Deceleration area and fetal acidemia

Aims: To compare the predictive ability for neonatal acidemia of individual components of intrapartum cardiotocography (CTG) described by National Institute of Child Health and Human Development (NICHD) system and deceleration area. Design: Case-control study. Setting: Spanish tertiary obstetrical hospital. Population: CTG patterns of 102 acidemic fetus (umbilical arterial cord gas pH =7.10, base deficit (BD>48) and 102 nonacidemic controls (umbilical arterial cord gas pH>7.10). Methods: Two reviewers blind to clinical and outcome data analyzed the last thirty minutes before delivery of 204 fetal heart rate (FHR) tracings, extracting those features defined by NICHD and certain measures of FHR decelerations, including deceleration area, not considered by this system. Outcome measures: The primary outcome was the predictive ability of NICHD features and non-NICHD deceleration measures for fetal acidemia. The secondary outcome was the impact of deceleration area in the last 30 min of labor on gasometry components (pH, BD and lactate). Results: Minimal variability (area under the curve (AUC) 0.74), total number of late (AUC: 0.75) and prolonged decelerations (0.77) were the three NICHD features with the greatest predictive ability for fetal acidemia in the last thirty minutes of labor. Total deceleration area demonstrated the highest discrimination power (AUC: 0.83) of all the analyzed elements. For each cm2 the area increases in the last 30 min of labor, pH decreases 0.08 units, BD increases 0.272 mEq/L and lactate 0.183 mEq/L. Conclusions: Total deceleration area showed the greatest predictive ability for fetal acidemia and its measure could help to estimate intrapartum fetal acid-base status

Effects of 3% trehalose as an adjuvant treatment after lasik

Purpose: To evaluate the effect of 3% trehalose as an adjuvant in the standard treatment after laser-assisted in situ keratomileusis. Design: Interventional prospective comparative single-blind study. Setting: Department of Ophthalmology, Hospital Quirón Zaragoza, Spain. Methods: A total of 26 eyes (13 patients) were included, of which 12 eyes (group 1) received conventional treatment with lubricant drops of hyaluronic acid (0.15%) and 14 eyes (group 2) received, additionally, an ophthalmic solution of 3% trehalose. Pre- and postoperative quality-of-life tests and vital stains, tear breakup time, and osmolarity measurements were made. Results: We obtained statistically significant differences between the groups in the Symptom Assessment in Dry Eye test in all visits with respect to severity, and in the postoperative day 1 visit with respect to frequency, in all cases favoring the trehalose treatment. The values of osmolarity were not significantly different between groups. However, we did find significant differences in the Oxford scale in day 90 for the trehalose treatment (P<0.001), and in the National Eye Institute scale in day 30 (P=0.02). Conclusion: The results of this exploratory study indicate that the adjuvant treatment with 3% trehalose could be superior with respect to the standard treatment, with improvements in the objective and subjective parameters of tear quality

Flexible Optical-Comb-Based Multi-Wavelength Conversion for Optical Switching and Multicast

Experimental results on multi-wavelength conversion based on optical comb generation for optical switching and multicast applications are presented. All the newly generated channels showed good performance with clear and open eye diagrams.The work of R. Vilar is supported by the Spanish Government through an FPU grant. This work was partially supported by the BONE NoE (FP7-ICT-2007-1-216863) and by the European Project FIVER (FP7-ICT-2009-4-249142).Vilar Mateo, R.; Marques, C.; Nogueira, RI.; Teixeira, A.; Llorente Sáez, R.; Ramos Pascual, F. (2011). Flexible Optical-Comb-Based Multi-Wavelength Conversion for Optical Switching and Multicast. En Proceedings of the 2011 16th European Conference on Networks and Optical Communications (NOC 2011). Institute of Electrical and Electronics Engineers (IEEE). 196-199. http://hdl.handle.net/10251/61358S19619

Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

<p>Abstract</p> <p>Background</p> <p>Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD).</p> <p>Methods</p> <p>Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression.</p> <p>Results</p> <p>There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype.</p> <p>Conclusion</p> <p>This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.</p

Genetic variation in the tau protein phosphatase-2A pathway is not associated with Alzheimer's disease risk

<p>Abstract</p> <p>Background</p> <p>Tau abnormal hyperphosphorylation and the formation of neurofibrillary tangles in AD brain is the result of upregulation of tau kinases and downregulation of tau phosphatases.</p> <p>Methods</p> <p>In a group of 729 Spanish late-onset Alzheimer's disease (AD) patients and 670 healthy controls, we examined variations into a set of candidate genes (PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1 and PIN1) in the tau protein phosphatase-2A (PP2A) pathway, to address hypotheses of genetic variation that might influence AD risk.</p> <p>Results</p> <p>There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by age, gender or APOE ε4 allele.</p> <p>Conclusion</p> <p>Our negative findings in the Spanish population argue against the hypothesis that genetic variation in the tau protein phosphatase-2A (PP2A) pathway is causally related to AD risk</p

Laforin, a Dual Specificity Phosphatase Involved in Lafora Disease, Is Present Mainly as Monomeric Form with Full Phosphatase Activity

Lafora Disease (LD) is a fatal neurodegenerative epileptic disorder that presents as a neurological deterioration with the accumulation of insoluble, intracellular, hyperphosphorylated carbohydrates called Lafora bodies (LBs). LD is caused by mutations in either the gene encoding laforin or malin. Laforin contains a dual specificity phosphatase domain and a carbohydrate-binding module, and is a member of the recently described family of glucan phosphatases. In the current study, we investigated the functional and physiological relevance of laforin dimerization. We purified recombinant human laforin and subjected the monomer and dimer fractions to denaturing gel electrophoresis, mass spectrometry, phosphatase assays, protein-protein interaction assays, and glucan binding assays. Our results demonstrate that laforin prevalently exists as a monomer with a small dimer fraction both in vitro and in vivo. Of mechanistic importance, laforin monomer and dimer possess equal phosphatase activity, and they both associate with malin and bind glucans to a similar extent. However, we found differences between the two states' ability to interact simultaneously with malin and carbohydrates. Furthermore, we tested other members of the glucan phosphatase family. Cumulatively, our data suggest that laforin monomer is the dominant form of the protein and that it contains phosphatase activity

Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level

<p>Abstract</p> <p>Background</p> <p>Malin is an E3-ubiquitin ligase that is mutated in Lafora disease, a fatal form of progressive myoclonus epilepsy. In order to perform its function, malin forms a functional complex with laforin, a glucan phosphatase that facilitates targeting of malin to its corresponding substrates. While laforin phylogeny has been studied, there are no data on the evolutionary lineage of malin.</p> <p>Results</p> <p>After an extensive search for malin orthologs, we found that malin is present in all vertebrate species and a cephalochordate, in contrast with the broader species distribution previously reported for laforin. These data suggest that in addition to forming a functional complex, laforin and perhaps malin may also have independent functions. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32, which belongs to the tripartite-motif containing family of proteins. We present experimental evidence that both malin and TRIM32 share some substrates for ubiquitination, although they produce ubiquitin chains with different topologies. However, TRIM32-specific substrates were not reciprocally ubiquitinated by the laforin-malin complex.</p> <p>Conclusions</p> <p>We found that malin and laforin are not conserved in the same genomes. In addition, we found that malin shares significant identity with the E3-ubiquitin ligase TRIM32. The latter result suggests a common origin for malin and TRIM32 and provides insights into possible functional relationships between both proteins.</p

X chromosome inactivation does not necessarily determine the severity of the phenotype in Rett syndrome patients

Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p&lt;00001), age 70 years or older versus younger than 70 years (230 [165-322], p&lt;00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p&lt;00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research