Case report: Efficacy of immunotherapy as conversion therapy in dMMR/MSI-H colorectal cancer: a case series and review of the literature.

Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.

Effects of 700 and 3500 MHz 5G radiofrequency exposure on developing zebrafish embryos.

Telecommunications industries are rapidly deploying the fifth generation (5G) spectrum and there is public concern about the safety and health impacts of this type of Radio Frequency Radiation (RFR), in part because of the lack of comparable scientific evidence. In this study we have used a validated commercially available setting producing a uniform field to expose zebrafish embryos (ZFe) to unmodulated 700 and 3500 MHz frequencies. We have combined a battery of toxicity, developmental and behavioral assays to further explore potential RFR effects. Our neurobehavioral profiles include a tail coiling assay, a light/dark activity assay, two thigmotaxis anxiety assays (auditory and visual stimuli), and a startle response - habituation assay in response to auditory stimuli. ZFe were exposed for 1 and 4 h during the blastula period of development and endpoints evaluated up to 120 hours post fertilization (hpf). Our results show no effects on mortality, hatching or body length. However, we have demonstrated specific organ morphological effects, and behavioral effects in activity, anxiety-like behavior, and habituation that lasted in larvae exposed during the early embryonic period. A decrease in acetylcholinesterase activity was also observed and could explain some of the observed behavioral alterations. Interestingly, effects were more pronounced in ZFe exposed to the 700 MHz frequency, and especially for the 4 h exposure period. In addition, we have demonstrated that our exposure setup is robust, flexible with regard to frequency and power testing, and highly comparable. Future work will include exposure of ZFe to 5G modulated signals for different time periods to better understand the potential health effects of novel 5G RFR.

The relationship between discrimination, alcohol use severity, and PTSD symptoms among Latinx heavy drinkers.

INTRODUCTION: Discrimination is linked to alcohol use severity among Latinx adults, who also show high prevalence rates of PTSD compared to non-Latinx adults. We know little about whether PTSD symptoms affects the relationship between discrimination and alcohol use severity. We hypothesized that the association between discrimination and alcohol use severity might differ by level of PTSD symptom severity. METHODS: This is a secondary cross-sectional analysis of data collected at baseline from a completed randomized clinical trial testing the relative efficacy of a culturally adapted motivational interview designed to address discrimination and drinking behavior against an unadapted motivational interview for Latinx adults. Eligible participants screened positive for the NIAAA Single Alcohol Screening Question for heavy drinking days, identified as Latinx, and were 18-65 years old. We assessed the Everyday Discrimination Scale, Primary Care PC-PTSD screener, Alcohol Use Disorder Identification Test, and the Short Acculturation Scale for Hispanics. The study analyzed the main and interactive effects of discrimination and PTSD symptoms on alcohol use severity, while controlling for age, sex, household income, and acculturation. RESULTS: After controlling for covariates in model 2, the interaction of discrimination and PTSD symptoms was significantly related to alcohol use severity. Simple slopes analysis indicated that discrimination was positively related to alcohol use severity among those with high (1 SD above the mean) but not low (1 SD below the mean) levels of PTSD symptoms. CONCLUSIONS: Evidence suggests that the experiences of discrimination were associated with alcohol use severity among those who reported more PTSD symptoms. Specifically, discrimination may have a stronger effect on alcohol use severity among Latinx adults who report more PTSD symptoms. Screening Latinx adults for heavy drinking days, discrimination, and PTSD symptoms is clinically important. Culturally adapted alcohol interventions that target discrimination may be particularly effective for Latinx individuals with more PTSD symptoms.

Cannabis as a shareable commodity in a social discounting task.

Cannabis use and cannabis use disorder diagnoses continue to increase in United States college-aged students as more states legalize recreational cannabis. Previous studies have attempted to associate cannabis use with delay discount rates, which involves participants making choices for smaller sooner versus larger later hypothetical rewards. More smaller sooner choices result in higher discount rates and suggest increased impulsivity. Delay discounting studies have shown a significant, but small effect size with people who use cannabis more likely to choose the smaller sooner rewards, relative to people who do not use cannabis. The present study tested whether students with different experience using cannabis (people who currently use cannabis, people who formerly used cannabis, or people who never used cannabis) would be sensitive to sharing a proportion of hypothetical marijuana with another individual at a given social distance, as a putative measure for cannabis value. Results from two separate data sets showed that students classified as current cannabis users were significantly less likely to share a proportion of hypothetical marijuana across a range of social distances, relative to students that self-reported never using cannabis. Students classified as either former or current users were not statistically different. These results were consistent with previous delay discounting results and showed a medium effect size (η² ≥ 0.10) for each data set, both separately and when combined. These results indicate that social distance is a meaningful variable that can be used in a modified discounting task to assess differential cannabis value in a student population who are increasingly susceptible to cannabis use disorder. These results may have future clinical implications. Social discount rates for cannabis may be able to differentiate individuals who will continue recreational use versus individuals that may develop cannabis dependence problems. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1.

Histone H2A lysine 119 (H2AK119Ub) is monoubiquitinated by Polycomb repressive complex 1 and deubiquitinated by Polycomb repressive deubiquitinase complex (PR-DUB). PR-DUB cleaves H2AK119Ub to restrict focal H2AK119Ub at Polycomb target sites and to protect active genes from aberrant silencing. The PR-DUB subunits (BAP1 and ASXL1) are among the most frequently mutated epigenetic factors in human cancers. How PR-DUB establishes specificity for H2AK119Ub over other nucleosomal ubiquitination sites and how disease-associated mutations of the enzyme affect activity are unclear. Here, we determine a cryo-EM structure of human BAP1 and the ASXL1 DEUBAD in complex with a H2AK119Ub nucleosome. Our structural, biochemical, and cellular data reveal the molecular interactions of BAP1 and ASXL1 with histones and DNA that are critical for restructuring the nucleosome and thus establishing specificity for H2AK119Ub. These results further provide a molecular explanation for how >50 mutations in BAP1 and ASXL1 found in cancer can dysregulate H2AK119Ub deubiquitination, providing insight into understanding cancer etiology.

Characterization of Polylepis tarapacana Life Forms in the Highest-Elevation Altiplano in South America: Influence of the Topography, Climate and Human Uses.

In the upper vegetation limit of the Andes, trees change to shrub forms or other life forms, such as low scrubs. The diversity of life forms decreases with elevation; tree life forms generally decrease, and communities of shrubs and herbs increase in the Andean highlands. Most of treeline populations in the northwestern Argentina Altiplano are monospecific stands of Polylepis tarapacana, a cold-tolerant evergreen species that is able to withstand harsh climatic conditions under different life forms. There are no studies for P. tarapacana that analyze life forms across environmental and human impact gradients relating them with environmental factors. This study aims to determine the influence of topographic, climatic, geographic and proxies to human uses on the occurrence of life forms in P. tarapacana trees. We worked with 70 plots, and a new proposal of tree life form classification was presented for P. tarapacana (arborescent, dwarf trees, shrubs and brousse tigrée). We describe the forest biometry of each life form and evaluate the frequency of these life forms in relation to the environmental factors and human uses. The results show a consistency in the changes in the different life forms across the studied environmental gradients, where the main changes were related to elevation, slope and temperature.

Impact of nutritional and educational support on home enteral nutrition.

BACKGROUND: Home Enteral Nutrition (HEN) is used to prevent or correct malnutrition in outpatients. Due to the complexity of this process, the indication, follow-up, and results of an educational program of HEN patients was evaluated. METHODS: A prospective, observational, real-life, multicenter study was performed in 21 Spanish Hospital. Patients receiving HEN by nasogastric tube or ostomy were included. The following variables were collected: age, gender, HEN indication, type of formula, nutritional requirements, laboratory variables, complications, and quality standards of the educational program. To calculate the energy and protein requirements, the FAO/WHO/UNU formula was used considering the adjusted weight of the patients. All data were analyzed using SPSS.24. RESULTS: 414 patients were included. Most conditions diagnosed were neurodegenerative diseases (64.8%). 100 (25.3%) were diabetic. The mean weight was 59.3 ± 10.4 kg and BMI 22.6 ± 3.2. Moderate protein-calorie malnutrition was predominant at baseline (46.4%). Improvement in nutritional status at six months was recorded in more than 75% of patients (p < 0.05). Tolerance problems, diarrhea and abdominal distension fell between the 3- and 6-month visits (p < 0.05). Patients who received intermittent EN had fewer tolerance-related effects (OR 0.042; 95% CI 0.006-0.279) and less diarrhoea (OR 0.042; 95% CI 0.006-0.279). At the baseline and 6-month visits, compliance with the educational measures proposed by the prescriber was ≥ 99%. CONCLUSION: The nutritional assessment to prescribe individualized HEN to each patient, together with educational measures and training in the proper use of this treatment for both patients and trainers, improves nutritional status and reduces the onset of adverse events.

Structural basis of histone H2A lysine 119 deubiquitination by Polycomb Repressive Deubiquitinase BAP1/ASXL1.

The maintenance of gene expression patterns during metazoan development is achieved by the actions of Polycomb group (PcG) complexes. An essential modification marking silenced genes is monoubiquitination of histone H2A lysine 119 (H2AK119Ub) deposited by the E3 ubiquitin ligase activity of the non-canonical Polycomb Repressive Complex 1. The Polycomb Repressive Deubiquitinase (PR-DUB) complex cleaves monoubiquitin from histone H2A lysine 119 (H2AK119Ub) to restrict focal H2AK119Ub at Polycomb target sites and to protect active genes from aberrant silencing. BAP1 and ASXL1, subunits that form active PR-DUB, are among the most frequently mutated epigenetic factors in human cancers, underscoring their biological importance. How PR-DUB achieves specificity for H2AK119Ub to regulate Polycomb silencing is unknown, and the mechanisms of most of the mutations in BAP1 and ASXL1 found in cancer have not been established. Here we determine a cryo-EM structure of human BAP1 bound to the ASXL1 DEUBAD domain in complex with a H2AK119Ub nucleosome. Our structural, biochemical, and cellular data reveal the molecular interactions of BAP1 and ASXL1 with histones and DNA that are critical for remodeling the nucleosome and thus establishing specificity for H2AK119Ub. These results further provide a molecular explanation for how >50 mutations in BAP1 and ASXL1 found in cancer can dysregulate H2AK119Ub deubiquitination, providing new insight into understanding cancer etiology. One Sentence Summary: We reveal the molecular mechanism of nucleosomal H2AK119Ub deubiquitination by human BAP1/ASXL1.

Gamma passing rates of daily EPID transit images correlate to PTV coverage for breast cancer IMRT treatment plans.

PURPOSE: The use of the transit image obtained with the electronic portal-imaging device (EPID) is becoming an extended method to perform in-vivo dosimetry. The transit images acquired during each fraction can be compared with a predicted image, if available, or with a baseline image, usually the obtained in the first fraction. This work aims to study the dosimetric impact of the failing fractions and to evaluate the appropriateness of using a baseline image in breast plans. MATERIAL AND METHODS: Twenty breast patients treated in a Halcyon were retrospectively selected. For each patient and fraction, the treatment plan was calculated over the daily CBCT image. For each fraction, the differences respect to the treatment plan values of OARs and PTV dosimetric parameters were analyzed: ΔDmean , ΔD95%, ΔD98%, ΔD2%, ΔV36Gy, ΔV38.5Gy, and ΔV43.5Gy. Daily fractions were ranked according to the differences found in the dosimetric parameters between the treatment plan and the daily CBCT to establish the best fraction. The daily transit images acquired in every fraction were compared to the first fraction using the global gamma index with the Portal Dosimetry tool. The comparison was repeated using the best fraction image as a baseline. We assessed the correlation of the dosimetric differences obtained from the CBCT images-based treatment plans with the gamma index passing rates obtained using first fraction and best fraction as baseline. RESULTS: Average values of -11.6% [-21.4%, -3.3%] and -3.2% [-1.0%, -10.3%] for the ∆PTVD98% and ∆PTVD95% per every 10% decrease in the passing rate were found, respectively. When using the best fraction as baseline patients were detected with failing fractions that were not detected with the first fraction as baseline. CONCLUSION: The gamma passing rates of daily transit images correlate with the coverage loss parameters in breast IMRT plans. Using first fraction image as baseline can lead to the non-detectability of failing fractions.

Farmers Experiencing Potato Seed Degeneration Respond but Do Not Adjust Their Seed Replacement Strategies in Ecuador.

In Ecuador, farmers poorly adopt practices to manage potato seed degeneration. This could be related to the deficient understanding of the farmers' capacity to experience seed degeneration and respond to it. We contribute to this understanding by answering: How do farmers experience seed degeneration?; What practices do farmers implement when their seed is degenerated?; and Is experiencing degeneration the pivotal factor determining how farmers replace their seed regardless their income? We analysed data collected in Ecuador through farmers' focus group discussions, farmers' surveys and interviews, and the Ecuadorian employment status survey. We found that approximately half of the farmers experienced degeneration. Farmers experienced it through low yields, change in seed appearance, crop weakening, and seed physiological problems. When farmers experienced degeneration, they replaced their seed, sought for technical advice, applied more agricultural inputs, or grew other crops. Income was an important trigger for farmers to change their seed replacement practices.

Age-dependent nasal immune responses in non-hospitalized bronchiolitis children.

Bronchiolitis in children is associated with significant rates of morbidity and mortality. Many studies have been performed using samples from hospitalized bronchiolitis patients, but little is known about the immunological responses from infants suffering from mild/moderate bronchiolitis that do not require hospitalization. We have studied a collection of nasal lavage fluid (NLF) samples from outpatient bronchiolitis children as a novel strategy to unravel local humoral and cellular responses, which are not fully characterized. The children were age-stratified in three groups, two of them (GI under 2-months, GII between 2-4 months) presenting a first episode of bronchiolitis, and GIII (between 4 months and 2 years) with recurrent respiratory infections. Here we show that elevated levels of pro-inflammatory cytokines (IL1ß, IL6, TNFα, IL18, IL23), regulatory cytokines (IL10, IL17A) and IFNγ were found in the three bronchiolitis cohorts. However, little or no change was observed for IL33 and MCP1, at difference to previous results from bronchiolitis hospitalized patients. Furthermore, our results show a tendency to IL1ß, IL6, IL18 and TNFα increased levels in children with mild pattern of symptom severity and in those in which non RSV respiratory virus were detected compared to RSV+ samples. By contrast, no such differences were found based on gender distribution. Bronchiolitis NLFs contained more IgM, IgG1, IgG3 IgG4 and IgA than NLF from their age-matched healthy controls. NLF from bronchiolitis children predominantly contained neutrophils, and also low frequency of monocytes and few CD4+ and CD8+ T cells. NLF from infants older than 4-months contained more intermediate monocytes and B cell subsets, including naïve and memory cells. BCR repertoire analysis of NLF samples showed a biased VH1 usage in IgM repertoires, with low levels of somatic hypermutation. Strikingly, algorithmic studies of the mutation profiles, denoted antigenic selection on IgA-NLF repertoires. Our results support the use of NLF samples to analyze immune responses and may have therapeutic implications.

Strategies to recover blood donors during the COVID-19 pandemic: a tertiary level hospital experience.

BACKGROUND: The SARS-CoV-2 pandemic has challenged blood banks. In Mexico, donors decreased 22% between April and May 2020 compared to the same months in 2019. This study analyzed the effect of the strategies to recover donors (altruistic and family) in a tertiary pediatric care center during the pandemic. METHODS: The Blood Bank of the Hospital Infantil de México Federico Gómez implemented strategies to obtain blood components to ensure self-sufficiency. The effect of these strategies on donor recovery was analyzed. RESULTS: There were 7,315 eligible donors in 2019 and 5,070 in 2020. Blood component requirements decreased from 10,037 units in 2019 to 8,619 in 2020. The strategies aimed at attracting altruistic donors managed to increase the percentage of this type of donor when comparing the months in which these strategies were applied with the same months in 2019. In addition, it was observed that the greater the number of methods used simultaneously, the higher the percentage of altruistic donors (rho = 0.846, p = 0.002). In contrast, strategies aimed at attracting family donors did not increase the number of this type of donor. CONCLUSIONS: Actions to recruit altruistic donors increased the number of this type of donor to meet the hospital's needs.

INTRODUCCIÓN: La pandemia por SARS-CoV-2 ha representado un reto en los bancos de sangre. En México, los donadores disminuyeron el 22% entre abril y mayo del 2020 en comparación con los mismos meses del 2019. Este estudio analizó el efecto de las estrategias realizadas para recuperar donantes, altruistas y familiares, en un centro de atención pediátrica de tercer nivel durante la pandemia. MÉTODOS: El Banco de Sangre del Hospital Infantil de México Federico Gómez implementó estrategias encaminadas a la obtención de componentes sanguíneos para asegurar la autosuficiencia. Se analizó el efecto de dichas estrategias en la recuperación de donantes. RESULTADOS: Se registraron 7,315 donadores aptos en el año 2019 y 5,070 en el 2020. Los requerimientos de componentes sanguíneos disminuyeron de 10,037 unidades en 2019 a 8,619 en 2020. Las estrategias que estaban destinadas a captar donadores altruistas lograron aumentar el porcentaje de este tipo de donadores al comparar los meses en que se aplicaron dichas estrategias con los mismos meses en el 2019. Además, se observó que, a mayor número de estrategias aplicadas de manera simultánea, mayor porcentaje de donadores altruistas (rho = 0.846, p = 0.002). Por el contrario, las estrategias con la finalidad de atraer donadores familiares no lograron aumentar la cantidad de este tipo de donadores. CONCLUSIONES: Las acciones para recabar donadores altruistas aumentaron la cantidad de este tipo de donadores para satisfacer las necesidades del hospital.

Strategies to recover blood donors during the COVID-19 pandemic: a tertiary level hospital experience / Estrategias para recuperar donantes de sangre durante la pandemia por COVID-19: experiencia de un hospital de tercer nivel

Abstract Background: The SARS-CoV-2 pandemic has challenged blood banks. In Mexico, donors decreased 22% between April and May 2020 compared to the same months in 2019. This study analyzed the effect of the strategies to recover donors (altruistic and family) in a tertiary pediatric care center during the pandemic. Methods: The Blood Bank of the Hospital Infantil de México Federico Gómez implemented strategies to obtain blood components to ensure self-sufficiency. The effect of these strategies on donor recovery was analyzed. Results: There were 7,315 eligible donors in 2019 and 5,070 in 2020. Blood component requirements decreased from 10,037 units in 2019 to 8,619 in 2020. The strategies aimed at attracting altruistic donors managed to increase the percentage of this type of donor when comparing the months in which these strategies were applied with the same months in 2019. In addition, it was observed that the greater the number of methods used simultaneously, the higher the percentage of altruistic donors (rho = 0.846, p = 0.002). In contrast, strategies aimed at attracting family donors did not increase the number of this type of donor. Conclusions: Actions to recruit altruistic donors increased the number of this type of donor to meet the hospital's needs.

Resumen Introducción: La pandemia por SARS-CoV-2 ha representado un reto en los bancos de sangre. En México, los donadores disminuyeron el 22% entre abril y mayo del 2020 en comparación con los mismos meses del 2019. Este estudio analizó el efecto de las estrategias realizadas para recuperar donantes, altruistas y familiares, en un centro de atención pediátrica de tercer nivel durante la pandemia. Métodos: El Banco de Sangre del Hospital Infantil de México Federico Gómez implementó estrategias encaminadas a la obtención de componentes sanguíneos para asegurar la autosuficiencia. Se analizó el efecto de dichas estrategias en la recuperación de donantes. Resultados: Se registraron 7,315 donadores aptos en el año 2019 y 5,070 en el 2020. Los requerimientos de componentes sanguíneos disminuyeron de 10,037 unidades en 2019 a 8,619 en 2020. Las estrategias que estaban destinadas a captar donadores altruistas lograron aumentar el porcentaje de este tipo de donadores al comparar los meses en que se aplicaron dichas estrategias con los mismos meses en el 2019. Además, se observó que, a mayor número de estrategias aplicadas de manera simultánea, mayor porcentaje de donadores altruistas (rho = 0.846, p = 0.002). Por el contrario, las estrategias con la finalidad de atraer donadores familiares no lograron aumentar la cantidad de este tipo de donadores. Conclusiones: Las acciones para recabar donadores altruistas aumentaron la cantidad de este tipo de donadores para satisfacer las necesidades del hospital.

Differential relationships between discount rates and health behaviors in an ethnically diverse college sample.

Previous research has demonstrated associations between delay discount rate and engagement in several health behaviors. The delay discount rate is also inversely associated with social discount rates, a putative measure for sharing. However, there is little research that examines whether delay and social discount rates are differentially associated with health behavior engagement, and even less research examining the impact of ethnicity on these relationships. This study investigated whether delay and/or social discount rates predict three health behaviors varying in sociality: sexually transmitted infection (STI) testing, alcohol consumption and exercise frequency in an ethnically diverse university sample. The results showed that neither delay nor social discount rate significantly predicted alcohol consumption and exercise frequency. However, increasing social discount rates (i.e., decreased sharing) was associated with a decreased likelihood to be tested for STIs. Ethnicity significantly contributed to two models, indicating differences in STI testing and alcohol consumption across ethnicities. Ethnic differences in these health behaviors were consistent with many previous health behavior studies, suggesting a profitable way to research cultural contingencies and test the reliability of the ethnically diverse data. These findings indicate that the social discount rate is differentially associated with health behaviors with more social aspects (i.e., health behaviors related to sex) in college students.

Medication errors in a children's inpatient antineoplastic chemotherapy facility.

BACKGROUND: Due to many antineoplastic drugs' toxicity and narrow therapeutic window, medication errors are a health concern in pediatric oncology patients. This study aimed to identify and classify medication errors in a pediatric inpatient chemotherapy facility and evaluate the outcomes of these medication errors. METHODS: We conducted an observational retrospective study over 5 months in a chemotherapy facility for pediatric patients. The evaluation consisted of the review of the available medical records. The medication errors detected were manually recorded in a medical logbook. The International Classification for Patient Safety was adjusted to our clinical setting for the analysis, the terminology, and the classification system. A descriptive analysis was performed. RESULTS: A total of 286 medical records were reviewed; one type of medication error was noted in at least 97.6%, and 962 errors were identified totally, with an overall rate of 3.36 errors per visit. Most errors occurred in the documentation stage (643; 66.8%), followed by the administration stage (227; 23.6%). Of all medication errors, 37.2% had the potential to cause injury, but only five reached the patient (0.5%), and only two (0.2%) resulted in a severe harmful incident. CONCLUSIONS: Medication errors were common, especially at the documentation stage. Better documentation strategies need to be implemented to reduce the rate of near misses and prevent potential adverse events.

INTRODUCCIÓN: Los errores de medicación son un problema de salud en niños con cáncer debido a la toxicidad y a la estrecha ventana terapéutica de muchos fármacos antineoplásicos. El objetivo de este estudio fue identificar y clasificar los errores de medicación en un centro de quimioterapia para pacientes pediátricos hospitalizados, así como evaluar los resultados de estos errores de medicación. MÉTODOS: Se llevó a cabo un estudio observacional retrospectivo realizado durante un periodo de 5 meses en un centro de quimioterapia para pacientes pediátricos. La evaluación consistió en la revisión de las historias clínicas disponibles. Los errores de medicación detectados fueron registrados manualmente en una bitácora. Para el análisis, la terminología y el sistema de clasificación, la Clasificación Internacional para la Seguridad del Paciente se ajustó a nuestro entorno clínico. Se realizó un análisis descriptivo. RESULTADOS: Se revisaron 286 historias clínicas; se observó un tipo de error de medicación al menos en el 97.6%. En total se identificaron 962 errores de medicación, con una tasa general de 3.36 errores por visita. En la etapa de documentación fue donde más errores ocurrieron (643; 66.8%), seguido de la etapa de administración (227; 23.6%). De todos los errores de medicación, el 37.2% tuvo el potencial de causar lesiones, pero solo cinco llegaron al paciente (0.5%) y solo dos (0.2%) provocaron un incidente dañino severo. CONCLUSIONES: Los errores de medicación fueron comunes, especialmente en la etapa de documentación. Es necesario implementar mejores estrategias de documentación para reducir la tasa de cuasi accidentes y prevenir posibles eventos adversos.

Medication errors in a children's inpatient antineoplastic chemotherapy facility / Errores de medicación en un centro de quimioterapia antineoplásica para pacientes pediátricos hospitalizados

Abstract Background: Due to many antineoplastic drugs' toxicity and narrow therapeutic window, medication errors are a health concern in pediatric oncology patients. This study aimed to identify and classify medication errors in a pediatric inpatient chemotherapy facility and evaluate the outcomes of these medication errors. Methods: We conducted an observational retrospective study over 5 months in a chemotherapy facility for pediatric patients. The evaluation consisted of the review of the available medical records. The medication errors detected were manually recorded in a medical logbook. The International Classification for Patient Safety was adjusted to our clinical setting for the analysis, the terminology, and the classification system. A descriptive analysis was performed. Results: A total of 286 medical records were reviewed; one type of medication error was noted in at least 97.6%, and 962 errors were identified totally, with an overall rate of 3.36 errors per visit. Most errors occurred in the documentation stage (643; 66.8%), followed by the administration stage (227; 23.6%). Of all medication errors, 37.2% had the potential to cause injury, but only five reached the patient (0.5%), and only two (0.2%) resulted in a severe harmful incident. Conclusions: Medication errors were common, especially at the documentation stage. Better documentation strategies need to be implemented to reduce the rate of near misses and prevent potential adverse events.

Resumen Introducción: Los errores de medicación son un problema de salud en niños con cáncer debido a la toxicidad y a la estrecha ventana terapéutica de muchos fármacos antineoplásicos. El objetivo de este estudio fue identificar y clasificar los errores de medicación en un centro de quimioterapia para pacientes pediátricos hospitalizados, así como evaluar los resultados de estos errores de medicación. Métodos: Se llevó a cabo un estudio observacional retrospectivo realizado durante un periodo de 5 meses en un centro de quimioterapia para pacientes pediátricos. La evaluación consistió en la revisión de las historias clínicas disponibles. Los errores de medicación detectados fueron registrados manualmente en una bitácora. Para el análisis, la terminología y el sistema de clasificación, la Clasificación Internacional para la Seguridad del Paciente se ajustó a nuestro entorno clínico. Se realizó un análisis descriptivo. Resultados: Se revisaron 286 historias clínicas; se observó un tipo de error de medicación al menos en el 97.6%. En total se identificaron 962 errores de medicación, con una tasa general de 3.36 errores por visita. En la etapa de documentación fue donde más errores ocurrieron (643; 66.8%), seguido de la etapa de administración (227; 23.6%). De todos los errores de medicación, el 37.2% tuvo el potencial de causar lesiones, pero solo cinco llegaron al paciente (0.5%) y solo dos (0.2%) provocaron un incidente dañino severo. Conclusiones: Los errores de medicación fueron comunes, especialmente en la etapa de documentación. Es necesario implementar mejores estrategias de documentación para reducir la tasa de cuasi accidentes y prevenir posibles eventos adversos.

The Effectiveness of Common Cannabis Products for Treatment of Nausea.

GOALS: We measure for the first time how a wide range of cannabis products affect nausea intensity in actual time. BACKGROUND: Even though the Cannabis plant has been used to treat nausea for millennia, few studies have measured real-time effects of common and commercially available cannabis-based products. STUDY: Using the Releaf App, 886 people completed 2220 cannabis self-administration sessions intended to treat nausea between June 6, 2016 and July 8, 2019. They recorded the characteristics of self-administered cannabis products and baseline symptom intensity levels before tracking real-time changes in the intensity of their nausea. RESULTS: By 1 hour postconsumption, 96.4% of people had experienced symptom relief with an average symptom intensity reduction of -3.85 points on a 0 to 10 visual analog scale (SD=2.45, d=1.85, P<0.001). Symptom relief was statistically significant at 5 minutes and increased with time. Among product characteristics, flower and concentrates yielded the strongest, yet similar results; products labeled as Cannabis indica underperformed those labeled as Cannabis sativa or hybrid; and joints were associated with greater symptom relief than pipes or vaporizers. In sessions using flower, higher tetrahydrocannbinol and lower cannabidiol were generally associated with greater symptom relief (eg, within 5 min). CONCLUSIONS: The findings suggest that the vast majority of patients self-selecting into cannabis use for treatment of nausea likely experience relief within a relative short duration of time, but the level of antiemetic effect varies with the characteristics of the cannabis products consumed in vivo. Future research should focus on longer term symptom relief, including nausea-free intervals and dosing frequency; the risks of consumption of medical cannabis, especially among high-risk populations, such as pregnant women and children; and potential interactions between cannabis, conventional antiemetics, other medications, food, tobacco, alcohol, and street drugs among specific patient populations.

Intrathymic SIRPa cDC subsets organization in normal and stress conditions reveal another level of cDCs heterogeneity.

Three major subsets constitute the dendritic cells (DCs) pool in the thymus. They play key roles in self-antigen-specific thymocyte deletion and in the development of immunoregulatory T cells. Resident SIRPa- conventional DCs (cDCs, CD11c+ PDCA1lo ) are derived from intrathymic progenitors, whereas migratory SIRPa+ cDCs and plasmacytoid DCs (pDCs, CD11c+ PDCA1+ ) originate from extrathymic sites. Here, we describe the organization and the shaping of cDC populations at the steady state and under stress conditions in wild-type and mutant mice (CD3eKO, IL7RaKO, and Flt3LKO). In neonates, the thymus is mainly composed of SIRPa- -resident cDCs, whereas both cDC subsets are present in equal proportions in the adult. Upon thymus colonization, migratory SIRPa+ cDCs gain expression of phenotypic markers in a microenvironment dependent way. Here, we show that both processes are deeply impacted by mutations affecting T cell development. Under stress conditions such as sublethal irradiation, intrathymic resident SIRPa- cDCs are the first to regenerate the thymic cDC pool. Upon bone marrow transplantation, migratory SIRPa+ cDCs become the main source of thymic cDCs. These successive waves of regeneration eventually lead to a balance between resident and migratory DCs within the newly colonized thymus. These findings highlight an unrevealed division of labor between resident and migratory subsets for the organization/establishment of the thymic cDC compartment.

Structural variation analysis of 6,500 whole genome sequences in amyotrophic lateral sclerosis.

There is a strong genetic contribution to Amyotrophic lateral sclerosis (ALS) risk, with heritability estimates of up to 60%. Both Mendelian and small effect variants have been identified, but in common with other conditions, such variants only explain a little of the heritability. Genomic structural variation might account for some of this otherwise unexplained heritability. We therefore investigated association between structural variation in a set of 25 ALS genes, and ALS risk and phenotype. As expected, the repeat expansion in the C9orf72 gene was identified as associated with ALS. Two other ALS-associated structural variants were identified: inversion in the VCP gene and insertion in the ERBB4 gene. All three variants were associated both with increased risk of ALS and specific phenotypic patterns of disease expression. More than 70% of people with respiratory onset ALS harboured ERBB4 insertion compared with 25% of the general population, suggesting respiratory onset ALS may be a distinct genetic subtype.