The gold standard for the treatment of pure aortic insufficiency (PAI) is surgical valve repair or replacement.1 With the newest transcatheter heart valve technologies and the accumulating years of experience of heart teams with the current transcatheter aortic valve replacement (TAVR) prostheses, implanters have push the envelope with off-label use of those valves designed and approved for aortic stenosis, in patients with pure aortic insufficiency especially those at higher risks or for compassionate use.3 However, new prostheses are currently under investigation in clinical use and evidences are provided on the safety and efficacy of those latter. It will be discussed in this commentary, the actual clinical evidences and the use of transcatheter heart valves, in and off label, for the treatment of pure aortic insufficiency.

Background: Kimura disease (KD) is a rare, chronic inflammatory disorder characterized by blood eosinophilia, general itching, and subcutaneous head and neck mass lesions; however, the etiology of this disease is unknown. We hypothesized that group 2 innate lymphoid cells (ILC2s) in peripheral blood may play an essential role in the pathogenesis of KD. Methods: The prevalence of blood ILC2s and their ability to produce interleukin (IL) -4, IL-5, IL-13, and IL-31 in patients with KD were compared with those in control subjects and in patients with house dust mite (HDM) -induced allergic rhinitis (AR). Changes in blood ILC2 prevalence, blood eosinophilia, and clinical symptoms after surgery and steroid therapy were evaluated. Results: Blood ILC2 prevalence in patients with KD were eight times and six times higher than those in control subjects and in patients with AR, respectively. There was a strong positive correlation between ILC2 prevalence and blood eosinophilia. Patients with KD showed increased serum IL-13 and decreased IL-31 levels. KD patient-derived blood ILC2s produced large amounts of IL-5 and IL-13 in response to prostaglandin (PG) D 2 and leukotriene (LT) D 4, compared to ILC2s derived from control subjects and patients with AR. Surgery and systemic steroid therapy ameliorated general itching with a concomitant decrease in blood ILC2s and blood eosinophilia. Upon disease recurrence, blood ILC2 prevalence and blood eosinophilia increased concurrently with general itching. Conclusion: Increased blood ILC2s may be involved in blood eosinophilia and general itching through the production of IL-5 and IL-13 in patients with KD.

Background and Purpose: Peptides derived from retroviral envelope proteins have been shown to possess a wide range of immunosuppressive and anti-inflammatory activities. We have previously reported identification of such a peptide derived from the envelope protein coded by a human endogenous retrovirus (HERV). In this study we assessed effects of this peptide treatment on inhibition of immune response in the DSS-induced mice model of colitis. Furthermore, we identified that in vitro the peptide inhibits the KCa3.1 potassium channel, a potential target for therapy of immune diseases. Experimental Approach: We characterized an immunosuppressive peptide ENV59, from a specific HERV envelope protein, in vivo effects on inflammation control in acute colitis mice model and in vitro on the production of pro-inflammatory cytokines. Furthermore, we described in vitro ENV59-GP3 effects with respect to potency of inhibition on KCa3.1 channels and calcium influx. Key Results: ENV59-GP3 peptide treatment showed reduction of the disease score in the DSS-induced acute colitis mice model, which was comparable to effects of the KCa3.1 channel blocker NS6180. Analysis of cytokine production from DSS-mice model treated animals revealed equipotent inhibitory effects of the ENV59-GP3 and NS6180 compounds on the production of IL-6, TNF-α, IL-1β. Patch clamp studies show that the peptide ENV59-GP3 is a blocker of the potassium channel KCa3.1. Conclusion and Implications: Env59-GP3 represents KCa3.1 channel inhibitor underlining the implications of using virus derived channel blockers for treatment of autoimmune diseases. There are no drugs with a similar mechanism of action currently on the market.

Redo aortic valve surgery for failure of a previously implanted valve is always challenging. In case of small-sized implanted valves, the use of a balloon-expanding Sapien-3 valve can enhance the final effective orifice area, avoid complex annulus enlargement techniques, and can reduce operative time and morbidities. We describe a case where after explanting a failed 19mm St. Jude mechanical aortic valve and further deployment of a 23mm Sapien-3 valve, the left coronary ostia was obstructed by the skirt of the transcatheter prosthesis. After careful removal of a little part of the skirt, we were able to restore the coronary flow and the patient had a favorable outcome.

Formal guidelines for awake tracheal intubation have recently been published providing a streamlined process for the first time. We present a case of awake videolaryngoscopy in the pediatric setting, not previously reported. Application of guidelines and careful team preparation facilitated performance of a novel technique in our pediatric institution.

Play behavior is a significant trait of immature nonhuman primates (hereafter primates), which may play important roles in sensory, locomotor, socio-cognitive, and developmental processes in primates. It has been suggested that function of play is to practice and improve motor skills related to foraging, avoiding predation, attracting mates, raising offspring, and also is to strength social skills concerning to cementing friendly relationships and defraying aggression among individuals. From September 2009 to August 2010, we investigated play behaviors of 1-12-month-old white-headed langur (Trachypithecus leucocephalus) which is a critically endangered primate endemic to China. During this study, we recorded 4,421 play bouts and 1,302 minutes of play time of 7 infants in total. We found that infants had different play behavior patterns at different ages. Specifically, non-social play behaviors appeared at 1 month of age, social play behaviors at 2 months, and all types of social and non-social play behaviors at 3 months. The frequency and duration of non-social play peaked at 5 months and then decreased, while social play appeared at 2 months and gradually increased with age. Non-social play did not differ between the sexes, whereas social play showed sex specificity, with higher frequency and duration of social play in male infants than in female infants. In addition, male and female white-headed langur infants appeared to prefer the individuals of same sex as social playmates. In conclusion, we first reported the pattern of play behavior of a critically endangered langur aged 1 to 12 months though the sample size is small, our results suggest they may have the adaptation of play behaviors in ages and sexes, which may help them adapt to their habitat and social system.

Amiodarone is commonly used in acute care due to its effectiveness in several arrythmias and safety if structural heart disease is present or unknown. However, it can have a proarrhythmic effect. We presented a case of iatrogenic arrhythmic storm due to concomitant use of amiodarone plus tiapride resolved with isoproterenol.

Background and Objectives Granular myringitis is troublesome for otologist because uncertain etiology and often been overlooked due to vague clinical symptoms and signs. The ideal treatment is elusive. Our study was to investigate the clinical characteristics of granular myringitis and analyzing the effect of the two different strategies, including carbon dioxide laser (CO2 laser) and caustic agent cauterization to manage granular myringitis. Study Design: Retrospective review Subjects and Methods One hundred and thirty patients with granular myringitis receiving treatment at a single medical center from July 2009 to January 2018 were enrolled. We retrospectively reviewed the charts and surgical records. The main two different strategies to manage focal refractory granular myringitis were analyzed, including carbon dioxide laser and caustic solution. We also recorded the clinical course and determine which strategy is better. Results One hundred and thirty patients with granular myringitis were enrolled. 47/130 (36.1%) had previous otologic procedures. Frequent ototrrhea is the most common symptom (66.1%). Posterior-inferior quadrant is the most common site of involvement (58%). The successful rate of CO2 laser, caustic agent were 94.9% and 79.2%. The recurrence rate was comparable between CO2 laser and caustic agent. No major complication was found in either individual group. Conclusion: Otologic procedure may be a predisposing factor of focal chronic myringitis. Ear drops had poor efficacy compared to other treatments. It can be apply only on minor and fresh symptom cases. In this study, we suggest CO2 laser can be the first line treatment, especially for the troublesome or refractory GM cases, which had the higher successful rate and less complication comparing to caustic agent cauterization.

Critical care provision is fundamental in all developed health systems in which severe disease and injury is managed. This is especially true in major trauma centres and high-acuity establishments, where acutely unstable patients can be admitted at any time, requiring clinical monitoring and interventions appropriate for their burden of illness. This single-centre, prospective service evaluation applied validated scoring systems to a surgical population, sampling and following those considered “high-risk” through to discharge or death, alongside all intensive care unit (ICU) admissions during 2019. Primarily we aimed to quantify the number of patients objectively suitable for Level 2 critical care, conventionally provided in a high-dependency unit (HDU) setting. Secondary outcome measures included ICU readmission rate, in-hospital mortality, and delays to ICU admission and discharge. Of the “high-risk” surgical patients, more than eight per week were found to have peri-operative Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) scores that would advocate critical care admission. Only one individual received scheduled peri-operative critical care. Post-operative mortality in this group was 6.1%, though none of these patients was admitted to ICU prior to death. There were 605 ICU admissions in 2019, with 32.1% of admitted days spent at the equivalent of Level 2 critical care, which could have been administered in a HDU if one was available. The ICU readmission rate was 6.45%. This data demonstrates substantial unmet critical care needs, with patients not uncommonly managed in clinically inappropriate areas for extended periods due to delays accessing ICU. A designated HDU may mitigate clinical risk from this subgroup, reducing morbidity and in-hospital mortality, and this methodology for assessing requirements could be used in other similar institutions.

Introduction Silver nitrate is commonly used within otolaryngology to treat granulation tissue in severe otitis externa. It appears radio-opaque on CT (computed tomography) imaging and therefore can mimic bony fragments and foreign bodies. This is particularly cumbersome when the phenomena correlates to the clinical complaint. Discussion We report two cases of 73-year-old and 75-year-old males who presented with chronic otalgia and discharge. Granulation tissue in the external auditory canal was identified and chemically cauterised with silver nitrate. Subsequent CT petrous bones demonstrated an unidentified foreign body in the canal with extensive soft tissue swelling giving an impression of a wick in situ and “minor bony erosion in the left external acoustic canal” respectively. An additional CT of a 57-year-old female who had been treated with silver nitrate for granulomatous tissue reported “multiple highly radiopaque foci in the external auditory canal, suggestive of foreign body”. Though relatively unknown, this phenomenon has been reported in literature. However, there are few reports of silver nitrate artefacts in CT images of the head no cases in the context of otitis externa. Our patients avoided further imaging or surgery following clarification with the radiologists and symptomatic improvement with long-term intravenous antibiotics. Conclusion Given the prevalence of CT imaging and cauterization in otolaryngology, we recommend contemporaneously documenting the use of silver nitrate and highlighting this on request forms to avoid alarming erroneous reports, unnecessary investigation and surgical procedures. We also recommend, where clinically acceptable, to use silver nitrate prior to imaging.

Introduction Spirometry plays an important role in the assessment of possible respiratory failure in children with neuromuscular disorders (NMDs). However, obtaining reliable spirometry results is a major challenge. We studied the relation between Forced Oscillation Technique (FOT) and spirometry results. FOT is an easy, non-invasive method to measure respiratory mechanics, i.e. respiratory resistance R and respiratory reactance X. We hypothesized an increased resistance R and reduced reactance X in patients with more reduced lung function. Methods In this prospective single center study we included all children with NMDs able to perform spirometry. We consecutively measured respiratory resistance R and reactance X at 5, 11 and 19 Hz and (Forced) Vital Capacity, Peak Expiratory Flow. Spearman correlation coefficients were calculated and regression curves were estimated. Results We included 148 patients, with a median age of 13 years (IQR 8-16). All correlation coefficients were statistically significant with p = 0.000. A negative correlation was found between resistance R and spirometry outcomes (spearman correlation coefficient (ρ) between -0.5 and -0.6). A positive correlation was found between reactance X (i.e. less negative outcomes) and spirometry outcomes (ρ between 0.4 and 0.6). Highest correlation was found at lower frequencies. Regression analysis showed a non-linear relation between FOT and spirometry results. Conclusion We found a non-linear relation between FOT and spirometry results with increased resistance R and reduced reactance X in patients with more restrictive lung function decline. Given the difficulties with performing spirometry, FOT may be a promising surrogate measure of lung function.

Cold-pressed hempseed oil (HSO) is known to have many health benefits due to many phytochemicals and high polyunsaturated fatty acids content. In this study, HSO oleogels were prepared with 3, 5, and 7% natural waxes including sunflower wax (SW), rice bran wax (RBW), beeswax, and candelilla wax to evaluate their potential as solid fat replacements in margarines and spreads. Firmness, crystal structures, and melting properties of these oleogels were evaluated. In general, wax-based HSO oleogels except for RBW-HSO oleogels had lower firmness and weaker crystal network than the corresponding soybean oil (SBO) oleogels. In contrast, RBW-HSO oleogels had similar firmness, comparable or stronger crystal network, and higher melting and crystallization enthalpies compared to those of SBO oleogels. After removing polar compounds from HSO, waxes except for RBW provided oleogels with greater firmness, higher melting and crystallization enthalpies, and stronger crystal network. Therefore, it was concluded that polar compounds negatively affected the physical properties of wax-HSO oleogels but not those of RBW-HSO oleogels. Margarine samples were prepared with SW- and RBW-HSO oleogels, and their firmness and melting properties were examined. The firmness of these margarines indicated that wax-HSO oleogels may achieve the firmness of commercial spreads with less than 3% wax while the firmness of stick margarines cannot be achieved even with 7% wax. Although the properties of wax-HSO oleogels should be further improved, they showed potential as solid fat replacements in margarines and spreads.

Abstract Objectives: To assess the impact of risk factors on the disease control among CRS patients, following 1 year of functional endoscopic sinus surgery (FESS), and combining the risk factors to formulate a convenient, visualized prediction model. Design: A retrospective and nonconcurrent cohort study Setting and Participants: A total of 325 patients with Chronic rhinosinusitis (CRS) from June 2018 to July 2020 at the First Affiliated Hospital, the Third Affiliated Hospital, and the Seventh Affiliated Hospital of Sun Yat-sen University. Main Outcomes Measures: Outcomes were time to event measures: the disease control of CRS after surgery 1 year. The presence of nasal polyps, smoking habits, allergic rhinitis (AR), the ratio of tissue eosinophil (TER), and peripheral blood eosinophil count (PBEC)and asthma was assessed. The logistic regression models were used to conduct multivariate and univariate analyses. Asthma, TER, AR, PBEC were also included in the nomogram. The calibration curve and AUC (Area Under Curve) were used to evaluate the forecast performance of the model. Results: In univariate analyses, most of the covariates had significant associations with the endpoints, except for age, gender, and smoking. The nomogram showed the highest accuracy with an AUC of 0.760 (95% CI, 0.688-0.830) in the training cohort. Conclusions: In this cohort study that included the asthma, AR, TER, PBEC had significantly affected the disease control of CRS after surgery. The model provided relatively accurate prediction in the disease control of CRS after FESS and served as a visualized reference for daily diagnosis and treatment.

Introduction: Voltage-gated sodium (Nav) channels encoded by SCNs are heteromeric protein complexes containing pore-forming α subunits together with non-pore-forming β subunits. Methods: To analyze the expression of SCNs in the samples of different types of breast cancer (BC) patients and the relationship between the expression of α and β subunits and the prognosis of in BC patients, the study investigated the roles of SCNs in the prognosis of BC using ONCOMINE, UALCAN, Kaplan-Meier Plotter, GEPIA, Metascape, LinkedOmics databases. The study analyzed significant changes of SCNs expression and prognosis in transcription level between BC and normal samples, and association of mRNA expression of distinct SCNs family members with prognosis in overall BC patients and HER2-positive/HER2-negative subgroups, respectively. Moreover, we predicted functions and pathways of the mutations in SCNs and their neighbor genes in BC patients by GO/KEGG and GSEA analysis. Results: The results showed that transcriptional and proteinic expressions of 9 SCNs were downregulated in patients with BC, including SCN1A~4A, 7A, 9A and SCN2B~4B. low expressions of 11 SCNs members were found to be significantly associated with poorer overall survival (OS) in BC patients (P＜0.01), including SCN2A, 3A, 5A, 7A, 9A~11A and SCN1B~4B. Moreover, prognostic value of mRNA expression of SCNs could only be seen in HER2-negative BC patients when we performed subgroup analysis. Conclusions: These results indicated that SCNs could be prognostic biomarkers for survivals of BC patients. Some medicines that regulate SCNs might provide new targets for BC treatment.

Children with chronic wet cough and without cystic fibrosis (non-CF) may suffer from chronic suppurative lung disease (CSLD) or bronchiectasis. Pseudomonas aeruginosa (Pa) can be one of the offending microbes in these children. The present study aimed to describe the clinical course of children with the above two conditions who were infected with Pa.

Gut microbiome is vertically transmitted by maternal lactation at birth in mammals. In this study, we investigated the gut microbiome and diet compositions of muskox, a large herbivore in the high Arctic. From muskox feces in Ella Island, East Greenland, we compared the microbiota composition using bacterial 16S rRNA gene sequencing and the dietary compositions of six female adults and four calves have been compared. Firmicutes was the most abundant bacterial phylum in both adults and calves, comprising 94.36% and 94.03%, respectively. There were significant differences in the relative abundance of two Firmicutes families: the adults were mainly dominated by Ruminococcaceae (73.90%), while the calves were dominated by both Ruminococcaceae (56.25%) and Lachnospiraceae (24.00%). Stable isotope analysis on the feces and eight referential plant samples in the study area showed that both adults and calves had similar ranges of 13C and 15N, possibly derived from the dominant diet plants of Empetrum nigrum and Salix glauca. Despite the similar diets, the different gut microbiome compositions in muskox adults and calves indicate that the gut microbiome of the calves may not be fully colonized yet as much as the one of the adults.

We report a case of a 9-day-old newborn who underwent arterial embolization for Kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP), combined with sirolimus treatment, and the outcome was favorable. To the best of our knowledge, there are no case reports of such small infants undergoing arterial embolization to treat KHE. Our successful experience of treating KHE with KMP showed that transcatheter arterial embolization is feasible and can be used as an alternative to surgical resection, even in small infants.

Minerva SinghCenter For Environmental Policy (CEP),Imperial College London, London, UKms507@ic.ac.uk

Aim: Study the influence of calcineurin inhibitors (CNI) and genetic polymorphisms of transporters on enterohepatic circulation (EHC) of mycophenolic acid (MPA) in Chinese adult renal allograft recipients and estimate the effect of various covariates on prediction performance of MPA AUC0-12h. Method: MPA concentrations of 125 Chinese patients were collected 0-12 hours after administration. Genotypes of transporters were determined in 64 patients. The influence of type of CNI and genetic polymorphisms on MPA exposure was studied. Shapley additive explanations method was used to study the impact of sampling times and covariates related to EHC on AUC0-12h. Extreme gradient boosting (XGboost) machine learning-based model was established to predict AUC0-12h. Results: Dn-AUC6-12h was significantly lower in patients co-administered with CsA (P<0.05). When co-administered with TAC, for SLCO1B1 T521C or ABCC C-24T, patients with wild-type genotype had significantly higher dn-AUC6-12h (P <0.05). Patients with SLCO1B3 334T/699G alleles had significantly lower dn-AUC6-12h than homozygotes (P=0.004). No significant difference was found in CsA subgroup. For estimating AUC0-12h, C0h, C2h, C8h, type of CNI, transporters genotypes and the difference between C0h and C2h were retained in the final model, which had good prediction performance (r2=0.9739). Conclusion: Patients co-administered with CsA had lower MPA EHC than those who received TAC. MPA EHC is affected by ABCC2 C-24T, SLCO1B3 T334G/G699A, and SLCO1B1 T521C genotypes in patients treated with TAC. Type of CNI and genetic polymorphisms of transporters can improve prediction performance of MPA AUC0-12h estimating model, developed using XGboost machine learning method.

Droplet breakup in micro-constrictions is an important phenomenon in industrial applications. This work aimed to investigate the droplet breakup in the square microchannel with a short square constriction to generate the slug flow, which drew little attention before. Mechanism analysis indicated that this breakup process included the shear-force-dominated, squeezing-force-dominated, and pinch-off stages. Non-uniform daughter droplets were generated in the constriction with their interface restricted in the horizontal and perpendicular directions by the microchannel walls. The average relative deviation of the daughter droplet size was < 30%, much lower than that for the breakup with the daughter droplet restricted only in one direction. An empirical equation with a deviation of < 20% was provided to show the dependence of the daughter droplet size on the operation conditions. The comparison results suggested that the different restriction effects of microchannel wall on daughter droplets led to the different breakup mechanisms in different constrictions.

Reactive polymer blending is basically a flow/mixing-driven process of interfacial generation, interfacial reaction for copolymer formation and morphology development. This work shows two antagonistic effects of mixing on this process: while mixing promotes copolymer formation by creating interfaces and enhancing collisions between reactive groups at the interfaces, excessive mixing may pull the in-situ formed copolymer out of the interfaces to one of the two polymer components of the blend, especially when the copolymer becomes highly asymmetrical. As such, the copolymer may loss its compatibilization efficiency. The mixing-driven copolymer pull-out from the interfaces is a catastrophic process (less than a minute), despite the high viscosity of the polymer blend. It depends on the molecular architecture of the reactive compatibilizer, polymer blend composition, mixing intensity and annealing. These findings are obtained using the concept of reactive tracer-compatibilizer and a model reactive polymer blend.

It is of great interest to elucidate the biogeographic patterns of soil microorganisms and their driving forces, which is fundamental to predicting alterations in microbial-mediated functions arising from environment changes. Although the vertical movement of dissolved organic matter (DOM) drives the cycle of nutrients such as soil carbon but, in the restored ecosystem, the relationship between DOM and soil microbial nutrient utilization remains to be determined. Here, we investigated the changes of soil microbial community at 0-40 cm depth profile in three stages (10-, 30-, 50-years) of succession in Larix olgensis plantations and the fluorescence spectrum composition of DOM. With the increase of soil depth, the signal source of microorganisms increases. In a coniferous forest soil environment, the possible main source of DOM in deep soil is the production of microbial metabolism. Difficulty in the decomposition of organic matter determines the distribution and composition of microorganisms. Increasing forest age makes bacteria and fungi more specific and bacterial-fungal associations greater. Overall, our work contributes to the understanding of factors underlying microbial community distribution in plantation forests and the importance of DOM quality in building microbial communities.

The acute and severe rise in systemic blood pressure during or after cardiac operations may be life-threatening and result in end-organ injury. This case is the first report of spontaneous left atrial appendage rupture following the hypertensive crisis in cardiac surgery

 In this paper in an elegant way will be presented the unity formulas for the coupling constants and the dimensionless physical constants. We reached the conclusion of the  simple unification of the fundamental interactions. We will find the formulas for the Gravitational constant. It will be presented that the gravitational fine-structure constant is a simple analogy between atomic physics and cosmology. We will find the expression that connects the gravitational fine-structure constant with the four coupling constants. Perhaps the gravitational fine-structure constant is the coupling constant for the fifth force. Also will be presented the simple unification of atomic physics and cosmology. We will find the formulas for the cosmological constant. This article will be followed by the energy wave theory and the fractal space-time theory.