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International Journal of Nanomedicine 2024Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts...
Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design-related insights.
Topics: Administration, Intranasal; Blood-Brain Barrier; Brain; Drug Delivery Systems; Lipids; Liposomes; Nanoparticles; Nasal Mucosa
PubMed: 38414526
DOI: 10.2147/IJN.S439181 -
Ear, Nose, & Throat Journal Nov 2023To summarize the current applications and potential uses of optical coherence tomography (OCT), a noninvasive imaging modality that uses near-infrared light to produce... (Review)
Review
To summarize the current applications and potential uses of optical coherence tomography (OCT), a noninvasive imaging modality that uses near-infrared light to produce cross-sectional, high-resolution images of biologic tissues, for evaluating the sinonasal mucosa in patients. Original articles utilizing OCT to image the sinonasal mucosa in patients were identified from the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases using the search phrase: "Optical Coherence Tomography" AND (sinonasal OR intranasal OR sinus OR nose OR sinusitis OR rhinitis OR olfactory). Strength of evidence, quality of evidence, and risk of bias were measured using validated scales. Study results were qualitatively assessed. Out of 1662 original records identified through database searching, 9 studies were included in the systematic review. Levels of evidence ranged from III to IV and quality of evidence ranged from moderate to very low. Endoscopic OCT systems as well as OCT systems integrated with surgical microscopes were described in the literature. Applications of OCT for imaging the sinonasal mucosa included identifying morphological patterns unique to individual diseases, detecting mucosal structural changes after medical therapies and procedures, and evaluating mucociliary clearance. Most studies investigating OCT imaging of the sinonasal mucosa featured small sample sizes and lacked control groups. While OCT imaging could be a useful adjunct for diagnosing sinonasal disorders and monitoring response to treatment in the future, additional high-quality studies are necessary to determine if the use of OCT imaging can lead to improved diagnostic accuracy and health outcomes for patients with sinonasal pathologies.
PubMed: 38032064
DOI: 10.1177/01455613231214622 -
World Neurosurgery Jan 2024To present strategies for managing tumor mass formation and their corresponding postoperative outcomes.
OBJECTIVE
To present strategies for managing tumor mass formation and their corresponding postoperative outcomes.
METHODS
We conducted a systematic literature review following the guidelines and protocol of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched the PubMed and EMBASE databases, screened titles and abstracts, and further evaluated full-text publications to select relevant studies. Additionally, a narrative review of other pertinent articles on PubMed was performed. Case reports, cohort studies, and clinical trials were included. Animal studies were excluded.
RESULTS
Of 6 patients enrolled in this study, most had American Spinal Injury Association Impairment Scale grade A (66.7%) following intramedullary injury, and 1 patient had American Spinal Injury Association Impairment Scale grade D (16.65%). The discovery time of the intramedullary mass formation ranged from approximately 5 to 14 years. Surgical intervention was performed in most cases (66.7%), with improvement reported in 3 of the surgical cases (75%). The majority of cases (83.3%) involved cervical lesions, while only 1 case (16.7%) involved a thoracic lesion.
CONCLUSIONS
Due to the scarcity of described cases, there is no specific treatment for this tumor. Although our patient remained stable after conservative treatment, other studies have shown improvement in symptoms after mass resection. It is essential that the management of this complication be researched further due to the variety of clinical characteristics presented.
Topics: Animals; Humans; Neoplasms; PubMed; Spinal Cord Injuries; Spinal Injuries; Transplantation, Autologous
PubMed: 37898276
DOI: 10.1016/j.wneu.2023.10.093 -
European Journal of Neurology Dec 2023Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is limited consensus regarding the diagnostic and differential diagnostic performance of α-syn SAAs on biofluids and peripheral tissues.
METHODS
A comprehensive research was performed in PubMed, Web of Science, Embase and Cochrane Library. Meta-analysis was performed using a random-effects model. A network meta-analysis based on an ANOVA model was conducted to compare the relative accuracy of α-syn SAAs with different specimens.
RESULTS
The pooled sensitivity and specificity of α-syn SAAs in distinguishing PD from healthy controls or non-neurodegenerative neurological controls were 0.91 (95% confidence interval [CI] 0.89-0.92) and 0.95 (95% CI 0.94-0.96) for cerebrospinal fluid (CSF); 0.91 (95% CI 0.86-0.94) and 0.92 (95% CI 0.87-0.95) for skin; 0.80 (95% CI 0.66-0.89) and 0.87 (95% CI 0.69-0.96) for submandibular gland; 0.44 (95% CI 0.30-0.59) and 0.92 (95% CI 0.79-0.98) for gastrointestinal tract; 0.79 (95% CI 0.70-0.86) and 0.88 (95% CI 0.77-0.95) for saliva; and 0.51 (95% CI 0.39-0.62) and 0.91 (95% CI 0.84-0.96) for olfactory mucosa (OM). The pooled sensitivity and specificity were 0.91 (95% CI 0.89-0.93) and 0.50 (95% CI 0.44-0.55) for CSF, 0.92 (95% CI 0.83-0.97) and 0.22 (95% CI 0.06-0.48) for skin, and 0.55 (95% CI 0.42-0.68) and 0.50 (95% CI 0.35-0.65) for OM in distinguishing PD from multiple system atrophy. The pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.84 (95% CI 0.73-0.91) for CSF, 0.92 (95% CI 0.83-0.97) and 0.88 (95% CI 0.64-0.99) for skin and 0.63 (95% CI 0.52-0.73) and 0.86 (95% CI 0.64-0.97) for OM in distinguishing PD from progressive supranuclear palsy. The pooled sensitivity and specificity were 0.94 (95% CI 0.90-0.97) and 0.95 (95% CI 0.77-1.00) for CSF and 0.94 (95% CI 0.84-0.99) and 0.86 (95% CI 0.42-1.00) for skin in distinguishing PD from corticobasal degeneration.
CONCLUSIONS
α-Synuclein SAAs of CSF, skin, saliva, submandibular gland, gastrointestinal tract and OM are promising diagnostic assays for PD, with CSF and skin α-syn SAAs demonstrating higher diagnostic performance.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Network Meta-Analysis; Biomarkers; Multiple System Atrophy
PubMed: 37573472
DOI: 10.1111/ene.16041 -
Biology Apr 2023The devastating effects of Alzheimer's disease (AD) are yet to be ameliorated due to the absence of curative treatment options. AD is an aging-related disease that...
The devastating effects of Alzheimer's disease (AD) are yet to be ameliorated due to the absence of curative treatment options. AD is an aging-related disease that affects cognition, and molecular imbalance is one of its hallmarks. There is a need to identify common causes of molecular imbalance in AD and their potential mechanisms for continuing research. A narrative synthesis of molecular mechanisms in AD from primary studies that employed single-cell sequencing (scRNA-seq) or spatial genomics was conducted using Embase and PubMed databases. We found that differences in molecular mechanisms in AD could be grouped into four key categories: sex-specific features, early-onset features, aging, and immune system pathways. The reported causes of molecular imbalance were alterations in bile acid (BA) synthesis, PITRM1, TREM2, olfactory mucosa (OM) cells, cholesterol catabolism, NFkB, double-strand break (DSB) neuronal damage, P65KD silencing, tau and APOE expression. What changed from previous findings in contrast to results obtained were explored to find potential factors for AD-modifying investigations.
PubMed: 37106802
DOI: 10.3390/biology12040602 -
Cureus Jan 2023The objective of this systematic review was to investigate the expression of angiotensin converting enzyme 2 (ACE 2) in the head and neck region. We examined the... (Review)
Review
The objective of this systematic review was to investigate the expression of angiotensin converting enzyme 2 (ACE 2) in the head and neck region. We examined the evidence of the association of ACE 2 expression in oral tissues, salivary glands, and head and neck carcinoma. We searched Pub Med/Medline, Biorxiv, and Google Scholar to identify relevant literature. Studies reporting ACE 2 expression in human oral tissues and with a focus on head and neck carcinoma samples were included. From 110 studies, we extracted 15 studies analyzing the distribution and expression of ACE 2 in different head and neck tissues - olfactory mucosa and nasopharynx n=5, oral mucosa n=5, salivary gland n=5, head and neck squamous cell carcinoma patients n=3. ACE 2 was found to be expressed at a 4.43-fold increase in the head and neck region (OR, 4.43; 95% CI, 3.76-5.22; I= 97%, P=<0.00001) when compared with controls (other tissues except for head and neck region). RNA expression of ACE 2 was 60% higher in head and neck squamous cell carcinoma patients than that in the normal tissues (OR=0.60, 95% CI, 0.04-9.26, P=0.00001). In conclusion, the meta-analysis of the studies indicated that ACE 2 is highly expressed in olfactory mucosa, nasopharynx, oral mucosa, and salivary glands. Furthermore, the results indicate that ACE 2 expression is increased in patients with head and neck cancer.
PubMed: 36819393
DOI: 10.7759/cureus.33673 -
Respiratory Physiology & Neurobiology May 2023The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on... (Review)
Review
The perception of breathlessness is mechanistically linked to the awareness of increased inspiratory neural drive (IND). Stimulation of upper airway cold receptors on the trigeminal nerve (TGN) with TGN agonists such as menthol or cool air to the face/nose has been hypothesized to reduce breathlessness by decreasing IND. The aim of this systematic scoping review was to identify and summarize the results of studies in animals and humans reporting on the impact of TGN stimulation or blockade on measures of IND. Thirty-one studies were identified, including 19 in laboratory animals and 12 in human participants. Studies in laboratory animals consistently reported that as TGN activity increased, measures of IND decreased (e.g., phrenic nerve activity). In humans, stimulation of the TGN with a stream of cool air to the face/nose decreased the sensitivity of the ventilatory chemoreflex response to hypercapnia. Otherwise, TGN stimulation with menthol or cool air to the face/note had no effect on measures of IND in humans. This review provides new insight into a potential neural mechanism of breathlessness relief with selected TGN agonists.
Topics: Animals; Humans; Menthol; Olfactory Nerve; Dyspnea; Nose; Trigeminal Nerve
PubMed: 36792044
DOI: 10.1016/j.resp.2023.104035 -
Parkinsonism & Related Disorders Nov 2022Alpha-synuclein(αSyn) aggregates are definite pathological hallmarks of α-synucleinopathies. Seeding amplification assays (SAAs) have been developed to detect trace... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Alpha-synuclein(αSyn) aggregates are definite pathological hallmarks of α-synucleinopathies. Seeding amplification assays (SAAs) have been developed to detect trace amounts of αSyn oligomers in vivo.. Herein, we assessed the diagnostic accuracy of the αSyn-SAAs across biospecimens, diagnostic references, methods, and subtypes.
METHODS
A systematic literature search yielded 36 eligible studies for a meta-analysis of the sensitivity and specificity of αSyn-SAAs in patients with α-synucleinopathies(n = 2722) and controls(n = 2278). Pooled sensitivities and specificities with 95% confidence intervals (CIs) were calculated using bivariate random-effects models and a meta-regression analysis was performed.
RESULTS
The summary sensitivity and specificity of αSyn-SAAs positivity for the diagnosis of α-synucleinopathies were 0.88(95% CIs = 0.84-0.91) and 0.95(0.93-0.97), respectively. Two covariates (biospecimen and diagnostic reference) were significant in fitting the meta-regression model (likelihood-ratio test for sensitivity and specificity, p < 0.01, p = 0.01, respectively). Skin αSyn-SAAs exhibited the highest sensitivity 0.92(0.87-0.95), which was not different from that of cerebrospinal fluid (CSF)(0.90(0.86-0.93), p = 0.39). Olfactory mucosa αSyn-SAAs exhibited a lower sensitivity 0.64(0.49-0.76) than those of the other two specimens(p = 0.02, 0.01, compared to CSF and skin, respectively). Application of pathological diagnostic standards were associated with a higher specificity of αSyn-SAAs compared to clinical diagnosis (p < 0.01). The diagnostic sensitivity and specificity of CSF αSyn-SAAs were 0.91(0.87-0.94) and 0.96(0.93-0.98) for Lewy body disease, 0.90(0.79-0.95) and 0.96(0.90-0.98) for prodromal α-synucleinopathies, and 0.63(0.24-0.90) and 0.97(0.93-0.99) for multiple system atrophy.
CONCLUSIONS
αSyn-SAAs are promising in vivo detectors of abnormal αSyn aggregates and may aid the early diagnosis of α-synucleinopathies.
Topics: Humans; alpha-Synuclein; Synucleinopathies; Lewy Body Disease; Multiple System Atrophy; Sensitivity and Specificity
PubMed: 36289019
DOI: 10.1016/j.parkreldis.2022.10.007 -
The Laryngoscope Jun 2022Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention.
METHODS
PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD.
RESULTS
We included 7 case-control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38-0.82) was significantly higher than that in controls (4%, 95% CI = 0.01-0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes.
CONCLUSION
Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 132:1260-1274, 2022.
Topics: Adolescent; Adult; COVID-19; Humans; Olfaction Disorders; Olfactory Bulb; Olfactory Mucosa; Smell
PubMed: 35318656
DOI: 10.1002/lary.30078 -
Environmental Research May 2022Air pollution is one of the most serious environmental problems that afflict our planet and one of the greatest risk factors for human health. In particular, PM is able...
Air pollution is one of the most serious environmental problems that afflict our planet and one of the greatest risk factors for human health. In particular, PM is able to cross the blood-alveolar and blood-brain barriers, thus increasing the onset of respiratory, cardiovascular and neurodegenerative diseases. Neurodegenerative disease is a progressive neuronal dysfunction that leads to neuronal lesions in both structure and function, and includes several diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), vascular dementia (VaD), multiple sclerosis (MS), and others. We carried out a systematic review using PRISMA approach to investigate on the possible association between exposure to PM and neurodegenerative diseases. The international databases (PubMed, Science Direct, Web of Sciences) were used to find published studies on the topic. The search period was between January 2011 and June 2021. About 2000 full research articles were selected, and finally, we included 20 full-research articles. Selected studies have highlighted how PM exposure can be associated with the onset of neurodegenerative diseases (AD, PD, MS, VaD). This association depends not only on age, PM levels and exposure time, but also on exposure to other air pollutants, proximity to areas with high vehicular traffic, and the presence of comorbidities. Exposure to PM promotes neuroinflammation processes, because through breathing the particles can reach the nasal epithelial mucosa and transferred to the brain through the olfactory bulb. Furthermore, exposure to PM has been associated with an increased expression of markers of neurodegenerative diseases (e.g. alpha-synuclein or beta-amyloid), which can contribute to the etiopathogenesis of neurodegenerative diseases. Although many studies have revealed the pathological relationship between PM exposure and cognitive impairment, the potential cellular and molecular mechanisms of PM leading to neurodegenerative disease remain not entirely clear, and then, further studies need to be carried out on the topic.
Topics: Air Pollutants; Air Pollution; Alzheimer Disease; Environmental Exposure; Humans; Neurodegenerative Diseases; Particulate Matter
PubMed: 34979121
DOI: 10.1016/j.envres.2021.112581