Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management.

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.

[COVID-19 in the city of Madrid and vulnerability. Analysis of the first two waves.] / COVID-19 en la ciudad de Madrid y vulnerabilidad. Análisis de las dos primeras olas.

OBJECTIVE: The advance of the pandemic in the large cities of the world with great virulence and the apparent heterogeneous distribution by factors of vulnerability, led us to propose this work. The objective of this study was to relate COVID-19 infection rates to the social vulnerability of the city of Madrid by district, in two different episodes, spring 2020 and summer 2020. METHODS: Analytical cross-sectional study. Taking sociodemographic data of the entire population of the city of Madrid between the months of April and October 2020, together with the cumulative incidence rates of COVID-19, a linear regression analysis, correlation and factor analysis was carried out, relating the cumulative incidence rate of COVID-19 and the vulnerability indicator of the districts of the city of Madrid. RESULTS: The results showed important differences between the two episodes of the pandemic: on one hand, the first had more relationship with health factors, while in the second, a relationship appeared with the groups of greater social vulnerability, territorially located in the South-East of the City and related in this case to social factors rather than health. Thus we see that the TIA x 100,000 in the first episode in Chamberí and Usera -two extreme districts in vulnerability- were 896 and 843 cases respectively, while in the second they were 3,708 and 6,258 cases. CONCLUSIONS: The territorial differences in the city become evident with the arrival of a generalised, universal event such as COVID-19, where vulnerability increases for everyone, with greater repercussions in those territories where it already had an impact.

OBJETIVO: El avance de la pandemia en las grandes ciudades del mundo con gran virulencia y la aparente distribución heterogénea por factores de vulnerabilidad, nos llevaron a plantear este trabajo. El objetivo de este estudio fue relacionar las tasas de infección por COVID-19 con la vulnerabilidad social de la ciudad de Madrid por distritos, en dos episodios distintos, primavera del 2020 y verano del 2020. METODOS: Estudio transversal analítico.Tomando los datos sociodemográficos de la totalidad de la población de la ciudad de Madrid entre los meses de abril y octubre de 2020, junto a las tasas de incidencia acumulada de la COVID-19, se realizó un análisis de regresión lineal, correlación y análisis factorial, relacionando la tasa de incidencia acumulada de la COVID-19 y el indicador de vulnerabilidad de los distritos de la ciudad de Madrid. RESULTADOS: Los resultados mostraron diferencias importantes entre los dos episodios de la pandemia: por una parte, el primero tuvo más relación con factores de salud, mientras en el segundo apareció una relación con los colectivos de mayor vulnerabilidad social, territorialmente localizados en la zona Sur-Este de la Ciudad y relacionándose en este caso con factores sociales más que de salud. Así vemos que las TIA x 100.000 en el primer episodio en Chamberí y Usera -dos distritos extremos en vulnerabilidad- fueron de 896 y 843 casos respectivamente, mientras que en el segundo fueron de 3.708 y 6.258 casos. CONCLUSIONES: Las diferencias territoriales de la ciudad de Madrid se hacen patentes ante la llegada de un suceso generalizado y universal como la COVID-19, dónde la vulnerabilidad se acrecienta para todo el mundo, repercutiendo en mayor medida en aquellos territorios donde ya incidía.

Merging α-Lithiation and Aldol-Tishchenko Reaction to Construct Polyols from Benzyl Ethers.

α-Lithiobenzyl ethers, generated by selective α-lithiation, undergo an aldol-Tishchenko reaction upon treatment with carboxylic esters and paraformaldehyde. The reaction of the organolithium with the carboxylate generates an intermediate enolate that, after formaldehyde addition, affords 1,2,3-triol derivatives in a straightforward and one-pot manner. These products are obtained as single diastereoisomers bearing a quaternary stereocenter. The complete diastereocontrol of the aldol-Tishchenko process is attributed to stereoelectronic preferences in the transition state.

α-Lithiobenzyloxy as a Directed Metalation Group in ortho-Lithiation Reactions.

The α-lithiobenzyloxy group, easily generated from aryl benzyl ethers by selective α-lithiation with t-BuLi at low temperature, behaves as a directed metalation group (DMG) providing a direct access to o-lithiophenyl α-lithiobenzyl ethers. This ortho-directing effect is reinforced in substrates bearing an additional methoxy group at the meta position. The generated dianions can be reacted with a selection of electrophiles including carboxylic esters and dihalosilanes or germanes, which afford interesting benzofuran, sila(germa)dihydrobenzofuran, and silachroman derivatives from simple aryl benzyl ethers.

Exploring the Reactivity of α-Lithiated Aryl Benzyl Ethers: Inhibition of the [1,2]-Wittig Rearrangement and the Mechanistic Proposal Revisited.

By carefully controlling the reaction temperature, treatment of aryl benzyl ethers with tBuLi selectively leads to α-lithiation, generating stable organolithiums that can be directly trapped with a variety of selected electrophiles, before they can undergo the expected [1,2]-Wittig rearrangement. This rearrangement has been deeply studied, both experimentally and computationally, with aryl α-lithiated benzyl ethers bearing different substituents at the aryl ring. The obtained results support the competence of a concerted anionic intramolecular addition/elimination sequence and a radical dissociation/recombination sequence for explaining the tendency of migration for aryl groups. The more favored rearrangements are found for substrates with electron-poor aryl groups that favor the anionic pathway.

Prevalence of sarcopenia in acute hip fracture patients and its influence on short-term clinical outcome.

AIM: Current international criteria provide standardized procedures to diagnose sarcopenia in older people. However, to date few data exist on patients with acute disease. The present study was carried out to determine the frequency of sarcopenia in acute hip fracture patients, and its association with their baseline characteristics and prognosis during hospitalization. METHODS: Data were collected from 509 consecutive patients hospitalized for hip fracture. The European Working Group on Sarcopenia in Older People Criteria for sarcopenia were applied in the first 72 h. Muscle mass was measured by electrical bioimpedance and grip strength by hydraulic dynamometer. Clinical, functional and cognitive characteristics were assessed at baseline and hospital discharge, and their association with the presence of sarcopenia was studied. RESULTS: A total of 479 patients (94%) met the inclusion criteria. The mean age was 85.3 (SD 6.8 years). The frequency of sarcopenia was 17.1% (12.4% in men, 18.3% in women). Sarcopenia was associated with residence in nursing homes (30.5% vs 19.6%, P = 0.030), older age (86.8, SD 6.2 vs 85.1, SD 6.9 years, P = 0.038), and lower body mass index (23.1, SD 3.6 vs 25.6, SD 4.23, P < 0.001). In the multivariate analysis, only low body mass index was predictive of sarcopenia (OR 0.85, 95% CI 0.80-0.91). Sarcopenia was associated with worse functional prognosis at discharge in the crude analysis (OR 1.88, 95% CI 1.15-3.07), but not in the multivariate analysis (OR 1.68, 95% CI 0.99-2.84). CONCLUSIONS: Sarcopenia was detected in almost one of five acute hip fracture patients and was associated with lower body mass index, but an association with worse prognosis at discharge could not be confirmed. Geriatr Gerontol Int 2016; 16: 1021-1027.

α-Lithiated Aryl Benzyl Ethers: Inhibition of [1,2]-Wittig Rearrangement and Application to the Synthesis of Benzo[b]furan Derivatives.

The use of t-BuLi at low temperature selectively leads to α-lithiation of benzyl phenyl ether generating a stable organolithium, which can be efficiently trapped with a variety of selected electrophiles prior to suffering the expected [1,2]-Wittig rearrangement. In the case of (o-alkynyl)phenyl benzyl ethers, the intermediate α-aryloxyorganolithium undergoes an unexpected anti intramolecular carbolithiation reaction leading to functionalized benzo[b]furan derivatives.

Synthesis of Hindered α-Amino Carbonyls: Copper-Catalyzed Radical Addition with Nitroso Compounds.

The synthesis of sterically hindered anilines has been a significant challenge in organic chemistry. Here we report a Cu-catalyzed radical addition with in situ-generated nitroso compounds to prepare sterically hindered amines directly from readily available materials. The transformation is conducted at room temperature, uses abundant copper salts, and is tolerant of a range of functional groups.

Evaluación de la eficacia de un tratamiento individual para mujeres víctimas de violencia de pareja con trastorno de estrés postraumático

El objetivo de esta investigación es evaluar la eficacia de un tratamiento breve e individual del trastornode estrés postraumático (TEPT) en mujeres víctimas de pareja. Participaron 20 mujeres víctimas de malos tratos por su pareja, todas con diagnóstico de TEPT (DSM-IV-TR). El tratamiento, aplicado enformato individual, consta de ocho sesiones, incluyendo psicoeducación, entrenamiento en control de la activación, terapia cognitiva y terapia de exposición. Se utilizó un diseño cuasiexperimental de medidas repetidas (en el pretratamiento, postratamiento y seguimientos). En el postratamientose consigue una mejora significativa en la sintomatología postraumática (superación del TEPT en más del 80% de las participantes) y en los problemas asociados: depresión, autoestima, inadaptación social y cogniciones postraumáticas. Mejorías que se mantienen, e incluso, se incrementan en el seguimiento a seis meses.

The aim of this research is to evaluate the effectiveness of a brief and specific treatment of the PosttraumaticStress Disorder (PSD) in women victims of domestic violence. The participants were 20 battered women, all of whom fulfilled the PSD diagnosis (DSM-IV-TR). The treatment, individually applied, consists of eight sessions and it includes psycho-education, training for the activation control, cognitive therapy and exposure therapy. A quasi-experimental design of repeated measures was used(pre-treatment, post-treatment and 6 month follow-up). The results at the post-treatment stage showeda significant improvement for the PSD symptoms (80% of the women no longer fulfilled the PSD criteria). Also, they presented significant improvements in other symptoms: depression, self-esteem, social adaptation problems, and posttraumatic beliefs. At the six month follow-up these improvementsremained constant, and even increased.

O objetivo desta investigação é avaliar a eficácia de um tratamento breve e individual do transtorno de stress pós-traumático (TEPT) em mulheres vítimas de casal. Participaram 20 mulheres vítimas de maus tratos pelo seu casal, todas com diagnóstico de TEPT (DSM-IV-TR). O tratamento, aplicado em formato individual, consta de oito sessões, incluindo psicoeducação, treinamento em controle da ativação, terapia cognitiva e terapia de exposição. Se utilizou um design cuaseexperimental de medidas repetidas (no pre-tratamiento, pós-tratamento e seguimentos). No pós-tratamento se consegue uma melhora significativa na sintomatologia post-traumática (superação do TEPT em mais de 80% das participantes) e nos problemas associados: Depressão, auto-estima, inadaptação social e cogniçõespós-traumáticas. Melhorias que se mantêm e inclusive se aumentam no seguimento a seis meses.

Tratamiento cognitivo-conductual de un caso de vaginismo y fobia a la exploración ginecológica / Cognitive-behavioural treatment of a case of vaginism and phobia about the pelvic examination

En el presente artículo se describe el tratamiento cognitivo-conductual de una mujer con vaginismo y fobia específica a la situación de exploración ginecológica. El tratamiento se lleva a cabo en la Unidad de Psicología Clínica y de la Salud de la Universidad Complutense de Madrid; consistió en 34 sesiones (28 individuales y 6 en pareja) con una distribución periódica bisemanal a lo largo de 12 meses. Los resultados de la intervención se mantienen tras el periodo de seguimiento, lo que demuestra la eficacia de dicho tratamiento. La paciente acude derivada por el Hospital Clínico San Carlos de Madrid, centro en el que estaba asignada a un Programa de Esterilidad. En la actualidad, la paciente ha superado el tratamiento psicológico y médico y se encuentra embarazada (AU)

A cognitive-behavioural treatment of a woman with vaginism and specific phobia about gynecological examination is described in the present article. The treatment takes place in the Clinical Psychology Unit of the U.C.M and consisted of 34 sessions (28 individual and 6 in couple) on a fortnightly basis over a period of 12 months. The results of the intervention persisted after a period of follow-up, which proves the efficacy of the intervention. The patient was referred from the Hospital Clínico San Carlos, Madrid, where she had been assigned to a sterility treatment program. Having got over the psychological and medical treatment, the patient is currently pregnant (AU)