Modified radical mastectomy (MRM) may be associated with severe post-operative pain, leading to chronic pain syndrome. We compared the post-operative analgesic profile of two ultrasound-guided nerve ...blocks: Paravertebral block (PVB) and serratus plane block (SPB).
This double-blind, randomised study was conducted on fifty adult females, scheduled for MRM with axillary dissection. After inducing general anaesthesia with intravenous midazolam 1 mg, fentanyl 1.5 mcg/kg, propofol 1-2 mg/kg and vecuronium 0.1 mg/kg, patients were administered either ultrasound-guided thoracic PVB at T4 (
= 25) or SPB at 5
rib (
= 25) with 20 ml of 0.5% bupivacaine, both as a single level injection. Time to first rescue analgesia and morphine consumption in 4, 6, 24, 48 and 72 h by PCA pump, visual analogue scale score and any adverse effects were recorded. Quantitative variables were compared using the unpaired
-test or the Mann-Whitney U test between the two groups. Qualitative variables were compared using the Chi-square test or Fisher's exact test.
The duration of analgesia (mean ± Standard deviation SD) was significantly longer in the PVB group compared to SPB group (346 ± 57 min vs. 245.6 ± 58 min,
< 0.001). The post-operative 24 h morphine consumption (mean ± SD) was significantly higher in the SPB group (9.7 ± 2.1 mg) compared to PVB group (6.5 ± 1.5 mg) (
< 0.001).
Ultrasound-guided SPB is an alternative analgesic technique to thoracic PVB for MRM although PVB provides a longer duration of analgesia.
Microglia are brain myeloid cells that play a critical role in neuroimmunity and the etiology of Alzheimer's disease (AD), yet our understanding of how the genetic regulatory landscape controls ...microglial function and contributes to AD is limited. Here, we performed transcriptome and chromatin accessibility profiling in primary human microglia from 150 donors to identify genetically driven variation and cell-specific enhancer-promoter (E-P) interactions. Integrative fine-mapping analysis identified putative regulatory mechanisms for 21 AD risk loci, of which 18 were refined to a single gene, including 3 new candidate risk genes (KCNN4, FIBP and LRRC25). Transcription factor regulatory networks captured AD risk variation and identified SPI1 as a key putative regulator of microglia expression and AD risk. This comprehensive resource capturing variation in the human microglia regulome provides insights into the etiology of neurodegenerative disease.
Abstract
Identifying functional variants underlying disease risk and adoption of personalized medicine are currently limited by the challenge of interpreting the functional consequences of genetic ...variants. Predicting the functional effects of disease-associated protein-coding variants is increasingly routine. Yet, the vast majority of risk variants are non-coding, and predicting the functional consequence and prioritizing variants for functional validation remains a major challenge. Here, we develop a deep learning model to accurately predict locus-specific signals from four epigenetic assays using only DNA sequence as input. Given the predicted epigenetic signal from DNA sequence for the reference and alternative alleles at a given locus, we generate a score of the predicted epigenetic consequences for 438 million variants observed in previous sequencing projects. These impact scores are assay-specific, are predictive of allele-specific transcription factor binding and are enriched for variants associated with gene expression and disease risk. Nucleotide-level functional consequence scores for non-coding variants can refine the mechanism of known functional variants, identify novel risk variants and prioritize downstream experiments.
Risk variants for schizophrenia affect more than 100 genomic loci, yet cell- and tissue-specific roles underlying disease liability remain poorly characterized. We have generated for two cortical ...areas implicated in psychosis, the dorsolateral prefrontal cortex and anterior cingulate cortex, 157 reference maps from neuronal, neuron-depleted and bulk tissue chromatin for two histone marks associated with active promoters and enhancers, H3-trimethyl-Lys4 (H3K4me3) and H3-acetyl-Lys27 (H3K27ac). Differences between neuronal and neuron-depleted chromatin states were the major axis of variation in histone modification profiles, followed by substantial variability across subjects and cortical areas. Thousands of significant histone quantitative trait loci were identified in neuronal and neuron-depleted samples. Risk variants for schizophrenia, depressive symptoms and neuroticism were significantly over-represented in neuronal H3K4me3 and H3K27ac landscapes. Our Resource, sponsored by PsychENCODE and CommonMind, highlights the critical role of cell-type-specific signatures at regulatory and disease-associated noncoding sequences in the human frontal lobe.
How simple is the underlying control mechanism for the complex locomotion of vertebrates? We explore this question for the swimming behavior of zebrafish larvae. A parameter-independent method, ...similar to that used in studies of worms and flies, is applied to analyze swimming movies of fish. The motion itself yields a natural set of fish "eigenshapes" as coordinates, rather than the experimenter imposing a choice of coordinates. Three eigenshape coordinates are sufficient to construct a quantitative "postural space" that captures >96% of the observed zebrafish locomotion. Viewed in postural space, swim bouts are manifested as trajectories consisting of cycles of shapes repeated in succession. To classify behavioral patterns quantitatively and to understand behavioral variations among an ensemble of fish, we construct a "behavioral space" using multi-dimensional scaling (MDS). This method turns each cycle of a trajectory into a single point in behavioral space, and clusters points based on behavioral similarity. Clustering analysis reveals three known behavioral patterns-scoots, turns, rests-but shows that these do not represent discrete states, but rather extremes of a continuum. The behavioral space not only classifies fish by their behavior but also distinguishes fish by age. With the insight into fish behavior from postural space and behavioral space, we construct a two-channel neural network model for fish locomotion, which produces strikingly similar postural space and behavioral space dynamics compared to real zebrafish.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES/GOALS: Using biomarkers to identify vulnerabilities from cocaine use disorder (CUD) is a focus of recent investigations. Current clinical efforts focus on psychiatric recovery in CUD, ...however other body systems are missed. Applying blood-based transcriptomics to investigate how clinical conditions relate to CUD can alter current treatment approaches. METHODS/STUDY POPULATION: We conducted a comprehensive longitudinal study of 12 individuals (mean 53 yrs.; M/F ratio 9: 3) with CUD abstinent from cocaine. 44 blood samples collected repeatedly every 3 months for 9 months were bulk RNA sequenced. We began with phenotype harmonization grouping individuals with the following metrics; cocaine withdrawal, cue craving, generalized craving, perceived stress, and days of abstinence. We ran differential gene and transcript expression with time across grouping of metrics using the dream software and used the multivariate test to examine their associations. We used the association of gene-transcripts to determine genetic predispositions with clinical traits using the Multi-marker Analysis of GenoMic Annotation assessing their overlap to a reference GWAS database. RESULTS/ANTICIPATED RESULTS: Individuals were grouped in 2 clusters based on scores of cue craving, generalized craving, cocaine withdrawal, and 3 clusters based on days of abstinence from cocaine use. Gene-transcript(s) associationsrevealed genetic predisposition towards certain clinical conditions and substance use traits. Cannabis use disorder showed significant enrichment between the greater vs. lesser abstinent days, and lesser vs. least abstinent days at 9 months. The “drinks per week” trait showed significant gene enrichment between greater vs. lesser abstinent days at 9 months. Coronary artery disease was also enriched with greater vs. least abstinent days at 3 months. Lastly, significant baseline differences in predisposition to small vessel ischemic stroke were seen in responders with high vs low perceived stress. DISCUSSION/SIGNIFICANCE: These results from a robust and feasible pipeline suggest genetic predisposition in CUD for other substances and cardio-neurovascular diseases. This pilot study may lead to larger studies into whole genome-based blood biomarker approaches for monitoring abstinence and other clinical co-morbidities to be addressed in cocaine addiction recovery.
The infants are explicitly vulnerable to develop anaesthesia-related complications, with micropreemies being at the end of the spectrum because of their unique morphological and physiological ...features. Airway changes in pediatric patients are most exaggerated in these tiny infants and their immature lungs provide a little reserve, and therefore, securing airways can be challenging in this population. Moreover, many devices available for managing difficult airways in adults are not available for use in this miniature version. Videolaryngoscopes are a useful addition to anaesthesiologists’ armamentarium but for micropreemies, size of videolaryngoscope can be a limiting factor as no vide- olaryngoscope comes in “00” size. The technique of videolaryngoscope may need to be modified in these patients. Regional anaesthesia can be an invaluable component of their perioperative care to facilitate a smooth recovery. The successful management of these vulnerable neonates requires a multidisciplinary team approach to maintain perioperative homeostasis of their immature organ systems.
Congenital diaphragmatic eventration is uncommon in adults and is caused by paralysis, aplasia or atrophy of the muscular fibers of the diaphragm. It may cause severe dyspnea, orthopnea and hypoxia ...in adult patients. Most symptomatic patients may be managed efficiently without the need for surgical correction, although any event that leads to an increase in intra-abdominal pressure puts them at the risk of spontaneous diaphragmatic rupture. This case report presents the successful anesthetic management of an adult female with congenital diaphragmatic eventration undergoing diagnostic laparoscopy and hysteroscopy using a total intravenous anesthesia technique. Essential steps to prevent any rise in intrathoracic and intra-abdominal pressures along with care to minimize intragastric volume were taken.
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