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Introduction: Dysgraphia, a recognized PD motor symptom, lacks effective clinical assessment. Current evaluation relies on motor assessment scales. Computational methods introduced over the past decade offer an objective dysgraphia assessment, considering size, duration, speed, and handwriting fluency. Objective evaluation of dysgraphia may be of help for early diagnosis of PD., Objective: Computerized assessment of dysgraphia in de novo PD patients and its correlation with clinical scales., Methods: We evaluated 38 recently diagnosed, premedication PD patients and age-matched controls without neurological disorders. Participants wrote "La casa de Pamplona es bonita" three times on paper and once on a Wacom tablet under the paper, totaling four phrases. Writing segments of 5-10 s were analyzed. The Wacom tablet captured kinematic data, including mean velocity, mean acceleration, and pen pressure. Data were saved in.svc format and analyzed using specialized software developed by Tecnocampus Mataró. Standard clinical practice data, Hoehn & Yahr staging, and UPDRS scales were used for evaluation., Results: Significant kinematic differences existed; patients had lower mean speed (27 ± 12 vs. 48 ± 18, p < 0.0001) and mean acceleration (7.2 ± 3.9 vs. 15.01 ± 7, p < 0.0001) than controls. Mean speed and mean acceleration correlated significantly with UPDRS III scores (speed: r = -0.52, p < 0.0007; acceleration: r = 0.60, p < 0.0001), indicating kinematic parameters' potential in PD evaluation., Conclusions: Dysgraphia is identifiable in PD patients, even de novo, indicating an early symptom and correlates with clinical scales, offering potential for objective PD patient evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Age-related macular degeneration (AMD) is a leading cause of severe, irreversible vision impairment in developed countries, and its prevalence is rising all over the world, increasing sharply with age. AMD represents an acquired degeneration of the retina that causes significant central visual impairment through a combination of noneovascular and neovascular derangement. The main risk factors for the development of advanced AMD are increasing age, genetic factors, and cigarette smoking; however, the exact pathophysiology of AMD is yet relatively poorly understood. In recent years, the gut microbiota has been intensively studied and linked to several pathologic processes, including ocular diseases. In this sense, the aim of this review is to gather published evidence about the relationship between gut microbiota and AMD., (Copyright © 2021. Published by Elsevier Inc.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The central nervous system (CNS) is vulnerable to pathologic processes that lead to the development of neurodegenerative disorders like Alzheimer's, Parkinson's and Huntington's diseases, Multiple sclerosis or Amyotrophic lateral sclerosis. These are chronic and progressive pathologies characterized by the loss of neurons and the formation of misfolded proteins. Additionally, neurodegenerative diseases are accompanied by a structural and functional dysfunction of the blood-brain barrier (BBB). Although serving as a protection for the CNS, the existence of physiological barriers, especially the BBB, limits the access of several therapeutic agents to the brain, constituting a major hindrance in neurotherapeutics advancement. In this regard, nanotechnology-based approaches have arisen as a promising strategy to not only improve drug targeting to the brain, but also to increase bioavailability. Lipid nanocarriers such as liposomes, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), microemulsions and nanoemulsions, have already proven their potential for enhancing brain transport, crossing more easily into the CNS and allowing the administration of medicines that could benefit the treatment of neurological pathologies. Given the socioeconomic impact of such conditions and the advent of nanotechnology that inevitably leads to more effective and superior therapeutics for their management, it is imperative to constantly update on the current knowledge of these topics. Herein, we provide insight on the BBB and the pathophysiology of the main neurodegenerative disorders. Moreover, this review seeks to highlight the several approaches that can be used to improve the delivery of therapeutic agents to the CNS, while also offering an extensive overview of the latest efforts regarding the use of lipid-based nanocarriers in the management of neurodegenerative diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Diabetic retinopathy (DR) is a consequence of diabetes mellitus at the ocular level, leading to vision loss, and contributing to the decrease of patient's life quality. The biochemical and anatomic abnormalities that occur in DR are discussed in this review to better understand and manage the development of new therapeutic strategies. The use of new drug delivery systems based on nanoparticles (e.g. liposomes, dendrimers, cationic nanoemulsions, lipid and polymeric nanoparticles) is discussed along with the current traditional treatments, pointing out the advantages of the proposed nanomedicines to target this ocular disease. Despite the multifactorial nature of DR, which is not entirely understood, some strategies based on nanoparticles are being exploited for a more efficient drug delivery to the posterior segment of the eye. On the other hand, the use of some nanoparticles also seems to contribute to the development of DR symptoms (e.g. retinal neovascularization), which are also discussed in light of an efficient management of this ocular chronic disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This work aims at studying the efficacy of a series of novel biocompatible, serine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine, combining an experimental and computational approach. The surfactants consist of gemini molecules structurally related, but with variations in headgroup charge (nonionic vs. cationic) and in the hydrocarbon chain lengths (main and spacer chains). In vitro permeation and molecular dynamics studies combined with cytotoxicity profiles were performed to investigate the permeation of both drugs, probe skin integrity, and rationalize the interactions at molecular level. Results show that these enhancers do not have significant deleterious effects on the skin structure and do not cause relevant changes on cell viability. Permeation across the skin is clearly improved using some of the selected serine-based gemini surfactants, namely the cationic ones with long alkyl chains and shorter spacer. This is noteworthy in the case of ropivacaine hydrochloride, which is not easily administered through the stratum corneum. Molecular dynamics results provide a mechanistic view of the surfactant action on lipid membranes that essentially corroborate the experimental observations. Overall, this study suggests the viability of these serine-based surfactants as suitable and promising delivery agents in pharmaceutical formulations., (Copyright © 2015. Published by Elsevier B.V.)

The present paper focuses on the development and characterization of silica nanoparticles (SiNP) coated with hydrophilic polymers as mucoadhesive carriers for oral administration of insulin. SiNP were prepared by sol-gel technology under mild conditions and coated with different hydrophilic polymers, namely, chitosan, sodium alginate or poly(ethylene glycol) (PEG) with low and high molecular weight (PEG 6000 and PEG 20000) to increase the residence time at intestinal mucosa. The mean size and size distribution, association efficiency, insulin structure and insulin thermal denaturation have been determined. The mean nanoparticle diameter ranged from 289 nm to 625 nm with a PI between 0.251 and 0.580. The insulin association efficiency in SiNP was recorded above 70%. After coating, the association efficiency of insulin increased up to 90%, showing the high affinity of the protein to the hydrophilic polymer chains. Circular dichroism (CD) indicated that no conformation changes of insulin structure occurred after loading the peptide into SiNP. Nano-differential scanning calorimetry (nDSC) showed that SiNP shifted the insulin endothermic peak to higher temperatures. The influence of coating on the interaction of nanoparticles with dipalmitoylphosphatidylcholine (DPPC) biomembrane models was also evaluated by nDSC. The increase of ΔH values suggested a strong association of non-coated SiNP and those PEGylated nanoparticles coated with DPPC polar heads by forming hydrogen bonds and/or by electrostatic interaction. The mucoadhesive properties of nanoparticles were examined by studying the interaction with mucin in aqueous solution. SiNP coated with alginate or chitosan showed high contact with mucin. On the other hand, non-coated SiNP and PEGylated SiNP showed lower interaction with mucin, indicating that these nanoparticles can interdiffuse across mucus network. The results of the present work provide valuable data in assessing the in vitro performance of insulin-loaded SiNP coated with mucoadhesive polymers., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Proinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients., Design and Methods: Serum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters., Results: IL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p=0.032, Mann-Whitney test) and presented a trend for lower levels of pain (p=0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR=4.074, p=0.010, Pearson χ(2) test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p=0.053, Pearson χ(2) test)., Conclusions: Our results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were developed as alternative to other colloidal carriers. They were designed to overcome lipid nanoemulsions and liposomes in stability and ability to control the release of an encapsulated substance, and at the same time to be better tolerated than polymeric nanoparticles. Since the patenting of SLN discovery, large amount of data became available on the behaviour of these systems in vitro. SLN/NLC have many prerequisites to be a well tolerated carrier - the currently available data seem to confirm it, but there are also some contradictory results. In this review, we collected the available data from cytotoxicity, oxidative stress and hemocompatibility studies in vitro and analysed their outcomes. We also provide a summary of the available data in a form of reference table., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The human population at large is exposed to many critical factors (e.g. bad food habits, chemical substances, and stress) leading to the development of serious diseases. Colon or colorectal cancer is one of the most prevalent types of cancer in many countries. Despite being a multi-factorial chronic disease, resulting from the interaction of multiple genetic and environmental factors, the critical factor is mostly a poor diet regimen. Therefore, an accumulation of constant mutations leads to a complex arrangement of events during tumor initiation, development and propagation. It is well known that many plants are rich in polyphenols with anti-oxidant, anti-atherogenic, anti-diabetic, anti-cancer, anti-viral, and anti-inflammatory properties. These compounds are secondary metabolites with the ability to donate electrons to free radicals through different mechanisms. In recent years, a large number of studies have attributed a protective effect to polyphenols and foods containing these compounds (e.g. plants, vegetables, cereals, tea, coffee or chocolate). Polyphenolic compounds have been described to inhibit cancer development and propagation, being used as chemopreventive agents. Some polyphenols reported a preventive action against colon cancer, e.g. curcumin, gallic acid, ellagic acid, and epigallocatechin-3-gallate. The present article focuses on the properties of these molecules as chemopreventive agents and the recent advances on their formulation in nanoparticulate systems for targeted therapy and increased bioavailability., (Copyright © 2012 Elsevier Inc. All rights reserved.)