scholarly journals Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1904
Author(s):  
Frank Maigler ◽  
Simone Ladel ◽  
Johannes Flamm ◽  
Stella Gänger ◽  
Barbara Kurpiers ◽  
...  
Keyword(s):  
Olfactory Mucosa ◽  
Brain Targeting ◽  
Olfactory Pathway ◽  
Delivery Methods ◽  
Major Drawback ◽  
Delivery Technique ◽  
Clinical Potential ◽  
Refined Technique ◽  
Murine Igg1

Intranasal drug delivery is a promising approach for the delivery of drugs to the CNS, but too heterogenous, unprecise delivery methods without standardization decrease the quality of many studies in rodents. Thus, the lack of a precise and region-specific application technique for mice is a major drawback. In this study, a previously developed catheter-based refined technique was validated against the conventional pipette-based method and used to specifically reach the olfactory or the respiratory nasal regions. This study successfully demonstrated region-specific administration at the olfactory mucosa resulting in over 20% of the administered fluorescein dose in the olfactory bulbs, and no peripheral bioactivity of insulin detemir and Fc-dependent uptake of two murine IgG1 (11C7 and P3X) along the olfactory pathway to cortex and hippocampus. An scFv of 11C7 showed hardly any uptake to the CNS. Elimination was dependent on the presence of the IgG’s antigen. In summary, it was successfully demonstrated that region-specific intranasal administration via the olfactory region resulted in improved brain targeting and reduced peripheral targeting in mice. The data are discussed with regard to their clinical potential.

Characteristics of the Frequency-Following Response to Speech in Neonates and Potential Applicability in Clinical Practice: A Systematic Review

2020 ◽  
Vol 63 (5) ◽  
pp. 1618-1635
Author(s):  
Céline Richard ◽  
Mary Lauren Neel ◽  
Arnaud Jeanvoine ◽  
Sharon Mc Connell ◽  
Alison Gehred ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cochrane Library ◽  
Neurodevelopmental Outcomes ◽  
Frequency Following Response ◽  
Ovid Medline ◽  
Published Evidence ◽  
Mesh Terms ◽  
Potential Applicability ◽  
Clinical Potential

Purpose We sought to critically analyze and evaluate published evidence regarding feasibility and clinical potential for predicting neurodevelopmental outcomes of the frequency-following responses (FFRs) to speech recordings in neonates (birth to 28 days). Method A systematic search of MeSH terms in the Cumulative Index to Nursing and Allied HealthLiterature, Embase, Google Scholar, Ovid Medline (R) and E-Pub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Web of Science, SCOPUS, COCHRANE Library, and ClinicalTrials.gov was performed. Manual review of all items identified in the search was performed by two independent reviewers. Articles were evaluated based on the level of methodological quality and evidence according to the RTI item bank. Results Seven articles met inclusion criteria. None of the included studies reported neurodevelopmental outcomes past 3 months of age. Quality of the evidence ranged from moderate to high. Protocol variations were frequent. Conclusions Based on this systematic review, the FFR to speech can capture both temporal and spectral acoustic features in neonates. It can accurately be recorded in a fast and easy manner at the infant's bedside. However, at this time, further studies are needed to identify and validate which FFR features could be incorporated as an addition to standard evaluation of infant sound processing evaluation in subcortico-cortical networks. This review identifies the need for further research focused on identifying specific features of the neonatal FFRs, those with predictive value for early childhood outcomes to help guide targeted early speech and hearing interventions.

scholarly journals PROSES PENYUNTINGAN BERITA PADA PERUSAHAAN JAWATAN TELEVISI REPUBLIK INDONESIA (TVRI) BENGKULU

2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Sapta Sari
Keyword(s):  
United States ◽  
Data Analysis ◽  
Television News ◽  
The United States ◽  
Delivery Technique ◽  
Qualitative Descriptive ◽  
Descriptive Approach ◽  
Editing Process ◽  
Movie Camera

In  line  with  times,  television  news  center  has  been  equipped  with  a  variety  of sophisticated tools, such as the ones used in the production and editing process of the Company Bureau (PERJAN) TVRI Bengkulu. Some of the tools used were: ENG (Electronic News Gathering), a large movie camera (Sound On Film) electronic editing tools, broadcasting space, VTR space, and various other supporting tools that are used to improve the quality of broadcasting. In this research, researchers used a qualitative descriptive approach by interview, observation and documentation, followed by data analysis. The result of this research found that the process of delivering news on TVRI Bengkulu, particularly on program Bengkulu dalam Berita, has been carried out by adjusting the news delivery technique through two ways: ie the way the British were serious and formal and casual events of the United States. Both methods have been implemented in the event of this program.Keywords: editing process, news 

scholarly journals SARS-CoV-2 and the Brain: What Do We Know about the Causality of ‘Cognitive COVID?

2021 ◽  
Vol 10 (15) ◽  
pp. 3441
Author(s):  
Hashir Ali Awan ◽  
Mufaddal Najmuddin Diwan ◽  
Alifiya Aamir ◽  
Muneeza Ali ◽  
Massimo Di Giannantonio ◽  
...  
Keyword(s):  
Olfactory Pathway ◽  
Cognitive Sequelae ◽  
Significant Burden ◽  
Inflammatory State ◽  
Underlying Mechanisms ◽  
Acute Changes ◽  
A Minor

The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual’s overall wellbeing, including adequate cognitive functioning. ‘Cognitive COVID’ is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of ‘Cognitive COVID’ as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of ‘Cognitive COVID.’ Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic’s unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.

scholarly journals Migraine: Experimental Models and Novel Therapeutic Approaches

2019 ◽  
Vol 20 (12) ◽  
pp. 2932 ◽  
Author(s):  
Giuseppe Tardiolo ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Experimental Models ◽  
Brain Targeting ◽  
Future Perspective ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Pharmacological Targets ◽  
Genetic Modifications ◽  
Inflammatory Soup ◽  
Calcitonin Gene

Migraine is a disorder affecting an increasing number of subjects. Currently, this disorder is not entirely understood, and limited therapeutic solutions are available. Migraine manifests as a debilitating headache associated with an altered sensory perception that may compromise the quality of life. Animal models have been developed using chemical, physical or genetic modifications, to evoke migraine-like hallmarks for the identification of novel molecules for the treatment of migraine. In this context, experimental models based on the use of chemicals as nitroglycerin or inflammatory soup were extensively used to mimic the acute state and the chronicity of the disorder. This manuscript is aimed to provide an overview of murine models used to investigate migraine pathophysiology. Pharmacological targets as 5-HT and calcitonin gene-related peptide (CGRP) receptors were evaluated for their relevance in the development of migraine therapeutics. Drug delivery systems using nanoparticles may be helpful for the enhancement of the brain targeting and bioavailability of anti-migraine drugs as triptans. In conclusion, the progresses in migraine management have been reached with the development of emerging agonists of 5-HT receptors and novel antagonists of CGRP receptors. The nanoformulations may represent a future perspective in which already known anti-migraine drugs showed to better exert their therapeutic effects.

scholarly journals Reducing Ensembles of Protein Tertiary Structures Generated De Novo via Clustering

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2228
Author(s):  
Ahmed Bin Zaman ◽  
Parastoo Kamranfar ◽  
Carlotta Domeniconi ◽  
Amarda Shehu
Keyword(s):  
Protein Structure ◽  
Structure Prediction ◽  
De Novo ◽  
Source Code ◽  
Protein Molecule ◽  
Biologically Active ◽  
Major Drawback ◽  
Tertiary Structures ◽  
Active Structure

Controlling the quality of tertiary structures computed for a protein molecule remains a central challenge in de-novo protein structure prediction. The rule of thumb is to generate as many structures as can be afforded, effectively acknowledging that having more structures increases the likelihood that some will reside near the sought biologically-active structure. A major drawback with this approach is that computing a large number of structures imposes time and space costs. In this paper, we propose a novel clustering-based approach which we demonstrate to significantly reduce an ensemble of generated structures without sacrificing quality. Evaluations are related on both benchmark and CASP target proteins. Structure ensembles subjected to the proposed approach and the source code of the proposed approach are publicly-available at the links provided in Section 1.

scholarly journals Informational Needs in Patients With Breast Cancer With Lymphedema: Is It Important?

2020 ◽  
Vol 14 ◽  
pp. 117822342091103
Author(s):  
Sara Dorri ◽  
Asiie Olfatbakhsh ◽  
Farkhondeh Asadi
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Social Networks ◽  
Breast Cancer Treatment ◽  
Informational Needs ◽  
Average Income ◽  
Delivery Methods ◽  
Convenience Sampling ◽  
Very High

Introduction: Lymphedema is one of the complications of breast cancer treatment. It has no cure yet and can affect the quality of life. This study aimed to identify and investigate informational needs, preferred delivery methods, and time of receiving information about lymphedema for these patients. Methods: One hundred participants were recruited through Lymphedema Clinic in Motamed Cancer Institute in Tehran, Iran, through convenience sampling and were asked to complete a self-administered survey. Data collection took place on all opening days between October 2018 and mid-March 2019. Results: Most of the participants were above 40 years, have a diploma, homemaker, and the average income of most of the participants (57.2%) was low. The importance of having lymphedema information was very high for them. Most of them wanted detailed information at diagnosis of breast cancer. The preferred information of delivery methods were private sessions and social networks. Conclusions: Patients with breast cancer who have lymphedema have high needs as regards concise lymphedema information. Private sessions with physicians and social networks can provide detailed information for them.

scholarly journals Efficacy of Vitamin D3 Buccal Spray Supplementation Compared to Other Delivery Methods: A Systematic Review of Superiority Randomized Controlled Trials

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 691 ◽  
Author(s):  
Maria G. Grammatikopoulou ◽  
Konstantinos Gkiouras ◽  
Meletios P. Nigdelis ◽  
Dimitrios P. Bogdanos ◽  
Dimitrios G. Goulis
Keyword(s):  
Health Status ◽  
Randomized Controlled Trials ◽  
Vitamin D3 ◽  
Health Concern ◽  
Controlled Trials ◽  
Post Intervention ◽  
Delivery Methods ◽  
Pubmed Central ◽  
Randomized Controlled

(1) Background: Vitamin D deficiency is an important public health concern and supplementation is common for this deficiency. Many different modes of delivering supplementation have been proposed in order to enhance absorption and utilization. The present review compared the efficacy of vitamin D3 buccal spray against other forms of supplementation delivery. (2) Methods: The protocol was registered at PROSPERO (CRD42019136146). Medline/PubMed, CENTRAL and clinicaltrials.gov were searched from their inception until September 2019, for randomized controlled trials (RCTs) that compare vitamin D3 delivery via sublingual spray against other delivery methods. Eligible RCTs involved humans, of any age and health status, published in any language that evaluated changes in plasma 25(OH)D concentrations. Three reviewers independently extracted data, assessed risk of bias (RoB) and the quality of the trials. (3) Results: Out of 9759 RCTs, four matched the predefined criteria. Intervention duration ranged from 30 days to 3 months whereas vitamin D3 dosage ranged between 800 and 3000 IU/day. One RCT advocated for the superiority of buccal spray in increasing plasma 25(OH)D concentrations, although several limitations were recorded in that trial. The rest failed to report differences in post-intervention 25(OH)D concentrations between delivery methods. Considerable clinical heterogeneity was observed due to study design, intervention duration and dosage, assays and labs used to perform the assays, population age and health status, not allowing for synthesis of the results. (4) Conclusions: Based on the available evidence, delivery of vitamin D3 via buccal spray does not appear superior to the other modes of delivery. Future RCTs avoiding the existing methodological shortcomings are warranted.

scholarly journals Intranasal Nanoemulsions for Direct Nose-to-Brain Delivery of Actives for CNS Disorders

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1230
Author(s):  
Shiv Bahadur ◽  
Dinesh M. Pardhi ◽  
Jarkko Rautio ◽  
Jessica M. Rosenholm ◽  
Kamla Pathak
Keyword(s):  
Rapid Development ◽  
Brain Targeting ◽  
Nasal Administration ◽  
Future Research ◽  
Brain Delivery ◽  
Olfactory Pathway ◽  
Nasal Drug Delivery ◽  
Cns Diseases ◽  
Biodistribution Studies ◽  
The Brain

The treatment of various central nervous system (CNS) diseases has been challenging, despite the rapid development of several novel treatment approaches. The blood–brain barrier (BBB) is one of the major issues in the treatment of CNS diseases, having major role in the protection of the brain but simultaneously constituting the main limiting hurdle for drugs targeting the brain. Nasal drug delivery has gained significant interest for brain targeting over the past decades, wherein the drug is directly delivered to the brain by the trigeminal and olfactory pathway. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research.

scholarly journals Penerapan Quality Function Deployment(QFD) Untuk Mengembangkan Kualitas Pelayanan Rawat Jalan Berorientasi Pelanggan Di Rumah Sakit Paru-Paru

2012 ◽  
Vol 1 (1) ◽  
pp. 65-75
Author(s):  
Rudy Joegijantoro
Keyword(s):  
Fuzzy Logic ◽  
Quality Function Deployment ◽  
House Of Quality ◽  
Customer Requirements ◽  
Linguistic Terms ◽  
Major Drawback ◽  
Quality Function ◽  
Structured Design ◽  
Functional Features

Quality Function Deployment (QFD) is defined as a method that supports the structured design of products or services. The method is based on the customer needs and involves all the relevant parties within an organization that develops and produces a product through teamwork. It is a method for mapping and prioritizing customer requirements into functional features and technical modules to optimize market performance. Although the quality of a service can be dramatically improved through a QFD exercise, the traditional crisp scoring approach has a major drawback. A wrong conclusion can be easily produced since the fuzzy nature of linguistic correlation terms from evaluation members is ignored. To overcome this problem, fuzzy scoring for linguistic terms is proposed in this paper. This study integrates fuzzy logic into House Of Quality to establish a framework for prioritizing customer requirements to simply, objectively, and scientifically analyze service features.

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