Differential Internalization of Amphotericin B - Conjugated Nanoparticles in Human Cells and the Expression of Heat Shock Protein 70

Although a variety of nanoparticles (NPs) functionalized with amphotericin B, an antifungal agent widely used in the clinic, have been studied in the last years their cytotoxicity profile remains elusive. Here we show that human endothelial cells take up high amounts of silica nanoparticles (SNPs) conjugated with amphotericin B (AmB) (SNP-AmB) (65.4 12.4 pg of Si per cell) through macropinocytosis while human fibroblasts internalize relatively low amounts (2.3 0.4 pg of Si per cell) because of their low capacity for macropinocytosis. We further show that concentrations of SNP-AmB and SNP up to 400 mg/mL do not substantially affect fibroblasts. In contrast, endothelial cells are sensitive to low concentrations of NPs (above 10 mg/mL), in particular to SNP-AmB. This is because of their capacity to internalize high concentration of NPs and high sensitivity of their membrane to the effects of AmB. Low-moderate concentrations of SNP-AmB (up to 100 mg/mL) induce the production of reactive oxygen species (ROS), LDH release, high expression of pro-inflammatory cytokines and chemokines (IL-8, IL-6, G-CSF, CCL4, IL-1b and CSF2) and high expression of heat shock proteins (HSPs) at gene and protein levels. High concentrations of SNP-AmB (above 100 ug/mL) disturb membrane integrity and kill rapidly human cells(60% after 5 h). This effect is higher in SNP-AmB than in SNP.

The Role of Psychological Adjustment in the Decision-Making Process for Voluntary Termination of Pregnancy

BACKGROUND: This study's objective was to evaluate the role of psychological adjustment in the decision-making process to have an abortion and explore individual variables that might influence this decision. METHODS: In this cross-sectional study, we sequentially enrolled 150 women who made the decision to voluntarily terminate a pregnancy in Maternity Dr. Alfredo da Costa, in Lisbon, Portugal, between September 2008 and June 2009. The instruments were the Depression, Anxiety and Stress Scale (DASS), Satisfaction with Social Support Scale (SSSS), Emotional Assessment Scale (EAS), Decision Conflict Scale (DCS), and Beliefs and Values Questionnaire (BVQ). We analyzed the data using Student's T-tests, MANOVA, ANOVA, Tukey's post-hoc tests and CATPCA. Statistically significant effects were accepted for p<0.05. RESULTS: The participants found the decision difficult and emotionally demanding, although they also identified it as a low conflict decision. The prevailing emotions were sadness, fear and stress; but despite these feelings, the participants remained psychologically adjusted in the moment they decided to have an abortion. The resolution to terminate the pregnancy was essentially shared with supportive people and it was mostly motivated by socio-economic issues. The different beliefs and values found in this sample, and their possible associations are discussed. CONCLUSION: Despite high levels of stress, the women were psychologically adjusted at the time of making the decision to terminate the pregnancy. However, opposing what has been previously reported, the women presented high levels of sadness and fear, showing that this decision was hard to make, triggering disruptive emotions.

Is This Septic Shock? A Rare Case of Distributive Shock

The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration - a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease.

Welfare analysis of regulating mobile termination rates in the UK with an application to the Orange/T-Mobile merger

We present a calibrated model of the UK mobile telephony market with four mobile networks; calls to and from the fixed network; network-based price discrimination; and call externalities. Our results show that reducing mobile termination rates broadly in line with the recent European Commission Recommendation to either pure long-run incremental cost ; reciprocal termination charges with fixed networks; or Bill & Keep (i.e. zero termination rates), increases social welfare, consumer surplus and networks profits. Depending on the strength of call externalities, social welfare may increase by as much as £ 990 million to £ 4.5 billion per year, with Bill & Keep leading to the highest increase in welfare. We also apply the model to estimate the welfare effects of the 2010 merger between Orange and T-Mobile under different scenarios concerning MTRs, and predict that consumer surplus decreases strongly.

Evaluation of the welfare impact of regulating mobile termination rates in Portugal

Following the European Commission’s 2009 Recommendation on the Regulatory Treatment of Fixed and Mobile Termination Rates in the EU, the Portuguese regulatory authority (ANACOM) decided to reduce termination prices in mobile networks to their long-run incremental cost (LRIC). Nevertheless, no serious quantitative assessment of the potential effects of this decision was carried out. In this paper, we adapt and calibrate the Harbord and Hoernig (2014) model of the UK mobile telephony market to the Portuguese reality, and simulate the likely impact on consumer surplus, profits and welfare of four different regulatory approaches: pure LRIC, reciprocal termination charges with fixed networks, “bill & keep”, and asymmetric termination rates. Our results show that reducing MTRs does increase social welfare, profits and consumer surplus in the fixed market, but mobile subscribers are seriously harmed by this decision.

Frequency of the toxic shock syndrome toxin-1 gene in methicillin-susceptible and -resistant Staphylococcus aureus isolates from teaching hospitals in Shiraz, Iran

INTRODUCTION: Staphylococcus aureus produces a range of virulence factors such as toxic shock syndrome toxin-1. METHODS: In this cross-sectional study of 345 clinical S. aureus isolates, the presence of the tst gene was assessed by polymerase chain reaction (PCR). RESULTS: The study revealed 53/345 (15.4%) isolates were positive for the tst gene. The tst gene was present in 18.1% of methicillin-susceptible S. aureus (MSSA) isolates and 11.6% of methicillin-resistant S. aureus (MRSA) isolates (p = 0.136). CONCLUSIONS: These results reveal the remarkable risk of S. aureus infections in hospitals, regardless of methicillin-resistance status.

Physiological stress responses in the warm-water fish matrinxã (Brycon amazonicus ) subjected to a sudden cold shock

The present work evaluated several aspects of the generalized stress response [endocrine (cortisol), metabolic (glucose), hematologic (hematocrit and hemoglobin) and cellular (HSP70)] in the Amazonian warm-water fish matrinxã (Brycon amazonicus ) subjected to an acute cold shock. This species farming has been done in South America, and growth and feed conversion rates have been interesting. However, in subtropical areas of Brazil, where the water temperature can rapidly change, high rates of matrinxã mortality have been associated with abrupt decrease in the water temperature. Thus, we subjected matrinxã to a sudden cold shock by transferring the fish directly to tanks in which the water temperature was 10ºC below the initial conditions (cold shock from 28ºC to 18ºC). After 1h the fish were returned to the original tanks (28ºC). The handling associated with tank transfer was also imposed on control groups (not exposed to cold shock). While exposure to cold shock did not alter the measured physiological conditions within 1h, fish returned to the ambient condition (water at 28º C) significantly increased plasma cortisol and glucose levels. Exposure to cold shock and return to the warm water did not affect HSP70 levels. The increased plasma cortisol and glucose levels after returning the fish to warm water suggest that matrinxã requires cortisol and glucose for adaptation to increased temperature.

Stenting of unprotected left main coronary artery in a patient with cardiogenic shock

A 64-year-old female presented with pulmonary edema and cardiogenic shock after coronary arteriography that showed severe suboclusive lesion in the left main coronary artery (LMCA) in a dominant left coronary system. The patient succesfully underwent urgent angioplasty with stent deployment in the LMCA. After an uneventful period, the patient was discharged at day six.