Rural to Urban Migration and Changes in Cardiovascular risk Factors in Tanzania: A Prospective Cohort Study.

High levels of rural to urban migration are a feature of most African countries. Our aim was to investigate changes, and their determinants, in cardiovascular risk factors on rural to urban migration in Tanzania. Men and women (15 to 59 years) intending to migrate from Morogoro rural region to Dar es Salaam for at least 6 months were identified. Measurements were made at least one week but no more than one month prior to migration, and 1 to 3 monthly after migration. Outcome measures included body mass index, blood pressure, fasting lipids, and self reported physical activity and diet. One hundred and three men, 106 women, mean age 29 years, were recruited and 132 (63.2%) followed to 12 months. All the figures presented here refer to the difference between baseline and 12 months in these 132 individuals. Vigorous physical activity declined (79.4% to 26.5% in men, 37.8% to 15.6% in women, p < 0.001), and weight increased (2.30 kg men, 2.35 kg women, p < 0.001). Intake of red meat increased, but so did the intake of fresh fruit and vegetables. HDL cholesterol increased in men and women (0.24, 0.25 mmoll-1 respectively, p < 0.001); and in men, not women, total cholesterol increased (0.42 mmoll-1, p = 0.01), and triglycerides fell (0.31 mmoll-1, p = 0.034). Blood pressure appeared to fall in both men and women. For example, in men systolic blood pressure fell by 5.4 mmHg, p = 0.007, and in women by 8.6 mmHg, p = 0.001. The lower level of physical activity and increasing weight will increase the risk of diabetes and cardiovascular disease. However, changes in diet were mixed, and may have contributed to mixed changes in lipid profiles and a lack of rise in blood pressure. A better understanding of the changes occurring on rural to urban migration is needed to guide preventive measures

What can we learn from facilitator and student perceptions of facilitation skills and roles in the first year of a problem-based learning curriculum?

BACKGROUND: The small group tutorial is a cornerstone of problem-based learning. By implication, the role of the facilitator is of pivotal importance. The present investigation canvassed perceptions of facilitators with differing levels of experience regarding their roles and duties in the tutorial. METHODS: In January 2002, one year after problem-based learning implementation at the Nelson R. Mandela School of Medicine, facilitators with the following experience were canvassed: trained and about to facilitate, facilitated once only and facilitated more than one six-week theme. Student comments regarding facilitator skills were obtained from a 2001 course survey. RESULTS: While facilitators generally agreed that the three-day training workshop provided sufficient insight into the facilitation process, they become more comfortable with increasing experience. Many facilitators experienced difficulty not providing content expertise. Again, this improved with increasing experience. Most facilitators saw students as colleagues. They agreed that they should be role models, but were less enthusiastic about being mentors. Students were critical of facilitators who were not up to date with curriculum implementation or who appeared disinterested. While facilitator responses suggest that there was considerable intrinsic motivation, this might in fact not be the case. CONCLUSIONS: Even if they had facilitated on all six themes, facilitators could still be considered as novices. Faculty support is therefore critical for the first few years of problem-based learning, particularly for those who had facilitated once only. Since student and facilitator expectations in the small group tutorial may differ, roles and duties of facilitators must be explicit for both parties from the outset

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

The broad-spectrum antimicrobial potential of [Mn(CO)4(S2CNMe(CH2CO2H))], a water-soluble CO-releasing molecule (CORM-401): intracellular accumulation, transcriptomic and statistical analyses, and membrane Polarization

Aims: Carbon monoxide (CO)-releasing molecules (CORMs) are candidates for animal and antimicrobial therapeutics. We aimed to probe the antimicrobial potential of a novel manganese CORM. Results: [Mn(CO)4S2CNMe(CH2CO2H)], CORM-401, inhibits growth of Escherichia coli and several antibiotic-resistant clinical pathogens. CORM-401 releases CO that binds oxidases in vivo, but is an ineffective respiratory inhibitor. Extensive CORM accumulation (assayed as intracellular manganese) accompanies antimicrobial activity. CORM-401 stimulates respiration, polarizes the cytoplasmic membrane in an uncoupler-like manner, and elicits loss of intracellular potassium and zinc. Transcriptomics and mathematical modeling of transcription factor activities reveal a multifaceted response characterized by elevated expression of genes encoding potassium uptake, efflux pumps, and envelope stress responses. Regulators implicated in stress responses (CpxR), respiration (Arc, Fnr), methionine biosynthesis (MetJ), and iron homeostasis (Fur) are significantly disturbed. Although CORM-401 reduces bacterial growth in combination with cefotaxime and trimethoprim, fractional inhibition studies reveal no interaction. Innovation: We present the most detailed microbiological analysis yet of a CORM that is not a ruthenium carbonyl. We demonstrate CO-independent striking effects on the bacterial membrane and global transcriptomic responses. Conclusions: CORM-401, contrary to our expectations of a CO delivery vehicle, does not inhibit respiration. It accumulates in the cytoplasm, acts like an uncoupler in disrupting cytoplasmic ion balance, and triggers multiple effects, including osmotic stress and futile respiration

CUSUM: A tool for early feedback about performance?

BACKGROUND: Modern day clinical practice demands evidence justifying our choice of treatment methods. Cumulative sum techniques (cusum) are amongst the simplest statistical methods known. They provide rapid analysis and identification of trends in a series of data. This study highlights use of these techniques as an early performance indicator of a clinical procedure before its implementation. METHODS: Twenty consecutive patients who underwent total hip or knee arthroplasty received a simple dressing – blue gauze and Tegaderm. Cusum charting was used to assess the dressing with regards to skin blistering. At an acceptable level of performance the curve would oscillate about the horizontal axis and the overall trend therefore said to be flat. If performance is unacceptable, the cusum slopes upward. RESULTS: The cusum plot for the twenty patients did not cross the specified control limits. This showed that our simple dressing met specified standards with regards to wound blistering postoperatively. CONCLUSION: We recommend the use of this simple, yet versatile cusum technique in the early evaluation of a clinical procedure before its implementation

Expanding dispersal studies at hydrothermal vents through species identification of cryptic larval forms

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Marine Biology 157 (2010): 1049-1062, doi:10.1007/s00227-009-1386-8.The rapid identification of hydrothermal vent-endemic larvae to the species level is a key limitation to understanding the dynamic processes that control the abundance and distribution of fauna in such a patchy and ephemeral environment. Many larval forms collected near vents, even those in groups such as gastropods that often form a morphologically distinct larval shell, have not been identified to species. We present a staged approach that combines morphological and molecular identification to optimize the capability, efficiency, and economy of identifying vent gastropod larvae from the northern East Pacific Rise (NEPR). With this approach, 15 new larval forms can be identified to species. A total of 33 of the 41 gastropod species inhabiting the NEPR, and 26 of the 27 gastropod species known to occur specifically in the 9° 50’ N region, can be identified to species. Morphological identification efforts are improved by new protoconch descriptions for Gorgoleptis spiralis, Lepetodrilus pustulosus, Nodopelta subnoda, and Echinopelta fistulosa. Even with these new morphological descriptions, the majority of lepetodrilids and peltospirids require molecular identification. Restriction fragment length polymorphism digests are presented as an economical method for identification of five species of Lepetodrilus and six species of peltospirids. The remaining unidentifiable specimens can be assigned to species by comparison to an expanded database of 18S ribosomal DNA. The broad utility of the staged approach was exemplified by the revelation of species-level variation in daily planktonic samples and the identification and characterization of egg capsules belonging to a conid gastropod Gymnobela sp. A. The improved molecular and morphological capabilities nearly double the number of species amenable to field studies of dispersal and population connectivity.Funding was provided by as Woods Hole Oceanographic Institution Deep Ocean Exploration Institute grant to L.M and S. Beaulieu, National Science Foundation grants OCE-0424953, OCE-9712233, and OCE-9619605 to L.M, OCE-0327261 to T.S., and OCE-0002458 to K. Von Damm, and a National Defense Science and Engineering Graduate fellowship to D.A

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

Differential neuromuscular training effects onACL injury risk factors in"high-risk" versus "low-risk" athletes

<p>Abstract</p> <p>Background</p> <p>Neuromuscular training may reduce risk factors that contribute to ACL injury incidence in female athletes. Multi-component, ACL injury prevention training programs can be time and labor intensive, which may ultimately limit training program utilization or compliance. The purpose of this study was to determine the effect of neuromuscular training on those classified as "high-risk" compared to those classified as "low-risk." The hypothesis was that high-risk athletes would decrease knee abduction moments while low-risk and control athletes would not show measurable changes.</p> <p>Methods</p> <p>Eighteen high school female athletes participated in neuromuscular training 3×/week over a 7-week period. Knee kinematics and kinetics were measured during a drop vertical jump (DVJ) test at pre/post training. External knee abduction moments were calculated using inverse dynamics. Logistic regression indicated maximal sensitivity and specificity for prediction of ACL injury risk using external knee abduction (25.25 Nm cutoff) during a DVJ. Based on these data, 12 study subjects (and 4 controls) were grouped into the high-risk (knee abduction moment >25.25 Nm) and 6 subjects (and 7 controls) were grouped into the low-risk (knee abduction <25.25 Nm) categories using mean right and left leg knee abduction moments. A mixed design repeated measures ANOVA was used to determine differences between athletes categorized as high or low-risk.</p> <p>Results</p> <p>Athletes classified as high-risk decreased their knee abduction moments by 13% following training (Dominant pre: 39.9 ± 15.8 Nm to 34.6 ± 9.6 Nm; Non-dominant pre: 37.1 ± 9.2 to 32.4 ± 10.7 Nm; p = 0.033 training X risk factor interaction). Athletes grouped into the low-risk category did not change their abduction moments following training (p > 0.05). Control subjects classified as either high or low-risk also did not significantly change from pre to post-testing.</p> <p>Conclusion</p> <p>These results indicate that "high-risk" female athletes decreased the magnitude of the previously identified risk factor to ACL injury following neuromuscular training. However, the mean values for the high-risk subjects were not reduced to levels similar to low-risk group following training. Targeting female athletes who demonstrate high-risk knee abduction loads during dynamic tasks may improve efficacy of neuromuscular training. Yet, increased training volume or more specific techniques may be necessary for high-risk athletes to substantially decrease ACL injury risk.</p

Evidence for the Decay D0→K+π−π+π−D^0\to K^+ \pi^-\pi^+\pi^-

We present a search for the ``wrong-sign'' decay D0 -> K+ pi- pi+ pi- using 9 fb-1 of e+e- collisions on and just below the Upsilon(4S) resonance. This decay can occur either through a doubly Cabibbo-suppressed process or through mixing to a D0bar followed by a Cabibbo-favored process. Our result for the time-integrated wrong-sign rate relative to the decay D0 -> K- pi+ pi- pi+ is (0.0041 +0.0012-0.0011(stat.) +-0.0004(syst.))x(1.07 +-0.10)(phase space), which has a statistical significance of 3.9 standard deviations.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR