Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial.

BACKGROUND: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. METHODS: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. FINDINGS: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. INTERPRETATION: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. FUNDING: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

Delamination of Novel Carbon Fibre-Based Non-Crimp Fabric-Reinforced Thermoplastic Composites in Mode I: Experimental and Fractographic Analysis.

Delamination, a form of composite failure, is a significant concern in laminated composites. The increasing use of out-of-autoclave manufacturing techniques for automotive applications, such as compression moulding and thermoforming, has led to increased interest in understanding the delamination resistance of carbon-fibre-reinforced thermoplastic (CFRTP) composites compared to traditional carbon-fibre-reinforced thermosetting (CFRTS) composites. This study evaluated the mode I (opening) interlaminar fracture toughness of two non-crimp fabric (NCF) biaxial (0/90°) carbon/thermoplastic composite systems: T700/polyamide 6.6 and T700/polyphenylene sulphide. The mode I delamination resistance was determined using the double cantilever beam (DCB) specimen. The results were analysed and the Mode I interlaminar fracture toughness was compared. Additionally, the fractographic analysis (microstructure characterisation) was conducted using a scanning electron microscope (SEM) to examine the failure surface of the specimens.

QbD-based fabrication of transferrin-anchored nanocarriers for targeted drug delivery to macrophages and colon cells for mucosal inflammation healing.

Colon mucosal inflammation attracts a plethora of immune cells with overexpressed surface receptors. Colon drug targeting can be aided by exploiting overexpressed cell surface receptors which improve drug site retention for an extended period. We developed Tofacitinib citrate (Tofa) loaded transferrin anchored PLGA nanocarriers (Tofa-P/tfr NCs) via the quality by design (QbD) approach for specific binding to the transferrin receptor (TFR-1/CD71) overexpressed on macrophages and colon epithelial cells. Nanocarriers were produced using a modified emulsion-evaporation method with a protein adsorption technique. The QbD-risk assessment method was adopted to screen the variables impacting the quality of nanocarriers, which were then optimized using the 33 Box-Behnken design of experiment (DOE). The obtained nanocarriers have the desired physicochemical properties, drug entrapment, tfr adsorption, stability, mucoadhesion, and sustained drug release pattern at pH 7.4 (colon pH). In vitro cell-based studies confirmed the cellular biocompatibility and considerable uptake of nanocarriers by colon and macrophage cells; the uptake was diminished by anti-CD71/TFR1 antibodies. Tofa-P/tfr NCs demonstrated good colon targeting potential in the dextran sulfate sodium (DSS) induced ulcerative colitis (UC) model. In vivo therapeutic efficacy against UC was established through restored morphological and histopathological scores, vascular integrity, antioxidant levels, hematological parameters, pro-inflammatory cytokine/marker levels, and microbial indices. Tofa-P/tfr NCs shut down the elevated STAT-1 and TFR-1 levels, demonstrating the enhanced efficacy of the encapsulated drug. Thus, the QbD-driven approach successfully developed Tofa-P/tfr NCs with good potential to mitigate mucosal inflammation by targeting colon and macrophage surface receptors.

Cadmium accumulation by Phragmites australis and Iris pseudacorus from stormwater in floating treatment wetlands microcosms: Insights into plant tolerance and utility for phytoremediation.

Environmentally sustainable remediation is needed to protect freshwater resources which are deteriorating due to severe industrial, mining, and agricultural activities. Treatment by floating wetlands could be a sustainable solution to remediate water bodies. The study aimed to examine the effects of Cd on Phragmites australis and Iris pseudacorus growth (height, biomass, root length and chlorophyll contents), anatomy, Cd accumulation in their biomass and their ability to remove Cd, N and P. Seedlings of both plants were grown in a greenhouse for 50 days in artificially prepared stormwater amended with Cd, N, and P. The treatments were: control (Cd _0), Cd_1, Cd_2, and Cd_4 mg L-1. N and P contents were 4 mg L-1 and 1.8 mg L-1, respectively. In the case of P. australis, the maximum plant height, root length, and total dry biomass production was increased in medium dose (Cd_2) treatment while the chlorophyll index (CCI) increased in high dose (Cd_4) treatment as compared to all treatments. For I. pseudacorus, the maximum plant height and total dry biomass production, root length and CCI values were improved in low dose (Cd_1) and high dose (Cd_4) treatments, respectively among all treatments. Results showed that P. australis accumulated 10.94-1821.59 µg · (0.05 m2)-1 in roots and 2.45-334.65 µg · (0.05 m2)-1 in shoots under Cd_0, Cd_1 and Cd_4 treatments. I. pseudacorus accumulated the highest Cd in roots up to 5.84-4900 µg · (0.05 m2)-1 and 3.40-609 µg · (0.05 m2)-1 in shoots under Cd_0, Cd_1 and Cd_4 treatments. The translocation factor was observed as <1 and the bioconcentration factor >1 for both species, which indicates their phytostabilization potential. Results demonstrate that P. australis and I. pseudacorus are suitable for use in floating wetlands to remediate contaminated sites.

Engineered Bacteria-Based Living Materials for Biotherapeutic Applications.

Future advances in therapeutics demand the development of dynamic and intelligent living materials. The past static monofunctional materials shall be unable to meet the requirements of future medical development. Also, the demand for precision medicine has increased with the progressively developing human society. Therefore, engineered living materials (ELMs) are vitally important for biotherapeutic applications. These ELMs can be cells, microbes, biofilms, and spores, representing a new platform for treating intractable diseases. Synthetic biology plays a crucial role in the engineering of these living entities. Hence, in this review, the role of synthetic biology in designing and creating genetically engineered novel living materials, particularly bacteria, has been briefly summarized for diagnostic and targeted delivery. The main focus is to provide knowledge about the recent advances in engineered bacterial-based therapies, especially in the treatment of cancer, inflammatory bowel diseases, and infection. Microorganisms, particularly probiotics, have been engineered for synthetic living therapies. Furthermore, these programmable bacteria are designed to sense input signals and respond to disease-changing environments with multipronged therapeutic outputs. These ELMs will open a new path for the synthesis of regenerative medicines as they release therapeutics that provide in situ drug delivery with lower systemic effects. In last, the challenges being faced in this field and the future directions requiring breakthroughs have been discussed. Conclusively, the intent is to present the recent advances in research and biomedical applications of engineered bacteria-based therapies during the last 5 years, as a novel treatment for uncontrollable diseases.

Remediation of pesticides using TiO2 based photocatalytic strategies: A review.

Nowadays, pesticides are regarded as the most dangerous of the various organic pollutants, posing substantial environmental and human threats worldwide. Pesticide contamination has become one of the most crucial environmental issues due to its bio-persistence and bioaccumulation. Different conventional methods are being utilized for pesticide removal, yet pesticides are thought to be significantly present in the environment. The development and application of sophisticated wastewater treatment methods are being pursued to remove contaminants effectively, particularly pesticides. In the past several decades, nanoscience and nanotechnology have emerged as essential tools for the identification, removal, and mineralization of persistent pesticides by employing advanced nanomaterials such as pristine titanium dioxide (TiO2), doped TiO2, nanocomposites (NCs) TiO2, and ternary nanocomposites (TNCs) TiO2 by advanced oxidation processes (AOPs). Advancement in the characteristics of TiO2 by doping, co-doping, construction of NCs and TNCs has contributed to the dramatic efficiency up-gradation by reducing band gap, solar active photocatalyst, enhancing PCA, high photostability, chemically inertness and multiple time reusability. Based on previous literature, utilizing La-TiO2 NCs photocatalyst, the mineralization of pesticide (imidacloprid) attained up to 98.17% that is almost 40-53% greater than pristine TiO2. The present review attempt to discuss the recent research performed on TiO2 based nanoparticles (NPs) and NCs for photocatalytic mineralization of various pesticides. The basic mechanism of TiO2 photocatalysis, types of reactors used for photocatalysis, and optimized experimental conditions of TiO2 for pesticides mineralization are discussed.

Evaluation of Occupational Health Risk Management and Performance in China: A Case Study of Gas Station Workers.

China has a large number of gas stations, with which thousands of workers are associated. There is abundant online literature documenting the various occupational health risks these workers face. However, this literature has many flaws to address, and it falls short of suggesting measures to manage these risks. This study strives to fill that gap, and aims to improve the occupational health of gas station workers through comprehensive risk management and performance analysis. To this end, a reasonable volume of reliable data, i.e., 208 completed questionnaires, were analyzed through current statistical routines, viz., fuzzy Analytical Hierarchy Process (AHP) and Importance Performance Analysis (IPA). These methods were employed to hierarchically organize the main factors and sub-factors of physical risk management, chemical risk management, biological risk management, physiological risk management and psychological risk management according to their appraised importance, and screen out the risk management stratagem for priority improvement. Research findings reveal that chemical risk and biological risk response schemes have the lowest performance, and need to be prioritized for improvement. Furthermore, this study argues that we can safeguard the occupational health of gas station workers through appropriate risk management strategies. It also elaborates on implications, limitations and future research directions.

Assessment of sustainability and uncertainties of oil markets: mediating determinants of energy use and CO2 emissions.

The current paper investigates the sustainability growth problem in the USA and evaluating the co-integration relationship among all variables, including oil, carbon emission, and consumption of energy. We also determine the impacts of energy consumption on the USA economic growth, government spending, and trade openness. We used the co-integration and popular lag model (ARDL) to find the long-term and short-term relationships between all study variables. The empirical results show that (1) the crude oil prices increase and adverse impact on energy demand and government expenditure during the study periods, and CO2 emission negatively affects USA economic growth. In addition, (2) the innovative accounting method (ICA) results, we used further research to research the causality between study variables. The empirical results propose that oil prices affect the country's economy responsible for more energy consumption, and the causal effect between consumption of energy and economic growth is not relevant. Wastage of energy allows the system to produce more CO2 emissions. Model results find that the one-sided causal effects of economic growth and CO2. We see during the analyses that (CO2) emissions will negatively impact the country's economy. Therefore, country policymakers are expected to change fossil fuel energy to non-fossil fuel energy as an essential component of the USA's economic growth policies.

A case of aortic dissection in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an ethnicity-specific autoinflammatory disease prevalent in the Arab world. It has various presentations including amyloidosis, small-vessel vasculitis, and pericarditis. Different mutations in the Mediterranean fever (MEFV) gene can cause this disorder and it is inherited in an autosomal recessive pattern. We present a case of a 23-year-old man of Iranian descent with history of periodic fever, diagnosed as Stanford type A aortic dissection secondary to an acute attack of FMF. To the best of our knowledge, this is the first case reported of such a complication. .

Experimental and Numerical Analysis of Low-Velocity Impact of Carbon Fibre-Based Non-Crimp Fabric Reinforced Thermoplastic Composites.

There has been a lot of interest in understanding the low-velocity impact (LVI) response of thermoplastic composites. However, little research has focussed on studying the impact behaviour of non-crimp fabric (NCF)-based fibre reinforced thermoplastic composites. The purpose of this study was to evaluate the LVI responses of two types of non-crimp fabric (NCF) carbon fibre reinforced thermoplastic laminated composites that have been considered attractive in the automotive and aerospace industry: (i) T700/polyamide 6.6 (PA6.6) and (ii) T700/polyphenylene sulphide (PPS). Each carbon/thermoplastic type was impacted at three different energy levels (40, 100 and 160 J), which were determined to achieve three degrees of penetrability, i.e., no penetration, partial penetration and full penetration, respectively. Two distinct non-destructive evaluation (NDE) techniques ((i) ultrasonic C-scanning and (ii) X-ray tomography) were used to assess the extent of damage after impact. The laminated composite plates were subjected to an out-of-plane, localised impact using an INSTRON® drop-weight tower with a hemispherical impactor measuring 16 mm in diameter. The time histories of force, deflection and velocity are reported and discussed. A nonlinear finite element model of the LVI phenomenon was developed using a finite element (FE) solver LS-DYNA® and validated against the experimental observations. The extent of damage observed and level of impact energy absorption calculated on both the experiment and FE analysis are compared and discussed.

Development of a SYBR Green-based real-time quantitative polymerase chain reaction assay to detect enzootic nasal tumor virus in goats.

Enzootic nasal adenocarcinoma is a contagious respiratory disease in goats that is caused by the enzootic nasal tumor virus 2 (ENTV-2). In order to increase the number of available detection methods for ENTV-2, we developed a SYBR Green real-time polymerase chain reaction (SGrPCR) assay that targets the gag gene of ENTV-2. The low limit of detection of the assay was 3.68 × 101 copies/µL, a hundredfold more sensitive than conventional PCR. The melt curve showed a single sharp melt peak at 83°C, which indicated that there was no non-specific amplification or primer dimer formation. The intra-assay and inter-assay coefficients of variation were 1.58% and 1.82%, respectively. There was no cross-reactivity with closely related goat viruses (i.e., orf virus, peste des petits ruminants virus, goatpox virus, foot-and-mouth disease virus) and endogenous retroviruses. In conclusion, the SGrPCR assay is specific for the gag gene of ENTV-2 and provides a rapid and sensitive approach for detecting ENTV-2 in clinical samples.

L'adénocarcinome nasal enzootique est une maladie respiratoire contagieuse chez les chèvres qui est causé par le virus de la tumeur nasale enzootique 2 (ENTV-2). Afin d'augmenter le nombre de méthodes de détection disponibles pour ENTV-2, nous avons développé un test de réaction en chaîne par polymérase en temps réel SYBR Green (SGrPCR) qui cible le gène gag de ENTV-2. La limite basse de détection du test était de 3,68 × 101 copies/µL, cent fois plus sensible que la PCR conventionnelle. La courbe de fusion montrait un seul pic de fusion net à 83 °C, ce qui indiquait qu'il n'y avait pas d'amplification non spécifique ou de formation de dimère d'amorce. Les coefficients de variation intra-essai et inter-essai étaient respectivement de 1,58 % et 1,82 %. Il n'y avait pas de réactivité croisée avec les virus caprins étroitement apparentés (c'est-à-dire le virus orf, le virus de la peste des petits ruminants, le virus de la variole caprine, le virus de la fièvre aphteuse) et les rétrovirus endogènes. En conclusion, le test SGrPCR est spécifique du gène gag de l'ENTV-2 et fournit une approche rapide et sensible pour la détection d'ENTV-2 dans des échantillons cliniques.(Traduit par Docteur Serge Messier).

Closure versus non-closure of mesenteric defects in laparoscopic Roux-en-Y gastric bypass: a systematic review and meta-analysis.

BACKGROUND: The comparative evidence regarding the outcomes of closure versus non-closure of mesenteric defects in laparoscopic Roux-en-Y gastric bypass (LRYGB) is poorly understood. We aimed to compare the outcomes of closure versus non-closure of mesenteric defects in LRYGB for morbid obesity. METHODS: We conducted a search of electronic information sources to identify all comparative studies investigating the outcomes of closure versus non-closure of mesenteric defects in patients undergoing LRYGB for morbid obesity. We used the Cochrane risk of bias tool and the ROBINS-I tool to assess the risk of bias of RCTs and observational studies, respectively. Random or fixed effects modelling was applied as appropriate. RESULTS: We included 10,031 patients from six observational studies and 2609 patients from two RCTs. Analysis of observational studies showed closure defects resulted in lower risks of internal hernia (OR 0.28, 95% CI 0.15, 0.54) and reoperation for small bowel obstruction (SBO) (OR 0.30, 95% CI 0.10, 0.83); no difference was found between the two groups in terms of SBO not related to internal hernia (OR 1.19, 95% CI 0.47, 2.99), early SBO (OR 0.74, 95% CI 0.04, 14.38), anastomotic leak (OR 0.84, 95% CI 0.45, 1.57), bleeding (OR 1.08, 95% CI 0.62, 1.89), and anastomotic ulcer (OR 2.08, 95% CI 0.62, 6.94). Analysis of RCTs showed closure of defects resulted in lower risks of internal hernia (OR 0.29, 95% CI 0.19,0.45) and reoperation for SBO (OR 0.51, 95% CI 0.38, 0.69) but higher risks of SBO not related to internal hernia (OR 1.90, 95% CI 1.09, 3.34) and early SBO (OR 2.63, 95% CI 1.16, 5.96); no difference was found between the two groups in terms of anastomotic leak (OR 1.95, 95% CI 0.80, 4.72), bleeding (OR 0.67, 95% CI 0.38, 1.17), and anastomotic ulcer (OR 2.08, 95% CI 0.62, 6.94). CONCLUSIONS: Our results suggest that closure of mesenteric defects in LRYGB may be associated with lower risks of internal herniation and reoperation for SBO compared with non-closure of the defects (moderate certainty). The available evidence is inconclusive regarding the risks of SBO not related to internal hernia and early SBO (low certainty). More RCTs are needed to improve the robustness of the available evidence.

Evaluation of clinical manifestations, health risks, and quality of life among women with polycystic ovary syndrome.

This study aimed to evaluate the clinical manifestations and health risks associated with polycystic ovary syndrome (PCOS) and its impact on quality of life (QOL) in Pakistan. A detailed cross-sectional study was conducted on PCOS among women of reproductive age visiting the gynecology and obstetrics and endocrinology departments at primary and tertiary care hospitals located in Abbottabad, Kohat, and Islamabad. In total, 440 patients meeting the inclusion criteria were included. A checklist was specifically designed to identify symptoms and health risks, including adverse drug reactions, complications, irrational prescription or underprescription, and drug-drug interactions. The Short Form-12 questionnaire was used to evaluate the QOL of patients with PCOS. Data collected were analyzed for descriptive and inferential statistics using chi-square test, analysis of variance, and post hoc analysis. All patients exhibited the cardinal symptoms of PCOS, including obesity (n = 352, 80%), acne (n = 296, 67.3), hirsutism (n = 299, 68%), hyperglycemia (n = 278, 63.2%), and irregular menstruation (n = 316, 71.8%). Ultrasonography confirmed that 268 (61%) patients had multiple cysts of >10 mm in diameter. Patients with untreated PCOS exhibited a high prevalence of health risks including hypertension (n = 87, 19.8%), diabetes (n = 268, 60.9%), sleep apnea (n = 11, 2.5%), infertility (n = 146, 33.2%), increased endometrial thickness (n = 21, 4.8%), miscarriages (n = 68, 15.5%), high cholesterol level (n = 85, 19.3%), and hyperandrogenism (n = 342, 77.7%). Most patients exhibited low QOL scores (n = 374, 85%), with depression being the largest contributor to low QOL. Apart from novel results, this study found an association between depression and low QOL in patients with PCOS, suggesting the need for reviewing the management guidelines and psychological health assessment of women with PCOS.

Short And Midterm Outcome Of Fallot's Tetralogy Repair In Infancy: A Single Center Experience In A Developing Country.

BACKGROUND: Primary repair of ToF between 3-12 months is the preferred mode of treatment worldwide, with low surgical mortality. This study reviews our experience of ToF repair in infancy and its short and midterm outcomes in a single centre from a developing country. METHODS: Data of all patients with Tetralogy of Fallot repair during infancy from January 2007 to Feb 2018 was reviewed. Preoperative, operative, and postoperative data was analysed. Outcome of the infants was assessed through discharge/death, low cardiac output syndrome (LCOS), prolonged intubation, duration of cardiac intensive care unit (CICU) and hospital stay. RESULTS: Forty-four patients who underwent TOF repair in infancy during this period were included. The mean age and weight were 9.39±2.32 and 7.20±1.30 respectively, 77.3% (34 patients) were male, 68.18% (30 patients) had saturation >75%. Mean intubation period was 4.05±6.58 days, 12 (27.3%) patients developed LCOS, mean cardiopulmonary bypass (CPB) time, aortic cross clamp (ACC) time and ionotropic score were 133.52±62.4, 98.66±58.62 and 33.27±71.13 respectively. Mean CICU and hospital stay was 6.60±7.18 and 12.05±7.74 respectively. Five (11.3%) patients expired in postoperative period. Baseline saturation ≤75% is independent risk factor for LCOS and prolong intubation period. In the last six years our mortality decreased to 8% from 15.7% during the previous six years, while our mean intubation duration, CPB time, ACC, hospital stay and CICU stay have all shown improvement. CONCLUSIONS: TOF repair during infancy is safe procedure in expert hands with acceptable morbidity and mortality. Baseline saturation ≤75% is independent risk factor for LCOS and prolonged intubation period. Last six years have shown considerable improvement in our surgical morbidity and mortality due to improvement in surgical expertise.

Oil-water de-emulsification using ultrasonic technology.

In this paper an oil-water de-emulsification process within large tanks using ultrasonic technology is presented. As the device would operate in hazardous areas, it should not consume an excessive amount of electrical power. Hence, the paper investigates the suitable oil-water concentrations (10-90% concentrations in step of 10%) which would lead to the fastest separation while consuming the minimum amount of power. Extensive experiments which were conducted using a powerful 20kHz ultrasonic sensor were indicative with good repeatability that the emulsion layer with less water content (i.e. 10 to 40% water-cut) gets significantly faster separation. The experimental study was then validated through a set of finite element-based simulations for different ratios of oil water emulsions. This led to suggest a new feasible de-emulsifying device which consists of a one dimensional array of ultrasonic sensors which are vertically distributed to emit ultrasonic waves in horizontal direction and in a time multiplexed manner.