Discovering the Potential of Natural Antioxidants in Age-Related Macular Degeneration: A Review

Age-related macular degeneration (AMD) is a multifactorial disease associated with anatomical changes in the inner retina. Despite tremendous advances in clinical care, there is currently no cure for AMD. This review aims to evaluate the published literature on the therapeutic roles of natural antioxidants in AMD. A literature search of PubMed, Web of Science and Google Scholar for peer-reviewed articles published between 1 January 2011 and 31 October 2021 was undertaken. A total of 82 preclinical and 18 clinical studies were eligible for inclusion in this review. We identified active compounds, carotenoids, extracts and polysaccharides, flavonoids, formulations, vitamins and whole foods with potential therapeutic roles in AMD. We evaluated the integral cellular signaling pathways including the activation of antioxidant pathways and angiogenesis pathways orchestrating their mode of action. In conclusion, we examined the therapeutic roles of natural antioxidants in AMD which warrant further study for application in clinical practice. Our current understanding is that natural antioxidants have the potential to improve or halt the progression of AMD, and tailoring therapeutics to the specific disease stages may be the key to preventing irreversible vision loss.

Everyday Functioning in a Community-Based Volunteer Population: Differences Between Participant- and Study Partner-Report

Introduction: Impaired awareness in dementia caused by Alzheimer’s disease and related disorders made study partner-report the preferred method of measuring interference in “instrumental activities of daily living” (IADL). However, with a shifting focus toward earlier disease stages and prevention, the question arises whether self-report might be equally or even more appropriate. The aim of this study was to investigate how participant- and study partner-report IADL perform in a community-based volunteer population without dementia and which factors relate to differences between participant- and study partner-report.Methods: Participants (N = 3,288; 18–97 years, 70.4% females) and their study partners (N = 1,213; 18–88 years, 45.8% females) were recruited from the Dutch Brain Research Registry. IADL were measured using the Amsterdam IADL Questionnaire. The concordance between participant- and study partner-reported IADL difficulties was examined using intraclass correlation coefficient (ICC). Multinomial logistic regressions were used to investigate which demographic, cognitive, and psychosocial factors related to participant and study partner differences, by looking at the over- and underreport of IADL difficulties by the participant, relative to their study partner.Results: Most A-IADL-Q scores represented no difficulties for both participants (87.9%) and study partners (89.4%). The concordance between participants and study partners was moderate (ICC = 0.55, 95% confidence interval [CI] = [0.51, 0.59]); 24.5% (N = 297) of participants overreported their IADL difficulties compared with study partners, and 17.8% (N = 216) underreported difficulties. The presence of depressive symptoms (odds ratio [OR] = 1.31, 95% CI = [1.12, 1.54]), as well as memory complaints (OR = 2.45, 95% CI = [1.80, 3.34]), increased the odds of participants overreporting their IADL difficulties. Higher IADL ratings decreased the odds of participant underreport (OR = 0.71, 95% CI = [0.67, 0.74]).Conclusion: In this sample of community-based volunteers, most participants and study partners reported no major IADL difficulties. Differences between participant and study partner were, however, quite prevalent, with subjective factors indicative of increased report of IADL difficulties by the participant in particular. These findings suggest that self- and study partner-report measures may not be interchangeable, and that the level of awareness needs to be considered, even in cognitively healthy individuals.

Prediction of chronic obstructive pulmonary disease stages using machine learning algorithms

Identifying chronic obstructive pulmonary disease (COPD) severity stages is of great importance to control the related mortality rates and reduce the associated costs. This study aims to build prediction models for COPD stages and, to compare the relative performance of five machine learning algorithms to determine the optimal prediction algorithm. This research is based on data collected from a private hospital in Egypt for the two calendar years 2018 and 2019. Five machine learning algorithms were used for the comparison. The F1 score, specificity, sensitivity, accuracy, positive predictive value and negative predictive value were the performance measures used for algorithms comparison. Analysis included 211 patients’ records. Our results show that the best performing algorithm in most of the disease stages is the PNN with the optimal prediction accuracy and hence it can be considered as a powerful prediction tool used by decision makers in predicting severity stages of COPD.

COMPARATIVE ANALYSIS OF ANTIBODY RESPONSES FROM COVID-19 CONVALESCENTS RECEIVING VARIOUS VACCINES REVEALS CONSISTENT HIGH NEUTRALIZING ACTIVITY FOR SARS-CoV-2 VARIANT OF CONCERN OMICRON.

The novel SARS-CoV-2 Omicron variant of concern (VOCs), with its escape from unboosted vaccines and monoclonal antibodies, is demanding for a return to COVID19 convalescent plasma therapies. Lessons learnt from previous usage of CCP suggests focusing on outpatients and using high nAb-titer units in early disease stages. In this systematic analysis, we show that CCP from unvaccinated donors is not effective against Omicron, while CCP from vaccinees convalescents from previous VOCs or third-dose uninfected vaccinees is likely to remain effective against Omicron. countries. CCP remains the only antibody-based therapy that keeps up with the variants and provides an effective tool to combat the emergence of variants that defeat monoclonal antibodies. Consequently, there is a need for continue study of the variables that determine CCP efficacy.

Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions

Multiple sclerosis (MS) is a multifaceted, complex and chronic neurological disease that leads to motor, sensory and cognitive deficits. MS symptoms are unpredictable and exceedingly variable. Pain is a frequent symptom of MS and manifests as nociceptive or neuropathic pain, even at early disease stages. Neuropathic pain is one of the most debilitating symptoms that reduces quality of life and interferes with daily activities, particularly because conventional pharmacotherapies do not adequately alleviate neuropathic pain. Despite advances, the mechanisms underlying neuropathic pain in MS remain elusive. The majority of the studies investigating the pathophysiology of MS-associated neuropathic pain have been performed in animal models that replicate some of the clinical and neuropathological features of MS. Experimental autoimmune encephalomyelitis (EAE) is one of the best-characterized and most commonly used animal models of MS. As in the case of individuals with MS, rodents affected by EAE manifest increased sensitivity to pain which can be assessed by well-established assays. Investigations on EAE provided valuable insights into the pathophysiology of neuropathic pain. Nevertheless, additional investigations are warranted to better understand the events that lead to the onset and maintenance of neuropathic pain in order to identify targets that can facilitate the development of more effective therapeutic interventions. The goal of the present review is to provide an overview of several mechanisms implicated in neuropathic pain in EAE by summarizing published reports. We discuss current knowledge gaps and future research directions, especially based on information obtained by use of other animal models of neuropathic pain such as nerve injury.

Prognostic Role of the Expression of Latent-Membrane Protein 1 of Epstein–Barr Virus in Classical Hodgkin Lymphoma

The prognostic impact of the presence of Epstein–Barr virus (EBV) in classical Hodgkin lymphoma (cHL) is controversial. Previous studies reported heterogeneous results, rendering difficult the clinical validation of EBV as a prognostic biomarker in this lymphoma. The objective of this study was to evaluate the survival impact of the expression of EBV Latent-Membrane Protein 1 (EBV-LMP1) in tumoral Hodgkin–Reed–Sternberg (HRS) cells of primary diagnostic samples of cHL. Formalin-Fixed Paraffin-Embedded (FFPE) lymph node samples from 88 patients with cHL were analyzed. Patients were treated with the standard first-line chemotherapy (CT) with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) followed by radiotherapy. The Kaplan–Meier method and the Cox proportional hazards model were used for carrying out the survival analysis. In order to investigate whether the influence of EBV was age-dependent, analyses were performed both for patients of all ages and for age-stratified subgroups. In bivariate analysis, the expression of EBV was associated with older age (p = 0.011), mixed cellularity subtype cHL (p < 0.001) and high risk International Prognostic Score (IPS) (p = 0.023). Overall survival (OS) and progression-free survival (PFS) were associated with the presence of bulky disease (p = 0.009) and advanced disease at diagnosis (p = 0.016). EBV-positive cases did not present a significantly lower OS and PFS in comparison with EBV-negative cases, for all ages and when stratifying for age. When adjusted for covariates, absence of bulky disease at diagnosis (HR: 0.102, 95% CI: 0.02–0.48, p = 0.004) and limited disease stages (I–II) (HR: 0.074, 95% CI: 0.01–0.47, p = 0.006) were associated with a significant better OS. For PFS, limited-disease stages also retained prognostic impact in the multivariate Cox regression (HR: 0.145, 95% CI: 0.04–0.57, p = 0.006). These results are of importance as the early identification of prognostic biomarkers in cHL is critical for guiding and personalizing therapeutic decisions. The prognostic role of EBV in cHL could be modulated by the type of CT protocol employed and interact with the rest of presenting features.

Molecular Identity and Location Influence Purkinje Cell Vulnerability in Autosomal-Recessive Spastic Ataxia of Charlevoix-Saguenay Mice

Patterned cell death is a common feature of many neurodegenerative diseases. In patients with autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and mouse models of ARSACS, it has been observed that Purkinje cells in anterior cerebellar vermis are vulnerable to degeneration while those in posterior vermis are resilient. Purkinje cells are known to express certain molecules in a highly stereotyped, patterned manner across the cerebellum. One patterned molecule is zebrin, which is expressed in distinctive stripes across the cerebellar cortex. The different zones delineated by the expression pattern of zebrin and other patterned molecules have been implicated in the patterning of Purkinje cell death, raising the question of whether they contribute to cell death in ARSACS. We found that zebrin patterning appears normal prior to disease onset in Sacs–/– mice, suggesting that zebrin-positive and -negative Purkinje cell zones develop normally. We next observed that zebrin-negative Purkinje cells in anterior lobule III were preferentially susceptible to cell death, while anterior zebrin-positive cells and posterior zebrin-negative and -positive cells remained resilient even at late disease stages. The patterning of Purkinje cell innervation to the target neurons in the cerebellar nuclei (CN) showed a similar pattern of loss: neurons in the anterior CN, where inputs are predominantly zebrin-negative, displayed a loss of Purkinje cell innervation. In contrast, neurons in the posterior CN, which is innervated by both zebrin-negative and -positive puncta, had normal innervation. These results suggest that the location and the molecular identity of Purkinje cells determine their susceptibility to cell death in ARSACS.

Comparative diagnostic sensitivity of the substantia nigra transcranial sonography and salivary gland biopsy in patients with Parkinson’s disease

Parkinsons disease is a chronic neurodegenerative disease, the diagnosis of which remains challenging at the early stages, although clinical diagnostic criteria are developed. The diagnostic accuracy is only 58% for patients at early Parkinsons disease stages. The sensitivity and specificity of transcranial sonography of the substantia nigra used for Parkinsons disease verification is about 85% and 71%, respectively. It has been shown that the aggregates of -synuclein in the nerve fibers in major salivary glands may be seen in Parkinsons disease patients. The availability of the salivary glands for morphological study made it possible to investigate the approaches of the in vivo histological diagnosis of Parkinsons disease based on the detection of -synuclein aggregates in the nerve fibers innervating the glands. Aim: To evaluate and compare the sensitivity of transcranial sonography of the substantia nigra and sublingual salivary gland biopsy. Materials and methods: Six patients with clinically verified Parkinsons disease were enrolled. Evaluation of the neurological state using special scales, transcranial sonography of the substantia nigra and sublingual salivary gland biopsy was performed. Results: Mean age of patients was 59 [58; 60.7] years, mean disease duration period was 5 [3; 7.75] years and the mean HoehnYahr stage was 2.25 [2; 2.5]. Hyperechogenicity of the substantia nigra was found in 3 of 6 patients and the substantia nigra sensitivity was shown to be 50%. Sublingual salivary gland biopsy was positive for -synuclein in 6 of 6 patients and the sensitivity of method was shown to be 100%. No adverse events after biopsy were registered. Conclusion: The sensitivity of sublingual salivary gland biopsy was higher than those of transcranial sonography of the substantia nigra, which indicates the prospect of using the biopsy method as a more sensitive diagnostic tool in Parkinsons disease (1 table, bibliography: 19 refs)

Investigation of Lupeol as Anti-Melanoma Agent: An In Vitro-In Ovo Perspective

Malignant melanoma (MM) represents the most life-threatening skin cancer worldwide, with a narrow and inefficient chemotherapeutic arsenal available in advanced disease stages. Lupeol (LUP) is a triterpenoid-type phytochemical possessing a broad spectrum of pharmacological properties, including a potent anticancer effect against several neoplasms (e.g., colorectal, lung, and liver). However, its potential as an anti-melanoma agent has been investigated to a lesser extent. The current study focused on exploring the impact of LUP against two human MM cell lines (A375 and RPMI-7951) in terms of cell viability, confluence, morphology, cytoskeletal distribution, nuclear aspect, and migration. Additionally, the in ovo antiangiogenic effect has been also examined. The in vitro results indicated concentration-dependent and selective cytotoxicity against both MM cell lines, with estimated IC50 values of 66.59 ± 2.20 for A375, and 45.54 ± 1.48 for RPMI-7951, respectively, accompanied by a reduced cell confluence, apoptosis-specific nuclear features, reorganization of cytoskeletal components, and inhibited cell migration. In ovo, LUP interfered with the process of angiogenesis by reducing the formation of neovascularization. Despite the potential anti-melanoma effect illustrated in our in vitro-in ovo study, further investigations are required to elucidate the underlying LUP-induced effects in A375 and RPMI-7951 MM cells.