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Alpha-defensin expression during myelopoiesis: identification of cis and trans elements that regulate expression of NP-3 in rat promyelocytes.

Alpha-defensins are antimicrobial peptides that contribute to innate-immune functions of neutrophils and intestinal Paneth cells. Transcription of alpha-defensin genes occurs early in neutrophilic myelopoeisis. To examine the mechanisms that regulate alpha-defensin gene expression, we analyzed transcription of rat neutrophil alpha-defensin NP-3 in D4 cells, a subclone of the promyelocytic cell line IPC-81. Northern blot analysis showed that D4 cells express fivefold higher levels of alpha-defensin mRNA than the parental cell line in a manner relatively independent of passage number. Increased levels of steady-state mRNA in D4 cells correlated with markedly elevated peptide levels detected by immunocytochemical staining. To identify the cis-acting DNA elements involved in tissue-specific expression, D4 cells were transfected with luciferase reporter constructs containing NP-3 gene 5'-flanking sequences. Analyses of transfected D4 cells demonstrated that the proximal 87 base pair (bp) sequence contained cis-acting DNA elements necessary for optimal promoter activity. Mutational analyses within the 87-bp region suggested the involvement of the CAAT box and a putative polyoma enhancer-binding protein 2/core-binding factor (PEBP2/CBF) site in defensin gene transcription. Transient transfection analyses using tandem repeats of oligonucleotides containing these sequences demonstrated that proximity of the CAAT box and PEBP2/CBF site was important for defensin promoter activity. Electrophoretic mobility shift assays indicated that PEBP2/CBF or a PEBP2/CBF-related protein was involved in a specific protein-DNA interaction occurring within a DNA fragment containing the CAAT and PEBP2/CBF sequences. These data identify functional trans- and cis-elements that regulate rat defensin gene expression in high defensin-expressing promyelocytic cells.

Animals↗

Recombinant human luteinizing hormone (LH) to support recombinant human follicle-stimulating hormone (FSH)-induced follicular development in LH- and FSH-deficient anovulatory women: a dose-finding study. The European Recombinant Human LH Study Group.

The efficacy of recombinant human LH (rhLH) for supporting human (rhFSH)-induced follicular development was investigated in hypogonadotropic hypogonadal women (WHO group I anovulation). Patients (n = 38) were randomized to receive rhLH (0, 25, 75, or 225 IU/day) in addition to a fixed dose of rhFSH (150 IU/day). rhLH was found 1) to promote dose-related increases in estradiol (E2) and androstenedione secretion by rhFSH-induced follicles, i.e. serum concentrations on the last day of FSH administration were 65 +/- 4, 195 +/- 94, 1392 +/- 585, and 2441 +/- 904 pmol/L for E2 and 3.6 +/- 0.9, 5.1 +/- 1.3, 6.4 +/- 1.3, and 6.7 +/- 1.3 nmol/L for androstenedione for patients treated with 0, 25, 75, and 225 IU rhLH, respectively; 2) to increase ovarian sensitivity to FSH, as demonstrated by the proportion of patients who developed follicles after the administration of a fixed dose of FSH, i.e. 1 of 8, 3 of 7, 7 of 9, and 8 of 10 in patients treated with 0, 25, 75, and 225 IU rhLH, respectively; and 3) to enhance the ability of these follicles to luteinize when exposed to hCG. A daily dose of 75 IU rhLH was effective in the majority of women in promoting optimal follicular development (defined as > or = 1 follicle > or = 17 mm; E2, > or = 400 pmol/L; midluteal phase progesterone, > or = 25 nmol/L) and maximal endometrial growth. A minority of patients may require up to 225 IU/day. rhLH, given sc at a dose up to 225 IU/day, was not immunogenic and was well tolerated.

Adult↗

Nutritional supplements and tube feeds: what is available?

A wide range of specialized nutritional feeding products are now available. One condition for which nutritional feeding products are commonly prescribed is disease-related malnutrition. Nutritional support for poorly nourished clients consists of more than simply prescribing a specialized product. Key nutrition messages need to be applied to individual situations to promote optimal nutritional intake. However, in many situations clients are unable to meet their nutritional requirements by food alone and nutritional supplement products are then extremely useful. The nutritional status of all those receiving nutritional support should be monitored regularly; as the client's nutritional status improves, his/her intake of these products may need to be reduced or stopped. If clients are unable to maintain or improve their nutritional status despite the use of nutritional supplements, additional help from an alternative feeding product may be required.

Dietary Supplements↗

Performance on extremely low birthweight children at 5 years of age on the Miller Assessment for Preschoolers.

The purpose of this geographically defined national study was to evaluate the performance of extremely low birthweight children (ELBW < 1000 g) born in Iceland in 1991-1995 and compare to a cohort of matched control children born full term. The Miller Assessment for Preschoolers (MAP) was used to provide an overall profile of 32 ELBW children and 55 control children at 5 years of age. The results indicated that score patterns on the MAP between ELBW and normal birthweigt children differ. The differences were significant on the Total Score, and the Foundations, Coordination, and Complex-Tasks Indices. This study found that the ELBW group had specific problems in basic motor tasks, coordination, and fine motor skills. The results validate the need for early assessment, regular follow up, and consultation to promote optimal task performance and social participation of children born prematurely.

Child Development↗

Understanding older women's health care concerns: a qualitative study.

BACKGROUND: Older women often have different physical and psychological health priorities compared to men, and health systems must strive to extend and improve health care delivery to meet older women's specific health care needs. The goal of this study was to obtain information from older women on how to improve health care services to best support their efforts to age successfully and receive optimal quality health care in later life. METHODS: Focus groups were conducted among women aged 65 or older recruited from the community in the Montreal, Quebec area. A total of 36 women participated. The focus group sessions were audiotaped, and the transcripts of each session were analyzed for issues and themes emerging from the text. Content analysis using the framework approach was used to explore and understand the experience of the focus group participants. The data from the text were then coded according to the relevant and emergent ideas and concepts. RESULTS: Participants felt that their physical health care needs were being met, but that a number of issues relating to psychological health were inadequately addressed by health care professionals. The importance of feeling validated as active participants in a health care relationship, recognition of fears and anxieties associated with aging, and the need for information-sharing and education were all viewed as important health care priorities for older women. Time and accessibility were identified as the most significant barriers towards receiving optimal health care in later life. INTERPRETATION: The current health care system does not meet the global health care needs of older women. Health care leaders must recognize that success in program development and delivery for older women will require designing clinical programs that address both the physiological and psychosocial requirements of women. Only when women feel that they are being cared for in a comprehensive manner, one that includes attention to physical, psychological and emotional health, are we likely to be delivering health care that optimally promotes successful aging.

Age Factors↗

Understanding older women's health care concerns: a qualitative study.

BACKGROUND: Older women often have different physical and psychological health priorities compared to men, and health systems must strive to extend and improve health care delivery to meet older women's specific health care needs. The goal of this study was to obtain information from older women on how to improve health care services to best support their efforts to age successfully and receive optimal quality health care in later life. METHODS: Focus groups were conducted among women aged 65 or older recruited from the community in the Montreal, Quebec, area. A total of 36 women participated. The focus group sessions were audiotaped, and the transcripts of each session were analyzed for issues and themes emerging from the text. Content analysis using the framework approach was used to explore and understand the experience of the focus group participants. The data from the text were then coded according to the relevant and emergent ideas and concepts. RESULTS: Participants felt that their physical health care needs were being met, but that a number of issues relating to psychological health were inadequately addressed by health care professionals. The importance of feeling validated as active participants in a health care relationship, recognition of fears and anxieties associated with aging, and the need for information-sharing and education were all viewed as important health care priorities for older women. Time and accessibility were identified as the most significant barriers towards receiving optimal health care in later life. INTERPRETATION: The current health care system does not meet the global health care needs of older women. Health care leaders must recognize that success in program development and delivery for older women will require designing clinical programs that address both the physiological and psychosocial requirements of women. Only when women feel that they are being cared for in a comprehensive manner, one that includes attention to physical, psychological and emotional health, are we likely to be delivering health care that optimally promotes successful aging.

Age Factors↗

ASCCP patient management guidelines: Pap test specimen adequacy and quality indicators.

Our objective was to provide management guidelines according to Papanicolaou (Pap) test specimen adequacy based on literature review and expert opinion. A task force named by the American Society for Colposcopy and Cervical Pathology (ASCCP) conducted a literature review and discussed appropriate management. The Steering Committee of the ASCCP and other experts reviewed the guidelines. The guidelines recommend a repeated Pap test in 12 months for most women undergoing routine annual/biennial screening if the current Pap test is negative but either lacks an endocervical/ transformation zone component or is partially obscured. Indications for considering an earlier repeat are also provided. The preferred managementfor unsatisfactory Pap tests is a repeated Pap test within a short interval of 2 to 4 months. The management guidelines will help promote optimal and uniform follow-up of women according to Pap test specimen adequacy.

Female↗

Drug and environmental factors associated with adverse pregnancy outcomes. Part III: Folic acid: pharmacology, therapeutic recommendations, and economics.

OBJECTIVE: To review folic acid's mechanism of action, adverse effects, therapeutic recommendations, compliance, and cost. DATA SOURCES: A MEDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect, homocysteine, and methylenetetrahydrofolate reductase. STUDY SELECTION: Animal and human studies examining the effects of folate were reviewed. DATA EXTRACTION: Data collected included mechanism of action, safety issues, dosing recommendations, compliance with recommendations, and economics. DATA SYNTHESIS: Folic acid decreases neural tube defect risk through an effect on methionine-homocysteine metabolism. In addition, increased folate intake may reduce cardiovascular morbidity and mortality. Since toxicity is minimal, everyone can potentially benefit from increased folate consumption. To help achieve this, the Food and Drug Administration has mandated that cereal grain be fortified with 140 micrograms of folic acid per 100 g of grain, which will add approximately 0.1 mg of folate to the average diet. Studies recommend supplementing with 0.2 mg to promote optimal homocysteine concentrations and for preventing neural tube defects. CONCLUSIONS: Despite fortification, most women will still receive less folate than the 0.4 mg/d recommended by the Public Health Service. All population groups would benefit from increased folate intake. Current studies indicate 200 micrograms/d may be the minimum effective amount of fortification needed for normalizing homocysteine concentrations and preventing a significant number of neural tube defects; thus, a higher level of food fortification may be warranted.

Environmental Exposure↗

Signs of resilience: assets that support deaf adults' success in bridging the deaf and hearing worlds.

A multiple-case exploratory study is used to describe intrapersonal, behavioral, and environmental assets that may build bridges for Deaf adults between the Deaf and hearing worlds. A study of three exemplary former community college students provides new information about internal resources that may empower Deaf individuals to achieve work and social success in interaction with environmental support, despite the vulnerabilities associated with their deafness. This study identifies 15 assets that may support resilience in Deaf adults, including authenticity and comfort with solitude. The authors hypothesize that social authenticity and comfort with solitude may be resilience-fostering intrapersonal assets of unique importance in the Deaf community. From the positive psychology perspective of recognizing and building on human strengths, the authors suggest that support of mutual asset-building with learning partners in the classroom is one way professors might promote optimal student achievement and life success for all students.

Affect↗

The fault lines of academic medicine.

Unprecedented advances in biomedical research and the upheaval in health care economics have converged to cause seismic changes in the traditional organization of medical schools and academic health centers. This process is particularly evident in departments of internal medicine. The activities and functions of academic medicine are in the midst of separation and realignment along lines that do not honor historical departmental and divisional boundaries. The organization of a successful medical school or department must be dynamic, constantly serving its constituents to accommodate progress and change and to promote optimal structure for academic productivity.

Academic Medical Centers↗

High bone mass in a female Hutterite population.

We examined a Hutterite population (n = 243) to determine if their agriculturally diverse, self-sufficient communal lifestyle promotes optimal bone mass attainment because of adequate calcium intake and high physical activity levels during growth and young adulthood. We measured total body (TB) and lumbar bone mineral content (BMC) and bone mineral density (BMD) in 39 school-age (younger) females and 204 working (older) females. Forty-five percent of older females and 79% of younger females currently consumed > or = 3 servings (svg) of dairy per day. Older females had lumbar (0.6 +/- 1.3) and TB (1.1 +/- 1.1) BMD Z scores greater than 0 (both, p < 0.001). The lumbar BMD Z score of younger females was not different from 0 (-0.1 +/- 1.0; p = 0.5). Both lumbar (r = 0.46; p < 0.001) and TB (r = 0.20; p = 0.02) BMD Z scores increased with increasing age. In multiple regression analyses for older females, lumbar bone area (p < 0.001), weight (p < 0.001), current hours on feet per day (p = 0.01), colony workload (p < 0.01), and estrogen status (p = 0.06) predicted lumbar BMC. TB bone area (p < 0.001), current hours on feet per day (p < 0.001), and colony workload (p < 0.01) predicted TB BMC. For younger females, lumbar bone area (p < 0.001), weight (p < 0.01), years in present colony (p = 0.02), and menses (p < 0.001) predicted lumbar BMC. TB bone area (p < 0.001), height (p < 0.01), years in present colony (p = 0.03), and menses (p < 0.01) predicted TB BMC. The effect of colony workload could not be separated from other factors different by colony. A heritability estimate of 0.66 was calculated for lumbar BMD using mother and daughter Z scores. Adequate calcium intake during growth, high physical activity early in life, and genetic factors may be contributing to above normal BMD levels in adult female Hutterites.

Adolescent↗

Fish oil supplementation in the treatment of cachexia in pancreatic cancer patients.

Patients with pancreatic cancer often experience a loss of weight and appetite, known as the anorexia-cachexia syndrome, which is associated with decreased quality of life and reduced survival. Research into the biological mechanisms of cachexia has demonstrated that an array of inflammatory mediators and tumor-derived factors cause appetite suppression, skeletal muscle proteolysis, and lipolysis,producing an overall hypercatabolic state that contributes to loss of fat and lean body mass. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to modulate levels of proinflammatory cytokines, hepatic acute phase proteins, eicosanoids, and tumor-derived factors in animal models of cancer and may reverse some aspects of the process of cachexia. Results of clinical trials of n-3 PUFAs in the form of fish oils have been mixed, but should encourage further investigation into dietary fish oil supplementation, including the most effective route of administration and the proper dosage to promote optimal weight maintenance and to limit side effects. Concerns about standardization and quality control should also be considered. With the current available evidence, a recommendation for the use of omega 3 polyunsaturated fatty acids in pancreatic cancer cachexia is premature.

Appetite↗

The role of docosahexaenoic acid containing phospholipids in modulating G protein-coupled signaling pathways: visual transduction.

In order to understand the role of the high levels of docosahexaenoic acid (DHA) in neuronal and retinal tissue, a study of the effect of membrane lipid composition on the visual pathway, a G protein-coupled system, was undertaken. The level of metarhodopsin II (MII) formation was determined to be a function of phospholipid acyl-chain unsaturation, with the highest levels seen in DHA-containing bilayers. Similarly, the rate of coupling of MII to the retinal G protein, Gt, to form a MII-Gt complex, was enhanced in DHA bilayers relative to less unsaturated phospholipids. Complex formation initiates the first stage of amplification in the visual pathway. The activation of the cGMP phosphodiesterase (PDE), the effector enzyme, represents the integrated pathway function. DHA-containing bilayers were found to support PDE levels comparable to those of the rod outer segment (ROS) disk membranes. Inclusion of 30 mol% cholesterol in the reconstituted bilayers had an inhibitory effect on each step in the visual pathway studied. Inclusion of cholesterol reduced MII formation and PDE activity and increased the lag time between the appearance of MII and the formation of the MII-Gt complex. However, signaling in DHA bilayers was far less affected by the addition of cholesterol than in bilayers containing less unsaturated phospholipids. These studies point up the importance of DHA acyl chains in promoting optimal function in G protein-coupled signaling pathways. The results reported here suggest that visual and cognitive deficits observed in n-3 deficiency may result from decreased efficiency in related neurotransmitter and visual signaling pathways in the absence of DHA.

3',5'-Cyclic-GMP Phosphodiesterases↗

The role of the pediatrician in youth violence prevention in clinical practice and at the community level. American Academy of Pediatrics Task Force on Violence.

Violence and violent injuries are a serious threat to the health of children and youth in the United States. It is crucial that pediatricians define their role and develop the appropriate skills to address this threat effectively. From a clinical perspective, pediatricians should incorporate into their practices preventive education, screening for risk, and linkages to necessary intervention and follow-up services. As advocates, pediatricians should become involved at the local and national levels to address key risk factors and assure adequacy of preventive and treatment programs. There are also educational and research needs central to the development of effective clinical strategies. This policy statement defines the emerging role of pediatricians in youth violence prevention and management. It reflects the importance of this issue in the strategic agenda of the American Academy of Pediatrics for promoting optimal child health and development.

Adolescent↗

The porcine insulin-like growth factor-I gene: characterization and expression of alternate transcription sites.

Genomic DNA encoding the 5' region of the porcine IGF-I gene was cloned and sequenced and shown to be highly homologous to that of man, rats and sheep. Two leader exons (exons 1 and 2), which are alternately spliced to exon 3 (encoding part of the mature IGF-I molecule), were identified by RNase protection analysis. In both cases, transcription initiates upstream from exons 1 and 2 at multiple dispersed start sites to yield two distinct IGF-I mRNA transcript classes (1 and 2) which differ in the precursor peptides predicted from their individual leader sequences. The expression of class 1 and 2 transcripts was measured in liver and muscle RNA from two groups of 2-month-old pigs whose energy status had been manipulated within physiological limits to produce marked differences in plasma IGF-I levels and growth rates. For this purpose, RNase protection probes were developed that contained the individual leader exons 1 and 2 linked separately to the common exon 3, so that class-specific and total IGF-I gene expression could be determined in a single assay. At normal plasma IGF-I concentrations (200 ng/ml), class 1 and 2 transcripts comprised 81 and 19% respectively of total liver IGF-I mRNA, while at a lower plasma concentration (90 ng/ml) the corresponding values were 95 and 5% respectively. Although both classes of transcript declined with the decrease in plasma IGF-I, the relative drop in levels of class 2 transcripts (84%) was substantially greater than that of class 1 (54%). In longissimus dorsi, cardiac and soleus muscles IGF-I mRNA was predominantly of class 1 and did not change in response to decreased plasma IGF-I. This suggests that liver-derived endocrine IGF-I has an important function in the regulation of muscle growth and that class 2 IGF-I transcripts are more sensitive to conditions that promote optimal growth.

Amino Acid Sequence↗

From neurons to King County neighborhoods: partnering to promote policies based on the science of early childhood development.

A diverse community partnership in the Seattle area developed a policy agenda based on science, organized community support, and committed to monitor policy changes. It found that public health agencies are well positioned to develop a common knowledge base on early childhood development and to initiate community coalitions promoting policies to strengthen environments. It was challenging to maintain participants' focus on environments over time. Providing access to conditions that promote optimal development for all children will require ongoing commitment and alignment of many sectors to move political will and mobilize for change.

Child↗

Overtraining in athletes. An update.

Overtraining appears to be caused by too much high intensity training and/or too little regeneration (recovery) time often combined with other training and nontraining stressors. There are a multitude of symptoms of overtraining, the expression of which vary depending upon the athlete's physical and physiological makeup, type of exercise undertaken and other factors. The aetiology of overtraining may therefore be different in different people suggesting the need to be aware of a wide variety of parameters as markers of overtraining. At present there is no one single diagnostic test that can define overtraining. The recognition of overtraining requires the identification of stress indicators which do not return to baseline following a period of regeneration. Possible indicators include an imbalance of the neuroendocrine system, suppression of the immune system, indicators of muscle damage, depressed muscle glycogen reserves, deteriorating aerobic, ventilatory and cardiac efficiency, a depressed psychological profile, and poor performance in sport specific tests, e.g. time trials. Screening for changes in parameters indicative of overtraining needs to be a routine component of the training programme and must be incorporated into the programme in such a way that the short term fatigue associated with overload training is not confused with the chronic fatigue characteristic of overtraining. An in-depth knowledge of periodisation of training theory may be necessary to promote optimal performance improvements, prevent overtraining, and develop a system for incorporating a screening system into the training programme. Screening for overtraining and performance improvements must occur at the culmination of regeneration periods.

Adaptation, Physiological↗

Empirical validation for a family-centered model of care.

OBJECTIVE: To examine whether family relations and family-life stress predict adherence behaviors and metabolic control in youths by testing a theoretically- and empirically-based model. RESEARCH DESIGN AND METHODS: HbA1c levels of 157 youths 12-20 years of age with insulin-dependent diabetes mellitus (IDDM) were evaluated, along with treatment adherence and psychosocial family data based on interviews and self-reports. A family-centered model for IDDM care was analyzed with the EQS structural modeling statistical program. An additional exploratory model including HbA1c levels 6 months earlier was also tested. RESULTS: Positive family relations (high family cohesion and low family conflict), especially during the first years of illness, indirectly related to good metabolic control through positive adherence behaviors. High levels of family-life stress related to worse metabolic control directly, and also indirectly via poor family relations, which in turn related to poor adherence to treatment. Longer illness duration related indirectly to metabolic control via adherence to treatment. Longer illness duration also related to maternal perceptions of higher family-life stress. Older youths perceived more family-life stress as well. The older age of the youths related indirectly to poor metabolic control through its association with poor adherence behaviors and less cohesive and more conflictual family relations. Results were consistent when earlier levels of metabolic control were included in the model, except that the direct relationship between family-life stress and metabolic control became nonsignificant. CONCLUSIONS: The findings suggest that a family-centered approach to diabetes care that facilitates positive family functioning and leads to lower levels of family-life stress may be useful in promoting optimal health outcomes.

Adolescent↗