Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning 'post-treatment control' remain unclear. Using RNA-Seq ...we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p < 0.01). These data link transcriptomic signatures associated with innate immunity with control following stopping ART. The results from this small sample need to be confirmed in larger trials, but could help define strategies for new therapies and identify new biomarkers for remission.
We report the facile removal of surfactants from colloidally synthesized nanocrystals via ligand exchange with N-heterocyclic carbenes (NHCs). Subsequent protonation of the NHC ligands in acid ...efficiently cleans the nanocrystals’ surface while preserving their uniform morphology and structure for catalysis. The broad efficacy of this strategy is validated using monodisperse Pt, Pd, and Au nanocrystals, each prepared with strongly bound phosphine stabilizers. The surface-activated nanocrystals exhibit significantly improved catalytic activities, superior to those obtained with other surface cleaning methods, as demonstrated in two centrally important electrochemical reactions (glycerol oxidation and CO2 reduction). This work highlights a new surface activation strategy for catalysis and other applications that enables the efficient use of well-defined nanocrystal libraries prepared by colloidal chemistry.
Research on the role of gut microbiota in behavior has grown dramatically. The probiotic
can alter social and stress-related behaviors - yet, the underlying mechanisms remain largely unknown. ...Although traditional laboratory rodents provide a foundation for examining the role of
on the gut-brain axis, they do not naturally display a wide variety of social behaviors. Using the highly-social, monogamous prairie vole (
), we examined the effects of
administration on behaviors, neurochemical marker expression, and gut-microbiome composition. Females, but not males, treated with live
displayed lower levels of social affiliation compared to those treated with heat-killed
. Overall, females displayed a lower level of anxiety-like behaviors than males. Live
-treated females had lower expression of corticotrophin releasing factor (CRF) and CRF type-2-receptor in the nucleus accumbens, and lower vasopressin 1a-receptor in the paraventricular nucleus of the hypothalamus (PVN), but increased CRF in the PVN. There were both baseline sex differences and sex-by-treatment differences in gut microbiome composition. Live
increased the abundance of several taxa, including
,
NK4A136, and
. Interestingly, heat-killed
increased abundance of the beneficial taxa
and
. There were significant correlations between changes in microbiota, brain neurochemical markers, and behaviors. Our data indicate that
impacts gut microbiota, gut-brain axis and behaviors in a sex-specific manner in socially-monogamous prairie voles. This demonstrates the utility of the prairie vole model for further examining causal impacts of microbiome on brain and behavior.
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It is crucial that the properties of engineered neocartilage match healthy native cartilage to promote the functional restoration of damaged cartilage. To accurately assess the ...quality of neocartilage and the degree of biomimicry achieved, its properties must be evaluated against native cartilage and tissue from which the cells for neocartilage formation were sourced. Fetal ovine cartilage is a promising and translationally relevant cell source with which to engineer neocartilage, yet, it is largely non-characterized. The influence of biomechanics during cartilage development, as well as their potential impact on structure-function relationships in utero motivates additional study of fetal cartilage. Toward providing tissue engineering design criteria and elucidating structure-function relationships, 11 locations across four regions of the fetal ovine stifle were characterized. Locational and regional differences were found to exist. Although differences in GAG content were observed, compressive stiffness did not vary or correlate with any biochemical component. Patellar cartilage tensile stiffness and strength were significantly greater than those of the medial condyle. Tensile modulus and UTS significantly correlated with pyridinoline content. More advanced zonal organization, more intense collagen II staining, and greater collagen and pyridinoline contents in the trochlear groove and patella suggest these regions exhibit a more advanced maturational state than others. Regional differences in functional properties and their correlations suggest that structure-function relationships emerge in utero. These data address the dearth of information of the fetal ovine stifle, may serve as a repository of information for cartilage engineering strategies, and may help elucidate functional adaptation in fetal articular cartilage.
Engineered neocartilage must be evaluated against healthy native cartilage and cell source tissue to determine its quality and degree of biomimicry. While fetal ovine cartilage has emerged as a promising and translationally relevant cell source with which to engineer neocartilage, it is largely non-characterized. Therefore, 11 locations across four regions (medial condyle, lateral condyle, trochlear groove, and patella) of the fetal ovine stifle were characterized. Importantly, locational and regional differences in functional properties were observed, and significant correlations of tensile properties to collagen and crosslink contents were detected, suggesting that functional adaptation begins in utero. This study provides a repository of quantitative information, clarifies the developmental order of cartilage functional properties, and informs future cartilage engineering efforts.
Larval and adult mosquitoes mount immune responses against pathogens that invade their hemocoel. Although it has been suggested that a correlation exists between immune processes across insect life ...stages, the influence that an infection in the hemocoel of a larva has on the immune system of the eclosed adult remains unknown. Here, we used Anopheles gambiae to test whether a larval infection influences the adult response to a subsequent bacterial or malaria parasite infection. We found that for both female and male mosquitoes, a larval infection enhances the efficiency of bacterial clearance following a secondary infection in the hemocoel of adults. The adults that emerge from infected larvae have more hemocytes than adults that emerge from naive or injured larvae, and individual hemocytes have greater phagocytic activity. Furthermore, mRNA abundance of immune genes—such as cecropin A, Lysozyme C1, Stat‐A, and Tep1—is higher in adults that emerge from infected larvae. A larval infection, however, does not have a meaningful effect on the probability that female adults will survive a systemic bacterial infection, and increases the susceptibility of females to Plasmodium yoelii, as measured by oocyst prevalence and intensity in the midgut. Finally, immune proficiency varies by sex; females exhibit increased bacterial killing, have twice as many hemocytes, and more highly express immune genes. Together, these results show that a larval hemocoelic infection induces transstadial immune activation—possibly via transstadial immune priming—but that it confers both costs and benefits to the emerged adults.
Mosquitoes undergo complete metamorphosis, which requires a larva to molt several times prior to reaching adulthood. This research demonstrates that an infection acquired during the immature stages affects the ability of adults to respond to a subsequent infection.
Background
Burnout in medicine, and specifically radiology, has been receiving more attention. Little data-driven literature is available regarding risk factors/causes to ultimately help guide the ...development of potential solutions.
Objective
To survey pediatric radiologists, a cohort with a documented high prevalence of burnout, and to understand the impact of clinical demands on nonclinical tasks and the implications of burnout on mental health.
Materials and methods
A survey of Society for Pediatric Radiology (SPR) North America attendings was performed regarding institutional factors contributing to burnout, including call burden, clinical demands, departmental support and administrative/academic tasks. Questions regarding mental health and wellness resources were also included. Generalized linear modeling assuming binomial distribution was used for analyses with SAS 9.4.
Results
The response rate was 305/1,282 (24%) with 53% of respondents female. Respondents reported that both the number and complexity of clinical cases have increased since they first started practice as an attending, while the time for interpretation has not changed,
P
<0.0001. Using a scale of 0 (never), 1 (rarely), 2 (sometimes), 3 (frequently) and 4 (always), covering multiple hospitals (2.2) and administrative tasks (2.4) were the most stressful job factors. For those in administrative roles, the most stressful job factors were job-related tasks affected teaching duties (2.0) and decreased overall job satisfaction (2.0). Of the respondents, 52% said they know a physician affected by work stress-related mental illness and 25% know a physician who has contemplated or committed suicide. While 39% of the respondents have resources available to address burnout, only 33% utilize these resources.
Conclusion
Increasing clinical demands and additional institutional/departmental factors play a potential role in burnout, which has serious implications for the mental health of pediatric radiologists.
Following the first peak of the COVID-19 pandemic, reports from around the world suggested a reduction in preterm deliveries during lockdown periods. We reviewed preterm admissions to a large ...tertiary neonatal unit in inner North East London during two United Kingdom (UK) national lockdowns in 2020 and 2021. We found no evidence of difference in admissions during two national lockdowns compared to previous years. Based on these findings, we recommend that neonatal services remain as vigilant and prepared as ever for the unpredictable nature of preterm birth, and their staff protected to provide this highly specialist care.
•Since the beginning of the COVID-19 pandemic, inconsistent reports of falling preterm births have emerged from around the world•We analysed admission rates for preterm babies to a large regional neonatal service over two national lockdowns•Preterm admissions were no different during two national lockdowns when compared to previous years
Abstract
The public, all-sky surveys Gaia and TESS provide the ability to identify new young associations and determine their ages. These associations enable study of planetary evolution by providing ...new opportunities to discover young exoplanets. A young association was recently identified by Tang et al. and Fürnkranz et al. using astrometry from Gaia (called “Group-X” by the former). In this work, we investigate the age and membership of this association, and we validate the exoplanet TOI 2048 b, which was identified to transit a young, late G dwarf in Group-X using photometry from TESS. We first identified new candidate members of Group-X using Gaia EDR3 data. To infer the age of the association, we measured rotation periods for candidate members using TESS data. The clear color–period sequence indicates that the association is the same age as the 300 ± 50 Myr old NGC 3532. We obtained optical spectra for candidate members that show lithium absorption consistent with this young age. Further, we serendipitously identify a new, small association nearby Group-X, which we call MELANGE-2. Lastly, we statistically validate TOI 2048 b, which is a 2.1 ± 0.2
R
⊕
radius planet on a 13.8-day orbit around its 300 Myr old host star.
BACKGROUND:Combined burn and traumatic brain injury (TBI) treatment priorities may not align due to opposing fluid resuscitation paradigms used in treating burns and TBI. We developed a porcine model ...of combined thermal injury/TBI and compared an “aggressive” fluid resuscitation strategy using the Parkland formula and a “restrictive” resuscitation strategy using the modified Brooke formula.
METHODS:Twenty eight swine were deeply anesthetized and received a 40% total body surface area full thickness burn injury and TBI. Swine were then randomized to receive restrictive or aggressive resuscitation for eight hours after which time animals were euthanized and necropsy was performed. Volume of brain injury was assessed after analyzing segmental slices of brain tissue.
RESULTS:There were no differences between the restrictive and aggressive resuscitation groups in blood pressure, heart rate, central venous pressure, intra-cranial pressure (ICP), or serum lactate levels after 8 hours of resuscitation. Urine output was higher in the aggressive resuscitation group. The restrictive group had a significantly higher serum BUN compared to baseline and compared to the aggressive group. There was no significant difference in size of brain injury between groups.
CONCLUSIONS:Both restrictive and aggressive resuscitation demonstrated adequate resuscitation at eight hours post-injury. Increased serum BUN in the restrictive group may be an indicator of early acute kidney injury, despite adequate urine output. Resuscitation strategy did not appear to affect ICP or the size of brain injury.
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