Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients

Testicular germ-cell tumors (TGCT) have been widely recognized for their outstanding survival rates, commonly attributed to their high sensitivity to cisplatin-based therapies. Despite this, a subset of patients develops cisplatin resistance, for whom additional therapeutic options are unsuccessful, and ~20% of them will die from disease progression at an early age. Several efforts have been made trying to find the molecular bases of cisplatin resistance. However, this phenomenon is still not fully understood, which has limited the development of efficient biomarkers and precision medicine approaches as an alternative that could improve the clinical outcomes of these patients. With the aim of providing an integrative landscape, we review the most recent genomic and epigenomic features attributed to chemoresponse in TGCT patients, highlighting how we can seek to combat cisplatin resistance through the same mechanisms by which TGCTs are particularly hypersensitive to therapy. In this regard, we explore ongoing treatment directions for resistant TGCT and novel targets to guide future clinical trials. Through our exploration of recent findings, we conclude that epidrugs are promising treatments that could help to restore cisplatin sensitivity in resistant tumors, shedding light on potential avenues for better prognosis for the benefit of the patients

Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy

SIMPLE SUMMARY: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Incidence and mortality of this disease has remained unchanged in Latin populations unlike the rest of the world. To date, the search for genetic variants in our population remains unexplored. The aim of this study is to identify predictive biomarkers of resistance to platinum-based therapy, whether general or specific to the Latin population. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. However, we identified amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population. ABSTRACT: Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population

PSYCHOLOGICAL WELL-BEING, FAMILY RELATIONS, AND DEVELOPMENTAL ISSUES OF CHILDREN LEFT BEHIND

The phrase \u201cchildren left behind\u201d refers to minors who are left in their home country while one or both of their parents emigrate for work for at least six months. From a quantitative point of view, children left behind in countries with strong migratory pressure are many. Separation of families in migration is tied to implications about well-being of the people involved \u2014 mainly the children \u2014 and of the communities to which they belong. The emotional neglect felt by these children is associated with lack of affection and physical intimacy. Through a review of the literature, the purpose of the article was to show that distress in this pattern of deprivation is manifested by the children in several ways and in different contexts: low school performance, drop-out from school, conflicts with teachers and peers, anxiety, low self-esteem, tendency to feel depressed, apathy, suicidal behaviour, and substance abuse

Single dose dipyrone for acute postoperative pain

[Background]: Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought.[Objectives]: To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain.[Search strategy]: The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010.[Selection criteria]: Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs.[Data collection and analysis]: Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected.[Main results]: Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)). Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248 participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No serious adverse events were reported.[Authors' conclusions]: Based on very limited information, single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and fewer would need rescue medication, over 4 to 6 hours.Peer reviewe

Single dose dipyrone for acute postoperative pain.

BACKGROUND: Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. OBJECTIVES: To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. SEARCH STRATEGY: The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. SELECTION CRITERIA: Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)). Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248 participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No serious adverse events were reported. AUTHORS' CONCLUSIONS: Based on very limited information, single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and fewer would need rescue medication, over 4 to 6 hours

Documenting the Recovery of Vascular Services in European Centres Following the Initial COVID-19 Pandemic Peak: Results from a Multicentre Collaborative Study

ObjectiveTo document the recovery of vascular services in Europe following the first COVID-19 pandemic peak.MethodsAn online structured vascular service survey with repeated data entry between 23 March and 9 August 2020 was carried out. Unit level data were collected using repeated questionnaires addressing modifications to vascular services during the first peak (March - May 2020, "period 1"), and then again between May and June ("period 2") and June and July 2020 ("period 3"). The duration of each period was similar. From 2 June, as reductions in cases began to be reported, centres were first asked if they were in a region still affected by rising cases, or if they had passed the peak of the first wave. These centres were asked additional questions about adaptations made to their standard pathways to permit elective surgery to resume.ResultsThe impact of the pandemic continued to be felt well after countries' first peak was thought to have passed in 2020. Aneurysm screening had not returned to normal in 21.7% of centres. Carotid surgery was still offered on a case by case basis in 33.8% of centres, and only 52.9% of centres had returned to their normal aneurysm threshold for surgery. Half of centres (49.4%) believed their management of lower limb ischaemia continued to be negatively affected by the pandemic. Reduced operating theatre capacity continued in 45.5% of centres. Twenty per cent of responding centres documented a backlog of at least 20 aortic repairs. At least one negative swab and 14 days of isolation were the most common strategies used for permitting safe elective surgery to recommence.ConclusionCentres reported a broad return of services approaching pre-pandemic "normal" by July 2020. Many introduced protocols to manage peri-operative COVID-19 risk. Backlogs in cases were reported for all major vascular surgeries

. 11-12 Año 6 (2017) enero-agosto. CR. Conservación y restauración

- Editorial por Manuel Alejandro González Gutiérrez y Magdalena Rojas Vences. -Proyecto de atención del acervo documental de Ixcamilpa de Guerrero por Patricia de la Garza Cabrera, Marie Vander Meeren, Laura Olivia Ibarra Carmona, Nora A. Pérez Castellanos, Carlos Orejel Delgadillo, Silvia Yocelin Pérez Ramírez, Débora Y. Ontiveros Ramírez, Denisse Ochoa Gutiérrez, Hugo Arriaga González y Gerardo Gutiérrez. - Haciendo frente a los embates medioambientales: conservación integral del sitio rupestre Cuevas Pintas,Baja California Sur por Sandra Cruz Flores, Alejandra Bourillón Moreno, Anacaren Morales Ortiz, Rodrigo Ruiz Herrera y María Fernanda López-Armenta. - Estrategia para la accesibilidad e inclusión de las personas con discapacidad a zonas arqueológicas “El pasado es de todos” por Daniela Tovar Ortiz y Luis Antonio Huitrón Santoyo. - Atención a grupos sociales. Sistematización de actividades por Manuel González Gutiérrez y Denisse Ochoa Gutiérrez. - Tañendo campanas: trabajando en equipo. Intervención de las campanas robadas en la capilla de Nuestra Señora de la Concepción, Escobedo, Nuevo León por Gabriela Peñuelas Guerrero, Carlos I. Cañete Ibáñez, Claudia Sánchez Gándara, Jannen Contreras Vargas e Ingrid K. Jiménez Cosme. - La apropiación del patrimonio cultural de El Ocote. Una aportación etnográfica para la sostenibilidad por Hugo Arriaga González. - Churubusco. 50 años en la memoria. Una muestra conmemorativa de la conservación en el INAH por Mónica Badillo Leal, Gabriela Gómez Llorente y Mariana Pascual Cáceres. - Los órganos y su conservación en la CNCPC por Norma Cristina Peña Peláez, Sandra María Álvarez Jacinto, José Luis Acevedo Guzmán y Fanny Magaña Nieto. - Conservación de cestería en espiral proveniente de la Cueva de la Candelaria, Torreón, Coahuila: criterios, tratamientos y líneas de investigación por Gloria Martha Sánchez Valenzuela, Miriam Elizabeth Castro Rodríguez y Adriana Reyes García. - Evaluación de recubrimientos de protección para metales. Caso de estudio: Imagen de México, relieve escultórico del Museo Nacional de Antropología. Primera etapa por Aline Moreno Núñez, Arturo A. Egea Salas, Gilda E. Salgado Manzanares, Mauricio B. Jiménez Ramírez, Armando Arciniega Corona y Nora A. Pérez Castellanos. - Patrimonio arqueológico digital. Uso de las tecnologías de la información y la comunicación para la divulgación del patrimonio arqueológico por Eduardo Andrés Escalante Carrillo y Luis Antonio Huitrón Santoyo. - El laboratorio de documentación y análisis tridimensional de la CNCPC. Resultados a un año de operación María Fernanda López-Armenta, Gilberto García Quintana y Celedonio Rodríguez Vidal. - La conservación-restauración de los bienes culturales en el Museo Regional de Querétaro: retos y perspectivas por María del Rosario Bravo Aguilar Conocer y reconocer a los actores sociales en la conservación de los bienes patrimoniales por Mitzi Vania García Toribio y Fanny Magaña Nieto. - Foro Anual de Trabajo. Una historia sin historia en el archivo de la CNCPC por Débora Y. Ontiveros Ramírez. - Expediente de incidentes en el tiempo. El Ehécatl-Quetzalcóatl de Coyoacán y cómo su caso puede ser usado para difundir la conservación en museos por Roberto Velasco Alonso. - Conservación en la vida cotidiana por María Bertha Peña Tenorio. - La Mediateca del INAH por Thalía E. Velasco Castelán. - Finaliza CNCPC la recuperación de sillares simulados originales en la bóveda del templo franciscano de Huaquechula, Puebla por Oscar Adrián Gutiérrez Vargas. - San Francisco de Asís en Huejotzingo, Puebla María Eugenia Rivera Pérez. - Investiga INAH factores de deterioro en la pirámide de la Serpiente Emplumada por Oscar Adrián Gutiérrez Vargas. - Lo que querías saber y no te atrevías a preguntar sobre el INAH en El Ocote por Oscar Adrián Gutiérrez Vargas. - Para saber más de El Caballito por Oscar Adrián Gutiérrez Vargas