The selective antagonism of adenosine A2Breceptors reduces the synaptic failure and neuronal death induced by oxygen and glucose deprivation in rat CA1 hippocampus in vitro

Ischemia is a multifactorial pathology characterized by different events evolving in time. Immediately after the ischemic insult, primary brain damage is due to the massive increase of extracellular glutamate. Adenosine in the brain increases dramatically during ischemia in concentrations able to stimulate all its receptors, A1, A2A, A2B, and A3. Although adenosine exerts clear neuroprotective effects through A1 receptors during ischemia, the use of selective A1 receptor agonists is hampered by their undesirable peripheral side effects. So far, no evidence is available on the involvement of adenosine A2B receptors in cerebral ischemia. This study explored the role of adenosine A2B receptors on synaptic and cellular responses during oxygen and glucose deprivation (OGD) in the CA1 region of rat hippocampus in vitro. We conducted extracellular recordings of CA1 field excitatory post-synaptic potentials (fEPSPs); the extent of damage on neurons and glia was assessed by immunohistochemistry. Seven min OGD induced anoxic depolarization (AD) in all hippocampal slices tested and completely abolished fEPSPs that did not recover after return to normoxic condition. Seven minutes OGD was applied in the presence of the selective adenosine A2B receptor antagonists MRS1754 (500 nM) or PSB603 (50 nM), separately administered 15 min before, during and 5 min after OGD. Both antagonists were able to prevent or delay the appearance of AD and to modify synaptic responses after OGD, allowing significant recovery of neurotransmission. Adenosine A2B receptor antagonism also counteracted the reduction of neuronal density in CA1 stratum pyramidale, decreased apoptosis at least up to 3 h after the end of OGD, and maintained activated mTOR levels similar to those of controls, thus sparing neurons from the degenerative effects caused by the simil-ischemic conditions. Astrocytes significantly proliferated in CA1 stratum radiatum already 3 h after the end of OGD, possibly due to increased glutamate release. A2Breceptor antagonism significantly prevented astrocyte modifications. Both A2B receptor antagonists did not protect CA1 neurons from the neurodegeneration induced by glutamate application, indicating that the antagonistic effect is upstream of glutamate release. The selective antagonists of the adenosine A2B receptor subtype may thus represent a new class of neuroprotective drugs in ischemia

New-Onset Refractory Status Epilepticus with Claustrum Damage: Definition of the Clinical and Neuroimaging Features

New-onset refractory status epilepticus (NORSE) is a rare but challenging condition occurring in a previously healthy patient, often with no identifiable cause. We describe the electro-clinical features and outcomes in a group of patients with NORSE who all demonstrated a typical magnetic resonance imaging (MRI) sign characterized by bilateral lesions of the claustrum. The group includes 31 patients (12 personal and 19 previously published cases; 17 females; mean age of 25 years). Fever preceded status epilepticus (SE) in 28 patients, by a mean of 6 days. SE was refractory/super-refractory in 74% of the patients, requiring third-line agents and a median of 15 days staying in an intensive care unit. Focal motor and tonic-clonic seizures were observed in 90%, complex partial seizures in 14%, and myoclonic seizures in 14% of the cases. All patients showed T2/FLAIR hyperintense foci in bilateral claustrum, appearing on average 10 days after SE onset. Other limbic (hippocampus, insular) alterations were present in 53% of patients. Within the personal cases, extensive search for known autoantibodies was inconclusive, though 7 of 11 patients had cerebrospinal fluid lymphocytic pleocytosis and 3 cases had oligoclonal bands. Two subjects died during the acute phase, one in the chronic phase (probable sudden unexplained death in epilepsy), and one developed a persistent vegetative state. Among survivors, 80% developed drug-resistant epilepsy. Febrile illness-related SE associated with bilateral claustrum hyperintensity on MRI represents a condition with defined clinical features and a presumed but unidentified autoimmune etiology. A better characterization of de novo SE is mandatory for the search of specific etiologies

Prevalenza di microalbuminuria e malattia renale cronica nei soggetti affetti da psoriasi

La psoriasi è una malattia infiammatoria cronica spesso associata a comorbidità quali l’artrite psoriasica, le malattie infiammatorie croniche intestinali, il diabete mellito, la dislipidemia, l’ipertensione, la steato-epatite non alcolica e la sindrome metabolica. Tuttavia, i dati sulla prevalenza di insufficienza renale e microalbuminuria sono limitati. 82 pazienti affetti da psoriasi sono stati sottoposti a prelievo ematico per la determinazione della creatinina sierica (sCr). La presenza di microalbuminuria su campione di urine del mattino è stata analizzata mediante metodo turbidimetrico. L’estensione e la severità della psoriasi è stata determinata mediante il PASI score. Sono stati utilizzati il test t di Student e il Test Chi quadro per il confronto dei dati; il valore p < 0.05 è stato considerato statisticamente significativo. 12 pazienti presentavano microalbuminuria positiva (> 30mg/g-creat); la prevalenza di microalbuminuria era pertanto 14.6%. I pazienti con microalbuminuria presentavano una psoriasi di più lunga durata (27.2 ± 11.8 vs 16.5 ± 12.1 anni; p = 0.005) and un eGFR ridotto rispetto ai pazienti con microalbuminuria negativa (80.1 ± 27.2 vs 124.1 ± 129.5 ml/min; p=0.007). Non vi erano differenze statisticamente significative per età, genere, BMI, prevalenza di ipertensione arteriosa e diabete mellito, PASI e Proteina C reattiva fra i due gruppi. I pazienti affetti da psoriasi e microalbuminuria positiva presentano una psoriasi di più lunga durata e un filtrato glomerulare stimato più basso rispetto ai paziente con microalbuminuria negativa. La presenza di microalbuminuria non è un reperto frequente nei pazienti affetti da psoriasi ma la sua correlazione con la durata della malattia cutanea potrebbe suggerire un interessamento glomerulare

Cardiac manifestations of MIS-C: cardiac magnetic resonance and speckle-tracking data

BackgroundCardiac involvement is central in MIS-C and represents the main cause of morbidity. In this study, we aimed to assess myocardial damage in patients with MIS-C using cardiac magnetic resonance (CMR) during the acute phase, as well as left ventricular and atrial longitudinal strain on admission, at discharge, and after 3 months.MethodsWe performed a single-center prospective cohort study and case–control study. Between September 2020 and February 2022, we enrolled 39 patients hospitalized for MIS-C at our center. We performed left ventricular and atrial longitudinal 2D strain analysis on admission and during follow-up; echocardiographic data were compared to a matched control population. Patients above 4 years old with increased troponin underwent CMR.ResultsOf 24 patients (mean age: 8.2 ± 4.9 years) who underwent CMR, 14 (58%) presented myocardial edema and 6 (25%) late gadolinium enhancement (LGE). LGE was associated with older age (p < 0.01), increased BMI (p = 0.03), increased ferritin levels (p < 0.001), lower left ventricular (LV) ejection fraction (p < 0.001), LV longitudinal strain (p = 0.004), left atrial (LA) strain (p = 0.05), and prolonged hospital stay (p = 0.02). On admission, LV ejection fraction, LV longitudinal strain, and LA strain were impaired, but each improved gradually over time; LVEF was the fastest to recover, while global LV longitudinal strain was still impaired as compared to controls after 3 months (p = 0.01).ConclusionOur study demonstrates that myocardial injury is present in a quarter of MIS-C patients, and impaired LA and LV myocardial deformation persist for at least several weeks after the acute phase. CMR and LV/LA strain could help us to individualize follow-up of MIS-C patients

Experimental equation of state in proton-proton and proton-antiproton collisions and phase transition to quark gluon plasma

We deduce approximate equations of state from experimental measurements in proton-proton and proton-antiproton collisions. Thermodynamic quantities are estimated combining the measure of average transverse momentum vs pseudorapidity density dN/deta with the estimation of the interaction region size from measures of Bose Einstein correlation, or from a theoretical model which relates dN/deta to the impact parameter. The results are very similar to theory predictions in case of crossover from hadron gas to quark gluon plasma. According to our analysis, the possible crossover should start at dN/deta about 6 and end at dN/deta about 24.Comment: 26 pages, 6 figure

Health-related quality of life of food-allergic children compared with healthy controls and other diseases

Background Food allergy is a potentially life-threatening disease, affecting up to 10% of the pediatric population. Objective The aim of our study was to assess the health-related quality of life (HRQL) of food-allergic patients compared with the general population and patients with other chronic diseases with dietary or allergic burden, in a cross-sectional study. Methods We recruited patients aged 8-17 years diagnosed with food allergy and matched healthy controls recruited in schools. We also included patients with asthma, inflammatory bowel disease, celiac disease, diabetes, obesity, and eating disorders. We used the CHQ-CF87 questionnaire for generic HRQL assessment. Food allergy HRQL was also assessed using specific questionnaires: Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM). Results One hundred and thirty-five food-allergic children, 255 children with chronic diseases, and 463 healthy controls were included in the analyses. Food-allergic patients had a better HRQL than healthy controls in the Behavior (BE), Bodily Pain (BP), Family Activities (FA), and Mental Health (MH) domains and a worse HRQL in the General Health Perception (GH) domain (p = .048). Food-allergic patients exhibited a better HRQL than patients affected by other chronic diseases, notably diabetes. Although an epinephrine autoinjector had been prescribed to 87.4% of the food-allergic children, only 54.2% of them carried it at all times. Conclusion Food-allergic patients display overall good HRQL compared with the general population and those with other diseases with daily symptoms and treatments, in line with recent improvements in food allergy management

Molecular gas and star formation in early-type galaxies

We present new mm interferometric and optical integral-field unit (IFU) observations and construct a sample of 12 E and S0 galaxies with molecular gas which have both CO and optical maps. The galaxies contain 2 x 10^7 to 5 x 10^9 M\odot of molecular gas distributed primarily in central discs or rings (radii 0.5 to 4 kpc). The molecular gas distributions are always coincident with distributions of optically-obscuring dust that reveal tightly-wound spiral structures in many cases. The ionised gas always approximately corotates with the molecular gas, evidencing a link between these two gas components, yet star formation is not always the domi- nant ionisation source. The galaxies with less molecular gas tend to have [O III]/H{\beta} emission-line ratios at high values not expected for star formation. Most E/S0s with molecular gas have young or intermediate age stellar populations based on optical colours, ultraviolet colours and absorption linestrengths. The few that appear purely old lie close to the limit where such populations would be undetectable based on the mass fractions of expected young to observed old stars. The 8{\mu}m polycyclic aromatic hydrocarbon (PAH) and 24{\mu}m emission yield similar star formation rate estimates of E/S0s, but the total infrared overpredicts the rate due to a contribution to dust heating from older stars. The radio-far infrared relation also has much more scatter than for other star-forming galaxies. However, despite these biases and additional scatter, the derived star formation rates locate the E/S0 galaxies within the large range of the Schmidt-Kennicutt and constant efficiency star formation laws. Thus the star formation process in E/S0s is not overwhelmingly different than in other star-forming galaxies, although one of the more reliable tracers (24{\mu}m) points to a possible lower star-formation efficiency at a given gas surface density.Comment: submitted to MNRA

Simultaneous editing of two DMR6 genes in grapevine results in reduced susceptibility to downy mildew

The reduction of pesticides’ treatments is of paramount importance for the sustainability of viticulture, and it can be achieved by a combination of strategies including the cultivation of vines (Vitis vinifera) that are resistant or tolerant to diseases such as downy mildew (DM). In many crops, the knock-out of Downy Mildew Resistant 6 (DMR6) proved successful in controlling DM-resistance, but the effect of mutations in DMR6 genes in not yet known in grapevine.Today, gene editing serves crop improvement with small and specific mutations while maintaining the genetic background of commercially important clones. Moreover, recent technological advances allowed to produce non-transgenic grapevine clones by regeneration of protoplasts edited with the CRISPR/Cas9 ribonucleoprotein. This approach may revolutionize the production of new grapevine varieties and clones, but it requires knowledge on the targets, and on the impact of editing on plant phenotype and fitness in different cultivars. In this work we generated single and double knock-out mutants by editing DMR6 susceptibility (S) genes using CRISPR/Cas9, and showed that only the combined mutations in VviDMR6-1 and VviDMR6-2 are effective in reducing susceptibility to DM in two table-grape cultivars by increasing the levels of endogenous salicylic acid. Therefore, editing both genes may be necessary for effective DM control in real-world agricultural settings, which could potentially lead to unwanted phenotypes. Additional research, including trials conducted in experimental vineyards, is required to gain a deeper understanding of DMR6-based resistance