Nerve Connections Research Articles

Progress in MGJWS: A 74-Year Review of Marcus Gunn Jaw-Winking Syndrome.

We present an overview of the epidemiology and differential diagnosis of Marcus Gunn jaw-winking syndrome. We scrutinize various hypotheses regarding its etiology and pathogenesis, encompassing abnormal nerve connections, heredity factors, genetic variation, and the release hypothesis, as proposed in prior studies. Furthermore, we discuss the clinical manifestations of Marcus Gunn jaw-winking syndrome and highlight cases with exceptional clinical presentations or concurrent diseases. Moreover, we not only describe the existing surgical and nonsurgical treatments for Marcus Gunn jaw-winking syndrome but also delineate therapies for related conditions such as Meige syndrome, sequelae of facial paralysis, and other oculopalpebral and facial synkinesis. This comprehensive approach serves as a valuable reference for the holistic management of Marcus Gunn jaw-winking syndrome.

The modulation of cholecystokinin receptor 1 in the NAc core input from VTA on METH-induced CPP acquisition

BackgroundMethamphetamine (METH) is a potent psychostimulant that interferes the functionality of various brain regions and nervous connections, leading to addiction. The nucleus accumbens core (NAcC), primarily composed of gamma-aminobutyric acid (GABAergic) neurons, serves as a critical nucleus intimately related to addictive behavior. Previous research has indicated the involvement of cholecystokinin (CCK) receptors in drug addiction, yet the precise function of CCK receptors within the neural circuitry mediating METH-induced addiction remains elusive. MethodsMETH-induced conditioned place preference (CPP) model was established in mice. In CCK receptor 1 conditional knockout (CCK1Rflox/flox) or CCK receptor 2 conditional knockout (CCK2Rflox/flox) mice, we then utilized the adeno-associated virus (AAV) transfection system to knock out the specific CCK receptor subtype and explore the function of the CCK receptors in the ventral tegmental area (VTA) to NAcC circuit during METH-induced CPP acquisition. ResultsDuring the acquisition of METH-induced CPP, the expression of CCK1R, but not CCK2R, was upregulated specifically in NAcC. Genetic disruption of either CCK1R in the NAcC effectively hindered METH-induced CPP acquisition and prevented the hyper-excitability of neurons triggered by METH. Furthermore, CCK is released by dopaminergic neurons in the VTA, projecting to the NAcC. Notably, specifically knocking out CCK1R in the VTADA → NAcCGABA circuit blocked the presynaptic release and synaptic plasticity enhancement induced by METH. ConclusionsThese discoveries highlight the critical effect of CCK1R in the VTADA → NAcCGABA circuit on METH-induced CPP acquisition and provide a more comprehensive understanding of the mechanisms underlying CCK receptors contributing to the METH-induced addictive behavior.

Microenvironment‐Responsive Injectable Conductive Hydrogel for Spinal Cord Injury Repair

AbstractSpinal cord injury (SCI) represents a severe neurological condition often coupled with a drastic secondary inflammatory response, which further exacerbates the damage in most cases. Due to their unique electrical and mechanical compatibilities with the spinal cord, the utilization of conductive hydrogels through injection for SCI repair, particularly in scenarios involving non‐uniform and large gaps, has emerged as a promising approach. Herein, leveraging the acidic microenvironment characteristic of acute SCI sites, an injectable conductive hydrogel with pH‐responsive immunoregulation is engineered for SCI repair. Based on the dynamic Schiff base chemistry and covalent photo‐crosslinking, this composite hydrogel, composed of gelatin methacryloyl, oxidized dextran, and MoS2, exhibits adjustable mechanical and conductive properties, enabling a customized match with the natural spinal cord's attributes. Additionally, the incorporation of Wnt5a and its selective release in acidic conditions prompt the immediate suppression of inflammatory factors and enhances neural differentiation and regeneration. In the 2‐mm hemisection mouse SCI model, the optimized conductive hydrogel can effectively bridge the injury gap, establish nerve connections and signal, mitigate inflammatory response, and promoted recovery of mobility. This novel injectable conductive hydrogel system offers a promising advance in therapeutic materials for SCI repair.

8638 NEGR1 is a Mediator of Exercise-Induced Neuritogenesis in Subcutaneous White Adipose Tissue, Implications for Improved Systemic Metabolism

Abstract Disclosure: P. Nigro: None. N.P. Carbone: None. T. Caputo: None. M. Vamvini: None. M.M. Columbus: None. M.F. Hirshman: None. R. Middelbeek: None. L.J. Goodyear: None. Emerging research shows that exercise training results in robust and beneficial adaptions to subcutaneous white adipose tissue (scWAT), leading to improved systemic metabolism. The mechanisms for these benefits of exercise on are not fully understood, but we have recently demonstrated that training in mouse scWAT refines nerve connections in scWAT promoting neurite outgrowth (neuritogenesis). Our multi-omics and advanced microscopy data identifies Neuronal Growth Regulator 1 (NEGR1) as a potential player in this process. Here, we determine the role of NEGR1 as a mediator of scWAT neuritogenesis and regulator of systemic metabolism. Exercise training in mice for 11 days significantly increased NEGR1 protein expression by 35% (p<0.05). Next, we directly injected NEGR1 AAV into the inguinal scWAT of untrained male mice for three weeks resulting in a 43% increase in NEGR1 protein (p<0.05). Overexpression of NEGR1 led to an increase in the innervation markers tyrosine hydroxylase (+38%, p<0.01) and synaptophysin (+39%, p<0.01), and remarkably, a 16% decrease in adipocyte cell size (p<0.05), and a 15% reduction in fasting blood glucose levels (p<0.05). This suggests that NEGR1 plays a fundamental role in regulating scWAT morphology and function, adaptations that improve systemic glucose homeostasis. To determine mechanisms for exercise training-induced increases in NEGR1 expression, we used in silico and cell culture experiments and found that NEGR1 is under the regulation of the Peroxisome Proliferator-Activated Receptor gamma (PPARg) transcription factor. Given that numerous natural and synthetic PPARg ligands are lipids, we used targeted lipidomics to identify exercise-induced lipids capable of binding and inducing PPARg expression in inguinal scWAT. We identified 13-oxo-octadecadienoic acid (13-oxo-ODE), an oxylipin derived from linoleic acid, as a potent agonist and inducer of PPARg expression. Exercise training increased 13-oxo-ODE by 3-fold (p<0.05), and 13-hydroxyoctadecadienoic acid (13-HODE), the 13-oxo-ODE precursor was also increased by 3-fold (p<0.01). To validate that 13-oxo-ODE increases NEGR1, adipocytes were incubated with 2μM of 13-oxo-ODE for 48 hours. 13-oxo-ODE increased NEGR1 expression by 27-fold (p<0.0001) and NEGR1 protein by 2-fold (p<0.01). In summary, NEGR1 is a novel exercise-induced molecule that regulates neuronal refinement in scWAT. Our data also suggest that the synthesis of 13-oxo-ODE leads to PPARγ activation that in turn promotes NEGR1 expression in scWAT. NEGR1 has beneficial effects on scWAT that are associated with improved systemic metabolism, making NEGR1 a novel target for treatment of obesity and cardiometabolic diseases. Presentation: 6/1/2024

Repeating ultrastructural motifs provide insight into the organization of the octopus arm nervous system

The peripheral nervous system of the octopus is among the most complex of any animal. In each arm, hundreds of serial ganglia form a central core of nervous tissue processing sensory input, issuing motor commands, and exchanging information with the central brain.1,2,3,4,5 In addition to the central cord, there are two other types of neural elements: fine intramuscular nerve cords (INCs)6,7 and small sucker ganglia at the base of each sucker.2,6,8,9 Connections between these different elements and the structural organization of the arm nervous system remain poorly understood, despite decades of interest and a more recent explosion of studies of the cephalopod nervous system.8,10,11,12,13,14,15 Here, we use serial blockface electron microscopy to reconstruct large volumes of an arm from Octopus bocki at the base and toward the tip, mapping connections between the various neural elements and their relationship to the muscle and skin. We show that the ganglia follow an alternating mirror-image pattern along the arm, where the left or right-sided location of successive suckers determines ganglionic orientation. We also describe previously unrecognized patterns in (1) continuity of oblique connectives between the INCs that encircle the arm; (2) repeatable structures of the major blood vessel branches and nerve connectives within each ganglion; (3) clustering of rare, unusually large neurons within the cell body layers; and (4) division of the cortex into repeating columns. These new findings from the first 3DEM reconstruction of the arm should greatly facilitate future studies of octopus neurobiology, particularly sensori-motor integration and arm control.

3D fascicular reconstruction of median and ulnar nerve: initial experience and comparison between high-resolution ultrasound and MR microscopy

BackgroundThe complex anatomy of peripheral nerves has been traditionally investigated through histological microsections, with inherent limitations. We aimed to compare three-dimensional (3D) reconstructions of median and ulnar nerves acquired with tomographic high-resolution ultrasound (HRUS) and magnetic resonance microscopy (MRM) and assess their capacity to depict intraneural anatomy.MethodsThree fresh-frozen human upper extremity specimens were prepared for HRUS imaging by submersion in a water medium. The median and ulnar nerves were pierced with sutures to improve orientation during imaging. Peripheral nerve 3D HRUS scanning was performed on the mid-upper arm using a broadband linear probe (10–22 MHz) equipped with a tomographic 3D HRUS system. Following excision, nerves were cut into 16-mm segments and loaded into the MRM probe of a 9.4-T system (scanning time 27 h). Fascicle and nerve counting was performed to estimate the nerve volume, fascicle volume, fascicle count, and number of interfascicular connections. HRUS reconstructions employed artificial intelligence-based algorithms, while MRM reconstructions were generated using an open-source imaging software 3D slicer.ResultsCompared to MRM, 3D HRUS underestimated nerve volume by up to 22% and volume of all fascicles by up to 11%. Additionally, 3D HRUS depicted 6–60% fewer fascicles compared to MRM and visualized approximately half as many interfascicular connections.ConclusionMRM demonstrated a more detailed fascicular depiction compared to 3D HRUS, with a greater capacity for visualizing smaller fascicles. While 3D HRUS reconstructions can offer supplementary data in peripheral nerve assessment, their limitations in depicting interfascicular connections and small fascicles within clusters necessitate cautious interpretation.Clinical relevance statementAlthough 3D HRUS reconstructions can offer supplementary data in peripheral nerve assessment, even in intraoperative settings, their limitations in depicting interfascicular branches and small fascicles within clusters require cautious interpretation.Key Points3D HRUS was limited in visualizing nerve interfascicular connections.MRM demonstrated better nerve fascicle depiction than 3D HRUS.MRM depicted more nerve interfascicular connections than 3D HRUS.Graphical

The LINGO-1-deficient neural stem cell-derived neural tissueoid showed enhanced retention and neuronal relay in the transected spinal cord

Neural stem cell (NSC)-derived neural tissueoids are a promising option to model spinal cord development and repair; however, the survival and integration ability with the host in vivo need to be improved. We aimed to determine if genetically engineered neural tissueoids in a NT-3 delivery scaffold exhibited increased retention and relay properties and to explore the underlying mechanisms. Gene expression screening of tissue and single-nucleus RNA sequencing revealed that leucine rich repeat and immunoglobin-like domain-containing protein 1 (LINGO-1) was significantly increased in neurons following spinal cord injury. The LINGO-1 protein accelerated cell death by increasing cleaved caspase-3 and interacting with TrkC to decrease NT-3-mediated phosphorylation of the PI3K/AKT/CREB axis, resulting in synaptic degradation. Subsequently, we seeded LINGO-1-deficient NSCs on a NT-3 delivery scaffold to construct an apoptosis resistant neural tissueoids, which was transplanted into a T9 complete spinal cord injury (SCI) rat model. The LINGO-1-deficient neural tissueoid was retained in the graft area, dramatically facilitated ascending and descending nerve fiber regeneration and connection, restored relay from brain to the caudal spinal cord, and improved the hindlimb movement function. This study demonstrates that transplantation of a LINGO-1-deficient tissueoid is an efficient pro-survival and neurogenesis strategy for the treatment of SCI.

Whole-Eye Transplantation: How Far Are We From a Breakthrough?

Traumatic facial injuries and resultant eye enucleation remain a devastating life-changing event for many. However, whole-eye transplantation (WET) has remained a distant goal until recently. This narrative review explores the existing literature on WET, assesses current hurdles to its success, and considers the ethical challenges to the expansion of WET programs globally. The authors identified pertinent keywords by conducting an initial literature exploration which were subsequently used to search scientific databases. In line with the narrative methodology employed in this article, specific inclusion and exclusion criteria were not explicitly defined. Nevertheless, the review focused exclusively on articles relating to ocular restoration and reconstructive surgery. Though vision restoration remains elusive, burgeoning surgical techniques such as vascularized composite allotransplantation have opened the scope for surgeons to consider WET when planning facial transplants. Dr. Rodriguez and the New York University Langone team's success supports the recent advancements made in surgical innovation and the potential of CD34-positive stem cells as neuroprotective agents when injected at the optic nerve connection of the recipient. For WET to succeed, vascular and neural structures and the transplanted eye must be considered. Such requirements have been strengthened by the development of microsurgical techniques. In addition to addressing the technical feasibility of WET, it is crucial to deliberate on ethical considerations such as the lifelong implications associated with immunosuppression and, challenges related to the fair division of ocular tissue for WET versus keratoplasty. WET amid significant facial trauma has great potential to restore the quality of life in patients, however, more research is required to demonstrate its long-term viability.

Clinico-anatomical insight into the unusual course, branching pattern and connections of ulnar nerve: A narrative review.

Ulnar nerve originates from the lower trunk as a branch from anterior division, continuing as a branch from medial cord of the brachial plexus. It receives fibres from anterior rami of cervical nerve root 8 and the first thoracic nerve root. Ulnar nerve injury accounts for being the most common vessel of upper limb that results in hospitalisation. Knowing the variability in the anatomical pattern of ulnar nerve and its communication with various branches of nerves in the vicinity can have implications. The current narrative review comprised literature search on Google, Google Scholar and PubMed databases for articles published between 2015 and 2023 on the subject. The insight and understanding of the related ulnar nerve anatomy is likely to be of prodigious help to anatomists, surgeons, physicians and radiologists in preventing unexpected outcomes in the future.

Whole eye transplantation: are we on the cusp of an inflection point?

Traumatic facial injury and resultant eye enucleation remains a devastatinglife-changing event for many. With advancements in surgical techniques andimmunosuppressive therapies, facial transplantation has been made viable.However, whole-eye transplantation (WET) has remained a distant goaluntil recently. Our aim was to review the existing literature on WET andassess current hurdles for its success. We identified pertinent keywords byconducting an initial literature exploration which was subsequently used tosearch scientific databases, including PubMed, Medline, and Embase. In linewith the narrative methodology employed in this article, specific inclusionand exclusion criteria were not explicitly defined. The review focused exclusivelyon articles relating to ocular restoration and reconstructive surgery.Though vision restoration remains elusive, burgeoning surgical techniquessuch as vascularised composite allotransplantation have openedthe scope for surgeons to consider WET when planning facial transplants.Dr. Rodriguez and the NYU Langone team’s transplantationhas remained viable at 10 months. Though it has not facilitated visualrestoration, it supports the potential of CD34-positive stem cells as neuroprotectiveagents when injected at the optic nerve connection of therecipient. Nevertheless, it is also crucial to deliberate on ethical considerationssuch as the lifelong implications associated with immunosuppressionand, challenges related to the equitable division of ocular tissue forWET versus keratoplasty. WET amid significant facial trauma has greatpotential to restore the quality of life in patients through improved cosmesis.Further research is required to demonstrate its long-term viabilityand potential for vision-restoration in humans.

ANATOMICAL VARIABILITY OF THE SEGMENTS OF THE INFERIOR ALVEOLAR NERVE IN THE PEOPLE OF SECOND PERIOD OF MATURE AND OLDER AGE

To avoid complications of bicortical implantation, great importance is attached to the study of individual morphological features of the mandible and its structures, in particular, the anatomical variability of the inferior alveolar nerve (IAN) and mandibular canal. The purpose of the study was to fi nd out the peculiarities of the structure, topography and individual anatomical variability of the IAN in persons of the second period of maturity and older age. Cone-beam computer tomography of 54 people of both sexes aged 45-65 years with three- dimensional reconstruction, morphometry and statistical analysis was studied. On the basis of our own research on the topographical and anatomical features of the IAN and its syntopy with the mandible, in particular, with the mandibular canal, we propose to distinguish 4 of its divisions: extra- canal – from the place of formation to the entrance to the mandibular canal; intracanal – from the mandibular foramen to the mental foramen; mental – after exiting the mandibular canal; incisive – after the departure of the mental branch. The topographical and anatomical features and anatomical variability of the IAN were studied. In people of the second period of mature and elderly age, anatomical variability of the macroscopic structure and topography of the IAN was established, which manifested itself in high (4.0-11.0 mm) and low (22.0-33.0 mm) levels, relative to the foramen ovale its beginning and form (one or two trunks) of departure from the mandibular nerve. The largest number of nerve connections with other branches of the mandibular nerve is formed by the extracanal section of the IAN: with the auriculo-t emporal nerve (29 cases – 53.7 %), with the lingual nerve (5 cases – 9.26 %), with the nerve of the medial pterygoid muscle (3 observations – 5.56 %) and with the nerve of the lateral pterygoid muscle (2 specimens – 3.7 %). A diff erent level of departure of the nerve to mylohyoid from the extracanal section of the IAN was established: high (5.0-7.0 mm) and low (27.0-31.0 mm). Anatomical variability of the intracanal part of the IAN was manifested by structural variants: a single trunk (43 cases, 79.6 %), rarely – two trunks (11 observations, 20.4 %) and very rarely – the lower dental plexus (6 specimens, 11,11 %). The proximity of the roots of the 7th and 8th teeth to the IAN can be the cause of severe pain in the pathology of these teeth and cause nerve damage during their removal. Nerve connections occur between the right and left incisive nerves, the knowledge of which is an important practical value for performing anesthesia of the front row of teeth. The number of branches to the teeth, interalveolar septa and gingiva from the IAN signifi cantly decreases with age and with a violation of the integrity of the dentition.

Radical Resection of Malignant Tumors of Major Salivary Glands: Is This Possible?

In primary therapy, a universally recognized surgical indication applies to all tumors of the salivary glands. According to the classic rule, radical resection of a head and neck tumor requires clean margins of at least 5 mm, although recent studies have shown that for certain locations, 1 mm may be sufficient. In the surgical resection of a tumor of the salivary glands, especially of the parotid gland, can these rules be respected? Owing to the complex branching and connections of the facial nerve within the parotid gland, even a medium-sized malignant tumor may be in contact with a branch of the nerve, thus raising the question of its preservation. The facial nerve is so important from a functional and aesthetic point of view that it is commonly believed that it should be preserved unless it is incorporated into the tumor. This is a compromise between an oncological resection, that is, the complete excision of the tumor with no residual cancer cells left behind, and quality of life. Almost all authors try to overcome this lack of radicality by indicating postoperative (chemo)radiotherapy. In this article, the pros and cons of nerve preservation will be analyzed by examining the published studies on this topic.

Systematic review on the centrocentral anastomosis technique for the surgical treatment of traumatic neuromas

Aim: Centrocentral anastomosis (CCA) can be applied in the treatment of painful neuromas, by connecting nerve ends or fascicles after neuroma resection, with or without an interposed nerve graft. While this technique was developed directly after the introduction of microsurgical techniques, it is currently not frequently applied in neuroma treatment. Methods: In this article, the literature on CCA was systematically reviewed, both for clinical and experimental studies. Specific attention was paid to the different surgical techniques, potential applications, and pathophysiologic mechanisms that might explain how CCA can prevent neuroma formation. Results: A total of 15 articles were found on this subject, 11 clinical and 4 experimental studies. In clinical studies, CCA was mostly applied for neuroma treatment following amputation of fingers and lower limbs. In experimental studies, different combinations of nerve connections and grafts were investigated in the rat sciatic nerve model. Pain reduction in the clinical studies overall was good to excellent, but only in two studies control groups were used. Results from experimental studies showed that the use of an interposed graft was beneficial by entrapment of axons inside the graft. Conclusion: Although CCA has shown promising results for neuroma treatment, there are only a few case series to date, one cohort and one randomized study, and in the latter two, no graft was used. More research is needed to investigate the outcome of CCA, especially for the option of an interposed nerve graft. This investigation should involve comparisons with alternative techniques, utilization of standardized outcome measures, and, preferably, inclusion of longer follow-up periods.

The Ability of Injections Versus Needle Insertion to Decrease the Severity and Frequency of Symptoms for Patients With Chronic Headaches: A Critically Appraised Topic

Clinical Scenario: Headaches can be categorized as tension-type headaches, migraine, trigeminal autonomic cephalgia, and other primary headache disorders according to the Third International Classification of Headache Disorders. Headaches are one of the most common disorders within the nervous system and have a prevalence of >48% within the general population. Nerve blocks are a type of nerve stimulation that is believed to help reduce the frequency and severity of headaches. The physiological effect of the greater occipital nerve block on headaches is thought to be due to the central nervous system connections of the greater occipital nerve and trigeminal and cervical afferent fibers, which is believed to be the prime origin of migraine headaches. Nerve blocks can contain a variety of drug regimens including steroids, local anesthetics, or a mixture of both. Trigger point injections (TPIs) are an invasive therapy where a needle is guided directly into a trigger point that has been previously identified upon examination. Botulinum toxin A is an alternative treatment modality that can be injected with TPIs. Botulinum toxin A is a potent naturally occurring toxin that causes dose-dependent muscular relaxation by inhibiting the release of acetylcholine at the neuromuscular junction. Summary of Key Findings: (1) Both greater occipital nerve blocks and TPIs have been shown to reduce headache frequency and severity in the short term; however, it appears to be due to the needle injected into the soft tissue structures and not due to the type of solution injected. (2) Ultrasound guidance allows for a more accurate and effective technique than a blind injection as it allows for accurate injection into the targeted muscles, thereby minimizing complications and increasing the chance of success. (3) Once symptoms have been alleviated, clinicians should evaluate the patient’s mechanics in the upper trunk to determine whether there are any mechanical abnormalities leading to the formation of myofascial pain and/or trigger points causing the headache symptoms. If identified and treated appropriately, this can allow for a long-term solution in correcting the cause rather than the symptoms alone. (4) Participants receiving a greater occipital nerve block or TPI, despite the drug regimen or dosage, experienced similar benefits with no statistical significance. In deciding which treatment approach to take, the clinician should speak with the patient to educate them on the available options and allow the patient to be part of the decision-making process to best meet their needs and include a rehabilitation plan with all the treatment approaches. Clinical Question: In patients who experience chronic headaches, was there a greater decrease in headache frequency and severity with a greater occipital nerve block or TPI? Clinical Bottom Line: Needles into the supraclavicular region for headaches lead to decreased severity and frequency of headaches in the short term but will not lead to headache resolution. Strength of Recommendation: B.

Three Blind Moles: Molecular Evolutionary Insights on the Tempo and Mode of Convergent Eye Degeneration in Notoryctes typhlops (Southern Marsupial Mole) and Two Chrysochlorids (Golden Moles).

Golden moles (Chrysochloridae) and marsupial moles (Notoryctidae) are textbook examples of convergent evolution. Both taxa are highly adapted to subterranean lifestyles and have powerful limbs for digging through the soil/sand, ears that are adapted for low-frequency hearing, vestigial eyes that are covered by skin and fur, and the absence of optic nerve connections between the eyes and the brain. The eyes of marsupial moles also lack a lens as well as retinal rods and cones. Two hypotheses have been proposed to account for the greater degeneracy of the eyes of marsupial moles than golden moles. First, marsupial moles may have had more time to adapt to their underground habitat than other moles. Second, the eyes of marsupial moles may have been rapidly and recently vestigialized to (1) reduce the injurious effects of sand getting into the eyes and (2) accommodate the enlargement of lacrimal glands that keep the nasal cavity moist and prevent the entry of sand into the nasal passages during burrowing. Here, we employ molecular evolutionary methods on DNA sequences for 38 eye genes, most of which are eye-specific, to investigate the timing of relaxed selection (=neutral evolution) for different groups of eye-specific genes that serve as proxies for distinct functional components of the eye (rod phototransduction, cone phototransduction, lens/cornea). Our taxon sampling included 12 afrothere species, of which two are golden moles (Amblysomus hottentotus, Chrysochloris asiatica), and 28 marsupial species including two individuals of the southern marsupial mole (Notoryctes typhlops). Most of the sequences were mined from databases, but we also provide new genome data for A. hottentotus and one of the two N. typhlops individuals. Even though the eyes of golden moles are less degenerate than the eyes of marsupial moles, there are more inactivating mutations (e.g., frameshift indels, premature stop codons) in their cone phototransduction and lens/cornea genes than in orthologous genes of the marsupial mole. We estimate that cone phototransduction recovery genes were inactivated first in each group, followed by lens/cornea genes and then cone phototransduction activation genes. All three groups of genes were inactivated earlier in golden moles than in marsupial moles. For the latter, we estimate that lens/cornea genes were inactivated ~17.8 million years ago (MYA) when stem notoryctids were burrowing in the soft soils of Australian rainforests. Selection on phototransduction activation genes was relaxed much later (5.38 MYA), during the early stages of Australia's aridification that produced coastal sand plains and eventually sand dunes. Unlike cone phototransduction activation genes, rod phototransduction activation genes are intact in both golden moles and one of the two individuals of N. typhlops. A second marsupial mole individual has just a single inactivating mutation in one of the rod phototransduction activation genes (PDE6B). One explanation for this result is that some rod phototransduction activation genes are pleiotropic and are expressed in extraocular tissues, possibly in conjunction with sperm thermotaxis.

Survey of the use of AI models and techniques in the analysis and prediction of neuro-degenerative diseases

Neurodegenerative diseases are caused by the gradual breakdown of the nerve connections. The detection and prediction of these diseases has been attempted with a variety of different artificial intelligence techniques, using the wide range of modalities available resulting in variations in accuracy and other metrics. This paper aims to offer a methodical as well as quantitative comparison among the various predictive methodologies that have been conducted for three neurodegenerative diseases, namely Alzheimer’s, Schizophrenia and Dementia. Lastly this paper focuses on the variation in occurrences of these diseases with changing demographics such as age, sex and location.

Connection between medial dorsal cutaneous nerve and saphenous nerve: case report.

There are no data on the connection of the saphenous nerve (SN), located on the medial side of the foot, with the terminal branches of the superficial fibular nerve. The aim of this study is to reveal the variation that surgeons should pay attention to for anesthesia applied in foot surgeries. In this study, the left foot of a 70-year-old female cadaver fixed with formalin was dissected. The distance to the medial malleolus and the incision line was recorded using digital caliper to determine the reference points in the resulting variation. It was observed that a branch from the SN, which arose from the SN and proceeded anteriorly to the upper part of the medial malleolus and continued towards the dorsum of the foot, hooked with a branch from the medial dorsal cutaneous nerve (MDCN). The branches arising from this hook were distributed on the medial edge of the foot up to the proximal metatarsophalangeal joint I. The distance of this nerve connection to the medial malleolus is 91.14mm, and the distance to the incision line is 15.76mm. It is suggested that the case presented as an unusual SN variation, which may affect the success of local anesthesia in invasive procedures to the medial part of the foot and could be considered in the evaluation of sensory loss after anteromedial surgical approach to the ankle, should be included in the classification of the cutaneous innervation pattern of the foot.

Vidian nerve neurofibroma.

Vidian nerve is created from the connection of the greater petrosal nerve and the deep petrosal nerve (Giraddi et al., 2010). These two nerves transmit parasympathetic and sympathetic fibers respectively. Vidian nerve tumour is one of the rarest known tumours (Hong et al., 2014). Genetic changes effectively play a role in the development of nerve sheath tumors. Of course, due to the rarity of this type of tumor, there is not much information about its causes and risk factors (Yamasaki et al., 2015). The incidence rate of malignant peripheral nerve sheath tumors is about 0.001 % (Fortes et al., 2019). Considering the low prevalence of this tumor and the type of treatment performed on this patient, the investigation of the case presented in this study can lead to a better understanding and more correct treatment. This case report has been proposed due to the very low prevalence of neurofibroma of the Vidian nerve in the world. Vidian nerve supplies sympathetic and parasympathetic fibers to the lacrimal glands and nasopalatine mucosa. In many cases, involvement of the Vidian nerve by neurofibroma can be misleading for doctors. Due to the very low prevalence of neurofibroma of the Vidin nerve, the possibility of its being missed and not diagnosed during the examination of patients by doctors is very high. This case report is presented in order to familiarize scientists with this lesion due to its very low prevalence. This therapeutic approach that was used in this case requires longer follow-up periods, but it can prevent possible complications after surgery.

COVID-19 Induced Enantiopathy to Hyperosmia (P6-10.005)

<h3>Objective:</h3> Pathophysiology behind reduced olfactory ability in hyperosmic individuals. <h3>Background:</h3> COVID-19 infection as an enantiopathy to hyperosmia has not been described. <h3>Design/Methods:</h3> A 63 year-right-handed male presented with hyperosmia of 150% of normal whereby aromas appeared distorted and disgusting. Shortly, he tested positive for COVID-19 which led to a resolution of his hyperosmia. Alcohol Sniff Test scores fluctuated between zero and three (anosmia). Gradually, his smell improved from 80% and 100% of normal. However, post COVID-19 infection, it returned to 130% of normal. <h3>Results:</h3> Neurological abnormalities: Olfactory Testing: Odor Discrimination Memory Test: Total 7/12 (hyposmia). Bilateral Olfactory Threshold Testing to Phenylethyl Alcohol: 3 (hyposmia). Taste Threshold and Suprathreshold Testing: Mild hypogeusia to Sucrose. Ageusia to Hydrochloric acid, urea and propothiocarbamide. Olfactometer Identification Testing: Left nostril: 10 (anosmia), Right nostril: 8 (anosmia). <h3>Conclusions:</h3> The mechanism whereby COVID-19 acts to reduce olfactory ability in normosmic individuals has been postulated as viral involvement of olfactory nerve at olfactory bulb (Lechien, 2020), pathology of sustentacular cells (Zhang, 2021), olfactory receptor site destruction (Xu, 2022) vasculopathy/arteriopathy of cranial nerve or central connections of olfactory nerve (Parry, 2020) or inflammatory response induced destruction of lamina propria and olfactory nerve apoptosis (Lechien, 2020). The same may have incited a reduced olfaction in hyperosmic individuals-such may be under grouped as understanding the pathophysiology of this subject’s hyperosmia. Perceived hyperosmia is often objectively hyposmic: pathology of inhibiting the inhibitory olfactory discharges that result in enhancement of perceived odor (Kalita, 2022). Elimination of hyperosmia reduces functionality of remaining normosmic neurons which then became relatively hyposmic, but were perceived as normal due to lack of the inhibitory factors. Recovery of hyperosmia upon recovery of olfactory function from COVID-19 would be consistent with such a postulation. Of those with preexisting chemosensory dysfunction, query as to impact of COVID-19 on remaining sensory function is warranted. <b>Disclosure:</b> Mrs. Kalita has nothing to disclose. Miss Birwatkar has nothing to disclose. Dr. Hirsch has nothing to disclose.

Editorial

Editorial