The analgesic effect of botulinum-toxin A on postwhiplash neck pain

BACKGROUND: The effectiveness of botulinum neurotoxin type A (BTXA) injections in relieving the neck pain and reduced motion that evolve after whiplash injury (WI) has been controversial. AIM OF STUDY: To test the long-term efficacy of a tender point injection of BTXA in relieving neck pain in patients with WI. METHODS: Twenty patients with cervical myofascial pain, 2 to 48 weeks after WI, were randomly assigned to receive either 200 U of BTXA or placebo at 4 tender points and were seen during the follow-ups 3, 6, 9, 12, and 24 weeks after the injections. Outcome measures included the intensity of pain as evaluated by a 10-cm Visual Analog Scale (VAS) and a 5-point Verbal Rating Scale (VRS), quality of life as evaluated by the SF-36 questionnaire, treatment efficacy as per the global assessment of the physician and patient, intensity of pain in response to mechanical pressure, range of cervical motion, and use of other therapies and their adverse effects. RESULTS: A time-dependent improvement in all the parameters was found in both groups, which was consistently larger in the BTXA-treated group, but mostly not at a significant level. Significant differences between the groups were found only in the percentages of patients who achieved 50% or more of reduction in intensity (VAS and average VRS) at 24 weeks (50% vs. 0%, P>0.05 and 70% vs. 11%, P>0.05, respectively). Systemic adverse effects tended to be more common in the BTXA-treated group (40% vs. 0%, P=0.07). CONCLUSIONS: Study results suggest that BTXA treatment has some efficacy when administered within 1 year of the WI. However, a large, well-designed clinical trial is needed to draw final conclusions.     

Vaccinia virus exhibits cell-type-dependent entry characteristics

Differing and sometimes conflicting data have been reported regarding several aspects of vaccinia virus (VV) entry. To address this, we used a β-galactosidase reporter virus to monitor virus entry into multiple cell types under varying conditions. Entry into HeLa, B78H1 and L cells was strongly inhibited by heparin whereas entry into Vero and BSC-1 cells was unaffected. Bafilomycin also exhibited variable and cell-type-specific effects on VV entry. Entry into B78H1 and BSC-1 cells was strongly inhibited by bafilomycin whereas entry into Vero and HeLa cells was only partially inhibited suggesting the co-existence of both pH-dependent and pH-independent VV entry pathways in these cell types. Finally, entry into HeLa, B78H1, L and BSC-1 cells exhibited a lag of 6-9 min whereas this delay was undetectable in Vero cells. Our results suggest that VV exploits multiple cell attachment and entry pathways allowing it to infect a broad range of cells.     

What do dental students think about mandatory laptop programs?

In spite of efforts by many dental schools to provide information technology resources for students, only a handful of studies have been conducted to determine what dental students think about these initiatives. There are no reports in the literature describing students' perceptions of mandatory laptop programs, which are now being implemented by at least 25 percent of North American dental schools. In schools that have implemented laptop programs, students are required either to enroll with their own laptops that meet specifications or to purchase a laptop from the school at matriculation. In some schools, students are also required to purchase curriculum support software that is bundled with the laptop. This study was conducted to determine students' opinions at U.S. dental schools with mandatory laptop programs about these aspects of this information technology initiative: frequency of use, perceived necessity of use, note-typing during lectures, effectiveness of training, influence on study habits, benefits, implementation problems, added value in relation to added tuition costs, impact on quality of dental education, overall rating of the laptop experience, and impact of the laptop on use of other electronic curriculum resources. Responses of students at schools that purchased packaged curriculum support software from a commercial vendor were compared with students' responses at schools where faculty provided their own educational software. Responses were also compared among freshmen, sophomores, and upperclassmen in a cross-sectional sample. In 2004, approximately 800 dental students at fourteen dental schools responded to eleven questions that requested their impressions and evaluation of mandatory laptop programs and associated educational software. These questions comprised one section of the IREC Students' Questionnaire (IREC=Institutional Readiness for Electronic Curriculum) that assessed students' perceptions of various aspects of information technology at their schools. The majority of students (63 percent) reported that the laptop and associated software were not essential for successful performance in their courses primarily because few instructors had modified their courses to take advantage of laptop capacities. Slightly more than half of the students reported their training was good or excellent, but felt that classroom-based "one size fits all" training was not effective. Less than 15 percent of the students reported that they had made substantial changes in their study habits as a consequence of the laptop program. The benefits perceived by students were primarily related to enhanced email communication with classmates and instructors and convenient access to the Internet and teachers' PowerPoint presentations. Implementation barriers included the inconvenience of carrying laptops to classes, lack of incentive to use the laptop and software because instructors did not require it, and poor quality software. Only 32 percent of students agreed that the value of the laptop and associated software was equal to the added tuition costs. Less than half of the students perceived that the laptop and software had improved the quality of their education, but more than 70 percent rated their overall experiences with laptops as "okay," "good," or "excellent." Freshmen expressed significantly more positive attitudes about the frequency of use, cost-effectiveness, educational value, and overall quality of laptops and bundled software than did upperclassmen. A significantly higher percentage of students at schools affiliated with a software vendor reported that laptops were essential in courses than students at schools with locally produced software, but students at vendor-supplied schools rated the cost-effectiveness significantly lower. Overall, students' assessment of mandatory laptop programs was mixed although freshmen provided significantly more positive responses than did upperclassmen. Incorporation of the e-curriculum into dental schools appears to be following a similar pattern as problem-based learning (PBL) in the 1980s and 1990s. Recommendations for enhancing future e-curricula are proposed based on lessons learned from both information technology and PBL implementation.     

Embryonic myocardium shows increased longevity as a functional tissue when cultured in the presence of a noncardiac tissue layer

A major aim of regenerative medicine is the construction of bioengineered organs and tissue for transplantation into human patients; yet living tissue is dynamic, and thus arranging cellular and extracellular constituents into an architecture resembling normal adult organs may not be sufficient to maintain tissue stability. In this study, we used cultures of embryonic chick heart tissue as a model to explore how newly formed cardiac tissue constructs can sustain their morphological structure and functional capabilities over extended periods. During the initial days of incubation, embryonic cardiac explants will thrive as beating three-dimensional tissue aggregates. However, within the first week of culture, cardiac aggregates lose their contractile function and flatten. After 2 weeks of incubation, the cardiac cells will have spread out into a homogeneous monolayer and dedifferentiated to a noncardiac phenotype. In contrast, when the embryonic heart tissue was co-cultured with a noncardiac cell layer obtained from adult bone marrow, the cardiac aggregates maintained their contractile function, three-dimensional tissue morphology, and myocyte phenotype for a full month of incubation. The capacity of this noncardiac cell layer to sustain the phenotype and morphology of the cardiac explants was partially replicated by treatment of the heart tissue with conditioned media from bone marrow cells. These findings are discussed in regard to the importance of adjacent cell layers for facilitating organogenesis in the developing embryo and having potential utility in producing stable bioengineered tissue constructs.     

Somatic mutations of GUCY2F, EPHA3, and NTRK3 in human cancers

Tyrosine kinases are major regulators of signal transduction cascades involved in cellular proliferation and have important roles in tumorigenesis. We have recently analyzed the tyrosine kinase gene family for alterations in human colorectal cancers and identified somatic mutations in seven members of this gene family. In this study we have used high-throughput sequencing approaches to further evaluate this subset of genes for genetic alterations in other human tumors. We identified somatic mutations in GUCY2F, EPHA3, and NTRK3 in breast, lung, and pancreatic cancers. Our results implicate these tyrosine kinase genes in the pathogenesis of other tumor types and suggest that they may be useful targets for diagnostic and therapeutic intervention in selected patients.     

The circadian clock gene BMAL1 is a novel therapeutic target for malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm arising from the mesothelial cells lining the parietal pleura and it exhibits poor prognosis. Although there has been significant progress in MPM treatment, development of more efficient therapeutic approaches is needed. BMAL1 is a core component of the circadian clock machinery and its constitutive overexpression in MPM has been reported. Here, we demonstrate that BMAL1 may serve as a molecular target for MPM. The majority of MPM cell lines and a subset of MPM clinical specimens expressed higher levels of BMAL1 compared to a nontumorigenic mesothelial cell line (MeT-5A) and normal parietal pleural specimens, respectively. A serum shock induced a rhythmical BMAL1 expression change in MeT-5A but not in ACC-MESO-1, suggesting that the circadian rhythm pathway is deregulated in MPM cells. BMAL1 knockdown suppressed proliferation and anchorage-dependent and independent clonal growth in two MPM cell lines (ACC-MESO-1 and H290) but not in MeT-5A. Notably, BMAL1 depletion resulted in cell cycle disruption with a substantial increase in apoptotic and polyploidy cell population in association with downregulation of Wee1, cyclin B and p21^WAF1/CIP1 and upregulation of cyclin E expression. BMAL1 knockdown induced mitotic catastrophe as denoted by disruption of cell cycle regulators and induction of drastic morphological changes including micronucleation and multiple nuclei in ACC-MESO-1 cells that expressed the highest level of BMAL1. Taken together, these findings indicate that BMAL1 has a critical role in MPM and could serve as an attractive therapeutic target for MPM.