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Nanobody-targeted photodynamic therapy (NB-PDT) has been developed as a potent and tumor-selective treatment, using nanobodies (NBs) to deliver a photosensitizer (PS) specifically to cancer cells. Upon local light application, reactive oxygen species are formed and consequent cell death occurs. NB-PDT has preclinically shown evident success and we next aim to treat cats with oral squamous cell carcinoma (OSCC), which has very limited therapeutic options and is regarded as a natural model of human head and neck SCC. Immunohistochemistry of feline OSCC tissue confirmed that the epidermal growth factor receptor (EGFR) is a relevant target with expression in cancer cells and not in the surrounding stroma. Three feline OSCC cell lines were employed together with a well-characterized human cancer cell line (HeLa), all with similar EGFR expression, and a low EGFR-expressing human cell line (MCF7), mirroring the EGFR expression level in the surrounding mucosal stroma. NBA was identified as a NB binding human and feline EGFR with comparable high affinity. This NB was developed into NiBh, a NB-PS conjugate with high PS payload able to effectively kill feline OSCC and HeLa cell lines, after illumination. Importantly, the specificity of NB-PDT was confirmed in co-cultures where only the feline OSCC cells were killed while surrounding MCF7 cells were unaffected. Altogether, NiBh can be used for NB-PDT to treat feline OSCC and further advance NB-PDT towards the human clinic.

Abstract Background Human bone marrow is a source of mesenchymal stem cells (MSCs), other progenitor cells, and factors with anti-inflammatory and regenerative capacity. Though the fraction of MSCs out of the nucleated cells is very small, bone marrow aspirate (BMA) for osteoarthritis (OA) has noteworthy effects. BMA is usually collected from the posterior or anterior iliac crest, and rarely from the proximal tibia. We investigated the clinically beneficial concentration of ex vivo MSCs, derived from BM harvested from the posterior iliac crest and proximal tibia by Marrow Cellution™ Aspiration System, and their phenotypic differences, in comparison to autologous Platelet-Rich Plasma (PRP) treatment prepared with a manual, closed system. Methods A single-center, parallel, randomized controlled study was designed to investigate the efficacy of BMA from the posterior iliac crest compared to BMA from the proximal tibia, against a control group treated with PRP, in knee OA. Thirty patients with knee OA grade I-IV, according to Kellgren-Lawrence (KL), were distributed into each group. Visual Analog Scale (VAS) and Western Ontario & McMaster Universities Arthritis Index (WOMAC) score were used for clinical outcome evaluation. Results Data from an intermediate analysis of 6-months follow-up, involving 15 patients in each arm, showed that the posterior iliac crest was significantly more densely populated with mononuclear cells, than the proximal tibia (p = 0.005). Flow cytometric analysis on ex vivo BMA showed a significantly greater number of MSCs in the BM-derived from the posterior iliac crest when compared with the proximal tibia (p 0.05). A better outcome, in terms of ΔVAS, was observed in patients classified as KL I-II, when treated with BMA from crest (p

This suspect case focuses on investigating the presence of halite (NaCl) crystals on the clothing of a deceased individual to determine whether they resulted from immersion in seawater or residual absorption after immersion (i.e., the crystals were left on the clothing after contact with the victim’s wet body). Thirteen clothing samples were collected from various garments worn by the victim and were subjected to optical stereomicroscopy, Scanning Electron Microscopy (SEM), coupled with Energy Dispersive Spectroscopy (EDS), and Simultaneous Thermal Analysis (STA). Optical stereomicroscopy revealed numerous white-colored, vitreous, and greasy luster microcrystals dispersed between fabric fibers, with higher concentrations observed near the hem seams and metal rivets. These microcrystals exhibited predominantly cubic and irregular morphologies. Additionally, sandy particles and organic elements, such as plant fragments and micro seashells, were detected, indicative of coastal environment exposure. SEM-EDS analysis confirmed the presence mainly of sodium and chlorine in stoichiometric ratios consistent with halite, with crystals exhibiting amorphous, needle-shaped, or cubic morphologies. Furthermore, STA analysis identified weight loss events attributed to organic decomposition and halite decomposition at high temperatures, corroborating SEM-EDS findings. The distribution and characteristics of halite crystals, along with other trace elements, support the hypothesis of immersion in seawater while wearing clothing. Specifically, the higher concentrations of halite crystals near thicker fabric portions and metal rivets suggest slower drying rates and longer evaporation times, indicative of immersion rather than residual absorption after swimming. This finding not only helps in determining the victim’s exposure to seawater but also establishes a methodology for distinguishing between different sources of halite residue on clothing. Overall, the comprehensive mineralogical characterization of halite crystals on clothing samples, using best practices of forensic mineralogy, provides valuable forensic insights related to the circumstances that led to the victim’s death. This approach aided investigators in reconstructing the sequence of events, enhancing the accuracy of forensic reconstructions. Moreover, this study contributes to the broader field of forensic geoscience by demonstrating the practical applications of mineralogical analysis in criminal investigations, potentially guiding future research and improving investigative techniques in similar cases.

IntroductionBehavioral and Psychological Symptoms of Dementia (BPSD) are a heterogeneous set of psychological reactions and abnormal behaviors in people with dementia (PwD). Current assessment tools, like the Neuropsychiatric Inventory (NPI), only rely on caregiver assessment of BPSD and are therefore prone to bias.Materials and methodsA multidisciplinary team developed the BPSD-SINDEM scale as a three-part instrument, with two questionnaires administered to the caregiver (evaluating BPSD extent and caregiver distress) and a clinician-rated observational scale. This first instrument was tested on a sample of 33 dyads of PwD and their caregivers, and the results were qualitatively appraised in order to revise the tool through a modified Delphi method. During this phase, the wording of the questions was slightly changed, and the distress scale was changed into a coping scale based on the high correlation between extent and distress (r = 0.94). The final version consisted of three 17-item subscales, evaluating BPSD extent and caregiver coping, and the unchanged clinician-rated observational scale.ResultsThis tool was quantitatively validated in a sample of 208 dyads. It demonstrated good concurrent validity, with the extent subscale correlating positively with NPI scores (r = 0.64, p

Abstract Achieving complete tumor resection is challenging and can be improved by real-time fluorescence-guided surgery with molecular-targeted probes. However, pre-clinical identification and validation of probes presents a lengthy process that is traditionally performed in animal models and further hampered by inter- and intra-tumoral heterogeneity in target expression. To screen multiple probes at patient scale, we developed a multispectral real-time 3D imaging platform that implements organoid technology to effectively model patient tumor heterogeneity and, importantly, healthy human tissue binding.

Asylum seekers experience conditions of social disadvantage, poor labor market outcomes, and low-paid jobs. Therefore, vocational guidance and career counseling must function as a supportive social practice for asylum seekers giving voice to them and focusing on their strengths, such as courage. The present study examined the personal stories of courage of 71 asylum seekers who migrated to Italy. Results highlight situations characterized by undignified living conditions, dehumanizing transitions, and barriers imposed on future aspirations. These voices could become a significant starting point to consider asylum seekers' future in the perspective of an inclusive and sustainable future.

IntroductionThe stromal vascular fraction (SVF) of human adipose tissue is an attractive cell source for engineering grafts with intrinsic vascularization potential, as it is rich in vasculogenic progenitors. However, in order to maintain their functional perfusion it is important to promote the in vivo stabilization of newly assembled microvascular networks. We previously found that Semaphorin 3A (Sema3A) promotes the rapid stabilization of new blood vessels induced by VEGF overexpression in skeletal muscle. Here we investigated whether Sema3A could promote the assembly, connection to circulation and persistence of human SVF-derived microvascular networks in engineered grafts.MethodsRecombinant Sema3A was engineered with a transglutaminase substrate sequence (TG-Sema3A) to allow cross-linking into fibrin hydrogels. Grafts were prepared with freshly isolated human SVF cells in fibrin hydrogels decorated with 0, 0.1 or 100 μg/ml TG-Sema3A and implanted subcutaneously in immune-deficient mice.ResultsAfter 1 week in vivo, the assembly of human-derived networks was similar in all conditions. The outer part of the grafts was populated by blood vessels of both human and mouse origin, which formed abundant hybrid structures within a common basal lamina. About 90% of human-derived blood vessels were functionally connected to the host circulation in all conditions. However, in the control samples human vessels were unstable. In fact, they significantly regressed by 6 weeks and could no longer be found by 12 weeks. In contrast, a low Sema3A dose (0.1 μg/ml) promoted further human vascular expansion by about 2-fold at 6 weeks and protected them from regression until 12 weeks. From a mechanistic point of view, the stabilization of SVF-derived vessels by 0.1 μg/ml of Sema3A correlated with the recruitment of a specific population of monocytes expressing its receptor Neuropilin-1.DiscussionIn conclusion, Sema3A is a potent stimulator of in vivo long-term persistence of microvascular networks derived from human SVF. Therefore, decoration of matrices with Sema3a can be envisioned to promote the functional support of tissue engineered grafts.

In the present study, in order to expand the knowledge on the distribution of parasites of the genus Eustrongylides in never investigated Italian lacustrine areas of Tuscany and Latium, fish specimens from four Tuscan lakes (Bilancino, Chiusi, Montedoglio and San Cipriano) and two Latium lakes (Bolsena and Bracciano) were collected and analyzed. The parasitological analysis, consisting of a visual inspection followed by a chloro-peptic digestion, was performed on 1650 specimens belonging to 17 species: European perch (Perca fluviatilis), Pumpkinseed (Lepomis gibbosus), Pike-perch (Sander lucioperca), Largemouth black bass (Micropterus salmoides), Pike (Esox lucius), Big-scale sand smelt (Atherina boyeri), Tench (Tinca), European Whitefish (Coregonus lavaretus), Channel catfish (Ictalurus punctatus), Chub (Squalius cephalus), Rudd (Scardinius erythrophthalmus), Common bleak (Alburnus alborella), South European roach (Sarmarutilus rubilio), South European nase (Protochondrostoma genei), Italian riffle dace (Telestes muticellus), Goldfish (Carassius auratus), and Freshwater bream (Abramis brama). Eustrongylides spp. larvae were only found in one specimen of European perch caught in Bracciano Lake and purchased from a local fishmonger (P = 3.3%; MI = 1; MA = 0.03). The only isolated Eustrongylides spp. larva was submitted to molecular analysis of the ITS gene region and identified as E. excisus. This finding adds Bracciano Lake to the list of the several Italian lakes in which nematodes belonging to this genus have been reported. Even if the observed prevalence is currently low, the presence of the parasite in this local freshwater fish supply chain requires FBOs to adopt risk management measures to prevent contaminated products from reaching final consumer. Moreover, future investigations will show if the parasite expands in these areas.

An online group of career counseling for unemployed young adults during the COVID-19 pandemic was developed. Twelve participants were involved in online group career counseling intervention, based on the Life Design for an inclusive and sustainable future. Results indicated at post-test on increased scores on career adaptability, resilience, future orientation, and propensity to identify inclusive and sustainable actions for the future than pre-test. Overall, the online group career counseling intervention effectively promoted particular aspects of young adults' life design for an inclusive e-sustainable future.

Abstract Silica hydrogels are used as fire-retardant materials due to the occurrence of intumescence that limits heat and mass transfer. They act as heat-sink, through continuous endothermic condensation reactions, meantime shrinking to a more connected network, towards the correspondent crystalline compound. Which compositions and treatments amplify this phenomenon is still of interest. To this aim, two silica sols containing two different complexing agents: ethylene glycol and glycerol has been prepared and analyzed. The samples were subjected to different treatments to induce gelation and densification: exposure to ultraviolet or microwave or infrared irradiation. Thermogravimetric analysis coupled with differential scanning calorimetry (TG-DSC) and scanning electron microscopy analyses has been also carried out. Moreover, dynamic mechanical spectroscopy (DMS) let to evaluate simultaneously the mechanical and intumescence behavior of the gels at increasing curing times for each type of irradiation. Intumescence of gels occurs up to 200 °C and appears as an endothermal group of peaks visible on the heat-flux DSC curves. DMS analyses let to assess that a MW cured glycerol-containing gel (GL-0-MW 6d) shows a glass transition above 150 °C, measured as the maximum of damping peak. Accordingly, this sample is a good option for the application: a few bubbles nucleate and grow fast at high temperature. Article Highlights Transparent fire doors contain silica gel, which absorbs heat and releases water by foaming. Two different silica gels were synthetized using different chelating agents. The foaming depends on the reagents used to produce the gel, on the treatments for stabilizing it and also on ageing. Both foaming and consolidation of the gel were studied with thermogravimetric and dynamic-mechanical analysis.

Forensic geoarchaeology provides a comprehensive and interdisciplinary approach to investigating crime scenes. This field combines the techniques and methods of archaeology, geology, geophysics, and remote sensing, to provide a more comprehensive picture of the events that have occurred at a site. Forensic geoarchaeologists can not only provide valuable information about the context of a crime scene but also help reconstruct past events and collect relevant information about missing persons. Moreover, the use of geospatial technologies and the analysis of evidence together with a vast range of scientific methods and techniques help forensic geoarchaeologists provide compelling and reliable evidence before courts and law enforcement agencies. Although some reticence still prevails among Italians about recognizing forensic geoarchaeology as a fundamental discipline vis-a-vis crime scenes, the recognition of its vital significance is growing in Italy, thanks to the decision of the Italian Standards Organization (UNI) to standardize it alongside other fields of criminalistic expertise.

In the present study, the linkages between study abroad participation, participation in other high-impact educational practices, and participation in co-curricular activities were examined. It was the purpose of the study to determine if study abroad participants also chose to participate in multiple other high-impact educational practices and co-curricular activities at significantly higher rates than their peers who did not study abroad. The present study demonstrated that many students who study abroad tend toward multiple-participation (e.g., participation in multiple voluntary activities) when controlling for race/ethnicity, gender, and academic major. While multiple-participation was established among many study abroad subgroups, the current study was not able to substantiate multiple-participation among all student subgroups.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by significant fibrosis of the skin and internal organs, with the main involvement of the lungs, kidneys, heart, esophagus, and intestines. SSc is also characterized by macro- and microvascular damage with reduced peripheral blood perfusion. Several studies have reported more than 240 pathways and numerous dysregulation proteins, giving insight into how the field of biomarkers in SSc is still extremely complex and evolving. Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, and anti-centromere and anti-topoisomerase I antibodies are considered classic biomarkers with precise clinical features. Recent studies have reported that trans-forming growth factor β (TGF-β) plays a central role in the fibrotic process. In addition, interferon regulatory factor 5 (IRF5), interleukin receptor-associated kinase-1 (IRAK-1), connective tissue growth factor (CTGF), transducer and activator of transcription signal 4 (STAT4), pyrin-containing domain 1 (NLRP1), as well as genetic factors, including DRB1 alleles, are implicated in SSc damage. Several interleukins (e.g., IL-1, IL-6, IL-10, IL-17, IL-22, and IL-35) and chemokines (e.g., CCL 2, 5, 23, and CXC 9, 10, 16) are elevated in SSc. While adiponectin and maresin 1 are reduced in patients with SSc, biomarkers are important in research but will be increasingly so in the diagnosis and therapeutic approach to SSc. This review aims to present and highlight the various biomarker molecules, pathways, and receptors involved in the pathology of SSc.

Abstract Paragonimiasis is a zoonotic, food-borne trematode infection that affects 21 million people globally. Trematodes interact with their hosts via extracellular vesicles (EV) that carry protein and RNA cargo. We analyzed EV in excretory-secretory products (ESP) released by Paragonimus kellicotti adult worms cultured in vitro (EV ESP) and EV isolated from lung cyst fluid (EV CFP) recovered from infected gerbils. The majority of EV were approximately 30–50 nm in diameter. We identified 548 P. kellicotti-derived proteins in EV ESP by mass spectrometry and 8 proteins in EV CFP of which 7 were also present in EV ESP. No parasite-derived proteins were reliably detected in EV isolated from plasma samples. A cysteine protease (MK050848, CP-6) was the most abundant protein found in EV CFP in all technical and biological replicates. Immunolocalization of CP-6 showed strong labeling in the tegument of P. kellicotti and in the adjacent cyst and lung tissue that contained worm eggs. It is likely that CP-6 present in EV is involved in parasite-host interactions. These results provide new insights into interactions between Paragonimus and their mammalian hosts, and they provide potential clues for development of novel diagnostic tools and treatments.

This short communication discusses how a specific geoarchaeological remote-sensing (RS) method, such as analyzing satellite images through NDWI (Normalized Difference Water Index), can be used to aid in searching and locating persons missing in watercourses. Thanks to its high capacity to analyze changes in the surface water area, this index can remotely detect the presence of anomalies related to disappearances in water bodies and provide valuable information that can reduce the use of human resources and help pinpoint likely areas of search. Two real-life cases of missing persons in rivers in which the NDWI index was used are presented, and the results obtained are discussed, emphasizing the importance of NDWI analysis as a complementary method to different approaches, especially non-invasive and remote-sensed ones, when positively searching for missing persons.

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes.

Abstract CRC cells evolve a variety of strategies to limit or circumvent apoptosis cell death. RNA binding proteins (RBPs) regulate many of the molecular mechanisms that underlie the development of cancer. The insulin-like growth factor II mRNA-binding proteins (IMP) family are oncofoetal RBPs, consisting of IMP1, IMP2 and IMP3, which have an important role in RNA metabolism. IMP3 is highly expressed in colorectal cancer (CRC) tissue, where its expression often correlates with poor prognosis. However, the role of IMP3 in CRC is not fully understood. IMP3 expression was analysed using a public database and by Western blotting and immunohistochemistry in human colon samples derived from patients with sporadic CRC and healthy subjects. To address whether IMP3 controls cancer cell survival, we analysed cell death pathways in in vitro and in vivo experiments after IMP3 downregulation by siRNA or an antisense oligonucleotide. IMP3 was highly expressed in CRC samples compared to normal control tissues. The knockdown of IMP3 enhanced a caspase-independent cell death in CRC cell lines. Furthermore, the treatment of CRC cells with IMP3 siRNA did not alter the expression of GSDMD, GPX-4 and the activated form of RIP3, three key molecules that govern pyroptosis, ferroptosis and necroptosis, respectively. Abrogation of IMP3 in CRC significantly reduced Bcl-2 and Bcl-xL mRNA and was associated with an altered mitochondrial membrane potential that allowed the nuclear migration of the apoptosis-inducing factor (AIF). Moreover, specific immunoprecipitation experiments on CRC human cell lines indicated that IMP3 binds Bcl-2 and Bcl-xL mRNA, suggesting that IMP3 acts as a regulator of the intrinsic apoptotic pathway through the surveillance of anti-apoptotic Bcl mRNA metabolism. Finally, we showed that IMP3 block inhibited the growth of CRC cell lines in vivo after transplantation into immunodeficient mice. Altogether, these data support a novel role for IMP3 in controlling the intrinsic caspase-independent apoptotic pathway in CRC.

Teachers' attitudes towards students with disabilities have a crucial role in the effective implementation of the school inclusion process. This study examined the relationship of relevant teachers' personal variables (gender, age, length of professional experience, and the grade of the school in which they teach), characteristics of the students with disabilities (type of disability, gender), and contextual factors (type of information provided in the students' profiles of children with disabilities) with teachers' attitudes towards students with disabilities. A sample of 336 mainstream Italian primary and secondary teachers was involved. Results showed that teachers' gender, age, and length of professional experience were not related to their attitudes. Secondary school teachers hold more negative attitudes related to the social acceptability of students with disabilities. More negative attitudes related to school performance towards boys and students with intellectual disability, and more negative attitudes related to social acceptability towards students with behaviour problems were found. Lastly, the type of information provided in the students' profiles of children with disabilities positively impacted teachers' attitudes towards the students when the descriptions focused on their strengths. Implications of the results are discussed in terms of promoting teachers' positive attitudes towards students with disabilities.