Update on Oxytocin, Phosphodiesterase, Neurokinin, Glycine as a Therapeutic Approach in the Treatment of Schizophrenia.

BACKGROUND: Schizophrenia is a chronic psychiatric disorder characterized by disrupted thoughts, perception, mood, and behavior. It has a heterogeneous genetic and neurobiological background and affects about 0.5-1% of the adult population worldwide. Herein, we review the current approaches and advances in schizophrenia. The potential therapeutic compounds for the treatment of schizophrenia act on the oxytocin receptor, phosphodiesterase system, neurokinin receptor, and glycine transport 1 receptor. Therefore, this article provides an update on the pharmacology of different receptors in addition to the dopaminergic system. These findings would guide the readers on novel targets for schizophrenia with the potential to be therapeutic agents in the future. OBJECTIVE: To provide the researchers an update on the emerging role of oxytocin, phosphodiesterase, neurokinin, and glycine which can be explored as potential pharmacotherapeutic targets in the treatment of schizophrenia. METHODS: An extensive literature search was conducted using PubMed, Science Direct, and NCBI with the following keywords: schizophrenia, novel receptors, oxytocin, phosphodiesterase, neurokinin, and glycine. Furthermore, to provide insights into newer drug treatments for Schizophrenia, Furthermore, Clinicaltrials.gov website was searched for newer receptor-based drugs. RESULTS: Current literature supported by preclinical and clinical provides substantial evidence that oxytocin, phosphodiesterase, neurokinin, and glycine play a crucial role in Schizophrenia. CONCLUSION: Our findings indicate that though multiple antipsychotic drugs are prescribed to treat schizophrenia, novel approaches and/or mechanisms are plausible. Moreover, sensitive and specific diagnostic tools and safe and effective interventions, including novel therapeutic agents, are required to yield substantially improved future outcomes.

Use of In silico tools for screening buffers to overcome physical instability of Abatacept.

Rheumatoid arthritis is an autoimmune disorder. Abatacept (CTLA4-Ig) is used for the treatment of Rheumatoid arthritis. Abatacept is a monoclonal antibody. Monoclonal antibodies undergo chemical (e.g. oxidation, deamidation, hydrolysis) and physical (e.g. aggregation, unfolding) instabilities while handling and storage. Abatacept is also prone to aggregation. Stabilizing agents such as buffers are used to stabilize monoclonal antibodies. But, the selection of the appropriate buffer is a time-consuming process because after testing many buffers based on the analysis of the results the appropriate buffer is identified. To overcome this issue in the current study computational tools were utilized to virtually screen different buffers to select the appropriate buffer. Ligand binding is the principal mechanism of conformational stability of proteins. For the buffers as well ligand binding is the most common mechanism for enhancing the thermodynamic stability of proteins. Generally it is observed that by enhancing the thermodynamic stability there is reduction in the rate of aggregation of proteins. Buffer (ligand) binds to the native state of the protein preferentially; it results in stabilization of the protein, while in the case of denatured protein it has no impact. There are many studies conducted involving the proteins in buffer solutions but very limited information is available about the mechanism of protein-buffer interactions. In the current study ligand binding mechanism of protein - buffer interaction was studied using molecular docking. After the docking buffers were ranked according to their energy value. The lower energy scores represent better protein-buffer (ligand) binding affinity compared to high energy values. It was observed that Phosphate with a binding affinity of -107.9 kcal/mol was the buffer with the least binding energy followed by Citrate (-70.6 kcal/mol), Melglumine (-66.6 kcal/mol), Arginine (-64.5 kcal/mol), Glucono delta lactone (-62.6 kcal/mol), Sodium citrate (-56.5 kcal/mol), Tromethamine (-52.3 kcal/mol), Glycine HCl (-37.2 kcal/mol), Sulfuric acid (-37.7 kcal/mol), Ammonium acetate (-31.1 kcal/mol), Acetic acid (-30.7 kcal/mol). With lower binding energy higher is the affinity between the ligand and protein. So phosphate was identified as a buffer with the highest affinity with Abatacept.

Spatio-angular filter (SAF) imaging device for deep interrogation of scattering media.

Optical microscopy is limited to shallow interrogation depths as high-resolution imaging in scattering media is challenging. Current methods require complex and expensive experimental setup or suffer from low resolution. Through gating of photons exiting the scattering media using a restricted numerical aperture (NA) fiber optic plate (FOP), we establish a novel spatio-angular filter imaging device that allows deeper imaging in scattering media. Using dilutions of Intralipid (1-4 v/v%) and a USAF resolution target, it is shown that by reducing the NA of the FOP from 0.55 to 0.17, the interrogation depth improves ~2 times using trans-illumination.

Diagnosis of Obstructive Sleep Apnea during Wakefulness Using Upper Airway Negative Pressure and Machine Learning.

Background and Rational: Obstructive Sleep Apnea (OSA) is a common disorder, affecting almost 10% of adults, but very underdiagnosed. This is largely due to limited access to overnight sleep testing using polysomnography (PSG). Our goal was to distinguish OSA from healthy individual using a simple maneuver during wakefulness in combination with machine learning methods. Methods: Participants have undergone an overnight PSG to determine their ground truth OSA severity. Separately, they were asked to breathe through a nasal mask or a mouth piece through which negative pressure (NP) was applied, during wakefulness. Airflow waveforms were acquired and several features were extracted and used to train various classifiers to predict OSA. Results and Discussion: The performance of each classifier and experimental setup was calculated. The best results were obtained using Random Forest classifier for distinguishing OSA from healthy individuals with a very good area under the curve of 0.80. To the best of our knowledge, this is the first study to deploy machine learning and NP with promising path to diagnose OSA during wakefulness.

The effect of continuous positive airway pressure on spectral encephalogram characteristics in stroke patients with obstructive sleep apnea

OBJECTIVES: To evaluate if treatment with continuous positive airway pressure (CPAP) compared to usual care in stroke patients with obstructive sleep apnea (OSA) over one month reduces delta and alpha oscillations on quantitative electroencephalography (EEG) in association with improvements in cognitive or functional outcomes. METHODS: Spectral EEG analysis was performed in patients with subacute stroke and OSA randomized to usual care or CPAP treatment from a previous study. RESULTS: A total of 23 subjects were included. Compared to CPAP (n = 14), those in the control (n = 9) group demonstrated a significant increase in alpha power (p = 0.042). There was no between group differences for delta, theta or beta power. No significant correlation was demonstrated between the change in alpha power and indices of OSA severity or sleepiness. The increase in alpha power did not correlate with improvements in outcomes. CONCLUSION: Contrary to expectations CPAP treatment of OSA did not significantly decrease alpha and delta oscillations in stroke subjects.

The effect of continuous positive airway pressure on spectral encephalogram characteristics in stroke patients with obstructive sleep apnea.

OBJECTIVES: To evaluate if treatment with continuous positive airway pressure (CPAP) compared to usual care in stroke patients with obstructive sleep apnea (OSA) over one month reduces delta and alpha oscillations on quantitative electroencephalography (EEG) in association with improvements in cognitive or functional outcomes. METHODS: Spectral EEG analysis was performed in patients with subacute stroke and OSA randomized to usual care or CPAP treatment from a previous study. RESULTS: A total of 23 subjects were included. Compared to CPAP (n = 14), those in the control (n = 9) group demonstrated a significant increase in alpha power (p = 0.042). There was no between group differences for delta, theta or beta power. No significant correlation was demonstrated between the change in alpha power and indices of OSA severity or sleepiness. The increase in alpha power did not correlate with improvements in outcomes. CONCLUSION: Contrary to expectations CPAP treatment of OSA did not significantly decrease alpha and delta oscillations in stroke subjects.

Non-labeled lensless micro-endoscopic approach for cellular imaging through highly scattering media.

We describe an imaging approach based on an optical setup made up of a miniature, lensless, minimally invasive endoscope scanning a sample and matching post processing techniques that enable enhanced imaging capabilities. The two main scopes of this article are that this approach enables imaging beyond highly scattering medium and increases the resolution and signal to noise levels reaching single cell imaging. Our approach has more advantages over ordinary endoscope setups and other imaging techniques. It is not mechanically limited by a lens, the stable but flexible fiber can acquire images over long time periods (unlike current imaging methods such as OCT etc.), and the imaging can be obtained at a certain working distance above the surface, without interference to the imaged object. Fast overlapping scans enlarge the region of interest, enhance signal to noise levels and can also accommodate post-processing, super-resolution algorithms. Here we present that due to the setup properties, the overlapping scans also lead to dramatic enhancement of non-scattered signal to scattered noise. This enables imaging through highly scattering medium. We discuss results obtained from in vitro investigation of weak signals of ARPE cells, rat retina, and scattered signals from polydimethylsiloxane (PDMS) microchannels filled with hemoglobin and covered by intralipids consequently mimicking blood capillaries and the epidermis of human skin. The development of minimally invasive procedures and methodologies for imaging through scattering medium such as tissues can vastly enhance biomedical diagnostic capabilities for imaging internal organs. We thereby propose that our method may be used for such tasks in vivo.