Experiences of husbands attending their wives’ childbirth

目的：本研究では，立ち会い分娩をした夫の体験を明らかにすることを目的とする． 方法：本研究に同意の得られた，初産婦の夫１１名を対象として，妻の産褥入院期間中に，インタビューガイドに基づき，入院から分娩後２時間までの体験についてインタビューを行い，質的記述的に分析した． 結果：立ち会い分娩における夫の体験として，１７１のエピソード，４４のコード，１６のサブカテゴリーが抽出され，【わが子を迎える喜びと感動が湧く】，【無力な自分にとにかくできることを手探りでやってみる】，【母親となる妻へ称賛の念を抱く】，【父親としての意識が芽生える】，【医療者にさまざまな感情を抱きながら，任せる】，【自分なりに分娩の様相を読み取ろうとする】の６つのカテゴリーが抽出された． 結論：夫は，わが子を迎える喜びと感動が湧く中で，自分の無力さを感じながら，それでも自分にできることを手探りでやろうとしている様子が伺えた．医療者には，苦しむ妻を前にして，自分の辛さや不安を表出することなく，ひたすら立ち会い続けている夫の心情を酌み取り，夫にとってもよい分娩体験となるような関わりが求められる．Objectives：To describe the experiences of husbands who attended their wives’ childbirth. Methods：Qualitative and descriptive analysis of narratives from eleven husbands of primipara women who consented to this study. A questionnaire was used as guide for participants based on the Guidelines for Interview Questions. Results：Six thematic categories were revealed from the narratives of husbands describing their experiences when they attended their wives’ childbirth. These are : ‘feeling pleasure and excitement to have my own baby’, ‘trying to do what I can do through trial and error although there may be little I can do’, ‘feeling respect for my wife who is becoming a mother’, ‘having a sense of being a father’, ‘trusting in healthcare professionals and having various feelings towards them’, and ‘trying to understand what childbirth is in my own way’. Conclusion：Although the husbands felt their helplessness, in this situation, they also felt the excitement of having their own baby- they were hopeful and tried to do what they could do through trial and error. Healthcare workers need to understand the husbands’ experiences while attending their wives’ childbirth, not showing their own hardships and anxiety in front of their wives who were experiencing the joys and pain of childbirth, and to help them to make the childbirth a wonderful experience for them and for their wives as well

Differential Requirements for Vav Proteins in DAP10- and ITAM-mediated NK Cell Cytotoxicity

Natural killer (NK) cells express multiple activating receptors that initiate signaling cascades through DAP10- or immunoreceptor tyrosine-based activation motif–containing adapters, including DAP12 and FcRγ. Among downstream signaling mediators, the guanine nucleotide exchange factor Vav1 carries out a key role in activation. However, whether Vav1 regulates only some or all NK cell–activating pathways is matter of debate. It is also possible that two other Vav family molecules, Vav2 and Vav3, are involved in NK cell activation. Here, we examine the relative contribution of each of these exchange factors to NK cell–mediated cytotoxicity using mice lacking one, two, or all three Vav proteins. We found that Vav1 deficiency is sufficient to disrupt DAP10-mediated cytotoxicity, whereas lack of Vav2 and Vav3 profoundly impairs FcRγ- and DAP12-mediated cytotoxicity. Our results provide evidence that these three Vav proteins function specifically in distinct pathways that trigger NK cell cytotoxicity

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

After a nascent chain of a membrane protein emerges from the ribosomal tunnel, the protein is integrated into the cell membrane. This process is controlled by a series of proteinaceous molecular devices, such as signal recognition particles and Sec translocons. In addition to these proteins, we discovered two endogenous components regulating membrane protein integration in the inner membrane of Escherichia coli. The integration is blocked by diacylglycerol (DAG), whereas the blocking is relieved by a glycolipid named membrane protein integrase (MPIase). Here, we investigated the influence of these integration-blocking and integration-promoting factors on the physicochemical properties of membrane lipids via solid-state NMR and fluorescence measurements. These factors did not have destructive effects on membrane morphology because the membrane maintained its lamellar structure and did not fuse in the presence of DAG and/or MPIase at their effective concentrations. We next focused on membrane flexibility. DAG did not affect the mobility of the membrane surface, whereas the sugar chain in MPIase was highly mobile and enhanced the flexibility of membrane lipid headgroups. Comparison with a synthetic MPIase analog revealed the effects of the long sugar chain on membrane properties. The acyl chain order inside the membrane was increased by DAG, whereas the increase was cancelled by the addition of MPIase. MPIase also loosened the membrane lipid packing. Focusing on the transbilayer movement, MPIase reduced the rapid flip-flop motion of DAG. On the other hand, MPIase could not compensate for the diminished lateral diffusion by DAG. These results suggest that by manipulating the membrane lipids dynamics, DAG inhibits the protein from contacting the inner membrane, whereas the flexible long sugar chain of MPIase increases the opportunity for interaction between the membrane and the protein, leading to membrane integration of the newly formed protein

VAV2 and VAV3 as Candidate Disease Genes for Spontaneous Glaucoma in Mice and Humans

Background: Glaucoma is a leading cause of blindness worldwide. Nonetheless, the mechanism of its pathogenesis has not been well-elucidated, particularly at the molecular level, because of insufficient availability of experimental genetic animal models. Methodology/Principal Findings: Here we demonstrate that deficiency of Vav2 and Vav3, guanine nucleotides exchange factors for Rho guanosine triphosphatases, leads to an ocular phenotype similar to human glaucoma. Vav2/Vav3-deficient mice, and to a lesser degree Vav2-deficient mice, show early onset of iridocorneal angle changes and elevated intraocular pressure, with subsequent selective loss of retinal ganglion cells and optic nerve head cupping, which are the hallmarks of glaucoma. The expression of Vav2 and Vav3 tissues was demonstrated in the iridocorneal angle and retina in both mouse and human eyes. In addition, a genome-wide association study screening glaucoma susceptibility loci using single nucleotide polymorphisms analysis identified VAV2 and VAV3 as candidates for associated genes in Japanese open-angle glaucoma patients. Conclusions/Significance: Vav2/Vav3-deficient mice should serve not only as a useful murine model of spontaneous glaucoma, but may also provide a valuable tool in understanding of the pathogenesis of glaucoma in humans, particularly the determinants of altered aqueous outflow and subsequent elevated intraocular pressure

D-dimer trends predict recurrent stroke in patients with cancer-related hypercoagulability

Abstract Introduction: In patients with cancer-associated hypercoagulability (CAH)-related stroke, D-dimer trends after anticoagulant therapy may offer a biomarker of treatment efficacy. The purpose of this study was to clarify the association between D-dimer trends and recurrent stroke after anticoagulant therapy in patients with CAH-related stroke. Methods: We performed retrospective cohort study of consecutive patients with CAH-related stroke at two stroke centers from 2011 through 2020. The ratio of post-treatment to pre-treatment D-dimer levels (post/pre ratio) was used as an indicator of D-dimer trends after anticoagulant therapy. Fine–Gray models were used to evaluate the association between post/pre ratio and recurrent stroke. Results: Among 360 acute ischemic stroke patients with active cancer, 73 patients with CAH-related stroke were included in this study. Recurrent stroke occurred in 13 patients (18%) during a median follow-up time of 28 days (interquartile range, 11–65 days). Multivariate analysis revealed that high post/pre ratio was independently associated with recurrent stroke (per 0.1 increase: hazard ratio 2.20, 95% confidence interval 1.61–3.01, p=0.012). Discussion and Conclusion: D-dimer levels after anticoagulant therapy were associated with recurrent stroke in CAH-related stroke patients. Patients with neutral trends in high D-dimer levels after anticoagulant therapy were at high risk of recurrent stroke

An ITAM-signaling pathway controls cross-presentation of particulate but not soluble antigens in dendritic cells

Dendritic cells (DC) possess a unique capacity for presenting exogenous antigen on major histocompatibility class I, a process that is referred to as cross-presentation, which serves a critical role in microbial and tumor immunity. During cross-presentation, antigens derived from pathogen-infected or tumor cells are internalized and processed by DCs for presentation to cytotoxic T lymphocytes (CTLs). We demonstrate that a signaling pathway initiated by the immunoreceptor tyrosine–based activation motif (ITAM)–containing adaptors DAP12 and FcRγ utilizes the Vav family of Rho guanine nucleotide exchange factors (GEFs) for processing and cross-presentation of particulate, but not soluble, antigens by DCs. Notably, this novel pathway is crucial for processing and presentation of particulate antigens, such as those associated with Listeria monocytogenes bacteria, yet it is not required for antigen uptake. Mechanistically, we provide evidence that in DCs, Vav GEFs are essential to link ITAM-dependent receptors with the activation of the NOX2 complex and production of reactive oxygen species (ROS), which regulate phagosomal pH and processing of particulate antigens for cross-presentation. Importantly, we show that genetic disruption of the DAP12/FcRγ–Vav pathway leads to antigen presentation defects that are more profound than in DCs lacking NOX2, suggesting that ITAM signaling also controls cross-presentation in a ROS-independent manner