A Mutual Nexus Between Epilepsy and α-Synuclein: A Puzzle Pathway.

Alpha-synuclein (α-Syn) is a specific neuronal protein that regulates neurotransmitter release and trafficking of synaptic vesicles. Exosome-associated α-Syn which is specific to the central nervous system (CNS) is involved in the pathogenesis of epilepsy. Therefore, this review aimed to elucidate the possible link between α-Syn and epilepsy, and how it affects the pathophysiology of epilepsy. A neurodegenerative protein such as α-Syn is implicated in the pathogenesis of epilepsy. Evidence from preclinical and clinical studies revealed that upregulation of α-Syn induces progressive neuronal dysfunctions through induction of oxidative stress, neuroinflammation, and inhibition of autophagy in a vicious cycle with subsequent development of severe epilepsy. In addition, accumulation of α-Syn in epilepsy could be secondary to the different cellular alterations including oxidative stress, neuroinflammation, reduction of brain-derived neurotrophic factor (BDNF) and progranulin (PGN), and failure of the autophagy pathway. However, the mechanism of α-Syn-induced-epileptogenesis is not well elucidated. Therefore, α-Syn could be a secondary consequence of epilepsy. Preclinical and clinical studies are warranted to confirm this causal relationship.

Prevalence and Risk Factors of Voice Disorders Among Teachers in Saudi Arabia.

Introduction Voice is a crucial tool for communication, and voice problems are more likely to occur in professionals who frequently use their voice for work. Teachers, whose profession requires sustained vocal use, are particularly susceptible to occupation-related voice disorders. This study aimed to quantify the prevalence of voice disorders among teachers in Saudi Arabia, with the general population serving as a control group, and to identify associated risk factors. Methods A cross-sectional study was conducted utilizing an online self-administered questionnaire, which was completed by both teachers and the general population in Saudi Arabia. The latter group acted as a control. The questionnaire included sections on sociodemographic data, teaching patterns, symptoms of voice issues, and the Voice Handicap Index-10 (VHI-10) for assessing voice disorders among participants. Results The study included 640 participants, with 438 (68.4%) being teachers, the majority of whom were females (N = 406; 63.4%). The most common voice-related symptoms reported by teachers were hoarseness (N = 210; 37.9%) and dry throat (N = 147; 26.9%). Voice disorders, as determined by the VHI, affected 355 (55.5%) of the teachers. A high VHI score was associated with a diagnosis of voice disorders and GERD. There was no significant difference in the VHI scores between teachers and the general population (p > 0.05). Conclusion Teachers in Saudi Arabia exhibited a higher prevalence of voice disorders compared to the general population. Risk factors, such as smoking, longer teaching experience, and more teaching hours per week, were more common among teachers with voice disorders. Further investigative studies are warranted to elucidate the causal relationships between these variables and voice disorders.

Potential acetylcholinesterase inhibitors to treat Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is identified by neuropathological symptoms, and there is now no effective treatment for the condition. A lack of the brain neurotransmitter acetylcholine has been related to the etiology of Alzheimer's disease. Acetylcholinesterase is an enzyme that breaks down acetylcholine to an inactive form and causes the death of cholinergic neurons. Conventional treatments were used but had less effectiveness. Therefore, there is a crucial need to identify alternative compounds with potential anti-cholinesterase agents and minimal undesirable effects. MATERIALS AND METHODS: Fluoroquinolones and benzimidazole-benzothiazole derivatives offer antimicrobial, anti-inflammatory, anti-oxidant, anti-diabetic, and anti-Alzheimer activities. To enhance the chemical portfolio of cholinesterase inhibitors, a variety of fluoroquinolones and benzimidazole-benzothiazole compounds were evaluated against acetylcholinesterase (AChE) butyrylcholinesterase (BChE) enzymes. For this purpose, molecular docking and adsorption, distribution, metabolism, excretion, and toxicology ADMET models were used for in-silico studies for both AChE and BChE enzymes to investigate possible binding mechanisms and drug-likeness of the compounds. The inhibitory effect of docked heterocyclic compounds was also verified in vitro against AChE and BChE enzymes. Fluoroquinolones (Z, Z3, Z4, Z6, Z8, Z12, Z15, and Z9) and benzimidazole-benzothiazole compounds (TBIS-16, TBAF-1 to 9) passed through the AChE inhibition assay and their IC50 values were calculated. RESULTS: The compound 1-ethyl-6-fluoro-7-(4-(2-(4-nitrophenylamino)-2-oxoethyl)piperazin-1-yl) -4-oxo-1,4 di-hydroquinoline-3-carboxylic acid and 2-((1H-benzo[d]imidazol-2-yl)methyl)-N'-(3-bromobenzyl)-4-hydroxy-2H-thiochromene-3-carbohydrazide 1,1-dioxide (Z-9 and TBAF-6) showed the lowest IC50 values against AChE/BChE (0.37±0.02/2.93±0.03 µM and 0.638±0.001/1.31±0.01 µM, respectively) than the standard drug, donepezil (3.9±0.01/4.9±0.05 µM). During the in-vivo investigation, behavioral trials were performed to analyze the neuroprotective impact of Z-9 and TBAF-6 compounds on AD mouse models. The groups treated with Z-9 and TBAF-6 compounds had better cognitive behavior than the standard drug. CONCLUSIONS: This study found that Z-9 (Fluoroquinolones) and TBAF-6 (benzimidazole-benzothiazole) compounds improve behavioral and biochemical parameters, thus treating neurodegenerative disorders effectively.

Evaluation of tear meniscus height and lipid layer patterns in the tear film in domestic cats: An observational study.

Background: Healthy vision in humans and animals requires a stable tear film. The environmental factor could affect the status of the tear film. Therefore, assessing the tear film in animals is essential to avoid visual system disturbance. Aim: The current research used a noninvasive device to evaluate the tear meniscus height (TMH) and lipid layer pattern (LLP) in domestic cats. In addition, the scores were compared with those of humans with healthy eyes. Methods: Fifty-four domestic cats (28 males and 26 females; mean ± SD = 13.9 ± 18.2 months) were randomly selected and included in the study. The cats were healthy, without any ocular disorders or diseases. Fifty-four healthy eye subjects (27 males and 27 females; mean ± SD = 25.6 ± 5.1 years) were randomly recruited and took part in the study for comparison. EASYTEAR View+ was used, for the first time, to assess the tear film parameters on the right eye of each subject. The examiner allowed a 5-minute gap between the tests. Each test was performed by the same examiner three times, followed by calculating the mean scores. Results: Significant differences (Mann-Whitney U test) were found in the median scores of LLP (p = 0.009) between cats and subjects with healthy eyes. The median TMH score was higher in cats (0.18 mm) than in humans (0.14). However, no significant difference (Mann-Whitney U Test, p = 0.210) exists in the TMH scores between cats and humans. The LLP analysis indicated that a dense white-blue lipid layer (grade 4 or D; lipid layer thickness, LLT, = approximately 80 nm) was predominant in both cats (N = 24, 44.4%) and humans (N = 29, 53.7%). In comparison, variable colors lipid layer (grade 5 or E; LLT = 90-140 nm) was a minority in cats (N = 5, 9.3%) and common in humans (N = 16, 29.6%). The statistical analysis indicated medium correlations between cats' TMH and LLP scores (r = 0.431, p < 0.01) and between age and TMH scores in humans (r = 0.440, p < 0.01). In addition, it indicated a weak correlation (r = 0.291, p < 0.05) between the LLP scores in cats and humans. Conclusion: Assessing animals' tear film is essential to avoid any ocular disorders. EASYTEAR View+ is efficiently used to evaluate domestic cats' TMH and LLP. Cats have thicker lipid layers and longer TMH comparable to those reported for humans with healthy eyes.

Assessment of lipid layer patterns in domestic dogs and rabbits: an observational study.

Background: Maintaining a stable tear film is crucial for having healthy human and animal vision. Animals are expected to have thicker lipid layers than humans due to living in high-temperature and humid environments. Aim: The study aimed to evaluate the lipid layer patterns (LLPs) in Arabian dogs and rabbits using a non-invasive, practical, and easy-to-use device and compare them to humans with healthy eyes. Methods: The study included 75 domestic Arabian dogs (42 males and 33 females; mean ± SD = 6.1 ± 12.7 months) and 75 rabbits (37 males and 38 females; mean ± SD = 3.1 ± 3.4 months). In addition, 75 individuals with healthy eyes (39 males and 36 females; mean ± SD = 25.7 ± 5.0 years) were included for comparison. EASYTEAR View+ assessed the LLP in each animal's and individual's right eye. Results: The median LLP grades significantly differed between dogs and humans (Mann-Whitney U test, p < 0.001). Similarly, the LLP grades differed significantly between rabbits and humans (Mann-Whitney U test, p < 0.001). No significant difference (Mann-Whitney U test) in the LLP grades between dogs and rabbits was found. The analysis indicated that most dogs had either an A (34.7%) or a B grade (37.3%). Similarly, rabbits had predominantly A or 1 (46.7%) and B (30.7%) grades. On the other hand, humans had predominantly D (53.3%) and E (30.7%) grades. Conclusion: The EASYTEAR View+ has been employed to assess LLP in dogs and rabbits, and the measurements were compared to those of humans with normal ocular health. Dogs and rabbits have thinner lipid layers than healthy humans.

HPV Vaccine Uptake, Willingness to Receive, and Causes of Vaccine Hesitancy: A National Study Conducted in Saudi Arabia Among Female Healthcare Professionals.

Background: Epidemiological evidence has shown that human papillomavirus (HPV) is the most frequent cause of sexually transmitted infection, and vaccination is an essential measure to prevent associated diseases and complications. This study aimed to assess the HPV vaccine uptake and its associated factors as well as HPV vaccine hesitancy by female healthcare workers (HCWs) in Saudi Arabia. Methods: This online, questionnaire-based, cross-sectional study involved female HCWs in Saudi Arabia between July and October 2022. The study tool included questions about sociodemographic, occupational, and reproductive characteristics, uptake of HPV vaccination, and reasons of hesitancy. Chi-squared and t-tests were used for bivariate analyses, and multivariable logistic regression was used to adjust for confounders. Results: The total number of participants was 1857. Around 20% of HCWs received at least one dose of the HPV vaccine, and around 45% were willing to take it this year. Lower odds of vaccine uptake were reported among older participants and those with a higher level of education. However, nurses, HCWs with a previous HPV infection, those with a family history of cervical cancer, or those with a previous cervical cancer screening test had higher odds of receiving the vaccine. On the other hand, older participants and diploma degree holders were less willing to take the HPV vaccine. Higher odds of willingness were reported in married HCWs, those with a previous HPV infection, those who received a previous HPV vaccine dose, or those who were screened for cervical cancer. Lack of knowledge and some misconceptions were the most reported reasons for hesitancy. Conclusion: Certain factors that affect HCWs personal decisions to take the vaccine were identified. By targeting these issues, epidemiologists, public health officials and women's health care providers can work to increase HPV vaccine uptake and reduce the burden of HPV-related diseases in this population.

Prediction of cardiovascular risk factors and metabolic syndrome in adults from Saudi Arabia using the logarithm of triglyceride/HDL-cholesterol ratio.

Objective: Cardiovascular diseases (CVD) are the leading cause of death globally. Metabolic syndrome (MtS) is a risk factor that increases the likelihood of CVD. The atherogenic index (AIP), calculated as the logarithm of the ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL) cholesterol in plasma, is a valuable marker for highly atherogenic small dense low-density lipoprotein cholesterol particles. This study aimed to explore MtS prevalence and investigate the potential of using the AIP as a predictor for CVD risk factors in adults from the Qassim region of Saudi Arabia. Methods: The cross-sectional study enrolled 589 participants from public hospitals in nine major cities who completed a detailed questionnaire on health, diet, and lifestyle. Anthropometric measurements and some clinical parameters were measured. Results: The findings indicated a significant prevalence of MtS (37.5%) among participants from the Qassim Area, which was higher in males (39.9%) than females (34.9%). Nevertheless, a significant prevalence was shown for CVD risk factors among participants, with hyperglycemia (78.1%), hypertriglyceridemia (39.0%), hypo-HDL-cholesterolemia (38.9%), and hypertension (21.6%) being common. The AIP's performance in identifying CVD risk factors showed a receiver operating characteristic value of 0.909 (P < 0.001). The optimal cutoff value for the AIP was determined to be 0.468, demonstrating high sensitivity (84.8%) and specificity (78.6%). Conclusion: Incorporating AIP into clinical practice could enhance CVD risk prediction compared to using lipid profiles alone. These findings suggest that there is a high prevalence of MtS among adults in the Qassim region of Saudi Arabia. Further longitudinal studies are needed to recommend AIP as a robust tool for predicting CVD in clinical settings.

Experimental treatment efficacy of dmrFABP5 on prostate cancer singly or in combination with drugs in use.

Enzalutamide is a drug used to treat prostate cancer (PC) and docetaxel is a drug for chemotherapeutic treatment of diverse cancer types, including PC. The effectiveness of these drugs in treating castration-resistant prostate cancer (CRPC) is poor and therefore CRPC is still largely incurable. However, the bio-inhibitor of fatty acid-binding protein 5 (FABP5), dmrFABP5, which is a mutant form of FABP5 incapable of binding to fatty acids, has been shown recently to be able to suppress the tumorigenicity and metastasis of cultured CRPC cells. The present study investigated the possible synergistic effect of dmrFABP5 combined with either enzalutamide or docetaxel on suppressing the tumorigenic properties of PC cells, including cell viability, migration, invasion and colony proliferation in soft agar. A highly significant synergistic inhibitory effect on these properties was observed when dmrFABP5 was used in combination with enzalutamide on androgen-responsive PC 22RV1 cells. Moreover, a highly significant synergistic inhibitory effect was also observed when dmrFABP5 was combined with docetaxel, and added to 22RV1 cells and to the highly malignant, androgen-receptor (AR)-negative Du145 cells. DmrFABP5 alone failed to produce any suppressive effect when added to the FABP5-negative cell line LNCaP, although enzalutamide could significantly suppress LNCaP cells when used as a single agent. These synergistic inhibitory effects of dmrFABP5 were produced by interrupting the FABP5-related signal transduction pathway in PC cells. Thus, dmrFABP5 appears to be not only a potential single therapeutic agent, but it may also be used in combination with existing drugs to suppress both AR-positive and AR-negative PC.

Bidirectional glenn surgery without palliative pulmonary artery banding in univentricular heart with unrestricted pulmonary flow. Retrospective multicenter experience.

BACKGROUND: Although pulmonary artery banding (PAB) has been generally acknowledged as an initial palliative treatment for patients having single ventricle (SV) physiology and unrestrictive pulmonary blood flow (UPBF), it may result in unfavorable outcomes. Performing bidirectional Glenn (BDG) surgery without initial PAB in some selected cases may avoid the complications associated with PAB and reduce the number of operative procedures for these patients. This research aimed to assess the outcome of BDG surgery performed directly without doing initial PAB in patients with SV-UPBF. METHODS: This Multicenter retrospective cohort includes all patients with SV-UPBF who had BDG surgery. Patients were separated into two groups. Patients in Group 1 included patients who survived till they received BDG (20 Patients) after initial PAB (28 patients), whereas patients in Group 2 got direct BDG surgery without first performing PAB (16 patients). Cardiac catheterization was done for all patients before BDG surgery. Patients with indexed pulmonary vascular resistance (PVRi) ≥ 5 WU.m2 at baseline or > 3 WU.m2 after vasoreactivity testing were excluded. RESULTS: Compared with patients who had direct BDG surgery, PAB patients had a higher cumulative mortality rate (32% vs. 0%, P = 0.016), with eight deaths after PAB and one mortality after BDG. There were no statistically significant differences between the patient groups who underwent BDG surgery regarding pulmonary vascular resistance, pulmonary artery pressure, postoperative usage of sildenafil or nitric oxide, intensive care unit stay, or hospital stay after BDG surgery. However, the cumulative durations in the intensive care unit (ICU) and hospital were more prolonged in patients with BDG after PAB (P = 0.003, P = 0.001respectively). CONCLUSION: Direct BDG surgery without the first PAB is related to improved survival and shorter hospital stays in some selected SV-UPBF patients.

Frequency and characteristics of chronic fatigue syndrome in multiple sclerosis patients at a university hospital in Eastern Saudi Arabia.

BACKGROUND: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease that affects various parts of the central nervous system. Fatigue, a common symptom, transient, prolonged, or chronic experienced by individuals with MS, can significantly impact daily functioning. It can be associated with underlying pathological processes or can have an idiopathic cause, such as chronic fatigue syndrome (CFS). The study aimed to assess the presence and etiology of fatigue in MS patients and its relationship with CFS. MATERIALS AND METHODS: This cross-sectional study was conducted in the Eastern Province of Saudi Arabia. Data were collected using a questionnaire from a sample of 225 MS patients receiving care at our university hospital. The questionnaire included the Centers for Disease Control and Prevention (CDC) criteria for diagnosing CFS and the Expanded Disability Status Scale to evaluate fatigue in MS patients. RESULTS: Of the total of 225 MS patients who participated in this study, 87.1% were diagnosed with relapsing-remitting MS, 6.7% with primary progressive MS, 3.6% with clinically isolated syndrome, and 2.7% with secondary progressive MS. About 53% had experienced fatigue that persisted for over 6 months. Analysis of CFS diagnosis revealed that 7.3% of patients met both CDC criteria and self-reported answers while 17.5% reported having CFS despite not meeting the CDC criteria. These findings highlight a significant lack of agreement between patient-reported diagnoses and established criteria, indicating poor agreement (P = 0.028). CONCLUSION: The study found an association between CFS and MS, and a significant impact on daily functioning. The study revealed lack of agreement between patient-reported diagnoses and established criteria for CFS. This emphasizes the need for a standardized approach to diagnosis and evaluation of fatigue in MS patients.

Awareness of Risk Factors for Coronary Artery Disease in the Population of Al-Majma'ah Region, Saudi Arabia.

BACKGROUND: Coronary artery disease (CAD) is a significant global health concern and a leading cause of morbidity and mortality. As a complex cardiovascular condition, CAD arises from the accumulation of atherosclerotic plaques within the coronary arteries, leading to restricted blood flow to the heart muscle. While CAD has been extensively studied, its prevalence remains a challenge, particularly in diverse populations with distinct cultural and lifestyle practices. OBJECTIVES:  To assess the awareness of risk factors for CAD in the population of Al-Majma'ah Region, Saudi Arabia. METHODS:  The purpose of this cross-sectional descriptive study was to determine participants' awareness of CAD risk factors among the population of Al-Majma'ah Region, Saudi Arabia. It was conducted by the use of a self-administered questionnaire that had been validated in prior research publications. Sociodemographic information as well as the prevalence of cardiovascular disease risk factors were covered in the survey. The data analysis was done using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States). RESULTS: A total of 919 individuals were enrolled in the current study after meeting the inclusion criteria. The results showed that most of the respondents 626 (68.1%) had a good level of awareness, 261 (28.4%) had a fair level of awareness, while only 32 (3.5%) of the respondents had a poor level of CAD risk factors awareness. CONCLUSION: The majority of participants had a good level of knowledge regarding CAD risk factors. The correlation between monthly income and awareness of coronary artery risk factors was statistically significant.

Synergistic Effect of Nilavembu Choornam-Gold Nanoparticles on Antibiotic-Resistant Bacterial Susceptibility and Contact Lens Contamination-Associated Infectious Pathogenicity.

Antibiotic-resistant bacterial colonies mitigate rapid biofilm formation and have complex cell wall fabrications, making it challenging to penetrate drugs across their biofilm barriers. The objective of this study was to investigate the antibacterial susceptibility of antibiotic-resistant bacteria and contact lens barrenness. Nilavembu Choornam-Gold Nanoparticles (NC-GNPs) were synthesized using NC polyherbal extract and characterized by UV-visible spectrophotometer, SEM-EDX, XRD, Zeta sizer, FTIR, and TEM analysis. Contact lenses with overnight cultures of antibiotic-resistant bacteria K. pneumoniae and S. aureus showed significant differences in growth, biofilm formation, and infection pathogenicity. The NC-GNPs were observed in terms of size (average size is 57.6 nm) and surface chemistry. A zone of inhibition was calculated for K. pneumoniae 18.8 ± 1.06, S. aureus 23.6 ± 1.15, P. aeruginosa 24.16 ± 0.87, and E. faecalis 24.5 ± 1.54 mm at 24 h of NC-GNPs alone treatment. In electron microscopy studies, NC-GNP-treated groups showed nuclear shrinkage, nuclear disintegration, degeneration of cell walls, and inhibited chromosomal division. In contrast, normal bacterial colonies had a higher number of cell divisions and routinely migrated toward cell multiplications. NC-GNPs exhibited antibacterial efficacy against antibiotic-resistant bacteria when compared to NC extract alone. We suggest that NC-GNPs are highly valuable to the population of hospitalized patients and other people to reduce the primary complications of contact lens contamination-oriented microbial infection and the therapeutic efficiency of antibiotic-resistant bacterial pathogenicity.

Endovascular thrombectomy for acute ischemic stroke in Saudi Arabia: A single-center experience.

PURPOSE: This study aimed to investigate the outcomes of endovascular thrombectomy-treated patients in King Fahad Medical City, Riyadh, Saudi Arabia. METHODS: A retrospective cohort study of acute ischemic stroke patients treated with endovascular thrombectomy. Patients were included in the study between January 2015 and December 2022. Good outcomes were defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Multivariate logistic regression analysis was performed to identify the independent factors associated with good outcomes. RESULTS: During the study period, 369 patients with acute ischemic stroke (mean ± SD age, 61/- 15.1 yrs; 55.4 % male) underwent mechanical thrombectomy. Median National Institute of Health Stroke Scale (NIHSS) 15. Intravenous thrombolysis was administered to 34.5 % of the patients. Successful recanalization in the anterior circulation was achieved in 84.8 % of patients. Data from mRS performed after 90 days in the anterior circulation were available for 71.2 % of the patients. Of these, 41 % showed a good outcome, and the mortality rate was 22.4 %. The significant factors associated with good outcomes were age, NIHSS score, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and short arterial puncture to recanalization. CONCLUSION: The number of patients who underwent endovascular thrombectomy has increased over time. The treatment outcomes and mortality were comparable with those of previous endovascular thrombectomy registries despite the high prevalence of DM, lower ASPECT score, and prolonged onset-to-recanalization time.

Laparo-Endoscopic Single-Site Left Donor Nephrectomy In Patients With Uncommon Renal Vascular Anatomy: Does the Technique Make a Difference?

BACKGROUND: To compare donor and recipient outcomes in patients with renal artery and ante-aortic renal vein vs unusual renal vascular anatomy undergoing laparoendoscopic single-site donor nephrectomy (LESSDN). METHODS: A retrospective chart review of the comparative study of donor and recipient outcomes of LESSDN in donors with venous abnormality (n = 28, group A), arterial abnormality (n = 74, group B), and standard donors (n = 248, group C). RESULTS: From September 2016 to August 2022, 350 left LESSDN were performed. The most common anomalies in group A were the retro-aortic and 2 renal veins in 12 patients each. In group B, 72 and 2 patients had 2 and 3 renal arteries, respectively. Operative and warm ischemia times were significantly longer in donors with vascular anomalies. Moreover, patient creatinine on discharge was significantly higher in arterial anomalies; it was 1.61 ± 0.22 compared with 1.26 ± 0.43 and 1.25 ± 0.32 mg/dL for patients with no anomalies and venous anomalies, respectively (P < .001). However, serum creatinine levels recovered after 1 month and were comparable between the study groups. Recipients, operative time, and vascular anastomosis time were significantly longer in recipients with vascular anomaly. Slow graft function was higher in group B (6.9%) than in the other groups. One-year graft survival rates were 96.4%, 94.6%, and 97.1% (P = .496). CONCLUSION: With increased experience, LESSDN in multiple renal arteries and uncommon venous anatomy cases is feasible and safe. Moreover, it does not influence donor or recipient outcomes.

Role of Brain Liver X Receptor in Parkinson's Disease: Hidden Treasure and Emerging Opportunities.

Parkinson's disease (PD) is a neurodegenerative disease due to the degeneration of dopaminergic neurons (DNs) in the substantia nigra (SN). The liver X receptor (LXR) is involved in different neurodegenerative diseases. Therefore, the objective of the present review was to clarify the possible role of LXR in PD neuropathology. LXRs are the most common nuclear receptors of transcription factors that regulate cholesterol metabolism and have pleiotropic effects, including anti-inflammatory effects and reducing intracellular cholesterol accumulation. LXRs are highly expressed in the adult brain and act as endogenous sensors for intracellular cholesterol. LXRs have neuroprotective effects against the development of neuroinflammation in different neurodegenerative diseases by inhibiting the expression of pro-inflammatory cytokines. LXRs play an essential role in mitigating PD neuropathology by reducing the expression of inflammatory signaling pathways, neuroinflammation, oxidative stress, mitochondrial dysfunction, and enhancement of BDNF signaling.In conclusion, LXRs, through regulating brain cholesterol homeostasis, may be effectual in PD. Also, inhibition of node-like receptor pyrin 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-κB) by LXRs could effectively prevent neuroinflammation in PD. Taken together, LXRs play a crucial role in PD neuropathology by inhibiting neuroinflammation and associated degeneration of DNs.

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aß). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aß. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aß and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aß. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aß clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon-like peptide 1 (GLP-1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP-1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

The probable role of tissue plasminogen activator/neuroserpin axis in Alzheimer's disease: a new perspective.

Alzheimer's disease (AD) is the most common type of dementia associated with amyloid beta (Aß) deposition. Dysfunction of the neuronal clearance pathway promotes the accumulation of Aß. The plasminogen-activating system (PAS) is controlled by various enzymes like tissue plasminogen activators (tPA). Neuronal tPA enhances the conversion of plasminogen to plasmin, which cleaves Aß; this function is controlled by many inhibitors of PAS, including a plasminogen-activating inhibitor (PAI-1) and neuroserpin. Therefore, the objective of the present narrative review was to explore the potential role of tPA/neuroserpin in the pathogenesis of AD. PAI-1 activity is increased in AD, which is involved in accumulating Aß. Progressive increase of Aß level during AD neuropathology is correlated with the over-production of PAI-1 with subsequent reduction of plasmin and tPA activities. Reducing plasmin and tPA activities promote Aß by reducing Aß clearance. Neuroserpin plays a critical role in the pathogenesis of AD as it regulates the expression and accumulation of Aß. Higher expression of neuroserpin inhibits the neuroprotective tPA and the generation of plasmin with subsequent reduction in the clearance of Aß. These observations raise conflicting evidence on whether neuroserpin is neuroprotective or involved in AD progression. Thus, neuroserpin over-expression with subsequent reduction of tPA may propagate AD neuropathology.

FABP5 can substitute for androgen receptor in malignant progression of prostate cancer cells.

Fatty acid­binding protein 5 (FABP5) and androgen receptor (AR) are critical promoters of prostate cancer. In the present study, the effects of knocking out the FABP5 or AR genes on malignant characteristics of prostate cancer cells were investigated, and changes in the expression of certain key proteins in the FABP5 (or AR)­peroxisome proliferator activated receptor­Î³ (PPARγ)­vascular endothelial growth factor (VEGF) signaling pathway were monitored. The results obtained showed that FABP5­ or AR­knockout (KO) led to a marked suppression of the malignant characteristics of the cells, in part, through disrupting this signaling pathway. Moreover, FABP5 and AR are able to interact with each other to regulate this pathway, with FABP5 controlling the dominant AR splicing variant 7 (ARV7), and AR, in return, regulates the expression of FABP5. Comparisons of the RNA profiles revealed the existence of numerous differentially expressed genes (DEGs) comparing between the parental and the FABP5­ or AR­KO cells. The six most abundant changes in DEGs were found to be attributable to the transition from androgen­responsive to androgen­unresponsive, castration­resistant prostate cancer (CRPC) cells. These findings have provided novel insights into the complex molecular pathogenesis of CRPC cells, and have demonstrated that interactions between FABP5 and AR contribute to the transition of prostate cancer cells to an androgen­independent state. Moreover, gene enrichment analysis revealed that the most highly enriched biological processes associated with the DEGs included those responsive to fatty acids, cholesterol and sterol biosynthesis, as well as to lipid and fatty acid transportation. Since these pathways regulated by FABP5 or AR may be crucial in terms of transducing signals for cancer cell progression, targeting FABP5, AR and their associated pathways, rather than AR alone, may provide a new avenue for the development of therapeutic strategies geared towards suppressing the malignant progression to CRPC cells.

Maxillary Sinus Lift Procedures: An Overview of Current Techniques, Presurgical Evaluation, and Complications.

A maxillary sinus lift procedure is indicated if a dental implant needs to be placed in the posterior maxilla with limited bone available to accommodate a dental implant. Both open and closed sinus lifting procedures are reliable approaches for increasing the bone volume needed to support proper implant positioning. However, these methods can lead to several complications. In addition to the general complications commonly linked to oral surgery, such as swelling or hematoma, the primary complication in open sinus lifting is typically the perforation of the Schneiderian membrane during osteotomy. Detailed and extensive presurgical evaluation is crucial to minimize such complications. The objective of this study was to delineate contemporary trends in sinus lift surgery, with a specific emphasis on different techniques of sinus lift procedure, anatomical and surgical factors, presurgical evaluation, bone grafting, and the practical implications of these factors in implant dentistry cases involving a deficient posterior maxilla. In conclusion, while both osteotome and lateral window techniques can assist clinicians in addressing the complexities of implant placement in a deficient posterior maxilla, bone height before implantation remains a critical factor in determining the success and longevity of implants.

Associations Among Knee Osteoarthritis Severity, Body Mass Index, and Physical Functions in Saudi Arabian Adults: A Multi-Center Cross-Sectional Study.

Background The purpose of this study was to investigate the associations among knee osteoarthritis severity, body mass index, and physical functions in Saudi Arabian adults. Methodology In this multi-center, cross-sectional study, we performed a secondary data analysis that included 189 adults aged 55 years or above with doctor-diagnosed knee osteoarthritis enrolled in five hospitals in Riyadh, Saudi Arabia, between March 2016 and March 2017. According to knee osteoarthritis severity, all of the individuals were divided into the following three groups: mild (n = 36), moderate (n = 75), and severe (n = 78). A high body mass index was defined as a body mass index score of >25 kg/m2. Physical function was evaluated using the 36-item physical functioning subscale. Results Severe knee osteoarthritis had a significantly 6.47-fold (95% confidence interval (CI) = 2.95-14.22, p < 0.0001) higher risk of physical function than those with mild knee osteoarthritis after adjusting for age, sex, educational status, occupational status, affected knee with osteoarthritis, knee pain, and body mass index. However, moderate knee osteoarthritis had a 1.22-fold higher risk of physical function, but the association was not statistically significant (95% CI = 0.60-2.49, p = 0.578). Conclusions Severe but not moderate knee osteoarthritis was more likely to have the worst physical function than mild knee osteoarthritis among adults with a high body mass index in Saudi Arabia.