Cystic echinococcosis in cattle dairy farms: spatial distribution and epidemiological dynamics

A study monitoring cystic echinococcosis (CE) in adult dairy cattle from intensive livestock farms located in the municipality of Arborea (Sardinia, Italy) was carried out between 2012 and 2015. A retrospective study of veterinary reporting forms of post-mortem inspections in 10 different Italian slaughterhouses was also performed. In addition, data on viability and molecular characterisation of hydatid cysts removed from parasitised organs in cattle was carried out. A geographical information system (GIS) with data layers of the study area and the geo-referenced points of 160 cattle farms was constructed. CE was found in 21.9% (35/160) of the surveyed farms. The retrospective study revealed that 0.05% (13/23,656) of adult slaughtered animals (over one year of age) from Arborea had tested positive to CE. The results stratified per year showed the following CE prevalences: 0.09% (5/5673) in 2012; 0.02% (1/5682) in 2013; 0.08% (5/6261) in 2014; and 0.03% (2/6040) in 2015 (χ2 with 3 degrees of freedom=3.81; P=0.282). The E. granulosus sensu stricto (formerly called G1 or sheep strain) was detected in all cysts subjected to molecular analysis. The GIS analysis showed that CE is fairly resilient in the Arborea territory where most of cattle farms are located, while a small cluster of cases was found located in the southeastern part of Arborea, close to districts where sheep farms are situated. The present survey reports the presence of CE in Sardinian dairy cattle intensive farms and suggests that the parasitic pressure of CE in the island continues to be very strong

O81 IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (ATEZO) monotherapy vs platinum-based chemotherapy (CHEMO) as first-line (1L) treatment in PD-L1–selected NSCLC

BackgroundPD-L1/PD-1 inhibitors (CPI) as monotherapy or in combination with platinum-based doublet chemo (± bevacizumab) are 1L treatment options in metastatic NSCLC, with choice of agent(s) determined by PD-L1 expression. For patients (pts) who may be ineligible for combination therapy, CPI monotherapy remains an attractive treatment choice. IMpower110 evaluated atezo as 1L treatment in PD-L1–selected pts independent of tumor histology.MethodsIMpower110 enrolled 572 chemo-naive pts with stage IV nonsquamous (nsq) or squamous (sq) NSCLC, PD-L1 expression ≥ 1% on TC or IC, measurable disease by RECIST 1.1 and ECOG PS 0-1. Pts were randomized 1:1 to receive atezo 1200 mg IV q3w (Arm A) or platinum-based chemo (Arm B; 4 or 6 21-day cycles). Arm B nsq pts received cisplatin (cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed 500 mg/m2 IV q3w; Arm B sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250 mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. Stratification factors were sex, ECOG PS, histology and tumor PD-L1 status (TC1/2/3 and any IC vs TC0 and IC1/2/3). The primary endpoint of OS is tested hierarchically in the wild-type (WT; EGFR/ALK-negative) population (TC3 or IC3 then TC2/3 or IC2/3 then TC1/2/3 or IC1/2/3).ResultsThe 3 primary efficacy populations included 554 TC1/2/3 or IC1/2/3 WT pts, 328 TC2/3 or IC2/3 WT pts and 205 TC3 or IC3 WT pts. Median follow-up was 15.7 months (range, 0-35) in TC3 or IC3 WT pts. In the TC3 or IC3 WT population, atezo monotherapy improved median OS by 7.1 months (HR, 0.595; P = 0.0106) compared with chemo (table 1). The safety population comprised 286 pts in Arm A and 263 in Arm B. Treatment-related AEs (TRAEs) and Grade 3-4 TRAEs occurred in 60.5% (Arm A) and 85.2% (Arm B), and 12.9% (Arm A) and 44.1% (Arm B), respectively.Abstract 081 Table 1ConclusionsAt this interim analysis, IMpower110 met the primary endpoint of OS with statistically significant and clinically meaningful improvement in the TC3 or IC3 WT population. The safety profile favored Arm A, with no new or unexpected safety signals identified.Trial RegistrationNCT02409342Ethics ApprovalThe trial was conducted according to the principles of the Declaration of Helsinki. All patients provided written informed consent. Protocol approval was obtained from independent review boards or ethics committees at each site

The SARS-CoV-2 receptor ACE2 is expressed in mouse pericytes but not endothelial cells : Implications for COVID-19 vascular research

Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is impor-tant to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, andin heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.Peer reviewe

Molecular anatomy of adult mouse leptomeninges.

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology

Long-term, Real-life, Observational Study in Treating Outpatient Ulcerative Colitis with Golimumab

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good

Dianas de fármacos antipsicóticos en neuronas de proyección de la corteza prefrontal

Peer Reviewe

Multi-objective Optimization of Energy Storage System in an Italian Local Energy Community

Energy Storage Systems are becoming necessary for the upcoming Smart Distribution Systems thanks to the flexibility they introduce in the network operation. Since their costs are still high, optimal planning and management of these devices are crucial to identify specific configurations that can support storage installation. This consideration has motivated a strong interest of the researchers in this field that, however, have separately solved the optimal storage systems location and their optimal schedule. In the paper, a novel Multi-Objective approach is presented, based on the Non-dominated Sorted Genetic Algorithm – II integrated with a real codification that allows joining in a single optimization all the main features of an optimal storage implementation project. The paper is focused on the potential of a Local Energy Community of residential prosumers (with photovoltaic and storage systems) that can support the operation of the distribution system. In particular, pilots selected in the EU project StoRES (Promotion of higher penetration of distributed PV through storage for all) constitutes the Local Energy Community. Application examples are presented to illustrate the algorithm effectiveness

Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action

The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. Classical antipsychotic drugs modulate information processing in cortico-limbic circuits via dopamine D2 receptor blockade in nucleus accumbens (NAc) whereas atypical antipsychotic drugs preferentially target cortical serotonin (5-HT) receptors. The brain networks involved in the therapeutic action of atypical drugs are not fully understood. Previous work indicated that medial PFC (mPFC) pyramidal neurons projecting to ventral tegmental area express 5-HT2A receptors suggesting that atypical antipsychotic drugs modulate dopaminergic activity distally, via 5-HT2A receptor (5-HT2A-R) blockade in PFC. Since the mPFC also projects heavily to NAc, we examined whether NAc-projecting pyramidal neurons also express 5-HT2A-R. Using a combination of retrograde tracing experiments and in situ hybridization we report that a substantial proportion of mPFC-NAc pyramidal neurons in rat brain express 5-HT2A-R mRNA in a layer- and area-specific manner (up to 68% in layer V of contralateral cingulate). The functional relevance of 5-HT2A-R to modulate mPFC-NAc projections was examined in dual-probe microdialysis experiments. The application of the preferential 5-HT2A-R agonist DOI into mPFC enhanced glutamate release locally (+66 ± 18%) and in NAc (+74 ± 12%) indicating that cortical 5-HT2A-R activation augments glutamatergic transmission in NAc. Since NAc integrates glutamatergic and dopaminergic inputs, blockade of 5-HT2A-R by atypical drugs may reduce cortical excitatory inputs onto GABAergic neurons of NAc, adding to dopamine D2 receptor blockade. Together with previous observations, the present results suggest that atypical antipsychotic drugs may control the activity of the mesolimbic pathway at cell body and terminal level.Support from grants SAF 2012-35183 (Ministry of Economy and Competitiveness; EU FEDER funds), PS09/01087 (Ministry of Health, ISCIII) and from the Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM. Support from Generalitat de Catalunya (SGR 20093) is also acknowledged. Giuseppe Mocci is recipient of a CSIC-JAE fellowship. Laura Jiménez-Sánchez is recipient of a predoctoral fellowship from IDIBAPS.Peer reviewe

Antipsychotic drugs may modulate the mesolimbic pathway via interaction with 5-HT receptors in prefrontal cortex

Trabajo presentado al Neuroscience celebrado en Nueva Orleans del 13 al 17 de octubre de 2012.Classical antipsychotic drugs modulate cortico-limbic circuits through D2 receptor blockade in ventral striatum (nucleus accumbens -NAc- and anatomaically-related structures), whereas atypical antipsychotics preferentially target cortical 5HT2 receptors. The prefrontal cortex (PFC) is involved in higher brain functions altered in schizophrenia. It contains a high density of serotoninergic receptors such as 5HT2A and 5HT1A for which atypical antipsychotic drugs exhibit high affinity. Previous studies indicate that a substantial proportion of PFC pyramidal neurons projecting to the ventral tegmental area or the dorsal raphe nucleus express 5HT2A receptor mRNA, which suggests that atypical antipsychotic drugs affect serotonergic and dopaminergic function by targeting PFC 5HT2A receptors. In a similar way, atypical antipsychotic drugs targeting 5HT2A or 5HT1A receptors in pyramidal neurons projecting to NAc may normalize the activity of cortico-limbic circuits by changing the excitatory input from PFC to NAc. Here we examined whether PFC neurons projecting to NAc express these 5-HT receptors. Fluorogold or choleratoxin B application into NAc showed retrogradely labeled neurons in PFC layer V of both hemispheres and in layer II of the ipsilateral PFC. Using a combination of retrograde tracing and in situ hybridization histochemistry we report that 39-48% of PFC pyramidal neurons projecting to NAc (ipsi- and contralateral in superficial and deep layers) express 5HT2A receptor mRNA while ca. 38-40% express 5HT1A receptor mRNA. The present and past data indicate that pyramidal neurons expressing 5-HT receptors sensitive to antipsychotic drugs can control the activity of the mesolimbic dopaminergic pathway at cell body and terminal levels.Peer Reviewe