A Study of Brain Networks Associated with Swallowing Using Graph-Theoretical Approaches

Functional connectivity between brain regions during swallowing tasks is still not well understood. Understanding these complex interactions is of great interest from both a scientific and a clinical perspective. In this study, functional magnetic resonance imaging (fMRI) was utilized to study brain functional networks during voluntary saliva swallowing in twenty-two adult healthy subjects (all females, 23.1±1.52 years of age). To construct these functional connections, we computed mean partial correlation matrices over ninety brain regions for each participant. Two regions were determined to be functionally connected if their correlation was above a certain threshold. These correlation matrices were then analyzed using graph-theoretical approaches. In particular, we considered several network measures for the whole brain and for swallowing-related brain regions. The results have shown that significant pairwise functional connections were, mostly, either local and intra-hemispheric or symmetrically inter-hemispheric. Furthermore, we showed that all human brain functional network, although varying in some degree, had typical small-world properties as compared to regular networks and random networks. These properties allow information transfer within the network at a relatively high efficiency. Swallowing-related brain regions also had higher values for some of the network measures in comparison to when these measures were calculated for the whole brain. The current results warrant further investigation of graph-theoretical approaches as a potential tool for understanding the neural basis of dysphagia. © 2013 Luan et al

Synthetic Receptors for the High-Affinity Recognition of O-GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water-soluble carbohydrate receptors ("synthetic lectins"). Both systems show outstanding affinities for derivatives of N-acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc-β-OMe with Ka ≈20,000 m(-1), whereas the other one binds an O-GlcNAcylated peptide with Ka ≈70,000 m(-1). These values substantially exceed those usually measured for GlcNAc-binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl-peptide complex can be explained by extra-cavity interactions, raising the possibility of a family of complementary receptors for O-GlcNAc in different contexts

ANALYTICAL METHOD EVELOPMENT AND VALIDATION FOR ANTI ASTHAMATIC DRUG OXYMETAZOLINE HYDROCHLORIDE IN NASAL SPRAY FORMULATIONS BY RP-HPLC

A new, simple, accurate and economic reverse-phase HPLC method has been developed for quantification of Oxymetazoline Hydrochloride in nasal spray formulations. This developed method has been validated according to International Conference on Harmonization (ICH) guideline with respect to system suitability, specificity, precision, linearity, accuracy, and robustness. An isocratic condition of mobile phase Phosphate buffer (pH 3.0): Acetonitrile in a ratio of 60:40, v/v at a flow rate of 1.0 mL/minute over RP C18 (octadecylsilane (ODS), 250 × 4.6 mm, 5 µm, ECLIPSE X DB C-18) column at ambient temperature was maintained. This method is specific and showed excellent linear response with correlation coefficient (R2) values of 0.999, which was within the limit of correlation coefficient (R2 0.995). A  simple  and accurate reversed-phase  HPLC  method  for  the  analysis  of  Oxymetazoline Hydrochloride in  nasal spray formulations was developed and validated successfully

A study of method development and validation for estimation of Azelastine hydrochloride in nasal spray formulations by RP-HPLC method

A simple reverse-phase HPLC method for the estimation of Azelastine hydrochloride in nasal spray formulations has been developed. The method is simple, accurate, precise, specific and linear over the analysis range. This developed method has been validated according to International Conference on Harmonization (ICH) guideline with respect to system suitability, specificity, precision, linearity, accuracy, and robustness. An isocratic condition of mobile phase comprising Phosphate buffer (pH 3.1): Acetonitrile in a ratio of 60:40, v/v at a flow rate of 1.0 mL/minute over RP C18 (octadecylsilane (ODS), 250 × 4.6 mm, 5 µm, CHROMOSIL) column at ambient temperature was maintained. Besides, the chromatographic peak was observed sharp & symmetric. The proposed method was successfully applied for the estimation of the Azelastine hydrochloride in nasal spray formulation

Perspectives and Emotional Experiences of Patients With Chronic Myeloid Leukemia During ENESTPath Clinical Trial and Treatment-Free Remission: Rationale and Protocol of the Italian Substudy

Achievement of deep molecular response following treatment with a tyrosine kinase inhibitor (TKI) allows for treatment-free remission (TFR) in many patients with chronic myeloid leukemia (CML). Successful TFR is defined as the achievement of a sustained molecular response after cessation of ongoing TKI therapy. The phase 3 ENESTPath study was designed to determine the required optimal duration of consolidation treatment with the second-generation TKI, nilotinib 300 mg twice-daily, to remain in successful TFR without relapse after entering TFR for 12 months. The purpose of this Italian ‘patient’s voice CML’ substudy was to evaluate patients’ psycho-emotional characteristics and quality of life through their experiences of stopping treatment with nilotinib and entering TFR. The purpose of the present contribution is to early present the study protocol of an ongoing study to the scientific community, in order to describe the study rationale and to extensively present the study methodology. Patients aged ≥18 years with a confirmed diagnosis of Philadelphia chromosome positive BCR-ABL1+ CML in chronic phase and treated with front-line imatinib for a minimum of 24 months from the enrollment were eligible. Patients consenting to participate the substudy will have quality of life questionnaires and in-depth qualitative interviews conducted. The substudy will include both qualitative and quantitative design aspects to evaluate the psychological outcomes as assessed via patients’ emotional experience during and after stopping nilotinib therapy. Randomization is hypothesized to be a timepoint of higher psychological alert or distress when compared to consolidation and additionally any improvement in health-related quality of life (HRQoL) due to nilotinib treatment is expected across the timepoints (from consolidation, to randomization, and TFR). An association is also expected between dysfunctional coping strategies, such as detachments and certain personality traits, and psychological distress and HRQoL impairments. Better HRQoL outcomes are expected in TFR compared to the end of consolidation. This substudy is designed for in-depth assessment of all potential psycho-emotional variables and aims to determine the need for personalized patient care and counselling, and also guide clinicians to consider the psychological well-being of patients who are considering treatment termination. NCT number: NCT01743989, EudraCT number: 2012-005124-1

Glycosylation Is Vital for Industrial Performance of Hyperactive Cellulases

In the terrestrial biosphere, biomass deconstruction is conducted by microbes employing a variety of complementary strategies, many of which remain to be discovered. Moreover, the biofuels industry seeks more efficient (and less costly) cellulase formulations upon which to launch the nascent sustainable bioenergy economy. The glycan decoration of fungal cellulases has been shown to protect these enzymes from protease action and to enhance binding to cellulose. We show here that thermal tolerant bacterial cellulases are glycosylated as well, although the types and extents of decoration differ from their Eukaryotic counterparts. Our major findings are that glycosylation of CelA is uniform across its three linker peptides and composed of mainly galactose disaccharides (which is unique) and that this glycosylation dramatically impacts the hydrolysis of insoluble substrates, proteolytic and thermal stability, and substrate binding and changes the dynamics of the enzyme. This study suggests that the glycosylation of CelA is crucial for its exceptionally high cellulolytic activity on biomass and provides the robustness needed for this enzyme to function in harsh environments including industrial settings

Two-photon, fiber-coupled, super-resolution microscope for biological imaging

Imaging sub-diffraction dynamics of neural nanostructures involved in behaviors such as learning and memory in a freely moving animal is not possible with existing techniques. Here, we present a solution in the form of a two-photon (2P), fiber-coupled, stimulated emission depletion microscope and demonstrate its capabilities by acquiring super-resolution imaging of mammalian cells. A polarization-maintaining fiber is used to transport both the 2P excitation light (915 nm) and the donut-shaped depletion beam (592 nm), which is constructed by adding two temporally incoherent and orthogonally polarized Hermite&ndash;Gaussian fiber modes. The fiber output is insensitive to bending or temperature changes and is the first demonstration toward deep tissue super-resolution imaging in awake behaving animals. &nbsp;</p

Chronic Myeloid Leukemia Patient&apos;s Voice About the Experience of Treatment-Free Remission Failure: Results From the Italian Sub-Study of ENESTPath Exploring the Emotional Experience of Patients During Different Phases of a Clinical Trial

Background: The main objective of this study is to gain further insights on how chronic myeloid leukemia (CML) patients involved in an interventional clinical trial with the purpose of reaching treatment free remission (TFR) phase, perceived and experienced TFR failure. TFR failure was defined for the individual patient as either not being eligible for drug discontinuation or as having relapse in the TFR phase with reintroduction of nilotinib treatment. Methods: Using a qualitative approach, out of 25 patients with CML who experienced TFR failure 14 were interviewed. Patients' views and experiences were explored using in-depth interviews, analyzed using the Interpretative Phenomenological Analysis (IPA). Results: The analysis of the interviews revealed that the experience of the diagnosis seems to have been lived as a traumatic break that has created a dichotomy, like an ambivalence in the ways in which CML patients perceived and experienced the whole disease journey, with contradictory feelings of both positive and negative emotions (e.g., a diagnosis of cancer, that is something distressing and of being afraid of, but also with a treatment and a life expectancies of which being grateful). This ambivalence of feelings was found to give meaning to the way in which patients cognitively and emotionally experienced the different steps of their disease history. Thus, four main issues, corresponding to different steps of the patients' journey, were identified: (1) the moment of the diagnosis, (2) the experience of the illness journey: disease and treatment, (3) the moment of "TFR failure," and (4) the impact of disease, treatment and relapse on the patient's life. Conclusion: This qualitative analysis helps in understanding patients' perspective, both in terms of getting access to the inner subjective experience of having CML and its strict relationship with the involvement in a trial or its cessation. Clinicians should consider that the way in which CML patients feel engaged in a clinical trial, create expectancies about TFR or experience the TFR failure is linked to the process of coping with the diagnosis, which is characterized by ambivalence

Graph Theoretical Analysis of Functional Brain Networks: Test-Retest Evaluation on Short- and Long-Term Resting-State Functional MRI Data

Graph-based computational network analysis has proven a powerful tool to quantitatively characterize functional architectures of the brain. However, the test-retest (TRT) reliability of graph metrics of functional networks has not been systematically examined. Here, we investigated TRT reliability of topological metrics of functional brain networks derived from resting-state functional magnetic resonance imaging data. Specifically, we evaluated both short-term (<1 hour apart) and long-term (>5 months apart) TRT reliability for 12 global and 6 local nodal network metrics. We found that reliability of global network metrics was overall low, threshold-sensitive and dependent on several factors of scanning time interval (TI, long-term>short-term), network membership (NM, networks excluding negative correlations>networks including negative correlations) and network type (NT, binarized networks>weighted networks). The dependence was modulated by another factor of node definition (ND) strategy. The local nodal reliability exhibited large variability across nodal metrics and a spatially heterogeneous distribution. Nodal degree was the most reliable metric and varied the least across the factors above. Hub regions in association and limbic/paralimbic cortices showed moderate TRT reliability. Importantly, nodal reliability was robust to above-mentioned four factors. Simulation analysis revealed that global network metrics were extremely sensitive (but varying degrees) to noise in functional connectivity and weighted networks generated numerically more reliable results in compared with binarized networks. For nodal network metrics, they showed high resistance to noise in functional connectivity and no NT related differences were found in the resistance. These findings provide important implications on how to choose reliable analytical schemes and network metrics of interest