Pediatric Esophageal Dilatations: A Cross-Specialty Experience

AIM OF THE STUDY: Esophageal dilatations are commonly performed in pediatric patients who have undergone an esophageal atresia/tracheoesophageal fistula (EA/TEF) repair or following caustic injury. We sought to compare the practice of esophageal dilatation across different specialties. METHODS: We analyzed all patients who had an esophageal dilatation at our center between April 2014 and December 2018. Patients were identified via prospectively maintained databases and clinical coding records. Patients had a combination of dilatations under each specialty: interventional radiology (IR), surgery, and gastroenterology. RESULTS: Thirty-five individual patients underwent 226 dilatations, median dilatations per patient was 3 (1–40). The median age at first dilatation was 18 months (1–194 months). Sixty-eight percent of patients had a previous EA/TEF repair. IR performed 59% of dilatations, surgeons 26%, and 15% by gastroenterologists. Surgeons more frequently were performing initial dilatations (P < .05) and performed more dilatations in EA/TEF patients (P < .0001). There was a significant difference between the time from a surgical dilatation until the next dilatation, 3.7 months, compared with an IR dilatation, 1.8 months (ANOVA, P < .05). Surgeons more frequently increased the size of balloon used (57% versus 33% versus 39%, P < .01). There was no significant difference in balloon size between specialties or in the incremental increase in size between subsequent dilatations. There was one postprocedure perforation, managed conservatively (complication rate = 0.4%). CONCLUSIONS: We have demonstrated that on average, patients wait longer after a surgical dilatation until their next procedure, and surgical teams are more likely to increase the size of the dilating balloon. Surgeons tend to be more involved in their postoperative patients in the initial phases of stricture management. Our results suggest the feasibility and safety of a multispecialty approach for these patients

The Multifaceted Function of Granzymes in Sepsis: Some Facts and a Lot to Discover

Sepsis is a serious global health problem. In addition to a high incidence, this syndrome has a high mortality and is responsible for huge health expenditure. The pathophysiology of sepsis is very complex and it is not well-understood yet. However, it is widely accepted that the initial phase of sepsis is characterized by a hyperinflammatory response while the late phase is characterized by immunosuppression and immune anergy, increasing the risk of secondary infections. Granzymes (Gzms) are a family of serine proteases classified according to their cleavage specificity. Traditionally, it was assumed that all Gzms acted as cytotoxic proteases. However, recent evidence suggests that GzmB is the one with the greatest cytotoxic capacity, while the cytotoxicity of others such as GzmA and GzmK is not clear. Recent studies have found that GzmA, GzmB, GzmK, and GzmM act as pro-inflammatory mediators. Specially, solid evidences show that GzmA and GzmK function as extracellular proteases that regulate the inflammatory response irrespectively of its ability to induce cell death. Indeed, studies in animal models indicate that GzmA is involved in the cytokine release syndrome characteristic of sepsis. Moreover, the GZM family also could regulate other biological processes involved in sepsis pathophysiology like the coagulation cascade, platelet function, endothelial barrier permeability, and, in addition, could be involved in the immunosuppressive stage of sepsis. In this review, we provide a comprehensive overview on the contribution of these novel functions of Gzms to sepsis and the new therapeutic opportunities emerging from targeting these proteases for the treatment of this serious health problem

Mesoscopic Stern-Gerlach device to polarize spin currents

Spin preparation and spin detection are fundamental problems in spintronics and in several solid state proposals for quantum information processing. Here we propose the mesoscopic equivalent of an optical polarizing beam splitter (PBS). This interferometric device uses non-dispersive phases (Aharonov-Bohm and Rashba) in order to separate spin up and spin down carriers into distinct outputs and thus it is analogous to a Stern-Gerlach apparatus. It can be used both as a spin preparation device and as a spin measuring device by converting spin into charge (orbital) degrees of freedom. An important feature of the proposed spin polarizer is that no ferromagnetic contacts are used.Comment: Updated to the published versio

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Spin injection and spin accumulation in all-metal mesoscopic spin valves

We study the electrical injection and detection of spin accumulation in lateral ferromagnetic metal-nonmagnetic metal-ferromagnetic metal (F/N/F) spin valve devices with transparent interfaces. Different ferromagnetic metals, permalloy (Py), cobalt (Co) and nickel (Ni), are used as electrical spin injectors and detectors. For the nonmagnetic metal both aluminium (Al) and copper (Cu) are used. Our multi-terminal geometry allows us to experimentally separate the spin valve effect from other magneto resistance signals such as the anomalous magneto resistance (AMR) and Hall effects. We find that the AMR contribution of the ferromagnetic contacts can dominate the amplitude of the spin valve effect, making it impossible to observe the spin valve effect in a 'conventional' measurement geometry. In a 'non local' spin valve measurement we are able to completely isolate the spin valve signal and observe clear spin accumulation signals at T=4.2 K as well as at room temperature (RT). For aluminum we obtain spin relaxation lengths (lambda_{sf}) of 1.2 mu m and 600 nm at T=4.2 K and RT respectively, whereas for copper we obtain 1.0 mu m and 350 nm. The spin relaxation times tau_{sf} in Al and Cu are compared with theory and results obtained from giant magneto resistance (GMR), conduction electron spin resonance (CESR), anti-weak localization and superconducting tunneling experiments. The spin valve signals generated by the Py electrodes (alpha_F lambda_F=0.5 [1.2] nm at RT [T=4.2 K]) are larger than the Co electrodes (alpha_F lambda_F=0.3 [0.7] nm at RT [T=4.2 K]), whereas for Ni (alpha_F lambda_F<0.3 nm at RT and T=4.2 K) no spin signal is observed. These values are compared to the results obtained from GMR experiments.Comment: 16 pages, 12 figures, submitted to PR

Comparison and evaluation of experimental mediastinitis models: precolonized foreign body implants and bacterial suspension inoculation seems promising

BACKGROUND: Post-sternotomy mediastinitis (PSM) is a devastating surgical complication affecting 1–3% of patients that undergo cardiac surgery. Staphylococcus aureus is one of the most commonly encountered bacterial pathogen cultured from mediastinal samples obtained from patients with PSM. A component of the membrane of the gram positive bacteria, lipoteichoic acid, stimulates the blood monocytes and macrophages to secrete cytokines, radicals and nitrogen species leading to oxido-inflammatory damage. This seems to be responsible for the high mortality rate in PSM. For the evaluation of the pathogenesis of infection or for the investigation of alternative treatment models in infection, no standard model of mediastinitis seems to be available. In this study, we evaluated four mediastinitis models in rats. METHODS: The rats were divided into four groups to form different infection models. Group A: A suspension of 1 × 10(7 )colony-forming units Staphylococcus aureus in 0,5 mL was inoculated from the right second intercostal space into the mediastinum. Group B: A hole was created in the right second intercostal space and a piece of stainless-steel implant with a length of 0.5 cm was inserted into the mediastinum and a suspension of 1 × 10(7 )cfu bacteria in 0,5 mL was administered via the tail vein. Group C: Precolonized stainless-steel implant was inserted into the mediastinum. Group D: Precolonized stainless-steel implant was inserted into the mediastinum and the bacteria suspension was also injected into the mediastinum. On the 10(th )day, rats were sacrificed and the extension of infection in the mediastenae was evaluated by quantitative cultures. Myeloperoxidase activity (MPO) and malondialdehyde (MDA) levels were determined in the sera to evaluate the neutrophil activation and assess the inflammatory oxidation. RESULTS: The degree of infection in group C and D were 83.3% and 100% respectively (P < 0.001). MDA levels were significantly higher in these two groups than the others (P < 0.001). CONCLUSION: Infected implants and high bacterial concentration administration were the two important components that played a significant role in the outcome of a successful infection in mediastinum in a rat model

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio