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Cytosolic lipopolysaccharides (LPSs) bind directly to caspase-4/5/11 through their lipid A moiety, inducing inflammatory caspase oligomerization and activation, which is identified as the noncanonical inflammasome pathway. Galectins, β-galactoside–binding proteins, bind to various gram-negative bacterial LPS, which display β-galactoside–containing polysaccharide chains. Galectins are mainly present intracellularly, but their interactions with cytosolic microbial glycans have not been investigated. We report that in cell-free systems, galectin-3 augments the LPS-induced assembly of caspase-4/11 oligomers, leading to increased caspase-4/11 activation. Its carboxyl-terminal carbohydrate-recognition domain is essential for this effect, and its N-terminal domain, which contributes to the self-association property of the protein, is also critical, suggesting that this promoting effect is dependent on the functional multivalency of galectin-3. Moreover, galectin-3 enhances intracellular LPS-induced caspase-4/11 oligomerization and activation, as well as gasdermin D cleavage in human embryonic kidney (HEK) 293T cells, and it additionally promotes interleukin-1β production and pyroptotic death in macrophages. Galectin-3 also promotes caspase-11 activation and gasdermin D cleavage in macrophages treated with outer membrane vesicles, which are known to be taken up by cells and release LPSs into the cytosol. Coimmunoprecipitation confirmed that galectin-3 associates with caspase-11 after intracellular delivery of LPSs. Immunofluorescence staining revealed colocalization of LPSs, galectin-3, and caspase-11 independent of host N-glycans. Thus, we conclude that galectin-3 amplifies caspase-4/11 oligomerization and activation through LPS glycan binding, resulting in more intense pyroptosis—a critical mechanism of host resistance against bacterial infection that may provide opportunities for new therapeutic interventions.

Galectin-4, a member of the galectin family of animal glycan-binding proteins (GBPs), is specifically expressed in gastrointestinal epithelial cells and is known to be able to bind microbes. However, its function in host-gut microbe interactions remains unknown. Here, we show that intracellular galectin-4 in intestinal epithelial cells (IECs) coats cytosolic Salmonella enterica serovar Worthington and induces the formation of bacterial chains and aggregates. Galectin-4 enchains bacteria during their growth by binding to the O-antigen of lipopolysaccharides. Furthermore, the binding of galectin-4 to bacterial surfaces restricts intracellular bacterial motility. Galectin-4 enhances caspase-1 activation and mature IL-18 production in infected IECs especially when autophagy is inhibited. Finally, orally administered S. enterica serovar Worthington, which is recognized by human galectin-4 but not mouse galectin-4, translocated from the intestines to mesenteric lymph nodes less effectively in human galectin-4-transgenic mice than in littermate controls. Our results suggest that galectin-4 plays an important role in host-gut microbe interactions and prevents the dissemination of pathogens. The results of the study revealed a novel mechanism of host–microbe interactions that involves the direct binding of cytosolic lectins to glycans on intracellular microbes.

We have tried to improve the responsivity of germanium-based thin-film photodetectors. It has been shown that applying a mechanical strain to the detector led to a 46.6% enhancement on the 1550 nm detection. This improvement is better than the 1310 nm case, because the bandgap shrinkage is more beneficial to the small-energy photon detection. The AuNP coating is even more attractive for responsivity enhancement of thin-film germanium (Ge) detectors. The responsivity enhancement due to the AuNP deposition is as high as 89% and 47%, for the 1310 nm and 1550 nm detections, respectively. To the best of our knowledge, this is the best responsivity enhancement for the thin-film Ge detectors reported to date.

The IL6-GP130-STAT3 pathway facilitates lung cancer progression and resistance to tyrosine kinase inhibitors. Although glycosylation alters the stability of GP130, its effect on the ligand IL6 remains unclear. We herein find that N-glycosylated IL6, especially at Asn73, primarily stimulates JAK-STAT3 signaling and prolongs STAT3 phosphorylation, whereas N-glycosylation-defective IL6 (deNG-IL6) induces shortened STAT3 activation and alters the downstream signaling preference for the SRC-YAP-SOX2 axis. This signaling shift induces e pithelial- m esenchymal t ransition (EMT) and migration in vitro and metastasis in vivo, which are suppressed by targeted inhibitors and shRNAs against SRC, YAP, and SOX2. Osimertinib-resistant lung cancer cells secrete a large amount of deNG-IL6 through reduced N-glycosyltransferase gene expression, leading to clear SRC-YAP activation. deNG-IL6 contributes to drug resistance, as confirmed by in silico analysis of cellular and clinical transcriptomes and signal expression in patient specimens. Therefore, the N-glycosylation status of IL6 not only affects cell behaviors but also shows promise in monitoring the dynamics of lung cancer evolution. Post-translational modifications regulate tumorigenesis and cancer therapy sensitivity. Here, the authors show that N-glycosylation defective Interleukin-6 (deNG-IL6) switches downstream signalling pathway from JAK-STAT3 to SRC-YAP axis and lung cancer cells secrete deNG-IL6 to promote metastasis and tyrosine kinase inhibitor resistance.

•52.6% of homeless children in DC were up to date with vaccinations.•This vaccination estimate is 12 percentage points lower than for US in poverty.•Young, homeless children may be at particularly high risk for under-vaccination. Comprehensive vaccination coverage among homeless children in the United States (US) is largely unknown although a few studies suggest low coverage with single vaccinations. This study compared vaccination coverage with a combined 7-vaccines series among homeless children in the District of Columbia (DC) to coverage among other US children. A cross-sectional survey of homeless children in DC was conducted from 2018 to 2019. Recruitment occurred at housing shelters, social services centers, and a diaper dispensary, and through limited chain referral. English-speaking parents of a child aged 19 to 35 months who spent the majority of the last 30 nights homeless were recruited. Participants consented for their child’s healthcare providers to submit vaccination records. The vaccination coverage estimate of this sample was compared with estimates of three populations in the 2018 National Immunization Survey (NIS): children in DC (NIS DC), children in the US (NIS US), and children in the US below the federal poverty level (NIS poor). Most of the 135 children had experienced at least two lifetime episodes (63.7%) and 12 months (57%) of homelessness. The estimated percent up to date was 52.6% (95% CI: 43.8%, 61.3%). This estimate was 20.4 (95% CI: 11.9, 28.8, p < .0001), 20 (95% CI: 11.5, 28.4, p < .0001), and 11.5 (95% CI: 3.1, 20, p < .01) percentage points lower than estimates for the NIS DC, NIS US and NIS poor populations, respectively. After adjusting for child’s age and race/ethnicity, vaccination coverage of the NIS DC sample was below that of NIS US (p < .01) and NIS poor samples (p < .05). Children experiencing homelessness may be at risk of under-vaccination, even when compared to a general population of children in poverty. Awareness of this heightened risk may allow for more precise targeting of vaccination delivery support specifically to children experiencing homelessness.

Lack of pediatric advance care planning has been associated with poor communication, increased hospitalization, poor quality of life, and legal actions. Clinicians presume that families understand adolescents' treatment preferences for end-of-life care. To examine patient-reported end-of-life values and needs of adolescents with cancer and congruence with their families' understanding of these needs. This cross-sectional survey was conducted among adolescent-family dyads from July 16, 2016, to April 30, 2019, at 4 tertiary care pediatric US hospitals. Participants included 80 adolescent-family dyads (160 participants) within a larger study facilitating pediatric advance care planning. Adolescent eligibility criteria included being aged 14 to 21 years, English speaking, being diagnosed with cancer at any stage, and knowing their diagnosis. Family included legal guardians for minors or chosen surrogate decision-makers for those aged 18 years or older. Data analysis was performed from April 2019 to November 2019. Session 1 of the 3-session Family Centered Pediatric Advance Care Planning for Teens With Cancer intervention. The main outcome was congruence between adolescents with cancer and their families regarding adolescents' values, goals, and beliefs about end-of-life care. Prevalence-adjusted and bias-adjusted κ (PABAK) values were used to measure congruence on the Lyon Advance Care Planning Survey-Revised (Patient and Surrogate versions). A total of 80 adolescent-family dyads (160 participants) were randomized to the intervention group in the original trial. Among the adolescents, 44 (55.0%) were female and 60 (75.0%) were white, with a mean (SD) age of 16.9 (1.8) years. Among family members, 66 (82.5%) were female and 65 (81.3%) were white, with a mean (SD) age of 45.3 (8.3) years. Family members' understanding of their adolescent's beliefs about the best time bring up end-of-life decisions was poor: 86% of adolescents wanted early timing (before getting sick, while healthy, when first diagnosed, when first sick from a life-threatening illness, or all of the above), but only 39% of families knew this (PABAK, 0.18). Families' understanding of what was important to their adolescents when dealing with their own dying was excellent for wanting honest answers from their physician (PABAK, 0.95) and understanding treatment choices (PABAK, 0.95) but poor for dying a natural death (PABAK, 0.18) and being off machines that extend life, if dying (PABAK, 0). Many families had a poor understanding of their adolescent's values regarding their own end-of-life care, such as when to initiate end-of-life conversations and preference for being off machines that extend life. Pediatric advance care planning could minimize these misunderstandings with the potential for a substantial impact on quality of care.

The associations of spiritual and religious factors with patient-reported outcomes among adolescents with cancer are unknown. To model the association of spiritual and religious constructs with patient-reported outcomes of anxiety, depressive symptoms, fatigue, and pain interference. This cross-sectional study used baseline data, collected from 2016 to 2019, from an ongoing 5-year randomized clinical trial being conducted at 4 tertiary-referral pediatric medical centers in the US. A total of 366 adolescents were eligible for the clinical trial, and 126 were randomized; participants had to be aged 14 to 21 years at enrollment and be diagnosed with any form of cancer. Exclusion criteria included developmental delay, scoring greater than 26 on the Beck Depression Inventory II, non-English speaking, or unaware of cancer diagnosis. Spiritual experiences, values, and beliefs; religious practices; and overall self-ranking of spirituality's importance. Variables were taken from the Brief Multidimensional Measurement of Religiousness/Spirituality (ie, feeling God's presence, daily prayer, religious service attendance, being very religious, and being very spiritual) and the spiritual well-being subscales of the Functional Assessment of Chronic Illness Therapy (meaning/peace and faith). Predefined outcome variables were anxiety, depressive symptoms, fatigue, and pain interference from Patient-Reported Outcomes Measurement Information System pediatric measures. A total of 126 individuals participated (72 [57.1%] female participants; 100 [79.4%] white participants; mean [SD] age, 16.9 [1.9] years). Structural equation modeling showed that meaning and peace were inversely associated with anxiety (β = -7.94; 95% CI, -12.88 to -4.12), depressive symptoms (β = -10.49; 95% CI, -15.92 to -6.50), and fatigue (β = -8.90; 95% CI, -15.34 to -3.61). Feeling God's presence daily was indirectly associated with anxiety (β = -3.37; 95% CI, -6.82 to -0.95), depressive symptoms (β = -4.50; 95% CI, -8.51 to -1.40), and fatigue (β = -3.73; 95% CI, -8.03 to -0.90) through meaning and peace. Considering oneself very religious was indirectly associated with anxiety (β = -2.81; 95% CI, -6.06 to -0.45), depressive symptoms (β = -3.787; 95% CI, -7.68 to -0.61), and fatigue (β = -3.11, 95% CI, -7.31 to -0.40) through meaning and peace. Considering oneself very spiritual was indirectly associated with anxiety (β = 2.11; 95% CI, 0.05 to 4.95) and depression (β = 2.8, 95% CI, 0.07 to 6.29) through meaning and peace. No associations were found between spiritual scales and pain interference. In this study, multiple facets of spirituality and religiousness were associated with anxiety, depression, and fatigue, all of which were indirectly associated with the participant's sense of meaning and peace, which is a modifiable process. Although these results do not establish a causal direction, they do suggest palliative interventions addressing meaning-making, possibly including a spiritual or religious dimension, as a novel focus for intervention development.

Purpose Physicians and caregivers rate patient quality of life (QOL) lower than patients rate their own QOL. This study investigated discrepancies between self-assessments of patient QOL by adults with HIV and their surrogate decision-makers. Methods We collected baseline data from 223 adult dyads in the FAmily-CEntered (FACE) Advance Care Planning (ACP) clinical trial, consisting of HIV positive patients and their chosen surrogates. Participants independently completed the Medical Outcome Study-HIV Survey (MOS-HIV) and the Palliative care Outcome Scale (POS). We used Wilcoxon Signed-Rank Test to assess differences in overall patient–surrogate means. We used Prevalence Adjusted Bias Adjusted Kappa (PABAK) statistics to assess dyadic agreement, with surrogate HIV status and cohabitation status as grouping variables. Results Patients were 56.1% male, 86.1% Black/African-American, aged 22–77 (mean = 50.83, SD = ± 12.33). Surrogates were 43.8% male, 84.1% Black/African-American, aged 18–82 (mean = 49.73, SD = ± 14.22). 46.2% of surrogates lived with the patient. 64.6% of surrogates reported negative HIV status. Surrogates were more likely to state patients were ill, p  = 0.032. Among patient–surrogate dyads, most QOL assessments showed poor (0.00–0.39) or fair (0.40–0.59) agreement and agreement tended to be even poorer among patient–surrogate dyads where the surrogate had a shared HIV diagnosis. Conclusions QOL discrepancies are said to arise from healthy surrogates overestimating the effects of chronic illness. In this novel assessment, many surrogates had a shared HIV diagnosis, without increased agreement. These findings highlight the challenge of accurately assessing patient QOL by surrogates, even when there is a shared HIV diagnosis. Improved communication is needed between patients and surrogates about the patients’ representation of illness. National Clinical Trial Number: NCT01775436.

Purpose Dexmedetomidine, a selective α 2 adrenoreceptor agonist, has analgesic and sedative properties, minimal impact on respiratory parameters, and reportedly decreases analgesic requirements after surgery. Given its pharmacodynamic profile, dexmedetomidine might have a role for postoperative pain control in children undergoing tonsillectomy. In this study, we hypothesized that dexmedetomidine would delay and decrease opioid requirements after tonsillectomy. Methods In a double-blind controlled trial, participants undergoing tonsillectomy were randomized to receive one intravenous dose of fentanyl (1 μg·kg −1 or 2 μg·kg −1 ) or dexmedetomidine (2 μg·kg −1 or 4 μg·kg −1 ) immediately after endotracheal intubation. Primary outcomes included requirement for rescue morphine in the initial postoperative period. Results One hundred and one children were enrolled. During the postoperative period, dexmedetomidine (2 and 4 μg·kg −1 groups combined) significantly prolonged the opioid-free interval of children who underwent tonsillectomy compared with fentanyl (1 and 2 μg·kg −1 groups combined) ( P  < 0.001). Children treated with dexmedetomidine 2 μg·kg −1 vs dexmedetomidine 4 μg·kg −1 had similar cumulative incidence curves for time to morphine rescue, whereas there was a small difference in time to first morphine rescue administration when comparing fentanyl 1 μg·kg −1 vs fentanyl 2 μg·kg −1 . Furthermore, length of stay in the postanesthesia care unit was significantly longer for children treated with dexmedetomidine vs children treated with fentanyl ( P  = 0.0016). Conclusions High-dose dexmedetomidine decreases opioid requirements, prolongs the opioid-free interval after tonsillectomy, and prolongs length of stay in the postanesthesia care unit. It is conceivable that these early opioid-sparing effects could benefit patients at risk for respiratory complications early in the postoperative course after tonsillectomy (e.g., patients with obstructive sleep apnea). (ClinicalTrials.gov number, NCT00654511).