Measurement of serum haptoglobin as an indicator of the efficacy of malaria intervention trials

Serum haptoglobin levels were measured by an enzyme-linked immunosorbent assay in Gambian children who participated in 3 malaria intervention trials with untreated or impregnated bed nets. In one study, in which a significant effect on clinical malaria was observed, the mean serum haptoglobin level was significantly higher in the intervention than in the control group. In the other 2 studies, in which no significant protection was observed, mean haptoglobin levels were similar in intervention and control groups. Measurement of serum haptoglobin may provide a useful indirect measure of the effectiveness of malaria control programme

Cell-Associated HIV-1 RNA in Blood as Indicator of Virus Load in Lymph Nodes

We have developed sensitive assays for viremia and cell-associated human immunodeficiency virus type 1 (HIV-1) RNA and DNA to assess the predictive value of virological parameters determined in blood for virus load in lymph nodes (LNs). Eighteen patients were included; 13 received stavudine/didanosine/hydroxyurea and 5 stavudine/didanosine, and all had viremia 3 months. At the time of LN biopsy (median, 10 months), the median viremia was 2.09 log copies/mL (range, <0.70-3.34). Cell-associated HIV-1 RNA and DNA were detectable in blood and LNs of all patients. The median cell-associated RNA and DNA were 2.16 log copies/106 cells and 2.60 log copies/106 cells in blood versus 4.31 log RNA copies/106 cells and 3.26 log DNA copies/106 cells in LNs. Regression analysis shows that, in treated patients with sustained low viremia, cell-associated RNA and DNA in blood are better predictors of virus load in LNs than viremi

Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults

Background. Cystatin C, a marker of renal function, has been shown to be an independent predictor of cardiovascular disease (CVD) in older adults, but few data are available in middle-aged adults. Moreover, no study has compared cystatin C and microalbuminuria as risk factors for CVD outcomes in middle-aged adults, and it is not known whether cystatin C is related to an early stage of atherosclerosis. Methods. We evaluated the relationships between serum creatinine, estimated glomerular filtration rate (GFR), serum cystatin C (all divided into tertiles), microalbuminuria and carotid atherosclerosis in a population-based random sample of 523 adults aged 35-64 years from the Seychelles (Indian Ocean). GFR was estimated using the modification of diet in renal disease (MDRD) equation. Intima-media thickness (IMT) was assessed by B-mode ultrasound. Results. The mean age of the study sample was 52 years, and 55% were women. Carotid IMT was higher in participants with microalbuminuria (802 vs 732 μm, P < 0.001) and was inversely associated with GFR tertiles (from 728 to 809 μm, P for trend = 0.002). IMT was not associated with cystatin C or creatinine (P for trend = 0.10 and 0.16, respectively). In multivariate analyses adjusted for cardiovascular risk factors, the association between microalbuminuria and IMT remained (P = 0.047), while the association between GFR and IMT disappeared (P for trend = 0.33). Conclusions. Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis beyond traditional cardiovascular risk factors among middle-aged adults. Cystatin C does not have a stronger relationship with carotid atherosclerosis in middle-aged adults than creatinin

Pattern formation in auxin flux

The plant hormone auxin is fundamental for plant growth, and its spatial distribution in plant tissues is critical for plant morphogenesis. We consider a leading model of the polar auxin flux, and study in full detail the stability of the possible equilibrium configurations. We show that the critical states of the auxin transport process are composed of basic building blocks, which are isolated in a background of auxin depleted cells, and are not geometrically regular in general. The same model was considered recently through a continuous limit and a coupling to the von Karman equations, to model the interplay of biochemistry and mechanics during plant growth. Our conclusions might be of interest in this setting, since, for example, we establish the existence of Lyapunov functions for the auxin flux, proving in this way the convergence of pure transport processes toward the set of equilibrium points

c-FOS drives reversible basal to squamous cell carcinoma transition.

While squamous transdifferentiation within subpopulations of adenocarcinomas represents an important drug resistance problem, its underlying mechanism remains poorly understood. Here, using surface markers of resistant basal cell carcinomas (BCCs) and patient single-cell and bulk transcriptomic data, we uncover the dynamic roadmap of basal to squamous cell carcinoma transition (BST). Experimentally induced BST identifies activator protein 1 (AP-1) family members in regulating tumor plasticity, and we show that c-FOS plays a central role in BST by regulating the accessibility of distinct AP-1 regulatory elements. Remarkably, despite prominent changes in cell morphology and BST marker expression, we show using inducible model systems that c-FOS-mediated BST demonstrates reversibility. Blocking EGFR pathway activation after c-FOS induction partially reverts BST in vitro and prevents BST features in both mouse models and human tumors. Thus, by identifying the molecular basis of BST, our work reveals a therapeutic opportunity targeting plasticity as a mechanism of tumor resistance

Minority Quasispecies of Drug-Resistant HIV-1 That Lead to Early Therapy Failure in Treatment-Naive and -Adherent Patients

Background.Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. Methods.We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. Results.Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07% 2.0%. A range of 1 4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. Conclusions.Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure in treatment-naive patients who receive antiretroviral therapy regimens with a low genetic resistance barrie

Reduced-iodine-dose dual-energy coronary CT angiography: qualitative and quantitative comparison between virtual monochromatic and polychromatic CT images.

To quantitatively evaluate the impact of virtual monochromatic images (VMI) on reduced-iodine-dose dual-energy coronary computed tomography angiography (CCTA) in terms of coronary lumen segmentation in vitro, and secondly to assess the image quality in vivo, compared with conventional CT obtained with regular iodine dose. A phantom simulating regular and reduced iodine injection was used to determine the accuracy and precision of lumen area segmentation for various VMI energy levels. We retrospectively included 203 patients from December 2017 to August 2018 (mean age, 51.7 ± 16.8 years) who underwent CCTA using either standard (group A, n = 103) or reduced (group B, n = 100) iodine doses. Conventional images (group A) were qualitatively and quantitatively compared with 55-keV VMI (group B). We recorded the location of venous catheters. In vitro, VMI outperformed conventional CT, with a segmentation accuracy of 0.998 vs. 1.684 mm &lt;sup&gt;2&lt;/sup&gt; , respectively (p &lt; 0.001), and a precision of 0.982 vs. 1.229 mm &lt;sup&gt;2&lt;/sup&gt; , respectively (p &lt; 0.001), in simulated overweight adult subjects. In vivo, the rate of diagnostic CCTA in groups A and B was 88.4% (n = 91/103) vs. 89% (n = 89/100), respectively, and noninferiority of protocol B was inferred. Contrast-to-noise ratios (CNR) of lumen versus fat and muscle were higher in group B (p &lt; 0.001) and comparable for lumen versus calcium (p = 0.423). Venous catheters were more often placed on the forearm or hand in group B (p &lt; 0.001). In vitro, low-keV VMI improve vessel area segmentation. In vivo, low-keV VMI allows for a 40% iodine dose and injection rate reduction while maintaining diagnostic image quality and improves the CNR between lumen versus fat and muscle. • Dual-energy coronary CT angiography is becoming increasingly available and might help improve patient management. • Compared with regular-iodine-dose coronary CT angiography, reduced-iodine-dose dual-energy CT with low-keV monochromatic image reconstructions performed better in phantom-based vessel cross-sectional segmentation and proved to be noninferior in vivo. • Patients receiving reduced-iodine-dose dual-energy coronary CT angiography often had the venous catheter placed on the forearm or wrist without compromising image quality

Fetal cardiac cine magnetic resonance imaging in utero.

Fast magnetic resonance imaging (MRI) led to the emergence of 'cine MRI' techniques, which enable the visualization of the beating heart and the assessment of cardiac morphology and dynamics. However, established cine MRI methods are not suitable for fetal heart imaging in utero, where anatomical structures are considerably smaller and recording an electrocardiogram signal for synchronizing MRI data acquisition is difficult. Here we present a framework to overcome these challenges. We use methods for image acquisition and reconstruction that robustly produce images with sufficient spatial and temporal resolution to detect the heart contractions of the fetus, enabling a retrospective gating of the images and thus the generation of images of the beating heart. To underline the potential of our approach, we acquired in utero images in six pregnant patients and compared these with their echocardiograms. We found good agreement in terms of diameter and area measurements, and low inter- and intra- observer variability. These results establish MRI as a reliable modality for fetal cardiac imaging, with a substantial potential for prenatal evaluation of congenital heart defects

Predictors for the Emergence of the 2 Multi-nucleoside/nucleotide Resistance Mutations 69 Insertion and Q151M and their Impact on Clinical Outcome in the Swiss HIV Cohort Study

The 69 insertion and Q151M mutations are multi-nucleoside/nucleotide resistance mutations (MNR). The prevalence among 4078 antiretroviral therapy (ART)-experienced individuals was <1.3%. Combined ART fully prevented MNR in subtype B infections. Case-control studies were performed to identify risk factors. Control subjects were patients with ≥3 thymidine-analogue mutations. The 69 insertion study (27 control subjects, 14 case patients) identified didanosine exposure as a risk (odds ratio, 5.0 per year; P = .019), whereas the Q151M study (which included 44 control subjects and 25 case patients) detected no associations. Following detection, individuals with Q151M tended to have lower suppression rates and higher mortality rates, relative to control subjects. Additional studies are needed to verify these findings in non-subtype B infection