Therapeutic Potential of the Ketogenic Diet: A Metabolic Switch with Implications for Neurological Disorders, the Gut-Brain Axis, and Cardiovascular Diseases.

The Ketogenic Diet (KD) is a dietary regimen that is low in carbohydrates, high in fats, and contains adequate protein. It is designed to mimic the metabolic state of fasting. This diet triggers the production of ketone bodies through a process known as ketosis. The primary objective of KD is to induce and sustain ketosis, which has been associated with numerous health benefits. Recent research has uncovered promising therapeutic potential for KD in the treatment of various diseases. This includes evidence of its effectiveness as a dietary strategy for managing intractable epilepsy, a form of epilepsy that is resistant to medication. We are currently assessing the efficacy and safety of KD through laboratory and clinical studies. This review focuses on the anti-inflammatory properties of the KD and its potential benefits for neurological disorders and the gut-brain axis. We also explore the existing literature on the potential effects of KD on cardiac health. Our aim is to provide a comprehensive overview of the current knowledge in these areas. Given the encouraging preliminary evidence of its therapeutic effects and the growing understanding of its mechanisms of action, randomized controlled trials are warranted to further explore the rationale behind the clinical use of KD. These trials will ultimately enhance our understanding of how KD functions and its potential benefits for various health conditions. We hope that our research will contribute to the body of knowledge in this field and provide valuable insights for future studies.

Hemodynamic Study of Cerebral Arteriovenous Malformation: Newtonian and Non-Newtonian Blood Flow.

OBJECTIVE: Arteriovenous malformation is a disease of the vascular system that occurs mainly in the cerebral arteries and spine. Numerical simulation as a powerful method is used to investigate the Cerebral Arteriovenous Malformation hemodynamic after occlusion of the abnormality step by step by embolization. METHODS: The computed tomography (CT) Angiographic imaging data of 2 patients are used and a geometric model is extracted by the Mimics software. Numerical simulation of blood flow is performed in both Newtonian and non-Newtonian models. The Navier-Stokes and continuity governing equations are solved by a finite element method using the COMSOL Multiphysics software (the commercial computational fluid dynamics (CFD) simulation software). To validate the numerical results, the real data on blood flow rate in the feeding artery and draining veins are used, as well as angiographic images at different times. RESULTS: Regarding the comparison of pressure contours for different occlusions of 0, 30, 50, and 90%, by increasing the amount of occlusion in the nidus, there is an increase in the blood pressure. Regarding the comparison of the blood flow velocity in the feeding artery, draining veins, and inside the AVM nidus for Newtonian and non-Newtonian models, there is a significant difference between these 2 simulations in vessels with smaller dimensions (such as vessels inside the nidus). CONCLUSIONS: By increasing the amount of nidus occlusion, the blood pressure is increased, so the blood supply process is better. According to a significant difference between the Newtonian and non-Newtonian simulations in vessels with smaller dimensions (such as vessels inside the nidus), therefore, non-Newtonian simulation should be done for different occlusions of 30, 50, and 90%.

Lysine ε-aminolysis and incorporation of sulfhydryl groups into human brain tau 4R/1N and 306VQIVYK311 enhances the formation of beta structures and toxicity.

In the present study, we investigated the effects of N-homocysteine thiolactone (tHcy) modification on expressed and purified tau protein and the synthesized VQIVYK target peptide. The modified constructs were subjected to comprehensive validation using various methodologies, including mass spectrometry. Subsequently, in vivo, in vitro, and in silico characterizations were performed under both reducing and non-reducing conditions, as well as in the presence and absence of heparin as a cofactor. Our results unequivocally confirmed that under reducing conditions and in the presence of heparin, the modified constructs exhibited a greater propensity for aggregation. This enhanced aggregative behavior can be attributed to the disruption of lysine positive charges and the subsequent influence of hydrophobic and p-stacking intermolecular forces. Notably, the modified oligomeric species induced apoptosis in the SH-SY5Y cell line, and this effect was further exacerbated with longer incubation times and higher concentrations of the modifier. These observations suggest a potential mechanism involving reactive oxygen species (ROS). To gain a deeper understanding of the molecular mechanisms underlying the neurotoxic effects, further investigations are warranted. Elucidating these mechanisms will contribute to the development of more effective strategies to counteract aggregation and mitigate neurodegeneration.

Plasma cytokines profile in patients with Alzheimer's and Parkinson's Disease: a comparative study in terms of inflammation.

BACKGROUND: Neurodegenerative disorders such as Alzheimer's and Parkinson's disease inflict economic and health burdens on societies. Alzheimer's disease (AD), the most prevalent form of dementia, is accompanied by progressive degradation of memory, decision-making, and judgment. Parkinson's disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and loss of balance. Extensive research has pinpointed inflammation as a cause of the onset and progression of both diseases. However, it has not been confirmed which one is more formidable in terms of inflammation. METHODS: To assess the extent of inflammation that is implicated in AD and PD and answer the question of which one is more inflammatory, serum levels of inflammatory biomarkers, including cytokines, chemokines, and prostaglandin E2 (PEG2), were measured in AD and PD patients as well as a healthy group. RESULTS: Our results showed a significant increase in IL-1α, IL-1ß, IL-4, IL-6, IL-10, IL-12p70, IP-10, MCP-1, PEG2, and TNF-α in AD and PD patients compared with the control. Interestingly, IFN-γ did not manifest any significant difference in AD or PD patients compared with the control. CONCLUSION: As a hallmark of our results, it could be inferred that inflammation, as the underlying etiological cause, plays a more crucial role in PD compared with AD. Based on our results, it is proposed that anti-inflammatory remedies would be putatively more effective in PD rather than AD.

Acetyl-11-Keto-Beta-Boswellic Acid Has Therapeutic Benefits for NAFLD Rat Models That Were Given a High Fructose Diet by Ameliorating Hepatic Inflammation and Lipid Metabolism.

Acetyl-11-keto-beta-boswellic acid (AKBA), a potent anti-inflammatory compound purified from Boswellia species, was investigated in a preclinical study for its potential in preventing and treating non-alcoholic fatty liver disease (NAFLD), the most common chronic inflammatory liver disorder. The study involved thirty-six male Wistar rats, equally divided into prevention and treatment groups. In the prevention group, rats were given a high fructose diet (HFrD) and treated with AKBA for 6 weeks, while in the treatment group, rats were fed HFrD for 6 weeks and then given a normal diet with AKBA for 2 weeks. At the end of the study, various parameters were analyzed including liver tissues and serum levels of insulin, leptin, adiponectin, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-ß), interferon gamma (INF-ϒ), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). Additionally, the expression levels of genes related to the inflammasome complex and peroxisome proliferator-activated receptor gamma (PPAR-ϒ), as well as the levels of phosphorylated and non-phosphorylated AMP-activated protein kinase alpha-1 (AMPK-α1) protein, were measured. The results showed that AKBA improved NAFLD-related serum parameters and inflammatory markers and suppressed PPAR-ϒ and inflammasome complex-related genes involved in hepatic steatosis in both groups. Additionally, AKBA prevented the reduction of the active and inactive forms of AMPK-α1 in the prevention group, which is a cellular energy regulator that helps suppress NAFLD progression. In conclusion, AKBA has a beneficial effect on preventing and avoiding the progression of NAFLD by preserving lipid metabolism, improving hepatic steatosis, and suppressing liver inflammation.

Inflawell® improves neutrophil-to-lymphocyte ratio and shortens hospitalization in patients with moderate COVID-19, in a randomized double-blind placebo-controlled clinical trial.

AIMS: COVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell® syrup, on moderate COVID-19 patients along with the current standard of care treatment. METHODS: A randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial. RESULTS: Our clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL - 6 and TNF - α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant. CONCLUSION: Overall, the treatment with Inflawell® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines. TRIAL REGISTRATION: The trial has been registered in  https://www.irct.ir  with unique identifier: IRCT20170315033086N10 ( https://en.irct.ir/trial/51631 ). IRCT is a primary registry in the WHO registry network ( https://www.who.int/clinical-trials-registry-platform/network/primary-registries ).

Strengths and weaknesses of frontal versus occipital ventriculoperitoneal shunt placement: A systematic review.

Excessive accumulation of cerebrospinal fluid within the brain ventricles is called hydrocephalus, which results in increased intracranial pressure preventing brain growth or causing damage to intracranial structures due to raised intracranial pressure. One of the most common treatment options for this pathology includes the placement of a ventriculoperitoneal shunt to drain the excess fluid. The location of catheterization is traditionally considered as an important factor affecting shunt survival. In this study, we aimed to systematically review all available documents to determine the advantage and superiority of frontal or occipital shunt entry points as the two main approaches. A database search was performed in PubMed, Scopus, Embase, Web of Science, Medline, Ovid, and Google Scholar using "ventriculoperitoneal", "shunt placement", and "hydrocephalus" as the main key terms. Resultant articles were screened for relevancy based on predefined inclusion and exclusion criteria by two authors independently. After excluding irrelevant documents, the data of 11 related articles consisting of 3947 patients were extracted and qualitative data synthesis and pooled analysis were performed. The results of the included studies showed that although the outcomes of a higher percentage of the total review population were in favor of frontal shunt placement, there was no significant superiority for neither of these two approaches after pooled analysis of available failure rates. Findings have shown that each approach has benefits and drawbacks, and there may be other factors such as age and valve design besides the position of shunt placement that may affect the survival rate. Also, the accuracy of shunt placement as an independent factor affects the failure rate and can be improved with various image-guidance methods to minimize shunt failure.

Effect of Preoperative Modic Change in the Outcome of Patients with Low Back Pain Following Posterior Spinal Fusion or Laminectomy.

BACKGROUND: Modic changes (MC), visible on magnetic resonance imaging (MRI) are associated with chronic low back pain (LBP). It is reported that different MC types could affect the surgical outcome in patients with LBP. OBJECTIVE: In this study, we evaluated the effect of MC Type I and II on patients with LBP and degenerative disc disease following posterior spinal fusion (PSF) or laminectomy. MATERIALS AND METHODS: We evaluated the outcome of 162 patients with LBP and MC Type I and II who underwent laminectomy (n = 72) or PSF (n = 90). Preoperative MRI was used to define MC types. Visual analog scale (VAS) was used to evaluate the pain intensity before and 3 months after surgery. RESULTS: Patients had MC Type I in 46.3% and Type II in 53.7%. Pain VAS significantly decreased following surgery (7.93 ± 1.27-5.98 ± 1.57, P < 0.001). There was no difference between MC Type I and II in pain VAS before (P = 0.51) and after treatment (P = 0.51). Among MC Type I, PSF compared to laminectomy had significantly more improvement in pain VAS (P = 0.01), but the changes in modic Type II were similar between groups (P = 0.89). CONCLUSION: Surgical treatment in patients with LBP with MC accompanies with significant improvement in pain. PSF seems better treatment in patients with MC Type I.

Clinical test to detect mecA and antibiotic resistance in Staphylococcus aureus, based on novel biotechnological methods.

BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common organisms isolated from clinical samples, and has been associated with morbidity and mortality among hospitalized patients. The aim of this study was to evaluate the prevalence and antibiotic susceptibility patterns among MRSA and methicillin-sensitive S. aureus (MSSA) isolates collected from four hospitals in Iran. MATERIAL AND METHODS: A total of 183 isolates of S. aureus were collected from various clinical specimens of four hospitals in Iran. The isolates were identified by using the conventional biochemical tests. Three methods-oxacillin agar disk diffusion, oxacillin agar screening, and PCR- were applied to determine susceptibility to oxacillin. The conventional disk agar diffusion test was used to evaluate the antibiotic sensitivity of our isolates against 15 antibiotics, according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). RESULTS: Of 183 isolates, 77 isolates (42.1%) were found to be MRSA, by the PCR method. The highest antibiotic resistance was found to be against penicillin, co-trimoxazole, erythromycin, and tetracycline respectively. All isolates were susceptible to vancomycin, according to the results of disk agar diffusion. Among other antibiotics, teicoplanin (84%) and fusidic acid (80.5%) were more active against MRSA isolates. For the different methods evaluated, the sensitivities and specificities were as follows: for disk agar diffusion (84.9% and 95.9%) and for agar screening test with oxacillin concentrations of 0.6 µg/ml (70.8% and 97.4%), 4 µg/ml (96.1%and 97.2%) and 6 µg/ml (96% and 96.3%), respectively. CONCLUSION: The results of our study showed that 47% of S. aureus isolates were MRSA. Overall, in this research study, resistance to all test antimicrobial agents in MRSA isolates were higher than that of MSSA isolates. Our results also revealed that 85% of mecA-positive isolates and 15% of mecA-negative isolates were resistant to methicillin; while 96% of mecA-negative isolates were sensitive to methicillin. Meanwhile 4% of mecA-positive isolates were also sensitive to methicillin.

Detection of Methicillin-Resistant Coagulase-Negative Staphylococci and Surveillance of Antibacterial Resistance in a Multi-Center Study from Iran.

BACKGROUND: Coagulase-negative staphylococci (CNS) are a common cause of nosocomial infections. In recent years, an increase in the incidence of methicillin-resistant coagulase-negative staphylococci (MRCNS) has led to the severity of the disease. OBJECTIVES: The aim of this study was to isolate and identify MRCNS strains by oxacillin disk agar diffusion, oxacillin agar screening, and polymerase chain reaction (PCR) and to evaluate their antibacterial resistance patterns. PATIENTS AND METHODS: Totally, 122 CNS isolates were collected from the clinical specimens of four hospitals in Iran. Susceptibility testing was performed by disk agar diffusion against 15 antimicrobial agents. Then, disk agar diffusion, agar screening, and PCR were applied to determine susceptibility to oxacillin. RESULTS: Out of the 122 isolates, 92 isolates were found to be MRCNS by PCR. The sensitivities and specificities of disk agar diffusion and agar screening were 89.2% and 69% and 93.8% and 96.3%, respectively. Also, 93 CNS isolates were resistant to Methicillin according to disk agar diffusion. DISCUSSION: Our results indicated that agar screening was superior to oxacillin disk agar diffusion. A comparison between the antibiotic sensitivity patterns of the MRCNS and the Methicillin-Susceptible Coagulase-Negative Staphylococci (MSCNS) showed that the MRCNS were predominantly multiple-drug resistant isolates as the simultaneous resistance rate to 4 or more antibiotics in the MRCNS and MSCNS was 93% and 56%, respectively.