The production of concentrated dispersions of few-layer graphene by the direct exfoliation of graphite in organosilanes

We report the formation and characterization of graphene dispersions in two organosilanes, 3-glycidoxypropyl trimethoxysilane (GPTMS) and phenyl triethoxysilane (PhTES) as new reactive solvents. The preparation method was mild and easy and does not produce any chemical modification. The dispersions, which exhibit the Tyndall effect, were characterized by TEM and Raman spectroscopy to confirm the presence of few-layer graphene. Concentrations as high as 0.66 and 8.00 mg/ml were found for PhTES and GPTMS, respectively. The latter is one of the highest values reported for a dispersion of graphene obtained by any method. This finding paves the way for the direct synthesis of polymer nanofiller-containing composites consisting of graphene and reactive silanes to be used in sol–gel synthesis, without any need for solvent removal, thus preventing graphene reaggregation to form graphite flakes.     

Detection of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by displacement of antibodies

A molecular layer with low non-specific binding enabling determination of low concentrations of 3,4-methylenedioxymethamphetamine (MDMA) by the displacement of antibodies has been developed. Antibody Fab′-fragments at various concentrations have been site-directly immobilised on gold and intercalated with a hydrophilic non-ionic polymer that reduces non-specific binding. Bovine serum albumin conjugated with MDMA and various concentrations of anti-MDMA antibodies were bound to the layer. The amount of conjugates and antibodies bound was dependent on the amount of Fab′-fragments in the layer. Antibodies were also bound to the conjugates physisorbed directly onto the gold surface and in mixtures with the polymer or with a lipoamide. A high displacement of antibodies was observed by surface plasmon resonance (SPR) on interaction of MDMA with the different layers in buffer solution. No displacement could, however, be observed in saliva with the pure conjugate layer because of a high non-specific binding of proteins. When the conjugates were coupled to the surface through the antibody Fab-fragment/polymer layer, MDMA concentrations as low as 0.02 ng mL⁻¹ (0.14 nM) could easily be detected in buffer. In diluted saliva the lowest limit of detection was 0.4 ng mL⁻¹ enabling determination of drugs from saliva with a cut-off concentration of 2 ng mL⁻¹. The molecular layer of antibody Fab′-fragments and polymer thus shows great potential for binding conjugates and antibodies that can be displaced on the interaction with very low concentrations of small-sized molecules. A low non-specific binding is guaranteed by the presence of the hydrophilic polymer.     

Cardiac involvement in HIV-related non-Hodgkin's lymphoma: a case report and short review of the literature

We report a case of secondary heart involvement in AIDS-related primary lymphoma of the liver. A worsening dyspnea led to the diagnosis of pericardial effusion, and transesophageal echocardiography revealed the presence of large endocardial ventricular masses. Clinical suspicion of a lymphomatous origin was confirmed at the autopsy, which showed an extranodal dissemination pattern (heart, liver, intestine, and lung). In AIDS patients, both primary and secondary lymphomatous heart involvement are increasing in incidence. Clinical symptoms and signs are vague. Since the hematogenous route is the most common pattern of involvement, even extrathoracic lymphomas can present heart dissemination. Thus, it should be suspected in lymphoma patients who present with even mild aspecific heart symptoms. Appropriate imaging procedures include transesophageal echocardiography and, if possible, ECG-gated MRI. A negative transthoracic echocardiograph does not exclude the presence of myocardial tumor. Chemotherapy is only occasionally beneficial, and the prognosis remains poor.     

The system of the modified transcochlear approach: a lateral avenue to the central skull base

OBJECTIVE: This study aimed to update the authors' experience with the modified transcochlear approach for the management of lesions of the central skull base. The surgical technique, classification, indications, and results also are presented. STUDY DESIGN: A retrospective review of the charts of 66 consecutive patients treated in our centers by the modified transcochlear approach was conducted. SETTING: The study was performed in two tertiary referral centers. PATIENTS: All patients treated by the modified transcochlear approach were included. Thirty-five patients had extradural lesions, whereas 31 lesions were intradural. INTERVENTION: All patients were treated surgically using the modified transcochlear approach either in its basic form (type A) or with its extensions (types B, C, and D). MAIN OUTCOME MEASURES: The outcome of surgery is evaluated with particular emphasis on the incidence of morbidity, mortality, and the degree of total tumor removal. RESULTS: Total tumor removal was accomplished in 58 cases either in single or staged procedures. A second-stage procedure for total tumor removal is planned in five other patients. Subtotal tumor removal was performed in three patients. Mortality occurred in two cases. Ipsilateral hearing loss and immediate facial nerve palsy constituted the major drawbacks of this approach. However, 67.5% recovered to grade III facial function or better 1 year after surgery. CONCLUSIONS: The modified transcochlear approach provides a relatively safe, wide, and versatile access to large lesions of the central skull base.     

Challenges of developing the complex socio-technical system: realising the present, acknowledging the past, and envisaging the future of vessel traffic services

This paper raises the question of how to guide the development of an emerging complex socio-technical system. The empirical basis for the discussion is a study of Vessel Traffic Services (VTS). We analysed the current state and the history of the service in Finland in four studies and identified several development needs. The results showed that there are differences between the outcome, practices and conceptions of the core task across different experts in the VTS centres, which can be explained by the current state of the constituents and the history of the activity system. Qualitatively different development phases characterised either by a top-down standardisation or bottom-up construction process were recognised. A combination of these processes was suggested for the future development strategy of the VTS. This could allow both continuous development within VTS and recognition of the need for a new system. A promising way to achieve continuous development is by creating reflective practices supported for instance with annual simulator exercises aimed at procedure development. We conclude that solving the current problems and promoting the development of the complex system call for a dynamic, open vision of the target future of the system, in which the pressures from the social, political and technological environments are taken into account. The results of ergonomics studies can help in self-reflecting, envisaging and developing supportive methods for the system but the persons within the system create the will to develop and find their way towards the development horizon.     

A transesophageal Doppler echo-color study of pulmonary venous flow before and after the correction of valvular defects

AIM OF THE STUDY: To verify changes of pulmonary venous flow pattern before and after surgical or percutaneous correction of valvular heart disease. METHODS: The pulmonary venous flow pattern was studied by transesophageal echocardiography in 27 patients affected with heart valve disease (11 mitral insufficiency, 10 mitral stenosis, 2 aortic stenosis and 4 pulmonary stenosis), before and after surgical or percutaneous correction. Pulmonary venous flow velocity variables measured included peak systolic and diastolic flow velocities (VmaxS and VmaxD), systolic and diastolic velocity time integrals (IS and ID) and their respective ratios (VmaxS/VmaxD and IS/ID). Paired Student's t-test was used for analysis of data; a p value < 0.05 was considered statistically significant. RESULTS: In mitral stenosis and insufficiency, as well as in pulmonary stenosis, the VmaxS/VmaxD and IS/ID ratios were constantly < 1. Aortic stenosis, on the contrary, showed a normal preoperative pattern of pulmonary venous flow, which did not change after correction. All other successful corrections (17 surgeries, 4 angioplasties) were characterised by an increase of VmaxS/VmaxD and IS/ID ratios. (Mitral stenosis: VmaxS/VmaxD 0.80 +/- 0.31 vs 1.4 +/- 0.5, p = 0.006; IS/ID 0.86 +/- 0.77 vs 1.62 +/- 0.62, p = 0.016. Severe mitral insufficiency: VmaxS/VmaxD -0.71 +/- 0.32 vs 1.19 +/- 0.32, p < 0.0001; IS/ID 0.41 +/- 0.19 vs 1.04 +/- 0.31, p = 0.006. Moderate mitral insufficiency: VmaxS/Vmax D 0.38 +/- 0.04 vs 0.95 +/- 0.06, p = 0.001; IS/ID 0.32 +/- 0.05 vs 0.95 +/- 0.07, p = 0.02. Pulmonary stenosis: VmaxS/VmaxD 0.43 +/- 0.23 vs 1.09 +/- 0.35, n.s. e IS/ID 0.49 +/- 0.34 vs 0.92 +/- 0.65, n.s.). Failure to return to a normal pulmonary venous pattern was observed in the 2 cases of partially successful mitral valvuloplasty (one of which was subsequently transformed into a mitral valve replacement with immediate normalisation of the pattern) and in the 2 cases of incomplete relief of a pulmonary stenosis after pulmonary valvuloplasty. CONCLUSIONS: Though preliminary, these observations suggest a high sensitivity of this method and, therefore, a possible role of pulmonary venous pattern studies in the assessment of the efficacy of treatment in mitral and pulmonary valve disease.     

Fatty Acid Fingerprints and Hyaluronic Acid in Extracellular Vesicles from Proliferating Human Fibroblast-like Synoviocytes

Extracellular vesicles (EVs) function as conveyors of fatty acids (FAs) and other bioactive lipids and can modulate the gene expression and behavior of target cells. EV lipid composition influences the fluidity and stability of EV membranes and reflects the availability of lipid mediator precursors. Fibroblast-like synoviocytes (FLSs) secrete EVs that transport hyaluronic acid (HA). FLSs play a central role in inflammation, pannus formation, and cartilage degradation in joint diseases, and EVs have recently emerged as potential mediators of these effects. The aim of the present study was to follow temporal changes in HA and EV secretion by normal FLSs, and to characterize the FA profiles of FLSs and EVs during proliferation. The methods used included nanoparticle tracking analysis, confocal laser scanning microscopy, sandwich-type enzyme-linked sorbent assay, quantitative PCR, and gas chromatography. The expression of hyaluronan synthases 1–3 in FLSs and HA concentrations in conditioned media decreased during cell proliferation. This was associated with elevated proportions of 20:4n-6 and total n-6 polyunsaturated FAs (PUFAs) in high-density cells, reductions in n-3/n-6 PUFA ratios, and up-regulation of cluster of differentiation 44, tumor necrosis factor α, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-γ. Compared to the parent FLSs, 16:0, 18:0, and 18:1n-9 were enriched in the EV fraction. EV counts decreased during cell growth, and 18:2n-6 in EVs correlated with the cell count. To conclude, FLS proliferation was featured by increased 20:4n-6 proportions and reduced n-3/n-6 PUFA ratios, and FAs with a low degree of unsaturation were selectively transferred from FLSs into EVs. These FA modifications have the potential to affect membrane fluidity, biosynthesis of lipid mediators, and inflammatory processes in joints, and could eventually provide tools for translational studies to counteract cartilage degradation in inflammatory joint diseases.     

Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment

Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological approach to inhibit MYC in cancer cells is represented by Bromodomain and Extra-Terminal motif (BET) protein inhibitors. In this paper, we evaluated the effects of BET inhibitor (+)-JQ1 (JQ1) on the viability of aRMS and eRMS cells. Interestingly, we found that the drug sensitivity of RMS cell lines to JQ1 was directly proportional to the expression of MYC. JQ1 induces G1 arrest in cells with the highest steady-state levels of MYC, whereas apoptosis is associated with MYC downregulation. These findings suggest BET inhibition as an effective strategy for the treatment of RMS alone or in combination with other drugs.     

Novel Anti-Neuroinflammatory Properties of a Thiosemicarbazone–Pyridylhydrazone Copper(II) Complex

Neuroinflammation has a major role in several brain disorders including Alzheimer’s disease (AD), yet at present there are no effective anti-neuroinflammatory therapeutics available. Copper(II) complexes of bis(thiosemicarbazones) (Cu^II(gtsm) and Cu^II(atsm)) have broad therapeutic actions in preclinical models of neurodegeneration, with Cu^II(atsm) demonstrating beneficial outcomes on neuroinflammatory markers in vitro and in vivo. These findings suggest that copper(II) complexes could be harnessed as a new approach to modulate immune function in neurodegenerative diseases. In this study, we examined the anti-neuroinflammatory action of several low-molecular-weight, charge-neutral and lipophilic copper(II) complexes. Our analysis revealed that one compound, a thiosemicarbazone–pyridylhydrazone copper(II) complex (CuL⁵), delivered copper into cells in vitro and increased the concentration of copper in the brain in vivo. In a primary murine microglia culture, CuL⁵ was shown to decrease secretion of pro-inflammatory cytokine macrophage chemoattractant protein 1 (MCP-1) and expression of tumor necrosis factor alpha (Tnf), increase expression of metallothionein (Mt1), and modulate expression of Alzheimer’s disease-associated risk genes, Trem2 and Cd33. CuL⁵ also improved the phagocytic function of microglia in vitro. In 5xFAD model AD mice, treatment with CuL⁵ led to an improved performance in a spatial working memory test, while, interestingly, increased accumulation of amyloid plaques in treated mice. These findings demonstrate that CuL⁵ can induce anti-neuroinflammatory effects in vitro and provide selective benefit in vivo. The outcomes provide further support for the development of copper-based compounds to modulate neuroinflammation in brain diseases.