Sensitivity and Specificity of Cystatin C in Detecting Early Renal Impairment in Hypertensive Pregnancies

Purpose: To determine the cutoff point of cystatin C for the detection of renal impairment in hypertensive pregnancies.Methods: A cross-sectional study was conducted in an antenatal clinic and ward at Hospital Universiti Sains Malaysia, Kelantan, Malaysia from January 2009 until January 2010. Sixty four pregnant patients beginning at 2nd trimester, aged of 16 to 55 years and hypertensive, including gestational hypertension, chronic hypertension with superimposed preeclampsia, preeclampsia and unclassified hypertension, were included in the study. Consenting patients were required to provide 5 ml of blood and 24-h urine. Serum and reagent, N Latex cystatin C, were equilibrated at room temperature and measured by particle-enhanced nephelometric immunoassay (PENIA) using a BN II Dade Behring Nephelometer SystemResults: The mean age of the patients was 37.06 ±4.32 (range: 24 to 46 years). A majority (64.1 %) of the patients were in the second trimester of pregnancy and delivered in the gestational period of 38 - 40 weeks (54.7 %). The number of patients in chronic kidney disease (CKD) stages I, II, III, IV and V were 25 (39.1 %), 18 (28.1 %), 18 (28.1 %), 2 (3.1 %) and 1 (1.6 %), respectively. The mean systolic blood pressure was 149.59 ± 18.79 mm Hg, and diastolic blood pressure 91.53 ± 10.33 mm Hg. The cutoff point in detecting renal impairment using cystatin C was > 0.74 with 84.6 % sensitivity and 86.7 % specificity for second trimester and > 0.81 with sensitivity of 76.9 % and specificity of 60.0 % in detecting renal impairment for third trimester.Conclusion: The cutoff point in detecting renal impairment for second trimester is better than for third trimester since it maximizes the value of sensitivity and specificity.Keywords: Cystatin C, Sensitivity, Specificity, Renal impairment, Hypertension; Pregnanc

Trends in hospital-based management of acute asthma from a teaching hospital in South Asia.

The aim of this study is to evaluate the hospital-based management of acute asthma in south Asia and to compare practices over a 10-year period. Adult patients (n = 102) admitted at a teaching hospital with acute asthma were studied. Documentation of precipitating factors, family history and physical signs were inadequate in more than half of patients. Pulse oximetry was documented in 95 (93%) patients, but peak flow monitoring was performed only in 50 (49%) patients. Ten-year trend showed deterioration in history and physical examination skills, under use of peak flow readings, and poor pre-discharge instructions. Some aspects of improved care included frequent use of pulse oximeter, preference of inhaled over systemic bronchodilators and increased use of systemic steroids. Significant deficiencies were identified in hospital-based management of acute asthma. Most aspects of asthma care continued to fall short of asthma guidelines

Global health education in U.S. medical schools.

Interest in global health (GH) among medical students worldwide is measurably increasing. There is a concomitant emphasis on emphasizing globally-relevant health professions education. Through a structured literature review, expert consensus recommendations, and contact with relevant professional organizations, we review the existing state of GH education in US medical schools for which data were available. Several recommendations from professional societies have been developed, along with a renewed emphasis on competencies in global health. The implementation of these recommendations was not observed as being uniform across medical schools, with variation noted in the presence of global health curricula. Recommendations for including GH in medical education are suggested, as well as ways to formalize GH curricula, while providing flexibility for innovation and adaptation.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Impacts of biological globalization in the Mediterranean: Unveiling the deep history of human-mediated gamebird dispersal

Humans have a long history of moving wildlife that over time has resulted in unprecedented biotic homogenization. It is, as a result, often unclear whether certain taxa are native to a region or naturalized, and how the history of human involvement in species dispersal has shaped present-day biodiversity. Although currently an eastern Palaearctic galliform, the black francolin (Francolinus francolinus) was known to occur in the western Mediterranean from at least the time of Pliny the Elder, if not earlier. During Medieval times and the Renaissance, the black francolin was a courtly gamebird prized not only for its flavor, but also its curative, and even aphrodisiac qualities. There is uncertainty, however, whether this important gamebird was native or introduced to the region and, if the latter, what the source of introduction into the western Mediterranean was. Here we combine historical documentation with a DNA investigation of modern birds and archival (13th–20th century) specimens from across the species’ current and historically documented range. Our study proves the black francolin was nonnative to the western Mediterranean, and we document its introduction from the east via several trade routes, some reaching as far as South Asia. This finding provides insight into the reach and scope of long-distance trade routes that serviced the demand of European aristocracy for exotic species as symbols of wealth and prestige, and helps to demonstrate the lasting impact of human-mediated long-distance species dispersal on current day biodiversity

MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation

G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand–receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice with Apln, Aplnr or endothelial-specific Aplnr deletion develop profound retinal vascular defects, which are at least in part due to dysregulated increase in endothelial CXCR4 expression. Endothelial CXCR4 is negatively regulated by miR-139-5p, whose transcription is in turn induced by laminar flow and APLN/APLNR signalling. Inhibition of miR-139-5p in vivo partially phenocopies the retinal vascular defects of APLN/APLNR deficiency. Pharmacological inhibition of CXCR4 signalling or augmentation of the miR-139-5p-CXCR4 axis can ameliorate the vascular phenotype of APLN/APLNR deficient state. Overall, we identify an important microRNA-mediated GPCR crosstalk, which plays a key role in vascular development

Polyimide Electrode-Based Electrical Stimulation Impedes Early Stage Muscle Graft Regeneration

Given the increasing use of regenerative free muscle flaps for various reconstructive procedures and neuroprosthetic applications, there is great interest and value in their enhanced regeneration, revascularization, and reinnervation for improved functional recovery. Here, we implant polyimide-based mircroelectrodes on free flap grafts and perform electrical stimulation for 6 weeks in a murine model. Using electrophysiological and histological assessments, we compare outcomes of stimulated grafts with unstimulated control grafts. We find delayed reinnervation and abnormal electromyographic (EMG) signals, with significantly more polyphasia, lower compound muscle action potentials and higher fatigability in stimulated animals. These metrics are suggestive of myopathy in the free flap grafts stimulated with the electrode. Additionally, active inflammatory processes and partial necrosis are observed in grafts stimulated with the implanted electrode. The results suggest that under this treatment protocol, implanted epimysial electrodes and electrical stimulation to deinnervated, and devascularized flaps during the early recovery phase may be detrimental to regeneration. Future work should determine the optimal implantation and stimulation window for accelerating free muscle graft regeneration

Macrophage Notch Ligand Delta-Like 4 Promotes Vein Graft Lesion Development, Implications for the Treatment of Vein Graft Failure

Objective—Despite its large clinical impact, the underlying mechanisms for vein graft failure remain obscure and no effective therapeutic solutions are available. We tested the hypothesis that Notch signaling promotes vein graft disease. Approach and Results—We used 2 biotherapeutics for Delta-like ligand 4 (Dll4), a Notch ligand: (1) blocking antibody and (2) macrophage- or endothelial cell (EC)–targeted small-interfering RNA. Dll4 antibody administration for 28 days inhibited vein graft lesion development in low-density lipoprotein (LDL) receptor-deficient (Ldlr−/−) mice, and suppressed macrophage accumulation and macrophage expression of proinflammatory M1 genes. Dll4 antibody treatment for 7 days after grafting also reduced macrophage burden at day 28. Dll4 silencing via macrophage-targeted lipid nanoparticles reduced lesion development and macrophage accumulation, whereas EC-targeted Dll4 small-interfering RNA produced no effects. Gain-of-function and loss-of-function studies suggested in vitro that Dll4 induces proinflammatory molecules in macrophages. Macrophage Dll4 also stimulated smooth muscle cell proliferation and migration and suppressed their differentiation. Conclusions—These results suggest that macrophage Dll4 promotes lesion development in vein grafts via macrophage activation and crosstalk between macrophages and smooth muscle cells, supporting the Dll4–Notch axis as a novel therapeutic target.United States. National Institutes of Health (R01HL107550)American Heart Association (0655878T)American Heart Association (12GRNT9510001)American Heart Association (12GRNT1207025)Good Samaritan FoundationShapiro Family Foundatio

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood–brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting. Recent discoveries in the genetic and epigenetic determinants of BTIC tumorigenesis offer novel opportunities for RNAi-mediated targeting of BTICs. Here we show that BTIC growth arrest in vitro and in vivo is accomplished via concurrent siRNA knockdown of four transcription factors (SOX2, OLIG2, SALL2, and POU3F2) that drive the proneural BTIC phenotype delivered by multiplexed siRNA encapsulation in the lipopolymeric nanoparticle 7C1. Importantly, we demonstrate that 7C1 nano-encapsulation of multiplexed RNAi is a viable BTIC-targeting strategy when delivered directly in vivo in an established mouse brain tumor. Therapeutic potential was most evident via a convection-enhanced delivery method, which shows significant extension of median survival in two patient-derived BTIC xenograft mouse models of GBM. Our study suggests that there is potential advantage in multiplexed targeting strategies for BTICs and establishes a flexible nonviral gene therapy platform with the capacity to channel multiplexed RNAi schemes to address the challenges posed by tumor heterogeneity. Keywords: siRNA; lipopolymeric nanoparticle; glioblastoma transcription factor; brain tumor-initiating; cells; convection-enhanced deliver

Tetraazamacrocyclic derivatives and their metal complexes as antileishmanial leads

© 2019 A total of 44 bis-aryl-monocyclic polyamines, monoaryl-monocyclic polyamines and their transition metal complexes were prepared, chemically characterized, and screened in vitro against the Leishmania donovani promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells. The IC 50 and/or IC 90 values showed that 10 compounds were similarly active at about 2-fold less potent than known drug pentamidine against promastigotes. The most potent compound had an IC 50 of 2.82 µM (compared to 2.93 µM for pentamidine). Nine compounds were 1.1–13.6-fold more potent than pentamidine against axenic amastigotes, the most potent one being about 2-fold less potent than amphotericin B. Fourteen compounds were about 2–10 fold more potent than pentamidine, the most potent one is about 2-fold less potent than amphotericin B against intracellular amastigotes in THP1 cells. The 2 most promising compounds (FeL7Cl 2 and MnL7Cl 2 ), with strong activity against both promastigotes and amastigotes and no observable toxicity against the THP1 cells are the Fe 2+ - and Mn 2+ -complexes of a dibenzyl cyclen derivative. Only 2 of the 44 compounds showed observable cytotoxicity against THP1 cells. Tetraazamacrocyclic monocyclic polyamines represent a new class of antileishmanial lead structures that warrant follow up studies

28.2%-efficient, outdoor-stable perovskite/silicon tandem solar cell

Stacking perovskite solar cells onto crystalline silicon bottom cells in a monolithic tandem configuration enables power-conversion efficiencies (PCEs) well above those of their single-junction counterparts. However, state-of-the-art wide-band-gap perovskite films suffer from phase stability issues. Here, we show how carbazole as an additive to the perovskite precursor solution can not only reduce nonradiative recombination losses but, perhaps more importantly, also can suppress phase segregation under exposure to moisture and light illumination. This enables a stabilized PCE of 28.6% (independently certified at 28.2%) for a monolithic perovskite/silicon tandem solar cell over ∼1 cm2 and 27.1% over 3.8 cm2, built from a textured silicon heterojunction solar cell. The modified tandem devices retain ∼93% of their performance over 43 days in a hot and humid outdoor environment of almost 100% relative humidity over 250 h under continuous 1-sun illumination and about 87% during a 85/85 damp-heat test for 500 h, demonstrating the improved phase stability