Differentiation of Schistosoma haematobium from related schistosomes by PCR amplifying an inter-repeat sequence.

Schistosoma haematobium infects nearly 150 million people, primarily in Africa, and is transmitted by select species of local bulinid snails. These snails can host other related trematode species as well, so that effective detection and monitoring of snails infected with S. haematobium requires a successful differentiation between S. haematobium and any closely related schistosome species. To enable differential detection of S. haematobium DNA by simple polymerase chain reaction (PCR), we designed and tested primer pairs from numerous newly identified Schistosoma DNA repeat sequences. However, all pairs tested were found unsuitable for this purpose. Differentiation of S. haematobium from S. bovis, S. mattheei, S. curassoni, and S. intercalatum (but not from S. margrebowiei) was ultimately accomplished by PCR using one primer from a newly identified repeat, Sh110, and a second primer from a known schistosomal splice-leader sequence. For evaluation of residual S. haematobium transmission after control interventions, this differentiation tool will enable accurate monitoring of infected snails in areas where S. haematobium is sympatric with the most prevalent other schistosome species

Adult Congenital Heart Disease in the Veteran Population: A Case-Based Report

Simple forms of congenital heart disease can allow patients to go undiagnosed until they reach adulthood. Furthermore, improvements in care of patients with complex congenital heart disease are now allowing most patients to reach adulthood. As some patients with adult congenital heart disease can remain asymptomatic until later in life, it is possible for them to serve in the military and eventually fall under the care of Veterans Administration (VA) providers. Therefore it is important for providers, especially cardiologists at VA centers, to have fundamental understanding of the management of adult congenital heart disease. This article provides multiple cases of adult congenital heart disease experienced at a single VA medical center and reviews the anatomy, physiology, and surgical management of each condition

Application of Global Positioning Measurements to Continental Collision in the Pamir-Tien Shan Region, Central Asia and GPS Survey of the Western Tien Shan

In this report, we summarize what we have accomplished with five years of funding from NASA under its DOSE program, and with a comparable level of funding from NSF. We describe the development of a GPS network in the Tien Shan of Kyrgyzstan and Kazakhstan of the former Soviet Union, the analysis of data, and the main results. This discussion presents the state of the current network, which has grown significantly since the termination of our DOSE grants, with continued support both from NSF through its continental dynamics program and from NASA's SENH program. Although grants from NASA's DOSE program did not support this growth not directly, it did so indirectly by building the infrastructure that has enabled further expansion in an area where otherwise there would be only a small GPS presence. We note how the network has grown over time, but the emphasis of this discussion is on the quantity and quality of measurements that we have made

GPS survey of the western Tien Shan

There were two major developments in 1994 in our collaborative GPS experiment in the Tien Shan of the Former Soviet Union (FSU). Both were motivated by our expectation that we will ultimately obtain better science at lower cost if we involve our colleagues in the FSU more deeply in (1) the collection and (2) the analysis of data. As an experimental test of the concept of having our local collaborators carry out the field work semi-autonomously, we sent 6 MIT receivers to the Tien Shan for a period of 3 months. To enable our collaborators to have the capability for data analysis, we provided computers for two data analysis centers and organized a two-week training session. This report emphasizes the rationale for deeper involvement of FSU scientists, describes the training sessions, discusses the data collection, and presents the results. We also discuss future plans. More detailed discussion of background, general scientific objectives, discussions with collaborators, and results for the campaigns in 1992 and 1993 have been given in previous reports

Nodule Organogenesis and Symbiotic Mutants of the Model Legume \u3ci\u3eLotus japonicus\u3c/i\u3e

A detailed microscopical analysis of the morphological features that distinguish different developmental stages of nodule organogenesis in wild-type Lotus japonicus ecotype Gifu B-129-S9 plants was performed, to provide the necessary framework for the evaluation of altered phenotypes of L. japonicus symbiotic mutants. Subsequently, chemical ethyl methanesulfonate (EMS) mutagenesis of L. japonicus was carried out. The analysis of approximately 3,000 M1 plants and their progeny yielded 20 stable L. japonicus symbiotic variants, consisting of at least 14 different symbiosis- associated loci or complementation groups. Moreover, a mutation affecting L. japonicus root development was identified that also conferred a hypernodulation response when a line carrying the corresponding allele (LjEMS102) was inoculated with rhizobia. The phenotype of the LjEMS102 line was characterized by the presence of nodule structures covering almost the entire root length (Nod++), and by a concomitant inhibition of both root and stem growth. A mutation in a single nuclear gene was shown to be responsible for both root and symbiotic phenotypes observed in the L. japonicus LjEMS102 line, suggesting that (a) common mechanism(s) regulating root development and nodule formation exists in legumes

Importance of obesity, race and age to the cardiac structural and functional effects of hypertension

AbstractObjectives. The purpose of this study was to determine the effects of obesity and its interaction with age, race and the magnitude of blood pressure elevation in a large cohort of patients with mild to moderate hypertension and a high prevalence of left ventricular hypertrophy.Background. Obesity, race and age each have important effects on the incidence and severity of hypertension and may contribute to the effects of blood pressure elevation on the cardiac manifestations of hypertension.Methods. Left ventricular structure and function were assessed with two-dimensional targeted M-mode echocardiography in 692 men with mild to moderate hypertension (average blood pressure 153/100 mm Hg), and the data were compared in relation to obesity (determined from body mass index), age, race, blood pressure, physical activity, plasma renin activity, urinary sodium excretion, hematocrit, heart rate and serum lipids.Results. Left ventricular hypertrophy was common (630% with increased left ventricular mass, 22% with left ventricular hypertrophy on the electrocardiogram [ECG]). On multivariable regression analysis, body mass index was the strongest predictor of left ventricular mass and magnified the slope relation of blood pressure to left ventricular mass. Despite a greater prevalence of ECG left ventricular hypertrophy in blacks (31%) than in whites (10%), left ventricular mass and echocardiographic prevalence of left ventricular hypertrophy did not differ by race. However, septal, posterior left ventricular and relative wall thickness were greater in black than in white men.Conclusions. Obesity is the strongest clinical predictor of left ventricular mass and left ventricular hypertrophy la men, even in those with mild to moderate hypertension of sufficient severity to be associated with a high prevalence of left ventricular hypertrophy. Moreover, independent effects of systolic blood pressure on left ventricular mass an amplified by obesity. Although race does not affect left ventricular mass or the prevalence of left ventricular hypertrophy, black race is associated with greater relative wall thickness, itself a predictor of unfavorable cardiovascular outcome

Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: Two randomized controlled trials

Context Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)–conjugated mammalian recombinant uricase, was developed to fulfill this need. Objective To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. Design, Setting, and Patients Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. Intervention Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). Main Outcome Measure Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. Results In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). Conclusion Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo

Local IRBs vs. Federal Agencies: Shifting Dynamics, Systems, and Relationships

How IRBs relate to federal agencies, and the implications of these relationships, have received little, if any, systematic study. I interviewed 46 IRB chairs, directors, administrators, and members, contacting the leadership of 60 U.S. IRBs (every fourth one in the list of the top 240 institutions by NIH funding), interviewing IRB leaders from 34 (response rate=55%). IRBs describe complex direct and indirect relationships with federal agencies that affect IRBs through audits, guidance documents, and other communications, and can generate problems and challenges. Researchers often blame IRBs for frustrations, but IRBs often serve as the “local face” of federal regulations and agencies and are “stuck in the middle.” These data have critical implications for policy, practice, and research

Intrinsically determined cell death of developing cortical interneurons

Cortical inhibitory circuits are formed by GABAergic interneurons, a cell population that originates far from the cerebral cortex in the embryonic ventral forebrain. Given their distant developmental origins, it is intriguing how the number of cortical interneurons is ultimately determined. One possibility, suggested by the neurotrophic hypothesis1-5, is that cortical interneurons are overproduced, and then following their migration into cortex, excess interneurons are eliminated through a competition for extrinsically derived trophic signals. Here we have characterized the developmental cell death of mouse cortical interneurons in vivo, in vitro, and following transplantation. We found that 40% of developing cortical interneurons were eliminated through Bax- (Bcl-2 associated X-) dependent apoptosis during postnatal life. When cultured in vitro or transplanted into the cortex, interneuron precursors died at a cellular age similar to that at which endogenous interneurons died during normal development. Remarkably, over transplant sizes that varied 200-fold, a constant fraction of the transplanted population underwent cell death. The death of transplanted neurons was not affected by the cell-autonomous disruption of TrkB (tropomyosin kinase receptor B), the main neurotrophin receptor expressed by central nervous system (CNS) neurons6-8. Transplantation expanded the cortical interneuron population by up to 35%, but the frequency of inhibitory synaptic events did not scale with the number of transplanted interneurons. Together, our findings indicate that interneuron cell death is intrinsically determined, either cell-autonomously, or through a population-autonomous competition for survival signals derived from other interneurons