Cannabinoids for Behavioral Symptoms in Dementia: An Overview.

Dementia, with loss of memory, cognitive abilities, and independent daily functioning, is increasing worldwide, related to an aging population. Currently, there is no curative treatment for dementia. Treatment of the frequently occurring behavioral and psychological symptoms of dementia (BPSD) is partially effective and associated with significant side effects. Cannabinoids are lipophilic molecules acting on the CB1 end CB2 receptors, essential for main biological processes such as sleep, appetite, memory, and pain. Cannabinoids might have a positive impact on amyloid formation in Alzheimer's disease, the main form of dementia, and on BPSD symptoms. Most knowledge currently concerns delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). In the context of dementia and BPSD, THC might be beneficial for associated spasticity and possible pain or lack of appetite and CBD probably works better on sleep, agitation, and anxiety. This overview of prospective clinical studies and randomized clinical trials, published between 2005 and April 2023, using cannabinoids for BPSD suggests that older studies using low-dose oral synthetic THC showed no positive results. Still, more recent studies using THC/CBD-based oral medication at higher doses show promising results and are feasible and safe in this elderly polymedicated population. Several RCTs are ongoing and planned worldwide, and we hope other trials will follow to establish clinical efficiency and optimal dosing, as well as other outcomes such as deprescribing other medications and facilitation of care. We suggest that researchers also address the more sociological aspects of prescribing cannabinoids for dementia and BPSD in their specific context.

Supramolecular Materials as Solid-Phase Microextraction Coatings in Environmental Analysis.

Solid-phase microextraction (SPME) has been widely proposed for the extraction, clean-up, and preconcentration of analytes of environmental concern. Enrichment capabilities, preconcentration efficiency, sample throughput, and selectivity in extracting target compounds greatly depend on the materials used as SPME coatings. Supramolecular materials have emerged as promising porous coatings to be used for the extraction of target compounds due to their unique selectivity, three-dimensional framework, flexible design, and possibility to promote the interaction between the analytes and the coating by means of multiple oriented functional groups. The present review will cover the state of the art of the last 5 years related to SPME coatings based on metal organic frameworks (MOFs), covalent organic frameworks (COFs), and supramolecular macrocycles used for environmental applications.

The Combined ICP-MS, ESEM-EDX, and HAADF-STEM-EDX Approach for the Assessment of Metal Sub-Micro- and Nanoparticles in Wheat Grain.

Metal sub-microparticles (SMPs) and nanoparticles (NPs) presence in food is attributable to increasing pollution from the environment in raw materials and finished products. In the present study, a multifaceted analytical strategy based on Environmental Scanning Electron Microscopy and High-Angle Annular Dark-Field-Scanning Transmission Electron Microscopy coupled with Energy-Dispersive X-ray Spectroscopy (ESEM-EDX, HAADF-STEM-EDX) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was proposed for the detection and characterization of metal and metal-containing SMPs and NPs in durum wheat samples, covering a size measurement range from 1 nm to multiple µm. ESEM-EDX and ICP-MS techniques were applied for the assessment of SMP and NP contamination on the surface of wheat grains collected from seven geographical areas characterized by different natural and anthropic conditions, namely Italy, the USA, Australia, Slovakia, Mexico, Austria, and Russia. ICP-MS showed significant differences among the mean concentration levels of metals, with the USA and Italy having the highest level. ESEM-EDX analysis confirmed ICP-MS concentration measurements and measured the highest presence of particles < 0.8 µm in size in samples from Italy, followed by the USA. Less marked differences were observed when particles < 0.15 µm were considered. HAADF-STEM-EDX was applied to a selected number of samples for a preliminary assessment of internal contamination by metal SMPs and NPs, and to expand the measurable particle size range. The multifaceted approach provided similar results for Fe-containing SMPs and NPs. ICP-MS and ESEM-EDX also highlighted the presence of a significant abundance of Ti- and Al-containing particles, while for STEM-EDX, sample preparation artifacts complicated the interpretation. Finally, HAADF-STEM-EDX results provided relevant information about particles in the low nm range, since, by applying this technique, no particles smaller than 50 nm were observed in accordance with ESEM-EDX.

Metrological traceability in process analytical technologies and point-of-need technologies for food safety and quality control: not a straightforward issue.

Traditional techniques for food analysis are based on off-line laboratory methods that are expensive and time-consuming and often require qualified personnel. Despite the high standards of accuracy and metrological traceability, these well-established methods do not facilitate real-time process monitoring and timely on-site decision-making as required for food safety and quality control. The future of food testing includes rapid, cost-effective, portable, and simple methods for both qualitative screening and quantification of food contaminants, as well as continuous, real-time measurement in production lines. Process automatization through process analytical technologies (PAT) is an increasing trend in the food industry as a way to achieve improved product quality, safety, and consistency, reduced production cycle times, minimal product waste or reworks, and the possibility for real-time product release. Novel methods of analysis for point-of-need (PON) screening could greatly improve food testing by allowing non-experts, such as consumers, to test in situ food products using portable instruments, smartphones, or even visual naked-eye inspections, or farmers and small producers to monitor products in the field. This requires the attention of the research community and devices manufacturers to ensure reliability of measurement results from PAT strategy and PON tests through the demonstration and critical evaluation of performance characteristics. The fitness for purpose of methods in real-life conditions is a priority that should not be overlooked in order to maintain an effective and harmonized food safety policy.

Evaluation of the Benefits of Bilateral Fitting in Bone-Anchored Hearing System Users: Spatial Resolution and Memory for Speech.

OBJECTIVES: The purpose of this study was to evaluate the benefits of bilateral implantation for bone-anchored hearing system (BAHS) users in terms of spatial resolution abilities and auditory memory for speech. DESIGN: This is a prospective, single-center, comparative, single-blinded study where the listeners served as their own control. Twenty-four experienced bone-anchored users with a bilateral conductive or mixed hearing loss participated in the study. After fitting the listeners unilaterally and bilaterally with BAHS sound processor(s) (Ponto 3 SuperPower), spatial resolution was estimated by measuring the minimum audible angle (MAA) to achieve an 80% correct response via a two-alternative-forced choice task (right-left discrimination of noise bursts) in two conditions: both sound processors active (bilateral condition) and only one sound processor active (unilateral condition). In addition, a memory recall test, the Sentence-final Word Identification and Recall (SWIR) test was performed with five lists of seven sentences for each of the two conditions (unilateral and bilateral). Self-reported performance in everyday life with the listener's own sound processors was also evaluated via a questionnaire (the abbreviated version of the Speech, Spatial and Qualities of Hearing scale). RESULTS: The MAA to discriminate noise bursts improved significantly from 75.04° in the unilateral condition to 3.61° in the bilateral condition ( p < 0.0001). The average improvement in performance was 54.28°. The SWIR test results showed that the listeners could recall, on average, 55.03% of the last words in a list of seven sentences in the unilateral condition and 57.23% in the bilateral condition. While the main effect of condition was not significant, there was a significant interaction between condition and repetition (list), revealing a significantly higher recall performance in the bilateral condition than in the unilateral condition for the second repetition/list out of five (10.2% difference; p = 0.022). Self-reported performance with bilateral BAHS obtained via the Speech, Spatial and Qualities of Hearing scale questionnaire was, on average, 4.4 for speech, 3.7 for spatial, and 5.1 for qualities of hearing. There was no correlation between self-reported performance in everyday life and bilateral performance in the MAA test, while significant correlations were obtained between self-reported performance and recall performance in the SWIR test. CONCLUSIONS: These results showed a large benefit in spatial resolution for users with symmetric BC thresholds when being fitted with two BAHS, although their self-reported performance with bilateral BAHS in everyday life was rather low. In addition, there was no overall benefit of bilateral fitting on memory for speech, despite observing a benefit in one out of five repetitions of the SWIR test. Performance in the SWIR test was correlated with the users' self-reported performance in everyday life, such that users with higher recall ability reported to achieve better performance in real life. These findings highlight the advantages of bilateral fitting on spatial resolution, although bilaterally fitted BAHS users continue to experience some difficulties in their daily lives, especially when locating sounds, judging distance and movement. More research is needed to support a higher penetration of bilateral BAHS treatment for bilateral conductive and mixed hearing losses.

Phthalate esters delivery to the largest European lagoon: Sources, partitioning and seasonal variations.

Phthalate esters (PAEs) due to their ability to leach from plastics, widely used in our daily life, are intensely accumulating in wastewater water treatment plants (WWTP) and rivers, before being exported to downstream situated estuarine systems. This study aimed to investigate the external sources of eight plasticizers to the largest European lagoon (the Curonian Lagoon, south-east Baltic Sea), focusing on their seasonal variation and transport behaviour through the partitioning between dissolved and particulate phases. The obtained results were later combined with hydrological inputs at the inlet and outlet of the lagoon to estimate system role in regulating the transport of pollutants to the sea. Plasticizers were detected during all sampling events with a total concentration ranging from 0.01 to 6.17 µg L-1. Di(2-ethylhexyl) phthalate (DEHP) was the most abundant PAEs and was mainly found attached to particulate matter, highlighting the importance of this matrix in the transport of such contaminant. Dibutyl phthalate (DnBP) and diisobutyl phthalate (DiBP) were the other two dominant PAEs found in the area, mainly detected in dissolved phase. Meteorological conditions appeared to be an important factor regulating the distribution of PAEs in environment. During the river ice-covered season, PAEs concentration showed the highest value suggesting the importance of ice in the retention of PAEs. While heavy rainfall impacts the amount of water delivered to WWTP, there is an increase of PAEs concentration supporting the hypothesis of their transport via soil leaching and infiltration into wastewater networks. Rainfall could also be a direct source of PAEs to the lagoon resulting in net surplus export of PAEs to the Baltic Sea.

From Ties to Events in the Analysis of Interorganizational Exchange Relations.

Relational event models expand the analytical possibilities of existing statistical models for interorganizational networks by: (i) making efficient use of information contained in the sequential ordering of observed events connecting sending and receiving units; (ii) accounting for the intensity of the relation between exchange partners, and (iii) distinguishing between short- and long-term network effects. We introduce a recently developed relational event model (REM) for the analysis of continuously observed interorganizational exchange relations. The combination of efficient sampling algorithms and sender-based stratification makes the models that we present particularly useful for the analysis of very large samples of relational event data generated by interaction among heterogeneous actors. We demonstrate the empirical value of event-oriented network models in two different settings for interorganizational exchange relations-that is, high-frequency overnight transactions among European banks and patient-sharing relations within a community of Italian hospitals. We focus on patterns of direct and generalized reciprocity while accounting for more complex forms of dependence present in the data. Empirical results suggest that distinguishing between degree- and intensity-based network effects, and between short- and long-term effects is crucial to our understanding of the dynamics of interorganizational dependence and exchange relations. We discuss the general implications of these results for the analysis of social interaction data routinely collected in organizational research to examine the evolutionary dynamics of social networks within and between organizations.

Reusable Cavitand-Based Electrospun Membranes for the Removal of Polycyclic Aromatic Hydrocarbons from Water.

The removal of toxic and carcinogenic polycyclic aromatic hydrocarbons (PAHs) from water is one of the most intractable environmental problems nowadays, because of their resistance to remediation. This work introduces a highly efficient, regenerable membrane for the removal of PAHs from water, featuring excellent filter performance and pH-driven release, thanks to the integration of a cavitand receptor in electrospun polyacrylonitrile (PAN) fibers. The role of the cavitand receptor is to act as molecular gripper for the uptake/release of PAHs. To this purpose, the deep cavity cavitand BenzoQxCav is designed and synthetized and its molecular structure is elucidated via X-Ray diffraction. The removal efficiency of the new adsorbent material toward the 16 priority PAHs is demonstrated via GC-MS analyses at ng L-1 concentration. A removal efficiency in the 32%, to 99% range is obtained. The regeneration of the membrane is performed by exploiting the pH-driven conformational switching of the cavitand between the vase form, where the PAHs uptake takes place, to the kite one, where the PAHs release occurs. The absorbance and regeneration capability of the membrane are successfully tested in four uptake/release cycles and the morphological stability.

4CMenB vaccine induces elite cross-protective human antibodies that compete with human factor H for binding to meningococcal fHbp.

Neisseria meningitidis serogroup B (MenB) is the leading cause of meningococcal meningitis and sepsis in industrialized countries, with the highest incidence in infants and adolescents. Two recombinant protein vaccines that protect against MenB are now available (i.e. 4CMenB and MenB-fHbp). Both vaccines contain the Factor H Binding Protein (fHbp) antigen, which can bind the Human Factor H (fH), the main negative regulator of the alternative complement pathway, thus enabling bacterial survival in the blood. fHbp is present in meningococcal strains as three main variants which are immunologically distinct. Here we sought to obtain detailed information about the epitopes targeted by anti-fHbp antibodies induced by immunization with the 4CMenB multicomponent vaccine. Thirteen anti-fHbp human monoclonal antibodies (mAbs) were identified in a library of over 100 antibody fragments (Fabs) obtained from three healthy adult volunteers immunized with 4CMenB. Herein, the key cross-reactive mAbs were further characterized for antigen binding affinity, complement-mediated serum bactericidal activity (SBA) and the ability to inhibit binding of fH to live bacteria. For the first time, we identified a subset of anti-fHbp mAbs able to elicit human SBA against strains with all three variants and able to compete with human fH for fHbp binding. We present the crystal structure of fHbp v1.1 complexed with human antibody 4B3. The structure, combined with mutagenesis and binding studies, revealed the critical cross-reactive epitope. The structure also provided the molecular basis of competition for fH binding. These data suggest that the fH binding site on fHbp v1.1 can be accessible to the human immune system upon immunization, enabling elicitation of human mAbs broadly protective against MenB. The novel structural, biochemical and functional data are of great significance because the human vaccine-elicited mAbs are the first reported to inhibit the binding of fH to fHbp, and are bactericidal with human complement. Our studies provide molecular insights into the human immune response to the 4CMenB meningococcal vaccine and fuel the rationale for combined structural, immunological and functional studies when seeking deeper understanding of the mechanisms of action of human vaccines.

Predictors of malnutrition risk in neurodegenerative diseases: The role of swallowing function.

BACKGROUND AND PURPOSE: Oropharyngeal dysphagia is generally recognized to increase the risk of malnutrition; however, its role in patients with neurodegenerative disease has yet to be determined. This cross-sectional study aimed to investigate the impact of swallowing function on malnutrition risk in patients with neurodegenerative diseases. METHODS: Patients with oral nutrition and diagnosis of Huntington disease (HD), Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS) were recruited. Demographic and clinical data were collected. The swallowing assessment included a fiberoptic endoscopic evaluation of swallowing, an oral phase assessment, and a meal observation scored with the Mealtime Assessment Scale (MAS). Malnutrition risk was assessed with the Mini Nutritional Assessment. RESULTS: Overall, 148 patients were recruited (54 HD, 33 PD, and 61 ALS). One hundred (67.6%) patients were considered at risk of malnutrition. In the multivariate analysis, age ≥ 65 years (odds ratio [OR] = 3.16, p = 0.014), disease severity (moderate vs mild OR = 3.89, severe vs mild OR = 9.71, p = 0.003), number of masticatory cycles (OR = 1.03, p = 0.044), and MAS safety (OR = 1.44, p = 0.016) were significantly associated with malnutrition risk. CONCLUSIONS: Prolonged oral phase and signs of impaired swallowing safety during meals, together with older age and disease severity, are independent predictors of malnutrition risk in neurodegenerative diseases. This study broadens the focus on dysphagia, stressing the importance of early detection not only of pharyngeal signs, but also of oral phase impairment and meal difficulties through a multidimensional swallowing assessment.