Partners in Growth: Implementing Family-Centered Changes in the Neonatal Intensive Care Unit

Although there are several forces driving changes with regard to parents within neonatal intensive care units (NICUs), they all culminate in the ideals represented in family-centered care. This article examined the variables that are perceived by parents to be barriers to their assumption of parental roles while their infants were hospitalized in the NICU. Data were used to support and implement pragmatic changes in program development and service delivery within the NICU.     

Modification of peanut allergen Ara h 3: effects on IgE binding and T cell stimulation

BACKGROUND: Peanut allergy is a major health concern due to the increased prevalence, potential severity, and chronicity of the reaction. The cDNA encoding a third peanut allergen, Ara h 3, has been previously cloned and characterized. Mutational analysis of the Ara h 3 IgE-binding epitopes with synthetic peptides revealed that single amino acid changes at critical residues could diminish IgE binding. METHODS: Specific oligonucleotides were used in polymerase chain reactions to modify the cDNA encoding Ara h 3 at critical IgE binding sites. Four point mutations were introduced into the Ara h 3 cDNA at codons encoding critical amino acids in epitopes 1, 2, 3 and 4. Recombinant modified proteins were used in SDS-PAGE/Western IgE immunoblot, SDS-PAGE/Western IgE immunoblot inhibition and T cell proliferation assays to determine the effects of these changes on in vitro clinical indicators of peanut hypersensitivity. RESULTS: Higher amounts of modified Ara h 3 were required to compete with the wild-type allergen for peanut-specific serum IgE. Immunoblot analysis with individual serum IgE from Ara-h-3-allergic patients showed that IgE binding to the modified protein decreased approximately 35-85% in comparison to IgE binding to wild-type Ara h 3. Also, the modified Ara h 3 retained the ability to stimulate T cell activation in PBMCs donated by Ara-h-3-allergic patients. CONCLUSIONS: The engineered hypoallergenic Ara h 3 variant displays two characteristics essential for recombinant allergen immunotherapy; it has a reduced binding capacity for serum IgE from peanut-hypersensitive patients and it can stimulate T-cell proliferation and activation.     

Population pharmacokinetic modeling for enterohepatic recirculation in Rhesus monkey.

Enterohepatic recirculation (EHR) occurs via biliary excretion and intestinal reabsorption of a drug. Drug recycling through EHR can lead to a change in pharmacokinetic (PK) properties, such as reduced clearance (CL), extended half-life (T(1/2)) and increased plasma exposure (AUC). As a result, EHR may prolong the pharmacological effect of drugs. In the present study, the compound (Cpd A) was found to exhibit EHR in Rhesus monkeys associated with a reduction in CL (from 3.8 to 0.33 Lh(-1), IV; from 2.3 to 0.4 Lh(-1), PO), and an increase in T(1/2) (from 0.9 to 18 h, IV) and in AUC (from 1.5 to 17.4 microg h/mL, IV; from 2.8 to 16.3 microg h/mL, PO), by comparing the PK in the monkeys via the interruption of EHR (bile-duct cannulation) with that in the intact monkeys. A population four-compartment model was constructed based on recirculation loops incorporating all possible inputs (bile secretion, a lag-time model for gall bladder emptying, routes and amounts of a single dose administration) to fully evaluate the EHR of Cpd A. The plasma concentrations versus time profiles predicted from the model had a good fit to the values observed in the subjects and were further simulated with 90% confidence interval to demonstrate its utility. Thus, the model could be applied as a useful tool to evaluate the drugs or compounds that undergo EHR in different species.     

MicroRNA Signature and Cellular Characterization of Undifferentiated and Differentiated House Ear Institute-Organ of Corti 1 (HEI-OC1) Cells

Journal of the Association for Research in Otolaryngology - MicroRNAs (miRNAs) regulate gene expressions and control a wide variety of cellular functions. House Ear Institute-Organ of Corti 1...     

Molecular fixative enables expression microarray analysis of microdissected clinical cervical specimens

Formalin-fixed tissue has been a mainstay of clinical pathology laboratories, but formalin alters many biomolecules, including nucleic acids and proteins. Meanwhile, frozen tissues contain better-preserved biomolecules, but tissue morphology is affected, limiting their diagnostic utility. Molecular fixatives promise to bridge this gap by simultaneously preserving morphology and biomolecules, enabling clinical diagnosis and molecular analyses on the same specimen. While previous reports have broadly evaluated the use of molecular fixative in various human tissues, we present here the first detailed assessment of the applicability of molecular fixative to both routine histopathological diagnosis and molecular analysis of cervical tissues. Ten specimens excised via the loop electrosurgical excision procedure, which removes conical tissue samples from the cervix, were cut into alternating pieces preserved in either formalin or molecular fixative. Cervical specimens preserved in molecular fixative were easily interpretable, despite featuring more eosinophilic cytoplasm and more recognizable chromatin texture than formalin-fixed specimens. Immunohistochemical staining patterns of p16 and Ki-67 were similar between fixatives, although Ki-67 staining was stronger in the molecular fixative specimens. The RNA of molecular fixative specimens from seven cases representing various dysplasia grades was assessed for utility in expression microarray analysis. Cluster analysis and scatter plots of duplicate samples suggest that data of sufficient quality can be obtained from as little as 50 ng of RNA from molecular fixative samples. Taken together, our results show that molecular fixative may be a more versatile substitute for formalin, simultaneously preserving tissue morphology for clinical diagnosis and biomolecules for immunohistochemistry and gene expression analysis.     

MicroRNAs in an oral cancer context - from basic biology to clinical utility

Oral cancer is one of the most commonly diagnosed malignancies worldwide. Its dismal five-year survival rate of ~50% has barely changed for decades. A better understanding of the molecular basis of tumorigenesis - with particular emphasis on disease initiation and progression - is needed to improve clinical outcomes, since this will facilitate the development of drugs and management strategies based on the specific genetic changes underpinning disease behaviors. MicroRNAs (miRNAs), a class of short non-coding RNAs that down-regulate gene expression, have been demonstrated to play essential roles in human cancers. miRNA deregulation has been observed in many tumor types and is implicated in oncogenic cell processes, including proliferation, survival, apoptosis, metastasis, and chemoresistance. In addition, miRNA alterations have been associated with specific clinical phenotypes such as disease progression or recurrence, development of metastases, and post-operative survival. Recent studies have explored the utility of miRNAs as diagnostic and prognostic tools and as potential therapeutic targets. Herein, we discuss miRNA biology and provide a summary of the key findings on the role of miRNAs in oral malignancies.     

First Nation Elders’ perspectives on healthy ageing in NSW,Australia

Objectives : Healthy ageing has been unattainable for many of Australia’s First Nation people, driven by an earlier onset of chronic disease when compared to the general Australian population. Our objective was to examine the perspectives of Australian First Nation people about healthy ageing. Methods : We used a conversational method to gather knowledge from older First Nation people from established communities in New South Wales, Australia. Discussions were audio recorded and transcribed and analysed using an Indigenous research standpoint methodology. Eight yarning circles were held in six locations with 76 participants aged 45 years and over. Results : Key issues around healthy ageing were identified; particularly, what the impact of chronic disease means to individuals. Study participants reported that healthy ageing is essential to continue to share knowledge of their history and culture. Conclusion : This article highlights the need for culturally appropriate healthy ageing programs addressing issues related to chronic disease among First Nation communities. Implications for public health : Research into what constitutes healthy ageing for older First Nation people is necessary for the development of culturally appropriate chronic disease interventions.     

Midwives and the fetal nuchal cord: a survey of practices and perceptions

A systematic search of studies of intrapartum management of the nuchal umbilical cord at term found no published controlled studies in this area. A postal survey containing both structured and open questions and a request for local protocols and guidelines was sent to all 637 midwives in 7 maternity units in England. There were 401 (63%) responses. There appeared to be no unit guidelines for this area of practice. Midwife approaches to nuchal cord during birth varied, and included clamping and cutting of loose nuchal cords and a hands-off approach to tight nuchal cords. Reasons for specific actions included doing what had been taught during midwifery training and learning from previous personal experiences. Theories of diffusion of innovation and of planned behaviour may provide a conceptual basis for understanding the adoption of specific practices. Future qualitative and controlled studies are needed to explore the nature and consequences of varying approaches to intrapartum nuchal cord management.