Summary Background Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue ...terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. Methods In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7–30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. Results Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2·5% vs 3·0%, p=0·1). Two versus 13 (0·03% vs 0·22%, p=0·0020) were permanently disabled; total dead or disabled: 156 versus 190 (2·6% vs 3·2%, p=0·0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 1·6% vs 82/4426 1·9%, risk ratio 0·86 95% CI 0·63–1·18, p=0·35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 1·9% vs 57/1519 3·8%, risk ratio 0·49 95% CI 0·32–0·77, p=0·0013). Interpretation If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. Funding UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).
The benefits of many breakthroughs in biotechnology, health, and medicine have often been restricted by the high cost and the limited availability of tests and application devices. There is a need ...for low-cost bioassays for biotechnological applications and health diagnostics. To facilitate quality health care to resource-limited regions, the point-of-care devices needs to be affordable, sensitive, user-friendly, rapid, and robust. Paper is an ideal ingredient to develop disposable bioassay devices. Bioactive papers can be used to develop paper-based analytical devices for clinical diagnosis, assessing organ dysfunction, and detecting infectious diseases and microorganisms. Bioactive papers can also be used as antibacterial papers in healthcare and food packaging. At present the paper diagnostics is a multibillion-dollar market. Considering the product range and applications in health sector the market potential of bioactive papers is very high. Synchronized scientific and industrial research is needed to develop high quality and consistent commercial products from laboratory proof of concept.
VEGF-A is increased in exogenous endophthalmitis Seamone, Mark E., MSc, MD; Lewis, Darrell R., MD; Haidl, Ian D., PhD ...
Canadian journal of ophthalmology,
06/2017, Letnik:
52, Številka:
3
Journal Article
Recenzirano
Abstract Objective Exogenous endophthalmitis is an ophthalmologic emergency defined by panocular inflammation. Vascular endothelial growth factor A (VEGF-A) contributes to inflammation by promoting ...chemotaxis of monocytes and granulocytes and by increasing vascular permeability. The purpose of this article is to determine if VEGF-A is elevated in the vitreous samples obtained from individuals with exogenous endophthalmitis. Methods Vitreous samples from individuals with exogenous endophthalmitis (n = 18) were analyzed via Luminex assay and enzyme-linked immunosorbent assay for the cytokines VEGF-A, tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8 (chemokine CXCL-8), IL-1β, IL-10, IL-12p70, IL-33, interferon (IFN)-γ, IFN-α, IFN-β, chemokine ligand (CCL)-3, IL-2, IL-5, IL-15, CXCL-10, CCL-2, IL-1Ra, CCL-5, IL-17, and CCL-11. Vitreous samples obtained at the time of macular hole surgery served as controls (n = 8). Results Concentrations of VEGF-A were significantly elevated in vitreous samples from individuals with exogenous endophthalmitis compared with macular hole ( p < 0.001). VEGF-A was significantly upregulated in individuals with exogenous endophthalmitis after cataract surgery ( p = 0.001), vitrectomy ( p = 0.024), and intravitreal injection ( p = 0.012). VEGF-A concentrations were similar in both culture-positive and culture-negative populations ( p > 0.05). In a linear regression model, levels of VEGF-A correlated significantly with the chemokine CXCL-8 ( p = 0.028). Conclusions We demonstrate that VEGF-A is potently upregulated in exogenous endophthalmitis. This observation provides a foundation for future studies of targeted VEGF-A blockade in the management of endophthalmitis.
Abstract Heterotopic ossification has been reported to occur after musculoskeletal trauma (including orthopedic procedures). This has been known to cause nerve entrapment syndromes and persistent ...pain, limiting joint mobility. We present a case of a 19-year old female collegiate athlete who had previously undergone ankle arthroscopy and arthrotomy to remove 2 ossicles. At approximately 1 year postoperatively, the patient developed pain when planting and pivoting her foot. Imaging revealed a radiodense lesion at the posteromedial ankle consistent with heterotopic ossification and entrapment of the tibial nerve within the tarsal tunnel. The patient underwent surgical resection and postoperative indomethacin prophylaxis. At the 1-year follow-up visit, the patient remained asymptomatic, without evidence of recurrence of the heterotopic ossification. In our review of the published data, we found no previously reported cases of heterotopic ossification causing entrapment of the tibial nerve within the tarsal tunnel. In the present case report, we describe this rare case and the postulated etiologies and pathophysiology of this disease process. In addition, we discuss the clinical signs and symptoms and recommended imaging modalities and treatment.
Objectives The aim of this study was to evaluate the impact of renal function by estimated glomerular filtration rate (eGFR) on risk stratification of diabetic and nondiabetic patients undergoing ...myocardial perfusion imaging (MPI) by single-photon emission computed tomography for suspected ischemia. Background Coronary artery disease is the leading cause of death among diabetic persons; however, diabetic persons are a very heterogeneous group in terms of cardiovascular risk, necessitating further risk stratification. Methods Patients (n = 1,747, age 65 ± 10 years, 37% diabetic) undergoing MPI were followed for cardiac death (CD) for a mean of 2.15 ± 0.8 years. Chronic kidney disease (CKD) was defined by an eGFR <60 ml/min. Results In the presence of a normal scan, annual CD rate was 0.9% for those with no diabetes mellitus (DM) and no CKD, 0.5% in the DM alone group, 2.35% in CKD alone, and 2.9% in those with both DM and CKD (p < 0.001). Patients with DM+CKD had a 2.7-fold risk of CD compared with no DM no CKD (p = 0.001) after controlling for age, ejection fraction, history of coronary artery disease, and other risk factors. The risk of CD increased as a function of the presence and severity of perfusion defects, regardless of CKD or DM status. Presence of CKD conferred a several-fold higher risk of CD for the various strata of perfusion defects. Log-rank test for difference in probability of CD was nonsignificant for comparison between patients with no DM no CKD and those with DM alone (p = 0.73) but was significant for comparison between patients with no DM no CKD and patients with CKD alone (p < 0.001) or DM+CKD (p < 0.001). Conclusions MPI and eGFR provide valuable risk stratification for diabetic and nondiabetic patients. Diabetic patients without CKD seem to have similar short-term cardiac outcomes compared with nondiabetic patients. Underlying CKD seems to identify a high-risk subgroup of diabetic patients.
Abstract
Denitrification is mediated by microbial, and physicochemical, processes leading to nitrogen loss via N
2
O and N
2
emissions. Soil pH regulates the reduction of N
2
O to N
2
, however, it ...can also affect microbial community composition and functional potential. Here we simultaneously test the link between pH, community composition, and the N
2
O emission ratio (N
2
O/(NO + N
2
O + N
2
)) in 13 temperate pasture soils. Physicochemical analysis, gas kinetics, 16S rRNA amplicon sequencing, metagenomic and quantitative PCR (of denitrifier genes:
nirS, nirK, nosZI and nosZII
) analysis were carried out to characterize each soil. We found strong evidence linking pH to both N
2
O emission ratio and community changes. Soil pH was negatively associated with N
2
O emission ratio, while being positively associated with both community diversity and total denitrification gene (
nir
&
nos
) abundance. Abundance of
nosZII
was positively linked to pH, and negatively linked to N
2
O emissions. Our results confirm that pH imposes a general selective pressure on the entire community and that this results in changes in emission potential. Our data also support the general model that with increased microbial diversity efficiency increases, demonstrated in this study with lowered N
2
O emission ratio through more efficient conversion of N
2
O to N
2
.
A study on the detection of probable radionuclides and their activity concentrations in the raw material (phosphate rock), final product (fertilizer) and waste samples collected from all the ...phosphate fertilizer factories (total two factories-A Diammonium Phosphate, DAP and a Triple Super Phosphate, TSP factory) in Bangladesh were carried out. A total of seven types of samples (grossly divided into solid and liquid types); liquid waste, waste-mixed river water, normal river water, phosphate rock, phosphate fertilizer, solid waste and normal soil; were analyzed under this study. Raw material samples were collected only from the TSP fertilizer factory. Fertilizer, solid and liquid waste samples were collected from both the factories under study. Moreover, normal soil and natural surface water samples from the suitable areas adjacent to the factories were also collected for the comparison purpose. The samples were analyzed by gamma ray spectrometry technique using a Hyper-Pure Germanium (HPGe) detector of 40% relative efficiency. The analysis of the samples showed that only natural radionuclides such as super(226)Ra, super(232)Th and super(40)K were present in the samples and no traces of artificial radioactivity were found in any of the samples. super(40)K was found below the detection limit in some samples. The analysis of the samples in the case of TSP fertilizer factory showed that the average activity concentrations of super(226)Ra and super(232)Th and super(40)K in raw materials were 851.27 plus or minus 7.10, 19.63 plus or minus 6.57 and 54.06 plus or minus 5.93 Bq/kg, respectively, in final product 211.90 plus or minus 4.74, 42.48 plus or minus 10.56 Bq/kg and ND (Not Detected), respectively, in solid waste 187.49 plus or minus 4.88, 70.06 plus or minus 11.76 and 289.27 plus or minus 40.24 Bq/kg, respectively and in liquid waste 6.26 plus or minus 0.63, 10.01 plus or minus 1.39 Bq/L and ND, respectively. The measured results in the case of samples collected from DAP fertilizer factory showed that the average activity concentrations of super(226)Ra and super(232)Th and super(40)K in the final product were 17.31 plus or minus 3.92, 69.74 plus or minus 9.88 and 48.46 plus or minus 17.22 Bq/kg, respectively, in solid waste 24.47 plus or minus 4.15, 164.62 plus or minus 11.08, 191.52 plus or minus 33.74 Bq/kg, respectively and in liquid waste 3.59 plus or minus 1.05, 37.08 plus or minus 3.30 Bq/L and ND, respectively. Considering the stored raw materials and wastes the part of the ambient environment of the factory, radium equivalent activity, radiation hazard index and external annual effective dose to the workers and public due to these materials were also calculated and compared with world average values.
Background We compared 30-day and 1-year survival among high-risk mitral regurgitation (MR) patients treated with the MitraClip (Abbott Vascular, Abbott Park, IL) with matched non-surgically treated ...patients from the Duke Echocardiography Laboratory Database (DELD). Methods and Results High-risk patients with 3+/4+ MR managed non-surgically between years 2000 and 2010 in the longitudinal DELD were matched to high-risk MitraClip patients. Patient matching was performed using the method of nearest available Mahalanobis distance metric within calipers defined by the propensity score. Kaplan-Meier estimates and stratified Cox proportional hazards models were used to compare survival at 30 days and 1 year. Among 953 high-risk DELD patients available for matching, 30-day and 1-year mortality were 6.5% and 26.2%. Close matches were obtained for 239 of the 351 MitraClip patients. The 30-day mortality in MitraClip patients was lower (4.2%) when compared with matched DELD patients (7.2%). The 1-year relative risk of mortality of the MitraClip compared with non-surgical treatment was 0.64 (95% CI 0.45-0.91; log-rank P = .013). These results in favor of the MitraClip remained significant upon further adjustment for baseline differences between groups ( P = .043). Conclusions This matched comparison of severe MR patients at high surgical risk supports the safety of the MitraClip relative to medical therapy at 30 days and a survival benefit at 1 year.
Denitrification in pasture soils is mediated by microbial and physicochemical processes leading to nitrogen loss through the emission of N2O and N2. It is known that N2O reduction to N2 is impaired ...by low soil pH yet controversy remains as inconsistent use of soil pH measurement methods by researchers, and differences in analytical methods between studies, undermine direct comparison of results. In addition, the link between denitrification and N2O emissions in response to carbon (C) mineralization and pH in different pasture soils is still not well described. We hypothesized that potential denitrification rate and aerobic respiration rate would be positively associated with soils. This relationship was predicted to be more robust when a high resolution analysis is performed as opposed to a single time point comparison. We tested this by characterizing 13 different temperate pasture soils from northern and southern hemispheres sites (Ireland and New Zealand) using a fully automated-high-resolution GC detection system that allowed us to detect a wide range of gas emissions simultaneously. We also compared the impact of using different extractants for determining pH on our conclusions. In all pH measurements, soil pH was strongly and negatively associated with both N2O production index (IN2O) and N2O/(N2O+N2) product ratio. Furthermore, emission kinetics across all soils revealed that the denitrification rates under anoxic conditions (NO+N2O+N2 μmol N/h/vial) were significantly associated with C mineralization (CO2 μmol/h/vial) measured both under oxic (r2 = 0.62, p = 0.0015) and anoxic (r2 = 0.89, p<0.0001) conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intensively managed agricultural pastures contribute to N
O and N
fluxes resulting in detrimental environmental outcomes and poor N use efficiency, respectively. Besides nitrification, ...nitrifier-denitrification and heterotrophic denitrification, alternative pathways such as codenitrification also contribute to emissions under ruminant urine-affected soil. However, information on codenitrification is sparse. The objectives of this experiment were to assess the effects of soil moisture and soil inorganic-N dynamics on the relative contributions of codenitrification and denitrification (heterotrophic denitrification) to the N
O and N
fluxes under a simulated ruminant urine event. Repacked soil cores were treated with
N enriched urea and maintained at near saturation (-1 kPa) or field capacity (-10 kPa). Soil inorganic-N, pH, dissolved organic carbon, N
O and N
fluxes were measured over 63 days. Fluxes of N
, attributable to codenitrification, were at a maximum when soil nitrite (NO
) concentrations were elevated. Cumulative codenitrification was higher (P = 0.043) at -1 kPa. However, the ratio of codenitrification to denitrification did not differ significantly with soil moisture, 25.5 ± 15.8 and 12.9 ± 4.8% (stdev) at -1 and -10 kPa, respectively. Elevated soil NO
concentrations are shown to contribute to codenitrification, particularly at -1 kPa.
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