Randomized Study Comparing Radiofrequency Ablation with the PVAC Gold System vs. Antiarrhythmic Drugs in Elderly Patients with Symptomatic Atrial Fibrillation. / Estudo Randomizado Comparando a Ablação por Cateter com o PVAC Gold vs. Tratamento com Fármacos Antiarrítmicos em Pacientes Idosos com Fibrilação Atrial Sintomática.

BACKGROUND: There are no randomized studies comparing the maintenance of sinus rhythm after catheter ablation (CA) concerning treatment with antiarrhythmic drugs (AA) in elderly patients with paroxysmal atrial fibrillation (AF). OBJECTIVES: To compare the clinical results of pulmonary vein (PV) isolation with the second-generation PVAC Gold catheter against AA treatment in elderly people with recurrent symptomatic paroxysmal AF, refractory to at least one AA, and without structural heart disease. METHODS: Sixty patients with paroxysmal AF ≥ 65 years old were randomized to two forms of treatment: group 1: CA and group 2: AA drugs. The primary outcome was the AF recurrence-free rate after at least one year of follow-up. Secondary outcomes were: progression to persistent forms of AF, impact on quality of life (QOLF), and complications. The significance level adopted in the statistical analysis was 5% (p<0.05). RESULTS: The AF recurrence-free rate was 80% (10% with amiodarone) in the CA group, after 1.3 procedures per patient and 65% in the AA group (60% with amiodarone), (p = 0.119) in an average follow-up of 719 days (Q1: 566; Q3: 730). The persistent AF free rate was 83.4% in the AC group and 67.7% in the AA group (p = 0.073) Both strategies showed an improvement in the AFQoL score during follow-up (p < 0.001), with no difference between the groups. Although without clinical repercussions or impact on the intellectual assessment test, 25% of patients in the CA group showed signs of cerebral embolization on brain MRI. CONCLUSIONS: Both strategies for maintaining sinus rhythm promoted an improvement in the quality of life of elderly patients with symptomatic AF, with no statistical difference in the clinical outcomes. Additional studies using technologies with a better safety profile are needed to evaluate the benefits of CA in elderly patients with AF.

FUNDAMENTO: Não existem estudos randomizados comparando a manutenção do ritmo sinusal após ablação por cateter (AC) em relação ao tratamento com fármacos antiarrítmicos (AA) em pacientes idosos portadores fibrilação atrial (FA) paroxística. OBJETIVOS: Comparar os resultados clínicos do isolamento das veias pulmonares (VPs) com o cateter PVAC Gold de segunda geração com o uso de AA em idosos com FA paroxística sintomática, recorrente, apesar do uso de fármacos AA. MÉTODOS: Sessenta pacientes com FA paroxística ≥ 65 anos e sem cardiopatias estruturais foram randomizados para duas formas de tratamento: grupo 1: AC e grupo 2: AA. O desfecho primário foi a taxa livre de recorrência de FA após pelo menos um ano de seguimento. Os desfechos secundários foram: progressão para formas persistentes de FA, impacto na qualidade de vida (QVFA) e complicações. O nível de significância adotado na análise estatística foi de 5% (p<0,05). RESULTADOS: A taxa livre de recorrência de FA foi de 80% (10% com amiodarona) no grupo AC, após 1,3 procedimentos por paciente e de 65% no grupo AA (60% com amiodarona), (p = 0,119) num seguimento médio de 719 dias (Q1: 566; Q3: 730). A taxa livre de FA persistente foi de 83,4% no grupo AC e de 67,7% no grupo AA (p = 0,073). Ambas as estratégias apresentaram melhora no escore de QVFA durante o seguimento (p < 0,001), sem diferença entre os grupos. Embora sem repercussão clínica ou impacto no teste de avaliação intelectual, 25% dos pacientes do grupo PVAC apresentou sinais de embolização cerebral na RNM cerebral. CONCLUSÕES: Ambas as estratégias para manutenção do ritmo sinusal promoveram melhora na qualidade de vida de pacientes idosos com FA sintomática, sem diferença estatística nos desfechos clínicos preconizados. Estudos adicionais usando tecnologias com melhor perfil de segurança são necessários para avaliar os benefícios da AC em pacientes idosos com FA.

Impact of the COVID-19 Pandemic on the Treatment of Cancer Patients at a Hospital in Peru.

BACKGROUND: The appearance of the new coronavirus, SARS-CoV-2, in Wuhan - China, in 2019 led to the declaration of a COVID-19 pandemic by the World Health Organization. Peru confirmed its first case on March 6, 2020, prompting a significant change in medical care. PURPOSE: Our objective was to determine the impact of the COVID-19 pandemic on cancer treatment in Peru. METHODS: A retrospective analysis of hospital data from the National Institute of Neoplastic Diseases revealed substantial decreases in oncological treatments in 2020 compared to 2019. RESULTS: Oncological treatments involving bone marrow transplantation had a greater impact between the months of April and September, at -100% (p=0.003). However, treatments involving surgery in April (-95% [p≤0.001]), radiotherapy in May (-76% [p=0.002]) and chemotherapy in June (-71% [p≤0.001]) also showed significant impacts. Comparative analysis with international data revealed similar trends in cancer care interruptions in different countries. However, variations in the magnitude of the impact were observed, influenced by regional health policies and the severity of the pandemic. CONCLUSIONS: The findings underscore the challenges cancer care providers face during public health crises, requiring adaptive strategies to ensure continued access to essential treatments. Addressing these challenges requires comprehensive public health responses to mitigate the impact of future crises on cancer care systems.

Impact of payment source, referral site, and place of residence on outcomes after allogeneic transplantation in Mexico.

BACKGROUND: The impact of social determinants of health in allogeneic transplant recipients in low- and middle-income countries is poorly described. This observational study analyzes the impact of place of residence, referring institution, and transplant cost coverage (out-of-pocket vs government-funded vs private insurance) on outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) in two of Mexico's largest public and private institutions. AIM: To evaluate the impact of social determinants of health and their relationship with outcomes among allogeneic transplant recipients in Mexico. METHODS: In this retrospective cohort study, we included adolescents and adults ≥ 16 years who received a matched sibling or haploidentical transplant from 2015-2022. Participants were selected without regard to their diagnosis and were sourced from both a private clinic and a public University Hospital in Mexico. Three payment groups were compared: Out-of-pocket (OOP), private insurance, and a federal Universal healthcare program "Seguro Popular". Outcomes were compared between referred and institution-diagnosed patients, and between residents of Nuevo Leon and out-of-state. Primary outcomes included overall survival (OS), categorized by residence, referral, and payment source. Secondary outcomes encompassed early mortality, event-free-survival, graft-versus-host-relapse-free survival, and non-relapse-mortality (NRM). Statistical analyses employed appropriate tests, Kaplan-Meier method, and Cox proportional hazard regression modeling. Statistical software included SPSS and R with tidycmprsk library. RESULTS: Our primary outcome was overall survival. We included 287 patients, n = 164 who lived out of state (57.1%), and n = 129 referred from another institution (44.9%). The most frequent payment source was OOP (n = 139, 48.4%), followed by private insurance (n = 75, 26.1%) and universal coverage (n = 73, 25.4%). No differences in OS, event-free-survival, NRM, or graft-versus-host-relapse-free survival were observed for patients diagnosed locally vs in another institution, nor patients who lived in-state vs out-of-state. Patients who covered transplant costs through private insurance had the best outcomes with improved OS (median not reached) and 2-year cumulative incidence of NRM of 14% than patients who covered costs OOP (Median OS and 2-year NRM of 32%) or through a universal healthcare program active during the study period (OS and 2-year NRM of 19%) (P = 0.024 and P = 0.002, respectively). In a multivariate analysis, payment source and disease risk index were the only factors associated with overall survival. CONCLUSION: In this Latin-American multicenter study, the site of residence or referral for alloHSCT did not impact outcomes. However, access to healthcare coverage for alloHSCT was associated with improved OS and reduced NRM.

Increasing access to transplantation through telemedicine and patient navigation.

BACKGROUND: Hematopoietic cell transplantation (HCT) is a promising treatment for hematological diseases, yet access barriers like cost and limited transplant centers persist. Telemedicine-based patient navigation (PN) has emerged as a solution. This study presents a cost-free PN telemedicine clinic (TC) in collaboration with the National Marrow Donor Program. AIM: to assess its feasibility and impac on HCT access determined by the cumulative incidence of transplantation. METHODS: In this single-center cohort study, patients of all ages and diagnoses referred for HCT participated. Two transplant physician-navigators established patient relationships via video calls, collecting medical history, offering HCT education and recommending pretransplant tests. The analysis involved descriptive statistics and intent-to-transplant survival assessment. RESULTS: One hundred and three patients were included of whom n = 78 were referred for allogeneic HCT (alloHCT), with a median age of 28 years. The median time from initial contact to the first consult was 5 days. The cumulative incidence of transplantation was 50% at 6 months and 61% at 12 months, with varying outcomes based on HCT type. Notably, 49 patients were not transplanted, primarily due to refractory disease, progression or relapse (57.1%). Autologous HCT candidates and physician referrals were correlated with higher transplant success compared to alloHCT candidates and patients who were not referred by a physician. CONCLUSION: Our pretransplant TC was feasible, facilitating access to HCT. Disease relapse posed a significant barrier. Enhancing timely physician referrals should be a focus for future efforts.

Tubulin Regulates Plasma Membrane Ca2+-ATPase Activity in a Lipid Environment-dependent Manner.

Ca2+ plays a crucial role in cell signaling, cytosolic Ca2+ can change up to 10,000-fold in concentration due to the action of Ca2+-ATPases, including PMCA, SERCA and SCR. The regulation and balance of these enzymes are essential to maintain cytosolic Ca2+ homeostasis. Our laboratory has discovered a novel PMCA regulatory system, involving acetylated tubulin alone or in combination with membrane lipids. This regulation controls cytosolic Ca2+ levels and influences cellular properties such as erythrocyte rheology. This review summarizes the findings on the regulatory mechanism of PMCA activity by acetylated tubulin in combination with lipids. The combination of tubulin cytoskeleton and membrane lipids suggests a novel regulatory system for PMCA, which consequently affects cytosolic Ca2+ content, depending on cytoskeletal and plasma membrane dynamics. Understanding the interaction between acetylated tubulin, lipids and PMCA activity provides new insights into Ca2+ signaling and cell function. Further research may shed light on potential therapeutic targets for diseases related to Ca2+ dysregulation. This discovery contributes to a broader understanding of cellular processes and offers opportunities to develop innovative approaches to treat Ca2+-related disorders. By elucidating the complex regulatory mechanisms of Ca2+ homeostasis, we advance our understanding of cell biology and its implications for human health.

Estudo Randomizado Comparando a Ablação por Cateter com o PVAC Gold vs. Tratamento com Fármacos Antiarrítmicos em Pacientes Idosos com Fibrilação Atrial Sintomática / Randomized Study Comparing Radiofrequency Ablation with the PVAC Gold System vs. Antiarrhythmic Drugs in Elderly Patients with Symptomatic Atrial Fibrillation

Resumo Fundamento Não existem estudos randomizados comparando a manutenção do ritmo sinusal após ablação por cateter (AC) em relação ao tratamento com fármacos antiarrítmicos (AA) em pacientes idosos portadores fibrilação atrial (FA) paroxística. Objetivos Comparar os resultados clínicos do isolamento das veias pulmonares (VPs) com o cateter PVAC Gold de segunda geração com o uso de AA em idosos com FA paroxística sintomática, recorrente, apesar do uso de fármacos AA. Métodos Sessenta pacientes com FA paroxística ≥ 65 anos e sem cardiopatias estruturais foram randomizados para duas formas de tratamento: grupo 1: AC e grupo 2: AA. O desfecho primário foi a taxa livre de recorrência de FA após pelo menos um ano de seguimento. Os desfechos secundários foram: progressão para formas persistentes de FA, impacto na qualidade de vida (QVFA) e complicações. O nível de significância adotado na análise estatística foi de 5% (p<0,05). Resultados A taxa livre de recorrência de FA foi de 80% (10% com amiodarona) no grupo AC, após 1,3 procedimentos por paciente e de 65% no grupo AA (60% com amiodarona), (p = 0,119) num seguimento médio de 719 dias (Q1: 566; Q3: 730). A taxa livre de FA persistente foi de 83,4% no grupo AC e de 67,7% no grupo AA (p = 0,073). Ambas as estratégias apresentaram melhora no escore de QVFA durante o seguimento (p < 0,001), sem diferença entre os grupos. Embora sem repercussão clínica ou impacto no teste de avaliação intelectual, 25% dos pacientes do grupo PVAC apresentou sinais de embolização cerebral na RNM cerebral. Conclusões Ambas as estratégias para manutenção do ritmo sinusal promoveram melhora na qualidade de vida de pacientes idosos com FA sintomática, sem diferença estatística nos desfechos clínicos preconizados. Estudos adicionais usando tecnologias com melhor perfil de segurança são necessários para avaliar os benefícios da AC em pacientes idosos com FA.

Abstract Background There are no randomized studies comparing the maintenance of sinus rhythm after catheter ablation (CA) concerning treatment with antiarrhythmic drugs (AA) in elderly patients with paroxysmal atrial fibrillation (AF). Objectives To compare the clinical results of pulmonary vein (PV) isolation with the second-generation PVAC Gold catheter against AA treatment in elderly people with recurrent symptomatic paroxysmal AF, refractory to at least one AA, and without structural heart disease. Methods Sixty patients with paroxysmal AF ≥ 65 years old were randomized to two forms of treatment: group 1: CA and group 2: AA drugs. The primary outcome was the AF recurrence-free rate after at least one year of follow-up. Secondary outcomes were: progression to persistent forms of AF, impact on quality of life (QOLF), and complications. The significance level adopted in the statistical analysis was 5% (p<0.05). Results The AF recurrence-free rate was 80% (10% with amiodarone) in the CA group, after 1.3 procedures per patient and 65% in the AA group (60% with amiodarone), (p = 0.119) in an average follow-up of 719 days (Q1: 566; Q3: 730). The persistent AF free rate was 83.4% in the AC group and 67.7% in the AA group (p = 0.073) Both strategies showed an improvement in the AFQoL score during follow-up (p < 0.001), with no difference between the groups. Although without clinical repercussions or impact on the intellectual assessment test, 25% of patients in the CA group showed signs of cerebral embolization on brain MRI. Conclusions Both strategies for maintaining sinus rhythm promoted an improvement in the quality of life of elderly patients with symptomatic AF, with no statistical difference in the clinical outcomes. Additional studies using technologies with a better safety profile are needed to evaluate the benefits of CA in elderly patients with AF.

The association of myocardial strain with cardiac magnetic resonance and clinical outcomes in patients with acute myocarditis.

Introduction: The role of myocardial strain in risk prediction for acute myocarditis (AMC) patients, measured by cardiac magnetic resonance (CMR), deserves further investigation. Our objective was to evaluate the association between myocardial strain measured by CMR and clinical events in AMC patients. Material and methods: This was a prospective single-center study of patients with AMC. We included 100 patients with AMC with CMR confirmation. The primary outcome was the composite of all-cause mortality, heart failure and AMC recurrence in 24 months. A subgroup analysis was performed on a sample of 36 patients who underwent a second CMR between 6 and 18 months. The association between strain measures and clinical events or an increase in left ventricular ejection fraction (LVEF) was explored using Cox regression analysis. Global peak radial, circumferential and longitudinal strain in the left and right ventricles was assessed. ROC curve analysis was performed to identify cutoff points for clinical event prediction. Results: The mean follow-up was 18.7 ± 2.3 months, and the composite primary outcome occurred in 26 patients. The median LVEF at CMR at baseline was 57.5% (14.6%). LV radial strain (HR = 0.918, 95% CI: 0.858-0.982, p = 0.012), LV circumferential strain (HR = 1.177, 95% CI: 1.046-1.325, p = 0.007) and LV longitudinal strain (HR = 1.173, 95% CI: 1.031-1.334, p = 0.015) were independently associated with clinical event occurrence. The areas under the ROC curve for clinical event prediction were 0.80, 0.79 and 0.80 for LV radial, circumferential, and longitudinal strain, respectively. LV longitudinal strain was independently correlated with prognosis (HR = 1.282, CI 95%: 1.022-1.524, p = 0.007), even when analyzed together with ejection fraction and delayed enhancement. LV and right ventricle (RV) strain were not associated with an increase in LVEF. Finally, when the initial CMR findings were compared with the follow-up CMR findings, improvements in the measures of LV and RV myocardial strain were observed. Conclusion: Measurement of myocardial strain by CMR can provide prognostic information on AMC patients. LV radial, circumferential and longitudinal strain were associated with long-term clinical events in these patients.

COVID-19 and Pulmonary Angiogenesis: The Possible Role of Hypoxia and Hyperinflammation in the Overexpression of Proteins Involved in Alveolar Vascular Dysfunction.

COVID-19 has been considered a vascular disease, and inflammation, intravascular coagulation, and consequent thrombosis may be associated with endothelial dysfunction. These changes, in addition to hypoxia, may be responsible for pathological angiogenesis. This research investigated the impact of COVID-19 on vascular function by analyzing post-mortem lung samples from 24 COVID-19 patients, 10 H1N1pdm09 patients, and 11 controls. We evaluated, through the immunohistochemistry technique, the tissue immunoexpressions of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis (ICAM-1, ANGPT-2, and IL-6, IL-1ß, vWF, PAI-1, CTNNB-1, GJA-1, VEGF, VEGFR-1, NF-kB, TNF-α and HIF-1α), along with the histopathological presence of microthrombosis, endothelial activation, and vascular layer hypertrophy. Clinical data from patients were also observed. The results showed that COVID-19 was associated with increased immunoexpression of biomarkers involved in endothelial dysfunction, microthrombosis, and angiogenesis compared to the H1N1 and CONTROL groups. Microthrombosis and vascular layer hypertrophy were found to be more prevalent in COVID-19 patients. This study concluded that immunothrombosis and angiogenesis might play a key role in COVID-19 progression and outcome, particularly in patients who die from the disease.

Postoperative myocardial fibrosis assessment in aortic valvular heart diseases-a cardiovascular magnetic resonance study.

AIMS: Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS. METHODS AND RESULTS: Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m2; AS: 86 vs. 68 g/m2, both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m2 vs. 22 mL/m2, P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m2, AS: 22-18.2 mL/m2, both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m2 vs. AS: 18.2 mL/m2, P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033). CONCLUSION: Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components.

Exploring the Non-Covalent Bonding in Water Clusters.

QTAIM and source function analysis were used to explore the non-covalent bonding in twelve different water clusters (H2O)n obtained by considering n = 2-7 and various geometrical arrangements. A total of seventy-seven O-H⋯O hydrogen bonds (HBs) were identified in the systems under consideration, and the examination of the electron density at the bond critical point (BCP) of these HBs revealed the existence of a great diversity of O-H⋯O interactions. Furthermore, the analysis of quantities, such as |V(r)|/G(r) and H(r), allowed a further description of the nature of analogous O-H⋯O interactions within each cluster. In the case of 2-D cyclic clusters, the HBs are nearly equivalent between them. However, significant differences among the O-H⋯O interactions were observed in 3-D clusters. The assessment of the source function (SF) confirmed these findings. Finally, the ability of SF to decompose the electron density (ρ) into atomic contributions allowed the evaluation of the localized or delocalized character of these contributions to ρ at the BCP associated to the different HBs, revealing that weak O-H⋯O interactions have a significant spread of the atomic contributions, whereas strong interactions have more localized atomic contributions. These observations suggest that the nature of the O-H⋯O hydrogen bond in water clusters is determined by the inductive effects originated by the different spatial arrangements of the water molecules in the studied clusters.

Tubulin-mediated anatomical and functional changes caused by Ca2+ in human erythrocytes.

In previous research, we observed that tubulin can be found in three fractions within erythrocytes, i.e., attached to the membrane, as a soluble fraction, or as part of a structure that can be sedimented by centrifugation. Given that its differential distribution within these fractions may alter several hemorheological properties, such as erythrocyte deformability, the present work studied how this distribution is in turn affected by Ca2+, another key player in the regulation of erythrocyte cytoskeleton stability. The effect of Ca2+ on some hemorheological parameters was also assessed. The results showed that when Ca2+ concentrations increased in the cell, whether by the addition of ionophore A23187, by specific plasma membrane Ca2 + _ATPase (PMCA) inhibition, or due to arterial hypertension, tubulin translocate to the membrane, erythrocyte deformability decreased, and phosphatidylserine exposure increased. Moreover, increased Ca2+ was associated with an inverse correlation in the distribution of tubulin and spectrin, another important cytoskeleton protein. Based on these findings, we propose the existence of a mechanism of action through which higher Ca2+ concentrations in erythrocytes trigger the migration of tubulin to the membrane, a phenomenon that results in alterations of rheological and molecular aspects of the membrane itself, as well as of the integrity of the cytoskeleton.

A Theoretical Study of the C-X Bond Cleavage Mediated by Cob(II)Aloxime.

The C-X bond cleavage in different methyl halides (CH3X; X = Cl, Br, I) mediated by 5,6-dimethylbenzimidazole-bis(dimethylglyoximate)cobalt(II) (CoIICbx) was theoretically investigated in the present work. An SN2-like mechanism was considered to simulate the chemical process where the cobalt atom acts as the nucleophile and the halogen as the leaving group. The reaction path was computed by means of the intrinsic reaction coordinate method and analyzed in detail through the reaction force formalism, the quantum theory of atoms in molecules (QTAIM), and the calculation of one-electron density derived quantities, such as the source function (SF) and the spin density. A thorough comparison of the results with those obtained in the same reaction occurring in presence of 5,6-dimethylbenzimidazole-bis(dimethylglyoximate)cobalt(I) (CoICbx) was conducted to reveal the main differences between the two cases. The reactions mediated by CoIICbx were observed to be endothermic and possess higher activation energies in contrast to the reactions where the CoICbx complex is present. The latter was supported by the reaction force results, which suggest a relationship between the activation energy and the ionization potentials of the different nucleophiles present in the cleavage reaction. Moreover, the SF results indicates that the lower axial ligand (i.e., 5,6-dimethylbenzimidazole) exclusively participates on the first stage of the reaction mediated by the CoIICbx complex, while for the CoICbx case, it appears to have an important role along the whole process. Finally, the QTAIM charge analysis indicates that oxidation of the cobalt atom occurs in both cases; at the same time, it suggests the formation of an uncommon two-center one-electron bond in the CoIICbx case. The latter was confirmed by means of electron localization calculations, which resulted in a larger electron count at the Co-C interatomic region for the CoICbx case upon comparison with its CoIICbx counterpart.

Dehydrochlorination of PCDDs on SWCN-Supported Ni10 and Ni13 Clusters, a DFT Study.

Polychlorinated dibenzo-p-dioxins (PCDDs) are known to be a group of compounds of high toxicity for animals and, particularly, for humans. Given that the most common method to destroy these compounds is by high-temperature combustion, finding other routes to render them less toxic is of paramount importance. Taking advantage of the physisorption properties of nanotubes, we studied the reactions of atomic hydrogen on physisorbed PCDDs using DFT; likewise, we investigated the reaction of molecular hydrogen on PCDDs aided by Ni10 and Ni13 clusters adsorbed on single-wall carbon nanotubes. Because dihydrogen is an easily accessible reactant, we found these reactions to be quite relevant as dehydrohalogenation methods to address PCDD toxicity.

An analysis of the influence of transfer learning when measuring the tortuosity of blood vessels.

BACKGROUND AND OBJECTIVE: Convolutional Neural Networks (CNNs) can provide excellent results regarding the segmentation of blood vessels. One important aspect of CNNs is that they can be trained on large amounts of data and then be made available, for instance, in image processing software. The pre-trained CNNs can then be easily applied in downstream blood vessel characterization tasks, such as the calculation of the length, tortuosity, or caliber of the blood vessels. Yet, it is still unclear if pre-trained CNNs can provide robust, unbiased, results in downstream tasks involving the morphological analysis of blood vessels. Here, we focus on measuring the tortuosity of blood vessels and investigate to which extent CNNs may provide biased tortuosity values even after fine-tuning the network to a new dataset under study. METHODS: We develop a procedure for quantifying the influence of CNN pre-training in downstream analyses involving the measurement of morphological properties of blood vessels. Using the methodology, we compare the performance of CNNs that were trained on images containing blood vessels having high tortuosity with CNNs that were trained on blood vessels with low tortuosity and fine-tuned on blood vessels with high tortuosity. The opposite situation is also investigated. RESULTS: We show that the tortuosity values obtained by a CNN trained from scratch on a dataset may not agree with those obtained by a fine-tuned network that was pre-trained on a dataset having different tortuosity statistics. In addition, we show that improving the segmentation accuracy does not necessarily lead to better tortuosity estimation. To mitigate the aforementioned issues, we propose the application of data augmentation techniques even in situations where they do not improve segmentation performance. For instance, we found that the application of elastic transformations was enough to prevent an underestimation of 8% of blood vessel tortuosity when applying CNNs to different datasets. CONCLUSIONS: The results highlight the importance of developing new methodologies for training CNNs with the specific goal of reducing the error of morphological measurements, as opposed to the traditional approach of using segmentation accuracy as a proxy metric for performance evaluation.

Web of Science como herramienta de investigación y apoyo a la actividad científica: luces y sombras de sus colecciones, productos e indicadores / Web of Science as a research tool and support for scientific activity: lights and shadows of their collections, products and indicators

Resumen Se realiza una descripción de las colecciones, productos e indicadores bibliométricos de Web of Science, con especial énfasis en su utilidad e importancia en actividades de evaluación científica. Se exponen además sus principales limitaciones de cobertura y de indicadores, que impactan en el análisis de la producción científica en países y/o regiones periféricas y en áreas del conocimiento con menor representación en la fuente. También se comentan los aportes específicos de la base de datos en las distintas actividades y fases de la investigación científica como investigadores, revistas, grupos editoriales y bibliotecas. En concreto, se muestra el volumen de datos, se detallan sus colecciones, productos e indicadores, junto a la valoración de algunos aspectos en lo positivo y negativo. Se realizan comparativos con otras fuentes de información existentes en el mercado de la investigación científica y que igualmente permiten la realización de investigación bibliométrica, brindando al lector una importante caracterización de la herramienta y sus competidores, que ayude a conocer sus perspectivas de uso dentro del escenario de investigación. Las ideas desarrolladas y sistematizadas en el texto, permiten concluir que, a pesar de la relevancia de la misma para la actividad científica en distintos niveles y agregados, los sesgos de sus indicadores, la imposibilidad de acceso a la fuente en muchas instituciones y la existencia de otras herramientas con similares prestaciones y facilidades de uso, son aspectos que se deben tener en cuenta porque inciden en su aplicación, uso futuro y permanencia en el ecosistema de investigación.

Abstract A description of the collections, products and bibliometric indicators of Web of Science is made, with special emphasis on its usefulness and importance in scientific evaluation activities. The main limitations of coverage and indicators, which have an impact on the analysis of scientific production in peripheral countries and/or regions and in areas of knowledge with less representation in the source, are also discussed. The specific contributions of the database to the different activities and phases of scientific research, such as researchers, journals, publishing groups and libraries, are also discussed. Specifically, the volume of data is shown, its collections, products and indicators are detailed, together with the evaluation of some positive and negative aspects. Comparisons are made with other sources of information existing in the scientific research market, which also allow bibliometric research to be carried out, providing the reader with an important characterization of the tool and its competitors, which helps to know its perspectives of use within the research scenario. The ideas developed and systematized in the text lead to the conclusion that despite its relevance for scientific activity at different levels and aggregates, the biases of its indicators, the impossibility of accessing the source in many institutions and the existence of other tools with similar features and ease of use, are aspects that should be taken into account because they affect its application, future use and permanence in the research ecosystem.

High dose melphalan is an adequate preparative regimen for autologous hematopoietic stem cell transplantation in relapsed/refractory lymphoma.

INTRODUCTION: High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft. MATERIAL AND METHODS: All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200 mg/m2). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS). RESULTS: Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant (p 0.5). The EFS was also similar in both groups (p 0.5). CONCLUSION: HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells.

Hibiscus Acid from Hibiscus sabdariffa L. Inhibits Flagellar Motility and Cell Invasion in Salmonella enterica.

Extracts of Hibiscus sabdariffa L. (commonly called Rosselle or "Jamaica flower" in Mexico) have been shown to have antibiotic and antivirulence properties in several bacteria. Here, an organic extract of H. sabdariffa L. is shown to inhibit motility in Salmonella enterica serovars Typhi and Typhimurium. The compound responsible for this effect was purified and found to be the hibiscus acid. When tested, this compound also inhibited motility and reduced the secretion of both flagellin and type III secretion effectors. Purified hibiscus acid was not toxic in tissue-cultured eukaryotic cells, and it was able to reduce the invasion of Salmonella Typhimurium in epithelial cells. Initial steps to understand its mode of action showed it might affect membrane proton balance.

Caracterización de una población pediátrica seguida en una clínica de anticoagulación / Description of a pediatric population followed at an anticoagulation clinic

Resumen Introducción: En la población pediátrica, el 95% de las tromboembolias venosas son secundarias a un factor de riesgo; la presencia de catéter venoso central es el factor de riesgo más importante para el desarrollo de trombosis venosa profunda en esta población. Los estudios en población adulta sobre el uso de anticoagulantes se han extrapolado a la población pediátrica, y por ello es importante tener en cuenta las características diferenciales entre ambas poblaciones. Método: Se realizó un estudio descriptivo en el que se revisaron 2300 registros clínicos de pacientes seguidos por la Clínica de Anticoagulación institucional desde 2011 hasta 2019, buscando identificar pacientes menores de 18 años que hubieran recibido manejo anticoagulante ambulatorio. Resultados: Se encontraron 43 pacientes menores de 18 años, el 60% de sexo femenino, con una edad promedio de 9.8 ± 5.2 años. El antecedente patológico más prevalente fueron las valvulopatías (28%). Las principales indicaciones para recibir manejo anticoagulante incluyeron cardiopatías congénitas (21%), prótesis valvular cardíaca mecánica (21%, 5 aórticas y 4 mitrales) y trombosis venosa profunda (14%). La warfarina se utilizó en el 72% de los pacientes. El 81% de los pacientes recibieron tratamiento anticoagulante extendido. Las principales complicaciones durante el tratamiento anticoagulante fueron sangrado ginecológico y cutáneo, así como trombocitopenia. Conclusiones: Las cardiopatías congénitas y las valvulopatías cardíacas son las principales indicaciones para considerar el manejo anticoagulante en la población pediátrica. La warfarina es el medicamento más utilizado en forma ambulatoria en esta población. La adherencia adecuada y el seguimiento ambulatorio en esta población requieren herramientas adicionales para lograr un excelente tratamiento anticoagulante.

Abstract Introduction: In pediatric patients, 95% of venous thromboembolisms are secondary to a risk factor; the presence of central venous catheter is the most important risk factor for the development of deep vein thrombosis in this population. Studies about anticoagulation treatment in adult patients have been extrapolated to the pediatric population, it is important to consider the differential characteristics between these two populations. Method: A descriptive study was conducted; there were reviewed 2300 clinical records of patients followed by the institutional anticoagulation clinic from 2011 to 2019, looking for underage patients who have received ambulatory anticoagulation treatment management. Results: 43 patients under the age of 18 years old were found. 60% were female and the average age was 9.8 ± 5.2 years. The most prevalent pathological antecedent was valve disease (28%). The main indications for anticoagulant treatment included congenital heart disease (21%), mechanical heart valves (21%, 5 aortic and 4 mitral) and deep vein thrombosis (14%). Warfarin was found in 72% of patients. 81% of patients received extended anticoagulation therapy. The main complications during anticoagulant treatment included gynecological and cutaneous bleeding, as well as thrombocytopenia. Conclusions: Congenital heart disease and heart valve disease are the main indications for considering anticoagulation treatment in the pediatric population. Warfarin is the most formulated anticoagulant in this outpatient population. Adequate adherence and outpatient follow-up in requires additional tools to achieve excellent anticoagulant treatment.