Predictors of medications-free and long-term remission in anti-neutrophil cytoplasmic antibody-associated vasculitis: Real-world evidence.

BACKGROUND AND AIM: In this study, we report the outcomes of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in daily practice based on Connective Tissue Diseases Research Center-Vasculitis Registry (CTDRC-VR) data. METHODS: Patients were included if they were 18 years or older, had a diagnosis of the groups of AAV based on 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis, and were followed for a period longer than 2 years or were died. Complete clinical remission was defined as granulomatosis with polyangiitis (BVAS/GPA) of 0. Sustained remission was defined as a complete clinical remission for at least six months and tapering prednisolone dose to ≤ 7.5 mg/d. Long-term remission was defined as complete clinical remission for ≥ 5 years and tapering prednisolone dose to ≤ 7.5 mg/d. Medications-free remission was defined as complete clinical remission and discontinuation of glucocorticoids, cytotoxic medications and biologics. RESULTS: Sixty patients with AAV were enrolled in this study. Sustained and long-term remission were developed in 91.7 and 72.1 percent of patients, respectively. Relapse was developed in 27 (45%) patients. Medications-free remission was developed in 23 (33.3%) patients. Vasculitis induced damage was developed in 40 (66.7%) patients. Patients with damage had significantly lower age and higher BVAS at the baseline. Upper airway and renal involvement, and non-adherence in patients with damage was significantly more common. CONCLUSIONS: Induction therapy leads to long-term and medications-free remission in 72% and 38% of patients with AAV, respectively.

Cerebral protection in acute type A aortic dissection surgery: a systematic review and meta-analysis.

Background: Acute type A aortic dissection (ATAAD) still challenges physicians and warrants emergent surgical management. Two main methods to reduce cerebrovascular events in ATAAD surgeries are antegrade cerebral perfusion (ACP) and retrograde cerebral perfusion (RCP). We conducted a systematic review and meta-analysis to compare the outcomes of ACP and RCP methods during the ATAAD surgery. Methods: In this study, we searched the databases until March 29th, 2023. Studies that reported the data for comparison of different types of brain perfusion protection during aortic surgery in patients with ATAAD were included. Results: Twenty-six studies met the eligibility criteria. All studies had a low risk of bias as they were evaluated by the Joanna Briggs Institute (JBI) critical appraisal tool. Eventually, we included 26 studies in the current meta-analysis, and a total of 13,039 patients were evaluated. The calculated risk ratio (RR) for permanent neurologic dysfunction (PND) in ACP and RCP comparison was RR =1.23, 95% confidence interval (CI): (0.84, 1.80) (P value =0.2662), and in unilateral ACP (uACP) and bilateral ACP (bACP) was RR =1.2786, 95% CI: (0.7931, 2.0615) (P value =0.3132). When comparing the ACP-RCP and uACP-bACP groups, significant differences were found between ACP-RCP the groups in terms of circulatory arrest time (P value =0.0017 and P value =0.1995, respectively), cardiopulmonary bypass time (P value =0.5312 and P value =0.7460, respectively), intensive care unit (ICU)-stay time (P value =0.2654 and P value =0.0099), crossclamp time (P value =0.6228 and P value =0.2625), and operative mortality (P value =0.9368 and P value =0.2398, respectively), and when comparing the u-ACP and b-ACP groups for transient neurologic deficit (TND), an RR of 1.32, 95% CI: (1.05, 1.67) (P value =0.0199). The results showed high heterogeneity and no publication bias. Conclusions: This study demonstrated that the ACP and RCP are both safe and acceptable techniques to use in emergent settings. The uACP technique is equivalent to bACP in terms of PND and mortality, however, uACP is preferred over bACP in terms of TND.

Pregnancy-associated osteoporosis following in vitro fertilization: A case report.

This case report illustrates that in vitro fertilization (IVF) may be a potential risk factor for pregnancy-associated osteoporosis (PAO), highlighting the need for awareness and monitoring of bone health in women undergoing IVF treatments. PAO is a rare disease resulting from an imbalance of calcium in the body during pregnancy and lactation and presenting with fragility fractures. PAO occurs in late pregnancy or early postpartum period. A 28-year-old woman who conceived through IVF experienced severe back pain 2 days after delivery. Magnetic resonance imaging of the spine showed wedge-shaped fractures of T9-T12 vertebrae. Bone mineral density (BMD) was low on dual-energy x-ray absorptiometry. The laboratory tests were within the normal range. Based on the clinical manifestations, osteoporotic spine fracture, results of BMD, and exclusion of other causes of osteoporosis, the patient was diagnosed with PAO. Considering the deleterious effect of treatment with gonadotropin-releasing hormone and repeated superovulation on bone, we hypothesized that IVF may be an etiological factor for PAO.

Outcomes of polymyalgia rheumatica in real-world practice: a longitudinal cohort study.

Background: Polymyalgia rheumatica (PMR) is an inflammatory condition closely linked with giant cell arteritis, which is a large vessel vasculitis. To provide real-world evidence on PMR outcomes and their determinants, we conducted a longitudinal study focusing on symptom relief and acute phase reactant normalization. Methods: We followed patients with PMR who were registered in Tabriz University of Medical Sciences Vasculitis Registry (TUOMS-VR) until February 2023. We measured sustained remission (primary outcome) and secondary outcomes including glucocorticoids (GCs)-free remission, medication-free remission, relapse rate and disease-induced damage. Results: We identified eighty-one patients with PMR and followed them for a median time of 57 months. In a median duration of 3 weeks, 98.8% of patients achieved symptom control, with 86.4% achieving sustained remission in a median duration of 9 weeks. Sustained remission was more common in non-smokers and adherent to therapy patients. Relapse occurred in 22.1% of patients, primarily due to non-adherence. Medication-free remission was observed in 30.9% of patients, especially among females and those with an initial prednisolone dose > 15 mg/d. Damage occurred in 42.0% of patients. Conclusion: Although sustained remission in PMR is not an unattainable goal in daily practice and most patients are in remission at the last visit, two-thirds of patients require long-term treatment.

Determining whether LV filling time contributes to HF symptoms in different widths of QRS in LBBB patients: A clinical study.

OBJECTIVES: Accurate assessment of left ventricular (LV) function is essential for managing patients with left bundle branch block (LBBB). This study aimed to evaluate the relationship between LV systolic function, left ventricular diastolic filling time (LVFT), QRS duration, and heart failure symptoms in patients with LBBB. METHODS: This study was conducted between June 2021 and June 2022. Patients with LBBB and sinus rhythm who were referred to the echocardiography department were included in the study. All the patients underwent electrocardiogram-gated echocardiography using the same machine. In this study, the LVFT value was measured in absolute terms and as a ratio to the R-R interval (LVFT/RR). RESULTS: A total of sixty-five patients were included, forty-two (64.6%) were women, and the mean age was 60.71 ± 8.72. We performed three one-way ANOVA tests that showed that LV filling time/RR ratio, QRS duration, and ejection fraction were significantly different between heart failure classes (p = 0.008, p = 0.001, and p < 0.001, respectively). A weak correlation was observed between LVEF and LVFT/RR (r = 0.349, p = 0.004). Additionally, QRS duration was negatively correlated with LVEF (r =  - 0.395, p = 0.004) and LVFT/RR (r =  - 0.350, p = 0.004), although these correlations were weak. CONCLUSION: We showed that LVFT/RR ratio differed significantly between HF functional classes and was lower in patients with more severe HF symptoms. Additionally, QRS duration was negatively correlated with LVEF and LVFT/RR, and patients with more severe HF symptoms had longer QRS durations.

Assessing cardiac power output values in a healthy adult population.

Cardiac power output (CPO), which combines pressure and flow capacities, directly measures the heart's pumping capability. It is proposed as a superior alternative to ejection fraction in assessing cardiac function. However, there is a lack of data on CPO in healthy individuals, prompting a study to determine the cardiac power output in healthy adults in the Iranian population. This cross-sectional descriptive study investigated cardiac power in a sample of healthy individuals. Participants were recruited from healthy individuals referred to the Echocardiography department using convenience sampling. In this study, we examined the echocardiographic parameters in 173 individuals, of which 52% were men. Men exhibited significantly higher values for stroke volume, cardiac output, and cardiac power output (CPO) in both ventricles, as well as larger body surface area (BSA) and systemic mean arterial pressure (MAP), compared to women. Individuals under the age of 40 had significantly higher BSA and right ventricular cardiac output compared to those aged 40 or above. Multivariate analysis revealed that MAP, left ventricular (LV) cardiac output, LVCPO, pulmonary MAP, right ventricular (RV) CPO, and RV cardiac power index (CPI) were significant predictors of LVCPI changes. Our findings emphasize the importance of cardiac power output as a comprehensive measure of cardiac function, complementing the traditional use of ejection fraction. Further research is warranted to validate these results, establish accurate reference ranges, and explore the clinical implications of cardiac power output in various patient populations.

Serum salusin-ß levels in patients with systemic lupus erythematosus.

OBJECTIVE: Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-ß with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-ß levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement. METHODS: In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit. RESULTS: Serum salusin-ß levels in SLE and control groups were 474.2 ± 117.1 pg/ml and 157.7 ± 88.7 pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-ß levels with age (r = - 0.06, P = 0.632) and SLEDAI (r = - 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-ß was significantly higher. In addition, in patients with serositis, serum salusin-ß was significantly lower. Multiple linear regression analysis showed that serum salusin-ß levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. CONCLUSIONS: Our findings showed that salusin-ß might have a possible role in the pathogenesis of SLE. Salusin-ß may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-ß levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-ß levels with age and SLEDAI. • Serum salusin-ß levels retained a significant association with nephritis and thrombosis.

Conventional and two-dimensional strain echocardiography in predicting postoperative atrial fibrillation after coronary artery bypass grafting surgery.

Background: Atrial fibrillation (AF) is a common complication after heart surgeries. Advances in imaging technologies and an understanding of the pathophysiology of preoperative left atrial (LA) dysfunction can lead to more definitive potential therapeutic approaches. This study aimed to determine the role of conventional echocardiography and LA two-dimensional (2D) strain echocardiography in assessing LA function and predicting POAF after CABG surgery. Methods: All patients with sinus rhythm who underwent CABG surgery were enrolled. All the patients had undergone conventional echocardiography and LA 2D-strain echocardiography 24 hours before surgery. In addition to demographic, clinical, and perioperative features, electrocardiogram (ECG) and Holter monitoring were recorded. Results: Of the 105 patients included, 85 patients (81%) were men with a mean age of 60.26±10.61 years. POAF was seen in 22.9% of patients during hospitalization, and AF duration was 10 hours (median; IQR: 2.0-19.5). AF patients had a higher LA volume index (LAVI) than patients with sinus rhythm (p=0.018). Patients with sinus rhythm had higher rates of LA reservoir (26.97±6.87 VS. 20.46±4.27, p<0.001), LA contractile (14.98±3.68 VS. 12.76±3.72, p =0.012) and LA global strain (24.28±6.57 VS. 17.71±4.11, p<0.001) than AF patients. The results of the multivariate logistic regression showed that LAVI (p=0.014) and LA global strain (p=0.027) were independent predictors of AF detection. Conclusion: Compared to conventional echocardiography, 2D-strain echocardiography is a more effective diagnostic method to predict the possibility of post-CABG AF.

Validity and reliability of the BODI for assessing damage in Behcet's disease.

OBJECTIVE: In the present study, we aimed to validate the Behçet's syndrome Overall Damage Index (BODI) and compare its performance with that of vasculitis damage index (VDI) in Iranian patients with BD. METHODS: This study included 274 patients with a diagnosis of BD and median follow-up of 40 months. The medical records of the patients were reviewed and the demographic characteristics, disease activity status, clinical manifestations, and data on organs damage were collected from all patients. RESULTS: To evaluate the construct/convergent validity, BODI and VDI were applied to all participants. We found a good correlation between BODI score and VDI score. There was a significant and strong correlation between physician global assessment with BODI (r = 0.869, P = 0.001) and VDI (r = 0.817, P = 0.001). The ability of BODI to determine the accumulation of damage over time was assessed by analyzing the changes in BODI score over time. The increase in BODI score was occurred in 53 (19.3%) patients. In comparison, the increase in VDI score occurred in 36 (13.1%) patients. The increase in median BODI was significantly more than median VDI (P < 0.001). Multiple linear regression analysis showed that age at disease onset, disease duration, and disease severity were independent predictors of BODI scores. Reliability of BODI was examined by comparing the BODI scores as determined by two independent assessors in 100 patients. Cronbach's α was 0.942. CONCLUSION: The BODI demonstrated acceptable validity and reliability in assessing BD-related damage in Iranian patients with BD.

In-hospital mortality of patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting in Iranian population.

BACKGROUND: Historically, coronary artery bypass grafting is associated with a higher mortality rate in patients with severe heart failure. This study aimed to assess the in-hospital mortality of CABG in patients with severe heart failure in Iranian patients and to identify factors associated with adverse outcomes. METHODS: This retrospective descriptive study enrolled patients with severe heart failure who underwent coronary artery bypass surgery from 2015 to 2020 in Madani Hospital, affiliated with Tabriz University of Medical Sciences. RESULTS: A total of 865 consecutive patients with a mean age of 60.65 ± 10.00 were enrolled in the study. Of all participants, 175 were female (20.4%), and 684 were male. The overall mortality rate was 9.5%. In the univariate analysis, predictors of ICU mortality were age, female sex, DM, and renal failure (P value < 0.05). None of the factors studied was an independent predictor of ICU mortality in the multivariate analysis. CONCLUSION: This study established that although coronary artery bypass surgery is reported to have low mortality and postoperative morbidity in patients with severe heart failure, there are still centers that face higher mortality rates in these patients. Improving these patients' outcomes would be possible through identifying the associated risk factors and pre-and postoperative management.

Effect of Endothelial Adhesion Molecules on Atrial Fibrillation: A Systematic Review and Meta-analysis.

Background: Endothelial adhesion molecules (EAMs), and more specifically vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), belong to a family of immunoglobulin-like molecules and are found to have increased expression in inflamed microvessels. Due to the growing evidence regarding EAM effects on cardiovascular diseases, we aimed to investigate the link between EAMs and atrial fibrillation (AF) to discover the efficacy of EAMs assessment as predictive markers in high-risk patients. Methods: We searched for articles published from January 1990 to April 2022. Two independent researchers selected studies that examined the relationship between VCAM-1 and ICAM-1 levels and AF. Study design, patient characteristics, VCAM-1 and ICAM-1 levels, and measurement methods were extracted from the selected articles. Results: Of 181 records, 22 studies were finally included in the systematic review. Meta-analyses showed a significant difference in serum levels of EAMs in patients with AF compared with patients with sinus rhythms (VCAM-1: mean difference [MD] 86.782, 95% CI 22.805-150.758, p=0.008; ICAM-1: MD 28.439 ng/mL, 95% CI 12.540-44.338, p<0.001). In subgroup analysis of persistent AF, the differences were still significant (VCAM-1: MD 98.046, 95% CI 26.582-169.510, p=0.007; ICAM-1: MD 25.091, 95% CI 12.952-37.230, p<0.001). We also found the mean ranges of VCAM-1 (95% CI 661.394-927.984 ng/mL) and ICAM-1 (95% CI 190.101-318.169 ng/mL) in patients with AF. Conclusion: This study suggests a positive association between serum levels of VCAM-1 and ICAM-1 with AF, but there is a need for further large-scale studies.

On the role of dauer in the adaptation of nematodes to a parasitic lifestyle.

Nematodes are presumably the most abundant Metazoa on Earth, and can even be found in some of the most hostile environments of our planet. Various types of hypobiosis evolved to adapt their life cycles to such harsh environmental conditions. The five most distal major clades of the phylum Nematoda (Clades 8-12), formerly referred to as the Secernentea, contain many economically relevant parasitic nematodes. In this group, a special type of hypobiosis, dauer, has evolved. The dauer signalling pathway, which culminates in the biosynthesis of dafachronic acid (DA), is intensively studied in the free-living nematode Caenorhabditis elegans, and it has been hypothesized that the dauer stage may have been a prerequisite for the evolution of a wide range of parasitic lifestyles among other nematode species. Biosynthesis of DA is not specific for hypobiosis, but if it results in exit of the hypobiotic state, it is one of the main criteria to define certain behaviour as dauer. Within Clades 9 and 10, the involvement of DA has been validated experimentally, and dauer is therefore generally accepted to occur in those clades. However, for other clades, such as Clade 12, this has hardly been explored. In this review, we provide clarity on the nomenclature associated with hypobiosis and dauer across different nematological subfields. We discuss evidence for dauer-like stages in Clades 8 to 12 and support this with a meta-analysis of available genomic data. Furthermore, we discuss indications for a simplified dauer signalling pathway in parasitic nematodes. Finally, we zoom in on the host cues that induce exit from the hypobiotic stage and introduce two hypotheses on how these signals might feed into the dauer signalling pathway for plant-parasitic nematodes. With this work, we contribute to the deeper understanding of the molecular mechanisms underlying hypobiosis in parasitic nematodes. Based on this, novel strategies for the control of parasitic nematodes can be developed.

The relationship between preoperative serum vitamin D deficiency and postoperative atrial fibrillation: A systematic review and meta-analysis.

Postoperative atrial fibrillation (POAF) is the most common arrhythmia seen in the first days following cardiac surgeries. Recently, there is a growing discussion regarding the link between vitamin D deficiency and POAF development. This systematic review and meta-analysis of the observational studies aimed at evaluating the association between preoperative vitamin D deficiency and Postoperative atrial fibrillation. In this study, using PubMed, Scopus, Google Scholar, EMBASE, Web of Science, and Cochrane Libraries, we searched for records published before July 2020. Two reviewers screened for studies that examined the relationship between preoperative vitamin D levels and the generation of POAF. Data regarding study design, patient characteristics, definition of atrial fibrillation (AF), type of surgery, vitamin D levels, and measurement methods were extracted. Five studies were included in the meta-analysis. Our primary analysis showed a significant relationship between preoperative levels of vitamin D and POAF development (mean differences (MD) = -2.851, 95% confidence interval (CI) =-5.506 to -0.195; P value 0.035). Our meta-analysis suggested serum vitamin D deficiency is associated with an increased risk of POAF development. Further large scale interventional studies are needed to explore whether vitamin D supplementation will prevent POAF.

Adaptation of the parasitic plant lifecycle: germination is controlled by essential host signaling molecules.

Parasitic plants are plants that connect with a haustorium to the vasculature of another, host, plant from which they absorb water, assimilates, and nutrients. Because of this parasitic lifestyle, parasitic plants need to coordinate their lifecycle with that of their host. Parasitic plants have evolved a number of host detection/host response mechanisms of which the germination in response to chemical host signals in one of the major families of parasitic plants, the Orobanchaceae, is a striking example. In this update review, we discuss these germination stimulants. We review the different compound classes that function as germination stimulants, how they are produced, and in which host plants. We discuss why they are reliable signals, how parasitic plants have evolved mechanisms that detect and respond to them, and whether they play a role in host specificity. The advances in the knowledge underlying this signaling relationship between host and parasitic plant have greatly improved our understanding of the evolution of plant parasitism and are facilitating the development of more effective control measures in cases where these parasitic plants have developed into weeds.

Are sesquiterpene lactones the elusive KARRIKIN-INSENSITIVE2 ligand?

MAIN CONCLUSION: The sunflower sesquiterpene lactones 8-epixanthatin and tomentosin can bind to the hydrophobic pocket of sunflower KAI2 with an affinity much higher than for the exogenous ligand KAR. Sesquiterpene lactones (STLs) are secondary plant metabolites with a wide range of biological, such as anti-microbial, activities. Intriguingly, the STLs have also been implicated in plant development: in several Asteraceae, STL levels correlate with the photo-inhibition of hypocotyl elongation. Although this effect was suggested to be due to auxin transport inhibition, there is no structural-functional evidence for this claim. Intriguingly, the light-induced inhibition of hypocotyl elongation in Arabidopsis has been ascribed to HYPOSENSITIVE TO LIGHT/KARRIKIN-INSENSITIVE2 (HTL/KAI2) signaling. KAI2 was discovered because of its affinity to the smoke-derived karrikin (KAR), though it is generally assumed that KAI2 has another, endogenous but so far elusive, ligand rather than the exogenous KARs. Here, we postulate that the effect of STLs on hypocotyl elongation is mediated through KAI2 signaling. To support this hypothesis, we have generated homology models of the sunflower KAI2s (HaKAI2s) and used them for molecular docking studies with STLs. Our results show that particularly two sunflower STLs, 8-epixanthatin and tomentosin, can bind to the hydrophobic pockets of HaKAI2s with high affinity. Our results are in line with a recent study, showing that these two STLs accumulate in the light-exposed hypocotyls of sunflower. This finding sheds light on the effect of STLs in hypocotyl elongation that has been reported for many decades but without conclusive insight in the elusive mechanism underlying this effect.

Incomplete Removal and Accidental Retention of Temporary Epicardial Pacing Wires in the Chest after Heart Surgery: A Case Report.

Temporary pacemaker wires are commonly used for the diagnosis and treatment of arrhythmias in the acute postoperative period. We herein describe a 65-year-old woman with a history of coronary artery bypass graft surgery who was referred to the hospital with a purulent discharge in the lower third of the sternal region while on antibiotics. Two years later, following treatment failure, 2 sternal wires were removed. Several years after the surgery, the patient developed a purulent discharge. On suspicion of rib osteomyelitis, the last left cartilage attached to the sternum was excised and removed together with an infectious tract. During the operation, the right ventricle was torn, and tampons were used to control bleeding. The patient was placed under cardiopulmonary bypass via the cannulation of the left femoral artery and the right femoral vein. The sternum was opened, and the rupture site was repaired. A temporary epicardial pacing wire was found at the site of the right ventricular rupture. Several days later, the patient was taken from the intensive care unit to the operating room due to a pulsatile hematoma in the left groin and a diagnosis of a pseudoaneurysm of the femoral artery. After a week, the purulent discharge at the lower sternum improved, and the patient was discharged. At 1 month's post-discharge follow-up, the infection was eradicated.

Predictors of ST Depression Resolution in STEMI Patients Undergoing Primary PCI and Its Clinical Significance.

PURPOSE: ST depression resolution (STD-R) in ECG is a prognostic factor indicative of successful fibrinolysis or angioplasty in the treatment of ST elevation myocardial infarction (STEMI) and subsequent mortality. We conducted this study to determine the clinical significance of STD-R and its predictors in patients with anterior STEMI undergoing primary percutaneous intervention (PPCI). METHODS: Admission documents of all patients with diagnosis of anterior STEMI who were admitted to a specialty heart center and underwent PPCI since July 2018 until July 2019 were examined. The amount of ST elevation and depression in all 12 leads of a standard ECG at admission and 90 minutes after PPCI was measured and resolution was determined. All patients were followed-up for 10.8±4.0 months. RESULTS: A total of 179 patients had ST depression besides elevation in the first ECG. Female gender, diabetes, not smoking, lower hemoglobin, and higher platelet counts were significantly more common in the group with less than 50% resolution of ST depression. STD-R <50% was significantly associated with the incidence of in-hospital acute heart failure and major adverse cardiac events (MACE) (p value: 0.025 and 0.012, respectively) and resolution of ST elevation ≥50% was associated with reduced in-hospital mortality (p value <0.0001). According to Kaplan-Meier curve, survival in the two groups of STE-R ≥50% and STE-R <50% was significantly different (Log rank: 31.18, p value<0.0001). CONCLUSION: STD-R can be considered to have high predictive power, like STE-R for predicting incidence of in-hospital acute heart failure and major adverse cardiac events.

The negative regulator SMAX1 controls mycorrhizal symbiosis and strigolactone biosynthesis in rice.

Most plants associate with beneficial arbuscular mycorrhizal (AM) fungi that facilitate soil nutrient acquisition. Prior to contact, partner recognition triggers reciprocal genetic remodelling to enable colonisation. The plant Dwarf14-Like (D14L) receptor conditions pre-symbiotic perception of AM fungi, and also detects the smoke constituent karrikin. D14L-dependent signalling mechanisms, underpinning AM symbiosis are unknown. Here, we present the identification of a negative regulator from rice, which operates downstream of the D14L receptor, corresponding to the homologue of the Arabidopsis thaliana Suppressor of MAX2-1 (AtSMAX1) that functions in karrikin signalling. We demonstrate that rice SMAX1 is a suppressor of AM symbiosis, negatively regulating fungal colonisation and transcription of crucial signalling components and conserved symbiosis genes. Similarly, rice SMAX1 negatively controls strigolactone biosynthesis, demonstrating an unexpected crosstalk between the strigolactone and karrikin signalling pathways. We conclude that removal of SMAX1, resulting from D14L signalling activation, de-represses essential symbiotic programmes and increases strigolactone hormone production.

Engineering a Promiscuous Tautomerase into a More Efficient Aldolase for Self-Condensations of Linear Aliphatic Aldehydes.

The enzyme 4-oxalocrotonate tautomerase (4-OT) from Pseudomonas putida mt-2 takes part in a catabolic pathway for aromatic hydrocarbons, where it catalyzes the conversion of 2hydroxyhexa-2,4-dienedioate into 2-oxohexa-3-enedioate. This tautomerase can also promiscuously catalyze carbon-carbon bond-forming reactions, including various types of aldol reactions, by using its amino-terminal proline as a key catalytic residue. Here, we used systematic mutagenesis to identify two hotspots in 4-OT (Met45 and Phe50) at which single mutations give marked improvements in aldolase activity for the self-condensation of propanal. Activity screening of a focused library in which these two hotspots were varied led to the discovery of a 4-OT variant (M45Y/F50V) with strongly enhanced aldolase activity in the self-condensation of linear aliphatic aldehydes, such as acetaldehyde, propanal, and butanal, to yield α,ß-unsaturated aldehydes. With both propanal and benzaldehyde, this double mutant, unlike the previously constructed single mutant F50A, mainly catalyzes the self-condensation of propanal rather than the cross-condensation of propanal and benzaldehyde, thus indicating that it indeed has altered substrate specificity. This variant could serve as a template to create new biocatalysts that lack dehydration activity and possess further enhanced aldolase activity, thus enabling the efficient enzymatic self-coupling of aliphatic aldehydes.