Chronic desipramine treatment rescues depression-related, social and cognitive deficits in Engrailed-2 knockout mice.

Engrailed-2 (En2) is a homeobox transcription factor that regulates neurodevelopmental processes including neuronal connectivity and elaboration of monoaminergic neurons in the ventral hindbrain. We previously reported abnormalities in brain noradrenergic concentrations in En2 null mutant mice that were accompanied by increased immobility in the forced swim test, relevant to depression. An EN2 genetic polymorphism has been associated with autism spectrum disorders, and mice with a deletion in En2 display social abnormalities and cognitive deficits that may be relevant to multiple neuropsychiatric conditions. This study evaluated the ability of chronic treatment with desipramine (DMI), a selective norepinephrine (NE) reuptake inhibitor and classical antidepressant, to reverse behavioral abnormalities in En2−/− mice. Desipramine treatment significantly reduced immobility in the tail suspension and forced swim tests, restored sociability in the three-chambered social approach task and reversed impairments in contextual fear conditioning in En2−/− mice. Our findings indicate that modulation of brain noradrenergic systems rescues the depression-related phenotype in En2−/− mice and suggest new roles for NE in the pathophysiology of the social and cognitive deficits seen in neuropsychiatric disorders such as autism or schizophrenia.

Genomic imprinting of a placental lactogen gene in Peromyscus.

The mammalian genome contains over 30 genes whose expression is dependent upon their parent-of-origin. Of these imprinted genes the majority are involved in regulating the rate of fetal growth. In this report we show that in the deer mouse Peromyscusthe placental lactogen-1-variant ( pPl1-v) gene is paternally expressed throughout fetal development, whereas the linked and closely related pPl1gene is expressed in a biallelic manner. Neither the more distantly related pPl2Agene, nor the Mus Pl1gene displays any preferential expression of the paternal allele, suggesting that the acquisition of imprinting of pPl1-v is a relatively recent event in evolution. Although pPl1 expression is temporally mis-regulated in the dysplastic placentae of hybrids between two Peromyscus species, its over-expression cannot account for the aberrant phenotypes of these placentae. We argue that the species-specific imprinting of pPl1-v, encoding a growth factor that regulates nutrient transfer from mothers to their offspring, is consistent with the parent-offspring conflict model that has been proposed to explain the evolution of genomic imprinting.

The Dlk1 and Gtl2 genes are linked and reciprocally imprinted.

Genes subject to genomic imprinting exist in large chromosomal domains, probably reflecting coordinate regulation of the genes within a cluster. Such regulation has been demonstrated for the H19, Igf2, and Ins2 genes that share a bifunctional imprinting control region. We have identified the Dlk1 gene as a new imprinted gene that is paternally expressed. Furthermore, we show that Dlk1 is tightly linked to the maternally expressed Gtl2 gene. Dlk1 and Gtl2 are coexpressed and respond in a reciprocal manner to loss of DNA methylation. These genes are likely to represent a new example of coordinated imprinting of linked genes.

Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in Peromyscus.

Crosses between the two North American rodent species Peromyscus polionotus (PO) and Peromyscus maniculatus (BW) yield parent-of-origin effects on both embryonic and placental growth. The two species are approximately the same size, but a female BW crossed with a male PO produces offspring that are smaller than either parent. In the reciprocal cross, the offspring are oversized and typically die before birth. Rare survivors are exclusively female, consistent with Haldane's rule, which states that in instances of hybrid sterility or inviability, the heterogametic sex tends to be more severely affected. To understand these sex- and parent-of-origin-specific patterns of overgrowth, we analysed reciprocal backcrosses. Our studies reveal that hybrid inviability is partially due to a maternally expressed X-linked PO locus and an imprinted paternally expressed autosomal BW locus. In addition, the hybrids display skewing of X-chromosome inactivation in favour of the expression of the BW X chromosome. The most severe overgrowth is accompanied by widespread relaxation of imprinting of mostly paternally expressed genes. Both genetic and epigenetic mechanisms underlie hybrid inviability in Peromyscus and hence have a role in the establishment and maintenance of reproductive isolation barriers in mammals.

Insect pest management in tropical Asian irrigated rice.

Abundant natural enemies in tropical Asian irrigated rice usually prevent significant insect pest problems. Integrated pest management (IPM) extension education of depth and quality is required to discourage unnecessary insecticide use that upsets this natural balance, and to empower farmers as expert managers of a healthy paddy ecosystem. Farmers' skill and collaboration will be particularly important for sustainable exploitation of the potential of new, higher-yielding and pest-resistant rice. IPM "technology transfer" through training and visit (T&V) extension systems failed, although mass media campaigns encouraging farmer participatory research can reduce insecticide use. The "farmer first" approach of participatory nonformal education in farmer field schools, followed by community IPM activities emphasizing farmer-training-farmer and research by farmers, has had greater success in achieving IPM implementation. Extension challenges are a key topic for rice IPM research, and new pest management technology must promote, rather than endanger, ecological balance in rice paddies.

Abnormal Papanicolaou smears, genital tract infections, and contraception.

Cervical cancer ranks second among all cancers in women world-wide, and the rate of invasive cervical cancer among women under 50 is rising in the United States. Risk factors for abnormal Papanicolaou (Pap) smears and invasive cervical cancer include genital tract infections. This study was designed to compare the rates of genital tract infections and the contraceptive choices of a random sample of 800 women, using an ex post facto design. The Pap positive women had a significantly higher rate of genital tract infections than did the Pap negative women but did not differ significantly in use of contraceptive methods. Findings support those of other researchers suggesting genital tract infections as risk factors for abnormal Pap smears and are consistent with the literature in suggesting a role for oral contraceptive pills (OCPs) in acquisition of the human papillomavirus (HPV). Caregivers can help empower women to reduce their risks through informed choices about protection and sexual behaviors.

Women's patterns of contraceptive use.

Our purpose in conducting this research was to examine women's patterns of contraceptive use. Records for 800 women receiving care at a private, nonprofit agency providing well-woman and contraceptive care over a 15-year period constitute the data set. The records were examined for patterns of reported method choice and use, method destinations, first method choice, and demographic variables. Women reported making 1,889 method choices from among 16 different methods. Seventy-five percent of the women changed methods at least once and the women gave 1,036 reasons for changing methods. Oral contraceptives and condoms were the methods most commonly tried by the women. The women's patterns of contraceptive use were very individualized, were neither linear nor predictive as other investigators have reported, and method destinations could not be predicted from previous method use.

PIP: Patterns of contraceptive use were investigated in a retrospective review of the records of 800 US women receiving well-woman and family planning care at a private, nonprofit agency in Massachusetts. Overall, women made 1889 method choices from among 16 different methods during the 15-year study period. Oral contraceptives and condoms were the methods most commonly selected. 75.2% changed methods at least once (mean number of changes, 2.2) and gave 1036 reasons for their method switching. The 55.5% of women whose first contraceptive method was hormonal reported fewer methods of any type over the 15-year study period than those who began with a non-hormonal method. This factor accounted for 12% of the variation in total number of methods women reported using. Overall, contraceptive use patterns were individualized and non-linear, with few women choosing the same methods in the same order. Method choices could not be predicted from previous method use. Contrary to the findings of other studies, no trend from less effective to more effective methods was observed.

The role of empowerment in neighborhood-based nursing education.

It is a challenge to prepare nursing students for practice in the rapidly changing healthcare arena. A longitudinal clinical education experience, external to tertiary institutions and supportive of lifelong learning, creative and critical thinking is one way to empower students to provide appropriate care within a diverse population and evolving healthcare system. Nursing faculty, nursing students, community providers and neighborhood residents participate as colleagues in a joint venture of assessment, intervention, and learning.

Nondisjunction rates and abnormal embryonic development in a mouse cross between heterozygotes carrying a (7, 18) robertsonian translocation chromosome.

Mice bearing Robertsonian translocation chromosomes frequently produce aneuploid gametes. They are therefore excellent tools for studying nondisjunction in mammals. Genotypic analysis of embryos from a mouse cross between two different strains of mice carrying a (7,18) Robertsonian chromosome enabled us to measure the rate of nondisjunction for chromosomes 7 and 18. Embryos (429) were harvested from 76 litters of mice and the parental origin of each chromosome 7 and 18 determined. Genotyping these embryos has allowed us to conclude the following: (1) there were 96 embryos in which at least one nondisjunction event had taken place; (2) the rate of maternal nondisjunction was greater than paternal nondisjunction for teh chromosomes sampled in these mice; (3) a bias against chromosome 7 and 18 nullisomic gametes was observed, reflected in a smaller than expected number of uniparental disomic embryos; (4) nondisjunction events did not seem to occur at random throughout the 76 mouse litters, but were clustered into fewer than would be expected cy chance; and (5) a deficiency of paternal chromosome 18 uniparental disomic embryos was observed along with a higher than normal rate of developmental retardation at 8.5 days post coitum, raising the possibility that this chromosome has at least one imprinted gene.

Developing a clinical site at a day camp.

In response to the changing focus of the healthcare delivery system, nursing educators have broadened clinical experiences to prepare students to deliver healthcare in community systems. Finding sites during the months of July and August is difficult because elementary and secondary schools are closed and healthcare agencies have decreased staffing because of vacations. When the philosophy of the college of nursing and the course objectives require that the clinical site must be within a specific community, the task is more difficult. The use of an inner city day camp is one way to successfully address this situation.

A high-resolution linkage map of the lethal spotting locus: a mouse model for Hirschsprung disease.

Mice homozygous for the lethal spotting (ls) mutation exhibit aganglionic megacolon and a white spotted coat owing to a lack of neural crest-derived enteric ganglia and melanocytes. The ls mutation disrupts the migration, differentiation, or survival of these neural crest lineages during mammalian development. A human congenital disorder, Hirschsprung disease (HSCR), is also characterized by aganglionic megacolon of the distal bowel and can be accompanied by hypopigmentation of the skin. HSCR has been attributed to multiple loci acting independently or in combination. The ls mouse serves as one animal model for HSCR, and the ls gene may represent one of the loci responsible for some cases of HSCR in humans. This study uses 753 N2 progeny from a combination of three intersubspecific backcrosses to define the molecular genetic linkage map of the ls region and to provide resources necessary for positional cloning. Similar to some cases of HSCR, the ls mutation acts semidominantly, its phenotypic effects dependent upon the presence of modifier genes segregating in the crosses. We have now localized the ls mutation to a 0.8-cM region between the D2Mit113 and D2Mit73/D2Mit174 loci. Three genes, endothelin-3 (Edn3), guanine nucleotide-binding protein alpha-stimulating polypeptide 1 (Gnas), and phosphoenolpyruvate carboxykinase (Pck1) were assessed as candidates for the ls mutation. Only Edn3 and Gnas did not recombine with the ls mutation. Mutational analysis of the Edn3 and Gnas genes will determine whether either gene is responsible for the neural crest deficiencies observed in ls/ls mice.

What family planning methods women use and why they change them.

Each woman in a sample of 800 women from a nonprofit, private family planning clinic reported using at least one contraceptive method at some time in her life. Over the 15-year period that the sample represented, women made from 1 to 26 family planning visits. The women reported using as many as eight different methods and making up to 11 changes in method. The reasons for changing methods were, for the most part, logically related to the method, at least as far as common user complaints and side effects were concerned, but they also reflected misperceptions regarding relative risk of methods and a low tolerance for a method's disadvantages. A lack of congruence between choice and use was revealed, as women returned for care and reported that they had not used the contraceptive method they had chosen at the last family planning visit or had changed methods one or more times since that visit.

Facilitating the nurse practitioner's research role: using a microcomputer for data entry in clinical settings.

Data coding and entry can be a tedious and error-prone component of research. Statistical packages for a microcomputer are now available that enable the researcher to create data entry forms in a spread sheet format. In this article the use of software that can be used for data entry, manipulation, and analysis is discussed. In a practice setting these features are particularly useful, because the nurse practitioner can take the microcomputer to the clinical facility and enter data directly from client-provider interactions or from records. In clinical settings where client data are entered directly into a computer database as part of assessment and care giving, data can be downloaded onto this or similar programs for manipulation and analysis.

Concept analysis of decision making.

Concept analysis allows us to examine the attributes and characteristics of a concept. The concept of decision making is central to the practice of nursing. Decision making occurs at all levels of human thought and action, so it has been explored in many disciplines. It is important to explore this concept from the perspective of the discipline of nursing, so that we can determine how definitions and theories apply to our practice. Investigating a concept adopted from other disciplines will eventually provide the profession with a basis for knowledge development.