Early-life and chronic exposure to high-fat diet alters noradrenergic and glutamatergic neurotransmission in the male rat amygdala and hippocampus under cognitive challenges.

Childhood obesity increases the risk of health and cognitive disorders in adulthood. Consuming high-fat diets (HFD) during critical neurodevelopmental periods, like childhood, impairs cognition and memory in humans and animals, affecting the function and connectivity of brain structures related to emotional memory. However, the underlying mechanisms of such phenomena need to be better understood. This study aimed to investigate the neurochemical profile of the amygdala and hippocampus, brain structures involved in emotional memory, during the acquisition of conditioned odor aversion in male rats that consumed a HFD from weaning to adulthood. The rats gained weight, experienced metabolic changes, and reduced insulin sensitivity and glucose tolerance. Rats showed enhanced odor aversion memory, contrary to the expected cognitive impairments. This memory enhancement was accompanied by increased noradrenergic and glutamatergic neurotransmission in the amygdala and hippocampus. Importantly, this upregulation was specific to stimuli exposure, as basal neurotransmitter levels remained unaltered by the HFD. Our results suggest that HFD modifies cognitive function by altering neurochemical signaling, in this case, upregulating neurotransmitter levels rendering a stronger memory trace, demonstrating that metabolic dysfunctions do not only trigger exclusively detrimental plasticity processes but also render enhanced plastic effects depending on the type of information.

Maintenance of conditioned place avoidance induced by gastric malaise requires NMDA activity within the ventral hippocampus.

It has been reported that during chemotherapy treatment, some patients can experience nausea before pharmacological administration, suggesting that contextual stimuli are associated with the nauseating effects. There are attempts to reproduce with animal models the conditions under which this phenomenon is observed to provide a useful paradigm for studying contextual aversion learning and the brain structures involved. This manuscript assessed the hippocampus involvement in acquiring and maintaining long-term conditioned place avoidance (CPA) induced by a gastric malaise-inducing agent, LiCl. Our results demonstrate that a reliable induction of CPA is possible after one acquisition trial. However, CPA establishment requires a 20-min confinement in the compartment associated with LiCl administration. Interestingly, both hippocampal regions seem to be necessary for CPA establishment; nonetheless, inactivation of the ventral hippocampus results in a reversion of avoidance and turns it into preference. Moreover, we demonstrate that activation of dorsal/ventral hippocampal NMDA receptors after CS-US association is required for long-term CPA memory maintenance.

Curcumin exerts anti-inflammatory and vasoprotective effects through amelioration of NFAT-dependent endothelin-1 production in mice with acute Chagas cardiomyopathy.

BACKGROUND: The anti-inflammatory and cardioprotective properties of curcumin (Cur), a natural polyphenolic flavonoid isolated from the rhizomes of Curcuma longa, are increasingly considered to have beneficial effects on the progression of Chagas heart disease, caused by the protozoan parasite Trypanosoma cruzi. OBJECTIVE: To evaluate the effects of oral therapy with Cur on T. cruzi-mediated cardiovasculopathy in acutely infected mice and analyse the in vitro response of parasite-infected human microvascular endothelial cells treated with this phytochemical. METHODS: Inflammation of heart vessels from Cur-treated and untreated infected mice were analysed by histology, with benznidazole (Bz) as the reference compound. Parasitaemia was monitored by the direct method. Capillary permeability was visualised by Evans-blue assay. Myocardial ET-1, IL-6, and TNF-α mRNA expressions were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Microvascular endothelial HMEC-1 cells were infected in vitro with or without addition of Cur or Bz. Induction of the Ca2+/NFAT pathway was assessed by fluorometry, immunoblotting, and reporter assay. FINDINGS: Oral Cur therapy of recently infected mice reduced inflammatory cell infiltration of myocardial arteries without lowering parasite levels. Compared to that of the phosphate-buffered saline-receiving group, hearts from Cur-treated mice showed significantly decreased vessel inflammation scores (p < 0.001), vascular permeabilities (p < 0.001), and levels of IL-6/TNF-α (p < 0.01) and ET-1 (p < 0.05) mRNA. Moreover, Cur significantly (p < 0.05 for transcript; p < 0.01 for peptide) downregulated ET-1 secretion from infected HMEC-1 cells. Remarkably, Cur addition significantly (p < 0.05 at 27.0 µM) interfered with T. cruzi-dependent activation of the Ca2+/NFATc1 signalling pathway that promotes generation of inflammatory agents in HMEC-1 cells. CONCLUSIONS: Oral treatment with Cur dampens cardiovasculopathy in acute Chagas mice. Cur impairs the Ca2+/NFATc1-regulated release of ET-1 from T. cruzi-infected vascular endothelium. These findings identify new perspectives for exploring the potential of Cur-based interventions to ameliorate Chagas heart disease.

Prognostic factors of weight loss after sleeve gastrectomy: Multi centre study in Spain and Portugal. / Factores predictivos de pérdida ponderal tras la gastrectomía vertical. Estudio multicéntrico hispano-portugués.

INTRODUCTION: Sleeve gastrectomy (SG) has become a technique in its own right although a selective or global indication remains controversial. The weight loss data at 5 years are heterogeneous. The aim of the study is to identify possible prognostic factors of insufficient weight loss after SG. METHODS: A SG retrospective multicenter study of more than one year follow-up was performed. Failure is considered if EWL>50%. Univariate and multivariate study of Cox regression were performed to identify prognostic factors of failure of weight loss at 1, 2 and 3 years of follow up. RESULTS: A total of 1,565 patients treated in 29 hospitals are included. PSP per year: 70.58±24.7; 3 years 69.39±29.2; 5 years 68.46±23.1. Patients with EWL<50 (considered failure): 17.1% in the first year, 20.1% at 3 years, 20.8% at 5 years. Variables with influence on the weight loss failure in univariate analysis were: BMI>50kg/m2, age>50years, DM2, hypertension, OSA, heart disease, multiple comorbidities, distance to pylorus> 4cm, bougie>40F, treatment with antiplatelet agents. The reinforcement of the suture improved results. In multivariate study DM2 and BMI are independent factors of failure. CONCLUSION: The SG associates a satisfactory weight loss in 79% of patients in the first 5 years; however, some variables such as BMI>50, age>50, the presence of several comorbidities, more than 5cm section of the pylorus or bougie>40F can increase the risk of weight loss failure.

Intragastric laparoscopic surgery: An option for gastric lesions not resectable by endoscopy.

Gastric mucosal and submucosal lesions can be resected by endoscopy, laparoscopy or open surgery. Operative methods have varied depending on the location, endophytic growth and size of the lesion. Interest in minimally invasive surgery has increased and many surgeons are attempting laparoscopic approaches, especially in lesions of the stomach near the esophagogastric junction not amendable to endoscopic removal, because conventional surgery can produce stenosis and distort the postoperative anatomy, and increase morbimortality. We report our experience with laparoscopic intragastric surgery in 3 consecutive patients, with no complications. Laparoscopic intragastric surgery extends the surgeons' armamentarium to resect complex gastric lesions, while offering patients the benefits of minimal access surgery.

Cardiopathogenic mediators generated by GATA4 signaling upon co-activation with endothelin-1 and Trypanosoma cruzi infection.

Trypanosoma cruzi (Tc), the etiological agent of Chagas disease, triggers multiple responses in the myocardium, a central organ of infection and pathology in the host. Parasite-driven induction of diverse regulators of cardiovascular function, including the vasoconstrictor endothelin-1 (ET-1), the inducible form of nitric oxide synthase (iNOS) and the B-type natriuretic peptide (BNP), has been linked to the development of severe chagasic cardiomyopathy. Our current goal was to analyze the participation of the zinc finger transcription factor GATA4, critically implicated in pathological cardiac hypertrophic response, in the generation of key mediators involved in the pathogenesis of Tc-elicited heart dysfunction. In this study, we found that the combined effects of Tc and ET-1 on atrial myocytes promoted the protein expression, phosphorylation and DNA-binding activity of GATA4, leading to augmented protein levels of iNOS and increased nitric oxide release. Moreover, Tc- and ET-1-co-activation of cardiomyocytes resulted in enhanced GATA4-dependent secretion of BNP. Accordingly, mice with chronic chagasic cardiomyopathy showed increased expression of GATA4, iNOS and BNP at inflammatory lesions in cardiac muscle. Our findings support a role for the GATA4 signaling pathway in the myocardial production of pathogenic mediators associated with Chagas heart disease, and may help define novel therapeutic targets.

Preserved endothelial function in human obesity in the absence of insulin resistance.

BACKGROUND: Insulin resistance (IR) is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD). On the other hand, obesity has long been related to IR and increased CVD. However it is not known if IR is a necessary condition for endothelial dysfunction in human obesity, allowing for preserved endothelial function in obese people when absent. Therefore, the purpose of the study was to assess the relationship between IR and endothelial dysfunction in human obesity and the mechanisms involved. METHODS: Twenty non-insulin resistant morbid obese (NIR-MO), 32 insulin resistant morbid obese (IR-MO), and 12 healthy subjects were included. Serum concentrations of glucose, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), resistin and adiponectin were determined. IR was evaluated by HOMA-index. Endothelium-dependent relaxation to bradykinin (BK) in mesenteric microvessels was assessed in wire myograph. RESULTS: Serum IL-6, and TNF-α levels were elevated only in IR-MO patients while resistin was elevated and adiponectin reduced in all MO individuals. Mesenteric arteries from IR-MO, but not from NIR-MO subjects displayed blunted relaxation to BK. Vasodilatation was improved in IR-MO arteries by the superoxide scavenger, superoxide dismutase (SOD) or the mitochondrial-targeted SOD mimetic, mito-TEMPO. NADPH oxidase inhibitors (apocynin and VAS2870) and the nitric oxide synthase (NOS) cofactor, tetrahydrobiopterin failed to modify BK-induced vasodilatations. Superoxide generation was higher in vessels from IR-MO subjects and reduced by mito-TEMPO. Blockade of TNF-α with infliximab, but not inhibition of inducible NOS or cyclooxygenase, improved endothelial relaxation and decreased superoxide formation. CONCLUSIONS: Endothelial dysfunction is observed in human morbid obesity only when insulin resistance is present. Mechanisms involved include augmented mitochondrial superoxide generation, and increased systemic inflammation mediated by TNF-α. These findings may explain the different vascular risk of healthy vs unhealthy obesity.

Seeds of Success: Empowering Latina STEM Girl Ambassadors Through Role Models, Leadership, and STEM-Related Experiences.

Gender stereotypes and lack of access to relatable role models, mentors, and STEM opportunities have been suggested to deter middle school girls and students from underrepresented backgrounds away from STEM. Seeds of Success, an out-of-school program, is designed to inspire girls to consider STEM careers by countering gender stereotypes through relatable role models, promoting STEM confidence through STEM workshops and hands-on activities, and encouraging alignment between cultural and STEM identities through community-based STEM projects that develop leadership skills. Since 2015, the program has impacted 453 students who in turn have reached more than 42,777 people in Puerto Rico through their STEM Ambassadors projects. A robust mix-method evaluation of the 2020 and 2021 cohorts demonstrates significant improvements in participants' STEM attitudes and science identity, as well as in their self-perception as a leader, confidence in their ability to succeed in science, knowledge about STEM careers and opportunities, and access to STEM role models. Moreover, 95% of participants intend to continue participating in STEM activities after the program and overall scores for the entire survey were significantly higher after the program than before. We discuss lessons learned for other programs seeking to empower girls from historically underserved backgrounds in STEM.

Resource predictability modulates spatial-use networks in an endangered scavenger species.

BACKGROUND: Changes in human-induced resource availability can alter the behaviour of free-living species and affect their foraging strategies. The future European Landfill Waste Directive and Circular Economy Action Plan will reduce the number of predictable anthropogenic food subsidies (PAFS), above all, by closing landfills to preclude negative effects on human health. Obligate avian scavengers, the most threatened group of birds worldwide, are the most likely group of species that will be forced to change their behaviour and use of space in response to landfill site closures. Here, we examine the possible consequences of these management decisions on the foraging patterns of Egyptian vultures (Neophron percnopterus) in an expanding population in the Iberian Peninsula. METHODS: We tracked 16 individuals in 2018-2021, including breeders and non-breeders, and, using a combination of spatial-use and spatial-network modelling, assessed landscape connectivity between key resources based on movement patterns. We then carried out simulations of future scenarios based on the loss of PAFS to predict likely changes in the movement patterns of both non-breeders and breeders. RESULTS: Our results show that foraging strategies in non-breeders and breeders differ significantly: non-breeders performed more dispersal movements than breeding birds across a spatial-use network. Non-breeding and breeding networks were found to be vulnerable to the removal of central foraging areas containing landfill sites, a highly predictable resource, while perturbation analysis showed dissimilar foraging responses to the gradual reduction of other predictable resources. Under a context of the non-availability of landfills for breeders and non-breeders, vultures will increase their use of extensive livestock as a trophic resource. CONCLUSIONS: Future environmental policies should thus extend the areas used by scavengers in which livestock carcasses are allowed to remain in the wild, a strategy that will also mitigate the lack of food caused by any reduction in available waste if landfills close. In general, our results emphasize the capabilities of a spatial network approaches to address questions on movement ecology. They can be used to infer the behavioural response of animal species and, also demonstrate the importance of applying such approaches to endangered species conservation within a context of changing humanized scenarios.

Key Factors behind the Dynamic Stability of Pairs of Egyptian Vultures in Continental Spain.

Conservation science aims to identify the factors influencing the distribution of threatened species, thereby permitting the implementation of effective management strategies. This is key for long-lived species that require long-term monitoring such as the worldwide endangered Egyptian vulture (Neophron percnopterus). We studied temporal and spatial variations in the distribution of breeding pairs and examined the intrinsic and anthropic factors that may be influencing the abundance of breeding territories in continental Spain. Based on the census data of breeding pairs from 2000, 2008, and 2018, we used Rank Occupancy-Abundance Profiles to assess the temporal stability of the population and identified the spatial heterogeneity through a Local Index of Spatial Autocorrelation analysis. The GLMs showed that the abundance distribution was mainly influenced by the abundance of griffon vultures (Gyps fulvus) and cattle at a regional scale. Nonparametric comparisons showed that the presence of wind farms had a significant negative effect on local breeding pairs abundance, but that supplementary feeding stations and food resource-related variables had a positive impact. In light of these findings, we recommend a hierarchical approach in future conservation programs involving actions promoting regional-scale food resource availability and highlight the need to address the negative impact of wind farms at local levels.

Health status of patients with liver transplantation by alcohol-related disease vs another etiology: A cohort study.

AIM: To study the health status of a group of patients with liver transplantation by alcohol-related disease vs another etiology before and after the transplantation. METHOD: Longitudinal cohort study of liver transplant patients from November 2019 to July 2022. Adult patients attended in the unit of transplantation of a hospital for a first liver transplant, both elective and urgent, were included. Patients who already had a transplanted organ and those who required liver re-transplantation in the first month after the first transplant were excluded. Sociodemographic and clinical variables, MELDNa, liver frailty index, emotional-behavioral effects of transplantation, level of anxiety and depression were collected. Pearson's chi-square, Student's t, Mann-Whitney U, and Wilcoxon sign tests were used for statistical analysis. RESULTS: The sample was n = 67 liver transplant patients with a mean age of 56.37 years, 67.2% being men and 39% due to alcohol-related liver disease. 9% of all included patients were urgent transplants. Alcohol consumption was associated with older age, a high rate of liver frailty, and a non-active work situation. Alcoholic etiology correlated with increased concern during the first six months after liver transplantation. CONCLUSION: There are differences in the health status between liver transplant patients for alcohol-related liver disease vs other etiology. Nurses must consider the etiology of liver disease to guide care and interventions throughout the transplant process.

Age-Specific Demographic Response of a Long-Lived Scavenger Species to Reduction of Organic Matter in a Landfill.

Food availability shapes demographic parameters and population dynamics. Certain species have adapted to predictable anthropogenic food resources like landfills. However, abrupt shifts in food availability can negatively impact such populations. While changes in survival are expected, the age-related effects remain poorly understood, particularly in long-lived scavenger species. We investigated the age-specific demographic response of a Griffon vulture (Gyps fulvus) population to a reduction in organic matter in a landfill and analyzed apparent survival and the probability of transience after initial capture using a Bayesian Cormack-Jolly-Seber model on data from 2012-2022. The proportion of transients among newly captured immatures and adults increased after the reduction in food. Juvenile apparent survival declined, increased in immature residents, and decreased in adult residents. These results suggest that there was a greater likelihood of permanent emigration due to intensified intraspecific competition following the reduction in food. Interestingly, resident immatures showed the opposite trend, suggesting the persistence of high-quality individuals despite the food scarcity. Although the reasons behind the reduced apparent survival of resident adults in the final four years of the study remain unclear, non-natural mortality potentially plays a part. In Europe landfill closure regulations are being implemented and pose a threat to avian scavenger populations, which underlines the need for research on food scarcity scenarios and proper conservation measures.

Joint estimation of survival and dispersal effectively corrects the permanent emigration bias in mark-recapture analyses.

Robust and reliable estimates of demographic parameters are essential to understand population dynamics. Natal dispersal is a common process in monitored populations and can cause underestimations of survival and dispersal due to permanent emigration. Here, we present a multistate Bayesian capture-mark-recapture approach based on a joint estimation of natal dispersal kernel and detection probabilities to address biases in survival, dispersal, and related demographic parameters when dispersal information is limited. We implement this approach to long-term data of a threatened population: the Bonelli's eagle in Catalonia (SW Europe). To assess the method's performance, we compare demographic estimates structured by sex, age, and breeding status in cases of limited versus large data scales, with those of classical models where dispersal and detection probabilities are estimated separately. Results show substantial corrections of demographic estimates. Natal dispersal and permanent emigration probabilities were larger in females, and consequently, female non-breeder survival showed larger differences between separate and joint estimation models. Moreover, our results suggest that estimates are sensitive to the choice of the dispersal kernel, fat-tailed kernels providing larger values in cases of data limitation. This study provides a general multistate framework to model demographic parameters while correcting permanent emigration biases caused by natal dispersal.

Analysis of the impact of liver transplantation as a condition of health.

AIM: To analyse the impact that liver transplantation has had on the patient as a condition of their health. METHOD: A prospective study was carried out, the sample of which was made up of liver transplant patients at the Gregorio Marañón General University Hospital from November 2019 to August 2021. The hospital anxiety and depression scale, the Model for End-stage liver disease sodium and liver fragility index and the Transplant Effects Questionnaire Spanish were used. The data were analysed using descriptive statistics. The student's t-test was used for continuous variables and the chi-square test for categorical variables. For non-parametric samples, the Wilcoxon, Mann-Whitney U test and Kruskal-Wallis's sign were used. RESULTS: The sample was made up of 60 patients with a mean age of 55.68 years, 70% being men. The mean anxiety and depression scores of the patients improved significantly after liver transplantation. The impact of physical health resulted that those patients with a higher Model for End-stage liver disease sodium were correlated with a greater feeling of guilt after transplantation. Furthermore, greater adherence to immunosuppressive treatment was directly correlated with greater disclosure and inversely with guilt, after transplantation. CONCLUSION: Liver transplantation is a process that impacts the health of patients. Those patients who arrive at the transplant with a more deteriorated physical situation present a greater guilt after the transplant. This impact is inversely correlated with adherence to immunosuppressive treatment. Nurses should intervene in such patients to reduce the impact on adherence to treatment.

Thrombotic and hemorrhagic risk in bariatric surgery with multimodal rehabilitation programs comparing 2 reduced guidelines for pharmacological prophylaxis.

OBJECTIVE: To determine the thrombotic and hemorrhagic risk in bariatric surgery with multimodal rehabilitation programs, comparing two guidelines of pharmacological prophylaxis recommended in the Guide to the Spanish Society for Obesity Surgery and the Obesity Section of the AEC. METHODS: Cohorts retrospective study from January-2010 to December-2019. Cases of vertical gastrectomy or gastric bypass were recorded, systematically applying multimodal rehabilitation protocols. Two reduced chemoprophylaxis regimens were analyzed, starting after surgery and maintained for 10 days; one with fondaparinux (Arixtra®) at a fixed dose of 2.5mg/day and the other with enoxaparin (Clexane®) with a single daily dose adjusted to BMI: 40mg/day for BMI of 35-40 and 60mg/day for BMI 40-60. RESULTS: 675 patients were included; 354 with Fondaparinux-Arixtra® during the period 2010-2015 and 321 with Enoxaparin-Clexane® during the period 2016-2019. There were no cases of DVT or clinical PE. However, the incidence of hemorrhage requiring reoperation, transfusion, or a decrease of more than 3g/dL hemoglobin was 4.7%, with no difference between groups. Mortality was nil. The average stay was 2.8 days and the outpatient follow-up was 100% during the first 6 months and 95% at 12 months. CONCLUSIONS: The combination of multimodal rehabilitation programs and mechanical and pharmacological thromboprophylaxis by experienced teams, reduces the risk of thromboembolic events and could justify reduced chemoprophylaxis regimens to decrease the risk of postoperative bleeding.

A 31-Year-Old Man With Seizures, Brain Lesion, and Lung Nodules.

CASE PRESENTATION: A 31-year-old man was admitted to our hospital with a recent history of generalized seizures. Three months earlier, he started with intermittent hemoptysis. CT scan showed a cavitary lung lesion in the upper segment of the right inferior lobe (RIL). Because of his job as a social worker in a high-risk population, he started treatment for Mycobacterium TB; however, the BAL culture result was negative. At the time of his current admission, he has continued taking rifampicin, isoniazid, pyrazinamide, and levofloxacin. He denied the use of any illicit drugs or alcohol. He had no history of smoking. One year earlier, he visited Southeast Asia, Oceania, and South Africa for several months. He reported a weight loss of 7 kg since then. Except for a recurrent oral candidiasis, he did not have a relevant medical history. His family history was notable for mother with lupus, and brother with sarcoidosis.

Dual chemotherapy with benznidazole at suboptimal dose plus curcumin nanoparticles mitigates Trypanosoma cruzi-elicited chronic cardiomyopathy.

Curcumin (Cur) is a natural polyphenolic flavonoid isolated from the rhizomes of Curcuma longa. Its anti-inflammatory and cardioprotective properties are increasingly considered to have beneficial effects on the progression of cardiomyopathy associated with Chagas disease, caused by Trypanosoma cruzi. However, the Cur therapeutic limitation is its bioavailability and new Cur nanomedicine formulations are developed to overcome this obstacle. In this research, we provide evidence showing that oral therapy with a suboptimal dose of the standard parasiticidal drug benznidazole (BZ) in combination with Cur-loaded nanoparticles is capable of reducing myocardial parasite load, cardiac hypertrophy, inflammation and fibrosis in mice with long-term infection by T. cruzi. Treatment with BZ plus Cur was highly effective in downregulating myocardial expression of proinflammatory cytokines/chemokines (IL-1ß, TNF-α, IL-6, CCL5), and the level/activity of matrix metalloproteinases (MMP-2, MMP-9) and inducible enzymes (cyclooxygenase, nitric oxide synthase) implicated in leukocyte recruitment and cardiac remodeling. Oral administration of a Cur-based nanoformulation displays potential as a complementary strategy to the conventional BZ chemotherapy in the treatment of chronic Chagas heart disease.

Thrombotic and hemorrhagic risk in bariatric surgery with multimodal rehabilitation programs comparing 2 reduced guidelines for pharmacological prophylaxis. / Riesgo trombótico y hemorrágico en cirugía bariátrica con programas de rehabilitación multimodal comparando 2 pautas reducidas de profilaxis farmacológica.

OBJECTIVE: to determine the thrombotic and hemorrhagic risk in bariatric surgery with multimodal rehabilitation programs, comparing 2guidelines of pharmacological prophylaxis recommended in the Guide to the Spanish Society for Obesity Surgery and the Obesity Section of the AEC. METHODS: Cohorts retrospective study from January-2010 to December-2019. Cases of vertical gastrectomy or gastric bypass were recorded, systematically applying multimodal rehabilitation protocols. Two reduced chemoprophylaxis regimens were analyzed, starting after surgery and maintained for 10 days; one with fondaparinux (Arixtra®) at a fixed dose of 2.5mg / day and the other with enoxaparin (Clexane®) with a single daily dose adjusted to BMI: 40mg / day for BMI of 35-40 and 60mg/day for BMI 40-60. RESULTS: 675 patients were included; 354 with Fondaparinux-Arixtra® during the period 2010-2015 and 321 with Enoxaparin-Clexane® during the period 2016-2019. There were no cases of DVT or clinical PE. However, the incidence of hemorrhage requiring reoperation, transfusion, or a decrease of more than 3g / dL hemoglobin was 4.7%, with no difference between groups. Mortality was nil. The average stay was 2.8 days and the outpatient follow-up was 100% during the first 6 months and 95% at 12 months. CONCLUSIONS: The combination of multimodal rehabilitation programs and mechanical and pharmacological thromboprophylaxis by experienced teams, reduces the risk of thromboembolic events and could justify reduced chemoprophylaxis regimens to decrease the risk of postoperative bleeding.

Clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 infection in a Latin American country: Results from the ECCOVID multicenter prospective study.

BACKGROUND: Clinical features and outcomes of SARS-CoV-2 infections diverge in different countries. The aim of this study was to describe clinical characteristics and outcomes in a cohort of patients hospitalized with SARS-CoV-2 in Argentina. METHODS: Multicenter prospective cohort study of ≥18 years-old patients with confirmed SARS-CoV-2 infection consecutively admitted to 19 hospitals in Argentina. Multivariable logistic regression models were used to identify variables associated with 30-day mortality and admission to intensive care unit (ICU). RESULTS: A total of 809 patients were analyzed. Median age was 53 years, 56% were males and 71% had at least one comorbidity. The most common comorbidities were hypertension (32%), obesity (23%) and diabetes (17%). Disease severity at admission was classified as mild 25%, moderate 51%, severe 17%, and critical 7%. Almost half of patients (49%) required supplemental oxygen, 18% ICU, and 12% invasive ventilation. Overall, 30-day mortality was 11%. Factors independently associated with ICU admission were male gender (OR 1.81; 95%CI 1.16-2.81), hypertension (OR 3.21; 95%CI 2.08-4.95), obesity (OR 2.38; 95%CI 1.51-3.7), oxygen saturation ≤93% (OR 6.45; 95%CI 4.20-9.92) and lymphopenia (OR 3.21; 95%CI 2.08-4.95). Factors independently associated with 30-day mortality included age ≥60 years-old (OR 2.68; 95% CI 1.63-4.43), oxygen saturation ≤93% (OR 3.19; 95%CI 1.97-5.16) and lymphopenia (OR 2.65; 95%CI 1.64-4.27). CONCLUSIONS: This cohort validates crucial clinical data on patients hospitalized with SARS-CoV-2 in Argentina.

Iron Chelator Transmetalative Approach to Inhibit Human Ribonucleotide Reductase.

Efforts directed at curtailing the bioavailability of intracellular iron could lead to the development of broad-spectrum anticancer drugs given the metal's role in cancer proliferation and metastasis. Human ribonucleotide reductase (RNR), the key enzyme responsible for synthesizing the building blocks of DNA replication and repair, depends on Fe binding at its R2 subunit to activate the catalytic R1 subunit. This work explores an intracellular iron chelator transmetalative approach to inhibit RNR using the titanium(IV) chemical transferrin mimetic (cTfm) compounds Ti(HBED) and Ti(Deferasirox)2. Whole-cell EPR studies reveal that the compounds can effectively attenuate RNR activity though seemingly causing different changes to the labile iron pool that may account for differences in their potency against cells. Studies of Ti(IV) interactions with the adenosine nucleotide family at pH 7.4 reveal strong metal binding and extensive phosphate hydrolysis, which suggest the capacity of the metal to disturb the nucleotide substrate pool of the RNR enzyme. By decreasing intracellular Fe bioavailability and altering the nucleotide substrate pool, the Ti cTfm compounds could inhibit the activity of the R1 and R2 subunits of RNR. The compounds arrest the cell cycle in the S phase, indicating suppressed DNA replication, and induce apoptotic cell death. Cotreatment cell viability studies with cisplatin and Ti(Deferasirox)2 reveal a promising synergism between the compounds that is likely owed to their distinct but complementary effect on DNA replication.