To Explore Nasal-Brain Lymphatic System for Brain-Targeted Drug Delivery and to Treat Neurodegenerative Diseases.

Brain-related Neurodegenerative Disorders (NDD) are the leading cause of low life expectancy globally. Brain-targeted drug delivery is required for treating most the NDD via bypassing the blood-brain barrier, and hepatic first-pass metabolism. The nasal-brain drug delivery route has the advantage of locally enhancing drug delivery to the brain, mainly through the olfactory route rather than systemic circulation. To overcome the limitations of nasal-brain drug delivery, a nanocarrier approach and mucoadhesive polymers are needed. Notwithstanding these constraints, various nanotechnology techniques have been created, including polymeric micelles, liposomes, polymeric nanoparticles, solid lipid nanoparticles, & nano-emulsions. This review aims to explore the intranasal pathway for drug delivery through the nasal-brain lymphatic systems, considering brain anatomy and physiology along with a drug formulation design approach.

Neural correlates of bilateral proprioception and adaptation with training.

Bilateral proprioception includes the ability to sense the position and motion of one hand relative to the other, without looking. This sensory ability allows us to perform daily activities seamlessly, and its impairment is observed in various neurological disorders such as cerebral palsy and stroke. It can undergo experience-dependent plasticity, as seen in trained piano players. If its neural correlates were better understood, it would provide a useful assay and target for neurorehabilitation for people with impaired proprioception. We designed a non-invasive electroencephalography-based paradigm to assess the neural features relevant to proprioception, especially focusing on bilateral proprioception, i.e., assessing the limb distance from the body with the other limb. We compared it with a movement-only task, with and without the visibility of the target hand. Additionally, we explored proprioceptive accuracy during the tasks. We tested eleven Controls and nine Skilled musicians to assess whether sensorimotor event-related spectral perturbations in µ (8-12Hz) and low-ß (12-18Hz) rhythms differ in people with musical instrument training, which intrinsically involves a bilateral proprioceptive component, or when new sensor modalities are added to the task. The Skilled group showed significantly reduced µ and low-ß suppression in bilateral tasks compared to movement-only, a significative difference relative to Controls. This may be explained by reduced top-down control due to intensive training, despite this, proprioceptive errors were not smaller for this group. Target visibility significantly reduced proprioceptive error in Controls, while no change was observed in the Skilled group. During visual tasks, Controls exhibited significant µ and low-ß power reversals, with significant differences relative to proprioceptive-only tasks compared to the Skilled group-possibly due to reduced uncertainty and top-down control. These results provide support for sensorimotor µ and low-ß suppression as potential neuromarkers for assessing proprioceptive ability. The identification of these features is significant as they could be used to quantify altered proprioceptive neural processing in skill and movement disorders. This in turn can be useful as an assay for pre and post sensory-motor intervention research.

Biomarkers in severe asthma: Identifying the treatable trait.

Asthma is a chronic condition of bronchial hyper-reactivity associated with inflammation ranges from mild to severe form. It affects 1 - 18% of the population globally and it is estimated that > 300million people in the world have asthma. Of this 5 - 10% have severe asthma. while the proportion of patients suffering from severe are smaller, the morbidity and mortality are higher in this group. With the advances in our understanding of the pathophysiology of asthma there is a need to understand the role of various biomarkers. We live in an era of precision medicine and today there is a clear unmet need to understand targeted therapies. This review aims to raise awareness to the available biomarkers used in clinical practice in India and their role in predicting response to targeted therapies.

Choosing Periodontology for Specialty Specialization: Perspective of Dental Undergraduate Students.

BACKGROUND: The attitudes of dental students to study a particular specialty of dentistry in post-graduation are of great importance as these facilitate workforce planning in the dental sector. AIM AND OBJECTIVE: To assess the attitude of dental students towards choosing periodontology as their future career and to explore demographic variables that affect their choice. MATERIALS AND METHODS: A cross-sectional survey based on a questionnaire was conducted, including students of the third and fourth years and interns of the dental college. Twenty-seven questions, graded on a Likert scale (5-point) were included in the questionnaire, and the responses were categorised via three attitudes: negative (score 0-21), neutral (score 22-44) and positive (score 45-64). The Chi-square test for proportions was used to examine the differences between groups. RESULTS: Among 114 participants, 53 (46.5%) were males and 61 (53.5%) were females. One-third of the respondents had a positive attitude towards selecting periodontology as their future career, and the majority had a neutral perspective, with a few students having a negative attitude (20.2%). Out of the total, 34.2% of respondents had a positive attitude, and 45.6% showed a neutral attitude or perspective. CONCLUSION: Efforts should be intensified, and undergraduate (UG) students should be motivated by broadening the scope of the field in the UG curriculum by the dental council so that the students show considerable interest in pursuing the field as their future career.

A Comparative Study to Confirm the Endotracheal Tube Placement Using Ultrasonography and Standard Auscultation Method in Children.

BACKGROUND: In pediatric patients due to shorter trachea suboptimal positioning of endotracheal tube (ETT) is seen in 20%-50% of patients triggering grave complications. We compared standard auscultation and ultrasound-guided lung sliding to confirm the position of ETT in children. METHODS: Seventy-five pediatric patients between 2-8 years of age, American Society of Anesthesiologists physical status classification I and II scheduled for surgery under general anesthesia with endotracheal intubation were studied. The position of ETT was confirmed by chest auscultation for the breath sounds bilaterally and by ultrasound on the same sites for lung-sliding signs. The data obtained were compared to findings on waveform capnography. Study outcomes included position of the ETT; tracheal or esophageal, accuracy of diagnosis and time taken till confirming the diagnosis. RESULTS: Compared to waveform capnography findings, an ultrasound revealed a sensitivity of 94.31%, a specificity of 72.33%, and an accuracy of 90.7% while that for standard auscultation were 82.8%, 47.28%, and 74.67%, respectively. The mean time taken for confirmation of ETT position was significantly shorter with waveform capnography (10.29 ± 2.25 s) compared to auscultation (12.96 ± 2.23 s) and ultrasonography (USG) (14.28 ± 3.77 s). CONCLUSION: Confirmation of ETT position using USG or waveform capnography is essential because of high false results using standard auscultation alone. Ultrasound-guided lung sliding method is a simple, fast, and a reliable method used for detecting tube malposition.

Comparative Evaluation of Clinical Efficacy of Diode LASER and Cryosurgery for Gingival Pigmentation: A Split-Mouth Randomized Clinical Study

ABSTRACT Objective: To compare and evaluate the clinical efficacy of diode laser and cryosurgery for treating melanin pigmentation of gingiva. Material and Methods: A total of twenty-five subjects with physiological gingival pigmentation on the facial aspect of both maxillary and mandibular anterior arches (50 sites), both male and female, with an average age ranging from 18-35 years, participated in the study. The sites were randomly divided into Group I: depigmentation by Laser and Group II: depigmentation by Cryosurgery. The following parameters were assessed for the evaluation of treatment results: Melanin Oral Pigmentation Index (PI), Visual Analogue Scale (VAS) for pain evaluation and Healing index (HI). The data collected was statistically evaluated. Results: On intergroup comparison, there was no statistical difference in the score from baseline (p>0.05); however, a statistically significant difference was seen at the end of 1 year (p<0.05). Moreover, 57-60% of arches showed recurrence of pigmentation in the laser group whereas; only 12.7-17% recurrence was seen in the cryosurgery group at the end of the first year. Conclusion: Treatment of gingival hyperpigmentation with laser and cryosurgery shows a marked improvement of gingival pigmentation in both groups, but the cryosurgery depigmentation sites showed more sustainability.

Comparative evaluation of midline versus parasagittal interlaminar epidural steroid injection for management of symptomatic lumbar intervertebral disc herniation.

Background and Aims: Epidural steroid injections (ESIs) with or without local anaesthetics have been used for the past several years for the treatment of back pain, especially for radicular symptoms. The aim of this prospective study was to compare the efficacy of midline with parasagittal approach for interlaminar ESI in the management of symptomatic lumbar intervertebral disc herniation. Methods: Sixty patients (aged 20-60 years) with pain pattern consistent with lumbar radiculopathy caused by lumbar intervertebral disc herniation and who did not respond to conservative treatment were included in the study. They were randomly divided in two groups of 30 each: group I (MILESI, n = 30) consisting of midline interlaminar ESI, and group II (PSILESI, n = 30) consisting of parasagittal interlaminar ESI. They were administered a combination of 80 mg of methylprednisolone acetate (40 mg/ml) and 6 ml of 0.25% bupivacaine (total volume of 8 ml). Pain, patient satisfaction, and the Oswestry Disability Index (ODI) were assessed at different time intervals before and after the procedure for up to six months. Results: The improvement in pain score after ESI was statistically significant in both the groups at all intervals of time, with no significant difference between the two groups. The mean pain score was <3 from two weeks onwards after the injection. The pain score decreased by more than five points and it was around two points at the end of the six-month study period. Around 50% of patients in both groups had excellent satisfaction. Conclusion: Both techniques were effective in providing good analgesia. Pain relief and improvement in disability were clinically better with the parasagittal interlaminar approach.

The Evoked Potential Operant Conditioning System (EPOCS): A Research Tool and an Emerging Therapy for Chronic Neuromuscular Disorders.

The Evoked Potential Operant Conditioning System (EPOCS) is a software tool that implements protocols for operantly conditioning stimulus-triggered muscle responses in people with neuromuscular disorders, which in turn can improve sensorimotor function when applied appropriately. EPOCS monitors the state of specific target muscles-e.g., from surface electromyography (EMG) while standing, or from gait cycle measurements while walking on a treadmill-and automatically triggers calibrated stimulation when pre-defined conditions are met. It provides two forms of feedback that enable a person to learn to modulate the targeted pathway's excitability. First, it continuously monitors ongoing EMG activity in the target muscle, guiding the person to produce a consistent level of activity suitable for conditioning. Second, it provides immediate feedback of the response size following each stimulation and indicates whether it has reached the target value. To illustrate its use, this article describes a protocol through which a person can learn to decrease the size of the Hoffmann reflex-the electrically-elicited analog of the spinal stretch reflex-in the soleus muscle. Down-conditioning this pathway's excitability can improve walking in people with spastic gait due to incomplete spinal cord injury. The article demonstrates how to set up the equipment; how to place stimulating and recording electrodes; and how to use the free software to optimize electrode placement, measure the recruitment curve of direct motor and reflex responses, measure the response without operant conditioning, condition the reflex, and analyze the resulting data. It illustrates how the reflex changes over multiple sessions and how walking improves. It also discusses how the system can be applied to other kinds of evoked responses and to other kinds of stimulation, e.g., motor evoked potentials to transcranial magnetic stimulation; how it can address various clinical problems; and how it can support research studies of sensorimotor function in health and disease.

Similar biologics in India: A story of access or potential for compromise?

Biosimilars or similar biotherapeutic products are the biological products approved by regulatory agencies based on the demonstration of similarity in quality, safety and efficacy with reference biologics (or original biologics). Though biosimilars could be considered as interchangeable therapeutic alternatives over original biologics, there are concerns regarding their similarity in effectiveness and safety with reference product along with the level of evidence of similarity required for approval. The biosimilars, particularly, monoclonal antibodies that are developed based on the complex manufacturing processes, require stringent comparative evaluations. The Indian Regulatory Authorities in July 2012 developed the first guidelines for approval of similar biologics, which comprised requirements for the manufacturing process, quality evaluation, preclinical and clinical studies, as well as post-marketing studies. The 2016 guidelines, an update to previous guidelines, were released with the intent to provide a well-defined pathway at par with international regulations for the approval of similar biologics in India. This article highlights the key attributes of the 2016 Regulatory Guidelines and also describes the aspects such as interchangeability, nomenclature and labelling of similar biologics in India. Rigorous consideration is imperative for highly complex similar biologics of monoclonal antibodies on a case-to-case basis.

Electronic and Geometric Structures of Rechargeable Lithium Manganese Sulfate Li2Mn(SO4)2 Cathode.

Here, we report the use of Li2Mn(SO4)2 as a potential energy storage material and describe its route of synthesis and structural characterization over one electrochemical cycle. Li2Mn(SO4)2 is synthesized by ball milling of MnSO4·H2O and Li2SO4·H2O and characterized using a suite of techniques, in particular, ex situ X-ray diffraction, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy on the Mn and S K-edges to investigate the electronic and local geometry around the absorbing atoms. The prepared Li2Mn(SO4)2 electrodes undergo electrochemical cycles to different potential points on the charge-discharge curve and are then extracted from the cells at these points for ex situ structural analysis. Analysis of X-ray absorption spectroscopy (both near and fine structure part of the data) data suggests that there are minimal changes to the oxidation state of Mn and S ions during charge-discharge cycles. However, X-ray photoelectron spectroscopy analysis suggests that there are changes in the oxidation state of Mn, which appears to be different from the conclusion drawn from X-ray absorption spectroscopy. This difference in results during cycling can thus be attributed to electrochemical reactions being dominant at the surface of the Li2Mn(SO4)2 particles rather than in the bulk.

Targeted Infarction of the Internal Capsule in the Rat Using Microstimulation Guidance.

Background and Purpose- Lacunar strokes are subcortical infarcts with small size and high disability rates, largely due to injury of the corticospinal tract in the internal capsule (IC). Current rodent models of lacunar infarcts are created based on stereotactic coordinates. We tested the hypothesis that better understanding of the somatotopy of the IC and guiding the lesion with electrical stimulation would allow a more accurate lesion to the forelimb axons of the IC. Methods- We performed electrophysiological motor mapping and viral tracing to define the somatotopy of the IC of Sprague Dawley rats. For the lesion, we used an optrode, which contains an electrode to localize forelimb responses and an optical fiber to deliver light. The infarct was induced when light activated the photothrombotic agent Rose Bengal, which was administered systemically. Results- We found largely a separate distribution of the forelimb and hindlimb axons in the IC, both by microstimulation mapping and tract tracing. Microstimulation-guided IC lesions ablated the forelimb axons of the IC in rats and caused lasting forelimb impairments while largely preserving the hindlimb axons of the IC and surrounding gray matter. Conclusions- Stimulation guidance enabled selective and reproducible infarcts of the forelimb axons of the IC in rats. Visual Overview- An online visual overview is available for this article.

Interaction of Self-Regulation and Contextual Effects on Pre-attentive Auditory Processing: A Combined EEG/ECG Study.

Environmental changes are not always within the focus of our attention, and sensitive reactions (i.e., quicker and stronger responses) can be essential for an organism's survival and adaptation. Here we report that neurophysiological responses to sound changes that are not in the focus of attention are related to both ambient acoustic contexts and regulation ability. We assessed electroencephalograph (EEG) mismatch negativity (MMN) latency and amplitude in response to sound changes in two contexts: ascending and descending pitch sequences while participants were instructed to attend to muted videos. Prolonged latency and increased amplitude of MMN at fronto-central region occurred in ascending pitch sequences relative to descending sequences. We also assessed how regulation related to the contextual effects on MMN. Reactions to changes in the ascending sequence were observed with the attention control (frontal EEG theta/beta ratio) indicating speed of reaction, and the autonomous regulation (heart-rate variability) indicating intensity of reaction. Moreover, sound changes in the ascending context were associated with more activation of anterior cingulate cortex and insula, suggesting arousal effects and regulation processes. These findings suggest that the relation between speed and intensity is not fixed and may be modified by contexts and self-regulation ability. Specifically, cortical and cardiovascular indicators of self-regulation may specify different aspects of response sensitivity in terms of speed and intensity.

Crystal Chemistry and Antibacterial Properties of Cupriferous Hydroxyapatite.

Copper-doped hydroxyapatite (HA) of nominal composition Ca10(PO4)6[Cux(OH)2-2xOx] (0.0 ≤ x ≤ 0.8) was prepared by solid-state and wet chemical processing to explore the impact of the synthesis route and mode of crystal chemical incorporation of copper on the antibacterial efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) strains. Apatites prepared by solid-state reaction showed unit cell volume dilation from 527.17 Å3 for copper-free HA to 533.31 Å3 for material of the putative composition Ca10(PO4)6[Cu0.8(OH)0.4O0.8] consistent with Cu+ insertion into the [001] hydroxyapatite channel. This was less pronounced (528.30 Å3 to 529.3 Å3) in the corresponding wet chemical synthesised products, suggesting less complete Cu tunnel incorporation and partial tenancy of Cu in place of calcium. X-ray absorption spectroscopy suggests fast quenching is necessary to prevent oxidation of Cu+ to Cu2+. Raman spectroscopy revealed an absorption band at 630 cm-1 characteristic of symmetric O-Cu+-O units tenanted in the apatite channel while solid-state 31P magic-angle-spinning nuclear magnetic resonance (MAS NMR) supported a vacancy-Cu+ substitution model within the apatite channel. The copper doping strategy increases antibacterial efficiency by 25% to 55% compared to undoped HA, with the finer particle sizes and greater specific surface areas of the wet chemical material demonstrating superior efficacy.

Motometrics: A Toolbox for Annotation and Efficient Analysis of Motor Evoked Potentials.

Stimulating the nervous system and measuring muscle response offers a unique opportunity to interrogate motor system function. Often, this is performed by stimulating motor cortex and recording muscle activity with electromyography; the evoked response is called the motor evoked potential (MEP). To understand system dynamics, MEPs are typically recorded through a range of motor cortex stimulation intensities. The MEPs increase with increasing stimulation intensities, and these typically produce a sigmoidal response curve. Analysis of MEPs is often complex and analysis of response curves is time-consuming. We created an MEP analysis software, called Motometrics, to facilitate analysis of MEPs and response curves. The goal is to combine robust signal processing algorithms with a simple user interface. Motometrics first enables the user to annotate data files acquired from the recording system so that the responses can be extracted and labeled with the correct subject and experimental condition. The software enables quick visual representations of entire datasets, to ensure uniform quality of the signal. It then enables the user to choose a variety of response curve analyses and to perform near real time quantification of the MEPs for quick feedback during experimental procedures. This is a modular open source tool that is compatible with several popular electrophysiological systems. Initial use indicates that Motometrics enables rapid, robust, and intuitive analysis of MEP response curves by neuroscientists without programming or signal processing expertise.

Corrigendum: Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

[This corrects the article DOI: 10.3389/fncir.2018.00028.].

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy.

Hybrid Nanomaterials with Single-Site Catalysts by Spatially Controllable Immobilization of Nickel Complexes via Photoclick Chemistry for Alkene Epoxidation.

Catalyst deactivation is a persistent problem not only for the scientific community but also in industry. Isolated single-site heterogeneous catalysts have shown great promise to overcome these problems. Here, a versatile anchoring strategy for molecular complex immobilization on a broad range of semiconducting or insulating metal oxide ( e. g., titanium dioxide, mesoporous silica, cerium oxide, and tungsten oxide) nanoparticles to synthesize isolated single-site catalysts has been studied systematically. An oxidatively stable anchoring group, maleimide, is shown to form covalent linkages with surface hydroxyl functionalities of metal oxide nanoparticles by photoclick chemistry. The nanocomposites have been thoroughly characterized by techniques including UV-visible diffuse reflectance spectroscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, infrared spectroscopy, and X-ray absorption spectroscopy (XAS). The IR spectroscopic studies confirm the covalent linkages between the maleimide group and surface hydroxyl functionalities of the oxide nanoparticles. The hybrid nanomaterials function as highly efficient catalysts for essentially quantitative oxidations of terminal and internal alkenes and show molecular catalyst product selectivities even in more eco-friendly solvents. XAS studies verify the robustness of the catalysts after several catalytic cycles. We have applied the photoclick anchoring methodology to precisely control the deposition of a luminescent variant of our catalyst on the metal oxide nanoparticles. Overall, we demonstrate a general approach to use irradiation to anchor molecular complexes on oxide nanoparticles to create recyclable, hybrid, single-site catalysts that function with high selectivity in a broad range of solvents. We have achieved a facile, spatially and temporally controllable photoclick method that can potentially be extended to other ligands, catalysts, functional molecules, and surfaces.