Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives.

In all cells, proteins are continuously synthesized and degraded to maintain protein homeostasis and modify gene expression levels in response to stimuli. Collectively, the processes of protein synthesis and degradation are referred to as protein turnover. At a steady state, protein turnover is constant to maintain protein homeostasis, but in dynamic responses, proteins change their rates of synthesis and degradation to adjust their proteomes to internal or external stimuli. Thus, probing the kinetics and dynamics of protein turnover lends insight into how cells regulate essential processes such as growth, differentiation, and stress response. Here, we outline historical and current approaches to measuring the kinetics of protein turnover on a proteome-wide scale in both steady-state and dynamic systems, with an emphasis on metabolic tracing using stable isotope-labeled amino acids. We highlight important considerations for designing proteome turnover experiments, key biological findings regarding the conserved principles of proteome turnover regulation, and future perspectives for both technological and biological investigation.

Evaluation of the Analgesic Effect of High-Cannabidiol-Content Cannabis Extracts in Different Pain Models by Using Polymeric Micelles as Vehicles.

Currently, cannabis is considered an attractive option for the treatment of various diseases, including pain management. Thus, developing new analgesics is paramount for improving the health of people suffering from chronic pain. Safer natural derivatives such as cannabidiol (CBD) have shown excellent potential for the treatment of these diseases. This study aimed to evaluate the analgesic effect of a CBD-rich cannabis extract (CE) encapsulated in polymeric micelles (CBD/PMs) using different pain models. The PEG-PCL polymers were characterized by gel permeation chromatography and 1H-NMR spectroscopy. PMs were prepared by solvent evaporation and characterized by dynamic light scattering (DLS) and transmission electron microscopy. The analgesic activity of CBD/PMs and nonencapsulated CE rich in CBD (CE/CBD) was evaluated using mouse thermal, chemical, and mechanical pain models. The acute toxicity of the encapsulated CE was determined by oral administration in mice at a dose of 20 mg/kg for 14 days. The release of CBD from the nanoparticles was assessed in vitro using a dialysis experiment. CBD/PMs with an average hydrodynamic diameter of 63.8 nm obtained from a biocompatible polyethylene glycol-block-polycaprolactone copolymer were used as nanocarriers for the extract formulations with 9.2% CBD content, which corresponded with a high encapsulation efficiency of 99.9%. The results of the pharmacological assays indicated that orally administered CBD/PMs were safe and exerted a better analgesic effect than CE/CBD. The micelle formulation had a significant analgesic effect in a chemical pain model, reaching a percentage of analgesia of 42%. CE was successfully encapsulated in a nanocarrier, providing better stability. Moreover, it proved to be more efficient as a carrier for CBD release. The analgesic activity of CBD/PMs was higher than that of free CE, implying that encapsulation is an efficient strategy for improving stability and functionality. In conclusion, CBD/PMs could be promising therapeutics for pain management in the future.

Translation, Cultural Adaptation, and Validation of the American Orthopedic Foot and Ankle Society Scale in Patients With Hallux Valgus in Colombia.

The American Orthopedic Foot and Ankle Society (AOFAS) scale for hallux metatarsophalangeal (MTP) and interphalangeal (IP) joints is used throughout the world for the clinical assessment of patients with hallux valgus, and it has 3 subscales: pain, function, and alignment. The objective of this prospective, observational study was to perform translation, cultural adaptation, and validation of this scale for Colombian Spanish. The Foot Function Index and Short Form-36 (SF-36) questionnaires were also used in the validation process. Patients who were 18 years or older, resided in the city of Bogota, were able to read and write in Spanish, and were within 4 years of corrective surgery for hallux valgus were included. A total of 79 patients were included in the study, 25 of whom were involved in the translation process and all of whom were involved in the validation process. Construct validity was demonstrated by significant positive Spearman's correlations between the AOFAS pain subscale and the AOFAS function subscale (rs = 0.483), total AOFAS scale (rs = 0.795), and SF-36 physical summary subscale (rs = 0.364); and between the AOFAS function subscale and the total AOFAS scale (rs = 0.894) and SF-36 physical summary subscale (rs = 0.310). The test-retest process for reliability yielded intraclass correlation coefficients between the AOFAS pain, function, and alignment subscales that were all 0.70 or higher. The AOFAS scale for hallux MTP and IP joints was successfully translated and adapted into Colombian Spanish, and this version demonstrated construct validity and reliability, rendering it suitable for clinical use in Colombian patients with hallux valgus.

Train at home, but not alone: a randomised controlled multicentre trial assessing the effects of live-streamed tele-exercise during COVID-19-related lockdowns.

OBJECTIVE: Public life restrictions associated with the COVID-19 pandemic caused reductions in physical activity (PA) and decreases in mental and somatic health. Considering the interplay between these factors, we investigated the effects of digital home exercise (DHE) during government-enforced lockdowns. METHODS: A multicentre randomised controlled trial was performed allocating healthy individuals from nine countries (N=763; 523 female) to a DHE or an inactive control group. During the 4-week main intervention, DHE members engaged in live-streamed multicomponent home exercise. Subsequently, both groups had access to prerecorded workouts for an additional 4 weeks. Outcomes, assessed weekly, included PA level (Nordic Physical Activity Questionnaire-Short), anxiety (Generalized Anxiety Disorder Scale-7), mental well-being (WHO-5 Questionnaire), sleep quality (Medical Outcome Study Sleep Scale), pain/disability (Chronic Pain Grade Scale) and exercise motivation (Self-Concordance Scale). Mixed models were used for analysis. RESULTS: Live-streamed DHE consistently increased moderate PA (eg, week 1: 1.65 times more minutes per week, 95% CI 1.40 to 1.94) and vigorous PA (eg, week 1: 1.31 times more minutes per week, 95% CI 1.08 to 1.61), although the effects decreased over time. In addition, exercise motivation, sleep quality and anxiety were slightly improved for DHE in the 4-week live streaming period. The same applied to mental well-being (mean difference at week 4: +0.99, 95% CI 0.13 to 1.86), but an inverted trend was observed after live streaming was substituted by prerecorded exercise. CONCLUSIONS: Live-streamed DHE represents an efficacious method to enhance PA and selected markers of health during pandemic-related public life restrictions. However, research on implementation is warranted to reduce dropout rates. TRIAL REGISTRATION NUMBER: DRKS00021273.

Improving Photostability of Photosystem I-Based Nanodevice by Plasmonic Interactions with Planar Silver Nanostructures.

One of the crucial challenges for science is the development of alternative pollution-free and renewable energy sources. One of the most promising inexhaustible sources of energy is solar energy, and in this field, solar fuel cells employing naturally evolved solar energy converting biocomplexes-photosynthetic reaction centers, such as photosystem I-are of growing interest due to their highly efficient photo-powered operation, resulting in the production of chemical potential, enabling synthesis of simple fuels. However, application of the biomolecules in such a context is strongly limited by the progressing photobleaching thereof during illumination. In the current work, we investigated the excitation wavelength dependence of the photosystem I photodamage dynamics. Moreover, we aimed to correlate the PSI-LHCI photostability dependence on the excitation wavelength with significant (ca. 50-fold) plasmonic enhancement of fluorescence due to the utilization of planar metallic nanostructure as a substrate. Finally, we present a rational approach for the significant improvement in the photostability of PSI in anoxic conditions. We find that photobleaching rates for 5 min long blue excitation are reduced from nearly 100% to 20% and 70% for substrates of bare glass and plasmonically active substrate, respectively. Our results pave promising ways for optimization of the biomimetic solar fuel cells due to synergy of the plasmon-induced absorption enhancement together with improved photostability of the molecular machinery of the solar-to-fuel conversion.

Impact of bile salts and a medium chain fatty acid on the physical properties of self-emulsifying drug delivery systems.

The aim of this study was the evaluation of the influence of bile salts and fatty acids, important components of intestinal fluids, on physical characteristics of self-emulsifying drug delivery systems (SEDDS) such as size, polydispersity (PDI), zeta potential (Zp), turbidity (T%), cloud point temperature (CPT) and drug release. At this purpose, nonionic (ni-SEDDS) and cationic (c-SEDDS) were emulsified in aqueous media containing increasing concentrations of bile salts (BS) and decanoate (Dec). Zp of ni-SEDDS and c-SEDDS became highly negative at 15 mM BS and Dec. Size of ni-SEDDS decreased of 112 nm and of 76 nm at 15 mM BS and Dec, respectively. Size of c-SEDDS decreased of 53 nm at 15 mM BS, but it was not affected by 15 mM Dec. PDI and T% of ni- and c-SEDDS were lowered as well. CPT of ni-SEDDS increased from 70 °C to 97 °C and 84 °C at 15 mM BS and Dec. CPT of c-SEDDS decreased from above 100 °C to 80 °C and to 85 °C at 1.5 mM BS and at 5 mM Dec, respectively. Generally, BS had a more pronounced effect on SEDDS Zp, size, PDI, T %, and CPT than Dec. The release of the model drug quinine was accelerated by BS and Dec. As BS and fatty acids affect the physical characteristics and drug release behavior of SEDDS, their impact should be addressed during the development process.

Functional changes induced by caloric restriction in cardiac and skeletal muscle mitochondria.

Caloric restriction (CR) is widely known to increase life span and resistance to different types of injuries in several organisms. We have previously shown that mitochondria from livers or brains of CR animals exhibit higher calcium uptake rates and lower sensitivity to calcium-induced mitochondrial permeability transition (mPT), an event related to the resilient phenotype exhibited by these organs. Given the importance of calcium in metabolic control and cell homeostasis, we aimed here to uncover possible changes in mitochondrial calcium handling, redox balance and bioenergetics in cardiac and skeletal muscle mitochondria in response to six months of CR. Unexpectedly, we found that CR does not alter the susceptibility to mPT in muscle (cardiac or skeletal), nor calcium uptake rates. Despite the lack in changes in calcium transport properties, CR consistently decreased respiration in the presence of ATP synthesis in heart and soleus muscle. In heart, such changes were accompanied by a decrease in respiration in the absence of ATP synthesis, lower maximal respiratory rates and a reduced rate of hydrogen peroxide release. Hydrogen peroxide release was unaltered by CR in skeletal muscle. No changes were observed in inner membrane potentials and respiratory control ratios. Together, these results highlight the tissue-specific bioenergetic and ion transport effects induced by CR, demonstrating that resilience against calcium-induced mPT is not present in all tissues.

Cosolvents in Self-Emulsifying Drug Delivery Systems (SEDDS): Do They Really Solve Our Solubility Problems?

The aim of this study was to investigate the fate and the impact of cosolvents in self-emulsifying drug delivery systems (SEDDS). Three different SEDDS comprising the cosolvents DMSO (FD), ethanol (FE), and benzyl alcohol (FBA) as well as the corresponding formulations without these cosolvents (FD0, FE0, and FBA0) were developed. Mean droplet size, polydispersity index (PDI), ζ potential, stability, and emulsification time were determined. Cosolvent release studies were performed via the dialysis membrane method and Taylor dispersion analysis (TDA). Furthermore, the impact of cosolvent utilization on payloads in SEDDS was examined using quinine as a model drug. SEDDS with and without a cosolvent showed no significant differences in droplet size, PDI, and ζ potential. The emulsification time was 3-fold (FD0), 80-fold (FE0), and 7-fold (FBA0) longer due to the absence of the cosolvents. Release studies in demineralized water provided evidence for an immediate and complete release of DMSO, ethanol, and benzyl alcohol. TDA confirmed this result. Moreover, a 1.4-fold (FD), 2.91-fold (FE), and 2.17-fold (FBA) improved payload of the model drug quinine in the selected SEDDS preconcentrates was observed that dropped after emulsification within 1-5 h due to drug precipitation. In parallel, the quinine concentrations decreased until reaching the same levels of the corresponding SEDDS without cosolvents. Due to the addition of hydrophilic cosolvents, the emulsifying properties of SEDDS are strongly improved. As hydrophilic cosolvents are immediately released from SEDDS during the emulsification process, however, their drug solubilizing properties in the resulting oily droplets are very limited.

Ligand-induced conformational dynamics of the Escherichia coli Na+/H+ antiporter NhaA revealed by hydrogen/deuterium exchange mass spectrometry.

Na+/H+ antiporters comprise a family of membrane proteins evolutionarily conserved in all kingdoms of life and play an essential role in cellular ion homeostasis. The NhaA crystal structure of Escherichia coli has become the paradigm for this class of secondary active transporters. However, structural data are only available at low pH, where NhaA is inactive. Here, we adapted hydrogen/deuterium-exchange mass spectrometry (HDX-MS) to analyze conformational changes in NhaA upon Li+ binding at physiological pH. Our analysis revealed a global conformational change in NhaA with two sets of movements around an immobile binding site. Based on these results, we propose a model for the ion translocation mechanism that explains previously controversial data for this antiporter. Furthermore, these findings contribute to our understanding of related human transporters that have been linked to various diseases.

Meshness of sewer networks and its implications for flooding occurrence.

Understanding the factors that affect the occurrence of failures in urban drainage networks (UDNs) is a key concept for developing strategies to improve the reliability of such systems. Although a lot of research has been done in this field, the relationship between UDN structure (i.e. layout) and its functional failures is still unclear. In this context, the present study focuses first on determining which are the most common sewer layout topologies, based on a data set of 118 UDNs, and then on analyzing the relationship between these and the occurrence of node flooding using eight subnetworks of the sewer system of Dresden, Germany, as a study case. A method to 'quantify' the topology of a UDN in terms of similarity to a branched or meshed system, referred to as Meshness, is introduced. Results indicate, on the one hand, that most networks have branched or predominantly branched topologies. On the other hand, node flooding events in networks with higher Meshness values are less likely to occur, and have shorter durations and smaller volumes than in predominantly branched systems. Predominantly meshed systems are identified then as more reliable in terms of flooded nodes and flooding volumes.

Unequal misses during the flash-induced advancement of photosystem II: effects of the S state and acceptor side cycles.

Photosynthetic water oxidation is catalyzed by the oxygen-evolving complex (OEC) in photosystem II (PSII). This process is energetically driven by light-induced charge separation in the reaction center of PSII, which leads to a stepwise accumulation of oxidizing equivalents in the OEC (Si states, i = 0-4) resulting in O2 evolution after each fourth flash, and to the reduction of plastoquinone to plastoquinol on the acceptor side of PSII. However, the Si-state advancement is not perfect, which according to the Kok model is described by miss-hits (misses). These may be caused by redox equilibria or kinetic limitations on the donor (OEC) or the acceptor side. In this study, we investigate the effects of individual S state transitions and of the quinone acceptor side on the miss parameter by analyzing the flash-induced oxygen evolution patterns and the S2, S3 and S0 state lifetimes in thylakoid samples of the extremophilic red alga Cyanidioschyzon merolae. The data are analyzed employing a global fit analysis and the results are compared to the data obtained previously for spinach thylakoids. These two organisms were selected, because the redox potential of QA/QA- in PSII is significantly less negative in C. merolae (Em = - 104 mV) than in spinach (Em = - 163 mV). This significant difference in redox potential was expected to allow the disentanglement of acceptor and donor side effects on the miss parameter. Our data indicate that, at slightly acidic and neutral pH values, the Em of QA-/QA plays only a minor role for the miss parameter. By contrast, the increased energy gap for the backward electron transfer from QA- to Pheo slows down the charge recombination reaction with the S3 and S2 states considerably. In addition, our data support the concept that the S2 → S3 transition is the least efficient step during the oxidation of water to molecular oxygen in the Kok cycle of PSII.

Exploring opportunities for embedding graduate attributes in a first-year undergraduate anatomy course for allied health students.

BACKGROUND: There is a growing discontent within the health care industry regarding the state of preparedness of graduates to adequately function in a dynamic work environment. It is therefore required of higher education institutions to equip graduates with skills beyond disciplinary expertise, which would allow them to function optimally in work environments. This study presents a team dissection project that incorporates graduate attributes in an undergraduate first-year anatomy course for the medical orthotics and prosthetics program. METHOD: Focus group interviews with students (n = 23) were used to demonstrate the achievement of graduate attributes by aligning student perceptions of the dissection project with graduate attributes and indicators thereof. RESULTS: Students were positive about the effectiveness of the dissection project in enforcing anatomical knowledge; ensuring active engagement with human material; enhancing communication skills and teamwork; and increasing sensitivity towards cultural diversity. These views related largely to those graduate attributes which engage students towards becoming active and reflective learners; creative thinkers; independent and collaborative workers; effective communicators; and culturally and socially aware citizens. Areas of dissatisfaction included challenges with the use of technology for the video preparation; repetition of presentations and large dissection teams. CONCLUSION: There is an emerging view that graduate attributes be integrated as early as possible into program curricula so as to become intrinsic in a student's academic and professional development. Through the expansion of a dissection project forming part of a subject taught very early on in a program's curriculum, the integration of graduate attributes and discipline-specific competencies are highlighted.

Nutritional planning for Nellore heifers post-weaning to conception at 15 months of age: performance and nutritional, metabolic, and reproductive responses.

The objective of this study was to evaluate the effects of strategic supplementation in the dry period and dry/rainy transition period on the performance and nutritional, metabolic, and reproductive responses of Nellore heifers grazing Urochloa decumbens. Forty-eight Nellore heifers with age and body weight (BW) of eight months and 235 ± 3.3 kg, respectively, were used. The experimental design was a completely randomized design, with four treatments, all with 12 replications. The evaluated strategies were as follows: low supplementation (LOHI; 0.2% of BW/heifer/day) in the first 90 days and high supplementation (0.6% of BW/heifer/day) in the 90 days thereafter; average supplementation (AVER) with 0.4% of BW/heifer/day for 180 days; high supplementation (HILO; 0.6% of BW/heifer/day) in the first 90 days and low supplementation (0.2% of BW/heifer/day) in the 90 days thereafter; only mineral mix (MM) ad libitum during the 180 days. Data were evaluated using orthogonal contrasts. Supplementation improved the performance of the animals during of dry period (P < 0.05) and dry/rainy transition period (P < 0.05). Supplemented animals had higher longissimus muscle area (LMA) and subcutaneous fat thickness (SFT) at the end of the experiment (P < 0.05). Multiple supplementation increased intake of dry matter (DM), organic matter (OM), and crude protein (CP) in kg/day throughout the experiment. The supplementation increased the digestibility of DM, OM, CP, apNDF, and TDN (P < 0.05). Serum urea nitrogen (SUN), glucose (GLUC), insulin (INS), and progesterone (PROG) were higher in supplemented heifers (P < 0.05). Supplementation reduced the concentrations of non-esterified fatty acids (NEFA) (P < 0.05) and increased conception rate (P < 0.05). In summary, the supplementation strategies adopted in this study improve the performance, metabolic status, and carcass traits of heifers under grazing, allowing an improvement in the conception rate of 15-month-old Nellore heifers.

Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases.

During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversed proton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, a translational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intracellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cells have never been described in any other disease and now appear to be a specific hallmark of malignancy. As a consequence of this intracellular acid-base homeostatic failure, the attempt to induce cellular acidification using proton transport inhibitors and other intracellular acidifiers of different origins is becoming a new therapeutic concept and selective target of cancer treatment, both as a metabolic mediator of apoptosis and in the overcoming of multiple drug resistance (MDR). Importantly, there is increasing data showing that different ion channels contribute to mediate significant aspects of cancer pH regulation and etiopathogenesis. Finally, we discuss the extension of this new pH-centric oncological paradigm into the opposite metabolic and homeostatic acid-base situation found in human neurodegenerative diseases (HNDDs), which opens novel concepts in the prevention and treatment of HNDDs through the utilization of a cohort of neural and non-neural derived hormones and human growth factors.

Ethical Challenges Inherent in the Evaluation of an American Indian/Alaskan Native Circles of Care Project.

This article provides first-person accounts of ethical issues inherent in an evaluation of the Native American Indian Center of Central Ohio (NAICCO) Circles of Care project. Circles of Care is a three-year, infrastructure development program funded through the Substance Abuse and Mental Health Services Administration (SAMHSA) which is part of the federal Department of Health and Human Services (DHHS). The grant program is for American Indian and Alaskan Native (AI/AN) tribes and urban Indian communities and includes a strong emphasis on community engagement and community ownership. The Native American Indian Center of Central Ohio received a Circles of Care grant in the fifth cohort of the program. The first author (Project Evaluator) presents views that typically represent a western approach to evaluation, while the second author (Project Director) presents a Native perspective. Ethical issues are defined as well as the authors' efforts to address these concerns.

Inhibition of the oxidative stress response by heat stress in Caenorhabditis elegans.

It has long been recognized that simultaneous exposure to heat stress and oxidative stress shows a synergistic interaction that reduces organismal fitness, but relatively little is known about the mechanisms underlying this interaction. We investigated the role of molecular stress responses in driving this synergistic interaction using the nematode Caenorhabditis elegans To induce oxidative stress, we used the pro-oxidant compounds acrylamide, paraquat and juglone. As expected, we found that heat stress and oxidative stress interact synergistically to reduce survival. Compared with exposure to each stressor alone, during simultaneous sublethal exposure to heat stress and oxidative stress the normal induction of key oxidative-stress response (OxSR) genes was generally inhibited, whereas the induction of key heat-shock response (HSR) genes was not. Genetically activating the SKN-1-dependent OxSR increased a marker for protein aggregation and decreased whole-worm survival during heat stress alone, with the latter being independent of HSF-1. In contrast, compared with wild-type worms, inactivating the HSR by HSF-1 knockdown, which would be expected to decrease basal heat shock protein expression, increased survival during oxidative stress alone. Taken together, these data suggest that, in C. elegans, the HSR and OxSR cannot be simultaneously activated to the same extent that each can be activated during a single stressor exposure. We conclude that the observed synergistic reduction in survival during combined exposure to heat stress and oxidative stress is due, at least in part, to inhibition of the OxSR during activation of the HSR.

Ab initio study of hydrogen chemisorption in nitrogen-doped carbon nanotubes.

The electronic structure of single walled nitrogen-doped carbon nanotubes is calculated by first principles using density functional theory within the supercell approach with periodic boundary conditions. The effect of the adsorption of hydrogen atoms on different sites, relative to the position of the nitrogen atom, is explicitly taken into account. Both non-chiral and chiral geometries are analyzed. The obtained band structure shows that the non-chiral (6,0) nanotube is a semimetal under all different doping and adsorption configurations treated. The non-chiral (10,0) nanotube behaves mostly as a semiconductor, with the band gap width modulated by nitrogen doping and the relative position of the adsorbed hydrogen atom. The increase of substitutional N doping from one to three atoms per cell turns a (6,5) single-walled carbon nanotube from a semiconductor into a semimetal at zero temperature. Optical absorption related to carrier transitions between the calculated states is investigated from the imaginary part of the dielectric function, constructed with the use of the calculated Kohn-Sham states. The importance of the variation of the relative position of the adsorbed hydrogen atom on the chemical and physical properties investigated is particularly highlighted.

[Gastroduodenal mucosal injuries by aspirine. Management of the risks]. / Lesiones mucosas gastroduodenales por aspirina. Administrando los riesgos.

BACKGROUND: Aspirin is one of the most used drugs around the Word, it has wide therapeutic indications. From its original indications, as analgesic and anti-inflammatory and due to its platelet antiaggregate properties, this drug has become in the most employed medicine to prevent cardiovascular disease. Never the less, it is a drug with adverse effects and gastrointestinal toxicity indeed. OBJECTIVES: To identify the reasons of using aspirin, endoscopic findings on gastropathy caused by ASA and the relative risk of developing mucosal lesions. This based on a sample of adult patients in a chosen particular institution. MATERIALS AND METHODS: Prospective study of cases and controls, from January 1 to June 31, 2014, with patients with high digestive endoscopy. In the medical center Endocentro Bogotá D.C. it was selected the people with aspirin consumption on 500 mg per day dose or less taken for more than six months prior the endoscopy. RESULTS: We selected 602 patients, 534 (88%) were women and 168 (12%) were men, with an age range from 17 to 92 years and with an average of 51.8 years. 107 patients were the aspirin users, 59 (55%) were women and 48 (45%) were men, with an range from 23 to 85 years and with an average of 58 years. The follow relative risks were found: gastroduodenal erosions RR=4.9 (95%IC 3.87-8.37), gastric ulcer RR=2.4 (95%IC 1.3-9.0), duodenal ulcer RR=2.8 (95%IC 1.3-7.0) any kind of gastrointestinal injury RR=5.5 (95%IC 4.1-7.2) aspirin users without any indication to the risk of develop any mucosa injury RR=2.0 (95%IC 1.4-3.0). CONCLUSIONS: This study showed an important proportion (18%) of dispatched aspirin users adults to digestive endoscopy, the 13.8% of them have a clear indication to use it, a substantial percent (13%) cannot inform any medical reason; the aspirin usage for more than six months in doses lower than 500 mg per day increases the mucosal gastroduodenal injury prevalence (58%)and relative risk of suffering these injuries are high.

Multiple-stressor interactions influence embryo development rate in the American horseshoe crab, Limulus polyphemus.

Fertilized eggs of the American horseshoe crab, Limulus polyphemus, are buried in shallow nests above the high tide line, where they are exposed to variations in abiotic conditions during early development. Using a multiple-stressors approach, we examined whether the rate of embryonic development is affected by exposure to combinations of three factors: temperature (25, 30 and 35°C), salinity (5, 15 and 34 ppt) and ambient O2 (5%, 13% and 21% O2). Newly fertilized eggs were incubated under 27 fully factorial stressor combinations for 14 days, then allowed to recover in control conditions (30°C, 34 ppt, 21% O2) for an additional 14 days. Growth rate was measured every 2 days throughout the experiment (N=1289). We found that the effect of isolated stressors (high temperature, low salinity or low O2) reduced developmental success by up to 72% (low salinity), and that stressor combinations showed stronger effects and evidence of complex interactions. For example, low O2 had little effect individually but was lethal in combination with high temperature, and low temperature in isolation slightly decreased the rate of development but reduced the negative effects of low salinity and low O2. Development was delayed under exposure to low O2 but resumed upon return to control conditions after a 10 day lag. These data demonstrate that complex, synergistic interactions among abiotic stressors can substantially alter the development of a coastal invertebrate in ways that may not be predicted from the effects of the stressors in isolation.

[Gastrosplenic fistula secondary to gastric adenocarcinoma]. / Fístula gastroesplénica secundaria a adenocarcinoma gástrico.

We present a case report of a patient with spontaneous gastro-splenic fistula due to gastric adenocarcinoma associated with Streptococcus anginosus bacteriemia and fatal outcome.