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Background/Objectives: Metabolic disorders, including diabetes, obesity, and cardiovascular diseases, are significant global health issues. Nutraceuticals, such as Sclerocarya birrea (SB), known for its high polyphenol content, are increasingly explored for managing these conditions. This study aims to evaluate the antihyperglycemic, hypolipidemic, and antihypertensive effects of SB in animal models to understand its potential as a natural intervention for metabolic diseases. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Searches across databases like PubMed, Web of Science, Embase, and Scopus identified studies using SB in animal models of metabolic disorders. Inclusion criteria were studies with SB intervention, control groups, and quantitative measures of metabolic parameters. The study was registered with INPLASY (INPLASY2024100031). Results: The meta-analysis revealed that SB significantly reduces blood glucose levels in diabetic animal models. Acute administration of SB showed a pooled standardized mean difference (SMD) of −7.13 (95% CI: −11.44 to −2.83) at 1 h and −9.75 (95% CI: −15.92 to −3.59) at 2–4 h post-administration. Chronic administration indicated a non-significant reduction in glucose levels (SMD: −5.69, 95% CI: −16.38 to 5.01). Conclusions: SB appears to have the potential for reducing blood glucose levels and may offer benefits for other cardiometabolic risk factors, including lipid profiles and oxidative stress. However, variability in the results underscores the need for further research, including standardized animal studies and clinical trials, to confirm these effects and clarify the mechanisms by which SB may impact metabolic disorders.

This report focused on a timely marine conservation issue in Pūpūkea, O‘ahu, Hawai’i regarding the lack of enforceable administrative rules in Kapoʻo, also known as the Pūpūkea or Sharks Cove tidepool, that is a part of the Pūpūkea Marine Life Conservation District (MLCD). To support the rule change process to revise the administrative rules, I worked with Mālama Pūpūkea-Waimea (MPW), a local nonprofit, to create and apply an ArcGIS Story Map. To build the Story Map, I explored available published literature, examined human use data from Kapo‘o, and observations from beach closures in response to the COVID-19 pandemic. From theliterature, I gleaned information on the role and function of tide pools in Hawai‘i, impacts from recreational use in coastal environments, marine managed areas in Hawai‘i. From the human use data, I found that the majority of visitors at Kapo‘o engaged in swimming, snorkeling, and shoreline use; and the monthly average number of people participating in these three activities combined increased by 58 people, or 7%, from 2017 to 2019. Observations during a two-month beach closure due to the pandemic included an anecdotal increase of juvenile fish, native algae, and sightings of rarely observed marine life, with no to minimal human disturbance. The Story Map will be used by MPW to educate the Pūpūkea community and visitors and will support the group through the future rulemaking process to make MLCD rules enforceable in Kapoʻo. Future studies will be conducted to understand Kapo‘o’s ecological role in the MLCD, to explore its role as a nursery and refuge for marine life, and to determine the magnitude of fishing andrecreational impacts on the ecosystem.

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders.

BackgroundThe availability of biosimilar medicines in Southern European markets has allowed purchasing biologics at a lower cost for healthcare systems. However, the capacity to seize this cost-reduction opportunity in the long run depends on fostering a sustainable competitive environment for all the market players involved. Diverse policies and information campaigns have been launched in Italy, Portugal and Spain to support uptake of “best-value” biologics (BVB). Despite these measures, the utilization of lower-cost biologics in certain regions is low, especially when it comes to the treatment of chronic conditions.ObjectiveWe aim to identify biosimilar uptake determinants in hospital environments in Italy, Portugal and Spain, using the class of TNF-alpha inhibitors as an example.MethodsThis is a mixed-methods study based on (1) the quantitative analysis of regional uptake data for TNF-alpha inhibitor biosimilars and (2) the qualitative processing of semi-structured interviews capturing experts’ views on uptake determinants for biosimilars.ResultsThe organization of multi-stakeholder information campaigns supporting TNF-alpha inhibitor biosimilars use in Italy, Portugal and Spain has resulted in an increased familiarity of healthcare professionals and patients with the prescription/use of these products. However, barriers persist that impede high biosimilars uptake, especially in chronic patient populations eligible for a switch. These are: (1) the late publication of position statements on biosimilars interchangeability by regulatory health authorities; (2) the vague positioning of (national/regional) health authorities on best switching practices (including multiple biosimilar-to-biosimilar switches); (3) the existence of policy frameworks that do not necessarily support the initiation of switching protocols; (4) the establishment of sometimes inefficient purchasing procedures that limit biosimilars potential to compete for market shares. Diverse approaches taken regionally to address these barriers have contributed to heterogeneous TNF-alpha inhibitor biosimilars uptake across Southern Europe.ConclusionOur research signaled the limited reach of biosimilar policies implemented locally, if not supported by a national policy framework. This study highlights the need for the coordinated implementation of policy measures fostering biosimilars use at the regional and national level in Italy, Portugal and Spain. These measures should account for the particularities of off-patent biologic and biosimilar markets and should jointly address supply- and demand-side challenges.

Background: The level of competition achieved following biosimilars market availability varies by country, care setting and molecule. Hence, biosimilars contribution to attaining price reductions and extended access to treatments can also vary.Objective: The aim of this study is to capture market dynamics for tumor necrosis factor (TNF)-alpha inhibitors and competing molecules in Southern European markets (2011–2020), and to evaluate the benefits of the competition generated by the availability of biosimilars.Methods: This study is based on a literature review examining market characteristics for TNF-alfa inhibitors and competing immunomodulator molecules, and on the quantitative analysis of market data for these molecules in Italy, Portugal and Spain.Results: Following biosimilars availability in Italian, Portuguese and Spanish markets, there has been an expansion in the overall access to TNF-alfa inhibitor pharmaceuticals. Further, savings have been generated within the TNF-alfa inhibitors class even after the increased use of these molecules. However, the potential of infliximab, etanercept and adalimumab biosimilars to generate price competition outside of their own drug class appeared limited in the studied markets. Considering this limitation and that shifts towards on-patent and higher-cost therapies have occurred after TNF-alfa inhibitor biosimilars availability, the importance of investing in biosimilars development for still on-patent immunology biologics is emphasized.Conclusion: This study highlights the need for policies that do not only seek higher utilization of biosimilars, but that also support a sustainable market for these products. This is expected to foster the future development of biosimilar medicines.

Background: Countries are struggling to provide affordable access to medicines while supporting the market entry of innovative, expensive products. This Perspective aims to discuss challenges and avenues for balancing health care system objectives of access, affordability and innovation related to medicines in Belgium (and in other countries).Methods: This Perspective focuses on the R&D, regulatory approval and market access phases, with particular attention to oncology medicines, precision medicines, orphan medicines, advanced therapies, repurposed medicines, generics and biosimilars. The authors conducted a narrative review of the peer-reviewed literature, of the grey literature (such as policy documents and reports of consultancy agencies), and of their own research.Results: Health care stakeholders need to consider various initiatives for balancing innovation with access to medicines, which relate to clinical and non-clinical outcomes (e.g. supporting the conduct of pragmatic clinical trials, treatment optimisation and patient preference studies, optimising the use of real-world evidence in market access decision making), value assessment (e.g. increasing the transparency of the reimbursement system and criteria, tailoring the design of managed entry agreements to specific types of uncertainty), affordability (e.g. harnessing the role of generics and biosimilars in encouraging price competition, maximising opportunities for personalising and repurposing medicines) and access mechanisms (e.g. promoting collaboration and early dialogue between stakeholders including patients).Conclusion: Although there is no silver bullet that can balance valuable innovation with affordable access to medicines, (Belgian) policy and decision makers should continue to explore initiatives that exploit the potential of both the on-patent and off-patent pharmaceutical markets.

Background/Objectives: The objective of this meta-analysis was to determine the impact of bariatric surgery on phase angle (PhA) and other bioimpedance measures among adults with obesity, comparing the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines, including studies up to May 2024 from MEDLINE, Scopus, Cochrane Library, and Web of Science. Eligible studies assessed PhA changes pre- and post-bariatric surgery in adults with BMI ≥ 30 kg/m2. Data on PhA, fat mass (FM), fat-free mass (FFM), body cell mass (BCM), weight, and BMI were extracted and analyzed. Results: Thirteen studies with a total of 1124 patients were included. Significant PhA reductions were observed at 6 months post-surgery (effect size: −1.00; 95% CI: −1.11 to −0.89; p < 0.001), with a more substantial reduction in RYGB patients compared to SG. FM and FFM decreased significantly at 12 months (FM: −27.58; 95% CI: −32.58 to −22.57; p < 0.001; FFM: −10.51; 95% CI: −12.81 to −8.94; p < 0.001). Weight and BMI showed marked reductions at 6 months (Weight: −31.42 kg; 95% CI: −37.28 to −25.26; p < 0.001; BMI: −11.39; 95% CI: −12.60 to −10.18; p < 0.001), with sustained decreases at 12 and 24 months. Conclusions: Bariatric surgery significantly reduces PhA, FM, FFM, weight, and BMI, with initial greater impacts observed in RYGB compared to SG. PhA shows potential as a marker for monitoring post-surgical recovery and nutritional status. Further long-term studies and standardized measurement protocols are recommended to optimize patient management. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction (ED) can stem from various organic and functional causes but is often linked to vascular health and cardiovascular disease. Limited data exist on how cardiovascular disease markers correlate with objective ED tests like the Nocturnal Penile Tumescence and Rigidity (NPTR) test and Penile Color Doppler Ultrasound (PCDU). Methods: A prospective observational study was performed, and 58 men with ED were assessed using the International Index of Erectile Function-15 (IIEF-15), NPTR test, and PCDU. Peripheral vascular health was evaluated through carotid intima-media thickness (cIMT) and brachial flow-mediated dilation (FMD). Results: Out of the participants, 44 had normal NPTR results, while 14 had abnormal results. The group with abnormal NPTR results was significantly older and had higher rates of hypertension and diabetes. Although the IIEF-15 scores were similar between the two groups, those with abnormal NPTR results had a lower peak systolic velocity (PSV) and a higher prevalence of impaired PSV. Correlations between the IIEF, NPTR, PCDU, and peripheral vascular markers lost significance after the age adjustment. Conclusions: This study suggests that abnormal NPTR results, combined with cardiovascular risk factors, may signal vascular ED and generalized vasculopathy, highlighting the need for cardiovascular assessment. An accurate ED diagnosis should integrate clinical evaluation with multiple tests while considering aging as a key risk factor. [ABSTRACT FROM AUTHOR]

Background/Objectives: Metabolic disorders, including diabetes, obesity, and cardiovascular diseases, are significant global health issues. Nutraceuticals, such as Sclerocarya birrea (SB), known for its high polyphenol content, are increasingly explored for managing these conditions. This study aims to evaluate the antihyperglycemic, hypolipidemic, and antihypertensive effects of SB in animal models to understand its potential as a natural intervention for metabolic diseases. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Searches across databases like PubMed, Web of Science, Embase, and Scopus identified studies using SB in animal models of metabolic disorders. Inclusion criteria were studies with SB intervention, control groups, and quantitative measures of metabolic parameters. The study was registered with INPLASY (INPLASY2024100031). Results: The meta-analysis revealed that SB significantly reduces blood glucose levels in diabetic animal models. Acute administration of SB showed a pooled standardized mean difference (SMD) of −7.13 (95% CI: −11.44 to −2.83) at 1 h and −9.75 (95% CI: −15.92 to −3.59) at 2–4 h post-administration. Chronic administration indicated a non-significant reduction in glucose levels (SMD: −5.69, 95% CI: −16.38 to 5.01). Conclusions: SB appears to have the potential for reducing blood glucose levels and may offer benefits for other cardiometabolic risk factors, including lipid profiles and oxidative stress. However, variability in the results underscores the need for further research, including standardized animal studies and clinical trials, to confirm these effects and clarify the mechanisms by which SB may impact metabolic disorders. [ABSTRACT FROM AUTHOR]

Afirmar que la categoría de “trabajo” es central en la obra de Karl Marx es algo que no exige justificaciones que vayan más lejos de un mero vistazo a cualquiera de sus textos. Este escrito pretende reconstruir la evolución de dicha categoría a lo largo de una producción intelectual que abarca varias décadas. El carácter de esta reconstrucción es doble. Por un lado, se buscará rastrear y fijar la dimensión teórica de dicha categoría desde el punto de vista de su posición en el sistema conceptual marxiano. Por otro, se tratará de demostrar la relación interna existente entre esta categoría y la acción política hacia la que se proyecta. Así, este escrito presenta desde el punto de vista de la categoría de trabajo en Marx la problemática universal de la relación entre teoría y praxis, que viene ocupando al pensamiento político desde Platón y Aristóteles.

Background: Nusinersen is an orphan drug intended for the treatment of spinal muscular atrophy (SMA), a severe genetic neuromuscular disorder. Considering the very high costs of orphan drugs and the expected market entry of cell and gene therapies, there is increased interest in the use of health technology assessment (HTA) for orphan drugs. This study explores the role of the economic evaluation and budget impact analysis on the reimbursement of nusinersen.Methods: Appraisal reports for nusinersen were retrieved from reimbursement and HTA agencies in Belgium, Canada, France, England and Wales, Germany, Italy, Ireland, Scotland, Sweden, the Netherlands, and the United States. Detailed information was extracted on the economic evaluation, the budget impact, the overall reimbursement decision, and the managed entry agreement (MEA). Costs were adjusted for inflation and currency.Results: Overall, the reports included limited data on budget impact, excluding information on the sources of data for cost and patient estimates. Only three jurisdictions reported on total budget impact, estimated between 30 and 40 million euros per year. For early-onset SMA, the incremental cost-effectiveness threshold (ICER) ranged from €464,891 to €6,399,097 per quality-adjusted life year (QALY) gained for nusinersen versus standard of care. For later-onset SMA, the ICER varied from €493,756 to €10,611,936 per QALY. Although none of the jurisdictions found nusinersen to be cost-effective, reimbursement was granted in each jurisdiction. Remarkably, only four reports included arguments in favor of reimbursement. However, the majority of the jurisdictions set up an MEA, which may have promoted a positive reimbursement decision.Conclusion: There is a need for more transparency on the appraisal process and conditions included in the MEA. Additionally, by considering all relevant criteria explicitly during the appraisal process, decision-makers are in a better position to justify their allocation of funds among the rising number of orphan drugs that are coming to the market in the near future.

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activa

Abstract Carotid artery atherosclerosis is a risk factor to develop cerebrovascular disease. Atheroma plaque can become instable and provoke a cerebrovascular event or else remain stable as asymptomatic type. The exact mechanism involved in plaque destabilization is not known but includes among other events smooth muscle cell (SMC) differentiation. The goal of this study was to perform thorough analysis of gene expression differences in SMCs isolated from carotid symptomatic versus asymptomatic plaques. Comparative transcriptomics analysis of SMCs based on RNAseq technology identified 67 significant differentially expressed genes and 143 significant differentially expressed isoforms in symptomatic SMCs compared with asymptomatic. 37 of top-scoring genes were further validated by digital PCR. Enrichment and network analysis shows that the gene expression pattern of SMCs from stable asymptomatic plaques is suggestive for an osteogenic phenotype, while that of SMCs from unstable symptomatic plaque correlates with a senescence-like phenotype. Osteogenic-like phenotype SMCs may positively affect carotid atheroma plaque through participation in plaque stabilization via bone formation processes. On the other hand, plaques containing senescence-like phenotype SMCs may be more prone to rupture. Our results substantiate an important role of SMCs in carotid atheroma plaque disruption.

The design of nanovectors able to overcome biological barriers is one of the main challenges in biomedicine. Gemini cationic lipids are considered potential candidates for gene therapy due to their high biocompatibility and capacity to condense nucleic acids safely in the form of lipoplexes. However, this approach presents difficulties regarding genetic unpacking and, therefore, control over this process becomes crucial to ensure successful transfection. In this work, gemini cationic lipoplexes were prepared in the presence of plasmonic gold nanostars (AuNSs) to afford a nanovector that efficiently releases plasmid DNA (pDNA) upon irradiation with near-infrared femtosecond laser pulses. A critical AuNSs concentration of 50 pM and optimized laser power density of 400 mW led to successful pDNA release, whose efficiency could be further improved by increasing the irradiation time. Agarose gel electrophoresis was used to confirm pDNA release. UV-Vis-NIR spectroscopy and transmission electron microscopy studies were performed to monitor changes in the morphology of the AuNSs and lipoplexes after irradiation. From a physicochemical point of view, this study demonstrates that the use of AuNSs combined with gemini cationic lipoplexes allows control over pDNA release under ultrafast laser irradiation.

Drug budget and prescription control measures are implemented regionally in Germany, meaning that the uptake of pharmaceuticals, including biosimilars, can vary by region. We examine regional market dynamics of tumor necrosis factor alpha (TNFα) inhibitor originators and biosimilars in Germany and studied the influence of biosimilar policies on these dynamics. This study is based on: (1) a literature review in which German biosimilar policies are identified, (2) the analysis of dispensing data (2010–2018) for the class of TNFα inhibitors, and (3) ten semi-structured interviews investigating prescribers’ and insurers’ views on factors potentially influencing biosimilar uptake. The analysis of biosimilar market shares of infliximab and etanercept revealed wide variations across the 17 German Regional Associations of Statutory Health Insurance Accredited Physicians (PA regions). Quantitative analyses indicated that biosimilar market shares for infliximab and etanercept were significantly lower in former East Germany when compared to former West Germany regions. Through qualitative interview analyses, this study showed that the use of infliximab and etanercept biosimilars across Germany is primarily influenced by (1) the regional-level implementation of biosimilar quotas and the presence of monitoring/sanctioning mechanisms to ensure adherence to these quotas, (2) the different insurer-manufacturer discount contracts, and (3) gainsharing arrangements established at the insurer-prescriber level.

A histidine-based gemini cationic lipid, which had already demonstrated its efficiency as a plasmid DNA (pDNA) nanocarrier, has been used in this work to transfect a small interfering RNA (siRNA) into cancer cells. In combination with the helper lipid monoolein glycerol (MOG), the cationic lipid was used as an antiGFP-siRNA nanovector in a multidisciplinary study. Initially, a biophysical characterization by zeta potential (ζ) and agarose gel electrophoresis experiments was performed to determine the lipid effective charge and confirm siRNA compaction. The lipoplexes formed were arranged in Lα lamellar lyotropic liquid crystal phases with a cluster-type morphology, as cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) studies revealed. Additionally, in vitro experiments confirmed the high gene knockdown efficiency of the lipid-based nanovehicle as detected by flow cytometry (FC) and epifluorescence microscopy, even better than that of Lipofectamine2000*, the transfecting reagent commonly used as a positive control. Cytotoxicity assays indicated that the nanovector is non-toxic to cells. Finally, using nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), apolipoprotein A-I and A-II followed by serum albumin were identified as the proteins with higher affinity for the surface of the lipoplexes. This fact could be beyond the remarkable silencing activity of the histidine-based lipid nanocarrier herein presented.

Background: Preclinical Alzheimer's disease may be linked to impaired cerebral amyloid clearance. We aim to obtain dynamic parameters of cortical and ventricular clearance of 11C‐PIB and compare them with CSF amyloid values in a population of healthy volunteers. Method: We evaluated 8 healthy volunteers (4 men and mean age: 64.2 years) without neurological or cognitive alterations by a dynamic PET/CT for 45' starting 40 min after administration of 370 MBq of 11C‐PIB. Cortical VOIs of 1 cm3 were drawn in the cerebellar, frontal, temporal, occipital, parietal, and posterior periventricular regions and in the posterior lateral ventricle obtaining SUVmean values at 45', 60' and 75'. For each area, clearance velocity slopes were calculated in the 40‐60' and 60‐75' temporal period and SUVr values at 45, 60 and 75' considering cerebellum cortex as reference region. Its correlation with the values of the Aβ1‐42/Aβ1‐40 ratio assessed in the cerebral spinal fluid (CSF) was analyzed. Result: Four of the eight controls showed a pathological Aβ1‐42/Aβ1‐40 ratio. The Aβ1‐42/Aβ1‐40 ratio correlated with SUVr values in all of the studied regions in the total group (n = 8). The best correlations were obtained at 40' in parietal cortex (r = ‐0.821), temporal cortex (r = ‐0.816), posterior periventricular region (r = ‐0.683) and frontal cortex (r = ‐0.617). The posterior ventricular region only showed correlation at 75' (r = ‐0.523). Significant correlations were observed with the slope of the first section (45‐60') in frontal (r = 0.796), occipital (r = 0.793), parietal (r = 0.556), temporal (r = 0.426), and especially in the periventricular region. (r = 0.964). However, when these parameters are compared between the subgroup of subjects with pathological Aβ1‐42/Aβ1‐40 ratio (n = 4) and with normal ratio (n = 4), these correlations worsen in all regions in the pathological group and improves in the normal group, especially in the temporal region (‐0.149 vs ‐0.924) and in periventricular (0.158 vs 0.844) at 60' and 75' respectively. Conclusion: In our control healthy population, there is a correlation between the dynamic parameters of cerebral clearance of 11C‐PIB and the CSF amyloid value, with differences between subjects with a pathological and normal CSF amyloid values. Larger studies are necessary to determine the value of these findings in the preclinical Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) age of onset (AO) is mainly determined by the length of the CAG repeat expansion in the huntingtin gene. The remaining AO variability has been attributed to other little-known factors. A factor that has been associated with other neurodegenerative diseases is arterial hypertension (AHT). The aim of this study is to evaluate the contribution of AHT to the AO of HD. We used data from a cohort of 630 European HD patients with adult onset collected by the REGISTRY project of the European Huntington's Disease Network. Multiple linear regression and ANOVA, controlling for the CAG repeat number of the expanded allele (CAGexp) of each patient, were performed to assess the association between the AHT condition and the AO of the motor symptoms (mAO). The results showed a significant association between AHT and mAO, especially when we only considered the patients diagnosed with AHT prior to manifesting any HD signs (pre-HD AHT). Remarkably, despite the low number of cases, those patients developed motor symptoms 5-8 years later than normotensive patients in the most frequent CAGexp range (40-44). AHT is an age-related condition and consequently, the age of the patient at the time of data collection could be a confounder variable. However, given that most pre-HD AHT patients included in our study had started treatment with antihypertensive drugs prior to the onset of HD, and that antihypertensive drugs have been suggested to confer a neuroprotective effect in other neurodegenerative diseases, raises the interest in elucidating the impact of AHT and/or AHT treatment in HD age of onset in further studies. A confirmation of our results in a larger sample set would open the possibility to significantly improve HD management.

Amphiphilic nonionic ligands, synthesized with a fixed hydrophobic moiety formed by a thiolated alkyl chain and an aromatic ring, and with a hydrophilic tail composed of a variable number of oxyethylene units, were used to functionalize spherical gold nanoparticles (AuNPs) in water. Steady-state and time-resolved fluorescence measurements of the AuNPs in the presence of α-cyclodextrin (α-CD) revealed the formation of supramolecular complexes between the ligand and macrocycle at the surface of the nanocrystals. The addition of α-CD induced the formation of inclusion complexes with a high apparent binding constant that decreased with the increasing oxyethylene chain length. The formation of polyrotaxanes at the surface of AuNPs, in which many α-CDs are trapped as hosts on the long and linear ligands, was demonstrated by the formation of large and homogeneous arrays of self-assembled AuNPs with hexagonal close packing, where the interparticle distance increased with the length of the oxyethylene chain. The estimated number of α-CDs per polyrotaxane suggests a high rigidization of the ligand upon complexation, allowing for nearly perfect control of the interparticle distance in the arrays. This degree of supramolecular control was extended to arrays formed by AuNPs stabilized with polyethylene glycol and even to binary arrays. Electromagnetic simulations showed that the enhancement and distribution of the electric field can be finely controlled in these plasmonic arrays.