Preparation of pH sensitive insulin-loaded nano hydrogels and evaluation of insulin releasing in different pH conditions.

In the recent years, temperature and pH-sensitive hydrogels were developed as suitable carriers for drug delivery. In this study, four different pH-sensitive nanohydrogels were designed for an oral insulin delivery modeling. NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction with 80:8:12 ratios respectively. Reactions were carried out in four conditions including 1,4-dioxan and water as two distinct solution under nitrogen gas-flow. The copolymers were characterized with FT-IR, SEM and TEM. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in pH 1.2 and pH 6.8 at 37 °C. For pH 6.8 and pH 1.2, 2 mg of the insulin loaded nanohydrogels was float in a beaker containing 100 mL of PBS with pH 6.8 and 100 mL of HCl solution with pH 1.2, respectively. Sample collection was done in different times and HPLC was used for analysis of samples using water/acetonitrile (65/35) as the mobile phase. Nanohydrogels synthesis reaction yield was 95 %, HPLC results showed that loading in 1,4-dioxan without cross-linker nanohydrogels was more than others, also indicated that the insulin release of 1,4-dioxan without cross-linker nanohydrogels at acidic pH is less, but in pH 6.8 is the most. Results showed that by opting suitable polymerization method and selecting the best nanohydrogels, we could obtain a suitable insulin loaded nanohydrogels for oral administration.

Burden from Study Questionnaire on Patient Fatigue in Qualitative Congestive Heart Failure Research.

Mixed methods research forms the backbone of translational research methodologies. Qualitative research and subjective data lead to hypothesis generation and ideas that are then proven via quantitative methodologies and gathering objective data. In this vein, clinical trials that generate subjective data may have limitations, when they are not followed through with quantitative data, in terms of their ability to be considered gold standard evidence and inform guidelines and clinical management. However, since many research methods utilise qualitative tools, an initial factor is that such tools can create a burden on patients and researchers. In addition, the quantity of data and its storage contributes to noise and quality issues for its primary and post hoc use. This paper discusses the issue of the burden of subjective data collected and fatigue in the context of congestive heart failure (CHF) research. The CHF population has a high baseline morbidity, so no doubt the focus should be on the content; however, the lengths of the instruments are a product of their vigorous validation processes. Nonetheless, as an important source of hypothesis generation, if a choice of follow-up qualitative assessment is required for a clinical trial, shorter versions of the questionnaire should be used, without compromising the data collection requirements; otherwise, we need to invest in this area and find suitable solutions.

Differential Contributions of Inhibitory Subnetwork to Visual Cortical Modulations Identified via Computational Model of Working Memory.

Extrastriate visual neurons show no firing rate change during a working memory (WM) task in the absence of sensory input, but both αß oscillations and spike phase locking are enhanced, as is the gain of sensory responses. This lack of change in firing rate is at odds with many models of WM, or attentional modulation of sensory networks. In this article we devised a computational model in which this constellation of results can be accounted for via selective activation of inhibitory subnetworks by a top-down working memory signal. We confirmed the model prediction of selective inhibitory activation by segmenting cells in the experimental neural data into putative excitatory and inhibitory cells. We further found that this inhibitory activation plays a dual role in influencing excitatory cells: it both modulates the inhibitory tone of the network, which underlies the enhanced sensory gain, and also produces strong spike-phase entrainment to emergent network oscillations. Using a phase oscillator model we were able to show that inhibitory tone is principally modulated through inhibitory network gain saturation, while the phase-dependent efficacy of inhibitory currents drives the phase locking modulation. The dual contributions of the inhibitory subnetwork to oscillatory and non-oscillatory modulations of neural activity provides two distinct ways for WM to recruit sensory areas, and has relevance to theories of cortical communication.

Frontotemporal coordination predicts working memory performance and its local neural signatures.

Neurons in some sensory areas reflect the content of working memory (WM) in their spiking activity. However, this spiking activity is seldom related to behavioral performance. We studied the responses of inferotemporal (IT) neurons, which exhibit object-selective activity, along with Frontal Eye Field (FEF) neurons, which exhibit spatially selective activity, during the delay period of an object WM task. Unlike the spiking activity and local field potentials (LFPs) within these areas, which were poor predictors of behavioral performance, the phase-locking of IT spikes and LFPs with the beta band of FEF LFPs robustly predicted successful WM maintenance. In addition, IT neurons exhibited greater object-selective persistent activity when their spikes were locked to the phase of FEF LFPs. These results reveal that the coordination between prefrontal and temporal cortex predicts the successful maintenance of visual information during WM.

Effect of perceived interpersonal closeness on the joint Simon effect in adolescents and adults.

Here, we explored the role of perceived interpersonal closeness in joint action using the joint Simon task in adolescents and adults. In a two-choice reaction time task, spatially assigned responses to non-spatial stimulus features are faster when the stimulus and response are in congruent locations than not. This phenomenon is called Simon effect and is absent or strongly attenuated when a participant responds to only one of the stimuli. However, the effect reappears when two participants carry out the same go/no-go tasks cooperatively. This re-emergence of the Simon effect in joint action is called the joint Simon effect (JSE). In this study, we first replicated the standard and joint Simon effects in adolescents (n = 43), as well as adults (n = 39) with similar magnitude of the effects in the two age groups. The magnitude of the JSE was positively correlated with the level of closeness as measured by Inclusion of Other in the Self scale. This correlation was not significantly different in adolescents (n = 73) compared to adults (n = 71). Our findings show that joint action is sensitive to the social factor such as interpersonal closeness, and the underlying mechanisms are already mature by adolescence.

Prefrontal Contributions to Attention and Working Memory.

The processes of attention and working memory are conspicuously interlinked, suggesting that they may involve overlapping neural mechanisms. Working memory (WM) is the ability to maintain information in the absence of sensory input. Attention is the process by which a specific target is selected for further processing, and neural resources directed toward that target. The content of WM can be used to direct attention, and attention can in turn determine which information is encoded into WM. Here we discuss the similarities between attention and WM and the role prefrontal cortex (PFC) plays in each. First, at the theoretical level, we describe how attention and WM can both rely on models based on attractor states. Then we review the evidence for an overlap between the areas involved in both functions, especially the frontal eye field (FEF) portion of the prefrontal cortex. We also discuss similarities between the neural changes in visual areas observed during attention and WM. At the cellular level, we review the literature on the role of prefrontal DA in both attention and WM at the behavioral and neural levels. Finally, we summarize the anatomical evidence for an overlap between prefrontal mechanisms involved in attention and WM. Altogether, a summary of pharmacological, electrophysiological, behavioral, and anatomical evidence for a contribution of the FEF part of prefrontal cortex to attention and WM is provided.

Working Memory Enhances Cortical Representations via Spatially Specific Coordination of Spike Times.

The online maintenance and manipulation of information in working memory (WM) is essential for guiding behavior based on our goals. Understanding how WM alters sensory processing in pursuit of different behavioral objectives is therefore crucial to establish the neural basis of our goal-directed behavior. Here we show that, in the middle temporal (MT) area of rhesus monkeys, the power of the local field potentials in the αß band (8-25 Hz) increases, reflecting the remembered location and the animal's performance. Moreover, the content of WM determines how coherently MT sites oscillate and how synchronized spikes are relative to these oscillations. These changes in spike timing are not only sufficient to carry sensory and memory information, they can also account for WM-induced sensory enhancement. These results provide a mechanistic-level understanding of how WM alters sensory processing by coordinating the timing of spikes across the neuronal population, enhancing the sensory representation of WM targets.

pH sensitive insulin-loaded nanohydrogel increases the effect of oral insulin in diabetic rats.

BACKGROUND: There are different methods for insulin administration in diabetic patient. Nano-hydrogel is one of the most talented drug carrier for its sensitivity to environmental stimulus. METHODS AND RESULTS: NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction. The copolymers were characterized with Scanning electron microscopy (SEM) and Transient electron microscopy (TEM). Copolymers were loaded with regular insulin by modified double emulsion method. Diabetic rats are used for feeding insulin-loaded nanohydrogel. Analysis of the results from the measurement of the amount of blood insulin from the rats blood that received insulin in nanohydrogel loaded form compared with rats that received pure insulin is significantly high, which confirm that insulin has been able to pass from the stomach acid barrier by nanohydrogel and is absorbed from the intestine. Blood sugar levels from tested rats indicate that with increasing amount of insulin, blood sugar levels fall down. CONCLUSION: Our study confirms that insulin has been able to pass from the stomach acid barrier by nanohydrogel and be absorbed from the intestine.