Project description:Symptomatic bradycardia may be iatrogenic or from a conduction system abnormality. Here we show an interesting case of iatrogenic symptomatic bradycardia that may be confused with a conduction system abnormality. (Level of Difficulty: Advanced.).
Project description:Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means of bioinformatics and enzyme engineering opens up an immense variety of selective reactions. Biocatalysis especially provides excellent opportunities for late-stage modification often superior to conventional de novo synthesis. Enzymes have proven to be useful for direct introduction of functional groups into complex scaffolds, as well as for rapid diversification of compound libraries. Particularly important and highly topical are enzyme-catalysed oxyfunctionalisations, halogenations, methylations, reductions, and amide bond formations due to the high prevalence of these motifs in pharmaceuticals. This Review gives an overview of the strengths and limitations of enzymatic late-stage modifications using native and engineered enzymes in synthesis while focusing on important examples in drug development.
Project description:Proteomics, the temporal study of proteins expressed by an organism, is a powerful technique that can reveal how organisms respond to biological perturbations, such as disease and environmental stress. Yet, the use of proteomics for addressing ecological questions has been limited, partly due to inadequate protocols for the sampling and preparation of animal tissues from the field. Although RNAlater is an ideal alternative to freezing for tissue preservation in transcriptomics studies, its suitability for the field could be more broadly examined. Moreover, existing protocols require samples to be preserved immediately to maintain protein integrity, yet the effects of delays in preservation on proteomic analyses have not been thoroughly tested. Hence, we optimised a proteomic workflow for wild-caught samples. First, we conducted a preliminary in-lab test using SDS-PAGE analysis on aquaria-reared Octopus berrima confirming that RNAlater can effectively preserve proteins up to 6 h after incubation, supporting its use in the field. Subsequently, we collected arm tips from wild-caught Octopus berrima and preserved them in homemade RNAlater immediately, 3 h, and 6 h after euthanasia. Processed tissue samples were analysed by liquid chromatography tandem mass spectrometry to ascertain protein differences between time delay in tissue preservation, as well as the influence of sex, tissue type, and tissue homogenisation methods. Over 3500 proteins were identified from all tissues, with bioinformatic analysis revealing protein abundances were largely consistent regardless of sample treatment. However, nearly 10 % additional proteins were detected from tissues homogenised with metal beads compared to liquid nitrogen methods, indicating the beads were more efficient at extracting proteins. Our optimised workflow demonstrates that sampling non-model organisms from remote field sites is achievable and can facilitate extensive proteomic coverage without compromising protein integrity.
Project description:Proteomics, the temporal study of proteins expressed by an organism, is a powerful technique that can reveal how organisms respond to biological perturbations, such as disease and environmental stress. Yet, the use of proteomics for addressing ecological questions has been limited, partly due to inadequate protocols for the sampling and preparation of animal tissues from the field. Although RNAlater is an ideal alternative to freezing for tissue preservation in transcriptomics studies, its suitability for the field could be more broadly examined. Moreover, existing protocols require samples to be preserved immediately to maintain protein integrity, yet the effects of delays in preservation on proteomic analyses have not been thoroughly tested. Hence, we optimised a proteomic workflow for wild-caught samples. First, we conducted a preliminary in-lab test using SDS-PAGE analysis on aquaria-reared Octopus berrima confirming that RNAlater can effectively preserve proteins up to 6 h after incubation, supporting its use in the field. Subsequently, we collected arm tips from wild-caught Octopus berrima and preserved them in homemade RNAlater immediately, 3 h, and 6 h after euthanasia. Processed tissue samples were analysed by liquid chromatography tandem mass spectrometry to ascertain protein differences between time delay in tissue preservation, as well as the influence of sex, tissue type, and tissue homogenisation methods. Over 3500 proteins were identified from all tissues, with bioinformatic analysis revealing protein abundances were largely consistent regardless of sample treatment. However, nearly 10% additional proteins were detected from tissues homogenised with metal beads compared to liquid nitrogen methods, indicating the beads were more efficient at extracting proteins. Our optimised workflow demonstrates that sampling non-model organisms from remote field sites is achievable and can facilitate extensive proteomic coverage without compromising protein integrity.
Project description:Decision-making is critical to everyday life. Here we ask: to what extent does music training benefit decision-making? Supported by strong associations between music training and enhanced cross-domain skills, we hypothesize that musicians may show decision-making advantages relative to non-musicians. Prior work has also argued for a "critical period" for cross-domain plasticity such that beginning music training early enhances sensorimotor brain regions that mature early in life. Given that brain regions supporting decision-making begin maturing late in childhood, we hypothesized that an advantage in decision-making may only be present in musicians who began music training later in childhood. To test this hypothesis, young adults who began music training before and after 8 years of age (early-trained musicians, ET; late-trained musicians, LT, respectively) and non-musicians (NM) performed a decision-making task. We found a decision-making advantage in LT relative to ET and NM. To better understand the mechanism of the LT advantage, we conducted computational modeling on participant responses and found that LT were less biased by recent outcomes and incorporated longer strings of outcomes when deciding among the choice options. These results tentatively suggest that music training may confer decision-making enhancements, and carry strong implications for the utility of music training in childhood.
Project description:While the benefits of sleep for associative memory are well established, it is unclear whether single-item memories profit from overnight consolidation to the same extent. We addressed this question in a preregistered, online study and also investigated how the temporal proximity between learning and sleep influences overnight retention. Sleep relative to wakefulness improved retention of item and associative memories to similar extents irrespective of whether sleep occurred soon after learning or following a prolonged waking interval. Our findings highlight the far-reaching influences of sleep on memory that can arise even after substantial periods of wakefulness.
Project description:The objective of this analysis was to explore temporal and spatial variation in teen birth rates TBRs across counties in the USA, from 2003 to 2012, by using hierarchical Bayesian models. Prior examination of spatiotemporal variation in TBRs has been limited by the reliance on large-scale geographies such as states, because of the potential instability in TBRs at smaller geographical scales such as counties. We implemented hierarchical Bayesian models with space-time interaction terms and spatially structured and unstructured random effects to produce smoothed county level TBR estimates, allowing for examination of spatiotemporal patterns and trends in TBRs at a smaller geographic scale across the USA. The results may help to highlight US counties where TBRs are higher or lower and to inform efforts to reduce birth rates to adolescents in the USA further.
Project description:Recent research suggests that search volumes of the most popular search engine worldwide, Google, provided via Google Trends, could be associated with national suicide rates in the USA, UK, and some Asian countries. However, search volumes have mostly been studied in an ad hoc fashion, without controls for spurious associations. This study evaluated the validity and utility of Google Trends search volumes for behavioral forecasting of suicide rates in the USA, Germany, Austria, and Switzerland. Suicide-related search terms were systematically collected and respective Google Trends search volumes evaluated for availability. Time spans covered 2004 to 2010 (USA, Switzerland) and 2004 to 2012 (Germany, Austria). Temporal associations of search volumes and suicide rates were investigated with time-series analyses that rigorously controlled for spurious associations. The number and reliability of analyzable search volume data increased with country size. Search volumes showed various temporal associations with suicide rates. However, associations differed both across and within countries and mostly followed no discernable patterns. The total number of significant associations roughly matched the number of expected Type I errors. These results suggest that the validity of Google Trends search volumes for behavioral forecasting of national suicide rates is low. The utility and validity of search volumes for the forecasting of suicide rates depend on two key assumptions ("the population that conducts searches consists mostly of individuals with suicidal ideation", "suicide-related search behavior is strongly linked with suicidal behavior"). We discuss strands of evidence that these two assumptions are likely not met. Implications for future research with Google Trends in the context of suicide research are also discussed.
Project description:The Authors of this letter look at consumption of opioids and a2- ligands, also known as "gabapentinoids", in Italy, and specifically in the Provincial Health District of Cosenza, as compared with USA trends of recent decades. Access to analgesic drugs since the introduction of Italian law 38/2010 is also evaluated and possible future measures for better management of chronic pain are proposed.
Project description:BackgroundPatients with congenitally corrected transposition of great arteries (ccTGA) not infrequently seek medical attention for the first time late in life. Optimal management of natural history ccTGA is debated and must be tailored.Case summaryA 38-year-old male patient was referred to our centre because of severe cyanosis and worsening dyspnoea. Investigations disclosed situs solitus, mesocardia, double discordance, large ventricular septal defect (VSD), severe pulmonary stenosis, and no significant atrio-ventricular valves regurgitation. The patient underwent physiologic repair: VSD closure, placement of a left ventricle to pulmonary artery conduit, and epicardial atrio-biventricular pacemaker implantation. The conduit was intentionally undersized to promote tricuspid valve continence. Post-operative course was uneventful, transthoracic echocardiography showed good biventricular function without significant tricuspid regurgitation. At 1 month after discharge, the patient is in New York Heart Association Class II.DiscussionManagement of late presenter patients with ccTGA depends on the associated lesion and estimation of surgical risk. In selected patients markedly symptomatic physiologic repair is a rationale option, providing a normal saturation and biventricular circulation with a significantly lower surgical risk as compared with an anatomic repair.