Building a neurocognitive profile of suicidal risk in severe mental disorders

Background Research on the influence of neurocognitive factors on suicide risk, regardless of the diagnosis, is inconsistent. Recently, suicide risk studies propose applying a trans-diagnostic framework in line with the launch of the Research Domain Criteria Cognitive Systems model. In the present study, we highlight the extent of cognitive impairment using a standardized battery in a psychiatric sample stratified for different degrees of suicidal risk. We also differentiate in our sample various neurocognitive profiles associated with different levels of risk. Materials and methods We divided a sample of 106 subjects into three groups stratified by suicide risk level: Suicide Attempt (SA), Suicidal Ideation (SI), Patient Controls (PC) and Healthy Controls (HC). We conducted a multivariate Analysis of Variance (MANOVA) for each cognitive domain measured through the standardized battery MATRICS Consensus Cognitive Battery (MCCB). Results We found that the group of patients performed worse than the group of healthy controls on most domains; social cognition was impaired in the suicide risk groups compared both to HC and PC. Patients in the SA group performed worse than those in the SI group. Conclusion Social cognition impairment may play a crucial role in suicidality among individuals diagnosed with serious mental illness as it is involved in both SI and SA; noteworthy, it is more compromised in the SA group fitting as a marker of risk severity

Isolation of a Complex Formed Between Acinetobacter baumannii HemA and HemL, Key Enzymes of Tetrapyrroles Biosynthesis

Plants, algae and most bacteria synthesize 5-aminolevulinic acid (ALA), the universal precursor of tetrapyrroles such as heme, chlorophyll and coenzyme B12, by a two-step transformation involving the NADPH-dependent glutamyl-tRNA reductase (HemA), which reduces tRNA-bound glutamate to glutamate-1-semialdehyde (GSA), and the pyridoxamine 5′-phosphate-dependent glutamate-1-semialdehyde-2,1-aminomutase (HemL), responsible for the isomerization of GSA into ALA. Since GSA is a very unstable compound at pH values around neutrality, the formation of a HemA-HemL complex has been proposed to occur, allowing for direct channeling of this intermediate from HemA to HemL. Experimental evidence of the formation of this complex has been obtained with the enzymes from Escherichia coli and Chlamydomonas reinhardtii. However, its isolation has never been attained, probably because HemA is degraded when intracellular heme accumulates. In this work, we devised a co-expression and co-purification strategy of HemA and HemL from Acinetobacter baumannii, which allowed the isolation of the HemA-HemL complex. Our results indicate that HemA is stabilized when co-expressed with HemL. The addition of citrate throughout the expression and purification procedure further promotes the formation of the HemA-HemL complex, which can be isolated in fair amount for functional and structural studies. This work lays the bases for a rational design of HemA-HemA inhibitors to be developed as antibacterial agents against A. baumannii, a multidrug resistant opportunistic pathogen responsible for a broad range of severe nosocomial infections

Serum High Mobility Group Box-1 Levels Associated With Cardiovascular Events After Lower Extremity Revascularization: A Prospective Study of a Diabetic Population

Background: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI). Methods: We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. Results: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p \u3c 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p \u3c 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75). Conclusions: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI

Development of a Biomarker Panel for Assessing Cardiovascular Risk in Diabetic Patients With Chronic Limb-Threatening Ischemia (Clti): A Prospective Study

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI. METHODS: In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes\u27 incidence was evaluated after 1, 3, 6 and 12 months. RESULTS: During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events. CONCLUSIONS: Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER

Deficit Irrigation and Partial Root-Zone Drying Techniques in Processing Tomato Cultivated under Mediterranean Climate Conditions

Due to climate change, the application of water saving strategies is of particular interest. The aim of this study was to evaluate the effects of deficit irrigation (DI) and partial root-zone drying (PRD) techniques on the crop water stress index (CWSI), water use efficiency (WUE), and quality parameters in processing tomatoes grown in open field conditions in a Mediterranean climate. Two cultivars were grown for two growing seasons under four irrigation regimes as follows: (i) IR100: full irrigation by restoring 100% of the maximum tomato evapotranspiration (ETc); (ii) IR70DI: 70% of the amount of water given to the IR100; (iii) IR70PRD: 70% of the amount of water given to the IR100 by applying partial root-zone drying and (iv) IR0: irrigation only at transplanting and during fertigation. During the flowering period, the first growing season was characterized by an absence of rainfall and by higher temperatures also showing a higher CWSI. Despite, under IR70PRD, the CWSI was significantly higher than under IR70DI, the marketable yield obtained was significantly higher. Both IR70DI and IR70PRD regimes received approximately 24% less water than IR100, but the yield reduction with relation to the optimum regime was equal to 16.2% under IR70DI, and only 7.6% under IR70PRD. The WUE increment of IR70PRD with respect to IR100 was equal to 27% in the first growing season and to 17% in the second one, showing that the positive effect of PRD on the WUE is more evident in the more stressed year. Finally, the results from the principal component analysis (PCA) showed that the two cultivars had different qualitative responses in the two extreme regimes (IR100 and IR0) but not under PRD and DI regimes

A case of gh deficiency in a patient with joubert syndrome

BACKGROUND Joubert syndrome (JS) and related disorders (JSRD) are a group of developmental delay/multiple congenital anomalies syndromes in which the obligatory hallmark is the molar tooth sign (MTS), a complex midbrain-hindbrain malformation visible on MRI, first recognised in JS. The neurological features of JSRD include hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing dysregulation. JSRD are classified in six subgroups: Pure JS; JS with ocular defect; JS with renal defect; JS with oculorenal defects; JS with hepatic defect; JS with orofaciodigital defects. JSRD follow autosomal recessive inheritance. CASE REPORT A13 years old boy was referred to our hospital for short stature. At the age of 2 years he was diagnosed with JS by clinical typical manifestations and by an MRI. Family history was negative for short stature and parental pubertal timing was within normal limits. The anthropometric measurements showed weight 48.500 kgs and height 134 cms. His height for age was below 3rd percentile (CDC) and weight for age was between 25th-50th percentiles (CDC). The mid parental height was 165 cms. Penis and pubic hair development were Tanner stage 2. Investigations showed that blood glucose, renal function test, liver function test, thyroid function tests and Tissue Transglutaminase Antibodies were all normal, while Testosterone was below the normal ranges (33,4 ng/dl; normal ranges 241–900 ng/dl). The left hand X ray showed a delayed bone age. Using GH stimulation testing with Arginine and Clonidine GH deficiency was confirmed, infact peak GH levels were 0,43 ng/ml and 2,99 ng/ml, respectively. Therefore, recombinant Human GH was introduced (2 ng a day for 6 days in a week). By a clinical and laboratory follow-up, an improvement of his growth was noticed (growth velocity 6 cm in 6 months). Conclution JS is a very variable condition and the full spectrum of symptoms has not yet been determined. Several conditions have been described in which characteristics of JS are present in addition to other findings. GH deficiency is not a common finding, but it can be found in the spectrum of JS and JSRD. Patients with JS need a multidisciplinary approach and a clinical and laboratory follow up to assess a multiorgan involvement and to identify hormone deficiency and, when it’s possible, to estabilish a treatment

The effect of strobilurin on ethylene production in flowers, yield and quality parameters of processing tomato grown under a moderate water stress condition in Mediterranean area

This research was conducted in Southern Italy over two growing seasons to evaluate the effect of strobilurin application on the ethylene production of flowers (EF) and on the yield and quality parameters of processing tomato grown under moderate water deficit conditions. The following two irrigation regimes were applied: IR100, full irrigation that restores 100% of the maximum crop evapotranspiration (ETc) and IR75, which is 75% of the amount of water of IR100. Furthermore, from the beginning of flowering two fungicide treatments were applied three times: fungicide treatment without strobilurin (ST0) and strobilurin fungicide with an azoxystrobin based product (STaz). At full flowering, ethylene production in the flowers (EF) was determined. At harvest, the main yield and qualitative parameters were evaluated. The strobilurin treatment caused a significant decrease of EF, which was less evident in the first warmer year than in the second. This result was presumably because of the interference of high temperatures on the inhibition of ethylene synthesis described for the strobilurin. In contrast, the decrease of EF due to strobilurin treatment was more evident under IR75 than under IR100. Finally, the decrease in the number of marketable fruits with respect to the EF increase was lower under strobilurin treatment presumably because of the protective effect of this molecule on the flower drop. Further studies are needed to investigate this hypothesis in greater detail

Human cytosolic and mitochondrial serine hydroxymethyltransferase isoforms in comparison: full kinetic characterization and substrate inhibition properties

Serine hydroxymethyltransferase (SHMT) catalyzes the reversible conversion of l-serine and tetrahydrofolate into glycine and 5,10-methylenetetrahydrofolate. This enzyme, which plays a pivotal role in one-carbon metabolism, is involved in cancer metabolic reprogramming and is a recognized target of chemotherapy intervention. In humans, two isoforms of the enzyme exist, which are commonly termed cytosolic SHMT1 and mitochondrial SHMT2. Considerable attention has been paid to the structural, mechanistic, and metabolic features of these isozymes. On the other hand, a detailed comparison of their catalytic and regulatory properties is missing, although this aspect seems to be considerably important, considering that SHMT1 and SHMT2 reside in different cellular compartments, where they play distinct roles in folate metabolism. Here we performed a full kinetic characterization of the serine hydroxymethyltransferase reaction catalyzed by SHMT1 and SHMT2, with a focus on pH dependence and substrate inhibition. Our investigation, which allowed the determination of all kinetic parameters of serine hydroxymethyltransferase forward and backward reactions, uncovered a previously unobserved substrate inhibition by l-serine and highlighted several interesting differences between SHMT1 and SHMT2. In particular, SHMT2 maintains a pronounced tetrahydrofolate substrate inhibition even at the alkaline pH characteristic of the mitochondrial matrix, whereas with SHMT1 this is almost abolished. At this pH, SHMT2 also shows a catalytic efficiency that is much higher than that of SHMT1. These observations suggest that such different properties represent an adaptation of the isoforms to the respective cellular environments and that substrate inhibition may be a form of regulation