Neurobiological After-Effects of Low Intensity Transcranial Electric Stimulation of the Human Nervous System: From Basic Mechanisms to Metaplasticity

Non-invasive low-intensity transcranial electrical stimulation (tES) of the brain is an evolving field that has brought remarkable attention in the past few decades for its ability to directly modulate specific brain functions. Neurobiological after-effects of tES seems to be related to changes in neuronal and synaptic excitability and plasticity, however mechanisms are still far from being elucidated. We aim to review recent results from in vitro and in vivo studies that highlight molecular and cellular mechanisms of transcranial direct (tDCS) and alternating (tACS) current stimulation. Changes in membrane potential and neural synchronization explain the ongoing and short-lasting effects of tES, while changes induced in existing proteins and new protein synthesis is required for long-lasting plastic changes (LTP/LTD). Glial cells, for decades supporting elements, are now considered constitutive part of the synapse and might contribute to the mechanisms of synaptic plasticity. This review brings into focus the neurobiological mechanisms and after-effects of tDCS and tACS from in vitro and in vivo studies, in both animals and humans, highlighting possible pathways for the development of targeted therapeutic applications

Short-term use of dexamethasone/netilmicin fixed combination in controlling ocular inflammation after uncomplicated cataract surgery

Purpose: To evaluate the short-term anti-inflammatory effect of dexamethasone/netilmicin fixed combination in the management of ocular inflammation after cataract surgery. Patients and methods: Open-label, randomized, active-controlled, clinical study conducted in 6 sites in Italy; 238 patients were randomized 2:1 to dexamethasone/netilmicin (dexa/net, n=158) or betamethasone/chloramphenicol (beta/chl, n=80). Treatment started the day of surgery and continued 4 times daily for 7 days. The primary efficacy parameter was the anterior chamber (AC) flare. The percentage of patients displaying none or mild (ie, only barely detectable) AC flare was defined as "efficacy rate", whereas the percentage of patients showing a decrease of AC flare score from baseline was defined as "percentage of responders". Additional parameters evaluated were AC cells, conjunctival hyperaemia, corneal and lid oedema, symptoms of ocular discomfort, visual acuity, and intraocular pressure. Dexa/net was considered effective if the efficacy rate was not inferior (by means of 97.5% confidence interval) to that of beta/chl. Results: After 7 days of treatment, no AC flare was observed in 92.8% (dexa/net) and 92.3% (beta/chl) of patients, whereas no AC cells were observed in 91.5% (dexa/net) and 93.6% (beta/chl) of patients, respectively. The "efficacy rate" was 100% in both groups, whereas the "percentage of responders" was 94.1% in the dexa/net and 93.6% in the beta/chl group. The p-value to reject the null hypothesis of inferiority was <0.001. Other efficacy parameters confirmed both treatments as highly effective, despite their difference in steroid content (2 mg/mL for beta/chl vs 1 mg/mL for dexa/net). IOP and visual acuity at the end of the study were comparable. Two cases of allergic conjunctivitis were considered adverse events and were both related to dexa/net. Conclusion: Short-term use of dexa/net fixed combination is safe and effective in the control of post-operative inflammation following uncomplicated cataract surgery

Bacterial Expression of Mouse Argonaute 2 for Functional and Mutational Studies

RNA interference (RNAi) is a post-transcriptional gene-silencing process that occurs in many eukaryotic organisms upon intracellular exposure to double-stranded RNA. Argonaute 2 (Ago2) protein is the catalytic engine of mammalian RNAi. It contains a PIWI domain that is structurally related to RNases H and possibly shares with them a two-metal-ion catalysis mechanism. Here we describe the expression in E. coli of mouse Ago2 and testing of its enzymatic activity in a RISC assay, i.e., for the ability to cleave a target RNA in a single position specified by a complementary small interfering RNA (siRNA). The results show that the enzyme can load the siRNA and cleave the complementary RNA in absence of other cellular factors, as described for human Ago2. It was also found that mutation of Arg669, a residue previously proposed to be involved in substrate and/or B metal ion binding, doesn’t affect the enzymatic activity, suggesting that this residue doesn’t belong to the active site

A new method for the determination of very small Γγ partial widths

We present a new method for the measurement of very small Γγ partial width that is important for the synthesis of elements in astrophysics. The method is based on the simultaneous detection of scattered beam, residual nucleus and decay γ rays. This method is optimized for the use of the CHIMERA detector at LNS. Experimental details are described

Uma Iniciativa Nacional de Melhoria da Qualidade em Cardiologia: O Programa de Boas Práticas em Cardiologia no Brasil

Resumo Fundamento Apesar de progresso significativo na melhoria da qualidade do tratamento de doenças cardiovasculares, lacunas persistem em termos de falha na adesão às recomendações de diretrizes. Objetivo Este estudo avalia os efeitos da implementação de um programa de melhoria da qualidade adaptado do Programa Get with the guidelines® da American Heart Association sobre a adesão às diretrizes para síndrome coronária aguda (SCA), fibrilação atrial (FA) e insuficiência cardíaca (IC). Métodos Avaliamos dados demográficos, medidas de qualidade, e desfechos em curto prazo em pacientes com SCA, FA, e IC incluídos no programa Boas Práticas em Cardiologia (BPC) entre 2016 e 2022. Resultados Este estudo incluiu 12167 pacientes em 19 hospitais no Brasil. A idade média foi 62,5 [53,8-71] anos, 61,1% eram do sexo masculino, 68,7% apresentaram hipertensão, 32% diabetes mellitus, e 24,1% dislipidemia. Os escores médios compostos tiveram desempenho sustentável entre o período inicial e o último trimestre do seguimento: 65,8±36,2% a 73± 31,2% para FA (p=0,024); 81,0± 23,6% a 89,9 ± 19,3% para IC (p<0,001), e de 88,0 ± 19,1 a 91,2 ± 14,9 para SCA (p<0,001). Conclusões O programa BPC é um programa de melhoria de qualidade no Brasil, em que dados em tempo real, obtidos usando métricas de diretrizes de cardiologia, foram implementados, resultando em uma melhora global no manejo da FA, IC e SCA

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study

Background: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. Methods: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. Results: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. Conclusion: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought