Allelic Variants of HLA-C Upstream Region, PSORS1C3, MICA, TNFA and Genes Involved in Epidermal Homeostasis and Barrier Function Influence the Clinical Response to Anti-IL-12/IL-23 Treatment of Patients with Psoriasis

Several biologic therapies have been developed to treat moderate-to-severe psoriasis, with patients exhibiting different clinical benefits, possibly due to the heterogeneity of pathogenic processes underlying their conditions. Ustekinumab targets the IL-12/IL-23-p40 subunit and inhibits type-1 and type-17 T-cell responses. Although ustekinumab is effective as both short- and long-term treatment, therapeutic response varies considerably among patients. Ustekinumab biosimilars will be commercialized in the very next future, likely broadening the use of this drug in the treatment of psoriasis patients. Our pharmacogenomic study evaluated the influence of 417 single-nucleotide polymorphisms (SNPs) in psoriasis-risk alleles on the clinical response to ustekinumab in a cohort of 152 patients affected by moderate-to-severe plaque-type psoriasis. Differences in SNP pattern characterizing HLA-Cw6(+) or HLA-Cw6(-) patients, showing high or low responses to ustekinumab, were also analysed. We identified twelve SNPs in HLA-C upstream region (rs12189871, rs4406273, rs9348862 and rs9368670), PSORS1C3 (rs1265181), MICA (rs2523497), LCE3A-B intergenic region (rs12030223, rs6701730), CDSN (rs1042127, rs4713436), CCHCR1 (rs2073719) and in TNFA (rs1800610) genes associated with excellent response to ustekinumab. We also found that HLA-Cw6(+) and HLA-Cw6(-) patients carried out distinct patterns of SNPs associated with different clinical responses. The assessment of HLA-C alleles, together with other genetic variants, could be helpful for defining patients who better benefit from anti-IL-12/IL-23 therapy

Biodiversity Studies for Sustainable Lagoon: Thermophilic and Tropical Fish Species vs. Endemic Commercial Species at Mellah Lagoon (Mediterranean, Algeria)

Lagoons play an important socio-economic role and represent a precious natural heritage at risk from fishing pressure and chemical and biological pollution. Our research focused on better understanding the discrimination of fish biodiversity, the detection of non-indigenous species, and the valorization of commercial indigenous species at Mellah lagoon (Algeria). Taxonomic characterization and barcoding for all fish species and Inkscape schematic drawings for the most common species are provided. A total of 20 families and 37 species were recorded. The thermophilic species Coris julis, Thalassoma pavo, and Aphanius fasciatus and tropical species such as Gambusia holbrooki and Parablennius pilicornis were identified. Numerous Mediterranean species of socio-economic importance are highlighted, and detailed information is summarized for the lagoon’s sustainability. This short-term evaluation goes hand in hand with long-term programs documenting the interaction between indigenous and non-indigenous species in the lagoon and will allow the development of a provisional relationship model for future studies. Thermophilic and tropical species patterns in the Mellah lagoon are presented. Taken together, we provide useful data that can guide future investigations and may become a potential management tool for achieving the Sustainable Development Goals and protecting species with large socio-economic roles from potential thermal stress impact

Post-exposure prophylaxis with sotrovimab for Omicron (B.1.1.529) SARS-CoV-2 variant during the aplastic phase of autologous stem cell transplantation

Background To date, there is no information on the safety and efficacy of the novel anti-sarbecoviruses monoclonal antibody sotrovimab administered, as a post-exposure prophylactic measure, during the aplastic phase of autologous stem cell transplantation (ASCT). Methods We describe the outcomes of a Multiple Myeloma (MM) patient, who was threateningly exposed to the Omicron (B.1.1.529) SARS-CoV-2 variant, two days after having received a myeloablative regimen of high-dose melphalan. The patient fulfilled all CDC criteria for prolonged close contacts with an index patient who tested positive for a molecular nasopharyngeal swab (Omicron; B.1.1.529) soon after admission to the ward. Given the high risks of morbidity and mortality in the case of COVID-19 developing during the aplastic phase of transplantation, we adopted a post-exposure prophylaxis intervention based on intravenous (i.v.) sotrovimab

The Assertive Brain : Anterior Cingulate Phosphocreatine plus Creatine Levels Correlate With Self-Directedness in Healthy Adolescents

Despite various advances in the study of the neurobiological underpinnings of personality traits, the specific neural correlates associated with character and temperament traits are not yet fully understood. Therefore, this study aims to fill this gap by exploring the biochemical basis of personality, which is explored with the temperament and character inventory (TCI), during brain development in a sample of adolescents. Twenty-six healthy adolescents (aged between 13 and 21 years; 9 males and 18 females) with behavioral and emotional problems underwent a TCI evaluation and a 3T single-voxel proton magnetic resonance spectroscopy (1H MRS) acquisition of the anterior cingulate cortex (ACC). Absolute metabolite levels were estimated using LCModel: significant correlations between metabolite levels and selective TCI scales were identified. Specifically, phosphocreatine plus creatine (PCr+Cre) significantly correlated with self-directedness, positively, and with a self-transcendence (ST), negatively, while glycerophosphocholine plus phosphocholine (GPC+PC) and myo-inositol negatively correlated with ST. To the best of our knowledge, this is the first study reporting associations of brain metabolites with personality traits in adolescents. Therefore, our results represent a step forward for personality neuroscience within the study of biochemical systems and brain structures

Potential clinical implications of CD4+CD26high T cells for nivolumab treated melanoma patients

Background Nivolumab is an anti-PD1 antibody that has dramatically improved metastatic melanoma patients’ outcomes. Nevertheless, many patients are resistant to PD-1 inhibition, occasionally experiencing severe of-target immune toxicity. In addition, no robust and reproducible biomarkers have yet been validated to identify the correct selection of patients who will beneft from anti-PD-1 treatment avoiding unwanted side efects. However, the strength of CD26 expression on CD4+ T lymphocytes permits the characterization of three subtypes with variable degrees of responsiveness to tumors, suggesting that the presence of CD26-expressing T cells in patients might be a marker of responsiveness to PD-1-based therapies. Methods The frequency distribution of peripheral blood CD26-expressing cells was investigated employing multiparametric fow cytometry in 69 metastatic melanoma patients along with clinical characteristics and blood count parameters at baseline (W0) and compared to 20 age- and sex-matched healthy controls. Percentages of baseline CD4+CD26high T cells were correlated with the outcome after nivolumab treatment. In addition, the frequency of CD4+CD26high T cells at W0 was compared with those obtained after 12 weeks (W1) of therapy in a sub-cohort of 33 patients. Results Circulating CD4+CD26high T cells were signifcantly reduced in melanoma patients compared to healthy subjects (p=0.001). In addition, a signifcant association was observed between a low baseline percentage of CD4+CD26high T cells (<7.3%) and clinical outcomes, measured as overall survival (p=0.010) and progression-free survival (p=0.014). Moreover, patients with clinical beneft from nivolumab therapy had signifcantly higher frequencies of circulating CD4+CD26high T cells than patients with non-clinical beneft (p=0.004) at 12 months. Also, a higher pre-treatment proportion of circulating CD4+CD26high T cells was correlated with Disease Control Rate (p=0.014) and best Overall Response Rate (p=0.009) at 12 months. Interestingly, after 12 weeks (W1) of nivolumab treatment, percentages of CD4+CD26high T cells were signifcantly higher in comparison with the frequencies measured at W0 (p<0.0001), aligning the cell counts with the ranges seen in the blood of healthy subjects

Understanding the heart-brain axis response in COVID-19 patients: A suggestive perspective for therapeutic development

In-depth characterization of heart-brain communication in critically ill patients with severe acute respiratory failure is attracting significant interest in the COronaVIrus Disease 19 (COVID-19) pandemic era during intensive care unit (ICU) stay and after ICU or hospital discharge. Emerging research has provided new insights into pathogenic role of the deregulation of the heart-brain axis (HBA), a bidirectional flow of information, in leading to severe multiorgan disease syndrome (MODS) in patients with confirmed infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Noteworthy, HBA dysfunction may worsen the outcome of the COVID-19 patients. In this review, we discuss the critical role HBA plays in both promoting and limiting MODS in COVID-19. We also highlight the role of HBA as new target for novel therapeutic strategies in COVID-19 in order to open new translational frontiers of care. This is a translational perspective from the Italian Society of Cardiovascular Researches

Four-dimensional distribution of the 2010 Eyjafjallajökull volcanic cloud over Europe observed by EARLINET

© Author(s) 2013. This work is distributed under the Creative Commons Attribution 3.0 License.The eruption of the Icelandic volcano Eyjafjallaj ökull in April-May 2010 represents a "natural experiment" to study the impact of volcanic emissions on a continental scale. For the first time, quantitative data about the presence, altitude, and layering of the volcanic cloud, in conjunction with optical information, are available for most parts of Europe derived from the observations by the European Aerosol Research Lidar NETwork (EARLINET). Based on multi-wavelength Raman lidar systems, EARLINET is the only instrument worldwide that is able to provide dense time series of high-quality optical data to be used for aerosol typing and for the retrieval of particle microphysical properties as a function of altitude. In this work we show the four-dimensional (4-D) distribution of the Eyjafjallajökull volcanic cloud in the troposphere over Europe as observed by EARLINET during the entire volcanic event (15 April-26 May 2010). All optical properties directly measured (backscatter, extinction, and particle linear depolarization ratio) are stored in the EARLINET database available at www.earlinet.org. A specific relational database providing the volcanic mask over Europe, realized ad hoc for this specific event, has been developed and is available on request at www.earlinet.org. During the first days after the eruption, volcanic particles were detected over Central Europe within a wide range of altitudes, from the upper troposphere down to the local planetary boundary layer (PBL). After 19 April 2010, volcanic particles were detected over southern and south-eastern Europe. During the first half of May (5-15 May), material emitted by the Eyjafjallajökull volcano was detected over Spain and Portugal and then over the Mediterranean and the Balkans. The last observations of the event were recorded until 25 May in Central Europe and in the Eastern Mediterranean area. The 4-D distribution of volcanic aerosol layering and optical properties on European scale reported here provides an unprecedented data set for evaluating satellite data and aerosol dispersion models for this kind of volcanic events.Peer reviewe