Corrigendum: Efficacy of a paper-based interleukin-6 test strip combined with a spectrum-based optical reader for sequential monitoring and early recognition of respiratory failure in elderly pneumonia-a pilot study.

[This corrects the article DOI: 10.3389/fphar.2023.1166923.].

Case report: Distinct neurologic manifestation and cytokine profile of a child with COVID-19-associated acute fulminant encephalitis.

The neurologic manifestations of coronavirus disease 2019 (COVID-19) may range from mild symptoms such as headache or confusion to profound encephalopathy with variable outcomes and sequelae. Here, we reported a case of fatal COVID-19-associated encephalitis with acute fulminant cerebral edema, presenting first with visual hallucination and then a rapid progression into comatose status in a few hours. Serial brain computed tomography depicted cerebral edematous changes from bilateral ventral temporal lobe to the whole brain leading to brain herniation. Multiple cytokines in serum and cerebrospinal fluid (CSF) were increased, with a more prominent rise in the CSF. Therefore, we postulated a hypothesis regarding the mechanism of this fulminant encephalitis that the SARS-CoV-2 virus attacked ventral temporal lobes initially, triggered a severe cytokine storm, and then led to subsequent disruption of the blood-brain barrier, diffuse brain edema, and brain herniation. The trend of cytokine profiles over time may aid in diagnosing and evaluating the severity and prognosis of COVID-19-associated encephalitis.

Efficacy of a paper-based interleukin-6 test strip combined with a spectrum-based optical reader for sequential monitoring and early recognition of respiratory failure in elderly pneumonia-a pilot study.

Introduction: Community-acquired pneumonia (CAP) is lethal in elderly individuals who are more vulnerable to respiratory failure and require more emergency ventilation support than younger individuals. Interleukin-6 (IL-6) plays a crucial role and has predictive value in CAP; high serum IL-6 concentrations in adults are associated with high respiratory failure and mortality rates. Early detection of IL-6 concentrations can facilitate the timely stratification of patients at risk of acute respiratory failure. However, conventional enzyme-linked immunosorbent assay (ELISA) IL-6 measurement is laborious and time-consuming. Methods: The IL-6 rapid diagnostic system combined with a lateral flow immunoassay-based (LFA-based) IL-6 test strip and a spectrum-based optical reader is a novel tool developed for rapid and sequential bedside measurements of serum IL-6 concentrations. Here, we evaluated the correlation between the IL-6 rapid diagnostic system and the ELISA and the efficacy of the system in stratifying high-risk elderly patients with CAP. Thirty-six elderly patients (median age: 86.5 years; range: 65-97 years) with CAP were enrolled. CAP diagnosis was established based on the Infectious Diseases Society of America (IDSA) criteria. The severity of pneumonia was assessed using the CURB-65 score and Pneumonia Severity Index (PSI). IL-6 concentration was measured twice within 24 h of admission. Results: The primary endpoint variable was respiratory failure requiring invasive mechanical or non-invasive ventilation support after admission. IL-6 rapid diagnostic readouts correlated with ELISA results (p < 0.0001) for 30 samples. Patients were predominantly male and bedridden (69.4%). Ten patients (27.7%) experienced respiratory failure during admission, and five (13.9%) died of pneumonia. Respiratory failure was associated with a higher mortality rate (p = 0.015). Decreased serum IL-6 concentration within 24 h after admission indicated a lower risk of developing respiratory failure in the later admission course (Receiver Operating Characteristic [ROC] curve = 0.696). Conclusion: Sequential IL-6 measurements with the IL-6 rapid diagnostic system might be useful in early clinical risk assessment and severity stratification of elderly patients with pneumonia. This system is a potential point-of-care diagnostic device for sequential serum IL-6 measurements that can be applied in variable healthcare systems.

Potential Application of the WST-8-mPMS Assay for Rapid Viable Microorganism Detection.

To ensure clean drinking water, viable pathogens in water must be rapidly and efficiently screened. The traditional culture or spread-plate process-the conventional standard for bacterial detection-is laborious, time-consuming, and unsuitable for rapid detection. Therefore, we developed a colorimetric assay for rapid microorganism detection using a metabolism-based approach. The reaction between a viable microorganism and the combination of 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt (WST-8) and 1-methoxy-5-methylphenazinium methyl sulfate (mPMS) results in a color change. In combination with a microplate reader, WST-8-mPMS reactivity was leveraged to develop a colorimetric assay for the rapid detection of various bacteria. The detection limit of the WST-8-mPMS assay for both gram-negative and gram-positive bacteria was evaluated. This WST-8-mPMS assay can be used to perform colorimetrical semi-quantitative detection of various bacterial strains in buffers or culture media within 1 h without incubation before the reaction. The easy-to-use, robust, rapid, and sensitive nature of this novel assay demonstrates its potential for practical and medical use for microorganism detection.

The potential use of Zymomonas mobilis for the food industry.

Zymomonas mobilis is a gram-negative facultative anaerobic spore, which is generally recognized as a safe. As a promising ethanologenic organism for large-scale bio-ethanol production, Z. mobilis has also shown a good application prospect in food processing and food additive synthesis for its unique physiological characteristics and excellent industrial characteristics. It not only has obvious advantages in food processing and becomes the biorefinery chassis cell for food additives, but also has a certain healthcare effect on human health. Until to now, most of the research is still in theory and laboratory scale, and further research is also needed to achieve industrial production. This review summarized the physiological characteristics and advantages of Z. mobilis in food industry for the first time and further expounds its research status in food industry from three aspects of food additive synthesis, fermentation applications, and prebiotic efficacy, it will provide a theoretical basis for its development and applications in food industry. This review also discussed the shortcomings of its practical applications in the current food industry, and explored other ways to broaden the applications of Z. mobilis in the food industry, to promote its applications in food processing.

Potential applications of Zymomonas mobilis in food industry summarized for the first time.Research status of Z. mobilis in food additive synthesis, fermentation applications, and probiotics are discussed in details.Future research perspectives of Z. mobilis in food industry further proposed.

Biomarkers during COVID-19: Mechanisms of Change and Implications for Patient Outcomes.

As the COVID-19 (Coronavirus disease 19) pandemic spreads worldwide, the massive numbers of COVID-19 patients have created a considerable healthcare burden for every country. The clinical spectrum of SARS-CoV-2 infection is broad, ranging from asymptomatic to mild, moderate, severe, and critical. Most COVID-19 patients present with no or mild symptoms, but nearly one-fifth of all patients develop severe or life-threatening complications. In addition to localized respiratory manifestations, severe COVID-19 cases also show extra-pulmonary complications or induce multiorgan failure. Identifying, triaging, and treating patients at risk early is essential and urgent. This article reviews the potential prognostic value of various biomarkers at different clinical spectrum stages of COVID-19 infection and includes information on fundamental prognostic mechanisms as well as potential clinical implications. Biomarkers are measurable biochemical substances used to recognize and indicate disease severity or response to therapeutic interventions. The information they provide is objective and suitable for delivering healthcare providers with a means of stratifying disease state in COVID-19 patients. This, in turn, can be used to help select and guide intervention efforts as well as gauge the efficacy of therapeutic approaches. Here, we review a number of potential biomarkers that may be used to guide treatment, monitor treatment efficacy, and form individualized therapeutic guidance based on patient response. Implementation of the COVID-19 biomarkers discussed here may lead to significantly improved quality of care and patient outcomes for those infected with SARS-CoV-2 worldwide.

Potential next-generation medications for self-administered platforms.

The Coronavirus Disease (COVID-19) pandemic has reshaped clinical chronic disease management. Patients reduced the number of physical clinic visits for regular follow-up care because of the pandemic. However, in developing countries, the scattered healthcare system hindered accessibility to clinical consultation, and poorly controlled chronic diseases resulted in numerous complications. Furthermore, the longer patients suffered from the chronic disease being treated, the more physical and psychological stress they experienced. "Diabetes Burnout," as an example, is a term to describe the phenomenon of psychological reluctance in long-term glycemic control. A comprehensive, patient-centered, and automatic drug administration and delivery model may reduce patient stress and increase compliance. Potential next-generation medication platforms, consisting of internal regulation and external interaction, may conduct autonomous dose adjustment and continuous selfmonitoring with the assistance of artificial intelligence, telemedicine, and wireless technologies. Internal regulation forms a closed-loop system in which drug administration is optimized in an implanted drug-releasing device according to a patient's physiopathological response. The other feature, external interaction, creates an ecosystem among patients, healthcare providers, and pharmaceutical researchers to monitor and adjust post-market therapeutic efficacy and safety. These platforms may provide a solution for self-medication and self-care for a wide variety of patients but may be life-changing for patients who live in developing countries where the healthcare system is scattered, as they could effectively remove healthcare barriers. As the technology matures, these self-administrated platforms may become more available and increasingly affordable, offering considerable impact to health and wellness efforts worldwide.

Detection of Microorganisms in Body Fluids via MTT-PMS Assay.

Early detection of microorganisms is essential for the management of infectious diseases. However, this is challenging, as traditional culture methods are labor-intensive and time-consuming. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-phenazine methosulfate (MTT-PMS) assay has been used to evaluate the metabolic activity in live cells and can thus be used for detecting living microorganisms. With the addition of NaOH and Tris-EDTA, the same approach can be accelerated (within 15 min) and used for the quick detection of common bacterial pathogens. The assay results can be evaluated colorimetrically or semi-quantitatively. Here, the quick detection by MTT-PMS assay was further investigated. The assay had a detection limit of approximately 104 CFU/mL. In clinical evaluations, we used the MTT-PMS assay to detect clinical samples and bacteriuria (>105 CFU/mL). The negative predictive value of the MTT-PMS assay for determining bacteriuria was 79.59% but was 100% when the interference of abnormal blood was excluded. Thus, the MTT-PMS assay might be a potential "rule-out" tool for bacterial detection in clinical samples, at a cost of approximately USD 1 per test. Owing to its low cost, rapid results, and easy-to-use characteristics, the MTT-PMS assay may be a potential tool for microorganism detection.

Urinalysis Using a Diaper-Based Testing Device.

Urinary tract infections (UTI), one of the most common bacterial infections, annually affect 150 million people worldwide. Infants and the elderly are likely to have missed or delayed diagnosis of UTI due to difficulty clearly describing their symptoms. A rapid screening method for UTI is a critical and urgent need for these populations. The aim of our study is to develop a diaper-based testing device to assay urine biomarkers including pH, leukocyte, and nitrite level. This all-in-one device assists in urine collection and testing using a colorimetric approach to provide easily read visual results on the outside surface of a test strip-integrated diaper. In this study, we tested samples from 46 patients using testing strips and examined the results from 7 patients recruited to validate the strip-integrated diaper. In conclusion, this new diaper-based testing device is easy to use, rapid, and inexpensive, all of which imbue it with tremendous potential for development into a commercially viable UTI screening system.

Comparison of in-hospital and out-of-hospital cardiac arrest patients receiving targeted temperature management: A matched case-control study.

BACKGROUND: Evidences that support the use of targeted temperature management (TTM) for in-hospital cardiac arrest (IHCA) are lacking. We aimed to investigate the hypothesis that TTM benefits for patients with IHCA are similar to those with out-of-hospital cardiac arrest (OHCA) and to determine the independent predictors of resuscitation outcomes in patients with cardiac arrest receiving subsequent TTM. METHODS: This is a retrospective, matched, case-control study (ratio 1:1) including 93 patients with IHCA treated with TTM after the return of spontaneous circulation, who were admitted to Partners HealthCare system in Boston from January 2011 to December 2018. Controls were defined as the same number of patients with OHCA, matched for age, Charlson score, and sex. Survival and neurological outcomes upon discharge were the primary outcome measures. RESULTS: Patients with IHCA were more likely to have experienced a witnessed arrest and receive bystander cardiopulmonary resuscitation, a larger total dosage of epinephrine, and extracorporeal membrane oxygenation. The time duration for ROSC was shorter in patients with IHCA than in those with OHCA. The IHCA group was more likely associated with mild thrombocytopenia during TTM than the OHCA group. Survival after discharge and favorable neurological outcomes did not differ between the two groups. Among all patients who had cardiac arrest treated with TTM, the initial shockable rhythm, time to ROSC, and medical history of heart failure were independent outcome predictors for survival to hospital discharge. The only factor to predict favorable neurological outcomes at discharge was initial shockable rhythm. CONCLUSION: The beneficial effects of TTM in eligible patients with IHCA were similar with those with OHCA. Initial shockable rhythm was the only independent predictor of both survival and favorable neurological outcomes at discharge in all cardiac arrest survivors receiving TTM.

Harnessing the versatility of PLGA nanoparticles for targeted Cre-mediated recombination.

Ligand-dependent Cre recombinases are pivotal tools for the generation of inducible somatic mutants. This method enables spatial and temporal control of gene activity through tamoxifen administration, providing new avenues for studying gene function and establishing animal models of human diseases. While this paved the way for developmental studies previously deemed impractical, the generation of tissue-specific transgenic mouse lines can be time-consuming and costly. Herein, we design a 'smart', biocompatible, and biodegradable nanoparticle system encapsulated with tamoxifen that is actively targeted to specific cell types in vivo through surface conjugation of antibodies. We demonstrate that these nanoparticles bind to cells of interest and activate Cre recombinase, resulting in tissue-specific Cre activation. This system provides a versatile, yet powerful approach to induce recombination in a ubiquitious Cre system for various biomedical applications and sets the stage for a time- and cost-effective strategy of generating new transgenic mouse lines.

Diabetes Shared Care Program (DSCP) and risk of infection mortality: a nationwide cohort study using administrative claims data in Taiwan.

OBJECTIVE: The Diabetes Shared Care Program (DSCP) is an integrated care model in Taiwan that has been proven to improve the care quality of patients with diabetes. We aimed to evaluate the efficacy of DSCP in decreasing the hospital mortality of infectious diseases. METHODS: From 1 662 929 patients with type 2 diabetes newly diagnosed between 1999 and 2013, we retrieved a total of 919 patients who participated in the DSCP with the first hospitalisation for an infectious disease as the study cohort and 9190 propensity score-matched patients with type 2 diabetes who did not participate as the comparison.The efficacy of DSCP was evaluated via the following comparisons between the DSCP and non-DSCP cohorts: hospital mortality, 1-year medical cost prior to and during the hospitalisation, and complications, such as receiving mechanical ventilation and intensive care unit admission. The ratio (OR) for hospital mortality of the DSCP participants was calculated by logistical regression. Further stratification analyses were conducted to examine which group of patients with type 2 diabetes benefited the most from the DSCP during hospitalisation for infectious diseases. RESULTS: The DSCP cohort had a lower hospital mortality rate than the non-DSCP participants (2.18% vs 4.82%, p<0.001). The total medical cost during the hospitalisation was lower in the DSCP cohort than in the non-DSCP cohort (NT$72 454±30 429 vs NT$86 385±29 350) (p=0.006). In the logistical regression model, the DSCP participants exhibited a significantly decreased adjusted OR for hospital mortality (adjusted OR=0.42, 95% CI 0.26 to 0.66, p=0.0002). The efficacy of the DSCP was much more prominent in male patients with type 2 diabetes and in patients with lower incomes. CONCLUSION: Participation in the DSCP was associated with a lower risk of hospital mortality for infectious diseases.

Mortality risk after transcatheter aortic valve implantation: analysis of the predictive accuracy of the Transcatheter Valve Therapy registry risk assessment model.

AIMS: The risk assessment tools currently used to predict mortality in transcatheter aortic valve implantation (TAVI) were designed for patients undergoing cardiac surgery. We aimed to assess the accuracy of the TAVI dedicated risk score in predicting mortality outcomes. METHODS AND RESULTS: Consecutive patients (n=1,038) undergoing TAVI at a single institution from 2014 to 2016 were included. The ACC/TVT registry mortality risk score, the STS-PROM score and the EuroSCORE II were calculated for all patients. In-hospital and 30-day all-cause mortality rates were 1.3% and 2.9%, respectively. The ACC/TVT risk stratification tool scored higher for patients who died in-hospital than for those who survived the index hospitalisation (6.4±4.6 vs. 3.5±1.6, p=0.03, respectively). The ACC/TVT score showed a high level of discrimination, C-index for in-hospital mortality 0.74, 95% CI: (0.59-0.88). There were no significant differences between the performance of the ACC/TVT registry risk score, the EuroSCORE II and the STS-PROM score for in-hospital and 30-day mortality rates. CONCLUSIONS: The ACC/TVT registry risk model is a dedicated tool to aid in the prediction of in-hospital mortality risk after TAVI.

Transcatheter Aortic Valve Replacement by a Novel Suprasternal Approach.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) provides therapy for patients with severe aortic stenosis at extreme, high, or intermediate surgical risk. Transfemoral access has been the preferred access route; however, this approach is not suitable for many TAVR candidates. A suprasternal approach may allow for earlier ambulation and shorter hospital stay as compared with other, nontransfemoral approaches. METHODS: A total of 11 patients with unsuitable transfemoral access underwent suprasternal TAVR. Propensity matching was used to compare suprasternal patients to patients undergoing transaortic, transapical, and trans-subclavian TAVR. RESULTS: Groups were well matched for baseline characteristics. A self-expanding valve device was used in 6 (54.5%) and a balloon-expandable valve in 5 (45.5%) of the 11 patients treated by the suprasternal route. Suprasternal and trans-subclavian patients were able to ambulate earlier than patients treated by the transaortic route, a median 1.6 days (interquartile range [IQR]: 0.9 to 1.8), 1.6 days (IQR: 0.9 to 2.7), and 3.9 days (IQR: 1.9 to 4.5) after the procedure for suprasternal, trans-subclavian, and transaortic patients, respectively (p = 0.001). Length of hospitalization was shorter for patients treated by suprasternal or trans-subclavian access in comparison with patients treated by the transaortic or transapical approach: median 4 days (IQR: 3 to 8) and 4 days (IQR: 4 to 8) versus 8 days (IQR: 6 to 14) and 6 days (IQR: 7 to 11) for suprasternal and trans-subclavian versus transaortic and transapical, respectively (p = 0.01). CONCLUSIONS: Suprasternal and trans-subclavian access are associated with earlier ambulation and shorter hospitalization than other nontransfemoral TAVR routes, without an increase in complications. Further study is required to determine if suprasternal is the alternative access of choice for TAVR patients with poor transfemoral vasculature.

Translational aspects of cardiac cell therapy.

Cell therapy has been intensely studied for over a decade as a potential treatment for ischaemic heart disease. While initial trials using skeletal myoblasts, bone marrow cells and peripheral blood stem cells showed promise in improving cardiac function, benefits were found to be short-lived likely related to limited survival and engraftment of the delivered cells. The discovery of putative cardiac 'progenitor' cells as well as the creation of induced pluripotent stem cells has led to the delivery of cells potentially capable of electromechanical integration into existing tissue. An alternative strategy involving either direct reprogramming of endogenous cardiac fibroblasts or stimulation of resident cardiomyocytes to regenerate new myocytes can potentially overcome the limitations of exogenous cell delivery. Complimentary approaches utilizing combination cell therapy and bioengineering techniques may be necessary to provide the proper milieu for clinically significant regeneration. Clinical trials employing bone marrow cells, mesenchymal stem cells and cardiac progenitor cells have demonstrated safety of catheter based cell delivery, with suggestion of limited improvement in ventricular function and reduction in infarct size. Ongoing trials are investigating potential benefits to outcome such as morbidity and mortality. These and future trials will clarify the optimal cell types and delivery conditions for therapeutic effect.

Myocardial Bridging: An Up-to-Date Review.

Myocardial bridging is a congenital anomaly in which a segment of a coronary artery takes a "tunneled" intramuscular course under a "bridge" of overlying myocardium. This causes vessel compression in systole, resulting in hemodynamic changes that may be associated with angina, myocardial ischemia, acute coronary syndrome, left ventricular dysfunction, arrhythmias, and even sudden cardiac death. While described on autopsy for centuries, technological advances such as coronary computed tomography angiography and intravascular ultrasound have contributed greatly to our understanding of the anatomic, hemodynamic, and pathophysiological consequences of systolic compression. Atherosclerosis preferentially develops immediately proximal to the bridged segment, likely due to alterations in shear stress, while the compressed segment itself is often spared. First-line therapy of symptomatic bridging remains medical treatment with beta-blockers and non-dihydropyridine calcium-channel blockers, and nitrates are contraindicated. Surgical myotomy, intracoronary stenting, and coronary artery bypass graft surgery have been used for refractory symptoms, but long-term outcomes remain uncertain. Further research is required to better define the patient population that would derive the greatest benefit from surgical and percutaneous intervention.

Emerging approaches for imaging vulnerable plaques in patients.

The diagnosis of vulnerable plaques, which have the propensity to develop atherothrombosis, remains an elusive goal in clinical medicine. The most accepted features of vulnerable plaques, such as a large lipid core, increased inflammatory milieu and thin fibrous caps, have been well characterized through pathological studies. The ability to image a vulnerable plaque in susceptible patients would theoretically result in useful prognostic information that can be used to either monitor or treat patients at risk more aggressively. Several invasive techniques, such as integrated backscatter, virtual histology, palpography, optical coherence tomography and thermal heterogeneity, have been validated ex vivo and are now being evaluated in clinical studies. Non-invasive techniques, such as nuclear imaging, show promise in identifying increased metabolic activity and characteristic features of vulnerable plaques in patients. Natural history and intervention studies will need to be performed to determine whether identifying and treating vulnerable plaques will lead to improved clinical outcomes.