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The genus Naegleria is a taxonomic subfamily consisting of 47 free-living amoebae. The genus can be found in warm aqueous or soil habitats worldwide. The species Naegleria fowleri is probably the best-known species of this genus. As a facultative parasite, the protist is not dependent on hosts to complete its life cycle. However, it can infect humans by entering the nose during water contact, such as swimming, and travel along the olfactory nerve to the brain. There it causes a purulent meningitis (primary amoebic meningoencephalitis or PAME). Symptoms are severe and death usually occurs within the first week. PAME is a frightening infectious disease for which there is neither a proven cure nor a vaccine. In order to contain the disease and give patients any chance to survival, action must be taken quickly. A rapid diagnosis is therefore crucial. PAME is diagnosed by the detection of amoebae in the liquor and later in the cerebrospinal fluid. For this purpose, CSF samples are cultured and stained and finally examined microscopically. Molecular techniques such as PCR or ELISA support the microscopic analysis and secure the diagnosis. [ABSTRACT FROM AUTHOR]

Behavioral plasticity allows animals to modulate their behavior based on experience and environmental conditions. Caenorhabditis elegans exhibits experience-dependent changes in its behavioral responses to various modalities of sensory cues, including odorants, salts, temperature, and mechanical stimulations. Most of these forms of behavioral plasticity, such as adaptation, habituation, associative learning, and imprinting, are shared with other animals. The C. elegans nervous system is considerably tractable for experimental studies—its function can be characterized and manipulated with molecular genetic methods, its activity can be visualized and analyzed with imaging approaches, and the connectivity of its relatively small number of neurons are well described. Therefore, C. elegans provides an opportunity to study molecular, neuronal, and circuit mechanisms underlying behavioral plasticity that are either conserved in other animals or unique to this species. These findings reveal insights into how the nervous system interacts with the environmental cues to generate behavioral changes with adaptive values. [ABSTRACT FROM AUTHOR]

The article explores the effectiveness and potential of aromatherapy for managing anxiety. It discusses the impact of anxiety in social, occupational and other areas of life. It examines the impact of essential oils and aromatherapy on various anxiety disorders including anxiety in academic and work environment, reproductive anxiety, pregnancy and labor/maternity anxiety, preoperative and surgery anxiety, dental anxiety, procedural anxiety and anxiety in cancer and palliative care.

Recently developed optogenetic technology, which allows high‐fidelity control of neuronal activity, has been applied to investigate the neural circuits underlying sensory processing and behavior. The nasal cavity is innervated by the olfactory nerve and trigeminal nerve, which are closely related to common symptoms of rhinitis, such as impairment of smell, itching, and sneezing. The olfactory system has an amazing ability to distinguish thousands of odorant molecules at trace levels. However, there are many issues in olfactory sensing mechanisms that need to be addressed. Optogenetics offers a novel technical approach to solve this dilemma. Therefore, we review the recent advances in olfactory optogenetics to clarify the mechanisms of chemical sensing, which may help identify the mechanism of dysfunction and suggest possible treatments for impaired smell. Additionally, in rhinitis patients, alterations in the other nerve (trigeminal nerve) that innervates the nasal cavity can lead to hyperresponsiveness to various nociceptive stimuli and central sensitization, causing frequent and persistent itching and sneezing. In the last several years, the application of optogenetics in regulating nociceptive receptors, which are distributed in sensory nerve endings, and amino acid receptors, which are distributed in vital brain regions, to alleviate overreaction to nociceptive stimuli, has gained significant attention. Therefore, we focus on the progress in optogenetics and its application in neuromodulation of nociceptive stimuli and discuss the potential clinical translation for treating rhinitis in the future. [ABSTRACT FROM AUTHOR]

This paper proposes a multi-method olfactory inquiry to document the rich ways in which children's sense of smell is embodied and embedded in an interplay of senses and socio-spatial relationships. I approach olfaction as a conceptual strategy and connect it to socio-material and socio-spatial theories to illustrate the ways in which close empirical attention to olfaction can provide new insights into children's sensory experiences. An olfactory research inquiry rests on traditional (e.g. SmellMaps and SmellLogs) and speculative (e.g. Ododata and Olfactoscapes) olfactory techniques that invite adults' and children's agentic responses to odours through relational, dynamic, and non-linguistic modes. As a critical sub-methodology of sensory inquiries, olfactory inquiry can help us re-think normative, homogenizing, mind-body relations in early childhood research and practice. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects and mechanisms of olfactory three-needle (OTN) electroacupuncture (EA) stimulation of the olfactory system on cognitive dysfunction, synaptic plasticity, and the gut microbiota in senescence-accelerated mouse prone 8 (SAMP8) mice. Methods: Thirty-six SAMP8 mice were randomly divided into the SAMP8 (P8), SAMP8+OTN (P8-OT), and SAMP8+nerve transection+OTN (P8-N-OT) groups according to a random number table (n=12 per group), and 12 accelerated senescence-resistant (SAMR1) mice were used as the control (R1) group. EA was performed at the Yintang (GV 29) and bilateral Yingxiang (LI 20) acupoints of SAMP8 mice for 4 weeks. The Morris water maze test, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, Nissl staining, Golgi staining, Western blot, and 16S rRNA sequencing were performed, respectively. Results: Compared with the P8 group, OTN improved the cognitive behavior of SAMP8 mice, inhibited neuronal apoptosis, increased neuronal activity, and attenuated hippocampal synaptic dysfunction (P<0.05 or P<0.01). Moreover, the expression levels of synaptic plasticity-related proteins N-methyl-D-aspartate receptor 1 (NMDAR1), NMDAR2B, synaptophysin (SYN), and postsynaptic density protein-95 (PSD95) in hippocampus were increased by OTN treatment (P<0.05 or P<0.01). Furthermore, OTN greatly enhanced the brain-derived neurotrophic factor (BDNF)/cAMP-response element binding (CREB) signaling and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling compared with the P8 group (P<0.05 or P<0.01). However, the neuroprotective effect of OTN was attenuated by olfactory nerve truncation. Compared with the P8 group, OTN had a very limited effect on the fecal microbial structure and composition of SAMP8 mice, while specifically increased the genera Oscillospira and Sutterella (P<0.05). Interestingly, the P8-N-OT group showed an abnormal fecal microbiota with higher microbial α-diversity, Firmicutes/Bacteroidetes ratio and pathogenic bacteria (P<0.05 or P<0.01). Conclusions: OTN improved cognitive deficits and hippocampal synaptic plasticity by stimulating the olfactory nerve and activating the BDNF/CREB and PI3K/AKT/mTOR signaling pathways. Although the gut microbiota was not the main therapeutic target of OTN for Alzheimer's disease, the olfactory nerve was essential to maintain the homeostasis of gut microbiota. [ABSTRACT FROM AUTHOR]

ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans. [ABSTRACT FROM AUTHOR]

Background: Pediatric headache is an increasing medical problem that has adverse effects on children's quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains. Methods: The study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache. Results: Patients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache. Conclusions: Children with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification. Trial registration: The study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062. [ABSTRACT FROM AUTHOR]

Pacific salmon (Oncorhynchus spp.) hatch and feed in freshwater habitats, migrate to sea to mature, and return to spawn at natal sites. The final, riverine stages of the return migrations are mediated by chemical properties of the natal stream that they learned as juveniles. Like some other fish, salmon growth is asymptotic; they grow continuously throughout life toward a maximum size. The continued growth of the nervous system may be plastic in response to environmental variables. Due to the ecological, cultural, and economic importance of Pacific salmon, individuals are often reared in hatcheries and released into the wild as juveniles to supplement natural populations. However, hatchery-reared individuals display lower survivorship and may also stray (i.e. spawn in a non-natal stream) at higher rates than their wild counterparts. Hatchery environments may lack stimuli needed to promote normal development of the nervous system, thus leading to behavioral deficits and a higher incidence of straying. This study compared the peripheral olfactory system and brain organization of hatchery-reared and wild-origin sockeye salmon fry (Oncorhynchus nerka). Surface area of the olfactory rosette, diameter of the olfactory nerve, total brain size, and size of major brain regions were measured from histological sections and compared between wild and hatchery-origin individuals. Hatchery-origin fish had significantly larger optic tecta, and marginally insignificant, yet noteworthy trends, existed in the valvula cerebelli (hatchery > wild) and olfactory bulbs (hatchery < wild). We also found a putative difference in olfactory nerve diameter (d min) (hatchery > wild), but the validity of this finding needs further analyses with higher resolution methods. Overall, these results provide insight into the potential effects of hatchery rearing on nervous system development in salmonids, and may explain behavioral deficits displayed by hatchery-origin individuals post-release. [ABSTRACT FROM AUTHOR]

Across vertebrate species, the olfactory epithelium (OE) exhibits the uncommon feature of lifelong neuronal turnover. Epithelial stem cells give rise to new neurons that can adequately replace dying olfactory receptor neurons (ORNs) during developmental and adult phases and after lesions. To relay olfactory information from the environment to the brain, the axons of the renewed ORNs must reconnect with the olfactory bulb (OB). In Xenopus laevis larvae, we have previously shown that this process occurs between 3 and 7 weeks after olfactory nerve (ON) transection. In the present study, we show that after 7 weeks of recovery from ON transection, two functionally and spatially distinct glomerular clusters are reformed in the OB, akin to those found in non‐transected larvae. We also show that the same odourant response tuning profiles observed in the OB of non‐transected larvae are again present after 7 weeks of recovery. Next, we show that characteristic odour‐guided behaviour disappears after ON transection but recovers after 7–9 weeks of recovery. Together, our findings demonstrate that the olfactory system of larval X. laevis regenerates with high accuracy after ON transection, leading to the recovery of odour‐guided behaviour. [ABSTRACT FROM AUTHOR]

Background: Olfactory disorders affect approximately 3 to 22% of the general population and impact on human quality of life. These symptoms have gained more attention after the COVID-19 pandemic, as anosmia emerged as a common presentation. A large number of patients with smell dysfunction have exhibited limited response to clinical therapy. Therefore, we propose a transnasal endoscopic nerve transfer technique for stimulate the olfactory neuroepithelium as a potential treatment option for olfactory dysfunction. We aimed to demonstrate preliminary results of nerve transfer surgery for the treatment of olfactory disorders, as well as to present the surgical technique. Methods: Eight patients with olfactory disorders, unresponsive to usually recommended treatments, underwent nerve transfer surgery between March 2022 and March 2023. The Connecticut olfactory test was administered to all patients before and after the surgery and quality of life was evaluated using the Visual Analogue Scale. Results: The average age of the patients was 46.3 years, and the olfactory disturbance has duration of approximately 27.5 months. Objective improvement in quality of life and olfactory scores was observed in 62,5% of the patients who underwent the surgery. Conclusions: Transnasal endoscopic nerve transfer technique may be a promissing therapeutic method in cases of olfactory dysfunction. The follow-up of these patients over a longer period, as well as more patients undergoing nerve transfer will provide more conclusive statistical data. Level of evidence: Level V, Therapeutic study. [ABSTRACT FROM AUTHOR]

Periglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone, migrate to the olfactory bulb via the Rostral Migratory Stream (RMS), and differentiate into mature cells within the olfactory bulb throughout postnatal life. While the regulation of neuroblast development is known to be affected by external stimuli, there is a lack of information concerning changes that occur during the recovery process after injury caused by external stimuli. To address this gap in research, the present study conducted histological observations to investigate changes in the olfactory bulb and RMS occurring after the degeneration and regeneration of olfactory neurons. To create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test. Olfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days. These results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input. [ABSTRACT FROM AUTHOR]

Background and objectives: Post-acute COVID-19 syndrome or “long COVID” affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent Headache (NDPH) is one of such symptoms. In this review, we will discuss about the case-reports of post covid-19 headache- NDPH phenotype both after and in the course of COVID-19 infection. Methods: Case reports/studies talked about patients having NDPH around the disease either immediately or late post COVID were included. Data was taken from the source and synthesised on a qualitative basis. Results: Literature search showed 3,538 articles, out of which 12 were screened as per the eligibility criteria and finally, 4 case reports on NDPH and Covid-19 were chosen for analysis from the database and by human search. All case reports justify the criteria for acceptability in quality for this systematic review. Conclusion: NDPH in and around Covid 19 infection is something that is currently an ingenious debated topic in the scientific community. More case studies should be written and published on the same subject so that a large systematic review could be conducted. [ABSTRACT FROM AUTHOR]

Aerotoxic Syndrome may develop as a result of chronic, low-level exposure to organophosphates (OPs) and volatile organic compounds in the airplane cabin air, caused by engine oil leaking past wet seals. Additionally, acute high-level exposures, so-called "fume events," may occur. However, air quality monitoring studies concluded that levels of inhaled chemicals might be too low to cause adverse effects. The presence of aerosols of nanoparticles (NPs) in bleed air has often been described. The specific hypothesis is a relation between NPs acting as a vector for toxic compounds in the etiology of the Aerotoxic Syndrome. These NPs function as carriers for toxic engine oil compounds leaking into the cabin air. Inhaled by aircrew NPs carrying soluble and insoluble components deposit in the alveolar region, where they are absorbed into the bloodstream. Subsequently, they may cross the blood-brain barrier and release their toxic compounds in the central nervous system. Olfactory absorption is another route for NPs with access to the brain. To study the hypothesis, all published in-flight measurement studies (2003–2023) of airborne volatile (and low-volatile) organic pollutants in cabin air were reviewed, including NPs (10–100 nm). Twelve studies providing data for a total of 387 flights in 16 different large-passenger jet aircraft types were selected. Maximum particle number concentrations (PNC) varied from 104 to 2.8 × 106 #/cm3 and maximum mass concentrations from 9 to 29 μg/m3. NP-peaks occurred after full-power take-off, in tailwind condition, after auxiliary power unit (APU) bleed air introduction, and after air conditioning pack failure. Chemical characterization of the NPs showed aliphatic hydrocarbons, black carbon, and metallic core particles. An aerosol mass-spectrometry pattern was consistent with aircraft engine oil. It is concluded that chronic exposure of aircrew to NP-aerosols, carrying oil derivatives, maybe a significant feature in the etiology of Aerotoxic Syndrome. Mobile NP measuring equipment should be made available in the cockpit for long-term monitoring of bleed air. Consequently, risk assessment of bleed air should include monitoring and analysis of NPs, studied in a prospective cohort design. [ABSTRACT FROM AUTHOR]

The ultrastructure of the olfactory system of most fossorial rodents remains largely unexplored. This study sought to investigate the functional structure of the olfactory mucosa and olfactory bulb of two species of fossorial rodents that have distinct behaviour and ecology, the East African root rat (RR) and the naked mole rat (NMR). Transmission electron microscopy and scanning electron microscopy were employed. The basic ultrastructural design of the olfactory system of the two species was largely comparable. In both species, the olfactory mucosa comprised an olfactory epithelium and an underlying lamina propria. The olfactory epithelium revealed olfactory knobs, cilia and microvilli apically and sustentancular cells, olfactory receptor neurons and basal cells in the upper, middle and basal zones, respectively. The lamina propria was constituted by Bowman's glands, olfactory nerve bundles and vasculature supported by loose connective tissue. Within the olfactory bulb, intracellular and extracellular structures including cell organelles, axons and dendrites were elucidated. Notable species differences were observed in the basal zone of the olfactory epithelium and on the luminal surface of the olfactory mucosa. The basal zone of the olfactory epithelium of the RR consisted of a single layer of flattened electron‐dense horizontal basal cells while the NMR had juxtaposed electron‐dense and electron‐lucent heterogenous cells, an occurrence seen as being indicative of quiescent and highly proliferative states of the olfactory epithelia in the two species, respectively. The olfactory epithelial surface of the NMR comprised an elaborate cilia network that intertwined extensively forming loop‐like structures whereas in the RR, the surface was rugged and consisted of finger‐like processes and irregular masses. With gross and histological studies showing significant differences in the olfactory structures of the two species, these findings are a further manifestation that the olfactory system of the RR and the NMR have evolved differently to reflect their varied olfactory functional needs. [ABSTRACT FROM AUTHOR]

Purpose: Olfactory dysfunction (OD) can be a long-term consequence of various viral infections, including COVID-19. Dysfunction includes hyposmia/anosmia and parosmia (odor distortions). Interactions of the virus with the olfactory nerve have been extensively researched, but little is known about the interactions of the intranasal trigeminal nerve system in modulating this sensory loss. Methods: We investigated intranasal trigeminal function across COVID-19 OD patients with and without parosmia compared to normosmic controls, to determine whether (1) post-viral hyposmia and/or (2) post-viral hyposmia with parosmia is associated with altered trigeminal function. OD patients (n = 27) were tested for olfactory function using the extended Sniffin' Sticks olfactory test and for trigeminal function through three methods—odor lateralization, subjective ratings of nasal patency, and ammonium vapor pain intensity ratings. This group was subsequently compared to controls, normosmic subjects (n = 15). Results: Our findings revealed that post-COVID OD patients without parosmia experienced decreased sensitivity in ammonium vapor pain intensity ratings and odor lateralization scores—but similar nasal patency ratings—compared to normosmic controls. There were no significant differences in trigeminal function between OD patients with and without parosmia. Conclusions: Based on our results, we conclude that the trigeminal nerve dysfunction may partially explain post-viral OD, but does not seem to be a major factor in the generation of parosmia pathophysiology. [ABSTRACT FROM AUTHOR]

Abstract ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.

Background: The endoscopic modified Lothrop procedure (EMLP) has become a frequently utilized procedure in rhinologic surgery. One of the most serious complications of the procedure is cerebrospinal fluid leak, which may occur due to lack of recognition of the anterior skull base in the region of the first olfactory filum (FOF), or direct injury to the FOF itself. Objectives: To evaluate the position of the head of the middle turbinate (MT) relative to the FOF, which is an important landmark in the EMLP. Methods: A series of previously obtained patient computed tomography scans of the sinus were reviewed. A reproducible process was implemented to obtain the measurements. First, the FOF was identified on an axial series. Using a localization feature of the radiographic software, this anteroposterior (AP) position could be visualized in a coronal plane. Subsequently, the MT was viewed in a sagittal plane, where a measurement between the head of the MT and the AP position of the FOF could be performed. Results: The AP distance between the head of the MT and the FOF was measured in 92 patients. The head of the MT was either at or anterior to the FOF in all measured subjects. The mean anterior distance of the head of the MT to FOF was 3.6 mm (±2.4 mm) on the right, and 3.8 mm (±2.2 mm) on the left. The range in AP distance was 0 to 12 mm. There was no significant difference in AP distance between the head of the MT and FOF based on gender (P =.413) or diagnosis (P =.254). Conclusions: In our study, the head of the MT was reliably at or anterior to the FOF in all subjects, suggesting its utility as a fixed landmark in endoscopic sinus surgery, particularly in the EMLP. Level of Evidence: N/A. [ABSTRACT FROM AUTHOR]

This article describes the process of reconstructing the scents of two perfumes used to prevent the plague during the reign of Marcus Aurelius and his son Commodus, as recorded by Herodian. Scent reconstructions have recently been proposed as a way of interpreting and presenting texts, similar to how visual figures have been traditionally used. However, issues of production, distribution, and scholarly methods and standards of evaluation are in flux and being refined. We began with the recent model published by Marx et al. from the Odeuropa project. Adapting their model required us to present and contrast two scents rather than one, and unlike Marx et al., we did not have detailed ancient recipes to work from. Therefore, we chose to interpret the contrast Herodian suggests rather than strive for strict historical accuracy of the two scents. Here, we present the texts we used and outline the methods and challenges involved when producing this olfactory interpretation. [ABSTRACT FROM AUTHOR]

Background: The worldwide mortality and morbidity rates are highest for traumatic brain injury (TBI), which frequently involves damage to the cranial nerves (CNs). The occurrence of CN injury (CNI) in craniocerebral trauma ranges from 5 to 23%. Aims and Objectives: The objective of this study is to evaluate the occurrence of CNI in TBI patients within our population and determine the association between CN involvement and the severity of head injuries. In addition, we aim to assess the outcomes of patients who experience CNI in cases of head trauma. Materials and Methods: In our institution, a prospective observational analytical study was conducted from July 2022 to June 2023. The study included 100 patients aged over 1 year who had sustained head injuries. These patients were followed up for a period of 6 months. Results: Our study included a total of 100 patients, revealing that the highest number of head injuries occurred within the age range of 20-60 years, with an average age of 46 years. Among the study population, males accounted for 74%. Of these patients, 66 had mild head injuries, 22 had moderate head injuries, and 12 were admitted with severe head injuries. We discovered that 15% of TBI patients experienced CNIs. Specifically, five patients had a single CN palsy, while three patients had multiple CN palsies. Road traffic accidents accounted for 78% of the cases, making them the most common cause of injury, while low-velocity injuries only made up 22% of the cases. The facial nerve was the CN most frequently affected, followed by the olfactory nerve, optic nerve, and vestibulocochlear nerve. Among the 15 patients with CNI, seven had delayed symptoms, whereas eight patients presented with immediate symptoms. Conclusion: A substantial proportion of patients experience a delayed onset of CNI symptoms. Therefore, it is essential to perform a comprehensive neurological examination of all CNs during follow-up for all TBI patients. [ABSTRACT FROM AUTHOR]

The objective of the current study was to assess the morphological and histological characteristics of the sheep olfactory bulb, six samples (n = 6) were used. Three samples for anatomical observation of olfactory bulb were record in adult sheep which involved the morphological study (stance, rapport, mass, length, and diameter). The width of the bulb was (7.28± 0.98mm), the length of the olfactory bulb in sheep was (30.5±1.28 mm), the diameters of the olfactory was (9.067-+0.01453). The olfactory bulbs were fixed in 10% formalin solution and subjected to standard histological processing, which included Mallory and Hematoxylin and Eosin staining. The olfactory bulb, located in the forebrain of vertebrates, has an elongated form with just a rostral ventral rough surface and a creamy color. It receives neurological input regarding odors identified by cells in the nasal cavity. The four separate layers that may be distinguished histologically in the sheep olfactory bulb are the olfactory nerve layer, the glomerular layer, the mitral cells layer, and the granule cells layer. [ABSTRACT FROM AUTHOR]

COVID-19, caused by the SARS-CoV-2 virus, can have neurological effects, including cognitive symptoms like brain fog and memory problems. Research on the neurological effects of COVID-19 is ongoing, and factors such as inflammation, disrupted blood flow, and damage to blood vessels may contribute to cognitive symptoms. Notably, some authors and existing evidence suggest that the SARS-CoV-2 virus can enter the central nervous system through different routes, including the olfactory nerve and the bloodstream. COVID-19 infection has been associated with neurological symptoms such as altered consciousness, headaches, dizziness, and mental disorders. The exact mechanisms and impact on memory formation and brain shrinkage are still being studied. This review will focus on pathways such as the olfactory nerve and blood–brain barrier disruption, and it will then highlight the interactions of the virus with different cell types in the brain, namely neurons, astrocytes, oligodendrocytes, and microglia. [ABSTRACT FROM AUTHOR]

The role of the hypothalamic neuropeptide oxytocin in influencing the brain and behavior has been the subject of widespread research over the last few decades due, most notably, to its reported involvement in promoting social cognition and motivation, reducing anxiety, and relieving pain. It is also increasingly being considered as an important therapeutic intervention in a variety of disorders with social dysfunction as a symptom. While, in recent years, studies in humans have administered oxytocin primarily via an intranasal route, since it may partly enter the brain directly this way via the olfactory and trigeminal nerves, there is increasing evidence that many of its functional effects can be peripherally mediated via increasing its concentration in the blood. This has opened up an oromucosal administration route as an alternative, which is beneficial since the oral consumption of peptides is problematic due to their rapid breakdown in the acidic environment of the gastrointestinal system. In this review we will discuss both the methodologies we have developed for administering oxytocin via lingual application and medicated lollipops, 'oxipops', in terms of increasing blood concentrations and the bioavailability of the peptide, and also their validation in terms of functional effects on the brain and behavior. While areas under the curve are significantly greater in terms of plasma oxytocin concentrations following intranasally relative to oromucosally administered oxytocin, with the estimated absolute bioavailability of the latter being around 4.4% compared with 11.1% for intranasal administration, the time to peak concentrations (around 30 min) and functional effects on the brain and behavior are broadly similar. We will also discuss potential therapeutic advantages of the oromucosal administration of oxytocin in different clinical contexts and its wider application for other peptides which are increasingly being developed for therapeutic use. [ABSTRACT FROM AUTHOR]

Olfactory disorders have a significant impact on patients' quality of life but are often underestimated in clinical practice. Upper respiratory tract infections (URTIs) are a common cause of olfactory loss. While most cases of olfactory loss due to URTIs are conductive and reversible, post-viral olfactory dysfunction (PVOD) persists despite symptom improvement. PVOD is attributed to damage to the olfactory epithelium and nerves or central olfactory pathway lesions. The Alcohol Sniff Test (AST) has been proposed as a tool to assess olfactory function in the acute phase and aid in differentiating PVOD from conductive disorders. This study aims to evaluate the effectiveness of the AST as a predictor of post-viral olfactory loss in patients with flu-like syndrome. An observational cross-sectional study was conducted among employees with flu-like syndrome at a tertiary hospital. Three groups were formed: flu-like syndrome with conductive disorder without COVID-19 (PVOD-), flu-like syndrome with neurosensory and/or central disorder due to COVID-19 (PVOD +), and an asymptomatic control group. The Alcohol Sniff Test was performed to assess olfactory function. Statistical analysis was conducted to evaluate the AST's performance. For a cut off of 10 cm, 88.57% of PVOD + patients and 60.53% of PVOD – patients showed AST alteration, respectively (p = 0.013, OR = 5.05, 95% CI [1.48–17.25]). There was a statistically significant difference in the mean distance between the PVOD + group (4.35 ± 4.1 cm) and the control group (20 ± 4.33 cm) (p < 0.05). This relationship was also observed between the PVOD + and PVOD- groups (9 cm ± 7.5) (p < 0.05) and between the PVOD- and control groups (p < 0.05). For a cut off of 10 cm, the AST showed a sensitivity of 88% and specificity of 41%, resulting in an Odds Ratio of 9.7 (95% CI 3.3–28.1) (p < 0.001) and a Positive Predictive Value of 69.4% for PVOD. PVOD, including cases associated with COVID-19, is a prevalent cause of olfactory loss. The Alcohol Sniff Test demonstrated promising results in identifying PVOD in patients with flu-like syndrome. The test's simplicity and accessibility make it a valuable tool for early screening and identifying individuals who may benefit from prompt treatment. The Alcohol Sniff Test (AST) shows potential as an effective tool for screening post-viral olfactory loss in patients with flu-like syndrome. It can aid in early identification of PVOD cases and facilitate timely interventions to reduce the likelihood of persistent hyposmia. [ABSTRACT FROM AUTHOR]

The article titled "The Anatomical Study of the Cribriform Plate—New Concept: Is the Cribriform Plate an Effective Border?" explores the importance of the cribriform plate in the anterior skull base area. The study examines the structure of the cribriform plate and its relationship to functions such as smelling, tasting, and sexual-behavioral functions. The research includes macroscopic bone study and microscopic study, revealing the complex labyrinth-like structure of the cribriform plate and the presence of vessels and nerves within it. The article concludes that the cribriform plate is a delicate border that plays a role in trauma and tumor development. [Extracted from the article]

The unique anatomical and physiological connections between the nasal cavity and brain provide a pathway for bypassing the blood--brain barrier to allow for direct brain-targeted drug delivery through nasal administration. There are several advantages of nasal administration compared with other routes; for example, the first-pass effect that leads to the metabolism of orally administered drugs can be bypassed, and the poor compliance associated with injections can be minimized. Nasal administration can also help maximize brain-targeted drug delivery, allowing for high pharmacological activity at lower drug dosages, thereby minimizing the likelihood of adverse effects and providing a highly promising drug delivery pathway for the treatment of central nervous system diseases. The aim of this review article was to briefly describe the physiological structures of the nasal cavity and brain, the pathways through which drugs can enter the brain through the nose, the factors affecting brain-targeted nasal drug delivery, methods to improve brain-targeted nasal drug delivery systems through the application of related biomaterials, common experimental methods used in intranasal drug delivery research, and the current limitations of such approaches, providing a solid foundation for further in-depth research on intranasal brain-targeted drug delivery systems (see Graphical Abstract). [ABSTRACT FROM AUTHOR]

Introduction: Nose‐to‐brain (N2B) insulin delivery has potential for Alzheimer's disease (AD) therapy. However, clinical implementation has been challenging without methods to follow N2B delivery non‐invasively. Positron emission tomography (PET) was applied to measure F‐18‐labeled insulin ([18F]FB‐insulin) from intranasal dosing to brain uptake in non‐human primates following N2B delivery. Methods: [18F]FB‐insulin was prepared by reacting A1,B29‐di(tert‐butyloxycarbonyl)insulin with [18F]‐N‐succinimidyl‐4‐fluorobenzoate. Three methods of N2B delivery for [18F]FB‐insulin were compared – delivery as aerosol via tubing (rhesus macaque, n = 2), as aerosol via preplaced catheter (rhesus macaque, n = 3), and as solution via preplaced catheter (cynomolgus macaque, n = 3). Following dosing, dynamic PET imaging (120 min) quantified delivery efficiency to the nasal cavity and whole brain. Area under the time‐activity curve was calculated for 46 regions of the cynomolgus macaque brain to determine regional [18F]FB‐insulin levels. Results: Liquid instillation of [18F]FB‐insulin by catheter outperformed aerosol methods for delivery to the subject (39.89% injected dose vs 10.03% for aerosol via tubing, 0.17% for aerosol by catheter) and subsequently to brain (0.34% injected dose vs 0.00020% for aerosol via tubing, 0.05% for aerosol by catheter). [18F]FB‐insulin was rapidly transferred across the cribriform plate to limbic and frontotemporal areas responsible for emotional and memory processing. [18F]FB‐insulin half‐life was longer in olfactory nerve projection sites with high insulin receptor density compared to the whole brain. Discussion: The catheter‐based liquid delivery approach combined with PET imaging successfully tracked the fate of N2B [18F]FB‐insulin and is thought to be broadly applicable for assessments of other therapeutic agents. This method can be rapidly applied in humans to advance clinical evaluation of N2B insulin as an AD therapeutic. Highlights for: [18F]FB‐insulin passage across the cribriform plate was detected by PET.Intranasal [18F]FB‐insulin reached the brain within 13 min.[18F]FB‐insulin activity was highest in emotional and memory processing regions.Aerosol delivery was less efficient than liquid instillation by preplaced catheter.Insulin delivery to the cribriform plate was critical for arrival in the brain. [ABSTRACT FROM AUTHOR]

Background: The classical supraorbital minicraniotomy (cSOM) constitutes a minimally invasive alternative for the resection of anterior skull base meningiomas (ASBM). Surgical success depends strongly on optimal patient selection and surgery planning, for which a careful assessment of tumor characteristics, approach trajectory, and bony anterior skull base anatomy is required. Still, morphometrical studies searching for relevant anatomical factors with surgical relevance when intending a cSOM for ASBM resection are lacking. Methods: Bilateral cSOM was done in five formaldehyde-fixed heads toward the areas of origin of ASBM. Morphometrical data with potential relevant surgical implications were analyzed. Results: The more tangential position of the cSOM with respect to the olfactory groove (OG) led to a reduction in surgical freedom (SF) in this area compared to others (P < 0.0001). Frontal lobe retraction (FLR) was also higher when approaching the OG (P < 0.05). Olfactory nerve mobilization was higher when accessing the planum sphenoidale (PS), tuberculum sellae (TS), and anterior clinoid process (ACP) (P < 0.0001). OG depth and the slope of the sphenoid bone between the PS and TS predicted lower SF and higher frontal retraction requirements along the OG and TS, respectively (P < 0.05). In contrast, longer distances to the ACP tip predicted lower SF over this structure (P < 0.01). Conclusion: Although clinical validation is still needed, the present anatomical data suggest that assessing minicraniotomy's position/extension, OG depth, the sphenoid's slope, and distance to ACP-tip might be of particular relevance to predict FLR, maneuverability, and accessibility when considering the cSOM for ASBM resection, thus helping surgeons optimize patient selection and surgical strategy. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb. [ABSTRACT FROM AUTHOR]

Cavernous sinus meningiomas (CSM) are complex skull base lesions that, due to their particular anatomical location, render surgical management difficult. Their symptomatology is versatile, and the clinical outcome is difficult to predict. We present the case of a 57-year old female patient who experienced phantosmia - an abnormal, persistent, olfactory sensation of cigarette smell for 18 months. MRI was performed and revealed a left cavernous sinus meningioma, extending into the left temporal fossa, with olfactory and optic nerve distortion. To our knowledge, this is the first reported case of phantosmia as the initial presentation of a lesion in the cavernous sinus. [ABSTRACT FROM AUTHOR]

Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usually the plasma. This is as close to the tissue of interest that we can get, although biopsies may be obtained to give "tissue levels" of drugs. Ultimately, the goal of PK is to understand how long the drug is actually engaged with the target in the tissue of interest after a dose has been administered. Most drugs at some point in their development will have been administered intravenously (IV), which acts as the standard for 100% bioavailability. By comparing various routes of administration to IV, the percentage of drug delivered to the plasma, on a dose-normalized basis, can be calculated and is referred to as the "absolute bioavailability". As pharmacology has advanced and more drugs have become available, many older products have been reformulated to be given by routes other than those originally intended (often oral). As the drawbacks of oral (or IV) administration have become better appreciated, non-oral, non-IV formulations and methods of administration have become more popular. Nasal administration is one route that has historically been overlooked as an alternative to oral administration—particularly for products needing rapid and non-invasive access to the target tissue—mostly via the blood stream. But attention is now focused on nasal administration for direct access to the brain, as that has the potential to bypass the blood-brain-barrier (BBB), which not even IV administration can always achieve. Assessing PK for these drugs targeting the brain may require serial sampling of the cerebrospinal fluid (CSF), making PK assessments of CNS drugs more invasive and complex, but still possible in future product development. However, we are now seeing more drugs reformulated for nasal delivery to gain faster systemic levels than oral administration (especially in patients with known or suspected gastrointestinal dysmotility), while avoiding the use of needles. For example, in recent years several different formulations and delivery methods for an old drug, dihydroergotamine (DHE), have been developed and these show very different characteristics, suggesting that delivery to different parts of the nose may have very different PK profiles. This review summarizes the systemic PK of different nasal DHE options that have been, or are being, developed and suggests that delivery of drugs to the upper nasal space (UNS) may represent an optimal target. Further research is required to ascertain if this route could also be utilized for direct administration to the CNS (as an attractive alternative to intrathecal delivery) via the olfactory or trigeminal nerves—but already preclinical data (and some human data) suggest this is entirely possible. [ABSTRACT FROM AUTHOR]

Highly pathogenic avian influenza (HPAI) H5Nx viruses can cause neurological complications in many mammalian species, including humans. Neurological disease induced by HPAI H5Nx viruses in mammals can manifest without clinical respiratory disease. HPAI H5Nx viruses are more neuropathogenic than other influenza A viruses in mammals. Severe neurological disease in mammals is related to the neuroinvasive and neurotropic potential of HPAI H5Nx viruses. Cranial nerves, especially the olfactory nerve, are important routes of neuroinvasion for HPAI H5Nx viruses. HPAI H5Nx viruses have a broad neurotropic potential and can efficiently infect and replicate in various CNS cell types. Vaccination and/or antiviral therapy might in part prevent neuroinvasion and neurological disease following HPAI H5Nx virus infection, although comprehensive studies in this area are lacking. Circulation of highly pathogenic avian influenza (HPAI) H5Nx viruses of the A/Goose/Guangdong/1/96 lineage in birds regularly causes infections of mammals, including humans. In many mammalian species, infections are associated with severe neurological disease, a unique feature of HPAI H5Nx viruses compared with other influenza A viruses. Here, we provide an overview of the neuropathogenesis of HPAI H5Nx virus infection in mammals, centered on three aspects: neuroinvasion, neurotropism, and neurovirulence. We focus on in vitro studies, as well as studies on naturally or experimentally infected mammals. Additionally, we discuss the contribution of viral factors to the neuropathogenesis of HPAI H5Nx virus infections and the efficacy of intervention strategies to prevent neuroinvasion or the development of neurological disease. [ABSTRACT FROM AUTHOR]

Diseases of the human nervous system such as neurological infections, Parkinson's, Alzheimer's, and other neurodegenerative diseases are severe pathological diseases and become a public health problem. Neurological disease in its treatment requires a drug distribution mechanism to reach the brain in sufficient quantities so that therapeutic effectiveness is achieved. This is very difficult to achieve with conventional treatment methods such as oral and injection because there are several obstacles in the process of drug distribution, one of which is an obstacle in the form of a Blood Brain Barrier (BBB). Along with current therapeutic developments, drug delivery modifications in the pharmaceutical field are increasingly being developed for the treatment of central nervous system (CNS) diseases. The intranasal drug delivery system to the brain via the nose is very interesting because this route can deliver drugs directly to the brain via the BBB. The intranasal route is preferred in brain targeting. This is due to the ability of the intranasal route to directly deliver drugs through the neural pathways, namely the olfactory nerve and the trigeminal nerve. By distributing the drug via the intranasal route, the drug will pass through the BBB and not undergo metabolism in the liver (first-pass metabolism), where this condition is a barrier that significantly inhibits the peripheral transport of drugs to the brain. There are several things that influence intranasal drug delivery, including parameters that affect intranasal drug administration, drug administration pathways, and mechanisms from the nose to the brain. An in vitro system that can be used to determine the permeability of drugs by means of nano and microparticles through olfactory mucosa cells. Positive results from in vitro experiments on rat test animals indicate that intranasal drug distribution guarantees the effectiveness of nanoparticle formulations in drug therapy. Seeing the big influence on the effectiveness of treatment methods in neurological diseases that must pass through the barrier in the form of the BBB, it is necessary to have further studies related to developing drug delivery via the intranasal route.

Background: The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results: A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion: Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation. [ABSTRACT FROM AUTHOR]

Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the efficacy and safety of OCU. A systematic review and meta-analysis of the published literature on this topic from 2003 to 2023 were conducted in accordance with the PRISMA guidelines. Rigorous statistical analysis with a p-value was performed for related change in visual improvement, gross total resection (GTR), visual deterioration, and olfactory nerve damage. The study included 15 articles with 384 patients in whom OCU was performed by the transcranial approach (TCA) or the endoscopic endonasal approach (EEA). Of these, 341 patients had preoperative visual loss, and 266 patients had postoperative visual recovery. The overall rate of visual improvement was 0.803 (95% CI: 0.733–0.874, p < 0.01). The rate of visual improvement in the EEA and TCA groups was 0.884 (95% CI: 0.803–0.965, p < 0.01) and 0.788 (95% CI: 0.700–0.875, p < 0.01). Further analysis of classification shows that the rate of visual improvement in Type I: < 2 cm was 0.889(95% CI: 0.739–0.969), Type II:2-4 cm was 0.844(95% CI: 0.755–0.910), Type III: > 4 cm was 0.500(95% CI: 0.068–0.932) and the total was 0.853(95% CI: 0.779–0.927 p < 0.01) with low heterogeneity of I2 = 20.80%.Twelve studies separately reported GTR with OCU was 293; the rate of GTR was 0.911 (95% CI: 0.848–0.961, p < 0.01). And the rate of GTR in Type I: < 2 cm was 0.933(95% CI: 0.817–0.986), Type II:2-4 cm was 0.880(95% CI: 0.800–0.936), Type III: > 4 cm was 0.600(95% CI: 0.147–0.947). The total was 0.897(95% CI: 0.830–0.965 p < 0.01) with low heterogeneity of I2 = 34.57%. The related complications of OCU were visual deterioration and olfactory nerve damage. Visual decline was reported in nine studies, and the rate was 0.077 (95% CI: 0.041–0.113, p < 0.01). Six studies reported olfactory nerve damage, and the overall rate was 0.054 (95% CI: 0.019–0.090, p < 0.01). OCU could significantly recover preoperative impaired vision and make GTR easier to achieve, which was also a safe and effective technique in TSM. [ABSTRACT FROM AUTHOR]

The review article analyzes the literature data on the role of molecular olfactory receptors (ORs) and cAMP in the topographic organization of the olfactory system. Sensory information, prior to being transmitted to the brain, is already organized in the peripheral olfactory system according to the one neuron–one receptor rule which also applies to the glomeruli in the olfactory bulb (OB) that obey the one glomerulus–one receptor principle. An important role in olfactory mapping is currently assigned to ORs which play a dual role as being located within the same olfactory sensory neuron (OSN) both in the olfactory cilia and in the membrane of the axonal growth cone, thus determining both odor detection and axon pathfinding toward its specific target in the OB. Meanwhile, there is strong evidence for the central role of the intracellular cAMP signaling pathway in olfactory map development. Using a mutation that abolishes cAMP synthesis, it was found that axons carrying this mutation never penetrate into the glomerular layer but remain in the layer of the olfactory nerve. While doing this, OSN axons targeting the OB fail to form distinct OR-specific glomeruli, many of which become heterogeneous as containing fibers from OSNs expressing ORs for different odorants. Thus, cAMP, synthesized at the OSN axon tip in response to OB signaling, regulates the expression of molecules of axonal navigation to its target in the OB, and also participates in establishing intrabulbar chemical and electrical synapses, forming thereby neuronal circuits. Ample clinical and experimental evidence suggests that the pathogenetic mechanisms of some psychiatric diseases are underlain by cAMP dysregulation. [ABSTRACT FROM AUTHOR]

Context • The phenomena of olfactory and gustatory dysfunction disorders (OGD) are hardly unique to COVID-19. However, the widespread incidence of OGD as sequelae of COVID-19 has provoked rejuvenated interest in these long existing, but poorly studied maladies. Objective • This second of a three-part review discusses past and current approaches for treatment of OGD, not restricted to those that COVID-19 has caused, with the intention to lay a foundation for consideration of new paradigms for evaluation and management of OGD. Design • The researcher performed a narrative review by searching databases including PubMed, Sciencedirect, Google Scholar, Old Dominion University Libraries, and the websites of various medical journals. Searches included numerous combinations of keywords accompanied by the phrases, loss of sense of smell and taste, olfactory and gustatory dysfunction disorders, as well as the terms anosmia, parosmia, ageusia, and parageusia. Such keywords included viruses, bacteria, fungi, protozoa, parasites, infection, COVID-19, treatments, medications, steroids, supplements, nutrients, alternative medicine, acupuncture, olfactory training, clinical trials, cranial nerves, pathogenesis, pathophysiology, and etiology. Setting • The Liebell Clinic, Virginia Beach, VA, USA Conclusions • The epidemiology and hypotheses of pathophysiology of post-COVID OGD has been addressed via numerous studies and reviews. However, extremely limited evidence of effective treatment for chronic OGD, in general, exists, Global demand for any treatment capable of reducing or resolving it is unprecedented. Past and present treatment approaches and recently initiated clinical trials, since the onset of the pandemic, have yet to yield any significant results. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 was first reported in November 2019 in China and rapidly spread across the globe. COVID-19 causes neurologic symptoms and complications, which may persist even after recovery in patients. The objective of this research was to determine the involvement of cranial nerves in COVID- 19 survivors. Method: This was a retrospective study. The study was conducted between March and July of 2022. The analysis included 98 patients with a certain positive polymerase chain reaction. SPSS software version 19 was utilized for data analysis. Results: The average age of the participants was 40.47 years (8.81). The olfactory nerve was found to be the most frequently involved cranial nerve (36.7%). Over 20% of participants had a taste disorder. The findings from the regression analysis indicated that lung involvement and age have a direct and significant relationship with cranial nerve involvement and can serve as its predictors (p = 0.001). Conclusion: It seems that cranial nerve involvement was sustained in COVID-19 patients who survived. In addition, elderly patients and patients with severe illnesses were more likely to show cranial symptoms. It is necessary to monitor COVID-19 survivors for neurological symptoms. [ABSTRACT FROM AUTHOR]

The article focuses on the commentary regarding the implications of altered angiotensin-converting enzyme 2 expression in distinct brain regions due to repeated ethanol exposure and withdrawal for SARS-CoV-2 neuroinvasion, highlighting neurobiological interactions, alcohol, neurology, COVID-19, angiotensin-converting enzyme 2.

With the COVID-19 pandemic, there is growing interest and research in olfactory and gustatory dysfunction (OGD). Drug-induced dysfunction is an often overlooked etiology. While several medications include smell or taste disturbance as a side effect, there are no publications describing which medications are most frequently implicated. We aim to describe the patterns of these adverse drug reactions (ADRs) using the FDA Adverse Events Reporting System (FAERS). The FAERS database was queried from 2011 to 2021 for terms describing ADRs related to OGD. Terms included anosmia, hyposmia, olfactory test abnormal, olfactory nerve disorder, hallucination olfactory, parosmia, ageusia, hypogeusia, dysgeusia, and taste disorder. We identified the top reported medications associated with general smell dysfunction, general taste dysfunction, reduced smell, and altered smell. From 2011 to 2021, 16,091 ADRs were reported with OGD, of which13,641 (84.8%) and 2,450 (15.2%) were associated with gustatory and olfactory reactions, respectively. Zinc products (370 reports) and fluticasone propionate (214) were most commonly associated with olfactory dysfunction, specifically reduced olfaction. Varenicline (24) and fluticasone propionate (23) were most commonly associated with altered smell. Lenalidomide (490) and sunitinib (468) were most commonly associated with gustatory dysfunction. Antineoplastic and immunomodulating medications accounted for 21.6% and 36.3% of olfactory and gustatory ADRs, respectively. Among this category, immunoglobulin drugs were the most commonly associated with OGD ADRs. Gustatory dysfunction is more commonly reported ADR compared with olfactory dysfunction. Immunologic/rheumatologic medications are the leading culprit of reported OGD. With increasing numbers of patients presenting to otolaryngologists for OGD, it is important to consider drug-induced etiology. III. [ABSTRACT FROM AUTHOR]

The article critiques a review on musculoskeletal issues related to SARS-CoV-2 infections and vaccinations, highlighting several overlooked conditions such as myasthenia, cranial nerve damage, and fasciitis. Topics include unaddressed muscular manifestations like myasthenia and myasthenic syndrome, damage to cranial nerves, and the occurrence of fasciitis in Covid-19 patients.

Crustacean olfaction is fundamental to most aspects of living and communicating in aquatic environments and more broadly, for individual‐ and population‐level success. Accelerated ocean acidification from elevated CO2 threatens the ability of crabs to detect and respond to important olfactory‐related cues. Here, we demonstrate that the ecologically and economically important Dungeness crab (Metacarcinus magister) exhibits reduced olfactory‐related antennular flicking responses to a food cue when exposed to near‐future CO2 levels, adding to the growing body of evidence of impaired crab behaviour. Underlying this altered behaviour, we find that crabs have lower olfactory nerve sensitivities (twofold reduction in antennular nerve activity) in response to a food cue when exposed to elevated CO2. This suggests that near‐future CO2 levels will impact the threshold of detection of food by crabs. We also show that lower olfactory nerve sensitivity in elevated CO2 is accompanied by a decrease in the olfactory sensory neuron (OSN) expression of a principal chemosensory receptor protein, ionotropic receptor 25a (IR25a) which is fundamental for odorant coding and olfactory signalling cascades. The OSNs also exhibit morphological changes in the form of decreased surface areas of their somata. This study provides the first evidence of the effects of high CO2 levels at multiple levels of biological organization in marine crabs, linking physiological and cellular changes with whole animal behavioural responses. [ABSTRACT FROM AUTHOR]

Purpose: Although the association between zinc deficiency and olfactory dysfunction is inconclusive, zinc deficiency causes apoptosis of the olfactory ensheathing cells which is involved in olfactory nerve turnover and axon regeneration, thereby suggesting a possible relationship. We investigated the relationship between serum zinc levels and olfactory function in patients with olfactory dysfunction. Methods: Ninety patients who had been diagnosed with post-infectious, posttraumatic, drug-induced, neurological and idiopathic olfactory dysfunction were included. Patients were divided into zinc normal group and zinc deficiency groups according to three reference values for serum zinc levels (60, 65, 70 µg/dL). The results of olfactory tests and patient backgrounds were used to compare the differences between the two groups. Results: There were significantly worse detection and recognition thresholds in the T&T olfactometer and Open Essence (odor identification test) results in the zinc deficiency group (< 60 µg/dL). In addition, significant correlations between olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence results) and serum zinc levels < 65 µg/dL were observed. The zinc deficiency group < 70 µg/dL with idiopathic olfactory dysfunction had significantly worse olfactory tests (detection/recognition thresholds in the T&T olfactometer and Open Essence). In addition, there was a significant correlation between the detection/recognition thresholds in the T&T olfactometer and serum zinc levels in idiopathic olfactory dysfunction. Conclusions: Our findings suggest that zinc deficiency may exacerbate the severity of olfactory dysfunction. Furthermore, idiopathic olfactory dysfunction may be partly caused by zinc deficiency. [ABSTRACT FROM AUTHOR]

The anatomy of the nasal cavity and its structures, as well as other elements building a scaffold for olfactory organs, differs significantly among various groups of mammals. Understanding anatomical conditions of quality of olfaction are being studied worldwide and is a complex problem. Among many studies regarding bone and epithelial structures of turbinates and connected anatomical structures, few studies describe the vascularization of turbinates. Ethmoid turbinates are above all covered in olfactory epithelium containing branched axons that receive olfactory stimuli and as olfactory nerves penetrate the cribriform lamina of the ethmoid bone conveying information from smell receptors to the brain. Differences in vascularization of the cribriform plate and turbinates may add crucial information complementing studies regarding the olfactory organ's bone and soft tissue structures. In the study, we describe the vascularization of the cribriform plate of the ethmoid bone of 54 Artiodactyla and Carnivora. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is the leading cause of irreversible blindness, and the loss of retinal ganglion cells (RGCs) is the most important pathological feature. During the progression of glaucoma, glutamate content in the optic nerve increases, and glutamate-induced excitotoxicity will aggregate the damage and death of RGCs. We have previously reported that olfactory ensheathing cells (OECs) transplantation preserved the visual function of the glaucoma model but the mechanism is unknown. Methods: Adult Long-Evans rats were used in the present study and injecting magnetic microspheres was used to establish a glaucoma model in rats. Optokinetic response test and Pattern electroretinogram recording were used to assess the visual functions of rats. RT-PCR, immunofluorescence, and co-culture experiments were performed to investigate the therapeutic effects and mechanisms of OECs for glaucoma. Results: In the glaucoma model, increased glutamate content and the damage of astrocytes (AC) and RGCs were observed. OECs transplantation reduced the glutamate concentration in the optic nerve, alleviated the apoptosis of AC and RGCs, and protected the visual function of the glaucoma model. Furthermore, we found that OECs possessed a stronger capacity to metabolize excessive glutamate compared with AC and Müller glia. OECs could improve the glutamate microenvironment of the optic nerve to prevent AC and RGCs from glutamate-induced excitotoxicity in glaucoma. And the recovery of AC function further supported the survival of RGCs. Conclusions: We demonstrate that OECs transplantation could play a neuroprotective role by regulating the glutamate microenvironment in glaucoma. [ABSTRACT FROM AUTHOR]

Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism. Due to these physiological peculiarities of the nasal cavity, compartmental modeling for nasal formulation is considered a demanding process. For this purpose, intravenous models have been proposed, based on the fast absorption from the olfactory nerve. However, most of the sophisticated approaches are required to describe the different absorption events occurring in the nasal cavity. Donepezil was recently formulated in the form of nasal film ensuring drug delivery in both bloodstream and the brain. In this work, a three-compartment model was first developed to describe donepezil oral brain and blood pharmacokinetics. Subsequently, using parameters estimated by this model, an intranasal model was developed dividing the administered dose into three fractions, corresponding to absorption directly to the bloodstream and brain, as well as indirectly to the brain expressed through transit compartments. Hence, the models of this study aim to describe the drug flow on both occasions and quantify the direct nose-to-brain and systemic distribution. [ABSTRACT FROM AUTHOR]

Since the first emergence of COVID-19 on the global stage, there has been a wealth of evidence to suggest that SARS-Cov2 is not merely a pulmonary pathogen. This virus is unique in its ability to disrupt cellular pathways related to protein homeostasis, mitochondrial function, stress response, and aging. Such effects raise concerns about the long-term fate of survivors of COVID-19 infection, particularly regarding neurodegenerative diseases. The concept of interaction between environmental factors and alpha-synuclein formation in the olfactory bulb and vagal autonomic terminals with subsequent caudo-cranial migration has received much attention in the context of PD pathogenesis. Anosmia and gastrointestinal symptoms are two well-known symptoms of COVID-19, with evidence of an olfactory bulb and vagal infiltration by SARS-CoV2. This raises the possibility of the spread of the viral particles to the brain along multiple cranial nerve routes. Neurotropism, coupled with the ability of the SARS-Cov2 virion to induce abnormal protein folding and stress responses in the central nervous system, in presence of an inflammatory milieu, reinforced by hypoxia, coagulopathy, and endothelial dysfunction, reverberates the intriguing possibility of activation of a neurodegenerative cascade leading to the development of pathological alpha-synuclein aggregates and thus, triggering the development of PD in survivors of COVID19. This review attempts to summarize and critically appraise existing evidence from basic science research and clinical reports of links between COVID-19 and PD and explores the prospect of a multi-hit pathophysiological process, induced by SARS-Cov2 infection, ultimately converging on perturbed cellular protein homeostasis, which although is intriguing, presently lacks robust evidence for confirmation.