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Despite the increased prevalence of psychiatric disorder amongst offenders with an intellectual disability (ID), there is very little known about the characteristics and needs of those with dual disability. A study of admissions to a new community forensic dual disability clinic during the first 10 months of its operation. Typically, the offenders are male, are older than other offenders, exhibit long-standing and continuing serious behavioural disturbance (independent of their psychiatric diagnosis or level of involvement with the criminal justice system) and require supported or custodial accommodation, despite only mild or borderline levels of ID. Although only one-third have a diagnosable major nonparaphilic psychiatric disorder, three-quarters have had prior or current contact with psychiatric services and two-thirds suffer chronic medical illness. These offenders suffer psychosocial disadvantages far more extensive than those implied by the psychiatric or disability label. The multiple services provided to this group have been ad hoc, poorly co-ordinated and sometimes dangerously inappropriate. A service provision model is required which must be integrative and consistent. We suggest the use of multiskilled key workers, who maintain close contact with individual clients. Their role will be to implement management plans from the various specialist agencies who become involved with this group and provide long-term follow-up of their recommendations.

From 2004 to 2006, a parasitological survey aimed at the detection of the microsporidian parasite Thelohania contejeani Henneguy was carried out on 177 wild white-clawed crayfish (Austropotamobius pallipes complex) captured in six streams and rivers of the province of Belluno in north-eastern Italy. Microscopical examination of the skeletal muscles, and histological analysis applying different histochemical stains to full transverse and sagittal sections of the cephalothorax and abdomen were carried out. Transmission electron microscopy (TEM) was also conducted on the parasites recovered during the survey. Out of 177 crayfish examined, Thelohania contejeani (Microsporidia, Thelohaniidae) was present in only one crayfish from the Vena d’oro creek. The parasite was detected in the skeletal muscles in several developmental stages, including mature spores, which represented the most common stage recovered. Sporophorous vesicles were also present. Histological examination revealed that the fibres of the skeletal, cardiac and intestinal muscles were filled with spores. Melanin infiltrations were focally present in the infected striated muscles. The gill phagocytic nephrocytes were engulfed by small masses of spores. Among the staining techniques applied, Crossman’s trichrome stain represented the most effective method of detecting T. contejeani.

Aims This comparative study investigated the occurrence of cadF, cj1349, ciaB, pldA, tlyA, hecA, hecB, mviN, irgA and IroE genes in 212 Arcobacter butzleri isolated from three different environmental sites linked to the dairy chain (farms, industrial and artisanal dairy plants) located in three Italian regions (Lombardy, Emilia-Romagna and Calabria). Methods and Results According to the presence of these genes, different pathotypes (P-types) were determined. The main genes detected were ciaB, mviN, tlyA, cj1349, pldA and cadF, while the least common genes were iroE, hecA, hecB and irgA. TlyA, irgA, hecA, hecB and iroE, which were significantly more frequent in isolates recovered in industrial dairy plants. Twelve P-types were detected. The occurrence of the most frequently detected P-types (P-types 1, 2, 3 and 5) differed significantly ( P < 0·001) in relation to both the environmental site and geographical area of isolation. The highest diversity in P-types was observed in industrial dairy plants and in the Calabria region. Conclusions The results of this study show a correlation between the occurrence of putative virulence genes and virulence genotype variability depending on the environmental site and geographical origin of the isolates. Significance and Impact of the Study The present study provides insights into the similar distribution of putative virulence genes in a dairy chain and other sources' isolates and also into a geographical distribution of some P-types. We have shown that industrial dairy plants may represent an environmental site favouring a selection of the isolates with a higher pathogenetic pattern. [ABSTRACT FROM AUTHOR]

The valence and size of cations influence mass diffusion and oxygen defects in ceria. Here we show that reduction of Ce4+ to Ce3+, at high temperatures and low oxygen activity, activates fast diffusion mechanisms which depend on the aliovalent cation concentration. As a result, polycrystalline solid solutions with enhanced electrochemical properties are formed. [ABSTRACT FROM AUTHOR]

The objectives of this study were to investigate the presence of Campylobacter spp. and Arcobacter spp. in dairy herds authorized for the production and sale of raw milk and in a water buffalo dairy farm, and to test the antimicrobial susceptibility of the isolates. A total of 196 in-line milk filters were collected from 14 dairy farms (13 bovine and 1 water buffalo) for detection of Campylobacter spp. and Arcobacter spp. by microbiological culture. For each farm investigated, 1 isolate for each Campylobacter and Arcobacter species isolated was tested using the Etest method (AB Biodisk, Solna, Sweden) to evaluate the susceptibility to ciprofloxacin, tetracycline, chloramphenicol, ampicillin, erythromycin, and gentamicin. A total of 52 isolates were detected in 49 milk filters in 12 farms (85.7%) out of 14 and the isolates were identified as Campylobacter jejuni (6), Campylobacter hyointestinalis ssp. hyointestinalis (8), Campylobacter concisus (1), Campylobacter fetus ssp. fetus (1), Arcobacter butzleri (22), and Arcobacter cryaerophilus (14). The small number of isolates tested for antimicrobial susceptibility precludes any epidemiological consideration but highlights that all Campylobacter isolates were susceptible to macrolides, which are the first-choice drugs for the treatment of campylobacteriosis, and that resistance to fluoroquinolones and tetracycline was detected; for Arcobacter isolates, resistance to ampicillin and chloramphenicol was detected. The sale of raw milk for human consumption by self-service automatic vending machines has been allowed in Italy since 2004 and the presence of C. jejuni in in-line milk filters confirms that raw milk consumption is a significant risk factor for human infection. The high occurrence of emerging Campylobacter spp. and Arcobacter spp. discovered in dairy farms authorized for production and sale of raw milk represents an emerging hazard for human health. [ABSTRACT FROM AUTHOR]

Nation β-relaxation was studied by detailed dielectric spectroscopy measurements carried out in a wide range of both temperature and relative humidity. Cast and extruded Nation were compared in the H+, Na+, and Cs+ forms to evaluate contributions arising from membrane morphology and ionic interactions. The experimental data indicated that β-relaxation is associated with the motion of side chains of the ionomer. The unusual shift to lower frequencies of the β-relaxation was shown to be more pronounced for samples containing high water content and at temperatures above the α-relaxation, evidencing that the electrostatic repulsions between bare sulfonic groups reduce the side chain mobility. A pronounced increase of relaxation times was observed at relative humidity >60% suggesting a change of the morphology of the ionomer, in agreement with recent descriptions of the Nation structure by small angle X-ray scattering analyzes. [ABSTRACT FROM AUTHOR]

The sintering behavior of gadolinia-doped ceria powders was studied by the master sintering curve (MSC). Dilatometric analyses of powders produced by a soft chemical method were performed to provide the experimental data set for the construction of the MSC. The assumed model provided good fittings of the MSC and the activation energy for the sintering of Ce1− xGd xO3−δ, with x = 0, 0.05, 0.1, and 0.2 were found to be in the 218–325 KJ/mol range, depending on the dopant content. The results supported that both the nanometric size of the particles and the difference in ionic radii between Gd3+ and Ce4+ affects the sintering of Gd-doped CeO2. [ABSTRACT FROM AUTHOR]

The occurrence of Mycobacterium spp. in freshwater and marine ornamental fish was studied in Italy from June 2002 to May 2005. Two surveys were carried out, one of aquarium fish sent to the Laboratory for diagnosis, and the other of prevalence of infection by mycobacteria in ornamental fish imported into Italy. Bacterial isolation was carried out from the spleen, kidney and liver, and the isolates were subsequently identified by biochemical tests. In the first survey, 387 fish were examined and Mycobacterium spp. were isolated from 181 (46.8%) fish. In the second survey 127 batches of ornamental fish from different countries were examined. Mycobacterium spp. were isolated from 38 (29.9%) batches. The following species were found: M. fortuitum, M. peregrinum, M. chelonae, M. abscessus, M. marinum, M. gordonae, M. nonchromogenicum and M. interjectum. There was a high prevalence of infection independent of the presence of macroscopic lesions. Mycobacterium fortuitum and M. chelonae were more prevalent than M. marinum in the samples examined. [ABSTRACT FROM AUTHOR]

ihe synthesis and electrical characterization of La1 ~Sr~Mn05Cr05O3 compounds are reported. These compounds, with perovskite structure, have been pointed Out as a promising alternative for the nickel-based cermet anode of solid oxide fuel cells. Polycrys- talline samples, with x = 0.3, 0.4, and 0.5, were prepared by the citrate technique. The crystalline phase and the chemical compatibility with zirconia-based electrolytes were studied by X-ray diffraction analyses. The electrical properties were studied by four-probe dc electrical conductivity cj(T) measurements during redox cycles under both oxidizing and reducing atmospheres. The main results show that the ff(7) has a thermally activated behavior, and increasing Sr content increases o(T). Compounds with = 0.3 exhibited no appreciable chemical reaction with the stabilized zirconia electrolyte after heat-treatment at high temperature. The y(T) measurements evidenced the redox stability of the ceramic anode. However, some degradation of the aliT) was observed ~n samples thermally treated at 1000°C under pure hydrogen. [ABSTRACT FROM AUTHOR]

A direct ethanol solid oxide fuel cell (SOFC) fabricated from conventional materials is described. The performance of Ni-cermet anodes with zirconia and ceria as the ceramic phase in SOFCs operating on hydrogen and ethanol is compared by means of current-voltage and impedance spectroscopy measurements in the 700-900°C temperature range. The experimental data indicate that the studied ethanol-fueled SOFCs have comparable performance. However, different ceramic matrix and metallic phase composition of cermets result in different behavior of the ethanol direct oxidation. Below 800°C, the performance of fuel cells is relatively more stable as compared to higher temperatures, but the catalytic activity for ethanol conversion of doped ceria is insufficient to prevent carbon formation. The experimental results provide evidence for the importance of an appropriate combination of fuel, operating conditions, and anode materials in designing SOFCs for direct operation using ethanol as fuel. [ABSTRACT FROM AUTHOR]

Introduction: According to the WHO, detainees attempt suicide ten times more than the general population. Objectives: To investigate the impact of migration traumas on suicide behaviours of migrants in jail and to explore how substance use and other psychiatric features affect this relation. Methods: Prospective cohort study, conducted at "Sant'Anna" jail in Modena (Italy). Socio-demographic, psychiatric features and previous suicide attempts were collected, and traumas assessed with the LiMEs (List of Migration Experiences) checklist. Every participant was followed-up until an episode of suicide behaviour or to September 2019 (end of study). Survival analysis was performed. Cox's Hazard Ratios were used as a measure of association for the comparison between groups. Results: We recruited 113 subject, 96% male, median age 33. Prevalence of mental disorders was 26% and substance abuse 59%. History of self-harm was present in 36% of the sample. Median follow-up time was 80 days. During follow-up, 11 events were observed (8 self-harm and 3 suicide attempts); cumulative survival probability was 85% (Figure 1). Having experienced traumas related to wars was significantly associated with suicide behaviours, HR: 5.168 (Figure 2, Figure 3). Interestingly, no subject without substance abuse presented the outcome. Conclusions: Migrants in custody who experienced traumas in the post-migration periods, attempt suicide 5 timesmore frequently than those without traumas at any time. War traumas seem to be more strongly associated with suicide attempts, also controlling for psychiatric diagnosis, ongoing psychopharmacological therapy and substance abuse. Further research and possible intervention programs should focus on addressing post-migration living-difficulties. [ABSTRACT FROM AUTHOR]

Multi-walled carbon nanotubes (MWNT) were produced by chemical vapor deposition using yttria-stabilized zirconia/nickel (YSZ/Ni) catalysts. The catalysts were obtained by a liquid mixture technique that resulted in fine dispersed nanoparticles of NiO supported in the YSZ matrix. High quality MWNT having smooth walls, few defects, and low amounts of by-products such as amorphous carbon were obtained, even from catalysts with large Ni concentrations (>50 wt. %). By adjusting the experimental parameters, such as flux of the carbon precursor (ethylene) and Ni concentration, both the MWNT morphology and the process yield could be controlled. The resulting YSZ/Ni/MWNT composites can be interesting due to their mixed ionic-electronic transport properties, which could be useful in electrochemical applications. [ABSTRACT FROM AUTHOR]

The fabrication of yttria stabilized-zirconia/single-wall carbon nanotube (YSZ/SWCNT) composites is reported. Electrical conductivity measurements from 25 to 800 °C revealed that the composites exhibit mixed ionic-electronic conduction. At room temperature, the conductivity increases by 11 orders of magnitude with the addition of SWCNT to the YSZ. At high temperatures (>300 °C), the ionic conduction of the YSZ becomes relevant and a mixed ionic-electronic transport is observed. It is found that the transport can be described by a sum of two parallel contributions: thermally activated ionic conduction from the YSZ and fluctuation-assisted tunneling within the SWCNT network. [ABSTRACT FROM AUTHOR]

The article describes a case of a 10-month-old female dog diagnosed with chronic rhinitis due to streptococcus equi subspecies zooepidemicus (S zooepidemicus). It notes that the dog was presented to the Veterinary Teaching Hospital of the University of Bologna in Italy because it had a bilateral nasal discharge. It cites that the morphological diagnosis revealed chronic diffuse moderate lymphoplasmacytic rhinitis, with various intravascular eosinophils. Also mentioned is the use of amoxicillin, clavulanic acid and marboflaxacin to treat the dog.

Inorganic medicinal compounds represent a unique and versatile source of potential therapeutics in many diseases and, more recently, in neurodegeneration. Herein we investigated the effects of two η 6 -arene Ru(II) complexes on the self-aggregation processes of several amyloidogenic peptides endowed with different kinetics and primary sequences. The Ru(II) complexes exhibit, around the metal ion, two chlorides, one NHC = N -heterocyclic carbene, with a glucosyl and a methyl substituent and separately a hexamethylbenzene, which is named Ru1 , and one benzene, named Ru2 . Both complexes were demonstrated to bind monomeric amyloids suppressing aggregation as evidenced in thioflavin T (ThT) binding assays and autofluorescence experiments. Electrospray ionization mass spectrometry (ESI-MS) indicated the formation of direct adducts between amyloid and metal complexes, which determined the marked conformational variation of peptides and a rescue of cellular viability in SH-SY5Y cells. The complex Ru2 was demonstrated to be a more potent inhibitor of amyloid aggregation compared to Ru1 likely because of the less hindrance of the arene moiety. The presented data strongly support the in vitro ability of η 6 -arene Ru(II) complexes to suppress amyloid aggregation, providing insights into their potential application as novel therapeutics in neurodegenerative diseases.

Histidine (His) plays a key role in mediating protein interactions and its unique side chain determines pH responsive self-assembling processes and thus in the formation of nanostructures. In this study, To identify novel self-assembling bioinspired sequences, we analyzed a series of peptide sequences obtained through the point mutation of aromatic residues of 264-277 fragment of nucleophosmin 1 (NPM1) with single and double histidines. Through several orthogonal biophysical techniques and under different pH and ionic strength conditions we evaluated the effects of these substitutions in the amyloidogenic features of derived peptides. The results clearly indicate that both the type of aromatic mutated residue and its position can have different effect on amyloid-like behaviors. They corroborate the crucial role exerted by Tyr 271 in the self-assembling process of CTD of NPM1 in AML mutated form and add novel insights in the accurate investigation of how side chain orientations can determine successful design of innovative bioinspired materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute myeloid leukemia (AML) is a heterogeneous group of diseases classified into various types on the basis of distinct features concerning the morphology, cytochemistry and cytogenesis of leukemic cells. Among the different subtypes, the group "AML with gene mutations" includes the variations of the gene of the multifunctional protein nucleophosmin 1 (NPM1). These mutations are the most frequent (~30-35% of AML adult patients and less in pediatric ones) and occur predominantly in the C-terminal domain (CTD) of NPM1. The most important mutation is the insertion at W288, which determines the frame shift W288Cfs12/Ffs12/Lfs*12 and leads to the addition of 2-12 amino acids, which hamper the correct folding of NPM1. This mutation leads to the loss of the nuclear localization signal (NoLS) and to aberrant cytoplasmic localization, denoted as NPM1c+. Many investigations demonstrated that interfering with the cellular location and oligomerization status of NPM1 can influence its biological functions, including the proper buildup of the nucleolus, and therapeutic strategies have been proposed to target NPM1c+, particularly the use of drugs able to re-direct NPM1 localization. Our studies unveiled a direct link between AML mutations and the neat amyloidogenic character of the CTDs of NPM1c+. Herein, with the aim of exploiting these conformational features, novel therapeutic strategies are proposed that rely on the induction of the selective self-cytotoxicity of leukemic blasts by focusing on agents such as peptides, peptoids or small molecules able to enhance amyloid aggregation and targeting selectively AML-NPM1c+ mutations.

This work aims to generate the data needed to set epidemiological cut-off values for minimum inhibitory concentration (MIC) and disc-diffusion zone measurements of Vibrio anguillarum. A total of 261 unique isolates were tested, applying standard methods specifying incubation at 28°C for 24-28 h. Aggregated MIC distributions for a total of 247 isolates were determined in 9 laboratories for 11 agents. Data aggregations of the disc zone for the 10 agents analysed contained between 157 and 218 observations made by 4 to 7 laboratories. Acceptable ranges for quality control (QC) reference strains were available for 7 agents and the related multi-laboratory aggregated data were censored, excluding the data of a laboratory that failed to meet QC requirements. Statistical methods were applied to calculate epidemiological cut-off values. Cut-off values for MIC data were calculated for florfenicol (≤1 µg ml-1), gentamicin (≤4 µg ml-1), oxytetracycline (≤0.25 µg ml-1) and trimethoprim/sulfamethoxazole (≤0.125/2.38 µg ml-1). The cut-off values for disc zone data were calculated for enrofloxacin (≥29 mm), florfenicol (≥27 mm), gentamicin (≥19 mm), oxolinic acid (≥24 mm), oxytetracycline (≥24 mm) and trimethoprim/sulfamethoxazole (≥26 mm). MIC and disc-diffusion zone data for the other agents where not supported by QC, thus yielding only provisional cut-off values (meropenem, ceftazidime). Regardless of whether QC is available, some of the aggregated MIC distributions (enrofloxacin, oxolinic acid), disc zone (sulfamethoxazole), and MIC and disc-diffusion distributions (ampicillin, chloramphenicol) did not meet the statistical requirements. The data produced will be submitted to the Clinical Laboratory Standards Institute for their consideration in setting international consensus epidemiological cut-off values.

The lack of internationally harmonised criteria for interpreting the data generated by standardised susceptibility testing methods presents a serious obstacle for the development of prudent use of antimicrobials in aquaculture. The data required to set epidemiological cut-off values for minimum inhibitory concentrations for antibiotic agents against Vibrio harveyi was determined using a standard microdilution method that specified the use of cation-adjusted Mueller Hinton broth and incubation at 28°C for 24 to 28 h. In total, 120 observations were made in 4 independent laboratories from 109 unique isolates. The aggregated data from these laboratories were analysed by the normalised resistance method and by ECOFFinder to calculate epidemiological cut-off values. The data for chloramphenicol, meropenem and sulfamethoxazole were not considered as suitable for analysis. The data for ampicillin indicated that this species is innately resistant to this agent. No acceptable ranges for quality control strains have been set for ceftazidime and, therefore, only provisional cut-off values could be generated for this agent. The epidemiological cut-off values were, however, calculated for the other 6 agents. These values were ≤0.5 µg ml-1 for enrofloxacin, ≤1 µg ml-1 for florfenicol, oxolinic acid and oxytetracycline, ≤4 µg ml-1 for gentamicin and ≤0.5/9.5 µg ml-1 for trimethoprim/sulfamethoxazole. Evidence is presented demonstrating that the data for these 6 antimicrobial agents was of sufficient quantity and quality that they could be used by the relevant authorities to set internationally harmonised, consensus epidemiological cut-off values for V. harveyi.

Self-assembling hydrogels are receiving great attention for both biomedical and technological applications. Self-assembly of protein/peptides as well as organic molecules is commonly induced in response to external triggers such as changes of temperature, concentration, or pH. An interesting strategy to modulate the morphology and mechanical properties of the gels implies the use of metal ions, where coordination bonds regulate the dynamic cross-linking in the construction of hydrogels, and coordination geometries, catalytic, and redox properties of metal ions play crucial roles. This review aims to discuss recent insights into the supramolecular assembly of hydrogels involving metal ions, with a focus on self-assembling peptides, as well as applications of metallogels in biomedical fields including tissue engineering, sensing, wound healing, and drug delivery., (© 2022 European Peptide Society and John Wiley & Sons Ltd.)

Neurodegenerative diseases are often characterized by the formation of aggregates of amyloidogenic peptides and proteins, facilitating the formation of neurofibrillary plaques. In this study, we investigate a series of Ru-complexes sharing three-legged piano-stool structures based on the arene ring and glucosylated carbene ligands. The ability of these complexes to bind amyloid His-peptides was evaluated by ESI-MS, and their effects on the aggregation process were investigated through ThT and Tyr fluorescence emission. The complexes were demonstrated to bind the amyloidogenic peptides even with different mechanisms and kinetics depending on the chemical nature of the ligands around the Ru(II) ion. TEM analysis detected the disaggregation of typical fibers caused by the presence of Ru-compounds. Overall, our results show that the Ru-complexes can modulate the aggregation of His-amyloids and can be conceived as good lead compounds in the field of novel anti-aggregating agents in neurodegeneration.

In a protein, point mutations associated with diseases can alter the native structure and provide loss or alteration of functional levels, and an internal structural network defines the connectivity among domains, as well as aggregate/soluble states' equilibria. Nucleophosmin (NPM)1 is an abundant nucleolar protein, which becomes mutated in acute myeloid leukemia (AML) patients. NPM1-dependent leukemogenesis, which leads to its aggregation in the cytoplasm (NPMc+), is still obscure, but the investigations have outlined a direct link between AML mutations and amyloid aggregation. Protein aggregation can be due to the cooperation among several hot spots located within the aggregation-prone regions (APR), often predictable with bioinformatic tools. In the present study, we investigated potential APRs in the entire NPM1 not yet investigated. On the basis of bioinformatic predictions and experimental structures, we designed several protein fragments and analyzed them through typical aggrsegation experiments, such as Thioflavin T (ThT), fluorescence and scanning electron microscopy (SEM) experiments, carried out at different times; in addition, their biocompatibility in SHSY5 cells was also evaluated. The presented data clearly demonstrate the existence of hot spots of aggregation located in different regions, mostly in the N-terminal domain (NTD) of the entire NPM1 protein, and provide a more comprehensive view of the molecular details potentially at the basis of NPMc+-dependent AML.

Supramolecular assemblies of short peptides are experiencing a stimulating flowering. Herein, we report a novel class of bioinspired pentapeptides, not bearing Phe, that form hydrogels with fibrillar structures. The inherent sequence comes from the fragment 269-273 of nucleophosmin 1 protein, that is normally involved in liquid-liquid phase separation processes into the nucleolus. By means of rheology, spectroscopy, and scanning microscopy the crucial roles of the extremities in the modulation of the mechanical properties of hydrogels were elucidated. Three of four peptide showed a typical shear-thinning profile and a self-assembly into hierarchical nanostructures fibers and two of them resulted biocompatible in MCF7 cells. The presence of an amide group at C-terminal extremity caused the fastest aggregation and the major content of structured intermediates during gelling process. The tunable mechanical and structural features of this class of hydrogels render derived supramolecular systems versatile and suitable for future biomedical applications.

The "Acute Myeloid Leukemia with gene mutations'' group includes mutations in Nucleophosmin 1(NPM1) that is an abundant multifunctional protein with chaperon functions. This protein also takes part to rRNA maturation in ribosome biogenesis, tumor suppression and nucleolar stress response. Mutations of NPM1 associated to AML present in its C-terminal domain (CTD) unable its correct folding and confer it an aberrant cytoplasmatic localization (NPMc+). AML cells with NPM1 mutations retain a certain amount of wt NPM1 in the nucleolus and since NPM1 acts as a hub protein, the nucleolus of AML cells are more vulnerable with respect to cells expressing only wt NPM1. Thus, interfering with the levels or the oligomerization status of NPM1 may influence its capability to properly build up the nucleolus in AML cells. Our biophysical recent results demonstrated that AML-CTDs contain regions prone to amyloid aggregation and, herein, we present results oriented to exploit this amylodogenesis in a potential therapeutic way. We evaluated the different ability of two small molecules to enhance amyloid aggregation through complementary biophysical approaches as fluorescence and Circular Dichroism spectroscopies, Scanning Electron Microscopy and cell-viability assays, to evaluate the cytoxicity of these molecules in AML cells lines. These findings could pave the way into molecular mechanisms of NPM1c and in novel therapeutic routes toward AML progression., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Nucleophosmin 1 (NPM1) protein is a multifunctional nucleolar chaperone and its gene is the most frequently mutated in Acute Myeloid Leukemia (AML). AML mutations cause the unfolding of the C-terminal domain (CTD) and the protein delocalizing in the cytosol (NPM1c+). Marked aggregation endowed with an amyloid character was assessed as consequences of mutations., Scope: Herein we analyzed the effects of type C mutation on two protein regions: i) a N-terminal extended version of the CTD, named Cterm&#95;mutC and ii) a shorter polypeptide including the sequences of the second and third helices of the CTD, named H2&#95;mutC., Major Conclusions: Both demonstrated able to self-assembly with different kinetics and conformational intermediates and to provide fibers presenting large flexible regions., General Significance: The present study adds a new piece of knowledge to the effects of AML-mutations on structural biology of Nucleophosmin 1, that could be exploited in therapeutic interventions targeting selectively NPMc+., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Animal-Visitor Interactions (AVI) are activities offered by zoos and other tourism facilities, in which visitors come into close contact with animals. These activities can promote conservational and educational content, raise conservation mindedness and responsibility for the environment and animal welfare, but if not properly managed can jeopardize visitors' and animals' well-being and conservation efforts. The Animal-Visitor Interaction assessment Protocol (AVIP) has been designed to perform an integrated and multidisciplinary assessment of these activities, encompassing the "One Health, One Welfare" approach. AVIP throughout six different steps allows to assess the effects of AVIs both on animals, visitors, and the staff involved. Results can assist zoos to improve management decisions, ensure a transparent evaluation of their activities and promote conservation education goals. Lemurs walk-in enclosures have become increasingly popular among zoos, nevertheless studies focused on their assessment are still scarce. To validate AVIP to this particular AVI, we applied it to assess a walk-in enclosure hosting five Lemur catta in an Italian zoo. Results of behavioural and physiological analyses suggested no changes in animal welfare level and the Animal Welfare Risk Assessment showed low animal welfare risks. Two Visitor Experience Surveys were used to interview 291 visitors, showing that the assessed AVI could help promote the zoo's conservation objectives and visitor education. Risk Assessment found low and medium risks to the health and safety of visitors. Results were then combined to perform a final ethical assessment. Some potential ethical concerns were detected, but the outcomes indicated that these conflicts were well managed. In the context of recent findings AVIP demonstrated its potential for application also in assessing AVIs involving primates. Our findings confirmed the usefulness of AVIP in assessing and monitoring AVIs, allowing to gain key information in a single process on multiple welfare-related parameters, educational impact, safety of the main stakeholders involved, and ethical concerns., Competing Interests: The authors have declared that no competing interests exist.

Background: According to the WHO, detainees attempt suicide ten times more than the general population., Aims: To investigate the impact of migration trauma on Suicidal and Self-Harm Behaviours (SSHB) of migrants in jail and to explore how substance use and other psychiatric features affect this relationship., Methods: Prospective cohort study, conducted at the 'Sant'Anna' jail in Modena (Italy) between February 2017 and September 2019. Socio-demographic, psychiatric features and records of previous SSHB were collected. Experience of migration-related trauma was assessed with the LiMEs (List of Migration Experiences) checklist. Participants were followed-up for the occurrence of further SSHB. Survival analysis was performed and Cox's Hazard Ratios (HR) were used as a measure of association of comparisons., Results: Amongst the 112 subjects (96% male, median age 33), the prevalence of any mental disorder was 26% and of substance abuse 59%. History of SSHB was present in 36% of the sample. Median follow-up time was 80 days. During follow-up, 11 events were observed (of which three were suicide attempts). Cumulative survival probability was 85%. Having experienced trauma related to war and violence was significantly associated with SSHB, HR: 7.05. No SSHB were recorded amongst subjects without substance abuse., Conclusions: Migrants in custody who experienced trauma in the post-migration period, attempt SSHB seven times more frequently than those without traumas at any time. War trauma and post-migration trauma due to exposure to violence seem to be more strongly associated with SSHB, also controlling for psychiatric diagnosis, ongoing psychopharmacological therapy and substance abuse. Further research and possible intervention programs should focus on addressing post-migration living-difficulties.

SOCS3 (suppressor of cytokine signaling 3) protein suppresses cytokine-induced inflammation and its deletion in neurons or immune cells increases the pathological growth of blood vessels. Recently, we designed several SOCS3 peptidomimetics by assuming as template structures the interfacing regions of the ternary complex constituted by SOCS3, JAK2 (Janus Kinase 2) and gp130 (glycoprotein 130) proteins. A chimeric peptide named KIRCONG chim, including non-contiguous regions demonstrated able to bind to JAK2 and anti-inflammatory and antioxidant properties in VSMCs (vascular smooth muscle cells). With the aim to improve drug-like features of KIRCONG, herein we reported novel cyclic analogues bearing different linkages. In detail, in two of them hydrocarbon cycles of different lengths were inserted at positions i/i+5 and i/i+7 to improve helical conformations of mimetics. Structural features of cyclic compounds were investigated by CD (Circular Dichroism) and NMR (Nuclear Magnetic Resonance) spectroscopies while their ability to bind to catalytic domain of JAK2 was assessed through MST (MicroScale Thermophoresis) assay as well as their stability in biological serum. Overall data indicate a crucial role exerted by the length and the position of the cycle within the chimeric structure and could pave the way to the miniaturization of SOCS3 protein for therapeutic aims.

Background: Adult spinal deformities (ASD) represent a growing clinical condition related to chronic pain, disability and reduction in quality of life (QoL). A strong correlation among spinal alignment, spinopelvic parameters and QoL after spinal fusion surgery in ASD patients was thoroughly investigated over the last decade, However, only few studies focused on the relationship between lumbo-pelvic-femoral parameters - such as Femoral Obliquity Angle (FOA), T1 Pelvic Angle (TPA) and QoL., Methods: Radiological and clinical data from 43 patients surgically treated with thoracolumbar posterior spinal fusion for ASD between 2015 and 2018 were retrospectively analyzed. The primary outcomes were the correlation between preoperative spino-pelvic-femoral parameters and postoperative clinical, functional outcomes and QoL. Secondary outcomes were: changes in sagittal radiographic parameters spino-pelvic-femoral, clinical and functional outcomes and the rate of complications after surgery., Results: Using Spearman's rank correlation coefficients, spinopelvic femoral parameters (FOA, TPA, pre and post-operative) are directly statistically correlated to the quality of life (ODI, SRS-22, pre and post-operative; > 0,6 strong correlation, p <  0.05). Stratifying the patients according pre preoperative FOA value (High FOA ≥ 10 and Normal/Low FOA <  10), those belonging to the first group showed worse clinical (VAS: 5.2 +/- 1.4 vs 2.9 +/- 0.8) and functional outcomes (ODI: 35.6+/- 6.8 vs 23.2 +/- 6.5) after 2 years of follow-up and a greater number of mechanical complications (57.9% vs 8.3% p <  0.0021)., Conclusion: Based on our results, preoperative FOA and TPA could be important prognostic parameters for predicting disability and quality of life after spinal surgery in ASD patients and early indicators of possible spinal sagittal malalignment. FOA and TPA, like other and better known spinopelvic parameters, should always be considered when planning corrective surgery in ASD patients., (© 2021. The Author(s).)

Protein aggregation is suggested as a reversible, wide-spread physiological process used by cells to regulate their growth and adapt to different stress conditions. Nucleophosmin 1(NPM1) protein is an abundant multifunctional nucleolar chaperone and its gene is the most frequently mutated in Acute Myeloid Leukemia (AML) patients. So far, the role of NPM1 mutations in leukemogenesis has remained largely elusive considering that they have the double effect of unfolding the C-terminal domain (CTD) and delocalizing the protein in the cytosol (NPM1c+). This mislocalization heavily impacts on cell cycle regulation. Our recent investigations unequivocally demonstrated an amyloid aggregation propensity introduced by AML mutations. Herein, employing complementary biophysical assays, we have characterized a N-terminal extended version of type F AML mutation of CTD and proved that it is able to form assemblies with amyloid character and fibrillar morphology. The present study represents an additional phase of knowledge to deepen the roles exerted by different types of cytoplasmatic NPM1c+ forms to develop in the future potential therapeutics for their selective targeting., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Peptide hydrogels, deriving from natural protein fragments, present unique advantages as compatibility and low cost of production that allow their wide application in different fields as wound healing, cell delivery and tissue regeneration. To engineer new biomaterials, the change of the chirality of single amino acids demonstrated a powerful approach to modulate the self-assembly mechanism. Recently we unveiled that a small stretch spanning residues 268-273 in the C-terminal domain (CTD) of Nucleophosmin 1 (NPM1) is an amyloid sequence. Herein, we performed a systematic D-scan of this sequence and analyzed the structural properties of obtained peptides. The conformational and kinetic features of self-aggregates and the morphologies of derived microstructures were investigated by means of different biophysical techniques, as well as the compatibility of hydrogels was evaluated in HeLa cells. All the investigated hexapeptides formed hydrogels even if they exhibited different conformational intermediates during aggregation, and they structural featured are finely tuned by introduced chiralities., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Often proteins association is a physiological process used by cells to regulate their growth and to adapt to different stress conditions, including mutations. In the case of a subtype of Acute Myeloid Leukemia (AML), mutations of nucleophosmin 1 (NPM1) protein cause its aberrant cytoplasmatic mislocalization (NPMc+). We recently pointed out an amyloidogenic propensity of protein regions including the most common mutations of NPMc+ located in the C-terminal domain (CTD): they were able to form, in vitro, amyloid cytotoxic aggregates with fibrillar morphology. Herein, we analyzed the conformational characteristics of several peptides including rare AML mutations of NPMc+. By means of different spectroscopic, microscopic and cellular assays we evaluated the importance of amino acid composition, among rare AML mutations, to determine amyloidogenic propensity. This study could add a piece of knowledge to the structural consequences of mutations in cytoplasmatic NPM1c+., (Copyright © 2021 Elsevier Inc. All rights reserved.)

During a sampling of wild red foxes (Vulpes vulpes) for the detection of Epsilonproteobacteria, 14 strains were isolated from the caecal contents of 14 epidemiologically-unrelated animals. A genus-specific PCR indicated that the isolates belonged to the genus Campylobacter. Based on the results of a species-specific PCR, the isolates were initially identified as C. upsaliensis. However, multi-locus sequence typing (MLST) revealed that the isolates were significantly different from the C. upsaliensis present in the MLST database. A polyphasic study, including conventional biochemical and tolerance characteristics, morphology by transmission electron microscopy (TEM), MALDI-TOF analysis, and genetic comparisons based on partial 16S rDNA and atpA gene sequences, was undertaken. Finally, the complete genome sequence of the type strain 251/13 T and the draft genome sequences of the other isolates were determined. Average nucleotide identity, average amino acid identity and in silico DNA-DNA hybridization analyses confirmed that the isolates represent a novel taxon for which the name Campylobacter vulpis sp. nov. is proposed, with isolate 251/13 T (=CCUG 70587 T  = LMG 30110 T ) as the type strain. In order to allow a rapid discrimination of C. vulpis from the closely-related C. upsaliensis, a specific PCR test was designed, based on atpA gene sequences., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Herein the effects of three platinum complexes, namely ( SP -4-2)-(2,2'-bipyridine)dichloridoplatinum(II), Pt-bpy, ( SP -4-2)-dichlorido(1,10-phenanthroline) platinum(II), Pt-phen, and ( SP -4-2)-chlorido(2,2':6',2''-terpyridine)platinum(II) chloride, Pt-terpy, on the aggregation of an amyloid model system derived from the C-terminal domain of Aβ peptide (Aβ 21-40 ) were investigated. Thioflavin T (ThT) binding assays revealed the ability of Pt(II) compounds to repress amyloid aggregation in a dose-dependent way, whereas the ability of Aβ 21-40 peptide to interfere with ligand field of metal complexes was analyzed through UV-Vis absorption spectroscopy and electrospray ionization mass spectrometry. Spectroscopic data provided micromolar EC 50 values and allowed to assess that the observed inhibition of amyloid aggregation is due to the formation of adducts between Aβ 21-40 peptide and complexes upon the release of labile ligands as chloride and that they can explore different modes of coordination toward Aβ 21-40 with respect to the entire Aβ 1-40 polypeptide. In addition, conformational studies through circular dichroism (CD) spectroscopy suggested that Pt-terpy induces soluble β-structures of monomeric Aβ 21-40 , thus limiting self-recognition. Noticeably, Pt-terpy demonstrated the ability to reduce the cytotoxicity of amyloid peptide in human SH-SY5Y neuroblastoma cells. Presented data corroborate the hypothesis to enlarge the application field of already known metal-based agents to neurodegenerative diseases, as potential neurodrugs.