Sulfur Starvation in Extremophilic Microalga Galdieria sulphuraria: Can Glutathione Contribute to Stress Tolerance?

This study reports the effects of sulfur (S) deprivation in cultures of Galdieria sulphuraria (Cyanidiophyceae). Galdieria is a unicellular red alga that usually grows, forming biomats on rocks, in S-rich environments. These are volcanic areas, where S is widespread since H2S is the prevalent form of gas. The glutathione content in Galdieria sulphuraria is much higher than that found in the green algae and even under conditions of S deprivation for 7 days, it remains high. On the other hand, the S deprivation causes a decrease in the total protein content and a significant increase in soluble protein fraction. This suggests that in the conditions of S starvation, the synthesis of enzy-matic proteins, that metabolically support the cell in the condition of nutritional stress, could be up regulated. Among these enzymatic proteins, those involved in cell detoxification, due to the accumulation of ROS species, have been counted

Potential harm caused by physicians' a-priori beliefs in the clinical effectiveness of hydroxychloroquine and its impact on clinical and economic outcome - A simulation approach

BACKGROUND: Despite growing controversies around Hydroxychloroquine's effectiveness, the drug is still widely prescribed by clinicians to treat COVID19 patients. Therapeutic judgment under uncertainty and imperfect information may be influenced by personal preference, whereby individuals, to confirm a-priori beliefs, may propose drugs without knowing the clinical benefit. To estimate this disconnect between available evidence and prescribing behavior, we created a Bayesian model analyzing a-priori optimistic belief of physicians in Hydroxychloroquine's effectiveness. METHODOLOGY: We created a Bayesian model to simulate the impact of different a-priori beliefs related to Hydroxychloroquine's effectiveness on clinical and economic outcome. RESULTS: Our hypothetical results indicate no significant difference in treatment effect (combined survival benefit and harm) up to a presumed drug's effectiveness level of 20%, with younger individuals being negatively affected by the treatment (RR 0.82, 0.55-1.2; (0.95 (1.1) % expected adverse events versus 0.05 (0.98) % expected death prevented). Simulated cost data indicate overall hospital cost (medicine, hospital stay, complication) of 18.361,41€ per hospitalized patient receiving Hydroxychloroquine treatment. CONCLUSION: Off-label use of Hydroxychloroquine needs a rational, objective and datadriven evaluation, as personal preferences may be flawed and cause harm to patients and to society

Environmental sustainability fruit quality and production in mycorrhizal tomato plants without P fertilizing

The influence of root colonization by arbuscular mycorrhizal (AM) fungus Funelliformis mosseae, on fruit quality, production and environmental sustainability were evaluated in field-tomato plants grown exposed to P-limited soil 5 µg g -1 soil (basal-soil) with nitrate fertilization (50 µg g -1 soil), after greenhouse germination and fungus colonization. After 60 days sowing (DAS), when the percentage of mycorrhizal root length (% RLC) raised at about 50%, the plants were transplanted in open field. During the experiment, the mycorrhization has affected a lot of physiological aspects like vegetative and reproductive growth, improving them and ended the fruiting with a major fruit production that was 50% higher than not mycorrhizal (NM) plants. The ripening process of the fruits was also followed by testing sugars content and ß-Amylase activity in fruits of NM and mycorrhizal (M) plants fruits. At 140 DAS, in the harvesting fruits stage, fruits of M plants showed significantly higher mineral nutrient sugars and organic nitrogen compounds as amino acids and protein, compared to fruits from NM plants. In particular, GLU-GLN-ASP and ASN raised about 35% more than fruits from NM plants, improving nutritional aspect and flavor of the product. THR-ILEU-LEU-VAL and LYS, essential amino acids in man nutrition, increased around 25% more than fruits from NM plants, too. In this contest, lycopene, total carotenoids, ascorbic acid and glutathione (GS) and reduced form (GSH) were also tested in ripe fruits. The overall results suggest that tomato roots colonization by mycorrhizal fungus Funelliformis mosseae affects host plant nutritional status, modifying reproductive behavior, fruits production and nutritional quality

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes

Objectives: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027– Clostridium difficile infection (CDI). Methods: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027– CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. Results: Overall, 238 patients with 027+ CDI and 267 with 027– CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549–3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906–5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051–3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281–4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437–9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155–125.000, p 0.007) were associated with recurrence in 027– CDI. Conclusions: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity

Simultaneous biochemical and physiological responses of the roots and leaves of pancratium maritimum (Amaryllidaceae) to mild salt stress

Pancratium maritimum (Amaryllidaceae) is a bulbous geophyte growing on coastal sands. In this study, we investigated changes in concentrations of metabolites in the root and leaf tissue of P. maritimum in response to mild salt stress. Changes in concentrations of osmolytes, glutathione, sodium, mineral nutrients, enzymes, and other compounds in the leaves and roots were measured at 0, 3, and 10 days during a 10‐day exposure to two levels of mild salt stress, 50 mM NaCl or 100 mM NaCl in sandy soil from where the plants were collected in dunes near Cuma, Italy. Sodium accumulated in the roots, and relatively little was translocated to the leaves. At both concentrations of NaCl, higher values of the concentrations of oxidized glutathione disulfide (GSSG), compared to reduced glutathione (GSH), in roots and leaves were associated with salt tolerance. The concentration of proline increased more in the leaves than in the roots, and glycine betaine increased in both roots and leaves. Differences in the accumulation of organic osmolytes and electron donors synthesized in both leaves and roots demonstrate that osmoregulatory and electrical responses occur in these organs of P. maritimum under mild salt stress

Impact of sulfur starvation in autotrophic and heterotrophic cultures of the Extremophilic Microalga Galdieria Phlegrea (Cyanidiophyceae)

In plants and algae, sulfate assimilation and cysteine synthesis are regulated by sulfur (S) accessibility from the environment. This study reports the effects of S deprivation in autotrophic and heterotrophic cultures of Galdieria phlegrea (Cyanidiophyceae), a unicellular red alga isolated in the Solfatara crater located in Campi Flegrei (Naples, Italy), where H2S is the prevalent form of gaseous S in the fumarolic fluids and S is widespread in the soils near the fumaroles. This is the first report on the effects of S deprivation on a sulfurous microalga that is also able to grow heterotrophically in the dark. The removal of S from the culture medium of illuminated cells caused a decrease in the soluble protein content and a significant decrease in the intracellular levels of glutathione. Cells from heterotrophic cultures of G. phlegrea exhibited high levels of internal proteins and high glutathione content, which did not diminish during S starvation, but rather glutathione significantly increased. The activity of O-acetylserine(thiol)lyase (OASTL), the enzyme synthesizing cysteine, was enhanced under S deprivation in a time-dependent manner in autotrophic but not in heterotrophic cells. Analysis of the transcript abundance of the OASTL gene supports the OASTL activity increase in autotrophic cultures under S deprivation

A parametric study of a multiphase porous media model for tumor spheroids and environment interactions

Computational models for tumor growth provide an effective in silico tool to investigate the different stages of cancer growth. Recently, a series of computational models based on porous media theory has been proposed to predict tumor evolution and its interactions with the host tissue. In addition, a specialization of the original models, adapted for tumor spheroids, has been proposed and validated experimentally. However, due to the complexity of the modeling framework, a systematic understanding of the role of the parameters governing the equations is still lacking. In this work, we perform a parametric analysis on a set of fundamental parameters appearing in the model equations. We investigate the effects of a variation of these coefficients on the spheroid growth curves and, in particular, on the final radii reached by the cell aggregates in the growth saturation stage. Finally, we provide a discussion of the results and give a brief summary of our findings

Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions

The first example of palladium-catalysed oxidative carbonylation of unprotected α-amino amides to hydantoins is described here. The selective synthesis of the target compounds was achieved under mild conditions (1 atm of CO), without ligands and bases. The catalytic system overrode the common reaction pathway that usually leads instead to the formation of symmetrical ureas

Recognition in emergency department of septic patients at higher risk of death: Beware of patients without fever

Background and Objectives: Chances of surviving sepsis increase markedly upon prompt diagnosis and treatment. As most sepsis cases initially show-up in the Emergency Department (ED), early recognition of a septic patient has a pivotal role in sepsis management, despite the lack of precise guidelines. The aim of this study was to identify the most accurate predictors of in-hospital mortality outcome in septic patients admitted to the ED. Materials and Methods: We compared 651 patients admitted to ED for sepsis (cases) with 363 controls (non-septic patients). A Bayesian mean multivariate logistic regression model was performed in order to identify the most accurate predictors of in-hospital mortality outcomes in septic patients. Results: Septic shock and positive qSOFA were identified as risk factors for in-hospital mortality among septic patients admitted to the ED. Hyperthermia was a protective factor for in-hospital mortality. Conclusions: Physicians should bear in mind that fever is not a criterium for defining sepsis; according to our results, absence of fever upon presentation might be indicative of greater severity and diagnosis of sepsis should not be delayed