The doll therapy as a first line treatment for behavioral and psychologic symptoms of dementia in nursing homes residents: a randomized, controlled study.

BACKGROUND: Patients living with dementia are severely affected by the development of behavioral and psychologic symptoms (BPSD) which represent a burden for patients and caregivers. The use of psychotropic drugs in the control of BPSD is widely diffused, however the use of a first line non-pharmacologic approach is highly recommended. Here we evaluate the effect of doll therapy (DT) in the management of BPSD, on the reduction of caregiver burden and delirium incidence in nursing home residents by a randomized controlled trial. METHODS: We enrolled fifty-two nursing homes residents living with dementia and BPSD. Subjects were randomized to DT (26) or standard treatment (ST, 26), we measured BPSD, caregiver burden and delirium with standard clinical scales at baseline, after 45 and 90 days. In order to evaluate the presence of BPSD we used Neuropsychiatric Inventory (NPI) scale and the A.Di.CO scale, the caregiver burden was measured by the Greutzner scale and delirium by the Confusion Assessment Method (CAM) scale. RESULTS: DT was more effective in reducing agitation and aggressiveness as respect to ST. Moreover DT globally reduced the presence of BPSD as dysphoria, wandering and apathy. We observed a significant reduction of the professional caregiver burden and the incidence of delirium was significantly reduced in subjects treated with DT. CONCLUSIONS: We show that DT is more effective that ST in the control of BSPD in patients affected by moderate to severe dementia. Moreover we suggest that DT may effective in reducing the incidence of delirium. TRIAL REGISTRATION: Retrospectively registered in ClinicalTrials.gov the 10th June 2, 2021 trial registration number NCT04920591.

Reminiscence intervention for community-dwelling older adults without dementia: a literature review.

The aim of the present integrative literature review is to summarise empirical evidence supporting the positive health benefits of reminiscence intervention for older adults without dementia who reside in community and long-term care settings. Reminiscence intervention may be used to improve cognitive ability in older adults by prompting them to share life stories and recall past events. Using Garrard's matrix method, 15 studies were identified and included in this review, with a total of 815 participants. The health outcomes of reminiscence intervention for older adults residing in the community and long-term care settings were improvements in depressive symptoms; greater wellbeing, peace and life satisfaction; and improvements in quality of life, social engagement, anxiety and cognitive skills/memory. Non-pharmacological approaches such as reminiscence intervention may contribute to a rich base for reformulating cognitive interpretations, increasing cognitive abilities, and improving social skills among older adults.

Involvement of phosphatidylinositol metabolism in aluminum-induced malate secretion in Arabidopsis.

To identify the upstream signaling of aluminum-induced malate secretion through aluminum-activated malate transporter 1 (AtALMT1), a pharmacological assay using inhibitors of human signal transduction pathways was performed. Early aluminum-induced transcription of AtALMT1 and other aluminum-responsive genes was significantly suppressed by phosphatidylinositol 4-kinase (PI4K) and phospholipase C (PLC) inhibitors, indicating that the PI4K-PLC metabolic pathway activates early aluminum signaling. Inhibitors of phosphatidylinositol 3-kinase (PI3K) and PI4K reduced aluminum-activated malate transport by AtALMT1, suggesting that both the PI3K and PI4K metabolic pathways regulate this process. These results were validated using T-DNA insertion mutants of PI4K and PI3K-RNAi lines. A human protein kinase inhibitor, putatively inhibiting homologous calcineurin B-like protein-interacting protein kinase and/or Ca-dependent protein kinase in Arabidopsis, suppressed late-phase aluminum-induced expression of AtALMT1, which was concomitant with the induction of an AtALMT1 repressor, WRKY46, and suppression of an AtALMT1 activator, Calmodulin-binding transcription activator 2 (CAMTA2). In addition, a human deubiquitinase inhibitor suppressed aluminum-activated malate transport, suggesting that deubiquitinases can regulate this process. We also found a reduction of aluminum-induced citrate secretion in tobacco by applying inhibitors of PI3K and PI4K. Taken together, our results indicated that phosphatidylinositol metabolism regulates organic acid secretion in plants under aluminum stress.

[Benefits and challenges of eHealth in depression]. / Intérêt et enjeux de la "e-santé" dans la dépression.

Depression is a common and debilitating pathology with a significant socioeconomic impact. Early and optimal treatment can help to reduce its progression towards chronicity and long-term cognitive disorders. In the context of falling numbers of medical professionals and the poor provision of validated tools, such as cognitive behavioural therapy, the use of eHealth in depression presents a clear benefit in terms of diagnostic efficacy, patient autonomy, prevention of relapse and health care costs. Innovation must however be associated with ethical deliberation, which respects the patients and their needs.

Mechanistic regulation of FOXO transcription factors in the nucleus.

FOXO proteins represent evolutionarily conserved transcription factors (TFs) that play critical roles in responding to various physiological signals or pathological stimuli, either through transcription-dependent or -independent mechanisms. Dysfunction of these proteins have been implicated in numerous diseases, including cancer. Although the regulation of FOXO TFs shuttling between the cytoplasm and the nucleus has been extensively studied and reviewed, there's still a lack of a comprehensive review focusing on the intricate interactions between FOXO, DNA, and cofactors in the regulation of gene expression. In this review, we aim to summarize recent advances and provide a detailed understanding of the mechanism underlying FOXO proteins binding to target DNA. Additionally, we will discuss the challenges associated with pharmacological approaches in modulating FOXO function, and explore the dynamic association between TF, DNA, and RNA on chromatin. This review will contribute to a better understanding of mechanistic regulations of eukaryotic TFs within the nucleus.

Neuroprotective Approaches for Brain Injury After Cardiac Arrest: Current Trends and Prospective Avenues.

With the implementation of improved bystander cardiopulmonary resuscitation techniques and public-access defibrillation, survival after out-of-hospital cardiac arrest (OHCA) has increased significantly over the years. Nevertheless, OHCA survivors have residual anoxia/reperfusion brain damage and associated neurological impairment resulting in poor quality of life. Extracorporeal membrane oxygenation or targeted temperature management has proven effective in improving post-cardiac arrest (CA) neurological outcomes, yet considering the substantial healthcare costs and resources involved, there is an urgent need for alternative treatment strategies that are crucial to alleviate brain injury and promote recovery of neurological function after CA. In this review, we searched PubMed for the latest preclinical or clinical studies (2016-2023) utilizing gas-mediated, pharmacological, or stem cell-based neuroprotective approaches after CA. Preclinical studies utilizing various gases (nitric oxide, hydrogen, hydrogen sulfide, carbon monoxide, argon, and xenon), pharmacological agents targeting specific CA-related pathophysiology, and stem cells have shown promising results in rodent and porcine models of CA. Although inhaled gases and several pharmacological agents have entered clinical trials, most have failed to demonstrate therapeutic effects in CA patients. To date, stem cell therapies have not been reported in clinical trials for CA. A relatively small number of preclinical stem-cell studies with subtle therapeutic benefits and unelucidated mechanistic explanations warrant the need for further preclinical studies including the improvement of their therapeutic potential. The current state of the field is discussed and the exciting potential of stem-cell therapy to abate neurological dysfunction following CA is highlighted.

Integrating nutrition, physical exercise, psychosocial support and antiemetic drugs into CINV management: The road to success.

Over the years, advancements in antiemetic drugs have improved chemotherapy-induced nausea and vomiting (CINV) control. However, despite the antiemetics therapies, in a relevant number of adult patients (∼30 %), CINV is still persistent, leading to several complications, such as electrolyte imbalances, anorexia, and treatment discontinuation. Supportive care interventions have gained credibility in cancer care, helping to improve patients' psycho-physical condition, quality of life, and managing symptoms, including CINV. Physical exercise and tailored nutritional counseling have demonstrated benefits in reducing the severity of nausea and vomiting. Psychological intervention has been postulated as a key approach in controlling anticipatory nausea/vomiting, as well as acupuncture/acupressure has been shown to decrease nausea and vomiting after chemotherapy treatments. In the current review, we aim to provide a clinical update on current prophylactic and delayed antiemetic guidelines for CINV and an overview of the non-pharmacological interventions tested for alleviating CINV in patients with cancer.

A systematic review and meta-analysis for the efficacy of transcranial direct current stimulation (tDCS) in OCD treatment: A non-pharmacological approach to clinical interventions.

Obsessive-compulsive disorder (OCD) is a prevalent mental condition characterized by recurrent, unwanted thoughts (obsessions) and repetitive behaviors (compulsions), significantly disrupting daily functioning and social interactions. Transcranial direct current stimulation (tDCS) presents a promising non-invasive treatment modality aimed at alleviating symptoms. However, the evidence regarding its effectiveness remains inconclusive. This study seeks to address this gap by conducting a systematic review and meta-analysis of clinical trials, offering improved guidance for clinical intervention. A comprehensive search strategy was implemented across multiple databases, including PubMed, Cochrane CENTRAL, Embase, Scopus, and Web of Science. This search focused strictly on randomized controlled trials (RCTs) involving 147 patients. These trials evaluated the efficacy of tDCS in OCD patients. Subsequent data extraction, risk of bias assessment, and statistical analysis using Review Manager software revealed the potential efficacy of tDCS in reducing OCD symptoms. The meta-analysis not only fails to demonstrate significant superiority of active tDCS over sham tDCS but also suggests that sham tDCS may be more effective than active tDCS in reducing OCD symptoms. This finding diminishes the promise of tDCS as an effective treatment for OCD. Larger trials are warranted to further elucidate these findings.

Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives.

Cardiovascular disease (CVD) is still a leading cause of morbidity and mortality, despite all the progress achieved as regards to both prevention and treatment. Having high levels of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease that operates independently. It can increase the risk of developing cardiovascular disease even when LDL cholesterol (LDL-C) levels are within the recommended range, which is referred to as residual cardiovascular risk. Lp(a) is an LDL-like particle present in human plasma, in which a large plasminogen-like glycoprotein, apolipoprotein(a) [Apo(a)], is covalently bound to Apo B100 via one disulfide bridge. Apo(a) contains one plasminogen-like kringle V structure, a variable number of plasminogen-like kringle IV structures (types 1-10), and one inactive protease region. There is a large inter-individual variation of plasma concentrations of Lp(a), mainly ascribable to genetic variants in the Lp(a) gene: in the general po-pulation, Lp(a) levels can range from <1 mg/dL to >1000 mg/dL. Concentrations also vary between different ethnicities. Lp(a) has been established as one of the risk factors that play an important role in the development of atherosclerotic plaque. Indeed, high concentrations of Lp(a) have been related to a greater risk of ischemic CVD, aortic valve stenosis, and heart failure. The threshold value has been set at 50 mg/dL, but the risk may increase already at levels above 30 mg/dL. Although there is a well-established and strong link between high Lp(a) levels and coronary as well as cerebrovascular disease, the evidence regarding incident peripheral arterial disease and carotid atherosclerosis is not as conclusive. Because lifestyle changes and standard lipid-lowering treatments, such as statins, niacin, and cholesteryl ester transfer protein inhibitors, are not highly effective in reducing Lp(a) levels, there is increased interest in developing new drugs that can address this issue. PCSK9 inhibitors seem to be capable of reducing Lp(a) levels by 25-30%. Mipomersen decreases Lp(a) levels by 25-40%, but its use is burdened with important side effects. At the current time, the most effective and tolerated treatment for patients with a high Lp(a) plasma level is apheresis, while antisense oligonucleotides, small interfering RNAs, and microRNAs, which reduce Lp(a) levels by targeting RNA molecules and regulating gene expression as well as protein production levels, are the most widely explored and promising perspectives. The aim of this review is to provide an update on the current state of the art with regard to Lp(a) pathophysiological mechanisms, focusing on the most effective strategies for lowering Lp(a), including new emerging alternative therapies. The purpose of this manuscript is to improve the management of hyperlipoproteinemia(a) in order to achieve better control of the residual cardiovascular risk, which remains unacceptably high.

Retromer stabilization using a pharmacological chaperone protects in an α-synuclein based mouse model of Parkinson's.

Background: In the present study we assessed the protective effects of a pharmacological approach to stabilize the retromer complex in a PD mouse model. Missense mutations in the VPS35 gene are a rare cause of familial PD. The VPS35 protein is a subunit of the retromer cargo recognition complex and has a variety of functions within neurons, many of which are potentially relevant for the pathophysiology of PD. Prior studies have revealed a role for the retromer complex in controlling accumulation and clearance of α-synuclein aggregates. We previously identified an aminoguanidine hydrazone, 1,3 phenyl bis guanylhydrazone (compound 2a), as a pharmacological stabilizer of the retromer complex that increases retromer subunit protein levels and function. Methods: Here, we validate the efficacy of 2a in protecting against αSynuclein pathology and dopaminergic neuronal degeneration in a PD mouse model generated by unilateral injection of AAV-A53T-αSynuclein in the substantia nigra. Results: Daily intraperitoneal administration of 2a at 10 mg/Kg for 100 days led to robust protection against behavioral deficits, dopaminergic neuronal loss and loss of striatal dopaminergic fibers and striatal monoamines. Treatment with 2a activated αSynuclein degradation pathways in the SN and led to significant reductions in aggregates and pathological αSynuclein. Conclusion: These data suggest retromer stabilization as a promising therapeutic strategy for Parkinson's disease leading to neuroprotection of dopaminergic neurons and rescue in the accumulation of pathological and aggregates αSynuclein. We identified 2a compound as potential clinical drug candidate for future testing in Parkinson's disease patients.

The impact of a preoperative nurse-led orientation program on postoperative delirium after cardiovascular surgery: a retrospective single-center observational study.

BACKGROUND: Postoperative delirium in intensive care is common and associated with mortality, cognitive impairment, prolonged hospital stays and high costs. We evaluate whether a nurse-led orientation program could reduce the incidence of delirium in the intensive care unit after cardiovascular surgery. METHODS: In this retrospective cohort study, we enrolled patients admitted to the intensive care unit for planned cardiovascular surgery between January 2020 and December 2021. A nurse-led orientation program based on a preoperative visit was routinely introduced from January 2021. We assessed the association between these visits and postoperative delirium in the intensive care unit. We also assessed predictors of postoperative delirium with baseline and intraoperative characteristics. RESULTS: Among 253 patients with planned cardiovascular surgery, 128 (50.6%) received preoperative visits. Valve surgery comprised 44.7%, coronary surgery 31.6%, and aortic surgery 20.9%. Cardiopulmonary bypass use and transcatheter surgery were 60.5% and 12.3%, respectively. Incidence of delirium was lower in patients that received preoperative visits, and median hospital stay was shorter than in those without visits (18 patients [14.1%] vs 34 patients [27.2%], P < 0.01; 14 days vs 17 days, P < 0.01). After adjusting predefined confounders, preoperative visits were independently associated with decreased incidence of delirium (adjusted odds ratio [aOR] 0.45; 95% confidence interval [95% CI] 0.22-0.84). Other predictors of delirium were higher European System for Cardiac Operative Risk Evaluation II score and lower minimum intraoperative cerebral oxygen saturation. CONCLUSIONS: A preoperative nurse-led orientation program was associated with reduction of postoperative delirium and could be effective against postoperative delirium after cardiovascular surgery. Trial registration UMIN Clinical Trial Registry no. UMIN000048142. Registered 22, July, 2022, retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054862 .

Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study.

Post-SSRI sexual dysfunction (PSSD) is a set of heterogeneous sexual problems, which may arise during the administration of selective serotonin reuptake inhibitors (SSRIs) and persist after their discontinuation. PSSD is a rare clinical entity, and it is commonly associated with non-sexual concerns, including emotional and cognitive problems and poor quality of life. To date, however, no effective treatment is available. The aim of this study was to retrospectively evaluate the potential efficacy of the different treatments used in clinical practice in improving male PSSD. Of the 30 patients referred to our neurobehavioral outpatient clinic from January 2020 to December 2021, 13 Caucasian male patients (mean age 29.53 ± 4.57 years), previously treated with SSRIs, were included in the study. Patients with major depressive disorder and/or psychotic symptoms were excluded a priori to avoid overlapping symptomatology, and potentially reduce the misdiagnosis rate. To treat PSSD, we decided to use drugs positively affecting the brain dopamine/serotonin ratio, such as bupropion and vortioxetine, as well as other compounds. This latter drug is known not to cause or reverse iatrogenic SD. Most patients, after treatment with vortioxetine and/or nutraceuticals, reported a significant improvement in all International Index of Erectile Function-(IIEF-5) domains (p < 0.05) from baseline (T0) to 12-month follow-up (T1). Moreover, the only patient treated with pelvic muscle vibration reached very positive results. Although our data come from a retrospective open-label study with a small sample size, drugs positively modulating the central nervous system serotonin/dopamine ratio, such as vortioxetine, could be used to potentially improve PSSD. Large-sample prospective cohort studies and randomized clinical trials are needed to investigate the real prevalence of this clinical entity and confirm such a promising approach to a potentially debilitating illness.

Sustainable policy: Don't get infected and don't infect others.

COVID-19 is an environmental policy problem. The goal of this paper is to show sustainable policies against the COVID-19 pandemic. Medical professionals tend to stick only to pharmacological approaches such as vaccination and boosting, but that is not sustainable. The scorecovid and hiscovid tools revealed that the sustainable and the best policy against COVID-19 is based on the mandatory test-and-isolation by law. Because COVID-19 variants have the ability to spike mutations and immune escape, pharmacological approaches such as vaccination alone cannot mitigate or end COVID-19. The scorecovid tool is a Python Package Index (PyPI) application for scoring individual policies against COVID-19. In scorecovid, scoring policies is calculated by dividing the number of deaths due to COVID-19 by the population in millions. The hiscovid tool was developed to identify mistakes by policymakers in order to monitor their policies in time-series scores. The lower the score, the better the policy.

Mitochondrial Cardiomyopathy: Molecular Epidemiology, Diagnosis, Models, and Therapeutic Management.

Mitochondrial cardiomyopathy (MCM) is characterized by abnormal heart-muscle structure and function, caused by mutations in the nuclear genome or mitochondrial DNA. The heterogeneity of gene mutations and various clinical presentations in patients with cardiomyopathy make its diagnosis, molecular mechanism, and therapeutics great challenges. This review describes the molecular epidemiology of MCM and its clinical features, reviews the promising diagnostic tests applied for mitochondrial diseases and cardiomyopathies, and details the animal and cellular models used for modeling cardiomyopathy and to investigate disease pathogenesis in a controlled in vitro environment. It also discusses the emerging therapeutics tested in pre-clinical and clinical studies of cardiac regeneration.

Treatment of Dyslipidaemia in Children.

Childhood dyslipidaemia is one of the main traditional cardiovascular risk factors that initiate and exacerbate the atherosclerotic process. Healthcare providers may play a key role in the management of children with lipid abnormalities; however, they have to properly evaluate the normal lipid values and know the available treatment options in children and adolescents. Current guidelines recommend healthy behaviours as the first-line treatment for childhood dyslipidaemia. The therapeutic lifestyle changes should focus on dietary modifications, daily physical activity, reduction in body weight and tobacco smoking cessation. Parents play a key role in promoting their children's healthy habits. In children with more severe forms of lipid abnormalities and in those who do not benefit from healthy behaviours, pharmacological therapy should be considered. Safe and effective medications are already available for children and adolescents. Statins represent the first-line pharmacological option, while ezetimibe and bile acid sequestrants are usually used as second-line drugs. Despite their limited use in children, other lipid-lowering agents (already approved for adults) are currently available or under study for certain categories of paediatric patients (e.g., familial hypercholesterolemia). Further studies are needed to evaluate the long-term efficacy, safety and tolerability of novel lipid-lowering drugs, especially in children.

CXCR1/2 Inhibitor Ladarixin Ameliorates the Insulin Resistance of 3T3-L1 Adipocytes by Inhibiting Inflammation and Improving Insulin Signaling.

Type 2 diabetes mellitus is a severe public health issue worldwide. It displays a harmful effect on different organs as the eyes, kidneys and neural cells due to insulin resistance and high blood glucose concentrations. To date, the available treatments for this disorder remain limited. Several reports have correlated obesity with type 2 diabetes. Mainly, dysfunctional adipocytes and the regulation of high secretion of inflammatory cytokines are the crucial links between obesity and insulin resistance. Several clinical and epidemiological studies have also correlated the onset of type 2 diabetes with inflammation, which is now indicated as a new target for type 2 diabetes treatment. Thus, it appears essential to discover new drugs able to inhibit the secretion of proinflammatory adipocytokines in type 2 diabetes. Adipocytes produce inflammatory cytokines in response to inflammation or high glucose levels. Once activated by a specific ligand, CXCR1 and CXCR2 mediate some cytokines' effects by activating an intracellular signal cascade once activated by a specific ligand. Therefore, it is conceivable to hypothesize that a specific antagonist of these receptors may ameliorate type 2 diabetes and glucose metabolism. Herein, differentiated 3T3-L1-adipocytes were subjected to high glucose or inflammatory conditions or the combination of both and then treated with ladarixin, a CXCR1/2 inhibitor. The results obtained point towards the positive regulation by ladarixin on insulin sensitivity, glucose transporters GLUT1 and GLUT4, cytokine proteome profile and lipid metabolism, thus suggesting ladarixin as a potentially helpful treatment in type 2 diabetes mellitus and obesity.

Role of the Purinergic P2Y2 Receptor in Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH), group 1 pulmonary hypertension (PH), is a fatal disease that is characterized by vasoconstriction, increased pressure in the pulmonary arteries, and right heart failure. PAH can be described by abnormal vascular remodeling, hyperproliferation in the vasculature, endothelial cell dysfunction, and vascular tone dysregulation. The disease pathomechanisms, however, are as yet not fully understood at the molecular level. Purinergic receptors P2Y within the G-protein-coupled receptor family play a major role in fluid shear stress transduction, proliferation, migration, and vascular tone regulation in systemic circulation, but less is known about their contribution in PAH. Hence, studies that focus on purinergic signaling are of great importance for the identification of new therapeutic targets in PAH. Interestingly, the role of P2Y2 receptors has not yet been sufficiently studied in PAH, whereas the relevance of other P2Ys as drug targets for PAH was shown using specific agonists or antagonists. In this review, we will shed light on P2Y receptors and focus more on the P2Y2 receptor as a potential novel player in PAH and as a new therapeutic target for disease management.

Current State and Promising Opportunities on Pharmaceutical Approaches in the Treatment of Polymicrobial Diseases.

In recent years, the emergence of newly identified acute and chronic infectious disorders caused by diverse combinations of pathogens, termed polymicrobial diseases, has had catastrophic consequences for humans. Antimicrobial agents have been clinically proven to be effective in the pharmacological treatment of polymicrobial diseases. Unfortunately, an increasing trend in the emergence of multi-drug-resistant pathogens and limited options for delivery of antimicrobial drugs might seriously impact humans' efforts to combat polymicrobial diseases in the coming decades. New antimicrobial agents with novel mechanism(s) of action and new pharmaceutical formulations or delivery systems to target infected sites are urgently required. In this review, we discuss the prospective use of novel antimicrobial compounds isolated from natural products to treat polymicrobial infections, mainly via mechanisms related to inhibition of biofilm formation. Drug-delivery systems developed to deliver antimicrobial compounds to both intracellular and extracellular pathogens are discussed. We further discuss the effectiveness of several biofilm-targeted delivery strategies to eliminate polymicrobial biofilms. At the end, we review the applications and promising opportunities for various drug-delivery systems, when compared to conventional antimicrobial therapy, as a pharmacological means to treat polymicrobial diseases.

Adjunctive Approaches to Aphasia Rehabilitation: A Review on Efficacy and Safety.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, unconventional rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the principal approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proven to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review reveals an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Characterizing the Secretion Systems of Magnaporthe oryzae.

Pharmacological approaches have made a tremendous impact on the field of microbial secretion systems. This protocol describes the inhibition of Golgi-dependent secretion in Magnaporthe oryzae though brefeldin A (BFA) treatment. State-of-the-art live-cell imaging allows tracking secreted proteins in their secretion pathways. Here we applied this protocol for defining the secretion systems of two fluorescently labeled effectors, Bas4 (apoplastic) and Pwl2 (cytoplasmic). Secretion of Bas4 is clearly inhibited by brefeldin A (BFA), indicating its Golgi-dependent secretion pathway. By contrast, secretion of Pwl2 is BFA insensitive and follows a nonconventional secretion pathway that is Snare and Exocyst dependent. The protocol is suitable to other plant-microbial systems and in vitro secreted microbial proteins.