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Globalization of infectious diseases: the impact of migration.

With up to 2% of the world's population living outside of their country of birth, the potential impact of population mobility on health and on use of health services of migrant host nations is increasing in its importance. The drivers of mobility, the process of the international movement, and the back-and-forth transitioning between differential risk environments has significance for the management of infectious diseases in migrant receiving areas. The management issues are broad, high-level, and cross-cutting, including policy decisions on managing the migration process for skilled-labor requirements, population demographic and biometric characteristics, and family reunification; to program issues encompassing health care professional education, training, and maintenance of competence; communication of global events of public health significance; development of management guidelines, particularly for nonendemic diseases; access to diagnostic and therapeutic interventions for exotic or rare clinical presentations; and monitoring of health service use and health outcomes in both the migrant and local populations.

Communicable Disease Control↗

Computer-based real-time analysis in mobile ocular screening.

Mobile ocular telemedicine is potentially an effective method to provide service in medically underserved areas and to screen large populations for abnormalities. Currently, digital images are acquired, stored, and transferred to readers for evaluation, after which the results are provided to the subjects. The transfer of large image files and the timeliness of the subsequent reading of images are significant factors for practical implementation of effective telemedicine screening. This work examines the feasibility of in situ real-time computer analysis of digital images to determine and classify the image results as normal and abnormal. This retrospective study used a photoscreening database of 360 patients ranging in ages from 6 months to 18 years. Computer analysis automatically classified the binocular photorefraction (PR) images, and these PR results were compared to those of the subjective clinical eye examinations provided. With an average processing time of approximately 15 seconds per examinee, the analysis found that the PR results can be categorized as: a positive group that requires referral (186 cases) with a predictive value of 98.9% (2 false-positives); a negative group (144 cases) with a predictive value of 89.6% (15 false-negatives); and an uncertain group (30 cases or 8.3%) that required resolution by readers. The real-time analysis code reduces by approximately 92% the manpower for image grading and electronic transmission at this stage of ocular evaluation. These results indicate the feasibility of this approach.

Algorithms↗

Evolutionary relationships among group II intron-encoded proteins and identification of a conserved domain that may be related to maturase function.

Many group II introns encode reverse transcriptase-like proteins that potentially function in intron mobility and RNA splicing. We compared 34 intron-encoded open reading frames and four related open reading frames that are not encoded in introns. Many of these open reading frames have a reverse transcriptase-like domain, followed by an additional conserved domain X, and a Zn(2+)-finger-like region. Some open reading frames have lost conserved sequence blocks or key amino acids characteristic of functional reverse transcriptases, and some lack the Zn(2+)-finger-like region. The open reading frames encoded by the chloroplast tRNA(Lys) genes and the related Epifagus virginiana matK open reading frame lack a Zn(2+)-finger-like region and have only remnants of a reverse transcriptase-like domain, but retain a readily identifiable domain X. Several findings lead us to speculate that domain X may function in binding of the intron RNA during reverse transcription and RNA splicing. Overall, our findings are consistent with the hypothesis that all of the known group II intron open reading frames evolved from an ancestral open reading frame, which contained reverse transcriptase, X, and Zn(2+)-finger-like domains, and that the reverse transcriptase and Zn(2+)-finger-like domains were lost in some cases. The retention of domain X in most proteins may reflect an essential function in RNA splicing, which is independent of the reverse transcriptase activity of these proteins.

Amino Acid Sequence↗

Assessment of ejaculate quality and sperm characteristics in turkeys: sperm mobility phenotype is independent of time.

Given a pool of genetically superior male turkeys, the subsequent selection of toms as semen donors for artificial insemination should be based upon criteria that are predictive of the tom's fertility and fecundity over the course of a production cycle. Recently, sperm mobility phenotype has been shown to correlate highly with fertility. Therefore, the objectives of this study were to determine: 1) whether sperm mobility phenotypes of individual toms were independent of time, and 2) the extent to which traditional semen quality variables changed as a function of time during the study interval. Sperm mobility phenotype was determined by objectively measuring the ability of sperm to penetrate 2% Accudenz solution at body temperature. During the initial assessments of a flock (n = 94), sperm mobility indexes (SMI) were significantly higher for the High Mobility Phenotype toms (56.61 +/-1.03% SMI) compared to the Low Mobility Phenotype (30.46+/-1.27% SMI, P < or = 0.0001) toms. Over the 5 mo of this study, the High Mobility Phenotype toms consistently had higher (P < or = 0.05) SMI values than the Low Mobility Phenotype toms, with SMI values similar to those of the initial screen. Ejaculate volume, concentration, and plasma membrane integrity showed no significant differences between phenotypes (P > or = 0.05). Sperm viability remained significantly lower (P < or = 0.05) over the course of this study for the High Mobility Phenotype toms than for the Low Mobility Phenotype toms. Because sperm mobility phenotype remained consistent through time, the Sperm Mobility Test provides a potentially important tool for selecting semen donors in turkeys.

Animals↗

F-18 FDG PET scan after radiotherapy for early-stage larynx cancer.

Fluorine-18-fluorodeoxyglucose (F-18 FDG) PET was used to evaluate early-stage larynx cancer before and after radiotherapy. Less radical salvage surgery might be possible after timely diagnosis of recurrent or persistent tumor after radiotherapy. Eight patients with early-stage laryngeal cancer (two carcinoma in situ; six stage T1: tumor limited to vocal cords with normal mobility) underwent irradiation for potential cure. Five patients had pre- and postradiotherapy F-18 FDG PET, and three had postradiotherapy F-18 FDG PET only. All patients underwent a CT scan of the neck at the time of the F-18 FDG PET scan. One patient had a positive result of postradiotherapy F-18 FDG PET but a negative result of a CT of the neck, and biopsy revealed recurrent squamous carcinoma. Seven patients who had negative results of postradiotherapy F-18 FDG PET were free of disease at the 15-month median follow-up evaluation. (Three of them had no cancer on biopsy of the larynx, and four others were followed with periodic endoscopic examinations that revealed complete disappearance of the tumor.) F-18 FDG PET scan may be useful for earlier diagnosis of recurrent or persistent laryngeal cancer after radiotherapy and is preferable to repeated biopsies, which would traumatize radiation-damaged tissues. A prompt early diagnosis of failure of radiotherapy will lead to less radical salvage surgery.

Carcinoma in Situ↗

Cytokine-mobilized peripheral blood progenitor cells for allogeneic reconstitution of miniature swine.

BACKGROUND: Because of the relative ease of acquisition, increased yield, and improved engraftment characteristics, mobilized peripheral blood progenitor (stem) cells (PBSCs) have recently become the preferred source for hematopoietic stem cell transplantation. In our laboratory, procurement of a megadose of PBSCs is necessary for on-going studies evaluating non-myelosuppressive transplant regimens for the induction of mixed chimerism and allograft tolerance. To exploit hematopoietic growth factor synergy, we have sought to combine growth factors with proven utility to improve PBSC mobilization and maximize our PBSC procurement through an automated collection procedure. METHODS: Mobilization characteristics of PBSCs were determined in 2-5-month-old miniature swine. Animals received either swine recombinant stem cell factor (pSCF, 100 microg/kg) and swine recombinant interleukin 3 (pIL-3, 100 microg/kg), administered intramuscularly for 8 days, or pSCF, pIL-3, and human recombinant granulocyte-colony stimulating factor (hG-CSF), at 10 microg/kg. Leukapheresis was performed beginning on day 5 of cytokine treatment and continued daily for 3 days. RESULTS: Collection of PBSCs from cytokine-mobilized animals via an automated leukapheresis procedure demonstrated a 10-fold increase in the number of total nucleated cells (TNC) (20-30 x 10(10) TNC) compared to bone marrow harvesting (2-3 x 10(10) total TNC). A more rapid rise in white blood cells (WBCs) was seen after administration of all three cytokines compared to pSCF and pIL-3 alone. An increase in colony-forming unit granulocyte-macrophage frequency measured daily from peripheral blood during cytokine treatment, was seen with the addition of hG-CSF to pSCF/pIL-3 correlating well with the rise in WBCs. Similarly, the addition of hG-CSF demonstrated a notable increase in the median progenitor cell yield from the 3-day leukapheresis procedure. Cytokine-mobilized PBSCs were capable of hematopoietic reconstitution. PBSCs mobilized with pSCF/pIL-3 were infused into an SLA-matched recipient conditioned with cyclophosphamide (50 mg/kg) and total body irradiation 1150 cGy. Neutrophil and platelet engraftment occurred on days 5 and 7, respectively, with minimal evidence of graft-versus-host disease. Complete donor chimerism has been demonstrated 331 days after transplant. CONCLUSIONS: Our preliminary results show that in this well-defined miniature swine model, recombinant swine cytokine combinations (pSCF, pIL-3 with or without hG-CSF) successfully mobilize a high yield of progenitor cells for allogeneic transplantation. Furthermore, these cytokine-mobilized PBSCs demonstrate the potential to reconstitute hematopoiesis and provide long-term engraftment in miniature swine.

Animals↗

What adolescents with type I diabetes and their parents want from testing technology: a qualitative study.

The presence of diabetes in an adolescent can significantly affect his/her normal development. Mobile technology may offer the ability to lessen this negative impact. We wished to learn from adolescents with diabetes and their parents how monitoring systems that incorporated mobile communication technology could potentially help to reduce hassles associated with testing, improve compliance, and ease adolescent-parent conflict about testing behavior. We recruited adolescents between the ages of 13 and 18 years, living with type 1 diabetes mellitus and their parents for focus groups. Qualitative analysis of the focus group data followed a set procedure. From the discussions, the following themes were identified: issues with blood glucose monitoring and desired technology. Elements of desired technology included hardware requirements, software requirements, communication, and miscellaneous requirements. The reported needs of this end-user group can help others to leverage maximally the capabilities of new and existing technology to care for children managing chronic disease.

Adolescent↗

Cementation for femoral head osteonecrosis: a preliminary clinic study.

Treatment for femoral head osteonecrosis has been less successful in late stages of the disease, after progression to collapse. The current authors treated 21 patients (22 hips) with Stage III osteonecrosis by a technique of open reduction and fixation with methylmethacrylate cement (cementation). The followup ranged from 1 to 3 years (average, 1.7 years). Patient progress was followed using preoperative and postoperative Harris hip scores, Western Ontario and McMaster Universities Osteoarthritis Index, and a health status questionnaire (Short Form-36). Patients were staged preoperatively using the Association Research Circulation Osseous international classification system and radiographic evaluation was done intraoperatively and postoperatively. The Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, and Short Form-36 physical health scores improved significantly from 53.5 to 78.0, 66.0 to 48.1, and 27.0 to 40.0, respectively. The outcome was worse for patients with more advanced disease. Six patients, all with severe disease, had total hip arthroplasty. Cementation is technically simple, enables patients' immediate postoperative pain relief and improvement in mobility, and has the potential to restore and maintain the sphericity of the femoral head after collapse. The high failure rate (27%) at short-term followup, although comparable with other reported techniques, does not support generalized use for Stage III disease. Currently the use of this procedure is restricted to symptomatic, young patients (younger than 40 years), preferably with mild to moderate Stage III disease (degree of head involvement < 30% and degree of collapse < 4 mm).

Adult↗

A mobile-bearing knee prosthesis can reduce strain at the proximal tibia.

Mobile and fixed-bearing knee prostheses are likely to generate distinct strain gradients in the proximal tibia. The resulting strain distribution in the proximal tibia governs bone remodeling and affects implant integration and stability. We determined the effects of fixed and mobile-bearing total knee prostheses on strain distribution at the proximal tibia. This mobile-bearing prosthesis was evaluated in cadaveric specimens under axial and torsional loading. Strain on the proximal tibial cortex was measured with rosette strain gages and an optical full-field strain acquisition system. Tibial torsion in response to combined axial and torsional loading was documented. There was no difference in cortex strain between the fixed and the mobile-bearing prostheses under 1.5 kN axial loading. Superimposing 10 degrees tibial internal rotation induced 22% less compressive strain in the mobile-bearing prosthesis compared with the fixed-bearing prosthesis. Under 10 degrees tibial external rotation, the mobile-bearing prosthesis induced 33% less compressive strain than the fixed-bearing prosthesis. Optically acquired strain fields showed peak compressive strain at the anteromedial aspect 30 mm below the joint line. The mobile-bearing prosthesis reduced torque in the proximal tibia during knee rotation by 68-73% compared with the fixed-bearing prosthesis. Our data suggest that the particular mobile-bearing prosthesis tested potentially reduces elevated strain levels in the proximal tibia.

Aged↗

Crystal structure of the catalytic domain of human bile salt activated lipase.

Bile-salt activated lipase (BAL) is a pancreatic enzyme that digests a variety of lipids in the small intestine. A distinct property of BAL is its dependency on bile salts in hydrolyzing substrates of long acyl chains or bulky alcoholic motifs. A crystal structure of the catalytic domain of human BAL (residues 1-538) with two surface mutations (N186D and A298D), which were introduced in attempting to facilitate crystallization, has been determined at 2.3 A resolution. The crystal form belongs to space group P2(1)2(1)2(1) with one monomer per asymmetric unit, and the protein shows an alpha/beta hydrolase fold. In the absence of bound bile salt molecules, the protein possesses a preformed catalytic triad and a functional oxyanion hole. Several surface loops around the active site are mobile, including two loops potentially involved in substrate binding (residues 115-125 and 270-285).

Amino Acid Sequence↗

Vertebroplasty and kyphoplasty for treatment of painful osteoporotic compression fractures.

PURPOSE: To review the pathophysiology of osteoporosis and describe vertebroplasty and kyphoplasty, which are minimally invasive procedures to treat the pain associated with vertebral compression fractures (VCFs). DATA SOURCES: Extensive literature review of osteoporosis, vertebroplasty, and kyphoplasty supplemented by case study and clinical experience in the minimally invasive interventional neuroradiology interventions. CONCLUSIONS: Osteoporosis is a progressive debilitating process that destroys the cancellous bone, weakening the overall integrity and stability of the bone. The loss of bone mass places the individual at increased risk for vertebral body, hip, and wrist fractures. In the past, there was no treatment option to repair vertebral body deformity or instability after osteoporotic VCFs. Management solely relied on the use of nonsteroidal anti-inflammatory drugs, narcotics, muscle relaxants, and/or orthotic bracing to provide pain relief. VCFs alter the stability of the vertebral body and column, and the lack of stabilization can lead to chronic pain syndrome, immobility, pulmonary compromise, progression of spinal deformity, increase in the risk for additional VCFs, and increase in the risk for comorbidities and mortality related to immobility. IMPLICATIONS FOR PRACTICE: Vertebroplasty and kyphoplasty are minimally invasive procedures aimed at pain control, stabilization of the vertebral body, and with kyphoplasty, the ability to provide some correction of deformity with partial restoration of vertebral body height. Providing pain control and stabilization of the vertebral column improves mobility, thus decreasing the potential risks associated with immobility.

Aged↗

Low-molecular-weight fucoidan promotes therapeutic revascularization in a rat model of critical hindlimb ischemia.

The therapeutic potential of low-molecular-weight (LMW) fucoidan, a sulfated polysaccharide extracted from brown seaweed devoid of direct antithrombin effect, was investigated in vitro and in a model of critical hindlimb ischemia in rat. In vitro results showed that LMW fucoidan enhanced fibroblast growth factor (FGF)-2-induced [(3)H]thymidine incorporation in cultured rat smooth muscle cells. Intravenous injection in rats of LMW fucoidan significantly increased the stromal-derived factor (SDF)-1 level from 1.2 +/- 0.1 to 6.5 +/- 0.35 ng/ml in plasma. The therapeutic effect of LMW fucoidan (5 mg/kg/day), FGF-2 (1 micro g/kg/day), and LMW fucoidan combined with FGF-2 was assessed 14 days after induction of ischemia by 1) clinical evaluation of claudication, 2) tissue blood flow analysis, 3) histoenzymology of muscle metabolic activity, and 4) quantification of capillary density. Both LMW fucoidan and FGF-2 similarly improved residual muscle blood flow (62.5 +/- 6.5 and 64.5 +/- 4.5%, respectively) compared with the control group (42 +/- 3.5%, p < 0.0001). The combination of FGF-2 and LMW fucoidan showed further significant improvement in tissue blood flow (90.5 +/- 3%, p < 0.0001). These results were confirmed by phosphorylase activity, showing muscle regeneration in rats treated with the combination of FGF-2 and LMW fucoidan. Capillary density count increased from 9.6 +/- 0.7 capillaries/muscle section in untreated ischemic controls to 14.3 +/- 0.9 with LMW fucoidan, 14.5 +/- 0.9 with FGF-2, and 19.1 +/- 0.9 in combination (p < 0.001). Thus, LMW fucoidan potentiates FGF-2 activity, mobilizes SDF-1, and facilitates angiogenesis in a rat model. This natural compound could be of interest as an alternative for conventional treatment in critical ischemia.

Animals↗

restless, an active Ac-like transposon from the fungus Tolypocladium inflatum: structure, expression, and alternative RNA splicing.

Elements of the hAT transposon family, such as the maize activator (Ac), have been discovered in a large number of eukaryotic species. This type of class II transposon, present in both plants and animals, has not been previously detected in any fungal organism. However, using a differential screening method to detect repetitive DNA, we have identified a hAT transposon in the hyphomycete Tolypocladium inflatum. The transposon, which we named restless, is 4,097 bp long, carries 20-bp inverted repeats and an 8-bp target site duplication, and encodes a long open reading frame which is interrupted by a single intronic sequence. The derived mRNA exhibits alternative splicing, resulting in the formation of two transcripts that may be translated into polypeptides of 157 or 803 amino acids. The predicted amino acid sequence of the larger polypeptide demonstrates significant homology with transposases from the hAT transposon family. A chromosomal analysis using pulsed-field gel electrophoresis showed that all seven chromosomal bands carry copies of the 4.1-kb transposon. This was confirmed in hybridization experiments with rare-cutting restriction endonucleases which indicate that about 15 copies are present in T. inflatum. The genomic distribution of restless and its transcriptional expression, alternative mRNA splicing, and genomic mobility all imply a potential role for this element in developing a transposon tagging system for use in filamentous fungi.

Alternative Splicing↗

Platelet-derived growth factor-stimulated superoxide anion production modulates activation of transcription factor NF-kappaB and expression of monocyte chemoattractant protein 1 in human aortic smooth muscle cells.

BACKGROUND: Platelet-derived growth factor (PDGF) and superoxide anion (O2.-) have been implicated in vascular diseases. We investigated whether PDGF stimulates the production of O2.- in human aortic smooth muscle cells (HSMCs) and whether O2.- leads in this way to the activation of nuclear factor-kappaB (NF-kappaB) and induction of monocyte chemoattractant protein 1 (MCP-1) in PDGF-stimulated HSMCs. METHODS AND RESULTS: PDGF-AB concentration- and time-dependently stimulated O2.- generation from HSMCs. The stimulatory effect of PDGF-AB was mimicked by PDGF-BB but not by PDGF-AA. The generation of O2.- by PDGF-AB was attenuated by the NAD(P)H oxidase inhibitor iodonium diphenyl, the specific protein kinase C (PKC) inhibitor Ro 31-8220, and the phosphatidylinositol 3-kinase inhibitor wortmannin. Allopurinol and nifedipine had no effect on PDGF-AB-induced O2.- release, whereas indomethacin potentiated this response. Gel mobility shift assay revealed that PDGF-AB increased the binding activity of NF-kappaB, which contained predominantly the p50/p65 heterodimer in nuclear extracts from HSMCs. Superoxide dismutase as well as iodonium diphenyl, Ro 31-8220, and wortmannin attenuated PDGF-AB-induced activation of NF-kappaB and expression of MCP-1 mRNA. In contrast, superoxide dismutase did not inhibit the interleukin-1beta-induced NF-kappaB activation. CONCLUSIONS: The results demonstrate that PDGF stimulates O2.- generation in HSMCs via PKC-dependent and wortmannin-sensitive pathways involving flavoenzyme(s). This PDGF-induced O2.- production may be involved in vascular lesion formation by mediating, at least in part, NF-kappaB activation and MCP-1 induction.

Allopurinol↗

Passive adsorption of human antirrabic immunoglobulin onto a polystyrene surface.

The latex agglutination immunoassay technique uses polymer colloids as carriers of adsorbed proteins to enhance the antigen-antibody reaction. The aim of the present work is to study the adsorption of Human Antirrabic Immunoglobulin (HA-IgG) on polystyrene latex (PS). The physical adsorption of HA-IgG on PS latex was investigated as a function of pH at 2 mM ionic strength. The amount of HA-IgG adsorbed onto PS latex greatly depends on pH; its value showed a maximum in the neighborhood of the IEP of HA-IgG. The electrophoretic method was applied to characterize latex particles. The influence of the amount of HA-IgG adsorbed (J(ads)) on the electrophoretic mobility and zeta-potential values was also studied.

Adsorption↗