3beta-Hydroxysteroid dehydrogenase in human aorta.
3beta-Hydroxysteroid dehydrogenase (3beta-HSD) is known to be involved in steroid production and/or metabolism and to be expressed in many tissues including adrenal cortex. Expression of this enzyme has also been elucidated in human cardiovascular system but its details remain largely unknown. Therefore, in this study, we examined the status of 3beta-HSD in postmortem human aorta utilizing RT-PCR and immunohistochemical analysis. Both mRNAs and immunoreactivity for the enzyme were detected predominantly in female aorta, and in those with mild atherosclerotic changes. In addition, immunohistochemical study demonstrated that immunoreactivity for 3beta-HSD was detected in vascular smooth muscle cells (VSMCs) of aorta. These findings all indicated that steroidogenesis via 3beta-HSD may occur in VSMCs of human aorta, possibly related to gender differences and/or the degree of atherosclerosis.


Australopithecus afarensis endocasts suggest ape-like brain organization and prolonged brain growth.
Human brains are three times larger, are organized differently, and mature for a longer period of time than those of our closest living relatives, the chimpanzees. Together, these characteristics are important for human cognition and social behavior, but their evolutionary origins remain unclear. To study brain growth and organization in the hominin species Australopithecus afarensis more than 3 million years ago, we scanned eight fossil crania using conventional and synchrotron computed tomography. We inferred key features of brain organization from endocranial imprints and explored the pattern of brain growth by combining new endocranial volume estimates with narrow age at death estimates for two infants. Contrary to previous claims, sulcal imprints reveal an ape-like brain organization and no features derived toward humans. A comparison of infant to adult endocranial volumes indicates protracted brain growth in A. afarensis, likely critical for the evolution of a long period of childhood learning in hominins.


Simple synthesis of conformationally fixed glycosamine analogues by beckmann rearrangement at the carbohydrate ring.
Conformationally fixed carbohydrate analogues are promising small-molecule inhibitors for hydrolases like O-GlcNAcase (OGA); however, their synthesis usually requires many steps. Herein we describe cycloadditions of dichloroketene to various glycals and subsequent Beckmann rearrangements, which offer an easy and stereoselective entry to glycosamine derivatives in good yields. The reactions are applicable for hexoses, pentoses, and disaccharides, and transformations to the corresponding imidates proceed smoothly. First biological tests reveal that such imidates indeed inhibit human OGA.


A Novel Role for the Endocannabinoid System in Ameliorating Motivation for Alcohol Drinking and Negative Behavioral Affect after Traumatic Brain Injury in Rats.
Traumatic brain injury (TBI) is associated with psychiatric dysfunction-including pain, cognitive impairment, anxiety, and increased alcohol use. We previously demonstrated that inhibiting endocannabinoid degradation post-TBI with JZL184 attenuates neuroinflammation and neuronal hyperexcitability at the site of injury and improves neurobehavioral recovery. This study aimed to determine the effect of JZL184 on post-TBI behavioral changes related to psychiatric dysfunction and post-TBI neuroadaptations in brain regions associated with these behaviors. We hypothesized that JZL184 would attenuate post-TBI behavioral and neural changes in alcohol-drinking rats. Adult male Wistar rats were trained to operantly self-administer alcohol before receiving lateral fluid percussion injury. Thirty minutes post-TBI, rats received JZL184 (16 mg/kg, i.p.) or vehicle. Spatial memory (Y-maze), anxiety-like behavior (open field), alcohol motivation (progressive ratio responding), and mechanosensitivity (Von Frey) were measured 3-10 days post-injury, and ventral striatum (VS) and central amygdala (CeA) tissue were collected for western blot analysis of phosphorylated glutamate receptor subunit 1 (GluR1) and glucocorticoid receptor (GR). TBI impaired spatial memory, increased anxiety-like behavior, and increased motivated alcohol drinking. JZL184 prevented these changes. TBI also increased phosphorylated GluR1 and GR in the CeA (but not the VS) compared with sham controls. JZL184 attenuated post-TBI GR phosphorylation in the CeA. These findings suggest that TBI produces comorbid cognitive dysfunction, increased alcohol motivation, and anxiety-like behavior, possibly related to amygdala dysfunction, and these changes are prevented by systemic post-TBI endocannabinoid degradation inhibition. Thus, boosting endocannabinoid tone post-TBI may represent a viable therapeutic strategy for TBI-related psychiatric comorbidities such as alcohol use disorder and anxiety.


Müller Glia Are a Major Cellular Source of Survival Signals for Retinal Neurons in Diabetes.
To dissect the role of vascular endothelial growth factor receptor-2 (VEGFR2) in Müller cells and its effect on neuroprotection in diabetic retinopathy (DR), we disrupted VEGFR2 in mouse Müller glia and determined its effect on Müller cell survival, neuronal integrity, and trophic factor production in diabetic retinas. Diabetes was induced with streptozotocin. Retinal function was measured with electroretinography. Müller cell and neuronal densities were assessed with morphometric and immunohistochemical analyses. Loss of VEGFR2 caused a gradual reduction in Müller glial density, which reached to a significant level 10 months after the onset of diabetes. This observation was accompanied by an age-dependent decrease of scotopic and photopic electroretinography amplitudes and accelerated loss of rod and cone photoreceptors, ganglion cell layer cells, and inner nuclear layer neurons and by a significant reduction of retinal glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor. Our results suggest that VEGFR2-mediated Müller cell survival is required for the viability of retinal neurons in diabetes. The genetically altered mice established in this study can be used as a diabetic animal model of nontoxin-induced Müller cell ablation, which will be useful for exploring the cellular mechanisms of neuronal alteration in DR.


The significance of combined OSTA, HU value and VBQ score in osteoporosis screening before spinal surgery.
This study aimed to assess the utility of a combined assessment using the Osteoporosis Self-Assessment Tool for Asians (OSTA), Hounsfield unit (HU) value, and vertebral bone quality (VBQ) score for preoperative osteoporosis (OP) screening in patients scheduled for spinal surgery. This study encompassed 288 participants, including 128 males and 160 females. Patients were stratified into two groups: the OP group (T-score ≤ -2.5) and the non-OP group (T-score > -2.5), determined by dual-energy X-ray absorptiometry (DEXA). Binary logistic regression was used to construct a combined diagnostic model, and the receiver operating characteristic (ROC) curve evaluated the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these metrics individually or in combination to screen for OP. Osteoporosis patients exhibited significantly lower OSTA and HU values in comparison to non-OP patients, while their VBQ scores were significantly higher (P < 0.001). The ROC curve analysis results indicated that within the male group, the combined diagnosis had a sensitivity of 93.8%, specificity of 82.3%, accuracy of 85.2%, PPV of 63.8%, and NPV of 97.5%. In the female group, the combined diagnosis had a sensitivity of 93.9%, specificity of 87.4%, accuracy of 90.0%, PPV of 83.6%, and NPV of 95.4%. The combined use of OSTA, HU values, and VBQ scores in preoperative OP screening for spinal surgery demonstrates significantly higher accuracy and superior screening value compared to individual assessments. These results establish a robust scientific foundation for conducting preoperative OP screening in patients undergoing spinal surgery.


Holographically controlled three-dimensional atomic population patterns.
The interaction of spatially structured light fields with atomic media can generate spatial structures inscribed in the atomic populations and coherences, allowing for example the storage of optical images in atomic vapours. Typically, this involves coherent optical processes based on Raman or EIT transitions. Here we study the simpler situation of shaping atomic populations via spatially dependent optical depletion. Using a near resonant laser beam with a holographically controlled 3D intensity profile, we imprint 3D population structures into a thermal rubidium vapour. This 3D population structure is simultaneously read out by recording the spatially resolved fluorescence of an unshaped probe laser. We find that the reconstructed atomic population structure is largely complementary to the intensity structure of the control beam, however appears blurred due to global repopulation processes. We identify and model these mechanisms which limit the achievable resolution of the 3D atomic population. We expect this work to set design criteria for future 2D and 3D atomic memories.


Rapid changes occur in the percentage of circulating bovine WC1(+)gamma delta Th1 cells.
gamma delta T cells found in the peripheral blood of cattle include a major subpopulation distinguished by expression of WC1. These cells are distinct from the WC1(-)gamma delta T cell population based on T cell receptor gene usage. We documented that a group of 6-month-old calves allowed free-range grazing and access to their mothers had a significantly greater proportion of total gamma delta T cells in their blood, attributable to the WC1(+)gamma delta T cell subpopulation, compared to age and breed-matched calves held in conventional housing. When the animals with the greater proportion of gamma delta T cells were transferred to conventional housing there was a decrease in the WC1(+)population so that by 3 weeks after transfer there was no longer a significant difference between the two groups. To investigate the biological activities of WC1(+)gamma delta T cells, the cells were purified by flow cytometric sorting. In vitro, they responded to stimulation by irradiated monocytes in autologous mixed leukocyte reaction (AMLR) cultures but not to direct stimulation through the T cell receptor (T c R) by anti-delta monoclonal antibody. After stimulation in the AMLR, WC1(+)gamma delta T cells had a Th1 cytokine profile characterised by production of IFN -gamma and lack of IL -4. Thus we propose that higher levels of the WC1(+)gamma delta T cells may provide calves with a mechanism to produce Th1 cytokines and that the level of these cells may be modulated according to environment or stress since both groups of calves were apparently disease-free.


Erythrocytes and proinflammatory mediators in wound drainage.
Retransfusion of shed blood collected after operation has become popular, but recent reports of side effects led to a search for possible causes. In a randomized study of 28 patients undergoing total hip arthroplasty, shed blood was collected in Solcotrans, Orth-Evac, and ordinary Redon drainage. Osmotic fragility was measured and electron-microscopic pictures of erythrocytes from selective samples were taken. Serotonin, prostaglandin E2 (PGE2), and histamine were measured with enzyme-linked immunosorbent assays. Higher osmotic fragility of erythrocytes collected with Solcotrans appeared to be due to ACD which was used only with that system. Serotonin concentrations did not differ significantly. However, there was a great increase in histamine (Solcotrans 477.7, Orth-Evac 344.0, Redon drainage 453.1 nmol/ml) and PGE2 (Solcotrans 1,908.3, Orth-Evac 1,225.0, Redon drainage 2,666.7 microgram/ml) in shed blood compared with venous blood (histamine 9.5 nmol/l, PGE2 4.2 microgram/ml). Unwashed wound drainage blood collected after operation contains levels of proinflammatory mediators that can account for the reported side effects.


Nontraumatic disorders of the clavicle.
Other than those resulting from trauma and arthritis, disorders of the clavicle are uncommon. Some nontraumatic disorders are found only in infancy and childhood, such as birth fracture, infantile cortical hyperostosis, congenital pseudarthrosis, cleidocranial dysplasia, and short clavicle syndrome. Other nontraumatic disorders occur in both children and adults; these include anterior subluxation of the sternoclavicular joint, Friedrich's disease, hypertrophic osteitis, chronic multifocal periosteitis and arthropathy, and osteomyelitis. Some nontraumatic clavicular disorders are found only in adults, such as distal osteolysis. Because the description and nomenclature of these disorders arise from several medical disciplines, they often are confusing. Until clear, distinguishing features are described, it is advisable to combine some of the entities. This is especially true of the nonsuppurative inflammatory disorders of the clavicle, which appear to fall under the heading of spondyloarthropathy. Treatment varies by disorder and may include symptomatic and expectant management, drug therapy, and nonsurgical or surgical treatment.


Daily high-dose aspirin does not lower APRI in the Aspirin-Myocardial Infarction Study.
Antiplatelet agents reduce liver fibrosis by inhibiting platelet activation and platelet-derived growth factor production. Previous cross-sectional epidemiological studies suggest that the use of aspirin is related to reduced liver fibrosis. The Aspirin-Myocardial Infarction Study (AMIS) aims to examine this relationship in a multicenter, randomized, double-blind and placebo-controlled trial. The existing clinical trial of aspirin was conducted to study the benefit of one gram aspirin daily among 4 524 individuals who had experienced at least one documented myocardial infarction. The aspartate aminotransferase (AST)-to-Platelet Ratio Index (APRI) was calculated at baseline and annually from the platelet count and AST levels. Participants in the AMIS trial had a mean baseline APRI of 0.34±0.36, and only 1% individuals had APRI scores higher than 1.0, a common cutoff for cirrhosis. The daily use of aspirin was associated with an increase, rather than a reduction of APRI, by 0.007 per year (95% CI 0.002-0.015, P=0.12). The use of aspirin did not significantly affect platelet counts. In a sensitivity analysis of individuals with probable significant fibrosis at baseline (APRI≥0.7), the aspirin group had a sustained reduction in APRI over time, although this change was not significant compared to that in the placebo group. In the AMIS trial, the daily use of high-dose aspirin did not significantly affect APRI, a surrogate index of liver fibrosis. This study highlights the need for de novo clinical trials to investigate the potential benefit of antiplatelet agents on liver fibrosis.


Specialty medications: traditional and novel tools can address rising spending on these costly drugs.
Spending on specialty medications, which represented a small proportion of US pharmacy spending at the beginning of this decade, is growing by more than 15 percent annually. It is expected to account for approximately half ($235 billion) of total annual pharmacy spending by 2018. Among the numerous reasons for the high cost of this heterogeneous group of medications are the increasing size of target patient populations, the high cost of drug development, and a complex and uncoordinated delivery system. In this article we describe the evolution of the specialty market, characterize the current state of specialty medication use, and articulate key challenges and potential solutions. Fully realizing the potential value of the expanding universe of specialty medications will require collaborative efforts to reduce waste and promote value. Those who prescribe, dispense, deliver, and pay for specialty medications will need to employ a combination of traditional and novel management approaches, such as prior authorization, step therapy, tiered formularies, administration at lower-cost sites, and the unique tools being developed for cancer medications.


Rifabutin pharmacokinetics and safety among TB/HIV-coinfected children receiving lopinavir/ritonavir-containing second-line ART.
Treatment options are limited for TB/HIV-coinfected children who require PI-based ART. Rifabutin is the preferred rifamycin for adults on PIs, but the one study evaluating rifabutin with PIs among children was stopped early due to severe neutropenia. We evaluated rifabutin safety and plasma pharmacokinetics among coinfected children 3-15 years of age receiving rifabutin 2.5 mg/kg daily with standard doses of lopinavir/ritonavir. The AUC0-24 at 2, 4 and 8 weeks after rifabutin initiation was described using intensive sampling and non-compartmental analysis. Clinical and laboratory toxicities were intensively monitored at 12 visits throughout the study. Among 15 children with median (IQR) age 13.1 (10.9-14.0) years and weight 25.5 (22.3-30.5) kg, the median (IQR) rifabutin AUC0-24 was 5.21 (4.38-6.60) μg·h/mL. Four participants had AUC0-24 below 3.8 μg·h/mL (a target for the population average exposure) at week 2 and all had AUC0-24 higher than 3.8 μg·h/mL at the 4 and 8 week visits. Of 506 laboratory evaluations during rifabutin, grade 3 and grade 4 abnormalities occurred in 16 (3%) and 2 (0.4%) instances, respectively, involving 9 (60%) children. Specifically, grade 3 (n = 4) and grade 4 (n = 1) neutropenia resolved without treatment interruption or clinical sequelae in all patients. One child died at week 4 of HIV-related complications. In children, rifabutin 2.5 mg/kg daily achieved AUC0-24 comparable to adults and favourable HIV and TB treatment outcomes were observed. Severe neutropenia was relatively uncommon and improved with ongoing rifabutin therapy. These data support the use of rifabutin for TB/HIV-coinfected children who require lopinavir/ritonavir.


Timing Effect on Training-Session Rating of Perceived Exertion in Top-Class Soccer Referees.
To examine the effect of recall timing on training-session rating of perceived exertion (sRPE) in a population of athletes well familiarized with the method and procedures during a 5-d training microcycle. Fifty-one top-class field referees (FRs) (age 38.4 ± 3.3 y, height 181 ± 5.6 cm, body mass 76.8 ± 6.8 kg, body-mass index 23.4 ± 1.7 kg/m2, body fat 20.4% ± 3.6%, international refereeing experience 5 ± 3.5 y) from 43 national football associations worldwide, preselected by the FIFA refereeing department for officiating during the FIFA World Cup 2014 Brazil, volunteered for this study. The FRs were randomly allocated into 3 assessment groups (n = 17 each), defined according to the timing of the sRPE, ie, immediately at the end of or 30 min or 7 h after the training sessions' end. The CR10 Borg scale was used to rate the training sessions (n = 5). All FRs again rated each training session of the 5-d training microcycle on the next morning (~20 h after) for confirmation (absolute and relative reliability). No significant timing effect was found between or within groups. Relative reliability ranged from large to very large with trivial within- and between-groups differences. This study showed no effect of recall timing on postexercise RPE when well-familiarized athletes are submitted to training during a weekly microcycle. Posttraining RPE was reported to be a reliable subjective measure; however, specific timing is advisable to reduce difference in RPE values.


Prediction of drinking outcomes for male alcoholics after 10 to 14 years.
This study reports on the long-term outcomes of 360 men who were hospitalized for alcoholism during 1980 to 1984 and followed at 12 months and again 10 to 14 years later. At the 10/14-year follow-up, 96 (26.7%) men were confirmed as deceased; 255 (70.8%) men participated in the assessment/interview battery completed during baseline hospitalization. The battery consisted of psychosocial, alcohol-related, and psychiatric measures. Two distinct but highly correlated outcome measures were selected: a clinical rating scale and a factor score. Overall, predictors from baseline and 12-month follow-up included age at intake hospitalization, alcoholism severity, social stability, drinking days, and antisocial personality disorder. Approximately 37% of the assessed survivors were either totally abstinent or drinking nonabusively throughout the 10/14-year follow-up, whereas another 37% continued to drink abusively. Men who abstained or reduced alcohol intake reported better physical health at follow-up than those who continued to drink. Although our findings did not directly link alcoholism to death, they strongly indicate that chronic alcohol abuse may lead to premature death.


Disjunct performance and distribution in the sedge Carex prasina.
Efforts to understand species distributions and predict responses to environmental changes depend on specifying how the abiotic environment determines distributions. At landscape scales, it is critical to distinguish effects of environmental factors from other mechanisms such as competition and dispersal limitation. We examined how environmental factors affect the distribution and performance of the sedge Carex prasina across a 10-km(2) old-growth forest in southern Québec. We isolated the effects of soil characteristics by conducting a greenhouse experiment that assessed the performance of C. prasina on soils from a range of wetland habitats where it could potentially occur. This allowed us to compare how the species' performance and its distribution across the landscape relate to the same soil characteristics. In the experiment, the biomass and leaf chlorophyll content of C. prasina increased with increasing soil organic matter (OM). Across the landscape, however, the species' probability of occurrence and abundance decreased with increasing soil OM. C. prasina had similar biomass on soils from sites where it did and did not occur, but it had higher leaf chlorophyll content on soils from sites where it did not occur. We found no evidence that differential performance across environments determines the distribution of this species, as C. prasina tended to occur on soils where it showed reduced performance. Rather, other processes such as competition or dispersal limitation likely override any direct effects of the soil environment on distribution. Our results caution against the common assumption that the environments where a species tends to occur or be most abundant are the environments where it performs best. C. prasina presents a clear example of a species whose performance, at least along edaphic gradients, cannot explain its distribution. This example highlights the importance of distinguishing the relative roles of biotic and abiotic factors that shape species distributions across landscapes.


Comparison of cellular proliferation on dense and porous PCL scaffolds.
In this contribution, PCL (poly-epsilon caprolactone) scaffolds were prepared by solvent-casting/particle-leaching technique in the presence of two pore formers, PEG(4000) or sucrose molecules in different quantities (0, 10, 20, 30, 40, 50, 55 w/w% PEG(4000)/PCL; 10, 20 w/w% Sucrose/PCL). The surface and bulk properties of the resulting scaffolds were studied by SEM, DSC and FTIR. SEM photographs showed that, macroporosity was obtained in the PCL structures prepared with sucrose crystals while microporous structure was obtained in the presence of PEG(4000) molecules. Average pore diameters calculated from SEM photographs were 40.1 and 191.2 mum for 40% PEG(4000)/PCL and 10% Sucrose/PCL scaffolds, respectively. The DSC and FTIR results confirmed that there is no any interaction between pore formers and PCL during structural formation, and both pore formers, PEG(4000) and sucrose, remained independently in the scaffolds. L929 mouse fibroblast cells were seeded onto PCL structures and maintained during 7 days to evaluate cell proliferation. Cell culture results showed that, 10% Sucrose/PCL scaffold was the most promising substrate for L929 cell growth due to 3-D architecture and macroporous structure of the scaffold.


Genome wide expression profiling of two accession of G. herbaceum L. in response to drought.
Genome-wide gene expression profiling and detailed physiological investigation were used for understanding the molecular mechanism and physiological response of Gossypium herbaceum, which governs the adaptability of plants in drought conditions. Recently, microarray-based gene expression analysis is commonly used to decipher genes and genetic networks controlling the traits of interest. However, the results of such an analysis are often plagued due to a limited number of genes (probe sets) on microarrays. On the other hand, pyrosequencing of a transcriptome has the potential to detect rare as well as a large number of transcripts in the samples quantitatively. We used Affymetrix microarray as well as Roche's GS-FLX transcriptome sequencing for a comparative analysis of cotton transcriptome in leaf tissues under drought conditions. Fourteen accessions of Gossypium herbaceum were subjected to mannitol stress for preliminary screening; two accessions, namely Vagad and RAHS-14, were selected as being the most tolerant and most sensitive to osmotic stress, respectively. Affymetrix cotton arrays containing 24,045 probe sets and Roche's GS-FLX transcriptome sequencing of leaf tissue were used to analyze the gene expression profiling of Vagad and RAHS-14 under drought conditions. The analysis of physiological measurements and gene expression profiling showed that Vagad has the inherent ability to sense drought at a much earlier stage and to respond to it in a much more efficient manner than does RAHS-14. Gene Ontology (GO) studies showed that the phenyl propanoid pathway, pigment biosynthesis, polyketide biosynthesis, and other secondary metabolite pathways were enriched in Vagad under control and drought conditions as compared with RAHS-14. Similarly, GO analysis of transcriptome sequencing showed that the GO terms responses to various abiotic stresses were significantly higher in Vagad. Among the classes of transcription factors (TFs) uniquely expressed in both accessions, RAHS-14 showed the expression of ERF and WRKY families. The unique expression of ERFs in response to drought conditions reveals that RAHS-14 responds to drought by inducing senescence. This was further supported by transcriptome analysis which revealed that RAHS-14 responds to drought by inducing many transcripts related to senescence and cell death. The comparative genome-wide gene expression profiling study of two accessions of G.herbaceum under drought stress deciphers the differential patterns of gene expression, including TFs and physiologically relevant processes. Our results indicate that drought tolerance observed in Vagad is not because of a single molecular reason but is rather due to several unique mechanisms which Vagad has developed as an adaptation strategy.


A novel intact circular dsDNA supercoil.
A novel intact circular dsDNA supercoil is proposed as an alternative to the conventional DNA supercoil, so that the two complementary strands of ssDNA circles are separable without any covalent bond breakage. This new structure can be visualized by using two tubings: one black and one clear. Twist the black tubing a number of times and connect its two ends. Do the same for the clear tubing. Then wrap the two tubings together. This forms the separable or novel supercoil. On the other hand, the conventional supercoil can be modeled by twisting the black and clear tubings together and then connect their respective ends, so that the two tubings are not separable unless one of them is cut. Experimentally, in the absence of any enzyme, many intact plasmid dsDNA circles give two bands on agarose gel electrophoresis under a certain given condition, while the same plasmid molecules after cutting once by a restriction enzyme give only one band under the same condition. In the case of intact pUC19 plasmids, these two bands can then be recovered and sequenced separately, using two primers in opposite directions. Each band gives mostly one sequence which is complementary to that of the other band. The combination of the above theoretical model and experimental results strongly suggests that there is an alternative structure of DNA which does not have the usual difficulty of unwinding, rewinding and requiring numerous covalent bond breakages and ligations during semiconservative.


IDH1/2 mutation is a prognostic marker for survival and predicts response to chemotherapy for grade II gliomas concomitantly treated with radiation therapy.
Reliable prognostic biomarkers of grade II gliomas remain unclear. This study aimed to examine the role of mutations of isocitrate dehydrogenase (IDH1/2), 1p/19q co-deletion, and clinicopathological factors in patients with grade II glioma who were primarily treated with radiotherapy or chemoradiotherapy after surgery. Seventy-two consecutive patients, including 49 cases of diffuse astrocytomas (DA), 4 oligodendrogliomas (OL) and 19 oligoastrocytomas (OA), who underwent treatment from 1991 to 2010 at a single institution were examined. The overall survival (OS) of the DA patients (8.3 years) was significantly shorter than that of the OL and OA patients (11.7 years). IDH1/2 mutations were found in 46.9% of the DA patients and 82.6% of the OL and OA patients. The progression-free survival (PFS) and OS of the patients with IDH1/2 mutations (8.4 and 16.3 years) were significantly longer than those of the patients without IDH1/2 mutations (3.3 and 4.5 years). Among the patients with IDH1/2 mutations, those who were initially treated with chemoradiotherapy including nimustine hydrochloride (ACNU), had significantly longer PFS than those treated with radiotherapy alone, whereas no significant difference in PFS was observed between the chemoradiotherapy and radiotherapy groups in the patients without IDH1/2 mutations. Oligodendroglial tumors, age <40 years, initial Karnofsky performance status (KPS) ≥80, and IDH1/2 mutations were favorable prognostic factors regarding PFS and OS. IDH1/2 mutation was a predictive factor of response to chemoradiotherapy in grade II gliomas. Patients with IDH1/2 mutations may benefit more from chemoraiotherapy than those without IDH1/2 mutations.


Molecular diagnostics in follicular non-Hodgkin's lymphoma: a review.
Follicular lymphoma is a low-grade, indolent non-Hodgkin's lymphoma characterized by the presence of the t(14;18) translocation. The detection of this translocation using polymerase chain reaction techniques has been increasingly studied. However, the diagnostic and prognostic value of detecting t(14;18) rearrangements has been questioned. Translocation has been identified in a significant proportion of healthy donors and patients with nonmalignant diseases. Clearance of t(14;18) rearrangements following conventional treatments, purging of bone marrow/peripheral blood stem cells, and transplantation is associated with improved long-term outcome of patients with follicular lymphoma. Until randomized studies confirm the clinical utility of polymerase chain reaction detection of the translocation, emphasis should be placed on improving the accuracy and reproducibility of polymerase chain reaction techniques, and standardizing assays among laboratories.


Porphyria cutanea tarda associated with disinfectant misuse.
Porphyria cutanea tarda was detected in a 44-year-old janitress. The illness was probably caused by the unintentional synthesis of a polychlorinated phenol as a result of mixing commonly available household ingredients in toilet bowls and shower stalls. Although the evidence for this hypothesis is circumstantial, its likelihood and the wide-spread household use of these reagents justify calling attention to the innovative misuse of disinfectants as a potential source of toxic exposure.


Bone Bruise and Anterior Cruciate Ligament Tears: Presence, Distribution Pattern, and Associated Lesions in the Pediatric Population.
Bone bruise characteristics after anterior cruciate ligament (ACL) injury have been correlated with the level of joint derangement in adults. However, the literature lacks information about younger patients, whose higher ligamentous laxity may lead to different lesion patterns. To investigate the prevalence, size, location, and role of bone bruise associated with ACL rupture in the pediatric population. Cross-sectional study; Level of evidence, 3. Knee magnetic resonance imaging scans (MRIs) of patients aged 8 to 16 years with ACL tears from 2010 to 2018 were selected from the institution database. Inclusion criteria were open or partially open physes, less than 90 days between trauma and MRI, and no history of injury or surgery. Presence, localization, and size of bone bruise were analyzed by 2 blinded researchers and scored with the Whole-Organ Magnetic Resonance Imaging Score (WORMS) bone bruise subscale. Ligamentous, cartilaginous, meniscal, and other lesions were documented. Of the 78 pediatric patients selected from the database, 54 (69%) had bone bruise. The mean area of bone bruise was larger in males than in females (femur, 3.8 ± 2.8 vs 2.2 ± 1.4 cm2, respectively, P = .006; tibia, 2.6 ± 1.6 vs 1.5 ± 0.8 cm2, respectively, P = .007). The subregions most affected by bone bruise were the lateral posterior tibia and the lateral central femur (in 83% and 80% of the knees affected, respectively). A low correlation was found between age and bone bruise area (biggest areas r = 0.30, P = .03, and sum of areas r = 0.27, P = .04), but no correlation was found between age and WORMS (femur, r = -0.03, P = .85; tibia, r = -0.04, P = .76). The injuries most associated with bone bruise were 23 meniscal lesions (43%), 10 lesions of other ligaments (19.0%), 2 cartilage lesions (3.7%), and 2 patellar fractures (3.7%). The prevalence of bone bruises in pediatric patients with ACL tears is high, although it seems slightly lower than the prevalence documented in adults but with similar localization. The area and the distribution pattern of bone bruises are similar among different ages. The pediatric patients had a lower presence of cartilage and meniscal lesions compared with that reported in adults, which suggests a different effect of this trauma on the knee of pediatric patients.


p53 and mitogen-activated protein kinase pathway protein profiles in fresh and frozen spermatozoa.
Sperm or testicular tissue cryopreservation is performed in cases of male infertility as a treatment for the preservation of fertility. When these sperm cells are used in assisted reproductive techniques, fertilisation rates, developmental and implantation potential of embryos decrease and the abortion rates increase. In the present work, differences of both phosphorylation and expression levels of p53 and Mitogen-activated protein kinases (MAPK) proteins were analysed in 61 individual sperm samples before and after cryopreservation. We observed that p53 protein residue at Ser 15 was phosphorylated after cryopreservation. Because MAPK pathway activations may be involved in p53 phosphorylation, MAPK/ERK, Stress-activated protein kinases (SAPK)/JNK and p38MAPK proteins were also investigated. Analysis showed that p38MAPK phosphorylations increased significantly. However, ERK and JNK expressions and phosphorylations decreased, although the differences were not statistically significant. According to our results, it may be suggested that cryopreservation process activates p53 via p38 MAPK pathway that subsequently causes apoptosis, which may be related to sperm parameters.


Phase-contrast microscopy at high x-ray energy with a laboratory setup.
We report on the design and realization of an x-ray imaging system for quantitative phase-contrast microscopy at high x-ray energy with laboratory-scale instrumentation. Phase and amplitude were separated quantitatively at x-ray energies up to 80 keV with micrometric spatial resolution. The accuracy of the results was tested against numerical simulations, and the spatial resolution was experimentally quantified by measuring a Siemens star phase object. This simple setup should find broad application in those areas of x-ray imaging where high energy and spatial resolution are simultaneously required and in those difficult cases where the sample contains materials with similar x-ray absorption.


Enhanced antitumor activity of combination radioimmunotherapy (131I-labeled monoclonal antibody A33) with chemotherapy (fluorouracil).
Monoclonal antibody (mAb) A33 reacts with an antigen expressed by >95% of colon cancer and normal colon epithelial cells. An earlier Phase I trial of 131I-labeled mAb A33 (131I-mAb A33) demonstrated bone marrow suppression as the dose-limiting toxicity, and although modest antitumor effects were seen, no normal colon toxicity was observed. In this study, a nude mouse model was used to test whether combinations of low-dose 131I-mAb A33 (0.1 mCi) and chemotherapy [5-fluorouracil (5-FU) or 5-FU + leucovorin, doxorubicin, or carmustine] enhance the antitumor effects, compared to 131I-mAb A33 alone or either drug regimen alone. 5-FU was administered either at 30 mg/kg/day for 5 days or at 75 mg/kg/day on days 1 and 5. In assessing the reduction in tumor volumes over the first 28 days of the experiment, 5-FU treatment (with or without leucovorin) in combination with 131I-mAb A33 showed a statistically significant additive antitumor effect compared to 131I-mAb A33 alone or to chemotherapy alone. When long-term survival was used as an end point, 38% of the mice treated with 5-FU and 131I-mAb A33 were disease free at 276 days compared to none from any other group, suggesting a synergistic effect. These data indicate that Phase II clinical trials combining radiolabeled antibody therapy with 5-FU-based treatments are warranted.


The NLRP3-Inflammasome-Caspase-1 Pathway Is Upregulated in Idiopathic Pulmonary Fibrosis and Acute Exacerbations and Is Inducible by Apoptotic A549 Cells.
Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease harboring significant morbidity and mortality despite recent advances in therapy. Regardless of disease severity acute exacerbations (IPF-AEs) may occur leading to considerable loss of function and are the leading cause of death in IPF. Histologic features of IPF-AE are very similar to acute respiratory distress syndrome (ARDS), but the underlying mechanisms are incompletely understood. We investigated the role of the NLRP3 inflammasome in IPF and IPF-AE. Bronchoalveolar lavage (BAL) cells were sampled from patients with IPF (n = 32), IPF-AE (n = 10), ARDS (n = 7) and healthy volunteers (HV, n = 37) and the NLRP3-inflammasome was stimulated in-vitro. We found the NLRP3 inflammasome to be hyper-inducible in IPF compared to HV with increased IL-1ß and pro-IL-1ß levels on ELISA upon stimulation as well as increased caspase-1 activity measured by caspase-1p20 immunoblotting. In IPF-AE, IL-1ß was massively elevated to an extent similar to ARDS. To evaluate potential mechanisms, we co-cultured BAL cells with radiated A549 cells (a model to simulate apoptotic alveolar epithelial cells), which led to increased NLRP3 mRNA expression and increased caspase-1 dependent IL-1ß production. In the presence of a reactive oxygen species (ROS) inhibitor (diphenyleneiodonium) and a cathepsin B inhibitor (E64D), NLRP3 expression was suppressed indicating that induction of NLRP3 activation following efferocytosis of apoptotic A549 cells is mediated via ROS and cathepsin-B. In summary, we present evidence of involvement of the NLRP3 inflammasome-caspase pathway in the pathogenesis of IPF-AE, similarly to ARDS, which may be mediated by efferocytosis of apoptotic alveolar epithelial cells in IPF.


Thalidomide impairs insulin action on glucose uptake and glycogen synthesis in patients with type 2 diabetes.
To investigate the effect of thalidomide on glucose turnover (glucose production and uptake), on intracellular pathways of glucose utilization (glycogen synthesis [GS], glycolysis [GLS], carbohydrate oxidation, and nonoxidative GLS), and on free fatty acid (FFA) turnover (lipolysis, FFA oxidation, and FFA reesterification). A total of 6 patients with type 2 diabetes were studied with 4-h isoglycemic-hyperinsulinemic clamps (approximately 8 mmol/l and 500-600 pmol/l, respectively) before treatment (Prestudy), after 3 weeks of thalidomide (150 mg orally at bedtime), and after 3 weeks of placebo. Thalidomide reduced insulin-stimulated glucose uptake by 31% (from 27.7 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 21% (from 24.2 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with placebo. Thalidomide also reduced insulin-stimulated GS by 48% (from 14.1 to 8.2 micromol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 40% (from 13.6 to 8.2 micromol x kg(-1) x min(-1), P < 0.5) compared with placebo. Thalidomide had no effect on rates of GLS, carbohydrate oxidation, nonoxidative GLS, lipolysis, FFA oxidation, and reesterification. We conclude that thalidomide increased insulin resistance in obese patients with type 2 diabetes by inhibiting insulin-stimulated GS and that patients taking thalidomide should be monitored for possible deterioration in their glucose tolerance.


[Post chemotherapy laparoscopic retroperitoneal lymph node dissection].
To describe the laparoscopic excision of a postchemotherapy retroperitoneal residual mass in a patient with mixed germ cell testicular tumor. We report the operative technique of laparoscopic excision of a retroperitoneal mass in a 33 year old patient with mixed germ cell testicular tumor. The patient is placed in a lateral decubitus right lumbotomy position and trocars are introduced into the abdominal cavity. Once the retroperitoneum is approached, and after a Kocher manoeuvre of the duodenum, the interaortocaval mass is identified and excised. The operation is completed with lympadenectomy down to the common iliac artery bifurcation bilaterally. The laparoscopic approach is another option for the surgical treatment of residual masses after chemotherapy in testicular tumors. Nevertheless, previous laparoscopic experience is necessary due to its difficulty.


[Light-reflexion rheography--possibilities and limitations].
Light reflection rheography (LRR) is a new technique for quantitative diagnostics of venous functions. It is non-invasive, easy to handle, well-suited for repetition and standardization, and there is no strain for the patient. This method is appropriate for global assessment of calf pump insufficiency regardless whether it may be caused by varicosis, postphlebitic syndrome, or deep venous thrombosis. With the application of tourniquets, LRR helps to predict the possible result of vein stripping and is likewise useful for the follow-up period. LRR promises to become a valuable screening method regarding the detection of deep venous thrombosis of the lower leg. A useful methodic variation is the passive manual compression of the calf instead of active dorsiflexion; thus the measurement becomes independent of the patient's cooperation. We must take into account, however, the high sensitivity of LRR depending on various known and still unknown factors. The measured values may differ to a considerable degree in one single patient, even under exact conditions of examination. Therefore we always perform three measurements and then take the average value. Critically applied, LRR represents a valuable technique of quantitative phlebological examination.


The origin of multiple clones in the parthenogenetic lizard species Darevskia rostombekowi.
The all-female Caucasian rock lizard Darevskia rostombekowi and other unisexual species of this genus reproduce normally via true parthenogenesis. Typically, diploid parthenogenetic reptiles exhibit some amount of clonal diversity. However, allozyme data from D. rostombekowi have suggested that this species consists of a single clone. Herein, we test this hypothesis by evaluating variation at three variable microsatellite loci for 42 specimens of D. rostombekowi from four populations in Armenia. Analyses based on single nucleotide polymorphisms of each locus reveal five genotypes or presumptive clones in this species. All individuals are heterozygous at the loci. The major clone occurs in 24 individuals and involves three populations. Four rare clones involve one or several individuals from one or two populations. Most variation owes to parent-specific single nucleotide polymorphisms, which occur as heterozygotes. This result fails to reject the hypothesis of a single hybridization founder event that resulted in the initial formation of one major clone. The other clones appear to have originated via post-formation microsatellite mutations of the major clone.


Non-smoker assertive behaviour against smoke exposure: Chinese and Korean American non-smokers.
Non-smokers' assertive behaviour towards smokers by asking them not to smoke is important in promoting smoke-free environments. Korean and Chinese Americans come from countries where most women are non-smokers and assertive behaviour may not be prevalent but may increase after migration because of social-ecological factors. This study assessed the extent to which Korean and Chinese American non-smokers ask someone not to smoke and associated factors. The 2003 California Chinese American and Korean American Tobacco Use Surveys were analysed. Multivariate logistic regression analyses examined factors related to non-smoker self-reports that they asked someone not to smoke within the past year. About 40% reported past-year assertive behaviour against smoking, with higher rates among Koreans than Chinese (60.4% vs. 34.5%), those living with smokers (63.5%), ever exposed with a smoke-free home rule (62.3%), recently exposed at work without a smoke-free work policy (67.6%) and regularly exposed at other locations (52.3%). In combined multivariate analyses of both ethnic groups, assertive behaviour was associated with individual factors (single vs. married; tobacco exposure knowledge), family factors (living with smokers, exposed at home despite a smoke-free rule), community factors (exposed at work with no smoke-free policy, exposed at other locations) and cultural factors (Korean vs. Chinese ethnicity; lower acculturation). Chinese and Korean American non-smokers report assertive behaviour against smoking, which is associated with social-ecological factors. Results help identify target groups and strategies for future intervention, including the need to implement or enforce smoke-free environments and promote empowerment. [Saw A, Tang H, Tsoh JY, Chen MS Jr, Tong EK. Non-smoker assertive behaviour against smoke exposure: Chinese and Korean American non-smokers.


Contemporary Applications of Thioamides and Methods for their Synthesis.
Thioamides are naturally occurring isosteres of amide bonds in which the chalcogen atom of the carbonyl is changed from oxygen to sulfur. This substitution gives rise to altered nucleophilicity and hydrogen bonding properties with importance for both chemical reactivity and non-covalent interactions. As such, thioamides have been introduced into biologically active compounds to achieve improved target affinity and/or stability towards hydrolytic enzymes but have also been applied as probes of protein and peptide folding and dynamics. Recently, a series of new methods have been developed for the synthesis of thioamides as well as their utilization in peptide chemistry. Further, novel strategies for the incorporation of thioamides into proteins have been developed, enabling both structural and functional studies to be performed. In this Review, we highlight the recent developments in the preparation of thioamides and their applications for peptide modification and study of protein function.


Physical activity, diet and behaviour modification in the treatment of overweight and obese adults: a systematic review.
The aim was to extend the body of knowledge through a systematic review that combines the strengths and partly fills the gaps from earlier reviews. The aim is to review randomized controlled trials of the long-term effectiveness of physical exercise/activity with or without diet and/or behaviour modification therapy in terms of training effect, weight loss and improvement of body composition in overweight and obese, healthy adults. Data for systematic review was collected via a search of databases for literature published between 1995 and 2006. The search yielded 12 articles. The studies showed that training intensity should be moderate. The treatment of overweight and obese individuals with training alone cannot be expected to result in any substantial weight loss but should be combined with diet and behaviour modification therapy. However training can be an important factor in preventing further weight gain, or in helping individuals maintain a lowered body weight. According to this systematic review of randomized controlled trials, the treatment that produced the best weight loss results included a combination of training, behaviour therapy and diet.


Prevalence and progression of aortic dilatation in adult patients with Turner syndrome: a cohort study.
Turner syndrome (TS) is a rare disorder affecting 1/2500 female newborn. Aortic dilatation (AD) and aortic dissection represent a major concern in TS. The aims of our study were to describe the aortic root growth, potential aortic dilatation (AD) risk factors and cardiovascular outcomes in a cohort of patients with TS. Among 204 adult patients included, 197 were studied using a standardized 1.5 Tesla MRI protocol. AD was defined as an aortic diameter ≥20 mm/m2 at the Valsalva sinuses and/or at the ascending aorta, when indexed to body surface area. At baseline, AD was present in 81/197 (41.1%) and 32/197 (16.2%) of patients, at the levels of Valsalva and ascending aorta, respectively. The aortic Valsalva diameter was larger in patients treated for thyroiditis (P < 0.001). Potential risk factors of AD were aging (P < 0.001) and the presence of bicuspid aortic valve (BAV) (P = 0.002). The hazard ratio (HR) of AD occurrence in the presence of BAV was 2.2 (95% CI: 1.33-3.71). After a median follow-up period of 5.1 years (n = 143), AD was present in 58/143 (40.6%) and 25/143 (17.5%) of patients at the levels of Valsalva and ascending aorta, respectively. The median aortic growth of the Valsalva sinuses remained stable. At the ascending aorta, it increased by 0.14 ± 0.61 mm/year. Only one aortic-related death was observed. AD is common in adult patients with TS. However, our results are rather reassuring, as the median aortic diameters remained stable after 5.1 years and few aortic events were observed.


From social-signal detection to higher social cognition: an fMRI approach.
Implicit or automatic detection of social signals, which discriminate animate, intentional objects in the environment, is essential for higher social cognition and its development. Using functional magnetic resonance imaging, we identified the neural substrate of detecting simple visual social signals and examined its functional link with the mechanism of inferring another's mental state. Healthy participants were presented with the eye-gaze shift (EG) and self-propelling motion (SP) under both implicit and explicit task conditions. They also performed a social role-playing game in which mental inference (MI) was implicitly prompted during the presentation of faces (implicit MI). Implicit detection of EG and SP activated the posterior middle temporal gyrus (pMTG) bilaterally, whereas the right posterior superior temporal sulcus was activated during the explicit conditions. We revealed that the individual variation in neural response in the right pMTG during implicit eye-gaze detection explains the individual tendency to recruit the regions implicated in mental-state inference (medial prefrontal cortex, temporal pole and striatum) during the implicit MI task. Our results suggest that the implicit detection of visual social signals involves the pMTG and underlies the development of higher social cognition.


Soft markers for aneuploidy following reassuring first trimester screening: what should be done?
The present article aims to review the current role of the soft markers on the second trimester ultrasound (STUS) in women after reassuring first trimester screening (FTS) in singleton pregnancies. Improvements in the FTS and the recent implementation of noninvasive prenatal testing (NIPT) for common aneuploidies have important impact on the prevalence of these conditions in the STUS. Some studies suggest that soft markers in the second trimester of the fetus without structural anomalies have a minor or no role in Down syndrome detection in a prescreened population with reassuring results. However, NIPT could be offered as a next step in the management of such pregnancies if the calculated new composite risk (NCR) for aneuploidy is increased. In the case of reassuring results, pregnancy follow-up for certain markers is advised. NIPT has emerged as a new method of prenatal testing and is feasible in the second trimester in women with increased NCR. However, apart from the Down syndrome screening, STUS screening remains a powerful tool in screening for other fetal aneuploidies, structural anomalies and pathological placental conditions and detection of specific soft markers that require pregnancy follow-up.


Glabridin, a Bioactive Flavonoid from Licorice, Effectively Inhibits Platelet Activation in Humans and Mice.
Platelets are crucial for hemostasis and arterial thrombosis, which may lead to severe cardiovascular diseases (CVDs). Thus, therapeutic agents must be developed to prevent pathological platelet activation. Glabridin, a major bioalkaloid extracted from licorice root, improves metabolic abnormalities (i.e., obesity and diabetes) and protects against CVDs and neuronal disorders. To the best of our knowledge, no studies have focused on glabridin's effects on platelet activation. Therefore, we investigated these effects in humans and mice. Glabridin exhibited the highest inhibitory effects on collagen-stimulated platelet aggregation and moderate effects on arachidonic-acid-stimulated activation; however, no effects were observed for any other agonists (e.g., thrombin or U46619). Glabridin evidently reduced P-selectin expression, ATP release, and intracellular Ca2+ ([Ca2+]i) mobilization and thromboxane A2 formation; it further reduced the activation of phospholipase C (PLC)γ2/protein kinase C (PKC), phosphoinositide 3-kinase (PI3K)/Akt/glycogen synthase kinase-3β (GSK3β), mitogen-activated protein kinase (MAPK), and NF-κB. In mice, glabridin reduced the mortality rate caused by acute pulmonary thromboembolism without altering bleeding time. Thus, glabridin effectively inhibits the PLCγ2/PKC cascade and prevents the activation of the PI3K/Akt/GSK3β and MAPK pathways; this leads to a reduction in [Ca2+]i mobilization, which eventually inhibits platelet aggregation. Therefore, glabridin may be a promising therapeutic agent for thromboembolic disorders.


Characterizing impaired functional alertness from diphenhydramine in the elderly with performance and neurophysiologic measures.
Psychometric task performance measures can be highly sensitive to manipulations that impair functional alertness in young adults; such measures have been shown to be less sensitive to reduced alertness in older adults. The purpose of this study is to determine whether neurophysiologic measures can aid in the detection and characterization of impairments in functional alertness in the elderly. Double-blind, placebo-controlled, counter-balanced, crossover study. Research laboratory. Twelve healthy older adults (62-75 years of age). Diphenhydramine, 50 mg. Behavioral performance and electroencephalogram measures were obtained while participants completed spatial working memory and word recognition episodic memory tasks in a baseline interval before drug ingestion and in 4 hourly test intervals following drug ingestion. Relative to placebo, diphenhydramine had marginal effects on task performance yet was effective in reducing alertness, as evidenced by subjective ratings and objective neurophysiologic (electroencephalogram) markers. Diphenhydramine significantly reduced the amplitude of alertness-sensitive event-related potentials recorded during working memory task performance, including the N160 and P300. It also affected neurophysiologic processes underlying episodic memory, as evidenced by a reduction in the difference in event-related potentials between old and new words in the word recognition task. Discriminant analyses incorporating neurophysiologic measures showed that the time course of the central effects of diphenhydramine in older subjects was similar to that previously observed in young adults. These results demonstrate that diphenhydramine has adverse neurocognitive effects in elderly individuals and highlights the utility of incorporating direct measures of brain function into assessments of functional alertness.


Sequence polymorphism of dotA and mip alleles mediating invasion and intracellular replication of Legionella pneumophila.
Legionella pneumophila inhabit a variety of natural and man-made aquatic environments, where they live primarily as intracellular parasites of protozoans. Given the proper exposure, however, they can cause opportunistic pneumonic infections in humans. The products of two L. pneumophila genes, dotA and mip, are part of the mechanism mediating the initial invasion of eukaryotic cells, and subsequent intracellular survival and multiplication. In this study, DNA polymorphism of the dotA and mip genes was assessed for 17 clinical and environmental isolates by nucleotide sequencing to determine the level of sequence variation, rates of molecular evolution, and history of gene divergence. The mip gene is highly conserved, whereas dotA is extremely variable, with an average level of nucleotide diversity four times greater than that of mip. Gene trees for each locus support a division of the L. pneumophila isolates into two clonal lineages. There are several disagreements between the gene trees suggesting that although L. pneumophila has a clonal population structure, genetic exchange has contributed to genotypic variation among strains in nature.


Knowledge, attitude, and practice regarding atrial fibrillation among primary care physicians: the potential role of postgraduate training.
Atrial fibrillation (AF) is known to lead to stroke and thromboembolism, causing a five-fold increase in the risk of stroke and almost doubling the mortality rate. Optimal anticoagulant therapy is effective in reducing AF-related death. However, prescription of anticoagulants in AF in East Asian countries has been low, ranging from 0.5% to 28%. This study aimed to determine whether vocational training in family medicine improves primary care physicians' knowledge, attitude, and practice in the management of AF. This investigation was a cross-sectional study carried out during centralized workshops for two groups of trainees using a validated questionnaire: (i) junior trainees were newly enrolled postgraduate trainees in the Graduate Certificate in Family Medicine (GCFM) program, and (ii) senior trainees were postgraduate trainees in Advance Training in Family Medicine (ATFM) programs of the Academy of Family Physicians of Malaysia (AFPM). A total of 223 trainees (127 junior and 96 senior) participated in this study. Only 55.2% of the trainees passed the knowledge test; senior trainees were more likely to pass the knowledge test compared to junior trainees (69.8% vs. 44.1%, p < 0.001). Female trainees were significantly more likely to pass the knowledge test than male trainees. While the attitude of senior and junior trainees was similar, more of the latter group worked in public clinic that provide better support where there is better support for outpatient anticoagulation treatment (e.g., same-day INR test, direct access echocardiogram, and warfarin in in-house pharmacy). Vocational training in family medicine appears to improve primary care physicians' knowledge regarding the management of AF. Better knowledge will help vocationally trained primary care physicians to provide anticoagulation treatment for AF within primary care clinics. More optimal AF management within primary care can take place if the identified barriers are addressed and a shared care plan can be implemented.


C-reactive protein as a prognostic tool in cardiovascular practices: should CRP testing be ordered along with lipid profiles?
CRP has a graded, dose-response relationship to the occurrence of clinical cardiovascular events that remains after adjustment for other risk factors, with moderately strong associations between the lower and upper tertiles (RR≈2). It may have clinical utility in improving the estimation of absolute risks of patients with a calculated ten-year risk between 10 and 20%. Individuals at low risk (<10% per 10 years) will be unlikely to have a high risk identified through CRP testing. Additional prospective studies or new statistical analysis of previous studies are needed to establish the added predictive value of CRP above that of currently established risk factors. Thus, currently available evidence suggests that CRP testing should not be ordered along with lipid profiles.


Trialling an electronic decision aid for policy developers to support ageing well.
The complex process of developing policies and planning services requires the compilation and collation of evidence from multiple sources. With the increasing numbers of people living longer there will be a high demand for a wide range of aged care services to support people in ageing well. The premise of ageing well is based on providing an ageing population with quality care and resources that support their ongoing needs. These include affordable healthcare, end of life care improvement, mental health services improvement, care and support improvement for people with dementia, and support for healthy ageing. The National Health and Medical Research Council funded a research project to develop a policy tool to provide a framework to assist policy makers and service planners in the area of ageing well in rural and regional Australia. It was identified that development of an electronic version of the policy tool could be useful resulting in a small pilot development being undertaken and tested with policy makers and service planners. This paper describes the development and trialling of a tablet based application used to assess the acceptability of computerised forms for participants actively involved in policy development. It reports on the policy developer's experience of the electronic tool to support ageing well policy making based on evidence.


Determinants of the nucleocytoplasmic shuttling of muscle glycogen synthase.
Muscle glycogen synthase (MGS) presents a nuclear speckled pattern in primary cultured human muscle and in 3T3-L1 cells deprived of glucose and with depleted glycogen reserves. Nuclear accumulation of the enzyme correlates inversely with cellular glycogen content. Although the glucose-induced export of MGS from the nucleus to the cytoplasm is blocked by leptomycin B, and therefore mediated by CRM1, no nuclear export signal was identified in the sequence of the protein. Deletion analysis shows that the region comprising amino acids 555-633 of human MGS, which encompasses an Arg-rich cluster involved in the allosteric activation of the enzyme by Glc6P, is crucial for its nuclear concentration and aggregation. Mutation of these Arg residues, which desensitizes the enzyme towards Glc6P, interferes with its nuclear accumulation. In contrast, the known phosphorylation sites of MGS that regulate its activity are not involved in the control of its subcellular distribution. Nuclear human MGS co-localizes with the promyelocytic leukaemia oncoprotein and p80-coilin, a marker of Cajal bodies. The subnuclear distribution of MGS is altered by incubation with transcription inhibitors. These observations suggest that, in addition to its metabolic function, MGS may participate in nuclear processes.


Distribution of aluminium between plasma and erythrocytes.
It is common use to monitor body burdens of toxic trace metals by measuring concentrations in whole blood. To monitor aluminium (Al) body burden in renal patients on haemodialysis, which is a high-risk group for Al poisoning, the concentrations of Al in plasma (AlP) or serum (AlS) are determined rather than Al in whole blood (AlB). To evaluate this custom, which exists in clinical laboratories, an investigation was made into the distribution of Al between the plasma and the blood-cell compartment and on the extent of binding of Al to the blood cells both in rats and in dialysed patients. The results show that Al is distributed between plasma and blood cells with only very small quantitative differences, that binding of Al to blood cells is very weak and that AlP and AlB have similar prognostic value for toxicity.


Dorsal lumbar interbody fusion for chronic axial, mechanical low back pain: a modification of two established techniques.
Lumbar spinal fusion is a popular method for treating degenerative disc disease leading to chronic low back pain. Some of the techniques most commonly undertaken are posterior lumbar interbody fusion and transforaminal lumbar interbody fusion. These techniques have their own advantages and disadvantages. In this article, we briefly describe a modified technique, dorsal lumbar interbody fusion, which retains the advantages and avoids the disadvantages of the others. The goal of this procedure is to combine the aggressive decompression of both the thecal sac and bilateral nerve roots and symmetrical bilateral graft placement obtained via the posterior lumbar interbody fusion with the transforaminal placement of interbody grafts obtained via the transforaminal lumbar interbody fusion procedure. This modification has several advantages: it permits more aggressive removal of the disc bilaterally, larger and more symmetrical lordotic-shaped carbon fiber cages and structural allograft can be placed bilaterally, and the nerve roots can be aggressively decompressed bilaterally.


Endogenous calcium buffering at photoreceptor synaptic terminals in salamander retina.
Calcium operates by several mechanisms to regulate glutamate release at rod and cone synaptic terminals. In addition to serving as the exocytotic trigger, Ca2+ accelerates replenishment of vesicles in cones and triggers Ca2+-induced Ca2+ release (CICR) in rods. Ca2+ thereby amplifies sustained exocytosis, enabling photoreceptor synapses to encode constant and changing light. A complete picture of the role of Ca2+ in regulating synaptic transmission requires an understanding of the endogenous Ca2+ handling mechanisms at the synapse. We therefore used the "added buffer" approach to measure the endogenous Ca2+ binding ratio (κendo ) and extrusion rate constant (γ) in synaptic terminals of photoreceptors in retinal slices from tiger salamander. We found that κendo was similar in both cell types-∼25 and 50 in rods and cones, respectively. Using measurements of the decay time constants of Ca2+ transients, we found that γ was also similar, with values of ∼100 s(-1) and 160 s(-1) in rods and cones, respectively. The measurements of κendo differ considerably from measurements in retinal bipolar cells, another ribbon-bearing class of retinal neurons, but are comparable to similar measurements at other conventional synapses. The values of γ are slower than at other synapses, suggesting that Ca2+ ions linger longer in photoreceptor terminals, supporting sustained exocytosis, CICR, and Ca2+ -dependent ribbon replenishment. The mechanisms of endogenous Ca2+ handling in photoreceptors are thus well-suited for supporting tonic neurotransmission. Similarities between rod and cone Ca2+ handling suggest that neither buffering nor extrusion underlie differences in synaptic transmission kinetics.


[Effect of alcohol on the 11-hydroxycorticosteroid and 17-ketogenic steroid levels in man taking into account biorhythms].
Circadian rhythms of 11-hydroxycorticosteroids (11-OHCS) in blood plasma and 17-ketogenic steroids (17-KGS) in urine in health and for 3 days after a single intake of 40 per cent alcohol (6.2 ml/kg) from 17.00 to 18.00 were studied in 20 healthy men volunteers aged 20 to 26 years. Alcohol considerably raised the level of 11-OHCS and 17-KGS during its circulation in the blood. After ethanol elimination was completed, there was a decrease in the level of corticosteroids, which was observed even on the 2nd day after alcoholization during rhythm acrophases. Alcoholization resulted in variations of the mesors, amplitudes and acrophases of circadian rhythms throughout two days. The recovery of normal time structure occurred on the 3d day.


[Effectiveness of the biological purification of sewage for removing carcinogenic polycyclic aromatic hydrocarbons].
The correlation between biological purification of sewage and concentrations of carcinogens in it is studied. The balance between the income and outcome of benza(a)pyrene (BP) with water and surplus active mud of paper in aero-tanks, performed under both industrial and laboratory conditions is examined. It is demonstrated that BP is not destroyed by biological purification but is accumulated by the active sludge cells. Thus, the biologic purification of sewage prevents from pollution by carcinogenic polycyclic hydrocarbons, but does not remove these agents from the environment.


Parkinson disease phenotype in Ashkenazi Jews with and without LRRK2 G2019S mutations.
The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studied 553 AJ PD patients, including 65 patients who were previously reported, from three sites (two in New York and one in Tel-Aviv). Glucocerebrosidase (GBA) mutation carriers were excluded. Evaluations included the Montreal Cognitive Assessment (MoCA), the Unified Parkinson's Disease Rating Scale (UPDRS), the Geriatric Depression Scale (GDS) and the Non-Motor Symptoms (NMS) questionnaire. Regression models were constructed to test the association between clinical and demographic features and LRRK2 status (outcome) in 488 newly recruited participants. LRRK2 G2019S carriers (n = 97) and non-carriers (n = 391) were similar in age and age at onset of PD. Carriers had longer disease duration (8.6 years vs. 6.1 years; P < 0.001), were more likely to be women (51.5% vs. 37.9%; P = 0.015), and more often reported first symptoms in the lower extremities (40.0% vs. 19.2%; P < 0.001). In logistic models that were adjusted for age, disease duration, sex, education, and site, carriers were more likely to have lower extremity onset (P < 0.001), postural instability and gait difficulty (PIGD) (P = 0.043), and a persistent levodopa response for >5 years (P = 0.042). Performance on the UPDRS, MoCA, GDS, and NMS did not differ by mutation status. PD in AJ LRRK2 G2019S mutation carriers is similar to idiopathic PD but is characterized by more frequent lower extremity involvement at onset and PIGD without the associated cognitive impairment.


Two-Stage Gene Therapy (VEGF, HGF and ANG1 Plasmids) as Adjunctive Therapy in the Treatment of Critical Lower Limb Ischemia in Diabetic Foot Syndrome.
One of the most serious problems in people with diabetes is diabetic foot syndrome. Due to the peripheral location of atherosclerotic lesions in the arterial system of the lower extremities, endovascular treatment plays a dominant role. However, carrying out these procedures is not always possible and does not always bring the expected results. Gene therapy, which stimulates angiogenesis, improves not only the inflow from the proximal limb but also the blood redistribution in individual angiosomes. Due to the encouraging results of sequential treatment consisting of intramuscular injections of VEGF/HGF bicistronic plasmids followed by a month of ANG1 plasmids, we decided to use the described method for the treatment of critical ischemia of the lower limbs in the course of diabetes and, more specifically, in diabetic foot syndrome. Twenty-four patients meeting the inclusion criteria were enrolled in the study. They were randomly divided into two equal groups. The first group of patients was subjected to gene therapy, where the patients received intramuscular injections of pIRES/VEGF165/HGF plasmids and 1 month of ANG-1 plasmids. The remaining patients constituted the control group. Gene therapy was well tolerated by most patients. The wounds healed significantly better in Group 1. The minimal value of ABI increased significantly in Group 1 from 0.44 ± 0.14 (± standard deviation) to 0.47 ± 0.12 (with p = 0.028) at the end of the study. There were no significant differences in the control group. In the gene treatment group, PtcO2 increased significantly (from 28.71 ± 10.89 mmHg to 33.9 ± 6.33 mmHg with p = 0.001), while in Group 2, no statistically significant changes were found. The observed resting pain decreased significantly in both groups (Group 1 decreased from 6.80 ± 1.48 to 2.10 ± 1.10; p < 0.001; the control group decreased from 7.44 ± 1.42 to 3.78 ± 1.64 with p < 0.001). In our study, we evaluated the effectiveness of gene therapy with the growth factors described above in patients with CLI in the course of complicated DM. The therapy was shown to be effective with minimal side effects. No serious complications were observed.


Student perceptions of effectiveness of the eight step preceptor (ESP) model in the ambulatory setting.
Balancing consistently effective clinical teaching with quality patient care is a crucial challenge for ambulatory preceptors. Educators have developed frameworks of specific teaching behaviors to facilitate consistent, efficient precepting, but few have evaluated their effectiveness. We modified an existing precepting model by incorporating additional adult learning principles to create the Eight Step Preceptor (ESP) model. We then determined if students perceived faculty to be more effective teachers when they incorporated more ESP components into their precepting sessions. The objective was to describe the association between faculty using the ESP behaviors during their precepting and medical students' satisfaction with their learning. A trained observer timed the duration of precepting sessions in a children's hospital ambulatory clinic between August and November 2001. Students rated faculty "teaching effectiveness," and both students and observer rated whether faculty effectively incorporated ESP behaviors during each session. Sessions lasted on average 26 +/- 14 min. Faculty gave a teaching point and feedback in over 50% of the precepting sessions but did not consistently incorporate the other ESP behaviors. Faculty use of more ESP behaviors correlated significantly with greater teaching effectiveness (r = .62, p < .003) but not significantly with duration of precepting sessions. Students perceived faculty as more effective teachers when they incorporated more ESP behaviors while precepting. The ESP model was associated with more effective ambulatory precepting in our study.


Photoelectron spectroscopy and density functional calculations of Fe(n)BO2- clusters.
We conducted a study of Fe(n)BO(2)(-) clusters by mass spectrometry and photoelectron spectroscopy. The vertical detachment energies and adiabatic detachment energies of these clusters were evaluated from their photoelectron spectra. We have also performed density-functional calculations of Fe(n)BO(2)(-) (n=1-5) clusters and determined their structures by comparison of theoretical calculations to experimental results. The studies show that BO(2) moiety still maintains its linear structure as the bare BO(2) cluster. BO(2) behaves as a superhalogen. Analysis of molecular orbitals reveals that the highest occupied molecular orbitals of Fe(n)BO(2)(-) clusters are mainly localized on the Fe(n) units.


[Influence of the daily ingestion of a total unsaponifiable extract from avocado and soy bean oils on cholesterol metabolism in the rat].
The effects of ingestion of an unsaponifiable avocado and soya extract (P.I.A.S.) on the rates of cholesterol turnover were studied in the Rat smaller than in toto greater than. The balance is the same as in control rats, but fecal and urinary excretions of cholesterol are well enhanced and transformation into bile acids is consequently reduced. The absorption coefficient of cholesterol is unchanged in spite of the presence of phytosterols in the extract. The extract having been said to have a beneficial effect on scleroderma a special study was undertaken of the skin. The GLC analysis of sterols show the very probable presence of phytosterols and a richer proportion of cholesterol, precursors particularly methostenol in the skin of rats fed on P.I.A.S. than in that of the controls. These modifications do not produce any variations in the rate of cholesterol synthesis as measured in vitro.


Low national breast and cervical cancer-screening rates in American Indian and Alaska Native women with diabetes.
The cervical cancer mortality rate for American Indian and Alaska Native women is twice that of all races in the United States. To date the only published national breast and cervical cancer-screening rates for American Indian and Alaska Native women are based on self-reported data. When the Indian Health Service (IHS) conducts an annual audit on patients with diabetes, it includes cancer screening. This observational study presents national breast and cervical cancer-screening rates for American Indian and Alaska Native women with diabetes. Cancer-screening rates were extracted from the 1995 diabetic audit for the 12 IHS areas. These rates were compared with rates for women without diabetes of the same age, 50 to 69 years, by chart review, at four IHS hospitals in the Aberdeen IHS area. Screening rates for women with diabetes in the 12 areas varied: mammogram (ever) 35% to 78%; clinical breast examination (last year) 28% to 70%, and Papanicolaou smear (last year) 26% to 69%. The Aberdeen IHS area women with diabetes had 51% more clinic visits per year than women without diabetes, but the groups had similar screening rates. Cancer-screening rates for American Indian and Alaska Native women vary by region. In the Aberdeen IHS area, women with diabetes had more visits (missed opportunities) but similar screening rates as women without diabetes. The diabetic audit could be used to monitor national IHS cancer-screening trends for women with diabetes and in the Aberdeen IHS area for all women aged 50 to 69 years.


Transmitter regulation of voltage-dependent K+ channels expressed in Xenopus oocytes.
Voltage-dependent K+ channels (RBK1, RBK2 and RGK5) were co-expressed in Xenopus oocytes with 5-hydroxytryptamine (5-HT2) receptors. K+ currents measured 2-4 days later were inhibited by 5-HT (100 nM-10 microM, 20-30 s application) by up to 90%. The effect of 5-HT was mimicked by intracellular injection of Ins(1,4,5)P3. Increasing the Ca2+ concentration at the inner surface of excised membrane patches did not decrease the K+ current.


Effectiveness of leech therapy in chronic lateral epicondylitis: a randomized controlled trial.
Leech therapy has been found to be effective in osteoarthritis of the knee and hand in previous trials. Chronic epicondylitis is a prevalent pain syndrome with limited treatment options. In this study, we tested whether leech therapy would be beneficial in the symptomatic treatment of chronic lateral epicondylitis. Forty patients with manifestation of epicondylitis of at least 1-month duration were randomized to a single treatment with 2 to 4 locally applied leeches or a 30-day course with topical diclofenac. The primary outcome was change of pain sum score on day 7 calculated from 3 visual analog scales for pain during motion, grip, and rest. Secondary outcomes included disability (Disability of the Arm, Shoulder, Hand questionnaire), physical quality of life (Short Form-36), and grip strength. Outcomes and safety were assessed on days -3, 0, 7, and 45. Leeches induced a significantly stronger decrease of the pain score (143.7±36.9 to 95.3±45.1) compared with topical diclofenac (131.6±29.6 to 134.7±70.7; mean difference -49.0; 95% confidence interval,-82.9--15.1; P=0.0075) after 7 days. On day 45, this group difference was reduced (-27.5; confidence interval, -60.8-5.8; P=0.110) due to delayed pain relief with diclofenac. Functional disability showed a stronger decrease in the leech group, which was most prominent after 45 days (P=0.0007). Quality of life increased nonsignificantly in the leech group. Results were not affected by outcome expectation. A single course of leech therapy was effective in relieving pain in the short-term and improved disability in intermediate-term. Leeches might be considered as an additional option in the therapeutic approach to lateral epicondylitis.


[Potentialities of preventing progressive and complicated myopia in the light of present-day knowledge].
The paper generalizes the present-day principles of prevention of progressive and complicated myopia. The risk factors of complications and disability due to congenital and acquired myopia are defined. Methods of spectacle, contact, and surgical correction in congenital myopia are discussed. There is evidence for the importance of studies dealing with the etiological factors and pathogenetic mechanisms in determining the ways of preventing myopia. Recommendations are given for the prevention of disabling forms of myopia.


Cathepsin B is not the processing enzyme for mouse prorenin.
Renin, an aspartyl protease that catalyzes the rate-limiting step in the renin-angiotensin system (RAS), is proteolytically activated by a second protease [referred to as the prorenin processing enzyme (PPE)] before its secretion from the juxtaglomerular cells of the kidney. Although several enzymes are capable of activating renin in vitro, the leading candidate for the PPE in the kidney is cathepsin B (CTSB) due to is colocalization with the renin precursor (prorenin) in juxtaglomerular cell granules and because of its site-selective activation of human prorenin both in vitro and in transfected tissue culture cell models. To verify the role of CTSB in prorenin processing in vivo, we tested the ability of CTSB-deficient (CTSB-/-) mice to generate active renin. CTSB-/- mice do not exhibit any overt symptoms (renal malformation, preweaning mortality) typical of an RAS deficiency and have normal levels of circulating active renin, which, like those in control animals, rise more than 15-fold in response to pharmacologic inhibition of the RAS. The mature renin enzyme detected in kidney lysates of CTSB-/- mice migrates at the same apparent molecular weight as that in control mice, and the processing to active renin is not affected by chloroquine treatment of the animals. Finally, the distribution and morphology of renin-producing cells in the kidney is normal in CTSB-/- mice. In conclusion, CTSB-deficient mice exhibit no differences compared with controls in their ability to generate active renin, and our results do not support CTSB as the PPE in mice.


Ward design and neonatal jaundice in the tropics: report of an epidemic.
Architectural modifications to an existing tropical obstetric ward involved extension of the roof overhangs to a width of several metres. These extensions excluded most of the daylight from the ward. An alarming increase in the incidence of jaundice (bilirubin concentration greater than or equal to 240 mumol/l (greater than or equal to 14 mg/100 ml] from 0.5% to 17% in newborn infants occurred after the modifications. Tropical obstetric wards and nurseries should continue to be built with windows facing north-south for coolness. They should, however, have as many windows as possible and the roof overhangs should be limited to about 1 m to allow adequate indirect sunlight to enter, giving a high intensity of illumination, and help prevent neonatal jaundice.


DOCK 6: Incorporating hierarchical traversal through precomputed ligand conformations to enable large-scale docking.
To allow DOCK 6 access to unprecedented chemical space for screening billions of small molecules, we have implemented features from DOCK 3.7 into DOCK 6, including a search routine that traverses precomputed ligand conformations stored in a hierarchical database. We tested them on the DUDE-Z and SB2012 test sets. The hierarchical database search routine is 16 times faster than anchor-and-grow. However, the ability of hierarchical database search to reproduce the experimental pose is 16% worse than that of anchor-and-grow. The enrichment performance is on average similar, but DOCK 3.7 has better enrichment than DOCK 6, and DOCK 6 is on average 1.7 times slower. However, with post-docking torsion minimization, DOCK 6 surpasses DOCK 3.7. A large-scale virtual screen is performed with DOCK 6 on 23 million fragment molecules. We use current features in DOCK 6 to complement hierarchical database calculations, including torsion minimization, which is not available in DOCK 3.7.


Trends in hospital admissions for pulmonary embolism in England: 1996/7 to 2005/6.
Pulmonary embolism (PE) can be difficult to diagnose and manage. This paper examines recent national trends in admission rates and mortality for PE to help inform clinical practice. Admissions to NHS hospitals in England between 1 April 1996 and 31 March 2006 were studied. Trends in admission rates, the proportion of all admissions with PE as primary or secondary diagnosis and hospital mortality following PE identified. There were 251,449 admissions with a diagnosis of pulmonary embolus in the study period. Non-elective admission rates rose from 28.0 per 100,000 in 1996/7 to 32.1 per 100,000 in 2005/6. There was a significant increase in secondary diagnosis rates and a clear seasonal pattern with excess admissions in winter. There was significant in-hospital mortality for both primary (13%) and secondary diagnosis (31%). Mortality decreased over time and was highest among the elderly. Pulmonary embolism is associated with a significant mortality although overall trends in mortality are improving in England. Age and comorbidities must be considered when developing guidelines and individual treatment plans.


Ophthalmology patients' religious and spiritual beliefs: an opportunity to build trust in the patient-physician relationship.
To assess the prevalence of religion and spirituality as a component of ophthalmology patients' value systems. A brief questionnaire distributed to 124 consecutive patients was self-administered by the patient and was collected without identifier so that participants could be assured that answers would not affect their care. The main outcome measure was the prevalence of religious and spiritual beliefs and behaviors in ophthalmology patients. The sample was predominantly Christian (76.6%). Of the participants, 82.3% reported that prayer was important (69.4% "very important" and 12.9% "moderately important") to their sense of well-being, and 45.2% reported weekly attendance at religious services. The prevalence of positive religious and spiritual interpretations of God's role in illness was higher than that of negative religious appraisals of God's role in illness. The prevalence and importance of religious and spiritual beliefs in this sample of ophthalmology patients suggests that, like other medical patient populations, religion and spirituality are significant, and often positive, components of patients' value systems. Attention to religion and spirituality is one aspect of acknowledging and respecting a patient's value system and of establishing a relationship that promotes trust for making joint therapeutic decisions.


The diversity of measles virus in the United Kingdom, 1992-1995.
Three distinct genotypes were identified amongst 50 measles virus (MV) strains characterized in the UK between 1992 and 1995 by direct sequencing of the RT-PCR products amplified from clinical specimens. All three genotypes were related to viruses previously reported in the United States or in continental Europe. Phylogenetic analyses of 255 and 152 nucleotide sequences from the N and M genes, respectively, generated very similar lineages. The degree of divergence between genotypes was 3.5-16% and 2.6-7.9% in the N and the M genes, respectively. MV genotypes which circulated during the 1970s and 1980s in the UK were not detected in this period. Comparison of the C-terminal regions of the N gene sequences of UK strains isolated or detected between 1974 and 1995 suggests that there have been multiple genotypes of MV circulating in the UK over the past 20 years.


Sea water quality assessment of Prince Islands' beaches in Istanbul.
In this study, seawater samples were subjected to microbiological and physicochemical analysis (water temperature, pH, Secchi disc depth and ammonia) in the Prince Islands which are located in Marmara Sea, being one of the most popular swimming areas in Istanbul. The monitoring program of the study has been carried out in the summer for 6 weeks at eight stations around the Prince Islands. Measured total coliform values were between 5 ± 2 and 26 ± 55 and faecal coliform values were between 4 ± 2 and 24 ± 50 in the monitoring stations. A statistical study has been conducted to find the relationship between total and faecal coliform concentrations, and t tests were applied. There was no significant difference in each location of the Islands, except one location. The results were evaluated by comparing with national and EU bathing water standards. Results of the study show that deep sea discharges and sea currents contribute dilution of coliform concentration in a positive way, and locations near coastal zones of the islands have acceptable values which are required by the regulations.


Evaluation of the number of colony forming units on the skin of dogs after clipping the hair with two sizes of clipper blades.
To evaluate erythema and number of CFUs on the skin of dogs with hair clipped by use of 2 sizes of clipper blades. 67 client-owned dogs receiving an epidural. Hair was clipped with a No. 10 blade (approx hair length, 1.5 mm) on one half and a No. 40 blade (approx hair length, 0.25 mm) on the other half of each epidural site. Skin was surgically scrubbed with 2% chlorhexidine gluconate and 70% isopropyl alcohol. Samples were obtained immediately after clipping, after skin was scrubbed, and again 24 hours after clipping. Number of CFUs for both sides of the clipped areas, types of microorganisms, and growth on MacConkey agar were evaluated every 24 hours for 72 hours. Colonies were evaluated for bacterial morphology and Gram stain characteristics. Sites were evaluated 24 hours after clipping for evidence of erythema. 24 hours after hair was clipped, there was a significantly higher incidence of erythema and higher number of Micrococcaceae bacteria for the side clipped with the No. 40 blade than the side clipped with the No. 10 blade. Number of CFUs did not differ significantly between size of clipper blades. Clipping hair with a No. 40 blade resulted in a significant increase in the incidence of erythema and higher number of Micrococcaceae bacteria, compared with results for clipping with a No. 10 blade. These results supported use of a No. 10 clipper blade to prevent erythema and reduce variation in the skin microbiome.


Uncovering an intermediate phenotype associated with rs2200733 at 4q25 in lone atrial fibrillation.
Genomewide association studies have reproducibly identified rs2200733T on chromosome 4q25 as a risk factor for the most common sustained arrhythmia, atrial fibrillation (AF). The biologic basis for cardiac electrical instability conferred by this noncoding variant is unknown. The aim of this study was to investigate potential relations between rs2200733 versus clinical and electrocardiographic traits in a cohort of patients with early-onset AF who lack traditional risk factors. Congruent with previous reports, the minor T allele was overrepresented in subjects with lone AF. All genotype groups were statistically similar for age at diagnosis, gender distribution, family history, body mass index, AF type, ventricular rate, QRS duration, corrected QT interval, and use of PR interval--prolonging medications. However, a novel association was identified between the TT genotype and duration of the PR interval. The TT group had a mean PR interval of 189.5 ± 35.8 ms in comparison to mean PR intervals of 172.0 ± 29.0 and 171.0 ± 27.1 ms for the CT and CC groups, respectively (p = 0.013 and p = 0.0056). In conclusion, PR interval length, an established risk factor for AF, represents an rs2200733-associated intermediate phenotype.


Interaction of selenoprotein PA and the thioredoxin system, components of the NADPH-dependent reduction of glycine in Eubacterium acidaminophilum and Clostridium litorale [corrected].
Purification of protein PA of the glycine reductase complex from Eubacterium acidaminophilum and Clostridium litorale [corrected] was monitored by a new spectrophotometric assay. The procedure depended on a specific two- to threefold stimulation of a dihydrolipoamide dehydrogenase activity that is elicited by the interaction of a thioredoxin reductase-like flavoprotein and thioredoxin from both organisms. Protein PA isolated from E. acidaminophilum by 75Se labeling and monitoring of the dithioerythritol-dependent glycine reductase activity was identical in its biochemical, structural, and immunological properties to the protein isolated by using the stimulation assay. Proteins PA from both organisms were glycoproteins of Mr about 18,500 and exhibited very similar N-terminal amino acid sequences. Depletion of thioredoxin from crude extracts of E. acidaminophilum totally diminished the NADPH-dependent but not the dithioerythritol-dependent glycine reduction. The former activity could be fully restored by adding thioredoxin. Antibodies raised against the thioredoxin reductase-like flavoprotein or thioredoxin inhibited to a high extent NADPH-dependent but not dithioerythritol-dependent glycine reductase activity. These results indicate the involvement of the thioredoxin system in the electron flow from reduced pyridine nucleotides to glycine reductase.


[Periodic uveitis in horses].
The aetiology, clinical symptoms and treatment of equine periodic ophthalmia are discussed. Particular attention is paid to the possible role in aetiology of Onchocerca cervicalis microfilariae. Corticosteroids and atropine are the most important therapeutic drugs.


A Content Analysis of Multidimensional Support Needs Regarding Fertility Among Cancer Patients: How Can Nonphysician Health Care Providers Support?
This study aimed to identify support needs among young cancer patients regarding fertility-related issues to describe multidimensional support provided by nonphysician health care providers. Participants were cancer patients and their families who contacted the Hotline for Cancer Treatment and Reproduction at National Cancer Center Hospital in Japan. Medical charts were analyzed through content analysis. A total of 51 participants met the inclusion criteria, of which 32 cases (63%) involved patients themselves, 13 (25%) patients' family members, and 6 (12%) both patients and their families. About patients' demographic status, 40% of the patients were female and 28% were in their thirties. Gynecological and breast cancer patients were the majority, and 24 patients (47%) had not yet started cancer treatment. As a result of content analysis regarding support needs, 9 categories and 55 codes were extracted. The categories included information about risk of infertility, information about means to maintain reproductive function, referral to specialists, support for economic burden, support for worry about cancer progression, support for psychological distress upon facing the risk of infertility, support for communication with oncologists, support for family relationships, and decisional aid. This study suggests that nonphysician health care providers should acquire knowledge about fertility preservation and provide psychological support within their specialties.


Chronically elevated contact stress exposure correlates with intra-articular cartilage degeneration in patients with concurrent acetabular dysplasia and femoroacetabular impingement.
Hip dysplasia is known to lead to premature osteoarthritis. Computational models of joint mechanics have documented elevated contact stresses in dysplastic hips, but elevated stress has not been directly associated with regional cartilage degeneration. The purpose of this study was to determine if a relationship exists between elevated contact stress and intra-articular cartilage damage in patients with symptomatic dysplasia and femoroacetabular impingement. Discrete element analysis was used to compute hip contact stresses during the stance phase of walking gait for 15 patients diagnosed with acetabular dysplasia and femoral head-neck offset deformity. Contact stresses were summed over the duration of the walking gait cycle and then scaled by patient age to obtain a measure of chronic cartilage contact stress exposure. Linear regression analysis was used to evaluate the relationship between contact stress exposure and cartilage damage in each of six acetabular subregions that had been evaluated arthroscopically for cartilage damage at the time of surgical intervention. A significant correlation (R2 = 0.423, p < 0.001) was identified between chondromalacia grade and chronic stress-time exposure above both a 1 MPa damage threshold and a 2 MPa-years accumulated damage threshold. Furthermore, an over-exposure threshold of 15% regional contact area exceeding the 1 and 2 MPa-years threshold values resulted in correct identification of cartilage damage in 83.3% (55/66) of the acetabular subregions loaded during gait. These results suggest corrective surgery to alleviate impingement and reduce chronic contact stress exposures below these damage-inducing thresholds could mitigate further cartilage damage in patients with hip dysplasia.