High-throughput mitochondrial genome screening method for nonmelanoma skin cancer using multiplexed temperature gradient capillary electrophoresis

BACKGROUND: We explored the utility of multiplexed temperature gradient capillary electrophoresis (TGCE) as a screening tool for identifying genetic changes in the human mitochondrial genome. We examined changes in mitochondrial DNA (mtDNA) in nonmelanoma skin cancers (NMSCs), using TGCE to resolve genetic differences contained within the tumors compared with the control DNA. METHODS: The entire mtDNA from NMSC tissue samples was amplified in 17 overlapping amplicons averaging 1.1 kb in size. Fourteen of these amplicons were digested with restriction endonucleases into as many as five smaller analyzable fragments. Digested tumor mtDNA amplicons were annealed with digested amplicons from the control DNA to form heteroduplexes in regions of DNA mismatch. TGCE was performed in a 96-well parallel format to detect mtDNA changes in a high-throughput fashion. RESULTS: TGCE resolved heteroduplexes from homoduplexes in singlet reactions and in multiplexed assays. Using a single programmed temperature gradient, we detected 18 of 20 mtDNA changes contained within the specimens. This system was also able to detect a single nucleotide change in a fragment as large as 2 kb. CONCLUSION: Multiplexed TGCE is a sensitive and high-throughput screening tool for identifying mtDNA variations.     

Post-acute intermediate care in nursing-led units: a systematic review of effectiveness

OBJECTIVE: In order to determine whether post-acute intermediate care in nursing-led inpatient units (NLUs) is effective in preparing patients for discharge from hospital we conducted a systematic review of the evidence. REVIEW METHODS: The Cochrane Library, Effective Practice and Organisation of Care specialist register, Medline, Cinahl, Embase, British Nursing Index and the HMIC databases were searched for all available dates up to mid-2003. The science and social science citation indices were searched for papers that cited key works. Authors of papers were asked to identify additional research. Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time-series designs that compared the NLU to usual post-acute inpatient care for adults were included in the review. Studies were assessed for quality. Statistical meta-analysis on the results of controlled trials was performed. Sensitivity analyses were conducted to determine the impact of methodological quality on conclusions. OUTCOMES: Outcomes considered were mortality, institutionalisation after discharge, functional status early readmission, length of inpatient stay and cost. RESULTS: Nine random or quasi-random controlled trials involving 1669 patients were reviewed. Quality was variable. The mean age of patients in all studies was over 70 years. There was no statistically significant difference in inpatient mortality between NLU and usual inpatient care (OR 1.10, 95% CI 0.56-2.16). The NLU was associated with reduced odds of discharge to institutional care (OR 0.44 95% CI 0.22-0.89), better functional status at discharge (SMD 0.37, 95% CI 0.20-0.54) and reduced odds of early readmission (OR 0.52 95% CI 0.34-0.80). Length of stay until discharge home was increased by 5.13 days (WMD) (95% CI-0.5-10.76 days). At longest follow up (3-6 months) there was no statistically significant difference in the proportion of patients in institutional care (OR 0.97, 95% CI 0.60-1.58). The results were not generally sensitive to study quality. CONCLUSIONS: The NLU successfully functions as a form of intermediate care, so far there is no evidence of adverse outcome from the lower level of routine medical care. However, more research is required to confirm safety. Patients discharged from NLUs have higher levels of function although it is unclear if the benefit is simply a product of an increased stay. There is no evidence of benefit over the longer term.     

Comparison of movement-to-music, rhythm activities, and competitive games on depression, stress, anxiety, and anger of females in substance abuse rehabilitation

Over the past several decades the number of females using addictive substances has continuously increased. Females have different reasons for initiating substance abuse and specific treatment needs that differ from males. Researchers suggested gender specific drug rehabilitation treatment, in which female clients developed or improved functional behaviors. The purpose of this study was to investigate the effects of 3 different types of music therapy interventions on levels of depression, stress, anxiety, and anger of female clients in substance abuse rehabilitation. Ten females in an outpatient substance abuse rehabilitation program participated twice a week for 6 weeks in a music therapy program, participating in movement-to-music activities, rhythm activities, and competitive games for 2 weeks, 4 sessions each. After each intervention state-trait anxiety and levels of anger were measured. A repeated-measures ANOVA indicated no significant differences for the three types of music therapy interventions; however, data collected on daily scores, immediately before and after each session, indicated that individuals reported a decrease in depression, stress, anxiety, and anger immediately following the music therapy sessions.     

Arg16 homozygosity of the beta2-adrenergic receptor improves the outcome after beta2-agonist tocolysis for preterm labor

BACKGROUND: Beta(2)-adrenergic receptor (beta(2)AR) agonists are not consistently successful when administered as tocolytic therapy. The beta(2)AR displays genetic variability; an arginine-to-glycine substitution at codon 16 (Arg16Gly) has been shown to increase receptor desensitization in response to agonist exposure, whereas a substitution of glutamate for glutamine at codon 27 (Gln27Glu) decreases down-regulation. We have demonstrated that homozygosity for Arg16 protects against preterm delivery. Our goal was to determine whether beta(2)-agonists are more effective in women with the Arg16 genotype and preterm labor. METHODS: Sixty white women with preterm labor between 24 and 34 weeks' gestation were treated for 48 hours with intravenous hexoprenaline. The effect of tocolysis and outcome of pregnancy were recorded. The beta(2)AR genotypes at codons 16 and 27 of ADRB2 were determined. A control group of 116 women delivered at term was also genotyped. RESULTS: Preterm labor was not associated with beta(2)AR genotype at codon 16 (17% of patients with preterm labor were Arg16 homozygotes versus 19% of control subjects) or codon 27. Gestation was significantly prolonged in Arg16 homozygotes (median, 69 days; interquartile range, 63-79 days) compared with the other 2 genotypes (median, 58 days; interquartile range, 2-72 days) (P = .04). Tocolysis was 100% successful in delaying delivery for 48 hours in Arg16 homozygotes (n = 10), just failing to achieve statistical significance (P = .069). In contrast, only 37 of 50 women carrying 1 or 2 glycine alleles (74%) had delivery delayed by more than 48 hours with tocolysis. Neonatal outcomes were significantly better in babies born to mothers homozygous for arginine than in women with 1 or 2 Gly16 alleles. CONCLUSIONS: This is the first study examining the pharmacogenetics of beta(2)AR agonist therapy for preterm labor. It appears that Arg16 homozygosity improves pregnancy outcome after beta(2)-agonist tocolysis. The relatively low frequency of Arg16 homozygotes in our population limited the power of this investigation. Future assessments of tocolytic therapy may need to assess beta(2)AR genotype.     

Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response

A long-standing paradox in the study of T cell antigen recognition is that of the high specificity-low affinity T cell receptor (TCR)-major histocompatibility complex peptide (MHCp) interaction. The existence of multivalent TCRs could resolve this paradox because they can simultaneously improve the avidity observed for monovalent interactions and allow for cooperative effects. We have studied the stoichiometry of the TCR by Blue Native-polyacrylamide gel electrophoresis and found that the TCR exists as a mixture of monovalent (alphabetagammaepsilondeltaepsilonzetazeta) and multivalent complexes with two or more ligand-binding TCRalpha/beta subunits. The coexistence of monovalent and multivalent complexes was confirmed by electron microscopy after label fracture of intact T cells, thus ruling out any possible artifact caused by detergent solubilization. We found that although only the multivalent complexes become phosphorylated at low antigen doses, both multivalent and monovalent TCRs are phosphorylated at higher doses. Thus, the multivalent TCRs could be responsible for sensing low concentrations of antigen, whereas the monovalent TCRs could be responsible for dose-response effects at high concentrations, conditions in which the multivalent TCRs are saturated. Thus, besides resolving TCR stoichiometry, these data can explain how T cells respond to a wide range of MHCp concentrations while maintaining high sensitivity.     

Creating a professional image

Teaching can be a rewarding experience and teaching can also be a terrifying adventure, especially for the beginner. As a teacher you are looked upon as an expert in your subject. You are also expected to know all the answers to all the questions. You are expected and expect yourself to be organized and to know how to present the material in a way that your students will gain information easily. If you are an experienced nurse this may be achieved with some work because you can pull from your past experience and you know what works and what doesn't work. However, for the first time teacher, this new and wonderful experience to teach others can be so overwhelming you don't know where to start. This paper provides tips for the new teacher in order to make teaching a satisfying experience for both nurse and patients.     

The value of mentorship within nursing organizations

PROBLEM: Hospitals are facing nurse retention challenges in the new millennium. Nurses are abandoning the bedside because of job dissatisfaction. Mentorship programs should be developed to enhance nursing satisfaction and thus improve retention and ultimately patient outcomes. FINDINGS: Mentorship training in hospitals and the support of formal mentorship programs for new nurses are ways in which hospitals can meet this challenge. CONCLUSIONS: This paper offers an overview of recent research on the value mentoring has for participants and healthcare organizations. The components of successful mentorship programs are discussed, and guidelines for implementation are recommended.     

At Grandma's Home. Interview by Charlotte Alderman

Among African countries, Uganda has been help up as an example in tackling HIV/AIDS. Ruth Sims has pioneered care and treatment for many in need.     

Positron emission tomography in the investigation of pediatric inflammatory bowel disease

BACKGROUND: Endoscopic and radiologic studies are frequently required in inflammatory bowel disease (IBD) to determine disease activity, extent of disease, and delineating disease type. Positron emission tomography (PET) using fluorine-18-fluoro-deoxyglucose to identify metabolically active tissues may offer a simple noninvasive alternative to conventional studies in identification and localization of active intestinal inflammation in children with IBD. The aim of this study was to assess the value of PET in identifying active intestinal inflammation compared with conventional endoscopic and radiologic studies, including small bowel follow-through and colonoscopy. METHODS: Sixty-five children were enrolled in the study. This included 55 children (mean age, 13.3 yr; range, 7-18 yr; 20 girls) with newly diagnosed IBD (37) or symptoms suggestive of recurrent disease (18) and 10 children with recurrent abdominal pain (mean age, 12.7 yr; range, 8-15 yr; 7 girls) who were studied with PET, and the results were compared with small bowel follow-through with pneumocolon and/or colonoscopy. Thirty-eight patients had Crohn's disease (17 ileal, 12 ileocolic, 5 pancolonic, 3 left-sided disease, 1 right-sided disease), and 17 had ulcerative colitis (15 pan-colitis, 2 left-sided colitis). Mean time interval between PET and other studies was 30 +/- 17.6 days. RESULTS: PET correctly identified active inflammatory disease in 80% of children with IBD (81.5% with Crohn's disease; 76.4% with ulcerative colitis) and correctly showed no evidence of inflammation in children with recurrent abdominal pain. Gluorine-18-fluoro-deoxyglucose accumulated at sites that corresponded with active disease at colonoscopy in 83.8% of patients and with small bowel follow-through with pneumocolon 75.0% of the time. CONCLUSION: This study suggests that PET offers a noninvasive tool for identifying and localizing active intestinal inflammation in children with IBD. PET may not be able to replace conventional studies; however, it may be useful when conventional studies cannot be performed or fail to be completed.