GRP-3 and KAPP, encoding interactors of WAK1, negatively affect defense responses induced by oligogalacturonides and local response to wounding

Conserved microbe-associated molecular patterns (MAMPs) and damage-associated molecular patterns (DAMPs) act as danger signals to activate the plant immune response. These molecules are recognized by surface receptors that are referred to as pattern recognition receptors. Oligogalacturonides (OGs), DAMPs released from the plant cell wall homogalacturonan, have also been proposed to act as local signals in the response to wounding. The Arabidopsis Wall-Associated Kinase 1 (WAK1), a receptor of OGs, has been described to form a complex with a cytoplasmic plasma membrane-localized kinase-associated protein phosphatase (KAPP) and a glycine-rich protein (GRP-3) that we find localized mainly in the cell wall and, in a small part, on the plasma membrane. By using Arabidopsis plants overexpressing WAK1, and both grp-3 and kapp null insertional mutant and overexpressing plants, we demonstrate a positive function of WAK1 and a negative function of GRP-3 and KAPP in the OG-triggered expression of defence genes and the production of an oxidative burst. The three proteins also affect the local response to wounding and the basal resistance against the necrotrophic pathogen Botrytis cinerea. GRP-3 and KAPP are likely to function in the phasing out of the plant immune response

Further Evidence on the Role of Thyroid Autoimmunity in Women with Recurrent Miscarriage

It has been twenty years since the first paper reporting the association between thyroid antibodies (TAIs) and spontaneous miscarriage was published. Following this observation, several studies have clearly demonstrated an increased prevalence of TAI in patients with recurrent miscarriage (RM). However, the exact mechanism underlying this association remains a matter of debate. The aim of the present study was to evaluate the thyroid function, throughout a specific test, in patient with RM and TAI focusing on the hypothesis that TAI should be an indirect sign of a mild thyroid dysfunction. 46 patients with RM and TAI were included in the study. All patients underwent short TRH stimulation test showing an abnormal response in the vast majority of cases (65%). Normal FT4 and FT3 mean values were found whereas TSH values were in the upper normal range (2.64 ± 1.3 mUI/L). Our data support the hypothesis that in patients with RM the presence of TAI is an indirect sign of a subtle thyroid dysfunction detectable by a specific test. This test give the possibility to identify women with RM in which specific therapeutic approaches could effectively improve the possibility for a successful pregnancy

CLaSSES: a New Digital Resource for Latin Epigraphy

CLaSSES (Corpus for Latin Sociolinguistic Studies on Epigraphic textS) is an annotated corpus aimed at (socio)linguistic research on Latin inscriptions. Provided with linguistic, extra- and meta-linguistic features, it can be used to perform quantitative and qualitative variationist analyses on Latin epigraphic texts. In particular, it allows the user to analyze spelling (and possibly phonetic-phonological) variants and to interpret them with reference to the dating, the provenance place, and the type of the texts. This paper presents the first macro-section of CLaSSES, focused on inscriptions of the archaic and early periods (CLaSSES I)

Brassica and Sinapis Seeds in Medieval Archaeological Sites:An Example of Multiproxy Analysis for Their Identification and Ethnobotanical Interpretation

The genus Brassica includes some of the most important vegetable and oil crops worldwide. Many Brassica seeds (which can show diagnostic characters useful for species identification) were recovered from two archaeological sites in northern Italy, dated from between the Middle Ages and the Renaissance. We tested the combined use of archaeobotanical keys, ancient DNA barcoding, and references to ancient herbarium specimens to address the issue of diagnostic uncertainty. An unequivocal conventional diagnosis was possible for much of the material recovered, with the samples dominated by five Brassica species and Sinapis. The analysis using ancient DNA was restricted to the seeds with a Brassica-type structure and deployed a variant of multiplexed tandem PCR. The quality of diagnosis strongly depended on the molecular locus used. Nevertheless, many seeds were diagnosed down to species level, in concordance with their morphological identification, using one primer set from the core barcode site (matK). The number of specimens found in the Renaissance herbaria was not high; Brassica nigra, which is of great ethnobotanical importance, was the most common taxon. Thus, the combined use of independent means of species identification is particularly important when studying the early use of closely related crops, such as Brassicaceae

Cutaneous manifestations of Mycobacterium gordonae infection described for the first time in Italy: a case report

Introduction: Mycobacterium gordonae is one of the least pathogenic of the mycobacteria. This pathogen may produce caseating or non-caseating granulomas, and skin lesions showing acute or chronic inflammation with scattered histiocytes and giant cells have been seen. The mortality rate is less than 0.1%. Mycobacterium gordonae may be a marker of severe immunosuppression in patients infected with human immunodeficiency virus. Case presentation: We report a case of Mycobacterium gordonae infection in an 86-year-old woman and discuss the problems inherent to the identification and treatment of this emerging pathogen. Mycobacterium gordonae strain we isolated was resistant to trimethoprim-sulfamethoxazole but sensitive to ciprofloxacin, and long term administration (six months) induced complete healing of the cutaneous abscesses. Conclusion: Advanced laboratory diagnostic techniques have improved the isolation and identification of nontuberculous mycobacteria. The diagnosis requires a high index of clinical suspicion, as detection by conventional methods is difficult. To our knowledge, this patient is the first documented case of cutaneous infection from this pathogen in Italy

Impaired NK-cell-mediated cytotoxic activity and cytokine production in patients with endometriosis: A possible role for PCBs and DDE

Endometriosis is a gynaecological disorder characterized by the presence and growth of endometrial tissue in ectopic sites. In this study we examined the immunological functions of patients with endometriosis and serum level of PCBs and p,p'-DDE to verify the impact of these environmental contaminants on the dysregulation of immune functions. We found that proliferative responses and immunoglobulin production were not dysregulated in patients with endometriosis while NK cell activity was significantly down-regulated in these patients. Moreover, a significant down-regulation of IL-1 beta and IL-12 production was found in patients with respect to controls. Serum levels of PCBs and p,p'-DDE were found to be significantly higher in women with endometriosis than in the control group, with respect to the sum of the congeners most prominent in human tissues. In particular, total PCBs concentration in patients with endometriosis and controls was respectively 330 and 160 ng/g fat with respect to the most abundant congeners, while pp-DDE concentration was of 770 and 3 10 ng/g fat. Moreover, we found that normal human PBMC pulsed with PCBs p,p'-DDE and their combination showed a significant down-regulation of NK cell cytotoxic activity and IL-1 beta and IL-12 production. These findings suggest that changes in specific immune parameters correlate with elevated serum PCBs and DDE levels and endometriosis. (c) 2006 Elsevier Inc. All rights reserved

West Nile Virus lineage 1 in Italy: newly introduced or a re-occurrence of a previously circulating strain?

In Italy, West Nile virus (WNV) appeared for the first time in the Tuscany region in 1998. After 10 years of absence, it re-appeared in the areas surrounding the Po River delta, affecting eight provinces in three regions. Thereafter, WNV epidemics caused by genetically divergent isolates have been documented every year in the country. Since 2018, only WNV Lineage 2 has been reported in the Italian territory. In October 2020, WNV Lineage 1 (WNV-L1) re-emerged in Italy, in the Campania region. This is the first occurrence of WNV-L1 detection in the Italian territory since 2017. WNV was detected in the internal organs of a goshawk (Accipiter gentilis) and a kestrel (Falco tinnunculus). The RNA extracted in the goshawk tissue samples was sequenced, and a Bayesian phylogenetic analysis was performed by a maximum-likelihood tree. Genome analysis, conducted on the goshawk WNV complete genome sequence, indicates that the strain belongs to the WNV-L1 Western-Mediterranean (WMed) cluster. Moreover, a close phylogenetic similarity is observed between the goshawk strain, the 2008–2011 group of Italian sequences, and European strains belonging to the Wmed cluster. Our results evidence the possibility of both a new re-introduction or unnoticed silent circulation in Italy, and the strong importance of keeping the WNV surveillance system in the Italian territory activ

Repeated exposure to JWH-018 induces adaptive changes in the mesolimbic and mesocortical dopamine pathways, glial cells alteration and behavioural correlates

Spice/K2 herbal mixtures, containing synthetic cannabinoids such as JWH-018, have been marketed as marijuana surrogates since 2004. We demonstrated that JWH-018 has cannabinoid CB1 receptor-dependent reinforcing properties and acutely increases dopamine transmission selectively in the NAc shell. Here we tested the hypothesis that repeated administration of JWH-018 (i) modulates behaviour, (ii) affects dopamine transmission and its responsiveness to motivational stimuli, and (iii) is associated with a neuroinflammatory phenotype

Machine Learning Prediction of Comorbid Substance Use Disorders among People with Bipolar Disorder

Substance use disorder (SUD) is a common comorbidity in individuals with bipolar disorder (BD), and it is associated with a severe course of illness, making early identification of the risk factors for SUD in BD warranted. We aimed to identify, through machine-learning models, the factors associated with different types of SUD in BD. We recruited 508 individuals with BD from a specialized unit. Lifetime SUDs were defined according to the DSM criteria. Random forest (RF) models were trained to identify the presence of (i) any (SUD) in the total sample, (ii) alcohol use disorder (AUD) in the total sample, (iii) AUD co-occurrence with at least another SUD in the total sample (AUD+SUD), and (iv) any other SUD among BD patients with AUD. Relevant variables selected by the RFs were considered as independent variables in multiple logistic regressions to predict SUDs, adjusting for relevant covariates. AUD+SUD could be predicted in BD at an individual level with a sensitivity of 75% and a specificity of 75%. The presence of AUD+SUD was positively associated with having hypomania as the first affective episode (OR = 4.34 95% CI = 1.42-13.31), and the presence of hetero-aggressive behavior (OR = 3.15 95% CI = 1.48-6.74). Machine-learning models might be useful instruments to predict the risk of SUD in BD, but their efficacy is limited when considering socio-demographic or clinical factors alone

AIRO Breast Cancer Group Best Clinical Practice 2022 Update

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine