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Abstract Amyloid‐β (Aβ) is a pivotal biomarker in Alzheimer's disease (AD), attracting considerable attention from numerous researchers. There is uncertainty regarding whether clearing Aβ is beneficial or harmful to cognitive function. This question has been a central topic of research, especially given the lack of success in developing Aβ‐targeted drugs for AD. However, with the Food and Drug Administration's approval of Lecanemab as the first anti‐Aβ medication in July 2023, there is a significant shift in perspective on the potential of Aβ as a therapeutic target for AD. In light of this advancement, this review aims to illustrate and consolidate the molecular structural attributes and pathological ramifications of Aβ. Furthermore, it elucidates the determinants influencing its expression levels while delineating the gamut of extant Aβ‐targeted pharmacotherapies that have been subjected to clinical or preclinical evaluation. Subsequently, a comprehensive analysis is presented, dissecting the research landscape of Aβ across the domains above, culminating in the presentation of informed perspectives. Concluding reflections contemplate the supplementary advantages conferred by nanoparticle constructs, conceptualized within the framework of multivalent theory, within the milieu of AD diagnosis and therapeutic intervention, supplementing conventional modalities.

IntroductionThis study aimed to evaluate the angular kinematics of the hip, knee, ankle, and the linear kinematics of the barbell during the back squat (BS) at different load intensities in powerlifters and weightlifters.MethodsSeventeen athletes were recruited (n = 14 powerlifters; n = 3 weightlifters). The 1-RM of the BS of each participant was calculated and, 1-week after, each participant was asked to perform 5 trials of the BS at different load intensities (i.e., 60%, 70%, 80%, 90%, 100%) of the 1-RM. An action camera recorded the execution of each BS trial in the sagittal plane and, afterward, the videos were analyzed by measuring the range of motion (ROM) of hip, knee, and ankle for the angular kinematics, and the timing, distances, speeds, and accelerations of the barbell for the linear kinematics.ResultsRegarding the angular kinematics, no significant differences were found in the parameters in the starting and ending positions among the 5 trials, while a significant decrease was found in the hip relative angle (p = 0.026) in the maximum flexion position as load intensity increased. Regarding the linear kinematics, a significant difference was found in the descent acceleration (p = 0.049) in the descent phase, while a significant difference was found in the ascent speed (p

We used light-sensitive drugs to identify the brain region-specific role of mGlu5 metabotropic glutamate receptors in the control of pain. Optical activation of systemic JF-NP-26, a caged, normally inactive, negative allosteric modulator (NAM) of mGlu5 receptors, in cingulate, prelimbic, and infralimbic cortices and thalamus inhibited neuropathic pain hypersensitivity. Systemic treatment of alloswitch-1, an intrinsically active mGlu5 receptor NAM, caused analgesia, and the effect was reversed by light-induced drug inactivation in the prelimbic and infralimbic cortices, and thalamus. This demonstrates that mGlu5 receptor blockade in the medial prefrontal cortex and thalamus is both sufficient and necessary for the analgesic activity of mGlu5 receptor antagonists. Surprisingly, when the light was delivered in the basolateral amygdala, local activation of systemic JF-NP-26 reduced pain thresholds, whereas inactivation of alloswitch-1 enhanced analgesia. Electrophysiological analysis showed that alloswitch-1 increased excitatory synaptic responses in prelimbic pyramidal neurons evoked by stimulation of presumed BLA input, and decreased BLA-driven feedforward inhibition of amygdala output neurons. Both effects were reversed by optical silencing and reinstated by optical reactivation of alloswitch-1. These findings demonstrate for the first time that the action of mGlu5 receptors in the pain neuraxis is not homogenous, and suggest that blockade of mGlu5 receptors in the BLA may limit the overall analgesic activity of mGlu5 receptor antagonists. This could explain the suboptimal effect of mGlu5 NAMs on pain in human studies and validate photopharmacology as an important tool to determine ideal target sites for systemic drugs.

Abstract Alterations in the kynurenine pathway of tryptophan metabolism have been implicated in the pathophysiology of schizophrenia. Here, we performed an in-depth analysis of all metabolites of the kynurenine pathway, i.e., tryptophan (TRY), kynurenic acid (KYNA), L-kynurenine (KYN), 3-hydroxykynurenine (3-HK), anthranylic acid (ANA), 3-hydroxyanthranylic acid (3-HANA), xanthurenic acid (XA) and quinolinic acid (QUINA), in postmortem samples of the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46, 9) of individuals affected by schizophrenia and non-schizophrenic controls. The analysis was carried out in the gray and white matter. Levels of KYN, 3-HK, ANA, and 3-HANA were significantly increased in both the gray and white matter of the DLPFC of individuals affected by schizophrenia, whereas levels of TRY, KYNA, and QUINA were increased exclusively in the white matter and remained unchanged in the gray matter. These increases in kynurenine metabolites did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication. These findings suggest that the two major branches of the kynurenine pathway, i.e., the transamination of KYN into KYNA, and hydroxylation of KYN into 3-HK are activated in the white matter of individuals affected by schizophrenia, perhaps as a result of neuroinflammation, and support the evidence that abnormalities of the white matter are consistenly associated with schizophrenia.

Abstract Current strategies to identify ligands for brain delivery select candidates based on preferential binding to cell-membrane components (CMC) on brain endothelial cells (EC). However, such strategies generate ligands with inherent brain specificity limitations, as the CMC (e.g., the transferrin receptor TfR1) are also significantly expressed on peripheral EC. Therefore, novel strategies are required to identify molecules allowing increased specificity of therapy brain delivery. Here, we demonstrate that, while individual CMC are shared between brain EC and peripheral EC, their endocytic internalization rate is markedly different. Such differential endocytic rate may be harnessed to identify molecular tags for brain targeting based on their selective retention on the surface of brain EC, thereby generating ‘artificial’ targets specifically on the brain vasculature. By quantifying the retention of labelled proteins on the cell membrane, we measured the general endocytic rate of primary brain EC to be less than half that of primary peripheral (liver and lung) EC. In addition, through bio-panning of phage-displayed peptide libraries, we unbiasedly probed the endocytic rate of individual CMC of liver, lung and brain endothelial cells. We identified phage-displayed peptides which bind to CMC common to all three endothelia phenotypes, but which are preferentially endocytosed into peripheral EC, resulting in selective retention on the surface of brain EC. Furthermore, we demonstrate that the synthesized free-form peptides are capable of generating artificial cell-surface targets for the intracellular delivery of model proteins into brain EC with increasing specificity over time. The developed identification paradigm, therefore, demonstrates that the lower endocytic rate of individual CMC on brain EC can be harnessed to identify peptides capable of generating ‘artificial’ targets for the selective delivery of proteins into the brain vasculature. In addition, our approach identifies brain-targeting peptides which would have been overlooked by conventional identification strategies, thereby increasing the repertoire of candidates to achieve specific therapy brain delivery.

IntroductionCharcot–Marie–Tooth disease (CMT) is an inherited neuropathy that affects the sensory and motor nerves. It can be considered the most common neuromuscular disease, with a prevalence of 1/2500.MethodsConsidering the absence of a specific medical treatment and the benefits shown by physical activity in this population, a systematic review was completed using several search engines (Scopus, PubMed, and Web of Science) to analyze the use, effectiveness, and safety of a training program performed in telecoaching (TC). TC is a new training mode that uses mobile devices and digital technology to ensure remote access to training.ResultsOf the 382 studies identified, only 7 met the inclusion criteria. The effects of a TC training program included improvements in strength, cardiovascular ability, and functional abilities, as well as gait and fatigue. However, the quality of the studies was moderate, the size of the participants in each study was small, and the outcome measured was partial.DiscussionAlthough many studies have identified statistically significant changes following the administration of the TC training protocol, further studies are needed, with appropriate study power, better quality, and a higher sample size.

Background: Prismatic adaptation (PA) is a visuomotor technique using prismatic glasses that are capable of moving the visual field and to affect the excitability of certain brain areas. The aim of this pilot study was to explore potential acute effects of PA on penalty kick accuracy and postural control in youth soccer players. Methods: In this randomized crossover study, seven young male soccer players performed three PA sessions (rightward PA, r-PA; leftward PA, l-PA; sham PA, s-PA) with a washout period of 1-week between them. Immediately before and after each PA session, penalty kick accuracy and postural control were assessed. Results: We detected an increase in penalty kick accuracy following PA, regardless of the deviation side of the prismatic glasses (F1,5 = 52.15; p = 0.08; ηp2 = 0.981). In detail, our results showed an increase in the penalty kick accuracy toward the right target of the football goal following r-PA and toward the left target of the football goal following l-PA. We detected a significant effect on the sway path length (F2,12 = 10.42; p = 0.002; ηp2 = 0.635) and the sway average speed (F2,12 = 9.17; p = 0.004; ηp2 = 0.605) parameters in the stabilometric test with open eyes following PA, regardless of the deviation side of the prismatic glasses. In detail, our results showed a significant difference in both the stabilometric parameters (p = 0.016 and p = 0.009, respectively) only following l-PA. Conclusion: The findings of this pilot study indicate that PA could positively affect penalty kick accuracy and postural control suggesting that PA could be used as a visual training technique in athletes.

Introduction: The objectives of the present study were twofold: first, to identify the specific relative load at which the concentric motion transforms into a purely propulsive action among women, and second, to compare the load-velocity relationships between men and women during the bench press throw.Methods: Fourteen men and fourteen women participated in a test where they progressively increased the load until reaching their one-repetition maximum (1RM) in the bench press exercise. Linear regression models were employed to elucidate the relationships between load and velocity, as well as load and the propulsive phase (% of total concentric time). Additionally, ANCOVA was utilized to compare the linear regression models between men and women.Results: The results revealed strong and linear associations between load and mean propulsive velocity (MPV) for both men and women, as well as between load and the propulsive phase. Notably, there were significant differences in MPV and the propulsive phase concerning load between men and women. Women transitioned into a fully propulsive concentric phase at approximately 80% of their 1RM, while men achieved this entirely propulsive phase at around 85% of their 1RM. Furthermore, women exhibited reduced velocities when handling lighter relative loads compared to men. Conversely, women demonstrated higher velocities when dealing with loads exceeding 85% of their 1RM in contrast to their male counterparts.Discussion: These findings hold notable implications for prescribing bench press throw loads for women, which should differ from those recommended for men. Further studies are necessary to validate the efficacy of the proposed load recommendations.

BackgroundGross motor coordination (GMC) development could be influenced by age, gender, weight status, geographical area, living setting, home environment, socio-economic status, sports practice.PurposeTo verify whether practicing sports and practicing different sports could influence children's GMC level.MethodsA total of 295 children aged 8–11 years were involved in the study and divided into 5 groups in relation to the sport they practiced: gymnastics group (n = 67; 51F, 16M), cycling group (n = 64; 15F, 49M), athletics group (n = 47; 22F, 25M), swimming group (n = 35; 20F, 15M), control group (n = 82; 42F, 40M). The four subtests of the Körperkoordinations Test für Kinder (KTK) assessed children's GMC level. The scores from each of the four subtests were summed into the KTK total raw score (RS) and then converted into a gender- and age-specific motor quotient (MQ).ResultsChildren practicing sports showed significantly higher RS and MQ score than children of control group (203.14 ± 38.55 vs. 163.63 ± 43.50 and 98.56 ± 15.79 vs. 83.01 ± 16.71, respectively; p

Polystyrene (PS) is an extremely stable polymer with a relatively high molecular weight and a strong hydrophobic character that makes it highly resistant to biodegradation. In this study, PS was subjected to biodegradation tests by Tenebrio Molitor (T. Molitor) and Zophobas Morio (Z. Morio) larvae. Specifically, six different experimental diets were compared: (i) T. Molitor fed with bran; (ii) T. Molitor fed only PS; (iii) T. Molitor fed only PS treated with H2O2; (iv) Z. Morio fed with bran; (v) Z. Morio fed only PS; and (vi) Z. Morio fed only PS treated with H2O2. Therefore, the mass change of the larvae and the survival rate were measured periodically, while the frass collected after 15 and 30 days was analyzed by different analyses, such as spectroscopy (FTIR), spectrometry (molecular weight and polydispersity), thermal analysis (TGA) and microscopy (scanning electron microscopy observations). The obtained results suggest that in the case of T. Molitor larvae, larvae feeding on bran showed the highest survival rate of ~94% at 30 days, while in the case of the Z. Morio larvae, the highest survival rate was exhibited by larvae eating PS-H2O2. Although not strongly pronounced, the Mw and Mn of PS in the frass of both T. Molitor and Z. Morio larvae decreased over 30 days, suggesting PS biodegradation. Finally, the morphological analysis shows that PS samples isolated from the frass of T. Molitor and Z. Morio larvae showed completely different, rough and irregularly carved surface structures, in comparison to PS before biodegradation.

Background: The ease of administration of the Cumberland Ankle Instability Tool (CAIT) could represent a methodology for periodically evaluating athletes, preventing ankle instability injuries. This study aimed to achieve three objectives: (a) to evaluate the applicability of the CAIT scale in volleyball; (b) to explore whether ankle instability presents a greater risk in lower-level volleyball categories and whether elite athletes demonstrate an ability to mitigate this risk; and (c) to identify potential predictors of ankle instability. Methods: Eighty female volleyball players participated in this cross-sectional observational study. The CAIT was administered to evaluate the athletes belonging to some teams in Series A, B, and C. Results: The Spearman’s ranks correlation coefficient showed significant correlations between CAIT items. Additionally, the Cronbach’s α showed a high internal consistency. Our results showed a significant difference between athletes who reported pain and those who did not (p < 0.001). The multiple linear regression model analysis showed that pain was a predictor of ankle instability (p < 0.001). Conclusions: Our findings suggest that the CAIT can be used to evaluate ankle stability in volleyball players. This scale could represent a valuable tool for implementing specific intervention programs to prevent ankle injuries in athletes.

Water, energy, and minerals are fundamental pillars for the future of humankind. Sustainable and renewable productive processes and resources are the only possibility to face the continuously growing global population and high living standards requirements. The present work introduces a proof of concept for the pilot scale production of magnesium hydroxide, Mg(OH)2, from waste saltworks bitterns located in the district of Trapani, Italy. Mg(OH)2 was produced by adopting a proprietary “Magnesium Crystals Granulometry Controlled Reactor”, Mg-CGCR. The influence of several parameters was investigated on Mg(OH)2 suspensions and powders characteristics: (i) the bittern flow rate, (ii) alkaline sodium hydroxide, NaOH, concentrations solutions (adopted as the precipitant agent) and (iii) the final suspension pH value (stoichiometric or OH- excess amounts). A Mg2+ recovery >99 % can be achieved thanks to the adoption of a product recycling strategy in the reactor. Furthermore, highly pure Mg(OH)2 powders, addressed by cationic purity, were synthesized. Results demonstrate the possibility of producing highly pure Mg(OH)2 products from waste-concentrated saline solutions, thus turning waste into valuable compounds.

Abstract Background Global Positioning System (GPS) devices are widely used in soccer for monitoring external load (EL) indicators with the aim of maximizing sports performance.The aim of this study was to investigate the EL indicators differences in players of different playing positions (i.e., central backs, external strikers, fullbacks, midfielders, strikers, wide midfielder) between and within different sport-specific tasks and official matches. Methods 1932 observations from 28 semi-professional soccer players (age: 25 ± 6 years, height: 183 ± 6 cm, weight: 75.2 ± 7 kg) were collected through GPS devices (Qstarz BT-Q1000EX, 10 Hz) during the season 2019–2020. Participants were monitored during Official Match (OM), Friendly Matches (FM), Small Sided Games (SSG), and Match-Based Exercises (MBE). Metabolic (i.e., metabolic power, percentage of metabolic power > 35w, number of intense actions per minute, distance per minute, passive recovery time per minute) and neuromuscular indicators (i.e., percentage of intense accelerations, percentage of intense decelerations, change of direction per min > 30°) were recorded during each task. Results Statistically significant differences were detected in EL indicators between playing positions within each task and between tasks. In particular, results from the two-way ANOVA tests showed significant interaction, but with small effect size, in all the EL indicators between playing positions for each task and within tasks. Moreover, statistical differences, but with small effect size, between playing positions were detected in each task and for each EL indicator. Finally, the strongest statistical differences (with large effect size) were detected between tasks for each EL indicator. Details of the Tukey post-hoc analysis reporting the pairwise comparisons within and between tasks with playing positions are also provided. Conclusion In semi-professional soccer players, different metabolic and neuromuscular performance were detected in different playing position between and within different tasks and official matches. Coaches should consider the different physical responses related to different physical tasks and playing position to design the most appropriate training program.

Background: The objective of soccer training load (TL) is enhancing players’ performance while minimizing the possible negative effects induced by fatigue. In this regard, monitoring workloads and recovery is necessary to avoid overload and injuries. Given the controversial results found in literature, this study aims to better understand the complex relationship between internal training load (IL) by using rating of perceived exertion (RPE), recovery, and availability (i.e., subjective players’ readiness status). Methods: In this cross-sectional study, twenty-two-professional soccer players (age: 18.5 ± 0.4 years, height: 177 ± 6 cm, weight: 67 ± 6.7 kg) competing in the U19 Italian Championship were monitored using RPE scale to assess IL, and TreS scale to detect information about recovery and training/match availability during an entire season (2021–2022). Results: Autocorrelation analysis showed a repeated pattern with 7 days lag (weekly microcycle pattern) for all the variables considered (i.e., TL, recovery, and availability). For recovery (r = 0.64, p

IntroductionInclusive physical activity games at school can be useful for teachers dealing with students with disabilities. The use of inclusive strategies and games can be directly linked to teachers’ self-efficacy and familiarity with the inclusive strategies, while it could be indirectly influenced by their attitude toward inclusion and, in a smaller part, by social desirability in their response. Moreover, teachers’ responses could be different among the different school grades. Therefore, the aim of the current study is to investigate the role of attitude toward inclusion, social desirability, self-efficacy, and familiarity in the use of physical activity games at school in teachers from all school grades.MethodsA sample of 1,583 schoolteachers was asked to fill out a questionnaire about their perceptions of governmental measures, self-efficacy, familiarity with inclusive strategies through physical activity, and two standardized questionnaires assessing attitudes toward inclusion and social desirability.ResultsTeachers from primary school reported lower scores in attitude toward inclusion total score and dimensions, namely impact on teacher, impact on the environment, impact on the other children, and impact on the student with disability. Moreover, the path analysis model showed that the attitude toward inclusion indirectly influenced the use of inclusive strategy and had a small direct effect on familiarity with inclusive strategies and self-efficacy. Social desirability slightly influenced both familiarity and self-efficacy but not the use of inclusive strategies. Familiarity and self-efficacy had a direct effect on the use of inclusive physical activity games.DiscussionThe results of the current study suggest that being familiar with and having a high self-efficacy in implementing inclusive strategies are well related to the use of inclusive strategies at school. In addition, more attention should be given to kindergarten and primary school teachers, who reported lower scores in the attitude toward inclusion and higher scores in social desirability.

Abstract Glycans are ubiquitously expressed sugars, coating the cell and protein surfaces. They are found on many proteins as either short and branched chains or long chains sticking out from special membrane proteins, known as proteoglycans. This sugar cushion, the glycocalyx, modulates specific interactions and protects the cell. Here it is shown that both the expression of proteoglycans and the glycans expressed on the surface of both the host and virus proteins have a critical role in modulating viral attachment to the cell. A mathematical model using SARS‐Cov‐2 as an archetypical virus to study the glycan role during infection is proposed. It is shown that this occurs via a tug‐of‐war of forces. On one side, the multivalent molecular recognition that viral proteins have toward specific host glycans and receptors. On the other side, the glycan steric repulsion that a virus must overcome to approach such specific receptors. By balancing both interactions, viral tropism can be predicted. In other words, the authors can map out the cells susceptible to virus infection in terms of receptors and proteoglycans compositions.

Magnesium hydroxide nanoparticles are widely employed in numerous industrial applications. Several preparation methods have been proposed using mainly synthetic Mg2+ containing solutions. In the present work, the possibility of producing Mg(OH)2 nanoparticles from real bitterns, the by-product of sea salt production, is investigated. Bitterns are highly concentrated Mg2+ containing solutions whose exploitation can turn a waste into valuable products embracing the circular economy idea. Two bitterns collected from Galia and Margi saltworks of the district of Trapani (Italy) were studied. Galia and Margi bitterns had a 1 M and 2.5 M Mg2+ concentration, respectively. A 2 mm diameter circular-cross sectional T-mixer was adopted to ensure fast reactant mixing. NaOH solutions were employed as precipitant agents. Mg(OH)2 nanoparticles characterized by cationic and mass purity higher than 99 % and 90 %, respectively, were successfully produced when treating Galia bitterns, while the excessive Margi Mg2+ concentration yielded stronger micrometer Mg(OH)2 agglomerates.

Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤−35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (

Assessment of motor competence (MC) is crucial to finding deficiencies in children's motor development. Because of the need to ensure validity, reliability, and feasibility, the selection of contemporary testing batteries is a difficult task. Many papers report the validity of the KTK test in describing MC in school aged children. KTK consists of 4 four separate items: walking back, jumping sideways, moving sideways, and hopping for height. Some authors suggested the use of a short version of KTK that includes 3 items excluding one subtest: hopping for height. This study aimed to evaluate the effectiveness of short versions of Körperkoordinationstest für Kinder (KTK). A sample of 2,231 participants (boys: n=1,188; girls: n = 1,043; age range: 6–12 years) were recruited from Italian schools between January 2019 and February 2020 and they performed the complete version of KTK. Stepwise linear regression was performed on the dataset to evaluate the ideal number of variables to describe the KTK short form version. Data for both the sexes and all ages indicated that considering the item combinations of each short version, the highest R squares were obtained in those that included exactly the deleted subtest (ranging from 0.881–0.979). The adoption of a short form does not seem to provide a fully satisfactory condition for measuring MC in children 6–12 years.

The epigenetic agents, L-acetylcarnitine (LAC) and L-methylfolate (MF) are putative candidates as add-on drugs in depression. We evaluated the effect of a combined treatment with LAC and MF in two different paradigms of chronic stress in mice and in human inducible pluripotent stem cells (hiPSCs) differentiated into dopaminergic neurons. Two groups of mice were exposed to chronic unpredictable stress (CUS) for 28 days or chronic restraint stress (CRS) for 21 day, and LAC (30 or 100 mg/kg) and/or MF (0.75 or 3 mg/kg) were administered i.p. once a day for 14 days, starting from the last week of stress. In both stress paradigms, LAC and MF acted synergistically in reducing the immobility time in the forced swim test and enhancing BDNF protein levels in the frontal cortex and hippocampus. In addition, LAC and MF acted synergistically in enhancing type-2 metabotropic glutamate receptor (mGlu2) protein levels in the hippocampus of mice exposed to CRS. Interestingly, CRS mice treated with MF showed an up-regulation of NFκB p65, which is a substrate for LAC-induced acetylation. We could also demonstrate a synergism between LAC and MF in cultured hiPSCs differentiated into dopamine neurons, by measuring dendrite length and number, and area of the cell soma after 3 days of drug exposure. These findings support the combined use of LAC and MF in the treatment of MDD and other stress-related disorders.

Cinnabarinic acid (CA) is a trace kynurenine metabolite, which activates both type-4 metabotropic glutamate (mGlu4) and arylic hydrocarbon (Ah) receptors. We examined the action of CA in models of inflammatory and neuropathic pain moving from the evidence that mGlu4 receptors are involved in the regulation of pain thresholds. Systemic administration of low doses of CA (0.125 and 0.25 mg/kg, i.p.) reduced nocifensive behaviour in the second phase of the formalin test. CA-induced analgesia was abrogated in mGlu4 receptor knockout mice, but was unaffected by treatment with the Ah receptor antagonist, CH223191 (1 mg/Kg, s.c.). Acute injection of low doses of CA (0.25 mg/kg, i.p.) also caused analgesia in mice subjected to Chronic Constriction Injury (CCI) of the sciatic nerve. Electrophysiological recording showed no effect of CA on spinal cord nociceptive neurons and a trend to a lowering effect on the frequency and duration of excitation of the rostral ventromedial medulla (RVM) ON cells in CCI mice. However, local application of CH223191 or the group-III mGlu receptor antagonist, MSOP disclosed a substantial lowering and enhancing effect of CA on both populations of neurons, respectively. When repeatedly administered to CCI mice, CA retained the analgesic activity only when combined with CH223191. Repeated administration of CA plus CH223191 restrained the activity of both spinal nociceptive neurons and RVM ON cells, in full agreement with the analgesic activity. These findings suggest that CA is involved in the regulation of pain transmission, and its overall effect depends on the recruitment of mGlu4 and Ah receptors.

Abstract mGlu5 metabotropic glutamate receptors are highly expressed and functional in the early postnatal life, and are known to positively modulate NMDA receptor function. Here, we examined the expression of NMDA receptor subunits and interneuron-related genes in the prefrontal cortex and hippocampus of mGlu5−/− mice and wild-type littermates at three developmental time points (PND9, − 21, and − 75). We were surprised to find that expression of all NMDA receptor subunits was greatly enhanced in mGlu5−/− mice at PND21. In contrast, at PND9, expression of the GluN2B subunit was enhanced, whereas expression of GluN2A and GluN2D subunits was reduced in both regions. These modifications were transient and disappeared in the adult life (PND75). Changes in the transcripts of interneuron-related genes (encoding parvalbumin, somatostatin, vasoactive intestinal peptide, reelin, and the two isoforms of glutamate decarboxylase) were also observed in mGlu5−/− mice across postnatal development. For example, the transcript encoding parvalbumin was up-regulated in the prefrontal cortex of mGlu5−/− mice at PND9 and PND21, whereas it was significantly reduced at PND75. These findings suggest that in mGlu5−/− mice a transient overexpression of NMDA receptor subunits may compensate for the lack of the NMDA receptor partner, mGlu5. Interestingly, in mGlu5−/− mice the behavioral response to the NMDA channel blocker, MK-801, was significantly increased at PND21, and largely reduced at PND75. The impact of adaptive changes in the expression of NMDA receptor subunits should be taken into account when mGlu5−/− mice are used for developmental studies.

Abstract mGlu5 metabotropic glutamate receptors are highly functional in the early postnatal life, and regulate developmental plasticity of parvalbumin-positive (PV+) interneurons in the cerebral cortex. PV+ cells are enwrapped by perineuronal nets (PNNs) at the closure of critical windows of cortical plasticity. Changes in PNNs have been associated with neurodevelopmental disorders. We found that the number of Wisteria Fluoribunda Agglutinin (WFA)+ PNNs and the density of WFA+/PV+ cells were largely increased in the somatosensory cortex of mGlu5−/− mice at PND16. An increased WFA+ PNN density was also observed after pharmacological blockade of mGlu5 receptors in the first two postnatal weeks. The number of WFA+ PNNs in mGlu5−/− mice was close to a plateau at PND16, whereas continued to increase in wild-type mice, and there was no difference between the two genotypes at PND21 and PND60. mGlu5−/− mice at PND16 showed increases in the transcripts of genes involved in PNN formation and a reduced expression and activity of type-9 matrix metalloproteinase in the somatosensory cortex suggesting that mGlu5 receptors control both PNN formation and degradation. Finally, unilateral whisker stimulation from PND9 to PND16 enhanced WFA+ PNN density in the contralateral somatosensory cortex only in mGlu5+/+ mice, whereas whisker trimming from PND9 to PND16 reduced WFA+ PNN density exclusively in mGlu5−/− mice, suggesting that mGlu5 receptors shape the PNN response to sensory experience. These findings disclose a novel undescribed mechanism of PNN regulation, and lay the groundwork for the study of mGlu5 receptors and PNNs in neurodevelopmental disorders.

Multivalent ligand-receptor interactions enhance binding selectivity in biological systems, and may be exploited to design synthetic systems. Here the authors demonstrate a multivalent behavior where the ability to bind the target occurs when the receptor density is within a specific range.

PurposeHereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. The clinical phenotype is heterogeneous, and characterized by a multisystemic disease affecting the sensorimotor and autonomic functions along with other organs.Materials and MethodsAll the patients were assessed by complete neurological assessment, neurophysiological evaluation, of the median nerve, and handgrip analysis. The data are presented as means and standard deviations. Parametric and non-parametric assessments have been performed to identify differences between groups. Pearson's correlation has been carried out when appropriate.ResultsTwenty patients with ATTRv (66.1 ± 8.4 years; eight females) and 30 controls (61.1 ± 11.6 years; 16 females) were enrolled. Handgrip strength was reduced in patients with ATTR in both right and left hands compared to the controls. Significant differences were found between patients and controls in the right (handgrip right, HGSR TTR 21.1 ± 13 kg vs. HGSR Control 29.4 ± 11.3 kg, p = 0.017) and left (handgrip left, HGSL TTR 22.2 ± 10.7 kg. vs. HGSL Control 31 ± 11.3 kg, p = 0.007). NIS and CMAP amplitude of the median nerve were related to HGS measures for both hands in patients with ATTRv.ConclusionsThe progression of bilateral carpal tunnel syndrome is related to neurophysiological data in the median nerve in ATTRv. Also, handgrip measures might represent an important tool for the assessment of disease progression in ATTRv. We propose using a combination of CMAP amplitude and HGS for the assessment of hand motor strength in ATTRv.

This study was aimed (i) to examine the effect of living setting (rural vs. urban), geographical area (North vs. Center vs. South), and gender (boys vs. girls) on weight status, motor coordination, and physical activity (PA) level of Italian school-age children; (ii) to examine differences in the neighborhood walkability of different school areas from different geographical areas and living settings; and (iii) to examine whether motor coordination, PA level, geographical areas, living setting, neighborhood walkability, and gender could predict children's weight status. We assessed anthropometric parameters, gross motor coordination, and PA level in 1,549 children aged between 8 and 13 years. Results revealed that Central children had higher BMI than Northern and Southern children (η2 = 0.01). Moreover, Northern children showed the highest motor quotient (η2 = 0.148) and PA level (η2 = 0.02), followed by Southern and Central children, respectively. Children from the South of Italy attended schools located in neighborhoods with the highest Walk Score®. Urban children attended schools located in neighborhoods with a higher Walk Score® than rural children. Lower motor quotient (MQ), lower PA level, and living in a rural setting and in a car-dependent neighborhood were associated with a higher relative risk for obesity. Being a girl was associated with a lower relative risk for obesity. The alarming high percentage of overweight and obesity in children as well as motor coordination impairments revealed the urgent need of targeted PA interventions in pediatric population.

The paper deals with the interaction between freight flows, land use, and economy of a suburban area. In urban freight distribution, the process of freight acquisition of commercial establishments represents a crucial element. Therefore, it is necessary to plan city logistics in order to reduce the negative externalities generated by freight transport without depressing the economic and social vitality. In order to estimate and evaluate the performance and impacts generated by urban freight distribution, Transport System Models (TSMs) play an important role in reproducing and forecasting the process of distribution of final products to retailers and consumers. In recent years, Information and Communication Technologies (ICTs) have made new sources of data in great amounts available at lower costs than data provided from traditional surveys. Among the different data sources, Floating Car Data (FCD), obtained through GPS trackers installed on board the vehicles, offer partial insights into the examined process with lower cost and provide continuous information in space and time. In order to obtain reliable results, it is necessary to combine TSMs and ICTs as observed data could feed Transport System Models and could allow their calibration and therefore their application in real cases. In the above context, the paper deals with TSMs related to estimating urban freight demand flows. The work carried out concerns the specification-calibration-validation of a freight zonal acquisition model by means of FCD related to interzonal trips of commercial vehicles inside the Locride area (Reggio Calabria, Italy). The obtained models, estimated from FCD, could support the a priori evaluation of city logistics measures. The results are more important considering that they are obtained in an area with a lack of transport monitoring technologies. They could be adopted in other similar areas and confirm that adequate planning of city logistics determines advantages for environmental, social, and economic sustainability.

Background: Wearable inertial sensors are poorly used in soccer to monitor external load (EL) indicators. However, these devices could be useful for improving sports performance and potentially reducing the risk of injury. The aim of this study was to investigate the EL indicators (i.e., cinematic, mechanical, and metabolic) differences between playing positions (i.e., central backs, external strikers, fullbacks, midfielders, and wide midfielder) during the first half time of four official matches (OMs). Methods: 13 young professional soccer players (Under-19; age: 18.5 ± 0.4 years; height: 177 ± 6 cm; weight: 67 ± 4.8 kg) were monitored through a wearable inertial sensor (TalentPlayers TPDev, firmware version 1.3) during the season 2021–2022. Participants’ EL indicators were recorded during the first half time of four OMs. Results: significant differences were detected in all the EL indicators between playing positions except for two of them (i.e., distance traveled in the various metabolic power zones (30° and with speed >2 m). Pairwise comparisons showed differences in EL indicators between playing positions. Conclusions: Young professional soccer players showed different loads and performances during OMs in relation to playing positions. Coaches should consider the different physical demands related to playing positions in order to design the most appropriate training program.

ABSTRACT: Sex differences in immune-mediated diseases are linked to the activity of estrogens on innate immunity cells, including macrophages. Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) used in estrogen receptor-alpha (ERα)-dependent breast cancers and off-target indications such as infections, although the immune activity of TAM and its active metabolite, 4-OH tamoxifen (4HT), is poorly characterized. Here, we aimed at investigating the endocrine and immune activity of these SERMs in macrophages. Using primary cultures of female mouse macrophages, we analyzed the expression of immune mediators and activation of effector functions in competition experiments with SERMs and 17β-estradiol (E2) or the bacterial endotoxin LPS. We observed that 4HT and TAM induce estrogen antagonist effects when used at nanomolar concentrations, while pharmacological concentrations that are reached by TAM in clinical settings regulate the expression of VEGFα and other immune activation genes by ERα- and G protein-coupled receptor 1 (GPER1)-independent mechanisms that involve NRF2 through PI3K/Akt-dependent mechanisms. Importantly, we observed that SERMs potentiate cell phagocytosis and modify the effects of LPS on the expression of inflammatory cytokines, such as TNFα and IL1β, with an overall increase in cell inflammatory phenotype, further sustained by potentiation of IL1β secretion through caspase-1 activation.Altogether, our data unravel a novel molecular mechanism and immune functions for TAM and 4HT, sustaining their repurposing in infective and other estrogen receptors-unrelated pathologies.

The main goal of our cross-sectional research was to determine the current values of gross motor coordination (GMC) of Italian boys and girls between 6 and 13 years of age. Secondary goals were to study gender differences, and the four subtests trend with ages. Results were compared with the references proposed by KTK authors and with similar searches. Anthropometric measurements and KTK data from 2,206 schoolchildren (girls: n = 1,050; boys: n = 1,156) were collected. The KTK raw score (RS) increased with the age of the subjects (r = 0.678; p < 0.001). In 11–13-year-old subjects, the increase in results is less than in younger subjects. RS showed differences by gender (F = 5.899; p = 0.015) and age (F = 269.193; p < 0.001) without interaction gender × age. Motor quotient (MQ) tended to decrease with age (r = −0.148; p < 0.001); it showed differences by gender (F = 79.228; p < 0.001), age (F = 14.217; p < 0.001), and an interaction gender × age (F = 2.249; p < 0.05). Boys showed better performance than did girls in the raw scores of three of four subtests (JS: F = 24.529; MS: F = 9.052; HH: F = 11.105). Girls show better performances than did boys in the WB (F = 14.52). Differences between genders make us believe it appropriate to maintain a differentiated standardization. RS increased with age, and it seems reasonable, therefore, to maintain a GMC age-based normalization. On the contrary, MQ tended to decrease. All this makes us speculate that today's young people accumulate less significant motor experiences over the years compared to those achieved by their peers in the 1970s. Italian data were lower than German references and Belgian results but slightly higher than the Brazilian ones. The comparison among these four searches confirmed a worrying downward trend in GMC and its characterization by geographical and sociocultural areas. Updated parameters of the KTK can provide helpful references to improve policies to support physical activity, sport, and physical education in youth.

Background and aims. Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv) is caused by mutations in the TTR gene, leading to misfolded monomers that aggregate generating amyloid fibrils. The clinical phenotype is heterogeneous, characterized by a multisystemic disease affecting the sensorimotor, autonomic functions along with other organs. Patisiran is a small interfering RNA acting as a TTR silencer approved for the treatment of ATTRv. Punctual and detailed instrumental biomarkers are on demand for ATTRv to measure the severity of the disease and monitor progression and response to treatment. Methods. Fifteen patients affected by ATTRv amyloidosis (66.4 ± 7.8 years, six males) were evaluated before the start of therapy with patisiran and after 9-months of follow-up. The clinical and instrumental evaluation included body weight and height; Coutinho stage; Neuropathy Impairment Score (NIS); Karnofsky performance status (KPS); Norfolk QOL Questionnaire; Six-minute walking test (6 MWT); nerve conduction studies; handgrip strength (HGS); and bioimpedance analysis (BIA). Results. Body composition significantly changed following the 9-months pharmacological treatment. In particular, the patients exhibited an increase in fat free mass, body cell mass, and body weight with a decrease in fat mass. A significant increase after 9 months of treatment was observed for the 6 MWT. Coutinho stage, KPS, NIS, NIS-W, nerve conduction studies, Norfolk, COMPASS-31 scale, and HGS remained unchanged. Conclusions. BIA might represent a useful tool to assess the effects of multiorgan damage in ATTRv and to monitor disease progression and response to treatments. More evidence is still needed for HGS. Patisiran stabilizes polyneuropathy and preserves motor strength by increasing muscle mass after 9 months of treatment.

Magnesium has been listed among the 30 critical raw materials by the European Union. In recent years, many green and sustainable alternative Mg2+ sources have been sought to satisfy the EU’s demand and to avoid mineral ore consumption. In this context, saltwork bitterns, the by-products of solar sea salt production, have attracted much attention thanks to their high Mg2+ concentrations (up to 80 g/L) and low Ca2+ and bicarbonate contents (2+ extraction from bitterns in the form of Mg(OH)2(s) have already been performed, product purity has never been properly addressed. Mg(OH)2(s) is a chemical compound of great interest and extensive utility in numerous industrial applications only if the powder’s purity is >95% (w/w). This work presents a comprehensive experimental effort of reactive precipitation tests with NaOH solutions at stoichiometric and over-stoichiometric concentrations to: (i) assess the technical feasibility of Mg2+ recovery from real bitterns collected in saltworks of the Trapani district (Italy) and, (ii) for the first time, conduct an extensive purity investigation of the precipitated magnesium hydroxide powders as brucite. This experimental investigation demonstrates the possibility of extracting highly valuable compounds from saltwork bittern waste, embracing the water valorization and resource recovery approach.

Type 1 spinocerebellar ataxia (SCA1) is a progressive neurodegenerative disorder with no effective treatment to date. Using mice modeling SCA1, it has been demonstrated that a drug that amplifies mGlu1 receptor activation (mGlu1 receptor PAM, Ro0711401) improves motor coordination without the development of tolerance when cerebellar dysfunction manifests (i.e., in 30-week-old heterozygous ataxin-1 [154Q/2Q] transgenic mice). SCA1 is also associated with cognitive dysfunction, which may precede cerebellar motor signs. Here, we report that otherwise healthy, 8-week-old SCA1 mice showed a defect in spatial learning and memory associated with reduced protein levels of mGlu1α receptors, the GluN2B subunit of NMDA receptors, and cannabinoid CB1 receptors in the hippocampus. Systemic treatment with Ro0711401 (10 mg/kg, s.c.) partially corrected the learning deficit in the Morris water maze and restored memory retention in the SCA1 mice model. This treatment also enhanced hippocampal levels of the endocannabinoid, anandamide, without changing the levels of 2-arachidonylglycerol. These findings suggest that mGlu1 receptor PAMs may be beneficial in the treatment of motor and nonmotor signs associated with SCA1 and encourage further studies in animal models of SCA1 and other types of SCAs.

Although numerous evidences reported a negative correlation between motor coordination (MC) and overweight/obesity in children and adolescents, the interrelationship between age, gender, and weight status is still debatable. Hence, the aim of this cross-sectional study was to examine the association between MC and weight status according to age and gender across childhood and early adolescence in a large sample of Italian elementary and middle school students. A number of 1961 Italian school students (1,026 boys, 935 girls) was stratified in three consecutive age groups (6–7, 8–10, and 11–13 years) and four weight status categories (underweight, normal weight, overweight, and obese) according to Cole's body mass index (BMI) cut-off points for children. MC performance was assessed measuring motor quotient (MQ) with the Körperkoordinationstest für Kinder (KTK). Results showed significantly lower MQ levels in children in overweight (OW) and with obesity (OB) in both sexes for all age groups than peers in normal weight (NW), except in 6–7-year-old boys. Girls in OW and with OB had similar MQ levels across all age groups, while younger boys in OW and with OB showed higher MQ levels than older ones (p < 0.05). The 6–7-year-old boys showed better MQ levels than girls peers in NW, OW, and with OB, while 8–10-year-old boys in underweight (UW), NW, and OW; and 11–13-year-old boys only in NW (p < 0.05). No interaction effect was found between age, gender, and weight status on MQ levels. These outcomes showed the negative impact of higher weight status on MC performance according to age and gender, pointing out the importance of planning targeted motor programs that consider these variables to improve MC performance.

Little is known about the dose–response of physical education interventions on motor coordination in preschoolers. Our aim was to investigate whether the development of motor skills changed depending on different amounts of a physical education program (PEP) in children aged 3–5 years. One hundred forty-five children were recruited from kindergartens and randomly divided into a control group (CG, n = 28), which did not perform any PEP, and two intervention groups, which performed 4 h/week (I1, n = 78) and 10 h/week (I2, n = 39) of a PEP for 16 weeks. Each lesson was set in the form of a programmed game in order to produce fun, thus increasing enthusiasm for participation. Before and after the intervention, locomotor and object control skills and the gross motor development quotient were assessed with the Italian version of the gross motor development test. Both intervention groups showed a significant increase in the motor skills compared with the control group. Moreover, the level of performance was significantly higher after 10 h/week compared to 4 h/week. These findings can be useful for standardizing PEPs in preschool settings so that they can be applied by teachers for planning effective programs for developing motor skills in early childhood.

Precipitation processes have been successfully proved to be a feasible route to extract high-value products from wastes. However, reactive crystallization is characterized by fast kinetics, especially when highly concentrated solutions are used or sparingly soluble compounds precipitate, thus requiring a fast mixing of the reactants. In this context, T-shaped mixers have been extensively investigated both experimentally and numerically as a mean to achieve a rapid reactants homogenization. Many research efforts have been focused on the analysis of rectangular cross-sectional T-shaped mixers, while less attention has been devoted to the study of circular cross-sectional ones. In the present work, mixing times in a 3 mm circular cross-sectional T-shaped mixer have been optically estimated by exploiting the extremely fast neutralization reaction between sodium hydroxide and hydrochloric acid solutions. Reynolds numbers ranging between 1,000 and 6,000 were investigated. Mixing phenomena were (i) captured by detecting the colour change of a pH indicator by means of a high frame rate camera and (ii) quantified by a suitable image analysis technique. The assessed mixing times were found in accordance with available data in the literature.

Backgroud: Type-3 metabotropic glutamate (mGlu3) receptors are found in both neurons and glial cells and regulate synaptic transmission, astrocyte function, and microglial reactivity. Here we show that the genetic deletion of mGlu3 receptors amplifies ischemic brain damage and associated neuroinflammation in adult mice. An increased infarct size was observed in mGlu3−/− mice of both CD1 and C57Black strains 24 h following a permanent occlusion of the middle cerebral artery (MCA) as compared to their respective wild-type (mGlu3+/+ mice) counterparts. Increases in the expression of selected pro-inflammatory genes including those encoding interleukin-1β, type-2 cycloxygenase, tumor necrosis factor-α, CD86, and interleukin-6 were more prominent in the peri-infarct region of mGlu3−/− mice. In contrast, the expression of two genes associated with the anti-inflammatory phenotype of microglia (those encoding the mannose-1-phosphate receptor and the α-subunit of interleukin-4 receptor) and the gene encoding the neuroprotective factor, glial cell line-derived neurotrophic factor, was enhanced in the peri-infarct region of wild-type mice, but not mGlu3−/− mice, following MCA occlusion. In C57Black mice, the genetic deletion of mGlu3 receptors worsened the defect in the paw placement test as assessed in the contralateral forepaw at short times (4 h) following MCA occlusion. These findings suggest that mGlu3 receptors are protective against ischemic brain damage and support the way to the use of selective mGlu3 receptor agonists or positive allosteric modulators in experimental animal models of ischemic stroke.

Purpose: The aim of this study was to examine systemic responses of oxidant/antioxidant status following 2 training sessions of different intensity in amateur rhythmic gymnasts. Methods: Before the experimental training, 10 female gymnasts performed a gradually increased exercise test to assess maximal heart rate, maximal oxygen consumption, and anaerobic threshold. They executed 2 intermittent training sessions separated by 48 h of recovery (48 h-post R): the first was performed at low-moderate intensity (LMI) and the second at high intensity (HI). Blood samples were collected immediately pre- and post-training and 48 h-post R. Hydroperoxide level (OxL) and total antioxidant capacity (TAC) were photometrically measured. Results: OxL was significantly higher in post-training and 48 h-post R following HI than the same conditions after an LMI session (HI vs. LMI post-training: 381.10 ± 46.17 (mean ± SD) vs. 344.18 ± 27.94 Units Carratelli (U.CARR); 48 h-post R: 412.21 ± 26.61 vs. 373.80 ± 36.08 U.CARR). There was no change in TAC between the 2 training sessions investigated. In LMI training, OxL significantly decreased in post-training and increased to reach the baseline at 48 h-post R, whereas TAC increased only at 48 h-post R. In HI training, OxL significantly increased to reach a high oxidative stress 48 h-post R, whereas TAC was lower in post-training than pre-training. Conclusion: The pattern of OxL and TAC levels implies different regulation mechanisms by HI and LMI training sessions. High oxidative stress induced by an HI protocol might be associated with both insufficient TAC and recovery time at 48 h necessary to restore redox balance. Keywords: Antioxidant capacity, Exercise physiology, Free radicals, Oxidative stress, Reactive oxygen species, Rhythmic gymnastics, Training intensity

Purpose: This study is aimed to preliminary investigate whether transcranial alternating current stimulation (tACS) could affect explosive power considering genetic background in sport subjects.Methods: Seventeen healthy sports volunteers with at least 3 years of sports activities participated in the experiment. After 2 weeks of familiarization performed without any stimulation, each participant received either 50 Hz-tACS or sham-tACS. Before and after stimulation, subjects performed the following tests: (1) the squat jump with the hands on the hips (SJ); (2) countermovement jump with the hands on the hips (CMJ); (3) countermovement jump with arm swing (CMJ-AS); (4) 15-s Bosco’s test; (5) seated backward overhead medicine ball throw (SBOMBT); (6) seated chest pass throw (SCPT) with a 3-kg rubber medicine ball; and (7) hand-grip test. Additionally, saliva samples were collected from each participant. Genotyping analysis was carried out by polymerase chain reaction (PCR).Results: No significant differences were found in sport performance of subjects after 50 Hz-tACS. Additionally, we did not find any influence of genetic background on tACS-related effect on physical performance. These results suggest that tACS at gamma frequency is not able to induce an after-effect modulating sport performance. Further investigations with larger sample size are needed in order to understand the potential role of non-invasive brain stimulation techniques (NIBS) in motor performances.Conclusions: Gamma-tACS applied before the physical performance fails to improve explosive power in sport subjects.

Many studies reported a positive relationship between motor skills, cognitive functions, and school performance in school-age children; however, little is known in preschool children. The aim of the present study was to demonstrate the effectiveness of a physical education program (PEP) on locomotor, object control skills, and pre-literacy cognitive functions in a wide population of preschoolers and verify whether weight status could influence these abilities. In the context of the Training-to-Health Project, a sample of 1,029 preschoolers was recruited in kindergartens from the urban area of Palermo (Italy). Their gross motor and pre-literacy skills were tested before (PRE) and after (POST) following 16 weeks (2 h/week) of a PEP, which included ludic-motor activities aimed at developing body awareness and fundamental motor and perceptual-sensory skills. Analyses of variance (ANOVA) were performed to assess the skills before and after the intervention and to evaluate the effect of different categories of weight status on the examined variables. Regression analyses were conducted to confirm the hypothesized interrelationship between motor and pre-literacy skills in the considered sample. Both locomotor/object control and pre-literacy skills were significantly higher in children after the PEP (p < 0.05). We found 23% of overweight children and no significant difference between weight status classes in both PRE and POST PEP groups. In the POST group, higher locomotor and object control skills were mostly associated with better pre-literacy skills. This study shows that PEP was effective in improving both motor and pre-literacy skills in preschoolers independently from age and gender, while weight status did not affect these skills suggesting that this program can be administrated indifferently in children with different categories of weight status. Therefore, PEP could be a decisive education strategy to enhance motor and cognitive learning in preschool children and to achieve successful academic outcomes.

Early-life stress involved in the programming of stress-related illnesses can have a toxic influence on the functioning of the nigrostriatal motor system during aging. We examined the effects of perinatal stress (PRS) on the neurochemical, electrophysiological, histological, neuroimaging, and behavioral correlates of striatal motor function in adult (4 months of age) and old (21 months of age) male rats. Adult PRS offspring rats showed reduced dopamine (DA) release in the striatum associated with reductions in tyrosine hydroxylase-positive (TH+) cells and DA transporter (DAT) levels, with no loss of striatal dopaminergic terminals as assessed by positron emission tomography analysis with fluorine-18-l-dihydroxyphenylalanine. Striatal levels of DA and its metabolites were increased in PRS rats. In contrast, D2 DA receptor signaling was reduced and A2A adenosine receptor signaling was increased in the striatum of adult PRS rats. This indicated enhanced activity of the indirect pathway of the basal ganglia motor circuit. Adult PRS rats also showed poorer performance in the grip strength test and motor learning tasks. The aged PRS rats also showed a persistent reduction in striatal DA release and defective motor skills in the pasta matrix and ladder rung walking tests. In addition, the old rats showed large increases in the levels of SNAP-25 and synaptophysin, which are synaptic vesicle-related proteins in the striatum, and in the PRS group only, reductions in Syntaxin-1 and Rab3a protein levels were observed. Our findings indicated that the age-dependent threshold for motor dysfunction was lowered in PRS rats. This area of research is underdeveloped, and our study suggests that early-life stress can contribute to an increased understanding of how aging diseases are programmed in early-life.

Background: The developing zebrafish is an emerging tool in nanomedicine, allowing non-invasive live imaging of the whole animal at higher resolution than is possible in the more commonly used mouse models. In addition, several transgenic fish lines are available endowed with selected cell types expressing fluorescent proteins; this allows nanoparticles to be visualized together with host cells. Methods: Here, we introduce the zebrafish neural tube as a robust injection site for cancer cells, excellently suited for high resolution imaging. We use light and electron microscopy to evaluate cancer growth and to follow the fate of intravenously injected nanoparticles. Findings: Fluorescently labelled mouse melanoma B16 cells, when injected into this structure proliferated rapidly and stimulated angiogenesis of new vessels. In addition, macrophages, but not neutrophils, selectively accumulated in the tumour region. When injected intravenously, nanoparticles made of Cy5-labelled poly(ethylene glycol)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-PDPA) selectively accumulated in the neural tube cancer region and were seen in individual cancer cells and tumour associated macrophages. Moreover, when doxorubicin was released from PEG-PDPA, in a pH dependant manner, these nanoparticles could strongly reduce toxicity and improve the treatment outcome compared to the free drug in zebrafish xenotransplanted with mouse melanoma B16 or human derived melanoma cells. Interpretation: The zebrafish has the potential of becoming an important intermediate step, before the mouse model, for testing nanomedicines against patient-derived cancer cells. Funding: We received funding from the Norwegian research council and the Norwegian cancer society

Background: Goalball is a Paralympic sport for visually impaired athletes. Although it is widely practiced, a great variety of tests are adopted to evaluate athletes' physical fitness. Therefore, the objective was to identify the physical fitness tests adopted in this sport to find the common aspects between them and, eventually, to propose a standard operating procedure. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines were adopted. The studies were extracted from PubMed, Web of Science, and Scopus. A selection process by title, abstract, and full-text, according to the inclusion and exclusion criteria, was performed. The results were discussed with narrative synthesis. Results: A total of 7 papers and 222 participants were included. A wide variety of tests were adopted and the Brockport Physical Fitness Test (BPFT) was the only battery included to evaluate general athletes' well-being. Conclusions: Although few literature exists on Goalball, the BPFT could be the battery for evaluating Goalball athletes though the test battery should be standardized to the characteristics of this sport.

The worldwide spread of COVID-19 has upset the normality of Italian daily life, forcing population to social distancing and self-isolation. Since the containment precautions also concern sport-related activities, home workout remained the only possibility to play sports and stay active during the pandemic.The present study aimed to examine changes in the physical activity levels during self-quarantine in Italy, and the impact of exercise on psychological health.A total of 2974 Italian subjects has completed an online survey, but only 2524 subjects resulted eligible for this study. The questionnaire measured the total weekly physical activity energy expenditure before and during quarantine (i.e. the sum of walking, moderate-intensity physical activities, and vigorous-intensity physical activities) in Metabolic Equivalent Task minutes per week (MET–min/wk) using an adapted version of International Physical Activity Questionnaire and their psychological well-being using the Psychological General Well Being Index. Of the 2524 Italian subjects included in the study, 1426 were females (56.4%) and 1098 males (43.6%). Total physical activity significantly decreased between before and during COVID-19 pandemic (Mean: 2429 vs. 1577 MET–min/wk, ∗∗∗∗p < 0.0001), in all age groups and especially in men (Female, mean: 1994 vs. 1443 MET–min/wk, ∗∗∗∗p < 0.0001; Male, mean: 2998 vs. 1754 MET–min/wk, ∗∗∗∗p < 0.0001). Furthermore, a significant positive correlation was found between the variation of physical activity and mental well-being (r = 0.07541, ∗∗∗p = 0.0002), suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population.Based on this scientific evidence, maintaining a regular exercise routine is a key strategy for physical and mental health during a forced rest period like the current coronavirus emergency.

We investigated how the shape of polymeric vesicles, made by the exact same material, impacts the replication activity and metabolic state of both cancer and non-cancer cell types. First, we isolated discrete geometrical structures (spheres and tubes) from a heterogeneous sample using density-gradient centrifugation. Then, we characterized the cellular internalization and the kinetics of uptake of both types of polymersomes in different cell types (either cancer or non-cancer cells). We also investigated the cellular metabolic response as a function of the shape of the structures internalized and discovered that tubular vesicles induce a significant decrease in the replication activity of cancer cells compared to spherical vesicles. We related this effect to the significant up-regulation of the tumor suppressor genes p21 and p53 with a concomitant activation of caspase 3/7. Finally, we demonstrated that combining the intrinsic shape-dependent effects of tubes with the delivery of doxorubicin significantly increases the cytotoxicity of the system. Our results illustrate how the geometrical conformation of nanoparticles could impact cell behavior and how this could be tuned to create novel drug delivery systems tailored to specific biomedical application.

Summary: Polymersomes are vesicles formed by the self-assembly of amphiphilic copolymers in water. They represent one of the most promising alternatives of natural vesicles as they add new possibilities in the amphiphiles' molecular engineering of aqueous compartments. Here we report the design of polymersomes using a bottom-up approach wherein self-assembly of amphiphilic copolymers poly(2-(methacryloyloxy) ethyl phosphorylcholine)-poly(2-(diisopropylamino) ethyl methacrylate) (PMPC-PDPA) into membranes is tuned using pH and temperature. We report evolution from disk micelles, to vesicles, to high-genus vesicles (vesicles with many holes), where each passage is controlled by pH switch or temperature. We show that the process can be rationalized, adapting membrane physics theories to disclose scaling principles that allow the estimation of minimal radius of vesiculation as well as chain entanglement and coupling. This approach allows us to generate nanoscale vesicles with genus from 0 to 70, which have been very elusive and difficult to control so far. : Polymer Chemistry; Materials Chemistry; Colloids Subject Areas: Polymer Chemistry, Materials Chemistry, Colloids

Electronic performance tracking devices are largely employed in team sports to monitor performance and improve training. To date, global positioning system (GPS) based devices are those mainly used in soccer training. The aim of this study was to analyse the validity and reliability of the inertial sensor device (ISD) in monitoring distance and speed in a soccer-specific circuit and how their performance compare to a GPS system. 44 young male soccer players (age: 14.9 ± 1.1, range 9–16, years, height: 1.65 ± 0.10 m, body mass: 56.3 ± 8.9 kg) playing in a non-professional soccer team in Italy, participated in the study. We assessed the players trough a soccer running sport-specific circuit. An ISD and a GPS were used to assess distance and speed. Data was compared to a video reference system, and the difference were quantified by means of the root mean square error (RMSE). Significant differences were found for both GPS and ISD devices for distance and speed. However, lower error for distance (dRMSE 2.23 ± 1.01 m and 5.75 ± 1.50 m, respectively) and speed (sRMSE 0.588 ± 0.152 m·s–1 and 1.30 ± 0.422 m·s–1, respectively) were attained by the ISD compared to the GPS. Overall, our results revealed a statistically significant difference between systems in data monitoring for either distance and speed. However, results of this study showed that a smaller error was obtained with the ISD than the GPS device. Despite caution is warranted within the interpretation of these results, we observed a better practical applicability of the ISD due to its small size, lower cost and the possibility to use the device indoor.