A novel COMP mutation in a pseudoachondroplasia family of Chinese origin

<p>Abstract</p> <p>Background</p> <p>Pseudoachondroplasia (PSACH) is caused exclusively by mutations in the gene for cartilage oligomeric matrix protein (<it>COMP</it>). Only a small number of studies have documented the clinical phenotype and genetic basis in Chinese PSACH patients.</p> <p>Case presentation</p> <p>We investigated a four-generation PSACH pedigree of Chinese Han origin. Two patients and two unaffected individuals were recruited for clinical evaluation and molecular genetic analysis. The genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction (PCR) was adopted to amplify the 8-19 exons of <it>COMP </it>gene. Then the products were sequenced bi-directionally for screening mutation. Clinical evaluation revealed that PSACH patients in this pedigree had a severe disproportionate short stature (-10SD). A heterozygous TGTCCCTGG insertion in exon 13, between nucleotide 1352T and 1353G, were identified in the patients except the unaffected individuals, which resulted in a three-amino-acid insertion (451V_452P ins VPG) in the sixth calmodulin-like repeat of the <it>COMP </it>protein.</p> <p>Conclusion</p> <p>This c. 1352_1353ins TGTCCCTGG is a novel mutation responsible for severe familial PSACH.</p

Use of eHealth technologies to enable the implementation of musculoskeletal Models of Care: Evidence and practice

Musculoskeletal (MSK) conditions are the second leading cause of morbidity-related burden of disease globally. EHealth is a potentially critical factor that enables the implementation of accessible, sustainable and more integrated MSK models of care (MoCs). MoCs serve as a vehicle to drive evidence into policy and practice through changes at a health system, clinician and patient level. The use of eHealth to implement MoCs is intuitive, given the capacity to scale technologies to deliver system and economic efficiencies, to contribute to sustainability, to adapt to low-resource settings and to mitigate access and care disparities. We follow a practice-oriented approach to describing the ‘what’ and ‘how’ to harness eHealth in the implementation of MSK MoCs. We focus on the practical application of eHealth technologies across care settings to those MSK conditions contributing most substantially to the burden of disease, including osteoarthritis and inflammatory arthritis, skeletal fragility-associated conditions and persistent MSK pain

Central nervous system and muscular bundles preserved in a 240 million year old giant bristletail (Archaeognatha: Machilidae)

Among the incomparably diverse group of insects no cases of central nervous system (CNS) preservation have been so far described in compression fossils. A third of the fossil insects collected from a 240-239 million year old (Ma) level at Monte San Giorgio UNESCO World Heritage (SwitzerlandItaly) underwent phosphatization, resulting in the extraordinary preservation of soft tissues. Here we describe Gigamachilis triassicus gen. et sp. nov. (Archaeognatha: Machiloidea: Machilidae) that, with an estimated total length of similar to 80 millimeters, represents the largest apterygote insect ever recorded. The holotype preserves: (i) components of the CNS represented by four abdominal ganglia, optic lobes with neuropils and compound retina;(ii) muscular bundles. Moreover, G. triassicus, possessing morphological features that prompt its assignment to the extant archaeognathan ingroup Machilidae, places the origin of modern lineages to Middle Triassic. Interestingly, at Monte San Giorgio, in the same stratigraphic unit the modern morphology of G. triassicus co-occurs with the ancient one represented by Dasyleptus triassicus (Archaeognatha: dagger Monura). Comparing these two types of body organization we provide a new reconstruction of the possible character evolution leading towards modern archaeognathan forms, suggesting the acquisition of novel features in a lineage of apterygote insects during the Permian or the Lower Triassic

Approach to the Immunosuppressed Patient with Pulmonary Infiltrates

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65614/1/j.1365-4362.1980.tb00811.x.pd

Dihydroartemisinin-Piperaquine vs. Artemether-Lumefantrine for First-Line Treatment of Uncomplicated Malaria in African Children: A Cost-Effectiveness Analysis.

Recent multi-centre trials showed that dihydroartemisinin-piperaquine (DP) was as efficacious and safe as artemether-lumefantrine (AL) for treatment of young children with uncomplicated P. falciparum malaria across diverse transmission settings in Africa. Longitudinal follow-up of patients in these trials supported previous findings that DP had a longer post-treatment prophylactic effect than AL, reducing the risk of reinfection and conferring additional health benefits to patients, particularly in areas with moderate to high malaria transmission. We developed a Markov model to assess the cost-effectiveness of DP versus AL for first-line treatment of uncomplicated malaria in young children from the provider perspective, taking into consideration the post-treatment prophylactic effects of the drugs as reported by a recent multi-centre trial in Africa and using the maximum manufacturer drug prices for artemisinin-based combination therapies set by the Global Fund in 2013. We estimated the price per course of treatment threshold above which DP would cease to be a cost-saving alternative to AL as a first-line antimalarial drug. First-line treatment with DP compared to AL averted 0.03 DALYs (95% CI: 0.006-0.07) and 0.001 deaths (95% CI: 0.00-0.002) and saved $0.96 (95$1.23 per course of treatment. DP is superior to AL from both the clinical and economic perspectives for treatment of uncomplicated P. falciparum malaria in young children. A paediatric dispersible formulation of DP is under development and should facilitate a targeted deployment of this antimalarial drug. The use of DP as first-line antimalarial drug in paediatric malaria patients in moderate to high transmission areas of Africa merits serious consideration by health policymakers

The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases

Background There are a lack of reliable data on the epidemiology and associated burden and costs of asthma. We sought to provide the first UK-wide estimates of the epidemiology, healthcare utilisation and costs of asthma. Methods We obtained and analysed asthma-relevant data from 27 datasets: these comprised national health surveys for 2010–11, and routine administrative, health and social care datasets for 2011–12; 2011–12 costs were estimated in pounds sterling using economic modelling. Results The prevalence of asthma depended on the definition and data source used. The UK lifetime prevalence of patient-reported symptoms suggestive of asthma was 29.5 % (95 % CI, 27.7–31.3; n = 18.5 million (m) people) and 15.6 % (14.3–16.9, n = 9.8 m) for patient-reported clinician-diagnosed asthma. The annual prevalence of patient-reported clinician-diagnosed-and-treated asthma was 9.6 % (8.9–10.3, n = 6.0 m) and of clinician-reported, diagnosed-and-treated asthma 5.7 % (5.7–5.7; n = 3.6 m). Asthma resulted in at least 6.3 m primary care consultations, 93,000 hospital in-patient episodes, 1800 intensive-care unit episodes and 36,800 disability living allowance claims. The costs of asthma were estimated at least £1.1 billion: 74 % of these costs were for provision of primary care services (60 % prescribing, 14 % consultations), 13 % for disability claims, and 12 % for hospital care. There were 1160 asthma deaths. Conclusions Asthma is very common and is responsible for considerable morbidity, healthcare utilisation and financial costs to the UK public sector. Greater policy focus on primary care provision is needed to reduce the risk of asthma exacerbations, hospitalisations and deaths, and reduce costs

Measurement and Computation of Movement of Bromide Ions and Carbofuran in Ridged Humic-Sandy Soil

Water flow and pesticide transport in the soil of fields with ridges and furrows may be more complex than in the soil of more level fields. Prior to crop emergence, the tracer bromide ion and the insecticide carbofuran were sprayed on the humic-sandy soil of a potato field with ridges and furrows. Rainfall was supplemented by sprinkler irrigation. The distribution of the substances in the soil profile of the ridges and furrows was measured on three dates in the potato growing season. Separate ridge and furrow systems were simulated by using the pesticide emission assessment at regional and local scales (PEARL) model for pesticide behavior in soil–plant systems. The substances travelled deeper in the furrow soil than in the ridge soil, because of runoff from the ridges to the furrows. At 19 days after application, the peak of the bromide distribution was measured to be in the 0.1–0.2 m layer of the ridges, while it was in the 0.3–0.5 m layer of the furrows. After 65 days, the peak of the carbofuran distribution in the ridge soil was still in the 0.1 m top layer, while the pesticide was rather evenly distributed in the top 0.6 m of the furrow soil. The wide ranges in concentration measured with depth showed that preferential water flow and substance transport occurred in the sandy soil. Part of the bromide ion distribution was measured to move faster in soil than the computed wave. The runoff of water and pesticide from the ridges to the furrows, and the thinner root zone in the furrows, are expected to increase the risk of leaching to groundwater in ridged fields, in comparison with more level fields

A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616]

BACKGROUND: IgAN is the most common type of glomerulonephritis in the world. Between 15 and 40 percent of adults and children diagnosed with IgAN eventually progress to ESRD. Despite the need for effective treatment strategies, very few RCTs for IgAN have been performed. The most effective therapies for IgAN appear to be corticosteroids, ACEi, and FOS that contain a high concentration of omega 3 fatty acids. While ACEi and FOS are generally well tolerated with minimal side effects, the use of high dose steroids over a long course of therapy is often associated with significant morbidity. OBJECTIVE OF THE STUDY: The objective of the study is to test the hypothesis that treatment with the immunosuppressive agent, MMF, will lead to significant and sustained improvement in urinary protein excretion in patients with IgAN who have been pre-treated (and continue to be treated) with ACE(i )and FOS compared to a placebo control group of patients receiving comparable doses of ACEi and FOS without MMF. DESIGN: After a three month treatment period with the ACEi, lisinopril and the FOS, Omacor(®), 100 (2 × 50) patients with IgAN and a urinary P/C ratio ≥ 0.6 (males) and ≥ 0.8 (females) and an estGFR ≥ 40 ml/min/1.73 m2 will be randomized to treatment with either MMF or placebo for one year. All patients will be followed off study drug for a second year, but will continue treatment with lisinopril and Omacor(® )for the two year duration of the study. The primary outcome measure of change in urine P/C ratio will be assessed at the end of years one and two

The Sleeping Brain's Influence on Verbal Memory: Boosting Resistance to Interference

Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater after sleep than after wakefulness. And when using interference testing, that difference was even more pronounced. By introducing interference after sleep, this study confirms an experimental paradigm that demonstrates the active role of sleep in consolidating memory, and unmasks the large magnitude of that benefit