Abstract Objectives A survey was developed to assess experience and opinions about Lyme disease and post-treatment Lyme disease syndrome (PTLDS) among faculties in public health. No previous surveys ...of public health faculties have been found in the literature. Study design This is a cross sectional study of public health school faculty members designed to measure knowledge and experience with Lyme disease and PTLDS using an internet survey instrument. Methods Participants were recruited using all the publicly available e-mail addresses of faculty members in all the 50 accredited Schools of Public Health in the United States. Results A 15% response rate was seen for the survey. 50% of respondents were from Lyme endemic states. Less than 5% of faculty members consider themselves expert in Lyme or PTLDS. Many faculty members had known someone with Lyme disease or PTLDS, but few had been diagnosed themselves. Most believe that PTLDS can be severe and chronic, is not easy to treat, and does not resolve on its own, but were uncertain about its aetiology. Most respondents also felt that the incidence of Lyme disease will increase and that more education is needed. Conclusions The need for further understanding and communication presents an opportunity for public health research and education in Lyme disease and the sequelae of PTLDS.
The present studies provide a three-dimensional model for the postulated ternary cleavable complex of topoisomerase I (top1), DNA, and camptothecin (CPT). Molecular simulations were done using the ...AMBER force field. The results suggest that a ternary cleavable complex might be stabilized by several hydrogen bonds in the binding site. In this proposed "drug-stacking" model, CPT is pseudointercalated in the top1-linked DNA cleavage site and interacts with the protein near its catalytic tyrosine through hydrogen bonding and stacking. The structural model is consistent with the following experimental observations: (i) the N3 position of the 5' terminal purine of the cleaved DNA strand is readily alkylated by 7-chloromethyl 10,11-methylenedioxy CPT; (ii) CPT generally tolerates substituents at positions 7, 9, and 10 but is inactivated by additions at position 12; (iii) 10,11-methylenedioxy (MDO) CPT is much more potent than 10,11-dimethoxy (DMO) CPT; (iv) the lactone portion of CPT is essential for top1 inhibitory activity; (v) 20S derivatives of CPT are much more potent than the 20R analogues; (vi) a catalytic tyrosine hydroxyl in top1 covalently links to the 3' terminal base, T, of the cleaved DNA strand; and (vii) top1 mutation Asn722Ser leads to CPT resistance. A total of 18 camptothecin derivatives with different DNA cleavage potencies were docked into the hypothetical cleavable complex binding site to test and refine the model. These studies provide insight into a possible mechanism of top1 inhibition by CPT derivatives and suggest rational approaches for the design of new CPT derivatives.
There are large variations in the use of knee arthroplasty among Medicare enrollees according to race or ethnic group and sex. Are racial and ethnic disparities more pronounced in some regions than ...in others, and if so, why?
We used all Medicare fee-for-service claims data for 1998 through 2000 to determine the incidence of knee arthroplasty according to Hospital Referral Region, sex, and race or ethnic group. A total of 430,726 knee arthroplasties were performed during the three-year study period.
At the national level, the annual rate of knee arthroplasty was higher for non-Hispanic white women (5.97 procedures per 1000) than for Hispanic women (5.37 per 1000) and black women (4.84 per 1000). The rate for non-Hispanic white men (4.82 procedures per 1000) was higher than that for Hispanic men (3.46 per 1000) and more than double that for black men (1.84 per 1000). The rates were significantly lower for black men than for non-Hispanic white men in nearly every region of the country (P<0.05). For the Hispanic population and for black women, racial or ethnic disparities at the national level were due in part to geographic differences rather than to differences in the rates for different racial and ethnic groups within geographic areas. Residential segregation and low income levels contributed to racial and ethnic disparities in arthroplasty rates.
In the Medicare population, the rate of surgical treatment for osteoarthritis of the knee varies dramatically according to sex, race or ethnic group, and region. These variations underscore the importance of geography and sex in determining racial or ethnic barriers to health care.
Caring for individuals with chronic conditions is labor intensive, requiring ongoing appointments, treatments, and support. The growing number of individuals with chronic conditions makes this ...support model unsustainably burdensome on health care systems globally. Mobile health technologies are increasingly being used throughout health care to facilitate communication, track disease, and provide educational support to patients. Such technologies show promise, yet they are not being used to their full extent within US health care systems.
The purpose of this study was to examine the use of staff and costs of a remote monitoring care model in persons with and without a chronic condition.
At Dartmouth-Hitchcock Health, 2894 employees volunteered to monitor their health, transmit data for analysis, and communicate digitally with a care team. Volunteers received Bluetooth-connected consumer-grade devices that were paired to a mobile phone app that facilitated digital communication with nursing and health behavior change staff. Health data were collected and automatically analyzed, and behavioral support communications were generated based on those analyses. Care support staff were automatically alerted according to purpose-developed algorithms. In a subgroup of participants and matched controls, we used difference-in-difference techniques to examine changes in per capita expenditures.
Participants averaged 41 years of age; 72.70% (2104/2894) were female and 12.99% (376/2894) had at least one chronic condition. On average each month, participants submitted 23 vital sign measurements, engaged in 1.96 conversations, and received 0.25 automated messages. Persons with chronic conditions accounted for 39.74% (8587/21,607) of all staff conversations, with higher per capita conversation rates for all shifts compared to those without chronic conditions (P<.001). Additionally, persons with chronic conditions engaged nursing staff more than those without chronic conditions (1.40 and 0.19 per capita conversations, respectively, P<.001). When compared to the same period in the prior year, per capita health care expenditures for persons with chronic conditions dropped by 15% (P=.06) more than did those for matched controls.
The technology-based chronic condition management care model was frequently used and demonstrated potential for cost savings among participants with chronic conditions. While further studies are necessary, this model appears to be a promising solution to efficiently provide patients with personalized care, when and where they need it.
The effect of epidural injection of betamethasone or bupivacaine was investigated in an animal model of lumbar radiculopathy.
To investigate the effects of an epidural steroid (betamethasone) or a ...local anesthetic (bupivacaine) in an animal model of radiculopathy produced by nerve root irritation.
Epidural injections are commonly used for the treatment of low back pain and sciatica. However, efficacy remains controversial, and there is a paucity of basic information to support clinical use or the injections.
Fifty-one rats were used. The left L4 and L5 nerve roots were loosely ligated with chromic gut, and either betamethasone, bupivacaine, betamethasone in combination with bupivacaine, or saline was injected using an epidurally placed catheter. The effects of epidural injection were evaluated using response to noxious stimuli and immunohistochemical methods.
In betamethasone-treated rats (either alone or in combination with bupivacaine), thermal hyperalgesia was significantly less (P < 0.010 after surgery than that in saline- or bupivacaine-treated groups, in which the hyperalgesia was maximum at 2-3 postoperative weeks before resolving 5 weeks after surgery. Immunohistochemical analysis did not correlate with these results.
Epidural steroid injection has a significant effect on the thermal hyperalgesia produced in a model of radiculopathy, which may provide clinical support for advocates of epidural steroids.
Alteration of CSF flow has been proposed to be an important mechanism leading to the development of syringomyelia. We hypothesize that a "presyrinx" condition attributable to a potentially reversible ...alteration in normal CSF flow exists and that its appearance may be caused by variations in the competence of the central canal of the spinal cord.
Five patients with clinical evidence of myelopathy, no history of spinal cord trauma, enlargement of the cervical spinal cord with T1 and T2 prolongation but no cavitation, evidence of altered or obstructed CSF flow, and no evidence of intramedullary tumor or a spinal vascular event underwent MR imaging before and after intervention that alleviated obstruction to CSF flow.
Preoperatively, all patients had enlarged spinal cords and parenchymal T1 and T2 prolongation without cavitation. Results of MR examinations after intervention showed resolution of cord enlargement and normalization or improvement of cord signal abnormalities. In one patient with severe arachnoid adhesions who initially improved after decompression, late evolution into syringomyelia occurred in association with continued CSF obstruction.
Nontraumatic obstruction of the CSF pathways in the spine may result in spinal cord parenchymal T2 prolongation that is reversible after restoration of patency of CSF pathways. We refer to this MR appearance as the "presyrinx" state and stress the importance of timely intervention to limit progression to syringomyelia.
Alternative RNA splicing greatly increases proteome diversity and may thereby contribute to tissue-specific functions. We carried out genome-wide quantitative analysis of alternative splicing using a ...custom Affymetrix microarray to assess the role of the neuronal splicing factor Nova in the brain. We used a stringent algorithm to identify 591 exons that were differentially spliced in the brain relative to immune tissues, and 6.6% of these showed major splicing defects in the neocortex of Nova2-/- mice. We tested 49 exons with the largest predicted Nova-dependent splicing changes and validated all 49 by RT-PCR. We analyzed the encoded proteins and found that all those with defined brain functions acted in the synapse (34 of 40, including neurotransmitter receptors, cation channels, adhesion and scaffold proteins) or in axon guidance (8 of 40). Moreover, of the 35 proteins with known interaction partners, 74% (26) interact with each other. Validating a large set of Nova RNA targets has led us to identify a multi-tiered network in which Nova regulates the exon content of RNAs encoding proteins that interact in the synapse.
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