Lafora disease offers a unique window into neuronal glycogen metabolism

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase

Quality Improvement in Sweet Red Wines Through an Alternative Grape-Drying System

A sensorial analysis was undertaken and the colour parameters and phenolic profile were measured fortwo types of Andalusian sweet red wines. Two wines types were studied, i.e. commercial and alternativewines elaborated with musts from grapes obtained by traditional sun drying and by chamber dryingunder controlled temperatures respectively. Results show that the alternative wines obtained in this studywere analytically closer to typical red wines in their lower concentration of browning compounds, a highcontribution of red and blue colour, and hence having a more suitable hue than the traditional sweetwines. Furthermore, the alternative wines were the richest in monomeric anthocyanins, flavan-3-ols andflavonols, which give these wines their antioxidant properties. Their sensorial characteristics were acceptedby consumers, which means that the alternative grape-drying system improves the quality of sweet redwines relative to those obtained by the traditional method

Sensory Analysis of Sweet Musts in Pedro Ximenez cv. Grapes Dried using Different Methods

The sensory properties of musts from Pedro Ximenez grapes chamber-dried at 40 or 50°C, with or withouta dipping treatment, are compared to musts from grapes subjected to the traditional sun-drying methodused in the production of sweet wines. The chamber-dried procedure, specifically at 50°C, decreased thedrying time, improved the health status of the grapes relative to the growth of fungi that produce toxins andyielded must with a very similar color to that of sun-dried grapes. Sensory evaluation has shown that mustfrom grapes dried at 50°C, after treatment with an alkaline emulsion of ethyl oleate, is unacceptable dueto the light color. The musts receiving the highest scores for color, aroma and flavor were from untreatedgrapes dried at 50ºC or potassium carbonate-treated grapes dried at the same temperature. However, thetreatment did not significantly accelerate drying

Characterisation of the Colour Fraction of Pedro Ximenez Andalusian Sweet Wines

Changes in colour fraction of commercially bottled Pedro Ximenez sweet wines, unaged and oxidatively agedin American oak casks and mostly produced in the Montilla-Moriles and Jerez-Xérès-Sherry Designations ofOrigin (Spain), have been studied. The total tannin content and the total polyphenol content (A280) increasedwith increased aging time, a trend clearly observed in the Jerez wines. Browning, as measured by the absorbanceat 420 nm, differed markedly between unaged and aged wines. Aged wines showed an increase in browning withtime and an increase in high molecular weight browning compounds, most probably Maillard compounds.Colour measurements based on the CIELab system showed a gradual decrease in hue and lightness with ageing

Eslicarbazepine acetate as monotherapy in clinical practice: Outcomes from Euro-Esli

OBJECTIVES: To assess the effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) monotherapy in clinical practice in Europe. MATERIALS AND METHODS: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit) were assessed after 3, 6 and 12 months of ESL treatment and at last visit. Adverse events (AEs) and AEs leading to ESL discontinuation were assessed throughout follow-up. A subanalysis was conducted to assess outcomes for patients treated initially with ESL monotherapy and for patients treated at the last visit with ESL monotherapy. RESULTS: ESL was used as monotherapy in 88/2045 (4.3%) patients initially and in 229/1340 (17.1%) patients at the last visit. At 12 months, responder and seizure freedom rates were 94.1% and 88.2%, respectively, in patients treated initially with ESL monotherapy, and 93.2% and 77.4%, respectively, in patients treated at the last visit with ESL monotherapy. Corresponding values for patients treated initially with ESL adjunctive therapy were 74.8% and 39.0%, respectively; and for patients treated at the last visit with ESL adjunctive therapy, corresponding values were 70.4% and 25.9%, respectively. Safety and tolerability were generally comparable in patients treated with ESL as monotherapy or adjunctive therapy. The most commonly reported AEs (≥5% of patients in any group) were dizziness, somnolence, instability/ataxia, and fatigue. CONCLUSIONS: These clinical practice data support the use of ESL as monotherapy, as well as adjunctive therapy, for focal-onset seizures, complementing evidence from clinical trials.info:eu-repo/semantics/publishedVersio

Fundamentos científicos de la rehabilitación tras la sustitución intraarticular del ligamento cruzado anterior

Hay pocos aspectos de la rehabilitación en nuestra especialidad que sean tan complejos y controvertidos como la rehabilitación después de la sustitución intraarticular del ligamento cruzado anterior (LCA). La tendencia actual es utilizar protocolos de rehabilitación acelerada y rápido funcionalismo, todo lo cual está en relación directa con el avance en la investigación sobre el comportamiento biológico de los implantes, una mayor sofisticación en la técnica quirúrgica y los adelantos en las técnicas de rehabilitación. El objetivo de este trabajo es analizar no protocolos concretos, sino los problemas que plantea la cirugía del LCA y como minimizarlos en la medida de lo posible, protegiendo al mismo tiempo la plastia.There are few aspects of rehabilitation in our speciality which are so complex and controversial like rehabilitation after intraarticular replacement of the anterior cruciate ligament (ACL). Nowadays there is a trend to use protocols of accelerated rehabilitation and rapid functioning, and all this is related to the advances in research on the biological behavior of the grafts, a major sophistication in surgical technique and advances in rehabilitation techniques. The objective of this paper is not to analyze concrete protocols but rather the problems that state the surgery of the ACL, and how to diminish them to maximum, protecting at the same time the graft

A new clinically applicable immune-metabolic signature (IMMETCOLS) reveals metabolic singularities in consensus molecular subtypes (CMS) in colorectal cancer

Background: In the last years, a great effort has been made to unify different independent colorectal cancer (CRC) molecular classification systems into four consensus molecular subtypes (CMS). The four subtypes are found to be associated with distinct microenvironmental features and clinical outcome, although metabolic singularities are not well established. Metabolic dysregulation has been reported as a hallmark of CMS3, but metabolic heterogeneity among other subtypes has not been investigated. Here, taking into account the increasing evidence on the importance, for determining response to therapies, of the metabolic crosstalk between cancer cells, tumor microenvironment and immune cells, we investigated the metabolic singularities in the four CMS using a genetic immune-metabolic signature (IMMETCOLS). Conclusions: IMMETCOLS signature refines CMS prognosis in CRC patients and potentially allows specific metabolic interventions in CMS subtypes

Generalised median of a set of correspondences based on the hamming distance.

A correspondence is a set of mappings that establishes a relation between the elements of two data structures (i.e. sets of points, strings, trees or graphs). If we consider several correspondences between the same two structures, one option to define a representative of them is through the generalised median correspondence. In general, the computation of the generalised median is an NP-complete task. In this paper, we present two methods to calculate the generalised median correspondence of multiple correspondences. The first one obtains the optimal solution in cubic time, but it is restricted to the Hamming distance. The second one obtains a sub-optimal solution through an iterative approach, but does not have any restrictions with respect to the used distance. We compare both proposals in terms of the distance to the true generalised median and runtime

Optimization of Xanthatin Extraction from Xanthium spinosum L. and its cytotoxic, anti-angiogenesis and antiviral properties

The aqueous extraction of the sesquiterpene lactone xanthatin from Xanthium spinosum L. favours the conversion of xanthinium to xanthatin via the loss of acetic acid. The cytotoxic (Hep-G2 and L1210 human cell lines) and antiviral activities of isolated xanthatin are established. This natural compound shows significant cytotoxicity against the Hep-G2 cell line and our experimental results reveal its strong anti-angiogenesis capacity in vitro. The structure of xanthatin is determined by spectroscopic methods and for the first time confirmed by X-ray diffraction

Lacosamide monotherapy in clinical practice: A retrospective chart review

Objective: To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. Materials and Methods: Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). Results: A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. At OP2, 66.3% of first-line and 63.0% of conversion to monotherapy patients were seizure free. At OP3, 60.2% of first-line and 52.5% of conversion to monotherapy patients were seizure free. In the ≥65 years subgroup, seizure freedom rates at OP2 were 72.0% and 68.0% for first-line and converted to monotherapy, respectively, and at OP3, 68.0% and 56.3%, respectively. Overall, 52 of 439 (11.8%) patients reported ADRs (16.4% in ≥65 years subgroup), most commonly dizziness (5.0%), headache (2.1%) and somnolence (1.6%). Conclusions: Lacosamide was effective and well tolerated as first-line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal seizuresThis study was supported by UCB Pharm