Aims It is unclear whether thyroid hormones are associated with functional outcome after ischemic stroke. We aimed to investigate the impact of thyroid hormones at admission on functional outcome at 3 months after acute ischemic stroke. Methods A total of 480 consecutive patients for ischemic stroke within 48 hours of onset were enrolled in this study. Thyroid hormones including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured at admission and functional outcomes were assessed at 3 months with the modified Rankin Scale (mRS) ranging from 0 to 6. Poor outcome was defined as mRS≥3. Results FT3 levels at admission were considerably lower in poor outcome patients than those with good outcome at 3 months (3.53±0.70pmol/L vs 4.04±0.68pmol/L, respectively; P＜0.001). Lower levels of FT3 were observed with higher mRS scores. Multivariable logistic regression analysis revealed that FT3 levels were significantly associated with risk of poor outcome at 3 months independent of conventional risk factors such as age, NIHSS score and recanalized therapy. In addition, patients in the bottom quartile of FT3 levels had a 2.56-fold higher risk of developing poor outcome compared with patients in the top quartile (OR=2.56; 95%CI 1.15-5.69, p =0.021). The sensitivity and specificity of FT3 (≤3.69pmol/L) predicting poor outcome were 62.70% and 72.03% respectively. Conclusion Our study suggests that FT3 levels at admission are significantly and independently associated with risk of poor outcome after ischemic stroke and lower FT3 levels can be regarded as a prognostic biomarker for poor outcome at 3 months.

Background: To evaluate the effects of baseline left ventricular restrictive filling pattern (RFP; E/A>2) in ischemic cardiomyopathy (ICM) patients on prognosis. Methods: Patient data was retrospectively analyzed over a period of 4.5 years to determine the effect of Echocardiographic factors on survival and re-admission for heart failure. Results: There were 102 ICM patients who had baseline RFP. We identified two sub-groups based on geometric phenotypes of left ventricular eccentric remodeling and dilated remodeling based on the relative wall thickness (RWT >0.34 or <0.34). The patients with preserved RWT had significantly more dilated ventricles ( LVIDd and LVIDs), greater pulmonary artery systolic pressures (PASP), greater diatolic dysfunction (E/A) and less left ventricular ejection fraction (LVEF); p<0.001. The number of deaths was higher in the reduced RWT patients, as were the number of re-admissions, although the time to survival and time to re-admission was not significant. Conclusions: In this pilot study on ICM patients in advanced heart failure with baseline RFP, the presence of preserved RWT indicative of eccentric remodelling demonstrated a better clinical outcome, leading to a hypothesis that the eccentric remodelling LV phenotype might benefit with SVR.

We have read with great interest the article by Papakonstantinou et al. providing a single-center analysis of the contemporary approach to tricuspid aortic valve (TAV) insufficiency with the use of HAART 300 annuloplasty ring [1].We believe that the presented concept of a robust circumferential aortic annuloplasty with separate sinus replacement, avoiding coronary re-implantations when allowed, can be successfully applied to many cases, including BAV.

Objectives: To compare the safety and effectiveness of tonsillectomy with three different techniques. Design: A double-blinded randomized prospective clinical trial Setting and Participants: Totally120 patients with recurrent tonsillitis between April 2018 and April 2020 were included. Main Outcome Measures: Operative time, intra and post operative bleeding loss, pseudomembrane growth time, pseudomembrane shedding time, postoperative pain, and necrosis depth of specimens were compared of harmonic scalpel(HS), coblation and cold dissection(CD) tonsillectomy. Results: The operative time and intraoperative bleeding loss was significantly less in HS and coblation group than CD group(p < 0.05). Pseudomembrane growth time and pseudomembrane shedding time were significantly longer in the HS group compared with the other groups(p < 0.05). The postoperative pain levels were significantly higher on the first postoperative day in CD group(p < 0.05), and significantly lower on the third and seventh postoperative day in coblation group(p < 0.05). There was no significant difference among three techniques in terms of postoperative bleeding loss(p > 0.05). The deepest necrosis depth in specimen was found in HS group(p > 0.05), while in CD group, only edema was observed without necrosis. Conclusion: To compared with HS and CD, coblation is a faster, safer and more painless technique for tonsillectomy in adult.

BACKGROUND AND PURPOSE Acute lung injury (ALI) is a critical disorder that has high mortality rates, and pharmacological therapies are so far ineffective. The pathophysiology of ALI involves pulmonary oxidative stress and inflammatory response. Fullerol is a carbon nanocomposite that possesses antioxidant and anti-inflammatory properties. Here, we evaluated the therapeutic potential of fullerol and its mechanisms in a model of paraquat-induced ALI. EXPERIMENTAL APPROACH Rats were divided into ALI (paraquat alone), fullerol (paraquat plus fullerol), and control groups. Survival curves were estimated using the Kaplan-Meier method. The myeloperoxidase assay, ELISA, and hematoxylin and eosin staining were used to determine neutrophils infiltration, cytokines production, and histopathological parameters in lung samples, respectively. The antioxidant effect of fullerol was evaluated in vitro and ex vivo. KEY RESULTS Fullerol (0.01 to 0.3 mg/kg) markedly reduced the severe lung injury and high mortality rates observed in ALI rats. Moreover, fullerol (0.03 mg/kg) inhibited the reactive oxygen species formation and lipid peroxidation seen in lungs from ALI rats, and exhibited a potent concentration-dependent (10-4 to 10-1 mg/ml) in vitro antioxidant activity. Importantly, fullerol (0.03 mg/kg) inhibited neutrophils accumulation in bronchoalveolar lavage and lungs, and the increase in pulmonary levels of TNF-α, IL-1β, IL-6, and CINC-1 in ALI rats. CONCLUSIONS AND IMPLICATIONS Fullerol treatment was effective in reducing pulmonary damage and ALI-induced mortality, highlighting its therapeutic potential in an ALI condition. Searching for new pharmacological therapies to treat ALI may be desirable especially in view of the new coronavirus disease 2019 that currently plagues the world.

Needle-free Epicutaneous For t 2 DNA Vaccine is Effective for Preventing and Treating Biting Midge (Forcipomyia taiwana) allergy in a murine modelTo the Editor,Allergen-specific immunotherapy (ASIT) remains the only treatment capable of inducing immune tolerance to the corresponding allergen and potentially treating the root cause of the allergic disease.1 As the treatment course of protein-based vaccines for ASIT is time-consuming, an easily administered epicutaneous anti-allergic DNA-based vaccine is an attractive method, especially in light of the COVID-19 pandemic.2The biting midge, Forcipomyia taiwana , is the most prevalent cause of biting insect allergy in Taiwan. It is a tiny hematophagous midge that attacks en masse. As many as 60% of exposed individuals develop allergic reactions to the bites.3 The midge is widely distributed throughout Taiwan and southern China. For t 2 is the most predominant,with 75% of midge-allergic patients showing specific IgE to For t 2.4 Allergic reactions to midge bites are not limited to humans but also seen in livestock, such as horses, cattle, sheep, and donkeys, causing significant veterinarian problems.E.coli -expressed For t 2 recombinant protein (rFor t 2) was used as an allergen to sensitize and challenge the mice.5For t 2-encoding fragment (GenBank accession EU678971) was amplified by PCR. The PCR products were subcloned into pVAX1 (Life Technologies, Carlsbad, CA) . The experiments were designed using two approaches: therapeutic and prophylactic (Fig 1). The therapeutic approach is to imitate ASIT in human with established allergy while the prophylactic approach to non-allergics. Twenty-five μg For t 2 DNA was determined as the optimal dose after dose-finding experiments (Supplementary Fig S1). For each treatment, the hair of the abdominal area of the mice was removed using a depilatory,tape-stripped,then patched with 25 μg For t 2 DNA vaccine for one hour and removed.A total of three treatments were given spaced one week apart (Fig 1 and Fig S2). For t 2 proteins were detected in the patched skin and the immune organ spleen at 24 hoursand had significantly increased at 48 hours after last treatment (Fig S3). Scratch bouts after rFor t 2 challenge were used as a clinical surrogate of itch. We measured For t 2-specific IgE, IgG1 and IgG2a in the sera as well as mRNA and proteins of IL-13, interferon-gamma, IL-10, and FOXP3 in the culture supernatants of splenocytes after stimulation with various doses of rFor t 2 at 37℃ for 3-5 days by ELISA and real-time quantitative PCR. Histopathology of the challenged skins was examined.After epicutaneous DNA vaccination, the allergen-induced itchin both groups significantly improved, and For t 2-specific IgE and IgG1/IgG2a ratio decreased significantly at week 6 or week 8 (Fig 2). Levels of mRNA and protein of IL-13 decreased significantly, but IFN-gamma and IL-10 remained unchanged. Expression of FOXP3 mRNA increased (Fig 2, protein data not shown). Eosinophils infiltration in the challenged skin significantly decreased (Fig S4).This is the first study to demonstrate an epicutaneous needless anti-allergic DNA vaccine that effectively treats an established allergic condition and prevents the development of an allergic disease using biting midge allergy as a model. After epicutaneous DNA vaccination, in addition to allergen-induced itch, the changes of multiple biomarkers suggest that immune tolerance was induced after the epicutaneous DNA vaccine.Our data show that though the molecular weight of the For t 2 DNA vaccine is as high as 4000 base pairs, it can penetrate the dermal barrier and translate the corresponding protein in the targeted skin and the spleen of the vaccinated mice. It is possible that the DNA vaccine passes the epidermis via the hair follicles as the skin is tape-stripped before epicutaneous vaccination.6The mode of this anti-allergic epicutaneous DNA vaccine may potentially be used in other specific immunotherapies for other allergens.Mey- Fann Lee1Chi-Sheng Wu2 Shyh-Jye Lin3Yi-Hsing Chen2,4*1Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan2Division of Allergy, Immunology and Rheumatology, Taichung Veterans General Hospital, Taichung, Taiwan3School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan4School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

BJOG-21-0722 Statistical associations versus causal inference.Øjvind Lidegaard, professor 11Department of Gynaecology, Rigshospitalet, University of Copenhagen, DenmarkMany clinicians are of the opinion that observational studies may provide only “statistical associations”, but not “causal inference”. And further, that only randomized designs ensure causal interpretation. For the same reason, many medical journals have made rules for all observational studies finding significant statistical associations to be presented as just “associations” often emphasizing that a causal inference is not possible.I hereby sign up to the growing group of epidemiologists, who are of the opinion that just well confounder controlled observational studies are the very design most often providing convincing evidence of a causal interference. Prospective cohort studies better than retrospective case-control studies, but even the latter design has given us important knowledge of risk factors of rare clinical outcomes such as thrombotic diseases, a long list of cancers, obstetrical complications, including latest stillbirths.In a new original Swedish study, Heiddis Valgeirsdottir et al. demonstrate in a nationwide historical follow-up study, that women with polycystic ovary syndrome (PCOS) once pregnant have a 50% increased risk of experiencing stillbirth, as compared to women without PCOS (1). Further, that the rate ratio of stillbirth between women with and without PCOS increased by increasing gestational age, peaking at 42 weeks with 4.3 deaths per 1000 ongoing pregnancies in women with PCOS versus 1.0 deaths per 1000 ongoing pregnancies in women without PCOS.Any such association should certainly be controlled for a long list of potential confounders, the most important being maternal age, calendar year, parity, hypertensive disorders, diabetes, and educational length. Adiposity (BMI) was undertaken in an additional adjustment, because this covariate correctly could be considered as both a confounder (adiposity being a risk factor for stillbirth, and PCOS women more often being adipose), but also as a mediator; women with PCOS are more likely to develop adiposity due to their PCOS. The authors chose carefully to present the BMI adjusted results as the main results, thereby if anything underestimating the risk of stillbirths in women with PCOS.This is far from the first contribution from Scandinavian National Health Registers, identifying and quantifying risk factors for different diseases. We should always be aware that some unknown or unmeasured potential confounders not being controlled for, could reduce (or enhance) the results, and that other research groups should confirm the Swedish findings. A causal inference was made more likely with a suggested biomedical mechanism by which PCOS could confer such a risk. But already with this new carefully provided observational evidence, we should reasonably consider pregnant women with PCOS not to go too far beyond term, to prevent stillbirths in this group, which according to the study results accounts about 5% of all stillbirths. A pragmatic first recommendation could be induction of women with PCOS at 41 gestational weeks.Valgeirsdottir H et al. BJOG 2021; 128: xxx-xxx.

In situation of a cat bite, although an external wound is small, prophylactic antibiotics should be used early and a closed observation is needed for sufficient periods. If symptoms continue, deep infection should be considered.

Recent studies have shown that T cell metabolism has become a key regulator of T cell function and even can determine T cell function at last. Naïve T cells use fatty acid oxidation (FAO) to meet their energetic demands. Effector T cells mainly rely on aerobic glycolysis to supply energy and synthesize intermediate products. Similar to naïve T cells, memory T cells primarily utilize FAO for energy. Exhausted T cells, which can be induced by continuous activation of T cells upon persistently chronic infections such as tuberculosis, mainly rely on glycolysis for energy. The prevention and treatment of T cell exhaustion is facing great challenges. Interfering T cell metabolism may achieve the goal of prevention and treatment of T cell exhaustion. In this review, we compiled the researches related to exhausted T cell metabolism and put forward the metabolic intervention strategies to reverse T cell exhaustion at different stages to achieve the purpose of preventing and treating T cell exhaustion.

Tourette's disorder is a complex neuropsychiatric condition, and consequently treatment options are also different.. A complicated case of Tourette's disorder was seen at our clinic. Treatment with standard medication was not successful. A trial of lithium seemed to provide significant cessation of both neurological as well as psychiatric symptom

The term “pseudodementia” has attracted much controversy. An elderly man with major depressive disorder, single episode, was misdiagnosed with dementia and subsequently Parkinson’s disease, A trial of high-dose Selegiline at 60 mg per day produced substantial improvement with complete resolution of cognitive impairment and disappearance of signs of “Parkinson’s disease”.

A document by Victor García-Hernando. Click on the document to view its contents.

Foundation species such as corals, trees, and bivalves enhance ecosystem function and biodiversity by creating habitat for associated organisms, ameliorating stress, and modifying energy flow. However, theory generally ignores their ecological functions after death. Here we review the traits and functions of dead foundation species relative to their living counterparts, and the processes that control their persistence. We also conduct a meta-analysis to quantify where the effect of dead foundation species on community functions is unique or redundant to their living counterparts. We focus on marine ecosystems due to the greater diversity of foundation species they support and the increasing prevalence of mass-mortality events in these systems. Our study reveals how foundation species continue to provide important functions after death and exhibit new functions that are distinct from when they are alive. We develop a framework using broad, trait-based functional differences among types of dead foundation species to predict whether they will promote stability by enhancing ecosystem resilience or promote shifts to alternate states. Our synthesis establishes how an understanding of the ecological importance of dead foundation species can assist in predicting system trajectories, enhance restoration and conservation efforts, and contribute to ecological theory on habitat heterogeneity and ecosystem function.

Introduction: In cases of recurrent ventricular arrythmias (RVA) after radiofrequency ablation (RFA), stereotactic body radiotherapy (SBRT) using a single high dose of has emerged as an effective treatment. Methods And Results: SBRT was performed as treatment of an Idiopathic Subtricuspid Ventricular Arrythmia recurrent to RFA with progressive cardiac function deterioration despite the staggered use of antiarrhythmic drugs. No sedation was required, and the patient tolerated the procedure with no related complications. During post-procedural follow-up the arrhythmic density dropped from 33% to 1% in 90 days. Conclusions: SBRT can be an effective treatment for RVA that should be further investigated.

Conflict of interest disclosureThe authors have no conflict of interest to declare.

Introduction: Prior to ablation, predicting the site of origin (SOO) of outflow tract ventricular arrhythmia (OTVA), can inform patient consent and facilitate appropriate procedural planning. We set out to determine if OTVA variability can accurately predict SOO. Methods: Consecutive patients with a clear SOO identified at OTVA ablation had their prior 24-hour ambulatory ECGs retrospectively analysed (derivation cohort). Percentage ventricular ectopic (VE) burden, hourly VE values, episodes of trigeminy/bigeminy, and the variability in these parameters were evaluated for their ability to distinguish right from left sided SOO. Effective parameters were then prospectively tested on a validation cohort of consecutive patients undergoing their first OTVA ablation. Results: High VE variability (coefficient of variation ≥ 0.7) and the presence of any hour with < 50 VE, were found to accurately predict RVOT SOO in a derivation cohort of 40 patients. In a validation cohort of 29 patients, the correct SOO was prospectively identified in 23/29 patients (79.3%) using CoV, and 26/29 patients (89.7%) using VE < 50. Including current ECG algorithms, VE < 50 had the highest Youden Index (78), the highest positive predictive value (95.0%) and the highest negative predictive value (77.8%). Conclusion: VE variability and the presence of a single hour where VE < 50 can be used to accurately predict SOO in patients with OTVA. Accuracy of these parameters compares favourably to existing ECG algorithms.

Brugada syndrome masked by complete left bundle branch blockAbbas Hoteit MD, Marwan M. Refaat, MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: Brugada Syndrome masked by LBBBWords: 741 (excluding the title page and references)Keywords: Brugada syndrome, Left bundle branch block, Cardiovascular Diseases, Heart Diseases, Cardiac ArrhythmiasFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FAAMAAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Brugada syndrome is a genetic disorder that affects the electrical activity of the heart. It is characterized by ST-segment elevations in the right precordial leads and right bundle branch morphology on ECG.1 These ECG changes are present in the absence of other causes of ST elevation or right bundle branch block morphology such as structural heart disease, ischemia, pacing or electrolyte disturbances.2 Clinical presentation varies between patients; it can range from asymptomatic changes seen on ECG to syncope, ventricular arrhythmias, and sudden cardiac death. 3So far, three types of ECG repolarization patterns have been identified (type 1, type 2, and type 3).4 Type 1 pattern is diagnostic of Brugada syndrome whereas types 2 and 3 are considered suggestive.5 According to the 2016 consensus conference of J-wave syndromes, the diagnosis of Brugada syndrome can only be made by finding a type 1 repolarization pattern. A type 1 pattern can either be spontaneous or unmasked by fever or medications. If it has been unmasked by either, then further evidence of patient clinical history, family history, or genetic testing should be present to fulfill a score of 3.5 or higher according to the Shanghai Scoring System.6 7 The Shanghai Scoring System does not include imaging; hence, even if changes in the right ventricle are found on cardiac MRI, they play no role in the diagnosis. 7In patients presenting with a non-type 1 pattern, a sodium channel blocker challenge is frequently used to unmask the type 1 pattern. Unmasking this pattern allows for diagnosis of Brugada syndrome which has a big impact on prognosis and management options. In some patients, an initial flecainide challenge test may be negative due to the variable sensitivity of this test. Some studies have shown that repeating the test may increase sensitivity, but, with increased risk of adverse drug effects. Prasad et al. showed that in patients with high clinical suspicion, family history of sudden cardiac death could serve as an indicator to repeat the flecainide test.5 8 9Several possible risk factors, that might predispose individuals to have a more severe presentation, have been identified. These include male gender, history of syncope, spontaneous type 1 pattern, family history of Brugada syndrome, and loss-of-function mutations in the SCN5A gene (which codes the alpha subunit of the cardiac sodium channel).10 Patients with SCN5A mutations tend to have earlier onset of symptoms, more noticeable electrophysiological defects (such as sick sinus syndrome and AV blocks), and increased risk of major arrhythmic events especially in Asian and Caucasian populations.11 High-risk patients are susceptible to sudden cardiac death; therefore, risk stratification helps in patient selection for Implantable Cardioverter Defibrillator placement.12 13In their article, Eduardo et al. presented the case of a 48-year-old lady who was initially diagnosed with Brugada syndrome after having a type 1 pattern on ECG. During follow-up, the patient’s ECG changed and showed a complete left bundle branch block instead of the typical type 1 pattern. Molecular studies showed the novel SCN5A p.1449Y>H variant and subsequent functional analysis showed a nonfunctional mutated membrane channel. SCN5A mutation can cause Brugada syndrome and conduction system abnormality as described in this lady. This variant generated minimal sodium currents. Such major decrease in current magnitude is associated with high penetrance as seen in the cases in this study. Although, during close follow-up, these patients did not have severe symptoms.14 What is most significant is that the authors presented a patient with Brugada syndrome who subsequently developed findings of complete left bundle branch block on ECG, making the diagnosis challenging due to masking of the type 1 pattern. This opens further discussion about diagnosis of the syndrome and potential maneuvers or procedures that would help unmask type 1 pattern under heart block. Since diagnosis can only be made by witnessing this pattern, this presents us a possibility where a diagnosis would be missed in such patients. SCN5A is the most common gene associated with this syndrome, accounting for around 20%. However, patient presentation varies widely with different mutations affecting channel function differently. In this case, the p.1449Y>H variant showed high penetrance and channel dysfunction despite relatively non-severe symptoms in patients affected. However, further observation is warranted to assess progression of the disease and the incidence of major arrhythmogenic events with aging and subsequent fibrosis. Further research is required to investigate the role of genetic studies in risk stratification and projecting patient clinical course depending on the presence of specific gene mutations/variants.References:Refaat MM, Hotait M, Scheinman MM. Brugada Syndrome. Card Electrophysiol Clin Mar 2016; 8(1): 239-45.Refaat M, Mansour M, Singh JP, Ruskin JN, Heist EK. Electrocardiographic Characteristics in Right Ventricular Versus Biventricular Pacing in Patients With Paced Right Bundle Branch Block QRS Pattern. J Electrocardiol Mar-Apr 2011; 44 (2): 289-95.Tse G, Liu T, Li KH, et al. Electrophysiological mechanisms of Brugada syndrome: insights from pre-clinical and clinical studies. Front Physiol 2016; 7: 467.Wilde, A. a. M.; Antzelevitch, C.; Borggrefe, M.; Brugada, J.; Brugada, R.; Brugada, P.; Corrado, D.; Hauer, R. N. W.; Kass, R. S.; Nademanee, K.; Priori, S. G. (November 2002). ”Proposed diagnostic criteria for the Brugada syndrome”. European Heart Journal . 23  (21): 1648–1654.Prasad S, Namboodiri N, Thajudheen A, Singh G, Prabhu MA, Abhilash SP, Mohanan Nair KK, Rashid A, Ajit Kumar VK, Tharakan JA. Flecainide challenge test: Predictors of unmasking of type 1 Brugada ECG pattern among those with non-type 1 Brugada ECG pattern. Indian Pacing Electrophysiol J. 2016 Mar-Apr;16(2):53-58. doi: 10.1016/j.ipej.2016.06.001. Epub 2016 Jun 20. PMID: 27676161; PMCID: PMC5031807.Antzelevitch C, Yan GX, Ackerman MJ, et al. J-wave syndromes expert consensus conference report: emerging concepts and gaps in knowledge.Heart Rhythm 2016;13:e295-324.Vutthikraivit W, Rattanawong P, Putthapiban P, Sukhumthammarat W, Vathesatogkit P, Ngarmukos T, Thakkinstian A. Worldwide Prevalence of Brugada Syndrome: A Systematic Review and Meta-Analysis. Acta Cardiol Sin. 2018 May;34(3):267-277. doi: 10.6515/ACS.201805_34(3).20180302B. Erratum in: Acta Cardiol Sin. 2019 Mar;35(2):192. PMID: 29844648; PMCID: PMC5968343.Gasparini M, Priori SG, Mantica M, Napolitano C, Galimberti P, Ceriotti C, Simonini S. Flecainide test in Brugada syndrome: a reproducible but risky tool. Pacing Clin Electrophysiol. 2003 Jan;26(1P2):338-41. doi: 10.1046/j.1460-9592.2003.00045.x. PMID: 12687841.Dubner S, Azocar D, Gallino S, Cerantonio AR, Muryan S, Medrano J, Bruno C. Single oral flecainide dose to unmask type 1 Brugada syndrome electrocardiographic pattern. Ann Noninvasive Electrocardiol. 2013 May;18(3):256-61. doi: 10.1111/anec.12052. PMID: 23714084; PMCID: PMC6932426.Bayoumy A, Gong MQ, Christien Li KH, Wong SH, Wu WK, Li GP, Bazoukis G, Letsas KP, Wong WT, Xia YL, Liu T, Tse G; International Health Informatics Study (IHIS) Network. Spontaneous type 1 pattern, ventricular arrhythmias and sudden cardiac death in Brugada Syndrome: an updated systematic review and meta-analysis. J Geriatr Cardiol. 2017 Oct;14(10):639-643. doi: 10.11909/j.issn.1671-5411.2017.10.010. PMID: 29238365; PMCID: PMC5721199.Chen C, Tan Z, Zhu W, Fu L, Kong Q, Xiong Q, Yu J, Hong K. Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta-analysis. Clin Genet. 2020 Jan;97(1):198-208. doi: 10.1111/cge.13552. Epub 2019 May 6. PMID: 30963536.Probst, V., Veltmann, C., Eckardt, L., Meregalli, P. G., Gaita, F., Tan, H. L., Wilde, A. A. (2010). Long‐term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry. Circulation , 121 (5), 635–643. https://doi.org/10.1161/circulationaha.109.887026.Rattanawong P, Chenbhanich J, Mekraksakit P, Vutthikraivit W, Chongsathidkiet P, Limpruttidham N, Prasitlumkum N, Chung EH. SCN5A mutation status increases the risk of major arrhythmic events in Asian populations with Brugada syndrome: systematic review and meta-analysis. Ann Noninvasive Electrocardiol. 2019 Jan;24(1):e12589. doi: 10.1111/anec.12589. Epub 2018 Aug 20. PMID: 30126015; PMCID: PMC6931443.

Fixed structure controllers (such as proportional-integral-derivative controllers) are used extensively in industry. Finding a practical and versatile method to tune these controllers, particularly with imprecise process models and limited online computational resources, is an industrially relevant problem which could improve the efficiency of many plants. In this paper, we present two flexible neural network-based approaches capable of tuning any fixed structure controller for any control objective and process model and compare their advantages and disadvantages. The first approach is derived from supervised learning and classical optimization techniques, while the second approach applies techniques used in deep reinforcement learning. Both approaches incorporate model uncertainties when selecting controller parameters, reducing the need for costly experiments to precisely estimate model parameters in a plant. Both methods are also computationally efficient online, enabling their widespread usage.

This work explores the model predictive controller design of the continuous pulp digester process consisting of the co-current zone and counter-current zone modelled by a set of nonlinear coupled hyperbolic partial differential equations (PDE). The distributed parameter system of interest is not spectral and slow-fast dynamic separation does not hold. To address this challenge, the nonlinear continuous-time model is linearized and discretized in time utilizing the Cayley-Tustin discretization framework, which ensures system theoretic properties and structure preservation without spatial discretization or model reduction. The discrete model is used in the full state model predictive controller design, which is augmented by the Luenberger observer design to achieve the output constrained regulation. Finally, a numerical example is provided to demonstrate the feasibility and applicability of the proposed controller designs.

The reaction kinetics and molecular mechanisms of CO2 absorption using nonaqueous and aqueous amine solutions were analyzed by the stopped-flow technique and ab initio molecular dynamics (AIMD) simulations. Pseudo first-order rate constants (k0) of reactions between CO2 and amines were measured. A kinetic model was proposed to correlate the k0 to the amine concentration, and was proved to perform well for predicting the relationship between k0 and the amine concentration. The experimental results showed that AMP/MDEA only took part in the deprotonation of MEA-zwitterion in nonaqueous MEA+AMP/MEA+MDEA. In aqueous solutions, AMP can also react with CO2 through base-catalyzed hydration mechanism beside the zwitterion mechanism. The molecular mechanisms of CO2 absorption were also explored by AIMD simulations coupled with metadynamics sampling. The predicted free-energy barriers of key elementary reactions verified the kinetic model and demonstrated the different molecular mechanisms for the reaction between CO2 and AMP in nonaqueous and aqueous systems.

The gas-liquid two-phase flow pattern, absorption rate and pressure drop of CO2 absorbed into the aqueous solution of the task-specific ionic liquid (1-aminopropyl-3-methylimidazole tetrafluoroborate [Apmim][BF4] and 1- hydroxyethyl-3-methylimidazole tetrafluoroborate [OHemim][BF4]) and halide-free ionic liquid 1- butyl -3-methylimidazolium methylsulfate [Bmim][CH3SO4] were investigated in a microreactor. The absorption mechanism of the three ionic liquids was analyzed employing the 13C NMR spectroscopy. The [Apmim][BF4] was found to have the best ability of CO2 capture compared to the other two ionic liquids, as chemical absorption occurred between [Apmim][BF4] and CO2, while only physical absorption took place between [OHemim][BF4] / [Bmim][CH3SO4] and CO2. The sequence of CO2 absorption rate in three ionic liquid aqueous solutions is: [Apmim][BF4] > [Bmim][CH3SO4] >[OHemim][BF4]. Furthermore, the effects of gas-liquid flow rate and ionic liquids concentration on CO2 absorption rate and pressure drop were studied, the pressure drop models based on various flow patterns were proposed.

A document by Motokazu Nishikado. Click on the document to view its contents.

Objectives: To review the evidence on Diaphragmatic Ultrasonography as a predictor of success in ventilatory weaning. Methodology:Systematically review using the PICO methodology and keywords: Ultrasound, Ultrasound, Diagnostic imaging, Diaphragm, Weaning, Intensive Care Unit, Artificial Respiration, Mechanical Ventilation, Ventilator Weaning. Published cohort studies were used without language and year restrictions that addressed the use of ultrasound to predict success in weaning and ventilatory extubation. Studies with patients under 18 years of age, case reports, literature reviews, results that do not bring a cutoff value for thickness and diaphragmatic excursion and the definition of failure in the weaning and extubation process were excluded. In addition, the Boolean operators “and” and “or” were used. Results:459 were found, which after exclusion due to duplication and reading of titles and abstract, only 11 were selected by the inclusion criteria. The samples ranged from 34 to 193 individuals. We can evidence that the use of USG to assess the thickness and excursion of the diaphragm in patients undergoing invasive ventilatory support is effective in predicting success in the weaning and extubation process. Conclusion: It is concluded that Diaphragmatic Ultrasonography has great applicability to assess the ability to predict success or failure in removing invasive ventilatory support.

Dear editor, we read with great interest the well written article by Dr Kerget et al with the main objective of investigating the role of TREM-1/TREM-2 ratio on patients with COVID-19 pneumonia. The article pointed that TREM-1 and TREM-2 have important role in inflammation and TREM-1/TREM-2 ratio was higher in severe COVID-19 patients compared with moderate COVID-19 patients. We have certain comments to understand the conclusions of this article. Firstly, triggering receptor expressed on myeloid cells-1 (TREM-1) is mainly express on neutrophils and monocytes in a cell membrane-bound form. A soluble form of TREM-1(sTREM-1), which lacks the cytoplasmic tail and transmembrane part, were detected in the blood in recent studies. Since you have mentioned “serum TREM-1”, we were confused whether you detected TREM-1 or sTREM-1. Secondly, we wanted to know more about the treatment and the kidney functions of the patients. Thirdly, We are curious to see if high TREM-1/TREM-2 ratio could predict the distribution of ILD. We would be glad to hear the opinion of the author on the points, to get a more convincing conclusion.