Circulating microvesicles miR139-3p from bronchopulmonary dysplasia aggravates pulmonary vascular simplification by targeting 4E binding protein 1.

BACKGROUND: Microvesicles (MVs) play a crucial role in bronchopulmonary dysplasia (BPD). There are many MVs in circulating plasma, and they are in direct contact with lung endothelial cells. However, the molecular mechanism and causative effect of circulating MVs on BPD remain unclear. METHODS: Clinical plasma samples were collected, circulating MVs were isolated, and microRNA (miRNA) sequencing was performed. The BPD model was established, and different MVs were administered. Alveoli and pulmonary vessels were examined by hematoxylin-eosin staining, and body weight and length were measured. In vitro, gene expression was disrupted by miRNA mimics, miRNA inhibitors or plasmid transfection. Cell proliferation and protein expression were detected by cell scratch assay, accurate 5-ethynyl-2-deoxyuridine test, western blotting, or immunofluorescence assay. RESULTS: BPD-derived MVs further aggravated pulmonary vascular simplification, while circulating MVs from control mice mitigated pulmonary vascular simplification. Micro-RNA sequencing and independent sample verification revealed that miR139-3p, but not miR6125 or miR193b-3p, was the most critical effector molecule in MVs. Mechanism studies showed that eukaryotic translation initiation factor 4E binding protein 1 was the target gene for miR139-3p. In addition, we found that supplementation of miR139-3p inhibitor partially alleviated pulmonary vascular simplification. CONCLUSIONS: These results indicate that circulating MVs are involved in forming BPD by carrying miR139-3p molecules and support miR139-3p inhibitors as a potential therapeutic strategy for alleviating pulmonary vascular simplification in BPD.

Improvement in insulin sensitivity after switching from an integrase inhibitor-based regimen to doravirine/tenofovir disoproxil fumarate/lamivudine in people with significant weight gain.

OBJECTIVES: We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. METHODS: All non-diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were evaluated every 6 months during a 12-month follow-up. RESULTS: Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA-IR index was 3.18 and insulin resistance (HOMA-IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (-3.54 mcrUI/L [interquartile range -4.22 to -2.87]; p = 0.012), associated with a significant reduction in mean HOMA-IR index (-0.54 [interquartile range -0.91 to -0.18]; p = 0.021). A significant reduction in total and low-density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. CONCLUSIONS: In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight.

Balloon predilation or direct valve implantation in TAVI for women: Insights from the DIRECTAVI study.

BACKGROUND: The randomized DIRECTAVI trial demonstrated safety and feasibility of transcatheter aortic valve implantation (TAVI) without balloon aortic valvuloplasty (BAV) using SAPIEN 3 balloon-expandable devices. However, the female population with smaller anatomy may have potential higher risk of residual gradient and/or mismatch. PURPOSE: We assessed the impact of BAV on the procedural success rate and clinical outcomes in the female population of the DIRECTAVI trial. METHODS: Between May 2016 and May 2018, 91 of the 250 patients included in the DIRECTAVI trial were women (38.6%), 45 of them (49.5%) were enrolled in the BAV group and 46 of them (50.5%) in the direct TAVI group. The primary endpoint was procedural success rate in women (Valve Academic Research Consortium-2 criteria). The secondary endpoint included evaluation of PPM and 1-month major adverse events according to the implantation stategy in women and comparison between men and women regarding major endpoints. RESULTS: The primary endpoint occurred in 29 women (64.4%) in the BAV group and in 34 women (73.9%) in the direct TAVI group (mean difference 9.47%; 95% confidence interval: 6.5%-25.4%; p = 0.045 for non-inferiority of the direct strategy). One-month major adverse events were similar between the 2 women groups. Procedural success was lower in women vs men (p = 0.01) due to higher incidence of moderate mismatches in women (p = 0.001) but with no significant difference regarding the implantation strategy (p = 0.4). CONCLUSION: Direct implantation of the balloon-expandable SAPIEN 3 valve was non-inferior to predilatation on procedural success in women. Incidence of moderate mismatch was higher in women but was not related to the implantation strategy.

Out of shape: Ocean acidification simplifies coral reef architecture and reshuffles fish assemblages.

Climate change stressors are progressively simplifying biogenic habitats in the terrestrial and marine realms, and consequently altering the structure of associated species communities. Here, we used a volcanic CO2 seep in Papua New Guinea to test in situ if altered reef architecture due to ocean acidification reshuffles associated fish assemblages. We observed replacement of branching corals by massive corals at the seep, with simplified coral architectural complexity driving abundance declines between 60% and 86% for an assemblage of damselfishes associated with branching corals. An experimental test of habitat preference for a focal species indicated that acidification does not directly affect habitat selection behaviour, with changes in habitat structural complexity consequently appearing to be the stronger driver of assemblage reshuffling. Habitat health affected anti-predator behaviour, with P. moluccensis becoming less bold on dead branching corals relative to live branching corals, irrespective of ocean acidification. We conclude that coral reef fish assemblages are likely to be more sensitive to changes in habitat structure induced by increasing pCO2 than any direct effects on behaviour, indicating that changes in coral architecture and live cover may act as important mediators of reef fish community structures in a future ocean.

Generative Pre-trained Transformer 4 makes cardiovascular magnetic resonance reports easy to understand.

BACKGROUND: Patients are increasingly using Generative Pre-trained Transformer 4 (GPT-4) to better understand their own radiology findings. PURPOSE: To evaluate the performance of GPT-4 in transforming cardiovascular magnetic resonance (CMR) reports into text that is comprehensible to medical laypersons. METHODS: ChatGPT with GPT-4 architecture was used to generate three different explained versions of 20 various CMR reports (n = 60) using the same prompt: "Explain the radiology report in a language understandable to a medical layperson". Two cardiovascular radiologists evaluated understandability, factual correctness, completeness of relevant findings, and lack of potential harm, while 13 medical laypersons evaluated the understandability of the original and the GPT-4 reports on a Likert scale (1 "strongly disagree", 5 "strongly agree"). Readability was measured using the Automated Readability Index (ARI). Linear mixed-effects models (values given as median [interquartile range]) and intraclass correlation coefficient (ICC) were used for statistical analysis. RESULTS: GPT-4 reports were generated on average in 52 s ± 13. GPT-4 reports achieved a lower ARI score (10 [9-12] vs 5 [4-6]; p < 0.001) and were subjectively easier to understand for laypersons than original reports (1 [1] vs 4 [4,5]; p < 0.001). Eighteen out of 20 (90%) standard CMR reports and 2/60 (3%) GPT-generated reports had an ARI score corresponding to the 8th grade level or higher. Radiologists' ratings of the GPT-4 reports reached high levels for correctness (5 [4, 5]), completeness (5 [5]), and lack of potential harm (5 [5]); with "strong agreement" for factual correctness in 94% (113/120) and completeness of relevant findings in 81% (97/120) of reports. Test-retest agreement for layperson understandability ratings between the three simplified reports generated from the same original report was substantial (ICC: 0.62; p < 0.001). Interrater agreement between radiologists was almost perfect for lack of potential harm (ICC: 0.93, p < 0.001) and moderate to substantial for completeness (ICC: 0.76, p < 0.001) and factual correctness (ICC: 0.55, p < 0.001). CONCLUSION: GPT-4 can reliably transform complex CMR reports into more understandable, layperson-friendly language while largely maintaining factual correctness and completeness, and can thus help convey patient-relevant radiology information in an easy-to-understand manner.

Low-field, not low quality: 1D simplification, selective detection, and heteronuclear 2D experiments for improving low-field NMR spectroscopy of environmental and biological samples.

Understanding environmental change is challenging and requires molecular-level tools to explain the physicochemical phenomena behind complex processes. Nuclear magnetic resonance (NMR) spectroscopy is a key tool that provides information on both molecular structures and interactions but is underutilized in environmental research because standard "high-field" NMR is financially and physically inaccessible for many and can be overwhelming to those outside of disciplines that routinely use NMR. "Low-field" NMR is an accessible alternative but has reduced sensitivity and increased spectral overlap, which is especially problematic for natural, heterogeneous samples. Therefore, the goal of this study is to investigate and apply innovative experiments that could minimize these challenges and improve low-field NMR analysis of environmental and biological samples. Spectral simplification (JRES, PSYCHE, singlet-only, multiple quantum filters), selective detection (GEMSTONE, DREAMTIME), and heteronuclear (reverse and CH3/CH2/CH-only HSQCs) NMR experiments are tested on samples of increasing complexity (amino acids, spruce resin, and intact water fleas) at-high field (500 MHz) and at low-field (80 MHz). A novel experiment called Doubly Selective HSQC is also introduced, wherein 1H signals are selectively detected based on the 1H and 13C chemical shifts of 1H-13C J-coupled pairs. The most promising approaches identified are the selective techniques (namely for monitoring), and the reverse and CH3-only HSQCs. Findings ultimately demonstrate that low-field NMR holds great potential for biological and environmental research. The multitude of NMR experiments available makes NMR tailorable to nearly any research need, and low-field NMR is therefore anticipated to become a valuable and widely used analytical tool moving forward.

Discovery of 4-(isopentyloxy)-3-nitrobenzamide derivatives as xanthine oxidase inhibitors through a non-anthraquinone exploration.

In our previous study, we reported a series of N-(9,10-anthraquinone-2-carbonyl) amino acid derivatives as novel inhibitors of xanthine oxidase (XO). Recognizing the suboptimal drug-like properties associated with the anthraquinone moiety, we embarked on a nonanthraquinone medicinal chemistry exploration in the current investigation. Through systematic structure-activity relationship (SAR) studies, we identified a series of 4-(isopentyloxy)-3-nitrobenzamide derivatives exhibiting excellent in vitro potency against XO. The optimized compound, 4-isopentyloxy-N-(1H-pyrazol-3-yl)-3-nitrobenzamide (6k), demonstrated exceptional in vitro potency with an IC50 value of 0.13 µM. Compound 6k showed favorable drug-like characteristics with ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of 0.41 and 3.73, respectively. In comparison to the initial compound 1d, 6k exhibited a substantial 24-fold improvement in IC50, along with a 1.6-fold enhancement in LE and a 3.7-fold increase in LLE. Molecular modeling studies provided insights into the strong interactions of 6k with critical amino acid residues within the active site. Furthermore, in vivo hypouricemic investigations convincingly demonstrated that 6k significantly reduced serum uric acid levels in rats. The MTT results revealed that compound 6k is nontoxic to healthy cells. The gastric and intestinal stability assay demonstrated that compound 6k exhibits good stability in the gastric and intestinal environments. In conclusion, compound 6k emerges as a promising lead compound, showcasing both exceptional in vitro potency and favorable drug-like characteristics, thereby warranting further exploration.

PRESTIGIO RING: "An 80-year-old man living with HIV resistant to all four antiretroviral classes and desiring treatment simplification".

People aging with 4 antiretroviral class resistant HIV are a very challenging population. It is difficult to build up a fully suppressive regimen, and the high prevalence of comorbidities and polypharmacy may cause drug-drug interactions and put adherence at risk. We herein present the case of an 80-year-old man, participating in the PRESTIGIO registry, asking for a reduction in his antiretroviral burden while on polypharmacy for his comorbidities.

Conspiring simplification strategies of [Obstruent+Liquid] clusters in a case study of child Greek: emergence of the marked.

This paper addresses the idiosyncratic cluster simplification patterns observed in a child with disordered phonological development, who is acquiring Greek. The child has mastered word-internal and word-final codas and clusters of reversed sonority. However, the child does not realise the target well-formed tautosyllabic [Obstruent+Liquid] clusters with rising sonority. The child's system requires a single onset with maximum sonority dispersion between the onset and the syllable nucleus. As a result, cluster simplification occurs, via reduction to the less sonorous Obstruent - the most prevalent reduction pattern cross-linguistically. However, at the same time, the grammar requires faithful realisation of the target segment number. This requirement is fulfiled through two distinct conspiring metathesis patterns, distributed complementarily, resulting in the realisation of marked structures. The patterns depend on the position of the cluster within the target word. In word internal position, a compensatory metathesis of the Liquid takes place in the preceding syllable coda. In word initial position, the Manner of Articulation of the metathesised Liquid is delinked, while its Coronal Place of Articulation is faithfully preserved, and is realised by default as a Coronal Sibilant [s]. The latter Sibilant is attached as an appendix to the syllable node at the word left-edge. We argue that, in the grammar of this child, there is a-synchronisation between the development of the prosodic word layer and the development of syllable layer. Specifically, a-synchronisation is evident in the development of the (branching) onset syllabic subconstituent.

Sustained Viral Suppression With Dolutegravir Monotherapy Over 192 Weeks in Patients Starting Combination Antiretroviral Therapy During Primary Human Immunodeficiency Virus Infection (EARLY-SIMPLIFIED): A Randomized, Controlled, Multi-site, Noninferiority Trial.

BACKGROUND: Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy. METHODS: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART <180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50 mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144, and 192 weeks; noninferiority margin was 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired. RESULTS: Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group versus 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13 308 and 4897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively. CONCLUSIONS: This trial suggests that early cART initiation during primary HIV infection allows sustained virological suppression after switching to DTG monotherapy.

Change in metabolic parameters after switching from triple regimens with tenofovir alafenamide to dolutegravir-based dual therapy. Bi-lipid study.

INTRODUCTION: The use of tenofovir alafenamide (TAF) has been associated with increased cholesterol and body weight. Real-life data on the metabolic effects of switching from a TAF-based triple regimen to a dolutegravir (DTG)-based two-drug regimen (2-DR) are scarce. METHODS: A retrospective cohort study of patients who have switched from a triple TAF-based regimen to a 2-DR [DTG-lamivudine (DTG-3TC) or DTG- rilpivirine (DTG-RPV]) with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were percentage changes in lipid fraction, effectiveness and safety at 6 and 12 months [intention to treat (ITT), missing = failures]. RESULTS: A total of 118 patients (87 on DTG-3TC, 31 on DTG-RPV) were included. Median age was 51 years (interquartile range: 43-59), 86% were male, CD4 T-cell count was 692 cells/µL, and 98% viral load (VL) < 50 copies/mL. At 6 months there was a decrease in total and low-density lipoprotein cholesterol of 10.7 mg/dL [95% confidence interval (CI): 2.2-19.1; p ≤ 0.001] and 8.3 mg/dL (95% CI: 0.74-15.9; p = 0.026), respectively. There was a reduction in cardiovascular risk from 4.5% at baseline to 4% at 12 months (p = 0.040). Virological effectiveness as determined by ITT analysis was 85.6% at 6 months and 66.1% at 12 months. Seven patients (5.9%) withdrew from the 2-DR and there was no virological failure. CONCLUSIONS: In real life, switching from a triple regimen with TAF to DTG-3TC or DTG-RPV dual therapy improves the lipid profile and is an effective and well-tolerated strategy.

Investigations into Simplified Analogues of the Herbicidal Natural Product (+)-Cornexistin.

We report the design, synthesis and biological evaluation of simplified analogues of the herbicidal natural product (+)-cornexistin. Guided by an X-Ray co-crystal structure of cornexistin bound to transketolase from Zea mays, we attempted to identify the key interactions that are necessary for cornexistin to maintain its herbicidal profile. This resulted in the preparation of three novel analogues investigating the importance of substituents that are located on the nine-membered ring of cornexistin. One analogue maintained a good level of biological activity and could provide researchers insights in how to further optimize the structure of cornexistin for commercialization in the future.

Towards the most prägnant Gestalt: Leveling and sharpening as contextually dependent adaptive strategies.

Gestalt psychologists posited that we always organize our visual input in the best way possible under the given conditions. Both weakening or removing unnecessary details (i.e., leveling) and exaggerating distinctive features (i.e., sharpening) can contribute to achieving a better organization. When is a feature leveled or sharpened, however? We investigated whether the importance of a feature for discrimination among alternatives influences which organizational tendency occurs. Participants were simultaneously presented with four figures composed of simple geometrical shapes, and asked to reconstruct one of these figures in such a way that another participant would be able to recognize it among the alternatives. The four figures differed either qualitatively or only quantitatively (i.e., far or close context). Regarding quantitative differences, two feature dimensions were varied, with one manifesting a wider range of variability across the alternatives than the other. In case of a smaller variability range, the target figure was either at the extreme of the range or had an in-between value. As expected, the results indicated that sharpening occurred more often for the feature with an extreme value, for the feature exhibiting more variability, and for the features of figures presented in the close context, than for the feature with a non-extreme value, exhibiting less variability, or in the far context. In line with Metzger's (1941) definition of prägnant Gestalts, the essence of a Gestalt is context-dependent, and this will influence whether leveling or sharpening of a feature will lead to the best organization in the specific context.

Simplification of Deep Neural Network-Based Object Detector for Real-Time Edge Computing.

This paper presents a method for simplifying and quantizing a deep neural network (DNN)-based object detector to embed it into a real-time edge device. For network simplification, this paper compares five methods for applying channel pruning to a residual block because special care must be taken regarding the number of channels when summing two feature maps. Based on the comparison in terms of detection performance, parameter number, computational complexity, and processing time, this paper discovers the most satisfying method on the edge device. For network quantization, this paper compares post-training quantization (PTQ) and quantization-aware training (QAT) using two datasets with different detection difficulties. This comparison shows that both approaches are recommended in the case of the easy-to-detect dataset, but QAT is preferable in the case of the difficult-to-detect dataset. Through experiments, this paper shows that the proposed method can effectively embed the DNN-based object detector into an edge device equipped with Qualcomm's QCS605 System-on-Chip (SoC), while achieving a real-time operation with more than 10 frames per second.

Efficient and Low-Complex Signal Detection with Iterative Feedback in Wireless MIMO-OFDM Systems.

To solve error propagation and exorbitant computational complexity of signal detection in wireless multiple-input multiple-output-orthogonal frequency division multiplexing (MIMO-OFDM) systems, a low-complex and efficient signal detection with iterative feedback is proposed via a constellation point feedback optimization of minimum mean square error-ordered successive interference cancellation (MMSE-OSIC) to approach the optimal detection. The candidate vectors are formed by selecting the candidate constellation points. Additionally, the vector most approaching received signals is chosen by the maximum likelihood (ML) criterion in formed candidate vectors to reduce the error propagation by previous erroneous decision, thus improving the detection performance. Under a large number of matrix inversion operations in the above iterative MMSE process, effective and fast signal detection is hard to be achieved. Then, a symmetric successive relaxation iterative algorithm is proposed to avoid the complex matrix inversion calculation process. The relaxation factor and initial iteration value are reasonably configured with low computational complexity to achieve good detection close to that of the MMSE with fewer iterations. Simultaneously, the error diffusion and complexity accumulation caused by the successive detection of the subsequent OSIC scheme are also improved. In addition, a method via a parallel coarse and fine detection deals with several layers to both reduce iterations and improve performance. Therefore, the proposed scheme significantly promotes the MIMO-OFDM performance and thus plays an irreplaceable role in the future sixth generation (6G) mobile communications and wireless sensor networks, and so on.

A High-Efficiency Side-Scan Sonar Simulator for High-Speed Seabed Mapping.

Side scan sonar (SSS) is a multi-purpose ocean sensing technology, but due to the complex engineering and variable underwater environment, its research process often faces many uncertain obstacles. A sonar simulator can provide reasonable research conditions for guiding development and fault diagnosis, by simulating the underwater acoustic propagation and sonar principle to restore the actual experimental scenarios. However, the current open-source sonar simulators gradually lag behind mainstream sonar technology; therefore, they cannot be of sufficient assistance, especially due to their low computational efficiency and unsuitable high-speed mapping simulation. This paper presents a sonar simulator based on a two-level network architecture, which has a flexible task scheduling system and extensible data interaction organization. The echo signal fitting algorithm proposes a polyline path model to accurately capture the propagation delay of the backscattered signal under high-speed motion deviation. The large-scale virtual seabed is the operational nemesis of the conventional sonar simulators; therefore, a modeling simplification algorithm based on a new energy function is developed to optimize the simulator efficiency. This paper arranges several seabed models to test the above simulation algorithms, and finally compares the actual experiment results to prove the application value of this sonar simulator.

Polygon Simplification for the Efficient Approximate Analytics of Georeferenced Big Data.

The unprecedented availability of sensor networks and GPS-enabled devices has caused the accumulation of voluminous georeferenced data streams. These data streams offer an opportunity to derive valuable insights and facilitate decision making for urban planning. However, processing and managing such data is challenging, given the size and multidimensionality of these data. Therefore, there is a growing interest in spatial approximate query processing depending on stratified-like sampling methods. However, in these solutions, as the number of strata increases, response time grows, thus counteracting the benefits of sampling. In this paper, we originally show the design and realization of a novel online geospatial approximate processing solution called GeoRAP. GeoRAP employs a front-stage filter based on the Ramer-Douglas-Peucker line simplification algorithm to reduce the size of study area coverage; thereafter, it employs a spatial stratified-like sampling method that minimizes the number of strata, thus increasing throughput and minimizing response time, while keeping the accuracy loss in check. Our method is applicable for various online and batch geospatial processing workloads, including complex geo-statistics, aggregation queries, and the generation of region-based aggregate geo-maps such as choropleth maps and heatmaps. We have extensively tested the performance of our prototyped solution with real-world big spatial data, and this paper shows that GeoRAP can outperform state-of-the-art baselines by an order of magnitude in terms of throughput while statistically obtaining results with good accuracy.

The Application of 3base™ Technology to Diagnose Eight of the Most Clinically Important Gastrointestinal Protozoan Infections.

Globally, over 3.5 billion people are infected with intestinal parasites each year, resulting in over 200,000 deaths. Three of the most common protozoan pathogens that affect the gastrointestinal tract of humans are Cryptosporidium spp., Giardia intestinalis, and Entamoeba histolytica. Other protozoan agents that have been implicated in gastroenteritis in humans include Cyclospora cayetanensis, Dientamoeba fragilis, Blastocystis hominis, and the microsporidia Enterocytozoon bieneusi and Encephalitozoon intestinalis. Genetic Signatures previously developed a 3base™ multiplexed Real-Time PCR (mRT-PCR) enteric protozoan kit (EP001) for the detection of Giardia intestinalis/lamblia/duodenalis, Cryptosporidium spp., E. histolytica, D. fragilis, and B. hominis. We now describe improvements to this kit to produce a more comprehensive assay, including C. cayetanensis, E. bieneusi, and E. intestinalis, termed EP005. The clinical performance of EP005 was assessed using a set of 380 clinical samples against a commercially available PCR test and other in-house nucleic acid amplification tests where commercial tests were not available. All methods provided at least 90% agreement. EP005 had no cross-reactivity against 82 organisms commonly found in the gut. The EP005 method streamlines the detection of gastrointestinal parasites and addresses the many challenges of traditional microscopic detection, resulting in cost savings and significant improvements in patient care.

Transcatheter aortic valve implantation in patients with uninterrupted vitamin K antagonists.

BACKGROUND: Bridging of vitamin K antagonist (VKA) with heparin is usually not promoted during interventional or surgical procedures related to increased risk of bleeding and thrombotic events but this strategy has not been evaluated during transcatheter aortic valve implantation (TAVI). PURPOSE: The aim of this study was to evaluate the rate of major bleeding and vascular complications after TAVI performed in patients with uninterrupted VKA. METHODS: From January 2016 to October 2017, consecutive patients who underwent TAVI with uninterrupted VKA (International Normalized Ratio [INR] between 1.5 and 3.5) were prospectively included in a monocentric registry. TAVI was performed according to current guidelines and a 50 U/kg bolus of heparin was injected at the beginning of the procedure for all patients. Vascular and bleeding complications were assessed using the Valve Academic Research Consortium 3 (VARC3) and the Bleeding Academic Research Consortium (BARC) definitions at a 30-day follow-up. RESULTS: A total of 88 patients were included with a median age of 84 years (81.8-87.0), 42% being female. The median society of thoracic surgeons score was 5.1 (4.1-7.5), the median CHADS2-VASc was 5.5 (5-6) and 60.2% had a chronic kidney failure. Median INR at the time of implantation was 2.1 (1.8-2.6). The main VKA indication was atrial fibrillation. Transfemoral access was used in 88.6% of the patients. Major bleeding (BARC ≥ 3b) occurred in five patients (5.7%) and major vascular complications occurred in seven patients (8.0%). At 1 month follow-up, major bleeding (BARC ≥ 3) or vascular complications occurred in 10 patients (11.4%). In patients with major bleeding peripheral arterial disease (RR = 10.95; 95% confidence interval (CI) 1.63-73.75; p = 0.014) and carotid access (RR = 8.56; 95% CI 1.19-1.51; p = 0.033) were more common. INR > 2.5 was significantly associated with vascular complications (RR = 7.14; 95% CI 1.29-39.63; p = 0.025). At 30 days, mortality and stroke rates were 2.3% and 4.5%, respectively. CONCLUSION: TAVI with uninterrupted VKA treatment seems feasible and safe with a low risk of major bleeding and vascular complications in this first single-center experience. Particular caution is advocated in high body mass index patients and to keep INR < 2.5.

Feasibility, effectiveness and cost of a decentralized HCV care model among the general population in Delhi, India.

BACKGROUND AND AIMS: India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population. METHODS: A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured. RESULTS: Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P < .001). Of those confirmed positive, treatment was initiated at significantly higher rates for participants in both Arms 1 (85.6%) and 2 (73.7%) compared to Arm 3 (41.8%, P < .001). Arm 1 was found to be a cost-saving strategy compared to Arm 2, Arm 3, and no action. CONCLUSIONS: Delivery of all services at a single site (district hospitals) resulted in a higher yield of HCV seropositive cases and retention compared with sites where participants were referred elsewhere for VL testing and/or treatment. The highest level of retention in the care cascade was also associated with the shortest turn-around times.