Life Extension Should Come with Wisdom: Reflections and Questions for the Geroscience and Longevity Community.

Geroscience, or longevity biotechnology, has made impressive advances in recent years that have led to the founding of dozens of start-ups, nonprofits and advocacy organizations, and the formation of a global movement to defeat aging. The community envisions changes at the regulatory and policy levels and calls for increased funding for research. Nevertheless, progress in the field has not been matched by discussions about ethical, legal, and social implications, as longevity advocates assume that seeking to expand lifespan or health span is inherently desirable and permissible. In this article, I make the case for the importance of putting ethics and society back into geroscience, along with three considerations for the longevity community. First, it should seek to understand the needs and attitudes of the public. Second, the community needs to define whether the field is primarily striving for healthy aging (increasing health span) or for extending years of life (lifespan). Third, it needs to define the role of investors and tech millionaires in shaping the field's priorities and direction. This last point raises the question of who is setting the direction of a field that can reshape the meaning of being human.

Comprehensive Two-Dimensional Gas Chromatography with Peak Tracking for Screening of Constituent Biodegradation in Petroleum UVCB Substances.

Petroleum substances, as archetypical UVCBs (substances of unknown or variable composition, complex reaction products, or biological substances), pose a challenge for chemical risk assessment as they contain hundreds to thousands of individual constituents. It is particularly challenging to determine the biodegradability of petroleum substances since each constituent behaves differently. Testing the whole substance provides an average biodegradation, but it would be effectively impossible to obtain all constituents and test them individually. To overcome this challenge, comprehensive two-dimensional gas chromatography (GC × GC) in combination with advanced data-handling algorithms was applied to track and calculate degradation half-times (DT50s) of individual constituents in two dispersed middle distillate gas oils in seawater. By tracking >1000 peaks (representing ∼53-54% of the total mass across the entire chromatographic area), known biodegradation patterns of oil constituents were confirmed and extended to include many hundreds not currently investigated by traditional one-dimensional GC methods. Approximately 95% of the total tracked peak mass biodegraded after 64 days. By tracking the microbial community evolution, a correlation between the presence of functional microbial communities and the observed progression of DT50s between chemical classes was demonstrated. This approach could be used to screen the persistence of GC × GC-amenable constituents of petroleum substance UVCBs.

Modeling the GCxGC Elution Patterns of a Hydrocarbon Structure Library To Innovate Environmental Risk Assessments of Petroleum Substances.

Comprehensive two-dimensional gas chromatography (GCxGC) offers unrivaled separation of petroleum substances, which can contain thousands of constituents or more. However, interpreting substance compositions from GCxGC data is costly and requires expertise. To facilitate environmental risk assessments, industries provide aggregated compositional information known as "hydrocarbon blocks" (HCBs), but these proprietary methods do not transparently associate the HCBs with GCxGC chromatogram data. These obstacles frustrate efforts to study the environmental risks of petroleum substances and associated environmental samples. To address this problem, we developed a GCxGC elution model for user-defined petroleum substance compositions. We calibrated the elution model to experimental GCxGC retention times of 56 known hydrocarbons by fitting three tunable model parameters to two candidate instrument methods. With the calibrated model, we simulated retention times for a library of 15,447-15,455 hydrocarbon structures (plus 40-48 predicted as chromatographically unretained) spanning 11 classes of petroleum substance constituents in the C10-C30 range. The resulting simulation data reveal that GCxGC retention times are quantitatively associated with hydrocarbon class and carbon number information throughout the GCxGC chromatogram. These innovations enable the development of transparent and efficient technical methods to investigate the chemical compositions and environmental properties of petroleum substances, including in environmental and lab-weathered samples.

Policy landscapes on human genome editing: a perspective from Latin America.

Policy landscapes are instruments that identify national regulations on human genome editing (HGE). After examining their ethical and political assumptions, we highlight their limitations and effects for Latin America. We suggest creating other landscapes, such as focusing on processes and drawing attention to potential 'circuits of use' within and across borders.

Análisis descriptivo de pacientes que requirieron manejo avanzado de vía aérea en emergencias prehospitalarias: complicaciones y factores asociados al fracaso en el primer intento de intubación / Advanced airway management: a descriptive analysis of complications and factors associated with first-attempt intubation failure in prehospital emergency care

Objetivos: Analizar las características del manejo de la vía aérea (VA) en emergencias prehospitalarias, sus complicaciones y establecer factores predictores de fracaso en el primer intento de intubación orotraqueal (FIPI). Método: Estudio observacional de cohortes retrospectivo de pacientes que precisaron intubación orotraqueal por el servicio de emergencias prehospitalarias de Castilla La Mancha, desde el 01-06-2017 hasta el 01-01-2021. Se analizaron características de los pacientes, del procedimiento y sus complicaciones, se realizó una regresión logística para detectar factores predictores de FIPI. Resultados: Se incluyeron 425 pacientes, 417 (98,1%) fueron intubados con éxito y 326 (76,7%) en el primer intento. Se registraron 183 complicaciones en 94 pacientes (22,1%). Los factores predictores de FIPI fueron la edad > 55 años (OR = 1,94; IC 95% 1,10-4,23), índice de masa corporal > 30 (OR = 9,14; IC 95% 4,40-19,00); saturación de oxígeno < 90% (OR = 3,33; IC 95% 1,06-10,58); puntuación en la Glasgow Coma Scale entre 9 y 13 (OR = 1,58; IC 95% 1,28-6,9); intubación realizada en vía pública (OR = 2,99; IC 95% 1,42-6,29); posición distinta a la bipedestación (OR = 2,09; IC 95% 1,08-7,25); laringoscopia directa (OR = 2,39; IC 95% 1,20-6,55); uso de estilete (OR = 1,80; IC 95% 1,40-3,78); y clasificación Cormack-Lehane $ 2 (OR = 6,50; IC 95% 3,96-30,68). Conclusiones: El procedimiento de intubación se realizó de forma habitual en el primer intento. Existen factores asociados a FIPI que permiten individualizar el manejo de la VA. (AU)

Objectives: To analyze the characteristics of prehospital emergency airway management, including complications; to explore predictors of first-attempt failure of orotracheal intubation. Material and methods: Observational retrospective cohort study of patients requiring orotracheal intubation by the prehospital emergency services of Castile-La Mancha between June 1, 2017, and January 1, 2021. We analyzed patient and procedure characteristics and complications using logistic regression analysis to detect factors that could predict firstattempt intubation failure. Results: A total of 425 patients were included; 417 (98.1%) were intubated successfully, including 326 (76.7%) on the first attempt. Complications occurred in 183 intubations in 94 patients (22.1%). Predictors of first-attempt failure were age over 55 years (odds ratio [OR], 1.94; 95% CI, 1.10-4.23), body mass index over 30 (OR, 9.14; 95% CI, 4.40-19.00), oxygen saturation less than 90% (OR, 3.33; 95% CI, 1.06-10.58), a Glasgow Coma Score between 9 and 13 (OR, 1.58; 95% CI, 1.28-6.9), intubation in a public place (OR, 2.99; 95% CI, 1.42-6.29), intubation done in any other than standing position (OR, 2.09; 95% CI, 1.08-7.25), direct laryngoscopy (OR, 2.39; 95% CI, 1.20- 6.55), use of a stylet (OR, 1.80; 95% CI, 1.40-3.78), and a Cormack-Lehane classification of 2 or higher (OR, 6.50; 95% CI, 3.96-30.68). Conclusion: Orotracheal intubation is generally accomplished on the first attempt. Factors associated with first-attempt failure can facilitate tailored approaches to upper airway management. (AU)

Advanced airway management: a descriptive analysis of complications and factors associated with first-attempt intubation failure in prehospital emergency care. / Análisis descriptivo de pacientes que requirieron manejo avanzado de vía aérea en emergencias prehospitalarias: complicaciones y factores asociados al fracaso en el primer intento de intubación.

OBJECTIVES: To analyze the characteristics of prehospital emergency airway management, including complications; to explore predictors of first-attempt failure of orotracheal intubation. MATERIAL AND METHODS: Observational retrospective cohort study of patients requiring orotracheal intubation by the prehospital emergency services of Castile-La Mancha between June 1, 2017, and January 1, 2021. We analyzed patient and procedure characteristics and complications using logistic regression analysis to detect factors that could predict firstattempt intubation failure. RESULTS: A total of 425 patients were included; 417 (98.1%) were intubated successfully, including 326 (76.7%) on the first attempt. Complications occurred in 183 intubations in 94 patients (22.1%). Predictors of first-attempt failure were age over 55 years (odds ratio [OR], 1.94; 95% CI, 1.10-4.23), body mass index over 30 (OR, 9.14; 95% CI, 4.40-19.00), oxygen saturation less than 90% (OR, 3.33; 95% CI, 1.06-10.58), a Glasgow Coma Score between 9 and 13 (OR, 1.58; 95% CI, 1.28-6.9), intubation in a public place (OR, 2.99; 95% CI, 1.42-6.29), intubation done in any other than standing position (OR, 2.09; 95% CI, 1.08-7.25), direct laryngoscopy (OR, 2.39; 95% CI, 1.20- 6.55), use of a stylet (OR, 1.80; 95% CI, 1.40-3.78), and a Cormack-Lehane classification of 2 or higher (OR, 6.50; 95% CI, 3.96-30.68). CONCLUSION: Orotracheal intubation is generally accomplished on the first attempt. Factors associated with first-attempt failure can facilitate tailored approaches to upper airway management.

OBJETIVO: Analizar las características del manejo de la vía aérea (VA) en emergencias prehospitalarias, sus complicaciones y establecer factores predictores de fracaso en el primer intento de intubación orotraqueal (FIPI). METODO: Estudio observacional de cohortes retrospectivo de pacientes que precisaron intubación orotraqueal por el servicio de emergencias prehospitalarias de Castilla La Mancha, desde el 01-06-2017 hasta el 01-01-2021. Se analizaron características de los pacientes, del procedimiento y sus complicaciones, se realizó una regresión logística para detectar factores predictores de FIPI. RESULTADOS: . Se incluyeron 425 pacientes, 417 (98,1%) fueron intubados con éxito y 326 (76,7%) en el primer intento. Se registraron 183 complicaciones en 94 pacientes (22,1%). Los factores predictores de FIPI fueron la edad > 55 años (OR = 1,94; IC 95% 1,10-4,23), índice de masa corporal > 30 (OR = 9,14; IC 95% 4,40-19,00); saturación de oxígeno 90% (OR = 3,33; IC 95% 1,06-10,58); puntuación en la Glasgow Coma Scale entre 9 y 13 (OR = 1,58; IC 95% 1,28-6,9); intubación realizada en vía pública (OR = 2,99; IC 95% 1,42-6,29); posición distinta a la bipedestación (OR = 2,09; IC 95% 1,08-7,25); laringoscopia directa (OR = 2,39; IC 95% 1,20-6,55); uso de estilete (OR = 1,80; IC 95% 1,40-3,78); y clasificación Cormack-Lehane $ 2 (OR = 6,50; IC 95% 3,96-30,68). CONCLUSIONES: El procedimiento de intubación se realizó de forma habitual en el primer intento. Existen factores asociados a FIPI que permiten individualizar el manejo de la VA.

Application of the Target Lipid Model to Assess Toxicity of Heterocyclic Aromatic Compounds to Aquatic Organisms.

Heterocyclic aromatic compounds can be found in crude oil and coal and often co-exist in environmental samples with their homocyclic aromatic counterparts. The target lipid model (TLM) is a modeling framework that relates aquatic toxicity to the octanol-water partition coefficient (KOW ) that has been calibrated and validated for hydrocarbons. A systematic analysis of the applicability of the TLM to heterocyclic aromatic compounds has not been performed. The objective of the present study was to compile reliable toxicity data for heterocycles and determine whether observed toxicity could be successfully described by the TLM. Results indicated that the TLM could be applied to this compound class by adopting an empirically derived coefficient that accounts for partitioning between water and lipid. This coefficient was larger than previously reported for aromatic hydrocarbons, indicating that these heterocyclic compounds exhibit higher affinity to target lipid and toxicity. A mechanistic evaluation confirmed that the hydrogen bonding accepting moieties of the heteroatoms helped explain differences in partitioning behavior. Given the TLM chemical class coefficient reported in the present study, heterocyclic aromatics can now be explicitly incorporated in TLM-based risk assessments of petroleum substances, other products, or environmental media containing these compounds. Environ Toxicol Chem 2021;40:3000-3009. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Mobile Intensive Care Unit versus Hospital walk-in patients, in the treatment of first episode ST- elevation myocardial infarction.

OBJECTIVE: To determine the impact of the attention given by emergency medical services teams working in mobile intensive care units (MICU) versus patients arriving at the hospital under their own means with ST-elevation myocardial infarction (STEMI) event in terms of time to reperfusion (TR), mortality at 30 days and six months. METHODS: We retrospectively studied 634 consecutive patients with STEMI who underwent primary a percutaneous coronary intervention from January 1st 2015 to December 31st 2018 in a single centre. Depending on the first medical contact patients were classified into two groups, MICU versus walk-in patients. We extracted data on patients' characteristics, symptoms, treatments, times to reperfusion and mortality. RESULTS: In our study 634 patients were included, of whom 59.0% were initially attended by the MICU. Differences were seen between the two groups in time delays to the first medical contact (120.0 vs 63.0 min; p < 0.001) and TR (208.0 Vs 150.0 min; p < 0.001). Patients attended by the MICUs presented a shorter ICU and hospital stay. The lowest 30-day mortality rate was observed in MICU group: 9.0% in contrast with 4.5%, p = 0.03; remaining after 6 months. The multivariable analysis showed that the initial attention given by MICU to STEMI patients was a protective agent against mortality [OR: 0.32 (0.11-0.90); p = 0.03]. CONCLUSION: Initial attention of the patients with STEMI by doctor-on-board-MICU and available 24 h a day 7 days a week as part of a regional network (CORECAM), was associated with a decrease in the ischemia time, hospital stay and mortality of these patients in our environment.

Algo más que un simple SCASEST: patrón de De Winter / Something more than simple non-STsegment elevation acute coronary syndrome: the De Winter pattern

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Alternative acute oral toxicity assessment under REACH based on sub-acute toxicity values.

The REACH Regulation requires information on acute oral toxicity for substances produced or imported in quantities greater than one ton per year. When registering, animal testing should be used as last resort. The standard acute oral toxicity test requires use of animals. Therefore, the European Chemicals Agency examined whether alternative ways exist to generate information on acute oral toxicity. The starting hypothesis was that low acute oral toxicity can be predicted from the results of low toxicity in oral sub-acute toxicity studies. Proving this hypothesis would allow avoiding acute toxicity oral testing whenever a sub-acute oral toxicity study is required or available and indicates low toxicity. ECHA conducted an analysis of the REACH database and found suitable studies on both acute oral and sub-acute oral toxicities for 1,256 substances. 415 of these substances had low toxicity in the sub-acute toxicity study (i.e., NO(A)EL at or above the limit test threshold of 1,000 mg/kg). For 98% of these substances, low acute oral toxicity was also reported (i.e., LD50 above the classification threshold of 2,000 mg/kg). On the other hand, no correlation was found between lower NO(A)ELs and LD50. According to the REACH Regulation, this approach for predicting acute oral toxicity needs to be considered as part of a weight of evidence analysis. Therefore, additional sources of information to support this approach are presented. Ahead of the last REACH registration deadline, in 2018, ECHA estimates that registrants of about 550 substances can omit the in vivo acute oral toxicity study by using this adaptation.

Resultados en el tratamiento quirúrgico de los neurinomas del acústico gigantes / Results in the surgical treatment of giant acoustic neuromas

Introducción y objetivos: Comparar los resultados obtenidos en la resección de 21 schwanomas vestibulares gigantes, mediante vía retrosigmoidea y combinada retrosigmoidea/translaberíntica en cuanto a complicaciones intra y postoperatorias, preservación del nervio facial y secuelas posquirúrgicas. Métodos: Se realiza un estudio retrospectivo de 21 pacientes a los que se practicó resección de neurinoma vestibular gigante según la escala de Tos & Thomsen (igual o mayor a 4cm), en un hospital de tercer nivel en el periodo entre 2000 y 2008. Se presentan las características más significativas de la serie estudiada, y se analizan las ventajas e inconvenientes de los distintos abordajes, comparando los resultados obtenidos. Asimismo, se analizan los resultados en cuanto a la preservación de la función del nervio facial. Resultados: Destaca la ausencia de mortalidad en el grupo de 21 pacientes estudiado. No hubo complicaciones intraoperatorias importantes. Se consiguió la resección total de la lesión en el 87% de los casos, con una preservación anatómica del nervio facial del 73% en el abordaje combinado retrosigmoideo/translaberíntico, respecto a un 40% en el retrosigmoideo. La función del nervio facial a los dos años fue aceptable o buena en un 67% (incluyendo los resultados de las anastomosis heteronerviosas). Se observó un porcentaje global del 14,3% de fístula de líquido cefalorraquídeo y un 9,5% de meningitis. Conclusiones: nuestros resultados demuestran que el abordaje combinado retrosigmoideo translaberíntico para el tratamiento de schwannomas gigantes ofrece mayor preservación del nervio facial y disminución de la morbilidad, siendo una importante opción en el tratamiento de estos tumores, gracias a un enfoque multidisciplinar(AU)

Introduction and objectives: To compare the results obtained in the resection of 21 giant vestibular schwannomas via retrosigmoid (RS) and combined retrosigmoid/translabyrinthine (RS/TL) approaches with respect to intra- and postoperative complications, facial nerve preservation and postsurgical sequelae. Methods: This was a retrospective study of 21 patients who underwent a resection of a giant vestibular neuroma according to the Tos & Thomsen Scale (greater than or equal to 4 centimetres) in a tertiary care centre in the period between 2000 and 2008. We present the most significant characteristics of the series studied and the analysis of the advantages and inconveniences of each approach. We also analyse the results regarding facial nerve function preservation. Results: We highlight the absence of mortality in the 21-patient group. There were no important intraoperative complications. Total resection of the lesion was achieved in the 87% of the cases, with facial nerve preservation of 73% using the combined RS/TL approach, in comparison to 40% using the RS. Facial nerve function after two years was acceptable or good in 67% (including those with heteronerve anastomosis). A global percentage of 14.3% of cerebrospinal liquid fistula was observed, as well as 9.5% of meningitis. Conclusions: The results of the study demonstrate that the combined retrosigmoid translabyrinthine approach for giant schwannoma treatment offers increased facial nerve preservation and lower morbidity, constituting an important option in the treatment of this kind of tumours thanks to a multidisciplinary approach(AU)

[Results in the surgical treatment of giant acoustic neuromas]. / Resultados en el tratamiento quirúrgico de los neurinomas del acústico gigantes.

INTRODUCTION AND OBJECTIVES: To compare the results obtained in the resection of 21 giant vestibular schwannomas via retrosigmoid (RS) and combined retrosigmoid/translabyrinthine (RS/TL) approaches with respect to intra- and postoperative complications, facial nerve preservation and postsurgical sequelae. METHODS: This was a retrospective study of 21 patients who underwent a resection of a giant vestibular neuroma according to the Tos & Thomsen Scale (greater than or equal to 4 centimetres) in a tertiary care centre in the period between 2000 and 2008. We present the most significant characteristics of the series studied and the analysis of the advantages and inconveniences of each approach. We also analyse the results regarding facial nerve function preservation. RESULTS: We highlight the absence of mortality in the 21-patient group. There were no important intraoperative complications. Total resection of the lesion was achieved in the 87% of the cases, with facial nerve preservation of 73% using the combined RS/TL approach, in comparison to 40% using the RS. Facial nerve function after two years was acceptable or good in 67% (including those with heteronerve anastomosis). A global percentage of 14.3% of cerebrospinal liquid fistula was observed, as well as 9.5% of meningitis. CONCLUSIONS: The results of the study demonstrate that the combined retrosigmoid translabyrinthine approach for giant schwannoma treatment offers increased facial nerve preservation and lower morbidity, constituting an important option in the treatment of this kind of tumours thanks to a multidisciplinary approach.

Identification of the sensorimotor cortex with functional MRI: frequency and actual contribution in a neurosurgical context.

BACKGROUND AND PURPOSE: We assessed the actual frequency of motor functional MRI (fMRI) in a neurosurgical environment and estimated the extent to which it aided surgeons' identifications of the sensorimotor cortex. METHODS: During five consecutive years, an fMRI protocol aimed at generating a selective activation of the hand cortical area was prescribed to 147 patients showing a centrally located space-occupying lesion, which represents 6.7% of all assisted surgical candidates showing an intracranial mass. Three senior neurosurgeons indicated the position of the sensorimotor cortex on two different anatomical displays, reporting confidence ratings for each decision. RESULTS: The sensorimotor cortex could not be identified in 16.5% of cases using conventional anatomical MRI, and in 15% of cases using 3-dimensional reconstructions. In an additional 12.5% of cases, the neurosurgeons were not confident when they correctly identified the sensorimotor cortex. The tumor distorting effect on central region anatomy significantly contributed to sensorimotor cortex misidentification. fMRI, by contrast, showed a selective activation indicating the position of the sensorimotor cortex in all but 4% of cases. CONCLUSIONS: In our neurosurgical environment, fMRI was prescribed to a selected group of surgical candidates showing a centrally located brain lesion. Compared to conventional anatomical imaging, fMRI does appear to improve the identification of sensorimotor cortex.

Contralateral hearing loss after vestibular schwannoma surgery: case report.

OBJECTIVE: To describe a case of contralateral hearing loss (CHL) in vestibular schwannoma (VS) surgery and to discuss the factors potentially related with this complication. CLINICAL PRESENTATION: A 48-year-old man awakened with complete bilateral hearing loss after an uneventful retrosigmoid excision of a 20 mm left-sided VS. The patient had no complaints of vertigo or facial palsy on the contralateral side. The hearing loss proved to be endocochlear in origin and no improvement was observed after a 24-month follow-up period. DISCUSSION: CHL in VS surgery is not commonly reported but can occur frequently as a subclinical phenomenon if it is specially addressed. The cause is a compensatory endolymphatic hydrops generated by the loss of cerebrospinal fluid. In this circumstance, the hearing loss is usually reversible within 3 months, but irreversible cases have been described. Vascular damage to the cochlea can be another explanation in irreversible cases. The significance of other potential factors described in the literature as a cause of CHL in VS surgery is less clear. CONCLUSION: A case of CHL after VS surgery is presented. The hearing loss proved to be endochlear in origin and irreversible in nature. Irreversible damage to the cochlea resulting from loss of cerebrospinal fluid or vascular injury is probably related in this case reported.

Effects of two chelating agents (EDTA and DTPA) on the autochthonous vegetation of a soil polluted with Cu, Zn and Cd.

Chelating agents are thought to be useful for the remediation of metal-polluted soils with adequate organic matter, but the effects of these substances on the plants or seed bank of plant communities that occur in the soils are relatively unknown. In this work, the effects of two chelating substances (EDTA and DTPA) on a wet grassland plant community affected by the presence of the abandoned copper mine "Fernandito" (Garganta de los Montes, Madrid) were compared. A microcosm bioassay (6 months) was designed using the soil's top layer containing the grassland's seed bank. This soil showed a high Cu pollution level, significant contents of Zn and Cd (1120, 190, and 15 ppm, respectively), a pH of 5 and an OM content of 6.2%. The soil was subjected to three different treatments: a) untreated soil (control), b) the addition of 1 g/kg EDTA, or of c) 1 g/kg DTPA. The results presented here are those related to the plant cover, species richness, aboveground and subterranean biomass and chemical composition of the most abundant plants. Neither EDTA nor DTPA caused intense negative effects on the plants rather they significantly increased the amount of copper accumulated in aboveground parts and roots. In particular, Agrostis castellana and Corrigiola telephiifolia extracted high amounts of copper when grown in the soil with added EDTA, although they showed some nutritional imbalances (lower P contents). In contrast, lower metal concentrations were detected in plants grown in the DTPA amended soil.