Introduction: Recent data showed that long QT syndrome (LQTS) patients with mutations in the pore region of the HERG (LQT2) gene have significantly higher risk of cardiac events than subjects with ...mutations in the non‐pore region. The aim of this study was to determine whether there is an association between the location of mutations in the KCNQ1 gene and cardiac events in LQT1 patients.
Methods and Results: The study population consisted of 294 LQT1 patients with KCNQ1 gene mutations. Demographic, clinical, and follow‐up information was compared among subjects with different locations of KCNQ1 mutations defined as pre‐pore region including N‐terminus (1–278), pore region (279–354), and post‐pore region including C‐terminus (>354). Cardiac events observed during follow‐up from birth until age of last contact or age 40 years were defined as syncope, cardiac arrest, or sudden death. There were 164 (56%) LQT1 patients with pre‐pore mutations, 101 (34%) with pore mutations, and 29 (10%) with post‐pore mutations. QTc duration did not differ significantly among the three subgroups (mean QTc = 494, 487, and 501 ms, respectively). There was no significant difference between groups with regard to the risk of cardiac events by age 40 years.
Conclusion: There are no significant differences in clinical presentation, ECG parameters, and cardiac events among LQT1 patients with different locations of KCNQ1 mutations. These findings indicate that factors other than location of mutation influence clinical phenotype in patients with LQT1 mutations. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1149‐1153, November 2003)
Ensuring students with severe disabilities access the rich relationship and learning opportunities available within general education classrooms is an important--but challenging--endeavor. Although ...one-to-one paraprofessionals often accompany students in inclusive classrooms and provide extensive assistance, the constant presence of an adult can inadvertently limit the social interactions and engagement of adolescents with severe disabilities within high school classrooms. Peer support arrangements can be a practical and promising alternative to exclusively relying on paraprofessionaldelivered support. We draw on our recent partnership with schools implementing these interventions for more than 50 high school students with severe disabilities and involving more than 100 peers without developmental disabilities. This article outlines practical steps for establishing these interventions in inclusive classrooms.
Sperm are motile cells. Thus, a significant component of the spermatogenic cycle is devoted to the formation of flagellum, a process that must be coordinated to insure proper construction. To ...document the temporal pattern of flagellar gene expression, we employed real-time PCR to assess changes in accumulation of a cohort of genes encoding axoneme, outer dense fibre (ODF) and fibrous sheath (FS) proteins during the first wave of spermatogenesis in the mouse. Axoneme genes were expressed first at the pachytene spermatocyte stage, followed by expression of transcripts encoding ODF and FS components. However, there were differences among these families with respect to the time of initial expression and the rate of mRNA accumulation. To gain understanding of factors that determine these patterns of expression, we cloned the promoters of three axoneme central apparatus genes (Pf6, Spag6 and Pf20). These promoters shared common features including the absence of a TATA box, and putative binding sites for several factors implicated in spermatogenesis (CREB/CREM, SOX17 and SPZ1) as well as ciliogenesis (FOXJ1). Collectively, our findings demonstrate a sequential pattern of expression of flagellar component genes, differential times of expression or rates of transcript accumulation within each class and shared promoter features within a class.
Dosing of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF) patients was based on single-dose pharmacokinetic studies. This investigation was prompted by evidence of possible ...antibiotic accumulation in respiratory secretions with repeated dosing. The objectives were to evaluate whether tobramycin accumulates in respiratory secretions with repeated inhalation, compare total and biologically active tobramycin concentrations in CF sputum, and evaluate sputum induction for obtaining secretions for drug concentration assay.
Individuals with CF ≥10 years of age were enrolled at the beginning of a course of TSI, 300 mg twice daily for 28 days. Two study visits were conducted, 1-2 days and 24-28 days after initiation of TSI treatment. Induced sputum and expectorated sputum samples were collected for measurement of trough and peak tobramycin concentrations at each visit. Total tobramycin concentrations were measured by high-pressure liquid chromatography and bioactive concentrations by bioassay.
Twenty participants completed the study. Trough concentrations were similar at visits 1 and 2, as were peak concentrations. Trough bioactive and total tobramycin concentrations were similar (mean ratio 1.2, 95% CI 0.56, 1.87), but peak bioactive concentrations were significantly lower than peak total concentrations (mean ratio 0.33, 95% CI 0.23, 0.44). Sputum induction was well tolerated.
No evidence of significant drug accumulation in respiratory secretions with repeat dosing of TSI was seen. Peak bioactive concentrations, although lower than peak total concentrations, were still generally well within the bactericidal range. Sputum induction as a method for determining airway drug concentrations appears safe and feasible.
Weather and Climate of Alaska is an undergraduate course for nonscience majors where students study meteorology from their home as part of a statewide network of classmates. The students draw on ...their experience of the weather and climate by observing weather locally and sharing their work with classmates across the state. The goal of the class is to have this cohort of students understand weather and climate through exploring the relationships between processes at the local, regional, and global scales. The class is organized around weekly investigations where the students use an equipment kit to make observations, report their work with videos, and discuss the work with the instructor and their peers. The students use NWS resources extensively, including station data to check the quality of their observations, weather maps and satellite images to understand the weather they have observed, weather forecasts to evaluate different forecasting techniques, and long-term data to compare their observations with the climate record. The course also includes traditional quizzes and exams. The instructor has regular teleconferences with students and discusses their work firsthand. A teaching assistant also supports the students. Students take pre- and postcourse tests and show gains typical of interactive science classes. The level of student support results in high student course completion rates.
A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted ...in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat.
It has been proposed that two distinct forms of intimate partner violence exist: intimate terrorism and situational couple violence. This article describes the distribution of factors that ...characterize intimate terrorism and situational couple violence, including controlling behaviors, violence escalation, and injury, among a representative sample of 331 physically assaulted women living in 11 North American cities. In addition, respondent, partner, and relationship characteristics associated with each form of violence are identified. Most women who experienced physical assault also experienced controlling behavior by their male partner. In multivariate analyses, respondent's young age, violence escalation in the relationship, partner's access to guns, previous arrests for domestic violence offenses, poor mental health, and previous suicide attempts or threats were associated with intimate terrorism, defined as experiencing one or more controlling behaviors. These results suggest that situational couple violence is rare and that moderate and high levels of controlling behaviors are associated primarily with partner factors.
Asphalts, biochemically degraded oil, contain persistent, water-soluble compounds that pose a significant challenge to the isolation of PCR quality DNA. The adaptation of existing DNA purification ...protocols and commercial kits proved unsuccessful at overcoming this hurdle. Treatment of aqueous asphalt extracts with a polyamide resin afforded genomic microbial DNA templates that could readily be amplified by PCR. Physicochemically distinct asphalt samples from five natural oil seeps successfully generated the expected 291bp amplicons targeting a region of the 16S rRNA gene, illustrating the robustness of the method. DNA recovery yields were in the 50–80% range depending on how the asphalt sample was seeded with exogenous DNA. The scope of the new method was expanded to include soil with high humic acid content. DNA from soil samples spiked with a range of humic acid concentrations was extracted with a commercial kit followed by treatment with the polyamide resin. The additional step significantly improved the purity of the DNA templates, especially at high humic acid concentrations, based on qPCR analysis of the bacterial 16S rRNA genes. The new method has the advantages of being inexpensive, simple, and rapid and should provide a valuable addition to protocols in the field of petroleum and soil microbiology.
•A new method for the isolation of PCR quality DNA from natural asphalt and soil•The method provides high (50-80%) DNA recovery yields.•A polyamide resin is used to remove PCR inhibitors from environmental samples.•Physicochemically distinct samples successfully generated the expected amplicons.•The method has the advantages of being inexpensive, simple, and rapid.
Purpose: A healthy diet and consistent physical activity (PA) form the foundation for effective self-management in adults with type 2 diabetes mellitus (T2DM). Behavioral interventions, which target ...diet and PA, can facilitate effective diabetes self-management practices. Greater clarity regarding the 'active ingredients' incorporated into behavioral interventions is needed to inform the evidence base about effective intervention techniques to advance behavioral theories and to improve clinical practice. The use of intervention mapping (IM) to develop a novel diabetes intervention to increase consumption of low glycemic index (GI) foods and to increase moderate-to-vigorous intensity PA is presented.
Methods: Determinants from self-regulation and the Health Action Process Approach theoretical framework formed the foundation of the intervention. The IM taxonomy of behavior change methods and strategies from Hope Therapy (e.g. goal maps) were used to guide techniques for changing selected theoretical determinants of behavior. A pilot study of the intervention among adults with T2DM (n = 12) was conducted using a pre-/post-test design to evaluate intervention components and participant acceptability.
Results: Participants attended a mean (±SD) of 8 (±1.4) of the 10 weekly 90-minute, group-based sessions. The magnitude of effect was moderate (d > 0.50) for the change in behavioral intentions, action control, and action and coping planning for engaging in PA and large (d > 0.80) for the change in action self-efficacy and action and coping planning for eating low GI foods post-intervention.
Conclusions: Greater emphasis on value-based decision-making, the goal mapping process, and successively progressive exercise goals should be included in future versions of the intervention. Based on pilot testing, a larger randomized controlled trial that incorporates these intervention modifications is warranted and the modified intervention has a greater likelihood for success.
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