Host Amplification in a Dithioacetal-Based Dynamic Covalent Library.

Molecular amplification in a dithioacetal-based dynamic library is described for the first time. The homatropine induced selection, amplification, and isolation of one cyclophane host demonstrates the utility of dithioacetal exchange for preparing responsive dynamic libraries. Nuclear magnetic resonance and isothermal titration calorimetry analysis suggest that the amplified macrocycle forms a 1:1 complex with the template.

Free Light Chains and Intrathecal B Cells Activity in Multiple Sclerosis: A Prospective Study and Meta-Analysis.

. The presence of CSF oligoclonal bands (OBs) is an independent prognostic factor for multiple sclerosis (MS), but the difficulties in the standardization of the test and the interlaboratory variation in reporting have contributed to its limited use in the diagnosis of the disease. Standard nephelometric assays to measure free light chains (FLC) levels have been recently developed and the test may improve the detection of intrathecal B cells activity.

The diagnostic yield of implantable loop recorders in unexplained syncope: A systematic review and meta-analysis.

Background: Guidelines recommend that implantable loop recorders (ILRs) are used in the evaluation of people with recurrent unexplained syncope in the absence of high-risk criteria, and in high-risk patients after a negative evaluation. The aim of this systematic review was to analyze the diagnostic yield of ILRs in these patients.

Methods: We performed a systematic search in order to retrieve studies enrolling adults undergoing ILR implantation for undetermined syncope.

Neural networks as a tool to predict syncope risk in the Emergency Department.

Aims: There is no universally accepted tool for the risk stratification of syncope patients in the Emergency Department. The aim of this study was to investigate the short-term predictive accuracy of an artificial neural network (ANN) in stratifying the risk in this patient group.

Methods And Results: We analysed individual level data from three prospective studies, with a cumulative sample size of 1844 subjects.

Reverse Phase Compatible TLC-Bioautography for Detection of Tyrosinase Inhibitors.

Introduction: Reverse phase chromatography and bioautographic assays are key tools for natural product bioguided isolation; however, their direct coupling has not been fully achieved.

Objectives: To develop a bioautographic assay to detect tyrosinase inhibitors present in complex matrices sorbed on reverse phase (RP) TLC-plates that can be used for bioguided isolation of bioactive compounds.

Methods: Enzyme gel entrapment with an amphiphilic copolymer was used for assay development.

MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis.

In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS).

Relationship between perception of tongue position and measures of tongue force on the teeth.

Purpose: To verify whether there are differences of tongue force on the teeth at rest and during swallowing between individuals who report appropriate tongue position and those who report tongue thrust.

Methods: Tongue forces on the teeth were evaluated in 28 participants aged 19 to 31 years. To this end, a Flexiforce® resistive sensor was fixed to the palatal surface of the maxillary right central incisor (tooth 8) and was connected to an amplifier circuit, a data acquisition board, and a computer.

IL4 induces IL6-producing M2 macrophages associated to inhibition of neuroinflammation in vitro and in vivo.

Background: Myeloid cells, such as macrophages and microglia, play a crucial role in neuroinflammation and have been recently identified as a novel therapeutic target, especially for chronic forms. The general aim would be to change the phenotype of myeloid cells from pro- to anti-inflammatory, favoring their tissue-trophic and regenerative functions. Myeloid cells, however, display a number of functional phenotypes, not immediately identifiable as pro- or anti-inflammatory, and associated to ambiguous markers.

A New Fluorinated Tyrosinase Inhibitor from a Chemically Engineered Essential Oil.

The generation of fluorinated essential oils as a source of bioactive compounds is described. Most of the components of the natural mixtures were altered, leading to the discovery of a new fluorinated tyrosinase inhibitor.

KIR2DL2 inhibitory pathway enhances Th17 cytokine secretion by NK cells in response to herpesvirus infection in multiple sclerosis patients.

We have previously demonstrated that multiple sclerosis (MS) patients with KIR2DL2 expression on Natural killer (NK) cells are more susceptible to herpes simplex virus 1 (HSV-1) infection. We explored cytokine expression by NK cells during HSV-1 infection in association with KIR2DL2 expression. MS KIR2DL2(+) NK cells failed to control HSV-1 infection and secreted high levels of Th17 cytokines, while MS KIR2DL2(-) NK cells released Th1 cytokines, mainly IFN-gamma.

Implantable loop recorder versus conventional diagnostic workup for unexplained recurrent syncope.

Background: The most recent syncope guideline recommends that implantable loop recorders (ILRs) are implanted in the early phase of evaluation of people with recurrent syncope of uncertain origin in the absence of high-risk criteria, and in high-risk patients after a negative evaluation. Observational and case-control studies have shown that loop recorders lead to earlier diagnosis and reduce the rate of unexplained syncopes, justifying their use in clinical practice. However, only randomised clinical trials with an emphasis on a primary outcome of specific ILR-guided diagnosis and therapy, rather than simply electrocardiogram (ECG) diagnosis, might change clinical practice.

NG2, a common denominator for neuroinflammation, blood-brain barrier alteration, and oligodendrocyte precursor response in EAE, plays a role in dendritic cell activation.

In adult CNS, nerve/glial-antigen 2 (NG2) is expressed by oligodendrocyte progenitor cells (OPCs) and is an early marker of pericyte activation in pathological conditions. NG2 could, therefore, play a role in experimental autoimmune encephalomyelitis (EAE), a disease associated with increased blood-brain barrier (BBB) permeability, inflammatory infiltrates, and CNS damage. We induced EAE in NG2 knock-out (NG2KO) mice and used laser confocal microscopy immunofluorescence and morphometry to dissect the effect of NG2 KO on CNS pathology.

Dithioacetal Exchange: A New Reversible Reaction for Dynamic Combinatorial Chemistry.

Reversibility of dithioacetal bond formation is reported under acidic mild conditions. Its utility for dynamic combinatorial chemistry was explored by combining it with orthogonal disulfide exchange. In such a setup, thiols are positioned at the intersection of both chemistries, constituting a connecting node between temporally separated networks.

Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine.

Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions.

Myeloid Extracellular Vesicles: Messengers from the Demented Brain.

Blood-borne monocyte derived cells play a pivotal, initially unrecognized, role in most central nervous system disorders, including diseases initially classified as purely neurodegenerative (i.e., Alzheimer's disease, Parkinson's disease, and ALS).

A new approach to follow a single extracellular vesicle-cell interaction using optical tweezers.

Extracellular vesicles (EVs) are spherical membrane structures released by most cells. These highly conserved mediators of intercellular communication carry proteins, lipids, and nucleic acids, and transfer these cellular components between cells by different mechanisms, such as endocytosis, macropinocytosis, or fusion. However, the temporal and spatial dynamics of vesicle-cell interactions still remain largely unexplored.

Artificial Neural Networks and risk stratification models in Emergency Departments: The policy maker's perspective.

The primary goal of Emergency Department (ED) physicians is to discriminate between individuals at low risk, who can be safely discharged, and patients at high risk, who require prompt hospitalization. The problem of correctly classifying patients is an issue involving not only clinical but also managerial aspects, since reducing the rate of admission of patients to EDs could dramatically cut costs. Nevertheless, a trade-off might arise due to the need to find a balance between economic interests and the health conditions of patients.

Evaluation of the correlation between cardiac and sympathetic baroreflex sensitivity before orthostatic syncope.

The study investigates the two different aspects of the baroreflex control resulting in two baroreflex sensitivity (BRS) indexes: i) sympathetic BRS (sBRS); ii) cardiac BRS (cBRS). sBRS was assessed as the slope of the regression line of the conditional probability of detecting a burst on the integrated muscle nerve sympathetic activity (MSNA) given an assigned diastolic arterial pressure (DAP) on DAP. cBRS was estimated from spontaneous heart period (HP) and systolic arterial pressure (SAP) via a spectral approach in the low (0.

Cardiovascular control indexes in amyotrophic lateral sclerosis patients and their relation with clinical markers.

We studied the autonomic response to an orthostatic challenge (i.e. head-up tilt) in 52 amyotrophic lateral sclerosis (ALS) patients and 16 healthy subjects by means of power spectral analysis of heart period (HP) and systolic arterial pressure (SAP) variability.

RANTES correlates with inflammatory activity and synaptic excitability in multiple sclerosis.

Background: Alterations of synaptic transmission induced by inflammatory activity have been linked to the pathogenic mechanisms of multiple sclerosis (MS). Regulated upon activation, normal T-cell expressed, and secreted (RANTES) is a pro-inflammatory chemokine involved in MS pathophysiology, potentially able to regulate glutamate release and plasticity in MS brains, with relevant consequences on the clinical manifestations of the disease.

Objective: To assess the role of RANTES in the regulation of cortical excitability.

Speech-Language and Nutritional Sciences in hospital environment: analysis of terminology of food consistencies classification.

Purpose: To verify if there is an agreement between speech-language pathologists and nutritionists about the classification of food textures used in hospitals and their opinions about the possible consequences of differences in this classification.

Methods: This is a descriptive, cross-sectional study with 30 speech-language pathologists and 30 nutritionists who worked in 14 hospitals of public and/or private network in Belo Horizonte, Brazil. The professionals answered a questionnaire, prepared by the researchers, and classified five different foods, with and without theoretical direction.

Patient and parent preferences for characteristics of prophylactic treatment in hemophilia.

Introduction: New longer-acting factor products will potentially allow for less frequent infusion in prophylactic treatment of hemophilia. However, the role of administration frequency relative to other treatment attributes in determining preferences for prophylactic hemophilia treatment regimens is not well understood.

Aim: To identify the relative importance of frequency of administration, efficacy, and other treatment characteristics among candidates for prophylactic treatment for hemophilia A and B.

Clinical significance of the number of oligoclonal bands in patients with clinically isolated syndromes.

CSF oligoclonal bands (OCBs) in patients with clinically isolated syndromes (CIS) are a risk factor for clinically definite multiple sclerosis (CDMS). We aimed to address the relevance of the number of OCBs in the prognosis of CIS patients. 219 CIS patients were included in the study, and 42% of them developed the disease during follow-up (median: 5.

Pentraxin-3 is upregulated in the central nervous system during MS and EAE, but does not modulate experimental neurological disease.

Pentraxin-3 (PTX3), an acute-phase protein released during inflammation, aids phagocytic clearance of pathogens and apoptotic cells, and plays diverse immunoregulatory roles in tissue injury. In neuroinflammatory diseases, like MS, resident microglia could become activated by endogenous agonists for Toll like receptors (TLRs). Previously we showed a strong TLR2-mediated induction of PTX3 in cultured human microglia and macrophages by HspB5, which accumulates in glia during MS.

Comparative Neuroregenerative Effects of C-Phycocyanin and IFN-Beta in a Model of Multiple Sclerosis in Mice.

Multiple Sclerosis (MS) therapies approved so far are unable to effectively reverse the chronic phase of the disease or improve the remyelination process. Here our aim is to evaluate the effects of C-Phycocyanin (C-Pc), a biliprotein from Spirulina platensis with anti-oxidant, anti-inflammatory and cytoprotective properties, in a chronic model of experimental autoimmune encephalomyelitis (EAE) in mice. C-Pc (2, 4 or 8 mg/kg i.