Efficacy and Safety Of Radiation Synovectomy with Yttrium-90

In this long term retrospective study of radiation synovectomy with Yttrium-90 (Y90), we evaluated the results of 164 applications in 82 patients with RA, OA with synovitis, ankylosing spondylitis and psoriatic arthritis. Radiation synovectomy with Y90 has an overall success rate of approximately 50% and is therefore an effective alternative to surgical synovectomy in chronic synovitis which fails to respond to conservative treatment. Elbow and knee responded significantly better than shoulder and ankle joints. Patients with radiological stages from 0 to 2 showed a significantly better success rate than those with stage 3 changes. In responders, repeat therapy for recurrence of symptoms or treatment of a symptomatic corresponding symmetrical joint is advisable. Repeat therapy in a previous non-responder is associated with an unacceptably high failure rate. Therefore, when a joint fails to respond after 6 months, arthroscopy should be performed to evaluate further treatment procedures. A successful result was found in only 11 of 25 joints treated with arthroscopic synovectomy followed by radiation synovectomy within 2 weeks, indicating no benefit of this combination

EFFICACY AND SAFETY OF RADIATION SYNOVECTOMY WITH YTTRIUM-90: A RETROSPECTIVE LONG-TERM ANALYSIS OF 164 APPLICATIONS IN 82 PATIENTS

In this long term retrospective study of radiation synovectomy with Yttrium-90 (Y90), we evaluated the results of 164 applications in 82 patients with RA, OA with synovitis, ankylosing spondylitis and psoriatic arthritis. Radiation synovectomy with Y90 has an overall success rate of approximately 50% and is therefore an effective alternative to surgical synovectomy in chronic synovitis which fails to respond to conservative treatment. Elbow and knee responded significantly better than shoulder and ankle joints. Patients with radiological stages from 0 to 2 showed a significantly better success rate than those with stage 3 changes. In responders, repeat therapy for recurrence of symptoms or treatment of a symptomatic corresponding symmetrical joint is advisable. Repeat therapy in a previous non-responder is associated with an unacceptably high failure rate. Therefore, when a joint fails to respond after 6 months, arthroscopy should be performed to evaluate further treatment procedures. A successful result was found in only 11 of 25 joints treated with arthroscopic synovectomy followed by radiation synovectomy within 2 weeks, indicating no benefit of this combinatio

Platelet-Induced Clumping of Plasmodium falciparum–Infected Erythrocytes from Malawian Patients with Cerebral Malaria—Possible Modulation In Vivo by Thrombocytopenia

Platelets may play a role in the pathogenesis of human cerebral malaria (CM), and they have been shown to induce clumping of Plasmodium falciparum–parasitized red blood cells (PRBCs) in vitro. Both thrombocytopenia and platelet-inducedPRBCclumping are associated with severe malaria and, especially, withCM.In the present study, we investigated the occurrence of the clumping phenomenon in patients with CM by isolating and coincubating their plasma and PRBCs ex vivo. Malawian children with CM all had low platelet counts, with the degree of thrombocytopenia directly proportional to the density of parasitemia. Plasma samples obtained from these patients subsequently induced weak PRBC clumping. When the assays were repeated, with the plasma platelet concentrations adjusted to within the physiological range considered to be normal, massive clumping occurred. The results of this study suggest that thrombocytopenia may, through reduction of platelet-mediated clumping of PRBCs, provide a protective mechanism for the host during CM

Preliminary Report of the AMS analysis of tsunami deposits in Tohoku – Japan – 18 th to the 21 st Century

Sedimentary records of tsunamis are a precious tool to assess the occurrence of past events, as attested by an abundant literature, which has seen a particular 'boom' in the aftermath of the 2004 Indian Ocean tsunami and the 2011 Tohoku tsunami. Despite an extensive literature, there is very little to no understanding of the role that the changing coastal environment is playing on the record of a tsunami, and for a given location, it is still unclear whether the largest tsunamis leave the largest amount of deposits. To research this question, the present study took place in Japan, in the Tohoku Region at Agawa-pond, because the pond act as a sediment trap. Using a sediment-slicer, a 1 m thick deposit was retrieved, from which 4 tsunami sequences were identified, including the latest 2011 tsunami. Using a series of sedimentary proxies: the AMS (Anisotropy of Magnetic Susceptibility), grain size analysis, quartz morphoscopy (morphology and surface characteristics) and the analysis of microfossils, disparities between the tsunami deposits were identified and most importantly a clear thinning of the tsunami deposit towards the top. Provided the present evidences, the authors discuss that the upward fining is due to at least two components that are seldom assessed in tsunami research (1) a modification of the depositional environment, with the progressive anthropization of the coast, providing less sediments to remobilize; and (2) a progressive filling of the Agawa pond, which progressively loses its ability to trap tsunami materials

Endotension is Influenced by Wall Compliance in a Latex Aneurysm Model

AbstractObjectives. Even though endovascular aneurysm repair (EVAR) creates a closed chamber except for patent branches, the intra-sac pressure is never zero. This study was designed to investigate whether, and to what extent, aneurysm wall compliance influences intra-sac pressure.Design. In vitro experimental study.Methods. Aneurysm models with six and 12 latex layers were produced, resulting in elastic and stiff circumferential compliance (3.5±0.5 and 0.9±0.3%/100 mmHg, respectively). The models with an 18 mm internal neck and maximum aneurysm diameter of 60 mm were inserted into an in vitro circulation system. The systemic mean pressure (SPmean) was varied from 50 to 120 mmHg. After the aneurysm was excluded with a knitted polyethylene graft, aneurysm sac mean pressure (ASPmean) and aneurysm sac pulse pressure (ASPpulse) were measured. Data are presented as mean±SD. Statistics were performed using repeated measurements of variance; p<0.05 was considered significant.Results. In the model EVAR created a closed chamber without endoleak, but with an aneurysm sac pressure related to wall compliance. In the elastic aneurysm model with six latex coats the aneurysm sac mean pressure (ASPmean) and the aneurysm sac pulse pressure (ASPpulse) at all systemic pressures were significantly lower than they were in the stiffer model with 12 latex coats (p<0.05). At a SPmean of 90 mmHg, the ASPmean was 21.0±0.9 mmHg (six latex coats) and 26.0±0.2 mmHg (12 latex coats) (p<0.05), the ASPpulse was 5.7±0.2 mmHg (six latex coats) and 8.8±0.3 mmHg (12 latex coats) (p<0.05).Conclusions. This in vitro model demonstrated that the aneurysm sac mean pressure (ASPmean) and the aneurysm sac pulse pressure (ASPpulse) were significantly influenced by the compliance of the aneurysm wall. These data highlight the need for further studies regarding endotension

Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency

Background Isolated complex II deficiency is a rare form of mitochondrial disease, accounting for approximately 2% of all respiratory chain deficiency diagnoses. The succinate dehydrogenase (SDH) genes (SDHA, SDHB, SDHC and SDHD) are autosomally-encoded and transcribe the conjugated heterotetramers of complex II via the action of two known assembly factors (SDHAF1 and SDHAF2). Only a handful of reports describe inherited SDH gene defects as a cause of paediatric mitochondrial disease, involving either SDHA (Leigh syndrome, cardiomyopathy) or SDHAF1 (infantile leukoencephalopathy). However, all four SDH genes, together with SDHAF2, have known tumour suppressor functions, with numerous germline and somatic mutations reported in association with hereditary cancer syndromes, including paraganglioma and pheochromocytoma. Methods and results Here, we report the clinical and molecular investigations of two patients with histochemical and biochemical evidence of a severe, isolated complex II deficiency due to novel SDH gene mutations; the first patient presented with cardiomyopathy and leukodystrophy due to compound heterozygous p.Thr508Ile and p.Ser509Leu SDHA mutations, while the second patient presented with hypotonia and leukodystrophy with elevated brain succinate demonstrated by MR spectroscopy due to a novel, homozygous p.Asp48Val SDHB mutation. Western blotting and BN-PAGE studies confirmed decreased steady-state levels of the relevant SDH subunits and impairment of complex II assembly. Evidence from yeast complementation studies provided additional support for pathogenicity of the SDHB mutation. Conclusions Our report represents the first example of SDHB mutation as a cause of inherited mitochondrial respiratory chain disease and extends the SDHA mutation spectrum in patients with isolated complex II deficiency

A Method for Amplicon Deep Sequencing of Drug Resistance Genes in Plasmodium falciparum Clinical Isolates from India.

A major challenge to global malaria control and elimination is early detection and containment of emerging drug resistance. Next-generation sequencing (NGS) methods provide the resolution, scalability, and sensitivity required for high-throughput surveillance of molecular markers of drug resistance. We have developed an amplicon sequencing method on the Ion Torrent PGM platform for targeted resequencing of a panel of six Plasmodium falciparum genes implicated in resistance to first-line antimalarial therapy, including artemisinin combination therapy, chloroquine, and sulfadoxine-pyrimethamine. The protocol was optimized using 12 geographically diverse P. falciparum reference strains and successfully applied to multiplexed sequencing of 16 clinical isolates from India. The sequencing results from the reference strains showed 100% concordance with previously reported drug resistance-associated mutations. Single-nucleotide polymorphisms (SNPs) in clinical isolates revealed a number of known resistance-associated mutations and other nonsynonymous mutations that have not been implicated in drug resistance. SNP positions containing multiple allelic variants were used to identify three clinical samples containing mixed genotypes indicative of multiclonal infections. The amplicon sequencing protocol has been designed for the benchtop Ion Torrent PGM platform and can be operated with minimal bioinformatics infrastructure, making it ideal for use in countries that are endemic for the disease to facilitate routine large-scale surveillance of the emergence of drug resistance and to ensure continued success of the malaria treatment policy

Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

Advances in Basic and Translational Research as Part of the Center for the Study of Complex Malaria in India.

The Center for the Study of Complex Malaria in India (CSCMi) is one of 10 International Centers of Excellence in Malaria Research funded by the National Institutes of Health since 2010. The Center combines innovative research with capacity building and technology transfer to undertake studies with clinical and translational impact that will move malaria control in India toward the ultimate goal of malaria elimination/eradication. A key element of each research site in the four states of India (Tamil Nadu, Gujarat, Odisha, and Meghalaya) has been undertaking community- and clinic-based epidemiology projects to characterize the burden of malaria in the region. Demographic and clinical data and samples collected during these studies have been used in downstream projects on, for example, the widespread use of mosquito repellants, the population genomics of Plasmodium vivax, and the serological responses to P. vivax and Plasmodium falciparum antigens that reflect past or present exposure. A focus has been studying the pathogenesis of severe malaria caused by P. falciparum through magnetic resonance imaging of cerebral malaria patients. Here we provide a snapshot of some of the basic and applied research the CSCMi has undertaken over the past 12 years and indicate the further research and/or clinical and translational impact these studies have had

Platelets Alter Gene Expression Profile in Human Brain Endothelial Cells in an In Vitro Model of Cerebral Malaria

Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM) in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC) and human brain microvascular endothelial cells (HBEC) and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF) and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM