Effect of magnesium therapy on nocturnal leg cramps: a systematic review of randomized controlled trials with meta-analysis using simulations

Background and objective. Nocturnal leg cramps (NLC) are common in primary care and may cause severe pain and sleep disturbance. We systematically reviewed the effectiveness of magnesium in treating NLC and the side-effect profile of magnesium compared to placebo. Methods. We searched Medline, Embase, Cochrane Library, ClinicalTrials.gov, the International Standard Randomised Controlled Trial Number and the International Clinical Trials Registry Platform registries until August 2012. All randomized controlled trials (RCTs) comparing magnesium therapy for NLC in adults with any other comparator were eligible. Two investigators independently selected, extracted data from and rated the risk of bias of relevant studies. To compensate for the heterogeneity in outcome measures, simulations were used to summarize the data. Results. Seven RCTs were included in the review (n = 361), all comparing magnesium to placebo. Three of these trials included only pregnant women. The difference in the median number of leg cramps per week between the placebo and the intervention groups was 0.345 (quantile 2.5%: −0.133, quantile 97.5%: 0.875). This difference was 0.807 (quantile 2.5%: 0.015, quantile 97.5%: 1.207) in the three studies involving only pregnant women and 0.362 (quantile 2.5%: −0.386, quantile 97.5%: 1.148) in the others. Overall gastrointestinal side effects were slightly more common with magnesium therapy than with placebo. The strength of this evidence was weak, mainly due to small study sizes and short follow-up. Conclusions. Magnesium therapy does not appear to be effective in the treatment of NLC in the general population, but may have a small effect in pregnant women. Further research using better designed RCTs is necessar

Individual heat map assessments demonstrate vestronidase alfa treatment response in a highly heterogeneous mucopolysaccharidosis VII study population.

Mucopolysaccharidosis (MPS) VII is an ultra-rare, progressively debilitating, life-threatening lysosomal disease caused by deficiency of the enzyme, β-glucuronidase. Vestronidase alfa is an approved enzyme replacement therapy for MPS VII. UX003-CL301 was a phase 3, randomized, placebo-controlled, blind-start study examining the efficacy and safety of vestronidase alfa 4 mg/kg intravenously administered every 2 weeks to 12 patients with MPS VII. Due to the rarity of disease, broad eligibility criteria resulted in a highly heterogeneous population with variable symptoms. For an integrated view of the diverse data, the changes from baseline (or randomization for the placebo period) in clinical endpoints were grouped into three functional domains (mobility, fatigue, and fine motor + self-care) and analyzed post-hoc as subject-level heat maps. Mobility assessments included the 6-minute walk test, 3-minute stair climb test, Bruininks-Oseretsky test (BOT-2) gross motor function subtests, and patient-reported outcome assessments (PROs) related to movement, pain, and ambulation. Fatigue assessments included the Pediatric Quality of Life Multidimensional Fatigue Scale and other fatigue-related PROs. Fine motor + self-care assessments included BOT-2 fine motor function subtests and PROs for eating, dressing, hygiene, and caregiver assistance. Most subjects showed improvement in at least one domain. Two subjects improved in two or more domains and two subjects did not show clear improvement in any domain. Both severely and mildly affected subjects improved with vestronidase alfa in clinical assessments, PRO results, or both. Heat map analysis demonstrates how subjects responded to treatment across multiple domains, providing a useful visual tool for studying rare diseases with variable symptoms

Rapidly evolving protointrons in Saccharomyces genomes revealed by a hungry spliceosome.

Introns are a prevalent feature of eukaryotic genomes, yet their origins and contributions to genome function and evolution remain mysterious. In budding yeast, repression of the highly transcribed intron-containing ribosomal protein genes (RPGs) globally increases splicing of non-RPG transcripts through reduced competition for the spliceosome. We show that under these "hungry spliceosome" conditions, splicing occurs at more than 150 previously unannotated locations we call protointrons that do not overlap known introns. Protointrons use a less constrained set of splice sites and branchpoints than standard introns, including in one case AT-AC in place of GT-AG. Protointrons are not conserved in all closely related species, suggesting that most are not under positive selection and are fated to disappear. Some are found in non-coding RNAs (e. g. CUTs and SUTs), where they may contribute to the creation of new genes. Others are found across boundaries between noncoding and coding sequences, or within coding sequences, where they offer pathways to the creation of new protein variants, or new regulatory controls for existing genes. We define protointrons as (1) nonconserved intron-like sequences that are (2) infrequently spliced, and importantly (3) are not currently understood to contribute to gene expression or regulation in the way that standard introns function. A very few protointrons in S. cerevisiae challenge this classification by their increased splicing frequency and potential function, consistent with the proposed evolutionary process of "intronization", whereby new standard introns are created. This snapshot of intron evolution highlights the important role of the spliceosome in the expansion of transcribed genomic sequence space, providing a pathway for the rare events that may lead to the birth of new eukaryotic genes and the refinement of existing gene function

Sexual and Reproductive Health Behaviors of Undocumented Migrants in Geneva: A Cross Sectional Study

Undocumented migrants face major barriers in accessing prevention and health care. Whereas the association between low socioeconomic status and poor health is well documented only few studies have addressed specific health issues in undocumented migrants. The aim of the present study is to describe sexual and reproductive health behaviors of undocumented migrants in Geneva. This descriptive cross sectional study included consecutive undocumented migrants presenting from November 2007 to February 2008 to a health facility offering free access to health care to this population. Following informed consent, they completed a self administered questionnaire about their socio-demographic profile and sexual and reproductive health behaviors. A total of 384 patients were eligible for the study. 313 (82%) agreed to participate of which 77% (241 patients) completed the survey. Participants were mainly young, Latino-American, single, well-educated and currently working women. They had multiple partners and reported frequently engaging in sexual intercourse. Use of contraceptive methods and strategies of prevention against sexually transmitted infections (STI) were rare. Nearly half of the women had had at least one induced abortion and 40% had had an unplanned pregnancy. One in four participants reported a current or past STI or other genital infection. The results of our study suggest that undocumented migrants engage in frequent and high risk sexual intercourse with insufficient use of contraceptive methods and suboptimal strategies of prevention against STI. Our study underlines the real need for specific sexual and reproductive educational programs targeting this hard to reach populatio

Fusion-Activated Ca2+ Entry: An “Active Zone” of Elevated Ca2+ during the Postfusion Stage of Lamellar Body Exocytosis in Rat Type II Pneumocytes

Background Ca2+ is essential for vesicle fusion with the plasma membrane in virtually all types of regulated exocytoses. However, in contrast to the well-known effects of a high cytoplasmic Ca2+ concentration ([Ca2+]c) in the prefusion phase, the occurrence and significance of Ca2+ signals in the postfusion phase have not been described before. Methodology/Principal Findings We studied isolated rat alveolar type II cells using previously developed imaging techniques. These cells release pulmonary surfactant, a complex of lipids and proteins, from secretory vesicles (lamellar bodies) in an exceptionally slow, Ca2+- and actin-dependent process. Measurements of fusion pore formation by darkfield scattered light intensity decrease or FM 1-43 fluorescence intensity increase were combined with analysis of [Ca2+]c by ratiometric Fura-2 or Fluo-4 fluorescence measurements. We found that the majority of single lamellar body fusion events were followed by a transient (t1/2 of decay = 3.2 s) rise of localized [Ca2+]c originating at the site of lamellar body fusion. [Ca2+]c increase followed with a delay of ∼0.2–0.5 s (method-dependent) and in the majority of cases this signal propagated throughout the cell (at ∼10 µm/s). Removal of Ca2+ from, or addition of Ni2+ to the extracellular solution, strongly inhibited these [Ca2+]c transients, whereas Ca2+ store depletion with thapsigargin had no effect. Actin-GFP fluorescence around fused LBs increased several seconds after the rise of [Ca2+]c. Both effects were reduced by the non-specific Ca2+ channel blocker SKF96365. Conclusions/Significance Fusion-activated Ca2+ entry (FACE) is a new mechanism that leads to [Ca2+]c transients at the site of vesicle fusion. Substantial evidence from this and previous studies indicates that fusion-activated Ca2+ entry enhances localized surfactant release from type II cells, but it may also play a role for compensatory endocytosis and other cellular functions

Integrating Incident Reporting into an Electronic Patient Record System

Developments in information technology offer new opportunities to design electronic patient record systems (EPR) which integrate a broad range of functions such as clinical decision support, order entry, or electronic alerts. It has been recently suggested that EPR could support new applications for disease surveillance and patient safety. We describe the integration of a voluntary incident reporting system into an EPR used in operating theatres, to allow the reporting of accidents and preventable complications. We assessed system's reliability and users' acceptance. During the 4-years observation period (2002-2006), 48,983 interventional procedures were performed. Clinicians documented 85.1% of procedures on the incident reporting form. Agreement between chart review and electronically reported incidents was 80.6%. The integration of an incident reporting system into an EPR is reliable and well supported by health care professional

Eyettention: An Attention-based Dual-Sequence Model for Predicting Human Scanpaths during Reading

Eye movements during reading offer insights into both the reader's cognitive processes and the characteristics of the text that is being read. Hence, the analysis of scanpaths in reading have attracted increasing attention across fields, ranging from cognitive science over linguistics to computer science. In particular, eye-tracking-while-reading data has been argued to bear the potential to make machine-learning-based language models exhibit a more human-like linguistic behavior. However, one of the main challenges in modeling human scanpaths in reading is their dual-sequence nature: the words are ordered following the grammatical rules of the language, whereas the fixations are chronologically ordered. As humans do not strictly read from left-to-right, but rather skip or refixate words and regress to previous words, the alignment of the linguistic and the temporal sequence is non-trivial. In this paper, we develop Eyettention, the first dual-sequence model that simultaneously processes the sequence of words and the chronological sequence of fixations. The alignment of the two sequences is achieved by a cross-sequence attention mechanism. We show that Eyettention outperforms state-of-the-art models in predicting scanpaths. We provide an extensive within- and across-data set evaluation on different languages. An ablation study and qualitative analysis support an in-depth understanding of the model's behavior

A NASA Lewis comparative propulsion system assessment for the High-Speed Civil Transport

The topics covered include the following: High Speed Research (HSR) Propulsion System Studies; HRS System Study flowpath; design point aircraft sizing - no noise constraint; impact of noise constraint; noise impact on aircraft size; takeoff gross weight assessment; impact of High Speed Civil Transport (HSCT) high-altitude flyover noise; HSR NO(x) reduction status; current assessment of HSCT ozone depletion; influence of non-optimum cruise altitude on range; and influence of subsonic leg on range