We propose and experimentally investigate a parity-time (PT) symmetric coupled optoelectronic oscillator (COEO) based on a polarization-dependent spatial structure. In such a COEO system, the gain/loss and coupling coefficients of two orthogonal-polarization optical waves can be controlled by adjusting the polarization controller (PC) and the bias voltage of the Mach-Zehnder Modulator (MZM). The single-mode selection can be implemented by the PT symmetry breaking of a special mode. The performance of the proposed COEO is experimentally examined, and a 10.0 GHz microwave signal with a phase noise of −109.1 dBc/Hz @10 kHz and a side mode suppression ratio of 51.4 dB is generated.

Pulmonary arterial hypertension (PAH) is a rare and devastating disease of the pulmonary vasculature with a high morbidity and mortality rate in infants and children. Currently, treatment approaches are mostly based on adult guidelines and pediatrician clinical experience, focusing on specific pulmonary antihypertensive therapy and conventional supportive care. The advent of targeted drugs has led to significant advances in the treatment of PAH in children, including endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins, which have been studied and proven to improve hemodynamics and functional class in children PAH. A new targeted drug, riociguat, is assessing its safety and efficacy in clinical trials. However, more randomized controlled studies are needed to evaluate the combination of drugs, treatment strategies, and clinical endpoints of targeted therapy in children PAH. In this review, we summarize the research advances of PAH-targeted therapy in children over the last decade in order to provide a theoretical basis for future studies.

Abstract Background and Purpose NFEPP is a newly-designed pain killer selectively activating G-protein coupled mu opioid receptors in injured tissues, and therefore devoid of central side effects. However, the cellular mechanisms underlying NFEPP’s antinociceptive effects were not examined in sufficient detail so far. Here we investigated the effects of NFEPP on G-protein activation, on voltage gated calcium channels and on mu opioid receptor phosphorylation. Experimental Approach HEK293 cells stably transfected with mu opioid receptors were used to study [35S]-GTPγS binding and mu opioid receptor phosphorylation. Voltage dependent calcium currents and intracellular calcium signals were examined in rat sensory neurons. All experiments were performed at acidic and physiological pH values using NFEPP compared to the conventional mu opioid receptor agonist fentanyl. To investigate the role of G protein subunits, we used pertussis toxin and gallein. Key Results At low pH, NFEPP produced more efficient G-protein activation and reduction of calcium currents in depolarized sensory neurons. The latter was mediated by G protein βγ subunits and NFEPP-mediated MOR phosphorylation was pH-dependent. Fentanyl-induced signaling was not affected by pH changes. Conclusion and Implications Our study shows that, at low pH, MOR signaling induced by NFEPP is more effective and neuronal calcium channels are directly modulated by G protein βγ subunits dissociated from G protein αi/o subunits. Apparently, the enhanced efficacy of NFEPP is dependent on extra- rather than intracellular effects on opioid receptor function.

Background and aims: We aimed to analyze the correlation of urinary with serum NT-proBNP concentrations in acute bronchiolitis and its association with the severity of the disease.  Material and Methods: A pilot observational study conducted between 1st October and 31st March 2022, including acute bronchiolitis cases who attended our institution. Serum and urinary NT-proBNP concentrations were determined using the Alere NT-proBNP assay in time-matched urine and blood samples. We explored the linear relationship between both concentrations and compared clinical outcomes indicative of severe acute bronchiolitis between groups of raised and normal urinary NT-proBNP.  Results: 17 infants (median age 68 (36-91) days) with 36 time-matched samples were included. The urinary and serum concentrations of NT-proBNP were significantly correlated with (r=0.867 & R-squared coefficient=0.751; p<0.001). The log-10-transformed urinary NT-proBNP concentrations were higher at the time of hospital admission in those infants that required PICU admission with ventilatory support compared with those without this outcome (1.85 (1.16-2.44) pg/mg vs 0.63 (0.45-0.84) pg/mg); p<0.001); and resulted positively and strongly correlated with the duration of the ventilatory support (rho=0.76; p<0.001) and the LOS hospitalization (rho=0.84; p<0.001) Conclusion: The measurement of urinary NT-proBNP concentrations could be a reliable surrogate for serum NT-proBNP levels highlighting the potential value of the urinary NT-proBNP as a non-invasive tool to assess severity in acute bronchiolitis.

Acute respiratory distress syndrome (ARDS) is an acute respiratory failure syndrome caused by non-cardiogenic pulmonary edema of various etiologies.[1](#ref-0001) When the fetus encounters asphyxia, acidosis, infection, meconium inhalation, et al. during childbirth, the inflammatory pathway will be activated. The systemic inflammatory response can remove pathogens, but the excessive inflammatory response will prompt pulmonary surfactant (PS) inactivation and increase the permeabilities of alveolar epithelial and endothelial cells, resulting in the accumulation of edema fluid in the alveoli and eventually leading to severe hypoxemia, respiratory distress and decreased lung compliance.[1,2](#ref-0001) Population-based studies in the United States, Australia, Europe, and New Zealand reported that the incidence of ARDS in children is 2.0-12.8 per 100000 person-years,[3](#ref-0003) and according to the interim report of the International Neonatal ARDS Multicenter Study, the mortality of neonatal ARDS (NARDS) is approximately 20%.[4](#ref-0004) Due to the high mortality of NARDS, the researchers try to explore potential new treatments to limit the incidence and mortality of NARDS. Systemic inflammatory response plays a significant role in the occurrence and development of NARDS, budesonide, a non-halogenated corticosteroid, has a potent local pulmonary anti-inflammatory effect, therefore, it may be an effective treatment option for NARDS. This article reviews the evolution of ARDS definition and diagnosis, pathophysiological mechanisms of NARDS, and gives an outlook on the application of budesonide in NARDS.

In conclusion, our data suggest that subjects with genotype 5T;TG12/VVCC likely have a very low risk of progressing to CF, as compared to those with F508del/5T;TG12. 4 This observation could lead to differentiate follow up in presence of at least one 5T;TG12. Knowing these data is crucial to offer a useful counseling for CRMS/CFSPID infants and for non‐CF adults with CBAVD alone. Anyway further data are needed to evaluate the outcomes after a longer follow up.

Based on Carpentier’s classification and principles, the techniques for mitral valve repair continue to evolve. We herein report our experience with the morpho-functional echocardiographic analysis of single mitral leaflets, as different anatomic features, even if conflicting, may coexist not only in the two leaflets, but in the same leaflet as well. A classification is proposed, based on the length (normal, short, or long) and mobility (normal, restricted, or excessive) of mitral leaflets. The surgical techniques adopted for mitral valve repair are the direct consequence of this analysis.

In this paper, we mainly study the dual problem of semi-infinite programming problem with mixed constraints. we introduce the concept of higher-order (φ,ρ)-V-invexity and construct Wolfe and Mond-Weir type dual models. Weak, strong and strict converse duality theorems are discussed under the assumptions of higher-order (φ,ρ)-V-invexity.

Mitral valve repair is the procedure of choice to correct mitral regurgitation. However, some dangerous complications, correlated to the surgical technique, can occur in the operating theatre, at the end of the procedure. The most frequent is the systolic anterior motion. Due to a systolic dislocation of the anterior leaflet toward the outflow tract, it causes both obstruction of the outflow tract and mitral regurgitation. Often it is due to excess of catecholamines or to reduced filling of the left ventricle, but sometimes needs further surgical maneuvers, focused on moving posteriorly the coaptation line. It can be obtained by shortening the posterior leaflet or increasing the size of the ring or applying an Alfieri stitch to limit the movements of the anterior leaflet. Another complication, often underdiagnosed and potentially lethal, is the injury of the circumflex artery that happens at the level of the anterolateral commissure or P1 zone. Two mechanisms are involved. The first one is direct injury of the artery by a stitch (roughly 25% of the patients present a distance artery-annulus<3 mm). The second one the distortion of the artery, attracted toward the annulus by a misplaced stitch. The attraction causes kinking with stenosis of different degrees till functional occlusion. However, the artery has to be far from the annulus and the atrial tissue has to be stiff and resistant, as after an infective process, to move the CX toward the annulus without tearing. Positioning the stitches very close to the mitral leaflets in the dangerous area is the only prevention to the complication. The treatment in the operating theatre is partial or total removal/re-implantation of the annular sutures or coronary artery bypass grafting to the circumflex area. If the injury is demonstrated only after a coronary angiography, percutaneous revascularization can be attempted before further surgical treatment.

The chordae tendinae connect the papillary muscles to the mitral valve. While the first-order chordae serve to secure the leaflets to maintain valve closure and prevent mitral valve prolapse, the second-order chordae are believed that they play a role in maintaining normal LV size and geometry. The papillary muscles, from where the chordae tendinae originate, function as shock absorbers that compensate for the geometric changes of the left ventricular wall. The second-order chordae connect the PMs to both trigons under tension. The tension distributed towards the second-order chordae has been demonstrate to be more than three-fold that in the first-order counterpart. Cutting the second-order chordae puts all the tension on the first-order chordae, that can go closer to their rupture point. However, it has been experimentally demonstrated that the tension where the first-order chordae break is 6.8 N, by far higher than the maximal tension reached, that is 0.4 N. Even if the clinical reports have been favorable, the importance of cutting the second-order chordae to recover curvature of the anterior leaflet and increasing the coaptation length between the mitral leaflet has been slowly absorbed by the surgical world. Nevertheless, there are progressive demonstrations that chordal tethering affects the anterior leaflet not only in secondary, but also in primary mitral regurgitation, having a not negligeable role in the long-term outcome of mitral repair.

Mutations in the PAX6 gene are generally associated with aniridia. We describe a family with Juvenile onset open angle glaucoma (JOAG), where two siblings were detected to have a pathogenic variant in the PAX6 gene in the absence of aniridia. Whole exome sequencing was performed for the family where the proband and her sibling were detected to have JOAG and Juvenile ocular hypertension respectively. None of the other family members had any ocular disease. All previously described gene mutations for glaucoma were looked for in the family. The potential pathogenicity of the identified variants was assessed by determining their frequency in large public exome databases; as well as using the current ACMG guidelines. Except, for PAX6 gene no pathogenic variants were found in any of the known genes for glaucoma. A de novo heterozygous variant at NM_001368894.2: c.1166C>A; p. Pro375Gln in the PAX6 gene was detected in the proband and her affected brother. The variant has been described in aniridia patients before and is known to be likely pathogenic by ACMG guidelines. This report expands the phenotypic spectrum of the PAX6 gene to include Juvenile onset open angle glaucoma.

This paper introduces coupled fixed points of maps in MIFSMS. The notion of compatible maps and weakly compatible maps is also defined. Common coupled fixed point theorem for weakly compatible maps have been proved in the setting of MIFSMS. Moreover, some corollaries and an example is given to validate our new result. Also, to show the usability of our findings, we have applied our new result to get the solution of nonlinear Fredholm integral equation.

The industrial production of plants promoter like auxins is gaining interest, in consequence it is important to un- derstand the metabolism of the microorganisms involved and the optimal conditions for their industrial production. In this study the metabolic model of Bacillus subtilis was used to estimate intracellular fluxes and the robustness of the principal branching points of aerobic propionate metabolism for the 3-indoleacetic acid (IAA) production. The robustness analyzes of the metabolic network showed the enzymes that participate in the synthesis of erythrose 4-phosphate and glyceraldehyde 3-phosphate as possible limiting metabolites in the synthesis of IAA and might be a target for metabolic engineering strategies. The phenotype phase plane analysis allowed the identification of the opti- mal rate growth conditions to produce the auxin (less than 0.1 h −1).

n this work, a class of nonlinear multi-point BVPs fractional differential equations involving the Riesz-Caputo derivative is proposed. The nonlinearity term f involves the left Caputo derivative. Under given some conditions, the existence and uniqueness of the solution are provided. Our analysis relies on the Krasnoselskii's fixed point theorem, Schauder fixed point theorem and the Banach contraction principle. Finally, some examples are given to illustrate our main results.

In this paper, we focus on the following nonlinear Schr\”odinger equations with linear couples \begin{equation*} \begin{cases} -\Delta u+V_1(x)u+\lambda_1u=\mu _1\int\limits_{\mathbb{R}^{3}}\frac{|u(y)|^p}{|x-y|}\,dy|u|^{p-2}u+\beta v \hspace{5mm} \text{in} \hspace{1mm}\mathbb R^{3},\\ -\Delta v+V_2(x)v+\lambda_2v=\mu _2\int\limits_{\mathbb{R}^{3}}\frac{|v(y)|^q}{|x-y|}\,dy|v|^{q-2}v+\beta u \hspace{5mm} \text{in} \hspace{1mm}\mathbb R^{3},\\ \int\limits_{\mathbb{R}^{3}}|u|^2\,dx=a, \hspace{1mm} \int\limits_{\mathbb{R}^{3}}|v|^2\,dx=b, \end{cases} \end{equation*} where $\frac{5}{3}0$, $a,b\geq 0$, $\beta \in \mathbb{R}\setminus\{0\}$, $\lambda_1,\lambda_2\in\mathbb{R}$ are Lagrange multipliers and $V_1(x),V_2(x):\mathbb{R}^{3}\to \mathbb{R}$ are trapping potentials. We prove the existence of the solutions with prescribed $L^2(\mathbb{R})$-norm with trivial trapping potentials and nontrivial trapping potentials by applying the rearrangement inequalities.

Ingested-derived DNA (iDNA) from insects can represent a powerful tool for assessing vertebrate diversity because insects are easy to sample, have a varied diet, and are widely distributed. Despite these advantages, the use of iDNA for mammalian detection is still little explored, especially in the neotropical region. Here we aimed to compare the effectiveness of mosquitoes and flies to detect mammals in a semi-controlled area of a Zoo that houses native and non-native species. We evaluated the number of mammal species detected by the iDNA samplers and verified the distance range of each sampler group for detecting the mammal species. To capture mosquitoes and flies we used CDC (Center for Disease Control) and fish-baited plastic bottle traps, respectively, distributed in eight sampling points during five days. Using two mini-barcodes (12SrRNA and 16SrRNA) and the metabarcoding approach, we identified 45 Operational Taxonomic Units from 10 orders. There was no difference between the number of species recovered per individual insect, although the number of flies captured was higher, resulting in more mammal species recovered by this insect group. Eight species were recorded exclusively by mosquitoes and 20 by flies, suggesting that using both samplers allowed a more comprehensive screening of the biodiversity. The maximum distance recorded was 337 m for flies and 289 m for mosquitoes, but the average range distance did not differ between insect groups. Our essay proved to be quite efficient for the mammal detection, considering the high number of species detected with a reduced sampling effort. Thus, combining iDNA from different samplers and metabarcoding can be a powerful tool for mammal survey and monitoring in the neotropics.

Background: Since circulating tumor cells (CTCs) are precursors of metastatic lesions, extracting CTCs from whole blood is useful in obtaining information for cancer treatment. One of the CTC extraction methods is the size selection method; however, since the conventional methods are expensive and cumbersome, we developed an affordable and simple filter, whose usefulness is verified in this study. Methods: The new filter (hereafter, soft micropore filter [SMPF]) is made up of a polyethylene film with a thickness of 15 μm and conical pores having a diameter of 8–10 μm, which are opened uniformly (opening rate, 20%). This filter can filter whole blood by free-falling under gravity. The possibilities of the filter’s usage for model CTC extraction, immunostaining, short-term cell culture, and gene mutation detection in extracted model CTCs were verified. Results: S-MPF was able to extract model CTCs with an extraction rate of up to 15%. These model CTCs were detected by cytology, immunostaining, and culture by short-term incubation of filtered cells. Furthermore, genetic mutations were identified in the cultured cells. In addition, CTC extraction from the peripheral blood of patients with lung cancer was demonstrated by setting the volume of collected blood to 15 mL to prevent a low recovery rate. Conclusions: The S-MPF can be used to extract model CTCs quickly and easily. Moreover, cytological diagnosis, immunostaining, short-term culture, and gene mutation search are possible with this filter. Given its proven applicability in clinical samples, this sample can be used in clinical settings.

Mitral valve regurgitation (MR) is a common valvular disorder occurring in up to 10% of the general population. Mitral valve reconstructive strategies may address any of the components, annulus, leaflets and chords, involved in the valvular competence. The classical repair technique involves the resection of the prolapsing tissue. Chordal replacement was introduced already in the ’60, but in the mid ’80, some surgeons started to use expanded polytetrafluoroethylene (ePTFE) Gore-Tex sutures. In the last years, artificial chords have been exploited because of transcatheter techniques such as NeoChord DS 1000 (Neochord, USA) and Harpoon TSD-5. The first step is to achieve a good exposure of the papillary muscles that before approaching the implant of the artificial chords. Then, the chords are attached to the papillary muscle, with or without the use of supportive pledgets. The techniques to correctly implant artificial chords are many and might vary considerably from one center to another, but they can be summarized into three big families of suturing techniques: single, running or loop. Regardless of how to anchor to the mitral leaflet, the real challenge that many surgeons have taken on, giving rise to some very creative solutions, has been to establish an adequate length of the chords. It can be established basing on anatomically healthy chords, but it is important to bear in mind that surgeons work on the mitral valve when the heart is arrested in diastole, so this length could fail to replicate the required length in the full, beating heart. Hence, some surgeons suggested techniques to overcome this problem. Herein, we aimed to describe the current use of artificial chords in real world surgery, summarizing all the tips and tricks.

Gastrointestinal stromal tumors (GISTs) are rare life-threatening forms of cancer representing 0.1%-3% of all gastrointestinal (GI) malignancies. Nursing has become a critical component in handling patients with gastrointestinal tumors. This case report investigates the role of nursing in ruptured GISTs in adolescents and young adults (AYA).

In vitro cell culture experiments are widely used to study cellular behavior in most biological research fields. Except for suspension cells, most human cell types are cultured as adherent monolayers on a plastic surface. While technically convenient, monolayer cultures can suffer from limitations in terms of physiological relevance, as their resemblance to complex in vivo tissue structures is limited. To address these limitations, three-dimensional (3D) cell culture systems have gained increased interest as they mimic key structural and functional properties of their in vivo tissue counterparts. Nevertheless, protocols established on monolayer cell cultures may require adjustments if they are to be applied to 3D cell cultures. As gene expression quantification is an essential part of many in vitro experiments, we evaluated and optimized a direct cell lysis, reverse transcription and qPCR protocol applicable for 3D cell cultures. The newly developed protocol wherein gene expression is determined directly from crude cell lysates showed improved cell lysis compared to the standard protocol, accurate gene expression quantification, hereby avoiding time-consuming cell harvesting and RNA extraction.

Coffin-Siris syndrome is a rare disorder which can be difficult to recognize. A broad spectrum of nonspecific clinical features is associated with Coffin-Siris syndrome and expression of these features is diverse. We describe two cases with Coffin-Siris syndrome with mutations in the ARID1A gene, with dissimilar presentation and clinical course.

We describe the initial results of Emicizumab prophylaxis in twins diagnosed with severe Hemophilia A and inhibitors with intron 22 inversion. Prophylaxis was initiated in both the twins showing high annual bleed rate and difficult venous access. The treatment resulted in zero spontaneous bleeds and there were no adverse events.

A document by Jiyun Han. Click on the document to view its contents.

Glycoprotein (GP) IIb/IIIa are now being widely used in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). With the growing use of these medications, there is an increase in adverse events related to them being reported in the literature, including severe thrombocytopenia.