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Isolation, characterization, inheritance and linkage of microsatellite DNA markers in white spruce (Picea glauca) and their usefulness in other spruce species.

Microsatellite DNA/simple-sequence-repeat (SSR) loci were identified, isolated and characterized in white spruce (Picea glauca) by screening both a non-enriched partial genomic library and a partial genomic library enriched for (AG/TC)n-containing clones. Inheritance and linkage of polymorphic SSR loci were determined in F1 progeny of four controlled crosses. We also assessed the compatibility and usefulness of the P. glauca microsatellite DNA markers in five other Picea species. Twenty-four microsatellites were identified by sequencing 32 clones selected from screens of 5,400 clones from the two libraries. The (AG/TC)n microsatellites were the most abundant in the non-enriched library. Eight microsatellite DNA loci were of the single-copy type, and six of these were polymorphic. A total of 87 alleles were detected at the six polymorphic SSR loci in 32 P. glauca individuals drawn from several populations. The number of alleles found at these six SSR loci ranged from 2 to 22, with an average of 14.5 alleles per locus, and the observed heterozygosity ranged from 0.48 to 0.91, with a mean of 0.66 per locus. Parents of the controlled crosses were polymorphic for five of the six polymorphic SSR loci. Microsatellite DNA variants at each of these five SSR loci followed a single-locus, codominant, Mendelian inheritance pattern. Joint two-locus segregation tests indicated complete linkage between PGL13 and PGL14, and no linkage between any of the remaining SSR loci. Each of the 32 P. glauca individuals examined had unique single or two-locus genotypes. With the exception of non-amplification of PGL12 in P. sitchensis, P. mariana, and P. abies and the monomorphic nature of PGL7 in P. mariana, primer pairs for all six polymorphic SSR loci successfully amplified specific fragments from genomic DNA and resolved polymorphic microsatellites of comparable sizes in P. engelmanni, P. sitchensis, P. mariana, P. rubens, and P. abies. The closely related species P. mariana and P. rubens, and P. glauca and P. sitchensiss could be distinguished by the PGL12 SSR marker. The microsatellite DNA markers developed and reported here could be used for assisting various genetics, breeding, biotechnology, tree forensics, genome mapping, conservation, restoration, and sustainable forest management programs in spruce species.

Base Sequence↗

Developmental mentoring match characteristics: correspondence between mentors' and mentees' assessments of relationship quality.

Understanding the factors that contribute to high-quality mentoring relationships is critical to developing and sustaining effective mentoring programs. In study 1, sixty-three adolescent mentors, from two high schools, were surveyed four to six weeks after being matched with elementary-age mentees. Hierarchical regression models revealed that mentees' academic and behavioral risk status, parental involvement, and program quality all explained variance in mentor-perceived relationship quality, but none remained significant predictors after mentors' self-efficacy, motivations for self-enhancement, and assessments of their mentees' support seeking behaviors were accounted for. Study 2 cross-validates the regression model in study 1 and examines the concurrent validity and predictive validity of a measure of mentoring match characteristics using mid-year and end-of-year assessments from mentees and mentors. Editors' Strategic Implications: The focus on mentors' initial impressions of their mentees and the relationship represents a novel contribution to the study of relationship formation and persistence. The authors provide a promising strategy - and descriptions of specific measures - to help programs study relationships that endure or terminate. Coordinators will benefit from the knowledge that if mentors feel efficacious and if the mentoring relationship is strong, mentors are more likely to persist.

Adult↗

The prognostic value of the changes in the mode of ventricular tachycardia induction noted during therapy with a marked reduction of ventricular ectopic activity.

The prognostic significance of changes in the mode of induction of ventricular tachycardia (VT) noted during therapy was studied in 49 patients with sustained VT or ventricular fibrillation. Before treatment, all patients had inducible sustained VT by programmed stimulation (one to three extrastimuli) and frequent (greater than or equal to 30/hr) ventricular premature complexes (VPCs). On the discharge regimen, VT was no longer inducible by programmed stimulation in 22 patients (group 1). Twenty-seven patients (group 2) with persistent induction of VT despite extensive serial drug testings were discharged on a regimen that resulted in a marked reduction of VPCs on Holter monitoring (greater than or equal to 50% reduction of VPCs, greater than or equal to 90% reduction of couplets, and abolition of nonsustained VT). The modes of induction at baseline and on the discharge regimen were compared in each patient in group 2. Induction of VT was more difficult, requiring more aggressive stimulation protocol in 5 of 27 patients, unchanged in 14 patients, and easier in 8 patients. The duration of follow-up was 20 +/- 13 months (mean +/- SD). Arrhythmia-free survival rates at 6, 12, 18, and 24 months were 95%, 89%, 82%, and 73% in group 1, 92%, 84%, 75%, and 75% in group 2, 93%, 83%, 77%, and 69% in 27 patients with noninducibility or harder induction, and 95%, 90%, 79%, and 79% in 22 patients with the same or easier induction, respectively. The differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Which hemisphere falls asleep first?

Behavioral tasks (reaction times to acoustic stimuli and finger tapping tasks) performed by normal subjects when sleepy or attempting to fall asleep have been used as indices of hemispheric asymmetries during the sleep onset period. Results show a stronger impairment of the left hemisphere (right hand) both in reacting to external stimuli and in sustaining endogenous motor programs. The left hemisphere seems to fall asleep earlier than the right hemisphere.

Acoustic Stimulation↗

Atmospheric dynamics and bioregenerative technologies in a soil-based ecological life support system: initial results from Biosphere 2.

Biosphere 2 is the first man-made, soil-based, bioregenerative life support system to be developed and tested. The utilization and amendment of local space resources, e.g. martian soil or lunar regolith, for agricultural and other purposes will be necessary if we are to minimize the requirement for Earth materials in the creation of long-term off-planet bases and habitations. Several of the roles soil plays in Biosphere 2 are 1) for air purification 2) as a key component in created wetland systems to recycle human and animal wastes and 3) as nutrient base for a sustainable agricultural cropping program. Initial results from the Biosphere 2 closure experiment are presented. These include the accelerated cycling rates due to small reservoir sizes, strong diurnal and seasonal fluxes in atmospheric CO2, an unexpected and continuing decline in atmospheric oxygen, overall maintenance of low levels of trace gases, recycling of waste waters through biological regeneration systems, and operation of an agriculture designed to provide diverse and nutritionally adequate diets for the crew members.

Agriculture↗

3D epigenomic remodelling mediated by Foxa1 drives gemcitabine resistance in pancreatic cancer.

Gemcitabine remains a cornerstone treatment for pancreatic ductal adenocarcinoma (PDAC), yet the emergence of resistance constitutes a major clinical challenge with poorly understood epigenomic mechanisms. Here, we identified the pioneer transcription factor Foxa1 as a master regulator of gemcitabine resistance through multi-omics analysis. Mechanistically, Foxa1 drives widespread super-enhancer (SE) reprogramming and 3D genome remodelling in resistant cells, which coordinately activates the expression of key resistance genes, notably Rrm1 and Cdadc1. This is accompanied by increased chromatin accessibility, elevated H3K27ac enrichment at SEs, and enhanced Foxa1 binding at regulatory elements. Moreover, post-translational stabilization of Foxa1 via USP7-mediated deubiquitination sustains this epigenomic program. Genetic ablation of Foxa1 or specific SE regions near Rrm1 resensitizes resistant cells to gemcitabine. Building upon this mechanism, we demonstrate that bromodomain and extraterminal (BET) inhibitors, which disrupt SE function, potently reverse resistance. Notably, the clinical-stage BET inhibitor AZD5153, in combination with gemcitabine, achieves robust tumor suppression and overcomes resistance in cell-derived xenograft (CDX) models by dismantling the Foxa1-mediated resistant transcriptome and reinvigorating drug sensitivity. Our findings establish Foxa1-orchestrated enhancer reprogramming as a fundamental mechanism of gemcitabine resistance and unveil a promising epigenetic therapy to restore treatment efficacy in PDAC.

Hepatocyte Nuclear Factor 3-alpha↗

Trends in linezolid susceptibility patterns in 2002: report from the worldwide Zyvox Annual Appraisal of Potency and Spectrum Program.

Oxazolidinones have become reliable clinical and candidate antimicrobial agents to be utilized for infections caused by multidrug-resistant Gram-positive cocci, especially vancomycin-resistant enterococci and methicillin-resistant staphylococci. However, mutational resistance of the ribosomal target has been described for several species. Longitudinal surveillance remains necessary to monitor for this evolving linezolid resistance pattern. A survey of linezolid and several comparison Gram-positive focused agents was initiated in 2002 (7971 strains, >99.0% compliance) for 54 participating sites in the United States, Canada, Europe (6 nations), Latin America (2 nations), and the Asia Pacific (2 nations). The 5 and 25 sites in Canada and the United States, respectively, submitted 200 strains each to a central laboratory for organism identification/confirmation and reference MIC processing. The 10 remaining nations had 200 strain samples from 1 to 4 separate institutions. Linezolid resistance (MIC >/= 8 microg/mL) was confirmed by alternative susceptibility testing methods (Etest, AB BIO Disk, Solna, Sweden; disk diffusion method) and target mutation characterization by PCR and sequence analysis. Linezolid activity against the 6 major organism groups did not vary between geographic areas. A total of 98.1% of linezolid MIC values were between 0.5 and 2 microg/mL, and only 0.5% of results were at 4 microg/mL, which included 32 Staphylococcus aureus (0.9%) and 5 (0.5%) enterococcal isolates. Linezolid resistance was detected in only 4 isolates (0.05%): 1 each Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecium, and a viridans group Streptococcus. All 4 isolates had a G2576U mutation in the 23S rRNA target. Linezolid activity as outlined by these Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program results demonstrate sustained, near complete activity against contemporary Gram-positive isolates on 4 monitored continents and in centers utilizing oxazolidinones. Rare linezolid-resistant strains were identified in the United States only (0.05% resistance overall).

Acetamides↗

Impaired low-frequency oscillations of heart rate in patients with prior acute myocardial infarction and life-threatening arrhythmias.

Myocardial infarction results in abnormal cardiac autonomic function, which carries an increased risk of cardiac mortality, but it is not well known whether autonomic dysfunction itself predisposes patients to life-threatening arrhythmias or whether it merely reflects the severity of underlying ischemic heart disease. To determine the significance of abnormalities of cardiovascular neural regulation on the risk for ventricular tachycardia (VT), heart rate (HR) variability in the time and frequency domain were compared in a case-control study between 30 patients with a prior myocardial infarction and a history of sustained VT (n = 18) or cardiac arrest (n = 12) (VT group) and 30 patients with a prior myocardial infarction but no arrhythmic events (control group). The patient groups were carefully matched with respect to age, sex, location, ejection fraction, number of prior infarctions, number of diseased coronary arteries, and beta-blocking medication. In all patients in the VT group, inducibility into sustained VT was achieved, but none of the control patients had inducible nonsustained or sustained VT during programmed electrical stimulation. Patients in the VT group had a significantly lower SD of the RR intervals (p < 0.01), and reduced ultra low-, very low-, and low-frequency power spectral components of HR variability (p < 0.001 for all) than controls, but the high-frequency component of HR variability did not differ significantly between groups. In multiple regression analysis, reduced very low-frequency power of HR variability was the strongest independent predictor of VT susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Effect of 6-month adherence to a very low carbohydrate diet program.

To determine the effect of a 6-month very low carbohydrate diet program on body weight and other metabolic parameters.Fifty-one overweight or obese healthy volunteers who wanted to lose weight were placed on a very low carbohydrate diet (<25 g/d), with no limit on caloric intake. They also received nutritional supplementation and recommendations about exercise, and attended group meetings at a research clinic. The outcomes were body weight, body mass index, percentage of body fat (estimated by skinfold thickness), serum chemistry and lipid values, 24-hour urine measurements, and subjective adverse effects.Forty-one (80%) of the 51 subjects attended visits through 6 months. In these subjects, the mean (+/- SD) body weight decreased 10.3% +/- 5.9% (P <0.001) from baseline to 6 months (body weight reduction of 9.0 +/- 5.3 kg and body mass index reduction of 3.2 +/- 1.9 kg/m(2)). The mean percentage of body weight that was fat decreased 2.9% +/- 3.2% from baseline to 6 months (P <0.001). The mean serum bicarbonate level decreased 2 +/- 2.4 mmol/L (P <0.001) and blood urea nitrogen level increased 2 +/- 4 mg/dL (P <0.001). Serum total cholesterol level decreased 11 +/- 26 mg/dL (P = 0.006), low-density lipoprotein cholesterol level decreased 10 +/- 25 mg/dL (P = 0.01), triglyceride level decreased 56 +/- 45 mg/dL (P <0.001), high-density lipoprotein (HDL) cholesterol level increased 10 +/- 8 mg/dL (P <0.001), and the cholesterol/HDL cholesterol ratio decreased 0.9 +/- 0.6 units (P <0.001). There were no serious adverse effects, but the possibility of adverse effects in the 10 subjects who did not adhere to the program cannot be eliminated.A very low carbohydrate diet program led to sustained weight loss during a 6-month period. Further controlled research is warranted.

Adult↗

The treatment of malignant ventricular arrhythmias with combined endocardial resection and implantation of the automatic defibrillator: preliminary report.

Fourteen patients with refractory ventricular tachyarrhythmias were treated with combined endocardial resection and implantation of the automatic defibrillator. There were 11 men and 3 women with a mean age of 53 years (range, 41 to 58 years). All patients had coronary artery disease; the mean ejection fraction was 26%, and the mean number of cardiac arrests was 2.6. Programmed electrical stimulation induced sustained ventricular tachycardia in 13 patients and nonsustained ventricular tachycardia in 1. Operative endocardial mapping in the 13 patients with sustained ventricular tachycardia demonstrated a septal focus of early activation in 9 patients and a nonseptal site in 4. Following resection, sustained ventricular tachycardia could not be reinduced. There was 1 operative death. Programmed electrical stimulation performed one month after operation induced ventricular tachycardia in 5 patients, but tachycardia could not be induced in the other 8 survivors. The longest follow-up was 32 months; the average was 17 months. There were 2 late deaths. One patient died of myocardial infarction and 1 of pulmonary edema following a routine cholecystectomy. In another patient, late ventricular tachycardia developed but was automatically terminated by the implanted defibrillator. These results suggest that endocardial resection combined with implantation of the automatic defibrillator may offer the greatest protection yet available to patients with malignant ventricular tachyarrhythmias.

Adult↗

Knowledge, beliefs and practices relevant for malaria control in an endemic urban area of the Colombian Pacific.

Research projects for malaria control must involve communities to elicit strategies to be successful and programs to be sustainable. Therefore, knowledge, beliefs and practices of the population concerned must be taken into account in the design of interventions against malaria transmission. We conducted a KAP study in Buenaventura, a port on the Pacific Coast of Colombia where transmission was on the increase at the beginning of this decade. The purpose of the study was to help in the design and implementation of a primary health care approach for malaria control. Both qualitative and quantitative research methods were used. The focus group technique was applied in five urban and peri-urban communities and a cross sectional survey was conducted on a random sample of 1380 subjects with a structured interview on knowledge, practices and also on demographic and epidemiological aspects. The information obtained by the two methods was comparable on knowledge of symptoms, causes and ways of malaria transmission, and prevention practices like the use of bednets or provision of health services. We discuss the relevance of obtaining this information and analyze the elements that must be taken into account for communities to become more involved in malaria control strategies.

Adult↗

Frontiers in anthelmintic pharmacology.

Research in anthelmintic pharmacology faces a grim future. The parent field of veterinary parasitology has seemingly been devalued by governments, universities and the animal industry in general. Primarily due to the success of the macrocyclic lactone anthelmintics in cattle, problems caused by helminth infections are widely perceived to be unimportant. The market for anthelmintics in other host species that are plagued by resistance, such as sheep and horses, is thought to be too small to sustain a discovery program in the animal health pharmaceutical industry. These attitudes are both alarming and foolish. The recent history of resistance to antibiotics provides more than adequate warning that complacency about the continued efficacy of any class of drugs for the chemotherapy of an infectious disease is folly. Parasitology remains a dominant feature of veterinary medicine and of the animal health industry. Investment into research on the basic and clinical pharmacology of anthelmintics is essential to ensure chemotherapeutic control of these organisms into the 21st century. In this article, we propose a set of questions that should receive priority for research funding in order to bring this field into the modern era. While the specific questions are open for revision, we believe that organized support of a prioritized list of research objectives could stimulate a renaissance in research in veterinary helminthology. To accept the status quo is to surrender.

ATP Binding Cassette Transporter, Subfamily B↗

Factors influencing smoking cessation in patients with coronary artery disease.

The purpose of this paper is to review the sociodemographic, clinical, and psychological characteristics suggested as being predictors of difficulty with smoking cessation in patients with coronary artery disease. These characteristics include age, gender, socioeconomic status, social support, intensity of smoking, severity of coronary artery disease, anxiety, depression, hostility/anger/aggression, and health locus of control. In addition, nicotine addiction is discussed as a factor which may further compound this problem. Consideration of these factors in relation to the patient with coronary artery disease may assist in the delivery of an optimal and individualized intervention program to facilitate sustained smoking cessation. A brief overview of intervention strategies is provided.

Coronary Disease↗

Economic aspects of vaccines and immunizations.

Several techniques are used to estimate whether investing in vaccines and immunization is worthwhile, including cost analysis, cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis. At least 162 published economic evaluations of vaccines have been carried out from 1969 to 1998. They consistently show that immunization is an excellent investment--highly cost-effective and usually cost-saving--for vaccines that are currently recommended for universal use. Although prices of newer vaccines are higher than prices of traditional vaccines, they are still highly cost-effective. The World Health Organization, UNICEF, and vaccine manufacturers have developed approaches to make newer vaccines available to developing countries at reduced prices. Sustainability of immunization programs (the ability of a country to continue its immunization program in the absence of external support) is an increasingly important goal. However, external assistance will be essential in the short term to ensure that all the world's people benefit fully from the new vaccines.

Cost-Benefit Analysis↗

Therapy for chronic hepatitis C.

BACKGROUND/AIMS: in Hungary, over the past 5 years more than 900 patients with chronic hepatitis C have been examined for treatment with interferon at 16 major hepatology centres, using unified diagnostic and therapeutical criteria. Authors give an account of their experiences on the clinical features of patients with chronic hepatitis C and report the results of the interferon therapy. METHODS: a total of 993 patients--virtually the entire Hungarian hepatitis C patient population who had been referred for interferon treatment--were included in the program. Actually, the sustained efficacy of the therapy was evaluated in 724 cases. Treatment protocols (dose of interferon and duration of therapy) have changed with time from a weekly dose of 3x3 MU IFN for 6 months in the first period, to 3x3-5 MU for 12 months in the second period, and finally in the third period a combination therapy with ribavirin has also been introduced. RESULTS: in the first period, the end-of-treatment response (ETR) was 35%, sustained response (SR) 13%, the second phase schedule resulted in 42% ETR and 22% SR, while in the third period, ETR was 49% and SR 36%, respectively. Fibrosis in histology and baseline pretreatment HCV-RNA level appeared as predictors of response. The duration of treatment and the total dose of interferon exerted a moderate effect on therapeutic efficacy. Neither age nor gender influenced the outcome. CONCLUSIONS: our results-obtained in a Central East European country-are in accordance with findings of suboptimal efficacy of traditional interferon monotherapy for chronic hepatitis C reported in the West, and suggest the benefit of the combination treatment of interferon with ribavirin.

Adult↗

DNA methylation and breast carcinogenesis.

Knowledge about breast carcinogenesis has accumulated during the last decades but has barely been translated into strategies for early detection or prevention of this common disease. Changes in DNA methylation have been recognized as one of the most common molecular alterations in human neoplasia and hypermethylation of gene-promoter regions is being revealed as one of the most frequent mechanisms of loss of gene function. The heritability of methylation states and the secondary nature of the decision to attract or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory. According to Hanahan and Weinberg, there are six novel capabilities a cell has to acquire to become a cancer cell: limitless replicative potential, self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of programmed cell death, sustained angiogenesis and tissue invasion and metastasis. This review highlights how DNA-methylation contributes to these features and offers suggestions about how these changes could be prevented, reverted or used as a 'tag' for early detection of breast cancer or, preferably, for detection of premalignant changes.

Breast Neoplasms↗

The effect of an educational program on transfusion practices in a regional blood program.

With the increased complexity of blood component therapy, it is important to be able to modify physician behavior with reliable educational programs. A standardized educational program on the use of red blood cells and whole blood was tested in 22 hospitals in a regional blood program using medical audit and computer monitoring to evaluate effectiveness. Most hospitals were eager to take advantage of the education program but were unwilling to use the audit-education cycle. At the same time, computer monitoring of indivisual hospital ordering and transfusion practices demonstrated an increased utilization of red blood cells in 64 per cent of hospitals with an overall improvement of 8 per cent. The improved use of red blood cells was appreciated within the month of the program and then sustained for six to twelve months at the new level.

Blood Transfusion↗

[Dermis collagens: beyond their structural properties].

The extracellular matrix is a complex network composed of macromolecules such as collagens, proteoglycans and elastin that strongly interact with each other and with cells to maintain the structural integrity of many tissues. These interactions also sustain important cell programs such as migration, proliferation, differentiation and apoptosis. The skin, and more specifically the dermis, contains an extreme diversity of macromolecules that reflects the importance of the composition and organization of the matrix components in providing physical properties and function of the tissues. The most abundant matrix components are the collagens that form a super-family of 27 different members which are divided into different subgroups. The fibrillar collagens, types I, III and V, the FACIT collagens, types XII, XIV and XVI, and collagen VI are all expressed in the collagen-rich dermis. Although the structural features of these collagens are now well characterized, their functions remain elusive. Mutations in human collagen genes give rise to numerous connective tissue diseases including dermis disorders. For example, clinical manifestations in the classical Elhers-Danlos syndrome caused by collagen V gene mutations occur predominantly in the dermis. However, the genotype-phenotype relationship is not clearly established as well as the relation between the distribution and the function of the collagens in dermis. There is no doubt that the ongoing and future work using in vivo approaches will provide new cues regarding the function of collagens in dermis.

ADAM Proteins↗