Objective (69) The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow’s triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation. Methods (42) With the authorization of the Ethics Committee, a research project was undertaken on intralesional and extralesional blood samples from 30 pediatric patients afflicted with spongiform VM. Thromboelastometry analyses were performed using ROTEM ® Sigma, and the concentration of syndecan-1 was determined by ELISA. Results (80) In the ROTEM ® analyses, the A5, A10, and MCF values were below the established reference ranges in the intralesional samples in both the EXTEM and INTEM assays indicating that intralesional clots had significant instability. Furthermore, during the investigation of the delayed fibrinolysis phase using recombinant tissue plasminogen activator (rtPA) in EXTEM analysis, widespread hyperfibrinolysis was observed intralesional. Additionally, analysis of syndecan-1 showed significant differences between extralesional and intralesional levels (p<0.026) and controls (p<0.03), suggesting differences in the state of endothelium. Conclusions (39) For the first time, we developed a comprehensive understanding of the coagulopathic profile of VM and the role of endothelial dysfunction in its pathogenesis. These findings will enable the implementation of targeted therapies based on the individual coagulation profiles.
INTRODUCTION: Inappropriate sinus tachycardia (IST) is a common condition with frequently not tolerated beta-blockers or ivabradine and a high rate of complication in ablation strategy; we describe an alternative anatomical approach of sinus node modulation. METHODOLOGY: This retrospective study describes a case series of 6 patients from two centers diagnosed with symptomatic IST undergoing sinus node ablation. RESULTS: The mean age was 40.6 ± 13.9 years; five of the six patients were female, 100% of patients reported heart palpitations, and 66% reported dizziness, the average HR on a 24-h Holter was 93.2 ±7.9 bpm. HR during the first stage of a stress test using a standard Bruce protocol was 150 ±70 bpm, The average HR on 24-hour Holter post-ablation was 75 ± 5.6 bpm, the sinus rate HR during stage 1 of a Bruce protocol exercise stress test was 120 ± 10 bpm. CONCLUSION: This is the first case series reporting the acute and long-term results of a novel anatomical approach for SNM to treat IST targeting the AR under ICE guidance, The novel anatomic ICE-guided catheter ablation approach aimed to identify the earliest activation at the AR with an extension of RF lesions towards its septal region seems effective and safe to modulate the SN in symptomatic patients with IST refractory to medical treatment.
Direct synthesis of layer-tunable and transfer-free graphene on technologically important substrates is highly valued for various electronics and device applications. Here, we report a novel synthesis approach combining ion implantation for a precise graphene layer control and dual-metal smart Janus substrate for a diffusion-limiting graphene formation, to directly synthesize layer-tunable graphene on arbitrary substrates without the post-synthesis layer transfer process. C ion implantation was performed on Cu-Ni film deposited on a variety of device-relevant substrates. Upon thermal annealing to promote Cu-Ni alloying, the pre-implanted C-atoms in the Ni layer are pushed towards the Ni/substrate interface by the top Cu layer due to the poor C-solubility in Cu. As a result, the expelled C-atoms precipitate into graphene structure at the interface facilitated by the Cu-like alloy catalysis. After removing the alloyed Cu-like surface layer, the layer-tunable graphene on the desired substrate is directly realized. ReaxFF was performed to elucidate the graphene formation mechanisms in this novel synthesis approach. Three ordinary devices using as-synthesized graphene were fabricated on Si, SiO2, and glass substrates to demonstrate the graphene quality of our layer-tunable and transfer-free synthesis approach and the excellent performance characteristics of these low-cost manufacturing devices: field-effect transistors, heating devices, and near-infrared photodetectors.
Introduction: Pulsed electric field (PEF) ablation relies on the intersection of a critical voltage gradient with tissue to cause cell death. Field-based lesion formation with PEF technologies may still depend on catheter-tissue contact (CTC). The purpose of this study was to assess the impact of CTC on PEF lesion formation with an investigational large area focal (LAF) catheter in a preclinical model. Methods: PEF ablation via a 10-spline LAF catheter was used to create discrete RV lesions and atrial lesion sets in 10 swine (8 acute, 2 chronic). Local impedance (LI) was used to assess CTC. Lesions were assigned to 3 cohorts using LI above baseline: No Tissue Contact (NTC: ≤∆10Ω, close proximity to tissue), Low Tissue Contact (LTC: ∆11-29Ω), and High Tissue Contact (HTC: ≥∆30Ω). Acute animals were infused with triphenyl tetrazolium chloride (TTC) and sacrificed ≥2hrs post-treatment. Chronic animals were remapped 30 days post-index procedure and stained with infused TTC. Results: Mean (±SD) RV treatment sizes between LTC (n=14) and HTC (n=17) lesions were not significantly different (depth: 5.65±1.96mm vs 5.68±2.05mm, p=0.999; width: 15.68±5.22mm vs 16.98±4.45mm, p=0.737) while mean treatment size for NTC lesions (n=6) was significantly smaller (1.67±1.16mm depth, 5.97±4.48mm width, p<0.05). For atrial lesion sets, acute and chronic conduction block were achieved with both LTC (N=7) and HTC (N=6), and NTC resulted in gaps. Conclusions: PEF ablation with a specialized LAF catheter in a swine model is dependent on CTC. LI as an indicator of CTC may aid in the creation of consistent transmural lesions in PEF ablation.
Most scientist agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in 9 gerbils to induce tinnitus and a sham exposure in 3 control animals. Tinnitus was assessed by a behavioral response paradigm. Four of the trauma animals did show tinnitus 13 days after trauma (T), the remaining 5 trauma (NT) and the 3 control animals (C) did not show the percept. The ECM density 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. We found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals’ ACs compared to NT or C animals’ cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus.
Background Approximately 70 % of individuals allergic to birch pollen (Bet v 1.01 [Bet]) develop a secondary food allergy (e.g. hazelnut: Cor a 1.04 [Cor]), due to allergen cross-reactivity. However, standard immunotherapy for type I allergies often does not improve the food allergy sufficiently. We analyzed the allergen-specific and cross-reactive suppressive capacity of primary human regulatory T cells (Treg) induced by autologous IL-10-modulated dendritic cells (IL-10 DC) in vitro and in vivo. Methods CD4 + T cells of patients with birch pollen and associated hazelnut allergies were differentiated into Bet-specific or non-specific induced Treg (iTreg). After Bet- or Cor- specific restimulation the phenotype, proliferation and suppressive capacity of iTreg subsets were analyzed. iTreg function was further investigated in humanized mouse models of airway and intestinal allergy, generated by engraftment of peripheral blood mononuclear cells from allergic donors into immunodeficient animals. Results After IL-10 DC priming and allergen-specific restimulation (Bet or Cor) non-specific control iTreg remained anergic, whereas Bet-specific iTreg proliferated extensively and exhibited a regulatory phenotype (enhanced expression of CTLA-4, PD-1, TNFR2, IL-10). Accordingly, activated Bet-specific iTreg displayed a high capacity to suppress Bet- and Cor-induced responder T H2 cell responses in vitro, indicating induction of both allergen-specific (birch) and cross-reactive tolerance (hazelnut). In vivo, the beneficial effect of Bet-specific iTreg was verified in humanized mouse models of allergic airway and intestinal inflammation, resulting in reduced allergen-induced clinical symptoms and immune responses. Conclusion Human IL-10 DC-induced iTreg facilitate allergen-specific and cross-reactive tolerance. Therefore, they are potential candidates for regulatory cell therapy in allergic and autoimmune diseases.
Aiming at the problem of weak yawing controllability of solar-powered Unmanned Aerial Vehicles (UAVs) with low-speed and high aspect-ratio Blended Wing Body (BWB) configuration, based on the large-scale aerodynamic characteristics of the biomimetic swallow tail, the influence of different opening methods and angles of the swallow tail on the aerodynamic characteristics and stability and controllability of an UAV was derived. The mechanism of the higher yawing control efficiency of the differential throttle compared to the conventional rudder is analyzed in order to significantly decrease the control efficiency at small throttle. We innovatively propose a yawing control method combining the opening of the swallow tail to a moderately separation state of local airflow and we validate it for the case of the landing control of a solar-powered UAV. The flight dynamics mode characteristics show that this control method has little impact on the lateral-directional stability of the UAV and that the control efficiency can be reserved to the same level of cruise state. Therefore, the control law of cruise state can be applied to landing state with swallow tail open directly, which enhances the lateral-directional control ability of the UAVs in a simple but efficiently way. Flight simulation and flight test results show that the proposed bionic control method of the swallow tail combined with differential throttle can effectively enhance the landing control ability of the UAVs, improve the response speed, and reduce the trajectory error.
Farmland habitats are witnessing steep declines in biodiversity. One rapidly declining farmland species is the Ortolan Bunting. In Finland, a staggering 99% of the population has been lost during the past 30 years. Changes in the breeding habitats have been proposed as a reason for the decline, although hazards during migration and wintering may also play a role. We gathered a 19-year data set of Finnish Ortolan Buntings and studied which spatial characteristics, habitat features, and climate factors might explain the population growth rate at the singing-group level. As explanatory variables we used region, density of small-scale landscape structures, proportion of agricultural area in the landscape, diversity of crop types, proportion of bare ground, and temperature and precipitation of previous breeding season. The only region with a marginally positive growth rate was North Ostrobothnia, where the species often occupies newly established fields. High crop type diversity mitigated the declines by perhaps providing a wide array of feeding, hiding and nesting places. Bare ground benefited Ortolan Buntings by perhaps providing an easy access to food. The last Ortolan Buntings occurred in landscapes dominated by interconnected agricultural land which, we think, reflects the species’ sociability and avoidance of forested areas. We suggest that agricultural intensification and the following potential reduction in food availability may be a cause of the decline of Ortolan Bunting. As general conservation measures, such as promoting set-aside land or field margins, have been inadequate, either in effect or in extent of application, it is evident that work remains. Northern populations of Ortolan Bunting should be targeted for further studies on feeding and breeding ecology as well as for urgent conservation actions, such as increasing crop type diversity and bare ground. Promoting more multi-functional and agro-ecologically managed agricultural landscapes would benefit a wider range of farmland species as well.
Scalable single use adherent cell-based biomanufacturing platforms are part of solutions to realize the full potential of cell and gene therapies. Here, we reported the development of an innovative fixed bed bioreactor platform for the scale-up of adherent cell culture. The bioreactor platform is centered on a packed bed of woven polyethylene terephthalate mesh discs that are vertically stacked and sandwiched between two fluid guide plates. Computational fluid dynamics modeling was used to direct the design and development of bioreactor series, targeting uniform flow with minimal shear stress. Residence time distribution measurements revealed that a pulse injected dye tracer solution passed through the bioreactors with great uniformity and narrow distribution of residence time, mimicking plug flow. Periodic media sampling with an offline analyzer showed that there was minimal gradient of four important metabolites (glucose, glutamine, lactate, and ammonia) across the bioreactor throughout cell growth. The bioreactor platform was further validated in automated cell harvesting with ~96% efficiency and ~98% viability, as well as linear scalability, in terms of both operational parameters and performance, for cell culture and adeno-associated virus vector production. Finally, mathematic models based on oxygen uptake rates were developed and proven effective to model cell growth curves and estimate biomass in real-time. This study shows that this innovative fixed bed bioreactor platform enables linearly scalable adherent cell-based biomanufacturing with high productivity.
Environmental change is becoming synchronous across sites with frequent emergence of extremes in recent years, with alarming potential impacts on species’ synchronous abundance over large scales. With 23 years of breeding bird survey data across North America, we found that some birds are becoming synchronously rare across sites, while others are becoming synchronously common. We evaluated the relative importance of two co-occurring mechanisms (environment-driven and dispersal-driven) to explain such spatial synchrony in extreme low or high abundance (i.e., tail-dependent synchrony). We found that spatial synchrony in temperature extremes (i.e., tail-dependence in climate) was the major driver for birds’ tail-dependent spatial synchrony up to 250 Km. In addition, temperature extremes and dispersal trait both favored synergistically some species making them synchronously common across sites. In a rapidly changing environment, these findings highlight the importance of considering synchronized climatic extremes to assess species’ tail-dependent spatial synchrony across large scale.
Animal societies use nestmate recognition to protect against social cheaters and parasites. In most social insect societies individuals recognize and exclude any non-nestmates and the roles of cuticular hydrocarbons as recognition cues are well documented. Some ambrosia beetles live in cooperatively breeding societies with farmed fungus cultures that are challenging to establish, but of very high value once established. Hence, social cheaters that sneak into a nest without paying the costs of nest foundation may be selected. Therefore, nestmate recognition is also expected to exist in ambrosia beetles, but so far nobody has investigated this behavior and its underlying mechanisms. Here we studied the ability for nestmate recognition in the cooperatively breeding ambrosia beetle Xyleborinus saxesenii, combining behavioural observations and cuticular hydrocarbon analyses. Laboratory nests of X. saxesenii were exposed to foreign adult females from the same population, another population and another species. Survival as well as behaviours of the foreign female were observed. Behaviours of the receiving individuals were also observed. We expected that increasing genetic distance would cause increasing distance in chemical profiles and increasing levels of behavioural exclusion and possibly mortality. Chemical profiles differed between populations and appeared as variable as in other highly social insects. However, we found only very little evidence for behavioural exclusion of foreign individuals. Interpopulation donors left nests at a higher rate than control donors, but neither their behaviours nor the behaviours of receiver individuals within the nest showed any response to the foreign individual in either of the treatments. These results suggest that cuticular hydrocarbon profiles might be used for communication and nestmate recognition, but that behavioural exclusion of non-nestmates is either absent in X. saxesenii or agonistic encounters are so rare or subtle that they could not be detected by our method. Additional studies are needed to investigate this further.
Ectopic duodenal mucosa with adenomatous hyperplasia in the stomach: a case reportXiaowei Cai1, Lin Li1, Yanxia Yang2, Kang Lu1, Peng Wang1*1The 985th Hospital of the Joint Logistics Support Force;2The 986th Hospital of the Joint Logistics Support Force;*Corresponding Author: Peng Wang, Master Degree of Pathology, Department of Pathology, the 985th Hospital of the Joint Logistics Support Force, Qiaodong Road No.30, Taiyuan 030001, China. Email:[email protected].[Abstract] Introduction: Space-occupying lesions in the stomach are common diseases in gastroenterology. The diagnosis often needs the support of pathological results, and the prognosis of different masses is very different. Patient concerns: A 49-year-old man presented with abdominal distension and loss of appetite for one month as the main symptoms. Gastroscopy revealed a space occupying lesion in the pylorus of the antrum. Interventions:The mass was removed by gastroscopy resection with high-frequency electrocautery. Diagnosis: After electroresection, pathological and immunohistochemical examination showed that it was “ectopic duodenal mucosa with adenomatous hyperplasia in the stomach”. This disease has not been reported. Outcomes: After short-term follow-up and endoscopic review of this patient, we concluded that this disease is an extremely rare gastric tumor with benign growth and good prognosis. Conclusion: This case helps us to recognize the pathology and treatment of this disease, which is helpful for the differential diagnosis of other gastric space-occupying diseases.Keywords: ectopic duodenal mucosa, adenomatous hyperplasia,stomach,tumor
Fusion of a maxillary third molar with a supernumerary fourth molar: a case reportCase ImageA 20-year-old Caucasian male consulted the Department of Dentoalveolar Surgery, School of Dentistry in February 2023 due to intermittent pain in the left side of maxilla and face. Intraoral examination revealed probing pocket depth distally to left maxillary second molar 7mm and bleeding on probing. No health problem arises from medical history. Panoramic radiograph revealed impacted mandibular third molar, mesially angulated, with medium impaction depth, abnormal shape and size in close proximity with maxillary sinus floor (Figure 1).Preoperatively 2gr of Amoxicillin were prescribed. Surgical extraction took place under local anesthesia. Infiltration anesthesia with Lidocaine 2% with 1:80000 epinephrine. A full thickness mucoperiosteal flap was prepared and raised, and then ostectomy was performed using surgical handpiece and sterile saline irrigation. Tooth extraction was performed using straight and Warwick-James elevators. Valsalva maneuver was negative. Extraction socket was flushed with saline and flap was repositioned and sutured. Niflumic acid 250mg was prescribed for 3-5 days. Ex vivo examination of the tooth confirmed “double” tooth diagnosis. In order to obtain as much information as possible regarding dental anatomy, photos of all aspects of the tooth were taken and ex vivo CBCT of the tooth was carried out (Figure 2, Figure 3). Additionally, tooth was submerged in epoxy resin. After setting, three sections of the tooth were cut with a low-speed precision sectioning machine (Isomet 11-1180 Buehler, Lake Bluff, IL, USA) with water cooling. The cut surface of each tooth specimen was ground on a polishing machine (Jean Wirtz TG 250, Dusseldorf, Germany) with 200 rpm under water cooling (50 mL/min) using gradually 600-, 800-, and 1000-grit silicon carbide abrasive papers (Apex S system, Buehler, Lake Bluff, IL, USA) for 20s each. Final tooth sections were <1mm. Tooth specimen was placed between two liner polarization filters. Afterwards flash (Speedlight SB-700, Nikon, Japan) with softbox (Godox, China) was held from one side and DSLR camera (D7200, Nikon, Japan) with macro lens (Micro Nikkor 105mm, Nikon, Japan) from the other side. Filters were crossed in different directions until intended result was obtained (Figure 4, 5, 6). Sutures were removed after one week, healing was unproblematic. Oral examination after six months revealed complete healing of soft tissues.Differential diagnosis between different subcategories of “double” tooth is difficult. The supposition that gemination displays a single root canal and fusion displays several root canals is controversial. Fusion of a normal tooth with supernumeraries will still result in a normal tooth count. Given the presence of features suggestive of both diagnoses, this case, actually, presented a diagnostic dilemma.Fusion of two impacted teeth apparently results in a larger dental structure that makes extraction more invasive and inevitably raises the possibility of complications. Close proximity of maxillary third molar with maxillary sinus floor has to be appreciated. Fracture of maxillary tuberosity may occur in cases with extensive ostectomy.Alterations in tooth size and shape during initial radiographic examination may be a primary sign of dental abnormalities. Utilizing contemporary imaging techniques, including CBCT and dental photography, may showcase such special dental anatomies and complement dentists’ education in this field. Dentists’ awareness will result in a meticulous treatment planning and ensure a successful outcome.Figure legendsFigure 1: Initial panoramic radiograph. White arrow shows impacted third molar with small changes in size and shapeFigure 2: Images of the extracted “double” tooth from different aspectsFigure 3: Images exported from ex vivo CBCT of extracted “double tooth”. Shared pulp canal system is noticed.Figure 4: Image of the first tooth section, using polarization filters, DSLR, macro lens and flashFigure 5: Image of the second tooth section, using polarization filters, DSLR, macro lens and flashFigure 6: Image of the third tooth section, using polarization filters, DSLR, macro lens and flash
Regression of kaposiform lymphangiomatosis and chronic disseminated intravascular coagulation after inhaled budesonide-formoterol treatmentMasaru Imamura1, Chansu Shin1, Akihiko Saitoh1, Michio Ozeki 2, Kentaro Matsuoka3 Chihaya Imai11Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan2Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan3Department of Pathology, Tokyo Metropolitan Children’s Medical Center, Tokyo, JapanCorresponding author: Masaru Imamura, Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuou-ku, Niigata City, Niigata 951-8510, Japan.Phone +81-25-227-2222FAX +81-25-227-0778Email: [email protected] Count for Main Text: 701 wordsNumber of Tables: 0Number of Figures: 2Running title: KLA IMPROVED AFTER INHALED STEROIDKeywords: kaposiform lymphangiomatosis, lymphatic malformation, inhaled corticosteroid, rare disease, progressive diseaseAbbreviations:
Background and Purpose Quetiapine is a second-generation atypical antipsychotic drug that has been commonly prescribed for the treatment of schizophrenia, major depressive disorder (depression), and other psychological disorders. Targeted inhibition of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels, which generate Ih, may provide effective resistance against schizophrenia and depression. We investigated if HCN channels could contribute to the therapeutic effect of quetiapine, and its major active metabolite norquetiapine. Experimental Approach Two-electrode voltage clamp recordings were used to assess the effects of quetiapine and norquetiapine on currents from wild-type and mutant HCN1 and HCN2 expressed in Xenopus laevis oocytes. Key Results Norquetiapine, but not quetiapine nor 7-hydroxy quetiapine, has an inhibitory effect on HCN1 channels. Norquetiapine selectively inhibited HCN1 currents by shifting the voltage-dependence of activation to more hyperpolarized potentials in a concentration-dependent manner with an IC50 of 13.9 ± 0.8 μM for HCN1 and slowing channel opening, without changing the kinetics of closing. Inhibition by norquetiapine primarily occurs from in the closed state. Norquetiapine inhibition is not sensitive to the external potassium concentration, and therefore, likely does not block the pore. Norquetiapine inhibition also does not dependent on the cyclic-nucleotide binding domain. Norquetiapine had no effect on HCN2 channels. Conclusions and Implications HCN channels are key targets of norquetiapine, the primary active metabolite of quetiapine. These data help to explain the therapeutic mechanisms by which quetiapine aids in the treatment of anxiety, major depressive disorder, bipolar disorder, and schizophrenia, and may represent a novel structure for future drug design of HCN inhibitors.
Many subcomponents of human language can be found within the vocal communication systems of other species, most notably songbirds. One of the most prominent of these subcomponents is syntax. While studies of syntax are abundant, a lack of consensus on the definition of syntax has led to much debate. The goal of this review paper is to solidify the definitions of syntax and to explore the mechanisms that shape syntax formation in songbirds and other species, with a specific focus on neurobiology, genetics, dopamine, and chunking organization.