Association of season of birth with DNA methylation and allergic disease.

BACKGROUND: Season of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy. METHODS: In a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation method examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third-generation cohort newborns. RESULTS: Autumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises post-natally. CONCLUSIONS: This study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.

Trends concerning a common medical school interview question, revisited.

PURPOSE: To assess the validity of asking prospective medical school students about their planned field of practice during their admissions interview at one United States allopathic medical school, and to compare and contrast the results with the results from a similar study conducted in 2004. METHODS: Anonymous one-page surveys were voluntarily filled out and immediately collected from matriculated freshman medical students who wished to participate in this Institutional Review Board (IRB) approved study. RESULTS: Ninety five medical students voluntarily completed and returned the anonymous survey; 82 were filled out correctly. Of the 82 respondents, 32 were uncertain about the field of medicine they plan to pursue. Of the 50 remaining respondents who felt certain of their future direction, 58% (29/50) reported telling the truth when asked about their future direction during the admissions interview, 34% (17/50) were not completely forthcoming and truthful, and 8% (4/50) were not asked at all. CONCLUSIONS: The findings of this study, along with the findings from our 2004 study, strongly suggest that asking prospective medical students during their medical school interview what type of medicine they wish to practice may not yield valid responses.

Neuronal nicotinic acetylcholine receptor subunits in autism: an immunohistochemical investigation in the thalamus.

The cholinergic system has been implicated in the development of autism on the basis of neuronal nicotinic acetylcholine receptor (nAChR) losses in cerebral and cerebellar cortex. In the present study, the first to explore nAChRs in the thalamus in autism, alpha4, alpha7 and beta2 nAChR subunit expression in thalamic nuclei of adult individuals with autism (n=3) and age-matched control cases (n=3) was investigated using immunochemical methods. Loss of alpha7- and beta2- (but not alpha4-) immunoreactive neurons occurred in the paraventricular nucleus (PV) and nucleus reuniens in autism. Preliminary results indicated glutamic acid decarboxylase immunoreactivity occurred at a low level in PV, co-expressed with alpha7 in normal and autistic cases and was not reduced in autism. This suggested loss of neuronal alpha7 in autism is not caused by loss of GABAergic neurons. These findings indicate nicotinic abnormalities that occur in the thalamus in autism which may contribute to sensory or attentional deficits.

Cholinergic nicotinic receptor involvement in movement disorders associated with Lewy body diseases. An autoradiography study using [(125)I]alpha-conotoxinMII in the striatum and thalamus.

The presence of alpha6 subunit containing nicotinic acetylcholine receptors on nigrostriatal dopaminergic neurons has been demonstrated in rodents and monkeys. [(125)I]alpha-conotoxinMII is a radioligand that binds to alpha6, and also alpha3 subunits of nicotinic acetylcholine receptors (nAChRs). In the present study, we have compared the distribution of [(125)I]alpha-conotoxinMII binding in post mortem human tissue from four groups of patients: individuals with dementia with Lewy bodies displaying extra-pyramidal features (DLB + EPF), DLB without extra-pyramidal features (DLB - EPF) Parkinson's disease without dementia (PD) and age-matched controls. Reduced binding was observed in the putamen and caudate in PD and both DLB groups. In DLB patients, the decline was greater in DLB + EPF compared to DLB - EPF group. The declines in nicotinic receptor binding in the striatum were in part paralleled by reductions in the striatal dopamine transporter. In the thalamus, [(125)I]alpha-conotoxinMII binding was significantly reduced in the centromedian nucleus in both DLB groups, and also in the parafascicular nucleus in the DLB - EPF group. In DLB + EPF and PD patients, there was decreased binding in the ventral lateral nucleus. This study demonstrates alterations of alpha6 and/or alpha3 nAChRs binding in DLB and PD, which are likely to relate to extra-pyramidal symptoms.

Differential nicotinic acetylcholine receptor subunit expression in the human hippocampus.

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels composed of alpha and beta subunits with specific structural, functional and pharmacological properties. In this study the distribution of alpha3, alpha4, alpha7, beta2 and beta4 nAChR subunits in the human hippocampus was investigated using immunohistochemistry. Most pyramidal neurons, pre-alpha cells of the entorhinal cortex and dentate granule cells were immunoreactive for all subunits. Small islands of alpha7 immunoreactive cells were present in the outer presubiculum. alpha4 and beta2, and alpha3, alpha4 and beta2 immunoreactive fibre tracts were present in the stratum radiatum and subiculum, respectively, suggesting nAChRs may play a role in modulating inputs to the hippocampus via Schaffer collaterals and along the perforant pathway. Some astrocytes were immunoreactive for alpha3, alpha7 and beta4 subunits. Immunoreactivity to all subunits was noted in association with blood vessels. These results indicate the involvement of multiple nAChR subtypes in the modulation of both neuronal and non-neuronal functions in the human hippocampus.

Human brain nicotinic receptors, their distribution and participation in neuropsychiatric disorders.

Mapping of nicotinic acetylcholine receptor (nAChR) subtypes and subunits in human brain is far from complete, however it is clear that multiple subunits are present (including alpha3, alpha4, alpha5, alpha6 and alpha7, beta2, alpha3 and beta4) and that these receptors are not solely distributed on neurones, but also on cerebral vasculature and astrocytes. It is important to elucidate subunit composition of receptors associated with different cell types and pathways within the human CNS in terms of potential nicotinic therapy for a range of both developmental and age-related disorders in which nAChR attenuation occurs. Reductions in nAChRs are reported in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies, schizophrenia and autism, but may not be associated with reduced cortical cholinergic innervation observed in vascular dementia or occur at an early stage in Down's syndrome. Changes in nAChR expression in neuropsychiatric disorders appear to be brain region and subtype specific and have been shown in some instances to be associated with pathology and symptomatology. It is likely that deficits in alpha4-containing receptors predominate in cortical areas in Alzheimer's disease and autism, whereas reduction of alpha7 receptors may be more important in schizophrenia. Changes in astrocytic and vascular nAChR expression in neurodegenerative diseases should also be considered. Studies using both animal models and human autopsy tissue suggest that nAChRs can play a role in neuroprotection against age-related pathology. It is possible that the development of nAChR subtype specific drugs may lead to advances in therapy for both age-related and psychiatric disorders.

Federal Nursing Service Award. Impact of TriCare/managed care on total force readiness.

Mission readiness is dependent on a healthy total force and the response of military medical and nursing services. Managed care has become the norm in U.S. health care, including the Department of Defense Military Health System. Cost management, health maintenance organizations, and other health plans are defined as "managed care," an aggressive cost-control effort by health care purchasers and insurers to limit health care spending and services and advance a market-oriented, profit-driven system. The impact of managed care on mission readiness and retention of active and reserve personnel is and will continue to be profound. The purpose of this research was to conduct a qualitative, phenomenological study (life experiences) of TriCare/managed care to explore the impact and the meaning of the experience on total force mission readiness of the U.S. Air Force and how managed care has changed nursing practice. The results reveal the significance of the impact of TriCare/managed care on total force readiness by identifying, through themes, meta-themes, and a representative model, the negative effect that economics is having on active duty and reserve force health and well-being.

A phenomenologic study of the interface of caring and technology in intermediate care: toward a reflexive ethics for clinical practice.

A phenomenologic research study of nurse caring was conducted in an intermediate care unit of a hospital. Three narratives from the data are presented as examples to illuminate the meaning of the experience of caring for technologically dependent patients. Results revealed that vulnerability, suffering, and the ethical situations of moral blurring and moral blindness were the dynamics of caring for these patients. Identification of these phenomena cells for a new reflexive ethics in health care to increase understanding of how deep values in relation to the status of vulnerable human beings, and how moral interactions among patients, families, and caregivers, shape ethical decisions.

Consciousness and the moral ideal: a transcultural analysis of Watson's theory of transpersonal caring.

The global society in which advanced practice nurses work calls for an appreciation of cultural diversity and transcultural care. Theories to guide education, research, and practice must therefore incorporate understanding of cultural concepts. Watson's transpersonal caring theory, which is shaped by the tenets of consciousness and the moral ideal, does not address cultural care per se but does bring into focus the forces of the moral and the spiritual in the event of caring. Thus, it has the potential to be valuable in culturally diverse transcultural nursing situations.

The ethical theory of existential authenticity: the lived experience of the art of caring in nursing administration.

The purpose of this research was to conduct a study of the art of caring in nursing administration. By means of a phenomenologic-hermeneutic approach, the caring experiences of six nurse administrators were revealed and analyzed. Essential themes emerged from their descriptions of their experiences. Interpretation of the data served as the lens through which the expressions of the art of caring related to archetypical philosophies of art: living form, imitation, and expression. An ethical theory, Existential Authenticity, was uncovered as the unity of meaning of nursing administrative caring art. This unity of meaning embodied statespersonship, which was viewed by Plato as the highest form of art. Implications for the transformation of nursing administrative practice as an ethical caring enterprise by the manifestation of statespersonship are presented.

The edge of chaos: caring and the bottom line.

Nurse managers need to provide quality health care within a framework of human caring with limited economic resources. Seeking only "bottom line" solutions would seriously affect the well-being of nurses and clients. On the other hand, seeking only human caring solutions would seriously influence the well-being of health care organizations. A composite model balances economics or the "bottom line" and human caring.

Trial of labor after cesarean delivery with a lower-segment, vertical uterine incision: is it safe?

OBJECTIVE: Our purpose was to assess maternal and perinatal outcomes associated with a trial of labor and attempted vaginal birth after prior low-segment vertical cesarean delivery. STUDY DESIGN: During a 10-year period in a single tertiary hospital, all patients with a prior low-segment uterine incision (whether vertical or transverse) were considered candidates for a trial of labor in the absence of other contraindications or patient refusal. Among the 1137 women who underwent low-segment vertical cesarean delivery, 262 were subsequently delivered of 322 live-born infants, and 174 (54%) of them were identified retrospectively as having attempted vaginal birth. The maternal and perinatal outcomes of patients who did or did not undergo a trial of labor were analyzed and compared. RESULTS: No significant differences between the two patient groups were observed regarding demographic characteristics, antepartum complications, gestational age at delivery (mean 37.4 weeks), birth weight, and cord pH at delivery. Vaginal delivery was accomplished successfully in 144 of 174 (83%) patients who underwent a trial of labor. Abdominal delivery was necessary for 17 mothers with labor disorders and 13 with suspected fetal distress. Postpartum hemorrhage occurred more often in the trial of labor group (7/174 [4.0%] vs 2/148 [1.4%], p not significant), but endometritis developed significantly more often in patients with elective repeat cesarean delivery (16.9% vs 6.3%, p = 0.006). Rupture of the low-segment vertical cesarean scar occurred in 2 patients during a trial of labor (1.1%) versus none in the elective repeat cesarean group. Neither mother experienced fetal extrusion or adverse maternal or fetal sequelae. Frequency of serious neonatal complications (8.1% vs 10%) and neonatal mortality (1.7% vs 2.0%) were similar between groups. All neonatal deaths were a result of extreme prematurity or congenital anomalies. CONCLUSIONS: Our experience indicates that a mother with a prior low-segment vertical cesarean delivery can undertake a trial of labor with relative maternal-perinatal safety. The likelihood of successful outcome and the incidence of complications are comparable to those of published experience with a trial of labor after a previous low-segment transverse incision.

Transcultural nursing ethics: a framework and model for transcultural ethical analysis.

Increased awareness of cultural diversity in contemporary society and nursing mandates the need for transcultural nursing ethics. The core of this ethics assumes that all discourse and interaction is transcultural because of strengths and differences in values and beliefs of individuals and groups within global society. Transcultural ethics addresses how people ought to live when subjectively sharing a common world. This article presents a framework and model with four parts: Transcultural Caring Dynamics, Principles, Transcultural Context, and Universal Source. These incorporate the ethics of virtue, principle, values, and belief, respectively. Interactive parts of the holistic process provide the foundation for assessing and analyzing transactions to facilitate understanding and direction toward culturally based ethical decision making.

A descriptive study of care processes using total quality management as a framework in a USAF regional hospital emergency service and related services.

The purpose of this descriptive study was to investigate access to care processes in a military regional hospital Emergency Service (ES) and related services using a Total Quality Management framework. Tabulations of demographic survey data revealed that the ES is used mainly as a primary care clinic, with a greater proportion of pediatric care provided during peak hours. An analysis of patterns of care processes in the organizational system revealed that there was little in common between Total Quality Management and Continuous Quality Improvement principles and the care processes. The results of the analysis lend support to the proposed USAF decentralized, coordinated health care system with more authority and control given to local commands and emphasis upon increased responsibility and accountability within professional and beneficiary communities.

Preoperative skin preparation and intraoperative pelvic irrigation: impact on post-cesarean endometritis and wound infection.

OBJECTIVE: To determine the impact of two skin preparation methods and two techniques of pelvic irrigation on the incidence of post-cesarean endometritis and wound infection in an indigent patient population. METHODS: A randomized study was performed in 100 cesarean patients. Subjects were assigned to one of four groups, involving either standard skin preparation (povidone-iodine [7.5%] scrub followed by povidone-iodine [10%] solution) or special skin preparation (5-minute scrub with parachlorometaxylenol followed by povidone scrub and solution), and either normal saline or antibiotic (cefazolin sodium, 1 g in 500 mL normal saline) irrigation of the pelvis and subcutaneous tissue at uterine and fascial closure. Four groups of patients were formed: standard skin preparation plus normal saline irrigation, standard preparation plus antibiotic irrigation, special preparation plus normal saline irrigation, and special preparation plus antibiotic irrigation. RESULTS: Endometritis occurred significantly more often in the combined groups that did not include antibiotic irrigation than in the combined groups involving antibiotic irrigation (P < .001). In contrast, comparison of skin preparation methods between povidone-iodine alone versus preparation including parachlorometaxylenol indicated no significant difference (P = .22). CONCLUSION: Skin preparation with an antibacterial scrub in addition to standard povidone-iodine scrub and solution does not appear to play as significant a role in the reduction of post-cesarean endometritis or wound infection as does intraoperative pelvic irrigation with antibiotic solution.