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Introduction: Extracellular vesicles from mesenchymal stromal cells (MSC-EVs) are potent stimulators of naïve cartilage and their injection is studied in clinical trials for cartilage lesions, since often cartilage repaired with conventional approaches is incomplete or less performant leading to joint degeneration. The main pitfall of these innovative approaches is the high EVs dispersion into the joint cavity and consequent low concentration at lesion site. Thus, biological scaffolds for concentration of EVs where needed might be a promising option. This work aimed at producing an enhanced platelet-derived fibrin gel loaded with adipose-derived MSCs (ASCs)-EVs. Methods: EVs’ embedment efficiency in platelet gel, their release and incorporation in OA chondrocytes and cartilage explants were monitored by flow cytometry, microfluidic approaches, scansion electron microscopy and real-time quantitative multimodal nonlinear optics imaging. The effect of released EVs was tested in OA chondrocytes by gene expression studies. Results: A protocol ensuring high incorporation EVs efficiency in platelet gels was defined, relying on a one-step modification of the standard procedure used in current clinical practice. Trapped EVs were released continuously for up to 4 weeks and uptaken in pathologic chondrocytes and cartilage explants. The release of the EVs-loaded platelet gel had stronger and synergic anti-inflammatory/matrix remodelling effects with respect to both EVs per se and unloaded gel released products. Conclusions: These results suggest the feasibility of producing a platelet gel loaded with MSC-EVs at high efficiency that can be used as an enhanced tool to foster chondrocyte homeostasis, a key requisite for proper cartilage healing.

The catastrophic failure of two dams in Libya on 10 and 11 September 2023 resulted in the devastating flooding of the city of Derna, which is located downstream of the dams, causing more than 6000 fatalities and displacing thousands of residents. The failure was attributed to heavy rainfall from Storm Daniel, leading to the dams reaching full capacity and subsequently overflowing and failing. This paper presents an analysis of the dam break, including the modelling of flow discharge and the resulting flooding of Derna. For validation purposes, this study compares the modelled quantities with post-event satellite imagery from UNOSAT and Copernicus, local reports, and data collected from social media using AI detection. The findings provide valuable insights into the dynamics of the dam break and its initial parameters, as well as an assessment of the accuracy of the results. The analysis is performed using a rapid estimation technique developed by JRC to provide the international emergency community with a swift overview of the impact and damage assessment of potential or actual dam break events. The use of all available data shows a satisfactory comparison with the calculated quantities. The rapid modelling of dam break events and combined analysis of multiple data types are proven suitable for promptly assessing the expected dynamic of the event, as well as reconstructing the unknown initial conditions before the break. Incorporating sensitivity analyses provides an estimate of the uncertainties associated with the deduced values of the unknown parameters and their relative importance in the analysis.

Development of key practical skills is fundamental to bioscience courses in higher education. With limitations on access to laboratory time due to the COVID-19 pandemic, a "Bioskills at home" kit was developed to create opportunities for first year undergraduate students to develop these skills using online support resources to guide their activities and build communities of learning. Equipment and activities in this kit enabled students to practice key skills such as pipetting, data handling, experimental design and microscopy, as well as build an online peer learning community through the use of discussion boards and microscopy competitions that encouraged students to explore their local environment. Students who engaged with these activities reported increased confidence in key practical skills. Practical assessment of skills showed that that there was no reduction in the proportion of students who succeeded in achieving the pipetting learning objective compared to previous years, despite a significantly reduced on-campus provision. Although the celebration event to choose the microscopy competition winners was well attended, there was limited use of the discussion boards by students to build a community of learning during the term. Refinement of this initiative will focus on providing greater scaffolding to encourage greater engagement with activities and enhance community building.

Abstract Background BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. Methods The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. Discussion BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. Trial registration: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.

Abstract The present work aimed to predict the fate of two pesticides, copper (Cu) and glyphosate in a Mediterranean basin with an intermittent river and to assess the ecotoxicological risk related to their presence in water bodies coupling field measurements of streamflow and pesticide concentrations, and an eco-hydrological model. The Soil and Water Assessment Tool (SWAT) model was calibrated and, subsequently used to assess predicted environmental concentrations of pesticides in surface waters. The ecotoxicological risk related to the presence of Cu and glyphosate in surface water was assessed at the reach scale by using the Toxicity to Exposure Ratio approach (TER). Measurements of glyphosate concentrations (

Due to the scientific success of in vitro and in vivo model studies, the interest in using mesenchymal stromal cells (MSCs) for the treatment of orthopaedic conditions is growing. In the context of osteoarthritis (OA), MSCs, and, in particular, those derived from adipose tissues (ASCs), have found broader access to clinical use as active components of minimally manipulated orthobiologics, as well as clinically expanded cell preparations, or to collect their released factors (secretome) for cell-free approaches. In this regard, while both inflammatory priming and starvation are common strategies used to empower cell potency or collect the secretome, respectively, little is known about the possible influence of these approaches on the stability of housekeeping genes (HKGs) for molecular studies able to fingerprint cell phenotype or potency. In this report, the reliability of five commonly used HKGs (ACTB, B2M, GAPDH, HPRT1 and RPLP0) was tested in ASCs cultured under standard protocol after inflammatory priming or starvation. Gene expression data were computed with four different applets able to rank genes depending on their stability in either single or combined conditions. The obtained final ranking suggests that for each treatment, a specific HKG is needed, and that starvation is the condition with the stronger effect on HKGs’ stability and, therefore, reliability. The normalization effect of proper HKGs’ use was then validated on three genes involved in OA and whose product is released by ASCs. Overall, data presented herein confirm that the choice of the best HKG has to be carefully considered and that each specific condition has to be tested to identify the most reliable candidate.

Abstract Background Many patients treated for breast cancer (BC) complain about cognitive difficulties affecting their daily lives. Recently, sleep disturbances and circadian rhythm disruptions have been brought to the fore as potential contributors to cognitive difficulties in patients with BC. Yet, studies on these factors as well as their neural correlates are scarce. The purpose of the ICANSLEEP-1 (Impact of SLEEP disturbances in CANcer) study is to characterize sleep using polysomnography and its relationship with the evolution of cognitive functioning at both the behavioral and the neuroanatomical levels across treatment in BC patients treated or not with adjuvant chemotherapy. Methods ICANSLEEP-1 is a longitudinal study including BC patients treated with adjuvant chemotherapy (n = 25) or not treated with adjuvant chemotherapy (n = 25) and healthy controls with no history of BC (n = 25) matched for age (45–65 years old) and education level. The evaluations will take place within 6 weeks after inclusion, before the initiation of chemotherapy (for BC patients who are candidates for chemotherapy) or before the first fraction of radiotherapy (for BC patients with no indication for chemotherapy) and 6 months later (corresponding to 2 weeks after the end of chemotherapy). Episodic memory, executive functions, psychological factors, and quality of life will be assessed with validated neuropsychological tests and self-questionnaires. Sleep quantity and quality will be assessed with polysomnography and circadian rhythms with both actigraphy and saliva cortisol. Grey and white matter volumes, as well as white matter microstructural integrity, will be compared across time between patients and controls and will serve to further investigate the relationship between sleep disturbances and cognitive decline. Discussion Our results will help patients and clinicians to better understand sleep disturbances in BC and their relationship with cognitive functioning across treatment. This will aid the identification of more appropriate sleep therapeutic approaches adapted to BC patients. Improving sleep in BC would eventually help limit cognitive deficits and thus improve quality of life during and after treatments. Trial registration NCT05414357, registered June 10, 2022. Protocol version Version 1.2 dated March 23, 2022.

Undisturbed home cage recording of mouse activity and behavior has received increasing attention in recent years. In parallel, several technologies have been developed in a bid to automate data collection and interpretation. Thanks to these expanding technologies, massive datasets can be recorded and saved in the long term, providing a wealth of information concerning animal wellbeing, clinical status, baseline activity, and subsequent deviations in case of experimental interventions. Such large datasets can also serve as a long-term reservoir of scientific data that can be reanalyzed and repurposed upon need. In this review, we present how the impact of Big Data deriving from home cage monitoring (HCM) data acquisition, particularly through Digital Ventilated Cages (DVCs), can support the application of the 3Rs by enhancing Refinement, Reduction, and even Replacement of research in animals.

Objectives: Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). Methods: All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count

Study region: Catchment in Southern Italy. Study focus: Mediterranean waterways are commonly non-perennial; they are vulnerable to climate change (CC). Their management is particularly complex due to limited data availability. This work aims to develop a methodology for setting an Environmental Flow regime (E-Flows) for a temporary river (Locone, Italy) under limited data availability and under CC. As observed long-term time series of streamflow under natural conditions were not available, the Soil and Water Assessment Tool model (SWAT+) was applied to simulate the daily streamflow for the baseline period (1980–2010) and future (2020–2050) based on observed and model climate projections, respectively. A specific workflow was developed for model calibration focusing on the low flows. The hydrological regime was characterized by means of Indicators of Hydrological Alteration (IHAs), whereas the Range of Variability Approach (RVA) was applied to define the E-Flows. New hydrological insights for the region: The basin is experiencing a statistically significant increase in the air temperatures observed from 1971 to 2020, which is also predicted to continue in the future. Consequently, the average annual streamflow and monthly streamflow in winter and spring is expected to decrease. The calibration, based on a multi-objective model evaluation, improved the low-flow simulation. The detected differences in IHAs for the predicted periods should be considered in future water management when setting E-Flows for temporary rivers.

Tissue-engineered skin substitutes are promising tools to cover large and deep skin defects. However, the lack of a synergic and fast regeneration of the vascular network, nerves, and skin appendages limits complete skin healing and impairs functional recovery. It has been highlighted that an ideal skin substitute should mimic the structure of the native tissue to enhance clinical effectiveness. Here, we produced a pre-vascularized dermis (PVD) comprised of fibroblasts embedded in their own extracellular matrix (ECM) and a capillary-like network. Upon implantation in a mouse full-thickness skin defect model, we observed a very early innervation of the graft in 2 weeks. In addition, mouse capillaries and complete epithelialization were detectable as early as 1 week after implantation and, skin appendages developed in 2 weeks. These anatomical features underlie the interaction with the skin nerves, thus providing a further cue for reinnervation guidance. Further, the graft displays mechanical properties, collagen density, and assembly features very similar to the host tissue. Taken together our data show that the pre-existing ECM components of the PVD, physiologically organized and assembled similarly to the native tissue, support a rapid regeneration of dermal tissue. Therefore, our results suggest a promising potential for PVD in skin regeneration.

People with schizophrenia spectrum disorders (SSD) show anomalies in language processing with respect to "who is doing what" in an action. This linguistic behavior is suggestive of an atypical representation of the formal concepts of "Agent" in the lexical representation of a verb, i.e., its thematic grid. To test this hypothesis, we administered a silent-reading task with sentences including a semantic violation of the animacy trait of the grammatical subject to 30 people with SSD and 30 healthy control participants (HCs). When the anomalous grammatical subject was the Agent of the event, a significant increase of Gaze Duration was observed in HCs, but not in SSDs. Conversely, when the anomalous subject was a Theme, SSDs displayed an increased probability of go-back movements, unlike HCs. These results are suggestive of a higher tolerability for anomalous Agents in SSD compared to the normal population. The fact that SSD participants did not show a similar tolerability for anomalous Themes rules out the issue of an attention deficit. We suggest that general communication abilities in SSD might benefit from explicit training on deep linguistic structures.

Abstract This study evaluated the relationship between negative symptoms, daily time use (productive/non-productive activities, PA/NPA), and negative emotions in schizophrenia-spectrum disorders (SSDs): 618 individuals with SSDs (311 residential care patients [RCPs], 307 outpatients) were surveyed about socio-demographic, clinical (BPRS, BNSS) and daily time use (paper-and-pencil Time Use Survey completed twice/week) characteristics. Among them 57 RCPs and 46 outpatients, matched to 112 healthy controls, also underwent ecological monitoring of emotions (8 times/day for a week) through Experience Sampling Method (ESM). RCPs spent significantly less time in PA than outpatients. Patients with more negative symptomatology spent more time in NPA and less in PA compared to patients with milder symptoms. Higher time spent in NPA was associated with negative emotions (p

Background: Nurses play a pivotal role in combating antimicrobial resistance (AMR). However, the success of local and national AMR containment efforts hinges on the knowledge, attitude, and practice (KAP) of nursing staff and undergraduate students. Objectives: This study aims to explore the determinants of nurses’ KAP regarding AMR, offering insights to control the emergence and spread of drug-resistant pathogens. Methods: This cross-sectional, multicenter survey involving Italian nurses, nursing students, and healthcare professionals was conducted administering an anonymous online questionnaire focusing on AMR. The median score of 12 was taken as the cutoff for “good KAP.” The association between study variables and good KAP was assessed using chi-square or t-tests, followed by multivariable logistic regression analysis for statistically significant (p < 0.05) variables. Findings: Among 848 participants, 61.9% (n = 525) were students, and 39.6% (n = 336) scored as having “low KAP.” High KAP was associated with being female and studying AMR independently. Conversely, living in southern Italy and receiving AMR training from pharmaceutical companies were associated with low KAP. Conclusions: Among Italian nurses, AMR awareness relies on those who have studied AMR as self-taught and is affected by gender and region. Italian universities lack in lectures on AMR management, and much needs to be done to improve awareness of antimicrobial stewardship among nonmedical health workers.

Osteoarthritis (OA) is a degenerative joint disorder characterized by the progressive deterioration of articular cartilage driven and sustained by catabolic and inflammatory processes that lead to pain and functional impairment. Adipose-derived stem cells (ASCs) have emerged as a promising therapeutic strategy for OA due to their regenerative potential, which mainly relies on the adaptive release of paracrine molecules that are soluble or encapsulated in extracellular vesicles (EVs). The biological effects of EVs specifically depend on their cargo; in particular, microRNAs (miRNAs) can specifically modulate target cell function through gene expression regulation. This study aimed to investigate the impact of collection site (abdominal vs. peri-trochanteric adipose tissue) and collection method (surgical excision vs. lipoaspiration) on the miRNAs profile in ASC-derived EVs and their potential implications for OA therapy. EV-miRNA cargo profiles from ASCs of different origins were compared. An extensive bioinformatics search through experimentally validated and OA-related targets, pathways, and tissues was conducted. Several miRNAs involved in the restoration of cartilage homeostasis and in immunomodulation were identified in all ASC types. However, EV-miRNA expression profiles were affected by both the tissue-harvesting site and procedure, leading to peculiar characteristics for each type. Our results suggest that adipose-tissue-harvesting techniques and the anatomical site of origin influence the therapeutic efficacy of ASC-EVs for tissue-specific regenerative therapies in OA, which warrants further investigation.

The limpet Patella aspera is an endemic species to the Macaronesian Islands. Its high economic value and vulnerability to exploitation has triggered the interest in the development of its aquaculture. Significant progress has been made in recent years, with the establishment of artificial fertilization and larval production protocols. However, there are at least two major challenges that need to be addressed before a commercial production can be achieved: larval settlement and juvenile grow-out. The aim of this research was to study the effect of different algae substrates (Ulvella lens, Amphora sp., Entomoneis sp., Navicula salinicola and Nitzschia sp.) on P. aspera settlement and to test the effect of two diets on juvenile growth: a mono diet based on U. lens versus a mixed diet composed by U. lens and the diatoms Nitzschia sp. and Navicula salinicola. Results showed that U. lens was the most efficient settlement cue, given that 84.6% of the post-larvae obtained were found on this algae substrate. In the following trial, U. lens was selected as the base diet for the grow-out phase. The rearing system used ensured juvenile survival percentages above 80%. The regular supply of the diatom mixture, as a dietary supplement, significantly enhanced juvenile growth performance. After 220 days post fertilization, limpets that grew on the mixed diet (U. lens plus diatoms) presented an average shell length of 19.280 ± 5.296 mm. Additionally, developed gonads were observed in females with less than 8 months. This study presents the first record of P. aspera juvenile grow-out, born from artificial fertilization, which represents a major step toward the development of limpet aquaculture.

BackgroundPatients with breast cancer (BC) exhibit circadian rhythm disruptions, mainly of rest-activity rhythm (RAR), of which sleep is an essential component, and cortisol rhythm. Sleep complaints such as insomnia and cognitive impairments are prevalent in BC. In general population, sleep is known to contribute greatly to cognition. Thus, improving RAR (and particularly sleep) could help limiting cognitive impairments in BC patients. It has recently been suggested that, in addition to its essential role in spatial memory, the vestibular system contributes to RAR synchronization. Its stimulation could therefore limit both sleep disturbances and spatial memory deficits in BC.ObjectivesThe main aim of the ICANSLEEP-2 study is to assess the effects of galvanic vestibular stimulation (GVS) on circadian rhythms. The secondary aim is to assess whether GVS improves sleep and spatial memory in BC patients.MethodsTwo groups with insomnia complaints (Insomnia Severity Index > 7) will be included: a patients' group with BC (n = 50) and a healthy control group without history of cancer (n = 25). There will be two assessment sessions, before and after 2 weeks of GVS. Patients will be randomly assigned to either a GVS group or a sham group (noneffective stimulation). Controls will receive GVS. GVS effects will be quantified and compared between groups. Assessments will include actigraphy, salivary cortisol, polysomnography, a cognitive test battery (including a computer-based task for spatial memory) and validated questionnaires (for psychological functioning and sleep complaints).DiscussionCurrent methods for improving sleep in BC have had controversial outcomes regarding sleep structure. We expect GVS to offer a new mean of directly targeting RAR disruptions in BC patients, with beneficial effects on sleep structure. Given the crucial impact of sleep on cognitive functioning, notably spatial memory, improving sleep of BC patients should enhance their cognitive functioning.Ethics and disseminationThis study received ethical approval from the Ile de France IV institutional review board on 19 April 2022 (no. ID-RCB: 2022-A00437-36). The findings yielded by this protocol will be presented at various conferences and in peer-reviewed journals.Clinicaltrials.gov registration numberNCT05414357.

IntroductionThe RISKMet project aims to: (1) identify risk factors for metabolic syndrome (MetS) by comparing patients with and without MetS; (2) characterise patients treated with second-generation antipsychotics (SGAs) about MetS diagnosis; (3) study behavioural patterns, including physical activity (PA) and dietary habits, in patients and healthy individuals using a prospective cohort design.MethodThe RISKMet project investigates MetS in individuals treated with SGAs, focusing on both adult and paediatric populations. The study utilizes a case-control design to examine potential risk factors for MetS, categorizing participants as MetS+ considered as "Cases" and MetS- considered as "Controls" matched by sex and age. The evaluation of factors such as MetS, lifestyle habits, and environmental influences is conducted at two time points, T0 and T3, after 3 months. Subsequently, the project aims to assess body parameters, including physical examinations, and blood, and stool sample collection, to evaluate metabolic markers and the impact of SGAs. The analysis includes pharmacological treatment data and genetic variability. Behavioural markers related to lifestyle, eating behaviour, PA, and mood are assessed at both T0 and T3 using interviews, accelerometers, and a mobile app. The study aims to improve mental and physical well-being in SGA-treated individuals, establish a biobank for MetS research, build an evidence base for physical health programs, and develop preventive strategies for SGA-related comorbidities.ConclusionsThis project innovates MetS monitoring in psychiatry by using intensive digital phenotyping, identifying biochemical markers, assessing familial risks, and including genetically similar healthy controls.Study registration numberISRCTN18419418 at www.isrctn.com.

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD.

Abstract Background Knee osteoarthritis (OA) is a progressive and degenerative condition. Several pharmacological and non-pharmacological treatments are able to improve the OA symptoms and the structural characteristics of the affected joints. Among these, infiltrative therapy with hyaluronic acid (HA) is the most used and consolidated procedure for the pain management. The addition of skin conditioning peptides to HA promotes the cartilage remodeling processes and a better permeation of the HA-based gel containing a peptide mixture, CR500®. Furthermore, the topic route of administration is convenient over the routinely used intra-articular injective procedures. In this study, the effectiveness of CR500® was evaluated in terms of improvement of the algo-functional symptoms related to unilateral knee OA. Methods 38 mild and moderate OA patients were enrolled at a screening visit (V-1), treated at baseline visit (V1), and then continued the topical application of CR500® twice a week for 4 weeks, and followed-up for 3 visits (V2-V4) from week 2 to 4. Lequesne Knee Index (LKI) and Knee injury and Osteoarthritis Outcome Score (KOOS) were collected. Synovial fluid was collected and used for the quantification of neoepitope of type II collagen (C2C), C-terminal telopeptide of type II collagen (CTX-II), type II collagen propeptide (CPII), tumor necrosis factor alpha (TNFα) and HA. The expression of CD11c and CD206 was evaluated on cell pellets. Results Three patients were excluded, thus 35 patients were included in the analysis. The treatment with CR500® was safe and well tolerated, with 7.9% patients had mild adverse events, not related to the device. The LKI total score showed a significant decrease from V1 to V4. KOOS score also showed a significant improvement of patient condition at V2, V3 and V4 in comparison with V1 for all subscales, except for KOOS sport subscale which improved only from V3. At V1 a negative correlation among KOOS pain subscale values and C2C, CPII and TNFα levels was observed, as well as a positive correlation between KOOS pain subscale and CD11c/CD206 ratio. Conclusion CR500® is safe and appear to be effective in improving pain and function in OA patients during the 4 weeks of treatment. Trial registration ClinicalTrials.gov ID: NCT05661162. This trial was registered on 22/12/2022.

Abstract In this longitudinal study we compare between and within-strain variation in the home-cage spatial preference of three widely used and commercially available mice strains—C57BL/6NCrl, BALB/cAnNCrl and CRL:CD1(ICR)—starting from the first hour post cage-change until the next cage-change, for three consecutive intervals, to further profile the circadian home-cage behavioural phenotypes. Cage-change can be a stressful moment in the life of laboratory mice, since animals are disturbed during the sleeping hours and must then rapidly re-adapt to a pristine environment, leading to disruptions in normal motor patterns. The novelty of this study resides in characterizing new strain-specific biological phenomena, such as activity along the cage walls and frontality, using the vast data reserves generated by previous experimental data, thus introducing the potential and exploring the applicability of data repurposing to enhance Reduction principle when running in vivo studies. Our results, entirely obtained without the use of new animals, demonstrate that also when referring to space preference within the cage, C57BL/6NCrl has a high variability in the behavioural phenotypes from pre-puberty until early adulthood compared to BALB/cAnNCrl, which is confirmed to be socially disaggregated, and CRL:CD1(ICR) which is conversely highly active and socially aggregated. Our data also suggest that a strain-oriented approach is needed when defining frequency of cage-change as well as maximum allowed animal density, which should be revised, ideally under the EU regulatory framework as well, according to the physiological peculiarities of the strains, and always avoiding the “one size fits all” approach.

Total Ankle Replacement (TAR) could, in theory, partially restore joint sensation and motion, enhancing motor coordination, functional stability, and proprioception in a joint affected by osteoarthritis. The aim of this study is to evaluate ankle proprioception before and after a Total Ankle Replacement via an instrumental objective assessment. The evaluation of proprioceptive stability was carried out using the dedicated Delos Postural Proprioceptive System (DPPS). The clinical evaluation was performed by administering validated questionnaires, namely the American Orthopaedic Foot and Ankle Society (AOFAS) score and Short Form-36 (SF-36). Twenty patients were selected, undergoing a complete procedure with clinical and instrumental pre-operative and post-operative evaluation at the end of the follow-up. AOFAS ankle–hindfoot and SF-36 both showed a statistically significant improvement between the pre-operative and post-operative state. The postural tests performed using the DPPS showed that the affected limb showed results slightly lower than in pre-operative. In conclusion, according to the current data, the TAR does not show an improvement in proprioceptive joint stability, and although the registered mean values do not present a statistical significance, the stabilometry shows data lower than the healthy limb. In this perspective, further studies are recommended to highlight any rehabilitation scheme or protocols, using wider case series.

Tendinopathies continue to be a challenge for both patients and the medical teams providing care as no universal clinical practice guidelines have been established. In general, tendinopathies are typically characterized by prolonged, localized, activity-related pain with abnormalities in tissue composition, cellularity, and microstructure that may be observed on imaging or histology. In the lower limb, tendinopathies affecting the Achilles and the patellar tendons are the most common, showing a high incidence in athletic populations. Consistent diagnosis and management have been challenged by a lack of universal consensus on the pathophysiology and clinical presentation. Current management is primarily based on symptom relief and often consists of medications such as non-steroidal anti-inflammatories, injectable therapies, and exercise regimens that typically emphasize progressive eccentric loading of the affected structures. Implementing the knowledge of tendon stem/progenitor cells (TSPCs) and assessing their potential in enhancing tendon repair could fill an important gap in this regard. In the present pilot in vivo study, we have characterized the structural and cellular alterations that occur soon after tendon insult in models of both Achilles and patellar tendinopathy. Upon injury, CD146+ TSPCs are recruited from the interfascicular tendon matrix to the vicinity of the paratenon, whereas the observed reduction in M1 macrophage polarization is related to a greater abundance of reparative CD146+ TSPCs in situ. The robust TSPCs’ immunomodulatory effects on macrophages were also demonstrated in in vitro settings where TSPCs can effectively polarize M1 macrophages towards an anti-inflammatory therapeutic M2 phenotype. Although preliminary, our findings suggest CD146+ TSPCs as a key phenotype that could be explored in the development of targeted regenerative therapies for tendinopathies.

Macrophage-based co-cultures are used to test the immunomodulatory function of candidate cells for clinical use. This study aimed to characterize a macrophage polarization model using human platelet lysate (hPL) as a GMP-compliant alternative to Fetal Bovine Serum (FBS). Primary human monocytes were differentiated into unpolarized (M0) or polarized (M1, M2a, and M2c) macrophages in an hPL- or FBS-based medium. The protein secretion profiles and expression of phenotypic markers (CD80 for M1, CD206 for M2a, and CD163 for M2c) were analyzed. Subsequently, chondrocytes were tested in an hPL-based co-culture model to assess their immunomodulatory function in view of their possible use in patients with osteoarthritis. The results showed similar marker regulation between hPL and FBS cultures, but lower basal levels of CD206 and CD163 in hPL-cultured macrophages. Functional co-culture experiments with chondrocytes revealed increased CD206 expression both in hPL and in FBS, indicating an interaction between macrophages and chondrocytes. While markers in FBS-cultured macrophages were confirmed in hPL-cultured cells, the interpretation of marker modulation in immunomodulatory assays with hPL-based cultures should be carried out cautiously due to the observed differences in the basal marker levels for CD206 and CD163. This research underscores the utility of hPL as a GMP-compliant alternative to FBS for macrophage-based co-cultures and highlights the importance of understanding marker expressions in different culture conditions.

Abstract Background Posttraumatic stress disorder (PTSD) is associated with significant morbidity, but efficacious pharmacotherapy and psychotherapy are available. Data from the World Mental Health Surveys were used to investigate extent and predictors of treatment coverage for PTSD in high-income countries (HICs) as well as in low- and middle-income countries (LMICs). Methods Seventeen surveys were conducted across 15 countries (9 HICs, 6 LMICs) by the World Health Organization (WHO) World Mental Health Surveys. Of 35,012 respondents, 914 met DSM-IV criteria for 12-month PTSD. Components of treatment coverage analyzed were: (a) any mental health service utilization; (b) adequate pharmacotherapy; (c) adequate psychotherapy; and (d) effective treatment coverage. Regression models investigated predictors of treatment coverage. Results 12-month PTSD prevalence in trauma exposed individuals was 1.49 (S.E., 0.08). A total of 43.0% (S.E., 2.2) received any mental health services, with fewer receiving adequate pharmacotherapy (13.5%), adequate psychotherapy (17.2%), or effective treatment coverage (14.4%), and with all components of treatment coverage lower in LMICs than HICs. In a multivariable model having insurance (OR = 2.31, 95 CI 1.17, 4.57) and severity of symptoms (OR = .35, 95% CI 0.18, 0.70) were predictive of effective treatment coverage. Conclusion There is a clear need to improve pharmacotherapy and psychotherapy coverage for PTSD, particularly in those with mild symptoms, and especially in LMICs. Universal health care insurance can be expected to increase effective treatment coverage and therefore improve outcomes.