Evento 4.2: Nuovi dati geochimici da speleotemi del Mediterraneo Centrale

La tesi propone nuovi dati geochimici da collocare nel quadro dello studio dell’evento di “megasiccità” di 4200 anni fa (BP) nell’area Mediterranea. I quattro speleotemi oggetto di studio, provenienti da Suttaterra de su Predargiu e S’Armidda in Sardegna, da Stiffe in Abruzzo e da Momichek in Macedonia del Nord, presentano record isotopici contrastanti: le grotte sarde sono soggette a una forte aridità e diminuzione delle temperature mentre le grotte di Momichek e Stiffe manifestano un incremento delle precipitazioni con un aumento delle temperature. Il quadro climatico presente nel bacino mediterraneo nel periodo 4.2-3.8 ka è il risultato di variazioni delle teleconnessioni atmosferiche (in particolare la North Atlantic Oscillation e l’Alto Siberiano) in seguito a tre grandi eventi, strettamente connessi tra loro e originati dalla diminuzione dell’attività solare: l’Evento di Bond 3 (IRD3), lo spostamento dell’ITCZ e l’indebolimento dei Monsoni asiatici e africani. Unendo i risultati ottenuti con i dati proxies, sia marini che terrestri, presenti in letteratura per l’area mediterranea, si delinea un quadro spaziale in cui: il mediterraneo occidentale risulta caratterizzato da condizioni aride e fredde, il Mediterraneo orientale presenta aridità e alte temperature, mentre l’area dei Balcani e la costa Adriatica della penisola italiana sono soggette a un incremento delle precipitazioni con alte temperature

Pimozide Increases a Delayed Rectifier K+ Conductance in Chicken Embryo Vestibular Hair Cells

Pimozide is a conventional antipsychotic drug largely used in the therapy for schizophrenia and Tourette’s syndrome. Pimozide is assumed to inhibit synaptic transmission at the CNS by acting as a dopaminergic D2 receptor antagonist. Moreover, pimozide has been shown to block voltage-gated Ca2+ and K+ channels in different cells. Despite its widespread clinical use, pimozide can cause several adverse effects, including extrapyramidal symptoms and cardiac arrhythmias. Dizziness and loss of balance are among the most common side effects of pimozide. By using the patch-clamp whole-cell technique, we investigated the effect of pimozide [3 μM] on K+ channels expressed by chicken embryo vestibular type-II hair cells. We found that pimozide slightly blocks a transient outward rectifying A-type K+ current but substantially increases a delayed outward rectifying K+ current. The net result was a significant hyperpolarization of type-II hair cells at rest and a strong reduction of their response to depolarizing stimuli. Our findings are consistent with an inhibitory effect of pimozide on the afferent synaptic transmission by type-II hair cells. Moreover, they provide an additional key to understanding the beneficial/collateral pharmacological effects of pimozide. The finding that pimozide can act as a K+ channel opener provides a new perspective for the use of this drug

Pimozide Increases a Delayed Rectifier K⁺ Conductance in Chicken Embryo Vestibular Hair Cells

Pimozide is a conventional antipsychotic drug largely used in the therapy for schizophrenia and Tourette’s syndrome. Pimozide is assumed to inhibit synaptic transmission at the CNS by acting as a dopaminergic D2 receptor antagonist. Moreover, pimozide has been shown to block voltage-gated Ca2+ and K+ channels in different cells. Despite its widespread clinical use, pimozide can cause several adverse effects, including extrapyramidal symptoms and cardiac arrhythmias. Dizziness and loss of balance are among the most common side effects of pimozide. By using the patch-clamp whole-cell technique, we investigated the effect of pimozide [3 μM] on K+ channels expressed by chicken embryo vestibular type-II hair cells. We found that pimozide slightly blocks a transient outward rectifying A-type K+ current but substantially increases a delayed outward rectifying K+ current. The net result was a significant hyperpolarization of type-II hair cells at rest and a strong reduction of their response to depolarizing stimuli. Our findings are consistent with an inhibitory effect of pimozide on the afferent synaptic transmission by type-II hair cells. Moreover, they provide an additional key to understanding the beneficial/collateral pharmacological effects of pimozide. The finding that pimozide can act as a K+ channel opener provides a new perspective for the use of this drug

A Child with Early-Onset Gorham-Stout Disease Complicated by Chylothorax: Near-Complete Regression of Bone Lesions with Interferon and Bisphosphonate Treatment

We report a case of Gorham-Stout disease (GSD) complicated by chylothorax and treated with a combination therapy with interferon and bisphosphonates. This treatment may be helpful in improving the usually unfavorable prognosis of GSD beginning with a chylothorax before 1 year of age, and in reducing bone lesions. Moreover, the use of bisphosphonates appears to be useful in treating pain

Clinical and genetic determinants of nevirapine plasma trough concentration

Background: Only few data are available on the influence of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations in the Caucasian population. Our aim was to assess the impact of CYP2B6 and CYP3A4/A5 polymorphisms on nevirapine plasma concentrations consecutively collected. Methods: We retrospectively analyzed clinical data of all HIV-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan between January 2000 and December 2015. All patients with at least one nevirapine plasma trough concentration (NVP C min ) determination were tested for CYP2B6 c.516 G>T, CYP3A4*22C>T and CYP3A5*3 A>G polymorphisms. Univariate and multivariate regression analyses were carried out considering NVP C min as the dependent variable and genetic polymorphisms and clinical characteristics as independent variables. Results: A total of 143 patients were evaluated. Most of them were males (61.5%) and Caucasian (92.3%). Overall, NVP C min varied from 1571 to 14,189  ng/mL (median  =  5063  ng/mL, interquartile range  =  3915–6854). The median NVP C min significantly differed in patients with different CYP2B6 genotypes, but did not vary in those with different CYP3A phenotypes. In the final general linear model, factors significantly associated with a higher NVP C min were each extra unit of T alleles of CYP2B6 rs3745274 (β  =  0.328, 95% confidence interval  =  0.172–0.484; p   <  0.0001), older age (β  =  0.362, 95% confidence interval  =  0.193–0.532; p   <  0.0001) and hepatitis C virus coinfection (β  =  0.161, 95% confidence interval  =  0.006–0.315; p   <  0.041). Conclusion: Our study, conducted in a prevalent Caucasian population, highlighted the importance of CYP2B6 genetic variants in influencing nevirapine plasma trough concentration. Furthermore, older age and hepatitis C virus coinfection significantly increase exposure to nevirapine

The Need for A Multidisciplinary Approach to Face Challenges Related to Food, Health, and Sustainability: The Contribution of CRC I-WE

The importance of the impact of the food system not only on human health but also on planet health is gaining growing attention, and there is now an urgent call to action for developing multi-stakeholder strategies able to end poverty and maintain prosperity and health for people and for the planet. To provide a better understanding of the complex relationships between food, well-being and environment, it is pivotal to generate multidisciplinary knowledge on the promotion of human well-being in relation to multiple interconnected factors such as diet and nutrition, environment, economic, social, and legal aspects. Based on these premises, the present paper aims at describing the proposed role of the Joint Research Center “Innovation for Well-Being and Environment” (CRC I-WE) that was brought to light in 2019 with a strong interdisciplinary nature at the University of Milan, Italy. In 2021, the Center hosted its first annual conference aimed at identifying case studies from the food, health, and sustainability fields particularly deserving an interdisciplinary approach, and which may provide the basis for opening a wider discussion with the scientific community

Testicular torsion during the COVID-19 pandemic: Results of a multicenter study in northern Italy

The literature reported an increased avoidance of the Emergency Department (ED) during COrona VIrus Disease 19 (COVID-19) pandemic, causing a subsequent increase of morbidity and mortality for acute conditions. Testicular torsion is a surgical emergency, which can lead to the loss of the affected testicle if a delayed treatment occurs. As testicular loss is time-related, outcome was hypothesized to be negatively affected by the pandemic

Thrombotic Features as the Primary Cause of SARS-CoV-2 Related Acute Abdomen in Children

Objectives:We performed a retrospective case control study to evaluate the histological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive pediatric patients undergoing laparoscopic exploration for acute abdomen symptoms. To our knowledge this is the first study that analyzes histopathological characteristics of abdominal tissues in SARS-CoV-2 children.Study design:We enrolled 8 multisystem inflammatory syndrome in children (MIS-C) patients and 4 SARS-CoV-2 positive patients who underwent intestinal resection versus 36 control appendectomies from 2 pediatric tertiary referral centers between March 2020 and July 2021. Surgical resection samples were evaluated on several histological sections focusing on general inflammatory pattern and degree of inflammation. Peculiar histological features (endotheliitis and vascular thrombosis) were semi-quantitatively scored respectively in capillary, veins, and arteries.Results:All SARS-CoV-2 related surgical samples showed thrombotic patterns. Those patterns were significantly less frequent in SARS-CoV-2 negative appendectomies (P = 0.004). The semi-quantitative score of thrombosis was significantly higher (P = 0.002) in patients with SARS-CoV-2 related procedures.Conclusions:Our results showed that SARS-CoV-2 can cause thrombotic damage in abdominal tissues both in the acute phase of the infection (SARS-CoV-2 related appendectomies) and secondary to cytokine storm (MIS-C)