title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Identification and characterization of lactococcal-prophage-carried superinfection exclusion genes. | Superinfection exclusion (Sie) proteins are prophage-encoded phage resistance systems. In this study, genes encoding Sie systems were identified on the genomes of Lactococcus lactis subsp. cremoris MG1363 and L. lactis subsp. lactis IL1403. These Sie systems are genetically distinct and yet were shown to act specifically against a particular subset of the 936 phage group. Each of the systems allows normal phage adsorption while affecting plasmid transduction and intracellular phage DNA replication, which points to the blocking of phage DNA injection as their common mode of action. Sie-specifying genes found on the MG1363 prophages are also present in various lactococcal strains, whereas the prophage-encoded Sie systems of IL1403 do not appear to be as widely disseminated. | 18,723,645 |
Characterization of DegQVh, a serine protease and a protective immunogen from a pathogenic Vibrio harveyi strain. | Vibrio harveyi is an important marine pathogen that can infect a number of aquaculture species. V. harveyi degQ (degQ(Vh)), the gene encoding a DegQ homologue, was cloned from T4, a pathogenic V. harveyi strain isolated from diseased fish. DegQ(Vh) was closely related to the HtrA family members identified in other Vibrio species and could complement the temperature-sensitive phenotype of an Escherichia coli strain defective in degP. Expression of degQ(Vh) in T4 was modulated by temperature, possibly through the sigma(E)-like factor. Enzymatic analyses demonstrated that the recombinant DegQ(Vh) protein expressed in and purified from E. coli was an active serine protease whose activity required the integrity of the catalytic site and the PDZ domains. The optimal temperature and pH of the recombinant DegQ(Vh) protein were 50 degrees C and pH 8.0. A vaccination study indicated that the purified recombinant DegQ(Vh) was a protective immunogen that could confer protection upon fish against infection by V. harveyi. In order to improve the efficiency of DegQ(Vh) as a vaccine, a genetic construct in the form of the plasmid pAQ1 was built, in which the DNA encoding the processed DegQ(Vh) protein was fused with the DNA encoding the secretion region of AgaV, an extracellular beta-agarase. The E. coli strain harboring pAQ1 could express and secrete the chimeric DegQ(Vh) protein into the culture supernatant. Vaccination of fish with viable E. coli expressing chimeric degQ(Vh) significantly (P < 0.001) enhanced the survival of fish against V. harveyi challenge, which was possibly due to the relatively prolonged exposure of the immune system to the recombinant antigen produced constitutively, albeit at a gradually decreasing level, by the carrier strain. | 18,723,647 |
Isolation and identification of bifidobacteriaceae from human saliva. | Bifidobacteriaceae were isolated from saliva and infected dentine by using a mupirocin-based selective medium. Of the saliva samples, 94% harbored bifids. The mean concentration (+/- the standard error) was 4.46 (+/-0.12) log(10)(CFU per ml + 1), and the predominant isolates were Bifidobacterium dentium, B. longum, Scardovia inopinata, Parascardovia denticolens, and Alloscardovia omnicolens. | 18,723,652 |
The genome of Polaromonas sp. strain JS666: insights into the evolution of a hydrocarbon- and xenobiotic-degrading bacterium, and features of relevance to biotechnology. | Polaromonas sp. strain JS666 can grow on cis-1,2-dichloroethene (cDCE) as a sole carbon and energy source and may be useful for bioremediation of chlorinated solvent-contaminated sites. Analysis of the genome sequence of JS666 (5.9 Mb) shows a bacterium well adapted to pollution that carries many genes likely to be involved in hydrocarbon and xenobiotic catabolism and metal resistance. Clusters of genes coding for haloalkane, haloalkanoate, n-alkane, alicyclic acid, cyclic alcohol, and aromatic catabolism were analyzed in detail, and growth on acetate, catechol, chloroacetate, cyclohexane carboxylate, cyclohexanol, ferulate, heptane, 3-hydroxybenzoate, hydroxyquinol, gentisate, octane, protocatechuate, and salicylate was confirmed experimentally. Strain JS666 also harbors diverse putative mobile genetic elements, including retrons, inteins, a miniature inverted-repeat transposable element, insertion sequence transposases from 14 families, eight genomic islands, a Mu family bacteriophage, and two large (338- and 360-kb) plasmids. Both plasmids are likely to be self-transferable and carry genes for alkane, alcohol, aromatic, and haloacid metabolism. Overall, the JS666 genome sequence provides insights into the evolution of pollutant-degrading bacteria and provides a toolbox of catabolic genes with utility for biotechnology. | 18,723,656 |
Genetic structure and aggressiveness of Erysiphe necator populations during grapevine powdery mildew epidemics. | Isolates of the causal ascomycete of grapevine powdery mildew, Erysiphe necator, correspond to two genetically differentiated groups (A and B) that coexist on the same host. This coexistence was analyzed by investigating temporal changes in the genetic and phenotypic structures of E. necator populations during three epidemics. Group A was present only at the start of the growing season, whereas group B was present throughout all three epidemics. Group A was less aggressive in terms of germination and infection efficiency but was more aggressive than group B in terms of the latency period, lesion diameter, and spore production. Our results are consistent with a temporal differentiation of niches, preventing recombination, and suggest an association between the disease level and the frequencies of genetic groups. | 18,723,657 |
Salmonella and Escherichia coli O157:H7 contamination on hides and carcasses of cull cattle presented for slaughter in the United States: an evaluation of prevalence and bacterial loads by immunomagnetic separation and direct plating methods. | The hide and carcass hygiene of cull cattle at slaughter in four geographically distant regions of the United States was examined from July 2005 to April 2006 by measuring the aerobic plate counts (APC) and the prevalences and loads of Salmonella and Escherichia coli O157:H7. The geometric mean log(10) APC CFU/100 cm(2) levels on hides and preevisceration and postintervention carcasses ranged from 6.17 to 8.19, 4.24 to 6.47, and 1.46 to 1.96, respectively, and were highest in the summer (P < 0.0001). The average prevalences of Salmonella on hides and preevisceration and postintervention carcasses were 89.6% (95% confidence interval [CI], 85.1 to 94.0), 50.2% (95% CI, 40.9 to 59.5), and 0.8% (95% CI, 0.18 to 1.42), respectively. The prevalences of E. coli O157:H7 were 46.9% (95% CI, 37.3 to 56.6) and 16.7% (95% CI, 9.8 to 23.6) on hides and preevisceration carcasses, respectively. Examination of the concomitant incidence of Salmonella and E. coli O157:H7 showed that, on average, 33.3% (95% CI, 15.9 to 69.8) of cattle hide and 4.1% (95% CI, 0.98 to 17.3) of preevisceration carcass samples were contaminated with both pathogens. The pathogen prevalence on hides and carcasses was not significantly affected by the season; however, significant differences were observed between plants with respect to the incoming pathogen load and the ability to mitigate hide-to-carcass transfer. In spite of these differences, postintervention carcass contamination was significantly reduced (P < 0.001), likely as a result of the use of one or more of the processing interventions employed at each of the four processing plants examined. | 18,723,661 |
Observational pain assessment versus self-report in paediatric triage. | To examine if observational pain assessment can be used for purposes of triage in children aged >3 years. A prospective, single blind, controlled trial was undertaken in children who presented to the emergency department (ED) with pain. Pain was assessed in the waiting room and again at triage before any treatment was administered using the Alder Hey Triage Pain Score (AHTPS), an observational tool designed for triage, and a self-report tool, either the Wong-Baker Faces Pain Rating Scale (WBS) for 3-7-year-old children or a visual analogue scale (VAS) for 8-15-year-old children. Scores were compared by instrument (observational and self-report) and ED location (waiting room and triage room). 75 children (29 aged 3-7 years and 46 aged 8-15 years) were enrolled in the study. The AHTPS scores were significantly lower than the scores measured by the WBS/VAS (p<0.001). The level of pain measured by both methods (self-report, observational) was lower in the triage room. Compared with the AHTPS, the WBS and VAS scored significantly lower in the triage room than in the waiting room (p<0.042 and p<0.006, respectively). Observational pain assessment underestimates children's perception of pain and should not be recommended in children aged >3 years. Triage has a calming effect on children. | 18,723,699 |
Meningitis in a butcher. | Streptococcus suis is a common pathogen in swine and infection in humans is rarely reported. When it does occur, it is considered an occupational risk associated with the handling of carcasses. Meningitis is one of the most life-threatening manifestations of S suis infection. This case of meningitis in a butcher is reported to create awareness of this zoonotic disease. The report highlights the importance of an occupational history and a meticulous general physical examination looking for cuts and abrasions in patients with suspicion of meningitis. | 18,723,720 |
Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma. | The aim of this study was to investigate the association between normal tension glaucoma and the candidate disease locus glaucoma 1, open angle, B (GLC1B) on chromosome 2. There are many reports describing the results of association or linkage studies for primary open angle glaucoma (POAG), with GLC1B as one of the loci associated with normal or moderately elevated intraocular pressure. However, there are few reports about the association of genes or defined genomic regions with normal tension glaucoma, which is the leading type of glaucoma in Japan. The GLC1B locus is hypothesized to be a causative region for normal tension glaucoma. Genomic DNA was extracted from whole blood of normal tension glaucoma (n = 143) and healthy controls (n = 103) of Japanese origin. Fifteen microsatellite markers within and/or near to the GLC1B locus were genotyped, and their association with normal tension glaucoma was analysed. Two markers D2S2264 and D2S176 had significant positive associations. The D2S176 marker had the strongest significant association and it is located 24 kb from the nearest gene NCK2, which now becomes an important new candidate gene for future studies of its association with normal tension glaucoma. | 18,723,748 |
Formation and function of ceramide-enriched membrane platforms with CD38 during M1-receptor stimulation in bovine coronary arterial myocytes. | CD38 contains an ADP ribosylcyclase domain that mediates intracellular Ca(2+) signaling by the production of cyclic ADP-ribose (cADPR), but the mechanisms by which the agonists activate this enzyme remain unclear. The present study tested a hypothesis that a special lipid-raft (LR) form, ceramide-enriched lipid platform, contributes to CD38 activation to produce cADPR in response to muscarinic type 1 (M(1)) receptor stimulation in bovine coronary arterial myocytes (CAMs). By confocal microscopic analysis, oxotremorine (Oxo), an M(1) receptor agonist, was found to increase LR clustering on the membrane with the formation of a complex of CD38 and LR components such as GM(1), acid sphingomyelinase (ASMase), and ceramide, a typical ceramide-enriched macrodomain. At 80 microM, Oxo increased LR clustering by 78.8%, which was abolished by LR disruptors, methyl-beta-cyclodextrin (MCD), or filipin. With the use of a fluorescence resonance energy transfer (FRET) technique, 15.5+/-1.9% energy transfer rate (vs. 5.3+/-0.9% of control) between CD38 and LR component, ganglioside M(1) was detected, further confirming the proximity of both molecules. In the presence of MCD or filipin, there were no FRET signals detected. In floated detergent-resistant membrane fractions, CD38 significantly increased in LR fractions of CAMs treated by Oxo. Moreover, MCD or filipin attenuated Oxo-induced production of cADPR via CD38. Functionally, Oxo-induced intracellular Ca(2+) release and coronary artery constriction via cADPR were also blocked by LR disruption or ASMase inhibition. These results provide the first evidence that the formation of ceramide-enriched lipid macrodomains is crucial for Oxo-induced activation of CD38 to produce cADPR in CAMs, and these lipid macrodomains mediate transmembrane signaling of M(1) receptor activation to produce second messenger cADPR. | 18,723,763 |
Neonatal intrahepatocellular lipid. | There is increasing evidence that preterm birth is a risk factor for the development of adiposity associated disease, although the pathophysiological basis is unclear. We have previously shown that preterm infants have increased internal abdominal (visceral) adiposity by term. In adults increased internal adiposity is associated with elevated intrahepatocellular lipid (IHCL). We measured IHCL using (1)H NMR spectroscopy in 26 infants (eight healthy preterm-at-term and 18 term-born) and compared values with a reference group of 32 adults. There was no significant difference between adult and term-born IHCL content. In preterm-at-term infants IHCL was significantly elevated when compared with term-born infants and with adults (IHCL CH2/water median (interquartile range): preterm 1.69 (1.04-3.53), term 0.21 (0-0.54) and adult 0.55 (0.08-1.57). | 18,723,779 |
Determining the role of Tie-dyed1 in starch metabolism: epistasis analysis with a maize ADP-glucose pyrophosphorylase mutant lacking leaf starch. | In regions of their leaves, tdy1-R mutants hyperaccumulate starch. We propose 2 alternative hypotheses to account for the data, that Tdy1 functions in starch catabolism or that Tdy1 promotes sucrose export from leaves. To determine whether Tdy1 might function in starch breakdown, we exposed plants to extended darkness. We found that the tdy1-R mutant leaves retain large amounts of starch on prolonged dark treatment, consistent with a defect in starch catabolism. To further test this hypothesis, we identified a mutant allele of the leaf expressed small subunit of ADP-glucose pyrophosphorylase (agps-m1), an enzyme required for starch synthesis. We determined that the agps-m1 mutant allele is a molecular null and that plants homozygous for the mutation lack transitory leaf starch. Epistasis analysis of tdy1-R; agps-m1 double mutants demonstrates that Tdy1 function is independent of starch metabolism. These data suggest that Tdy1 may function in sucrose export from leaves. | 18,723,774 |
Veterinarians and public practice at the Virginia-Maryland Regional College of Veterinary Medicine: building on a tradition of expertise and partnership. | The Virginia-Maryland Regional College of Veterinary Medicine (VMRCVM), a regional veterinary college for Maryland and Virginia, has a long and unique tradition of encouraging careers in public and corporate veterinary medicine. The VMRCVM is home to the Center for Public and Corporate Veterinary Medicine (CPCVM), and each year approximately 10% of the veterinary students choose the public/corporate veterinary medicine track. The faculty of the CPCVM, and their many partners from the veterinary public practice community, teach in the veterinary curriculum and provide opportunities for students locally, nationally, and internationally during summers and the final clinical year. Graduates of the program work for government organizations, including the US Department of Agriculture, the Food and Drug Administration, and the Centers for Disease Control and Prevention, as well as in research, in industry, and for non-governmental organizations. Recent activities include securing opportunities for students, providing career counseling for graduate veterinarians interested in making a career transition, delivering continuing education, and offering a preparatory course for veterinarians sitting the board examination for the American College of Veterinary Preventive Medicine. As the VMRCVM moves forward in recognition of the changing needs of the veterinary profession, it draws on its tradition of partnership and capitalizes on the excellence of its existing program. Future plans for the CPCVM include possible expansion in the fields of public health, public policy, international veterinary medicine, organizational leadership, and the One Health initiative. Quality assurance and evaluation of the program is ongoing, with recognition that novel evaluation approaches will be useful and informative. | 18,723,808 |
Teaching nutrition to student veterinary technicians. | Graduates of veterinary technology programs must have the knowledge and skills to understand, implement, and encourage owner compliance with appropriate feeding recommendations for healthy animals and therapeutic regimens to promote optimal health, enhance recovery, and manage chronic disease conditions. This article describes nutrition education for veterinary technology students at the College of Veterinary Medicine, Michigan State University. Veterinary technology students are novice learners in nutrition who prefer visual, applied, and experiential modes of instruction. The program uses the American College of Veterinary Nutrition's "Circle of Nutrition," concept maps, and case-based delivery and assessment. | 18,723,817 |
Resident and graduate training in veterinary nutrition. | Training programs for veterinarians seeking board certification by the American College of Veterinary Nutrition (ACVN) are structured in one of two ways: (1) as programs similar to specialty training in other clinical disciplines or (2) as graduate programs leading to advanced degrees combined with clinical training. Residency training occurs through a variety of approaches, including didactic coursework, case-based and applied learning, clinical training, teaching, research, and self-study. Challenges to successful residency and graduate training include low numbers of diplomates, particularly at veterinary schools; low numbers of applicants; small numbers of funded programs; and faculty promotion systems that do not reward residency or graduate training and program development. The mentoring of individuals seeking both board certification and a graduate degree presents additional considerations, including recruitment of individuals motivated in research and structuring a combined program that facilitates completion of both tasks in a timely fashion. | 18,723,818 |
Estimates of cancer potency of 2,3,4,7,8-pentachlorodibenzofuran using both nonlinear and linear approaches. | Cancer potency estimates were derived for 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF) using data collected from the recently published National Toxicology Program bioassay in female Sprague-Dawley rats. By using a toxicokinetic model for 4-PeCDF, the dose-response relationship for combined liver tumors (hepatocellular adenomas and cholangiocarcinomas) in rats was assessed in terms of lifetime average liver concentration and lifetime average adipose concentration with data from both the lifetime and the stop-exposure components of the bioassay. Benchmark dose modeling was performed to estimate tissue concentrations at two points of departure (EC(10) and EC(01) and their 95% upper and lower confidence limits). The same toxicokinetic model with human input values was then used to back-extrapolate human equivalent doses that corresponded to the internal tissue concentration measures at the points of departure. Information regarding the cancer mode of action was used to support the development of several toxicity criterion values based on a nonlinear method, e.g., reference dose or tolerable daily intake. Nonlinear estimates of toxicity criteria based on observed noncancer toxic events as possible precursors to tumor formation were also derived and were similar in value to those based on combined liver tumors. For comparison purposes, linear estimates of cancer potency were also derived. | 18,723,826 |
Impaired arterial baroreflex function before nitrate-induced vasovagal syncope during head-up tilt test. | The aim of this study was to evaluate arterial baroreflex control of heart rate immediately before head-up tilt test (HUT)-induced vasovagal syncope (VVS). We enrolled 97 otherwise healthy subjects with recurrent unexplained syncope. After 10 min of rest in supine position, they underwent a passive HUT potentiated with nitroglycerin administration after 20 min. Beat-to-beat heart rate and systolic blood pressure were continuously recorded. Sequence method was used to measure two complementary parameters reflecting arterial baroreflex control of heart rate: the baroreflex sensitivity (BRS) and the baroreflex effectiveness index (BEI). Twenty-one patients fainted before nitrate administration (HUT+) and 37 after nitrate administration (NTG+). Immediately before syncope, the NTG+ patients showed significantly lower BRS values than those observed at the end of the test in the patients without syncope (5.5 +/- 2.8 vs. 7.7 +/- 3.4 ms/mmHg; P = 0.004) and a significantly lower BEI (30 +/- 20% vs. 53 +/- 24%; P < 0.001). The HUT+ patients did not show any significant differences in BRS and BEI before syncope from the values observed during the corresponding tilt period in the other groups. A significant depression in BRS and BEI occurs immediately before syncope in patients who faint after nitrate administration, thus suggesting that arterial baroreflex dysfunction plays a role in mediating nitrate-induced VVS. | 18,723,851 |
From enzyme to zymogen: engineering Vip2, an ADP-ribosyltransferase from Bacillus cereus, for conditional toxicity. | The adenosine diphosphate (ADP)-ribosyltransferase, Vip2 (vegetative insecticidal protein), from Bacillus cereus in combination with another protein from the same organism, Vip1, has insecticidal activity against western corn rootworm larvae. The Vip2 protein exerts its intracellular poisoning effect by modifying actin and preventing actin polymerization. Due to the nature of this toxin, expression of Vip2 in planta is lethal. In this work, we attempted to build an enzyme precursor (proenzyme, zymogen) that would silently reside in one biological system (e.g. plants or yeast) and be activated in the other (insect larvae). Our approach involved engineering a random propeptide library at the C-terminal end of Vip2 and selecting for malfunctional enzyme variants in yeast. A selected proenzyme (proVip2) possesses reduced enzymatic activity as compared with the wild-type Vip2 protein, but remains a potent toxin toward rootworm larvae. In addition, upon analysis of the digestive fate of the engineered enzyme precursor in rootworm larvae, we demonstrated that 'zymogenized' Vip2 can be proteolytically activated by rootworm digestive enzyme machinery. This report represents an example of applying a protein engineering strategy for the creation of a plant-tolerated, zymogen-like form of an otherwise toxic protein. This approach may outline a novel path to address challenges associated with utilizing toxic proteins in certain biotechnological applications. | 18,723,852 |
Tissue-specific defects are caused by loss of the Drosophila MAN1 LEM domain protein. | The nuclear lamina represents a protein network required for nuclear structure and function. One family of lamina proteins is defined by an approximately 40-aa LAP2, Emerin, and MAN1 (LEM) domain (LEM-D) that binds the nonspecific DNA-binding protein, barrier-to-autointegration factor (BAF). Through interactions with BAF, LEM-D proteins serve as a bridge between chromosomes and the nuclear envelope. Mutations in genes encoding LEM-D proteins cause human laminopathies that are associated with tissue-restricted pathologies. Drosophila has five genes that encode proteins with LEM homology. Using yeast two-hybrid analyses, we demonstrate that four encode proteins that bind Drosophila (d)BAF. In addition to dBAF, dMAN1 associates with lamins, the LEM-D protein Bocksbeutel, and the receptor-regulated Smads, demonstrating parallel protein interactions with vertebrate homologs. P-element mobilization was used to generate null dMAN1 alleles. These mutants showed decreased viability, with surviving adults displaying male sterility, decreased female fertility, wing patterning and positioning defects, flightlessness, and locomotion difficulties that became more severe with age. Increased phospho-Smad staining in dMAN1 mutant wing discs is consistent with a role in transforming growth factor (TGF)-beta/bone morphogenic protein (BMP) signaling. The tissue-specific, age-enhanced dMAN1 mutant phenotypes are reminiscent of human laminopathies, suggesting that studies in Drosophila will provide insights into lamina dysfunction associated with disease. | 18,723,885 |
A practical exposure-equivalent metric for instrumentation noise in x-ray imaging systems. | The performance of high-sensitivity x-ray imagers may be limited by additive instrumentation noise rather than by quantum noise when operated at the low exposure rates used in fluoroscopic procedures. The equipment-invasive instrumentation noise measures (in terms of electrons) are generally difficult to make and are potentially not as helpful in clinical practice as would be a direct radiological representation of such noise that may be determined in the field. In this work, we define a clinically relevant representation for instrumentation noise in terms of noise-equivalent detector entrance exposure, termed the instrumentation noise-equivalent exposure (INEE), which can be determined through experimental measurements of noise-variance or signal-to-noise ratio (SNR). The INEE was measured for various detectors, thus demonstrating its usefulness in terms of providing information about the effective operating range of the various detectors. A simulation study is presented to demonstrate the robustness of this metric against post-processing, and its dependence on inherent detector blur. These studies suggest that the INEE may be a practical gauge to determine and compare the range of quantum-limited performance for clinical x-ray detectors of different design, with the implication that detector performance at exposures below the INEE will be instrumentation-noise limited rather than quantum-noise limited. | 18,723,932 |
Reflections on humanizing biomedicine. | Although biomedicine is responsible for the "miracles" of modern medicine, paradoxically it has also led to a quality-of-care crisis in which many patients feel disenfranchised from the health-care industry. To address this crisis, several medical commentators make an appeal for humanizing biomedicine, which has led to shifts in the philosophical boundaries of medical knowledge and practice. In this paper, the metaphysical, epistemological, and ethical boundaries of biomedicine and its humanized versions are investigated and compared to one another. Biomedicine is founded on a metaphysical position of mechanistic monism, an epistemology of objective knowing, and an ethic of emotionally detached concern. In humanizing modern medicine, these boundaries are often shifted to a metaphysical position of dualism/holism, an epistemology of subject knowing, and an ethic of empathic care. In a concluding section, the question is discussed whether these shifts in the philosophical boundaries are adequate to resolve the quality-of-care crisis. | 18,723,943 |
Medicine and the call for a moral epistemology, part II: constructing a synthesis of values. | The demands and needs of an individual patient require diverse value judgments to interpret and apply clinical data. Indeed, objective assessment takes on particular meaning in the context of the social and existential status of the patient, and thereby a complex calculus of values determines therapeutic goals. I have previously formulated how this moral thread of care becomes woven into the epistemological project as a "moral epistemology." Having argued its ethical justification elsewhere, I offer another perspective here: clinical choices employ diverse values directed at an array of goals, some of which are derived from a universal clinical science and others from the particular physiological, psychological, and social needs of the patient. Integrating these diverse elements that determine clinical care requires a complex synthesis of facts and judgments from several domains. This constructivist process relies on clinical facts, as well as on personal judgments and subjective assessments in an ongoing negotiation between patient and doctor. A philosophy of medicine must account for the conceptual basis of this process by identifying and addressing the judgments that govern the complex synthesis of these various elements. | 18,723,947 |
Mesangioproliferative glomerulonephritis: an important glomerulonephritis in nephrotic syndrome of young adult. | Mesangioproliferative glomerulonephritis (MesPGN) consists 10% of the total renal biopsy of glomerulonephritis. Aim of the present study was to find out clinicopathological changes in MesPGN and differences between diffuse and focal variety. MesPGN was seen mostly in young adults with mean age of 28.63 years for males and 26.3 years for females. Male predominance was noted (M:F ratio - 1.4:1). About 70.83% patient presented with edema feet, followed by hypertension (29.19%), fever (16.66%), oliguria, nausea and vomiting (10.41%). Urine analysis in 50 patients revealed that 70% patients presented with nephrotic-range proteinuria, 36% patients with microscopic hematuria and 56% patients with leukocyturia. Statistically, no significant difference was found in clinical features of diffuse and focal MesPGN. Microscopic comparison between diffuse and focal variety showed that significant increase of focal glomerular basement membrane thickening, focal endothelial cell proliferation, focal smooth muscle hyperplasia, hyaline sclerosis and vasculitis was more common in diffuse variety. In focal variety, Capillary loop congestion, periglomerulitis, cloudy swelling and vacuolar degeneration in tubules were significantly more as compared to diffuse variety. Details of the clinical features, special laboratory tests and histological details revealed that diffuse variety had systemic diseases, which included Wegner's granulomatosis, microscopic polyangitis, Henoch's schonlein purpura, systemic lupus erythematosus (two cases) and one case each of Kimura's disease, pyelonephritis and tuberculosis. Only one case of focal MesPGN showed tuberculosis. Thus, our study concludes that MesPGN is an important cause of nephrotic syndrome among young adults. Secondly, search for some other diseases should be made and thirdly, if biopsy shows focal mesangial cell proliferations in minimal change glomerulonephritis (MCGN), it should be diagnosed as focal MesPGN rather than MCGN because these cases show recurrences. | 18,723,953 |
Hepatic tuberculosis mimicking Klatskin tumor: a diagnostic dilemma. | Tubercular involvement of liver is rare and usually occurs in association with pulmonary or miliary tuberculosis, as diffuse involvement without recognizable pulmonary tuberculosis or rarely in a localized form, which presents as a tuberculoma or tubercular abscess. We report the case of a 22-year-old boy presenting with features of obstructive jaundice and a clinico-radiological picture highly suggestive of a perihilar cholangiocarcinoma (Klatskin tumor), but found to have tubercular involvement of porta hepatis. We review the literature on this unusual presentation, highlight the considerable diagnostic challenge such cases can pose, and also emphasize the need to consider tuberculosis in differential diagnosis of lesions involving the porta hepatis, particularly in areas endemic for the disease. | 18,723,964 |
Primary marginal zone B-cell lymphoma of appendix. | Primary lymphomas of appendix are extremely rare tumors. The first case of primary lymphoma of appendix was reported by Warren in the year 1898. Incidence of primary lymphoma of appendix is 0.015% of all gastrointestinal lymphomas. This is a report of primary marginal zone B-cell lymphoma of appendix which presented as appendicular mass. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory. | 18,723,967 |
Parvovirus-induced dyserythropoeisis in a child. | Most persons with parvovirus B19 infection are asymptomatic or exhibit mild, nonspecific, cold-like symptoms. However, hematologic problems associated with the infection include transient aplastic crisis, chronic red cell aplasia, mild neutropenia and thrombocytopenia. A rare hematologic manifestation is in the form of dyserythropoeisis. Herein, we present the case of a 9-year-old female with severe dyserythropoeisis associated with parvovirus infection. | 18,723,978 |
Prone position is essential for detection of pulmonary vein pseudostenosis by enhanced multidetector computed tomography in patients who undergo pulmonary vein isolation. | Pulmonary vein (PV) stenosis is a major complication of PV isolation (PVI) by catheter ablation, so in the present study the optimal position for detecting PV stenosis on enhanced multidetector computed tomography (MDCT) image acquisition was determined. The 64-slice enhanced MDCT was carried out before and after PVI in 116 consecutive patients with atrial fibrillation while they were in the prone position, as well as while supine. The supine position MDCT image showed >50% diameter stenosis of the PV in 11 (9%) patients before PVI (% diameter stenosis: mean 55+/-4%, range 51-65%). Greater than 50% diameter stenosis was seen in the left inferior PV in all 11 patients. The prone position attenuated the PV stenosis findings in the MDCT images in all 11 patients (mean 9+/-6%, range 2-18%). Stenosis visualized on images acquired in the supine position was, therefore, concluded to be pseudostenosis caused by descending aorta compression. At 3 months after PVI, no significant changes in PV diameter were observed in these 11 patients. The present study demonstrated that the prone position is essential for eliminating PV pseudostenosis observed on supine-position enhanced MDCT images. The results also indicate that preexisting PV organic stenosis is rare. | 18,724,022 |
Congenital atresia of unilateral pulmonary veins associated with a single ventricle: a rare case report and literature review. | Congenital atresia or extreme hypoplasia of individual pulmonary veins is a rare condition that is usually asymptomatic if it only involves 1 or 2 segments of the lungs. It may be fatal if it occurs in combination with other complex cardiac defects. The patients often present with recurrent pulmonary infections, hemoptysis, or cyanosis in the latter case. A definitive diagnosis can be made by cardiac catheterization with selective pulmonary wedge angiography. The treatment of this condition is a challenge and is controversial, and the prognosis is usually poor. We describe the case of a male infant who suffered from shortness of breath and cyanosis since birth. On echocardiography and cardiac catheterization, he was found to have a complex congenital heart disease with a single ventricle (right ventricle morphology), mitral atresia, large atrial septal defect, and atresia of the right pulmonary veins; severe pulmonary hypertension was also observed. He underwent pulmonary artery banding at the age of 2.5 months, but he died because of a pulmonary infection at the age of 6 months. In this report, we present this rare case and review the previous literature. | 18,724,038 |
Some translations in vascular neurology. The Johann Jacob Wepfer Award 2008. | 'Translation' in medicine immediately suggests 'translational research', but there are many other varieties of 'translation'. I have selected 4 translations in the field of vascular neurology in which I have been involved in different respects: (1) the translation of results from men to women, taking the example of aspirin which, in primary prevention, decreases the risk of myocardial infarction in men and the risk of cerebral infarction in women, the reason for this sex difference being so far unknown; (2) the 'inverse translational research', from bedside to bench, taking the example of the disease we have identified--CADASIL--and showing how the study of one patient and his family led to the identification of a gene, Notch3, so far unknown in humans and to the discovery of its key role in the physiology of vascular smooth muscle cells; (3) the translation from individual case reports to multidisciplinary trials taking the example of hemicraniectomy in malignant cerebral infarction and emphasizing the interest in such rare and severe conditions of pooling and reporting the results of randomized clinical trials before the results of individual trials, and (4) the translation from research to practice, emphasizing not the well-known 'evidence to practice gap' but the slippery slope of 'lack of evidence to overpractice', taking the example of patent foramen ovale closure in migraine. | 18,724,046 |
Dominant non-coding repeat expansions in human disease. | The general model that dominant diseases are caused by mutations that result in a gain or change in function of the corresponding protein was challenged by the discovery that the myotonic dystrophy type 1 mutation is a CTG expansion located in the 3' untranslated portion of a kinase gene. The subsequent discovery that a similar transcribed but untranslated CCTG expansion in an intron causes the same multisystemic features in myotonic dystrophy type 2 (DM2), along with other developments in the DM1 field, demonstrate a mechanism in which these expansion mutations cause disease through a gain of function mechanism triggered by the accumulation of transcripts containing CUG or CCUG repeat expansions. A similar RNA gain of function mechanism has also been implicated in fragile X tremor ataxia syndrome (FXTAS) and may play a role in pathogenesis of other non-coding repeat expansion diseases, including spinocerebellar ataxia type 8 (SCA8), SCA10, SCA12 and Huntington disease-like 2. | 18,724,054 |
Pancreatic ductal adenocarcinoma: cellular origin, signaling pathways and stroma contribution. | Pancreatic cancer has a very poor prognosis, in part due to its diagnosis at late stages of the disease and to limited response to chemotherapy and radiotherapy. The vast majority of pancreatic cancers are classified as pancreatic ductal adenocarcinomas (PDACs). Despite advances in knowledge on the cellular origin of PDAC or the involvement of signal transduction pathways therein, many questions remain unanswered. In this review, we summarize recent findings and current hypotheses regarding these two questions. Since pancreatitis is a risk factor for human PDAC, and the latter proceeds with an intense fibrotic reaction, we also analyze the role of the stroma in PDAC progression. An improved understanding of these key aspects for PDAC ontogeny will open new avenues for tumor prevention, early detection, and improved therapy. | 18,724,072 |
Nurturing natural resources: the ecology of interpersonal relationships in women who have thrived despite childhood maltreatment. | Childhood maltreatment and its consequences are a public health issue. There continues to be a need for improving the lives and life prospects for survivors of child abuse. The important role that positive interactions can play was evident in a large study of women who considered themselves successful despite maltreatment. Interactions of import ranged from brief encounters with strangers to enduring relationships. Two distinct motifs emerged: The "Saw something in me" and "No matter what" relationships. Findings will be discussed within the context of extant theories with possible implications for researchers, practitioners, and careful, caring adults in any setting. | 18,724,109 |
Influencing factors of outcome after lower-limb amputation: a five-year review in a plastic surgical department. | The crude major lower limb amputation procedure rate is 8.8 per 100,000 of the population per year in Taiwan. From January 2002 to October 2006, patients that received major lower limb amputation in our department were enrolled in this study. Retrospective chart reviews concerning different factors that can affect the eventual postoperative functional status were investigated. Factors that affected the length of hospital stay included duration before amputation (P < 0.001) and renal function (P = 0.045). Phantom limb pain was affected by wound healing time (P = 0.006). Factors that affected the daily prosthesis usage time were initial infection status (P = 0.021), renal function (P = 0.01), patient educational level (P = 0.016), and pretraining waiting time (P = 0.003). The duration of prosthetic training was affected by patient educational level (P = 0.004) and marital status (P = 0.024). In addition, subjective satisfaction about the usage of prosthesis was affected by pretraining waiting time (P = 0.001) and daily prosthesis usage time (P < 0.001). The daily prosthesis usage time was closely related to life quality improvement (P < 0.001) and subjective satisfaction of prosthesis usage (P < 0.001). Despite reported unchangeable factors like age, end-stage renal disease, dementia, coronary artery disease, and level of amputation, preprosthesis training waiting time significantly affected the satisfaction and daily usage time of the prosthesis. Surgeons can make some contribution to accelerate amputation wound healing and stump maturation by choosing the correct operating procedure, delicately managing the soft tissue, and ascertaining proper wound care to improve the outcome. | 18,724,135 |
Kappa-opioid receptor agonist protects the microcirculation of skeletal muscle from ischemia reperfusion injury. | Previous research has demonstrated that pretreatment with kappa opioid receptor (KOR) agonist protects against ischemia reperfusion (I/R) injury in cardiomyocytes and neuron cells through activation of protein kinase C. The purpose of this study is to investigate the KOR agonist's effect on I/R-injured cremaster muscle and its underlying mechanism. Male Sprague Dawley rats were randomized into 3 groups (n = 6 each group). Group I was the ischemia reperfusion (I/R) injury group (4 hours of ischemia followed by 90 minutes of reperfusion). Group II was the U-50488H (selective KOR agonist)-pretreated group (KOR agonist + I/R injury). Group III was pretreated with U-50488H + nor-binaltorphimine (NBI, a selective KOR antagonist) (KOR agonist + antagonist + I/R injury). The numbers of leukocyte rolling, adhering, and transmigrating, functional capillary, and swelling index of the vessel wall of the postcapillary venule were observed under intravital videomicroscopy. Biochemically, the lactate dehydrogenase, creatine phosphokinase isoenzyme, expression of E-selectin, and intercellular adhesion molecule-1 (ICAM-1) were analyzed. The U-50488H-pretreated group had significantly decreased the number of leukocyte sticking (P < 0.001) and transmigrating (P < 0.001) as compared with the I/R-injury group and the U-50488H + NBI-pretreated group. The numbers of functional capillary in the U-50488H-pretreated group were significantly less attenuated compared with the I/R-injury group and U-50488H + NBI-pretreated group (P < 0.001). The expression of the ICAM-1 in the cremaster muscle was evidently reduced in the U-50488H-pretreated group than in the I/R-injury group or the U-50488H + NBI-pretreated group. Administration of KOR agonist protects the muscle flap microcirculation from I/R injury, which can be abolished by concomitant KOR antagonist administration. The KOR agonist-induced protection from ischemia reperfusion injury may be related to decreased expression of adhesion molecule ICAM-1. | 18,724,138 |
Use of systemic T-lymphocyte signal transduction inhibitors in the treatment of atopic keratoconjunctivitis. | Topical immunomodulators such as tacrolimus have revolutionized the treatment of atopic dermatitis. Because T lymphocytes are integral to the pathogenesis of atopic dermatitis, systemic treatment with T-lymphocyte signal transduction inhibitors should ameliorate both the dermatologic and ocular manifestations. We describe the successful treatment of 6 patients with severe atopic keratoconjunctivitis (AKC) resistant to conventional therapies. Retrospective observational case series. The charts of patients with AKC assessed by 1 of the authors were reviewed to identify those treated with systemic T-cell signal transduction inhibitors. Visual acuities, previous treatments, and the response to systemic signal transduction inhibitors were observed and reported in 6 patients. The patients had a mean duration of AKC of 21 years. Topical corticosteroids and antihistamines had failed to control signs and symptoms of the disease in all patients, and in some patients, systemic corticosteroids and topical cyclosporine were ineffective. Three patients were treated with systemic cyclosporine, and 3 were treated with systemic tacrolimus. One patient was subsequently treated with daclizumab in addition to tacrolimus. All 6 patients experienced complete remission of their AKC and an increase in visual acuity. Selective systemic immunosuppression of T lymphocytes with cyclosporine or tacrolimus has proved effective in the treatment of both atopic dermatitis and atopic keratoconjunctivitis. We advocate the consideration of systemic therapy in cases that are resistant to conventional treatment to resolve inflammation and preserve vision. Further studies in this area are advocated. | 18,724,148 |
Corneal abnormalities in the NC/Nga mouse: an atopic dermatitis model. | To study corneal abnormalities in the NC/Nga mouse, which is an animal model of atopic dermatitis. To study histopathologic changes of the eyelid, conjunctiva, and cornea, we extracted the eyeballs together with upper and lower eyelids and fixed them for examination by light and electron microscopy or snap-froze them for immunohistochemistry. Transferase mediated-dUTP digoxigenin nick-end labeling staining was performed to detect apoptotic cells. In order to assess eye scratching behavior and the effect of tacroliums hydrate ointment, we made video recordings. Mice kept in a conventional room suffered from various grades of blepharoconjunctivitis and scratched their eyes furiously. Tacrolimus hydrate ointment reduced their eye-scratching behavior. Histopathologic study of the eyelid and conjunctiva showed that this blepharoconjunctivitis was caused by allergic inflammation. Mice with severe blepharoconjunctivitis showed thinning of the corneal epithelium, an irregular interface between the epithelium and stroma, subepithelial deposition of materials, and neovascularization of the stroma. Their corneas were cone shaped. Many transferase mediated-dUTP digoxigenin nick-end labeling-positive cells were recognized among superficial epithelial cells and keratocytes. NC/Nga mice are a useful animal model of atopic blepharoconjunctivitis. Various corneal disorders in these mice may depend on their eye-scratching behavior. | 18,724,155 |
Eban health promotion intervention: conceptual basis and procedures. | This article concerns the health promotion intervention that served as the comparison condition in Project Eban, the NIMH Multisite HIV/STD Prevention Trial for African American Couples. Considerable research has documented the high rates of chronic diseases, including heart disease, cancer, stroke, and diabetes, among African Americans. Many of these diseases are tied to behavioral risk factors-the things that people do or do not do, their diet, the amount of exercise they get, and their substance use practices. The Eban Health Promotion Intervention was designed to increase healthful behaviors, including physical activity, healthful dietary practices, ceasing cigarette smoking and alcohol abuse, practicing early detection and screening behaviors, and improving medication adherence. As a comparison condition, the Eban Health Promotion Intervention was designed to be structurally similar to the Eban HIV/STD Risk Reduction Intervention. This article describes the intervention and how it was developed, integrating social cognitive theory with information collected in formative research to ensure that the intervention was appropriate for African Americans affected by HIV. Project Eban not only tests the efficacy of an HIV/STD risk reduction intervention for African American serodiscordant couples, but also tests the efficacy of an intervention addressing many of the other health problems common in this population. | 18,724,187 |
Guided growth for fixed knee flexion deformity. | Fixed knee flexion deformity (FKFD) is an insidious problem that may complicate the management of patients with neuromuscular compromise due to cerebral palsy, spina bifida, arthrogryposis, and other conditions. The energy costs associated with crouch gait may become prohibitive and, with the inexorable progression of fixed knee flexion, secondary pain may ensue as a result of fragmentation of the patella and/or tibial tubercle. Concomitant or compensatory flexion deformity of the hips and lumbar lordosis may develop, along with "pseudo equinus" of the ankles. Recommended treatments for FKFD have included bracing; physical therapy; and, in recalcitrant cases, distal femoral osteotomy, posterior release, or frame distraction. However, these latter modalities are fraught with potential complications including neurovascular damage, loss of fixation, undercorrection malunion, fracture, and recurrent deformity. Considering that FKFD is often bilateral, the complication risks for a given patient are doubled. In a previous study, the senior author reported successful hemiepiphysiodesis of the distal anterior femur using staples. However, further experience has demonstrated some of the limitations of stapling including relatively slow correction and occasional hardware migration. This led to the development of a more versatile and reliable solution using a pair of anterior tension band plates. In this retrospective clinical study, we are reporting this new technique of promoting gradual correction through guided growth of the distal femur, using a pair of anterior 8-plates. The correction is accomplished simultaneously and bilaterally, without immobilization, and may be combined with other operative procedures as indicated. We reviewed the charts, radiographs in a group of patients treated accordingly. In this group of 18 patients with 29 deformities, we noted correction averaging 1.3 degrees (range, 0.0 [1 patient]-4.8 degrees), with minimal complications. No inadvertent coronal plane deformities were created. Upon full correction, the plates were removed so as to avoid recurvatum. As an alternative to posterior capsulotomy or supracondylar extension osteotomy, we have found that guided growth is an effective and safe method of gradually correcting FKFD in growing children and adolescents. 4 (retrospective clinical series). | 18,724,198 |
Inflatable bouncer-related fractures in children. | Inflatable bouncers or moonbouncers are very popular in private and public settings and are usually perceived as very safe attractions, but are associated with frequent fractures in children. To date, there are no publications in the medical literature about these types of injuries. The purpose of this study was to show skeletal injuries related to inflatable bouncer use, describe their characteristics, and determine possible risk factors and preventive measures. Demographic data and injury characteristics were analyzed for all patients who were treated for inflatable bouncer-associated injuries in the pediatric fracture clinic of a level I trauma center from October 2002 to March 2007. Forty-nine patients were treated for inflatable bouncer-related fractures. Children ranged in age from 1.5 to 15 years old (mean age, 7.8 years) with a male-female ratio of approximately 3:1. The most commonly injured region was the upper extremity (65.5%, n = 32). The most commonly injured area was the elbow (31%, n = 15), and the most common single diagnosis was supracondylar humerus fracture (22%, n = 11). Diaphyseal long bone fractures were found in 18% (n = 9) of the patients and nondiaphyseal in 71% (n = 35). One patient (2%) had an open fracture. Mechanisms of injury included collision of 1 person with another (67%), falling out of a bouncer onto a hard object outside the device (19%), and twisting motion to the leg (14%). There was no adult supervision in many of the incidents (43%), and the presence of different-aged children inside the jumper took place in 52% cases. Inflatable bouncers can cause serious orthopaedic injuries. Children playing in the bouncer should be placed in small groups according to their size and should be closely supervised at all times. Case series. Level IV evidence. | 18,724,203 |
Determination of lowest possible creatinine in living-donor kidney renal transplant recipients based on donor kidney function. | The objective of this study was to use information from a donor to establish the lowest possible serum creatinine (SCr) of the recipient as a means of identifying early graft dysfunction. We analyzed retrospectively 58 pairs of living donors and recipients. The lowest possible SCr was calculated from four different formulae derived from Cockcroft-Gault formula: Ax(140-recipient age)xrecipient weight/donor GFR (A, women: 1.04, men: 1.23). Donor GFR was represented by the following values (a) mSCrD0: measured pretransplant GFR for both kidneys, (b) mSCrSKD0: single transplanted kidney GFR on day 0, (c) eSCrD0: estimated GFR based on SCr at day 0, or (d) eSCrD30: on day 30. These resulting estimated SCr were tested for correlation coefficient, bias, precision, and accuracy in predicting the lowest observed recipient SCr during the first year posttransplant. The lowest possible SCr was 80+/-22 micromol/L for mSCrD0, 79.1+/-23 micromol/L for mSCrSKD0, 83+/-27 micromol/L for eSCrD0, and 115+/-22 micromol/L for eSCrD30. Mean values for lowest possible SCr correlated significantly with the lowest observed SCr for all four formulae. The eSCrD0 formula showed the best correlation (r=0.47), the smallest positive bias (20.5 micromol/L), the highest precision (21.9 micromol/L), and the second highest percentage of predicted values that fell within 30% of the observed SCr (69%). The use of the Cockcroft-Gault derived formula with eSCrD0 may be a useful tool to detect early discrepancy between observed and lowest possible SCr value. This could help to identify patients who may require invasive investigations. | 18,724,226 |
Multiple hybrid granular cell tumor-perineuriomas. | Hybrid peripheral nerve sheath tumors (PNSTs) are recently recognized, rarely reported entities. Very few hybrid PNSTs with elements of perineurioma have been reported. We report a case of a 47-year-old man who presented with multiple (>20) cutaneous nodules on all 4 extremities, present since childhood. The patient and his family had no history of other PNSTs, other neural-origin tumors, or genetic disorders, including neurofibromatosis. Five excised lesions are well circumscribed but unencapsulated nodular tumors composed of cytologically bland spindled cells with tapering nuclei and indistinct cytoplasm arranged in a storiform pattern in a collagenous matrix. Scattered among these cells are large granular eosinophilic cells. The spindled cells are epithelial membrane antigen-positive and S-100 protein negative. The cytoplasm of the granular cells contains abundant S-100 protein, NK1/C3, and CD68-positive granules. Sparse nerve fascicles contain neurofilament-positive axons. Each tumor also contains poorly marginated areas that histologically resemble pure granular cell tumor, and superficial biopsies of these tumors can histologically resemble pure granular cell tumors. Considering a Schwannian origin for both perineurial and granular cells can provide a logical explanation for the pathogenesis of this case. To the best of our knowledge, our case is the first report of multiple hybrid granular cell tumor-perineurioma. | 18,724,242 |
Acinar cell carcinoma of the pancreas metastatic to the ovary: a report of 4 cases. | We report 4 cases of acinar cell carcinoma of the pancreas, 3 presenting as metastases in the ovary, the first report of this circumstance, which may pose a broad differential diagnosis and caused significant diagnostic difficulty in all the cases. The average patient age was 57 (range: 28 to 81) years. In 3 cases, the ovarian tumors were detected before the pancreatic tumor; in 1 case, a large abdominal mass and ovarian tumors were discovered synchronously. The ovarian tumors were large, solid, white-tan on gross examination, and bilateral in 3 cases; the single case involving only 1 ovary had 2 discrete masses of tumor. Microscopic examination showed highly cellular neoplasms with a small amount of fibrous stroma. Two cases had a predominant acinar growth pattern of cells with brightly eosinophilic, granular cytoplasm. In 2 cases, the pattern was predominantly solid-cribriform with areas of comedolike necrosis, and the cells had pale eosinophilic, finely granular cytoplasm. Nuclei in all cases were uniform with prominent nucleoli. The main differential diagnostic consideration was well-differentiated neuroendocrine neoplasm (carcinoid tumor); positive immunostaining with antibodies against chymotrypsin and trypsin and negative immunostaining with antibodies against synaptophysin and chromogranin helped exclude this diagnosis. We observed focal alpha-inhibin immunostaining in 2 cases, which may represent a potential diagnostic pitfall, as a Sertoli cell tumor or unusual granulosa cell tumor may also enter the differential diagnosis. Inclusion of antibodies against the pancreatic enzymes chymotrypsin and trypsin in the immunohistochemical panel is critical in establishing the correct diagnosis and should be considered when evaluating ovarian tumors with architectural (mainly acinar) and cytologic (granular eosinophilic cytoplasm) characteristics that should bring a metastatic acinar cell carcinoma into consideration. | 18,724,247 |
Comparison of commercially available serologic kits for the detection of celiac disease. | The sensitivity and specificity of current antihuman tissue transglutaminase (tTG) IgA assays used to detect celiac disease reportedly approach 100%. In addition, the sensitivity of new generation deamidated gliadin peptide (alpha-DGP) antibody assays has also been reported to be similar to the tTG IgA assays. In routine clinical practice, however, the sensitivities and specificities of these tests for diagnosing celiac disease seem to be lower. We analyzed sensitivities and specificities of 4 IgA tTG and 3 deamidated gliadin peptide (alpha-DGP) kits. The performance of 4 tTG IgA assays, A: Inova (Hu red blood cell), B: Binding site (rHu Ag), C: Eurospital (rHu Ag), D: Immco (rHu Ag) and 3 Inova alpha-DGP assays, E: alpha-DGP-IgA, F: alpha-DGP-IgG, and G: alpha-DGP-IgA+G was evaluated using sera from different subsets of celiac disease patients and controls; group 1: active celiac disease n=28, group 2: gluten-free diet n=54, group 3: healthy controls n=40, group 4: disease controls n=57(Crohn's disease n=17, chronic hepatitis n=40). Using the manufacturer's cut-off values, the sensitivities and specificities of different kits ranged from 71.4% to 96.4% and 87.5% to 100%, respectively. When group 1 was compared with disease controls, sensitivities remained the same but specificities decreased. Receiver operating characteristic plot derived cut-off values modified decision thresholds in all assays except kit (G). Kappa analysis demonstrated variable degrees of agreement. All assays demonstrated higher sensitivities for patients with higher grades of villous atrophy. Overall sensitivity was at or below 90%, which is lower than that reported in the literature. Performance of the recombinant and red blood cell antigen-based tTG assays was similar, whereas the alpha-DGP assays demonstrated lower values. Receiver operating characteristic plot derived cut-off values altered test results. Many factors affect the results of these tests and clinicians should be aware of their limitations. | 18,724,250 |
The impact of surgery in the management of the head and neck carcinoma involving the carotid artery. | To demonstrate the feasibility of the carotid artery dissection and/or resection and reanastomosis, and to show its positive impact on survival and disease control rates for the head and neck carcinomas involving the carotid artery. Tertiary center (Comprehensive Cancer Center). Case series review. The data of 90 patients with head and neck malignancies involving the carotid artery were operated for the carotid artery dissection and/or resection, and reanastomosis in the last 10 years were retrospectively reviewed and analyzed. Eighty (89%) of the 90 patients' head and neck malignancies were squamous cell carcinoma. Fifty-two (65%) and 28 (35%) of 80 patients were recurrent and stage IV disease, respectively. There was no stage I to III disease. Carotid artery was dissected and preserved in 64 (71.1%) of the 90 patients. Eighteen (20%) of 90 patients needed carotid artery dissection with resection and reanastomosis. Eight (8.9%) patients were unresectable. Sixty (75%) of 80 patients needed reconstruction with regional or free flaps and grafts. Overall 2- and 5-year estimated survivals were 32.4% and 27.8% for all; 14.3% and 10.7% for recurrent; 64.3% and 57.8% for stage IV previously untreated; and 22.0% and 22.0% for carotid artery resected-reanastomosed patients, respectively. The carotid artery dissection without resection is an achievable goal in majority of patients with the advanced stage head and neck carcinoma involving the carotid artery. Resection and reanastomosis of carotid artery, especially in the previously untreated carotid involved patients, is a feasible surgery and achieves better survival and disease control rates when compared with the unresected or recurrent disease patients. | 18,724,260 |
Host's response in otitis media: understanding genetic susceptibility. | Increasing evidence is emerging on genetic factors affecting host's response to infection in the middle ear. This review summarizes current knowledge on the field and on the contribution of nonspecific barriers, innate, and adaptive immunity. Better understanding of susceptibility to this very common disease will facilitate identification of high-risk individuals and optimization of prevention and treatment. | 18,724,267 |
Allogeneic stem cell transplantation for chronic myeloid leukemia-status in 2007. | Whereas until 2000 allo-SCT was the recommended treatment for all new patients with CML who were eligible on grounds of age and donor availability, approaches to initial therapy have changed very substantially since the introduction of imatinib mesylate. Today topical questions are (1) Should any newly diagnosed patient receive SCT as primary therapy? (2) How should imatinib failure be defined? (3) Should a patient who has failed imatinib but is still in chronic phase be offered an SCT or further treatment with a 'second-generation' TKI? (4) Would prior treatment with imatinib or concomitant delay to transplant adversely affect the subsequent results of allo-SCT? (5) Once the decision to proceed with allo-SCT is taken, how exactly should this be performed? (6) If a patient relapses after allo-SCT, how should he/she be treated? These questions will be addressed, but definitive answers may not yet be possible. | 18,724,281 |
Immunohematopoietic stem cell transplantation: introduction and 35 years of development in South Africa--the historical and scientific perspective. | Bone marrow was the traditional graft source when we introduced these procedures to South Africa. Technical details were established using rabbits as the experimental model with translation into a formally structured clinical programme at the University of Cape Town, based in the Groote Schuur Hospital, in 1972. Lack of any infrastructure was overcome by the acquisition of the first continuous-flow cell separator in sub-Sahara to provide for granulocyte transfusions. This was shortly followed by creating a dedicated platelet donor panel and establishing a specialized laboratory for clonogenic assays, flow cytometry, and programmed freezing and by including cryopreservation. Development was constant and seamless but four distinct periods are recognizable. First, guided and constantly encouraged by Professor E Donnall Thomas, was the use of an unfractionated mononuclear population derived from multiple sternal and iliac crest aspirations where complications, as in other centres, included rejection and, particularly troublesome, acute as well as chronic GVHD. The second was centred on CsA in association with Professor Jean Borel at Sandoz in Basle, leading to a decrease in the incidence and severity of the latter immunologic phenomena but not to their abrogation. Third was the opportunity of working with Professor Herman Waldmann and Dr Geoff Hale, first in Cambridge and latterly in Oxford, on immunosuppression achieved by ex vivo T-cell depletion within the broad ambit of the Campath users group. It was here that there was pioneered the alternative new approach of adding the anti-CD 52 MoAb only to the graft in what has become known as the in-the-bag technique. The fourth, securely based on early laboratory and clinical experiences, was a switch to the use of PBSCs mobilized into the circulation with stimulatory peptides. In 1995, this original transplant team relocated to a new academic centre in the private sector and has continued to actively refine the programme over the subsequent decade: the facility at Groote Schuur hospital continues independently. Early recognition that accountability for these expensive and high profile procedures was an important obligation led to consecutive transplants being reported to the International and Autologous registries and now continuing to the Centre for Bone Marrow Transplant Research concurrently with the European Bone Marrow Transplant Registry. This disciplined approach has ensured that all data undergo constant audit and, on such a basis, underpin the unbroken accreditation extending over more than three and a half decades. With difficulties in finding sibling donors, a further achievement was the creation of The South African Bone Marrow Registry and now a proposal to also start a national transplant registry that will complement the survey currently being conducted, on a worldwide basis, by the European Group for Blood and Marrow Transplantation. It is concluded that a properly constituted and functioning multidisciplinary team can cost-effectively carry out immunohematopoietic stem cell grafting even in an under-resourced country with an outcome approximating that reported from recognized First World reference centres. The caveat is that, outside such comprehensive units, results may be less impressive, thereby arguing for resource allocation being directed to academically designated, rather than incentive-driven, preferred providers. | 18,724,285 |
Allogeneic transplantation following nonmyeloablative conditioning for aggressive lymphoma. | Allogeneic hematopoietic SCT following myeloablative conditioning is associated with a high nonrelapse mortality and usually reserved for young, medically fit patients. The use of allogeneic stem cells is associated with a less risk of relapse, but is also associated with the risk of GVHD. The increased antitumor activity is due to graft-vs-tumor immune responses. The newer use of nonmyeloablative or reduced-intensity conditioning has decreased the toxicity of this approach and allows the treatment of older patients or those with medical comorbidities that preclude the use of a myeloablative regimen. A nonmyeloablative regimen using fludarabine and 2 Gy TBI was developed in Seattle that reliably allows allogeneic engraftment from either matched related or unrelated donor stem cell sources. Here we describe our results using this regimen in multicenter studies for the treatment of aggressive non-Hodgkin's lymphoma (NHL) and mantle cell NHL. | 18,724,296 |
High-dose chemotherapy and autologous stem cell transplantation for Hodgkin's lymphoma in the kingdom of Saudi Arabia: King Faisal specialist hospital and research center experience. | We report our experience with high-dose chemotherapy (HDC) and autologous SCT (ASCT) in 66 patients out of 113 (113 patients out of 153 had complete analysis) with primary refractory Hodgkin's lymphoma (PR-HL) who received salvage chemotherapy followed by BEAM as HDC. Median age at ASCT was 23 years. Before salvage chemotherapy, stages I:II:III:IV were 2:21:14:29, bulky disease 27%, involvement of mediastinum 79%, spleen 26% and extranodal site 47%; 92% had ESHAP (etoposide, methylprednisolone, high-dose cytarabine, cisplatin) as salvage. Post-ASCT evaluation showed response in 50 patients (76%), complete response (CR) in 37 (56%), partial response in 14 (21%), no response or stable disease in three (5%) and progressive disease in 10 (15%) patients. Six patients achieved CR after XRT (5) or surgery (1), making a total with CR of 43 (65%). From diagnosis and HDC, median follow-up is 38.5 and 22.8 months and median overall survival 78 and 57 months, respectively. EFS and overall survival (OS) are 36 and 64%, respectively. In all 47% patients are in CR. Twenty-two (33%) patients died of the disease. Multivariate analysis showed elevated lactic dehydrogenase (LDH) for EFS (P=0.041) and mediastinal involvement for OS (P=0.038) as negative prognostic factors. In conclusion, EFS and OS are only 36 and 64%, respectively. Elevated LDH and mediastinal involvement are poor prognostic factors. | 18,724,297 |
The Japan Marrow Donor Program, the Japan Cord Blood Bank Network and the Asia Blood and Marrow Transplant Registry. | The annual number of hematopoietic stem cell transplants in Japan is about 3500, which are performed by more than 300 medical teams throughout the country. The Japan Marrow Donor Program (JMDP), initiated in 1991, has recruited 300,000 volunteer donors, accepted 20,000 patients and has facilitated more than 8000 unrelated bone marrow transplants. The Japan Cord Blood Bank Network (JCBN), which started in 1999, has collected 20,000 cord blood units and facilitated 4000 cord blood transplants up to now. To fulfill the requirement for HSCT, international collaborations as well as domestic efforts are considered to be important for the future. The Center for International Blood and Marrow Transplant Research (CIBMTR) and European Blood and Marrow Transplant Group (EBMT) initiated a movement to create a common clinical record form last winter and called on the Asia-Pacific Blood and Marrow Transplantation Group (APBMT) to join them. Globalization of patient and donor registration for HSCT has become realistic and this could contribute to both the further improvement of patient outcomes and to further donor safety. | 18,724,304 |
The activity of hematopoietic stem cell transplantation in Korea. | Since the first successful allogeneic hematopoietic SCT (HSCT) was performed in Korea in 1983, there has been a noticeable progress in both the quantity and quality of HSCT over 24 years. There are 38 HSCT centers in Korea and the number of both allogeneic and autologous HSCTs has been increasing every year. As of December 2006, a total of 9561 HSCTs have been carried out in Korea, including 5617 allogeneic (59%) and 3944 autologous HSCTs (41%). The main indications were acute leukemia (3979, 78% allogeneic); lymphoma (1244, 90% autologous); myeloma (939, 92% autologous) and aplastic anemia (938). Characteristically, severe aplastic anemia accounts for a considerable proportion of transplants (10%), compared with western countries. Recently, there has been a marked increase in the number of unrelated transplants and the usage of PBSCs. The pattern of infectious diseases associated with HSCT is quite different. The rapid expansion of unrelated donor pools worldwide has changed the outlook of an unrelated donor search in Korea. | 18,724,315 |
Critical function for Naip5 in inflammasome activation by a conserved carboxy-terminal domain of flagellin. | Inflammasomes are cytosolic multiprotein complexes that sense microbial infection and trigger cytokine production and cell death. However, the molecular components of inflammasomes and what they sense remain poorly defined. Here we demonstrate that 35 amino acids of the carboxyl terminus of flagellin triggered inflammasome activation in the absence of bacterial contaminants or secretion systems. To further elucidate the host flagellin-sensing pathway, we generated mice deficient in the intracellular sensor Naip5. These mice failed to activate the inflammasome in response to the 35 amino acids of flagellin or in response to Legionella pneumophila infection. Our data clarify the molecular basis for the cytosolic response to flagellin. | 18,724,372 |
Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells. | Cell-matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled. | 18,724,374 |
A dichotic listening study of attention control in older adults. | The influence of age on attentional control of bottom-up processing was investigated with a dichotic-listening paradigm. The typical right-ear-advantage (REA) without specific attentional instructions was used as a measure of bottom-up processing (non-forced condition). Top-down attentional control was evaluated by instructing subjects to report only the right or left ear stimulus of the dichotic pair (forced-right, forced-left conditions). Both young and old participants showed a REA in the non-forced condition and an increased REA in the forced-right condition. The old group failed, however, to use attention to modulate the REA to the same degree as the younger participants in the forced-left condition. Only the young group showed a significant left ear advantage (LEA). The results are discussed in relation to cognitive decline in normal aging and in early stages of dementia. | 18,724,404 |
Organ donation regulations limit donations from gay men. | New federal regulations intended to protect the health and safety of transplant recipients came into force on 7 December 2007. | 18,724,453 |
[Purification and reactivity of foot-and-mouth disease virus non-structural protein 3A, 3B and 2C expressed in E. coli]. | To purify and to detect reactivity of non-structural proteins 3A, 3B and 2C expressed in the Escherichia coli. FMDV NSP 3A, 3B and 2C containing the major B-cell antigenic sites were expressed in E. coli. We got renatured 2C protein by lysing of isolated inclusion body using high concentration of urea, and then diluted in a buffer system containing oxidized/reduced glutathione. Purified 3A, 3B and 2C were obtained by Ni-NTA His Bind Resin affinity chromatography. The reactivity of three NSPs with sera of different origin was measured using an indirect ELISA and Western-blot. The reactivity of three proteins was compared with 3ABC and 3D by detecting sera of clinically healthy sheep that were collected from epidemic region of Asia I FMD. Proteins 3A and 3B were solubly expressed in bacteria, and 2C was expressed to form inclusion body. All three products could react specifically with sera from FMDV infected animal by western-blot and ELISA. The high coincident rates were observed between 3A, 3B, 2C and 3ABC. The results would provide useful materials for establishment of immunoelectro-transfer blot (EITB) diagnostic method, which could be used for differentiation of the FMDV infected animals from the vaccinated animals. | 18,724,495 |
The View-Master Health Study Focus Groups. | Trichloroethylene (TCE), a common groundwater contaminant, was found at high levels at an Oregon work site in 1998. According to a recent report released by the National Research Council, "the evidence on carcinogenic risk and other health hazards from exposure to trichloroethylene has strengthened since 2001." A convenience sample of 13 former workers from the Oregon work site was recruited for a series of focus groups. Information obtained on plant processes, safety procedures, attitudes regarding medical record access, and opinions about proxy accuracy was subjected to qualitative content analysis. Workers recalled few safety policies and no training or support for control of safety. Most thought co-workers and family members would be the best source of proxy exposure information and favored granting access to medical records. Job-role mobility confirmed the importance of using a job or task exposure matrix. Information obtained will be used in development of an exposure assessment interview tool. | 18,724,499 |
[Informed consent. Efficient communication and autonomous decision-making]. | Informed consent belongs to a new way to understand doctor-patient relationships from a perspective permitting a principle of autonomy. Seen from this viewpoint, we speak of a medical relationship understood as being a mutual relationship. For a decision to be autonomous, it must be intentional, taken after adequately understanding all the pertinent information and totally free from outside influences. We must realize that from both theoretical and practical views objections exist; these include paternalism, comprehension difficulties, or patient refusal to exercise informed consent. Informed consent presents a reality and a challenge for our profession since it is much more complex than a simple signature on a document. | 18,724,513 |
[Effect of growth factor on the phenotype of subpopulations and on the kinetics of CD34+ cells in the peripheral blood and in grafts of peripheral stem cells in patients with non-Hodgkin's lymphoma indicated for autologous peripheral blood stem cell transplantation]. | Peripheral blood stem cells are the preferred source for transplantation of hematopoiesis in patients with non-Hodgkin's lymphoma. Application of hematopoietic growth factors is a part of the mobilization chemotherapy regimen. Time overlap of the highest leukocyte and CD34+ cell count is required for optimal graft collection. Authors analyzed the effect of two growth factors (leridistim and filgrastim) on the kinetics and phenotype of CD34+ cells in patients with non-Hodgkin's lymphoma indicated for autologous peripheral blood stem cell transplantation. Authors analyzed phenotype of CD34+ cell subpopulations and their kinetics in peripheral blood and leukapheresis products by flow cytometry during mobilization and graft collection. Statistically significant differences in expression of lineage-committed antigens between growth factors were found (CD3, CD5--T-lineage, CD56 NK-lineage, CD20 for B-lineage, p < 0.05), as well as for lineage non-specific antigens (CD38, p < 0.05 and CD54, p < 0.01). The most significant divergence was observed between CD34+CD19+ subpopulations of leridistim and filgrastim stimulated blood and graft (p < 0.001). Expression of lineage-committed antigens on CD34+ subpopulations between two growth factors was statistically different. Kinetics of CD34+ cells during mobilization regimen with leridistim was not superior to filgrastim concerning the quality of graft. | 18,724,529 |
Esophageal stenting for the palliation of malignant dysphagia. | Self-expanding metal stents (SEMS) are currently the standard for palliation of malignant dysphagia. Innovations in stent technology, including the advent of retrievable stents and the development of self-expanding plastic stents (SEPS), show promise to increase the possible applications for esophageal stents. This article reviews the indications and usage of both SEMS and SEPS in patients with malignant dysphagia as well as the potential complications of their use. | 18,724,535 |
[Physiological maternal changes during pregnancy and their consequence in GP-practice]. | Physiological maternal changes, as well as signs and symptoms during pregnancy were presented. Changes in cardiopulmonary, urinary, digestive tract, metabolic and endocrinal changes in the light of practical application in G-P practice were presented. | 18,724,547 |
[Sinusoidal obstruction disease (SOS), previous hepatic venoocclusive disease (VOD)--still serious complication after hematopoietic stem cell transplantation]. | Hepatic venocclusive disease (VOD) lastly named sinusoidal obstruction syndrome (SOS) is a serious toxicity associated with high dose therapy used to prepare patients for stem cell transplantation. A sizable proportion of patients who develop VOD/SOS die. It is clear that injury to endothelial cells and hepatocytes in zone 3 of the liver acinus is the initial event in the pathogenesis of VOD/SOS. Although clinical presentation and diagnostic criteria are well known, the cause of VOD/SOS, its prevention and treatment remain still unclear. Currently treatment of VOD/SOS has largely consisted of supportive measures designed to maintain intravascular volume and decrease interstitial edema. Other treatments used with various measures of success have included substitution of antitrombine and glutamine or aggressive fibrinolitic and antithrombotic therapy. Despite these treatments, the outcome remains fairly dismal. | 18,724,548 |
Visual analogue scales and assessment of quality of life in cancer. | Assessment of quality of life (QOL) in cancer clinical trials is important when comparing treatments, especially when prolonged survival is not expected. QOL scores may reflect physical or psychosocial functioning or distress. The choice of QOL instrument depends upon the definition, research hypothesis, cancer population, depth and sensitivity of information required, and frequency of measurement. A visual analogue scale (VAS) is commonly used to rate various subjective experiences. Potential advantages of these scales include their wide score range and high sensitivity; disadvantages include lower completion rates than other rating scales. Single-item VASs are validated for cancer QOL, reliable, and responsive to change. These scales may best represent an individual's global QOL without the constraints of predetermined domains. Single items are useful for frequent measurements in palliative or advanced populations and when information about domains is less important. Multi-item VAS QOL instruments vary in length and domains; they are useful in clinical trials enrolling patients with good performance status, but some are long and disease-specific. | 18,724,538 |
History of analgesia and regional anaesthesia through philately. | Medical philately is the study of postage stamps commemorating events and pioneers in the field of medicine. In 1929, Dr Fielding H. Garrison, doyen of medical history, remarked that stamps were a great resource for the medical fraternity, something he hoped that physicians would soon recognise. His prediction has hardly come to fruition in the years since then, with medical philatelic articles rarely seen in the medical press. The history of pain medicine is unique, diverse and extremely interesting, with many chemists, physicists, philosophers, contributing in their own way over centuries to pave the path to present day pain medicine. | 18,724,553 |
Clinical trials in Canada: whose interests are paramount? | More than 80 percent of clinical drug trials in Canada are funded by the pharmaceutical industry. This article evaluates the overall state of clinical trials in Canada and looks at the interplay between public and private interests. Health Canada has adopted standards developed by the International Conference on Harmonization, a body that is heavily influenced by industry. Commercial interests are increasingly involved in recruiting patients into clinical trials and in running these trials. It is in industry's interests to conduct drug tests on people for which it is easiest to see benefits. These interests are not fundamentally challenged by Health Canada's policy of issuing nonmandatory guidelines on who should and should not be included in clinical trials. The outcome of clinical trials is heavily influenced by commercial sponsorship, with the result that trials may favor corporate interests rather than the interests of the public. How Health Canada deals with that possibility is not known, because of its strict policy of treating clinical trial data as private property. If clinical trials are to serve the purpose for which they are designed, developing reliable and objective information about new drugs, then commercial interests cannot be allowed to take precedence over health interests. | 18,724,580 |
Clinical update: melatonin and sleep disorders. | The hormone melatonin is increasingly used for the treatment of certain sleep disorders, particularly those related to disturbed biological rhythms. This article summarises current knowledge of its mechanism of action and identifies situations where there is good evidence for its efficacy. The authors provide advice, based on their own experience and consistent published data, concerning the dose range of melatonin to be used and the critically important question of the timing of treatment. Anecdotal evidence for the use of melatonin needs to be replaced by data from well-controlled, preferably multi-centre, randomised clinical trials. | 18,724,603 |
Cardiovascular disease--the silent killer in rheumatoid arthritis. | Rheumatoid arthritis (RA) is a multisystem disease with high rates of morbidity and mortality. In recent years, there has been increasing focus on the growing rates of cardiovascular disease (CVD) in RA, over and above expected levels allowing for 'traditional' risk factors. In this paper the impact of CVD in RA, the relative contributions of traditional risk factors and novel risk factors (including homocysteine, oxidised low-density lipoprotein, high-sensitivity C-reactive protein and leptin), and the need to address cardiovascular risk in the fight against premature death from coronary artery and stroke disease in RA are discussed. | 18,724,604 |
MPs consider UK engineering's future. | The Government's Parliamentary Innovation, Universities, Science and Skills Committee (IUSSC), which in January launched an enquiry into the current "state" of the UK engineering sector, recently held a session in Westminster to hear evidence on the topic from expert bodies. IHEEM chief executive John Long was among those to draft written evidence for the Committee that not only provides an overview of the current UK engineering sector and its major challenges, but also recommends ways to maximise engineers' contribution in the future. | 18,724,629 |
Methodologies for determining the bioavailability and biodegradability of sludges. | The measurement of sludge bioavailability and biodegradability is important to assess the sludge potential as a source of carbon and energy during its biological stabilization. As the majority of biological sludge (secondary sludge) consists of biomass, an increase in sludge bioavailability can be achieved by using different techniques for cell lysis, which is aimed at releasing intracellular organics into the bulk solution and enhancing hydrolysis of particulate organic matter. This paper reviews the main methodologies currently used for cell lysis, which include thermal, ultrasonic and chemical techniques and a combination of these, as well as the analytical procedures that can be employed to assess the degree of lysis and sludge solubilization. In addition, this paper also discusses common techniques that can be used for measuring the biodegradability of sludge under aerobic and anaerobic conditions. | 18,724,640 |
Tretinoin microsphere gel in facial acne vulgaris: a meta-analysis. | Acne vulgaris can persist beyond adolescence into the fourth decade of life or later; most patients have a combination of inflammatory and noninflammatory lesions. To determine whether tretinoin microsphere gel (TMG) 0.04% applied once nightly is well tolerated and effective in reducing inflammatory and noninflammatory lesions in adolescents and adults with mild to moderate facial acne. The results of 3 randomized, double-blind, vehicle-controlled studies of TMG 0.04% applied once nightly for 12 consecutive weeks in a total of 629 patients, ages 11 to 49 years, were combined. Reductions in acne lesion counts were assessed twice monthly, and an investigator's global evaluation (IGE) was performed at the study endpoint (week 12). Tretinoin microsphere gel 0.04% was significantly superior to the vehicle gel in reducing both inflammatory and noninflammatory lesions over the 12-week treatment period, and produced a higher successful treatment rate than the vehicle gel, as judged by IGE ratings at week 12. The most frequent adverse events were erythema, peeling, and dryness, which were mostly mild and occurred in 59.7% to 63.3% of patients with TMG 0.04%, as compared with 26.9% to 51.0% of patients with the vehicle gel (placebo). The TMG 0.04% formulation is significantly superior when compared to its vehicle gel in reducing inflammatory and noninflammatory acne lesions over a period of 12 weeks and is well tolerated. | 18,724,648 |
Prevention of methamphetamine abuse: can existing evidence inform community prevention? | Little research exists on effective strategies to prevent methamphetamine production, distribution, sales, use, and harm. As a result, prevention practitioners (especially at the local level) have little guidance in selecting potentially effective strategies. This article presents a general causal model of methamphetamine use and harms that reflects the available findings from either research specific to methamphetamine or from alcohol and other illegal drugs, and suggests prevention approaches and strategies that communities might use based upon research evidence and experience. Community methamphetamine prevention can use the public health and safety perspective applied to other substance abuse prevention. Analyses of the complex system of intermediate variables that interact to affect methamphetamine use and harms suggest that multiple reinforcing prevention interventions may have the greatest potential effectiveness. | 18,724,655 |
[Developments of microfluidic chip-based capillary electrophoresis for protein separation]. | In this paper, the developments of microfluidic chip-based capillary electrophoresis (CE) for protein separation in recent years are reviewed. Various chip-based CE systems for protein separation based on different CE separation modes are introduced. The approaches to suppress the adsorption of proteins on the surface of microchannel on chips are discussed. The application prospect for chip-based CE in protein separation is also proposed. Forty-seven references are cited. | 18,724,658 |
[Determination of monoethylglycinexylidide concentration in serum using solid phase extraction and capillary gas chromatography-mass spectrometry]. | A novel method for the determination of monoethylglycinexylidide (MEGX) (lidocaine metabolin) in serum using solid phase extraction (SPE) and capillary gas chromatography-mass spectrometry (GC-MS) was established. The serum sample was extracted with a CN-SPE column. An HP-5MS capillary column (15 m x 0.25 mm x 0.1 microm) was used. The initial temperature of the column was set at 100 degrees C, held for 1 min, then raised to 200 degrees C at 40 degrees C/min, and held at 200 degrees C for 0.5 min. The sample size was 2 microL, and the split ratio was set at 1 : 1. The carrier gas was high purity helium with a flow rate of 1.0 mL/min. The monitoring ions for the determination were m/z 58 for MEGX and m/z 86 for procaine (internal standard). The calibration curve of MEGX had good linear relationship in the range of 1.562 - 25 ng/mL ( r = 0.998 1). The limit of detection was 0.5 ng/mL. The extraction recovery ranged from 80.1% to 85.7%. The method advanced the quantitative analysis of MEGX in serum by combining rapid and efficient SPE with specific and sensitive quantitation by GC-MS. | 18,724,665 |
[Preparation of asiaticoside and madecassoside from the extract of Centella asiatica (L.) Urb using preparative high performance liquid chromatography]. | A high performance liquid chromatographic (HPLC) method was successfully used to separate asiaticoside and madecassoside from the extract of Centella asiatica (L.) Urb. The raw material containing 20% asiaticoside and 45% madecassoside was dissolved in methanol and used for the preparation of the pure compounds. The flow rate of the mobile phase, injection volume and detection wavelength were optimized. The optimum operation parameters were then selected as follows: a C18 column (50 mm x 200 mm, 5 microm) with methanol-water (60 : 40, v/v) as the mobile phase at a flow rate of 100 mL/min, the detection wavelength of 220 nm, and the injection volume of 1.5 mL at the concentration of 40 mg/mL. Asiaticoside and madecassoside the can be obtained in a 20 min runtime, and the purities of the products were detected by melting point, thin layer chromatography (TLC) and HPLC method. The results showed that the purities of products were above 98%. The effective and rapid method has been successfully applied and to the preparation of asiaticoside and madecassoside from Centella asiatica (L. ) Urb. | 18,724,677 |
[Preparation of three capsaicinoid components using preparative high performance liquid chromatography]. | A method was established for the isolation of three capsaicinoid components from capsaicinoids using preparative high performance liquid chromatography (Pre-HPLC). A preparative PRC-ODS column (250 mm x 21.5 mm, 13 microm) was used in the preparation process. By isocratic elution with methanol-water (70 : 30, v/v) as the mobile phase at a flow rate of 15 mL/min followed by concentration, three capsaicinoid components were obtained from 80% capsaicinoids, and subsequently identified by 1H NMR (nuclear magnetic resonance) and EI-MS (electron impact-mass spectrometry) as nordihydrocapsaicin, capsaicin and dihydrocapsaicin, and the purities of the three components analyzed by HPLC were 98.12%, 99.93% and 100.7% with yields of 60.1%, 58.9% and 72.3%, respectively. | 18,724,678 |
[Establishment and application of a two-dimensional liquid chromatographic system (NPLC x RPLC)]. | A two-dimensional liquid chromatographic system (NPLC x RPLC) has been developed. Normal phase liquid chromatography (NPLC) with a Hypersil SiO2 column (50 mm x 4.6 mm) was used as the first dimension, and reversed-phase liquid chromatography (RPLC) with a Kromasil C18 column (250 mm x 4.6 mm) was used as the second dimension. The interface was a ten-port, two-position valve with two storage loops. As to improve the compatibility of the two dimensional mobile phase and be good for adjusting the selectivity of separation, 1,4-dioxane was used in the mobile phase of the first dimension, and isopropyl alcohol was used in the mobile phase of the second dimension based on the characters of the organic solvents. By raising the temperature of the second dimension, the incompatibility of the two dimensional mobile phases was avoided. A Chinese potent medicine, Zhengtian Wan, was analyzed by this system. The total peak capacity reached 1 220. | 18,724,680 |
[Construction of adenoviral vector encoding soluble human sTNFRI-IgGFc cDNA and its expression in human airway smooth muscle cells (HASMCs)]. | Tumour necrosis factor (TNF-a) is a pro-inflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma, and which has recently been highlighted as potentially important in refractory asthma. To study the feasibility of local treatment of asthma with recombinant adenovirus vector carrying soluble extra-cellular region of TNF receptor I-IgGFc (sTNFRI-IgGFc) fusion protein, The sTNFRI-IgGFc gene was subcloned into the adenovirus shuttle plasmid pDC316, the products were co-transfected into HEK293 cell line with helper plasmid pBHGloxDeltaE1,3Cre. The recombinant adenovirus (Ad-sTNFRI-IgGFc) was produced by homologous recombination of above 2 plasmids in HEK293 cells. After identification with PCR, Ad-sTNFRI-IgGFc was amplified and purified, its titer was measured by TCID50 assay. The transcription and expression of sTNFRI-IgGFc gene in transfected human airway smooth muscle cells (HASMCs) was detected by RT-PCR, ELISA and immunological histochemistry. The anti-TNF activity assay of transfected HASMCs culture supernatant was measured by MTT. Ad-sTNFRI-IgGFc was successfully constructed with the titer of 3x10(10) TCID50/mL. Ad-sTNFRI-IgGFc can transfect HASMC with high efficacy. The transcription of sTNFRI-IgGFc mRNA and the expression of protein were confirmed in the transfected HASMCs. Moreover, the product in 100 microL expression supernatant could completely antagonize the cytolytic effect of 2ng TNFa on L929 cells, even at 1/64 dilution. This study forms the basement of the experiment study on local treatment of asthma with adenovirus expressing sTNFRI-IgGFc. | 18,724,696 |
[Cutinase production from short-chain organic acids by Thermobifida fusca]. | We studied cutinase production from short-chain organic acids by Thermobifida fusca WSH03-11 to evaluate the possibility of converting municipal sludge to high value-added products. The optimum organic acid (8.0 g/L) and nitrogen source (1.5 g/L) concentrations were determined by the single factor experiments with butyric acid, propionic acid and acetic acid as the carbon sources. When lactic acid was used as the carbon source, the optimum organic acid (3.0 g/L) and nitrogen source (1.0 g/L) concentrations were obtained. Cutinase production by T. fusca WSH03-11 was further improved with butyric acid (by 31.0%), propionic acid (by 13.3%), acetic acid (by 43.8%) and lactic acid (by 73.2%) as carbon source, respectively, with the optimized cutin concentrations. Among these four short-chain organic acids, the average specific consumption rate of acetic acid was the highest, higher than that of propionic acid 1.3-folds, butyric acid 2.0-folds and lactic acid 2.2-folds. The highest cutinase activity reached 52.4 u/mL with butyric acid (8 g/L) as the sole carbon source, higher than that of lactic acid (3 g/L) 1.7-folds, acetic acid (8 g/L) 2.5-folds and propionic acid (8 g/L) 3.2-folds. The yield of cutinase activity on lactic acid (12.70 u/mg) higher than that of butyric acid 1.4-folds, propionic acid 3.0-folds and acetic acid 3.8-folds. T. fusca WSH03-11 consumed acetic acid firstly in mixed acids carbon sources, and the consumption of butyric acid was inhibited. Further studies indicated that the consumption rate of butyrate was decreased by 66.7% in the presence of 0.5 g/L acetic acid in the mixed acids. This was the first report concerning the production of cutinase by T. fusca with mixed organic acids as the carbon sources. The results presented here provided a novel and efficient approach to produce high value-add products from municipal sludge, and also established a foundation for the industrial production of cutinase by T. fusca WSH03-11 with cheap carbon sources from the processing of municipal sludge. | 18,724,703 |
[Development and application of real-time quantitative RT- PCR assay for the detection of hepatitis E virus]. | Hepatitis E virus (HEV) sequences including four major genotypes representative strains available in GenBank were aligned with the DNAMAN software. The highly conserved internal region of ORF2 was then subjected to design primers and a probe. Furthermore, a 0.3 kb fragment of HEV ORF2 containing the amplification region was transcribed in vitro to synthese cRNA standard and a universal real-time TaqMan PCR assay was optimized and developed to detect and quantify main genotypes RNA of HEV. The specificity and reliability of the real-time RT-PCR was confirmed by testing genotype I HEV, genotype IV HEV and clinical samples. The detection limit of real-time RT-PCR was found 2.0 x 10(1) copies per reaction using in vitro transcribed cRNA. Compared with nested RT-PCR in diagnosis of HEV, the real-time RT-PCR developed was 10 to 100-fold more sensitive than the nested RT-PCR. The detection results from 54 clinical specimens indicated real-time RT-PCR was a rapid, sensitive and reproducible diagnostic method for HEV. This assay will be useful as an early and rapid diagnostic assay for HEV. | 18,724,714 |
[Effect of different tags on pulldown assays implemented by LMO2 fusion protein]. | Pulldown assay is an in vitro method for studies of protein-protein interactions, in which tagged proteins are usually expressed as the bait to enrich other proteins that could bind to them. In this technology, the GST tag is broadest used for its modest size and hydrophilic property. In most cases, the GST tag could increase the hydrophility of the fusion protein and help to avoid the formation of inclusion bodies. However, in the other few cases, the target protein may be strongly hydrophobic or have complicated structures that were hard to fold and assemble in correct conformations without champerons, and even the existence of GST tag could not make them soluble. These proteins were always expressed as inclusion bodies and had no functions. LMO2 was a small molecular weight and insoluble protein, in this study, GST system and MBP system were used to express GST-LMO2 and MBP-LMO2 fusion proteins, respectively. We found that GST-LMO2 fusion protein was expressed as inclusion bodies whereas MBP-LMO2 fusion protein was expressed in soluble form. Moreover, the production rate of MBP-LMO2 was also much higher than GST-LMO2. Then MBP-LMO2 fusion proteins and renatured GST-LMO2 fusion proteins were used as bait in pulldown assay to study the interaction between LMO2 and endogenous GATA1 in K562 cells. Western blot analyses showed that both of these proteins could bind to endogenous GATA1 in K562 cells, but recovered GATA1 protein by MBP-LMO2 fusion protein was much more than GST-LMO2 fusion protein. These results suggest that using of MBP system is a helpful attempt in the case of studying small molecular weight, strong hydrophobic proteins. | 18,724,713 |
An unusual trophic subsidy and species dominance in a tropical stream. | In classical theory, species are assumed to achieve dominance through competitive exclusion, but if food resources are limiting, cross-habitat trophic subsidies could also underpin dominance. The impact of dominant species on community dynamics may depend on the energy base of population size. We report on an unusual, spatially subsidized population of a tropical, stream-dwelling crab that dominates the benthic fauna of a Kenyan stream. Diet and stable isotope analyses indicated that this crab is a true omnivore, with terrestrial subsidies dominating both plant and animal resources. Unusually, the animal prey included almost no aquatic invertebrates. Instead, a single species of ant constituted approximately 35% of the annual diet (stomach contents analysis) and up to 90% of assimilated nitrogen (estimates from stable isotope analysis). Ants may be pivotal to enabling crab dominance, and this crab may be largely disconnected from the local trophic network for its dietary needs. The paucity of other invertebrates in the stream community suggests that this super-dominant crab is a strong interactor that suppresses aquatic invertebrate populations. Common stabilizing attributes of spatially subsidized food webs (e.g., asynchronous prey availability, wide feeding niche, consumer migration) were absent from this system, and although apparently stable, it may be vulnerable to disturbance in the donor habitat. | 18,724,742 |
60-day aging requirement does not ensure safety of surface-mold-ripened soft cheeses manufactured from raw or pasteurized milk when Listeria monocytogenes is introduced as a postprocessing contaminant. | Because of renewed interest in specialty cheeses, artisan and farmstead producers are manufacturing surface-mold-ripened soft cheeses from raw milk, using the 60-day holding standard (21 CFR 133.182) to achieve safety. This study compared the growth potential of Listeria monocytogenes on cheeses manufactured from raw or pasteurized milk and held for > 60 days at 4 degrees C. Final cheeses were within federal standards of identity for soft ripened cheese, with low moisture targets to facilitate the holding period. Wheels were surface inoculated with a five-strain cocktail of L. monocytogenes at approximately 0.2 CFU/ cm2 (low level) or 2 CFU/cm2 (high level), ripened, wrapped, and held at 4 degrees C. Listeria populations began to increase by day 28 for all treatments after initial population declines. From the low initial inoculation level, populations in raw and pasteurized milk cheese reached maximums of 2.96 +/- 2.79 and 2.33 +/- 2.10 log CFU/g, respectively, after 60 days of holding. Similar growth was observed in cheese inoculated at high levels, where populations reached 4.55 +/- 4.33 and 5.29 +/- 5.11 log CFU/g for raw and pasteurized milk cheeses, respectively. No significant differences (P < 0.05) were observed in pH development, growth rate, or population levels between cheeses made from the different milk types. Independent of the milk type, cheeses held for 60 days supported growth from very low initial levels of L. monocytogenes introduced as a postprocess contaminant. The safety of cheeses of this type must be achieved through control strategies other than aging, and thus revision of current federal regulations is warranted. | 18,724,749 |
Androgen resistance in squirrel monkeys (Saimiri spp.). | The goal of this study was to understand the basis for high androgen levels in squirrel monkeys (Saimiri spp.). Mass spectrometry was used to analyze serum testosterone, androstenedione, and dihydrotestosterone of male squirrel monkeys during the nonbreeding (n = 7) and breeding (n = 10) seasons. All hormone levels were elevated compared with those of humans, even during the nonbreeding season; the highest levels occurred during the breeding season. The ratio of testosterone to dihydrotestosterone in squirrel monkeys is high during the breeding season compared to man. Squirrel monkeys may have high testosterone to compensate for inefficient metabolism to dihydrotestosterone. We also investigated whether squirrel monkeys have high androgens to compensate for low-activity androgen receptors (AR). The response to dihydrotestosterone in squirrel monkey cells transfected with AR and AR-responsive reporter plasmids was 4-fold, compared with 28-fold in human cells. This result was not due to overexpression of cellular FKBP51, which causes glucocorticoid and progestin resistance in squirrel monkeys, because overexpression of FKBP51 had no effect on dihydrotestosterone-stimulated reporter activity in a human fibroblast cell line. To test whether the inherently low levels of FKBP52 in squirrel monkeys contribute to androgen insensitivity, squirrel monkey cells were transfected with an AR expression plasmid, an AR-responsive reporter plasmid, and a plasmid expressing FKBP52. Expression of FKBP52 decreased the EC50 or increased the maximal response to dihydrotestosterone. Therefore, the high androgen levels in squirrel monkeys likely compensate for their relatively low 5 alpha-reductase activity during the breeding season and AR insensitivity resulting from low cellular levels of FKBP52. | 18,724,781 |
Determination of serum creatinine by Jaffe method and how to calibrate to eliminate matrix interference problems. | The calibration of Jaffe method for serum creatinine using one serum-based standard complemented with artificial matrix compensating standard's Jaffe-interfering substances allows two-point calibration with results well comparable with enzymatic methods. Spectrophotometry was used. Jaffe procedures compensating serum/plasma intereferents by subtracting a constant amount of creatinine poorly overcompensate creatinine in children. Two-point calibration with a pair of primary serum standards certified by the reference measurement procedure (isotope-dilution, mass spectrometry) or with a pair of secondary standards linked to primary materials could provide results well agreeable with enzymatic determination. Such a calibration comprises an absorbance offset corresponding to other-than-creatinine Jaffe-interfering chromogens present in standards in the calibration line, while a two-point calibration combining one standard with physiological saline/water always grossly distorts calibration line. We calculated/prepared artificial serum matrices capable of compensating Jaffe-interfering chromogens in serum standards. The combination of even one standard with its artificial matrix also enables two-point calibration with practically the same results as with a pair of primary standards. A two-point calibration of Jaffe method for serum creatinine combining only one serum standard with creatinine solution matching standard's allow matrix-present interferents present results well comparable with enzymatic determination, providing the standard is attested/linked to the reference measurement procedure. | 18,724,810 |
Peri-implant diseases: Consensus Report of the Sixth European Workshop on Periodontology. | Issues related to peri-implant disease were discussed. It was observed that the most common lesions that occur, i.e. peri-implant mucositis and peri-implantitis are caused by bacteria. While the lesion of peri-implant mucositis resides in the soft tissues, peri-implantitis also affects the supporting bone. Peri-implant mucositis occurs in about 80% of subjects (50% of sites) restored with implants, and peri-implantitis in between 28% and 56% of subjects (12-40% of sites). A number of risk indicators were identified including (i) poor oral hygiene, (ii) a history of periodontitis, (iii) diabetes and (iv) smoking. It was concluded that the treatment of peri-implant disease must include anti-infective measures. With respect to peri-implant mucositis, it appeared that non-surgical mechanical therapy caused the reduction in inflammation (bleeding on probing) but also that the adjunctive use of antimicrobial mouthrinses had a positive effect. It was agreed that the outcome of non-surgical treatment of peri-implantitis was unpredictable. The primary objective of surgical treatment in peri-implantitis is to get access to the implant surface for debridement and decontamination in order to achieve resolution of the inflammatory lesion. There was limited evidence that such treatment with the adjunctive use of systemic antibiotics could resolve a number of peri-implantitis lesions. There was no evidence that so-called regenerative procedures had additional beneficial effects on treatment outcome. | 18,724,855 |
Predictors of HIV infection and prevalence for syphilis infection among injection drug users in China: community-based surveys along major drug trafficking routes. | To assess the predictors and prevalence of HIV infection among injection drug users in highly endemic regions along major drug trafficking routes in three Chinese provinces. We enrolled participants using community outreach and peer referrals. Questionnaire-based interviews provided demographic, drug use, and sexual behavior information. HIV was tested via ELISA and syphilis by RPR. Of the 689 participants, 51.8% were HIV-infected, with persons living in Guangxi having significantly lower prevalence (16.4%) than those from Xinjiang and Yunnan (66.8% and 67.1%, respectively). Syphilis seropositivity was noted in 5.4%. Longer duration of IDU, greater awareness of HIV transmission routes, and living in Xinjiang or Yunnan were associated with HIV seropositivity on multivariable analysis. Independent risk factors differed between sites. In Guangxi, being male and having a longer duration of IDU were independent risk factors for HIV infection; in Xinjiang, older age and sharing needles and/or syringes were independent factors; in Yunnan, more frequent drug injection, greater awareness of HIV transmission routes, and higher income were independent predictors of HIV seropositivity. Prevalence rates of HIV among IDUs in China are more than two out of three in some venues. Risk factors include longer duration of IDU and needle sharing. Also associated with HIV were factors that may indicate some success in education in higher risk persons, such as higher knowledge. A systemic community-level intervention with respect to evidenced-based, population-level interventions to stem the spread of HIV from IDU in China should include needle exchange, opiate agonist-based drug treatment, condom distribution along with promotion, and advocacy for community-based VCT with bridges to HIV preventive services and care. | 18,724,872 |
[mRNA expression levels of p53 and DNA damage and repair genes in peripheral blood lymphocytes of benzene-exposed workers]. | To investigate the relationship between the mRNA expression levels of p53-mediating DNA damage and repair genes in the peripheral blood lymphocytes of workers and their exposures to benzene in their working environment. The mRNA expression levels of p53 and related genes were determined by SYBR Green I chimeric fluorescence quantitative real-time RT-PCR analysis in peripheral blood lymphocytes of 72 workers, who were classified into group A (46 direct exposure to benzene) and group B (26 indirect exposure to benzene) based on their positions, and 29 controls. The differences of gene expression levels were analyzed by software REST 2005. Meanwhile, the peripheral blood leukocytes, hemoglobin and platelet of workers and controls were counted. Benzene content was measured in the samples of toluene, used as raw material, and spraying agents and benzene, toluene and xylene concentrations in the air of workplaces were monitored. There were no significant differences in the mRNA expression levels of p53, Ku80, Ape1 and Mdm-2 between group A or group B and control group (P > 0.05). The expression up-regulation of p21 mRNA was found, but without significant difference (P > 0.05). However, the mRNA expression levels of Rad51, Bcl-2, Bax, Xpa and Xpc in group A and Rad51 in group B were downregulated significantly (P < 0.05 or P < 0.01). Moreover, both the counts of white blood cell, hemoglobin and platelet in group A were (4.93 +/- 1.27) x 10(9)/L, (123.97 +/- 11.80) g/L and (124.02 +/- 41.22) x 10(9)/L respectively and platelet in group B (135.80 +/- 39.44) x 10(9)/L were significantly lower than in control group (P < 0.05 or P < 0.01). The mRNA expression levels of some p53-mediating DNA damage and repair genes are downregulated in the workers chronically exposed to low benzene concentration. The working environment impacts on health of group A workers are greater than the ones of group B. | 18,724,895 |
[Knowledge of and opinions on violence against women among health professionals in specialized care]. | The aim of this study was to evaluate knowledge of gender violence among health workers/medical staff in specialized healthcare and their opinions on the subject. A further aim was to identify the organizational barriers perceived by these workers and their proposals to enhance the early detection of this phenomenon and care of victims. We performed an observational, cross sectional study based on an anonymous survey of health workers/medical staff working in the pediatrics, obstetrics or emergency departments of two hospitals in health district 8 of Madrid. Overall, health professionals had average knowledge about gender violence. A total of 58.2% believed that physical abuse of women was associated with the lower social classes, while 72.8% believed that victims were uneducated women, housewives or foreigners; 67.6 % believed that aggressors were alcoholic, drug addicted or unemployed men. Almost all health professionals (97.7%) considered that gender violence against women was an important problem that usually went undetected. However, 66.7% did not include this phenomenon in the differential diagnosis of women with physical injuries. Notable among the organizational obstacles identified were workload, lack of training and information, and the absence of a protocol. Knowledge of gender violence among health professionals was average, with no significant differences between hospitals or among the three categories of staff surveyed. Stereotyped beliefs were found among health professionals who, nevertheless, believed they had an important role in detecting battered women. Reducing the organizational barriers detected could improve the care of these patients. | 18,724,913 |
A tale of too many centrosomes. | Having the correct number of centrosomes is crucial for proper chromosome segregation during cell division and for the prevention of aneuploidy, a hallmark of many cancer cells. Several recent studies (Basto et al., 2008; Kwon et al., 2008; Yang et al., 2008) reveal the importance of mechanisms that protect against the consequences of harboring too many centrosomes. | 18,724,931 |
Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies. | Posttranslational modification of proteins with polyubiquitin occurs in diverse signaling pathways and is tightly regulated to ensure cellular homeostasis. Studies employing ubiquitin mutants suggest that the fate of polyubiquitinated proteins is determined by which lysine within ubiquitin is linked to the C terminus of an adjacent ubiquitin. We have developed linkage-specific antibodies that recognize polyubiquitin chains joined through lysine 63 (K63) or 48 (K48). A cocrystal structure of an anti-K63 linkage Fab bound to K63-linked diubiquitin provides insight into the molecular basis for specificity. We use these antibodies to demonstrate that RIP1, which is essential for tumor necrosis factor-induced NF-kappaB activation, and IRAK1, which participates in signaling by interleukin-1beta and Toll-like receptors, both undergo polyubiquitin editing in stimulated cells. Both kinase adaptors initially acquire K63-linked polyubiquitin, while at later times K48-linked polyubiquitin targets them for proteasomal degradation. Polyubiquitin editing may therefore be a general mechanism for attenuating innate immune signaling. | 18,724,939 |
Computer screen photo-excited surface plasmon resonance imaging. | Angle and spectra resolved surface plasmon resonance (SPR) images of gold and silver thin films with protein deposits is demonstrated using a regular computer screen as light source and a web camera as detector. The screen provides multiple-angle illumination, p-polarized light and controlled spectral radiances to excite surface plasmons in a Kretchmann configuration. A model of the SPR reflectances incorporating the particularities of the source and detector explain the observed signals and the generation of distinctive SPR landscapes is demonstrated. The sensitivity and resolution of the method, determined in air and solution, are 0.145 nm pixel(-1), 0.523 nm, 5.13x10(-3) RIU degree(-1) and 6.014x10(-4) RIU, respectively, encouraging results at this proof of concept stage and considering the ubiquity of the instrumentation. | 18,724,996 |
Hospital mortality among adults admitted to and discharged from intensive care on weekends and evenings. | Patient care may be inconsistent during off hours. We sought to determine whether adults admitted to or discharged from intensive care units (ICUs) on evenings and weekends have increased mortality rates. All adults admitted to ICUs in the Calgary Health Region, Alberta, Canada, during 2000 to 2006 were included. The in-hospital mortality risk was assessed with admissions or discharges on weekdays (Monday to Friday) and daytime (8:00 am to 5:59 pm) as compared with weekends (Saturday and Sunday) and nights (6:00 pm to 7:59 am). Intensive care unit admissions (n = 20466) occurred during weekends in 18%, nights in 41%, and nights and/or weekends in 49%. Among the 17864 survivors to ICU discharge, 26% were discharged on weekends, 21% at night, and 41% on nights and/or weekends. Increased crude mortality rates were associated with both admission (24% vs 14%, P < .0001) and discharge (12% vs 5%, P < .0001) during nights as compared with days. Admission to (26% vs 16%, P < .0001) but not discharge from (6% vs 7%, P = .42) ICU during weekends as compared with weekdays was associated with increased mortality. After controlling for confounding variables using logistic regression analyses, neither weekend admission nor discharge was associated with death. However, both night admission and discharge were independently associated with mortality. Our observations of excess risk associated with admission to or discharge from ICU at night merits further exploration as to whether it may reflect inconsistencies in care after hours. | 18,725,035 |
Polymorphism of glutathione S-transferases as genetic risk factors for the development of complications in type 2 diabetes mellitus. | Diabetes is characterized by chronic hyperglycemia that produces dysregulation of cellular metabolism and result in excess free radical production and oxidative stress. Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that work as antioxidants. Therefore, diminished expression of GSTs may result in a reduced body defense against oxidative stress, followed by development of diabetic complications. To investigate the possible association between GSTM1 and GSTT1 polymorphism and the occurrence of complications in type 2 DM and to study the other risk factors for complications in DM. Twenty noncomplicated type 2 diabetic patients and 40 complicated type 2 diabetic patients were enrolled in the study. The GSTM1 and GSTT1 genotypes were identified by polymerase chain reaction of peripheral blood DNA samples. Analysis of data was done by using SPSS (SPSS, Chicago, Ill). The frequencies of null GSTM1 and GSTT1 genotypes were 55% (11/20) and 40% (8/20), respectively, in noncomplicated DM group. The frequencies of null GSTM1 and GSTT1 genotype in complicated DM group were 57.5% (23/40) and 60% (24/40), respectively. The null GSTT1 genotype was more prevalent in the group of complicated DM with odds ratio (odds ratio, 2.3; 95% confidence interval, 0.75-6.7) when compared with noncomplicated DM. Our data provide evidence that diabetics with null GSTT1 genotypes are substantially at higher risk for developing complications. | 18,725,054 |
Neural networks of several novel neuropeptides involved in feeding regulation. | Novel neuropeptides acting as G-protein-coupled receptor (GPCR) ligands are known to be localized in the brain and play a range of physiologic functions, one of which is feeding regulation. We describe the distribution and localization of these recently identified GPCR ligands and review their involvement in neuronal networks, particularly in feeding regulation. This review addresses aspects of some novel GPCR ligands, including feeding-regulating neuropeptides such as orexin, ghrelin, and galanin-like peptide and other known neuropeptides such as neuropeptide Y and pro-opiomelanocortin. These neuropeptides have been studied by our research group and others, particularly with regard to interactions in the hypothalamus of neurons containing these neuropeptides. In the hypothalamus, cross-talk among such neurons plays a key role in determining feeding states and feeding behavior. We describe some structural and functional characteristics of these neuropeptides and summarize the known interactions between the different kinds of feeding-regulating neurons and leptin-targeting neurons in the hypothalamus. Moreover, we present a new strategy for analyzing neural circuits involving these feeding-regulating GPCR ligands in the brain, with research in this field aided by the use of transgenic mouse models. We also present our recent results that involve aspects of feeding regulation, energy homeostasis, and body temperature regulation. Research in this field will serve the important role of clarifying neurologically based causes for appetite dysfunctions and diseases and may help in establishing new therapies for patients with such conditions. | 18,725,082 |
Clinical experience shows that catastrophic late effects associated with ablative fractionation can be avoided by technological innovation. | The development of high-precision radiation therapy delivery technology has expedited a burgeoning interest in ultrabrief, intensified treatment courses that yield tumoricidal effects of unprecedented potency. Whereas novel medical treatments that provide enhanced clinical benefits can be associated with escalated risks of toxicity, it is absolutely essential for radiation oncologists to exercise caution and discipline as these new strategies are evaluated and implemented in the clinic. However, it is argued here that clinical experiences reported to date already support the durable safety and efficacy of so-called "ablative" schedules of radiation therapy. Furthermore, until the cancer problem is solved once and for all, it is the obligation of the radiation oncology community to continue to pursue new means to improve on results of the past. | 18,725,107 |
Some cases of severe normal tissue toxicity can be anticipated with ablated fractionated radiation with appropriate long-term follow-up. | As new technologies have allowed physicians to both better image and characterize malignant disease as well as deliver radiation dose with high precision and accuracy, there has been a resurgence in interest in hypofractionated or even single-fraction radiation therapy schemas. Late-reacting tissues have a low alpha/beta ratio (compared with early reacting tissues) and are therefore more sensitive to increments in fraction size. When we hypofractionate, we may lose some of the biological advantages associated with fractionation while we may simultaneously increase our risk of damaging late-responding normal tissues. The ideal 4 R's for tumor cells are exactly opposite those 4 R's ideally desired for normal tissues, and this represents the major dilemma to the practicing radiation oncologist. The long-term safety profile for modern hypofractionated radiation schemes will depend on the area and volume treated, the total dose delivered, and the level of baseline function observed before initiating radiation therapy. These issues are raised in the context of hypofractionation for central nervous system malignancies, lung cancers, pelvic malignancies, head and neck cancers, and breast cancers. If we are careful when choosing the site (and most importantly the volume), it is likely that hypofractionation may benefit our patients. However, history has taught us to be very careful when using hypofractionation to large volumes or when incorporating critical structures. With appropriate long-term follow-up, some cases of severe normal tissue toxicity can be anticipated. Hypofractionation should continue to be studied in randomized clinical trials, with a particular focus on careful follow-up. | 18,725,108 |
The linear-quadratic model is an appropriate methodology for determining isoeffective doses at large doses per fraction. | The tool most commonly used for quantitative predictions of dose/fractionation dependencies in radiotherapy is the mechanistically based linear-quadratic (LQ) model. The LQ formalism is now almost universally used for calculating radiotherapeutic isoeffect doses for different fractionation/protraction schemes. In summary, the LQ model has the following useful properties for predicting isoeffect doses: (1) it is a mechanistic, biologically based model; (2) it has sufficiently few parameters to be practical; (3) most other mechanistic models of cell killing predict the same fractionation dependencies as does the LQ model; (4) it has well-documented predictive properties for fractionation/dose-rate effects in the laboratory; and (5) it is reasonably well validated, experimentally and theoretically, up to about 10 Gy/fraction and would be reasonable for use up to about 18 Gy per fraction. To date, there is no evidence of problems when the LQ model has been applied in the clinic. | 18,725,109 |
Use of an acellular regenerative tissue matrix in combination with vacuum-assisted closure therapy for treatment of a diabetic foot wound. | Diabetic foot ulcers can be difficult to treat for a variety of reasons, and may result in amputation. The use of skin grafts can often be a useful method of achieving wound coverage and subsequent healing of diabetic foot ulcers; however, this method of treatment requires creation of a donor site wound that adds to the patient's overall wound burden. Application of an acellular regenerative tissue matrix may eliminate the need for harvesting a skin graft in order to cover a nonhealing wound. The use of vacuum-assisted wound closure has been shown to promote an environment that enhances wound bed contraction and surface epithelialization. The combination of an acellular regenerative tissue matrix with vacuum-assisted wound closure can be used to promote healing in the management of a nonhealing diabetic foot wound. x. | 18,725,123 |
Radiographic evaluation of endoscopic gastrocnemius recession, subtalar joint arthroereisis, and flexor tendon transfer for surgical correction of stage II posterior tibial tendon dysfunction: a pilot study. | The best procedure for surgical correction of stage II posterior tibial tendon dysfunction has long been a source of debate among foot and ankle surgeons. A combination of endoscopic gastrocnemius recession, subtalar joint arthroereisis, and flexor digitorum longus tendon transfer has been used in an attempt to avoid some of the complications seen with calcaneal osteotomies, and to allow an earlier return to function and weight bearing. A retrospective analysis of preoperative and postoperative radiographic changes in 10 patients for whom surgical correction of the deformity was performed between 2003 and 2006 is presented as a pilot study. Seven radiographic variables considered standard for the radiographic assessment of posterior tibial tendon dysfunction were measured. The outcome measure of interest was the return of radiographic variables to normal ranges following surgical correction of the deformity. In addition, preoperative and postoperative clinical outcomes were assessed to evaluate the long-term clinical benefits of this trio of procedures. Radiographic values were noted to return to normal ranges in all cases following this trio of surgical procedures; these changes were statistically significant (P < or = .05). These preliminary results suggest that this surgical combination provides satisfactory correction of deformity in patients presenting with stage II posterior tibial tendon dysfunction. 4. | 18,725,119 |
Correction of severe foot and ankle contracture due to CRPS using external fixation and pain management: report of a pediatric case. | Complex regional pain syndrome-induced dystonia is a severe deformity that can affect the lower extremities and hinder ambulation. Although a number of conservative treatments have been described for this condition, we are not aware of any publications describing the use of surgical intervention for the treatment of this condition. In this report, we describe the case of a pediatric patient with a severe lower extremity deformity in conjunction with chronic pain syndrome. A concerted, interdisciplinary treatment approach was undertaken for the management of this patient, and this included contributions from a foot and ankle surgeon, a pain specialist, an internist, a physical therapist, and a psychiatrist. The primary goal of the treatment strategy was to recreate a plantigrade, weight-bearing lower extremity, while controlling pain. To this end, gradual correction of deformity was achieved using an external fixator and, by 6 months after the surgery, the patient was for the first time in years ambulating on the realigned lower extremity. After 3 years of follow-up, she maintained an activity level that was equal to that which she enjoyed before the injury. 4. | 18,725,124 |
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