Association of the apoptotic markers Apo1/Fas and cCK-18 and the adhesion molecule ICAM-1 with Type 1 diabetes mellitus in children and adolescents.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by immune and metabolic dysregulation. Apo1/Fas is implicated in maintaining homeostasis of the immune system. Cytokeratin-18 (cCK-18) is a predictive marker of liver disorders in T2DM. Intercellular adhesion molecule-1 (ICAM-1) is considered to increase susceptibility to diabetes mellitus. All three markers are associated with endothelial function, apoptosis and diabetes-related complications. The possible role of Apo1/Fas, cCK-18 and ICAM-1 was investigated in children and adolescents with T1DM. METHOD: Forty-nine (49) children and adolescents with T1DM and 49 controls were included in the study. Somatometric measurements were obtained and the Body Mass Index (BMI) of the participants was calculated. Biochemical parameters were measured by standard laboratory methods and Apo1/Fas, cCK-18 and ICAM-1 were measured using appropriate ELISA kits. The statistical analysis was performed using the IBM SPSS Statistics 23 program. RESULTS: Apo1/Fas (p = 0.001), cCK-18 (p < 0.001) and ICAM-1 (p < 0.001) were higher in patients with T1DM compared to the controls. Apo1Fas was negatively correlated with glucose (p = 0.042), uric acid (p = 0.026), creatinine (p = 0.022), total cholesterol (p = 0.023) and LDL (p = 0.005) in the controls. In children and adolescents with T1DM, Apo1/Fas was positively correlated with total cholesterol (p = 0.013) and LDL (p = 0.003). ICAM-1 was negatively correlated with creatinine (p = 0.019) in the controls, whereas in patients with T1DM it was negatively correlated with HbA1c (p = 0.05). CONCLUSIONS: Apo1/Fas, cCK-18 and ICAM-1 may be useful as serological markers for immune and metabolic dysregulation in children and adolescents with T1DM. Also, Apo1/Fas may have a protective role against metabolic complications in healthy children.

Atypical cancer risk profile in carriers of Italian founder BRCA1 variant p.His1673del: Implications for classification and clinical management.

BACKGROUND: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. METHODS: Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1-ABRAXAS1 interaction was assessed using a GFP-fragment reassembly-based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. RESULTS: Variant-carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0-155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6-40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2-2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03-61.6) emerged, warranting further evaluation. Likelihood-ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1-ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule-based model. Collectively, these findings allowed to classify the variant as pathogenic. CONCLUSION: Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype.

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). Methods: We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed. OCAC and CIMBA data were used to develop PGS which were trained on FinnGen data and validated in UKBB and BioBank Japan. Results: Eight novel variants were associated with HGSOC risk. An interesting discovery biologically was finding that TP53 3'-UTR SNP rs78378222 was associated with HGSOC (per T allele relative risk (RR)=1.44, 95%CI:1.28-1.62, P=1.76×10-9). The optimal PGS included 64,518 variants and was associated with an odds ratio of 1.46 (95%CI:1.37-1.54) per standard deviation in the UKBB validation (AUROC curve=0.61, 95%CI:0.59-0.62). Conclusions: This study represents the largest GWAS for HGSOC to date. The results highlight that improvements in imputation reference panels and increased sample sizes can identify HGSOC associated variants that previously went undetected, resulting in improved PGS. The use of updated PGS in cancer risk prediction algorithms will then improve personalized risk prediction for HGSOC.

Whole Genome Sequence Dataset of Mycobacterium tuberculosis Strains from Patients of Campania Region.

Tuberculosis (TB) is one of the deadliest infectious disorders in the world. To effectively TB manage, an essential step is to gain insight into the lineage of Mycobacterium tuberculosis (MTB) and the distribution of drug resistance. Although the Campania region is declared a cluster area for the infection, to contribute to the effort to understand TB evolution and transmission, still poorly known, we have generated a dataset of 159 genomes of MTB strains, from Campania region collected during 2018-2021, obtained from the analysis of whole genome sequence. The results show that the most frequent MTB lineage is the 4 according for 129 strains (81.11%). Regarding drug resistance, 139 strains (87.4%) were classified as multi susceptible, while the remaining 20 (12.58%) showed drug resistance. Among the drug-resistance strains, 8 were isoniazid-resistant MTB, 4 multidrug-resistant MTB, while only one was classified as pre-extensively drug-resistant MTB. This dataset expands the existing available knowledge on drug resistance and evolution of MTB, contributing to further TB-related genomics studies to improve the management of this disease.

Antimicrobial Resistance in Physiological and Potentially Pathogenic Bacteria Isolated in Southern Italian Bats.

The spread of antimicrobial resistance is one of the major health emergencies of recent decades. Antimicrobial-resistant bacteria threaten not only humans but also populations of domestic and wild animals. The purpose of this study was to evaluate the distribution of antibiotic resistance (AMR) and multidrug resistance (MDR) in bacterial strains isolated from six Southern-Italian bat populations. Using the disk diffusion method, we evaluated the antimicrobial susceptibility of 413 strains of Gram-negative bacteria and 183 strains of Gram-positive bacteria isolated from rectal (R), oral (O) and conjunctival (C) swabs of 189 bats belonging to 4 insectivorous species (Myotis capaccinii, Myotis myotis, Miniopterus schreibersii and Rhinolophus hipposideros). In all bat species and locations, numerous bacterial strains showed high AMR levels for some of the molecules tested. In both Gram-negative and Gram-positive strains, the resistance patterns ranged from one to thirteen. MDR patterns varied significantly across sites, with Grotta dei Pipistrelli in Pantalica displaying the highest levels of MDR (77.2% of isolates). No significant differences were found across different bat species. Monitoring antibiotic resistance in wildlife is a useful method of evaluating the impact of anthropic pressure and environmental pollution. Our analysis reveals that anthropic contamination may have contributed to the spread of the antibiotic resistance phenomenon among the subjects we examined.

Brain sex-dependent alterations after prolonged high fat diet exposure in mice.

We examined effects of exposing female and male mice for 33 weeks to 45% or 60% high fat diet (HFD). Males fed with either diet were more vulnerable than females, displaying higher and faster increase in body weight and more elevated cholesterol and liver enzymes levels. Higher glucose metabolism was revealed by PET in the olfactory bulbs of both sexes. However, males also displayed altered anterior cortex and cerebellum metabolism, accompanied by a more prominent brain inflammation relative to females. Although both sexes displayed reduced transcripts of neuronal and synaptic genes in anterior cortex, only males had decreased protein levels of AMPA and NMDA receptors. Oppositely, to anterior cortex, cerebellum of HFD-exposed mice displayed hypometabolism and transcriptional up-regulation of neuronal and synaptic genes. These results indicate that male brain is more susceptible to metabolic changes induced by HFD and that the anterior cortex versus cerebellum display inverse susceptibility to HFD.

Cultivable Bacteria Associated with the Microbiota of Troglophile Bats.

BACKGROUND: The study of bats is of significant interest from a systematic, zoogeographic, ecological, and physiological point of view. The aim of this study is to investigate the culturable aerobic enteric, conjunctival, and oral bacterial flora of bats to determine their physiological microbiome and to investigate the possible occurrence of pathogenic bacteria. METHODS: Five hundred and sixty-seven samples were collected from 189 individuals of four species of troglophile bats (Myotis myotis, Myotis capaccinii, Miniopterus schreibersii, and Rhinolophus hipposideros) living in Sicilian and Calabrian territory (Italy). All samples were tested for Gram-negative bacteria; conjunctival and oral swabs were also submitted to bacteriological examination for Gram-positive bacteria. RESULTS: Four hundred thirteen Gram-negative strains were isolated. Of these, 377 belonged to 17 different genera of the family Enterobacteriaceae and 30 to five other families. One hundred eighty-three Gram-positive strains were isolated. Of these, 73 belonged to the Staphylococcaceae family, 72 to the Bacillaceae family and 36 to four other families. Besides some potentially pathogenic strains, several bacterial species have been found that are common to all the bat species studied. These could perhaps play a physiological or nutritional role. CONCLUSION: A great variety of bacterial species were identified in the cultivable microbiota of southern-Italian troglophile bats, including several potentially pathogenic strains and numerous putatively symbiotic species.

A TLR/CD44 axis regulates T cell trafficking in experimental and human multiple sclerosis.

In the pathogenesis of autoimmune disorders, the modulation of leukocytes' trafficking plays a central role, still poorly understood. Here, we focused on the effect of TLR2 ligands in trafficking of T helper cells through reshuffling of CD44 isoforms repertoire. Concurrently, strain background and TLR2 haplotype affected Wnt/ß-catenin signaling pathway and expression of splicing factors. During EAE, mCD44 v9- v 10 was specifically enriched in the forebrain and showed an increased ability to bind stably to osteopontin. Similarly, we observed that hCD44 v7 was highly enriched in cells of cerebrospinal fluid from MS patients with active lesions. Moreover, TLRs engagement modulated the composition of CD44 variants also in human T helper cells, supporting the hypothesis that pathogens or commensals, through TLRs, in turn modulate the repertoire of CD44 isoforms, thereby controlling the distribution of lesions in the CNS. The interference with this mechanism(s) represents a potential tool for prevention and treatment of autoimmune relapses and exacerbations.

Phenotypic and genotypic study on antibiotic resistance and pathogenic factors of Staphylococcus aureus isolates from small ruminant mastitis milk in South of Italy (Sicily).

Staphyloccoccus aureus is the major cause of mastitis in small ruminants in the Mediterranean farms causing severe losses to dairy industry. Antibiotic treatment has been the most common approach to control these infections. Aim of this study was to investigate antimicrobial resistance (AMR), virulence factors and biofilm-related genes of 84 Sicilian strains of S. aureus isolated from sheep and goats milk during two different periods δT1 (2006-2009) and δT2 (2013-2015). Kirby Bauer method and Polymerase Chain Reaction (PCR) were utilized to monitor AMR and related genes (mecA, tetK, tetM, ermA, ermC). Moreover, toxin genes (tsst-1, sea-see, seg-sej, and sep) and biofilm genes (bap, ica, sasC) were studied. Twenty-six isolates (30.9%) showed multidrug resistance. The two groups showed similar results with exception for higher values of resistance for tilmicosin and lower for sulfamethoxazole and vancomycin of the second group. MecA gene was detected in one isolate. Tetracycline resistance was higher than 20%, with an increase in δT2 group. Toxin genes were found in 5 isolates (5.9%), belonging of δT2 group, while 57 of isolates (67.8%) showed biofilm related genes. The high presence of multi-resistant isolates suggests the need of more responsible use of antibiotic therapy for the control of these infections.

Human Monocytes Plasticity in Neurodegeneration.

Monocytes play a crucial role in immunity and tissue homeostasis. They constitute the first line of defense during the inflammatory process, playing a role in the pathogenesis and progression of diseases, making them an attractive therapeutic target. They are heterogeneous in morphology and surface marker expression, which suggest different molecular and physiological properties. Recent evidences have demonstrated their ability to enter the brain, and, as a consequence, their hypothetical role in different neurodegenerative diseases. In this review, we will discuss the current knowledge about the correlation between monocyte dysregulation in the brain and/or in the periphery and neurological diseases in humans. Here we will focus on the most common neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis.

Analysis of Eurasian Stone curlew (Burhinus oedicnemus) microbial flora reveals the presence of multi-drug resistant pathogens in agro-pastoral areas of Sicily (Italy).

Spread of multi-drug resistant (MDR) bacteria in natural environments pose a risk to human and animal health. Wild birds are considered to be reservoirs of human pathogens and vectors of antimicrobial resistance distribution in the environment. The aim of this study is to assess the occurrence of antibiotic resistant bacteria in isolates from bird specimens living in three agro-pastoral areas of the southeastern Sicily. We analyzed the microbiomes of the Eurasian Stone curlew Burhinus oedicnemus (Charadriiformes, Aves) and identified 91 Gram positive and 212 Gram negative strains, whose antimicrobial susceptibility to 11 and 9 antibiotic classes (respectively) was evaluated using agar disk diffusion test. Isolates showed significant levels of antimicrobial resistance, and a high percentage of MDR strains was found both between the Gram positive (49.4%) and the Gram negative (34.9%). Multi-drug resistance levels are higher among strains isolated in the beak and the eye than among enteric (faeces and cloaca) strains. Our results indicate high levels of MDR strains among wild bird populations, with a potential threat to wildlife and human populations.

Detection of multidrug resistance and extended-spectrum/plasmid-mediated AmpC beta-lactamase genes in Enterobacteriaceae isolates from diseased cats in Italy.

OBJECTIVES: The aim of this study was to determine the antimicrobial susceptibility of Enterobacteriaceae isolated from cats affected by diseases commonly encountered in practice, and to characterise the third-generation cephalosporin (3GC)-resistance molecular mechanisms involved. METHODS: Clinical samples (n = 100) included 58 rectal swabs from cats with diarrhoea, 31 nasal swabs from cats with clinical signs of upper respiratory tract disease, four ear swabs from cats with otitis, three conjunctival swabs from cats with conjunctivitis, two oral swabs from cats with stomatitis, one swab from a skin abscess and one urine sample from a cat with cystitis. A total of 125 Enterobacteriaceae were isolated from 90 cats. Escherichia coli was the most frequently isolated species (n = 65), followed by Enterobacter species (n = 20), Proteus species (n = 13), Citrobacter species (n = 12) and others (n = 15). Bacterial susceptibility testing was performed with respect to eight antimicrobial classes. Beta (ß)-lactamase genes were identified by PCR and nucleotide sequencing. RESULTS: Overall, the higher frequency of resistance was to amoxicillin-clavulanate (61.3%), trimethoprim/sulfamethoxazole (33.6%) and cefotaxime (32.8%). Thirty-six percent of the isolates (n = 45) were resistant to 3GCs. Of these isolates, 34 were tested by PCR and nucleotide sequencing and 23 were confirmed as encoding ß-lactamase genes. Fourteen 3GC-resistant isolates harboured extended-spectrum ß-lactamases (ESBLs) belonging to groups CTX-M-1 (n = 12, two of which were CTX-M-79), CTX-M-2 (n = 1) and CTX-M-9 (n = 1), as well as SHV-12 (n = 1) and TEM-92 (n = 1). Nine isolates had CMY-2 plasmid-mediated AmpC ß-lactamases (pAmpC). Thirty-one percent (n = 39) of the isolates were multidrug resistant (MDR) and were isolated from 34% (n = 31/90) of the cats. CONCLUSIONS AND RELEVANCE: A high frequency of MDR and ESBL/pAmpC ß-lactamase-producing Enterobacteriaceae were detected among bacteria isolated from a feline population in southern Italy with a variety of common clinical conditions, which poses limitations on therapeutic options for companion animals. We describe the first detection of CTX-M-79 and TEM-92 ESBL genes in isolates from cats.

Egg parasitoid exploitation of plant volatiles induced by single or concurrent attack of a zoophytophagous predator and an invasive phytophagous pest.

Zoophytophagous insect predators can induce physiological responses in plants by activating defence signalling pathways, but whether plants can respond to facultative phytophagy by recruiting natural enemies remains to be investigated. In Y-tube olfactometer bioassays, using a system including a Vicia faba plant, the zoophytophagous predator Podisus maculiventris and the egg parasitoid Telenomus podisi, we first demonstrated that T. podisi females are attracted by broad bean plants damaged by feeding activity of P. maculiventris and on which host egg masses had been laid, while they are not attracted by undamaged plants or plants damaged by feeding activity alone. In a second experiment, we evaluated the impact of the invasive phytophagous pest Halyomorpha halys on this plant volatile-mediated tritrophic communication. Results showed that the invasive herbivorous adults do not induce plants to recruit the native egg parasitoid, but they can disrupt the local infochemical network. In fact, T. podisi females are not attracted by volatiles emitted by plants damaged by H. halys feeding alone or combined with oviposition activity, nor are they attracted by plants concurrently infested by P. maculiventris and H. halys, indicating the specificity in the parasitoid response and the ability of the invasive herbivore in interrupting the semiochemical communication between plants and native egg parasitoids. To the best of our knowledge, this is the first study showing that zoophytophagous predator attacks induce indirect plant defences similarly to those defence strategies adopted by plants as a consequence of single or concurrent infestations of herbivorous insects.

Differential Modulation of NF-κB in Neurons and Astrocytes Underlies Neuroprotection and Antigliosis Activity of Natural Antioxidant Molecules.

Neuroinflammation, a hallmark of chronic neurodegenerative disorders, is characterized by sustained glial activation and the generation of an inflammatory loop, through the release of cytokines and other neurotoxic mediators that cause oxidative stress and limit functional repair of brain parenchyma. Dietary antioxidants may protect against neurodegenerative diseases by counteracting chronic neuroinflammation and reducing oxidative stress. Here, we describe the effects of a number of natural antioxidants (polyphenols, carotenoids, and thiolic molecules) in rescuing astrocytic function and neuronal viability following glial activation by reducing astrocyte proliferation and restoring astrocytic and neuronal survival and basal levels of reactive oxygen species (ROS). All antioxidant molecules are also effective under conditions of oxidative stress and glutamate toxicity, two maladaptive components of neuroinflammatory processes. Moreover, it is remarkable that their antioxidant and anti-inflammatory activity occurs through differential modulation of NF-κB binding activity in neurons and astrocytes. In fact, we show that inflammatory stimuli promote a significant induction of NF-κB binding activity in astrocytes and its concomitant reduction in neurons. These changes are prevented in astrocytes and neurons pretreated with the antioxidant molecules, suggesting that NF-κB plays a key role in the modulation of survival and anti-inflammatory responses. Finally, we newly demonstrate that effective antigliosis and neuroprotective activity is achieved with a defined cocktail of four natural antioxidants at very low concentrations, suggesting a promising strategy to reduce inflammatory and oxidative damage in neurodegenerative diseases with limited side effects.

The Effects of Endurance Exercise and Diet on Atherosclerosis in Young and Aged ApoE-/- and Wild-Type Mice.

BACKGROUND: Atherosclerosis is the leading cause of death worldwide. The disease development is by and large driven by old age and lifestyle factors, such as diet, physical activity, and smoking. In the present study, we have investigated the effect of exercise and diet on the development of atherosclerosis in young and aged mice. OBJECTIVE: This study aimed at comparing multiple age-dependent factors that may influence atherosclerosis in a transgenic mouse model. METHODS: Young (14 weeks) and aged (49-52 weeks) C57BL/6 wild-type (WT) and atherosclerosis-prone ApoE-/- mice were subjected to physical endurance exercise on a treadmill, with or without a high-fat diet. Five weeks later, the frequencies of regulatory T cells (TREGs) in lymph nodes were assessed by flow cytometry, plasmatic cytokines (interleukin [IL]-1ß, IL-6, IL-10, IL-17, interferon-γ, tumor necrosis factor-α, and transforming growth factor [TGF]-ß1) levels were determined by Luminex assay. Lipids (cholesterol and triglycerides) and anti-heat shock protein 60 (HSP60) autoantibodies were measured by ELISA. Aortic lesion sizes were assessed by en face imaging. Microarray analysis and qPCR of skeletal muscle gene expression were also performed. RESULTS: Exercise leads to a reduction of aortic lesions in young ApoE-/- and aged WT mice independent of diet. In most groups, this reduction was followed by an increased proportion of TREGs and TGF-ß1 levels. Moreover, gene expression analysis showed that exercise seems to affect the AMPK signaling pathway. In particular, PGC-1α1 mRNA was induced in aged WT mice, whereas it was reduced in young ApoE-/- mice. In addition, GSEA analysis showed a marked reduction in the insulin signaling pathway in aged ApoE-/- mice. CONCLUSION: Practicing endurance exercise seems to be enough for reducing early aortic lesion formation, independent of diet. However, this was only true in mice with smaller aortic lesions, since mice with large, advanced, complicated atherosclerotic plaques did not show any reduction in lesion size with exercise training.

Study of the spread of antimicrobial-resistant Enterobacteriaceae from wild mammals in the National Park of Aspromonte (Calabria, Italy).

Antimicrobial-resistant (AMR) bacteria are a threat to global health. Epidemiological studies are necessary to gain a more detailed understanding of the transmission modality of resistant bacteria to wild animals and their diffusion into the environment to ensure a broader evaluation of the epidemiological role of wildlife. The study aimed to identify little-known epidemiological aspects by focusing on the isolation of Enterobacteriaceae in order to bring knowledge on the bacterial flora of wild mammals living in the National Park of Aspromonte (Calabria, Italy). Two hundred twenty-five faecal samples of wild mammals were collected and submitted to standard bacteriological examination for Enterobacteriaceae detection. Isolates were identified by mass spectrometry MALDI-TOF (matrix assisted laser desorption/ionisation - time of fligt mass spectrometry). The 30 isolates showing the highest number of resistances were screened for Extended Spectrum Beta Lactamase (ESBL) production. Antimicrobial susceptibility testing of the bacterial isolates was performed by the disk diffusion method. Two hundred sixty-three strains were isolated. The most frequently recovered bacterial species were Hafnia alvei, Escherichia coli and Citrobacter spp.. Potentially pathogenic species including Salmonella spp., Yersinia enterocolitica and Serratia marcescens have also been identified. Isolates displayed significant frequencies of antibiotic resistance. The resistance to amoxicillin (71.4%) was the most frequent, followed by amoxicillin/clavulanic acid (55.5%), ampicillin (49.8%), streptomycin (35.7%), doxycycline (16.3%), tobramycin (15.2%), tetracycline (13.3%) and gentamicin (10.6%). Nine strains showed resistance to imipenem and 1 to meropenem. All isolates were negative for the presence of ESBL-encoding genes. Wild animals can be regarded as sentinel species and used as environmental health indicators.

Analysis of microRNA expression in the thymus of Myasthenia Gravis patients opens new research avenues.

In early-onset Myasthenia Gravis (MG) with anti-acetylcholine receptor antibodies, thymic abnormalities associated with ectopic germinal centers are frequent. miRNAs by acting as post-transcriptional regulators are involved in autoimmunity. To investigate the implication of miRNAs in thymic changes associated with early-onset MG, we performed a miRnome study and data were analyzed with different approaches. miRNAs of interest were further investigated by RT-PCR and transfection experiments for functional tests. First, analyzing specific dysregulated miRNAs, we focused our attention on miR-7-5p and miR-125a-5p, and confirmed by RT-PCR their respective down- and up-regulation in MG thymuses. miR-7 was the most down-regulated thymic miRNA in MG and we observed an inverse correlation between its expression and CCL21 mRNA expression. We next showed that miR-7 down-regulation was due to thymic epithelial cells and by transfecting these cells with miR-7, we demonstrated that it controlled CCL21 release. As CCL21 is essential for germinal center development, we suggested that miR-7 could be involved in thymic changes associated with MG. miR-125a was up-regulated in MG thymuses and is of great interest as it is known to regulate FoxP3 expression, and to modulate the different inflammatory signaling pathways. Thanks to this thymic miRnome study, we also showed the specific dysregulation of miRNA clusters. In particular, we observed that miRNAs localized at the extremity of the X chromosome were down-regulated. This effect seemed linked to their close localization to the fragile X mental retardation 1 gene (FMR1) and the DNA methylation status. Altogether, this miRnome analysis demonstrated that specific thymic miRNAs can be associated with MG and provides novel insights into the pathogenesis of MG.

Qualitative Analysis of Mini Mental State Examination Pentagon in Vascular Dementia and Alzheimer's Disease: A Longitudinal Explorative Study.

BACKGROUND: Vascular dementia and Alzheimer's disease are the most diffuse forms of dementia. Sometimes, they are difficult to distinguish due to overlaps in symptomatology, pathophysiology, and comorbidity. Visual constructive apraxia is very common in dementia and impairment in these abilities can provide clinical information for differential diagnosis. MATERIALS AND METHODS: All patients underwent Mini Mental State Examination (MMSE) at basal visit (T0) and after 1 year (T1). We analyzed differences in Qualitative Scoring Method for the Pentagon Copying Test and we explored the visual constructive apraxia evolution in these 2 types of dementia. RESULTS: In intragroup analysis, we found a significant difference in each group between T0 and T1 in MMSE score (P < .001) and total qualitative scores (P < .001). In intergroup analysis, at T0, we found significance difference in total qualitative scores (P < .001), in numbers of angles (P = .005), in distance/intersection (P < .001), in closure/opening (P = .01), in rotation (P < .001), and in closing-in (P < .001). At T1, we found significance difference in total qualitative scores (P < .001), in particular, in numbers of angles (P < .001), in distance/intersection (P < .001), in closure/opening (P < .001), in rotation (P < .001), and in closing-in (P < .001). The total score showed the highest classification accuracy (.90, 95%CI = .81-0.96) in differentiating patients with Alzheimer's disease from patients with vascular dementia. The optimal threshold value was k = 5. with .84 (95%CI = .69-0.93) sensitivity and .81 (95%CI = .64-0.93) specificity. CONCLUSION: Patients with vascular dementia showed more accuracy errors and graphic difficulties than patients with Alzheimer's disease. Qualitative analysis of copy provided a sensitive measure of visual constructive abilities in differentiating dementias, underlining a particularly vulnerability of visuoconstructive functions in vascular dementia compared with Alzheimer's disease.

NO donors exhibit anti-inflammatory properties by modulating inflammatory signatures and by regulating the life cycle of dendritic cells.

NO mediates a variety of physiologic processes and is considered an important intracellular messenger in different cellular systems. Because of its complex regulation and multiple molecular and cellular targets, NO provides both stimulatory and suppressive properties in the immune system. Dendritic cells (DCs) are considered the most potent APCs, whose regulation has important implications in the induction of an effective immune response. In this study, we analyzed the effect of the compound NCX 2057, a new class of NO-releasing derivatives of ferulic acid, on activation and functional properties of DCs. NCX 2057 was able to modulate the inflammatory program, the cytokines production, and the cellular life cycle but not the maturation markers and the T cells stimulatory capacity of DCs in the presence or absence of LPS. The results indicate that NCX 2057 may modulate different aspects of the activation of DCs and suggest novel applications of NO donors in the contest of inflammatory response modulation through the life cycle regulation of DCs.

An invasive insect herbivore disrupts plant volatile-mediated tritrophic signalling.

Plants respond to insect attack by emission of volatile organic compounds, which recruit natural enemies of the attacking herbivore, constituting an indirect plant defence strategy. In this context, the egg parasitoid Trissolcus basalis is attracted by oviposition-induced plant volatiles emitted by Vicia faba plants as a consequence of feeding and oviposition by the pentatomid host Nezara viridula. However, this local tritrophic web could be affected by the recent invasion by the alien pentatomid bug Halyomorpha halys, an herbivore that shares the same environments as native pentatomid pests. Therefore, we investigated in laboratory conditions the possible impact of H. halys on the plant volatile-mediated signalling in the local tritrophic web V. faba-N. viridula-T. basalis. We found that T. basalis wasps were not attracted by volatiles induced in the plants by feeding and oviposition activities of H. halys, indicating specificity in the wasps' response. However, the parasitoid attraction towards plant volatiles emitted as a consequence of feeding and oviposition by the associated host was disrupted when host, N. viridula, and non-associated host, H. halys, were concurrently present on the same plant, indicating that invasion by the alien herbivore interferes with established semiochemical webs. These outcomes are discussed in a context of multiple herbivory by evaluating the possible influences of alien insects on local parasitoid foraging behaviour.