Oleic Acid and Hydroxytyrosol Inhibit Cholesterol and Fatty Acid Synthesis in C6 Glioma Cells

Recently, the discovery of natural compounds capable of modulating nervous system function has revealed new perspectives for a healthier brain. Here, we investigated the effects of oleic acid (OA) and hydroxytyrosol (HTyr), two important extra virgin olive oil compounds, on lipid synthesis in C6 glioma cells. OA and HTyr inhibited both de novo fatty acid and cholesterol syntheses without affecting cell viability. The inhibitory effect of the individual compounds was more pronounced if OA and HTyr were administered in combination. A reduction of polar lipid biosynthesis was also detected, while triglyceride synthesis was marginally affected. To clarify the lipid-lowering mechanism of these compounds, their effects on the activity of key enzymes of fatty acid biosynthesis (acetyl-CoA carboxylase-ACC and fatty acid synthase-FAS) and cholesterologenesis (3-hydroxy-3-methylglutaryl-CoA reductase-HMGCR) were investigated in situ by using digitonin-permeabilized C6 cells. ACC and HMGCR activities were especially reduced after 4 h of 25 μM OA and HTyr treatment. No change in FAS activity was observed. Inhibition of ACC and HMGCR activities is corroborated by the decrease of their mRNA abundance and protein level. Our results indicate a direct and rapid downregulatory effect of the two olive oil compounds on lipid synthesis in C6 cells

The SIFIPAC/WSES/SICG/SIMEU guidelines for diagnosis and treatment of acute appendicitis in the elderly (2019 edition).

The epidemiology and the outcomes of acute appendicitis in elderly patients are very different from the younger population. Elderly patients with acute appendicitis showed higher mortality, higher perforation rate, lower diagnostic accuracy, longer delay from symptoms onset and admission, higher postoperative complication rate and higher risk of colonic and appendiceal cancer. The aim of the present work was to investigate age-related factors that could influence a different approach, compared to the 2016 WSES Jerusalem guidelines on general population, in terms of diagnosis and management of elderly patient with acute appendicitis. During the XXIX National Congress of the Italian Society of Surgical Pathophysiology (SIFIPAC) held in Cesena (Italy) in May 2019, in collaboration with the Italian Society of Geriatric Surgery (SICG), the World Society of Emergency Surgery (WSES) and the Italian Society of Emergency Medicine (SIMEU), a panel of experts participated to a Consensus Conference where eight panelists presented a number of statements, which were developed for each of the four topics about diagnosis and management of acute appendicitis in elderly patients, formulated according to the GRADE system. The statements were then voted, eventually modified and finally approved by the participants to the Consensus Conference. The current paper is reporting the definitive guidelines statements on each of the following topics: diagnosis, non-operative management, operative management and antibiotic therapy

The SIFIPAC/WSES/SICG/SIMEU guidelines for diagnosis and treatment of acute appendicitis in the elderly (2019 edition).

The epidemiology and the outcomes of acute appendicitis in elderly patients are very different from the younger population. Elderly patients with acute appendicitis showed higher mortality, higher perforation rate, lower diagnostic accuracy, longer delay from symptoms onset and admission, higher postoperative complication rate and higher risk of colonic and appendiceal cancer. The aim of the present work was to investigate age-related factors that could influence a different approach, compared to the 2016 WSES Jerusalem guidelines on general population, in terms of diagnosis and management of elderly patient with acute appendicitis. During the XXIX National Congress of the Italian Society of Surgical Pathophysiology (SIFIPAC) held in Cesena (Italy) in May 2019, in collaboration with the Italian Society of Geriatric Surgery (SICG), the World Society of Emergency Surgery (WSES) and the Italian Society of Emergency Medicine (SIMEU), a panel of experts participated to a Consensus Conference where eight panelists presented a number of statements, which were developed for each of the four topics about diagnosis and management of acute appendicitis in elderly patients, formulated according to the GRADE system. The statements were then voted, eventually modified and finally approved by the participants to the Consensus Conference. The current paper is reporting the definitive guidelines statements on each of the following topics: diagnosis, non-operative management, operative management and antibiotic therapy

A pandemic recap : lessons we have learned

On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.Non peer reviewe

Neurosurgeons perspective on the shift towards earlier use of deep brain stimulation for Parkinson disease

Background: The US Food and Drug Administration approved in 2015 the use of deep brain stimulation for Parkinson disease after “four years duration and with recent onset of motor complications”. The aim of this study was to identify neurosurgeons’ attitudes and perspectives around the use of deep brain stimulation for Parkinson disease earlier in the disease course. Methods: An anonymous survey examining attitudes and perceptions towards deep brain stimulation practice and timing in Parkinson disease was developed by the study team and distributed by the American Society for Stereotactic and Functional Neurosurgeons to its members. Results from 32 subjects with answers to at least 50% of the survey were included. Data were analyzed with descriptive statistics and chi-square test. Results: Motor fluctuations, dyskinesia, quality of life impairment, and medically refractory tremor were the most important reasons to proceed with deep brain stimulation, which was overall considered more useful after the onset of motor symptoms. Unresponsiveness to levodopa, cognitive impairment, and unclear diagnosis were important reasons not to consider deep brain stimulation. Earlier surgery was considered to be less risky compared to later in the disease progression. Ten out of 25 neurosurgeons reported considering deep brain stimulation as a therapeutic option after a minimum disease duration of three to four years. Conclusions: We conclude that neurosurgeons support the use of earlier deep brain stimulation, but not preceding motor complications. Further research surrounding the benefits and adverse effects of earlier deep brain stimulation is needed to guide practice and better inform potential candidates

Deep brain stimulation for Tourette’s syndrome: the case for targeting the thalamic centromedian-parafascicular complex.

Tourette syndrome is a neurologic condition characterized by both motor and phonic tics and is typically associated with psychiatric comorbidities, including obsessive-compulsive disorder/behavior and attention deficit hyperactivity disorder and can be psychologically and socially debilitating. It is considered a disorder of the cortico-striato-thalamo-cortical circuitry, as suggested by pathophysiology studies and therapeutic options. Among these, deep brain stimulation of the centromedian-parafascicular nuclear complex (CM-Pf) of the thalamus is emerging as a valuable treatment modality for patients affected by severe, treatment resistant TS. Here we review the most recent experimental evidence for the pivotal role of CM-Pf in the pathophysiology of Tourette syndrome, discuss potential mechanisms of action that may mediate the effects of CM-Pf deep brain stimulation in Tourette syndrome, and summarize its clinical efficacy

Global network modulation during thalamic stimulation for Tourette syndrome

Background and objectives: Deep brain stimulation (DBS) of the thalamus is a promising therapeutic alternative for treating medically refractory Tourette syndrome (TS). However, few human studies have examined its mechanism of action. Therefore, the networks that mediate the therapeutic effects of thalamic DBS remain poorly understood.Methods: Five participants diagnosed with severe medically refractory TS underwent bilateral thalamic DBS stereotactic surgery. Intraoperative fMRI characterized the blood oxygen level-dependent (BOLD) response evoked by thalamic DBS and determined whether the therapeutic effectiveness of thalamic DBS, as assessed using the Modified Rush Video Rating Scale test, would correlate with evoked BOLD responses in motor and limbic cortical and subcortical regions.Results: Our results reveal that thalamic stimulation in TS participants has wide-ranging effects that impact the frontostriatal, limbic, and motor networks. Thalamic stimulation induced suppression of motor and insula networks correlated with motor tic reduction, while suppression of frontal and parietal networks correlated with vocal tic reduction. These regions mapped closely to major regions of interest (ROI) identified in a nonhuman primate model of TS.Conclusions: Overall, these findings suggest that a critical factor in TS treatment should involve modulation of both frontostriatal and motor networks, rather than be treated as a focal disorder of the brain. Using the novel combination of DBS-evoked tic reduction and fMRI in human subjects, we provide new insights into the basal ganglia-cerebellar-thalamo-cortical network-level mechanisms that influence the effects of thalamic DBS. Future translational research should identify whether these network changes are cause or effect of TS symptoms