Endocannabinoids as Amyloid-Beta (Aβ) Aggregation Inhibitors

The endocannabinoid system, including endogenous cannabinoids and their corresponding receptors, has received extensive attention in the last few years for their neuroprotective effect in the central nervous system. The regulation and metabolism of these molecules are potential therapeutic targets for neurodegenerative diseases such as Alzheimer's disease, which is characterized by Aβ aggregation-induced cell toxicity, inflammation, tau phosphorylation, disruption of neurotransmitters pathways, mitochondrial dysfunction, and oxidative stress. The endocannabinoids, such as 2-AG, AEA, NADA, noladin, OAE, and their main metabolite, arachidonic acid, may be involved in the multiple neuroprotective effects, including excitotoxicity attenuation, oxidative stress reduction, and inflammation prevention through CB1, CB2 receptors as well as other possible pathways, including inhibition of Aβ oligomer formation via interactions with these toxic peptides. However, the interactions of endocannabinoids with Aβ species and their mechanisms have not been fully explored. Therefore, we hypothesized that endocannabinoids might reduce amyloid β-protein deposition and inhibit neuronal cell death through CB1 or other possible pathways. In vitro experiments, including cell studies using two cell lines (HTT22 and CB1-CHO), ThT based kinetic assay, and TEM studies were used to determine the effects of above mentioned five endocannabinoids, arachidonic acid, and a CB1 antagonist to understand the role of endocannabinoid ligands and pathways involved in Aβ-induced neurotoxicity. The results of this study on HT22 cells showed that some, but not all of the endocannabinoids were able to exhibit neuroprotective effects against Aβ-induced toxicity. However, AM251, as a CB1 receptor antagonist, could not reverse this neuroprotection. On the other hand, AM251 was able to inhibit the protective effects of some, but not all, of the endocannabinoids in CB1-CHO cells

COVID-19 and conjunctivitis: A contemporary literature review

Coronavirus disease 2019 (COVID-19) is a viral respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first appearance in December 2019, COVID-19 has been responsible for a number of global outbreaks and has claimed the lives of nearly three million people as of April 2021. High infection rate, loss of taste and smell, fever, cough, and severely adverse effects on the respiratory system have been the chief attributes of the virus. However, SARS-CoV-2 has been linked to other symptoms, many of which are extra-pulmonary or not directly related to the respiratory system. The impact of SARS-CoV-2 on various ophthalmic outcomes has been manifested in many reports and literature tracing the link between COVID-19 and ocular findings in patients suffering from COVID-19. One recurrent case report presented in the literature is related to the presentation of conjunctivitis in COVID-19 patients. Conjunctivitis is a viral infection causing inflammation in conjunctiva, episclera and eyelids resulting in a change of color in eyes, called pink eyes. Swelling, itching, pain, and eye burn are some of the common symptoms. The present study reviews the latest literature on the subject by focusing on the reports of conjunctivitis symptoms in patients with COVID-19

Accommodative spasm as the main manifestation of topical eye contact with insecticide

The patient is a 23-year-old Caucasian male farmer who, after topical eye contact with an insecticide, developed accommodative spasm and blurred vision in one eye. He was treated with frequent doses of 2% homatropine drop and recovered within a week

Viscoelastic properties of multi-walled carbon nanotube/epoxy composites using two different curing cycles

Along with carbon nanotubes (CNT) morphology, impurity, and functionalization, polymer curing cycle is another important factor in determining the mechanical properties of the CNT/polymer composite samples. This work investigates the effect of two different curing cycles on mechanical and thermo-mechanical properties of the nanotube in the composite in order to optimize the curing condition in term of time and temperature. Nanocomposite samples were prepared by mixing multi-wall carbon nanotubes with epoxy resin using sonication method. The mechanical and viscoelastic properties of the resulting composite samples were evaluated by performing tensile and dynamic mechanical thermal analyses (DMTA) test. The results indicate that the mechanical and viscoelastic properties of pure epoxy and composite samples have been affected by the condition curing process. Concerning viscoelastic modeling, the COLE-COLE diagram has been plotted by the result of DMTA tests. These results show a good agreement between the Perez model and the viscoelastic behavior of the composite

Synthesis, optimization, and cell response investigations of natural-based, thermoresponsive, injectable hydrogel: An attitude for 3D hepatocyte encapsulation and cell therapy

For the purpose of developing a 3D vehicle for the delivery of hepatocytes in cell therapy, the improved system of crosslinker and new gelling agent combinations consisting of glycerophosphate and sodium hydrogen carbonate have been employed to produce injectable, thermoresponsive hydrogels based on chitosan and silk fibroin. Adjusting the polymer-to-gelling agent ratio and utilizing a chemical crosslinker developed hydrogel scaffolds with optimal gelling time and pH. Applying sodium hydrogen carbonate neutralizes chitosan while keeping its thermoresponsive characteristics and decreases glycerophosphate from 60% to 30%. Genipin boosts the mechanical properties of hydrogel without affecting the gel time. Due to their stable microstructure and lower amine availability, genipin-containing materials have a low swelling ratio, around six compared to eight for those without genipin. Hydrogels that are crosslinked degrade about half as fast as those that are not. The slowerr degradation of Silk fibroin compared to chitosan makes it an efficient degradation inhibitor in silk-containing formulations. All of the optimized samples showed less than 5% hemolytic activity, indicating that they lacked hemolytic characteristics. The acceptable cell viability in crosslinked hydrogels ranges from 72% to 91% due to the decreasing total salt concentration, which protects cells from hyperosmolality. The pH of hydrogels and their interstitial pores kept most encapsulated cells alive and functioning for 24 h. Urea levels are higher in the encapsulation condition compared to HepG2 cultivated alone, and this may be due to cell-matrix interactions that boost liver-specific activity. Urea synthesis in genipin crosslinked hydrogels increased dramatically from day 1 (about 4 mg dl−1) to day 3 (approximately 6 mg dl−1), suggesting the enormous potential of these hydrogels for cell milieu preparation. All mentioned findings represent that the optimized system may be a promising candidate for liver regeneration

Haematological abnormalities in new onset rheumatoid arthritis and risk of common infections:a population-based study

Objectives To describe the prevalence of haematological abnormalities in individuals with rheumatoid arthritis (RA) at the point of diagnosis in primary care, and the associations between haematological abnormalities, vaccinations and subsequent risk of common infections. Methods We studied 6,591 individuals with newly diagnosed RA between 2004 and 2016 inclusive using the UK Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) primary care database. The prevalence of haematological abnormalities at diagnosis (anaemia, neutropenia and lymphopenia) was established. Cox proportional hazards models were used to evaluate i) the association between each haematological abnormality and time to common infections; ii) the influence of vaccination status (influenza and pneumococcal vaccine) on time to common infections in individuals with RA, compared with a matched cohort of individuals without RA. Results Anaemia was common at RA diagnosis (16.1% of individuals), neutropenia (0.6%) and lymphopenia (1.4%) less so. Lymphopenia and anaemia were associated with increased infection risk (respective hazard ratios (HR) 1.18 (95%CI 1.08-1.29); HR 1.37 (95%CI 1.08-1.73)). There was no evidence of an association between neutropenia and infection risk (HR 0.94 (95%CI 0.60-1.47). Pneumonia was much more common in individuals with early RA compared with controls. Influenza vaccination was associated with reduced risk of influenza-like illness only for individuals with RA (HR 0.58 (95% CI 0.37-0.90). Conclusion At diagnosis, anaemia and lymphopenia, but not neutropenia, increase the risk of common infections in individuals with RA. Our data support the effectiveness of the influenza vaccination in individuals with RA.</p

MARCKS mediates vascular contractility through regulating interactions between voltage-gated Ca2+ channels and PIP2.

Phosphatidylinositol 4,5-bisphosphate (PIP2) acts as substrate and unmodified ligand for Gq-protein-coupled receptor signalling in vascular smooth muscle cells (VSMCs) that is central for initiating contractility. The present work investigated how PIP2 might perform these two potentially conflicting roles by studying the effect of myristoylated alanine-rich C kinase substrate (MARCKS), a PIP2-binding protein, on vascular contractility in rat and mouse mesenteric arteries. Using wire myography, MANS peptide (MANS), a MARCKS inhibitor, produced robust contractions with a pharmacological profile suggesting a predominantly role for L-type (CaV1.2) voltage-gated Ca2+ channels (VGCC). Knockdown of MARCKS using morpholino oligonucleotides reduced contractions induced by MANS and stimulation of α1-adrenoceptors and thromboxane receptors with methoxamine (MO) and U46619 respectively. Immunocytochemistry and proximity ligation assays demonstrated that MARCKS and CaV1.2 proteins co-localise at the plasma membrane in unstimulated tissue, and that MANS and MO reduced these interactions and induced translocation of MARCKS from the plasma membrane to the cytosol. Dot-blots revealed greater PIP2 binding to MARCKS than CaV1.2 in unstimulated tissue, with this binding profile reversed following stimulation by MANS and MO. MANS evoked an increase in peak amplitude and shifted the activation curve to more negative membrane potentials of whole-cell voltage-gated Ca2+ currents, which were prevented by depleting PIP2 levels with wortmannin. This present study indicates for the first time that MARCKS is important regulating vascular contractility and suggests that disinhibition of MARCKS by MANS or vasoconstrictors may induce contraction through releasing PIP2 into the local environment where it increases voltage-gated Ca2+ channel activity

The malignant epidemic-changing patterns of trauma

Objectives and Setting. The worldwide burden of trauma is increasing, but is unequally distributed between nations. Trauma in South Africa targets the young and productive in society and imposes a major burden on the health infrastructure. We undertook a review of injury trends among patients attending the Johannesburg Hospital Trauma Unit (JHTU) and the Johannesburg Medicolegal Laboratory (JMLL) in order to document the evolution in patterns of trauma over a 17-year period of great social and political change. Design, subjects and outcome measures. This was a retrospective review of all priority-one patients attending the JHTU from January 1985 to December 2001. The JHTU trauma database was used to retrieve information on patient demographics, wound mechanism and injury severity. The database at the JMLL, maintained since 1996, was examined and the manner and place of death were analysed.Results. The JHTU has seen an unprecedented increase in the number of trauma patients over the last 17 years. The patients' demographic profiles have altered and injury is now predominantly due to interpersonal violence. Unnatural deaths examined at the JMLL have declined by 19% since 1996; however, the proportion of those deaths due to gunshot wounds has risen.Conclusions. The social and political changes in South Africa in recent years have led to changes in the injury profiles seen at the JHTU. Part of the increase can be explained by desegregation and a reduction in the provision of local hospital services; however, the impact of urbanisation within South Africa, cross-border migration and the high incidence of substance abuse are recognised. Evidence supports the implementation of legislative, environmental, social and behavioural interventions to contain and reduce the incidence and impact of violence and injury. Concerted efforts must be made at all levels to curb South Africa's  trauma  epidemic

Prognostic value of comorbidity indices and lung diseases in early rheumatoid arthritis:a UK population-based study

We assessed comorbidity burden in people with RA at diagnosis and early disease (3 years) and its association with early mortality and joint destruction. The association between lung disease and mortality in RA is not well studied; we also explored this relationship.From a contemporary UK-based population (n = 1, 475 762) we identified a cohort with incident RA (n = 6591). The prevalence of comorbidities at diagnosis of RA and at 3 years was compared with age- and gender-matched controls (n = 6591). In individuals with RA we assessed the prognostic value of the Charlson Comorbidity Index and Rheumatic Disease Comorbidity Index calculated at diagnosis for all-cause mortality and joint destruction (with joint surgery as a surrogate marker). We separately evaluated the association between individual lung diseases [chronic obstructive pulmonary disease (COPD), asthma and interstitial lung disease] and mortality.Respiratory disease, cardiovascular disease, stroke, diabetes, previous fracture and depression were more common (P &lt; 0.05) in patients with RA at diagnosis than controls. Comorbidity (assessed using RDCI) was associated with all-cause mortality in RA [adjusted hazard ratio (HR) 1.26, 95% CI 1.00–1.60]. There was no association with joint destruction. COPD, but not asthma, was associated with mortality (COPD HR 2.84, 95% CI 1.13–7.12).There is an excess burden of comorbidity at diagnosis of RA including COPD, asthma and interstitial lung disease. COPD is a major predictor of early mortality in early RA. Early assessment of comorbidity including lung disease should form part of the routine management of RA patients