Outer Membrane Vesicles Derived from Escherichia coli Induce Systemic Inflammatory Response Syndrome

Sepsis, characterized by a systemic inflammatory state that is usually related to Gram-negative bacterial infection, is a leading cause of death worldwide. Although the annual incidence of sepsis is still rising, the exact cause of Gram-negative bacteria-associated sepsis is not clear. Outer membrane vesicles (OMVs), constitutively secreted from Gram-negative bacteria, are nano-sized spherical bilayered proteolipids. Using a mouse model, we showed that intraperitoneal injection of OMVs derived from intestinal Escherichia coli induced lethality. Furthermore, OMVs induced host responses which resemble a clinically relevant condition like sepsis that was characterized by piloerection, eye exudates, hypothermia, tachypnea, leukopenia, disseminated intravascular coagulation, dysfunction of the lungs, hypotension, and systemic induction of tumor necrosis factor-α and interleukin-6. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of sepsis, suggesting OMVs as a new therapeutic target to prevent and/or treat severe sepsis caused by Gram-negative bacterial infection

Multifaceted roles of GSK-3 and Wnt/β-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention

Glycogen synthase kinase-3 (GSK-3) is well documented to participate in a complex array of critical cellular processes. It was initially identified in rat skeletal muscle as a serine/threonine kinase that phosphorylated and inactivated glycogen synthase. This versatile protein is involved in numerous signaling pathways that influence metabolism, embryogenesis, differentiation, migration, cell cycle progression and survival. Recently, GSK-3 has been implicated in leukemia stem cell pathophysiology and may be an appropriate target for its eradication. In this review, we will discuss the roles that GSK-3 plays in hematopoiesis and leukemogenesis as how this pivotal kinase can interact with multiple signaling pathways such as: Wnt/β-catenin, phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt/mammalian target of rapamycin (mTOR), Ras/Raf/MEK/extracellular signal-regulated kinase (ERK), Notch and others. Moreover, we will discuss how targeting GSK-3 and these other pathways can improve leukemia therapy and may overcome therapeutic resistance. In summary, GSK-3 is a crucial regulatory kinase interacting with multiple pathways to control various physiological processes, as well as leukemia stem cells, leukemia progression and therapeutic resistance. GSK-3 and Wnt are clearly intriguing therapeutic targets

Comparison of breast milk and sucrose in neonatal pain relief and coping with stress of ROP examination using ALPS-Neo

Background: Examination for retinopathy of prematurity (ROP) is one of the procedures that can be stressful for neonates admitted to a neonatal intensive care unit. This study compared breast milk and sucrose in pain relief and coping with the stress of ROP examination using the Astrid Lindgren and Lund Children�s Hospital Pain and Stress Assessment Scale for Preterm and Sick Newborn Infants (ALPS-Neo). Methods: The present study was carried out on a total of 63 preterm infants (including breast milk group n=21, sucrose group n=21, and distilled water group n=21). The neonates were given 0.5 ml/kg of breast milk, sucrose, or distilled water 2 min before the examination. The ROP eye examinations were video recorded from 5 min before to 15 min after the examination, and infants� pain and stress levels were assessed using the ALPS-Neo by two blinded evaluators 5 min before, during, and 5, 10, and 15 min after the examination. Results: No statistically significant differences were observed during the examinations in the mean scores of the ALPS-Neo among the three groups (P>0.05). However, there were statistically significant differences among the three groups after the examinations (P<0.05) and in the mean duration of stress adaptation (P<0.05). The duration of stress adaptation in the breast milk group was 11.4 min on average which was lower than that reported for the other groups. Conclusion: Breast milk was more effective in the reduction of pain and stress after ROP examinations, compared to sucrose or distilled water. © 2021 Mashhad University of Medical Sciences. All rights reserved

What is it like to be the wife of an addicted man in Iran? A qualitative study

Drug misuse is increasing and diversifying in Iran. This study is the first to explore in detail the impact on, and ways of coping used by, spouses of addicted men in Iran. Semi-structured interviews were conducted with 24 spouses. Four main themes were identified in the data: heart-breaking news of the husband's addiction; coping alone; progressive deterioration and suffering; and disruption of family relationships and finances. Reactions upon learning of the husband's addiction involved shock and collapse, and/or fear, disbelief and confusion. Spouses tried to hide the problem and to solve the problem alone, feeling for a long time as if they were "walking in the dark" without any social support and exposed to stigma. As time had gone on they had experienced distress and turmoil, and mixed feelings towards, and loss of trust and confidence in, their husbands, whose behaviour was increasingly unreliable. This had led to impairment in the relationship, and financial stress, and a general degradation and disruption of normal family life, leading to strain for spouses, akin to a state of burnout. Present findings confirm the conclusions of similar research conducted in other countries, that substance misuse in the family can have devastating effects for spouses, on children and all aspects of family life. The situation for Iranian wives may be compounded by the relatively closed nature of family life, and the existence of culturally based attitudes, including shame, towards "family defects" such as addiction. More information and support is needed for Iranian families of addicted individuals. © 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted

The effect of a group discussion about premature newborns between mothers and healthcare team on mother� stress and coping in neonatal intensive care unit

Background: Premature birth is a source of severe stress for parents. The current study aimed to determine the effect of group discussion between mothers and the healthcare team on mothers' stress and coping strategies. Methods: This non-randomized, prospective, interventional study was conducted in 2017. Eighty mothers with premature infants were enrolled in the study (40 mothers in each group). Four sessions of group discussion focusing on family-centered care were conducted for the intervention group. Parental Stress Scale and the Brief COPE were completed for the first three days and two weeks later, and the data were analyzed using t-test and repeated measure ANOVA. Results: Differences in maternal stress reduction between the intervention and control groups were statistically significant (p=0.002). Problem-focused coping strategies were increased significantly in the intervention group (P = 0.01). Conclusions: Group discussions between mothers and healthcare team members as a way to improve the quality of care in the neonatal intensive care unit (NICU) can help mothers stress reduction and improving positive coping strategies. © 2020 Neonatal Nurses Associatio

An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions

The conserved oligomannose epitope, Man9GlcNAc2, recognized by the broadly neutralizing human mAb 2G12 is an attractive prophylactic vaccine candidate for the prevention of HIV-1 infection. We recently reported total chemical synthesis of a series of glycopeptides incorporating one to three copies of Man9GlcNAc2 coupled to a cyclic peptide scaffold. Surface plasmon resonance studies showed that divalent and trivalent, but not monovalent, compounds were capable of binding 2G12. To test the efficacy of the divalent glycopeptide as an immunogen capable of inducing a 2G12-like neutralizing antibody response, we covalently coupled the molecule to a powerful immune-stimulating protein carrier and evaluated immunogenicity of the conjugate in two animal species. We used a differential immunoassay to demonstrate induction of high levels of carbohydrate-specific antibodies; however, these antibodies showed poor recognition of recombinant gp160 and failed to neutralize a panel of viral isolates in entry-based neutralization assays. To ascertain whether antibodies produced during natural infection could recognize the mimetics, we screened a panel of HIV-1-positive and -negative sera for binding to gp120 and the synthetic antigens. We present evidence from both direct and competitive binding assays that no significant recognition of the glycopeptides was observed, although certain sera did contain antibodies that could compete with 2G12 for binding to recombinant gp120