Electrochemical synthesis of the protected cyclic (1,3;1,6)-ß-glucan dodecasaccharide.

Automated electrochemical assembly is an electrochemical method to synthesise middle-sized molecules, including linear oligosaccharides, and some linear oligosaccharides can be electrochemically converted into the corresponding cyclic oligosaccharides effectively. In this study, the target cyclic oligosaccharide is a protected cyclic (1,3;1,6)-ß-glucan dodecasaccharide, which consists of two types of glucose trisaccharides with ß-(1,3)- and ß-(1,6)-glycosidic linkages. The formation of the protected cyclic dodecasaccharide was confirmed by the electrochemical one-pot dimerisation-cyclisation of the semi-circular hexasaccharide. The yield of the protected cyclic dodecasaccharide was improved by using a stepwise synthesis via the linear dodecasaccharide.

Use of the Newborn Behavioral Observations System as an early intervention for infants and their parents: A scoping review.

BACKGROUND: The Newborn Behavioral Observations (NBO) system is an infant-focused, family-centered, relationship-based tool designed to help parents become aware of their baby's abilities and to promote a positive parent-child relationship from the very beginning of birth. AIMS: The aim of this scoping review was to provide an overview of the key characteristics of the research and evidence accumulated over the past 17 years on the early NBO intervention for infants and their parents to identify the existing research gaps and to inform the future direction of research on the NBO System. STUDY DESIGN: A scoping review guided by Arksey and O'Malley's methodological framework and the PRISMA-ScR Checklist was conducted. This review used six databases (PubMed, CINAHL, MEDLINE, Google Scholar, Ichushi-Web, and CiNii) and was limited to English and Japanese language articles from January 2006, when the NBO was developed, to September 2022. Reference lists were also hand-searched to further identify relevant articles from the NBO site. RESULTS: A total of 29 articles were selected. Through the analysis of included articles, four overarching themes were identified: (1) usage pattern of the NBO; (2) participants, setting, duration, and frequency of the NBO intervention; (3) outcome measures and effects of the NBO intervention; and (4) findings from a qualitative perspective. The review suggested that early NBO intervention had a positive impact on maternal mental health and sensitivity to the infant, confidence and knowledge of practitioners, and infant development. CONCLUSIONS: This scoping review shows that the early NBO intervention has been implemented in a variety of cultures and settings and by professionals of various disciplines. However, research to evaluate the long-term effects of this intervention on a wider range of subjects is needed.

Genetically and chemically tuned haemoglobin-albumin trimers with superior O2 transport efficiency.

Haemoglobin (Hb)-albumin (HSA) trimers were synthesized using five distinct Hb variants in which the structures were genetically and chemically tuned as an artificial O2 carrier and used as a red blood cell (RBC) substitute. The trimers were found to have moderately low O2 affinity (p50 = 23-34 Torr, 37 °C) and high co-operativity, yielding a maximum O2 transport efficiency 1.8-fold higher than that of human RBCs.

Effectiveness of parenting education for expectant primiparous women in Asia: a systematic review.

OBJECTIVE: This review evaluated the effectiveness of antenatal parenting education versus usual care for maternal confidence, maternal depressive symptoms, and parenting stress among expectant primiparous women in Asia. INTRODUCTION: Previous reviews on parenting education have mostly examined practices in non-Asian countries and found that no single parenting education program met the needs of all parents. Given that there may be some common characteristics in Asian cultures, such as grandparents' involvement with child care, this review focused on specific interventions in determining the effects of practices on particular outcomes in these populations, so that providers of antenatal education can tailor interventions that are more culturally appropriate for Asian women. INCLUSION CRITERIA: Studies published in English or Japanese that included expectant primiparous women and couples in Asia who received antenatal parenting education were considered. The outcomes were maternal confidence, maternal depressive symptoms, and parenting stress. METHODS: The authors searched for English-language articles up to February 2019 using MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and PsycINFO. They also searched Ichushi-Web for Japanese articles. A gray literature search was conducted using Google Scholar and ProQuest Health and Medical Collection. Two independent reviewers selected studies, and a critical appraisal was undertaken using appropriate JBI tools. Data were presented in narrative form owing to the heterogeneity of the included studies. RESULTS: Four studies involving 652 pregnant women were included: three were randomized controlled trials, and one was a quasi-experimental study. The studies were conducted in China, Hong Kong, and Taiwan, and included the following antenatal parenting education interventions: interpersonal, psychotherapy-oriented childbirth education; childbirth psychoeducation based on the concept of learned resourcefulness; and Internet newborn-care education based on self-efficacy theory. Overall, the methodological quality of the included studies was moderate. Meta-analysis was not possible owing to the heterogeneity, including small sample sizes and differences in intervention content, populations, and follow-up times. A subsequent narrative synthesis was undertaken for each outcome. Of three studies with maternal confidence as an outcome (n = 496), two showed significantly higher maternal confidence at six weeks' (P = 0.000, Cohen's d = 1.41) and three months' postpartum (P = 0.016, Cohen's d = 0.35) in the intervention groups; however, one study showed no significant group differences. Of three studies with maternal depressive symptoms as an outcome (n = 534), two found significantly fewer depressive symptoms at three months' (P = 0.018, Cohen's d = -0.34) and six months' postpartum (P = 0.005, Cohen's d = -0.42) in the intervention groups; however, one study revealed no significant group differences. Parenting stress was examined in one study (n = 156); it showed significantly lower parenting stress (P = 0.017, Cohen's d = 0.38) immediately after the intervention. CONCLUSIONS: There is insufficient evidence to support the effectiveness of a specific type of antenatal parenting education for maternal confidence, maternal depressive symptoms, and parenting stress for expectant primiparous women in Asia. However, the findings suggest that specific theory-oriented antenatal parenting education is potentially effective for those women. Further high-quality studies are needed for antenatal parenting education among expectant primiparous women, especially in Asia.

Haemoglobin(ßK120C)-albumin trimer as an artificial O2 carrier with sufficient haemoglobin allostery.

The allosteric O2 release of haemoglobin (Hb) allows for efficient O2 delivery from the lungs to the tissues. However, allostery is weakened in Hb-based O2 carriers because the chemical modifications of the Lys- and Cys-ß93 residues prevent the quaternary transition of Hb. In this paper, we describe the synthesis and O2 binding properties of a recombinant Hb [rHb(ßK120C)]-albumin heterotrimer that maintains sufficient Hb allostery. The rHb(ßK120C) core, with two additional cysteine residues at the symmetrical positions on its protein surface, was expressed using yeast cells. The mutations did not influence either the O2 binding characteristics or the quaternary transition of Hb. Maleimide-activated human serum albumins (HSAs) were coupled with rHb(ßK120C) at the two Cys-ß120 positions, yielding the rHb(ßK120C)-HSA2 trimer, in which the Cys-ß93 residues were unreacted. Molecular dynamics simulation demonstrated that the HSA moiety does not interact with the amino acid residues around the haem pockets and the α1ß2 surfaces of the rHb(ßK120C) core, the alteration of which retards Hb allostery. Circular dichroism spectroscopy demonstrated that the quaternary transition between the relaxed (R) state and the tense (T) state of the Hb core occurred upon both the association and dissociation of O2. In phosphate-buffered saline solution (pH 7.4) at 37 °C, the rHb(ßK120C)-HSA2 trimer exhibited a sigmoidal O2 equilibrium curve with the O2 affinity and cooperativity identical to those of native Hb (p 50 = 12 Torr, n = 2.4). Moreover, we observed an equal Bohr effect and 2,3-diphosphoglycerate response in the rHb(ßK120C)-HSA2 trimer compared with naked Hb.

Bi-allelic CSF1R Mutations Cause Skeletal Dysplasia of Dysosteosclerosis-Pyle Disease Spectrum and Degenerative Encephalopathy with Brain Malformation.

Colony stimulating factor 1 receptor (CSF1R) plays key roles in regulating development and function of the monocyte/macrophage lineage, including microglia and osteoclasts. Mono-allelic mutations of CSF1R are known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS), an adult-onset progressive neurodegenerative disorder. Here, we report seven affected individuals from three unrelated families who had bi-allelic CSF1R mutations. In addition to early-onset HDLS-like neurological disorders, they had brain malformations and skeletal dysplasia compatible to dysosteosclerosis (DOS) or Pyle disease. We identified five CSF1R mutations that were homozygous or compound heterozygous in these affected individuals. Two of them were deep intronic mutations resulting in abnormal inclusion of intron sequences in the mRNA. Compared with Csf1r-null mice, the skeletal and neural phenotypes of the affected individuals appeared milder and variable, suggesting that at least one of the mutations in each affected individual is hypomorphic. Our results characterized a unique human skeletal phenotype caused by CSF1R deficiency and implied that bi-allelic CSF1R mutations cause a spectrum of neurological and skeletal disorders, probably depending on the residual CSF1R function.

Microneedle pH Sensor: Direct, Label-Free, Real-Time Detection of Cerebrospinal Fluid and Bladder pH.

Acid-base homeostasis (body pH) inside the body is precisely controlled by the kidneys and lungs and buffer systems, such that even a minor pH change could severely affect many organs. Blood and urine pH tests are common in day-to-day clinical trials and require little effort for diagnosis. There is always a great demand for in vivo testing to understand more about body metabolism and to provide effective diagnosis and therapy. In this article, we report the simple fabrication of microneedle-based direct, label-free, and real-time pH sensors. The reference and working electrodes were Ag/AgCl thick films and ZnO thin films on tungsten (W) microneedles, respectively. The morphological and structural characteristics of microneedles were carefully investigated through various analytical methods. The developed sensor exhibited a Nernstian response of -46 mV/pH. Different conditions were used to test the sensor to confirm their accuracy and stability, such as various buffer solutions, with respect to time, and we compared the reading with commercial pH electrodes. Besides that, the fabricated microneedle sensor ability is proven by in vivo testing in mouse cerebrospinal fluid (CSF) and bladders. The pH sensor procedure reported here is totally reversible, and results were reproducible after several rounds of testing.

Real-time imaging of mast cell degranulation in vitro and in vivo.

Mast cells undergo degranulation in response to various stimuli and rapidly release pre-formed mediators present in secretory granules, leading to immediate-type allergic reactions. Mast cell degranulation is commonly detected and quantified in vitro by measuring histamine or ß-hexosaminidase released to culture medium. However, this type of assay cannot monitor degranulation of individual cells in real time, and it is not suitable for in vivo detection of degranulation. At the aim of real time imaging of mast cell degranulation at single cell level, we here developed a fluorescent protein-based indicator of degranulation, designated immuno-pHluorin (impH). When expressed in mast cells, impH is located in the membrane of secretory granules and non-fluorescent under homeostatic conditions while it turns fluorescent following degranulation, due to the pH change inside of granules during exocytosis. impH enabled us to detect polarized degranulation within one single cell when mast cells were stimulated via the small area of cell surface. Transplantation of impH-expressing mast cells into mast cell-deficient mice demonstrated that impH could function as a real-time indicator of degranulation in vivo. Thus, impH is a useful tool for imaging of mast cell activation and degranulation in vitro and in vivo, and may be applied for screening of reagents regulating mast cell degranulation.