Diffusion MRI-guided theta burst stimulation enhances memory and functional connectivity along the inferior longitudinal fasciculus in mild cognitive impairment.

Mild cognitive impairment (MCI) during aging is often a harbinger of Alzheimer's disease, and, therefore, early intervention to preserve cognitive abilities before the MCI symptoms become medically refractory is particularly critical. Functional MRI­guided transcranial magnetic stimulation is a promising approach for modulating hippocampal functional connectivity and enhancing memory in healthy adults. Here, we extend these previous findings to individuals with MCI and leverage theta burst stimulation (TBS) and white matter tractography derived from diffusion-weighted MRI to target the hippocampus. Our preliminary findings suggested that TBS could be used to improve associative memory performance and increase resting-state functional connectivity of the hippocampus and other brain regions, including the occipital fusiform, frontal orbital cortex, putamen, posterior parahippocampal gyrus, and temporal pole, along the inferior longitudinal fasciculus in MCI. Although the sample size is small, these results shed light on how TBS propagates from the superficial cortex around the parietal lobe to the hippocampus.

Concurrent expectation and experience-based metacontrol: EEG insights and the role of working memory capacity.

We investigated the simultaneous influence of expectation and experience on metacontrol, which we define as the instantiation of context-specific control states. These states could entail heightened control states in preparation for frequent task switching or lowered control states for task repetition. Specifically, we examined whether "expectations" regarding future control demands prompt proactive metacontrol, while "experiences" with items associated with specific control demands facilitate reactive metacontrol. In Experiment 1, we utilized EEG with a high temporal resolution to differentiate between brain activities associated with proactive and reactive metacontrol. We successfully observed cue-locked and image-locked ERP patterns associated with proactive and reactive metacontrol, respectively, supporting concurrent instantiation of two metacontrol modes. In Experiment 2, we focused on individual differences to investigate the modulatory role of working memory capacity (WMC) in the concurrent instantiation of two metacontrol modes. Our findings revealed that individuals with higher WMC exhibited enhanced proactive metacontrol, indicated by smaller response time variability (RTV). Additionally, individuals with higher WMC showed a lower tendency to rely on reactive metacontrol, indicated by a smaller item-specific switch probability (ISSP) effect. In conclusion, our results suggest that proactive and reactive metacontrol can coexist, but their interplay is influenced by individuals' WMC. Higher WMC promotes the use of proactive metacontrol while attenuating reliance on reactive metacontrol. This study provides insights into the interplay between proactive and reactive metacontrol and highlights the impact of WMC on their concurrent instantiation.

A multicenter phase Ia study of AbGn-107, a novel antibody-drug conjugate, in patients with advanced gastrointestinal cancer.

AbGn-107 is an antibody-drug conjugate directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in a variety of gastrointestinal (GI) malignancies. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a GI cancer-specific Phase I trial. Standard 3 + 3 dose escalation was used evaluating intravenous doses ranging from 0.1 mg/kg every 4 weeks to 1.0 mg/kg every 2 weeks. Key eligibility included chemo-refractory locally advanced, recurrent, or metastatic gastric, colorectal, pancreatic, or biliary cancer, with ECOG PS 0-1; positive AG-7 expression was not required during dose escalation phase. Patients were treated until disease progression or unacceptable toxicity, with tumor assessments every 8 weeks. Primary objectives included safety and determination of maximum tolerated dose; secondary objectives included efficacy defined by objective response rate. Thirty-nine patients were enrolled across seven dose levels during dose escalation phase. Based on safety profile and pharmacokinetic data, 1.0 mg/kg Q2W was selected as the dose schedule for cohort expansion phase, in which an additional seven patients were enrolled. Median number of lines of prior therapy was 3 (range 1-7). AbGn-107 was generally well-tolerated, with infections, cytopenias, hyponatremia, fatigue, abdominal pain, and diarrhea representing the most common grade 3 or higher treatment-emergent adverse events. One subject achieved a partial response, while 18 (46.2%) achieved a best response of stable disease. Disease control lasting > 6 months was observed in 6 subjects (13.0%), including 4 of 15 (26.7%) treated at the highest dose level. AbGn-107 showed a reasonable safety profile and modest clinical activity in this highly pretreated patient population. Further evaluation is required to assess the clinical validity of AG-7 as a suitable antigen for therapeutic targeting. Clinical Trial information: NCT02908451.

A Computational Study of Reactions with Boric Acid Aimed to Promote the Utilization of Lignin.

For exploring the reaction between the hydroxyl groups of lignin and boric acid under the alkaline condition, we study three proposed mechanisms for the formation of the anionic borate diester (ABDE) using the salicyl alcohol anion as the model compound by the density functional theory. ABDE has high flame retardancy and is a potentially practical application of lignin. The catalysis of sodium cation is found to enhance the deprotonation of the water cluster. The deprotonated product, hydroxide anion, is essential to the critical step, which is the cleavage of B-O bonds of the boric acid molecule, in reaction mechanisms. The energy profiles of the mechanisms show that the reaction between lignin and boric acid may start from the hydroxymethyl moieties of lignin since it requires less energy for the aforementioned critical step than from the phenol moieties of lignin. Moreover, the hydroxide anions compete with the hydroxymethyl groups in lignin for the formation of B-O bonds by forming tetrahydroxyborate anion (TBA) which requires very high activation energies to further react to the desired product ABDE. The optimal condition is to enhance the catalytic effect of sodium cations and meanwhile to control the formation of TBA.

Eu Doping in the GdCd7.88 Quasicrystal and Its Approximant Crystal GdCd6.

The effect of Eu doping in the Tsai quasicrystal (QC) GdCd7.88 and its periodic 1/1 approximant crystal (AC) GdCd6 are investigated. This represents the first synthesis of Eu-containing stable QC samples, where three samples with the final composition Gd1-xEuxCd7.6±α at Eu doping concentrations x = 0.06, 0.13, and 0.19 are obtained (α ∼ 0.2). They are compared to two 1/1 ACs with compositions Gd1-xEuxCd6 (x = 0.12, 0.16). In addition, a new type of 1/1 AC, differing only by the inclusion of extra Cd sites unique to the Eu4Cd25 1/1 AC, has been discovered and synthesized for the concentrations Gd1-xEuxCd6+δ (x = 0.25, 0.33, 0.45, 0.69, 0.73, and 0 < δ ≤ 0.085). Due to the preferred cube morphology of its single grains, we refer to them as c-type 1/1 ACs and to the conventional standard ones as s-type. In both QCs and s-type ACs, the Eu content appears to saturate at a concentration of ∼20%. On the other hand, any Gd| Eu ratio is allowed in the c-type ACs, varying continuously between GdCd6 and Eu4Cd25. We describe and contrast the changes in composition, atomic structure, specific heat, and magnetic properties induced by Eu doping in the quasicrystalline phase and the s-type and c-type 1/1 ACs. By comparing our results to the literature data, we propose that the occupancy of the extra Cd sites can be used to predict the stability of Tsai-type quasicrystalline phases.

Frailty in the prediction of delirium in the intensive care unit: A secondary analysis of the Deli study.

BACKGROUND: Delirium is an acute disorder of attention and cognition with an incidence of up to 70% in the adult intensive care setting. Due to the association with significantly increased morbidity and mortality, it is important to identify who is at the greatest risk of an acute episode of delirium while being cared for in the intensive care. The objective of this study was to determine the ability of the cumulative deficit frailty index and clinical frailty scale to predict an acute episode of delirium among adults admitted to the intensive care. METHODS: This study is a secondary analysis of the Deli intervention study, a hybrid stepped-wedge cluster randomized controlled trial to assess the effectiveness of a nurse-led intervention to reduce the incidence and duration of delirium among adults admitted to the four adult intensive care units in the south-west of Sydney, Australia. Important predictors of delirium were identified using a bootstrap approach and the absolute risks, based on the cumulative deficit frailty index and the clinical frailty scale are presented. RESULTS: During the 10-mth data collection period (May 2019 and February 2020) 2566 patients were included in the study. Both the cumulative deficit frailty index and the clinical frailty scale on admission, plus age, sex, and APACHE III (AP III) score were able to discriminate between patients who did and did not experience an acute episode of delirium while in the intensive care, with AUC of 0.701 and 0.703 (moderate discriminatory ability), respectively. The addition of a frailty index to a prediction model based on age, sex, and APACHE III score, resulted in net reclassified of risk. Nomograms to individualize the absolute risk of delirium using these predictors are also presented. CONCLUSION: We have been able to show that both the cumulative deficits frailty index and clinical frailty scale predict an acute episode of delirium among adults admitted to intensive care.

Influences of Genetic and Environmental Factors on Chronic Migraine: A Narrative Review.

PURPOSE OF REVIEW: In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM). RECENT FINDINGS: Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.

Learned switch readiness via concurrent activation of task sets: Evidence from task specificity and memory load.

Cognitive flexibility increases when switch demands increase. In task switching experiments, repeated pairing of flexibility-demanding situations with specific contexts leads subjects to become more prepared to adapt to changing task demands in those contexts. One form of such upregulated cognitive flexibility has been demonstrated with a list-wide switch probability (LWSP) effect, where switch costs are smaller in lists with frequent switches than in lists with rare switches. According to a recent proposal, the LWSP effect is supported by a concurrent activation mechanism whereby both task rules are kept available simultaneously in working memory. We conducted four experiments to test two key features in this concurrent activation account of LWSP effects. First, we asked whether the LWSP effects are limited to only the trained tasks, and second, we asked whether concurrent working memory load would reduce the LWSP effects. In Experiment 1, we replicated and extended previous findings that the LWSP manipulation modulates both performance (switch costs) and voluntary switch rates, indicating that context-driven increases in flexibility are generalizable so long as the task-sets remain the same. Results of Experiments 2 and 3 showed that novel tasks do not benefit from the concurrent activation of the two other tasks, suggesting that the LWSP effect is task specific. Experiment 4 showed that holding additional information in working memory reduces the LWSP effect. While these findings support the hypothesis of concurrent activation underlying the increased flexibility in the LWSP effect, caveats remain; additional research is needed to further test this account.

Athletes with meditation experience counteract the detrimental effect of mental fatigue on endurance performance and neurocognitive functions.

The current study examined whether meditation experience is associated with changes in endurance performance and inhibitory control-relevant neurocognitive functions caused by mental fatigue. Twenty-four athletes with meditation experience (AME) and twenty-five athletes without meditation experience (AWME) underwent a 30-min incongruent Stroop test in mental fatigue condition (MF) and a 30-min congruent Stroop test in control condition (CON) in a randomised-counterbalanced order. Inhibitory control-relevant neurocognitive functions were assessed using Flanker task and event-related potentials, followed by an endurance task using the Bruce treadmill protocol. Visual analogue scale was used to evaluate perceived mental fatigue (VAS-MF) before (T1), after Stroop test (T2) and after Flanker task (T3), and VAS for motivation (VAS-M) was used to evaluate motivation in Flanker task and endurance task. Results indicated that, compared to the CON, AWME in the MF exhibited overall lower accuracy, smaller incongruent N2 amplitude of the Flanker task (ps < .05), and shorter time to exhaustion (TTE) of the endurance task (p < .001), whereas AME did not exhibited difference in these outcomes between the conditions. Along with athletes in the MF reported lower VAS-M in endurance task. These findings suggest the benefits of meditation experience in mitigating the negative effects of mental fatigue.

Cerebrospinal fluid soluble programmed death-ligand 1 is a useful prognostic biomarker in primary central nervous system lymphoma.

The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.

Acetylation regulates the nucleocytoplasmic distribution and oncogenic function of karyopherin alpha 2 in lung adenocarcinoma.

Karyopherin subunit alpha 2 (KPNA2, importin α1) is a nucleoplasmic protein responsible for the nuclear import of proteins with classical nuclear localization signals. Aberrant nuclear accumulation of KPNA2 has been observed in numerous cancer tissues. AMP-activated protein kinase (AMPK) is involved in the phosphorylation and acetylation of KPNA2 in enterocytes. However, the impact of these post-translational modifications on modulating the nucleocytoplasmic distribution of KPNA2 and its oncogenic role remain unclear. Unlike nuclear accumulation of wild-type KPNA2, which promoted lung cancer cell migration, KPNA2 Lys22 acetylation-mimicking mutations (K22Q and K22Q/S105A) prevented nuclear localization of KPNA2 and reduced the cell migration ability. Cytosolic KPNA2 K22Q interacted with and restricted the nuclear entry of E2F transcription factor 1 (E2F1), an oncogenic cargo protein of KPNA2, in lung cancer cells. Intriguingly, the AMPK activator EX229 promoted the nuclear export of KPNA2 S105A. However, the CBP/p300 inhibitor CCS-1477 abolished this phenomenon, suggesting that CBP/p300-mediated acetylation of KPNA2 promoted KPNA2 nuclear export in lung cancer cells. Collectively, our findings suggest that the CBP/p300 positively regulates KPNA2 acetylation, which enhances its cytosolic localization and suppresses its oncogenic activity in lung cancer.

MIB2: metal ion-binding site prediction and modeling server.

MOTIVATION: MIB2 (metal ion-binding) attempts to overcome the limitation of structure-based prediction approaches, with many proteins lacking a solved structure. MIB2 also offers more accurate prediction performance and more metal ion types. RESULTS: MIB2 utilizes both the (PS)2 method and the AlphaFold Protein Structure Database to acquire predicted structures to perform metal ion docking and predict binding residues. MIB2 offers marked improvements over MIB by collecting more MIB residue templates and using the metal ion type-specific scoring function. It offers a total of 18 types of metal ions for binding site predictions. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://bioinfo.cmu.edu.tw/MIB2/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Structural Analysis of the Gd-Au-Al 1/1 Quasicrystal Approximant Phase across Its Composition-Driven Magnetic Property Changes.

Gd14AuxAl86-x Tsai-type 1/1 quasicrystal approximants (ACs) exhibit three magnetic orders that can be finely tuned by the valence electron concentration (e/a ratio). This parameter has been considered to be crucial for controlling the long-range magnetic order in quasicrystals (QCs) and ACs. However, the nonlinear trend of the lattice parameter as a function of Au concentration suggests that Gd14AuxAl86-x 1/1 ACs are not following a conventional solid solution behavior. We investigated Gd14AuxAl86-x samples with x values of 52, 53, 56, 61, 66, and 73 by single-crystal X-ray diffraction. Our analysis reveals that increasing Au/Al ordering with increasing x leads to distortions in the icosahedral shell built of the Gd atoms and that trends observed in the interatomic Gd-Gd distances closely correlate with the magnetic property changes across different x values. Our results demonstrate that the e/a ratio alone may be an oversimplified concept for investigating the long-range magnetic order in 1/1 ACs and QCs and that the mixing behavior of the nonmagnetic elements Au and Al plays a significant role in influencing the magnetic behavior of the Gd14AuxAl86-x 1/1 AC system. These findings will contribute to improved understanding towards tailoring magnetic properties in emerging materials.

Community-Based Digital Contact Tracing of Emerging Infectious Diseases: Design and Implementation Study With Empirical COVID-19 Cases.

BACKGROUND: Contact tracing for containing emerging infectious diseases such as COVID-19 is resource intensive and requires digital transformation to enable timely decision-making. OBJECTIVE: This study demonstrates the design and implementation of digital contact tracing using multimodal health informatics to efficiently collect personal information and contain community outbreaks. The implementation of digital contact tracing was further illustrated by 3 empirical SARS-CoV-2 infection clusters. METHODS: The implementation in Changhua, Taiwan, served as a demonstration of the multisectoral informatics and connectivity between electronic health systems needed for digital contact tracing. The framework incorporates traditional travel, occupation, contact, and cluster approaches and a dynamic contact process enabled by digital technology. A centralized registry system, accessible only to authorized health personnel, ensures privacy and data security. The efficiency of the digital contact tracing system was evaluated through a field study in Changhua. RESULTS: The digital contact tracing system integrates the immigration registry, communicable disease report system, and national health records to provide real-time information about travel, occupation, contact, and clusters for potential contacts and to facilitate a timely assessment of the risk of COVID-19 transmission. The digitalized system allows for informed decision-making regarding quarantine, isolation, and treatment, with a focus on personal privacy. In the first cluster infection, the system monitored 665 contacts and isolated 4 (0.6%) cases; none of the contacts (0/665, 0%) were infected during quarantine. The estimated reproduction number of 0.92 suggests an effective containment strategy for preventing community-acquired outbreak. The system was also used in a cluster investigation involving foreign workers, where none of the 462 contacts (0/462, 0%) tested positive for SARS-CoV-2. CONCLUSIONS: By integrating the multisectoral database, the contact tracing process can be digitalized to provide the information required for risk assessment and decision-making in a timely manner to contain a community-acquired outbreak when facing the outbreak of emerging infectious disease.

Comparisons on the intraoperative desaturation and postoperative outcomes in non-intubated video-assisted thoracic surgery with supraglottic airway devices or high-flow nasal oxygen: A retrospective study.

BACKGROUND: Few studies have compared intraoperative oxygenation and perioperative outcomes between non-intubated video-assisted thoracic surgery (NIVATS) with supraglottic airway devices (SADs) and NIVATS with high flow nasal oxygenation (HFNO). The aim of this retrospective study was to compare the intraoperative desaturation rate and postoperative outcomes between NIVATS with SADs and NIVATS with HFNO. METHODS: Data regarding NIVATS performed for lung cancer from January 2020 to December 2021 were collected. Intraoperative anesthetic results, post-anesthetic adverse effects, and surgical outcomes for patients who received SAD or HFNO were analyzed using propensity score-matched and unmatched analysis. RESULTS: In total, 199 patients with i-gel™ and 95 patients with HFNO were included. Significantly more female patients (91.6 vs. 82.4%, p = 0.0378) and fewer wedge resections (78.9 vs. 85.4%, p = 0.0258) were observed in the HFNO group. Among 250 patients who underwent NIVATS wedge resections under total intravenous anesthesia, those who received HFNO had a significantly higher desaturation event rate (19.8% vs. 7.9% in i-gel™ group; p = 0.0063), lower nadir SPO2 (94.0% vs. 96.1% in i-gel™ group; p = 0.0012), and longer hospitalization (4.0 ± 0.8 vs. 3.6 ± 0.6 in i-gel™ group; p < 0.0001). However, propensity score matching analysis revealed no significant between-group difference in the desaturation rate. A log-rank test revealed that smoking (p = 0.0005) and HFNO (p = 0.0074) were associated with intraoperative desaturation. CONCLUSION: The rate of SAD use in NIVATS was twice the rate of HFNO use, especially for wedge resections. There is uncertain airway patency and limited flow through HFNO during one-lung ventilation, whereas SADs like i-gel™ presented a significantly less intraoperative desaturation rate over time and similar postoperative outcomes.

Transcranial Magnetic Stimulation for the Treatment of Chemo Brain.

This pilot feasibility study aimed to evaluate the effects of transcranial magnetic stimulation (TMS) on chemotherapy-related cognitive impairment (CRCI), and we report here on the first patient. BACKGROUND: Deleterious cognitive changes due to chemotherapy or CRCI are commonly referred to as "chemo brain". With the increasing survival of cancer patients, this poorly understood and inadequately treated condition will likewise have an increasing toll on individuals and society. Since there is no approved treatment for chemo brain, we have initiated a therapeutic trial using transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique approved in many countries for the treatment of neurologic and psychiatric conditions like migraine and depression. CASE PRESENTATION: A 58-year-old woman, diagnosed 7 years prior with left breast cancer, underwent partial mastectomy with sentinel lymph node biopsy. She then received four cycles of adjuvant chemotherapy followed by radiation therapy. Afterwards, she was on tamoxifen for 4 years and then switched to aromatase inhibitors. The patient's CRCI started during chemotherapy and severely impaired her quality of life for an additional two years. In the third year after chemotherapy, the CRCI partially cleared to stabilize to the level at the time of presentation for this trial. The patient continues to have memory difficulties and decreased concentration, which makes multi-tasking very difficult to impossible. She is reliant on memory aids at work and at home. The participant underwent 10 consecutive sessions of TMS during weekdays for 2 weeks. Stimulation was directed to the left dorsolateral prefrontal cortex. After TMS, the participant significantly improved in memory function on neuropsychological testing. While she reported no subjective differences in concentration or memory, she did report an improvement in her sleep. Functional magnetic resonance imaging of the brain before and after TMS showed increased resting-state functional connectivity between the stimulation site and several brain regions. Remarkably, after 6 years of chemo brain and remaining in the same position at work due to her inability to concentrate and multi-task, she applied for and received a promotion 5-6 months after her TMS treatments. CONCLUSIONS: This first patient in the phase 1 clinical trial testing of TMS for the treatment of "chemo brain" provided important lessons for feasibility and insights into mechanisms of potential benefit.

Differences in Treatment Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients in 6 Countries.

Importance: Differences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries. Objective: To determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. Design, Setting, and Participants: Serial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. Exposures: Being in the top and bottom quintile of income within and across countries. Main Outcomes and Measures: Thirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates. Results: We studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, -2.8 percentage points [95% CI, -4.1 to -1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, -9.1 percentage points [95% CI, -16.7 to -1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients. Conclusions and Relevance: High-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems.

H2S- and Redox-State-Mediated PTP1B S-Sulfhydration in Insulin Signaling.

Because hydrogen sulfide (H2S) is classified as a gaseous signaling molecule, protein S-sulfhydration is known to be one of the mechanisms by which H2S signals are conducted. PTP1B, a negative regulator in insulin signaling, has been found to be S-sulfhydrated at Cys215-SH to form Cys215-SSH in response to endoplasmic reticulum (ER) stress. Therefore, we aimed to understand the change in PTP1B S-sulfhydration and cellular redox homeostasis in response to insulin stimulation. We demonstrated a feasible PEG-switch method to determine the levels of PTP1B S-sulfhydration. According to the results obtained from HEK293T and MDA-MB-231 cells, insulin induced a change in PTP1B S-sulfhydration that was similar to the change in Insulin receptor substrate 1 (IRS1) phosphorylation in both cell lines. However, insulin-induced PTP1B S-sulfhydration and IRS1 phosphorylation were only significantly affected by metformin in HEK293T cells. Insulin also induced an increase in reactive oxygen species (ROS) in both cell lines. However, the level of H2S, GSH, and GSSG was only significantly affected by insulin and metformin in HEK293T cells. HEK293T cells maintained high levels of H2S and cysteine, but low levels of GSSG and GSH in general compared to MDA-MB-231 cells. From these findings, we suggest that PTP1B activity is modulated by H2S and redox-regulated S-sulfhydration during insulin signaling.

Maresin: Macrophage Mediator for Resolving Inflammation and Bridging Tissue Regeneration-A System-Based Preclinical Systematic Review.

Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term "Maresin (NOT) Review" on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies (n = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies (n = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 µg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.

Reducing Medication Errors by Adopting Automatic Dispensing Cabinets in Critical Care Units.

Medication errors can have severe consequences and threaten patient safety. The patient safety-related benefits of automated dispensing cabinets (ADCs) have been reported by several previous studies, including a reduction in medication errors in intensive care units (ICUs) and emergency departments. However, the benefits of ADCs need to be assessed, given the different healthcare practice models. This study aimed to compare the rates of medication errors, including prescription, dispensing, and administrative, before and after using ADCs in intensive care units. The prescription, dispensing, and administrative error data before and after the adoption of ADCs were retrospectively collected from the medication error report system. The severity of medication errors was classified according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines. The study outcome was the rate of medication errors. After the adoption of ADCs in the intensive care units, the rates of prescription and dispensing errors reduced from 3.03 to 1.75 per 100,000 prescriptions and 3.87 to 0 per 100,000 dispensations, respectively. The administrative error rate decreased from 0.046 to 0.026%. The ADCs decreased National Coordinating Council for Medication Error Reporting and Prevention category B and D errors by 75% and category C errors by 43%. To improve medication safety, multidisciplinary collaboration and strategies, such as the use of automated dispensing cabinets, education, and training programs from a systems perspective, are warranted.