Duration of antibiotic treatment for Gram-negative bacteremia - Systematic review and individual participant data (IPD) meta-analysis

Background: We aim to compare the effect of short versus long treatment duration in Gram-negative bacteremia on all-cause mortality in pre-specified sub-groups. Methods: Individual participant data meta-analysis of randomized controlled trials (RCTs) comparing short (≤7) versus longer (>7 days) antibiotic treatment for Gram-negative bacteremia. Participants were adults (≥18 years), with Gram-negative bacteremia during hospital stay. We searched PubMed, Cochrane Central Register of Controlled Trials, and Web of Science to identify trials conducted up to May 2022. Primary outcome was 90-day all-cause mortality. Secondary outcomes were 30-day mortality, relapse of bacteremia, length of hospital stay, readmission, local or distant infection complications, adverse events, and resistance emergence.Outcomes were assessed in pre-specified subgroups: women vs men; non-urinary vs urinary source; presence vs absence of hypotension on initial presentation; immunocompromised patients versus non-immunocompromised patients, and age (above/below 65). Fixed-effect meta-analysis model was used to estimate pooled odds ratio (OR) and 95% confidence interval (CI). All three trials had low risk of bias for allocation generation and concealment. Findings: Three RCTs (1186 patients) were included; 1121 with enterobacterales bacteremia. No significant difference in mortality was demonstrated between 7- and 14-days treatment (90-day mortality: OR 1.08, 95% CI 0.73-1.58; 30-day mortality: 1.08, 0.62-1.91). Relapse (1.00, 0.50-1.97); length of hospital stay (P = 0.78); readmission (0.96, 0.80-1.22); and infection complications (local: 1.62 0.76-3.47; distant: 2.00, 0.18-22.08), were without significant difference, and so were adverse events or resistance emergence.No significant difference in clinical outcomes between 7 and 14 days of antibiotics was demonstrated in the subgroups of gender, age, hemodynamic status, immune status, and source of infection. Interpretation: For patients hemodynamically stable and afebrile at 48 h prior to discontinuation, seven days of antibiotic therapy for enterobacterales bacteremia result in similar outcomes as 14 days, in terms of mortality, relapse, length of hospital stay, complications of infection, resistance emergence, and adverse events. These results apply for any adult age group, gender, source of infection, immune status, and hemodynamic status on presentation. Funding: There was no funding source for this study

Epigenetic Regulation of Fatty Acid Amide Hydrolase in Alzheimer Disease

OBJECTIVE: Alzheimer disease (AD) is a progressive, degenerative and irreversible neurological disorder with few therapies available. In search for new potential targets, increasing evidence suggests a role for the endocannabinoid system (ECS) in the regulation of neurodegenerative processes. METHODS: We have studied the gene expression status and the epigenetic regulation of ECS components in peripheral blood mononuclear cells (PBMCs) of subjects with late-onset AD (LOAD) and age-matched controls (CT). RESULTS: We found an increase in fatty acid amide hydrolase (faah) gene expression in LOAD subjects (2.30 ± 0.48) when compared to CT (1.00 ± 0.14; *p<0.05) and no changes in the mRNA levels of any other gene of ECS elements. Consistently, we also observed in LOAD subjects an increase in FAAH protein levels (CT: 0.75 ± 0.04; LOAD: 1.11 ± 0.15; *p<0.05) and activity (pmol/min per mg protein CT: 103.80 ± 8.73; LOAD: 125.10 ± 4.00; *p<0.05), as well as a reduction in DNA methylation at faah gene promoter (CT: 55.90 ± 4.60%; LOAD: 41.20 ± 4.90%; *p<0.05). CONCLUSIONS: Present findings suggest the involvement of FAAH in the pathogenesis of AD, highlighting the importance of epigenetic mechanisms in enzyme regulation; they also point to FAAH as a new potential biomarker for AD in easily accessible peripheral cells

Modulation of the endocannabinoids N-Arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) on Executive Functions in Humans

Animal studies point to an implication of the endocannabinoid system on executive functions. In humans, several studies have suggested an association between acute or chronic use of exogenous cannabinoids (Δ9-tetrahydrocannabinol) and executive impairments. However, to date, no published reports establish the relationship between endocannabinoids, as biomarkers of the cannabinoid neurotransmission system, and executive functioning in humans. The aim of the present study was to explore the association between circulating levels of plasma endocannabinoids N-arachidonoylethanolamine (AEA) and 2-Arachidonoylglycerol (2-AG) and executive functions (decision making, response inhibition and cognitive flexibility) in healthy subjects. One hundred and fifty seven subjects were included and assessed with the Wisconsin Card Sorting Test; Stroop Color and Word Test; and Iowa Gambling Task. All participants were female, aged between 18 and 60 years and spoke Spanish as their first language. Results showed a negative correlation between 2-AG and cognitive flexibility performance (r = −.37; p<.05). A positive correlation was found between AEA concentrations and both cognitive flexibility (r = .59; p<.05) and decision making performance (r = .23; P<.05). There was no significant correlation between either 2-AG (r = −.17) or AEA (r = −.08) concentrations and inhibition response. These results show, in humans, a relevant modulation of the endocannabinoid system on prefrontal-dependent cognitive functioning. The present study might have significant implications for the underlying executive alterations described in some psychiatric disorders currently associated with endocannabinoids deregulation (namely drug abuse/dependence, depression, obesity and eating disorders). Understanding the neurobiology of their dysexecutive profile might certainly contribute to the development of new treatments and pharmacological approaches

DEMOCRITOS Demonstrators for Realization of Nuclear Electric Propulsion of the European Roadmaps MEGAHIT & DiPoP

The European Commission Horizon 2020 funded DEMOCRITOS project (2015-2017) will be primary focused to prepare preliminary design of the ground, core and space demonstrators and their test benches for the mega-watt class nuclear electric space propulsion INPPS flagship (International Nuclear Power and Propulsion System). In addition programmatic, organizational and funding aspects for international cooperation related to INPPS realization are sketched. The new project includes partners from Europe, Russia and the Brazilian guest observer IEAv and is the follow-up of the mega-watt class nuclear electric propulsion European-Russian MEGAHIT project (www.megahit-eu.org). In Europe was already established the high power nuclear MEGAHIT and the low power nuclear (20 to 200 kW NEP) DiPoP (www.DiPoP.eu) roadmaps. Because Europe has started the implementations for INPPS flagship in the 2030-2040 timeframe, both roadmaps will be also described – from MEGAHIT the INPPS technology options, the launcher, assembly and system architecture, space mission requirements, communications and public support. In case of DiPoP it will be explained the survey of European capabilities, technical options, potential space missions and the public acceptance as well

Síndrome de Dravet, un reto diagnóstico: Reporte de Caso

Abstract. Dravet syndrome is a severe epileptic encephalopathy of very low incidence (1 pe 20,000-40,000), it is classified as rare and of little medical knowledge and suspicion, which makes its diagnosis difficult. It is an alteration in the SCN1A gene, the main encoder of the alpha 1 subunit of the sodium channel. Case presentation: 6-month-old female patient, born by cesarean section, normal pregnancy course, without complications, mother with a history of a previous abortion, no significant family history and motor development according to age. She went to the emergency room for presenting an unquantified thermal rise and seizure, which occurred after the third dose of pentavalent vaccine corresponding to her age, this not being a triggering factor for the seizure. Having very frequent episodes and not obtaining an adequate control, several diagnostic tests are performed including genetic studies of WES to reach a treatment according to a specific diagnosis, for this reason the parents of the minor decide to go to countries of technology to perform this type of diagnosis. The relevance of the case lies in demonstrating that Dravet syndrome is an underdiagnosed and inadequately treated disease, however, currently the use of tools, especially genetic methods and early control prevents patients from presenting several repeated episodes and improves their quality of life. &nbsp;&nbsp; Keywords: Dravet's Syndrome, Epilepsy, Seizures, SCN1AResumen. El síndrome de Dravet es una encefalopatía epiléptica severa de muy poca incidencia (1 por cada 20.00040.000), es catalogada como rara y de poco conocimiento y sospecha médica, por tal razón dificulta su diagnóstico. Se trata de una alteración en el gen SCN1A, principal codificador de la subunidad alfa 1 del canal de sodio. Presentación del caso: Paciente femenino de 6 meses de vida, nacimiento por cesárea, embarazo de curso normal, sin complicaciones, madre con antecedente de un aborto previo, sin antecedentes familiares de importancia y desarrollo motriz acorde con la edad. Acude a urgencia por presentar alza térmica no cuantificada y crisis convulsiva, que se presenta posteriormente a la tercera dosis de vacuna pentavalente correspondiente a la edad, no siendo este factor desencadenante de la crisis. Al tener episodios muy frecuentes y no obtener un control adecuado, se realizan varias pruebas diagnósticas incluyendo estudios genéticos de WES para llegar a un tratamiento acorde a un diagnóstico específico, por esta los padres de la menor deciden acudir a países de tecnología para realizar este tipo de diagnósticos. La relevancia del caso radica en demostrar que el síndrome de Dravet es una enfermedad subdiagnosticada y tratada de manera inadecuada; sin embargo, en la actualidad el uso de herramientas, especialmente métodos genéticos y un control temprano evita a que los pacientes presenten varios episodios a repetición y mejores su calidad de vida. Palabras clave:&nbsp; Síndrome de Dravet, Epilepsia, Convulsiones, SCN1

Using Hypnotic Suggestion to Model Loss of Control and Awareness of Movements: An Exploratory fMRI Study

The feeling of voluntary control and awareness of movement is fundamental to our notions of selfhood and responsibility for actions, yet can be lost in neuropsychiatric syndromes (e.g. delusions of control, non-epileptic seizures) and culturally influenced dissociative states (e.g. attributions of spirit possession). The brain processes involved remain poorly understood. We used suggestion and functional magnetic resonance imaging (fMRI) to investigate loss of control and awareness of right hand movements in 15 highly hypnotically suggestible subjects. Loss of perceived control of movements was associated with reduced connectivity between supplementary motor area (SMA) and motor regions. Reduced awareness of involuntary movements was associated with less activation in parietal cortices (BA 7, BA 40) and insula. Collectively these results suggest that the sense of voluntary control of movement may critically depend on the functional coupling of SMA with motor systems, and provide a potential neural basis for the narrowing of awareness reported in pathological and culturally influenced dissociative phenomena

Performance of the motor task (joystick movement) in the non-hypnosis condition (nhyp-vol condition) engaged established components of the ‘motor network’, including a) right cerebellum b) left thalamus c) left postcentral gyrus (M1) and d) left SMA.

<p>Crosshairs show peak activation at each cluster.</p

Suggested loss of awareness (hyp-involA versus hyp-involNA , 2>3)) was associated with reduced activation in a) left SPL (BA 7) and IPL (BA 40) and b) left supramarginal, left middle occipital and left superior temporal gyri (p<0.001).

<p>Suggested loss of awareness (hyp-involA versus hyp-involNA , 2>3)) was associated with reduced activation in a) left SPL (BA 7) and IPL (BA 40) and b) left supramarginal, left middle occipital and left superior temporal gyri (p<0.001).</p