Expedited Recovery Pain Management Pathway for Minimally Invasive Repair of Pectus Excavatum (MIRPE)

Introduction: Pectus Excavatum (PEX) is the most common anterior chest wall deformity. While minimally invasive repair of pectus excavatum (MIRPE) has improved perioperative outcomes, there continue to be opportunities to optimize postoperative pain management and reduce length of stay (LOS). We compared the impact of a multimodal expedited protocol utilizing a combination of systemic and regional analgesia (with single shot paravertebral truncal blocks), along with coping techniques (such as meditation), and physical therapy, with systemic analgesia on LOS and opioid requirements. Methods: 51 patients underwent MIRPE with an expedited recovery protocol in comparison with 112 historical control patients at a single center over 18 years. LOS and opioid analgesic morphine milliequivalent (MME) were compared. Data were stratified for age, biological sex, and Haller index (HI) to identify potential confounding variables. Results: There was no difference in age or HI between cohorts. LOS was reduced by 59.1% in the enhanced recovery group compared to the historic group (1.8 days vs 4.4 days, SD=0.5664 and 0.9503 respectively, P\u3c 0.0001). On postoperative day (POD)1, the expedited patients required an average of 100.7 MME (IQR 61.65-124.3) compared to 123.6 MME (IQR 79.5-161.1) for historic control patients (P=0.04). Cumulative MME for POD0-2 was 34.8% less in the expedited recovery patients (P= Conclusions: This MIRPE expedited recovery pain protocol using a standardized multimodal analgesia strategy and regional anesthesia is a safe and effective therapeutic plan that results in decreased opioid analgesic requirements and a significantly decreased LOS

Viral Perturbations of Host Networks Reflect Disease Etiology

Many human diseases, arising from mutations of disease susceptibility genes (genetic diseases), are also associated with viral infections (virally implicated diseases), either in a directly causal manner or by indirect associations. Here we examine whether viral perturbations of host interactome may underlie such virally implicated disease relationships. Using as models two different human viruses, Epstein-Barr virus (EBV) and human papillomavirus (HPV), we find that host targets of viral proteins reside in network proximity to products of disease susceptibility genes. Expression changes in virally implicated disease tissues and comorbidity patterns cluster significantly in the network vicinity of viral targets. The topological proximity found between cellular targets of viral proteins and disease genes was exploited to uncover a novel pathway linking HPV to Fanconi anemia

Interpreting Cancer Genomes Using Systematic Host Perturbations by Tumour Virus Proteins

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations. However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Does size really matter? How synchrony and size affect the dynamic of aggression between two sympatric species of dolphin in the Bahamas

Bottlenose (Tursiops truncatus) and spotted ( Stenella frontalis) dolphins are sympatric species, resident to Little Bahama Bank, Bahamas. A unique, dynamic methodology quantified how interspecific aggression changed over time in terms of the individuals participating, context, and behaviors used. The timing of human observation relative to the onset of aggression did not result in differences in the proportion of behaviors observed. Highly intense behaviors were used most often. The synchronous state of spotted dolphin groups, not the presence alone, was a crucial factor in determining the onset and progression of aggression. When synchronous, spotted dolphins successfully dominated the larger bottlenose dolphins. Two levels of dominance were observed. Within a single encounter (“encounter level”), one species did dominate the other. When all aggressive encounters were considered collectively over the long term (“gross level”), one species did not dominate the other. The combination of contextual factors best determined the dynamic of interspecific aggression

Information on data files used for this publication

Information on data files used for this publicatio

Data from: Manipulated sex ratios alter group structure and cooperation in the brown-headed nuthatch

A biased adult sex ratio (ASR) can influence cooperative breeding behavior if the bias limits mating opportunities for the more abundant sex. We tested predictions associated with the ASR-cooperation hypothesis in the brown-headed nuthatch (Sitta pusilla). We manipulated ASR by cross-fostering known-sex nestlings within 2 large (≥100 ha) experimental plots for 5 years using a crossover design where each plot received an opposing male- or female-biased treatment for 2 consecutive years. A year with no manipulations followed before the bias was reversed on each plot for 2 additional years. Variation in ASR (adult males/total adults) was pronounced compared to background proportions (0.55) and ranged from a female bias in female-biased plots (0.47) to a strong male bias in male-biased plots (0.71). Sex ratios during the post-breeding period ranged more broadly (0.33 in female-biased plots vs. 0.74 in male-biased plots). Territory densities did not change significantly and allowed six predictions to be assessed. Consistent with predictions, the prevalence of cooperative breeding groups doubled under male-biased treatments and large cooperative groups appeared (≥ 2 male helpers vs. the single male helper most common prior to the experiment). These changes occurred despite increased dispersal of cross-fostered males in male-biased plots. Most juvenile females dispersed, but, consistent with predictions, the prevalence of female helpers increased under female-biased treatments. Manipulations did not alter the sex of nestlings produced nor extend the time that males served as helpers. Taken collectively, results support the ASR-cooperation hypothesis and the role that mate limitations play in cooperative breeding behavior