The relevance of cognitive,clinical and premorbid variables in predicting functional outcome for individuals with first-episode psychosis: A 3 year longitudinal study

Real-world functional deficits are common and persistent in individuals with psychosis. Cognitive deficits have been shown to compromise functioning. We aimed to study the predictive values of premorbid, sociodemographic, and baseline clinical and neurocognitive factors on long-term functional outcome for individuals with first episode non-affective psychosis. We failed to demonstrate a significant relationship between cognitive deficits at baseline and functional disability at 3 year follow-up. Diagnosis of schizophrenia (OR=2.457, p=0.011), shorter education (OR=1.177, p=0.005) and poor premorbid social adjustment (OR=1.628, p=0.013) emerged as the strongest predictors for the 114 subjects (56%) that exhibited functional disability at 3-year follow-up. A considerable proportion of the variance in functioning (74% at 1 year and 77% at 3 year) remained unexplained by baseline variables. The set of variables that predicted functional outcome at medium- (1 year) and long-term (3 years) differed. In conclusion, the length of follow-up influenced the relationship between baseline variables and functional outcome. A substantial proportion of the variance in function was not explained by these variables and therefore the influence of other factors warrants further investigation. The data support the notion that premorbid social adjustment is an important aspect in functional outcome over the course of the illness.     

Estudio de factores predictivos para complicaciones tras nefrolitotomía percutánea ajustado a la clasificación de Clavien

ObjectiveSet predictors of complications in percutaneous nephrolithotomy (PCNL) using the modified Clavien system.Material and methodsRetrospective study included 172 PCNL in Galdakao position made in the La Ribera Hospital between January 2005 and December 2011. They classified the complications of these procedures using the modified Clavien system. We performed a univariate analysis (Chi² Test and Cramer's V) and multivariate (logistic regression) of predictors of these complications (P < .05).ResultsIn 49 of the 172 procedures complications were detected (28.5%).The most frequent complications were grade 1 (9.9%), 12 complications (6.9%) were classified as grade 2 by requiring additional medical treatment, 6 as grade 3A (3.5%), 7 as grade 3B (4.1%), 2 and 4A (1.1%), 4 and 4B (2.3%) and one and 5 (0.6%). In the univariate analysis, positive urine culture before surgery, the stones complex and larger than 40 mm of the same, showed a statistically significant association with the occurrence of complications (P < .05). The positive culture (OR: 2.96) and complex stones (OR: 3.03) proved to be independent variables predicting complications in multivariate analysis.ConclusionsClavien system allows a common language for classifying complications, expressing the degree of the same as the complexity of treatment required for resolution. The preoperative urine culture positivity and complex stone proved predictors of these complications in our serie.     

DNA methylation clocks for dogs and humans

DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging, but their underlying principles appear to be evolutionarily conserved, as they have now been successfully developed for many mammalian species. Here, we describe reliable and highly accurate epigenetic clocks shown to apply to 93 domestic dog breeds. The methylation profiles were generated using the mammalian methylation array, which utilizes DNA sequences that are conserved across all mammalian species. Canine epigenetic clocks were constructed to estimate age and also average time to death. We also present two highly accurate human–dog dual species epigenetic clocks (R = 0.97), which may facilitate the ready translation from canine to human use (or vice versa) of antiaging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies here reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan. Overall, we describe robust biomarkers to measure aging and, potentially, health status in canines.

Ideally, model species for antiaging research should be representative of human characteristics such as size and genetic diversity, as well as shared environment. Domestic dogs (Canis lupus familiaris) fulfill most of these criteria, offering a unique opportunity to evaluate the effectiveness of emerging antiaging interventions (1–5). There is also a significant need to develop health-monitoring tools for dogs, as there are more than 76 million companion dogs in the United States alone (6).Over 340 dog breeds are recognized worldwide, which are each a closed breeding population under strong selection for morphologic and behavioral traits. As a result, dogs share extensive phenotypic and genetic homogeneity within breeds and increased heterogeneity between breeds (7). Small breeds live considerably longer than large breeds (8), offering the rare chance to understand the relationship between size and lifespan within a single mammalian species. Dogs also share a similar yet accelerated trajectory of development as humans including infancy, puberty, adulthood, and senescence in about 20% of the human lifespan (5, 9). As a result, dogs represent an ideal system for studies of comparative aging, where intrabreed studies can be conducted on a background of limited diversity.Our previous work on DNA-methylation-based age estimators (i.e., epigenetic clocks) for dogs and wolves (10) described one of the first nonhuman epigenetic clocks. We determined that the age dependence of DNA methylation (DNAm) is conserved at syntenic sites in the genomes of multiple mammalian species including humans. However, a small sample size (n < 150) and technical limitations associated with the measurement platform (reduced representation bisulfite sequencing) limited the generalizability of the results. Furthermore, our initial study utilized only a few canine breeds, which prevented testing the relationship between epigenetic aging and breed lifespan. Here, we report the development of a canine epigenetic clock based on 93 recognized dog breeds (11) using a mammalian array (HorvathMammalMethylChip40) that profiles highly conserved cytosines across mammalian species (12).In this study, we present dual-species epigenetic clocks that apply to both humans and dogs. We test whether short-lived breeds exhibit faster epigenetic aging than long-lived breeds and develop epigenetic predictors of the average time to death. Finally, we investigate the relationship between breed size and lifespan and characterize 5''-C-phosphate-G-3'' regions (CpGs) that are correlated with age or breed characteristics such as median lifespan or average adult weight.     

Electrocardiographic Characteristics and Associated Outcomes in Patients with Takotsubo Syndrome. Insights from the RETAKO Registry

Electrocardiographic disturbances in Takotsubo syndrome have been previously partially described but their consequences remain mostly unknown. Our aim was to describe the prevalence and prognostic significance of different electrocardiographic features in patients with Takotsubo syndrome. Our data come from the Spanish multicenter REgistry of TAKOtsubo syndrome (RETAKO). All patients with an available 12-lead surface electrocardiogram at admission and 48 hours post-admission were included. A total of 246 patients were studied, mean age was 71.3 ± 11.5 and 215 (87.4%) were women. ST-segment elevation was seen in 143 patients (59.1%) and was present in ≥2 wall leads in 97 (39.8%). Exclusive elevation in inferior leads was infrequent (5% - 2.0%). After 48 hours, 198 patients (88.0%) developed negative T waves in a median of 8 leads with a mean amplitude of 0.7 ± 0.5 mV and 137 (60.9%) had pathological Q waves. The mean corrected QT interval was 520 ± 72 ms. Corrected QT interval was independently associated with the primary endpoint of all-cause death and nonfatal cardiovascular events (P = 0.002) and all-cause death (P = 0.008). A higher heart rate at admission was an independent predictor of the primary endpoint (P = 0.001) and of acute pulmonary edema (P = 0.04). ST-segment elevation with reciprocal depression was an independent predictor of all-cause death (P = 0.04). Absence of ST-segment deviation was a protective factor (P = 0.005) for the primary endpoint. Tachyarrhythmias were independently associated with cardiogenic shock (P< 0.001). Takotsubo syndrome patients present with distinct electrocardiographic features. Prolonged corrected QT interval, tachyarrhythmias, heart rate at admission, and more extensive repolarization alterations are associated with poor outcomes.     

ICAM-1 (Lys469Glu) and PECAM-1 (Leu125Val) polymorphisms in diffuse astrocytomas

Cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) play an important role in glioma invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and PECAM-1 could be associated with glioma development and progression. Single-nucleotide polymorphism in codon 469 of ICAM-1 and codon 125 of PECAM-1 were examined in 158 patients with astrocytomas and 162 controls using polymerase chain reaction and restriction enzyme analysis. The distribution of PECAM-1 polymorphic genotypes in astrocytomas did not show any significant difference. However, a specific ICAM-1 genotype (G/G, corresponding to Lys469Glu) exhibited higher frequency in grade II astrocytomas compared to controls, grade III, and grade IV astrocytomas; suggesting that this polymorphism could be involved in the development of grade II astrocytomas.