Customized Application of tDCS for Clinical Rehabilitation in Alzheimer's Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive-behavior deficits, which strongly impact daily-life activities (Weintraub et al., 2012). Currently, the limited efficacy of pharmacological treatments has encouraged researchers to develop nonpharmacological interventions, such as cognitive training and non-invasive brain stimulation (NIBS) treatments, designed to prevent or delay cognitive impairment (Cass, 2017; Cespón et al., 2018)

Behavioural and electrophysiological modulations induced by transcranial direct current stimulation in healthy elderly and Alzheimer's disease patients: A pilot study

Objective: To investigate whether anodal and cathodal transcranial direct current stimulation (tDCS) can modify cognitive performance and neural activity in healthy elderly and Alzheimer's disease (AD) patients. Methods: Fourteen healthy elderly and twelve AD patients performed a working memory task during an electroencephalogram recording before and after receiving anodal, cathodal, and sham tDCS over the left dorsolateral prefrontal cortex. Behavioural performance, event-related potentials (P200, P300) and evoked cortical oscillations were studied as correlates of working memory. Results: Anodal tDCS increased P200 and P300 amplitudes in healthy elderly. Cathodal tDCS increased P200 amplitude and frontal theta activity between 150 and 300 ms in AD patients. Improved working memory after anodal tDCS correlated with increased P300 in healthy elderly. In AD patients, slight tendencies between enhanced working memory and increased P200 after cathodal tDCS were observed. Conclusions: Functional neural modulations were promoted by anodal tDCS in healthy elderly and by cathodal tDCS in AD patients. Significance: Interaction between tDCS polarity and the neural state (e.g., hyper-excitability exhibited by AD patients) suggests that appropriate tDCS parameters (in terms of tDCS polarity) to induce behavioural improvements should be chosen based on the participant's characteristics. Future studies using higher sample sizes should confirm and extend the present findings

Brain Networks Modulation in Young and Old Subjects during Transcranial Direct Current Stimulation Applied on Prefrontal and Parietal Cortex

Evidence indicates that the transcranial direct current stimulation (tDCS) has the potential to transiently modulate cognitive function, including age-related changes in brain performance. Only a small number of studies have explored the interaction between the stimulation sites on the scalp, task performance, and brain network connectivity within the frame of physiological aging. We aimed to evaluate the spread of brain activation in both young and older adults in response to anodal tDCS applied to two different scalp stimulation sites: Prefrontal cortex (PFC) and posterior parietal cortex (PPC). EEG data were recorded during tDCS stimulation and evaluated using the Small World (SW) index as a graph theory metric. Before and after tDCS, participants performed a behavioral task; a performance accuracy index was computed and correlated with the SW index. Results showed that the SW index increased during tDCS of the PPC compared to the PFC at higher EEG frequencies only in young participants. tDCS at the PPC site did not exert significant effects on the performance, while tDCS at the PFC site appeared to influence task reaction times in the same direction in both young and older participants. In conclusion, studies using tDCS to modulate functional connectivity and influence behavior can help identify suitable protocols for the aging brain

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis

The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript

Biomarkers of Inflammation in Obesity-Psoriatic Patients

Psoriasis is a common chronic inflammatory multisystemic disease with a complex pathogenesis consisting of genetic, immunological, and environmental components. It is associated with a number of comorbidities, including diabetes, metabolic syndrome, obesity, and myocardial infarction. In addition, the severity of psoriasis seems to be related to the severity of obesity. Patients with higher levels of obesity show poorer response to systemic treatments of psoriasis. Several studies have demonstrated that white adipose tissue is a crucial site of the formation of proinflammatory adipokines such as leptin, adiponectin, and resistin and classical cytokines such as interleukin-(IL-) 6 and tumour necrosis factor-In psoriasis, due to the proliferation of Th1, Th17, and Th22 cells, IL-22, among others, is produced in addition to the abovementioned cytokines. With respect to leptin and resistin, both of these adipokines are present in high levels in obese persons with psoriasis. Further, the plasma levels of leptin and resistin are related to the severity of psoriasis. These results strongly suggest that obesity, through proinflammatory pathways, is a predisposing factor to the development of psoriasis and that obesity aggravates existing psoriasis. Different inflammatory biomarkers link psoriasis and obesity. In this paper, the most important ones are described

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB