Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

BACKGROUND: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone. METHODS: We performed a retrospective cohort study of 120 531 patients with AMI and AIS from the national stroke and AMI registries in Singapore. Patients were categorized into AMI only, AIS only, synchronous CCI (same-day), and metachronous CCI (within 1 week). The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The mortality risks were compared using Cox regression. Multivariable models were adjusted for baseline demographics, clinical variables, and treatment for AMI or AIS. RESULTS: Of 127 919 patients identified, 120 531 (94.2%) were included; 74 219 (61.6%) patients had AMI only, 44 721 (37.1%) had AIS only, 625 (0.5%) had synchronous CCI, and 966 (0.8%) had metachronous CCI. The mean age was 67.7 (SD, 14.0) years. Synchronous and metachronous CCI had a higher risk of 30-day mortality (synchronous: adjusted HR [aHR], 2.41 [95% CI, 1.77-3.28]; metachronous: aHR, 2.80 [95% CI, 2.11-3.73]) than AMI only and AIS only (synchronous: aHR, 2.90 [95% CI, 1.87-4.51]; metachronous: aHR, 4.36 [95% CI, 3.03-6.27]). The risk of cardiovascular mortality was higher in synchronous and metachronous CCI than AMI (synchronous: aHR, 3.03 [95% CI, 2.15-4.28]; metachronous: aHR, 3.41 [95% CI, 2.50-4.65]) or AIS only (synchronous: aHR, 2.58 [95% CI, 1.52-4.36]; metachronous: aHR, 4.52 [95% CI, 2.95-6.92]). In synchronous CCI, AMI was less likely to be managed with PCI and secondary prevention medications (P<0.001) compared with AMI only. CONCLUSIONS: Synchronous CCI occurred in 1 in 200 cases of AIS and AMI. Synchronous and metachronous CCI had higher mortality than AMI or AIS alone.

Neurologic Manifestations of Long COVID Differ Based on Acute COVID-19 Severity.

OBJECTIVE: To characterize neurologic manifestations in post-hospitalization Neuro-PASC (PNP) and non-hospitalized Neuro-PASC (NNP) patients. METHODS: Prospective study of the first 100 consecutive PNP and 500 NNP patients evaluated at a Neuro-COVID-19 clinic between 5/2020 and 8/2021. RESULTS: PNP were older than NNP patients (mean 53.9 vs 44.9 y; p < 0.0001) with a higher prevalence of pre-existing comorbidities. An average 6.8 months from onset, the main neurologic symptoms were "brain fog" (81.2%), headache (70.3%), and dizziness (49.5%) with only anosmia, dysgeusia and myalgias being more frequent in the NNP compared to the PNP group (59 vs 39%, 57.6 vs 39% and 50.4 vs 33%, all p < 0.003). Moreover, 85.8% of patients experienced fatigue. PNP more frequently had an abnormal neurologic exam than NNP patients (62.2 vs 37%, p < 0.0001). Both groups had impaired quality of life in cognitive, fatigue, sleep, anxiety, and depression domains. PNP patients performed worse on processing speed, attention, and working memory tasks than NNP patients (T-score 41.5 vs 55, 42.5 vs 47 and 45.5 vs 49, all p < 0.001) and a US normative population. NNP patients had lower results in attention task only. Subjective impression of cognitive ability correlated with cognitive test results in NNP but not in PNP patients. INTERPRETATION: PNP and NNP patients both experience persistent neurologic symptoms affecting their quality of life. However, they harbor significant differences in demographics, comorbidities, neurologic symptoms and findings, as well as pattern of cognitive dysfunction. Such differences suggest distinct etiologies of Neuro-PASC in these populations warranting targeted interventions. ANN NEUROL 2023;94:146-159.

Polymer-Based Nanoparticles with Probucol and Lithocholic Acid: A Novel Therapeutic Approach for Oxidative Stress-Induced Retinopathies.

Oxidative stress is pivotal in retinal disease progression, causing dysfunction in various retinal components. An effective antioxidant, such as probucol (PB), is vital to counteract oxidative stress and emerges as a potential candidate for treating retinal degeneration. However, the challenges associated with delivering lipophilic drugs such as PB to the posterior segment of the eye, specifically targeting photoreceptor cells, necessitate innovative solutions. This study uses formulation-based spray dry encapsulation technology to develop polymer-based PB-lithocholic acid (LCA) nanoparticles and assesses their efficacy in the 661W photoreceptor-like cell line. Incorporating LCA enhances nanoparticles' biological efficacy without compromising PB stability. In vitro studies demonstrate that PB-LCA nanoparticles prevent reactive oxygen species (ROS)-induced oxidative stress by improving cellular viability through the nuclear erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. These findings propose PB-LCA nanoparticles as a promising therapeutic strategy for oxidative stress-induced retinopathies.

Impact of COVID-19 pandemic early response measures on myocardial infarctions and acute cardiac care in Singapore.

The COVID -19 pandemic impacted acute myocardial infarction (AMI) attendances, ST-elevation myocardial infarction (STEMI) treatments, and outcomes. We collated data from majority of primary percutaneous coronary intervention (PPCI)-capable public healthcare centres in Singapore to understand the initial impact COVID-19 had on essential time-critical emergency services. We present data comparisons from 'Before Disease Outbreak Response System Condition (DORSCON) Orange', 'DORSCON Orange to start of circuit breaker (CB)', and during the first month of 'CB'. We collected aggregate numbers of weekly elective PCI from four centres and AMI admissions, PPCI, and in-hospital mortality from five centres. Exact door-to-balloon (DTB) times were recorded for one centre; another two reported proportions of DTB times exceeding targets. Median weekly elective PCI cases significantly decreased from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (34 vs 22.5, P = 0.013). Median weekly STEMI admissions and PPCI did not change significantly. In contrast, the median weekly non-STEMI (NSTEMI) admissions decreased significantly from 'Before DORSCON Orange' to 'DORSCON Orange to start of CB' (59 vs 48, P = 0.005) and were sustained during CB (39 cases). Exact DTB times reported by one centre showed no significant change in the median. Out of three centres, two reported significant increases in the proportion that exceeded DTB targets. In-hospital mortality rates remained static. In Singapore, STEMI and PPCI rates remained stable, while NSTEMI rates decreased during DORSCON Orange and CB. The severe acute respiratory syndrome (SARS) experience may have helped prepare us to maintain essential services such as PPCI during periods of acute healthcare resource strain. However, data must be monitored and increased pandemic preparedness measures must be explored to ensure that AMI care is not adversely affected by continued COVID fluctuations and future pandemics.

Optimal glucose, HbA1c, glucose-HbA1c ratio and stress-hyperglycaemia ratio cut-off values for predicting 1-year mortality in diabetic and non-diabetic acute myocardial infarction patients.

BACKGROUND: Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition to glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia ratio (SHR) are potential predictors of clinical outcomes following AMI. However, the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting 1-year all cause mortality in diabetic and non-diabetic ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients. METHODS: We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values using the Youden's formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-off values in the diabetic and non-diabetic subgroups, stratified by the type of AMI. RESULTS: There were 5841 STEMI and 4105 NSTEMI in the study. In STEMI patients, glucose, GHR, and SHR were independent predictors of 1-year all-cause mortality [glucose: OR 2.19 (95% CI 1.74-2.76); GHR: OR 2.28 (95% CI 1.80-2.89); SHR: OR 2.20 (95% CI 1.73-2.79)]. However, in NSTEMI patients, glucose and HbA1c were independently associated with 1-year all-cause mortality [glucose: OR 1.38 (95% CI 1.01-1.90); HbA1c: OR 2.11 (95% CI 1.15-3.88)]. In diabetic STEMI patients, SHR performed the best in terms of area-under-the-curve (AUC) analysis (glucose: AUC 63.3%, 95% CI 59.5-67.2; GHR 68.8% 95% CI 64.8-72.8; SHR: AUC 69.3%, 95% CI 65.4-73.2). However, in non-diabetic STEMI patients, glucose, GHR, and SHR performed equally well (glucose: AUC 72.0%, 95% CI 67.7-76.3; GHR 71.9% 95% CI 67.7-76.2; SHR: AUC 71.7%, 95% CI 67.4-76.0). In NSTEMI patients, glucose performed better than HbA1c for both diabetic and non-diabetic patients in AUC analysis (For diabetic, glucose: AUC 52.8%, 95% CI 48.1-57.6; HbA1c: AUC 42.5%, 95% CI 37.6-47. For non-diabetic, glucose: AUC 62.0%, 95% CI 54.1-70.0; HbA1c: AUC 51.1%, 95% CI 43.3-58.9). The optimal cut-off values for glucose, GHR, and SHR in STEMI patients were 15.0 mmol/L, 2.11, and 1.68 for diabetic and 10.6 mmol/L, 1.72, and 1.51 for non-diabetic patients respectively. For NSTEMI patients, the optimal glucose values were 10.7 mmol/L for diabetic and 8.1 mmol/L for non-diabetic patients. CONCLUSIONS: SHR was the most consistent independent predictor of 1-year all-cause mortality in both diabetic and non-diabetic STEMI, whereas glucose was the best predictor in NSTEMI patients.

Tungsten Ligand-Based Sulfur-Atom-Transfer Catalysts: Synthesis, Characterization, Sustained Anaerobic Catalysis, and Mode of Aerial Deactivation.

The synthesis, properties, X-ray structures, and catalytic sulfur-atom-transfer (SAT) reactions of W2(µ-S)(µ-S2)(dtc)2(dped)2 [1; dtc = S2CNR2-, where R = Me, Et, iBu, and Bn; dped = S2C2Ph22-] and W2(µ-S)2(dtc)2(dped)2 (2) are reported. These complexes represent the oxidized (1) and reduced (2) forms of anaerobic SAT catalysts operating through the bidirectional, ligand-based half-reaction (µ-S)(µ-S2) ↔ (µ-S)2 + S0. The catalysts are deactivated in air through the formation of catalytically inactive oxo complexes, (dtc)WO(µ-S)(µ-dped)W(dtc)(dped) (3), prompting us to recommend that group 6 SAT activity be assessed under strictly anaerobic conditions.

Prediction of Survival in Asian Patients Hospitalized With Heart Failure: Validation of the OPTIMIZE-HF Risk Score.

BACKGROUND: Risk scores predicting in-patient mortality in heart failure patients have not been designed specifically for Asian patients. We aimed to validate and recalibrate the OPTIMIZE-HF risk model for in-hospital mortality in a multiethnic Asian population hospitalized for heart failure. METHODS AND RESULTS: Data from the Singapore Cardiac Databank Heart Failure on patients admitted for heart failure from January 1, 2008, to December 31, 2013, were included. The primary outcome studied was in-hospital mortality. Two models were compared: the original OPTIMIZE-HF risk model and a modified OPTIMIZE-HF risk model (similar variables but with coefficients derived from our cohort). A total of 15,219 patients were included. The overall in-hospital mortality was 1.88% (n = 286). The original model had a C-statistic of 0.739 (95% CI 0.708-0.770) with a good match between predicted and observed mortality rates (Hosmer-Lemeshow statistic 13.8; P = .086). The modified model had a C-statistic of 0.741 (95% CI 0.709-0.773) but a significant difference between predicted and observed mortality rates (Hosmer-Lemeshow statistic 17.2; P = .029). The modified model tended to underestimate risk at the extremes (lowest and highest ends) of risk. CONCLUSIONS: We provide the first independent validation of the OPTIMIZE-HF risk score in an Asian population. This risk model has been shown to perform reliably in our Asian cohort and will potentially provide clinicians with a useful tool to identify high-risk heart failure patients for more intensive management.

Tracking quicksilver: estimation of mercury waste from consumer products and subsequent verification by analysis of soil, water, sediment, and plant samples from the Cebu City, Philippines, landfill.

Source attribution of mercury (Hg) is critical for policy development to minimize the impact of Hg in wastes. Mercury content of consumer products and its subsequent release into the waste stream of Cebu City, Philippines, is estimated through surveys that employed validated, enumerator-administered questionnaires. Initially, a citywide survey (n = 1636) indicates that each household annually generates 1.07 ppm Hg (i.e., mg Hg/kg waste) and that linear and compact fluorescent lamps (17.2 %) and thermometers (52.1 %) are the major sources of Hg. A subsequent survey (n = 372) in the vicinity of the city's municipal solid waste landfill shows that residents in the area annually generate 0.38 ppm Hg per household, which is less than the citywide mean; surprisingly though, less affluent respondents living closer to the landfill site reported more Hg from thermometers and sphygmomanometers. Analysis of collected soil (0.238 ppm), leachate water (6.5 ppb), sediment (0.109 ppm), and three plants (0.393 to 0.695 ppm) shows no significant variation throughout five stations in and around the landfill site, although the period of collection is significant for soil (P = 0.001) and Cenchrus echinatus (P = 0.016). Detected Hg in the landfill is considerably less than the annual estimated release, indicating that there is minimal accumulation of Hg in the soil or in plants. As a result of this project, a policy brief has been provided to the Cebu City council in aid of hazardous waste legislation.

A meta-analysis on the effect of sham feeding following colectomy: should gum chewing be included in enhanced recovery after surgery protocols?

BACKGROUND: Sham feeding has been shown to hasten the return of GI function following colorectal surgery, before the advent of enhanced recovery after surgery protocols. Few data exist regarding the efficacy of sham feeding in the modern era, with rapid postoperative feeding. OBJECTIVE: We sought to perform a meta-analysis on the effect of sham feeding in colorectal surgery, with a separate analysis on trials that used rapid postoperative feeding. DATA SOURCES: Cochrane, MEDLINE, EMBASE, Scopus, and PubMed were searched by using the terms gum OR sham feeding OR chew AND (colorect OR resect). STUDY SELECTION: All studies were randomized controlled trials (in any language) performed on adults, comparing standard care with gum chewing following colorectal resection. From 439 citations, 10 articles were included. INTERVENTION: The intervention was sham feeding by means of gum chewing. MAIN OUTCOME MEASURES: The outcome measures were time to return of flatus, time to first bowel movement, complication rates, length of hospital stay, readmission rates, and reoperation rates. RESULTS: Ten randomized controlled trials (n = 612) were included. Sham feeding resulted in a reduction in time to flatus of 31 minutes (p = 0.003) and time to first bowel movement of 30 minutes (p = 0.05). Sham feeding also resulted in a reduction in length of stay by 0.5 days (p = 0.007), and a reduction in complication rates (relative risk = 0.687, p = 0.017), although this appeared to be associated with publication bias. Analysis of trials that used rapid postoperative feeding (n = 282) revealed no difference in postoperative GI function. LIMITATIONS: This review was limited by the heterogeneity of postoperative feeding regimes, in addition to limited reporting by trials of postoperative morbidity. CONCLUSIONS: Sham feeding following colorectal surgery is safe, results in small improvements in GI recovery, and is associated with a reduction in the length of hospital stay. It confers no advantage if patients are placed on a rapid postoperative feeding regime.

Exploring delivery systems for targeted nanotechnology-based gene therapy in the inner ear.

Hearing loss places a significant burden on our aging population. However, there has only been limited progress in developing therapeutic techniques to effectively mediate this condition. This review will outline several of the most commonly utilized practices for the treatment of sensorineural hearing loss before exploring more novel techniques currently being investigated via both in vitro and in vivo research. This review will place particular emphasis on novel gene-delivery technologies. Primarily, it will focus on techniques used to deliver genes that have been shown to encourage the proliferation and differentiation of sensory cells within the inner ear and how these technologies may be translated into providing clinically useful results for patients.

[Box: see text].

Polymer-Based Nanoparticles for Inner Ear Targeted Trans Differentiation Gene Therapy.

Hearing loss is a significant disability that often goes under recognised, largely due to poor identification, prevention, and treatment. Steps are being made to amend these pitfalls in the investigation of hearing loss, however, the development of a cure to reverse advanced forms remains distant. This review details some current advances in the treatment of hearing loss, with a particular focus on genetic-based nanotechnology and how it may provide a useful avenue for further research. This review presents a broad background on the pathophysiology of hearing loss and some current interventions. We also highlight some potential genes that may be useful in the amelioration of hearing loss. Pathways of cellular differentiation from stem or supporting cell to functional hair cell are covered in detail, as this mechanism represents a key means of regenerating these cell types. Overall, we believe that polymer-based nanotechnology coupled with novel excipients represents a useful area of further research in the treatment of hearing loss, although further studies in this area are required.

Mild Primary or Breakthrough SARS-CoV-2 Infection Promotes Autoantibody Production in Individuals with and without Neuro-PASC.

Patients with long COVID can develop humoral autoimmunity after severe acute SARS-CoV-2 infection. However, whether similar increases in autoantibody responses occur after mild infection and whether vaccination prior to SARS-CoV-2 breakthrough infection can limit autoantibody responses is unknown. In this study, we demonstrate that mild SARS-CoV-2 infection increases autoantibodies associated with rheumatic autoimmune diseases and diabetes in most individuals, regardless of vaccination status prior to infection. However, patients with long COVID and persistent neurologic and fatigue symptoms (neuro-PASC) have substantially higher autoantibody responses than convalescent control subjects at an average of 8 mo postinfection. Furthermore, high titers of systemic lupus erythematosus- and CNS-associated autoantibodies in patients with neuro-PASC are associated with impaired cognitive performance and greater symptom severity. In summary, we found that mild SARS-CoV-2 primary and breakthrough infections can induce persistent humoral autoimmunity in both patients with neuro-PASC and healthy COVID convalescents, suggesting that a reappraisal of mitigation strategies against SARS-CoV-2 is warranted to prevent transmission and potential development of autoimmunity.

Sham feeding with chewing gum after elective colorectal resectional surgery: a randomized clinical trial.

OBJECTIVE: To determine whether sham feeding with chewing gum improved gastrointestinal recovery after colorectal resection surgery, in the presence of routine postoperative feeding. BACKGROUND: Sham feeding with chewing gum has been shown to accelerate the return of gut function after colorectal surgery. This study sought to determine whether sham feeding with gum, after colorectal resection, accelerates return of gastrointestinal function in patients on a rapid feeding enhanced recovery program. METHODS: A randomized "two armed" controlled clinical trial was performed. Equal groups of open and laparoscopic colorectal resection surgical patients were recruited. Patients in the intervention arm received chewing gum 4 times a day postoperatively. All patients in the trial were placed on an established, standardized Enhanced Recovery After Surgery program. The primary outcome was time to return of gut function, assessed by time to flatus and first bowel motion. Secondary outcomes were time to tolerate diet, symptoms of ileus in the form of nausea, vomiting and distension, pain as assessed by analgesic consumption and visual analogue scales, complications, and length of hospital stay. RESULTS: A total of 161 patients were recruited. Postoperative morbidity was equivalent between groups, with no complications related to gum chewing. There was no difference between groups with respect to the primary outcomes of time to flatus and bowel motion. There was less perception of pain in the intervention group on days 2 to 5, and no difference with respect to all other secondary outcomes. CONCLUSIONS: Sham feeding with gum, after open and laparoscopic colorectal resectional surgery is safe, but does not hasten the return of gastrointestinal function in patients who receive accelerated postoperative feeding. (ACTRN12607000538448).

(N,N-diethyldithiocarbamato)[tris(3,5-dimethylpyrazol-1-yl)hydroborato]copper(II): a new copper(II) dithiocarbamate compound with the classic Tp(Me2) scorpionate.

The title complex, [Cu(C5H10NS2)(C15H22BN6)] or (Tp(Me2))Cu(S2CNEt2), incorporating the classic Tp(Me2) scorpionate, is relevant to blue copper protein models and to Cu extraction from waste treatment and mine-tailing leachate. The IR and UV-Vis spectra are consistent with the crystal structure.

Poly-L-lysine as a crosslinker in bile acid and alginate nanoaggregates for gene delivery in auditory cells.

Background: Hearing loss is a condition that may affect a wide array of patients from various backgrounds. There are no cures for sensorineural hearing loss. Gene therapy is one possible method of improving hearing status; however, gene delivery remains challenging. Materials & methods: Polymer nanoaggregates of alginate and poly-L-lysine were prepared with and without bile acid. The nanoaggregates had physical properties, cytotoxicity, gene release and gene expression analyzed. Results & discussion: The nanoparticles produced had appropriate size and charge, low cytotoxicity between 0.5 and 1.0 mg/ml and linear gene release but poor transfection efficiency. Conclusion: The present study provides preliminary evidence for the efficacy of polymer nanotechnology with bile acids for inner ear gene delivery; optimization is required to improve transfection efficiency.

Hearing loss is a global issue with significant consequences. Gene therapy is an emerging technique in the management of various conditions, including hearing loss. This involves the delivery of a new copy of a gene to a cell with a missing or defective copy of that gene. The delivery of genes such as ATOH1 has been shown to encourage cell differentiation into new functional hair cells to potentially reverse hearing loss. Unfortunately, effective and safe delivery of genes remains challenging. Polymer nanoparticles represent one method for delivering genes that allows for customizability in size, structure and function. In this study, the authors developed nanoparticles with a polymer derived from algae called alginate, an amino acid polymer called poly-L-lysine and bile acid to improve gene delivery to inner ear cells. A cell line derived from the inner ear of a mouse was used to test the effectiveness of these particles at delivering genes. A gene that makes cells that uptake these particles fluoresce was included in the nanoparticles, to demonstrate they are capable of gene delivery. In the future, this gene could be replaced with genes associated with encouraging cell differentiation. The preliminary results of this study suggest that such nanoparticles may be capable of gene delivery, although further optimization is required.

Fluorescent protein lifetimes report densities and phases of nuclear condensates during embryonic stem-cell differentiation.

Fluorescent proteins (FP) are frequently used for studying proteins inside cells. In advanced fluorescence microscopy, FPs can report on additional intracellular variables. One variable is the local density near FPs, which can be useful in studying densities within cellular bio-condensates. Here, we show that a reduction in fluorescence lifetimes of common monomeric FPs reports increased levels of local densities. We demonstrate the use of this fluorescence-based variable to report the distribution of local densities within heterochromatin protein 1α (HP1α) in mouse embryonic stem cells (ESCs), before and after early differentiation. We find that local densities within HP1α condensates in pluripotent ESCs are heterogeneous and cannot be explained by a single liquid phase. Early differentiation, however, induces a change towards a more homogeneous distribution of local densities, which can be explained as a liquid-like phase. In conclusion, we provide a fluorescence-based method to report increased local densities and apply it to distinguish between homogeneous and heterogeneous local densities within bio-condensates.

Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARS-CoV-2 Nucleocapsid protein.

Introduction: Many people with long COVID symptoms suffer from debilitating neurologic post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). Although symptoms of Neuro-PASC are widely documented, it is still unclear whether PASC symptoms impact virus-specific immune responses. Therefore, we examined T cell and antibody responses to SARS-CoV-2 Nucleocapsid protein to identify activation signatures distinguishing Neuro-PASC patients from healthy COVID convalescents. Results: We report that Neuro-PASC patients exhibit distinct immunological signatures composed of elevated CD4+ T cell responses and diminished CD8+ memory T cell activation toward the C-terminal region of SARS-CoV-2 Nucleocapsid protein when examined both functionally and using TCR sequencing. CD8+ T cell production of IL-6 correlated with increased plasma IL-6 levels as well as heightened severity of neurologic symptoms, including pain. Elevated plasma immunoregulatory and reduced pro-inflammatory and antiviral response signatures were evident in Neuro-PASC patients compared with COVID convalescent controls without lasting symptoms, correlating with worse neurocognitive dysfunction. Discussion: We conclude that these data provide new insight into the impact of virus-specific cellular immunity on the pathogenesis of long COVID and pave the way for the rational design of predictive biomarkers and therapeutic interventions.

Corrigendum: Neuro-PASC is characterized by enhanced CD4+ and diminished CD8+ T cell responses to SARSCoV-2 Nucleocapsid protein.

[This corrects the article DOI: 10.3389/fimmu.2023.1155770.].

Clinical characteristics and outcomes in Asian patients with heart failure with mildly reduced ejection fraction.

Introduction: Data on heart failure (HF) with mildly reduced ejection fraction (HFmrEF) is still emerging, especially in Asian populations. This study aims to compare the clinical characteristics and outcomes of Asian HFmrEF patients with those of HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Methods: Patients admitted nationally for HF between 2008 and 2014 were included in the study. They were categorised according to ejection fraction (EF). Patients with EF <40%, EF 40%-49% and EF ≥50% were categorised into the following groups: HFrEF, HFmrEF and HFpEF, respectively. All patients were followed up till December 2016. Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular death and/or HF rehospitalisations. Results: A total of 16,493 patients were included in the study - HFrEF, n = 7,341 (44.5%); HFmrEF, n = 2,272 (13.8%); and HFpEF n = 6,880 (41.7%). HFmrEF patients were more likely to be gender neutral, of mid-range age and have concomitant diabetes mellitus, hyperlipidaemia, peripheral vascular disease and coronary artery disease (P < 0.001). The two-year overall mortality rates for HFrEF, HFmrEF and HFpEF were 32.9%, 31.8% and 29.1%, respectively. HFmrEF patients had a significantly lower overall mortality rate compared to HFrEF patients (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.83-0.95; P < 0.001) and a significantly higher overall mortality rate (adjusted HR 1.25, 95% CI 1.17-1.33; P < 0.001) compared to HFpEF patients. This was similarly seen with cardiovascular mortality and HF hospitalisations, with the exception of similar HF hospitalisations between HFmrEF and HFpEF patients. Conclusion: HFmrEF patients account for a significant burden of patients with HF. HFmrEF represents a distinct HF phenotype with high atherosclerotic burden and clinical outcomes saddled in between those of HFrEF and HFpEF. Further therapeutic studies to guide management of this challenging group of patients are warranted.

Pharmaceutical characterization of probucol bile acid-lithocholic acid nanoparticles to prevent chronic hearing related and similar cellular oxidative stress pathologies.

Background: Sensorineural hearing loss has been associated with oxidative stress. However, an antioxidant that passes effectively through the ear remains elusive. Method: Probucol (PB)-based nanoparticles were formed using a spray-drying encapsulation technique, characterized and tested in vitro. Results: Uniform, spherical nanoparticles were produced. The addition of lithocholic acid to PB formulations did not affect drug content or production yield, but it did modify capsule size, surface tension, electrokinetic stability and drug release. Cell viability, bioenergetics and inflammatory profiles were improved when auditory cells were exposed to PB-based nanoparticles, which showed antioxidant properties (p < 0.05). Conclusion: PB-based nanoparticles can potentially protect the auditory cell line from oxidative stress and could be used in future in vivo studies as a potential new therapeutic agent for sensorineural hearing loss.

Oxidative stress is an imbalance of cellular processes in which the production of free radicals outweighs the cellular defense mechanism. The association of oxidative stress with the pathophysiology of sensorineural hearing loss (SHL) is well established. SHL development is associated with chronic damage in the structure of the inner ear or auditory nerve. Therefore, potent antioxidants such as probucol could be one way to prevent or treat SHL. However, due to its isolated position, SHL is challenging to treat, imposing a desperate need for refining existing therapeutic methods; one way to do this is by optimizing the formulation using nanoparticles. We aimed to design a novel, stable formulation of PB using polymers and excipients to develop nanoparticles and examine the efficiency of these formulations on the HEI-OC1 stress cell line. We found that the prepared nanoparticle is robust and stable and protects HEI-OC1 from cellular toxicity and oxidative stress. It could be a novel therapeutic agent to treat or prevent SHL.