Directing novel ChoKα1 inhibitors using MamC-mediated biomimetic magnetic nanoparticles: a way to improve specificity and efficiency.

Targeting phospholipid biosynthesis, specifically phosphatidylcholine (PC), which is enhanced in tumor cells, has been proven a suitable antitumor strategy. In fact, the overexpression of the choline kinase α1 (ChoKα1) isoform has been found in malignant cells and tumors, thus becoming an excellent antitumor target. ChoKα1 inhibitors are being synthesized at the present that show a large inhibitory activity. Two of them have been chosen in this study as representatives of different structural families: a biscationic biphenyl derivative of thieno[3,2-d]pyrimidinium substituted with a cyclic amine (here referred to as Fa22) and a biscationic biphenyl thioethano derivative of 7-chloro-quinolinium substituted with a pyrrolidinic moiety (here referred to as PL48). However, the potential use of these types of compounds in systemic treatments is hampered because of their low specificity. In fact, to enter the cell and reach their target, these inhibitors use choline transporters and inhibit choline uptake, being that one of the causes of their toxicity. One way to solve this problem could be allowing their entrance into the cells by alternative ways. With this goal, MamC-mediated magnetic nanoparticles (BMNPs), already proven effective drug nanocarriers, have been used to immobilize Fa22 and PL48. The idea is to let BMNPs enter the cell (they enter the cell by endocytosis) carrying these molecules, and, therefore, offering another way in for these compounds. In the present study, we demonstrate that the coupling of Fa22 and PL48 to BMNPs allows these molecules to enter the tumoral cell without completely inhibiting choline uptake, so, therefore, the use of Fa22 and PL48 in these nanoformulations reduces the toxicity compared to that of the soluble drugs. Moreover, the nanoassemblies Fa22-BMNPs and PL48-BMNPs allow the combination of chemotherapy and local hyperthermia therapies for a enhanced cytotoxic effect on the tumoral HepG2 cell line. The consistency of the results, independently of the drug structure, may indicate that this behavior could be extended to other ChoKα1 inhibitors, opening up a possibility for their potential use in clinics.

P2Y12 receptor antagonism inhibits proliferation, migration and leads to autophagy of glioblastoma cells.

Glioblastoma (GBM) is the most aggressive and lethal among the primary brain tumors, with a low survival rate and resistance to radio and chemotherapy. The P2Y12 is an adenosine diphosphate (ADP) purinergic chemoreceptor, found mainly in platelets. In cancer cells, its activation has been described to induce proliferation and metastasis. Bearing in mind the need to find new treatments for GBM, this study aimed to investigate the role of the P2Y12R in the proliferation and migration of GBM cells, as well as to evaluate the expression of this receptor in patients' data obtained from the TCGA data bank. Here, we used the P2Y12R antagonist, ticagrelor, which belongs to the antiplatelet agent's class. The different GBM cells (cell line and patient-derived cells) were treated with ticagrelor, with the agonist, ADP, or both, and the effects on cell proliferation, colony formation, ADP hydrolysis, cell cycle and death, migration, and cell adhesion were analyzed. The results showed that ticagrelor decreased the viability and the proliferation of GBM cells. P2Y12R antagonism also reduced colony formation and migration potentials, with alterations on the expression of metalloproteinases, and induced autophagy in GBM cells. Changes were observed at the cell cycle level, and only the U251 cell line showed a significant reduction in the ADP hydrolysis profile. TCGA data analysis showed a higher expression of P2Y12R in gliomas samples when compared to the other tumors. These data demonstrate the importance of the P2Y12 receptor in gliomas development and reinforce its potential as a pharmacological target for glioma treatment.

Risk factors for intensive care unit admission and death from COVID-19 in fully vaccinated patients hospitalized for severe COVID-19, Brazil, 2021-2022.

Objectives: To assess factors associated with admission to an intensive care unit (ICU) and death from coronavirus disease 2019 (COVID-19) in fully vaccinated patients with severe COVID-19 in Brazil and the association between ICU admission and death from COVID-19. Methods: This was retrospective study of patients hospitalized for COVID-19 from February 12, 2021 to January 10, 2022 across Brazil who were fully vaccinated against COVID-19 before hospitalization. Outcomes were admission in an ICU for COVID-19 and death from COVID-19. Variables evaluated were: sex; age; self-reported skin color; macroregion; comorbidities; time between full vaccination and onset of symptoms; and time between onset of symptoms and hospitalization. A Poisson regression model was used to estimate crude and adjusted risk ratios. Results: Of 74 991 patients hospitalized for severe COVID-19, 67.28% were ≥ 70 years and 68.32% had at least one comorbidity. Men, patients aged 60-69 years, and patients aged 18-39 years with obesity had the greatest risk of ICU admission. Patients aged 18-39 years with obesity, diabetes, or renal diseases had the highest risk of death from COVID-19. When age and time between onset of symptoms and hospitalization were considered effect modifiers, patients admitted to an ICU 9-13 days after symptom onset in each age category had the greatest risk of death from COVID-19. Conclusion: Although older patients were at greatest risk of ICU admission and death from COVID-19, the difference in the risk of dying from COVID-19 between patients admitted to an ICU and those not admitted was greatest for young adults.

P2Y12 Purinergic Receptor and Brain Tumors: Implications on Glioma Microenvironment.

Gliomas are the most common malignant brain tumors in adults, characterized by a high proliferation and invasion. The tumor microenvironment is rich in growth-promoting signals and immunomodulatory pathways, which increase the tumor's aggressiveness. In response to hypoxia and glioma therapy, the amounts of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) strongly increase in the extracellular space, and the purinergic signaling is triggered by nucleotides' interaction in P2 receptors. Several cell types are present in the tumor microenvironment and can facilitate tumor growth. In fact, tumor cells can activate platelets by the ADP-P2Y12 engagement, which plays an essential role in the cancer context, protecting tumors from the immune attack and providing molecules that contribute to the growth and maintenance of a rich environment to sustain the protumor cycle. Besides platelets, the P2Y12 receptor is expressed by some tumors, such as renal carcinoma, colon carcinoma, and gliomas, being related to tumor progression. In this context, this review aims to depict the glioma microenvironment, focusing on the relationship between platelets and tumor malignancy.

Fully endoscopic transoral resection of high cervical osteophyte. How I do it?

BACKGROUND: Fully endoscopic transoral approaches (FETOA) constitute a reasonable option for the treatment of middling compressive pathology that involve the craniocervical junction and higher cervical levels. METHODS: We describe, step by step, the FETOA for the treatment of upper cervical lesions. More specifically, the ones that are located between C1 and C3. A giant anterior C1-C2 osteophyte resection will be used as an illustration of these approaches. CONCLUSIONS: This technique represents a minimally invasive treatment option for these kinds of high cervical lesions. It offers optimal visualization, maximizing the resection of these lesions and decreasing the morbidity and mortality.

The clinical dilemma of heart failure with preserved ejection fraction: an update on pathophysiology and management for physicians.

The prevalence of heart failure with preserved ejection fraction (HFpEF) continues to grow at alarming rates and is predicted to become the most prevalent phenotype of heart failure over the next decade. Recent data show a higher non-cardiac comorbidity burden associated with HFpEF, and similar overall hospitalisation rates when compared with patients with heart failure with reduced ejection fraction (HFrEF). Unfortunately, clinicians mainly focus their efforts in diagnosis of HFrEF despite HFpEF accounting for 50% of the cases of heart failure. Therefore, this review is intended to create awareness on the pathophysiology, risk factors, diagnosis and management of patients with HFpEF and its core mechanical abnormality left ventricular diastolic dysfunction. Clinical distinction between HFpEF and HFrEF should be of particular interest to internal medicine physicians and general practitioners as this distinction is seldom made and early diagnosis can lag if appropriate risk factors are not promptly recognised.

Non-Invasive Therapy of Peripheral Arterial Disease.

Peripheral arterial disease (PAD) is a significant cause of morbidity and mortality worldwide. Lifestyle changes, like the cessation of the use of tobacco as well as a modification of dietary and exercise habits, can be the most cost-effective interventions in patients with PAD. Smocking cessation is the most important intervention, since it increases survival in these patients. Antiplatelet therapy is an essential component in the treatment of peripheral arterial disease (PAD) of the lower extremities. In addition to delaying arterial obstructive progression, these agents are most usefull in reducing adverse cardiovascular events such as non-fatal myocardial infarction (MI), stroke and vascular death. Mainstay of treatment continues to be aspirin monotherapy (75-325mg daily). Current treatment for lower extremity PAD is directed towards the relief of symptoms and improvement in QoL. The two agents which have consistently been found to be most efficient in achieving these goals are cilostazol and naftidrofuryl oxalate. Naftidrofuryl oxalate may emerge as the most efficient and cost-effective treatment for symptom relief.

Association between fractional exhaled nitric oxide and therapeutic adherence to controller management in pediatric asthma patients.

OBJECTIVES: Guidelines for asthma management recommend, before establishing additional therapeutic behaviors, to confirm correct use and adequate therapeutic adherence to treatment. Evidence exists on the use of fractional exhaled nitric oxide (FeNO) values for monitoring therapeutic adherence in adults. It is important to establish whether there is a correlation between FeNO and therapeutic adherence in children. This study aims to provide new knowledge about the relationship between FeNO and therapeutic adherence in asthmatic children. MATERIALS AND METHODS: Analytical cross-sectional study including asthma patients 5-18 years of age, attending follow-up at Hospital Militar Central (HMC) between May and November 2022 in Colombia. A sociodemographic survey was carried out, followed by the Pediatric Inhaler Adherence Questionnaire (PIAQ), and asthma control test (ACT) or childhood asthma control test (cACT). We defined adequate therapeutic adherence as not missing a single application of inhaled steroids in the last 15 days according to PIAQ. A poisson regression model was carried out including relevant predictors for therapeutic adherence such as FeNO values, age, tobacco exposure at home, atopy, and time since initiation of use of inhaled controller. RESULTS: Eighty-two children with a median age of 10 years (interquartile range: 7-12 years) were included. Adequate therapeutic adherence was reported by 68.3%. After adjusting for age, sex, exposure to cigarette smoke, duration of controller therapy, and atopy, FeNO < 20 ppb was independently associated with adequate therapeutic adherence (RR = 1.5, p = .04, 95% confidence interval: 1.03-2.19). CONCLUSIONS: FeNO values seem to be useful to identify pediatric patients with asthma who have adequate adherence to inhaled steroids in a MIC.

Evaluation of the implantation of transpedicular screws in spinal instrumentation with free-hand technique and navigation-assisted with intraoperative computed tomography: An analytical-positional study.

BACKGROUND: Spinal instrumentation using transpedicular screws has been used for decades to stabilize the spine. In October 2018, an intraoperative CT system was acquired in the Neurosurgery service of the University Hospital Complex of Vigo, this being the first model of these characteristics in the Spanish Public Health System, so we began a study from January 2015 to December 2019 to assess the precision of the transpedicular screws implanted with this system compared with a control group performed with the classical technique and final fluoroscopic control. METHODS: The study was carried out in patients who required transpedicular instrumentation surgery, in total 655 screws were placed, 339 using the free-hand technique (Group A) and 316 assisted with intraoperative CT navigation (Group B) (p>0.05). Demographic characteristics, related to surgery and the screw implantation grades were assessed using the Gertzbein-Robbins classification. RESULTS: 92 patients were evaluated, between 12 and 86 years (average: 57.1 years). 161 thoracic screws (24.6%) and 494 lumbo-sacral screws (75.4%) were implanted. Of the thoracic screws, 33 produced a pedicle rupture. For the lumbo-sacral screws, 71 have had pedicle violation. The overall correct positioning rate for the free-hand group was 72.6% and for the CT group it was 96.5% (p<0.05). CONCLUSION: The accuracy rate is higher in thoracic-lumbar instrumentation in the navigation group versus free-hand group with fluoroscopic control.

Cardiopulmonary Imaging Utilization and Findings among Hospitalized COVID-19 Patients in Latin America: (From "RIMAC: Registry IMAging Cardiopulmonary among Hospitalized COVID-19 Patients in LATAM").

Objectives: Describe the use and findings of cardiopulmonary imaging-chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS), and/or cardiac magnetic resonance imaging (cMRI)-in COVID-19 hospitalizations in Latin America (LATAM). Background: There is a lack of information on the images used and their findings during the SARS-CoV-2 pandemic in LATAM. Methods: Multicenter, prospective, observational study of COVID-19 inpatients, conducted from March to December 2020, from 12 high-complexity centers, in nine LATAM countries. Adults (>18 years) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included. Results: We studied 1,435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: Mexico (Mx), 262; Central America and Caribbean (CAC), 428; and South America (SAm), 745. More frequent comorbidities were overweight/obesity, hypertension, and diabetes. During hospitalization, 58% were admitted to the ICU. The in-hospital mortality was 28%, and it was highest in Mx (37%).The most frequent images performed were cCT (61%), mostly in Mx and SAm, and cX-ray (46%), significant in CAC. The cEcho was carried out in 18%, similarly among regions, and LUS was carried out in 7%, with a higher frequently in Mx. Abnormal findings on the cX-ray were peripheral or basal infiltrates, and in cCT abnormal findings were the ground glass infiltrates, more commonly in Mx. In LUS, interstitial syndrome was the most abnormal finding, predominantly in Mx and CAC.Renal failure was the most prevalent complication (20%), predominant in Mx and SAm. Heart failure developed in 13%, predominant in Mx and CAC. Lung thromboembolism was higher in Mx while myocardial infarction was in CAC.Logistic regression showed associations of abnormal imaging findings and their severity, with comorbidities, complications, and evolution. Conclusions: The use and findings of cardiopulmonary imaging in LATAM varied between regions and had a great impact on diagnosis and prognosis.

[Bone mineral density in patients with type 2 diabetes]. / Densidad mineral ósea en pacientes con diabetes tipo 2.

OBJECTIVE: To establish whether type 2 diabetes (T2D) is associated with changes in the bone mineral density (BMD) of femoral neck, total hip and lumbar spine. MATERIAL AND METHODS: Comparative cross-sectional study that included 450 patients aged 30 years or more; 245 with, and 205 without T2D. Groups were matched by age. Degenerative joint disease, rheumatoid arthritis, neoplasia, renal failure, chronic liver disease, alcohol intake, prior treatment with drugs that modulate the BMD, Diabetes Mellitus Type 1 and other endocrinopathies were exclusion criteria. RESULTS: In the overall group, the presence of menopause was associated with osteoporosis in the hip (odds ratio -OR-4.2; CI95% 1.4-6.1), whereas T2D was a protective factor (OR 0.8; CI95% 0.4-0.9). Among premenopausal women, central obesity and total adiposity were associated with osteoporosis in the hip (OR 1.9; CI95% 1.1-3.9 and OR 2.1; CI95% 1.2-8.7) and femoral areas (OR 2.1; CI95% 1.2-4.1 and OR 2.3; CI95% 1.3-7.1); T2D remained as protective factor (OR 0.7; CI95% 0.5-0.9 and OR 0.6; CI95% 0.4-0.9). The adjusted analysis by BMI, waist circumference, and total adiposity showed that T2D remained as a protective factor for osteoporosis in the hip (OR 0.8; CI95% 0.6-0.9) and femoral areas (OR 0.7; CI95% 0.5-0.9). CONCLUSIONS: Our results suggest that T2D is an independent protective factor for osteoporosis.

Evaluation of the implantation of transpedicular screws in spinal instrumentation with free-hand technique and navigation-assisted with intraoperative computed tomography: An analytical-positional study.

BACKGROUND: Spinal instrumentation using transpedicular screws has been used for decades to stabilize the spine. In October 2018, an intraoperative CT system was acquired in the Neurosurgery service of the University Hospital Complex of Vigo, this being the first model of these characteristics in the Spanish Public Health System, so we began a study from January 2015 to December 2019 to assess the precision of the transpedicular screws implanted with this system compared with a control group performed with the classical technique and final fluoroscopic control. METHODS: The study was carried out in patients who required transpedicular instrumentation surgery, in total 655 screws were placed, 339 using the free-hand technique (Group A) and 316 assisted with intraoperative CT navigation (Group B) (p>0.05). Demographic characteristics, related to surgery and the screw implantation grades were assessed using the Gertzbein-Robbins classification. RESULTS: 92 patients were evaluated, between 12 and 86 years (average: 57.1 years). 161 thoracic screws (24.6%) and 494 lumbo-sacral screws (75.4%) were implanted. Of the thoracic screws, 33 produced a pedicle rupture. For the lumbo-sacral screws, 71 have had pedicle violation. The overall correct positioning rate for the free-hand group was 72.6% and for the CT group it was 96.5% (p<0.05). CONCLUSION: The accuracy rate is higher in thoracic-lumbar instrumentation in the navigation group versus free-hand group with fluoroscopic control.

Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study.

Background: Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown. Methods: We prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes. Results: Among 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]). Conclusion: Increased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted.

Interactions of Botryococcus braunii cultures with bacterial biofilms.

Unicellular microalgae generally grow in the presence of bacteria, particularly when they are farmed massively. This study analyzes the bacteria associated with mass culture of Botryococcus braunii: both the planktonic bacteria in the water column and those forming biofilms adhered to the surface of the microalgal cells (∼107-108 culturable cells per gram microalgae). Furthermore, we identified the culturable bacteria forming a biofilm in the microalgal cells by 16S rDNA sequencing. At least eight different culturable species of bacteria were detected in the biofilm and were evaluated for the presence of quorum-sensing signals in these bacteria. Few studies have considered the implications of this phenomenon as regards the interaction between bacteria and microalgae. Production of C4-AHL and C6-AHL were detected in two species, Pseudomonas sp. and Rhizobium sp., which are present in the bacterial biofilm associated with B. braunii. This type of signal was not detected in the planktonic bacteria isolated from the water. We also noted that the bacterium, Rhizobium sp., acted as a probiotic bacterium and significantly encouraged the growth of B. braunii. A direct application of these beneficial bacteria associated with B. braunii could be, to use them like inoculants for large-scale microalgal cultures. They could optimize biomass production by enhancing growth, particularly in this microalga that has a low growth rate.

Immunosuppression in Gliomas via PD-1/PD-L1 Axis and Adenosine Pathway.

Glioblastoma is the most malignant and lethal subtype of glioma. Despite progress in therapeutic approaches, issues with the tumor immune landscape persist. Multiple immunosuppression pathways coexist in the tumor microenvironment, which can determine tumor progression and therapy outcomes. Research in immune checkpoints, such as the PD-1/PD-L1 axis, has renewed the interest in immune-based cancer therapies due to their ability to prevent immunosuppression against tumors. However, PD-1/PD-L1 blockage is not completely effective, as some patients remain unresponsive to such treatment. The production of adenosine is a major obstacle for the efficacy of immune therapies and is a key source of innate or adaptive resistance. In general, adenosine promotes the pro-tumor immune response, dictates the profile of suppressive immune cells, modulates the release of anti-inflammatory cytokines, and induces the expression of alternative immune checkpoint molecules, such as PD-1, thus maintaining a loop of immunosuppression. In this context, this review aims to depict the complexity of the immunosuppression in glioma microenvironment. We primarily consider the PD-1/PD-L1 axis and adenosine pathway, which may be critical points of resistance and potential targets for tumor treatment strategies.

Hemangiopericytoma/Solitary Fibrous Tumor in the central nervous system. Experience with surgery and radiotherapy as a complementary treatment: A 10-year analysis of a heterogeneous series in a single tertiary center.

Hemangiopericytoma and Solitary Fibrous Tumor are tumors with low incidence. They have a tendency to recur locally and to metastasize. The WHO integrated both tumors into a new entity but one of the pending issues is to demonstrate the effectiveness of surgery plus complementary radiotherapy (RT) and standardize the use of it. We reviewed the data from 10 years. We assessed pathologic and radiologic characteristics. The operation records were evaluated to determine the features and extent of tumor resection. We compared the outcomes in patients using or not RT. The mean follow-up was 74.8 months, with a range of 12 and 210 months. The population included 3 males (30%) and 7 females (70%). The most common location was brain convexity (30%), the remaining were cervical and lumbar spine, sacrum, intraventricular, torcular, sphenoid ridge and intraorbital. Postoperative external beam radiotherapy was delivered in 7 patients (70%), the criteria were a partial resection or WHO II and III histological grades. 2 patients developed local recurrences at 12 and 19 months after initial surgery. 1 patient underwent 2 surgeries, and the other, 4 surgeries. The mean recurrence free survival rate was 15.5 months. Distant metastases were found in 4 patients. 3 of the 10 patients died. Five-year overall survival rate was 66% and mean overall survival was 76 months. A safe and complete resection in the first surgery is the most important prognostic factor. Complementary RT can be helpful, even in cases of complete resection in WHO low-grade.

La marihuana de hoy no es la que fumaba tú abuela

Johnny Stack, como nos lo relata Isabella Backman, se inició en la marihuana en una fiesta de la escuela a sus 14 años, cuando apenas se había legalizado su uso medicinal en Colorado. Esa marihuana la había obtenido el hermano mayor de unos de sus amigos, quien tenía una tarjeta para marihuana medicinal. A los 19 años, después de 5 años de estar luchando contra adicción y psicosis, Johnny muere por suicidio. Tres días antes, nos dice Backman, le dijo a su madre que la marihuana le había arruinado su mente y su vida. Nunca se probó, a pesar de múltiples pruebas de laboratorio, que usara ninguna otra droga. (provisto por Infomedic International)

Johnny Stack, as Isabella Backman tells us, was introduced to marijuana at a school party when he was 14 years old, when its medical use had just been legalized in Colorado. That marijuana had been obtained by the older brother of one of her friends, who had a medical marijuana card. At 19, after five years of struggling with addiction and psychosis, Johnny died by suicide. Three days earlier, Backman tells us, he told his mother that marijuana had ruined his mind and his life. It was never proven, despite multiple lab tests, that he used any other drug. (provided by Infomedic International)

Heart failure readmissions: a losing battle or an opportunity for improvement?

Despite great strides in diagnosis and management of heart failure (HF), this chronic illness continues to be a worldwide epidemic with approximately 23 million people afflicted across the globe. In the US, over 6.5 million carry a HF diagnosis with almost 90% of all HF deaths occurring in patients over the age of 70. Since one in five Americans are expected to be older than 65 years by 2050, almost 1,000,000 new HF cases are expected to be diagnosed every year. The staggering nature of these numbers only pales in comparison to current dismal HF survival statistics. The unavoidable natural history of HF continues to be characterized by the occurrence of repetitive hospital admissions. Not only are hospital readmissions demarcated as one of the most important risk factors associated with mortality; but also, a well-recognized trigger for additional hospital readmissions. Even when HF treatment guidelines have been recently updated; the mere fact that four HF societies have issued individual recommendations without reaching a common unifying consensus statement adds to the complexity of HF patient management. The purpose of this Editorial not only to fuel more interest on this topic but also to spark the notion that we have a potential catastrophe in our hands and is the responsibility of all health-care professionals to attend to this vital issue.

A1 asynchrony, a potential risk factor for the rupture of anterior communicating artery aneurysms: A computational fluid dynamics study.

INTRODUCTION AND OBJECTIVES: The anterior communicating complex is one the most common locations for aneurysm development. It receives blood from both carotid circulations and the effect of synchrony on the arrival of blood flow has not been previously studied. The objective of this study was to compare the asynchrony conditions of the A1 pulse and its effects on the haemodynamic conditions of anterior communicating artery (ACoA) aneurysms. MATERIALS AND METHODS: From 2008 to 2017, 54 anterior communicating artery aneurysms treated at our centre were included in the study. Computational fluid dynamics (CFD) techniques were employed and simulations consisted of complete conditions of synchrony and introducing a delay of 0.2s in the non-dominant A1 artery. Time-averaged wall shear stress (TAWSS), low shear area (LSA), A1 diameter and ACoA angles were measured. RESULTS: The difference in the LSA in conditions of synchrony and asynchrony resulted in a broad range of positive and negative values. The symmetry index (p=0.04) and A1/A2 angle on the dominant artery (p=0.04) were associated with changes in LSA. CONCLUSIONS: In asynchrony, LSA increased in the absence of A1 asymmetry and low A1/A2 angles, potentially increasing the risk of aneurysm rupture in this location.

Human erythrocytes are affected in vitro by flavonoids of Aristotelia chilensis (Maqui) leaves.

Aristotelia chilensis (Mol.) Stuntz (A. chilensis), also known as maqui, is a plant of the Elaeocarpaceae family that grows in central and southern Chile as well as southwestern Argentina. Infusions of its leaves have long been used in the traditional native herbal medicine to treat different ailments. Phytochemical studies of the plant's chemical composition of the plant indicate the presence of indolic alkaloids, flavonoids, cianidine glucosides, delfidine, malvidine, petunidine, cumarines and triterpenes. These compounds, particularly the flavonoids, have antioxidant properties. In order to evaluate the mechanisms of its toxicity and their antioxidant properties, the leaves' aqueous extracts were induced to interact with human red cells, their isolated unsealed membranes (IUM), and molecular models of the human erythrocyte membrane. These consisted of multibilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, and large unilamellar vesicles (LUV) of DMPC. The capacity of A. chilensis aqueous extracts to perturb the bilayer structure of DMPC and DMPE was evaluated by X-ray diffraction, DMPC LUV and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). Results of the present study indicate that aqueous extracts of A. chilensis induced an alteration of human erythrocyte morphology from the normal discoid shape to an echinocytic form, changes that are explained in terms of the extract interaction with the membrane's outer phospholipid monolayer.