A man with hypophosphataemia

Case report; A section on BMJ, 2011, v. 342, p. 715published_or_final_versio

Pesticide Leaching from Agricultural Fields with Ridges and Furrows

In the evaluation of the risk of pesticide leaching to groundwater, the soil surface is usually assumed to be level, although important crops like potato are grown on ridges. A fraction of the water from rainfall and sprinkler irrigation may flow along the soil surface from the ridges to the furrows, thus bringing about an extra load of water and pesticide on the furrow soil. A survey of the literature reveals that surface-runoff from ridges to furrows is a well-known phenomenon but that hardly any data are available on the quantities of water and pesticide involved. On the basis of a field experiment with additional sprinkler irrigation, computer simulations were carried out with the Pesticide Emission Assessment at Regional and Local scales model for separate ridge and furrow systems in a humic sandy potato field. Breakthrough curves of bromide ion (as a tracer for water flow) and carbofuran (as example pesticide) were calculated for 1-m depth in the field. Bromide ion leached comparatively fast from the furrow system, while leaching from the ridge system was slower showing a maximum concentration of about half of that for the furrow system. Carbofuran breakthrough from the furrow system began about a month after application and increased steadily to substantial concentrations. Because the transport time of carbofuran in the ridge soil was much longer, no breakthrough occurred in the growing season. The maximum concentration of carbofuran leaching from the ridge–furrow field was computed to be a factor of six times as high as that computed for the corresponding level field. The study shows that the risk of leaching of pesticides via the furrow soil can be substantially higher than that via the corresponding level field soil

The influence of long-term treadmill exercise on bone mass and articular cartilage in ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>Loss of bone quality and deterioration of articular cartilage are commonly seen after menopause. While exercise may protect against tissue degeneration, a clear link has yet to be established. The aim of the present study is to investigate the influence of long-term treadmill exercise on changes in bone mass and articular cartilage in ovariectomized rats.</p> <p>Methods</p> <p>Sixty female Sprague-Dawley rats were randomly assigned to 4 groups: ovariectomized (OVX), ovariectomized plus treadmill exercise (OVX-RUN), treadmill exercise alone (RUN), and control (CON) groups. After 36 weeks, the following variables were compared among the 4 groups. Bone mass was evaluated by trabecular bone volume and bone mineral density (BMD). Articular cartilage in the knee joints was evaluated by histology analysis and a modified Mankin score.</p> <p>Results</p> <p>Rats in the ovariectomized groups (OVX and OVX-RUN) had significantly lower BMD and bone mass than the non-ovariectomized rats (CON and RUN), indicating that exercise did little to preserve bone mass. However, the sedentary OVX group had a significantly worse modified Mankin score (7.7 ± 1.4) than the OVX-RUN group (4.8 ± 1.0), whose scores did not differ significantly from the other 2 non-operated groups. The articular cartilage in the sedentary OVX rats was relatively thinner, hypocellular, and had more clefts than in the other 3 groups.</p> <p>Conclusion</p> <p>This study suggests that long-term exercise protects articular cartilage in OVX rats but does not retard the loss of bone mass seen in after menopause.</p

What have transgenic and knockout animals taught us about respiratory disease?

Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokines and growth related peptides in disease pathogenesis. Furthermore, the receptors and the intracellular signalling pathways that are subsequently activated are amenable for study because of the availability of monoclonal antibodies and techniques for targeted gene disruption and gene incorporation for individual mediators, receptors and proteins. However, it is clear that extrapolation from these models to the human condition is not straightforward, as reflected by some recent clinical disappointments. This is not necessarily a problem with the use of mice itself, but results from our continued ignorance of the disease process and how to improve the modelling of complex interactions between different inflammatory mediators that underlie clinical pathology. This review highlights some of the strengths and weaknesses of murine models of respiratory disease

Identification of alternative splice variants in Aspergillus flavus through comparison of multiple tandem MS search algorithms

<p>Abstract</p> <p>Background</p> <p>Database searching is the most frequently used approach for automated peptide assignment and protein inference of tandem mass spectra. The results, however, depend on the sequences in target databases and on search algorithms. Recently by using an alternative splicing database, we identified more proteins than with the annotated proteins in <it>Aspergillus flavus</it>. In this study, we aimed at finding a greater number of eligible splice variants based on newly available transcript sequences and the latest genome annotation. The improved database was then used to compare four search algorithms: Mascot, OMSSA, X! Tandem, and InsPecT.</p> <p>Results</p> <p>The updated alternative splicing database predicted 15833 putative protein variants, 61% more than the previous results. There was transcript evidence for 50% of the updated genes compared to the previous 35% coverage. Database searches were conducted using the same set of spectral data, search parameters, and protein database but with different algorithms. The false discovery rates of the peptide-spectrum matches were estimated < 2%. The numbers of the total identified proteins varied from 765 to 867 between algorithms. Whereas 42% (1651/3891) of peptide assignments were unanimous, the comparison showed that 51% (568/1114) of the RefSeq proteins and 15% (11/72) of the putative splice variants were inferred by all algorithms. 12 plausible isoforms were discovered by focusing on the consensus peptides which were detected by at least three different algorithms. The analysis found different conserved domains in two putative isoforms of UDP-galactose 4-epimerase.</p> <p>Conclusions</p> <p>We were able to detect dozens of new peptides using the improved alternative splicing database with the recently updated annotation of the <it>A. flavus </it>genome. Unlike the identifications of the peptides and the RefSeq proteins, large variations existed between the putative splice variants identified by different algorithms. 12 candidates of putative isoforms were reported based on the consensus peptide-spectrum matches. This suggests that applications of multiple search engines effectively reduced the possible false positive results and validated the protein identifications from tandem mass spectra using an alternative splicing database.</p

Rapid, Specific Detection of Alphaviruses from Tissue Cultures Using a Replicon-Defective Reporter Gene Assay

We established a rapid, specific technique for detecting alphaviruses using a replicon-defective reporter gene assay derived from the Sindbis virus XJ-160. The pVaXJ expression vector containing the XJ-160 genome was engineered to form the expression vectors pVaXJ-EGFP expressing enhanced green fluorescence protein (EGFP) or pVaXJ-GLuc expressing Gaussia luciferase (GLuc). The replicon-defective reporter plasmids pVaXJ-EGFPΔnsp4 and pVaXJ-GLucΔnsp4 were constructed by deleting 1139 bp in the non-structural protein 4 (nsP4) gene. The deletion in the nsP4 gene prevented the defective replicons from replicating and expressing reporter genes in transfected BHK-21 cells. However, when these transfected cells were infected with an alphavirus, the non-structural proteins expressed by the alphavirus could act on the defective replicons in trans and induce the expression of the reporter genes. The replicon-defective plasmids were used to visualize the presence of alphavirus qualitatively or detect it quantitatively. Specificity tests showed that this assay could detect a variety of alphaviruses from tissue cultures, while other RNA viruses, such as Japanese encephalitis virus and Tahyna virus, gave negative results with this system. Sensitivity tests showed that the limit of detection (LOD) of this replicon-defective assay is between 1 and 10 PFU for Sindbis viruses. These results indicate that, with the help of the replicon-defective alphavirus detection technique, we can specifically, sensitively, and rapidly detect alphaviruses in tissue cultures. The detection technique constructed here may be well suited for use in clinical examination and epidemiological surveillance, as well as for rapid screening of potential viral biological warfare agents

A descriptive study of older adults with persistent pain: Use and perceived effectiveness of pain management strategies [ISRCTN11899548]

BACKGROUND: Persistent pain is a common, often debilitating, problem in older adults; however, few studies have focused on the experiences of older adults in managing their pain. The objective of this study was to describe the use and perceived effectiveness of pain management strategies in a sample of older adults and to explore the associations of these variables with demographic and psychosocial characteristics. METHODS: Adults ≥ 65 years old and living in retirement facilities who reported persistent pain (N = 235, mean age = 82 years, 84% female, 94% white) completed measures of demographics, pain, depression, self-efficacy for managing pain, and a Pain Management Strategies Survey. Participants identified current and previous-year use of 42 pain management strategies and rated helpfulness of each on a 5-point scale. RESULTS: Acetaminophen, regular exercise, prayer, and heat and cold were the most frequently used pain management strategies (61%, 58%, 53%, and 48%, respectively). Strategies used by >25% of the sample that were rated moderately or more helpful (i.e., >2 on a 0 to 4 scale) were prayer [mean (SD) = 2.9 (0.9)], opioids [2.6 (0.8)], regular exercise [2.5 (1.0)], heat/cold [2.5 (1.0)], nonsteroidal anti-inflammatory drugs [2.4 (1.0)], and acetaminophen [2.3 (1.0)]. Young-old (65–74 years) study participants reported use of more strategies than did old-old (85+ years) participants (p = .03). Perceived helpfulness of strategy use was significantly associated with pain intensity (r = -.14, p < .0001), self-efficacy (r = .28, p < .0001), and depression (r = -.20, p = .003). CONCLUSION: On average, older adults view the strategies they use for persistent pain as only moderately helpful. The associations between perceived helpfulness and self-efficacy and depression suggest avenues of pain management that are focused less on specific treatments and more on how persons with persistent pain think about their pain

Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) and serine biosynthetic pathway genes are co-ordinately increased during anabolic agent-induced skeletal muscle growth

We aimed to identify novel molecular mechanisms for muscle growth during administration of anabolic agents. Growing pigs (Duroc/(Landrace/Large-White)) were administered Ractopamine (a beta-adrenergic agonist; BA; 20ppm in feed) or Reporcin (recombinant growth hormone; GH; 10mg/48hours injected) and compared to a control cohort (feed only; no injections) over a 27-day time course (1, 3, 7, 13 or 27-days). Longissimus Dorsi muscle gene expression was analyzed using Agilent porcine transcriptome microarrays and clusters of genes displaying similar expression profiles were identified using a modified maSigPro clustering algorithm. Anabolic agents increased carcass (p=0.002) and muscle weights (Vastus Lateralis: p<0.001; Semitendinosus: p=0.075). Skeletal muscle mRNA expression of serine/one-carbon/glycine biosynthesis pathway genes (Phgdh, Psat1 and Psph) and the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase-M (Pck2/PEPCK-M), increased during treatment with BA, and to a lesser extent GH (p<0.001, treatment x time interaction). Treatment with BA, but not GH, caused a 2-fold increase in phosphoglycerate dehydrogenase (PHGDH) protein expression at days 3 (p<0.05) and 7 (p<0.01), and a 2-fold increase in PEPCK-M protein expression at day 7 (p<0.01). BA treated pigs exhibit a profound increase in expression of PHGDH and PEPCK-M in skeletal muscle, implicating a role for biosynthetic metabolic pathways in muscle growth

Early glandular neoplasia of the lung

Although bronchogenic carcinomas progress through a very well defined sequence of metaplasia, dysplasia and carcinoma in situ, very little is known about the early progression of glandular neoplasms of the lung. In particular, the early precursor lesion from which fully malignant adenocarcinomas arise has effectively eluded recognition, at least until recently. Several lines of evidence now implicate atypical adenomatous hyperplasia (AAH) as an initial morphologic stage in multistep lung tumorigenesis. Despite its small size, AAH can be appreciated at the light microscopic level and characterized at the molecular genetic level. Indeed, the genetic characterization of AAH promises to further our understanding of lung cancer development and might facilitate the design of novel strategies for early detection of lung cancer

Association of temporal factors and suicides in the United States, 2000–2004

The purpose of the study was to examine the association of temporal factors, in particular days of the week and seasons of the year and death from suicide in the United States. Data were pooled from the Multiple Cause of Death Files. Hierarchical logistic regression models were fitted to all deaths occurring in 2000 through 2004 by suicide. The incidence of suicide was significantly higher on Wednesdays, compared to Sunday. Specifically, individuals were 99% more likely to kill themselves on Wednesday than on Sunday. Suicides were more prevalent in the summer months, and they were less likely to occur in winter. The state suicide rate significantly elevated individual suicide risk. The results held even after controlling for the potentially confounding effects of socio-economic and demographic variables at both the individual and state levels. It was concluded that the observed association between seasonality and suicide cannot be discounted as a mere coincidence. Future research ought to focus on integrating individual level data and contextual variables when testing for seasonality effects