Fronterizas in Resistance: Feminist Demands within Social Movements Organizations

Latin America is one of the most unequal continents in the world. This inequality translates into marked limitations in the possibilities of having a decent life for a high percentage of the population. Within the groups that are affected, women are undoubtedly even more so, because, in addition to shared economic and social inequalities with other vulnerable groups, they face discrimination based on gender. In Latin America, political protest has been undertaken by women who wish to denounce and abate the injustices of which they are victims. These struggles have been analyzed by different thinkers. For the most part, feminist theories deal with the struggle of women against the oppressive behavior of patriarchy from the State or society. Others highlight the ability of women to contribute to social changes from socially accepted roles such as mothers, daughters, wives. These approaches ignore the difficulties experienced by female activists within the political mobilization. In this essay then we seek to document, analyze, and theorize about the patriarchal practices suffered by women activists - qua women- within the social organizations in Ciudad Juárez, as well as the forms of resistance they have opposed

Síntesis de nuevos ésteres y fosfatos del ácido meso-dihidroguaiarético; determinación de su actividad contra bacterias resistentes y Mycobacterium tuberculosis así como su interacción con la enzima DXR in silico.

Propósito y método de estudio: La tuberculosis (TB) es una de las mayores amenazas para la salud pública mundial. En 2014 se reportaron 1.5 millones de personas que fallecieron a consecuencia de esta enfermedad además es la principal causa de defunciones en personas infectadas con VIH en 2015. La OMS ha elaborado una lista para guiar y promover la investigación de nuevos antibióticos en la que se incluyen 12 bacterias más peligrosas para la salud humana como Acinetobacter, Pseudomonas, Klebsiella, etc. En estudios previos de nuestro grupo de investigación, se aisló y caracterizó de L. tridentata el lignano ácido meso dihidroguaiarético (AmDG) que posee actividad antimicobacteriana con una CMI en un rango de 12.5 a 50 µg/mL contra aislados clínicos de M. tuberculosis MFR, y con una CMI de 50 µg/mL contra M. tuberculosis H37Rv y S. aureus resistente a meticilina. Reyes-Melo y colaboradores sintetizaron y caracterizaron 28 derivados del AmDG a los cuales se les determinó su actividad contra bacterias resistentes y contra M. tuberculosis. Los resultados de este estudio indicaron que ocho ésteres presentaron actividad antimicobacteriana con una CMI en el rango de 12.5 a 50 µg/mL. La presencia de un grupo benzoilo parece ser un factor determinante en la actividad antimicobacteriana ya que estos derivados presentaron una actividad 4 veces mayor que los análogos que poseen grupos acetilo. Adicionalmente, los derivados semisintéticos con un grupo éster presentaron actividad contra S. aureus resistente a meticilina con una CMI de 25-50 g/ml. Por lo anterior se sintetizaron nuevos ésteres del AmDG con el anillo benzoico y diferentes sustituyentes. La enzima 1-desoxi-D-xilulosa 5-fosfato reductoisomerasa (DXR) forma parte de la vía no mevalonato en la biosíntesis de precursores básicos de isoprenoides esenciales para M. tuberculosis. Teniendo como blanco esta enzima se sintetizaron fosfonatos a partir de cinamaldehídos teniendo como concentración inhibitoria 50 (IC50): 0.7-21.5 M. Por lo que el objetivo de este proyecto fue sintetizar derivados del AmDG incluyendo esteres y fosfatos, determinar su actividad contra bacterias resistentes y M. tuberculosis y finalmente determinar la interacción de los derivados obtenidos con la enzima DXR. Las hojas secas de L. tridentata (808 g) se maceraron con CHCl3/MeOH y se obtuvieron 205.8g de extracto del cual se aislaron y caracterizaron el flavonoide 5,8,4´-trihidroxi-3,7-dimetoxiflavona, los lignanos ácido meso dihidroguaiarético (AmDG) y 4,4´-dihidroxi-3-metoxi-6,7´- ciclolignano. A partir del AmDG se sintetizaron 7 ésteres por medio de la reacción de Steglich, 5 fosfatos por medio de la reacción de Atherton Todd y un derivado metilado del 4,4´-dihidroxi-3-metoxi-6,7´-ciclolignano. Los productos naturales y derivados semi-sintéticos se purificaron mediante cromatografía en columna y placas preparativas y su estructura química se determinó por RMN1H, RMN13C y HRMS. Los derivados se evaluaron contra M. tuberculosis H37Rv la cual es sensible a fármacos de primera línea y una cepa TB-MFR (G122) resistente a Rifampicina, Etambutol y Estreptomicina, así como también contra ocho aislados clínicos de bacterias farmacorresistentes. Conclusiones y contribuciones: Se aislaron, purificaron y caracterizaron tres productos naturales: un flavonoide: 5,8,4´-trihidroxi-3,7-dimetoxiflavona, y dos lignanos: ácido meso dihidroguaiarético y 4,4´-dihidroxi-3-metoxi-6,7´- ciclolignano. Se sintetizaron 13 nuevos derivados semisintéticos los cuales incluyen: 7 ésteres, 5 fosfatos y 1 derivado metilado. De los 13 derivados evaluados, los ésteres monosustituidos 1, 5 y el fosfato 11 presentaron actividad contra la cepa H37Rv (CMI de 25-50 g/mL), los derivados 5 y 11 también presentaron actividad contra la cepa G122 (CMI de 50g/mL), los demás derivados no presentaron actividad a las concentraciones ensayadas (CMI >50g/mL). A los derivados 1 y 5 se les determino la citotoxicidad en macrófagos J774A.1 donde resultaron ser más citotóxicos que el AmDG, y el índice de selectividad de los derivados y el producto natural fue menor de 10 lo que indica que no son selectivos para la micobacteria. Adicionalmente se realizó el docking a los ésteres, fosfatos y al AmDG con la enzima DXR, los ésteres 1, 4, 5 y 6 y los fosfatos 11 y 13 mostraron mayor afinidad hacia la enzima DXR que el AmDG. Los compuestos 1, 5 y 11 mostraron cierta afinidad teórica a la enzima DXR lo que podría explicar su posible mecanismo de acción

Nuevas terapias dirigidas para el tratamiento del cáncer

El cáncer es el término que se utiliza para englobar un conjunto de enfermedades que se caracterizan por el crecimiento descontrolado de células alteradas molecularmente por mutaciones o modificaciones epigenéticas.En la presente revisión describimos algunas terapias dirigidas que se están utilizando actualmente en clínic

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Marco activo de recursos de innovación docente: Madrid

Una guía de espacios e instituciones para actividades educativas complementarias en enseñanza secundaria y Formación Profesional

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes

Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 μg/dL (confirmed ACS if >5 μg/dL and possible ACS if 1.8–5 μg/dL) in the absence of spe cific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS–PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS–PA and PA-only patients was simil ar, except for older age and larger tumor size of the adrenal lesion in the ACS–PA group. When comparing the ACS–PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64–22.32)) and cardiovascular events (OR 5.0 (2.29–11.07)) was higher in ACS–PA patients than in ACS patients. The coexistence of ACS in patien ts with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS–PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-thi rd of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS–PA and PA-only are similar