HCM is associated with an increased risk of various cardiac arrhythmias, including atrial fibrillation (AF), nonsustained ventricular tachycardia (NSVT), and sustained ventricular tachycardia (VT). Furthermore, the presence of cardiac arrhythmias has an important effect on the prognosis of HCM patients, especially with respect to ventricular arrhythmias as a major cause of sudden cardiac death (SCD). In this issue of Journal of Cardiovascular Electrophysiology, Magnusson and Mörner describe the incidence of NSVT, AF, and bradycardia in thirty patients at relatively low risk of SCD by utilizing an implantable cardiac monitor (ICM). These data are useful in demonstrating a fairly significant arrhythmia burden in a low risk population. The ramifications of these findings are a bit unclear, however. Certainly, atrial fibrillation is important to detect in order to mitigate the increased stroke risk by instituting anticoagulation. Detection of NSVT was less useful in this low risk population, but could be potentially more actionable in intermediate risk HCM patients. Thus, although further investigation is needed, the authors have taken the first step in determining appropriate treatment strategies for arrhythmias in HCM by helping to define the scope of the problem.

In this work, the effect of residual stress on mixed-mode crack propagation behavior in friction stir welded (FSW) 7075-T6 panel under biaxial loading was investigated. The cruciform sample was designed and manufactured by FSW. Residual stress profiles across the welded sample were measured by the X-ray diffraction technique. Crack propagation behaviors were simulated with five different biaxial loading ratios. Stress intensity factors (KΙ and KΙΙ) were evaluated by finite element method (FEM) and used to study the effects of residual stress on crack behaviors. It was observed that residual stress has a considerable effect on the mixed-mode crack growth. In most of the cases, the crack deflection is mainly affected by residual stress at the beginning of crack propagation. The variation of crack propagation path is strongly linked with the residual stress as well as the biaxial loading ratio. In addition, KΙ and KΙΙ are susceptible to residual stress under biaxial loading conditions. Residual stresses contribute to a higher proportion of KΙΙ compared to that of KΙ. KΙ and KΙΙ in the retreating side are more affected by the residual stress.

Concerns about climate change and the search for renewable energy sources together with the goal of attaining sustainable product manufacturing have boosted the use of microbial platforms to produce fuels and high-value chemicals. In this regard, Y. lipolytica has been known as a promising yeast with potentials in diverse array of biotechnological applications such as being a host for different oleochemicals, organic acid and recombinant protein production. Having a rapidly increasing number of molecular and genetic tools available, Y. lipolytica has been well studied amongst oleaginous yeasts and metabolic engineering has been used to explore its potentials. More recently, with the advancement in systems biotechnology and the implementation of mathematical modeling and high throughput omics data-driven approaches, in-depth understanding of cellular mechanisms of cell factories have been made possible resulting in enhanced rational strain design. In case of Y. lipolytica, these systems-level studies and the related cutting-edge technologies have recently been initiated which is expected to result in enabling the biotechnology sector to rationally engineer Y. lipolytica-based cell factories with favorable production metrics. In this regard, here, we highlight the current status of systems metabolic engineering research and assess the potential of this yeast for future cell factory design development.

Utility of the E/e’ index in ventilated patients and those with sepsisImran Sunderji 1, Alan G Fraser 2(Reply to the letter from Filippo Sanfilippo and colleagues, ECHO-2020-0930)1 Department of Cardiology, Castle Hill Hospital, Hull, U.K.2 Department of Cardiology, University Hospital of Wales, Cardiff, U.K.Address for correspondence :Professor Alan G. Fraser,University Hospital of Wales,Heath Park,Cardiff, CF14 4XW,Wales, [email protected]: +44 (0)29 2074 5366Fax: +44 (0)29 2074 4473915 wordsWe thank Sanfilippo and his colleagues for their interest in our paper, and for the opportunity thus afforded to comment on the E/e’ index in critically ill patients and in those who have severe sepsis.We agree that the E/e’ index has some utility in predicting successful weaning from mechanical ventilation, as they have shown in their most recent meta-analysis,1 but published studies show high heterogeneity, there are often only small initial differences in mean E/e’ between patients who will remain off ventilation and those who will not, and average E/e’ values in both groups are sometimes within normal or intermediate ranges. Earlier systematic reviews also concluded that a higher E/e′ ratio is associated with weaning failure in ventilated patients2 and that E/e′ (as well as other markers of diastolic dysfunction) predicts mortality in critically ill patients.3 In a large study of 161 patients, however, neither E/e’ at the lateral mitral annulus nor any other echocardiographic index predicted success in weaning.4The heterogeneity of criteria for diastolic dysfunction in these studies is illustrated by cut-points for abnormal E/e’ varying between 8 and 12 at the lateral mitral annulus and 8 and 9.6 at the medial (septal) annulus.3In ventilated as in other patients, both E and e’ are preload-dependent.5 Positive end-expiratory pressure (PEEP) reduces both; for example PEEP of 12 cm H2O decreased lateral e’ by 19.7% and E by 13.7%, so E/e’ was unchanged.6 An increase in e’ when a patient is taken off a ventilator could indicate a response to changed loading rather than an improvement in intrinsic diastolic function. Before concluding that observed changes in E/e’ imply corresponding changes in left ventricular (LV) filling pressures, we should consider if E/e’ has been validated by correlation with pulmonary capilllary wedge pressure (PCW) measured with Swan Ganz catheters, specifically in ventilated and critically ill patients.In 39 patients there was no difference in E/e’ before a trial of spontaneous breathing, between those subjects in whom it was successful (defined as PCW remaining <18 mmHg after 60 minutes; mean baseline E/e’ 8.0) and those in whom it was not (PCW increasing to >18 mmHg; baseline E/e’ 7.6).7 The area under the receiver operating characteristic curve (AUC) for E/e’ as a guide to PCW at the end of the trial of spontaneous breathing was 0.8. In an earlier study of patients in intensive care who were also breathing spontaneously, E/e’ had a modest correlation with PCW (r=0.69); a patient with E/e’ of around 10 could have a PCW ranging from <10 to >20 mmHg.8 In other studies of ventilated patients, the correlation of lateral E/e’ with PCW was 0.849 and its AUC was 0.91.10Recently, Brault et al reported that the 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines for diastolic dysfunction did not accurately assess PCW in 98 ventilated and critically ill patients, of whom 54% experienced septic shock. The diagnostic score was indeterminate in 49% of patients, sensitivity and specificity were both 74%, and agreement between echocardiography and PCW was moderate (Cohen’s Kappa, 0.48). The best echocardiographic predictor of a normal PCW was not the E/e’ ratio but a lateral e′ >8.11From experimental and clinical observations it is clear that severe sepsis can depress myocardial contractile function, probably through multiple mechanisms.12 In 40 patients with sepsis, however, there were no significant correlations between serum concentrations of inflammatory cytokines and measurements of e’ or calculated E/e’.13 In another study, mortality was predicted by the APACHE II score and mitral annular systolic excursion (MAPSE) with an AUC of 0.88, while the E/e’ index was not selected as a predictor in a logistic regression analysis.14Reproducibility of echocardiographic measurements in patients with septic shock is moderate to good15 but it is difficult to rely on single observations to guide clinical decisions.In patients with sepsis and severe diastolic dysfunction, failure to respond to volume replacement may be caused by impaired early diastolic relaxation and LV suction, which cannot be detected by the E/e’ index. In a randomised trial, an intravenous infusion of esmolol to slow the heart rate prolonged LV filling and increased stroke volume, with a subsequent reduction in mortality.16 In a prospective observational study, levosimendan increased the probability of successful weaning from ventilation, and averted any increase in E/e’;17 that could also be explained by improved early diastolic relaxation and filling, since levosimendan is positively lusitropic.18 Detailed echocardiographic assessment of ventilated patients after cardiac surgery showed that levosimendan increased early diastolic strain rate by 30%.19 Thus changes in E/e’ as a marker of mean PCW do not necessarily confirm a causal relationship with any particular aspect of LV diastolic function, while more comprehensive echocardiographic analysis of pathophysiological mechanisms may be more informative.These thoughts reinforce some of the conclusions that we drew in our review. Many studies are difficult to interpret because the E/e’ index is reported without information on changes in its individual components, and because dichotomising patients into normal or diastolic dysfunction (grades) loses information from multiple continuous variables that are inter-related but may change with differing patterns according to particular circumstances. It is unwise to use discrete cut-points especially if they are unadjusted for age and gender, and mistaken to conclude that LV diastolic function has changed when there are significant differences in the E/e’ index but its mean values remain within the normal range. The optimal assessment of diastolic dysfunction in septic and ventilated patients requires a multiparametric approach and we caution against over-reliance on E/e’.

Background: Chronic spontaneous urticaria is well-described in adults, but less so in children. The aim of this study is to describe the demographics, clinical characteristics, comorbidities, and outcomes of children with chronic, spontaneous urticaria. Methods: This retrospective study followed children up to 18 years-old, diagnosed with chronic spontaneous urticaria, between the years 2002-2018 and treated in a tertiary referral allergy and clinical immunology center. Data including demographics, clinical characteristics, comorbidities, treatments and outcomes was extracted from electronic medical records. Results: Records of 380 children coded to have chronic urticaria were reviewed, of which 250 (65.8%) fulfilled the diagnostic criteria for chronic spontaneous urticaria. There were 136 females (54.4%). Mean age at diagnosis was 11.4 years, 122 (48%) were adolescents. The average duration of chronic spontaneous urticaria was 12.25±15.2 months. The urticaria in 208 children )83.2%) resolved within 24 months. Eighty-seven patients (34.8%) had at least one atopic disease. Atopic comorbidities included atopic dermatitis in 17.2%, allergic rhinitis in 16%, asthma in 13.2% and food allergy in 3.2%. Eighteen patients (7.2%) had a concomitant autoimmune disease. Nine (3.6%) had thyroid disease. Conclusions and clinical relevance: Chronic spontaneous urticaria in children is a self-limited disease with favorable prognosis. Atopic diseases are more prevalent in children with chronic spontaneous urticaria than in the general pediatric population; increasing the possibility of a special subgroup of TH2-related chronic urticaria in children.

Background: Selective IgM deficiency (sIgMD), classified under primary immunodeficiencies, is characterized by low serum IgM(<2SD for age), normal IgG and IgA levels. The aim of this study was to define immunologic and clinical features of sIgMD. Method: We assessed a retrospective medical record of patients who fullfilled the criteria for sIgMD in a Pediatric Immunology department. Results: There were 55 patients with sIgMD. Out of 55 patients, thirteen(23.6%) diagnosed with a well-defined primary immunodeficiency (PID) during the follow-up.The ratio of the sIgMD was %0.12 in the out-patient clinic of pediatric immunology. Out of 33 patients, 8(23.5%) were asymtomatic during the follow-up period. Fifteen(45.4%) patients presented with several type of infections). Six patients (18%) had chromosomal anomaly, or syndrome (trisomy 21, 22q11.2 deletion 1p deletion, CHARGE syndrome, and Cohen Syndrome). Six (18%) had autoimmune/inflammatory diseases, such as Behcet’s disease, immune thrombocytopenic purpura, Crohn disease, Guillain Barre syndrome, and diabetes mellitus. Five(15%) had allergic disorders. Three(9%) have developed malignancy. The diagnoses of thirteen PID patients were combined immunodeficiency, common variable immunodeficiency, autoimmune lymphoproliferative syndrome, chronic granulomatous disease, adenosine deaminase deficiency, and congenital neutropenia. Genetic disorders, autoimmune/inflammatory and allergic diseases may accompany sIgMD. Approximately one third of the patients were asymptomatic in our series. Malignancy risk is relatively increased. We observed that an important ratio of patients with low IgM (23.6%) got sooner the diagnosis of a specific PID in the follow-up period. Conclusion: Thus, patients with sIgMD should be followed regularly in immunology clinics.

We present a class of higher-dimensional Hilbert-type inequalities on a fractal set $(\mathbb{R}_+^{\alpha n})^{k}$. The crucial step in establishing our results are higher-dimensional spherical coordinates on a fractal space. Further, we impose the corresponding conditions under which the constants appearing in the established Hilbert-type inequalities are the best possible. As an application, our results are compared with the previous results known from the literature.

We report on pregnant woman affected by NF1 and HIV infection. So far, both NF1 and HIV in pregnancy had never reported. During 7-year follow-up, she experienced 4 pregnancies without any complication linked to NF1. The newborns were HIV-negative. A multidisciplinary counseling could improve ante and post-partum management.

For nearly all organisms, dispersal is a fundamental life history trait that can shape their ecology and evolution. Variation in dispersal capabilities within a species exists and can influence population genetic structure and ecological interactions. In fungus-gardening (attine) ants, co-dispersal of ants and mutualistic fungi is crucial to the success of this obligate symbiosis. Female-biased dispersal (and gene flow) may be favored in attines because virgin queens carry the responsibility of dispersing the fungi, but a paucity of research has made this conclusion difficult. Here, we investigate dispersal of the fungus-gardening ant Trachymyrmex septentrionalis using a combination of maternally- (mitochondrial DNA) and biparentally-inherited (microsatellites) markers. We found three distinct, spatially isolated mitochondrial DNA haplotypes. Two were found in the Florida panhandle and the other was found in the Florida peninsula. In contrast, biparental markers illustrated significant gene flow across this region and minimal spatial structure. The differential patterns uncovered from mitochondrial DNA and microsatellite markers suggest that most long-distance ant dispersal is male-biased and that females (and concomitantly the fungus) have more limited dispersal capabilities. Consequently, the limited female dispersal is likely an important bottleneck for the fungal symbiont. This bottleneck could slow fungal genetic diversification, which has significant implications for both ant hosts and fungal symbionts regarding population genetics, species distributions, adaptive responses to environmental change, and coevolutionary patterns.

Carcinoid disease is a rare neoplasm but it's an important etiology of intrinsic right heart valve disorders that leads to right heart failure. carcinoid heart involvement is a common complication of disease that effects on morbidity and mortality of the patient.

In this paper, a dynamic biomass gasification model was developed based on the hybrid peripheral fragmentation and shrinking-core (HPFS) model. To improve the accuracy of syngas generation transient prediction, the chemical kinetic model was trained using global surrogate optimization techniques. The pre-exponential factors of kinetic reactions are calibrated under non-catalytic conditions, employing experimental transient data of syngas generation rate and compositions under different temperatures and gasifying agents. The DYCORS and GOMORS were employed as the numerical solvers for finding the global optimum solution of the pre-exponential factors. The calibrated kinetic models based on both single-objective and multi-objective approaches have been validated by experimental data in four different biomass gasification scenarios. The calibrated kinetic model shows an over 95% decrease in terms of integrated squared error (ISE)-based model mismatch when compared to the original kinetic model.

Background and Purpose: Cigarette smoking (CS) is the major risk factor for developing COPD and related skeletal muscle dysfunction. It has been postulated that CS exposure may directly causes muscle dysfunction via the induction of oxidative stress. The present study examined the effect of a potent Nox inhibitor and ROS scavenger, apocynin on CS-induced muscle dysfunction. Experimental Approach: Male BALB/c mice were exposed to either room air (sham) or CS generated from 9 cigarettes per day, 5 days a week for 8 weeks with or without apocynin treatment (5 mg·kg-1 w/v, intraperitoneal injection). C2C12 myotubes exposed to either hydrogen peroxide (H2O2) or water-soluble cigarette smoke extract (CSE) with or without apocynin (500 nM), was set up as an experimental model in vitro. Key Results: Eight weeks of CS exposure caused significant lung inflammation and muscle dysfunction in mice; evidenced by a 10% loss in muscle mass and 54% loss in contractile function of tibialis anterior, attributable to altered myogenic homeostasis and protein oxidation. These effects were prevented by apocynin administration. In C2C12 myotubes, direct exposure to H2O2 or CSE caused myofiber wasting, which was associated with altered myogenic homeostasis marked by ~50% loss in muscle-derived insulin-like growth factor (IGF)-1 and 1.5-fold increase in myostatin expression. Apocynin treatment completely attenuated CSE-induced Nox2 expression, preserving muscle-derived IGF-1 expression and downstream mammalian target of rapamycin (mTOR) signaling pathway, thereby preventing myofiber wasting. Conclusion and Implications: Targeted pharmacological inhibition of Nox-derived ROS may alleviate the lung and systemic manifestations in smokers with COPD.

Aim: Aspects of parenting is an under-investigated topic among children with voiding complaints. We aimed to investigate the association between voiding complaints among children and two specific parenting related behaviors: 1) parental availability during the child’s leisure time and 2) frequency of witnessing interparental conflict. Material and Method: Children aged between 6 and 11 years with their parents were the participants. Two survey forms and informed consent form were sent to potential participants via children’s teacher. Voiding dysfunction complaints were evaluated with the Dysfunctional Voiding and Incontinence Symptom Scale (DVISS). Results: Data analyses were performed with 1101 eligible participants. Mean duration of parental availability during the child’s leisure time was below 2 hours per day. Nearly one out of every four children witnessed interparental conflict at least once a month. Age, educational level of the mother, parental availability for the child’s leisure time, and frequency of witnessing parental conflicts were found to be significantly associated with DVISS ratings. Adjusting age, socioeconomic level, and educational level of the parents and later adjusting parental availability during the child’s leisure time did not change the association of frequency of witnessing interparental conflict with DVISS rates. Increase in the age, educational level of the mother, and parental availability during the child’s leisure time were correlated with better scores on DVISS while increase in the frequency of witnessing interparental conflict strongly correlated with worse scores. Conclusion: Exposing children to interparental conflicts and shorter togetherness with their leisure time is associated with voiding complaints.

Abstract: Critical airway stenosis presents a challenge for surgeons and anesthesiologists alike in securing a reliable airway for adequate ventilation. The use of veno-venous (VV) extra-corporeal membrane oxygenation (ECMO) has been described as a strategy to provide adequate gas exchange in such instances. We present a case of a young female with a complex paratracheal mass significantly compressing the trachea in whom a planned intra-operative VV ECMO was instituted to allow safe oro-tracheal intubation of a double lumen endotracheal tube for lung isolation and tumor resection.

Objectives: In this paper we outline how inflammation related to oral disease such as periodontitis, bacteraemia and pulpal lesions have been linked to cardiovascular disease and undertake a systematic review of the literature focused on acute dental infection and cardiac arrhythmia. We also describe an illustrative case where an acute oral infection was associated with occurrence of new onset atrial fibrillation (AF). Methods: An electronic search was undertaken using MEDLINE and SCOPUS from 01 Jan 1970 until 30 June 2020. We also undertook manual searches using forward and backward citation chasing. Inclusion criteria were any primary research studies investigating symptomatic apical infections or dental abscess with outcomes of arrythmia. Results Over the last fifty years, only two low quality studies have been investigated this area. Our illustrative case involved a 58-year-old who was diagnosed with an acute dental infection from an upper canine tooth. The patient later developed tachycardia and new-onset AF. Conclusions: Based on the biological plausibility of a link between acute dental infection and arrythmia, together with the case report presented, it is evident that further study in this area is needed. If there are possible cardiovascular consequences for patients suffering acute dental infections, this has future implications for healthcare staff as they can integrate professional advice related to oral health and cardiovascular disease. Screening programmes situated in dental settings can also facilitate early intervention and prevention producing benefits not just for patients, but in savings to the health system.

BACKGROUND:There are studies reporting that uric acid elevation is a marker for hypoxemia and pulmonary hypertension secondary to some diseases. AIM: The aim of this study is to investigate the relationship between serum uric acid level and uric acid/creatinine ratio with COPD exacerbation, hypoxemia in exacerbation and development of cor pulmonale. METHODS: A total of 96 COPD patients who were admitted to Ondokuz Mayıs University Faculty of Medicine emergency department and Chest Diseases outpatient clinic and whose written consent was obtained, were included in our study. 43 of these patients were in the period of exacerbation (Group 1) and 53 were in the stable period (Group 2). Complete blood count, blood biochemistry (including serum uric acid level) and arterial blood gas analysis were performed in our patients. In addition, spirometry and echocardiography findings were examined. RESULTS: Serum uric acid level of Group 1 was 6.97 ± 1.34 and Group 2 was 4.30 ± 1.01 (p <0.05). Uric acid/creatinine ratios; in group 1; 8.00 ± 2.06, in group 2; It was 5.52 ± 1.57 (p <0.05). In patients with hypoxemia, serum uric acid level and uric acid / creatinine ratio were significantly higher than non-hypoxemic (p <0.05). Serum uric acid level and serum uric acid/creatinine ratio of Group 1 were significantly higher than Group 2 (p <0.001). Serum uric acid level and serum uric acid / creatinine ratio of patients who developed cor-pulmonale were significantly higher than patients without cor-pulmonale (p <0.05). CONCLUSION: Serum uric acid level and uric acid/creatinine ratio were found to be higher in patients with exacerbation of COPD and those developing cor pulmonale. Consequently, it suggests that serum uric acid level and serum uric acid/creatinine ratio may be a stimulating laboratory test for the severity of COPD and the development of COPD based cor pulmonale.

We examined whether the presence or absence of different environmental stressors influenced the reproductive potential of a saltmarsh species - Plantago maritima. We focused on total seed output, seed quality and biomass of progeny. So far, there are no studies trying to answer the question of how different saltmarsh management affects the quality of seed in saltmarsh species. For the purposes of the study, plots subjected to light mowing, light or heavy grazing, trampling or rooting were designated in three nature reserves in Poland. On each plot, the abundance of infructescences per sq. metre was calculated. Mature infructascences were collected and their length and no of fruit capsules were measured. The seeds obtained from fruit capsules were weighted and sown in controlled conditions. The germination rate and the final germination percentage were calculated. A representative number of sprouts were grown. After a period of two months, the specimens were harvested and their total dry mass was measured. It was found that heavy grazing had the greatest effect on all of the studied characteristics. The presence of this factor resulted in shorter infructescences with a smaller number of fruit capsules. However, this phenomenon was compensated by the higher abundance of infructescences per sq. metre. At the same time seeds produced by grazed specimens were significantly lighter. Intensive trampling by people affected specimens in a similar way to heavy grazing, while mowing and rooting had less impact on the considered characteristics. Although a positive correlation between seed mass and germination success was found, the altogether lower seed mass had a negligible effect on germination parameters. Also, the differences in seed parameters did not affect dry mass of obtained progeny grown in lab conditions.

Objective: The aim of this research was to compare the sensitivity and positive predictive value of contrast transcranial Doppler (c-TCD), contrast- transthoracic echocardiography (c-TTE) and contrast- transesophageal echocardiography (c-TEE), to determine the best method for diagnosing patent foramen ovale (PFO) and to provide a reference for the further improvement of clinical practice. Methods: We investigated 161 patients who suffered from migraines, cryptogenic stroke, TIA, and cerebral infarction of unknown cause. All patients underwent transcatheter examination, and the results of the right heart catheterization (RHC) were considered the gold standard for PFO diagnosis. Results: The present study revealed that c-TTE with the Valsalva maneuver had a higher sensitivity in detecting PFO related right-to-left shunt (PFO-RLS), but it might have a higher rate of misdetection than c-TCD. Conclusion: Patients with suspected PFO can be examined with c-TCD first, and if positive results are obtained, then c-TTE and c-TEE should be performed for further confirmation.