Plasma free choline, betaine and cognitive performance: the Hordaland Health Study

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70–74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P= 0·004), m-DST (10·5 v. 9·8, P= 0·005) and m-MMSE (11·5 v. 11·4, P= 0·01). A generalised additive regression model showed a positive dose–response relationship between the m-MMSE and choline (P= 0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B12 ( ≤ 257 pmol/l) concentrations (RRKOLT= 2·6, 95 % CI 1·1, 6·1; RRm-MMSE= 2·7, 95 % CI 1·1, 6·6; RRCOWAT= 3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) ( ≥ 3·95 μmol/l) concentrations (RRm-BD= 2·8, 95 % CI 1·3, 6·1). Low betaine ( ≤ 31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RRKOLT= 2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B12 or high MMA on cognitive performance.publishedVersio

Experienced stressors and coping strategies among Iranian nursing students

<p>Abstract</p> <p>Background</p> <p>College students are prone to stress due to the transitional nature of college life. High levels of stress are believed to affect students' health and academic functions. If the stress is not dealt with effectively, feelings of loneliness, nervousness, sleeplessness and worrying may result. Effective coping strategies facilitate the return to a balanced state, reducing the negative effects of stress.</p> <p>Methods</p> <p>This descriptive cross-sectional study was performed to determine sources of stress and coping strategies in nursing students studying at the Iran Faculty of Nursing & Midwifery. All undergraduate nursing students enrolled in years 1-4 during academic year 2004-2005 were included in this study, with a total of 366 questionnaires fully completed by the students. The Student Stress Survey and the Adolescent Coping Orientation for Problem Experiences Inventory (ACOPE) were used for data collection.</p> <p>Results</p> <p>Most students reported "finding new friends" (76.2%), "working with people they did not know" (63.4%) as interpersonal sources of stress, "new responsibilities" (72.1%), "started college" (65.8%) as intrapersonal sources of stress more than others. The most frequent academic source of stress was "increased class workload" (66.9%) and the most frequent environmental sources of stress were being "placed in unfamiliar situations" (64.2%) and "waiting in long lines" (60.4%). Interpersonal and environmental sources of stress were reported more frequently than intrapersonal and academic sources. Mean interpersonal (P=0.04) and environmental (P=0.04) sources of stress were significantly greater in first year than in fourth year students. Among coping strategies in 12 areas, the family problem solving strategies, "trying to reason with parents and compromise" (73%) and "going along with family rules" (68%) were used "often or always" by most students. To cope with engaging in demanding activity, students often or always used "trying to figure out how to deal with problems" (66.4%) and "trying to improve themselves" (64.5%). The self-reliance strategy, "trying to make their own decisions" (62%); the social support strategies, "apologizing to people" (59.6%), "trying to help other people solve their problems" (56.3%), and "trying to keep up friendships or make new friends" (54.4%); the spiritual strategy, "praying" (65.8%); the seeking diversions strategy, "listening to music" (57.7%), the relaxing strategy "day dreaming" (52.5%), and the effort to "be close with someone cares about you" (50.5%) were each used "often or always" by a majority of students. Most students reported that the avoiding strategies "smoking" (93.7%) and "drinking beer or wine" (92.9%), the ventilating strategies "saying mean things to people" and "swearing" (85.8%), the professional support strategies "getting professional counseling" (74.6%) and "talking to a teacher or counselor" (67.2%) and the humorous strategy "joking and keeping a sense of humor" (51.9%) were used "seldom or never".</p> <p>Conclusion</p> <p>First year nursing students are exposed to a variety of stressors. Establishing a student support system during the first year and improving it throughout nursing school is necessary to equip nursing students with effective coping skills. Efforts should include counseling helpers and their teachers, strategies that can be called upon in these students' future nursing careers.</p

CRISPR/Cas9 DNA cleavage at SNP-derived PAM enables both in vitro and in vivo KRT12 mutation-specific targeting

CRISPR/Cas9-based therapeutics hold the possibility for permanent treatment of genetic disease. The potency and specificity of this system has been used to target dominantly inherited conditions caused by heterozygous missense mutations through inclusion of the mutated base in the short-guide RNA (sgRNA) sequence. This research evaluates a novel approach for targeting heterozygous single-nucleotide polymorphisms (SNPs) using CRISPR/Cas9. We determined that a mutation within KRT12, which causes Meesmann's epithelial corneal dystrophy (MECD), leads to the occurrence of a novel protospacer adjacent motif (PAM). We designed an sgRNA complementary to the sequence adjacent to this SNP-derived PAM and evaluated its potency and allele specificity both in vitro and in vivo. This sgRNA was found to be highly effective at reducing the expression of mutant KRT12 mRNA and protein in vitro. To assess its activity in vivo we injected a combined Cas9/sgRNA expression construct into the corneal stroma of a humanized MECD mouse model. Sequence analysis of corneal genomic DNA revealed non-homologous end-joining repair resulting in frame-shifting deletions within the mutant KRT12 allele. This study is the first to demonstrate in vivo gene editing of a heterozygous disease-causing SNP that results in a novel PAM, further highlighting the potential for CRISPR/Cas9-based therapeutics

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Plasma free choline, betaine and cognitive performance: the Hordaland Health Study

Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70–74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P= 0·004), m-DST (10·5 v. 9·8, P= 0·005) and m-MMSE (11·5 v. 11·4, P= 0·01). A generalised additive regression model showed a positive dose–response relationship between the m-MMSE and choline (P= 0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B12 ( ≤ 257 pmol/l) concentrations (RRKOLT= 2·6, 95 % CI 1·1, 6·1; RRm-MMSE= 2·7, 95 % CI 1·1, 6·6; RRCOWAT= 3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) ( ≥ 3·95 μmol/l) concentrations (RRm-BD= 2·8, 95 % CI 1·3, 6·1). Low betaine ( ≤ 31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RRKOLT= 2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B12 or high MMA on cognitive performance

Bleb Revision for Resolution of Hypotony Maculopathy Following Primary Trabeculectomy

PURPOSE: To describe a surgical method of bleb revision for hypotony maculopathy, to evaluate its long-term efficacy, and to define the relationship between the duration of hypotony maculopathy and visual acuity (VA) outcomes. DESIGN: Noncomparative retrospective case series. METHODS: Medical records of 33 patients with hypotony maculopathy who underwent primary bleb revision between June 1999 and September 2012 by a single surgeon at an academic medical center were reviewed. Hypotony maculopathy was characterized by the presence of a decrease in VA, retinal striae, and macular edema in the setting of decreased intraocular pressure (IOP) after glaucoma filtering surgery. The main outcome measure was final logMAR VA after bleb revision at 6 and 12 months. RESULTS: Thirty-three eyes of 33 patients were followed for 4.68 ± 3.56 years (range 0.55–12.69 years). Mean duration of hypotony maculopathy was 4.98 ± 8.93 months. LogMAR VA improved from 0.78 ± 0.40 at baseline to 0.34 ± 0.34 (P < .001) 6 months after bleb revision and to 0.45 ± 0.55 (P < .001) 12 months after bleb revision. Spearman rank coefficient (r(s)) correlating duration of hypotony and BCVA at both 6 and 12 months was significant (P = .015 and r(s) = 0.426, P = .028 and r(s) = 0.416, respectively). Mean IOP increased from 3.51 ± 2.27 mm Hg to 12.06 ± 4.06 mm Hg (P < .001) at 12 months. Fifty-two percent were on no antiglaucoma medications at last follow-up. Five eyes (15%) required a second bleb revision to correct persistent hypotony maculopathy. CONCLUSION: Surgical repair for hypotony maculopathy provided a significant improvement in VA at 6 and 12 months. Surgical bleb revision is associated with good long-term control of IOP and improved VA in eyes with hypotony maculopathy after previous glaucoma filtering surgery