Phosphorylation of aryl hydrocarbon receptor interacting protein by TBK1 negatively regulates IRF7 and the type I interferon response.

The innate antiviral response to RNA viruses is initiated by sensing of viral RNAs by RIG-I-like receptors and elicits type I interferon (IFN) production, which stimulates the expression of IFN-stimulated genes that orchestrate the antiviral response to prevent systemic infection. Negative regulation of type I IFN and its master regulator, transcription factor IRF7, is essential to maintain immune homeostasis. We previously demonstrated that AIP (aryl hydrocarbon receptor interacting protein) functions as a negative regulator of the innate antiviral immune response by binding to and sequestering IRF7 in the cytoplasm, thereby preventing IRF7 transcriptional activation and type I IFN production. However, it remains unknown how AIP inhibition of IRF7 is regulated. We show here that the kinase TBK1 phosphorylates AIP and Thr40 serves as the primary target for TBK1 phosphorylation. AIP Thr40 plays critical roles in regulating AIP stability and mediating its interaction with IRF7. The AIP phosphomimetic T40E exhibited increased proteasomal degradation and enhanced interaction with IRF7 compared with wildtype AIP. AIP T40E also blocked IRF7 nuclear translocation, which resulted in reduced type I IFN production and increased viral replication. In sharp contrast, AIP phosphonull mutant T40A had impaired IRF7 binding, and stable expression of AIP T40A in AIP-deficient mouse embryonic fibroblasts elicited a heightened type I IFN response and diminished RNA virus replication. Taken together, these results demonstrate that TBK1-mediated phosphorylation of AIP at Thr40 functions as a molecular switch that enables AIP to interact with and inhibit IRF7, thus preventing overactivation of type I IFN genes by IRF7.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Patients With and Without Diabetes: Long-Term Outcomes From the CONFIRM Registry.

BACKGROUND: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known. METHODS: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis). RESULTS: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879). CONCLUSION: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM.

Mixotrophy in a Local Strain of Nannochloropsis granulata for Renewable High-Value Biomass Production on the West Coast of Sweden

A local strain of Nannochloropsis granulata (Ng) has been reported as the most productive microalgal strain in terms of both biomass yield and lipid content when cultivated in photobioreactors that simulate the light and temperature conditions during the summer on the west coast of Sweden. To further increase the biomass and the biotechnological potential of this strain in these conditions, mixotrophic growth (i.e., the simultaneous use of photosynthesis and respiration) with glycerol as an external carbon source was investigated in this study and compared with phototrophic growth that made use of air enriched with 1-2% CO2. The addition of either glycerol or CO2-enriched air stimulated the growth of Ng and theproduction of high-value long-chain polyunsaturated fatty acids (EPA) as well as the carotenoid canthaxanthin. Bioassays in human prostate cell lines indicated the highest antitumoral activity for Ng extracts and fractions from mixotrophic conditions. Metabolomics detected betaine lipids specifically in the bioactive fractions, suggesting their involvement in the observed antitumoral effect. Genes related to autophagy were found to be upregulated by the most bioactive fraction, suggesting a possible therapeutic target against prostate cancer progression. Taken together, our results suggest that the local Ng strain can be cultivated mixotrophically in summer conditions on the west coast of Sweden for the production of high-value biomass containing antiproliferative compounds, carotenoids, and EPA.

Valve-in-valve transcatheter aortic valve replacement versus redo surgical valve replacement for degenerated bioprosthetic aortic valve: An updated meta-analysis comparing midterm outcomes.

BACKGROUND: Redo surgical aortic valve replacement (redo SAVR) and valve-in-valve transcatheter aortic valve replacement (ViV TAVR) are the two treatment strategies available for patients with severe symptomatic bioprosthetic aortic valve dysfunction. Herein, we performed a systematic review and meta-analysis comparing both early and mid-term outcomes of ViV TAVR versus redo SAVR in patients with bioprosthetic aortic valve disease. METHODS: PubMed, Cochrane reviews, and Google scholar electronic databases were searched and studies comparing ViV TAVR versus redo SAVR were included. The primary outcome of interest was mid-term (1-5 years) and 1-year all-cause mortality. Secondary outcomes included were 30-day all-cause mortality, myocardial infarction, pacemaker implantation, stroke, acute kidney injury, major or life-threatening bleeding, and postprocedural aortic valve gradients. Pooled risk ratios (RR) with their corresponding 95% confidence intervals (CIs) were calculated for all outcomes using the DerSimonian-Laird random-effects model. RESULTS: Nine observational studies with a total of 2,891 individuals and mean follow-up of 26 months met the inclusion criteria. There is no significant difference in mid-term and 1-year mortality between ViV-TAVR and redo SAVR groups with RR of 1.15 (95% CI 0.99-1.32; p = .06) and 1.06 (95% CI 0.69-1.61; p = .8). 30-day mortality rate was significantly lower in ViV-TAVR group with RR of 0.65 (95% CI 0.45-0.93; p = .02). ViV-TAVR group had lower 30-day bleeding, length of stay, and higher postoperative gradients. CONCLUSION: Our study demonstrates a lower 30-day mortality and similar 1-year and mid-term mortality for ViV TAVR compared to redo SAVR despite a higher baseline risk. Given these findings and the ongoing advances in the transcatheter therapeutics, VIV TAVR should be preferred over redo SAVR particularly in those at intermediate-high surgical risk.

Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial.

AIMS: Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients. METHODS AND RESULTS: A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053). CONCLUSIONS: Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.

Correlation between Academic Performance and Anxiety in Medical Students of Majmaah University - KSA.

OBJECTIVE: To study the prevalence of anxiety and its correlation with the academic performance among medical students.. METHODS: The analytical cross-sectional study was conducted over six months from March 2018 to August 2018, at the male and female campuses of the College of Medicine, Majmaah University, Majmaah, Saudi Arabia, and comprised medical students of either gender. Data on anxiety was collected using a selfreporting questionnaire that included the Beck Anxiety Inventory. Academic performance was taken as a measurable record from the cumulative grade point average. Data was analysed using SPSS 24. RESULTS: Of the 247 subjects, 170(68.8%) were males. Anxiety was found in 97(39.3%) of the students. The level of anxiety was significantly higher among females compared to males (p=0.001), among those in the final year (p=0.002), and in those with low academic grades (p=0.016). CONCLUSIONS: Anxiety was found to be common among medical students and it was associated with female gender, low grades and advanced year of studies.

Thromboelastography-Guided Therapy of Hemorrhagic Complications after Craniopharyngioma Resection: Case-Based Update.

PURPOSE: Thromboelastography (TEG) is a point-of-care test that evaluates the entire hemostatic process. The use of TEG is expanding in multiple pediatric surgical disciplines. However, there is very little literature regarding its application in pediatric neurosurgical patients. METHODS: The authors provide a case-based update and literature review regarding potential applications of TEG to pediatric neurosurgical patients. RESULTS: The authors describe a 12-year-old female who experienced a number of complications after a craniopharyngioma resection. The patient suffered multiple new intraventricular hemorrhages with removal of external ventricular drains. Standard coagulopathy tests did not reveal any abnormalities. However, an abnormal TEG value suggested primary hyperfibrinolysis, which led to a change in medical management. The patient did not suffer any further bleeding episodes after the change in treatment. CONCLUSIONS: The authors discuss a case where TEG influenced patient management and identified a problem despite normal values of standard laboratory tests. Neurosurgeons should be aware of the potential benefits for TEG testing in pediatric patients.

Randomized trial of rivaroxaban versus warfarin in the evaluation of progression of coronary atherosclerosis.

Warfarin, a vitamin K antagonist, is associated with systemic vascular calcification. We evaluated whether rivaroxaban (a direct oral factor Xa inhibitor with no interaction with vitamin K) will slow the progression in coronary plaque volumes compared with warfarin in patients with nonvalvular atrial fibrillation using coronary computed tomography angiography.

Evaluating the quality of implantation of percutaneous ventricular restoration device (Parachute®) by cardiac computed tomography.

BACKGROUND: The Parachute is a novel percutaneously implanted ventricular partitioning device (VPD) that has emerged as a safe and feasible treatment option for patients with heart failure following anterior wall myocardial infarction. VPD efficacy is likely dependent on optimal device placement, but to date there are no published data examining the effect of device positioning on patient outcomes. METHODS AND RESULTS: We retrospectively identified 32 patients successfully implanted with the Parachute device, all of whom underwent cardiac computed tomography (CCT) at baseline and after 6 months of follow-up. Patients were divided into two groups based on self-reported improvement in New York Heart Association (NYHA) functional class: "not improved NYHA" (n = 12) and "improved NYHA" (n = 20). There were significant differences between both groups with regard to device positioning on follow-up CCT. Compared to patients with "improved NYHA," patients with "not improved NYHA" had longer distances from device foot to left ventricular apex (8.0 ± 4.9 vs. 2.9 ± 4.6 mm; P = 0.01), and higher lateral angles (18.0 ± 14 vs. 9.1 ± 6.8 degrees; P = 0.02), respectively. There was no significant difference between the two groups in landing zone (45.4 ± 7. vs. 45.1 ± 6.9 mm; P = 0.92) and inferior angle (14.0 ± 11.9 vs. 14.3 ± 10.1 degrees; P = 0.95). There was a numerically larger malapposition area in the "not improved NYHA" group (5.1 ± 4.5 vs. 3.2 ± 2.2 cm2; P = 0.12). CONCLUSION: Quality of Parachute implant impacted clinical outcome, these findings should be applied prospectively in helping operators to achieve optimal implant. © 2016 Wiley Periodicals, Inc.

Simultaneous Onset of Deep Vein Thrombosis, Pulmonary Embolism, Cerebral Infarction, and Myocardial Infarction in a Patient with Patent Foramen Ovale.

Paradoxical embolism is a known complication with intra-cardiac shunts. It should be considered in the differential as the pathophysiologic mechanism of simultaneous thromboembolism in the venous and systemic vasculature. We present a case of simultaneous deep venous thrombosis, pulmonary embolism and myocardial infarction in the presence of a confirmed patent foramen ovale on echocardiography. Thrombolytic therapy was administered. Subsequent concerns of intracranial hemorrhage on imaging of the brain complicated the management and added to the challenge of co-managing the clot burden in our patient. This rare presentation highlights the importance of multisystem evaluation in making the best medical decision for the patient.

Laboratory Diagnosis of Malaria: Comparison of Manual and Automated Diagnostic Tests.

Malaria is the second most prevalent disease in Pakistan resulting in ~30,000 annual deaths. In endemic countries like Pakistan precise and timely diagnosis of malaria is imperative to overcome the associated risks of fatal outcomes. Malarial parasite was screened in 128 malaria suspected patients and 150 healthy controls, by species-specific PCR, microscopy of blood smears, hemoanalyzer Sysmex XE-2100, and rapid test devices (First Response Malaria® and ICT Malaria Combo®). The microscopy detected MP in 126 samples (parasite load/µl 386-53712/µl); 71.094% were infected with Plasmodium vivax and 14.844% with P. falciparum while 14.062% had mixed P. vivax and P. falciparum infection. The mean parasite load for P. vivax and P. falciparum was 14496/µl and 24410/µl, respectively. The abnormal scattergrams of DIFF, WBC/ Baso, IMI channel, and RET-EXT on Sysmex XE-2100 supported 99.2% parasite detection, whereas only 93% of confirmed malaria cases were detected by both rapid tests. About 127 samples were positive by PCR. Since Sysmex XE-2100 automatically detected the presence of malarial parasite with high sensitivity, it can be a good option for presumptive diagnosis in endemic areas. Microscopy remains the gold standard to confirm MP in suspected patients. Rapid diagnostic tests have acceptable sensitivity and specificity.

Cardiac computed tomography assessment of the near term impact of percutaneous ventricular restoration therapy (parachute(®) ) on mitral valve geometry.

OBJECTIVES: The aim of current study is to assess the near term impact of percutaneous ventricular restoration therapy (PVR), Parachute(®) on mitral valve (MV) geometry by cardiac computed tomography (CCT). BACKGROUND: Recent data demonstrates the feasibility of PVR for treatment of post anterior myocardial infarction (MI) heart failure. Little is known, however, about the interaction of the device and left ventricular structures, particularly the MV apparatus. METHODS: This is a retrospective Core Laboratory analysis of Parachute Trials' CCT data. Patients with paired (before and after Parachute implant) CCT acquisitions were included into analysis. MV geometric parameters were measured. RESULTS: Thirty-three patients were included in the analysis. The mean time of follow-up CCT post procedure was 188 ± 52 days. There were significant reduction in tenting height (A1P1: -1.70 ± 1.89 mm, -17.40 ± 20.20%; A2P2: -1.43 ± 1.89 mm, -12.10 ± 15.00%; A3P3: -1.54 ± 1.58 mm, -15.50 ± 15.20%, P < 0.001), tenting volume (-0.93 ± 0.60 mm3, -22.00 ± 11.40%, P < 0.001), systolic interpapillary muscle distance (-2.22 ± 2.11 mm, -7.51 ± 7.23%, P < 0.001) and diastolic interpapillary muscle distance (-3.14 ± 2.20 mm, -8.46 ± 5.73%, P < 0.001) post PVR. CONCLUSIONS: In post anterior MI heart failure patients, PVR has favorable near term impact on MV geometry as assessed by CCT. © 2015 Wiley Periodicals, Inc.

An Unusual Presentation of an Unusual Disease: Spontaneous Pneumomediastinum.

We report a case of spontaneous pneumomediastinum with unusual clinical presentation. The most common symptoms of spontaneous mediastinum are chest pain and shortness of breath. Our patient presented with neck swelling and change in voice, an unusual presentation for spontaneous pneumothorax. A 30-year-old previously healthy man presented with complaints of neck swelling and hoarseness of voice beginning after an intense coughing spell. He had no other complaints. He denied any trauma to the chest, nausea, vomiting, recent air travel, scuba diving or recreational drug use. His vital signs were stable with an O2 saturation of 97 percent on room air. Chest examination was remarkable for palpable crepitus over lower neck as well as bilateral upper and mid anterior chest. Chest radiograph as well as chest computed tomography (CT) demonstarted a massive pneumomediastinum with free air dissecting throughout the soft tissues of the neck. The patient was admitted for observation. Neck swelling and hoarseness of voice resolved in less than 24 hours with conservative management of cough. He was discharged without incident. Spontaneous pneumomediastinum is an uncommon, self-limiting condition in which air is present in the mediastinum with no obvious precipitating factor. Cough, inhaled drugs, physical exercise, labor, and diabetic ketoacidosis have been reported to trigger spontaneous pneumomediastinum. Our patient developed the condition after an intense coughing spell following smoking cessation. CT scan is considered gold standard for the diagnosis. Spontaneous pneumomediastinum is characterized by spontaneous recovery and can be treated with short period of observation and symptomatic management.

Current Guidelines on Syncope.

Syncope is a very commonly encountered clinical problem in general practice and in the emergency department. In the evaluation of syncope, it is important to identify the specific cause to determine the treatment, to estimate the precise risk to a patient, and to reduce recurrence. Sometimes, making a diagnosis of syncope is difficult, as different mechanisms may often coexist. Syncope causes a significant impact on quality of life due to associated risk of physical injury. In particular, syncope can be a precursor to sudden cardiac death in patients with underlying cardiac disease. It is crucial to identify patients at increased risk of death, such as those with myocardial ischemia and/or potentially life-threatening genetic diseases (e.g., Long-QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and arrhythmogenic right ventricular dysplasia). After these conditions have been excluded, other benign conditions that cause syncope must be identified, and efforts should be made to improve quality of life. The lack of a gold-standard clinical tool to aid in diagnosing syncope as well as improper use of various diagnostic tests, are leading to high economic burdens in this area.

A Case of Silent Q Fever Endocarditis.

Q fever endocarditis is a rare, culture negative endocarditis caused by Coxiella burnetii, a spore-forming gram negative coccobacillus. Presenting symptoms can be very non-specific; thus, diagnosis may be delayed. We present a case of a 65-year-old male patient with history of aortic aneurysm who complained of chronic fatigue. He was found to have aortic valve vegetation on routine echocardiography. Q fever endocarditis was diagnosed based on elevated Q fever serology; there was absence of fever. This case illustrated a rare, under-recognized and atypical manifestation of Q fever endocarditis. We would like to encourage physicians of rural states like South Dakota to remain vigilant when it comes to screening for the suspected cases of Q fever, specifically in cases of unexplained fatigue and valvulopathy.

Analysis of the potential risk of central intravenous lines and/or total parenteral nutrition with ventriculoatrial shunts.

OBJECT: The distal catheter of a ventriculoatrial (VA) cerebrospinal fluid shunt is potentially exposed to bacterial seeding from a subclavian central line. The risk of blood stream infections (BSIs) from central lines increases with administration of total parenteral nutrition (TPN). The potential risks of shunt malfunction or infection in patients with a VA shunt and a concurrent subclavian central line and/or TPN administration have not been studied. METHODS: A retrospective review of 49 pediatric patients with placement of a VA shunt was performed. Three outcome measures were studied: shunt malfunction, shunt infection, and bacteremia/fungemia requiring shunt removal. All outcomes were measured by 1 year after shunt insertion. We analyzed the following potential risk factors: age at shunt insertion, prior ventriculoperitoneal (VP) shunt, prior shunt infection, abdominal infection/necrotizing enterocolitis (NEC), concurrent subclavian central line, and administration of TPN. The association between each risk factor and outcome was evaluated using Fisher's exact test to generate the relative risk. Additionally, a logistic regression analysis was performed to evaluate the odds ratio of the outcomes to risk factors considering age as a covariate. RESULTS: The average age at shunt insertion was 6.3 ± 7.6 years. The most common diagnosis was posthemorrhagic hydrocephalus of prematurity (53.1 %). Fifteen patients (30.1 %) had a shunt malfunction within 1 year, 6 (12.2 %) had a shunt infection, and 3 (6.1 %) required removal of the shunt due to bacteremia/fungemia. The age at shunt insertion was not a statistically significant independent risk factor for any of the three outcomes. Prior shunt infection predicted an increased risk for both future shunt malfunction and infection in both the associative relative risk analysis and the age-dependent logistic regression analysis, although the correlation did not reach statistical significance. The presence of a subclavian central line or TPN administration did not statistically increase the risk over baseline for any of the outcomes in either analysis. CONCLUSIONS: The relatively small number of patients limits the power of the study. Considering this limitation, the data suggests that the presence of a concurrent subclavian central line or administration of TPN does not increase the risk of shunt malfunction or infection over the baseline of this high-risk cohort.

Clinical outcomes of the surgical treatment of isolated unilateral facet fractures, subluxations, and dislocations in the pediatric cervical spine: report of eight cases and review of the literature.

PURPOSE: We present a small series consisting of eight children with unilateral facet injury of the cervical spine treated surgically. METHODS: A retrospective review was performed. Injury data, radiographs, surgical data, and outcomes (Neck Disability Index (NDI), Short Form 36 (SF-36), and Visual Analog Scale for Neck Pain (VAS-NP)) were collected from seven patients. A literature review was performed for one additional case. RESULTS: Motor vehicle accidents (62 %, n = 5) and falls (38 %, n = 3) accounted for all injuries. The C6-7 level accounted for most of the injuries (37.5 %, n = 3). The mean NDI score with at least 3 months follow-up was 5.3 (n = 6, range, 1-12; standard deviation, 4.5), corresponding to mild disability. Of the norm-based SF-36 scale scores available (n = 6), the mean physical functioning (PF), role-physical (RP), and role-emotional (RE) scores were significantly less than the adult, age 18-24, norm-based means, with a mean difference of -6.4, -9.13, and -11.3, respectively (p value = 0.03, 0.001, and 0.01, respectively). The mean general health (GH) and vitality (VT) scores, however, were significantly greater than the adult, age 18-24, norm-based mean, with a mean difference of 7.82 and 10.3 (p = 0.04 and 0.02, respectively). VAS-NP showed a return to the "no pain" level at 3 months or more follow-up in all patients. CONCLUSIONS: We suggest that surgical treatment of these injuries in the pediatric age group may lead to satisfactory clinical and radiographic outcomes, but HRQoL analysis suggests that patients remain physically and emotionally disabled to some degree after surgery.

Evaluation of stable angina by coronary computed tomographic angiography versus standard of care: A systematic review and meta-analysis.

INTRODUCTION: There is limited data comparing Coronary Computed Tomography Angiography (CCTA) versus the usual Standard of care (SOC) in patients with suspected stable coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis to compare CCTA versus SOC in patients with stable CAD. METHODS: We searched multiple databases for randomized controlled trials (RCTs) comparing CCTA with SOC, which included various functional testing approaches for evaluating stable CAD. We used a random-effects model to calculate risk ratios (RRs) with 95 % confidence intervals (CIs). Outcomes included all-cause mortality, myocardial infarction (MI), hospitalization for unstable angina (UA), invasive angiography, revascularization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). RESULTS: We identified 6 RCTs with 19,881 patients with stable CAD, of which 9995 underwent CCTA, and 9886 underwent SOC. There were no significant differences between CCTA and SOC in terms of all-cause mortality (RR: 0.91; 95 % CI: 0.70-1.19; p = 0.50), MI (RR: 0.78; 95 % CI: 0.58-1.05; p = 0.11), hospitalizations for UA (RR: 1.20; 95 % CI: 0.95-1.51;p = 0.12), invasive angiography (RR: 0.71; 95 % CI: 0.32-1.61; p = 0.42), revascularization (RR:1.25; 95 % CI: 0.83-1.89; p = 0.29), PCI (RR: 1.20; 95 % CI: 0.78-1.85; p = 0.40), and CABG rates (RR: 0.89; 95 % CI: 0.530-1.49; p = 0.65). CONCLUSION: In patients with stable CAD, CCTA is associated with similar outcomes compared to the usual Standard of care. Given its potential to quickly rule out severe obstructive disease, its ability to provide non-invasive physiology and identify non-obstructive CAD with plaque information makes it an attractive addition to the available armamentarium to evaluate chest pain.

Two-phase microalgae cultivation for RAS water remediation and high-value biomass production.

The overall goal of this study was to provide solutions to innovative microalgae-based technology for wastewater remediation in a cold-water recirculating marine aquaculture system (RAS). This is based on the novel concept of integrated aquaculture systems in which fish nutrient-rich rearing water will be used for microalgae cultivation. The produced biomass can be used as fish feed, while the cleaned water can be reused, to create a highly eco-sustainable circular economy. Here, we tested three microalgae species Nannochloropis granulata (Ng), Phaeodactylum tricornutum (Pt), and Chlorella sp (Csp) for their ability to remove nitrogen and phosphate from the RAS wastewater and simultaneously produce high-value biomass, i.e., containing amino acids (AA), carotenoids, and polyunsaturated fatty acids (PUFAs). A high yield and value of biomass were achieved for all species in a two-phase cultivation strategy: i) a first phase using a medium optimized for best growth (f/2 14x, control); ii) a second "stress" phase using the RAS wastewater to enhance the production of high-value metabolites. Ng and Pt performed best in terms of biomass yield (i.e., 5-6 g of dry weight, DW.L-1) and efficient cleaning of the RAS wastewater from nitrite, nitrate, and phosphate (i.e., 100% removal). Csp produced about 3 g L-1 of DW and reduced efficiently only nitrate, and phosphate (i.e., about 76% and 100% removal, respectively). The biomass of all strains was rich in protein (30-40 % of DW) containing all the essential AA except Methionine. The biomass of all three species was also rich in PUFAs. Finally, all tested species are excellent sources of antioxidant carotenoids, including fucoxanthin (Pt), lutein (Ng and Csp) and ß-carotene (Csp). All tested species in our novel two-phase cultivation strategy thus showed great potential to treat marine RAS wastewater and provide sustainable alternatives to animal and plant proteins with extra added values.

Chloroplast magnesium transporters play essential but differential roles in maintaining magnesium homeostasis.

Magnesium (Mg2+) is essential for photosynthesis in the chloroplasts of land plants and algae. Being the central ion of chlorophyll, cofactor and activator of many photosynthetic enzymes including RuBisCO, magnesium-deficient plants may suffer from leaf chlorosis symptoms and retarded growth. Therefore, the chloroplast Mg2+ concentration is tightly controlled by magnesium transport proteins. Recently, three different transporters from two distinct families have been identified in the chloroplast inner envelope of the model plant Arabidopsis thaliana: MGT10, MGR8, and MGR9. Here, we assess the individual roles of these three proteins in maintaining chloroplast Mg2+ homeostasis and regulating photosynthesis, and if their role is conserved in the model green alga Chlamydomonas reinhardtii. Phylogenetic analysis and heterologous expression revealed that the CorC-like MGR8 and MGR9 transport Mg2+ by a different mechanism than the CorA-like MGT10. MGR8 and MGT10 genes are highest expressed in leaves, indicating a function in chloroplast Mg2+ transport. MGR9 is important for chloroplast function and plant adaptation in conditions of deficiency or excess of Mg2+. Transmission electron microscopy indicated that MGT10 plays a differential role in thylakoid stacking than MGR8 and MGR9. Furthermore, we report that MGR8, MGR9, and MGT10 are involved in building up the pH gradient across the thylakoid membrane and activating photoprotection in conditions of excess light, however the mechanism has not been resolved yet. While there are no chloroplast MGR-like transporters in Chlamydomonas, we show that MRS4 is a homolog of MGT10, that is required for photosynthesis and cell growth. Taken together, our findings reveal that the studied Mg2+ transporters play essential but differential roles in maintaining chloroplast Mg2+ homeostasis.