led to the development of a series of DNA‐based materials for treating diseases because of their structural programmability. Current discussions on biosafety and immunogenicity of artificial DNA materials are insufficient. This issue severely restricts the clinical translation of these novel biotechnologies. The present review attempts to bridge the gap between natural extracellular DNA and their derivatives, DNA‐based materials. The pathological attributes of endogenous extracellular DNA motivate the design of targeting DNA materials. In addition, the fate of exogenous DNA in the host inspires the optimization of DNA materials in reducing immune rejection. These bioinspired strategies provide the blueprint for utilizing DNA materials in the management of diseases that are currently challenging to diagnose or treat.
Highly Adhesive Epidermal Sensors with Superior Water‐Interference‐Resistance for Aquatic Applications
Authors: Wang Shuai , Li Shuo , Wang Haomin , Lu Haojie , Zhu Mengjia , Wu Xun‐En , Liang Huarun , Liang Xiaoping , Zhang Yingying
Published: June 2023

Grand challenges exist in the fabrication of robust skin electronics that are resistant to water interference, which can play vital roles in healthcare and lifesaving in activities such as showering, surfing, and swift water rescue. Particularly, dynamic water impingement is very destructive to skin electronics by causing device–skin delamination and sensing malfunctions. Herein, an anemone‐inspired self‐adhesive epidermal sensor with superior ability to resist water interference in various aquatic environments is developed. The epidermal sensor consists of a strain sensing layer composed of interconnected graphene flakes wrapped in ultrathin Ecoflex and a self‐adhesive layer composed of semi‐crosslinked polydimethylsiloxane, which is named as an adhesive graphene encapsulated in Ecoflex (a‐G@E) sensor. The a‐G@E sensor can conformally and stably attach on the skin under the synergy effect of the ultrathin thickness and the self‐adhesive layer. Remarkably, it can maintain a highly stable device–skin interface even under extreme aquatic conditions such as intense water impingement (up to 4 m s−1). As examples, this study demonstrates its applications in transmitting information, controlling robotics underwater, and tracking swimming modes of a fish. It is believed that the a‐G@E sensor can play a unique role in health‐care, sports‐monitoring, and human–machine interactions, especially for aquatic scenarios.
Designed Multifunctional Spider Silk Enabled by Genetically Encoded Click Chemistry
Authors: Jiang Bojing , Tan Sin Yen , Fang Shiyu , Feng Xiaohan , Park Byung Min , Fok Hong Kiu Francis , Yang Zhongguang , Wang Ri , Kou Songzi , Wu Angela Ruohao , Sun Fei
Published: June 2023

Spider silk is recognized for its exceptional mechanical properties and biocompatibility, making it a versatile platform for developing functional materials. In this study, a modular functionalization strategy for recombinant spider silk is presented using SpyTag/SpyCatcher chemistry, a prototype of genetically encoded click chemistry. The approach involves AlphaFold2‐aided design of SpyTagged spider silk coupled with bacterial expression and biomimetic spinning, enabling the decoration of silk with various SpyCatcher‐fusion motifs, such as fluorescent proteins, enzymes, and cell‐binding ligands. The silk threads can be coated with a silica layer using silicatein, an enzyme for silicification, resulting in a hybrid inorganic–organic 1D material. The threads installed with RGD or laminin cell‐binding ligands lead to enhanced endothelial cell attachment and proliferation. These findings demonstrate a straightforward yet powerful approach to 1D protein materials.
A Multifunctional Nanozyme with NADH Dehydrogenase‐Like Activity and Nitric Oxide Release under Near‐Infrared Light Irradiation as an Efficient Therapeutic for Antimicrobial Resistance Infection and Wound Healing
Authors: Wang Yi , Shi Hong‐dong , Zhang Hai‐Lin , Yu Chen Yu‐ , Ren Bing , Tang Qi , Sun Qi , Zhang Qian‐Ling , Liu Jin‐Gang
Published: June 2023

In recent years, antimicrobial resistance (AMR) has become one of the greatest threats to human health. There is an urgent need to develop new antibacterial agents to effectively treat AMR infection. Herein, a novel nanozyme platform (Cu,N‐GQDs@Ru‐NO) is prepared, where Cu,N‐doped graphene quantum dots (Cu,N‐GQDs) are covalently functionalized with a nitric oxide (NO) donor, ruthenium nitrosyl (Ru‐NO). Under 808 nm near‐infrared (NIR) light irradiation, Cu,N‐GQDs@Ru‐NO demonstrates nicotinamide adenine dinucleotide (NADH) dehydrogenase‐like activity for photo‐oxidizing NADH to NAD+, thus disrupting the redox balance in bacterial cells and resulting in bacterial death; meanwhile, the onsite NIR light‐delivered NO effectively eradicates the methicillin‐resistant Staphylococcus aureus (MRSA) bacterial and biofilms, and promotes wound healing; furthermore, the nanozyme shows excellent photothermal effect that enhances the antibacterial efficacy as well. With the combination of NADH dehydrogenase activity, photothermal therapy, and NO gas therapy, the Cu,N‐GQDs@Ru‐NO nanozyme displays both in vitro and in vivo excellent efficacy for MRSA infection and biofilm eradication, which provides a new therapeutic modality for effectively treating MRSA inflammatory wounds.
Revolutionizing Porous Liquids: Stabilization and Structural Engineering Achieved by a Surface Deposition Strategy
Authors: Qiu Liqi , Peng Honggen , Yang Zhenzhen , Fan Juntian , Li Meijia , Yang Shize , Driscoll Darren M. , Ren Lei , Mahurin Shannon M. , He Liang‐Nian , Dai Sheng
Published: June 2023

Facile approaches capable of constructing stable and structurally diverse porous liquids (PLs) that can deliver high‐performance applications are a long‐standing, captivating, and challenging research area that requires significant attention. Herein, a facile surface deposition strategy is demonstrated to afford diverse type III‐PLs possessing ultra‐stable dispersion, external structure modification, and enhanced performance in gas storage and transformation by leveraging the expeditious and uniform precipitation of selected metal salts. The Ag(I) species‐modified zeolite nanosheets are deployed as the porous host to construct type III‐PLs with ionic liquids (ILs) containing bromide anion , leading to stable dispersion driven by the formation of AgBr nanoparticles. The as‐afforded type‐III PLs display promising performance in CO2 capture/conversion and ethylene/ethane separation. Property and performance of the as‐produced PLs can be tuned by the cation structure of the ILs, which can be harnessed to achieve polarity reversal of the porous host via ionic exchange. The surface deposition procedure can be further extended to produce PLs from Ba(II)‐functionalized zeolite and ILs containing [SO4]2− anion driven by the formation of BaSO4 salts. The as‐produced PLs are featured by well‐maintained crystallinity of the porous host, good fluidity and stability, enhanced gas uptake capacity, and attractive performance in small gas molecule utilization.
Bioinspired Luminescent HOF‐Based Foam as Ultrafast and Ultrasensitive Pressure and Acoustic Bimodal Sensor for Human–Machine Interactive Object and Information Recognition
Authors: Xu Xin , Yan Bing
Published: June 2023

Bionic sensors have extensively served smart robots, medical equipment, and flexible wearable devices. The luminescent pressure‐acoustic bimodal sensor can be treated as a remarkable, multifunctional, integrated bionic device. Here, a blue‐emitting hydrogen‐bonded organic framework (HOF‐TTA) as luminogen combines with melamine foam (MF), generating the flexible and elastic HOF‐TTA@MF (1 and 2) as a pressure–auditory bimodal sensor. In the luminescent pressure sensing process, 1 has excellent maximum sensitivity (132.02 kPa−1), low minimum detection limit (0.0 1333 Pa), fast response time (20 ms), high precision and great recyclability. 2 as a luminescent auditory sensor exhibits the highest response to the 520 Hz sound at 255−1453 Hz. In the process of sensing sound at 520 Hz, 2 possesses high sensitivity (1 648 441.3 cps Pa−1 cm−2), low detection limit (0.36 dB) and ultrafast response time (10 ms) within 11.47−91.77 dB. The sensing mechanisms toward pressure and auditory are analyzed in detail by finite element simulation. Furthermore, 1 and 2, as a human–machine interactive bimodal sensor, can recognize nine different objects and word information of “Health”, “Phone”, and “TongJi” with high accuracy and strong robustness. This work provides a facile fabricated method of luminescent HOF‐based pressure–auditory bimodal sensors and endows them with new recognition functions and dimensions.
Lattice Strain Regulation Enables High‐Performance Formamidinium Perovskite Photovoltaics
Authors: Wang Rui , Li Xinhao , Qi Jiahui , Su Chao , Yang Jien , Yang Shaopeng , Yuan Mingjian , He Tingwei
Published: June 2023

Formamidinium lead iodide (FAPbI3) perovskite possesses an ideal optical bandgap and is a potential material for fabricating the most efficient single‐junction perovskite solar cells (PSCs). Nevertheless, large formamidinium (FA) cations result in residual lattice strain, which reduces the power conversion efficiency (PCE) and operational stability of PSCs. Herein, the modulation of lattice strain in FAPbI3 crystals via a π‐conjugated organic amine, i.e., 4‐pyrene oxy butylamine (PYBA), is proposed. PYBA pairs at the grain boundary serve as a template for the crystallization of FAPbI3 perovskite, thereby inducing a highly oriented crystal and a pure α‐phase film. The PYBA pairs with strong π–π interactions provide a solid fulcrum for external compression strain, thus compensating for the inherent tension strain of FAPbI3 crystals. The strain release elevates the valence band of the perovskite crystals, thereby decreasing the bandgap and trap density. Consequently, the PYBA‐regulated FAPbI3 PSC achieves an excellent PCE of 24.76%. Moreover, the resulting device exhibits improves operational stability and maintains over 80% of its initial PCE after 1500 h under maximum power point tracking conditions.
How to Adequately Describe Full Range Intercalation—A Two‐Sided Approach
Authors: Zhu Yue , Maier Joachim
Published: June 2023

One of the key challenges in battery research is to quantitatively describe the intercalation storage capacity as a function of the reversible cell voltage. The reason that such endeavors are not yet very successful, lies in the lack of an adequate charge carrier treatment. Using the most challenging example of nanocrystalline lithium iron phosphate, where the full range from FePO4 to LiFePO4 is accessible without miscibility gap, this study shows how a quantitative description of literature results can be achieved even for such a huge window. For this purpose, point‐defect thermodynamics is applied and the problem is tackled from the two end‐member sides including saturation effects. A first, rather heuristic treatment interpolates in‐between using the safe thermodynamic criterion of local phase stability. Already this straightforward approach works very satisfactorily. In order to also gain mechanistic insight, interactions among and between ions and electrons have to be taken account of. This study shows how to implement them into the analysis.
Jointless Bioinspired Soft Robotics by Harnessing Micro and Macroporosity
Authors: Joe Seonggun , Bliah Ouriel , Magdassi Shlomo , Beccai Lucia
Published: June 2023

Although natural continuum structures, such as the boneless elephant trunk, provide inspiration for new versatile grippers, highly deformable, jointless, and multidimensional actuation has still not been achieved. The challenging pivotal requisites are to avoid sudden changes in stiffness, combined with the capability of providing reliable large deformations in different directions. This research addresses these two challenges by harnessing porosity at two levels: material and design. Based on the extraordinary extensibility and compressibility of volumetrically tessellated structures with microporous elastic polymer walls, monolithic soft actuators are fabricated by 3D printing unique polymerizable emulsions. The resulting monolithic pneumatic actuators are printed in a single process and are capable of bidirectional movements with just one actuation source. The proposed approach is demonstrated by two proof‐of‐concepts: a three‐fingered gripper, and the first ever soft continuum actuator that encodes biaxial motion and bidirectional bending. The results open up new design paradigms for continuum soft robots with bioinspired behavior based on reliable and robust multidimensional motions.
TEMPO‐Oxidized Cellulose Nanofibers as Pseudocatalysts for in Situ and on‐Demand Hydrogen Generation via Aluminum Powder/Pure Water Reactions at a Temperature below 50 °C
Authors: Fugetsu Bunshi , Yoshinaga Shuri , Kimura Ayumi , Hoshino Takeo , Sakata Ichiro , Isogai Akira
Published: June 2023

Cellulose nanofibers (CNFs) prepared via 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO)‐mediated oxidation of the C6 primary hydroxyls of native cellulose to carboxylates are used as pseudocatalysts for enhancing the aluminum powder/pure water reactions. The Al powder/pure water reaction is a stepwise reaction. It starts from hydration of the outmost native Al2O3 thin layer and then the reaction of the inner metallic Al with water. At lower temperatures (<50 °C), OH− and Al3+ ions are the preliminary products of the native Al2O3 thin layer hydration. Once Al powders are mixed with pure water containing 0.1–0.5 wt% TEMPO‐CNFs, condensed networks consisting of TEMPO‐CNFs self‐establish over the native Al2O3 thin layer. Al3+ ions are captured by TEMPO‐CNFs via the formation of insoluble Al3+/TEMPO‐CNFs complexing nanostructures and the conjugated OH− ions are being restricted nearby the native Al2O3‐based thin layer via electrostatic repulsion. A highly alkaline condition (pH > 11) is dynamically generated, and as a result, the native Al2O3 thin layer dissolves rapidly via the reaction with OH− ions. The OH− ions function also as catalysts, accelerating the reaction of metallic Al with water. Al powders (2–200 μm) react promptly and a nearly 100% Al/H2 conversion is obtained at the reaction temperature below 50 °C.
New and simple synthetic strategy for two‐dimensional ultra‐microporous aromatic framework for selective uranium capture in liquid
Authors: Ahmad Mudasir , Ren Jianquan , Naik Mehraj‐ud‐din , Wang Yabin , Khosla Ajit , Zhang Qiuyu , Zhang Baoliang
Published: June 2023

Uranium is a key element to improve nuclear energy demands, and thereby the extraction of uranium from seawater is a strategic way to address uranium sustainability. Herein, a novel two‐dimensional porous aromatic framework (AO‐PAF), which possesses an ultra‐microporous architecture with an ordered structure, excellent stability and selectivity of uranium extraction from a liquid phase. AO‐PAF shows excellent uranium adsorption capacities of 637 (mg/g) and 3.22 (mg/g) in simulated and natural seawater attributable to the selective uranium coordinating groups on highly accessible pores on the walls of open channels. In addition, benefiting from the super‐hydrophilicity due to the presence of amidoxime groups attributes high selectivity and ultrafast kinetics with an uptake rate of 0.43 ± 0.03 (mg/g·day) and allowing half‐saturation within 1.35 ± 0.09 days. This strategy demonstrates the potential of PAF not only recovery of uranium and can be extended for other applications by sensible planning of target ligands.
Desymmetrization of Oxabenzonorbornadienes through Brønsted Acid‐Catalyzed Enantioselective (3+2) Cycloaddition with Hydrazones
Authors: Prieto Liher , Reyes Efraim , Uria Uxue , Carrillo Luisa , Vicario Jose L.
Published: June 2023

This work presents the desymmetrization of oxabenzonorbornadienes through the (3+2) cycloaddition reaction with hydrazones using a chiral Brønsted acid such as a BINOL‐derived phosphoramide. This chiral acid catalyst appears as the most effective mediator for the activation of the hydrazone via hydrazonium cation that reacts in a (3+2) fashion with the oxabenzonorbornadiene as the olefinic counterpart. Under the optimized conditions, the reaction provided selectively exo cycloaddition products in satisfactory yields and moderate stereoselectivities. The scope of the reaction was explored displaying 21 examples of these highly functionalized tetrahydroepoxybenzoindazole compounds. A reaction mechanism is proposed to explain the outcome of the reaction.
Version comparison of AccuBrain for automated brain volumetry regarding accuracy, reproducibility and application for diagnosis
Authors: Zhao Lei , Luo Yishan , Mok Vincent C.T. , Shi Lin ,   the Alzheimer Disease Neuroimaging Initiative
Published: June 2023

Background

Automated brain volumetry has been widely used to assess brain volumetric changes that may indicate clinical states and progression. Among the tools that implement automated brain volumetry, AccuBrain has been validated for its accuracy, reliability and clinical applications for the older version (IV1.2). Recently, AccuBrain underwent a substantial revision update (IV2.0) for segmentation algorithms. Here, we aim to compare the performance of the two versions of AccuBrain for future use from several aspects.

Method

Public datasets with 3D T1‐weighted scans were included for version comparisons, each with Alzheimer’s disease (AD) patients and normal control (NC) subjects that were matched in age and gender (Table 1). For the comparisons of the brain volumetric measures quantified from the same scans, we investigated the difference of hippocampal segmentation accuracy (using Dice similarity coefficient [DSC] as the major measurement). As AccuBrain generates a composite index (AD resemblance atrophy index, AD‐RAI) that indicates similarity with AD‐like brain atrophy pattern, we also compared the two versions for the diagnostic accuracy of AD vs. NC with AD‐RAI. Also, we examined the intra‐scanner reproducibility of the two versions for the scans acquired with short‐intervals using intraclass correlation coefficient (ICC).

Result

Regarding hippocampal segmentation, AccuBrain IV2.0 presented significantly higher accuracy than IV1.2 with manual segmentation as the reference, both in the entire cohort (DSC: 0.91 vs. 0.89, p<0.001) and in the subgroups (all with p<0.001) defined by diagnosis, field strength or manufacturer (Table 2 and Figure 1). Also, AccuBrain IV2.0 showed better diagnostic accuracy of AD (AUC: 0.977 vs. 0.921, p<0.001) than IV1.2 (Figure 2). Regarding the analyses of intra‐scanner reproducibility (Table 3 and Table 4), the point estimates of ICC values were all >0.95 for absolute volumes and AD‐RAI, and generally >0.90 for relative volumetric measures. These two versions generally presented no significant differences for ICC values for most brain volumetric measures in NC or AD.

Conclusion

AccuBrain IV2.0 presented better segmentation accuracy and diagnostic accuracy of AD, and similar intra‐scanner reproducibility compared with IV1.2. Both versions should be feasible for use due to the small magnitude of differences.
Management of epilepsy in Alzheimer’s disease in Down syndrome
Authors: Altuna Miren , Sierra Alba , Carmona‐Iragui Maria , Fernandez Susana , Barroeta Isabel , Giménez Sandra , Arranz Javier , Pegueroles Jordi , Ribas Laia , Videla Laura , Benejam Bessy , Padilla Concepcion , Iulita M. Florencia , Blesa Rafael , Lleó Alberto , Fortea Juan
Published: June 2023

Introduction

Down syndrome (DS) is a genetically determined form of Alzheimer’s disease (AD) and a specific form of epilepsy is strongly associated with AD in DS (DSAD), late onset myoclonic epilepsy (LOMEDs), but, there are no clinical trials evaluating the efficacy and tolerability of antiseizure medications in this epilepsy

Aims

To describe our experience in the treatment of LOMEDs.

Material and Methods

We recruited patients with symptomatic AD (prodromal –pAD‐ or AD dementia –dAD‐ stages) in the context of a health plan for adult population with DS between January 2013 and November 2021. This health plan included semiannual follow‐ups (or as clinically needed) and an anamnesis and structured questionnaire including the personal history of epilepsy (duration of epilepsy, semiology, frequency, efficacy and tolerability of ASM).

Results

The study included 72 patients with pAD (48.6% females) and 257 with dAD (50.6% females). Bilateral tonic‐clonic seizures (BTCS) were the most frequent type (85.7% in pAD and 70.7% in dDS) and frequentlly coexisted with myoclonic seizures (16.7% and 57.6% in pDS and dAD respectively). The most frequent treatment after the first seizure was levetiracetam (LEV) (61.5%) followed by valproate (VPA) (19.6%). During follow‐up, 75.8% were on monotherapy with LEV (56.3%), VPA (25.5%) or brivaracetam (BRV) (8.2%). LEV was discontinued due to irritability in 21.9% of patients (interestingly 48% tolerated BRV after LEV discontinuation).VPA was abandoned in 14% due to motor worsening. Seizure control at one year was achieved in 65.9%, when considering BTCS, but only 30.2% were free of of myoclonic seizures.

Discussion

LOMEDs is a very common comorbidity in DSAD that responds partially to treatment. BTCS seem to have a better response to treatment compared to myoclonic seizures.
eHealth interventions for informal caregivers of people with dementia
Authors: Bui Linh Khanh , Park Myonghwa , Giap Thi‐Thanh‐Tinh
Published: June 2023

Background

Informal caregivers of people with dementia are considered as second invisible patients due to a huge burden from providing care. eHealth interventions are becoming a preferable option with promising impacts, however current studies showed heterogeneous results in terms of the implementation and efficacy of eHealth interventions. This review aims to systematically evaluate the implementation and effectiveness of eHealth interventions for informal caregivers of people with dementia based on existing evidence from systematic reviews.

Method

The review is a systematic review of systematic reviews following the PRISMA statement. A comprehensive search was undertaken in six databases MEDLINE/Ovid, Embase, CINAHL, Web of Science, Cochrane Library and PsycINFO until November 2021. Keywords for searching included dementia, informal caregivers, eHealth, systematic reviews, and meta‐analyses. Two reviewers independently appraised the quality of evidence by AMSTAR II.

Result

The searches resulted in a total of 1684 records, of which 19 systematic reviews covering 97 unique studies were included. There was a moderate overlap of primary studies within included studies, the corrected covered area was 10.3. The quality of included reviews varied from high to critical low according to AMSTAR II. Only two reviews were rated as high quality, five reviews were categorized as moderate, the remaining reviews were rated as low or critical low quality. The eHealth interventions were provided through multiple components covering (1) information, (2) psychoeducation, (3) communication and interaction, (4) psycho‐therapeutic interventions, and (5) psycho‐social support. Interventions were delivered through various technology formats such as the Internet, telephone, and a combination of the Internet, telephone and additionally supplemental modes. Promising evidence about the effectiveness in reducing depression and anxiety for caregivers was extracted. The evidence was quite mixed but generally positive in terms of caregiver burden, stress, self‐efficacy, knowledge and skill improvements; the effect sizes tended to be small. Meanwhile, limited evidence supported the efficacy of eHealth interventions on improving quality of life and coping competence for caregivers.

Conclusion

eHealth interventions are widely applied and promising. Nevertheless, the lack of high methodological quality across systematic reviews was revealed. Future research should be more rigorous to create robust evidence for this rapidly changing field.
Risk factors of brain atrophy in cognitively normal elderly
Authors: Zhao Lei , Luo Yishan , Mok Vincent C.T. , Liu Jun , Shi Lin ,   for the Alzheimer Disease Neuroimaging Initiative
Published: June 2023

Background

Lifestyle‐related risk factors (e.g., smoking) and common health problems (e.g., hypertension) have been found to be associated with brain atrophy. However, it is still not clear about their independent contribution to brain atrophy, especially among the elderly with normal cognition. Here, we aim to identify the independent risk factors of brain atrophy in cognitively normal elderly.

Method

We included 419 elderly subjects with normal cognition (Table 1) from the ADNI database (ADNI1/ADNI2/ADNI‐GO) who had available data of lifestyle‐related risk factors (alcohol abuse, smoking) and common health problems (obesity, hypertension, high cholesterol, high triglycerides, sleep disturbance) and underwent 3D T1‐weighted MRI scans at baseline. The T1‐weighted images were processed with AccuBrain IV2.0 to quantify the brain volumetric measures as listed in Table 2. Univariate analyses were performed with ANCOVA to investigate the influence of the risk factors for each brain volumetric measure, while age, gender, education and APOE4 carrier were covaried out. The independent contribution of the risk factors were further identified by entering them together in a multivariate linear regression model as predictors of brain atrophy using backward elimination.

Result

In the univariate analyses, obesity showed the most widely influence of brain atrophy throughout the brain, followed by hypertension which contributed to atrophy in cerebellum and part of cortical gray matter (GM), alcohol abuse that contributed to atrophy in part of basal ganglia structures, high triglycerides for atrophy of pons and cerebellum, and smoking for medial temporal lobe atrophy (Table 3). When other risk factors were also considered (Table 4), the contribution of obesity to the atrophy of most brain regions remained significant. Hypertension, alcohol abuse and smoking also showed independent contributions (p<0.05) to the atrophy of several brain regions, while sleep disturbance (for brain parenchyma) and high triglycerides (for cerebellum) only presented mild independent contribution (0.05<p<0.10) to brain atrophy.

Conclusion

Obesity presented most independent contribution to brain atrophy in cognitively normal elderly, followed by hypertension, alcohol abuse and smoking. These results may facilitate the interpretation of brain atrophy in normal subjects and intervention of reversible brain atrophy caused by specific risk factors.
Social connection in long‐term care home residents: A review of research on health outcomes and strategies during COVID‐19
Authors: Bethell Jennifer , Aelick Katelynn , Babineau Jessica , Bretzlaff Monica , Edwards Cathleen , Colborne Debbie Hewitt , Iaboni Andrea , Schon Denise , Sommerlad Andrew , McGilton Katherine S
Published: June 2023

Background

The infection control measures enacted to prevent COVID‐19 in long‐term care (LTC) homes have highlighted the important role of social connection in the wellbeing and care of people living in these settings. Yet, issues of loneliness and social isolation in LTC home residents pre‐date COVID‐19, as does the research to address them.

Method

We conducted a scoping review of published research that quantified the association of any aspect of social connection among LTC residents with mental health outcomes. We also sought studies of modifiable risk factors and interventions that identified strategies that could be implemented and adapted by LTC residents, families and staff during COVID‐19. We searched eight databases from inception to search date (July 2019), extracted data and conducted a narrative synthesis of evidence. We involved knowledge users representing LTC residents, families and staff in priority‐setting (defining the review questions), analyzing data, interpreting and contextualizing the results, and disseminating the findings. In this presentation, to further characterize the evidence, we compare the measures used in these studies to those identified from an ongoing systematic review of measures developed specifically to assess social connection in people living in LTC homes.

Result

We located 61 studies that reported the association between social connection and mental health outcomes, including depression; responsive behaviors; mood, affect, and emotions; anxiety; medication use; cognitive decline; and, others. We located 72 studies that informed 12 strategies for building and maintaining social connection during COVID‐19; some strategies represented fundamental aspects of resident care whereas others that would need to be considered in context with a LTC resident’s and home’s needs and circumstances.

Conclusion

Our review identifies a body of research on social connection in LTC that pre‐dates the COVID‐19 pandemic. The evidence points to quality of social connection for residents being associated with better mental health, and we identified strategies that may help to build and maintain social connection in this setting. We found that the studies assessed numerous aspects of social connection, however, only some used measures developed specifically for this population.
The longitudinal course and determinants of apathy in UK care home residents with dementia
Authors: Sommerlad Andrew , Park Hee Kyung , Marston Louise , Livingston Gill
Published: June 2023

Background

Apathy in dementia is a common and troubling symptom associated with worse disease outcomes but its longitudinal course is unclear We aimed to 1) describe the prevalence and persistence of clinically‐significant apathy in UK care home residents with dementia, 2) investigate the association of other neuropsychiatric symptoms in people with clinically‐significant apathy, and 3) identify sociodemographic and disease related factors associated with worse apathy trajectory.

Method

Prospective cohort study of residents with dementia recruited from 86 voluntary, state or private UK care homes. At baseline, and 4, 8, 12, and 16 months, care home staff rated apathy using the Neuropsychiatric Inventory (clinically‐significant apathy if score ≥4, sub‐clinical if 1‐3). Staff also rated dementia severity using the Clinical Dementia Rating scale, and provided other sociodemographic information about each participant. We examined the prevalence and persistence of apathy and, in mixed linear models, its association with time, age, sex, dementia severity, antipsychotic use, and baseline apathy and other neuropsychiatric symptoms.

Results

Of 1419 included participants (mean age 85 years (SD 8.5), 975 (68.7%) women), 30% had mild dementia, 33% moderate, and 37% severe. The point prevalence of clinically‐significant apathy was 21.4% (n = 304) and the period prevalence during 16 months follow‐up was 47.3% (n = 671). The point‐prevalence and 16‐month period prevalence of any apathy was 33.3% and 85.1% respectively. The longitudinal course is shown in the figure. Of participants who had follow‐up data, 45 (3.8%) were always clinically‐significantly apathetic, 3 (0.3%) were always sub‐clinically apathetic, and 420 (36.2%) were never apathetic until death or end of follow‐up. In adjusted models, apathy increased over time and was associated with having more severe dementia, worse baseline apathy and other neuropsychiatric symptoms.

Conclusion

Most people with dementia are not apathetic but it is common and frequently fluctuates in its course. It is important for clinicians to know that most people with dementia do not develop apathy and it is not an inevitable symptom and often remits. People with more severe dementia and other neuropsychiatric symptoms are more likely to have an adverse apathy course, so may be a priority group for current and future treatments.
Antioxidant and anti‐inflammatory effects of Rooibos on cognitive signs of Alzheimer’s Disease in the context of early life adversity
Authors: Minné Donné , Docrat Taskeen , Marnewick Jeanine , Engel‐Hills Penelope
Published: June 2023

Background

Medicinal plants are important in traditional healthcare in Africa especially in low‐resourced communities living under conditions of adversity. In South Africa, the fynbos plant Aspalathus linearis, or Rooibos, has been used for centuries as a restorative herbal tea. Over the past few decades, the immuno‐modulating properties of Rooibos have been firmly established with studies demonstrating potent antioxidant, anti‐inflammatory and anti‐cancer properties. These indications suggest that Rooibos can aid in prevention of Alzheimer’s Disease (AD), which is strongly linked to immune dysregulation. However, the overall efficacy of Rooibos supplementation may depend on individual differences in neuro‐inflammatory priming, which occurs in early development, partly as a result of stress.

Method

In a double‐blind, placebo‐controlled intervention trial, we aimed to investigate the effects of 12 weeks' supplementation with green or fermented rooibos following a washout period on biophysical and behavioural risk profiles for AD. Using a mixed‐factorial design in a sample of 340 adults, we assessed early life stress history and evaluatedclinical signs of neurodegenerationusing a standardised neuropsychological battery, and cognitive effort based on a pupil dilation task. Biochemical profiles were assessed using patient plasma samples for indices of antioxidant and anti‐inflammatory activity using ELISAs.

Result

Results are currently pending.

Conclusion

This study contributes to our growing understanding of the medicinal properties of Rooibos and how early life stress influences neuro‐immune processes. Given that tea drinking is an economical and widely adopted social‐cultural practice across all age groups, tea is ideal to target in designing low‐cost dietary interventions for neurodegenerative diseases like Alzheimer’s.
Improving collaboration between palliative care and neurology: Focus on patient, family & healthcare provider experience
Authors: Salwierz Patrick , Sumra Vishaal , Gumus Melisa , Lewin Warren , Martinez Maria , Patel Archna , Salvo Cristina , Swinkin Emily , Tartaglia Carmela , Tang‐Wai David F. , Li Melissa
Published: June 2023

Background

The prevalence of neurodegenerative diseases is increasing as the population ages. As these diseases are often incurable, progressive, and associated with significant loss of ability to communicate over time, it is paramount that advanced care planning (ACP) take place early in the disease trajectory to facilitate goal‐concordant care. There is increasing recognition of the barriers for neurologists to facilitate ACP and end‐of‐life care. Palliative care is a medical speciality that focuses on improving quality of life for patients living with serious illness, including helping with healthcare planning and decision‐making that align with the individual’s values and goals. However, there is a paucity of literature on how to best integrate palliative care or which elements of an integrated neuro‐palliative approach are the most beneficial to patients, caregivers, and clinicians.

Our study aims to assess the experience of an embedded pilot clinic between Neurology and Palliative Care at the University Health Network (UHN) Memory Clinic on patients/caregivers and health care practitioners.

Methods

We aim to recruit 60 participants, including patients and family members, seen at the UHN Supportive Care Memory Clinic, and who screen positive for three of seven triggers for palliative care involvement for neurological patients as proposed by the National End of Life Care Programme of National Health Service in England. ACP conversations will follow an evidence‐based semi‐structured conversation guide. The impact of the clinic will be evaluated using patient, caregiver, and both Neurology and Palliative Care team member experience surveys. Secondary measures will include the percentage change in ACP and Power of Attorney documentation pre and post initiation of the clinic.

Results

From clinic inception in June 2020, 19 patients were seen (all‐virtual). Due to the COVID‐19 pandemic, the clinic was paused for the majority of 2021. Our study received UHN Quality Improvement approval in March 2021, and we began enrolling patients into our study in November 2021; enrolment is ongoing.

Conclusions

The results of this study will serve as a guide for quality improvement of our existing clinic and can inform future implementation of scalable integrated models of care between palliative care and neurology, and for other subspecialties and centres.