In past ten years, microRNAs (miRNAs) have gained scientific attention due to their importance in the pathophysiology of allergic diseases and their potential as biomarkers in liquid biopsies. They act as master post-transcriptional regulators that control most cellular processes. As one miRNA can target several mRNAs, often within the same pathway, dysregulated expression of miRNAs may alter particular cellular responses and contribute or lead to the development of various diseases. In this review, we give an overview of the current research on miRNAs in allergic diseases, including atopic dermatitis, allergic rhinitis and asthma. Specifically, we discuss how individual miRNAs function in the regulation of immune responses in epithelial cells and specialized immune cells in response to different environmental factors and respiratory viruses. In addition, we review insights obtained from experiments with murine models of allergic airway and skin inflammation and offer an overview of studies focusing on miRNA discovery using profiling techniques and bioinformatic modelling of the network effect of multiple miRNAs. In conclusion, we highlight the importance of research into miRNA function in allergy and asthma to improve our knowledge of the molecular mechanisms involved in the pathogenesis of this heterogeneous group of diseases.

The fretting damage and wear debris on the dental implant-abutment interface (IAI) are unclear. In this study, fatigue cycle loading (FT) and chewing cycle loading (CW) test were applied to two implant systems, the fretting damage morphology and wear debris generation on the IAI were observed by a scanning electron microscope. The torque value of the central screw was measured by electronic torque tester. The fretting damage on the IAI was relatively slight and mainly plastic deformation in the FT group, which was more serious and mainly furrow wear in the CW group. Various forms of wear debris were generated. The removal torques were lower than its pre-tightening value in both groups, the decline and loss rate of the CW group was significantly higher. This study confirmed the critical roles of fretting damages and metal wear debris on the IAI in the implant-supported prosthesis.

Osmotic adjustment is recognized as an important mechanism of maintaining turgor under water stress. However, the metabolic basis of this process has been documented in some few forest tree species. The leaf water relations of four Quercus species were studied from P-V curves in well-watered (WW) and water-stressed (WS) seedlings. Lowest values of osmotic potential at full turgor (Ψπ100) followed the ranking Q. ilex < Q. faginea < Q. pyrenaica < Q. petraea. The leaf osmotic potential at the turgor loss point (ΨTLP) kept up with the patterns of the Ψπ100 across species and treatments. The leaf metabolome pointed out to the pool of carbohydrates, some organic acids, and cyclitols as main contributors to osmotic potential. Amino-acids, although very reactive to WS particularly in Q. pyrenaica accounted quantitatively less to osmotic potential than rest of the compounds. The relevance of proto-quercitol was high as a contributor to osmotic potential regardless treatment or species. Other metabolites as quinic acid played a more relevant role in osmoregulation specifically in Q. ilex. The study shows leaf osmotic potential is underpinned by a metabolic response shaped according to phylogenetic history and ecology of the species.

The purpose of our study was to assess the frequency of occult foreign body aspiration (FBA) and to evaluate the diagnostic difficulties and therapeutic methods for these patients. Between February 2000 and February 2020, 3557 patients with the diagnosis of FBA were treated in our department. Thirty-five patients with occult FBA were included in this study. A retrospective analysis of medical records was performed. Twenty-three male patients (65.7%) and 12 female patients (34.3%) were hospitalized due to occult FBA. The average age was 3.60 years (range 9 months-12 years). Most of the patients were younger than 3 years old (n=25, 71.4%). Coughing (n=35, 100%) and wheezing (n=18, 51.4%) were the main symptoms and signs. All the patients were found to have a FBA under the fiberoptic bronchoscope. The most common organic foreign bodies were peanuts (n=10) and the most common inorganic foreign bodies were pen caps (n=5). The extraction of foreign bodies under rigid bronchoscopy was applied successfully in 34 patients. Only one patient needed a surgical intervention. Occult FBA should always be considered in the differential diagnosis of chronic or recurrent respiratory diseases that are poorly explained, even in the absence of a previous history of aspiration.

Background: Asthmatic children present variable degrees of airway inflammation, remodeling and resistance, which correlates with disease control and severity. Chronic inflammatory process of the airways triggers airway remodeling, which reflects the degree of airway resistance. Pro-inflammatory and pro-fibrotic mediators are centrally involved in this process. This study has investigated for the first time, whether the levels of pulmonary and systemic pro-inflammatory and pro-fibrotic mediators present correlation with the resistance of respiratory system and of proximal and distal airways. Methods: 24 asthmatic children (persistent mild and moderate) and 24 non-asthmatic children (both between 6-13 years old) were evaluated for anthropometric characteristics, lung function and mechanics, pulmonary and systemic immune response. Results: Asthmatic children showed an increased number of blood eosinophils (p<0.04), basophils (p<0.04), monocytes (p<0.002) and lymphocytes (p<0.03). In addition, asthmatic children showed an impaired lung function, as demonstrated by FEV1%pred. (p<0.0005) and FEV1/FVC (p<0.004), decreased total resistance of respiratory system (R5Hz; p<0.009), increased resistance of proximal airways (R20Hz; p<0.02), increased elastance (Z5Hz; p<0.02) and increased reactance (X5Hz; p<0.002). Moreover, the following inflammatory factors were significantly higher in asthmatic than non-asthmatic children: GM-CSF in the breath condensate (BC) (p<0.0001) and in the serum (p<0.0001); TGF-beta in the BC (p<0.0001) and in the serum (p<0.004); IL-5 in the BC (p<0.02) and in the serum (p<0.01); IL-4 in the serum (p<0.0002). Conclusions: Impulse oscillometry is a sensitive method to detect airway resistance in asthmatic children, reflecting airway remodeling, an event followed by increased levels of pro-inflammatory and pro-fibrotic mediators.

SARS-CoV-2 infection has caused a pandemic which has resulted in more severe disease in adults than children. We report an ex-premature infant with bronchopulmonary dysplasia who developed COVID-19 associated severe acute respiratory distress syndrome causing bradycardic cardiac arrest and seizures.

At present, Corona virus disease 2019(COVID-19) has become a major concern all over the world and leads to huge medical pressure. Antibody-dependent enhancement (ADE) of viral infection has been researched extensively in many viruses. It is not yet clear whether SARS-CoV-2 infection causes ADE effects. However, there is evidence that ADE may be found in COVID-19. We have discussed the possibilities of ADE effect induced by COVID-19 and proposed a series of measures to deal with it.

Secondary pneumomediastinum in patients with ARDS is often related to invasive mechanical ventilation due to high airway pressures leading to alveolar rupture.1 The pathophysiologic mechanism through which this occurs is known as the Macklin effect which describes the idea that alveolar rupture causes a leakage of air along the bronchovascular bundle whereby it extends into the mediastinum.2 Another contributing factor to alveolar rupture is the diffuse alveolar damage seen in patients with severe ARDS.3   Here we present a case series from a major New York City academic hospital of 18 patients with Covid-19 complicated by pneumomediastinum in the setting of both invasive and noninvasive ventilation.             The data collected was obtained on April 19th during which 130 Covid-19 infected patients were intubated and in the intensive care unit since March 26th 2020. Four patients were excluded from analysis due to inability to exclude pneumomediastinum as a line-associated complication. All intubations were done by the most senior clinician available. The median age of the patients was 60 years and 55.6% were men. The most common comorbidities were hypertension (38.9%) and diabetes mellitus (33.3%). Most pneumomediastinum cases (83.3%) were in association with invasive mechanical ventilation and 46.7% occurred within the first day of intubation. An additional 40% of pneumomediastinum cases occurred between day 1 and day 6. Those intubated were placed on an average of 6.58 cc/kg of tidal volume. Only 20% of patients experienced peak inspiratory pressures greater than 35 mm Hg and 13.3% had plateau pressures greater than 30 mm Hg. High PEEP strategy defined as greater than 12 mm Hg was used in 40% of patients. The most frequent concurrent complications observed were subcutaneous emphysema (72.2%) and pneumothorax (55.6%). Figure 1 shows a single axial cut of a CT scan of the Chest of one patient who experienced severe subcutaneous emphysema, pneumomediastinum and diffuse bilateral lung infiltrates due to Covid-19. The in hospital mortality rate at the time of publication is 44.4%.             The prevalence of pneumomediastinum cases due to COVID-19 in this study was 13.8%. This is significantly more frequent than that observed with protective ventilation strategy which was as low as 7%.4 Interestingly, a previous study of SARS-Cov1 estimated a total incidence of 12% of patients with pneumomediastum.5             The large number of pneumomediastinum cases observed in this case series seems to be unexplained solely by barotrauma from mechanical ventilation in these patients treated with protective lung strategy and may be specific to the underlying pathology of Covid-19. Of note, three patients who developed this complication were receiving noninvasive ventilation further supporting this hypothesis.  Conflict of Interest: None  References:1.   Ioannidis G, Lazaridis G, Baka S, et al. Barotrauma and pneumothorax. J Thorac DIs. 2015;7(Suppl 1):S38-S43 2.   Jacobi A, Chung M, Bernheim A, Eber C. Portable chest X-ray in coronavirus disease-19 (COVID-19): A pictorial review. Clinical Imaging. 2020;64:35–42. 3. Murayama S. Spontaneous pneumomediastinum and Macklin effect: Overview and appearance on computed tomography. World Journal of Radiology. 2014;6(11):850.4. Passos Amato M, Valente Barbas C, Medeiros D, et al. Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome. New England Journal of Medicine. 1998;338:347-3545. Peiris J, Chu C, Cheng V, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet. 2003;361(9371):1767–72.

Severe metabolic acidosis and respiratory distress due to acute starvation in pregnancy: a case report K de Jonga, CJC Stewartb, GCR van Hoeckea, HH Ponssenb.a Department of Obstetrics and Gynaecology, Albert Schweitzer Hospital, Dordrecht, the Netherlandsb Department of Intensive Care, Albert Schweitzer Hospital, Dordrecht, the Netherlands.Correspondence : drs K de Jong, Albert Schweitzer Hospital, Albert Schweitzerplaats 25, 3318 AT Dordrecht, The Netherlands, 0031-7865-51948. Email k.dejong2@asz.nl.

Objective: To investigate the incidence, risk factors and clinical characteristics of periaortic VTs after AVR. Background: The periaortic region is the origin of some ventricular tachycardias (VTs) after aortic valve replacement (AVR). However, the clinical characteristics of periaortic VTs after AVR are yet to be clarified. Methods: We retrospectively analyzed clinical courses of 109 patients who had undergone surgical AVR (SAVR) without other structural heart diseases between April 2009 and Jun 2019 and evaluated the incidence and characteristics of periaortic VTs after SAVR. Results: Three patients (2.8%) developed periaortic VTs after SAVR. The average duration of onset was 12.3±6.6 years. All VTs arose from the inferior axis; they included both left and right bundle branch block configuration (LBBB and RBBB). Two patients underwent cardiac magnetic resonance imaging; late gadolinium enhancement (LGE) was observed in the mid-layer of the left ventricle basal anteroseptal wall in both cases. Patients with periaortic VTs had significantly wider interventricular septum, lower left ventricular ejection fraction (LVEF), larger LV diameter at systole, and higher positive rates of signal-averaged ECG and non-sustained VTs on Holter. On ablation, local fragmented potentials with low voltage zones were observed in accordance with the distribution of LGE. Multiple VTs originating from the periaortic region were provoked in the sessions. Conclusions: Periaortic VTs long after surgical AVR are not rare, and arrhythmia risk stratification, including that by signal averaged electrocardiogram (SAECG), Holter, and cardiac magnetic resonance imaging (MRI) should be considered.

Introduction: His-bundle pacing (HBP) and left bundle branch area pacing (LBBAP) are novel techniques that have demonstrated their efficacy in patients needing right ventricular pacing and in candidates for resynchronization therapy. The purpose of this study was to compare acute and short-term outcomes between HBP and LBBAP. Methods: Retrospective review of the success rate and change in QRS duration obtained by HBP and LBBAP in patients requiring anti-bradycardia pacing or cardiac resynchronization, evaluating the complications and pacing parameters at implantation and at 3 months. Results. The study included 90 procedures (46 HBP and 44 LBBAP) in 87 patients. Success was achieved in 77 procedures (85.6%): 37 (80.4%) in the HBP group and 40 (90.9%) in the LBBAP group (P = .23). Paced QRS duration was shorter in the LBBAP patients (109 ± 8 vs. 117 ± 19 ms; P < .05), who had a lower threshold during implantation (0.5 V/0.5 ms vs. 1.5 V/1 ms; P < .001) and at 3 months (0.72 V/0.5 ms vs. 1.75 V/1 ms; P < .001) and an increased sensed R-wave amplitude. The fluoroscopy time was shorter in the LBBAP group (10 vs. 19 minutes; P < .001). The complication rate was similar (6.8% vs. 12.8%; P = .48). Conclusion. In our experience, LBBAP obtains a similar success rate to that of HBP and achieves a shorter paced QRS duration, greater R-wave detection, lower threshold, and shorter fluoroscopy time, with a similar complication rate.

Objective: To determine whether cardiac functional and structural changes in fetuses of mothers with gestational diabetes mellitus (GDM) persist in the offspring beyond the neonatal period. Design: Longitudinal study Setting: Fetal Medicine Unit in a UK teaching hospital Population: 73 women with GDM and 73 women with uncomplicated pregnancy were recruited and fetal cardiac scans were performed at 35-36 weeks’ gestation. Repeat echocardiogram was performed in their offspring during infancy. Main outcome measures: Fetal and infant cardiac functional and structural changes Results: Fetuses of mothers with GDM, compared to controls, had more globular right ventricles (sphericity index 0.7, IQR 0.6/0.7 vs 0.6, IQR 0.5/ 0.6, p<0.001) and reduced right global longitudinal systolic strain (-16.4, IQR -18.9/-15.3 vs -18.5, IQR -20.6/-16.8, p=0.001) and left global longitudinal systolic strain (-20.1, IQR -22.5/-16.9 vs -21.3, IQR -23.5/-19.5), p=0.021). In the GDM group, compared to controls, in infancy there was higher left ventricular E/e’ (8.7, IQR 7.3/9.7 vs 7.9 IQR, 6.8/8.9 p=0.011) and lower left ventricular global longitudinal systolic strain (-21.0, IQR -22.5/-19.4 vs -22.3, IQR -23.5/-20.7, p=0.001) and tricuspid annular plane systolic excursion (13.8, IQR 12.7/16.1 vs 15.2, IQR 13.8/16.8, p=0.003). These differences remained following multivariable analysis. Conclusion: GDM is associated with alterations in fetal cardiac function and structure compared to controls and persistent cardiac changes in infancy.

Background. This study examines the influence of contextual factors on the initial phases of the COVID-19 outbreak across U.S. counties. Methods. Contextual factors are simultaneously tested at the county- and state-level with a multilevel linear model using full maximum likelihood. Results. The variation between states is substantial and significant (ICC = 0.243, u0 = 4.50E-04, p < 0.001). At the state-level, the cultural value of collectivism is positively associated with the outbreak rate. At the county-level, the racial and ethnic composition contributes to outbreak differences, affecting Black/African and Asian Americans most. Counties with a higher median age have a stronger outbreak, as do counties with more people below the age of 18. Higher income, education, and personal health are generally associated with a lower outbreak. Obesity is negatively related to the outbreak, in agreement with the value expectancy concepts of the health belief model. Smoking is also negatively related, but only directionally informative. Air pollution is another significant contributor to the outbreak, but population density does not give statistical significance. Conclusions. Because of a high variation in contextual factors, policy makers need to target pandemic responses to the smallest subdivision possible, so that countermeasures can be implemented effectively.

Sir, We would like to thank Sharma and colleagues for their interest in our recent study evaluating the effectiveness and safety of surgical interventions for Bartholin’s cyst or abscess.1Their response highlights the unique opportunity offered by randomised trials, and their syntheses into meta‐analyses, to assess patient reported outcomes. We would strongly encourage researchers to select, collect and report patient reported outcomes in future research evaluating interventions for Bartholin’s cyst or abscess.2The primary outcome should be the outcome of greatest therapeutic importance to the study’s prospective hypothesis. There is currently no consensus regarding the selection of outcomes and methods of definition or measurement for randomized trials evaluating interventions for Bartholin’s cyst or abscess.3 In the absence of a standardized approach, researchers have made arbitrary decisions when choosing among several important outcomes.4 It would be useful for healthcare professionals, researchers, and women with lived experience of Bartholin’s cyst or abscess to engage in a formal consensus development process to agree appropriate primary and secondary outcomes.3We agree the use of adjuvant antibiotics is an important consideration. They were not reported by any of the included trials.5We have no experience of marsupialization performed under local anaesthetic. In our opinion, this approach would need to be evaluated within a research setting. The recent COVID-19 pandemic would provide additional impetus to undertake this much needed research.James M. N. Duffy 1,2, Emma Kirk 3, BJG Illingworth 4, K Stocking 5,Marian Showell 61 Institute for Women’s Health, University College London, London, United Kingdom.2 King’s Fertility, Fetal Medicine Research Foundation, London, United Kingdom.3 Department of Obstetrics and Gynaecology, Royal Free London NHS Trust, London, United Kingdom.4 North West Anglia NHS Foundation Trust, Peterborough City Hospital, Peterborough, UK5 Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK6 Cochrane Gynaecology and Fertility Group, University of Auckland, Auckland, New Zealand.

Aim: We hypothesize that the efficacy of COVID-19 therapeutic candidates will be better predicted by understanding their effects at various points on a viral cell cycle, in particular, the specific rate constants, and that drugs acting independently of these specific discrete sites may not yield expected efficacy. We hypothesize that drugs, or combinations of drugs that act at specific multiple sites on the viral life cycle have the highest probability of success in the treatment of early infection phase in COVID-19 patients. Methods: Using a target cell limited model structure that had been used to characterize viral load dynamics from COVID-19 patients, we performed simulations to show that combinations of therapeutics targeting specific rate constants have greater probability of efficacy and supportive rationale for clinical trial evaluation. Results: Based on the known kinetics of the SARS-CoV-2 life cycle, we rank ordered potential targeted approaches involving repurposed, low-potency agents. We suggest that targeting multiple points central to viral replication within infected host cells or release from those cells is a viable strategy for reducing both viral load and host cell infection. In addition, we observed that the time-window opportunity for a therapeutic intervention to effect duration of viral shedding exceeds the effect on sparing epithelial cells from infection or impact on viral load AUC. Furthermore, the impact on reduction on duration of shedding may extend further in patients who exhibit a prolonged shedder phenotype. Conclusions: Our work highlights the use of model-informed tools to better rationalize effective treatments for COVID-19.

The aim of the present study is to introduce the concepts of deferred statistically convergence, deferred statistical Cauchy sequence and deferred Cesàro summability in paranormed spaces. We investigate some properties of these concepts and some inclusion relations with examples.

Aluminum alloy materials is an important component material in the safe flight of aircraft. It is very important and necessary to predict the fatigue crack growth between holes of aviation aluminum alloy materials. At present, the investigation on the prediction of the cracks between two holes and multi-holes is a key problem to be solved. Due to the fatigue crack growth test of aluminum alloy plate with two or three holes was carried out by MTS fatigue testing machine, the crack length growth data under different test conditions were obtained. In this paper, support vector regression (SVR) was used to fit the crack data, and the parameters of SVR are optimized by grid search algorithm at the same time. And then the model of SVR to predict the crack length was established. Discussion on the results show that the prediction model is effective. Furthermore, the crack growth between three holes were predicted accurately through the model of the crack law between two holes under the same load form.

In this study, we consider conformable type Coudrey-Dodd-Gibbon-Sawada-Kotera (CDGSK) equation. Three powerful analytical methods are employed to obtain generalized solutions of the nonlinear equation of interest. First, the sub-equation method is used as baseline where generalized closed form solutions are obtained and are exact for any fractional order alpha. Furthermore, Residual power series (RPSM) and q-homotopy (q-HAM) analysis techniques are then applied to obtain approximate solutions. These are possible using some properties of conformable derivative. These approximate methods are very powerful and efficient due to the absence of the need for linearization, discretization and perturbation. Numerical simulations are carried out showing error values, h-curve for q-HAM and the effects of fractional order on the solution profiles.

In this paper, we study the following quasilinear Choquard equations of the form $$\ -\Delta u+V(x)u-\Delta (|u|^{2\alpha})|u|^{2\alpha-2}u=(|x|^{-\mu}\ast G(u))g(u), \ x \ \in R^N,$$ where $1\geq\alpha>\frac{1}{2}$, $V \in C(\mathbb{R}^N, \mathbb{R})$, $g \in C(\mathbb{R}^N, \ \mathbb{R})$. Distinguished from two situations $\lim\limits_{|x|\rightarrow\infty}V(x)=+\infty$ or $\lim\limits_{|x|\rightarrow\infty}V(x)<+\infty$, we research the existence of nontrivial solutions and a sequence of high energy solutions.

The work reported here concerns with study a generalized nonlinear fractional boundary value problems involving $ \vartheta $- fractional derivative in the Riemann-Liouville sense. The existence and uniqueness of positive solutions to the problem at hand are proved. Our discussion relies on the properties of the Green’s function, the upper and lower solutions method, and the classical fixed point theorems in a cone. Moreover, building upper and lower control functions have an effective role in the analysis. Some examples are offered to justify the validity of theoretical findings.

Cracked tooth syndrome is a common well documented condition that many occur due to morphologic, physical and iatrogenic factors. Epidemiologic data revealed that splits or fractures are the third most common cause of tooth loss. Simvastatin allowed a good management for a case suffered from cracked tooth.

This paper discusses a spectral collocation method for numerically solving linear and nonlinear fractal Mobile/Immobile transport model with Caputo and Caputo-Fabrizio fractional derivatives. In the time direction, a finite difference scheme is used to approximate the differential term. Also, for space discretization, we apply the Chebyshev-spectral method. The unconditional stability and convergence of the proposed method are investigated, which provides the theoretical basis of the proposed method for solving the considered equation. Finally, some numerical experiments are considered to examine the efficiency and applicability of it in the sense of accuracy and convergence ratio.

Ecological traps are a challenge to conservation, potentially increasing extinction risk. However, not all traps were made equal. We suggest that sites that usually constitute ecological traps may benefit populations of r-selected species. As a model system we investigate the effects of man-made ephemeral pools such as storm-water catchments on the population dynamics of an r-selected amphibian species, and compare it to a k-selected species. Ephemeral pools may act as breeding sites and habitat for adult individuals however they often desiccate too early for tadpole metamorphosis, leading to offspring mortality. We use agent-based simulations over multi-generational timescales to study a range of ecologically-reasonable parameters. We find that the contribution of traps to population viability, thanks to rare years in which their hydro-period suffices for metamorphosis, exceeds the detrimental effects in other years. Counterintuitively, eliminating such potential traps from the environment may reduce the viability of meta-populations and increase extinction risk.

We experienced refeeding syndrome (RFS) with an eating disorder and distal renal tubular acidosis (dRTA). A low body mass is high-risk factors for RFS development. Therefore, frequently measurement of serum phosphorus levels at the initiation of nutrition and rapid administration of phosphate preparations are required to prevent RFS-related organ failure.