A defective ABC transporter of the MRP family, responsible for the bean lpa1 mutation, affects the regulation of the phytic acid pathway, reduces seed myo-inositol and alters ABA sensitivity

We previously identified the lpa1 (low phytic acid) 280-10 line that carries a mutation conferring a 90% reduction in phytic acid (InsP6) content. In contrast to other lpa mutants, lpa1(280-10) does not display negative pleiotropic effects. In the present paper, we have identified the mutated gene and analysed its impact on the phytic acid pathway. Here, we mapped the lpa1(280-10) mutation by bulk analysis on a segregating F2 population, an then, by comparison with the soybean genome, we identified and sequenced a candidate gene. The InsP6 pathway was analysed by gene expression and quantification of metabolites. The mutated Pvmrp1(280-10) cosegregates with the lpa1(280-10) mutation, and the expression level of several genes of the InsP6 pathway are reduced in the lpa1(280-10) mutant as well as the inositol and raffinosaccharide content. PvMrp2, a very similar paralogue of PvMrp1 was also mapped and sequenced. The lpa1 mutation in beans is likely the result of a defective Mrp1 gene (orthologous to the lpa genes AtMRP5 and ZmMRP4), while its Mrp2 paralog is not able to complement the mutant phenotype in the seed. This mutation appears to down-regulate the InsP6 pathway at the transcriptional level, as well as altering inositol-related metabolism and affecting ABA sensitivity

Sagittal abdominal diameter as a surrogate marker of insulin resistance in an admixtured population—brazilian metabolic syndrome study (BRAMS)

Sagittal abdominal diameter (SAD) has been proposed as a surrogate marker of insulin resistance (IR). However, the utilization of SAD requires specific validation for each ethnicity. We aimed to investigate the potential use of SAD, compared with classical anthropometrical parameters, as a surrogate marker of IR and to establish the cutoff values of SAD for screening for IR. Methods A multicenter population survey on metabolic disorders was conducted. A race-admixtured sample of 824 adult women was assessed. The anthropometric parameters included: BMI, waist circumference (WC), waist-to-hip ratio and SAD. IR was determined by a hyperglycemic clamp and the HOMA-IR index. Results After adjustments for age and total body fat mass, SAD (r = 0.23 and r = -0.70) and BMI (r = 0.20 and r = -0.71) were strongly correlated with the IR measured by the HOMA-IR index and the clamp, respectively (p < 0.001). In the ROC analysis, the optimal cutoff for SAD in women was 21.0 cm. The women with an increased SAD presented 3.2 (CI 95%: 2.1-5.0) more likelihood of having IR, assessed by the HOMA-IR index compared with those with normal SAD (p < 0.001); whereas women with elevated BMI and WC were 2.1 (95% CI: 1.4-3.3) and 2.8 (95% CI: 1.7-4.5) more likely to have IR (p < 0.001), respectively. No statistically significant results were found for waist-to-hip ratio. Conclusions SAD can be a suitable surrogate marker of IR. Understanding and applying routine and simplified methods is essential because IR is associated with an increased risk of obesity-related diseases even in the presence of normal weight, slight overweight, as well as in obesity. Further prospective analysis will need to verify SAD as a determinant of clinical outcomes, such as type 2 diabetes and cardiovascular events, in the Brazilian population105CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ563664/2010-

Distributed Joint Attack Detection and Secure State Estimation

The joint task of detecting attacks and securely monitoring the state of a cyber-physical system is addressed over a cluster-based network wherein multiple fusion nodes collect data from sensors and cooperate in a neighborwise fashion in order to accomplish the task. The attack detection–state estimation problem is formulated in the context of random set theory by representing joint information on the attack presence/absence, on the system state, and on the attack signal in terms of a hybrid Bernoulli random set (HBRS) density. Then, combining previous results on HBRS recursive Bayesian filtering with novel results on Kullback–Leibler averaging of HBRSs, a novel distributed HBRS filter is developed and its effectiveness is tested on a case study concerning wide-area monitoring of a power network

Haemodynamics and oxygenation improvement induced by high frequency percussive ventilation in a patient with hypoxia following cardiac surgery: a case report

<p>Abstract</p> <p>Introduction</p> <p>High frequency percussive ventilation is a ventilatory technique that delivers small bursts of high flow respiratory gas into the lungs at high rates. It is classified as a pneumatically powered, pressure-regulated, time-cycled, high-frequency flow interrupter modality of ventilation. High frequency percussive ventilation improves the arterial partial pressure of oxygen with the same positive end expiratory pressure and fractional inspiratory oxygen level as conventional ventilation using a minor mean airway pressure in an open circuit. It reduces the barotraumatic events in a hypoxic patient who has low lung-compliance. To the best of our knowledge, there have been no papers published about this ventilation modality in patients with severe hypoxaemia after cardiac surgery.</p> <p>Case presentation</p> <p>A 75-year-old Caucasian man with an ejection fraction of 27 percent, developed a lung infection with severe hypoxaemia [partial pressure of oxygen/fractional inspiratory oxygen of 90] ten days after cardiac surgery. Conventional ventilation did not improve the gas exchange. He was treated with high frequency percussive ventilation for 12 hours with a low conventional respiratory rate (five per minute). His cardiac output and systemic and pulmonary pressures were monitored.</p> <p>Compared to conventional ventilation, high frequency percussive ventilation gives an improvement of the partial pressure of oxygen from 90 to 190 mmHg with the same fractional inspiratory oxygen and positive end expiratory pressure level. His right ventricular stroke work index was lowered from 19 to seven g-m/m²/beat; his pulmonary vascular resistance index from 267 to 190 dynes•seconds/cm⁵/m²; left ventricular stroke work index from 28 to 16 gm-m/m²/beat; and his pulmonary arterial wedge pressure was lowered from 32 to 24 mmHg with a lower mean airway pressure compared to conventional ventilation. His cardiac index (2.7 L/min/m²) and ejection fraction (27 percent) did not change.</p> <p>Conclusion</p> <p>Although the high frequency percussive ventilation was started ten days after the conventional ventilation, it still improved the gas exchange. The reduction of right ventricular stroke work index, left ventricular stroke work index, pulmonary vascular resistance index and pulmonary arterial wedge pressure is directly related to the lower respiratory mean airway pressure and the consequent afterload reduction.</p

CO rebinding kinetics and molecular dynamics simulations highlight dynamic regulation of internal cavities in human cytoglobin

Cytoglobin (Cygb) was recently discovered in the human genome and localized in different tissues. It was suggested to play tissue-specific protective roles, spanning from scavenging of reactive oxygen species in neurons to supplying oxygen to enzymes in fibroblasts. To shed light on the functioning of such versatile machinery, we have studied the processes supporting transport of gaseous heme ligands in Cygb. Carbon monoxide rebinding shows a complex kinetic pattern with several distinct reaction intermediates, reflecting rebinding from temporary docking sites, second order recombination, and formation (and dissociation) of a bis-histidyl heme hexacoordinated reaction intermediate. Ligand exit to the solvent occurs through distinct pathways, some of which exploit temporary docking sites. The remarkable change in energetic barriers, linked to heme bis-histidyl hexacoordination by HisE7, may be responsible for active regulation of the flux of reactants and products to and from the reaction site on the distal side of the heme. A substantial change in both protein dynamics and inner cavities is observed upon transition from the CO-liganded to the pentacoordinated and bis-histidyl hexacoordinated species, which could be exploited as a signalling state. These findings are consistent with the expected versatility of the molecular activity of this protein

Study protocol for a multicenter randomized controlled trial to compare radiofrequency ablation with surgical resection for treatment of pancreatic insulinoma

Background: Insulinoma is the most common functional pancreatic neuroendocrine tumor and treatment is required to address symptoms associated with insulin hypersecretion. Surgical resection is effective but burdened by high rate of adverse events (AEs). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) demonstrated encouraging results in terms of safety and efficacy for the management of these tumors. However, studies comparing surgery and EUS-RFA are lacking. Aims: The primary aim is to compare EUS-RFA with surgery in term of safety (overall rate of AEs). Secondary endpoints include: (a) severe AEs rate; (b) clinical effectiveness; (c) patient's quality of life; (d) length of hospital stay; (e) rate of local/distance recurrence; (f) need of reintervention; (g) rate of endocrine and exocrine pancreatic insufficiency; (h) factors associated with EUS-RFA related AEs and clinical effectiveness. Methods: ERASIN-RCT is an international randomized superiority ongoing trial in four countries. Sixty patients will be randomized in two arms (EUS-RFA vs surgery) and outcomes compared. Two EUS-RFA sessions will be allowed to achieve symptoms resolution. Randomization and data collection will be performed online. Discussion: This study will ascertain if EUS-RFA can become the first-line therapy for management of small, sporadic, pancreatic insulinoma and be included in a step-up approach in case of clinical failure. &amp; COPY; 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Healthcare resource consumption and related costs of patients estimated with treatment-resistant depression in Italy

Purpose: To analyse the healthcare resource consumption and related costs for the Italian National Health System of patients estimated to be affected by treatment-resistant depression (TRD) in Italy. Patients and methods: This was an observational retrospective study based on administrative databases, including those related to residential/semiresidential structures, of Veneto Region and the Local Health Unit of Bergamo in Italy (for a total of around 6 million health-assisted subjects). Between July 2011 and December 2017, all adult patients with a third antidepressant (AD) after ≥2 AD (each one with at least ≥4 weeks duration, ≥1 prescription at maximum dosage reported in datasheets, a grace period ≤30 days when switching AD and treatment maintained ≥9 months) were included. Overall and psychiatry-related healthcare resources consumption and related costs were estimated on a 12-months based analysis. Data were re-proportioned to the Italian population. Results: We have previously estimated a total of 101,455 patients with TRD in Italy (130,049 considering the mean maximum dosage of AD). Of them, 44.2% had at least a psychiatric hospitalization/visit or accessed a residential/semiresidential structure, and 31% added another AD or a mood stabilizer/antipsychotic drug. Patients with at least one psychiatry-related hospitalization increased over the number of antidepressant lines from 12.0% during first line up to 24.5% during fourth line. Direct healthcare costs increased from €4,405 for first line to €9,251 from fifth line onwards. Psychiatry-related costs went from €1,817 (first line) to €4,606 (fifth line onwards) and were mainly driven by residential/semiresidential structures and hospitalizations. Conclusion: An upward trend with number of AD lines was observed for all healthcare resource utilization and consequently for all direct costs, thus indicating an increasing burden for patients as they move forward AD lines

Ligation Tunes Protein Reactivity in an Ancient Haemoglobin: Kinetic Evidence for an Allosteric Mechanism in Methanosarcina acetivorans Protoglobin

Protoglobin from Methanosarcina acetivorans (MaPgb) is a dimeric globin with peculiar structural properties such as a completely buried haem and two orthogonal tunnels connecting the distal cavity to the solvent. CO binding to and dissociation from MaPgb occur through a biphasic kinetics. We show that the heterogenous kinetics arises from binding to (and dissociation from) two tertiary conformations in ligation-dependent equilibrium. Ligation favours the species with high binding rate (and low dissociation rate). The equilibrium is shifted towards the species with low binding (and high dissociation) rates for the unliganded molecules. A quantitative model is proposed to describe the observed carbonylation kinetics