Group membership and staff turnover affect outcomes in group CBT for persistent pain

The effects of two contextual factors, group membership and staff turnover, on the outcome of group cognitive behavioral therapy (CBT) for persistent pain were investigated. The data came from end of treatment and one month follow-up assessments of 3050 individuals who attended an intensive group programme over sixteen years. Intraclass correlations (ICC) showed significant intragroup effects on self-efficacy (ICC = 0.16 at end of treatment; 0.12 at one month), catastrophizing (ICC = 0.06; 0.13) and distance walked (ICC = 0.20; 0.19). This underlines the importance of modelling group membership when analyzing data from group interventions. Linear regression showed that high periods of staff turnover were significantly related to poorer outcomes on self-efficacy and distance walked at end of treatment, with the effect on self-efficacy persisting to one month follow-up. Having demonstrated significant contextual effects in an existing data set, further research is needed to explore the mechanisms by which these effects operate

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

The risk of pollen-mediated gene flow from exotic Corymbia plantations into native Corymbia populations in Australia

Sectors of the forest plantation industry in Australia are set to expand in the near future using species or hybrids of the spotted gums (Corymbia, Section Politaria). Plantations of these taxa have already been introduced across temperate and subtropical Australia, representing locally exotic introductions from native stands in Queensland and New South Wales. A literature review was undertaken to provide insights into the potential for pollen-mediated gene flow from these plantations into native populations. Three factors suggest that such gene flow is likely; (1) interspecific hybridisation within the genus has frequently been recorded, including between distantly related species from different sections, (2) apparent high levels of vertebrate pollinator activity may result in plantation pollen being moved over hundreds of kilometres, (3) much of the plantation estate is being established among closely related taxa and therefore few barriers to gene flow are expected. Across Australia, 20 of the 100 native Corymbia taxa were found to have regional level co-occurrence with plantations. These were located most notably within regions of north-east New South Wales and south-east Queensland, however, co-occurrence was also found in south-west Western Australia and eastern Victoria. The native species found to have co-occurrence were then assessed for the presence of reproductive barriers at each step in the process of gene flow that may reduce the number of species at risk even further. The available data suggest three risk categories exist for Corymbia. The highest risk was for gene flow from plantations of spotted gums to native populations of spotted gums. This was based on the expected limited existence of pre- and post-zygotic barriers, substantial long-distance pollen dispersal and an apparent broad period of flowering in Corymbia citriodora subsp. variegata plantations. The following risk category focussed on gene flow from Corymbia torelliana × C. c. variegata hybrid plantations into native C. c. variegata, as the barriers associated with the production and establishment of F1 hybrids have been circumvented. For the lowest risk category, Corymbia plantations may present a risk to other non-spotted gum species, however, further investigation of the particular cross-combinations is required. A list of research directions is provided to better quantify these risks. Empirical data will need to be combined within a risk assessment framework that will not only estimate the likelihood of exotic gene flow, but also consider the conservation status/value of the native populations. In addition, the potential impacts of pollen flow from plantations will need to be weighed up against their various economic and environmental benefits

Time-course of the physiological-stress response in bronze bream Pachymetopon grande following a simulated catch-and-release angling event

Catch-and-release (C&R) angling has increased in popularity through its mandatory and voluntary use in fisheries conservation and management. However, research has shown that fish can experience considerable stress during a C&R event. The physiological response of fishes is typically assessed by measuring the concentrations of blood-plasma cortisol, blood glucose and blood lactate. Members of the family Sparidae are extensively targeted in many warm-temperate coastal fisheries, and the bronze bream Pachymetopon grande is one of the most commonly captured sparids in the South African marine shore-based fishery. The aim of this study was to map the time-course of the physiological-stress response (PSR) after a simulated C&R event to determine the optimal blood-sampling time for assessing the physiological impact of C&R angling in the field. A general additive mixed model identified a significant effect of time on plasma cortisol (p = 0.005), blood glucose (p < 0.001) and blood lactate (p = 0.037), with plasma cortisol peaking at approximately 65 minutes and blood glucose at 86 minutes post-stress. In contrast, blood lactate continued to rise with no clear peak during the 125-minute sampling period. These results suggest that blood sampling should take place between 50 and 75 minutes after a C&R event. Despite a clear response, the PSR of P. grande will likely be greater in a true C&R event as this study made use of a simulated fight and used best handling practices. In addition, the prolonged physiological impacts of C&R may have negative consequences for the survival of this species in the high-energy, predator-rich coastal marine environment. Keywords: catch-and-release simulation, blood chemistry, marine fish, physiology, recreational fisheries, southern Africa, Sparida