Bereaved families’ perspectives provide insight into quality decision-making for major interventions and end-of-life care in pediatric patients with chronic illness who face decisions regarding technology dependence.

Bereaved families’ perspectives provide insight into quality decision-making for major interventions and end-of-life care in pediatric patients with chronic illness who face decisions regarding technology dependence.

Multimodality treatment improves survival for gastric cancer (GC). However, the effect of treatment sequence by stage remains unclear. We aim to compare outcomes between patients receiving neoadjuvant(neoadj) and adjuvant chemotherapy (adj).

Nonmetastatic GC patients with clinical stage ≥ T2N0 who underwent both resection and neoadj or adj were identified using the National Cancer Database (2005-2014). Multivariable Cox regression analyses were performed on propensity score-matched (PSM) cohorts stratified by stage to compare overall survival (OS).

We identified 11 984 patients; 55% stage I (SI), 76% stage II (SII) and 57% stage III (SIII) received neoadj. Unadjusted analysis showed worse survival among SI neoadj patients (hazard ratio [HR] 1.195, confidence interval [CI] 1.04-1.38) and improved survival for SII (HR 0.93 CI 0.87-0.998) and SIII (HR 0.75, CI 0.68-0.84). After PSM, SI patients with neoadj had worse OS with increased risk of death compared to Adj (HR 1.186, CI 1.004-1.402). SII patients had no difference in OS (HR 0.98, CI 0.91-1.07) and SIII patients had improved OS (HR 0.78, CI 0.69-0.90).

In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

In patients who received surgery and chemotherapy, the benefit of neoadj was limited to SIII with worse survival for SI. A clinical trial to examine the optimal sequence of chemotherapy is warranted.

Understanding the association between sleep traits and tinnitus could help prevent and provide appropriate interventions against tinnitus. Therefore, this study aimed to assess the relationship between different sleep patterns and tinnitus.

A cross-sectional analysis using baseline data (2006-2010, n = 168,064) by logistic regressions was conducted to evaluate the association between sleep traits (including the overall health sleep score and five sleep behaviors) and the occurrence (yes/no), frequency (constant/transient), and severity (upsetting/not upsetting) of tinnitus. Further, a prospective analysis of participants without tinnitus at baseline (n = 9581) was performed, who had been followed-up for 7 years (2012-2019), to assess the association between new-onset tinnitus and sleep characteristics. Moreover, a subgroup analysis was also carried out to estimate the differences in sex by dividing the participants into male and female groups. A sensitivity analysis was also conducted by excluding ear-relitive correlations with „upsetting tinnitus.” In the prospective analysis, sleeplessness presented a consistently significant association with „upsetting tinnitus” (RR 2.28, p = 0.001). Consistent results were observed in the sex subgroup analysis, where a much more pronounced trend was identified in females compared with the males. The results of the sensitivity analysis were consistent with those of the cross-sectional and prospective analyses.

Different types of sleep disturbance may be associated with the occurrence and severity of tinnitus; therefore, precise interventions for different types of sleep disturbance, particularly sleeplessness, may help in the prevention and treatment of tinnitus.

Different types of sleep disturbance may be associated with the occurrence and severity of tinnitus; therefore, precise interventions for different types of sleep disturbance, particularly sleeplessness, may help in the prevention and treatment of tinnitus.Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens that have evolved to bind the major negative regulator of the complement system, complement factor H (CFH). However, little is known about the interaction of pathogens with CFH-related proteins (CFHRs) which are structurally similar to CFH but lack the main complement regulatory domains found in CFH. Insights into the role of CFHRs have been hampered by a lack of specific reagents. We generated a panel of CFHR-specific monoclonal antibodies and demonstrated that CFHR5 was bound by both pathogenic Neisseria spp. We showed that CFHR5 bound to PorB expressed by both pathogens in the presence of sialylated lipopolysaccharide and enhanced complement activation on the surface of N. gonorrhoeae. Our study furthered our understanding of the interactions of CFHRs with bacterial pathogens and revealed that CFHR5 bound the meningococcus and gonococcus via similar mechanisms.People infected with the mosquito-borne Rift Valley fever virus (RVFV) can suffer from eye-related problems resulting in ongoing vision issues or even permanent blindness. Despite ocular disease being the most frequently reported severe outcome, it is vastly understudied compared to other disease outcomes caused by RVFV. Ocular manifestations of RVFV include blurred vision, uveitis, and retinitis. When an infected individual develops macular or paramacular lesions, there is a 50% chance of permanent vision loss in one or both eyes. The cause of blinding ocular pathology remains unknown in part due to the lack of a tractable animal model. Using 3 relevant exposure routes, both subcutaneous (SC) and aerosol inoculation of Sprague Dawley rats led to RVFV infection of the eye. Surprisingly, direct inoculation of the conjunctiva did not result in successful ocular infection. The posterior segment of the eye, including the optic nerve, choroid, ciliary body, and retina, were all positive for RVFV antigen in SC-infeflammation within the posterior eye. Infection of human ocular cells induced inflammatory responses and required host entry factors for RVFV infection similar to rodents. This work provides evidence of how RVFV infects the eye, and this information can be applied to help mitigate the devastating outcomes of RVF ocular disease through vaccines or treatments.Sex Ratio chromosomes in Drosophila pseudoobscura are selfish X chromosome variants associated with 3 nonoverlapping inversions. In the male germline, Sex Ratio chromosomes distort the segregation of X and Y chromosomes (991), thereby skewing progeny sex ratio. In the female germline, segregation of Sex Ratio chromosomes is mendelian (5050), but nonoverlapping inversions strongly suppress recombination establishing a 26-Mb haplotype (constituting ∼20% of the haploid genome). Rare crossover events located between nonoverlapping inversions can disrupt this haplotype, and recombinants have sometimes been found in natural populations. We recently reported on the first lab-generated Sex Ratio recombinants occurring at a rate of 0.0012 crossovers per female meiosis. An improved experimental design presented here reveals that these recombination events were at least 4 times more frequent than previously estimated. Furthermore, recombination events were strongly clustered, indicating that the majority arose from mitotic exchange in female germline stem cells and not from meiotic crossing-over in primary oocytes. Finally, asymmetric recovery of complementary recombinants was consistent with unequal exchange causing the recombination-induced viability defects. Incorporating these experimental results into population models for Sex Ratio chromosome evolution provided a substantially better fit to natural population frequencies and allowed maintenance of the highly differentiated 26-Mb Sex Ratio haplotype without invoking strong epistatic selection. This study provides the first estimate of spontaneous mitotic exchange for naturally occurring chromosomes in Drosophila female germline stem cells, reveals a much higher Sex Ratio chromosome recombination rate, and develops a mathematical model that accurately predicts the rarity of recombinant Sex Ratio chromosomes in natural populations.Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function at different developmental stages. Here, we investigated the genetic determinants of how animal’s sensitivity to drugs that alter synaptic activity is regulated at a specific developmental stage using the free-living nematode Caenorhabditis elegans. C. elegans enters the stress-resistant dauer larval stage under harsh conditions. Although dauer is known to have reduced permeability and increased resistance to most known exogenous chemicals, we discovered that dauer is hypersensitive to a cholinesterase inhibitor, aldicarb. To investigate genes regulating dauer-specific acetylcholine transduction, we first screened for aldicarb-resistant mutations in dauer and then performed a secondary screen to rule out aldicarb-resistant mutations that also affect adults. We isolated 2 different mutations of a single gene called cyp-34A4 or dach-1 encoding a cytochrome P450. In the nondauer stages, dach-1 is mainly expressed in the intestine, but its expression is robustly increased in the epidermis of dauers. By tissue-specific rescue experiments, we found that dach-1 modulates aldicarb sensitivity in a cell nonautonomous manner. In addition, dach-1 plays pleiotropic functions in dauers by regulating quiescence and surviving heat shock and hyperosmolar stress. Our study reveals novel functions of the cytochrome P450 in synaptic and physiological changes during the developmental plasticity.Adjusting the crystal and band structures is of great significance for phonon or carrier transport in functional materials. Lattice contraction was designed to adjust the crystal and energy band structures, which bring about energy valley degeneracy and a band gap decrease in the SnSe system. The Seebeck coefficient of the rapid cooling sample increases significantly due to the energy valley degeneracy. The multichannel effect based on the energy valley degeneracy weakens scattering among the carriers and maintains a high σ along the „⊥” direction. The PF for the rapid cooling sample at 773 K reaches 686 μW m-1 K-2, which is boosted by 66.13% compared with that of the slow cooling sample. Due to the contribution from the high power factor, the ZT value of the rapid cooling sample reaches 0.86, which is an increase of 26% compared with the 0.69 of the slow cooling sample.

Cytokine release syndrome (CRS) is a potentially lethal toxicity associated with chimeric antigen receptor T cell therapy for pediatric acute lymphoblastic leukemia (ALL). Outcomes after critical illness due to severe CRS are poorly described. Our aim was to characterize critical illness outcomes across a multicenter cohort of PICU patients with ALL and CRS.

Multicenter retrospective cohort study.

Twenty-one PICUs contributing data to Virtual Pediatric Systems, LLC (January 2020-December 2021).

PICU patients with ALL or unclassified leukemia and CRS.

None.

We identified 55 patients; 34 (62%) were 12 years or older, 48 (87%) were admitted from a hospital inpatient ward, and 23 (42%) received advanced organ failure support or monitoring. Fifty-one survived to PICU discharge (93%) including 19 of 23 (83%) who received advanced organ failure support or monitoring defined as receipt of noninvasive or invasive ventilation, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, continuous renal replacement therapy, or placement of a tracheostomy, arterial catheter, hemodialysis catheter, or intracranial catheter.