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Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma.

This study introduces a new automated system that blends multi-satellite information and citizen science data for reliable and timely observations of lake and river ice in under-observed northern regions. The system leverages the Google Earth Engine resources to facilitate the analysis and visualization of ice conditions. The adopted approach utilizes a combination of moderate and high-resolution optical data, along with radar observations. The results demonstrate the system's capability to accurately detect and monitor river ice, particularly during key periods, such as the freeze-up and the breakup. The integration citizen science data showed added values in the validation of remote sensing products, as well as filling gaps whenever satellite observations cannot be collected due to cloud obstruction. Moreover, it was shown that citizen science data can be converted to valuable quantitative information, such as the case of ice thickness, which is very useful when combined with ice extent derived from remote sensing. In this study, citizen science data were employed for the quantitative assessment of the remote sensing product. Obtained results showed a good agreement between the product and observed river status, with a Critical Success Index of 0.82. Notably, the system has shown effectiveness in capturing the spatial and temporal evolution of snow and ice conditions, as evidenced by its application in analyzing specific ice jam events in 2023. The study concludes that the developed system marks a significant advancement in river ice monitoring, combining technological innovation with community engagement. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the prevalence of hypertensive phase (HP) and failure in patients who underwent Ahmed Glaucoma Valve (AGV) implantation and identify the possible risk factors for both HP and failure. Methods: A cross-sectional, observational study was conducted. Medical records of patients who underwent AGV implantation and had at least 1 year of follow-up were reviewed. HP was defined as an intraocular pressure (IOP) greater than 21 mmHg between the first week and the third postoperative month not attributable to other causes. Success was defined as an IOP between 6 and 21 mmHg, with preservation of light perception and no additional glaucoma surgeries. Statistical analysis was conducted to identify possible risk factors. Results: A total of 193 eyes of 177 patients were included. HP was present in 58%; a higher preoperative IOP and younger age were associated with HP. Pseudophakic or aphakic eyes had a lower HP rate. Failure was present in 29%; neovascular glaucoma, worse basal best corrected visual acuity (BCVA), higher baseline IOP, and postoperative complications were linked to a higher likelihood of failure. No difference in the HP rate between the failure and success groups was found. Conclusion: A higher baseline IOP and younger age are associated with HP development; pseudophakia and aphakia might be protective factors. Factors for AGV failure are a worse BCVA, neovascular glaucoma, postoperative complications, and a higher baseline IOP. At 1 year, a higher number of medications were needed to achieve IOP control in the HP group. [ABSTRACT FROM AUTHOR]

Learning from multiple related tasks by knowledge sharing and transfer has become increasingly relevant over the last two decades. In order to successfully transfer information from one task to another, it is critical to understand the similarities and differences between the domains. In this paper, we introduce the notion of performance gap, an intuitive and novel measure of the distance between learning tasks. Unlike existing measures which are used as tools to bound the difference of expected risks between tasks (e.g., H-divergence or discrepancy distance), we theoretically show that the performance gap can be viewed as a data- and algorithm-dependent regularizer, which controls the model complexity and leads to finer guarantees. More importantly, it also provides new insights and motivates a novel principle for designing strategies for knowledge sharing and transfer: gap minimization. We instantiate this principle with two algorithms: 1. gapBoost, a novel and principled boosting algorithm that explicitly minimizes the performance gap between source and target domains for transfer learning; and 2. gapMTNN, a representation learning algorithm that reformulates gap minimization as semantic conditional matching for multitask learning. Our extensive evaluation on both transfer learning and multitask learning benchmark data sets shows that our methods outperform existing baselines. [ABSTRACT FROM AUTHOR]

Urban dengue is common in most countries of the Americas, but has been rare in the United States for more than half a century. In 1999 we investigated an outbreak [...]

Salmonella enterica serovar Typhimurium (S. Typhimurium) is one of the leading causes of food-borne illnesses worldwide. To colonize the gastrointestinal tract, S. Typhimurium produces multiple virulence factors that facilitate cellular invasion. Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species, and the S. Typhimurium genome contains two annotated chitinases: STM0018 (chiA) and STM0233. However, the role of these chitinases during S. Typhimurium pathogenesis is unknown. The putative chitinase STM0233 has not been studied previously, and only limited data exists on ChiA. Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. S. Typhimurium lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. In a gastroenteritis mouse model, chitinase-deficient S. Typhimurium strains were also significantly attenuated in the invasion of small intestinal tissue. This reduced invasion resulted in significantly delayed S. Typhimurium dissemination to the spleen and the liver, but chitinases were not required for systemic survival. The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type S. Typhimurium, suggesting that chitinases are secreted. By analyzing N-linked glycans of small intestinal cells, we identified specific N-acetylglucosamine-containing glycans as potential extracellular targets of S. Typhimurium chitinases. This analysis also revealed a differential abundance of Lewis X/A-containing glycans that is likely a result of host cell modulation due to the detection of S. Typhimurium chitinases. Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. Overall, our results demonstrate that S. Typhimurium chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome. Author summary: Salmonella Typhimurium infection is one of the leading causes of food-borne illnesses worldwide. In order for S. Typhimurium to effectively cause disease, it has to invade the epithelial cells lining the intestinal tract. This invasion step allows S. Typhimurium to replicate efficiently, causing further tissue damage and inflammation. In susceptible patients, S. Typhimurium can spread past the intestines and infect peripheral organs. It is essential to fully understand the invasion mechanism used by S. Typhimurium to design better treatments for infection. Here, we demonstrate that the two chitinases produced by S. Typhimurium are involved in this invasion process. We show that S. Typhimurium chitinases interact with surface glycans of intestinal epithelial cells and promote adhesion and invasion. Using a mouse infection model, we show that S. Typhimurium chitinases are required for the invasion of the small intestine and enhance the dissemination of S. Typhimurium to other organs. This study reveals an additional mechanism by which S. Typhimurium invades and causes infection. [ABSTRACT FROM AUTHOR]

Abstract Background Achieving sustainable economic and social growth through advances in health is crucial in Latin America within the framework of the United Nations Millennium Development Goals. Discussion Health-related Millennium Development Goals need to incorporate a multidimensional approach addressing the specific epidemiologic profile for each region of the globe. In this regard, addressing the cycle of destitution and suffering associated with infection with Trypanosoma cruzi, the causal agent of Chagas disease of American trypanosomiasis, will play a key role to enable the most impoverished populations in Latin America the opportunity to achieve their full potential. Most cases of Chagas disease occur among forgotten populations because these diseases persist exclusively in the poorest and the most marginalized communities in Latin America. Summary Addressing the cycle of destitution and suffering associated with T. cruzi infection will contribute to improve the health of the most impoverished populations in Latin America and will ultimately grant them with the opportunity to achieve their full economic potential.

Introduction: Cardiology is characterized by its state-of-the-art biomedical technology and the predominance of Evidence-Based Medicine. This predominance makes it difficult for healthcare professionals to deal with the ethical dilemmas that emerge in this subspecialty. This paper is a first endeavor to empirically investigate the axiological foundations of the healthcare professionals in a cardiology hospital. Our pilot study selected, as the target population, cardiology personnel not only because of their difficult ethical deliberations but also because of the stringent conditions in which they have to make them. Therefore, there is an urgent need to reconsider clinical ethics and Value-Based Medicine. This study proposes a qualitative analysis of the values and the virtues of healthcare professionals in a cardiology hospital in order to establish how the former impact upon the medical and ethical decisions made by the latter. Results: We point out the need for strengthening the roles of healthcare personnel as educators and guidance counselors in order to meet the ends of medicine, as well as the need for an ethical discernment that is compatible with our results, namely, that the ethical values developed by healthcare professionals stem from their life history as well as their professional education. Conclusion: We establish the kind of actions, communication skills and empathy that are required to build a stronger patient-healthcare professional relationship, which at the same time improves prognosis, treatment efficiency and therapeutic adhesion. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the oxidation of l-[1-13C]phenylalanine (13C-PheOx) in patients with chronic liver failure due to different etiologies using l-[1-13C]phenylalanine breath test. Breath samples were collected before the administration of 100 mg l-[1-13C]phenylalanine, and every 10 min thereafter until completion of 1 h. Control subjects (n=9) presented a larger cumulative percentage of 13C dose recovery (CPDR) than patients (n=124) with chronic liver disease, regardless of the etiology (7.5±0.7 vs. 4.2±0.2, p=0.001). No differences in CPDR were found considering the Child-Pugh (CP) class or etiology: alcoholic (CP A=7.7±0.7, CP B=4.1±0.5, CP C=2.0±0.3), hepatitis C virus (CP A=5.4±0.5, CP B=4.0±0.2, CP C=2.2±0.3), hepatocellular carcinoma (CP A=5.5±1.6, CP B=3.6±1.8, CP C=2.2±1.0); or cryptogenic cirrhotic patients (CP A=7.4±1.5, CP B=4.4±0.4, CP C=2.1±0.7). Results confirm that 13C-PheOx decreases in patients with cirrhosis with respect to controls, notwithstanding the etiology. [ABSTRACT FROM AUTHOR]

Using a newly assembled data set on procedures filed in Mexican labor tribunals, we study the determinants of final awards to workers. On average, workers recover less than 30 percent of their claim. Our strongest result is that workers receive higher percentages of their claims in settlements than in trial judgments. We also find that cases with multiple claimants against a single firm are less likely to be settled, which partially explains why workers involved in these procedures receive lower percentages of their claims. Finally, we find evidence that a worker who exaggerates his or her claim is less likely to settle. [ABSTRACT FROM AUTHOR]

Although the subtypes of serotonin 5-HT1 receptors have distinct structure and pharmacology, it has not been clear if they also exhibit differences in coupling to cellular signals. We have sought to compare directly the coupling of 5-HT1A and 5-HT1B receptors to adenylyl cyclase and to the mitogen-activated protein kinase ERK2 (extracellular signal-regulated kinase-2). We found that 5-HT1B receptors couple better to activation of ERK2 and inhibition of adenylyl cyclase than do 5-HT1A receptors. 5-HT stimulated a maximal fourfold increase in ERK2 activity in nontransfected cells that express endogenous 5-HT1B receptors at a very low density and a maximal 13-fold increase in transfected cells expressing 230 fmol of 5-HT1B receptor/mg of membrane protein. In contrast, activation of 5-HT1A receptors stimulated only a 2.8-fold maximal activation of ERK2 in transfected cells expressing receptors at 300 fmol/mg of membrane protein but did stimulate a 12-fold increase in activity in cells expressing receptors at 3,000 fmol/mg of membrane protein. Similarly, 5-HT1A, but not 5-HT1B, receptors were found to cause significant inhibition of forskolin-stimulated cyclic AMP accumulation only when expressed at high densities. These findings demonstrate that although both 5-HT1A and 5-HT1B receptors have been shown to couple to G proteins of the Gi class, they exhibit differences in coupling to ERK2 and adenylyl cyclase. [ABSTRACT FROM AUTHOR]

It has been shown that the variability of the marginal capital product ratio is what determines the growth rate of economies according to Harrod's model; therefore, it is important to predict its behavior. This paper develops a methodology based on probabilistic random walk to predict the annual marginal capital product ratio of Colombia for the year 2017 based on information from the Penn World Table database from 1993 to 2016. It was found that this variable has underlying mathematical orders, which allows its prediction with an accuracy of 97.69%. [ABSTRACT FROM AUTHOR]

Introduction: Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. Methodology: We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. Results: A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. Conclusions: Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality. [ABSTRACT FROM AUTHOR]