<![CDATA[Meningitis]]> https://www.eurekaselect.com RSS Feed for Disease Wise Article | BenthamScience EurekaSelect (+http://eurekaselect.com) Fri, 29 Mar 2024 09:41:56 +0000 <![CDATA[Meningitis]]> https://www.eurekaselect.com https://www.eurekaselect.com <![CDATA[Hydralazine-Induced ANCA Associated Vasculitis (AAV) Presenting with Pulmonary-Renal Syndrome (PRS): A Case Report with Literature Review]]>https://www.eurekaselect.comarticle/106734 <![CDATA[<i>In silico</i> and <i>in vitro</i> Studies of Imidazolium Ionic Liquids as Effective Antibacterial Agents against Multidrug Resistant <i>Escherichia coli</i> Strains]]>https://www.eurekaselect.comarticle/106009Background: Escherichia coli especially its multiresistant strains as the common foodborne pathogens cause bloodstream infections, nosocomial pneumonia, infections of the skin and soft tissues. Therefore, the search for new effective biologically active compounds has been rapidly increasing in recent few decades. In this paper, we describe Quantitative Structure-Activity Relationships (QSAR) studies, molecular docking and in vitro antibacterial activity evaluation of a series of imidazolium-based Ionic Liquids (ILs) against E. coli spp.

Methods: M2D fragment-based, classification and regression QSAR models were created using machine learning methods and types of descriptors via the OCHEM server. Biological testing of a series of synthesized imidazolium ILs with predicted activity was performed by the disc diffusion method. The most typical structures of symmetric and asymmetric ILs with high anti-E. coli activity (1e, 1h) were docked into the active site of Enoyl-Acyl Carrier Protein Reductase (ENR) in E. coli.

Results: Symmetric imidazolium ILs with C8 alkyl chain length demonstrated the highest antibacterial activity in comparison to the high antibacterial potential of asymmetric ILs with C12 alkyl chain length against drug-sensitive and drug-resistant E. coli strains including hemolytic E. coli. It should be noted that symmetric ILs with C6 or C9 alkyl chain length have a slightly lower activity against certain E. coli strains. The key role in the binding of compounds (1e, 1h) in the E. coli ENR active site is associated with the NAD molecule and the amino acid residue Tyr146.

Conclusion: The highly active symmetric and asymmetric imidazolium ILs can be considered as promising drug-candidates effective against E. coli spp. pathogens including multidrug-resistant strains.

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<![CDATA[Recent Advances in Peptide Nucleic Acids as Antibacterial Agents]]>https://www.eurekaselect.comarticle/107042 <![CDATA[Organic Lesions in the Brain MRI of Children with Febrile Seizure]]>https://www.eurekaselect.comarticle/104849 Materials and Methods: This cross-sectional study included children presented with fever-unrelated seizures. The MRI was examined by a radiologist to identify abnormal findings in each patient. A researcher-made questionnaire including general information, history of head trauma, obstructed labor and the history of seizure was completed for the patients.

Results: Of 287 children with fever-related seizure, 127 (45.7%) were male and 151 (54.3%) were female. History of seizure, history of obstructed labor, abnormal MRI, complete delay, use of antiepileptic drug and history of trauma were 22(9.9%), 1 (0.4%), 11(4%), 5(1.8%), 259(93.2%) and 12 (4.3%), respectively. Of 11 patients with abnormal MRI, 4 had MTS lesions, 2 had tumor lesions, 2 had scarring trauma, 1 had an epidural abscess and 1 had meningitis. The frequency of organic lesions had no significant differences based on gender, use of antiepileptic drug and traumatic history, but it had a significant relation with obstructed labor andthehistory of seizure.

Conclusion: The results showed that organic brain lesions in children with fever-unrelated seizure had a significant relationship with the history of seizure and obstructed maternal labor.]]> <![CDATA[Neuro-AIDS: Current Status and Challenges to Antiretroviral Drug Therapy (ART) for Its Treatment]]>https://www.eurekaselect.comarticle/107090Introduction: The infiltration of HIV into the brain alters the functions of the nervous system known as Neuro-AIDS. It leads to neuronal defects clinically manifested by motor and cognitive dysfunctions.

Materials and Methods: Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy is used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which act as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders, including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination of antiretroviral therapy.

Results and Conclusions: Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful in treating neuro-AIDS and related disorders effectively.

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<![CDATA[Dural Venous Sinuses: What We Need to Know]]>https://www.eurekaselect.comarticle/104847Background: The dural venous sinuses (DVS), in general, are frequently asymmetrical and display far more anatomical variations than arterial systems. A comprehensive study of the anatomy and variants of the DVS can help surgeons in the preoperative evaluation and management as well as minimizing possible complications in the following treatment.

Methods: The current review was designed to provide a general overview of the normal anatomy and notable variants of the cerebral venous system as surveyed from the available literature. The pros and cons of different multimodal imaging methods for investigating DVS are also outlined. Finally, cases of various pathological entities are illustrated from our clinical practice.

Conclusion: There are many anatomical variations and lesions involving the DVS. MRI examination can provide essential information both on anatomical variation and morphological or functional change of the offending DVS in most circumstances. Multimodal non-invasive venography protocols may become a feasible alternative to the classical digital subtraction angiography and would improve the diagnostic accuracy in future studies.

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<![CDATA[Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle]]>https://www.eurekaselect.comarticle/105376Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors.

In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine- glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.

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<![CDATA[Bacterial Siderophores and Their Potential Applications: A Review]]>https://www.eurekaselect.comarticle/106737 <![CDATA[Coexistence of Ectopic Posterior Pituitary and Sellar/Suprasellar Arachnoid Cyst: A Case Report]]>https://www.eurekaselect.comarticle/106987 Case Report: A 67-year-old woman presented with 6 months history of fatigue. Her medical history was positive for irregular menstruation. Her endocrine examinations indicated low free thyroxine level with low TSH level, low oestradiol with low gonadotrophin level, slightly elevated prolactin level. Her Insulin-like growth factor-1 was below the normal levels. Dynamic contrast hypophysis MRI revealed a sellar cystic lesion with a dimension of 18 × 14 × 14 mm, extending from the suprasellar cistern, traversing the diaphragma sellae and reaching the level of the floor of the 3rd ventricle, consistent with sellar/suprasellar AC. There was no wall enhancement. The optic chiasm was compressed. The precontrast T1-weighted magnetic resonance images did not demonstrate the characteristic bright spot of posterior pituitary within the sella, which was higher in position, in the region of the median eminence. The pituitary stalk was not present.

Conclusion: Although speculative, we have a hypothesis to explain how the EPP and sellar/- suprasellar AC coexist in this patient. Due to the absence of stalk, CSF may enter the sella tursica from the central aperture of the diaphragma sellae through which normally the stalk passes.]]>
<![CDATA[Lignans and Neolignans Anti-tuberculosis Identified by QSAR and Molecular Modeling]]>https://www.eurekaselect.comarticle/104839Background: Tuberculosis is a disease with high incidence and high mortality rate, especially in Brazil. Although there are several medications available for treatment, in cases of resistance, there is a need to use more than one medication.

Objective: Therefore, cases of toxicity increase and reports of resistance have been worrying the population. In addition, some medications have a short period of effectiveness. To achieve the goal, ligand-based and structure-based approaches were used.

Methods: Thus, in an attempt to discover potent inhibitors against Mycobacterium tuberculosis enzymes, we sought to identify natural products with high therapeutic potential for the treatment of Tuberculosis through QSAR, Molecular Modeling and ADMET studies.

Results: The results showed that the models generated from two sets of molecules with known activity against M. tuberculosis enzymes InhA and PS were able to select 11 and 8 compounds, respectively, between Lignans and Neolignans with 50 to 60% activity probability. In addition, molecular docking contributed to confirm the mechanism of action of compounds and increase the accuracy of methodologies. All molecules showed higher binding energy values for the drug Isoniazid. We conclude that compounds 33, 34, 110, 114 and 133 are promising for InhA target and compounds 07, 08, 19, 21, 42, 48, 75 and 141 for target PS. In addition, most molecules did not show any toxicity according to the evaluated parameters.

Conclusion: Therefore, Lignans and Neolignans may be an alternative for the treatment of Tuberculosis.

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<![CDATA[Real-time Polymerase Chain Reaction for Mycobacterium tuberculosis Meningitis is More Sensitive in Patients with HIV Co-Infection]]>https://www.eurekaselect.comarticle/106351

Methods: A total of 334 consecutive participants with suspected TbM were divided into two groups: HIV co-infected and HIV-negative; each group was categorized into definite TbM, probable TbM, possible TbM, and TbM-negative subgroups based on clinical, laboratory and imaging data. We evaluated the diagnostic characteristics of MTb qPCR analysis to detect TbM in CSF by comparing the results to those obtained for definite TbM (i.e., positive MTb culture) and/or probable TbM in CSF, as gold standard.

Results: The sensitivity of MTb qPCR in the definite and probable subgroups of the HIV coinfected participants (n = 14) was 35.7%, with a specificity of 93.8%, negative predictive value (NPV) of 94.4%, and negative clinical utility index (CUI−) of 0.89. Results of the HIV-negative group (n = 7) showed lower sensitivity (14.3%) and similar specificity, NPV, and CUI−.

Conclusion: The findings confirmed our hypothesis, despite the low sensitivity. MTb qPCR may significantly contribute to diagnosis when associated with clinical criteria and complementary examinations.]]>
<![CDATA[Effective Antiviral Medicinal Plants and Biological Compounds Against Central Nervous System Infections: A Mechanistic Review]]>https://www.eurekaselect.comarticle/99613Background and Objective: Infectious diseases are amongst the leading causes of death in the world and central nervous system infections produced by viruses may either be fatal or generate a wide range of symptoms that affect global human health. Most antiviral plants contain active phytoconstituents such as alkaloids, flavonoids, and polyphenols, some of which play an important antiviral role. Herein, we present a background to viral central nervous system (CNS) infections, followed by a review of medicinal plants and bioactive compounds that are effective against viral pathogens in CNS infections.

Methods: A comprehensive literature search was conducted on scientific databases including: PubMed, Scopus, Google Scholar, and Web of Science. The relevant keywords used as search terms were: “myelitis”, “encephalitis”, “meningitis”, “meningoencephalitis”, “encephalomyelitis”, “central nervous system”, “brain”, “spinal cord”, “infection”, “virus”, “medicinal plants”, and “biological compounds”.

Results: The most significant viruses involved in central nervous system infections are: Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), West Nile Virus (WNV), Enterovirus 71 (EV71), Japanese Encephalitis Virus (JEV), and Dengue Virus (DENV). The inhibitory activity of medicinal plants against CNS viruses is mostly active through prevention of viral binding to cell membranes, blocking viral genome replication, prevention of viral protein expression, scavenging reactive Oxygen Species (ROS), and reduction of plaque formation.

Conclusion: Due to the increased resistance of microorganisms (bacteria, viruses, and parasites) to antimicrobial therapies, alternative treatments, especially using plant sources and their bioactive constituents, appear to be more fruitful.

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<![CDATA[Preliminary Anti-Coxsackie Activity of Novel 1-[4-(5,6-dimethyl(H)- 1H(2H)-benzotriazol-1(2)-yl)phenyl]-3-alkyl(aryl)ureas]]>https://www.eurekaselect.comarticle/103239Background: Coxsackievirus infections are associated with cases of aseptic meningitis, encephalitis, myocarditis, and some chronic disease.

Methods: A series of benzo[d][1,2,3]triazol-1(2)-yl derivatives (here named benzotriazol-1(2)-yl) (4a-i, 5a-h, 6a-e, g, i, j and 7a-f, h-j) were designed, synthesized and in vitro evaluated for cytotoxicity and antiviral activity against two important human enteroviruses (HEVs) members of the Picornaviridae family [Coxsackievirus B 5 (CVB-5) and Poliovirus 1 (Sb-1)].

Results: Compounds 4c (CC50 >100 μM; EC50 = 9 μM), 5g (CC50 >100 μM; EC50 = 8 μM), and 6a (CC50 >100 μM; EC50 = 10 μM) were found active against CVB-5. With the aim of evaluating the selectivity of action of this class of compounds, a wide spectrum of RNA (positive- and negativesense), double-stranded (dsRNA) or DNA viruses were also assayed. For none of them, significant antiviral activity was determined.

Conclusion: These results point towards a selective activity against CVB-5, an important human pathogen that causes both acute and chronic diseases in infants, young children, and immunocompromised patients.

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<![CDATA[Spontaneous Chest Abscess Caused by Salmonella Enterica subsp. Arizonae in the Desert Southwest; A Case Report and Review of the Current Literature]]>https://www.eurekaselect.comarticle/94269Salmonella enterica subspecies arizonae is a rare pathogen but has been reported in the literature in immunosuppressed and rarely immunocompetent patients. Most disease states have been reported in animals and reptiles. Human exposure has resulted in a range of complications from skin and soft tissue infections to bacteremia and periprosthetic joint infections. Predisposing factors such as age, comorbidities, and use of Mexican folk healing practices increase the risk of developing an infection. S. arizonae has been associated with gastrointestinal infections in several parts of the country and on rare occasions have been isolated from skin and soft tissues, prosthetic joints, and empyema.

Case: This is a unique case of a large de novo chest abscess that developed in a 59-year-old diabetic male from the Southwest region with cultures growing Salmonella enterica subspecies arizonae. This patient presented without predisposing factors and did not appear to be ill at the time of admission. He was treated successfully by aspirating the abscess along with a 2-week course of ceftriaxone intravenously.

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<![CDATA[B7-H3-targeted Radioimmunotherapy of Human Cancer]]>https://www.eurekaselect.comarticle/96941Background: Targeted Radioimmunotherapy (RIT) is an attractive approach to selectively localize therapeutic radionuclides to malignant cells within primary and metastatic tumors while sparing normal tissues from the effects of radiation. Many human malignancies express B7-H3 on the tumor cell surface, while expression on the majority of normal tissues is limited, presenting B7-H3 as a candidate target for RIT. This review provides an overview of the general principles of targeted RIT and discusses publications that have used radiolabeled B7-H3-targeted antibodies for RIT of cancer in preclinical or clinical studies.

Methods: Databases including PubMed, Scopus, and Google Scholar were searched for publications through June 2018 using a combination of terms including “B7-H3”, “radioimmunotherapy”, “targeted”, “radiotherapy”, and “cancer”. After screening search results for relevancy, ten publications were included for discussion.

Results: B7-H3-targeted RIT studies to date range from antibody development and assessment of novel Radioimmunoconjugates (RICs) in animal models of human cancer to phase II/III trials in humans. The majority of clinical studies have used B7-H3-targeted RICs for intra- compartment RIT of central nervous system malignancies. The results of these studies have indicated high tolerability and favorable efficacy outcomes, supporting further assessment of B7-H3-targeted RIT in larger trials. Preclinical B7-H3-targeted RIT studies have also shown encouraging therapeutic outcomes in a variety of solid malignancies.

Conclusion: B7-H3-targeted RIT studies over the last 15 years have demonstrated feasibility for clinical development and support future assessment in a broader array of human malignancies. Future directions worthy of exploration include strategies that combine B7-H3- targeted RIT with chemotherapy or immunotherapy.

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<![CDATA[HPLC-DAD-Q-TOF/MS-Based Screening and Analysis of the Multiple Absorbed Bioactive Components in Rat Serum after Oral Administration of Xiexin Tang]]>https://www.eurekaselect.comarticle/97334Background: Xiexin Tang (XXT) is a classic Traditional Chinese Medicine (TCM) formula that has been used in herbal clinics for more than 1800 years. Recently, many studies have investigated the pharmacological effects and chemical composition of XXT. However, there is little information about systematic studies on the material basis of its efficacy. In the present study, the serum pharmacochemistry technique and HPLC-DAD-Q-TOF/MS were performed to screen and analyze the multiple absorbed bioactive components and metabolites of orally dosed XXT in rat serum.

Methods: Bio-samples and herbal extracts were analyzed and detected by HPLC-DAD-Q-TOF/MS. Upon comparison of the chromatograms of the single-constituent decoctions with that of the XXT formulation, the peak quantity and peak intensity of the formulated decoction showed some variation from those of the single-constituent decoctions.

Results: Twenty-one serum-adsorbed constituents were identified after intragastric administration of herbal extracts, of which 8 originated from Rhei Radix et Rhizoma (RRR), 5 from Coptidis Rhizoma (CR), and 8 from Scutellariae Radix (SR). The results showed that the main adsorbed constituents in the serum were anthraquinones, anthrones, chromones, and butyrophenones, alkaloids, and flavonoids.

Conclusion: The results demonstrate that an effective and reliable analytical method is set up for screening the bioactive components of Chinese herbal medicine, which provided a meaningful basis for further pharmacology and active mechanism research of XXT.

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<![CDATA[The Possible Role of Pathogenic and Non-Pathogenic Bacteria in Initiation and Exacerbation of Celiac Disease; A Comprehensive Review]]>https://www.eurekaselect.comarticle/103099 <![CDATA[Biological Signatures of Alzheimer’s Disease]]>https://www.eurekaselect.comarticle/104895 <![CDATA[Allopurinol and Loss of Consciousness in a 78-old Year Man Suffering from Gout]]>https://www.eurekaselect.comarticle/96167Allopurinol is an FDA -Approved xanthine oxidase inhibitor, which is effective in the treatment of gout, hyperuricemia and uremic kidney stones in patients with an increased level of uric acid excretion. Xanthine oxidase acts by converting hypoxanthine and xanthine into uric acid, and therefore its inhibition results in decreased production of uric acid. The most common side effects of this medication are as follows: maculopapular rashes, hives, itching, headache, dizziness, abnormal hair loss, fever and hypersensitivity reaction.

Case Presentation: This report represents a case of drug-induced meningitis of a senile man who ended up in the ICU due to the remarkably reduced state of consciousness.

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<![CDATA[The Causative Organisms of Bacterial Meningitis and their Antimicrobial Resistance Profiles in Iranian Children in 2011-2016]]>https://www.eurekaselect.comarticle/94744Objectives: The study aimed to describe the identity and antimicrobial resistance patterns of the causative agents of bacterial meningitis in children referred to Children’s Medical Center (CMC) Hospital, Tehran, Iran.

Methods: This retrospective study was performed at CMC Hospital during a six-year period from 2011 to 2016. The microbiological information of the patients with a diagnosis of bacterial meningitis was collected and the following data were obtained: patients’ age, sex, hospital ward, the results of CSF and blood cultures, and antibiotic susceptibility profiles of isolated organisms.

Results: A total of 118 patients with bacterial meningitis were admitted to CMC hospital. Sixty-two percent (n=73) of the patients were male. The median age of the patients was ten months (interquartile range [IQR]: 2 months-2 years) and the majority of them (n=92, 80%) were younger than two years of age. The highest number of patients (n=47, 40%) were admitted to the surgery department. Streptococcus epidermidis was the most frequent isolated bacterium (n=27/127, 21%), followed by Klebsiella pneumoniae (n=20/127, 16%), and Staphylococcus aureus (n=16/127, 12.5%). Blood culture was positive in 28% (n=33/118) of patients. Ampicillin-sulbactam and imipenem were the most effective antibiotics against Gram-negative bacteria isolated from CSF cultures. In the case of Gram-positive organisms, ampicillinsulbactam, vancomycin, and linezolid were the best choices. Imipenem was the most active drug against Gram-negative blood pathogens. Also, ampicillin and vancomycin had the best effect on Gram-positive bacteria isolated from blood cultures.

Conclusion: Results of this study provide valuable information about the antibiotic resistance profiles of the etiologic agents of childhood meningitis, which can be used for prescription of more effective empirical therapies.

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<![CDATA[Identification of Antibacterial Molecule(s) from Animals Living in Polluted Environments]]>https://www.eurekaselect.comarticle/101145

Methods: Snake (Reticulatus malayanus), rats (Rattus rattus), water monitor lizard (Varanus salvator), frog (Lithobates catesbeianus), fish (Oreochromis mossambicus), chicken (Gallus gallus domesticus), and pigeon (Columba livia) were dissected and their organ lysates/sera were collected. Crude extracts were tested for bactericidal effects against neuropathogenic E. coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Bacillus cereus and Klebsiella pneumoniae. To determine whether lysates/sera protect human cells against bacterialmediated damage, cytotoxicity assays were performed by measuring lactate dehydrogenase release as an indicator of cell death. Lysates/sera were partially characterized using heat-treatment and pronasetreatment and peptide sequences were determined using the Liquid Chromatography Mass Spectrometry (LC-MS).

Results: Snake and water monitor lizard sera exhibited potent broad-spectrum bactericidal effects against all bacteria tested. Heat inactivation and pronase-treatment inhibited bactericidal effects indicating that activity is heat-labile and pronase-sensitive suggesting that active molecules are proteinaceous in nature. LCMS analyses revealed the molecular identities of peptides.

Conclusion: The results revealed that python that feeds on germ-infested rodents and water monitor lizards that feed on rotten organic waste possess antibacterial activity in a heat-sensitive manner and several peptides were identified. We hope that the discovery of antibacterial activity in the sera of animals living in polluted environments will stimulate research in finding antibacterial agents from unusual sources as this has the potential for the development of novel strategies in the control of infectious diseases.]]>
<![CDATA[Bacterial Resistance: Antibiotics of Last Generation used in Clinical Practice and the Arise of Natural Products as New Therapeutic Alternatives]]>https://www.eurekaselect.comarticle/104762 <![CDATA[The Role and Mechanism of Thiol-Dependent Antioxidant System in Bacterial Drug Susceptibility and Resistance]]>https://www.eurekaselect.comarticle/98608 <![CDATA[<i>In Silico</i> Studies for Bacterystic Evaluation against <i>Staphylococcus aureus</i> of 2-Naphthoic Acid Analogues]]>https://www.eurekaselect.comarticle/102809Background: Staphylococcus aureus is a gram-positive spherical bacterium commonly present in nasal fossae and in the skin of healthy people; however, in high quantities, it can lead to complications that compromise health. The pathologies involved include simple infections, such as folliculitis, acne, and delay in the process of wound healing, as well as serious infections in the CNS, meninges, lung, heart, and other areas.

Aim: This research aims to propose a series of molecules derived from 2-naphthoic acid as a bioactive in the fight against S. aureus bacteria through in silico studies using molecular modeling tools.

Methods: A virtual screening of analogues was done in consideration of the results that showed activity according to the prediction model performed in the KNIME Analytics Platform 3.6, violations of the Lipinski rule, absorption rate, cytotoxicity risks, energy of binder-receptor interaction through molecular docking, and the stability of the best profile ligands in the active site of the proteins used (PDB ID 4DXD and 4WVG).

Results: Seven of the 48 analogues analyzed showed promising results for bactericidal action against S. aureus.

Conclusion: It is possible to conclude that ten of the 48 compounds derived from 2-naphthoic acid presented activity based on the prediction model generated, of which seven presented no toxicity and up to one violation to the Lipinski rule.

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<![CDATA[Recent Advances in Peptide-Based Approaches for Cancer Treatment]]>https://www.eurekaselect.comarticle/87083Background: Peptide-based pharmaceuticals have recently experienced a renaissance due to their ability to fill the gap between the two main classes of available drugs, small molecules and biologics. Peptides combine the high potency and selectivity typical of large proteins with some of the characteristic advantages of small molecules such as synthetic accessibility, stability and the potential of oral bioavailability.

Methods: In the present manuscript we review the recent literature on selected peptide-based approaches for cancer treatment, emphasizing recent advances, advantages and challenges of each strategy.

Results: One of the applications in which peptide-based approaches have grown rapidly is cancer therapy, with a focus on new and established targets. We describe, with selected examples, some of the novel peptide-based methods for cancer treatment that have been developed in the last few years, ranging from naturally-occurring and modified peptides to peptidedrug conjugates, peptide nanomaterials and peptide-based vaccines.

Conclusion: This review brings out the emerging role of peptide-based strategies in oncology research, critically analyzing the advantages and limitations of these approaches and the potential for their development as effective anti-cancer therapies.

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<![CDATA[An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population]]>https://www.eurekaselect.comarticle/92811 <![CDATA[Tuberculosis - Present Medication and Therapeutic Prospects]]>https://www.eurekaselect.comarticle/94656Background: Tuberculosis (TB) has been present in the history of human civilization since time immemorial and has caused more deaths than any other infectious disease. It is still considered one of the ten most common epidemiologic causes of death in the world. As a transmissible disease, it is initiated by rod-shaped (bacillus) mycobacteria. The management of tuberculosis became possible owing to several discoveries beginning in 1882 with the isolation of the TB bacillus by Robert Koch. The diagnosis of TB was enabled by finding a staining method for TB bacteria identification (1883). It was soon realized that a large-scale policy for the treatment and prevention of tuberculosis was necessary, which resulted in the foundation of International Union against Tuberculosis and Lung Diseases (1902). An antituberculosis vaccine was developed in 1921 and has been in therapeutic use since then. TB treatment regimens have changed over the decades and the latest recommendations are known as Directly Observed Treatment Short-course (DOTS, WHO 1993).

Methods: A search of bibliographic databases was performed for peer-reviewed research literature. A focused review question and inclusion criteria were applied. Standard tools were used to assess the quality of retrieved papers.

Results: A total of 112 papers were included comprising original publications and reviews. The paper overviews anti-TB drugs according to their mechanism of action. The chemical structure, metabolism and unwanted effects of such drugs have been discussed. The most recent treatment regimens and new drugs, including those in clinical trials, are also presented.

Conclusion: Despite a 22% decrease in the tuberculosis fatality rate observed between 2000 and 2015, the disease remains one of the ten prime causes of death worldwide. Increasing bacterial resistance and expensive, prolonged therapies are the main reasons for efforts to find effective drugs or antituberculosis regimens, especially to cure multidrug-resistant tuberculosis.

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<![CDATA[Efficient Synthesis and Antibacterial Profile of Bis(2-hydroxynaphthalene- 1,4-dione)]]>https://www.eurekaselect.comarticle/102900Background: Antibacterial resistance is a serious public health problem infecting millions in the global population. Currently, there are few antimicrobials on the market against resistant bacterial infections. Therefore, there is an urgent need for new therapeutic options against these strains.

Objective: In this study, we synthesized and evaluated ten Bis(2-hydroxynaphthalene-1,4-dione) against Gram-positive strains, including a hospital Methicillin-resistant (MRSA), and Gram-negative strains.

Methods: The compounds were prepared by condensation of aldehydes and lawsone in the presence of different L-aminoacids as catalysts in very good yields. The compounds were submitted to antibacterial analysis through disk diffusion and Minimal Inhibitory Concentration (MIC) assays.

Results: L-aminoacids have been shown to be efficient catalysts in the preparation of Bis(2- hydroxynaphthalene-1,4-dione) from 2-hydroxy-1,4-naphthoquinones and arylaldehydes in excellent yields of up to 96%. The evaluation of the antibacterial profile against Gram-positive strains (Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, S. epidermidis ATCC 12228) also including a hospital Methicillin-resistant S. aureus (MRSA) and Gram-negative strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Klebsiella pneumoniae ATCC 4352), revealed that seven compounds showed antibacterial activity within the Clinical and Laboratory Standards Institute (CLSI) levels mainly against P. aeruginosa ATCC 27853 (MIC 8-128 µg/mL) and MRSA (MIC 32-128 µg/mL). In addition, the in vitro toxicity showed all derivatives with no hemolytic effects on healthy human erythrocytes. Furthermore, the derivatives showed satisfactory theoretical absorption, distribution, metabolism, excretion, toxicity (ADMET) parameters, and a similar profile to antibiotics currently in use. Finally, the in silico evaluation pointed to a structure-activity relationship related to lipophilicity for these compounds. This feature may help them in acting against Gram-negative strains, which present a rich lipid cell wall selective for several antibiotics.

Conclusion: Our data showed the potential of this series for exploring new and more effective antibacterial activities in vivo against other resistant bacteria.

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<![CDATA[Natural Compounds Therapeutic Features in Brain Disorders by Experimental, Bioinformatics and Cheminformatics Methods]]>https://www.eurekaselect.comarticle/94145Background: Synthetic compounds with pharmaceutical applications in brain disorders are daily designed and synthesized, with well first effects but also seldom severe side effects. This imposes the search for alternative therapies based on the pharmaceutical potentials of natural compounds. The natural compounds isolated from various plants and arthropods venom are well known for their antimicrobial (antibacterial, antiviral) and antiinflammatory activities, but more studies are needed for a better understanding of their structural and pharmacological features with new therapeutic applications.

Objectives: Here we present some structural and pharmaceutical features of natural compounds isolated from plants and arthropods venom relevant for their efficiency and potency in brain disorders. We present the polytherapeutic effects of natural compounds belonging to terpenes (limonene), monoterpenoids (1,8-cineole) and stilbenes (resveratrol), as well as natural peptides (apamin, mastoparan and melittin).

Methods: Various experimental and in silico methods are presented with special attention on bioinformatics (natural compounds database, artificial neural network) and cheminformatics (QSAR, drug design, computational mutagenesis, molecular docking).

Results: In the present paper we reviewed: (i) recent studies regarding the pharmacological potential of natural compounds in the brain; (ii) the most useful databases containing molecular and functional features of natural compounds; and (iii) the most important molecular descriptors of natural compounds in comparison with a few synthetic compounds.

Conclusion: Our paper indicates that natural compounds are a real alternative for nervous system therapy and represents a helpful tool for the future papers focused on the study of the natural compounds.

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<![CDATA[Multiple Myeloma or Brucellosis: A Case Report]]>https://www.eurekaselect.comarticle/97139

Case: A 65-year-old male whose occupation was shepherding was referred to our hospital as a known case of multiple myeloma with continuous fever, muscle weakness, and night sweating after taking 2 courses of chemotherapy. The laboratory diagnosis of multiple myeloma had been based on the observation of a high percent of plasma cells in the bone marrow aspiration. At follow- up, the result of patient's fever workup, with 2 sets of blood cultures, was positive for Brucella melitensis. Isolated brucella was confirmed as B. melitensis by 16S rRNA sequencing. Brucellosis serologic test was performed by agglutination test and positive results were obtained. The patient was discharged with the cessation of fever and general improvement after the end of the parental treatment phase of brucella bacteremia.

Conclusions: Brucella infection may cause a severe disease, mimicking a primary hematological disease, which could complicate the correct diagnosis. In brucellosis cases, due to the wide range of symptoms, in addition to cultivation and serological methods, molecular methods should also be used to prevent inappropriate diagnosis and additional costs.]]>
<![CDATA[The Cooperative Effect between Polybasic Region (PBR) and Polysialyltransferase Domain (PSTD) within Tumor-Target Polysialyltranseferase ST8Sia II]]>https://www.eurekaselect.comarticle/102527 <![CDATA[In-silico Subtractive Proteomic Analysis Approach for Therapeutic Targets in MDR Salmonella enterica subsp. enterica serovar Typhi str. CT18]]>https://www.eurekaselect.comarticle/102083Objective: In the present study, an attempt has been made for subtractive proteomic analysis approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using computational tools.

Methods: Paralogous, redundant and less than 100 amino acid protein sequences were removed by using CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative Metabolic pathways analysis was performed to find unique and common metabolic pathways. The non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for drug targets while Psortb and CELLO were used to predict subcellular localization.

Results: There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp. enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways. These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins showed druggability and can be used as a therapeutic target.

Conclusion: Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic druggable proteins which are essential for the pathogen survival and non-homologous to human proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat against salmonellosis.

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<![CDATA[Bactericidal Activity of a Cationic Peptide on Neisseria meningitidis]]>https://www.eurekaselect.comarticle/92441

Objective: Identification of effective AMPs against Neisseria meningitidis, which represents a pathogen of great public health importance worldwide that is intrinsically resistant to some AMPs, such as polymyxin B.

Methods: A cationic 11-residue peptide (KLKLLLLLKLK), referred to as poly-Leu, was synthesized and its antimeningococcal activity was compared to cecropin A and poly-P (KLKPPPPPKLK) through a variety of assays. Flow cytometry was used to measure propidium iodide uptake by N. meningitidis serotype B as an indicator of the effectiveness of each peptide when added to cultures at different concentrations.

Results: The addition of the poly-Leu peptide led to a 90.3% uptake of the dye with an EC50 value of 7.9 µg mL-1. In contrast, uptake was <10% in cells grown in the absence of peptides or with an identical concentration of cecropin and poly-Pro peptides. Electron micrographs indicated that the integrity of the cellular wall and internal membrane was impacted in relation to peptide concentrations, which was confirmed by the detection of released alkaline phosphatase from the periplasmic space due to disruption of the external membrane.

Conclusion: Poly-Leu peptide demonstrated definitive antimicrobial activity against N. meningitidis.

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<![CDATA[The Patenting and Technological Trends in Candidiasis Treatment: A Systematic Review (2014-2018)]]>https://www.eurekaselect.comarticle/102005Background: In the last few decades, mycoses caused by opportunistic fungi namely Candida species has gained significant attention. Such infections are very common and present high mortality rates, especially in immunocompromised patients. Currently, a limited number of antifungal drugs are available for the treatment of these infections and are also often related to severe adverse side effects. Therefore, new drugs and innovative technologies for the treatment of this infection are necessary.

Objective: The aim of this study was to evaluate the development of new drugs, formulations, as well as patents for the treatment of infections caused by Candida spp.

Methods: The present patent review was carried out through a specialized search database Espacenet. The patent selection was based on the following inclusion criteria: Recent patents published in English or Spanish containing candidiasis as the keyword in the title, abstract or full text. This survey was conducted in October and November 2018.

Results: As a result of that, 22 patents were selected to the final selection, the most common routes of application were oral (n = 6), vaginal (n = 6), topical (n = 5) and others (n = 5). This fact is related to the clinical manifestations of candidiasis.

Conclusion: Through this review, it was possible to identify significant improvements and advances in the area of antifungal therapeutic innovation research. In addition, we demonstrated the growing interest of academic and industrial groups in pharmaceutical development and novel formulations for the treatment of candidiasis. New therapeutic options can contribute to improve the quality of patient’s life, prevent infections and promote the search for an innovative and effective treatment of Candida infections.

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<![CDATA[New and Promising Chemotherapeutics for Emerging Infections Involving Drug-resistant Non-albicans Candida Species]]>https://www.eurekaselect.comarticle/101912 <![CDATA[Neuroleptic Malignant Syndrome: A Pilot Study on Psychiatric Inpatients in Iran]]>https://www.eurekaselect.comarticle/101188Background: Neuroleptic malignant syndrome is a life-threatening complication that can occur anytime during antipsychotic treatment.

Objective: The present assessment has probed the incidence and clinical profile of neuroleptic malignant syndrome among a sample of non-western psychiatric patients and compared with the available data in the literature with regard to prevalence and other associated clinical physiognomies.

Methods: As a retrospective, record-based evaluation, all cases with diagnosis of neuroleptic malignant syndrome during the last sixty-two months, after ruling out other imaginable differential diagnoses, like encephalitis, meningitis and serotonin syndrome, entered the present investigation. Clinical diagnosis, was in essence also based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. The assessment of independent variables was analyzed by ‘Compression of proportions’. Statistical significance is, defined as p value ≤0.05.

Results: Among 19814 psychiatric patients, during a sixty-two months’ period, eighteen cases received the diagnosis of neuroleptic malignant syndrome. The most prevalent symptom was fever, which was observed in 100% of cases. Also, there was no significant difference between the first generation versus second-generation antipsychotics. Neuroleptic malignant syndrome was meaningfully more prevalent among male patients suffering from schizophrenia. Similarly, it was significantly more widespread amid 18-65 years old agegroup.

Conclusion: While no significant difference was found between first-generation as opposed to second-generation antipsychotics, neuroleptic malignant syndrome was significantly more prevalent among young and male patients suffering from schizophrenia.

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<![CDATA[A New Comprehensive Index for Evaluating the Quality of Infant Formula under the Framework of Chinese Food Standards]]>https://www.eurekaselect.comarticle/97941Objective: We proposed a new comprehensive index, the food quality index (FQI), to effectively evaluate food quality.

Methods: The food quality index is based on chemical and biological indicators of the Chinese food standards framework. We evaluated the limit value regulations for infant formula standards and then established a comprehensive index and grading standard. Finally, we applied the index to evaluate data obtained from the Shenyang Product Quality Supervision and Inspection Institute.

Results: The results showed that the quality of older infant and young children formula (OF) was good, and the infant formula (IF) was acceptable.

Conclusion: The quality of OF was observably higher than that of IF, and they were significantly different with a p-value < 0.01. The most influencing factor of the IF and OF was minerals, followed by major components, optional ingredients, vitamins, and pathogenic bacteria had no effect. In IF, The number of the main influencing single indicators were 36 and 20 in IF and OF, respectively. Statistical analysis showed that index values of vitamins in the two kinds of milk powders were significantly different, with a p-value < 0.01. Optional ingredients were significantly correlated, with a p-value < 0.05.

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<![CDATA[Integrating Pathophysiology in Migraine: Role of the Gut Microbiome and Melatonin]]>https://www.eurekaselect.comarticle/100933

Methods: The current article reviews the wide array of data associated with the biological underpinnings of migraine and provides a framework that integrates previously disparate bodies of data.

Results: The importance of alterations in stress- and pro-inflammatory cytokine- induced gut dysbiosis, especially butyrate production, are highlighted. This is linked to a decrease in the availability of melatonin, and a relative increase in the N-acetylserotonin/melatonin ratio, which has consequences for the heightened glutamatergic excitatory transmission in migraine. It is proposed that suboptimal mitochondria functioning and metabolic regulation drive alterations in astrocytes and satellite glial cells that underpin the vasoregulatory and nociceptive changes in migraine.

Conclusion: This provides a framework not only for classical migraine associated factors, such as calcitonin-gene related peptide and serotonin, but also for wider factors in the developmental pathoetiology of migraine. A number of future research and treatment implications arise, including the clinical utilization of sodium butyrate and melatonin in the management of migraine.]]>
<![CDATA[Novelty in Inflammation and Immunomodulation in Migraine]]>https://www.eurekaselect.comarticle/99506Background: Migraine is a diffuse and disabling disease. Its pathophysiology is complex and involves both central and peripheral dysfunctions.

Objective: This review will discuss the pathogenesis of migraine from the origin of the neuro-inflammatory theory, to the modern pathophysiological model and the latest therapies.

Methods: PUBMED and EMBASE (up to May 2019) were searched for: migraine, inflammation, immunomodulation. An additional search was carried out from the bibliography of previous review articles.

Results: Migraine was thought to be mainly a vascular disorder, according to the so-called “vascular theory”. Based on animal models, a new hypothesis called “the neuro-inflammatory” was conceived at the end of the 20th century. The growing knowledge about the trigeminovascular system and its role in the inflammatory-pain pathway, allowed to identify other specific neurotransmitters, such as the Calcitonin Gene-Related Peptide and Pituitary Adenylate Cyclase-Activating Peptide. Evidence was provided that the inflammatory-pain system could become sensitised and, due to this sensitisation, the pain could also perpetuate, even in the absence of any triggers of the migraine attack. At last, brain immune cells modification during cortical spreading depression in migraine was demonstrated, along with the existence and function of the glymphatic system. The better comprehension of the immune system abnormalities allowed the development of new immunomodulating drugs: the monoclonal antibodies against the CGRP or the CGRP receptor. Moreover, new insights into the molecular mechanism of CGRP, and the function of C-fibres and Aδ-fibres, highlighted the mechanism of action of Botulinum Toxin type A in the treatment of chronic migraine.

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<![CDATA[Carbohydrates in Vaccine Development]]>https://www.eurekaselect.comarticle/99348 <![CDATA[Osimertinib Quantitative and Gene Variation Analyses in Cerebrospinal Fluid and Plasma of a Non-small Cell Lung Cancer Patient with Leptomeningeal Metastases]]>https://www.eurekaselect.comarticle/93752Background: Leptomeningeal metastases (LM) are much more frequent in patients of non-small lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFRTKI) shows promising efficacy for LM.

Objective: The aim of this study was to analyze the concentration of osimertinib and gene variation of circulating tumor DNA (ctDNA) in human plasma and cerebrospinal fluid (CSF). Furthermore, we explored whether ctDNA in CSF might be used as a biomarker to predict and monitor therapeutic responses.

Methods: The dynamic paired CSF and blood samples were collected from the NSCLC patient with LM acquired EGFR-TKI resistance. A method based on ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) was developed and validated for detecting osimertinib in CSF and plasma samples. Gene variations of ctDNA were tested by next-generation sequencing with a panel of 1021 genes.

Results: The concentrations of osimertinib in CSF were significantly lower than that in plasma (penetration rate was 1.47%). Mutations included mTOR, EGFR, CHECK1, ABCC11, and TP53 were explored in ctDNA from plasma and CSF samples. The detected mutation rate of CSF samples was higher than that of plasma samples (50% vs. 25%). Our data further revealed that the variations allele frequency (VAF) and molecular tumor burden index (mTBI) of ctDNA derived from CSF exhibited the negative correlation with efficacy of treatment.

Conclusion: ctDNA from CSF might be a useful biomarker for monitoring the efficacy of treatment and an effective complement to nuclear magnetic resonance imaging (MRI) for LM.

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<![CDATA[High Contrast and Resolution Labeling of Amyloid Plaques in Tissue Sections from APP-PS1 Mice and Humans with Alzheimer’s Disease with the Zinc Chelator HQ-O: Practical and Theoretical Considerations]]>https://www.eurekaselect.comarticle/99974Background: Various methodologies have been employed for the localization of amyloid plaques in numerous studies on Alzheimer’s disease. The majority of these stains are thought to label the plaques by virtue of their affinity for aggregated Aβ. However, plaques are known to contain numerous other components, including multivalent metals such as zinc.

Objective: This investigates whether it is possible to localize the presence of zinc in parenchymal and vascular amyloid plaques in afflicted brains. To accomplish this, a novel fluorescent zinc chelator, HQO, was investigated to determine its mechanism of binding and to optimize a stain for the high contrast and resolution histological localization of amyloid plaques.

Methods: A novel zinc chelator, HQ-O, was developed for localizing zinc within amyloid plaques. The histology involves incubating tissue sections in a dilute aqueous solution of HQ-O. Its compatibility with a variety of other fluorescent methodologies is described.

Results: All amyloid plaques are stained in fine detail and appear bright green under blue light excitation. The staining of parenchymal plaques correlates closely with that seen following staining with antibodies to Aβ, however, the HQ-O sometimes also label additional globular structures within blood vessels. In situ mechanistic studies revealed that fluorescent plaque-like structures are only observed with HQ-O when synthetic Aβx-42 is aggregated in the presence of zinc.

Conclusion: Zinc is intimately bound to all amyloid plaques, which was demonstrated by its histological localization using a novel fluorescent zinc chelator, HQ-O. Additionally, the tracer is also capable of labeling intravascular leucocytes due to their high zinc content.

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<![CDATA[Perspectives and New Aspects of Metalloproteinases’ Inhibitors in the Therapy of CNS Disorders: From Chemistry to Medicine ]]>https://www.eurekaselect.comarticle/90370Matrix metalloproteinases (MMPs) play a key role in remodeling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation, and survival. Their importance in a variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders.

Till now, there are not many well documented physiological MMP target proteins in the brain but only some pathological ones. Numerous neurodegenerative diseases are a consequence of or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development of these diseases.

In the present review, we discuss the role of metalloproteinase inhibitors, from the wellknown natural endogenous tissue inhibitors of metalloproteinases (TIMPs) to the exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplastic diseases, the knowledge about the enzymatic system in mammalian brain tissue still remains poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of the physiological function of the adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries, and others.

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<![CDATA[Neuroprotective Methodologies of Co-Enzyme Q10 Mediated Brain Hemorrhagic Treatment: Clinical and Pre-Clinical Findings]]>https://www.eurekaselect.comarticle/98724 <![CDATA[Ganglioside GM3 and Its Role in Cancer ]]>https://www.eurekaselect.comarticle/88237 <![CDATA[Recent Trends in Antifungal Agents: A Reference to Formulation, Characterization and Applications]]>https://www.eurekaselect.comarticle/98408Background & Objectives: Fungi are the heterotrophic eukaryotic organisms which are useful as they causes the biodegradation. There are still some harmful species like yeasts, molds and dermatophytes which cause the infections. As the fungi are eukaryotics, they do not respond to the antibiotic therapy due to the limitations associated with the traditional antibiotic therapies. There are several antifungal agents introduced to treat such infections. These antifungal agents posses severe problems like drug resistance and toxicity due to the higher dose which comprises the need for newer alternatives over conventional dosage forms. Novel drug delivery systems proved to be a better approach to enhance the effectiveness of the antifungals and enhance patient compliance by reducing the adverse effect.

Discussion: This review focused on the general information about fungal infections, types and mechanism of action of antifungal agents and overview of formulation approaches such as vesicular system, colloidal system, nanoparticulate system and in situ gelling which are often studied for antifungal treatments.

Conclusion: We concluded that the novel drug delivery systems are the essential techniques for delivering the antifungal agents to their target site with desired concentration. Moreover, the researchers focused on these novel drug deliveries which mainly concentrate on controlling & sustaining the release of antifungal agents.

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<![CDATA[Recent Status and Advancements in the Development of Antifungal Agents: Highlights on Plant and Marine Based Antifungals]]>https://www.eurekaselect.comarticle/98033 <![CDATA[Recent Advances in Rational Diagnosis and Treatment of Normal Pressure Hydrocephalus: A Critical Appraisal on Novel Diagnostic, Therapy Monitoring and Treatment Modalities ]]>https://www.eurekaselect.comarticle/96650Background: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess Cerebrospinal Fluid (CSF) is accumulated in the brain’s ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, slurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

Objective: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.

Results: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.

Conclusion: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

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<![CDATA[Structure-Activity Relationship of Dicoumarol Derivatives as anti- Staphylococcus aureus (Staph Infection) Agents]]>https://www.eurekaselect.comarticle/94449Introduction: Staph infection, caused by a bacterium known as Staphylococcus aureus, results in a range of diseases from cellulitis to meningitis. Dicoumarol compounds are now emerging as new anti-Staph infection agents as they possess a different chemical structure than compounds used in previous treatments, in order to combat antibiotic-resistant strains. However, it is unclear how such chemical modulations to the dicoumarol backbone structure achieve higher drug performance.

Methods: The following review analyzed various quantitative structure-activity relationship (QSAR) studies on dicoumarol compounds and compared them against the corresponding minimum inhibitory concentration and binding affinity values.

Results: Compared to the antimicrobial activity, the dicoumarol derivatives with electron withdrawing substituents, CL, NO2, and CF3 showed an inverse correlation; whereas, the opposite was observed with electron donating compounds such as OH, OMe, and amine groups. Based on the interactions of dicoumarol at the active site, an “aromatic donor-acceptor” relationship was proposed as the method of action for this drug. Furthermore, substituent positioning on the benzene ring was found to exert a greater effect on the binding affinity, speculating that the mechanism of action is two characteristics based, needing, both, the proper aromatic pi-pi interaction for stabilization and direct binding to the OH group in the Tyrosine residue, affected by the steric hindrance.

Conclusion: This foundational review can enhance productivity sought by the pharmaceutical agency to use combinational chemistry to increase the efficiency to discover new hits in the synthesis of dicoumarol drugs against Staph infection.

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<![CDATA[Current Challenges and Updates on the Therapy of Fungal Infections]]>https://www.eurekaselect.comarticle/98674 <![CDATA[Retinoic Acid and the Gut Microbiota in Alzheimer’s Disease: Fighting Back-to-Back?]]>https://www.eurekaselect.comarticle/97507Background: There is growing evidence that the gut microbiota may play an important role in neurodegenerative diseases such as Alzheimer’s disease. However, how these commensals influence disease risk and progression still has to be deciphered.

Objective: The objective of this review was to summarize current knowledge on the interplay between gut microbiota and retinoic acid. The latter one represents one of the important micronutrients, which have been correlated to Alzheimer’s disease and are used in initial therapeutic intervention studies.

Methods: A selective overview of the literature is given with the focus on the function of retinoic acid in the healthy and diseased brain, its metabolism in the gut, and the potential influence that the bioactive ligand may have on microbiota, gut physiology and, Alzheimer’s disease.

Results: Retinoic acid can influence neuronal functionality by means of plasticity but also by neurogenesis and modulating proteostasis. Impaired retinoid-signaling, therefore, might contribute to the development of diseases in the brain. Despite its rather direct impact, retinoic acid also influences other organ systems such as gut by regulating the residing immune cells but also factors such as permeability or commensal microbiota. These in turn can also interfere with retinoid-metabolism and via the gutbrain- axis furthermore with Alzheimer’s disease pathology within the brain.

Conclusion: Potentially, it is yet too early to conclude from the few reports on changed microbiota in Alzheimer’s disease to a dysfunctional role in retinoid-signaling. However, there are several routes how microbial commensals might affect and might be affected by vitamin A and its derivatives.

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<![CDATA[Multimodalities Imaging of Immunoglobulin 4-related Cardiovascular Disorders]]>https://www.eurekaselect.comarticle/95848 <![CDATA[Can IL-33 and Endocan be New Markers for Retinopathy of Prematurity?]]>https://www.eurekaselect.comarticle/97520Background: Retinopathy of Prematurity (ROP) is a pathophysiologic condition of the retina due to abnormal proliferation of retinal vessels.

Objective: The study aimed too ascertain the importance of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), interleukin-33 (IL-33) and endocan in the diagnosis and follow-up of ROP.

Methods: This prospective cohort study was conducted in the neonatal intensive care unit (NICU) of Health Science University, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey, between February 2017 and August 2018. Preterm infants (gestational age (GA) of ≤32 weeks and birth weight of ≤1500 gr), diagnosed ROP were included in the study. VEGF, IGF-1, IL-33 and endocan levels were evaluated in the cord blood and in the serum before and after treatment of infants in the ROP and control groups.

Results: A final number of 146 infants were included in the study. During the study period, 73 infants were identified as the ROP group, and 73 infants were allocated as the control group. In the ROP group, the cord blood VEGF value was higher than the control group (p <0.05). However, IGF-1 levels in the cord blood were lower in the ROP group than control (P<0.05). IL-33 and endocan values in the cord blood were similar in both control and ROP groups (p>0.05). Although serum levels of IL-33, VEGF and endocan were higher before laser treatment, these biomarkers decreased significantly after laser treatment (p <0.05).

Conclusion: We determined that serum IL-33 and endocan levels might be suggested as sensitive novel markers for the prediction of severe ROP.

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<![CDATA[Recent Advances in Azole Based Scaffolds as Anticandidal Agents]]>https://www.eurekaselect.comarticle/93109Aim: The present review aims to explore the development of novel antifungal agents, such as pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and other aspects that involve drug-drug interactions of the azole antifungal agents.

Introduction: Fungal infections in critically ill and immune-compromised patients are increasing at alarming rates, caused mainly by Candida albicans an opportunistic fungus. Despite antifungal annihilators like amphotericin B, azoles and caspofungin, these infections are enormously increasing. The unconventional increase in such patients is a challenging task for the management of antifungal infections especially Candidiasis. Moreover, problem of toxicity associated with antifungal drugs on hosts and rise of drug-resistance in primary and opportunistic fungal pathogens has obstructed the success of antifungal therapy.

Conclusion: Hence, to conflict these problems new antifungal agents with advanced efficacy, new formulations of drug delivery and novel compounds which can interact with fungal virulence are developed and used to treat antifungal infections.

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<![CDATA[Does the Development of Vaccines Advance Solutions for Tuberculosis?]]>https://www.eurekaselect.comarticle/94790Background: Mycobacterium tuberculosis (Mtb) is considered as one of the most efficacious human pathogens. The global mortality rate of TB stands at approximately 2 million, while about 8 to 10 million active new cases are documented yearly. It is, therefore, a priority to develop vaccines that will prevent active TB. The vaccines currently used for the management of TB can only proffer a certain level of protection against meningitis, TB, and other forms of disseminated TB in children; however, their effectiveness against pulmonary TB varies and cannot provide life-long protective immunity. Based on these reasons, more efforts are channeled towards the development of new TB vaccines. During the development of TB vaccines, a major challenge has always been the lack of diversity in both the antigens contained in TB vaccines and the immune responses of the TB sufferers. Current efforts are channeled on widening both the range of antigens selection and the range of immune response elicited by the vaccines. The past two decades witnessed a significant progress in the development of TB vaccines; some of the discovered TB vaccines have recently even completed the third phase (phase III) of a clinical trial.

Objective: The objectives of this article are to discuss the recent progress in the development of new vaccines against TB; to provide an insight on the mechanism of vaccine-mediated specific immune response stimulation, and to debate on the interaction between vaccines and global interventions to end TB.

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<![CDATA[Antimicrobial Stewardship in the Neonatal Intensive Care Unit: An Update]]>https://www.eurekaselect.comarticle/95878 <![CDATA[Closed-loop Neuropharmacology for Epilepsy: Distant Dream or Future Reality?]]>https://www.eurekaselect.comarticle/89007 <![CDATA[Recent Advances and Challenges in Steroid Metabolomics for Biomarker Discovery]]>https://www.eurekaselect.comarticle/86827

Methods: We have performed an extensive literature search applying various bibliographic databases for peer-reviewed articles concentrating on the applications of hyphenated techniques and pattern recognition methods incorporated into the steroid metabolomic approach for biomarker discovery.

Results: The review discusses strengths, challenges and recent developments in steroidbased metabolomics. We present methods of sample collection and preparation, methods of separation and detection of steroid hormones in biological material, data analysis, and interpretation as well as examples of applications of steroid metabolomics for biomarker discovery (cancer, mental and central nervous system disorders, endocrine diseases, monitoring of drug therapy and doping control).

Conclusion: Information presented in this review will be valuable to anyone interested in the application of metabolomics for biomarker discovery with a special emphasis on disorders of steroid hormone synthesis and metabolism.]]> <![CDATA[Fungal Bioactive Compounds in Pharmaceutical Research and Development]]>https://www.eurekaselect.comarticle/91213

Methods: We undertook structured searches of bibliographic databases of peer-reviewed research literature which pertained to natural products, medicinal chemistry of natural products and drug discovery from fungi. With the strategic improvement in screening and identification methods, fungi are still a potential resource for novel chemistries. Thus the searches also comprised of bioactive agents from fungi isolated or derived from special ecological groups and lineages. To find different molecules derived or isolated from fungi under clinical studies, clinical trial data from the NIH as well as from pharmaceutical companies were also explored. This comprised of data wherein the pharmaceutical industries have acquired or licensed a fungal bioactive compound for clinical study or a trial.

Results: Natural product chemistry and medicinal chemistry continue to play an important role in converting a bioactive compound into therapeutic moieties or pharmacophores for new drug development.

Conclusion: Thus one can say fungal bioactive compounds are alive and well for development into new drugs as novel ecological groups of fungi as well as novel chemistries are being uncovered. This review further emphasizes the collaboration of fungal biologists with chemists, pharmacologists and biochemists towards the development of newer drugs for taking them into the drug development pipeline.]]> <![CDATA[Screening of Natural Lead Molecules Against Putative Molecular Targets of Drug-resistant Cryptococcus spp: An Insight from Computer-aided Molecular Design]]>https://www.eurekaselect.comarticle/95944 <![CDATA[Virtual Screening for the Development of New Effective Compounds Against Staphylococcus aureus]]>https://www.eurekaselect.comarticle/89315 <![CDATA[Current Limitations in the Treatment of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Future Perspective of Polymeric Carriers]]>https://www.eurekaselect.comarticle/88708 <![CDATA[Early Detection of Central Nervous System Relapse of Pediatric Leukemia with Measurement of Optic Nerve Sheath Diameter on MRI]]>https://www.eurekaselect.comarticle/94567

Objective: To determine if Magnetic Resonance Imaging (MRI) findings of optic nerves should contribute to early detection of CNS relapse in pediatric leukemia.

Methods: Twenty patients (10 boys, 10 girls; mean age 8,3 years, range 4-16 years) with proven CNS relapse of leukemia followed up between 2009 and 2017 in our institution were included. Orbital MRI exams performed before and during CNS relapse were reviewed retrospectively. Forty optic nerves with Optic Nerve Sheaths (ONS) and Optic Nerve Heads (ONH) were evaluated on fat-suppressed T2-weighted TSE axial MR images. ONS diameter was measured from the point 10 mm posterior to the globe. ONS distension and ONH configuration were graded as 0, 1 and 2.

Results: Before CNS relapse, right mean ONS diameter was 4.52 mm and left was 4.61 mm which were 5.68 mm and 5.66 mm respectively during CNS relapse showing a mean increase of 25% on right and 22% on left. During CNS relapse, ONS showed grade 0 distension in 15%, grade 1 in 60%, grade 2 in 25% and ONH demonstrated grade 0 configuration in 70%, grade 1 in 25% and grade 2 in 5% of the patients.

Conclusion: MRI findings of optic nerves may contribute to diagnose CNS relapse by demonstrating elevated intracranial pressure in children with leukemia.]]> <![CDATA[A Hybrid Approach for Sub-Acute Ischemic Stroke Lesion Segmentation Using Random Decision Forest and Gravitational Search Algorithm]]>https://www.eurekaselect.comarticle/88436

Objective: The main objective of this paper is to segment the ischemic stroke lesions in Magnetic Resonance (MR) images in the presence of other pathologies like neurological disorder, encephalopathy, brain damage, Multiple sclerosis (MS).

Methods: In this paper, we utilize a hybrid way to deal with segment the ischemic stroke from alternate pathologies in magnetic resonance (MR) images utilizing Random Decision Forest (RDF) and Gravitational Search Algorithm (GSA). The RDF approach is an effective machine learning approach.

Results: The RDF strategy joins two parameters; they are; the number of trees in the forest and the number of leaves per tree; it runs quickly and proficiently when dealing with vast data. The GSA algorithm is utilized to optimize the RDF data for choosing the best number of trees and the number of leaves per tree in the forest.

Conclusion: This paper provides a new hybrid GSA-RDF classifier technique to segment the ischemic stroke lesions in MR images. The experimental results demonstrate that the proposed technique has the Root Mean Square Error (RMSE), Mean Absolute Percentage Error (MAPE), and Mean Bias Error (MBE) ranges are 16.5485 %, 7.2654 %, and 2.4585 %individually. The proposed RDF-GSA algorithm has better precision and execution when compared with the existing ischemic stroke segmentation method.]]> <![CDATA[Tuberculosis and HIV Coinfection–the Challenge in the Prevention, Detection and Treatment of Tuberculosis]]>https://www.eurekaselect.comarticle/91201

Objective: In this review we focused on the challenges of epidemiological and clinical feature of tuberculosis presented by the HIV coinfection.

Method: The article consists of a summary of the most important effects presented by the HIV coinfection on epidemiological and clinical feature of tuberculosis. The article analyzes and summary the causes for these challenges.

Results: The major challenges to strategy of TB control and clinical feature of TB-HIV coinfection are presented in this paper.

Conclusion: HIV/TB co-infection is synergic, interactive and reciprocal with significant impact. The infection of HIV and Mtb affect each other and the breakdown the immune function in TB/HIV coinfected individual. HIV infection has changed the strategy of TB control, however HIV increases global burden of TB, the reduction in the TB incidence rate is far from sufficient. Atypically clinical manifestations in TB/HIV co-infected patients and increased MDR-TB and XDR-TB contribute to the challenges in the diagnosis and treatment. Increased complexity of managing patients requires expertise in the clinical m knowledge. The focused efforts to control HIV-related TB are of great urgency. These findings will provide insight into the prevention, detection and treatment of tuberculosis and will guide advances towards tuberculosis control.]]> <![CDATA[Nanoneuromedicines for Neurodegenerative Diseases]]>https://www.eurekaselect.comarticle/87337

Conclusion: In this article, a comprehensive overview of the application of nanoneuromedicines in neurodegenerative diseases such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) is provided.]]> <![CDATA[Implications of Nanotechnology in Healthcare]]>https://www.eurekaselect.comarticle/87816

Conclusion: Finally, conclusion with the future scope and challenges of nanotechnology in health will be described and discussed.]]> <![CDATA[FDG-PET Scan in Sarcoidosis: Clinical and Imaging Indications]]>https://www.eurekaselect.comarticle/91258

Discussion: The areas of the body usually affected by sarcoidosis are lungs, skin, or lymph nodes; pulmonary and mediastinal involvement is seen in over of 90% of patients. Less commonly eyes, liver, heart, and brain are involved. Any organ, however, can be affected.

Early diagnosis of sarcoidosis can be difficult due to few signs and symptoms in its early stages, and when disease does occur, it may mimic other pathologies, and is made up with chest X-ray, Computed Tomography (CT)-High Resolution CT (HRCT), gallium scans. Fluoro-Deoxy Glucose– Positron Emission Tomography (FDG-PET) is another useful tool to assess the extent of disease and has a potential to evaluate the clinical management of patients responding or not to the treatment.

Conclusion: In this review, we would summarize in brief the clinical indications of PDG-PET in sarcoidosis and report the imaging features of the main organs involved in this disease.]]> <![CDATA[LC-MS for Simultaneous Determination of Vancomycin and Teicoplanin in Patient Plasma and its Application to Therapeutic Drug Monitoring]]>https://www.eurekaselect.comarticle/92090

Objective: The study aimed at developing and validating a Liquid Chromatography-Mass Spectrometry (LC-MS) method for simultaneous determination and therapeutic drug monitoring of vancomycin and teicoplanin in patients with severe infection.

Method: Plasma was processed by protein precipitation extraction. The analytes were separated on a C18 column by gradient elution with 0.1% formic acid and acetonitrile as mobile phase and measured by electrospray ionization source in positive selective ion monitoring mode at m/z 724.7 (vancomycin), 940.7 (teicoplanin) and 329.0 (bergenin). The plasma samples (104) were obtained from patients who were taking vancomycin or teicoplanin for further analysis.

Results: The calibration curves were linear within the range of 0.25–40 µg/mL for vancomycin, and 0.5-40 µg/mL for teicoplanin. Either inter- or intra-day precision was less than 10.01 %. The extraction recoveries ranged from 89.99 to 94.29% for vancomycin and from 39.83 to 40.16 % for teicoplanin. Vancomycin and teicoplanin in plasma were stable at various storage conditions. The measured mean trough concentrations were 12.313 µg/mL for vancomycin and 8.765 µg/mL for teicoplanin.

Conclusion: This method was successfully applied to therapeutic drug monitoring of vancomycin and teicoplanin in patients. It is with great clinic value for monitoring and predicting the individual response of patients under treatment.]]> <![CDATA[Cerebrospinal Fluid, Brain Electrolytes Balance, and the Unsuspected Intrinsic Property of Melanin to Dissociate the Water Molecule]]>https://www.eurekaselect.comarticle/92788

Conclusion: The recent hypothesis based on glucose and ATP as sources of energy presents numerous contradictions and controversies. The discovery of the unsuspected intrinsic ability of melanin to dissociate and reform water molecules, similar to the role of chlorophyll in plants, was confirmed in the study of ISF and CSF biology.]]> <![CDATA[Medication Conveyance Through Nose: Factors Affecting and Novel Applications]]>https://www.eurekaselect.comarticle/89937

Discussion: Nasal route provides a unique micro-environment due to absence of deactivating enzymes and abundant vascular tissues which bring about direct systemic display, along with these lines abstaining the first pass hepatic metabolism.

Conclusion: The present article provides in-depth information about the physicochemical parameters associated with drug absorption in nasal mucosa and factors influencing it. The pathways and mechanisms associated with nasal drug uptake alongside current pharmaceutical applications are additionally summarized.]]> <![CDATA[The Role of VE-cadherin in Blood-brain Barrier Integrity Under Central Nervous System Pathological Conditions]]>https://www.eurekaselect.comarticle/88756 <![CDATA[Inflammatory Events Following Subarachnoid Hemorrhage (SAH)]]>https://www.eurekaselect.comarticle/89668

Mechanisms of secondary brain injury are of utmost interest not only to scientists, but also to clinicians, as they often provide possibilities for translational approaches as well as distinct time windows for tailored treatment options.

In this article, we review secondary brain injury due to inflammatory changes, that occur on cellular, as well as on molecular level in the various different compartments of the CNS: the brain vessels, the subarachnoid space, and the brain parenchyma itself and hypothesize about possible signaling mechanisms between these compartments.]]> <![CDATA[Serum Tryptophan, Tryptophan Catabolites and Brain-derived Neurotrophic Factor in Subgroups of Youngsters with Autism Spectrum Disorders]]>https://www.eurekaselect.comarticle/91865

Objective: This study aimed to delineate whether ASD subgroups or characteristics show aberrations in tryptophan and brain-derived neurotrophic factor (BDNF) metabolism.

Methods: 65 individuals with ASD (diagnosed according to ICD criteria) and 30 healthy control patients were included. Measured were serum levels of tryptophan, kynurenine (KYN), kynurenic acid (KA), quinolinic acid (QA), BDNF and PRO-BDNF and total blood 5-HT and 5-OH-tryptophan (5-HTP).

Results: Elevated BDNF levels and lower tryptophan and KA levels were characteristics of both childhood autism and intellectual disability disorder, whilst elevated tryptophan and lower 5-HT synthesis were hallmarks of Asperger syndrome. A pathological MRI was associated with elevated tryptophan and lowered KA. Abnormal EEG results and dysmorphology were both associated with an elevated BDNF/ PRO-BDNF ratio. Any brain pathology and gastro-intestinal symptoms were accompanied by lowered KA.

Conclusions: Increased BDNF production and changes in the metabolism of tryptophan are associated with many ASD characteristics, showing particularly strong associations with childhood autism and Intellectual and Developmental Disabilities. Peripheral BDNF and tryptophan metabolism appear to take part in the pathophysiology of autism spectrum disorders and their phenotypes.]]> <![CDATA[Community-Acquired Pneumonia in Children]]>https://www.eurekaselect.comarticle/91204

Objective: To provide an update on the evaluation, diagnosis, and treatment of community-acquired pneumonia in children.

Methods: A PubMed search was completed in Clinical Queries using the key term “communityacquired pneumonia”. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. Patents were searched using the key term “community-acquired pneumonia” from www.google.com/patents, http://espacenet.com, and www. freepatentsonline.com.

Results: Generally, viruses, notably respiratory syncytial virus, are the most common cause of community- acquired pneumonia in children younger than 5 years. Streptococcus pneumoniae is the most common bacterial cause across all age groups. Other important bacterial causes in children younger than 5 years include Haemophilus influenzae, Streptococcus pyogenes, Staphylococcus aureus, and Moraxella catarrhalis. In children 5 years or older, in addition to S. pneumoniae, other important bacterial causes include Mycoplasma pneumoniae and Chlamydophila pneumonia. In the majority of cases, bacterial and viral pneumonia cannot be reliably distinguished from each other on clinical grounds. In practice, most children with pneumonia are treated empirically with antibiotics; the choice of which depends on the patient’s age and most likely pathogen. Recent patents related to the management of community-acquired pneumonia are discussed.

Conclusion: In previously healthy children under the age of 5 years, high dose amoxicillin is the treatment of choice. For those with type 1 hypersensitivity to penicillin, clindamycin, azithromycin, clarithromycin, and levofloxacin are reasonable alternatives. For children with a non-type 1 hypersensitivity to penicillin, cephalosporins such as cefixime, cefprozil, cefdinir, cefpodoxime, and cefuroxime should be considered. In previously healthy children over the age of 5 years, macrolides such as azithromycin and clarithromycin are the drugs of choice.]]> <![CDATA[Hyaluronidases: A Therapeutic Enzyme]]>https://www.eurekaselect.comarticle/91371

Conclusion: In this review an attempt was made to summarize the physiological, adjuvaent and therapeutic significance of hyaluronidase enzymes from different animal sources.]]> <![CDATA[Is there a Relationship Between Keros Classification of Olfactory Fossae Depth, Septal Deviation Angle and the Distance Between Infraorbital Foramens?]]>https://www.eurekaselect.comarticle/81294

Methods: Computerized Tomography (CT) images of 315 adult subjects were used. Paranasal sinus dimensions; Keros classification of olfactory fossae, length of Crista Galli (CG), the distance between IOFs (ZP), The distance between inferior part of crista galli and basal-inferior part of the nasal septum at the midline (CG-Sbasal) (XY), ZP/XY ratio, septal deviation side and angle were measured.

Results: Keros type I was detected in males (50.3%) and Keros type II was detected in females (59.5%) mainly. In females, Keros type was highly related to the males. Both right-deviated and left deviated subjects, Keros type II (49.7% and 54.3% respectively) was the most detected Keros-type for olfactory fossae. Higher ethmoid sinus-height, maxillary sinus-width; and lower maxillary sinusheight values were related to higher Keros types. As IOFs (ZP) distance increased, Keros type also increased.

Conclusion: When Endoscopic Sinus Surgery (ESS) is performed in patients having nasal septal deviation, surgeons should be careful for Keros type II olfactory fossae to avoid intracranial penetration. If possible, navigation systems should be used in these patients.]]> <![CDATA[The Clinical and Immunological Features of Patients with Primary Antibody Deficiencies]]>https://www.eurekaselect.comarticle/89704

Methods: A total of 461 patients (311 males and 150 females) with PADs enrolled in the retrospective cohort study and for all patients’ demographic information, clinical records and laboratory data were collected to investigate clinical complications.

Results: The most prevalent first presentations of immunodeficiency were respiratory tract infections in 63.5% and chronic diarrhea in 17.2%. Common variable immune deficiency (CVID) patients had a higher diagnostic delay than class switching defect (CSD), and agammaglobulinemia. Among the noninfectious complications, autoimmunity (26.2%), and splenomegaly (23.4%) were the most common. Lymphadenopathy was higher in CSD patients than other PADs, while splenomegaly, hepatomegaly, autoimmunity and bronchiectasis were more common in CVID patients than others. Atopic manifestations were mostly recorded in patients with selective IgA deficiency. Malignancy was only reported in 5.8% of patients with CVID. There was a higher prevalence of autoimmune manifestations in CVID comparing to other PADs.

Conclusion: PADs are relatively rare diseases and these patients have a variety of first clinical manifestations, such as diverse infections, autoimmunity, lymphoproliferation, allergy, enteropathy and malignancy. Practitioner’s awareness about the heterogeneous presentations of PAD disorders is poor, therefore patients often are lately diagnosed, and they are complicated with several clinical complications before the certain diagnosis.]]> <![CDATA[Recent Advances in Pathophysiology of Traumatic Brain Injury]]>https://www.eurekaselect.comarticle/84044

Methods: Initial damage force results in Primary brain injury, causing tissue destruction and distortion in the early post-injury period. These secondary injuries from TBI cause changes in cell performance and dissemination of trauma via activities like free-radical generation, depolarization, and formation of edema, excitotoxicity, and disruption of blood brain barrier, calcium homeostasis, and intracranial hematoma. The expectation for developing effect in TBI sufferers is the best knowledge of these activities and enhancement of remedies that restrict secondary brain damage.

Results: The focal point of this study is on knowing the complex outburst of secondary impairments and studying the pathophysiology of TBI which provides alternative treatment benefits.

Conclusion: While injured persons demonstrate dissimilar levels of harm and every case is novel with specific recovery profiles, this article strengthens the recent pathophysiological sight of TBI mainly attention on oxidative stress, excitotoxicity, cerebral oxygenation and cerebral blood flow (CBF), development of edema, and inflammatory activities. For initial research acknowledgment of these recurring factors could permit clarification of possible beneficial targets.]]> <![CDATA[Neonatal Systemic Thrombosis: An Updated Overview]]>https://www.eurekaselect.comarticle/87985 <![CDATA[Frontier View on Nanotechnological Strategies for Neuro-therapy]]>https://www.eurekaselect.comarticle/88904

Objective: Nanotechnology based approaches (NBA) favours transcytosis-mediated delivery of nanoparticles to the brain by crossing the BBB. The last five years have witnessed the successful applications of NBA to treat neurological disorders. It is expected that the development of novel NBA will result in important insights on the brain mechanisms, and eventually provide better medical care to patients suffering from neurological disorders.

Conclusion: This review introduces the emerging work in this area and summarizes the successful NBA used in recent past for treating various neurological disorders ike Alzheimer’s disease, Parkinson's disease, amyotrophic lateral sclerosis, meningitis and glioblastoma.]]> <![CDATA[Colored Representation of Brain Gray Scale MRI Images to Potentially Underscore the Variability and Sensitivity of Images]]>https://www.eurekaselect.comarticle/83162

Background: In daily health care environments, medical scanners are being used to generate gray scale images of anatomical structures.

Method: Severity of diseases is determined from this luminance component only. Irrefutably, if this high dimensional gray scale, medical data is visualized in colored versions, the definitive and more accurate the pathological assessment process will be. A number of methods have been reported to represent brain Magnetic Resonance Images (MRI) data in color with the cost of computational complexity. In this research work, an efficient method of colorization using frequencies from visible range of color spectrum, has been proposed to embody the variations and sensitivity of the brain MRI images.

Conclusion: Side by side, visual comparison based on multiple MRI sequences of identical subjects, by domain experts, proved adequate success and fruitfulness of the story.]]> <![CDATA[Tuberculosis Detection from Chest Radiographs: A Comprehensive Survey on Computer-Aided Diagnosis Techniques]]>https://www.eurekaselect.comarticle/86891

Discussion: The research on the development of CADx systems started four decades ago, and a large number of CADx systems have been developed till date. However, no independent survey focussing on the advancements in these systems has been presented. This paper fills this gap by consolidating the advancements and presents a comprehensive survey of CADx systems for TB detection developed till date with a focus on their underlying principles. It also discusses a practical model using which CADx systems can be used for screening TB in places where medical facilities and experts are not adequately available.

Conclusion: The paper also presents an overview of the current state of deep learning-based CADx systems. The development of these systems will remain in focus in the near future and will improve state-of-the-art performance in various medical domains.]]> <![CDATA[Repositioning Drugs for Rare Immune Diseases: Hopes and Challenges for a Precision Medicine]]>https://www.eurekaselect.comarticle/85542 Discovery and development of new therapies for rare diseases has long been de-privileged due to the length and cost of the processes involved. Interest has increased due to stimulatory regulatory and supportive reimbursement environments enabling viable business models.

Advancements in biomedical and computational sciences enable the development of rational, designed approaches for identification of novel indications of already approved drugs allowing faster delivery of new medicines. Drug repositioning is based either on clinical analogies of diseases or on understanding of the molecular mode of drug action and mechanisms of the disease. All of these are the basis for the development of precision medicine.]]> <![CDATA[A Review of Epidemic Models Related to Meteorological Factors]]>https://www.eurekaselect.comarticle/84192

Objective: Review various epidemic models related to meteorological factors.

Results: We discuss two kinds of epidemic models: deterministic models and stochastic models. The deterministic models include switched SIR model, seasonal SIR model, periodic SEIR system and seasonal SEIQR model. And the stochastic models involve multiple regression models, auto-regressive moving average model, autoregressive distributed lag model, time series Poisson regression models and generalized additive models. Furthermore, we introduce the latest applications of these models, respectively.

Conclusion: In our work, these deterministic models and stochastic models can successfully predict the diseases outbreak using meteorological factors, and they all are now widely used in the field. However, few meteorological factors are used in these models. With the development of Meteorological Science, large amounts of Meteorological factor data will be obtained. More key Meteorological factors causing an epidemic will be identified. Therefore, in the future, more key meteorological factors will be considered in models and they will further improve the accuracy of the forecast.]]> <![CDATA[A Rare Case of Tricuspid Valve Endocarditis Caused by Enterococcus Gallinarum in a Patient with Recurrent Urinary Tract Infection]]>https://www.eurekaselect.comarticle/88885

Methods: Echocardiography was a useful diagnostic method in the present case, showing the vegetation on the tricuspid valve.

Results: This case is notable because tricuspid valve endocarditis due to Enterococcus Gallinarum is a rare clinical condition and improves knowledge of disease and management in patients with endocarditis.]]> <![CDATA[Metals and Parkinson's Disease: Mechanisms and Biochemical Processes]]>https://www.eurekaselect.comarticle/87134 <![CDATA[Perspectives of Medieval Persian Medicine on Multiple Sclerosis]]>https://www.eurekaselect.comarticle/85050

Material & Method: This paper represents a comprehensive search through TPM texts and manuscripts with the intention to seek possible clues on MS from potentially valuable age-old resources. We predominantly focused our search on the works of five eminent physicians of Medieval Persia: Avicenna (980-1037 AD), Haly Abbas (949-982 AD), Rhazes (865-925 AD), Averroes (1126-1198 AD) and Jorjani (1042-1137 AD).

Results: In this paper, the authors attempt a theory and conclude with high probability that a conjunction of a series of signs, symptoms found in TPM texts under the terms khadar, isterkha and falej form the symptoms and the disease pattern of modern day MS. This theory draws upon existent similarities in terms of disease pathology, disease patterns and predisposing factors seen between MS and the related morbidities within Persian Medicine.

Conclusion: We recommend further examinations of such potentially valuable long-standing resources, examining the diagnoses and treatments as set forth by Persian Medicine through international collaboration within the global scientific community.]]> <![CDATA[Dementia Etiologies and Remedies in Traditional Persian Medicine; A Review of Medicinal Plants and Phytochemistry]]>https://www.eurekaselect.comarticle/85237

Objective: The aim of this study was to determine the etiologies of dementia according to the Traditional Persian Medicine scientists' viewpoint and introduce their recommended herbal remedies for this disease.

Method: The authors explored six main Traditional Persian Medicine textbooks for the disease of dementia, its etiologies and related recommended herbal treatments. Two main keywords of “Lisarghes” and “Nesyan” were searched for this purpose. Medical databases, including PubMed, Scopus, Google Scholar, and Science Direct were searched for related articles published between 1966 and 2016 to review the pharmacological components and active ingredients of suggested herbal medicines.

Results: According to the Traditional Persian Medicine, dementia is resulted from brain dystemperament, a condition caused by cold and moist or cold and dry tempers. To treat this disease, Traditional Persian scientists recommended various herbal remedies. Current studies have demonstrated that some of these medicinal plants have beneficial effects for the aforementioned disease, including acetyl cholinesterase inhibitory function, neuroprotective effects, and memory enhancing role.

Conclusion: The Traditional Persian Medicine literature suggested different herbal remedies for treating dementia. Modern studies support the usefulness of some of these medicines. However, the effect of a large number of these remedies has remained unexamined, a matter which needs to be investigated in future researches.]]> <![CDATA[Antibiotics Associated Disorders and Post-biotics Induced Rescue in Gut Health]]>https://www.eurekaselect.comarticle/87602 <![CDATA[Imaging the Role of Inflammation in Mood and Anxiety-related Disorders]]>https://www.eurekaselect.comarticle/87078

Methods: This review summarized clinical and translational work demonstrating the impact of peripheral inflammation on brain regions and neurotransmitter systems relevant to both reward and threat sensitivity, with a focus on neuroimaging studies involving administration of inflammatory stimuli. Recent translation of these findings to further understand the role of inflammation in mood and anxiety-related disorders is also discussed.

Results: Inflammation was consistently found to affect basal ganglia and cortical reward and motor circuits to drive reduced motivation and motor activity, as well as anxiety-related brain regions including amygdala, insula and anterior cingulate cortex, which may result from cytokine effects on monoamines and glutamate. Similar relationships between inflammation and altered neurocircuitry have been observed in MDD patients with increased peripheral inflammatory markers, and such work is on the horizon for anxiety disorders and PTSD.

Conclusion: Neuroimaging effects of inflammation on reward and threat circuitry may be used as biomarkers of inflammation for future development of novel therapeutic strategies to better treat mood and anxiety-related disorders in patients with high inflammation.]]> <![CDATA[Melatonin Treatment Enhances Aβ Lymphatic Clearance in a Transgenic Mouse Model of Amyloidosis]]>https://www.eurekaselect.comarticle/89644

Objective: To confirm and expand our initial finding that Aβ is cleared through the lymphatic system. Lymphatic clearance of metabolic and cellular “waste” products from the brain into the peripheral lymphatic system has been known for a long time. However, except for our prior report, there is no additional experimental data published about Aβ being cleared into peripheral lymph nodes.

Methods: For these experiments, we used a transgenic mouse model (Tg2576) that over-expresses a mutant form of the Aβ precursor protein (APP) in the brain. We examined levels of Aβ in plasma and in lymph nodes of transgenic mice as surrogate markers of vascular and lymphatic clearance, respectively. Aβ levels were also measured in the brain and in multiple tissues.

Results: Clearance of Aβ peptides through the lymphatic system was confirmed in this study. Treatment with melatonin led to the following changes: 1-A statistically significant increase in soluble monomeric Aβ40 and an increasing trend in Aβ42 in cervical and axillary lymph nodes of treated mice. 2- Statistically significant decreases in oligomeric Aβ40 and a decreasing trend Aβ42 in the brain.

Conclusion: The data expands on our prior report that the lymphatic system participates in Aβ clearance from the brain. We propose that abnormalities in Aβ clearance through the lymphatic system may contribute to the development of cerebral amyloidosis. Melatonin and related indole molecules (i.e., indole- 3-propionic acid) are known to inhibit Aβ aggregation although they do not reverse aggregated Aβ or amyloid fibrils. Therefore, these substances should be further explored in prevention trials for delaying the onset of cognitive impairment in high risk populations.]]> <![CDATA[Nanoemulsion for the Effective Treatment and Management of Anti-tubercular Drug Therapy]]>https://www.eurekaselect.comarticle/83246

Methods: The conventional drug therapy employed for the treatment of tuberculosis is not highly satisfactorily owing to low oral bioavailability of the drugs. The evolution of nano-technology recently in few decades has completely revolutionized the treatment of diverse diseases and so is the tuberculosis. Nanotechnology not only possesses enormous potential for improving the biopharmaceutical performance, but also allows the delivery of therapeutic molecules to the desired site of action. Diverse types of nanocarriers have been employed for the treatment of tuberculosis infections. In this regard, nanoemulsions are considered as one of the promising alternatives for augmenting the bioavailability of the antitubercular drugs through oral route for improving their therapeutic efficacy.

Conclusion: The nanoemulsion loaded with antitubercular drugs can easily cross the biological barriers to reach the systemic circulation and consequently in the target for reducing the load of Mycobacterium tuberculosis. Besides, the lipidic nature of such systems facilitates targeting of the drugs to the lymph nodes, thus improves drug bioavailability and reduction of the dosing frequency. In lieu of this, the present article compiles the basics of nanoemulsions in brief along with an updated account on their applications in delivering antitubercular drugs for enhanced immunization. Moreover, overview of patent literature published in this area has also been included in the manuscript. ]]> <![CDATA[Optimization of Drug Safety Profile in Inflammatory Bowel Disease Through a Personalized Approach]]>https://www.eurekaselect.comarticle/83658 <![CDATA[Synthesis of New α-Amino Phosphonates Containing 3-Amino-4(3H) Quinazolinone Moiety as Anticancer and Antimicrobial Agents: DFT, NBO, and Vibrational Studies]]>https://www.eurekaselect.comarticle/84441

Material and Method: The structures of the synthesized compounds are confirmed by FT-IR, 1H NMR, 13C NMR, 31P NMR and MS spectral data. The synthesized compounds show significant antimicrobial and also remarkable cytotoxicity anticancer activities against liver carcinoma cell line (HepG2). Density functional theory (DFT) was performed to study the effect of the molecular and electronic structure changes on the biological activity.

Results: It was found that the electronic structure of the substituents affects on the reaction yield. The electron withdrawing substituent, NO2 group 3b, on the aromatic aldehydes gave a good yield more than the electron donating substituent, OH group 3c. The electron deficient on the carbon atom of the aldehydic group may increase the interaction of the Lewis acid (Cu(OTf)2) and the Lewis base (imine nitrogen), and accordingly, facilitate the formation of imine easily, which is attacked by the nucleophilic phosphite species to give the α- aminophosphonates.

Conclusion: The newly synthesized compounds exhibit a remarkable inhibition of the growth of Grampositive, Gram-negative bacteria and fungi at low concentrations. The cytotoxicity of the synthesized compounds showed a significant cytotoxicity against the liver cancer cell line (HepG 2). Also, it was shown from the quantum chemical calculations that the electron-withdrawing substituent increases the biological activity of the α-aminophosphonates more than the electron donating group which was in a good agreement with the experimental results. Also, a good agreement between the experimental FT-IR and the calculated one was found.]]> <![CDATA[MG17, A Novel Triazole Derivative Abrogated Neuroinflammation and Related Neurodegenerative Symptoms in Rodents]]>https://www.eurekaselect.comarticle/85875

Methods: We have done some preliminary behavioral studies to shortlist the derivatives using rodent models of peripheral nerve injury in our earlier publication and now we extended our screening studies to explore the test compounds efficacy on other related peripheral neurological disorders such as Streptozotocin- induced diabetic peripheral neuropathy (DPN) and methyl mercury (MeHg) induced neurodegeneration in rats. Pro-inflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were quantified with RT-qPCR studies and histopathology studies were performed taking tissue samples from MeHg induced neurodegeneration rats. The effect of MG17 was assessed on local and acute inflammation through carrageenan-induced rat paw edema model.

Results: We observed the reduction in nociceptive responses in DPN rats. Pain threshold was reduced greater than 50% in various pain assessment modules. Upregulated pro-inflammatory cytokines which are thought to have a prominent role in neuroinflammation was controlled near to normal level quantified by RT-PCR studies. However, MG17 was able to regulate IL-6 and TNF-α but not IL-1β.

Conclusion: Our results clearly suggest the beneficial potential of compound MG17 through inhibition of pro-inflammatory cytokines upregulation. MG17 could be an intriguing therapeutic approach in diabetesrelated neuro-pathophysiological conditions.]]> <![CDATA[Advances in Drug Delivery from Nose to Brain: An Overview]]>https://www.eurekaselect.comarticle/85937 <![CDATA[Tuberculosis Treated by Multiple Drugs: An Overview]]>https://www.eurekaselect.comarticle/86980

Objective: The aim of this paper is to introduce readers to the platforms on which Tuberculosis participants interact, to discuss reasons for and risks associated with TB-related activity, and to review research related to the potential impact of individual participation on TB outcomes.

Methods: Research and online content related to Tuberculosis online activity is reviewed, however, the difficulty in accurate prescribing and adhering to these protocols and the emergence of M. tuberculosis strains resistant to multiple drugs and drug-drug interactions that interfere with optimal treatment of Tuberculosis and co-infected patients with the different disease has generated a pressing need for improved Tuberculosis therapies.

Results: Together with the ominous global burden of Tuberculosis, those shortcomings of current medication have contributed to a renewed interest in the development of improved drugs and protocols for the medication of Tuberculosis. This article features obstacles related with the enhanced utilization of existing drugs and difficulties related with the advancement of enhanced products, concentrating on perspectives characteristic in Tuberculosis drug clinical improvement. The participation includes peer support, advocacy, self-expression, seeking and sharing TB information, improving approaches to Tuberculosis data management, and humour.

Conclusion: This article highlights hurdles related to the optimised use of existing drugs and challenges related to the development of improved products, focusing on aspects inherent in Tuberculosis drug clinical development. Concluding comments offer processes for more efficient development of Tuberculosis therapies and increase the quality of life.]]> <![CDATA[Diagnostic Value of the Leukocyte Esterase Test for Early Detection of Pleocytosis in Cerebrospinal Fluid of Patients with Suspected Acute Bacterial Meningitis]]>https://www.eurekaselect.comarticle/82347

Methods: A total of 126 patients with suspected meningitis were enrolled in this prospective study. Microscopic examination (cell count and differential) and leukocyte esterase (LE) rapid strip test were performed on cerebrospinal fluid (CSF) samples. Sensitivity, specificity, positive predictive value and negative predictive value of the LE test were determined.

Results: Fifty-two patients (41%) had pleocytosis in the CSF, while 48 (38%) patients had a positive rapid LE strip test result. The diagnostic accuracy of this test for pleocytosis was translated to a sensitivity of 84.6% (95%CI 71.9, 93.1) and a specificity of 94.5% (95%CI 86.7, 98.5), with an area under the receiver operating curve of 0.88.

Conclusion: The LE strip test, through rapid and accurate determination of CSF pleocytosis, could be considered as an additional test in the diagnosis of bacterial meningitis. It can be tested at bedside and is feasible to do in resource-limited settings.]]> <![CDATA[The Correlations between Postmortem Brain Pathologies and Cognitive Dysfunction in Aging and Alzheimer's Disease]]>https://www.eurekaselect.comarticle/86705

Objective: This study aims to investigate the correlations between the antemortem clinical cognitive performances and the postmortem neuropathological changes in the aging and AD brains collected in a human brain bank in China.

Method: A total of 52 human brains with antemortem cognitive status information [Everyday Cognition (ECog)] were collected through the willed donation program by CAMS/PUMC Human Brain Bank. Pathological changes were evaluated with the “ABC” score following the guidelines of NIA-AA. The clinicopathological relationship was analyzed with correlation analysis and general linear multivariate model.

Results: The general ABC score has a significant correlation with global ECog score (r=0.37, p=0.014) and most of ECog domains. The CERAD score of neuritic plaques (C score) has a significant correlation with global ECog score (r=0.40, p=0.007) and the majority of ECog domains, such as memory (r=0.50, p=0.001), language (r=0.45, p=0.002), visuospatial functions (r=0.31, p=0.040), planning (r=0.35, p=0.021) and organization (r=0.39, p=0.010). The Braak stage of neurofibrillary tangles (NFTs) (B score) has a moderate correlation with memory (r=0.32, p=0.035). The Thal phases of amyloid-β (Aβ) deposits (A score) present no significant correlation with any of ECog domains.

Conclusion: In this study, we verified the correlation of postmortem C and B scores, but not the A score with cognition performance in a collection of samples from the Chinese human brain bank.]]>