Exploring the Fatty Acid Binding Pocket in the SARS-CoV-2 Spike Protein - Confirmed and Potential Ligands.

Severe Acute Respiratory syndrome 2 (SARS-CoV-2) is a respiratory virus responsible for coronavirus disease 19 (COVID-19) and the still ongoing and unprecedented global pandemic. The key viral protein for cell infection is the spike glycoprotein, a surface-exposed fusion protein that both recognizes and mediates entry into host cells. Within the spike glycoprotein, a fatty acid binding pocket (FABP) was confirmed, with the crystallization of linoleic acid (LA) occupying a well-defined site. Importantly, when the pocket is occupied by a fatty acid, an inactive conformation is stabilized, and cell recognition is hindered. In this review, we discuss ligands reported so far for this site, correlating their activity predicted through in silico studies with antispike experimental activity, assessed by either binding assays or cell-infection assays. LA was the first confirmed ligand, cocrystallized in a cryo-EM structure of the spike protein, resulting in increased stability of the inactive conformation of the spike protein. The next identified ligand, lifitegrast, was also experimentally confirmed as a ligand with antiviral activity, suggesting the potential for diverse chemical scaffolds to bind this site. Finally, SPC-14 was also confirmed as a ligand, although no inhibition assays were performed. In this review, we identified 20 studies describing small-molecule compounds predicted to bind the pocket in in silico studies and with confirmed binding or in vitro activity, either inhibitory activity against the spike-ACE2 interaction or antiviral activity in cell-based assays. When considering all ligands confirmed with in vitro assays, a good overall occupation of the pocket should be complemented with the ability to make direct interactions, both hydrophilic and hydrophobic, with key amino acid residues defining the pocket surface. Among the active compounds, long flexible carbon chains are recurrent, with retinoids capable of binding the FABP, although bulkier systems are also capable of affecting viral fitness. Compounds able to bind this site with high affinity have the potential to stabilize the inactive conformation of the SARS-CoV-2 spike protein and therefore reduce the virus's ability to infect new cells. Since this pocket is conserved in highly pathogenic human coronaviruses, including MERS-CoV and SARS-CoV, this effect could be exploited for the development of new antiviral agents, with broad-spectrum anticoronavirus activity.

Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients.

BACKGROUND: The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients. METHODS: Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT). RESULTS: 184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation. CONCLUSIONS: A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.

Thyroid hormone induces restrictive cardiomyopathy in ß1-adrenoceptor knockout mice.

The purpose of this study was to characterize the role of ß1-AR signaling and its cross-talk between cardiac renin-angiotensin system and thyroid-hormone-induced cardiac hypertrophy. T3 was administered at 0.5 mg·kg-1·day-1 for 10 days in ß1-KOT3 and WTT3 groups, while control groups received vehicle alone. Echocardiography and myocardial histology was performed; cardiac and serum ANGI/ANGII and ANP and cardiac levels of p-PKA, p-ERK1/2, p-p38-MAPK, p-AKT, p-4EBP1, and ACE were measured. WTT3 showed decreased IVSTd and increased LVEDD versus WTsal (p < 0.05). ß1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus ß1-KOsal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WTT3 versus ß1-KOT3 (p < 0.05). Cardiac ACE expression was increased in T3-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or ß1-KOT3, p-4EBP1 was elevated in ß1-KO animals, and p-ERK1/2 was up-regulated in ß1-KOT3. These findings suggest that ß1-AR signaling is crucial for TiCH.

Minimal-Resource Home Exercise Program Improves Activities of Daily Living, Perceived Health Status, and Shortness of Breath in Individuals with COPD Stages GOLD II to IV.

Home exercises (HE) with minimal resources seem to be useful in individuals with COPD. The objective was to evaluate the effects of HE, on activities of daily living (ADL), dyspnea, on the health status(CAT) and quality of life (HRQoL) of individuals with COPD GOLD II to IV. Quasi-experimental study of the effects of HE, for 2 months, 3 times a week. Individuals with COPD(n = 45) were recruited, 37 started the protocol(9 did not complete it). 28 individuals (mean age 62.04 ± 5.8 years, FEV1: 44.7 ± 2.25%, FEV1/FVC 59.8 ± 6.9%) were evaluated before and after training. We observed improvements in the ADL-Glittre (4.9 ± 1.4 vs 3.9 ± 1.1 min; mean difference: -0.9 ± 0.2 min [95%CI: -1.3 to -0.2]; p = 0.008), as well as the mMRC score(2.8 ± 1.1 vs 2.07 ± 0.81; mean difference: 0.7 ± 0.3 [95%CI: -1.20.18 to -0.2]; p = 0.009), and in the CAT (25.6 ± 4.8 vs 18.9 ± 3.1; mean difference: -6.6 ± 3.4 [95%CI: -10.6 to -1.6]; p = 0.042). Analyzing the mean change before and after the intervention, a weak correlation was observed between ADL-Glittre and mMRC (r = 0.35; [95% CI 0.09; 0.56]; p = 0.009); moderate between ADL-Glittre and CAT (r = 0.52; [95% CI 0.30; 0.69]; p < 0.001) and between ADL-Glittre and SGRQ (r = 0.50; [95% CI 0 .27; 0.67]; p < 0.001). Individuals with COPD can benefit from HE performed autonomously and with minimal resources, as this proposal improves functional capacity for ADL, health perception and dyspnea.

Alternate-day fasting, a high-sucrose/caloric diet and praziquantel treatment influence biochemical and behavioral parameters during Schistosoma mansoni infection in male BALB/c mice.

Schistosoma mansoni-induced granulomas result in severe damage to the host's liver, as well as neurological and metabolic disorders. We evaluated the biochemical and behavioral changes during schistosomiasis under three diet protocols: ad libitum (AL), alternate-day fasting (ADF) and a high-sucrose/caloric diet (HSD). Healthy male BALB/c mice were divided into noninfected, matched infected and infected/treated [praziquantel (PZQ)] groups. Caloric intake and energy efficiency coefficients associated with diets were measured. Behavioral (exploratory and locomotor) and biochemical (glucose, triglycerides, total cholesterol, AST, ALT, ALP, and γ-GT) tests and histological analysis were performed. Fifteen weeks postinfection, HSD and PZQ promoted weight gain, with higher caloric consumption than ADF (p < 0.05), reflecting serum glucose levels and lipid profiles. HSD and PZQ prevented liver dysfunction (AST and ALT) and significantly prevented increases in granuloma area (p < 0.05). HSD and PZQ also significantly improved mouse physical performance in exploratory and locomotor behavior (p < 0.05), reversing the impaired motivation caused by infection. These findings showed that ADF worsened the course of S. mansoni infection, while HSD and PZQ, even with synergistic effects, prevented and/or attenuated biochemical and behavioral impairment from infection.

Association of Functional Characteristics and Physiotherapy with COVID-19 Mortality in Intensive Care Unit in Inpatients with Cardiovascular Diseases.

Background and Objectives: To estimate the association between admission functional outcomes and exposure to physiotherapy interventions with mortality rate in intensive care unit (ICU) inpatients with cardiovascular diseases and new coronavirus disease (COVID-19). Materials and Methods: Retrospective cohort including 100 ICU inpatients (mean (standard deviation), age 75 (16) years) split into COVID-19+ or COVID-19−. The association of in-ICU death with admission functional outcomes and physiotherapy interventions was investigated using univariable and multivariable regression models. Results: In total, 42 (42%) patients tested positive for COVID-19. In-ICU mortality rate was 37%, being higher for the COVID-19+ group (odds ratio, OR (95% CI): 3.15 (1.37−7.47), p = 0.008). In-ICU death was associated with lower admission ICU Mobility Scale score (0.81 (0.71−0.91), p = 0.001). Restricted mobility (24.90 (6.77−161.94), p < 0.001) and passive kinesiotherapy (30.67 (9.49−139.52), p < 0.001) were associated with in-ICU death, whereas active kinesiotherapy (0.13 (0.05−0.32), p < 0.001), standing (0.12 (0.05−0.30), p < 0.001), or walking (0.10 (0.03−0.27), p < 0.001) were associated with in-ICU discharge. Conclusions: In-ICU mortality was higher for inpatients with cardiovascular diseases who had COVID-19+, were exposed to invasive mechanical ventilation, or presented with low admission mobility scores. Restricted mobility or passive kinesiotherapy were associated with in-ICU death, whereas active mobilizations (kinesiotherapy, standing, or walking) were associated with in-ICU discharge in this population.

Physiological and Transcriptomic Changes in the Hypothalamic-Neurohypophysial System after 24 h of Furosemide-Induced Sodium Depletion.

BACKGROUND/AIMS: Furosemide is a loop diuretic widely used in clinical practice for the treatment of oedema and hypertension. The aim of this study was to determine physiological and molecular changes in the hypothalamic-neurohypophysial system as a consequence of furosemide-induced sodium depletion. METHODS: Male rats were sodium depleted by acute furosemide injection (10 and 30 mg/kg) followed by access to low sodium diet and distilled water for 24 h. The renal and behavioural consequences were evaluated, while blood and brains were collected to evaluate the neuroendocrine and gene expression responses. RESULTS: Furosemide treatment acutely increases urinary sodium and water excretion. After 24 h, water and food intake were reduced, while plasma angiotensin II and corticosterone were increased. After hypertonic saline presentation, sodium-depleted rats showed higher preference for salt. Interrogation using RNA sequencing revealed the expression of 94 genes significantly altered in the hypothalamic paraventricular nucleus (PVN) of sodium-depleted rats (31 upregulated and 63 downregulated). Out of 9 genes chosen, 5 were validated by quantitative PCR in the PVN (upregulated: Ephx2, Ndnf and Vwf; downregulated: Caprin2 and Opn3). The same genes were also assessed in the supraoptic nucleus (SON, upregulated: Tnnt1, Mis18a, Nr1d1 and Dbp; downregulated: Caprin2 and Opn3). As a result of these plastic transcriptome changes, vasopressin expression was decreased in PVN and SON, whilst vasopressin and oxytocin levels were reduced in plasma. CONCLUSIONS: We thus have identified novel genes that might regulate vasopressin gene expression in the hypothalamus controlling the magnocellular neurons secretory response to body sodium depletion and consequently hypotonic stress.

Supplementation with L-Arginine Decreases Jejunal Lesions and Micronucleus Formation Induced by 5-Fluorouracil in Rats.

The objective of this study was to evaluate the effect of L-arginine supplementation on the formation of jejunal lesions and micronuclei in Wistar rats following 5-fluorouracil (5-FU) treatment. Fifty rats were separated into five groups: CG served as the control group, GArg was supplemented L-arginine, G5-FU was administered 5-FU, GArg+5-FU was supplemented L-arginine/day and administered 5-FU, and Gciclo served as a positive control group for micronuclei formation. Jejunal lesions were assessed by histopathological analysis using a scoring system with a maximum of 39 points, based on the following lesions: lymph vessel dilatation, cubic enterocytes, villous flattening, villus fusion, interstitial edema, and apical necrosis of the villi. Micronuclei were counted in polychromatic erythrocytes from the femur bone marrow. The control and GArg rats had the lowest number of jejunal lesions (6.4 ± 2.8 and 5.3 ± 2.4, respectively) and micronuclei (1.9 ± 0.6 and 1.1 ± 0.3, respectively) while the G5-FU rats had the highest number of jejunal lesions (24.2 ± 4.9) and micronuclei (36.0 ± 8.5). The GArg+5-FU rats showed significantly reduced (P < 0.05) jejunal lesions (10.2 ± 4.9) and micronuclei (15.4 ± 5.9). In conclusion L-arginine supplementation potentially reduces the jejunal lesions and DNA damage caused by 5-FU.

Uncertainties Involved in the Use of Thresholds for the Detection of Water Bodies in Multitemporal Analysis from Landsat-8 and Sentinel-2 Images.

Although the single threshold is still considered a suitable and easy-to-do technique to extract water features in spatiotemporal analysis, it leads to unavoidable errors. This paper uses an enumerative search to optimize thresholds over satellite-derived modified normalized difference water index (MNDWI). We employed a cross-validation approach and treated accuracy as a random variable in order to: (a) investigate uncertainty related to its application; (b) estimate non-optimistic errors involving single thresholding; (c) investigate the main factors that affect the accuracy's model, and (d) compare satellite sensors performance. We also used a high-resolution digital elevation model to extract water elevations values, making it possible to remove topographic effects and estimate non-optimistic errors exclusively from orbital imagery. Our findings evidenced that there is a region where thresholds values can vary without causing accuracy loss. Moreover, by constraining thresholds variation between these limits, accuracy is dramatically improved and outperformed the Otsu method. Finally, the number of scenes employed to optimize a single threshold drastically affects the accuracy, being not appropriate using a single scene once it leads to overfitted threshold values. More than three scenes are recommended.

SARS-CoV-2 Virus-Host Interaction: Currently Available Structures and Implications of Variant Emergence on Infectivity and Immune Response.

Coronavirus disease 19, or COVID-19, is an infection associated with an unprecedented worldwide pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has led to more than 215 million infected people and more than 4.5 million deaths worldwide. SARS-CoV-2 cell infection is initiated by a densely glycosylated spike (S) protein, a fusion protein, binding human angiotensin converting enzyme 2 (hACE2), that acts as the functional receptor through the receptor binding domain (RBD). In this article, the interaction of hACE2 with the RBD and how fusion is initiated after recognition are explored, as well as how mutations influence infectivity and immune response. Thus, we focused on all structures available in the Protein Data Bank for the interaction between SARS-CoV-2 S protein and hACE2. Specifically, the Delta variant carries particular mutations associated with increased viral fitness through decreased antibody binding, increased RBD affinity and altered protein dynamics. Combining both existing mutations and mutagenesis studies, new potential SARS-CoV-2 variants, harboring advantageous S protein mutations, may be predicted. These include mutations S13I and W152C, decreasing antibody binding, N460K, increasing RDB affinity, or Q498R, positively affecting both properties.

Pockels-effect-based adiabatic frequency conversion in ultrahigh-Q microresonators.

Adiabatic frequency conversion has some key advantages over nonlinear frequency conversion. No threshold and no phase-matching conditions need to be fulfilled. Moreover, it exhibits a conversion efficiency of 100 % down to the single-photon level. Adiabatic frequency conversion schemes in microresonators demonstrated so far suffer either from low quality factors of the employed resonators resulting in short photon lifetimes or small frequency shifts. Here, we present an adiabatic frequency conversion (AFC) scheme by employing the Pockels effect. We use a non-centrosymmetric ultrahigh-Q microresonator made out of lithium niobate. Frequency shifts of more than 5 GHz are achieved by applying just 20 V to a 70-µm-thick resonator. Furthermore, we demonstrate that with the same setup positive and negative frequency chirps can be generated. With this method, by controlling the voltage applied to the crystal, almost arbitrary frequency shifts can be realized. The general advances in on-chip fabrication of lithium-niobate-based devices make it feasible to transfer the current apparatus onto a chip suitable for mass production.

Frequency Comb Generation via Cascaded Second-Order Nonlinearities in Microresonators.

Optical frequency combs are revolutionizing modern time and frequency metrology. In the past years, their range of applications has increased substantially, driven by their miniaturization through microresonator-based solutions. The combs in such devices are typically generated using the third-order χ^{(3)} nonlinearity of the resonator material. An alternative approach is making use of second-order χ^{(2)} nonlinearities. While the idea of generating combs this way has been around for almost two decades, so far only few demonstrations are known, based either on bulky bow-tie cavities or on relatively low-Q waveguide resonators. Here, we present the first such comb that is based on a millimeter-sized microresonator made of lithium niobate, that allows for cascaded second-order nonlinearities. This proof-of-concept device comes already with pump powers as low as 2 mW, generating repetition-rate-locked combs around 1064 and 532 nm. From the nonlinear dynamics point of view, the observed combs correspond to Turing roll patterns.

Stress among Portuguese Medical Students: the EuStress Solution.

There has been an increasing attention to the study of stress. Particularly, college students often experience high levels of stress that are linked to several negative outcomes concerning academic functioning, physical, and mental health. In this paper, we introduce the EuStress Solution, that aims to create an Information System to monitor and assess, continuously and in real-time, the stress levels of the students in order to predict burnout. The Information System will use a measuring instrument based on wearable device and machine learning techniques to collect and process stress-related data from the students without their explicit interaction. In the present study, we focus on heart rate and heart rate variability indices, by comparing baseline and stress condition. We performed different statistical tests in order to develop a complex and intelligent model. Results showed the neural network had the better model fit.

Photoinactivation of Pseudomonas syringae pv. actinidiae in kiwifruit plants by cationic porphyrins.

MAIN CONCLUSION: The studied cationic porphyrins formulation allows an effective photoinactivation of Pseudomonas syringae pv. actinidiae in kiwifruit leaves under sunlight irradiation, without damaging the plant. Pseudomonas syringae pv. actinidiae (Psa) is a Gram-negative phytopathogenic bacterium responsible for canker on kiwifruit plant. Over the last decade, this bacterium dramatically affected the production of this fruit worldwide, causing significant economic losses. In general, Psa control consists in the application of copper which are toxic and persist in the environment. The application of antimicrobial photodynamic therapy (aPDT) as an alternative to inactivate Psa has already been demonstrated in recent studies that showed a 4 log Psa reduction using the cationic porphyrin Tetra-Py+-Me as photosensitizer (PS) and 3 consecutive cycles of treatment with a light irradiance of 150 mW cm-2. The present work aimed to evaluate the photodynamic efficiency of a new formulation constituted with five cationic porphyrins as PS in Psa inactivation. This new formulation was prepared to have as main component the tri-cationic porphyrin which is considered one of the most efficient photosensitizers in the photoinactivation of microorganisms. The in vitro study with a PS concentration of 5.0 µM and low irradiance, showed a 7.4 log photoinactivation after 60 min. Posteriorly, several assays were performed with the PS at 50 µM on kiwifruit leaves (ex vivo), under different conditions of light and inoculation. The ex vivo assays with artificially contaminated leaves showed a 2.8 and 4.5 log inactivation with low irradiance and sunlight, respectively, after 90 min. After a second treatment with sunlight, a 6.2 log inactivation was achieved. The photoinactivation on naturally contaminated leaves was about 2.3 log after 90 min sunlight irradiation. Ten consecutive cycles of phototreatment in sub-lethal conditions showed that Psa does not develop resistance, nor recover viability. The results suggest that aPDT can be an alternative to the current methods used to control Psa, since it was possible to inactivate this bacterium under sunlight, without damaging the leaves.

Effects of L-Arginine Supplementation on Leukogram, Inflammatory Bowel Infiltrates and Immunoglobulins with 5-FU Use in Rats.

This study evaluated the effects of L-arginine supplementation on blood parameters, kidney and liver function, immunoglobulins and noninflammatory infiltrates in the small intestines of rats subjected to chemotherapy with 5-fluorouracil (5-FU). Thirty-two Wistar rats were randomly distributed into 4 groups (8 rats/group): an untreated control group, and test groups receiving one dose of 5-FU (G5-FU group), one dose of 5-FU and 295 mg L-arginine/day (GArg295 group) or one dose of 5-FU and 458 mg L-arginine/day (GArg458 group). Neutrophil count, platelet count, serum IgA, and fibrinogen levels in GArg295 and GArg458 remained within normal limits after chemotherapy. In addition, in GArg458 the inflammatory bowel infiltrates improved in 57% of the rats, which showed mild inflammation. The results suggest that daily supplementation with 295 or 458 mg L-arginine attenuates the side effects of 5-FU, including thrombocytopenia and neutropenia, and modulates IgA production. Supplementation with 458 mg of L-arginine/day can also reduce mucositis levels in the small intestine after 5-FU chemotherapy.

An insight into the photodynamic approach versus copper formulations in the control of Pseudomonas syringae pv. actinidiae in kiwi plants.

In the last decade, the worldwide production of kiwi fruit has been highly affected by Pseudomonas syringae pv. actinidiae (Psa), a phytopathogenic bacterium; this has led to severe economic losses that are seriously affecting the kiwi fruit trade. The available treatments for this disease are still scarce, with the most common involving frequently spraying the orchards with copper derivatives, in particular cuprous oxide (Cu2O). However, these copper formulations should be avoided due to their high toxicity; therefore, it is essential to search for new approaches for controlling Psa. Antimicrobial photodynamic therapy (aPDT) may be an alternative approach to inactivate Psa. aPDT consists in the use of a photosensitizer molecule (PS) that absorbs light and by transference of the excess of energy or electrons to molecular oxygen forms highly reactive oxygen species (ROS) that can affect different molecular targets, thus being very unlikely to lead to the development of microbe resistance. The aim of the present study was to evaluate the effectiveness of aPDT to photoinactivate Psa, using the porphyrin Tetra-Py+-Me and different light intensities. The degree of inactivation of Psa was assessed using the PS at 5.0 µM under low irradiance (4.0 mW cm-2). Afterward, ex vivo experiments, using artificially contaminated kiwi leaves, were conducted with a PS at 50 µM under 150 mW cm-2 and sunlight irradiation. A reduction of 6 log in the in vitro assays after 90 min of irradiation was observed. In the ex vivo tests, the decrease was lower, approximately 1.8 log reduction at an irradiance of 150 mW cm-2, 1.2 log at 4.0 mW cm-2, and 1.5 log under solar radiation. However, after three successive cycles of treatment under 150 mW cm-2, a 4 log inactivation was achieved. No negative effects were observed on leaves after treatment. Assays using Cu2O were also performed at the recommended concentration by law (50 g h L-1) and at concentrations 10 times lower, in which at both concentrations, Psa was efficiently inactivated (5 log inactivation) after a few minutes of treatment, but negative effects were observed on the leaves after treatment.

A Review of Commercial and Medical-Grade Physiological Monitoring Devices for Biofeedback-Assisted Quality of Life Improvement Studies.

With the rise in wearable technology and "health culture", we are seeing an increasing interest and affordances in studying how to not only prolong life expectancy but also in how to improve individuals' quality of life. On the one hand, this attempts to give meaning to the increasing life expectancy, as living above a certain threshold of pain and lack of autonomy or mobility is both degrading and unfair. On the other hand, it lowers the cost of continuous care, as individuals with high quality of life indexes tend to have lower hospital readmissions or secondary complications, not to mention higher physical and mental health. In this paper, we evaluate the current state of the art in physiological therapy (biofeedback) along with the existing medical grade and consumer grade hardware for physiological research. We provide a quick primer on the most commonly monitored physiologic metrics, as well as a brief discussion on the current state of the art in biofeedback-assisted medical applications. We then go on to present a comparative analysis between medical and consumer grade biofeedback devices and discuss the hardware specifications and potential practical applications of each consumer grade device in terms of functionality and adaptability for controlled (laboratory) and uncontrolled (field) studies. We end this article with some empirical observations based on our study so that readers might use take them into consideration when arranging a laboratory or real-world experience, thus avoiding costly time delays and material expenditures.

Central angiotensin-(1-7) increases osmotic thirst.

NEW FINDINGS: What is the central question of this study? The central goal of this study was to understand the effects of central angiotensin-(1-7) on basal and osmotically stimulated water intake in rats. What is the main finding and its importance? This study demonstrated that central administration of angiotensin-(1-7) did not induce thirst in basal conditions but increased water intake after osmotic stimulation, such as water deprivation and salt loading. These results indicate a new function for this peptide, which, in turn, allows for future research on the mechanisms through which angiotensin-(1-7) influences osmotic thirst. Angiotensin-(1-7) [Ang-(1-7)] is generated by type 2 angiotensin-converting enzyme (ACE2) and binds to the MAS receptor. Although it is well known that Ang-(1-7) functionally antagonizes the effects of the classical renin-angiotensin system in several situations, the role of Ang-(1-7) in hydromineral homeostasis is not clear. The aim of this study was to assess the role of Ang-(1-7) on neuroendocrine responses to hyperosmolality in rats. Male Wistar rats were divided into the following three groups: control; 24 h of water deprivation (WD); and 24 h of salt loading (SL; 1.8% NaCl). Intracerebroventricular (i.c.v.) injections of Ang-(1-7) or vehicle were given to assess water intake and plasma concentration of vasopressin. Additionally, the brains from control and WD groups were collected to evaluate gene expression in the subfornical organ (SFO), paraventricular nucleus (PVN) and supraoptic nucleus (SON). It was found that i.c.v. Ang-(1-7) did not change water and salt intake in control rats; however, Ang-(1-7) increased water intake after WD and SL, with no change in salt intake. Plasma vasopressin was not changed by i.c.v. Ang-(1-7) in control or WD rats. Moreover, WD increased Mas gene expression in the SON and PVN, with no changes in Ace2 mRNA levels. In conclusion, Ang-(1-7) increases thirst after osmotic stimuli, indicating that a previous sensitization to its action is necessary. This finding is consistent with the increased Mas gene expression in the PVN and SON after water deprivation.

Data Mining in HIV-AIDS Surveillance System : Application to Portuguese Data.

The Human Immunodeficiency Virus (HIV) is an infectious agent that attacks the immune system cells. Without a strong immune system, the body becomes very susceptible to serious life threatening opportunistic diseases. In spite of the great progresses on medication and prevention over the last years, HIV infection continues to be a major global public health issue, having claimed more than 36 million lives over the last 35 years since the recognition of the disease. Monitoring, through registries, of HIV-AIDS cases is vital to assess general health care needs and to support long-term health-policy control planning. Surveillance systems are therefore established in almost all developed countries. Typically, this is a complex system depending on several stakeholders, such as health care providers, the general population and laboratories, which challenges an efficient and effective reporting of diagnosed cases. One issue that often arises is the administrative delay in reports of diagnosed cases. This paper aims to identify the main factors influencing reporting delays of HIV-AIDS cases within the portuguese surveillance system. The used methodologies included multilayer artificial neural networks (MLP), naive bayesian classifiers (NB), support vector machines (SVM) and the k-nearest neighbor algorithm (KNN). The highest classification accuracy, precision and recall were obtained for MLP and the results suggested homogeneous administrative and clinical practices within the reporting process. Guidelines for reductions of the delays should therefore be developed nationwise and transversally to all stakeholders.

A Serious Games Platform for Cognitive Rehabilitation with Preliminary Evaluation.

In recent years Serious Games have evolved substantially, solving problems in diverse areas. In particular, in Cognitive Rehabilitation, Serious Games assume a relevant role. Traditional cognitive therapies are often considered repetitive and discouraging for patients and Serious Games can be used to create more dynamic rehabilitation processes, holding patients' attention throughout the process and motivating them during their road to recovery. This paper reviews Serious Games and user interfaces in rehabilitation area and details a Serious Games platform for Cognitive Rehabilitation that includes a set of features such as: natural and multimodal user interfaces and social features (competition, collaboration, and handicapping) which can contribute to augment the motivation of patients during the rehabilitation process. The web platform was tested with healthy subjects. Results of this preliminary evaluation show the motivation and the interest of the participants by playing the games.