The role of membrane trafficking and retromer complex in Parkinson's and Alzheimer's disease.

Membrane trafficking is a physiological process encompassing different pathways involved in transporting cellular products across cell membranes to specific cell locations via encapsulated vesicles. This process is required for cells to mature and function properly, allowing them to adapt to their surroundings. The retromer complex is a complex composed of nexin proteins and peptides that play a vital role in the endosomal pathway of membrane trafficking. In humans, any interference in normal membrane trafficking or retromer complex can cause profound changes such as those seen in neurodegenerative disorders such as Alzheimer's and Parkinson's. Several studies have explored the potential causative mechanisms in developing both disease processes; however, the role of retromer trafficking in their pathogenesis is becoming increasingly significant with promising therapeutic applications. This manuscript describes the processes involved in membrane transport and the roles of the retromer in the onset and progression of Alzheimer's and Parkinson's. Moreover, we will also explore how these aberrant mechanisms may serve as possible avenues for treatment development in both diseases and the prospect of its future application.

Postoperative Otoplasty Care With ChatGPT-4: A Study on Artificial Intelligence (AI)-Assisted Patient Concern and Education.

BACKGROUND: Otoplasty is a cosmetic surgery that is performed to alter the size, shape, or position of the ear by using permanent stitches. Its main purpose is to correct protruding ears, a condition known as prominauris. After the surgery, it is crucial to provide proper care to ensure successful recovery. However, obtaining timely medical advice can be difficult, especially in remote areas or places with limited resources. To address this issue, incorporating advanced artificial intelligence (AI) tools like Chat Generative Pre-trained Transformer (ChatGPT)-4 into postsurgical care could help fill the gap in patient education and support. AIM: This study aims to assess whether ChatGPT4 can be a reliable, accurate, and effective method for answering the most common patient questions and concerns post-otoplasty. The main objective was to assess the AI chatbot's capacity to deliver precise, concise, and pertinent information, especially in situations where health care professionals are limited in availability. MATERIALS AND METHODS: In this study, over 50 patients were engaged, and ChatGPT4 was employed to present the same 5 common postoperative questions post-otoplasty surgery care. The AI chatbot's responses were analyzed for accuracy, response time, clarity, and relevance. RESULTS: The chatbot could potentially provide timely assistance, answer questions, and address concerns related to postsurgical care in otoplasty. The responses exhibited a perfect accuracy rate of 100%, closely corresponding to existing medical guidelines. CONCLUSION: This study explores the potential of AI-driven solutions to enhance patient education and support, especially in areas where access to health care professionals may be limited. However, professional medical advice is crucial in postoperative care and cannot be replaced by ChatGPT-4. By leveraging AI tools like chatbots, individuals in remote or resource-limited settings can potentially receive valuable information and guidance, contributing to successful rehabilitation and overall health care outcomes. Ethical considerations around the use of AI in health care must also be carefully addressed to ensure patient privacy, data security, and appropriate clinical oversight.

Correction: Ashraf et al. Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches. Molecules 2022, 27, 4652.

The updated affiliation information can be seen in the affiliation part of this correction [...].

Prevalence of post-COVID symptoms of obsessive-compulsive disorder in Saudi Arabia.

OBJECTIVES: To determine the prevalence of Obsessive-Compulsive Disorder (OCD) symptoms in patients who have survived COVID-19. METHODS: The study used an observational cross-sectional design between July and October 2021. The target population was adult patients who had confirmed COVID-19 infection prior to joining the study, OCD symptoms were assessed using the Arabic OCD scale created by Abohendy and colleagues, which included 83 questions covering 12 different domains and was administired online. RESULTS: A total of 356 patients were included in the analysis. Approximately 9.0% and 1.7% of the patients had a history of psychiatric disease and OCD diagnosis (respectively). The total symptom score was 32.8%. The most frequently reported domains were rumination of ideas (55.5%), re-checking compulsions (37.0%), and slowness (34.0%), while the least frequently reported domains included obsessive impulses (26.3%), obsessive images (26.5%), and religious compulsions (26.8%). Unlike other domains, the purity and cleanliness compulsions scores were significantly higher than the scale reference population. A higher total symptom score was observed in psychiatric patients (p=0.004) and, to a lesser extent, in OCD patients (p=0.250). CONCLUSION: Overall, OCD symptoms, including cleanliness and fear of disease obsessions, tend to be higher in psychiatric and OCD patients, these findings are valuable for future studies.

Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches.

Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP's). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer's disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson's disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of -6.9 kcal/mol forming interactions with binding pocket's critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M-1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

Trigeminal Neuralgia Secondary to Herpes Simplex Virus Type 1 Infection Treated With Oral Acyclovir.

Trigeminal neuralgia (TN) is characterized by episodic electric, shock-like facial pain. Though often idiopathic, herpes simplex virus type 1 (HSV-1) reactivation can rarely cause symptomatic TN. We report the case of a 30-year-old woman who developed oral HSV-1 lesions followed by right-sided TN pain. MRI of the brain did not reveal neurovascular compression. TN pain completely resolved with oral acyclovir treatment alone, without anticonvulsants. This highlights the importance of considering atypical etiologies such as HSV-1 reactivation in TN evaluation. Early antiviral therapy may treat underlying inflammation and provide sustained symptom relief in HSV-associated TN.

Optimized Management of Patulous Eustachian Tube: Shim Size Modifications to Minimize Middle Ear Effusion and Enhancing Treatment Outcomes.

Objective: In this retrospective case series, we reported 4 patients presenting with a patulous Eustachian tube (PET) to highlight our institutional management approach to PET with shim insertion and a modified shim with hydroxyapatite injection. Methods: A single institution retrospective review. Results: One case was complicated by otitis media effusion; thus, the shim was downsized under local anesthesia with an immediately improved effusion. Another patient managed with a bilateral shim of the same size but is still symptomatic on one side; therefore, we upsized it, and the symptoms disappeared. The last one developed biofilm formation and thick secretion even after downsizing. Hydroxyapatite injection was performed under local anesthesia using the same shim insertion protocol. Conclusion: Shim insertion for the treatment of PET is considered a safe, reversible, and adjustable technique, giving satisfactory results while avoiding middle ear effusion. It can be performed under local or topical anesthesia in the clinic, and size adjustment can be considered to get maximum relief without middle ear effusion. This case series highlights that adjusting the size of the shim is a suggested method to eliminate symptoms and avoid complications of shim without the need for myringotomy and ventilation tube.

Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

Awareness and attitude of ENT surgeons towards various dental implants or oral surgery procedures: a cross-sectional survey in the UK.

OBJECTIVE: To assess the level of awareness and attitude of ENT surgeons towards dental implants and oral surgery procedures that involve the maxillary sinus. METHODS: A cross-sectional survey was conducted using a closed-ended questionnaire on 40 UK-based ENT surgeons. RESULTS: Within the study population, 45 per cent of ENT surgeons were not aware of sinus lift augmentation in implant dentistry. Only 25 per cent of respondents were aware of the two subtypes of sinus lift techniques. Thirty per cent of the respondents were aware of or had heard of benign positional paroxysmal vertigo following dental treatment. Fifty-two per cent of respondents came across a dental foreign body, most commonly a tooth that had been displaced into the maxillary sinus. It was also reported that 82.5 per cent of respondents had liaised with an oral surgeon for an oroantral communication problem or a dental infection. CONCLUSION: Dental awareness among ENT surgeons needs to be raised for optimum interdisciplinary communication and patient safety.

Assessing the Satisfaction and Usability of Patient Families in the ICU With the Use of the Telehealth Communication Application myVisit.

BACKGROUND: During the Covid-19 pandemic, there were many restrictions on family meetings, especially on patients' families meeting their dear ones in hospitals. We aimed to evaluate patients' family members' experience using the mobile application myVisit which was developed in KAMC, to connect patients in the ICU to their families and allow them to talk to them securely. METHODOLOGY: We conducted a cross-sectional study with mixed qualitative and quantitative methods, using the technique of thematic analysis for a qualitative approach to assess user satisfaction responses and a quantitative approach to using a validated survey and comparing our findings in both methods to determine existing usability issues and potential improvements. The survey included two sections, closed and open-ended questions, which were distributed online to 63 patient family members. RESULTS: The response rate was 85%, the overall mean score for the first part of the closed questions (advantages of using myVisit telehealth) was 4.32 and for the second part of the scale on the ease of use of the system (advantages of using myVisit telehealth) was 3.52. Three useful topics were generated concerning the open questions, covering 220 codes from the participants' responses. In general, there is a great interest in technology and its ability to improve people's lives, especially in the medical field and cases where things do not go normally, as well as in exceptional circumstances. CONCLUSIONS: The overall evaluation of the myVisit application was positive in terms of the idea and content, as usability of the system is very good at 71%, plus the users' opinions of the myVisit application are that it saves time at 96%, and save money and effort for the patient's family 74%.

Issues Faced by Pharmacy Technicians While Maintaining Automated Dispensing Cabinets and How to Overcome Them in the National Guard Health Affairs in Riyadh: A Qualitative Study.

Objectives Technology is rapidly evolving to improve patient safety and increase healthcare providers' efficiency. Automated dispensing cabinets (ADCs) are an example of a technology that has been used to facilitate patient safety. As with any other technology, there are benefits and drawbacks associated with the use of ADCs. In this study, we aim to identify the issues related to maintaining ADCs in National Guard Health Affairs (NGHA) hospitals from the pharmacy technicians' perspective and find some solutions to overcome the problems that complicate the usability of the ADCs. Methods A cross-sectional qualitative study was conducted using an open-ended questionnaire. It was completed by 30 pharmacy technicians who deal with ADCs in NGHA hospitals. Results Three themes were extracted from the questionnaire: "issues faced by pharmacy technicians before filling the ADCs," "issues faced by pharmacy technicians during filling the ADCs," and "issues faced by pharmacy technicians after filling the ADCs." Discussion and conclusion This study portrayed a better understanding of the issues faced by pharmacy technicians who deal with ADCs based on their experience. It will help stakeholders to make appropriate decisions and improve the workflow for a successful ADC implementation.

Outcome and Safety of Insulin in the Management of Smell Loss: A Systematic Review.

Background: Olfactory dysfunction can negatively impact the quality of life and increase the risk of danger from warning odors. Various factors can cause olfactory dysfunction, including COVID-19 infection, which has increased anosmia cases. No medications are approved; however, recent studies have suggested that intranasal insulin could effectively treat olfactory dysfunction. Aim: To comprehensively evaluate the effectiveness and safety of intranasal insulin in treating olfactory dysfunction. Materials and Methods: PubMed, Google Scholar, and CENTRAL databases were searched using specific keywords, and the outputs were screened using the Rayyan AI system. Original research articles published without time frame limitations that reported the relevant outcomes were included. The reviewers performed the screening and data extraction, and any disagreements were resolved by a third senior author. Results: This systematic review identified 66 references from 3 databases, with 45 articles meeting the criteria for review after duplicates were removed. Six articles met the inclusion criteria and were selected, including 177 subjects. The selected studies consisted of various study designs, including pilot studies, placebo-controlled trials, crossover studies, and randomized clinical trials. The findings showed that intranasal insulin therapy had beneficial effects on olfactory function. Specifically, improvements were observed in olfactory detection and discrimination in patients with post-COVID-19 anosmia, olfactory threshold performance in healthy participants, and odor identification in hyposmic patients. However, there were variations in the observed effects based on different doses of insulin administered and gender differences. It also shows that using insulin provides good outcomes. Using it intranasally was safe and did not cause any complications. Conclusion: Intranasal insulin has shown promising results as a potentially safe treatment for olfactory dysfunction. Studies suggest that it can improve olfactory thresholds. Further studies are needed to investigate optimal doses and potential gender differences in response.

Fluoroscopy-Guided Metallic Foreign Body Removal: A Report of Three Cases and Literature Review.

Ingested foreign objects that become trapped in the upper aerodigestive tract is a common issue that arises in Otolaryngology-Head and Neck Surgery practice. In these circumstances, it is advised to explore the neck using an external method to remove the item. However, locating the foreign body might be challenging. Not all metallic foreign body (MFB) patients require surgery, especially those without symptoms or complications. The standard X-ray and CT images are routinely examined for preoperative assessment and localization. Removal can be accomplished via flexible pharyngo-laryngoscopy or upper gastrointestinal endoscopy. Fluoroscopy is a widely accessible, minimally invasive, but underutilized tool during procedures. It offers an accurate intraoperative assessment of the foreign body in real-time. To allow the planning of a secure extraction pathway, the target should be radiopaque. In this report, we present three unique cases in which we used fluoroscopic imaging for guidance to remove a foreign body in the head and neck region in Prince Sultan Military Medical City in Riyadh, Saudi Arabia. In the first case, a young male presented with a history of foreign body sensation and odynophagia in the throat after eating a (shawarma) sandwich. In the second case, a six-year-old boy presented to the emergency department (ED) with epistaxis after being exposed to an air gun shot to his face. In the third case, a 40- year-old male presented after exposure to an air gun shot to the neck. After identification of the foreign body, all three patients were referred to Otolaryngology-Head and Neck. After radiological images have been done to confirm the presence of foreign objects, all three had a minimally invasive procedure to remove the metallic foreign bodies under fluoroscopic guidance without needing extensive surgery. All the procedures went well with no immediate complications with discharge on the same day. Fluoroscopy-guided removal of foreign bodies related to metabolic forging is a promising technique with several advantages, including real-time visualization, reduced invasiveness, and shorter recovery times. However, it is essential to weigh the benefits against the risks associated with radiation exposure and inherent limitations in detecting non-metallic objects. Further research and clinical studies are needed to optimize this technique and establish evidence-based guidelines for its application in the field of metabolic forging bodies.

Mitochondrial Medicine: A Promising Therapeutic Option Against Various Neurodegenerative Disorders.

Abnormal mitochondrial morphology and metabolic dysfunction have been observed in many neurodegenerative disorders (NDDs). Mitochondrial dysfunction can be caused by aberrant mitochondrial DNA, mutant nuclear proteins that interact with mitochondria directly or indirectly, or for unknown reasons. Since mitochondria play a significant role in neurodegeneration, mitochondriatargeted therapies represent a prosperous direction for the development of novel drug compounds that can be used to treat NDDs. This review gives a brief description of how mitochondrial abnormalities lead to various NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We further explore the promising therapeutic effectiveness of mitochondria- directed antioxidants, MitoQ, MitoVitE, MitoPBN, and dimebon. We have also discussed the possibility of mitochondrial gene therapy as a therapeutic option for these NDDs.

Evaluation of Breastfeeding Applications Through the Eyes of Saudi Mothers.

INTRODUCTION: Breastfeeding is crucial for an infant's health and plays a significant role in mothers' well-being. The recommendation from WHO is to breastfeed your baby for the first six months exclusively, then complementary food is introduced with the continuity of breastfeeding until 24 months or more. Breastfeeding can be challenging, especially for a first-time mom; some mothers also lack knowledge about breastfeeding benefits. Thus, mobile health (mHealth) intervention can raise awareness, provide educational information and emotional support, and offer consultation. Saudi mothers seek an application designed based on their needs. OBJECTIVES: The objective of this study was to analyze the most common breastfeeding application, then extract standard and valuable features. The most useful features were added to the survey and distributed among Saudi mothers. Next, participants' responses to these features were evaluated for recommendation when building a breastfeeding application for Saudi mothers. METHOD: This is a quantitative cross-sectional study designed to analyze and explore what Saudi women need in a breastfeeding application to help them make better decisions and provide support. The data was collected through a questionnaire instrument designed after collecting the most valuable features in mobile breastfeeding applications. RESULTS: The number of Saudi mothers enrolled in this study was 492. Most mothers (90%) were currently breastfeeding or had previous experience with breastfeeding. The participant responses divided results into three categories: essential, recommended, and nice-to-be-added features. One of the highest percentages of important features was adding a section for baby food recipes and how to introduce food. CONCLUSION: Saudi mothers need a trustable source of information, consultation, support, and tools to guide them through breastfeeding. With the help of the mHealth application, the breastfeeding experience can be improved.

Impact of COVID-19 on otolaryngology head & neck speciality and residency program in Saudi Arabia.

The SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19), has rapidly swept worldwide since its identification in December 2019. As the spread of the disease accelerated both in Wuhan and elsewhere globally, the WHO declared it a pandemic. There is sound evidence to argue that otolaryngologists run high risks of occupational SARS-COV2 among health care workers due to high viral load in upper respiratory examinations. This review article was conducted to determine the effect of the COVID 19 pandemic on the otolaryngology department and residency program in Saudi Arabia. Since the pandemic outbreak, the government of Saudi Arabia has taken severe measures and issued several decisions to limit the spread of the virus. These decisions included operations, procedures, outpatient clinics by prioritizing emergency and time-sensitive cases while rescheduling all electives and routines once. As a result, the residency program was also affected by the substantial reduction of daily surgical activity and preventing endoscopic tests in the clinics, which led to a notable decrease in residents' involvement and risk of procedural skills deterioration which became a concern to many doctors of residency programs. It is difficult to deny that the epidemic will negatively impact. However, adhering to well-prepared guidelines and giving residents an excellent opportunity to overcome the defects will deliver training and patients' care while also protecting safety and health.

Reciprocal Translocation T(Y;16) in a Male Patient With Non-obstructive Azoospermia: A Case Report and Literature Review.

Translocation of sex/autosome chromosomes is uncommon, but they have a stronger impact on fertility than autosome/autosome translocation. Y/autosome translocation is associated with azoospermia in 80% of cases. To our knowledge, there have been only eight cases reported of a balanced reciprocal (Y;16) translocation associated with male infertility.Here we report an infertile man with azoospermia who has a reciprocal translocation t(Y;16) (q12; p13.2).  A 38-year-old Saudi medically free male presented with primary infertility and azoospermia for six years. He has a positive family history of male infertility. Physical examination was unremarkable. Investigations showed normal hormonal panel and azoospermia. He has a male karyotype with a reciprocal chromosome Y,16 translocation. Histopathology report of bilateral testicular sperm extraction (TESE) revealed most tubules show early maturation arrest and few show either Sertoli-cell only syndrome or are completely hyalinized and atrophic.  This case illustrates a rare cause of non-obstructive azoospermia in a male with chromosome Y,16 translocation as a result of a meiotic arrest. Medical practitioners should be aware of the genetic abnormalities of male patients who present with primary infertility. Karyotyping has the capability to diagnose genetic abnormalities in this patient.

Pseudotumor after total disc replacement in the lumbar spine: A case report and review of the literature.

Background: Total disc replacement as a treatment for degenerative disc disease is gaining increased popularity. There is limited data in the literature about formation of a pseudotumor as a complication following this procedure. We report a very rare case of a pseudotumor after a lumbar total disc replacement with a review of the literature. Methods: A case study of a 49-year-old lady, who underwent L4-L5 total disc replacement and presented one year later with progressive back pain radiating to both lower extremities. Imaging revealed a soft tissue mass around the prosthesis. A review of the literature for similar cases has been done and reviewed. Results: Imaging revealed a soft tissue mass around the prosthesis and left hydronephrosis. CT venogram for leg swelling showed total occlusion of the left common iliac vein. CT myelogram showed compression of the cauda from the pseudotumor. The prosthesis was removed and replaced by an allograft fusion cage and plate. Intraoperatively both extremities became pulseless and bilateral common iliac arteries thrombectomy was carried out. This occurred again after closure immediately and bilaterally femoral artery exploration and thrombectomy was carried out. Histopathology showed a soft tissue with fibrinous necrosis and lymphohistiocytic inflammation. Conclusion: Soft tissue reaction and pseudotumor formation can be induced by Metal-on-Metal total disc replacement prostheses. Neurologic, vascular, and visceral complications may occur. In this case implant removal can stopped progression of the soft tissue reaction. Most patients in the literature benefit from implant removal followed by spinal fusion.

Unravelling Binding of Human Serum Albumin with Galantamine: Spectroscopic, Calorimetric, and Computational Approaches.

Human serum albumin (HSA), an abundant plasma protein, binds to various ligands, acting as a transporter for numerous endogenous and exogenous substances. Galantamine (GAL), an alkaloid, treats cognitive decline in mild to moderate Alzheimer's disease and other memory impairments. A vital step in pharmacological profiling involves the interaction of plasma protein with the drugs, and this serves as an essential platform for pharmaceutical industry advancements. This study is carried out to understand the binding mechanism of GAL with HSA using computational and experimental approaches. Molecular docking revealed that GAL preferentially occupies Sudlow's site I, i.e., binds to subdomain IIIA. The results unveiled that GAL binding does not induce any conformational change in HSA and hence does not compromise the functionality of HSA. Molecular dynamics simulation (250 ns) deciphered the stability of the HSA-GAL complex. We performed the fluorescence binding and isothermal titration calorimetry (ITC) to analyze the actual binding of GAL with HSA. The results suggested that GAL binds to HSA with a significant binding affinity. ITC measurements also delineated thermodynamic parameters associated with the binding of GAL to HSA. Altogether, the present study deciphers the binding mechanism of GAL with HSA.