Securing Internet-of-Medical-Things networks using cancellable ECG recognition.

Reinforcement of the Internet of Medical Things (IoMT) network security has become extremely significant as these networks enable both patients and healthcare providers to communicate with each other by exchanging medical signals, data, and vital reports in a safe way. To ensure the safe transmission of sensitive information, robust and secure access mechanisms are paramount. Vulnerabilities in these networks, particularly at the access points, could expose patients to significant risks. Among the possible security measures, biometric authentication is becoming a more feasible choice, with a focus on leveraging regularly-monitored biomedical signals like Electrocardiogram (ECG) signals due to their unique characteristics. A notable challenge within all biometric authentication systems is the risk of losing original biometric traits, if hackers successfully compromise the biometric template storage space. Current research endorses replacement of the original biometrics used in access control with cancellable templates. These are produced using encryption or non-invertible transformation, which improves security by enabling the biometric templates to be changed in case an unwanted access is detected. This study presents a comprehensive framework for ECG-based recognition with cancellable templates. This framework may be used for accessing IoMT networks. An innovative methodology is introduced through non-invertible modification of ECG signals using blind signal separation and lightweight encryption. The basic idea here depends on the assumption that if the ECG signal and an auxiliary audio signal for the same person are subjected to a separation algorithm, the algorithm will yield two uncorrelated components through the minimization of a correlation cost function. Hence, the obtained outputs from the separation algorithm will be distorted versions of the ECG as well as the audio signals. The distorted versions of the ECG signals can be treated with a lightweight encryption stage and used as cancellable templates. Security enhancement is achieved through the utilization of the lightweight encryption stage based on a user-specific pattern and XOR operation, thereby reducing the processing burden associated with conventional encryption methods. The proposed framework efficacy is demonstrated through its application on the ECG-ID and MIT-BIH datasets, yielding promising results. The experimental evaluation reveals an Equal Error Rate (EER) of 0.134 on the ECG-ID dataset and 0.4 on the MIT-BIH dataset, alongside an exceptionally large Area under the Receiver Operating Characteristic curve (AROC) of 99.96% for both datasets. These results underscore the framework potential in securing IoMT networks through cancellable biometrics, offering a hybrid security model that combines the strengths of non-invertible transformations and lightweight encryption.

Biomechanical strength of triceps tendon repairs: systematic review and meta-regression analysis of human cadaveric studies.

PURPOSE: It is unclear which triceps tendon repair constructs and techniques produce the strongest biomechanical performance while minimizing the risk of gap formation and repair failure. We aimed to determine associations of construct and technique variables with the biomechanical strength of triceps tendon repairs. PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov were systematically searched for peer-reviewed studies on biomechanical strength of triceps tendon repairs in human cadavers. 6 articles met the search criteria. Meta-regression was performed on the pooled dataset (123 specimens). Outcomes of interest included gap formation, failure mode, and ultimate failure load. Covariates were fixation type; number of implants; and number of sutures. Stratification by covariates was performed. We found no association between fixation type and ultimate failure load; however, suture anchor fixation was associated with less gap formation compared with transosseous direct repair (ß = - 1.1; 95% confidence interval [CI]:- 2.2, - 0.04). A greater number of implants was associated with smaller gap formation (ß = - 0.77; 95% CI: - 1.3, - 0.28) while a greater number of sutures was associated with higher ultimate failure load ( ß= 3; 95% CI: 21, 125). In human cadaveric models, the number of sutures used in triceps tendon repairs may be more important than the fixation type or number of implants for overall strength. If using a transosseous direct repair approach to repair triceps tendon tears, surgeons may choose to use more sutures in their repair in order to balance the risk of larger gap formation when compared to indirect repair techniques. LEVEL OF EVIDENCE: Level III.

The compelling role of allopurinol in hyperuricemia-induced epilepsy: Unrecognized like tears in rain.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

Organic geochemistry of the middle Paleozoic Ora Formation in Iraq: Implications for source rock assessment and hydrocarbon potentiality.

The Ora Formation (late Devonian-early Carboniferous) is thought to be a potential source rocks for the Paleozoic petroleum system of Iraq. The source potential from the Ora Formation is evaluated for the first time ever in this study from western and northern Iraq which integrates data from organic geochemistry including Total Organic Carbon (TOC) analysis, HAWK pyrolysis, gas chromatography (GC), and gas chromatography mass spectrometry (GC-MS) and mineralogical X-ray diffraction and scanning electron microscopy. The shale and muddy carbonate succession within the Ora Formation from surface section in northernmost Iraq and subsurface section from two wells (Akkas-1 and Akkas -3) from western Iraq have been employed to assess the source rock potentiality, thermal maturity, kerogen type, organic content, and depositional environment. In addition to organic geochemical analyses, mineralogical XRD and SEM-EDS were used to support the paleoenvironmental interpretation of the Ora Formation. The results from TOC and HAWK analyses reveal that the Ora Formation ranges from poor to good as a source rock. However, the HAWK data suggests that the surface samples from northernmost Iraq are highly mature, highly weathered, or both. Kerogen analysis revealed that the Ora Formation contains immature type III and mixed II-III kerogens. Low TOC values were attributed to factors such as significant clastic input, weathering effects, and the prevailing oxic environment during deposition. The presence of detrital influx of quartz and feldspars, along with the occurrence of illite and kaolinite clay minerals, suggest a detrital input with weathering influence under hot arid and warm humid conditions. Biomarker analysis of the light hydrocarbons using GC and GC-MS revealed that these light hydrocarbons were generated from marine planktonic algae sources, possibly with some contributions from terrestrial and/or microbially reworked organic matter. These high mature light hydrocarbons in subsurface section were originated from anoxic marine shale source rocks. They were most likely from the Cambro-Ordovician Khabour Formation and were contaminated from another source.

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.

Barriers to Neurosurgical Care of Brain Tumors in Low- and Middle-Income Countries: A Systematic Review of the Service Delivery Challenges.

INTRODUCTION: Brain tumors pose a major challenge in low- and middle-income countries (LMICs) due to limited resources and high costs, resulting in an hampered service delivery of neurosurgical care and significant disparities in patient outcomes compared to high-income nations. Therefore, our systematic review aims to identify barriers to service delivery in providing adequate surgical care for the management of brain tumors in LMICs. METHODS: We searched Scopus, PubMed, Google Scholar, and CINAHL, from inception to October 20, 2022. The data from the eligible studies was extracted and analyzed qualitatively. RESULTS: The final analysis included 35 articles, which highlighted significant challenges in providing adequate surgical care for brain tumors in LMICs. Among the cited studies, 10% reported lack of multidisciplinary team structures, 61% noted delayed patient presentation, 16% highlighted delays in neuroimaging, 10% reported delays in scheduling surgery, lack of training for specialized surgery (3%), lack of intra-operative facilities (19%), power supply interruption (6%), and lack of advanced diagnostic and specialized surgery facilities (19%). Strategies for addressing these challenges include cross-border collaboration (7%), public education, and awareness (13%), establishing multidisciplinary teams (20%), utilizing alternative surgical techniques (13% awake craniotomy, 7% intraoperative ultrasound, 13% intraoperative cytology smear), and establishing satellite hospitals for low-risk care (7%), standard operating procedure and infection control (13%). CONCLUSION: Targeted interventions considering economic constraints are essential to improve the availability, affordability, and quality of neuro-oncological services in developing countries. International collaborations and building capacity are vital for improving patient outcomes and service delivery, as well as forming multidisciplinary teams and utilizing resource-saving, innovative methods.

The functional and molecular roles of p75 neurotrophin receptor (p75NTR) in epilepsy.

Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated. Therefore, this review aimed to revise the mechanistic pathway of p75NTR in epilepsy.

Roles of p75 neurotrophin receptor (p75NTR) in epilepsy: Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated.

Biological evaluation of levofloxacin and its thionated derivatives: antioxidant activity, aldehyde dehydrogenase enzyme inhibition, and cytotoxicity on A549 cell line.

Levofloxacin (LVX) is among the fluoroquinolones antibiotics that has also been studied in vitro and in vivo for its anticancer effects. In this study, we used LVX and novel LVX thionated derivatives; compounds 2 and 3, to evaluate their antioxidant activity, aldehyde dehydrogenase (ALDH) enzymes activity inhibition, and anticancer activity. Combination treatments with doxorubicin (DOX) were investigated as well. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to determine the antioxidant activity. The NADH fluorescence spectrophotometric activity assay was used to determine the ALDH inhibitory effects. Resazurin dye method was applied for cell viability assays. Molecular Operating Environment software was used for the molecular docking experiments. Compared to ascorbic acid, DPPH assay showed that compound 3 had the highest antioxidant activity among the tested compounds with approximately 35% scavenging activity. On ALDH enzymes, compound 3 showed a significant ALDH activity inhibition compared to compound 2 at 200 µM. The IC50 values for the tested compounds were approximately 100 µM on A549 cell line, a non-small cell lung cancer (NSCLC) cell line. However, significant enhancement of cytotoxicity and reduction of IC50 values were observed by combining DOX and synergism was achieved with LVX with a combination index value of 0.4. The molecular docking test showed a minimum binding energy with a good affinity for compound 3 towards ALDH enzymes. Thionated LVX derivatives, may be repurposed for NSCLC therapy in combination with DOX, taking into account the antioxidant activity, ALDH activity inhibition, and the molecular docking results of compound 3.

Role of CD44 in Chemotherapy Treatment Outcome: A Scoping Review of Clinical Studies.

Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review, following PRISMA-ScR guidelines, systematically identified and evaluated clinical studies on the impact of CD44 expression on chemotherapy treatment outcomes across various cancer types. The search encompassed PubMed (1985-2023) and SCOPUS (1936-2023) databases, yielding a total of 12,659 articles, of which 40 met the inclusion criteria and were included in the qualitative synthesis using a predefined data extraction table. Data collected included the cancer type, sample size, interventions, control, treatment outcome, study type, expression of CD44 variants and isoforms, and effect of CD44 on chemotherapy outcome. Most of the studies demonstrated an association between increased CD44 expression and negative chemotherapeutic outcomes such as shorter overall survival, increased tumor recurrence, and resistance to chemotherapy, indicating a potential role of CD44 upregulation in chemoresistance in cancer patients. However, a subset of studies also reported non-significant relationships or conflicting results. In summary, this scoping review highlighted the breadth of the available literature investigating the clinical association between CD44 and chemotherapeutic outcomes. Further research is required to elucidate this relationship to aid clinicians in managing CD44-positive cancer patients.

Neoadjuvant nivolumab or nivolumab plus LAG-3 inhibitor relatlimab in resectable esophageal/gastroesophageal junction cancer: a phase Ib trial and ctDNA analyses.

Gastroesophageal cancer dynamics and drivers of clinical responses with immune checkpoint inhibitors (ICI) remain poorly understood. Potential synergistic activity of dual programmed cell death protein 1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) inhibition may help improve immunotherapy responses for these tumors. We report a phase Ib trial that evaluated neoadjuvant nivolumab (Arm A, n = 16) or nivolumab-relatlimab (Arm B, n = 16) in combination with chemoradiotherapy in 32 patients with resectable stage II/stage III gastroesophageal cancer together with an in-depth evaluation of pathological, molecular and functional immune responses. Primary endpoint was safety; the secondary endpoint was feasibility; exploratory endpoints included pathological complete (pCR) and major pathological response (MPR), recurrence-free survival (RFS) and overall survival (OS). The study met its primary safety endpoint in Arm A, although Arm B required modification to mitigate toxicity. pCR and MPR rates were 40% and 53.5% for Arm A and 21.4% and 57.1% for Arm B. Most common adverse events were fatigue, nausea, thrombocytopenia and dermatitis. Overall, 2-year RFS and OS rates were 72.5% and 82.6%, respectively. Higher baseline programmed cell death ligand 1 (PD-L1) and LAG-3 expression were associated with deeper pathological responses. Exploratory analyses of circulating tumor DNA (ctDNA) showed that patients with undetectable ctDNA post-ICI induction, preoperatively and postoperatively had a significantly longer RFS and OS; ctDNA clearance was reflective of neoantigen-specific T cell responses. Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .

Sleep disorders cause Parkinson's disease or the reverse is true: Good GABA good night.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative brain disease due to degeneration of dopaminergic neurons (DNs) presented with motor and non-motor symptoms. PD symptoms are developed in response to the disturbance of diverse neurotransmitters including γ-aminobutyric acid (GABA). GABA has a neuroprotective effect against PD neuropathology by protecting DNs in the substantia nigra pars compacta (SNpc). It has been shown that the degeneration of GABAergic neurons is linked with the degeneration of DNs and the progression of motor and non-motor PD symptoms. GABA neurotransmission is a necessary pathway for normal sleep patterns, thus deregulation of GABAergic neurotransmission in PD could be the potential cause of sleep disorders in PD. AIM: Sleep disorders affect GABA neurotransmission leading to memory and cognitive dysfunction in PD. For example, insomnia and short sleep duration are associated with a reduction of brain GABA levels. Moreover, PD-related disorders including rigidity and nocturia influence sleep patterns leading to fragmented sleep which may also affect PD neuropathology. However, the mechanistic role of GABA in PD neuropathology regarding motor and non-motor symptoms is not fully elucidated. Therefore, this narrative review aims to clarify the mechanistic role of GABA in PD neuropathology mainly in sleep disorders, and how good GABA improves PD. In addition, this review of published articles tries to elucidate how sleep disorders such as insomnia and REM sleep behavior disorder (RBD) affect PD neuropathology and severity. The present review has many limitations including the paucity of prospective studies and most findings are taken from observational and preclinical studies. GABA involvement in the pathogenesis of PD has been recently discussed by recent studies. Therefore, future prospective studies regarding the use of GABA agonists in the management of PD are suggested to observe their distinct effects on motor and non-motor symptoms. CONCLUSION: There is a bidirectional relationship between the pathogenesis of PD and sleep disorders which might be due to GABA deregulation.

Posteroinferior Glenosphere Positioning is Associated with Improved Range of Motion Following Reverse Shoulder Arthroplasty with a 135° Inlay Humeral Component and Lateralized Glenoid.

BACKGROUND: Optimal glenosphere positioning in a lateralized reverse shoulder arthroplasty (RSA) to maximize functional outcomes has yet to be clearly defined. Center of rotation (COR) measurements have largely relied on AP radiographs which allow assessment of lateralization and inferior position, but ignore scapular Y radiographs which may provide an assessment of posterior and inferior position relative to the acromion. The purpose of this study was to evaluate the COR in the sagittal plane and assess the effect of glenosphere positioning with functional outcomes utilizing a 135° inlay stem with a lateralized glenoid. METHODS: A retrospective review was performed on a prospectively maintained multicenter database on patients who underwent primary RSA from 2015-2021 with a 135° inlay stem. The COR was measured on minimum 2-year postoperative sagittal plain radiographs using a perfect-circle fit method. A perfect circle was made on the glenosphere and the center was marked. From there, four measurements were made: 1) center to the inner cortex of the coracoid, 2) center to the inner cortex of the anterior acromion, 3) center to the inner cortex of the middle acromion, 4) center to the inner cortex of the posterior acromion. Regression analysis was performed to evaluate any association between the position of the COR relative to bony landmarks with functional outcomes. RESULTS: A total of 136 RSAs met the study criteria. There was no relation with any of the distances with outcome scores (ASES, VAS). In regards to range of motion (ROM), each distance had an effect on at least one parameter. The COR to coracoid distance had the broadest association with ROM with improvements in forward flexion (FF), external rotation (ER0), and internal rotation with arm at 90° (IR90) (p = <0.001, 0.031, <0.001; respectively). The COR to coracoid distance was also the only distance to affect the final FF and IR90. For every 1 mm increase in this distance, there was a 1.8° increase in FF and 1.5° increase in IR90 (ß = 1.78; 95% CI 0.85 - 2.72, p = <0.001, ß = 1.53; 95% CI 0.65 - 2.41, p = <0.001; respectively). CONCLUSION: Evaluating the COR following RSA in the sagittal plane suggests that posteroinferior glenosphere position may improve ROM when using a 135° inlay humeral component and a lateralized glenoid.

Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit.

Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.

Defective autophagy and autophagy activators in myasthenia gravis: a rare entity and unusual scenario.

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ) that results from autoantibodies against nicotinic acetylcholine receptors (nAchRs) at NMJs. These autoantibodies are mainly originated from autoreactive B cells that bind and destroy nAchRs at NMJs preventing nerve impulses from activating the end-plates of skeletal muscle. Indeed, immune dysregulation plays a crucial role in the pathogenesis of MG. Autoreactive B cells are increased in MG due to the defect in the central and peripheral tolerance mechanisms. As well, autoreactive T cells are augmented in MG due to the diversion of regulatory T (Treg) cells or a defect in thymic anergy leading to T cell-mediated autoimmunity. Furthermore, macroautophagy/autophagy, which is a conserved cellular catabolic process, plays a critical role in autoimmune diseases by regulating antigen presentation, survival of immune cells and cytokine-mediated inflammation. Abnormal autophagic flux is associated with different autoimmune disorders. Autophagy regulates the connection between innate and adaptive immune responses by controlling the production of cytokines and survival of Tregs. As autophagy is involved in autoimmune disorders, it may play a major role in the pathogenesis of MG. Therefore, this mini-review demonstrates the potential role of autophagy and autophagy activators in MG.Abbreviations: Ach, acetylcholine; Breg, regulatory B; IgG, immunoglobulin G; MG, myasthenia gravis; NMJ, neuromuscular junction; ROS, reactive oxygen species; Treg, regulatory T; Ubl, ubiquitin-like.

The therapeutic value of Myrtus communis L.: an updated review.

Myrtus communis L. (Family: Myrtaceae) is naturally found in the western part of Asia, Southern Europe, and North Africa. It has been reportedly applied in pharmaceutical industry, traditional medicine, cosmetics, spices, and food. Pubmed, Google scholar, Web of Science, and Scopus were utilized to seek out relevant content concerning the therapeutic potential of M. communis. Subsequently, we conducted a review to identity noteworthy updates pertaining to M. communis. Myrtle berries, leaves, seeds, and essential oils are natural sources of several nutrients and bioactive compounds with marked health effects. The chemical analysis showed that M. communis contained oils, alkaloids, flavonoids, phenolics, coumarins, saponosides, tannins, quinines, and anthraquinones. A pharmacological investigation revealed that M. communis possessed anti-inflammatory, analgesic, antimicrobial, antiparasitic, antioxidant, antidiabetic, anticancer, antimutagenic, immunomodulatory, dermatological, cardiovascular, central nervous system, and gastrointestinal protective effects, among numerous other biological effects. This current review focused on the biochemical, pharmacological, therapeutic effects, and various biological activities of different parts of M. communis. It signifies that M. communis is a therapeutic plant with numerous applications in medicine and could be used as a drug isolate based on its safety and effectiveness.

Role of ketogenic diet in neurodegenerative diseases focusing on Alzheimer diseases: The guardian angle.

The ketogenic diet (KD) is a low-carbohydrate, adequate protein and high-fat diet. KD is primarily used to treat refractory epilepsy. KD was shown to be effective in treating different neurodegenerative diseases. Alzheimer disease (AD) is the first common neurodegenerative disease in the world characterized by memory and cognitive impairment. However, the underlying mechanism of KD in controlling of AD and other neurodegenerative diseases are not discussed widely. Therefore, this review aims to revise the fundamental mechanism of KD in different neurodegenerative diseases focusing on the AD. KD induces a fasting-like which modulates the central and peripheral metabolism by regulating mitochondrial dysfunction, oxidative stress, inflammation, gut-flora, and autophagy in different neurodegenerative diseases. Different studies highlighted that KD improves AD neuropathology by regulating synaptic neurotransmission and inhibiting of neuroinflammation and oxidative stress. In conclusion, KD improves cognitive function and attenuates the progression of AD neuropathology by reducing oxidative stress, mitochondrial dysfunction, and enhancing neuronal autophagy and brain BDNF.

Depositional environment of the late Paleocene-early Eocene Sinjar Formation, Iraq: Implications from facies analysis, mineralogical and geochemical proxies.

Reconstruction of the depositional environment of the Paleocene-Eocene Sinjar Formation from two outcrop sections in northwestern and northeastern Iraq has been evaluated using the traditional petrographic and facies analysis supported by X-ray diffraction and scanning electron microscopy with a focus on the Paleocene-Eocene (P-E) transition boundary. To this end, major and trace elemental geochemistry was conducted and various paleoenvironmental proxies for the paleoredox, paleoclimate, paleosalinity and paleoproductivity were determined in order to evaluate the changes in widely acknowledged environmental and climatic indicators and the elemental enrichment/depletion across the P-E boundary. The redox-sensitive trace element enrichment and the ir ratios (V/V + Ni, V/Cr, and U/Th) indicate that normal oxygenated circumstances prevailed during the late Paleocene deposition, and that anoxic conditions and a gradual commencement of oxygen depletion occurred during the early Eocene deposition. The coeval increase in the P2O5 content, P/Ti, and P/Al ratios in the Eocene sediments suggests an increase in nutrients and primary productivity due to the effect of upwelling currents during early Eocene. The conditions can be verified by observing a small change in salinity levels from low to high across the P-E boundary, which can be indicated by the Sr/Ba ratios. In addition, certain minerals such as Mg-calcite, dolomite, and palygorskite are commonly present, and paleoclimatic changes can be observed across the P-E transition from arid to semiarid and then to humid conditions, which can be recorded from C-values, Sr-Cu, Rb/Sr ratios, and clay mineralogy. These conditions were noted in the Sinjar Formation, which is made up of many microfacies such as lime mudstone, wackstone, packstone, grainstone and boundstone. These microfacies were deposited in a shallow marine environment that extended from tidal flats to reef slopes, with a developed reef environment that included back reef, reef core, and fore reef environments.

Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3ß) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.

Parkinson's disease (PD) is a progressive neurodegenerative disease of the brain due to degeneration of dopaminergic neurons in the substantia nigra (SN). Glycogen synthase kinase 3 beta (GSK-3ß) is implicated in the pathogenesis of PD. Therefore, the purpose of the present review was to revise the mechanistic role of GSK-3ß in PD neuropathology, and how GSK-3ß inhibitors affect PD neuropathology. GSK-3 is a conserved threonine/serine kinase protein that is intricate in the regulation of cellular anabolic and catabolic pathways by modulating glycogen synthase. Over-expression of GSK-3ß is also interconnected with the development of different neurodegenerative diseases. However, the underlying mechanism of GSK-3ß in PD neuropathology is not fully clarified. Over-expression of GSK-3ß induces the development of PD by triggering mitochondrial dysfunction and oxidative stress in the dopaminergic neurons of the SN. NF-κB and NLRP3 inflammasome are activated in response to dysregulated GSK-3ß in PD leading to progressive neuronal injury. Higher expression of GSK-3ß in the early stages of PD neuropathology might contribute to the reduction of neuroprotective brain-derived neurotrophic factor (BDNF). Thus, GSK-3ß inhibitors may be effective in PD by reducing inflammatory and oxidative stress disorders which are associated with degeneration of dopaminergic in the SN.

Role of fenofibrate in multiple sclerosis.

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the central nervous system (CNS). The underlying pathophysiology of MS is the destruction of myelin sheath by immune cells. The formation of myelin plaques, inflammation, and injury of neuronal myelin sheath characterizes its neuropathology. MS plaques are multiple focal regions of demyelination disseminated in the brain's white matter, spinal cords, deep grey matter, and cerebral cortex. Fenofibrate is a peroxisome proliferative activated receptor alpha (PPAR-α) that attenuates the inflammatory reactions in MS. Fenofibrate inhibits differentiation of Th17 by inhibiting the expression of pro-inflammatory signaling. According to these findings, this review intended to illuminate the mechanistic immunoinflammatory role of fenofibrate in mitigating MS neuropathology. In conclusion, fenofibrate can attenuate MS neuropathology by modulating different pathways, including oxidative stress, autophagy, mitochondrial dysfunction, inflammatory-signaling pathways, and neuroinflammation.