Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015-2022): 2022 interim analysis.

OBJECTIVE: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, international, multicenter registry of real-world ataluren use in individuals with nonsense mutation Duchenne muscular dystrophy (nmDMD) in clinical practice. This updated interim report (data cut-off: January 31, 2022), describes STRIDE patient characteristics and ataluren safety data, as well as the effectiveness of ataluren plus standard of care (SoC) in STRIDE versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS). METHODS: Patients are followed up from enrollment for at least 5 years or until study withdrawal. Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established predictors of disease progression. RESULTS: As of January 31, 2022, 307 patients were enrolled from 14 countries. Mean (standard deviation [SD]) ages at first symptoms and at genetic diagnosis were 2.9 (1.7) years and 4.5 (3.7) years, respectively. Mean (SD) duration of ataluren exposure was 1671 (56.8) days. Ataluren had a favorable safety profile; most treatment-emergent adverse events were mild or moderate and unrelated to ataluren. Kaplan-Meier analyses demonstrated that ataluren plus SoC significantly delayed age at loss of ambulation by 4 years (p < 0.0001) and age at decline to %-predicted forced vital capacity of < 60% and < 50% by 1.8 years (p = 0.0021) and 2.3 years (p = 0.0207), respectively, compared with SoC alone. CONCLUSION: Long-term, real-world treatment with ataluren plus SoC delays several disease progression milestones in individuals with nmDMD. NCT02369731; registration date: February 24, 2015.

Combating hospital-acquired C. diff.

A successful collaboration between clinical nurse leaders and clinical nurse specialists.

Electromyographic analysis of an eccentric calf muscle exercise in persons with and without Achilles tendinopathy.

OBJECTIVES: To compare surface electromyographic (EMG) activity of the gastrocnemius and soleus muscles between persons with and without Achilles tendinopathy (AT) during an eccentric muscle exercise in different knee joint positions. DESIGN: Repeated measures design. SETTING: Research laboratory. PARTICIPANTS: Participants (n = 18) diagnosed with AT and 18 control subjects were recruited. MAIN OUTCOME MEASURES: Gastrocnemius and soleus muscle activity was examined by surface (EMG) during extended and flexed knee joint conditions while performing the eccentric training technique. The EMG data were expressed as a percentage of a maximum voluntary contraction (MVC). RESULTS: EMG activity was notably higher (mean difference: 10%, effect size: 0.59) in those subjects with AT. Irrespective of the presence of AT, there was a significant interaction effect between muscle and joint position. The gastrocnemius muscle was significantly more active in the extended knee condition and soleus muscle activity was unchanged across joint positions. CONCLUSIONS: The results indicated that the presence of AT influenced calf muscle activity levels during performance of the eccentric exercise. There were differences in muscle activity during the extended and flexed knee conditions. This result does support performing Alfredson, Pietila, Jonsson, and Lorentzon (1998) eccentric exercise in an extended knee position but the specific effects of the knee flexed position on the Achilles tendon during eccentric exercise have yet to be determined, particularly in those with AT.

Interactions between Controlled Atmospheres and Low Temperature Tolerance: A Review of Biochemical Mechanisms.

Controlled atmosphere treatments using carbon dioxide, oxygen, and/or nitrogen, together with controlled temperature and humidity, form an important method for post-harvest sterilization against insect-infested fruit. However, in insects, the cross tolerance and biochemical interactions between the various stresses of modified gas conditions and low temperature may either elicit or block standard stress responses which can potentiate (or limit) lethal low temperature exposure. Thus, the success of such treatments is sometimes erratic and does not always result in the desired pest mortality. This review focuses on the biochemical modes of action whereby controlled atmospheres affect insects low temperature tolerance, making them more (or occasionally, less) susceptible to cold sterilization. Insights into the integrated biochemical modes of action may be used together with the pests' low temperature tolerance physiology to determine which treatments may be of value in post-harvest sterilization.

Nectar xylose metabolism in a rodent pollinator (Aethomys namaquensis): defining the role of gastrointestinal microflora using 14C-labeled xylose.

The Namaqua rock mouse Aethomys namaquensis, a rodent pollinator of certain geoflorous Protea species, consumes nectar containing xylose. Xylose is not known to be efficiently utilized by mammals. However, it is fermented by certain bacteria, yeasts, and fungi, particularly gastrointestinal bacteria. The end products of microbial fermentation are utilized by the host in oxidative metabolism. Here we investigate the degree to which intestinal bacteria of A. namaquensis contribute to xylose metabolism. Mice were caught during Protea humiflora flowering and nonflowering seasons and given an oral dose of 14C-labeled xylose. Exhaled CO2 and excreted urine and feces were continuously collected for 30 h thereafter, and label recovery was determined. Each mouse was then treated with antibiotics to reduce gut microflora, and the experiment was repeated. With their natural gut flora population intact, mice caught during the flowering season exhaled significantly more 14CO2 than did mice caught during the nonflowering season. Also, during both seasons, mice exhaled significantly more 14CO2 before antibiotic treatment than after. Antibiotic treatment caused a significant increase in the proportion of 14C-labeled xylose that was excreted in the urine. The mouse diet likely influences the composition of the gastrointestinal community. Aethomys namaquensis relies on its gut microflora to ferment xylose, thereby converting it into end products that are used by the mice for metabolism.

Workshop proceedings: managing conflict of interest in science. A little consensus and a lot of controversy.

There is no doubt that participants in the Conflict of Interest (COI) Workshop at the Society of Toxicology (SOT) 2005 Annual Meeting (New Orleans, 6-10 March 2005) engaged in a vigorous and useful exchange of diverse ideas and viewpoints. While there was consensus on the value and interest of this Workshop, there was less consensus and more controversy over many of the issues discussed during the Workshop, which included the distinction between bias and conflict, the success or failure of policies of disclosure, whether waivers should or should not be granted to conflicted individuals in order to seat a "balanced" committee with appropriate expertise, whether conflicted individuals retain the ability to recognize their own conflict, and more. The discussion left no doubt, however, that conflict of interest will remain an important and controversial issue in the scientific community for some time to come.

Association of genomic O island 122 of Escherichia coli EDL 933 with verocytotoxin-producing Escherichia coli seropathotypes that are linked to epidemic and/or serious disease.

The distribution of EDL 933 O island 122 (OI-122) was investigated in 70 strains of Verocytotoxin-producing Escherichia coli (VTEC) of multiple serotypes that were classified into five "seropathotypes" (A through E) based on the reported occurrence of serotypes in human disease, in outbreaks, and/or in the hemolytic-uremic syndrome (HUS). Seropathotype A comprised 10 serotype O157:H7 and 3 serotype O157:NM strains. Seropathotype B (associated with outbreaks and HUS but less commonly than serotype O157:H7) comprised three strains each of serotypes O26:H11, O103:H2, O111:NM, O121:H19, and O145:NM. Seropathotype C comprised four strains each of serotypes O91:H21 and O113:H21 and eight strains of other serotypes that have been associated with sporadic HUS but not typically with outbreaks. Seropathotype D comprised 14 strains of serotypes that have been associated with diarrhea but not with outbreaks or HUS, and seropathotype E comprised animal VTEC strains of serotypes not implicated in human disease. All strains were tested for four EDL 933 OI-122 virulence genes (Z4321, Z4326, Z4332, and Z4333) by PCR. Negative PCRs were confirmed by Southern hybridization. Overall, 28 (40%) strains contained OI-122 (positive for all four virulence genes), 27 (38.6%) contained an "incomplete" OI-122 (positive for one to three genes), and 15 (21.4%) strains did not contain OI-122. The seropathotype distribution of complete OI-122 was as follows: 100% for seropathotype A, 60% for B, 36% for C, 15% for D, and 0% for E. The differences in the frequency of OI-122 between seropathotypes A, B, and C (associated with HUS) and seropathotypes D and E (not associated with HUS) and between seropathotypes A and B (associated with epidemic disease) and seropathotypes C, D, and E (not associated with epidemic disease) were highly significant (P < 0.0001).

School violence: an insider view.

PURPOSE: To discover what teachers perceive to be contributing factors to violence in schools. STUDY DESIGN AND METHODS: Open-ended questions were asked of a convenience sample of teachers ( = 396) during an in-service education program on school violence. The teachers were in a semi-rural school district in a Mid-Atlantic state. Answers were analyzed using content analysis; all responses were reviewed and important themes were extracted. Identified themes were then placed into suitable categories and studied to determine relationships. RESULTS: Of the surveys analyzed ( = 239), 13 themes were identified. The three categories which then identified probable causes of school violence were (1) lack of knowledge, (2) lack of support, and (3) inadequate safety measures. CLINICAL IMPLICATIONS: Nurses can use the results of this study in multiple ways. One is to help parents understand their role in preventing school violence. Because violence in the home and violence in the media seem to foster violent acting-out behavior, nurses can teach parents about these correlations and seek solutions such as the elimination of family violence, and monitoring television viewing and video games. Nursing assessments of school-aged children and their families can include these elements. School nurses in particular can use these study results as an opportunity to develop interventions for students, teachers, and families that stress knowledge building about impulse control, anger management, appropriate parenting, and early intervention for at-risk children.

PCR for detection of cdt-III and the relative frequencies of cytolethal distending toxin variant-producing Escherichia coli isolates from humans and cattle.

A PCR assay that uses primers whose sequences were obtained from the published sequence of the cdt-III gene was developed to determine the frequencies of the cdt-I, cdt-II, and cdt-III genes in Escherichia coli isolates from humans and animals. E. coli isolates producing cytolethal distending toxin (CDT) were infrequently detected. The cdt-I gene was preferentially detected in strains with the cnf1 gene, while the cdt-III gene was found in strains carrying the cnf2 gene. The cdt-III genotype was more prevalent in animal isolates, while the cdt-I and cdt-II genotypes were more evident in human isolates. The presence of further cdt gene variants was indicated by the presence of toxin activity in cell culture in the absence of PCR amplification of the cdt-I, cdt-II, or cdt-III gene.