Alkylamine-tethered molecules recruit FBXO22 for targeted protein degradation.

Targeted protein degradation (TPD) relies on small molecules to recruit proteins to E3 ligases to induce their ubiquitylation and degradation by the proteasome. Only a few of the approximately 600 human E3 ligases are currently amenable to this strategy. This limits the actionable target space and clinical opportunities and thus establishes the necessity to expand to additional ligases. Here we identify and characterize SP3N, a specific degrader of the prolyl isomerase FKBP12. SP3N features a minimal design, where a known FKBP12 ligand is appended with a flexible alkylamine tail that conveys degradation properties. We found that SP3N is a precursor and that the alkylamine is metabolized to an active aldehyde species that recruits the SCFFBXO22 ligase for FKBP12 degradation. Target engagement occurs via covalent adduction of Cys326 in the FBXO22 C-terminal domain, which is critical for ternary complex formation, ubiquitylation and degradation. This mechanism is conserved for two recently reported alkylamine-based degraders of NSD2 and XIAP, thus establishing alkylamine tethering and covalent hijacking of FBXO22 as a generalizable TPD strategy.

Resection of the quadrangular lobule of the cerebellum to increase exposure of the cerebellomesencephalic fissure: an anatomical study with clinical correlation.

OBJECTIVE: The lateral aspect of the cerebellomesencephalic fissure frequently harbors vascular pathology and is a common surgical corridor used to access the pons tegmentum, as well as the cerebellum and its superior and middle peduncles. The quadrangular lobule of the cerebellum (QLC) represents an obstacle to reach these structures. The authors sought to analyze and compare exposure of the cerebellar interpeduncular region (CIPR) before and after QLC resection and provide a case series to evaluate its clinical applicability. METHODS: Forty-two sides of human brainstems were prepared with Klingler's method and dissected. The exposure area before and after resection of the QLC was measured and statistically studied. A case series of 59 patients who underwent QLC resection for the treatment of CIPR lesions was presented and clinical outcomes were evaluated at 1-year follow-up. RESULTS: The anteroposterior surgical corridor of the CIPR increased by 10.3 mm after resection of the QLC. The mean exposure areas were 42 mm2 before resection of the QLC and 159.6 mm2 after resection. In this series, ataxia, extrapyramidal syndrome, and akinetic mutism were found after surgery. However, all these cases resolved within 1 year of follow-up. Modified Rankin Scale score improved by 1 grade, on average. CONCLUSIONS: QLC resection significantly increased the exposure area, mainly in the anteroposterior axis. This surgical strategy appears to be safe and may help the neurosurgeon when operating on the lateral aspect of the cerebellomesencephalic fissure.

Recurrent Artery of Heubner Guiding the Clip Application for Internal Carotid Artery Bifurcation Aneurysm: 2-Dimensional Operative Video.

Aneurysms of the bifurcation of the internal carotid artery (ICA) represent approximately 5% of intracranial aneurysms and tend to occur in younger patients.1-3 They typically have a superior orientation, in close relationship with the medial (branches of the anterior cerebral artery, segment A1) and lateral (branches of the middle cerebral artery, segment M1) lenticulostriate arteries (LSA), including recurrent artery of Heubner (RAH). RAH commonly originates in the junction of A1 and A2, courses medially to laterally between LSA and anterior cerebral artery, ICA bifurcation, and middle cerebral artery before entering the lateral portion of the anterior perforated substance.4-7 Damage to these arteries are catastrophic. This complex vascular anatomy makes treatment challenging, either endovascular or microsurgical.8-13 We present a video case of microsurgical clipping for the left ICA bifurcation aneurysm. This study was approved by the ethics committee of our institution. The patient, a 46-year-old man, was diagnosed with an unruptured ICA bifurcation aneurysm during workup for intermittent headache. Morphological characteristics of the aneurysm supported intervention over conservative treatment. Digital subtraction angiography showed a prominent proximal RAH crossing between the aneurysm neck and LSA, providing anatomical protection for clip application. Microsurgical clipping was chosen, and the procedure went uneventfully. The patient consented to the procedure and to the publication of his/her image. We discussed and demonstrated throughout the video how we used this anatomic variation and trajectory of the RAH to prevent clipping of LSA unwittingly and achieve complete occlusion of the aneurysm neck.

Risk stratification model for the pharmaceutical care of oncology patients with solid or hematologic neoplasms. / [Artículo traducido] Modelo de estratificación de riesgo de atención farmacéutica para pacientes oncológicos con neoplasias sólidas o hematológicas.

OBJECTIVE: We aimed to develop of a risk stratification model for the pharmaceutical care (PC) of patients with solid or hematologic neoplasms who required antineoplastic agents or supportive treatments. METHOD: The risk stratification model was collaboratively developed by oncology pharmacists from the Spanish Society of Hospital Pharmacy (SEFH). It underwent refinement through three workshops and a pilot study. Variables were defined, grouped into four dimensions, and assigned relative weights. The pilot study collected and analyzed data from participating centers to determine priority levels and evaluate variable contributions. The study followed the Kaiser Permanente pyramid model, categorizing patients into three priority levels: Priority 1 (intensive PC, 90th percentile), Priority 2 (60th-90th percentiles), and Priority 3 (60th percentile). Cut-off points were determined based on this stratification. Participating centers recorded variables in an Excel sheet, calculating mean weight scores for each priority level and the total risk score. RESULTS: The participants agreed to complete a questionnaire that comprised 22 variables grouped into 4 dimensions: demographic (maximum score =11); social and health variables and cognitive and functional status (maximum = 19); clinical and health services utilization (maximum = 25); and treatment-related (maximum = 41). From the results of applying the model to the 199 patients enrolled, the cutoff points for categorization were 28 or more points for priority 1, 16 to 27 points for priority 2 and less than 16 for priority 3; more than 80% of the total score was based on the dimensions of 'clinical and health services utilization' and 'treatment-related'. Interventions based on the pharmaceutical care model were recommended for patients with solid or hematological neoplasms, according to their prioritization level. CONCLUSION: This stratification model enables the identification of cancer patients requiring a higher level of pharmaceutical care and facilitates the adjustment of care capacity. Validation of the model in a representative population is necessary to establish its effectiveness.

Dietary Intake of (Poly)phenols and Risk of All-Cause and Cause-Specific Mortality in the Mexican Teachers' Cohort Study.

BACKGROUND: Observational studies have reported that total (poly)phenol intake is associated with a reduction in all-cause and cardiovascular mortality, but mainly from high-income countries, where (poly)phenol intake may differ from that of low- and middle-income countries. OBJECTIVES: Our objective was to evaluate the association between the intake of total, all classes, and subclasses of (poly)phenols and risk of all-cause and cause-specific mortality in a Mexican cohort. METHODS: We used data from the Mexican Teachers' Cohort, which included 95,313 adult females. After a median follow-up of 11.2 y, 1725 deaths were reported, including 674 from cancer and 282 from cardiovascular diseases. (Poly)phenol intake was estimated using a validated food frequency questionnaire and the Phenol-Explorer database. Multivariable Cox models were applied to estimate the association between (poly)phenol intake and all-cause mortality and competitive risk models for cause-specific mortality. RESULTS: Comparing extreme quartiles, total (poly)phenol intake was associated with lower risk of all-cause [hazard ratio (HR)Q4vs.Q1: 0.88; 95% CI: 0.76, 0.99; P-trend = 0.01] and cancer mortality (HRQ4vs.Q1: 0.81; 95% CI: 0.64, 0.99; P-trend = 0.02). Among (poly)phenol classes, phenolic acids, particularly hydroxycinnamic acids from coffee, showed an inverse association with all-cause (HRQ4vs.Q1: 0.79; 95% CI: 0.69, 0.91; P-trend = 0.002) and cancer mortality (HRQ4vs.Q1: 0.75; 95% CI: 0.61, 0.94; P-trend = 0.03). No associations were observed with flavonoids or with cardiovascular mortality. CONCLUSION: Our study suggests that high (poly)phenol intake, primarily consisting of phenolic acids such as hydroxycinnamic acids, may have a protective effect on overall and cancer mortality. Null associations for flavonoid intake might be due to the potential underestimation of their intake in this population.

Subcellular localisation of truncated MAGEL2 proteins: insight into the molecular pathology of Schaaf-Yang syndrome.

Schaaf-Yang syndrome (SYS) is an ultra-rare neurodevelopmental disorder caused by truncating mutations in MAGEL2 Heterologous expression of wild-type (WT) or a truncated (p.Gln638*) C-terminal HA-tagged MAGEL2 revealed a shift from a primarily cytoplasmic to a more nuclear localisation for the truncated protein variant. We now extend this analysis to six additional SYS mutations on a N-terminal FLAG-tagged MAGEL2. Our results replicate and extend our previous findings, showing that all the truncated MAGEL2 proteins consistently display a predominant nuclear localisation, irrespective of the C-terminal or N-terminal position and the chemistry of the tag. The variants associated with arthrogryposis multiplex congenita display a more pronounced nuclear retention phenotype, suggesting a correlation between clinical severity and the degree of nuclear mislocalisation. These results point to a neomorphic effect of truncated MAGEL2, which might contribute to the pathogenesis of SYS.

Criteria and indicators to evaluate quality of care in genitourinary tumour boards.

PURPOSE: Genitourinary (GU) multidisciplinary tumour boards (GUMTBs) are key components of patient care, as they might lead to changes in treatment plan, improved survival, and increased adherence to guidelines. However, there are no guidelines on how GUMTBs should operate or how to assess their quality of performance. METHODS: A systematic literature review was conducted to identify criteria and indicators to evaluate quality in GUMTBs. A scientific committee-comprising 12 GU cancer specialists from seven disciplines-proposed a list of criteria and developed indicators, evaluated in two rounds of Delphi method. Appropriateness and utility of indicators were scored using a 9-point Likert scale. Consensus was defined as at least two-thirds of Delphi respondents selecting a score sub-category that encompassed the median score of the group. RESULTS: Forty-five criteria were selected to evaluate the quality of GUMTBs covering five dimensions: organisation, personnel, protocol and documentation, resources, and interaction with patients. Then, 33 indicators were developed and evaluated in the first round of Delphi, leading to a selection of 26 indicators in two dimensions: function, governance and resources, and GUMTB sessions. In the second round, consensus was reached on the appropriateness of all 26 indicators and on the utility of 24 of them. Index cards for criteria and indicators were developed to be used in clinical practice. CONCLUSIONS: Criteria and indicators were developed to evaluate the quality of GUMTBs, aiming to serve as a guide to improve quality of care and health outcomes in patients with GU cancer.

Progress towards elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology Commission update.

The top 20 highest burdened countries (in disability-adjusted life years) account for more than 75% of the global burden of viral hepatitis. An effective response in these 20 countries is crucial if global elimination targets are to be achieved. In this update of the Lancet Gastroenterology & Hepatology Commission on accelerating the elimination of viral hepatitis, we convene national experts from each of the top 20 highest burdened countries to provide an update on progress. Although the global burden of diseases is falling, progress towards elimination varies greatly by country. By use of a hepatitis elimination policy index conceived as part of the 2019 Commission, we measure countries' progress towards elimination. Progress in elimination policy has been made in 14 of 20 countries with the highest burden since 2018, with the most substantial gains observed in Bangladesh, India, Indonesia, Japan, and Russia. Most improvements are attributable to the publication of formalised national action plans for the elimination of viral hepatitis, provision of publicly funded screening programmes, and government subsidisation of antiviral treatments. Key themes that emerged from discussion between national commissioners from the highest burdened countries build on the original recommendations to accelerate the global elimination of viral hepatitis. These themes include the need for simplified models of care, improved access to appropriate diagnostics, financing initiatives, and rapid implementation of lessons from the COVID-19 pandemic.

Disparities on prostate cancer survival in Mexico: a retrospective cohort study.

OBJECTIVE: To estimate prostate cancer (PC) survival in Mexico and explore survival disparities according to the marginalization level of residence place. MATERIALS AND METHODS: A nationwide administrative claims database (4 110 men) whose PC treatment was financed by Seguro Popular between 2012-2016, was cross-linked to the National Mortality Registry up to December 2019. Patients were classified according to their oncological risk at diagnosis and the marginalization level of the residence municipality. Cox proportional hazards regression was used to estimate multivariable survival functions. RESULTS: Five-years PC survival (69%; 95%CI: 68,71%) ranged from 72% to 54% at very low and very high marginalization, respectively (p for trend<0.001). The lowest PC survival was observed in men with high-risk PC (47%; 95%CI: 33,66%) residents in very high marginalization municipalities. CONCLUSIONS: Overall, PC survival was lower than that reported in other Latin American countries. The distribution of oncologic risk and survival differences across marginalization levels suggests limited early detection and cancer health disparities.

The Omicron wave in Mexico: vaccine protection against progression to severe Covid-19 in SARS-CoV-2-infected workers.

OBJECTIVE: To assess the effectiveness of seven Covid-19 vaccines in preventing disease progression (DP) using data from national private sector workers during the Omicron wave in Mexico from January 2 to March 5, 2022. MATERIALS AND METHODS: This study employed an administrative retrospective cohort design, analyzing DP (hospitalization or death due to respiratory disease) among workers who filed a respiratory short-term disability claim and tested positive for SARS-CoV-2. Risk ratios (RRadj) were estimated using Poisson regression models adjusted for various factors. RESULTS: Vaccinated individuals had a lower risk of hospitalization and death compared with unvaccinated individuals. The overall RRadj for hospitalization and death were 0.36 (95%CI 0.32, 0.41) and 0.24 (0.17, 0.33), respectively. When evaluating vaccines individually, the RRadj for hospitalization were as follows Pfizer BioNTech 0.27 (95%CI 0.22, 0.33), Moderna 0.29 (95%CI 0.15, 0.57), Sinovac 0.32 (95%CI 0.25, 0.41), AstraZeneca 0.39 (95%CI 0.34, 0.46), Sputnik 0.39 (95%CI 0.28, 0.53), CanSino 0.41 (95%CI 0.24, 0.7), and Janssen 0.53 (95%CI 0.39, 0.72). The RRadj for death were as follows: Pfizer BioNTech 0.12 (95%CI 0.07, 0.19), Sputnik 0.15 (95%CI 0.06, 0.38), Sinovac 0.29 (95%CI 0.16, 0.53), AstraZeneca 0.30 (95%CI 0.20, 0.44), CanSino 0.38 (95%CI 0.1, 1.4), and Janssen 0.50 (95%CI 0.26, 0.97). CONCLUSION: Covid-19 vaccines significantly reduced the risk of severe disease during the Omicron wave in Mexico.

Impacto del COVID-19 en la esperanza de vida en los municipios de los estados del noreste de México / COVID-19 impact on life expectancy among municipalities of Northeastern states of Mexico

RESUMEN La mortalidad causada por COVID-19 en México se ha situado entre las más altas del mundo, por lo que es de interés epidemiológico estudiar su impacto respecto a la esperanza de vida (EV). El objetivo del presente trabajo fue analizar el impacto de la pandemia por COVID-19 en la esperanza de vida, comparando datos de 2019 y 2020, y evaluando su efecto por densidad poblacional de los municipios de los estados del noreste de México. La información sobre mortalidad para 2019 y 2020 se obtuvo de la Secretaría de Salud, y la demográfica del Consejo Nacional de Población. Se construyeron tablas de vida mediante el método actuarial estándar; se calcularon percentiles ≤ 25 y ≥ 75 de la diferencia en la EV; se evaluó la relación entre el tamaño de la población de los municipios y la magnitud de la diferencia en la pérdida de años en la EV. La pandemia por COVID-19 impactó en la EV en los estados del noreste de México, con gran heterogeneidad al interior en cada uno de ellos. La pérdida en años en promedio fue, para Coahuila de 5.4, Nuevo León 4.1 y Tamaulipas 4.9. Los municipios del percentil ≥ 75 mostraron una pérdida promedio de 9.2 años y los del percentil ≤ 25 de -0.35 años. La diferencia en la pérdida en años de EV, entre 2019 y 2020, se vio influenciada por el tamaño de la población, tendiendo a ser mayor en aquellos con mayor densidad demográfica, sin ser el único factor determinante.

ABSTRACT COVID-19 mortality in Mexico is among the highest in the world. Therefore, it is of epidemiologic interest to study its impact on life expectancy. The aim of the present paper was to analyze the impact of the COVID-19 pandemic on life expectancy through a comparison of data from 2019 and 2020. Specifically, the effect of population density in municipalities of Northeastern Mexican states. Information regarding 2019 and 2020 mortality rates for was obtained from the Ministry of Health, and demographics from the National Population Council. Life tables were constructed using the standard actuarial method. Percentiles ≤ 25 and ≥ 75 of the difference in life expectancy in the period were calculated. The relationship between the size of the population of the municipalities and the magnitude of the difference in life expectancy loss of years was evaluated. COVID-19 pandemic impacted on life expectancy with great heterogeneity in each of the northeastern states of Mexico. The loss in years in average life expectancy was 5.4 for Coahuila, 4.1 for Nuevo Leon and 4.9 for Tamaulipas. Municipalities above the ≥ 75th percentile showed an average loss of 9.2 years. Those in the lower than ≤ 25th percentile showed a decrease, of -0.35 years. The difference in the loss of life expectancy during 2019 and 2020 was influenced by population size, tending to be greater in those municipalities with higher population density, but was not the only determining factor.

Effect of COVID-19 mortality on life expectancy in municipalities of Mexico. Comparison between 2019 and 2020.

BACKGROUND: Life expectancy (LE) is an indicator related to medical, demographic, social and geographic conditions. OBJECTIVES: To analyze the effect of the COVID-19 pandemic on LE and of its distribution according to sociodemographic variables in municipalities of Mexico. METHODS: Information on mortality was collected from data published by the Ministry of Health, and demographic information, from the 2020 Population and Housing Census. LE was calculated according to the standard actuarial method. A risk analysis was carried out between expected years of life lost and the size of the economically active population, years of education and indigenous-speaking population. RESULTS: In 2020, there was a nation-wide average drop of 4.7 years in LE, but its distribution was heterogeneous at the municipal level, with extreme values of -2.8 years and 12.6 years. The risk analysis showed an inverse relationship between sociodemographic variables and expected years of life lost, except for the indigenous-speaking population. CONCLUSIONS: The impact of the COVID-19 pandemic on LE in Mexico was significant and was influenced by the analyzed sociodemographic variables, particularly by the municipalities' population size.

ANTECEDENTES: La esperanza de vida es un indicador relacionado con condiciones médicas, demográficas, sociales y geográficas. OBJETIVOS: Analizar el efecto de la pandemia de COVID-19 en la esperanza de vida y de su distribución según variables sociodemográficas en municipios de México. MATERIAL Y MÉTODOS: Se recabó información sobre mortalidad de la Secretaría de Salud, así como información demográfica del Censo de Población y Vivienda de 2020. La esperanza de vida se calculó conforme el método actuarial estándar. Se realizó análisis de riesgo entre la pérdida de la esperanza de vida en años y el tamaño de la población, población económicamente activa, años de escolaridad y población de habla indígena. RESULTADOS: En 2020 se registró una caída promedio de 4.7 años en la esperanza de vida a nivel nacional, pero su distribución fue heterogénea en los municipios, con valores extremos de −2.8 años y 12.6 años. El análisis de riesgo mostró una relación inversa entre las variables sociodemográficas y la pérdida de años de esperanza de vida, con excepción de la población de habla indígena. CONCLUSIONES: El impacto de la pandemia de COVID-19 en la esperanza de vida en México fue significativo, matizado por las variables sociodemográficas analizadas, particularmente por el tamaño de la población de los municipios.

DNA oxidative damage in oral cancer: 8-hydroxy-2´-deoxyguanosine immunoexpression assessment

Background: The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´- deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication. Material and Methods: We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of followup. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus. Results: Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value ≤ 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001). Conclusions: All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death. (AU)

Risk stratification model for the pharmaceutical care of oncology patients with solid or hematologic neoplasms.

OBJECTIVE: We aimed to develop of a risk stratification model for the pharmaceutical care of patients with solid or hematologic neoplasms who required antineoplastic agents or supportive treatments. METHOD: The risk stratification model was collaboratively developed by oncology pharmacists from the Spanish Society of Hospital Pharmacy (SEFH). It underwent refinement through 3 workshops and a pilot study. Variables were defined, grouped into 4 dimensions, and assigned relative weights. The pilot study collected and analyzed data from participating centers to determine priority levels and evaluate variable contributions. The study followed the Kaiser Permanente pyramid model, categorizing patients into 3 priority levels: Priority 1 (intensive PC, 90th percentile), Priority 2 (60th-90th percentiles), and Priority 3 (60th percentile). Cut-off points were determined based on this stratification. Participating centers recorded variables in an Excel sheet, calculating mean weight scores for each priority level and the total risk score. RESULTS: The participants agreed to complete a questionnaire that comprised 22 variables grouped into 4 dimensions: demographic (maximum score=11); social and health variables and cognitive and functional status (maximum=19); clinical and health services utilization (maximum=25); and treatment-related (maximum=41). From the results of applying the model to the 199 patients enrolled, the cut-off points for categorization were 28 or more points for priority 1, 16-27 points for priority 2, and less than 16 for priority 3; more than 80% of the total score was based on the dimensions of "clinical and health services utilization" and "treatment-related." Interventions based on the pharmaceutical care model were recommended for patients with solid or hematological neoplasms, according to their prioritization level. CONCLUSION: This stratification model enables the identification of cancer patients requiring a higher level of pharmaceutical care and facilitates the adjustment of care capacity. Validation of the model in a representative population is necessary to establish its effectiveness.

Efecto de la mortalidad por COVID-19 en la esperanza de vida en los municipios de México. Comparación 2019 y 2020 / Effect of COVID-19 mortality on life expectancy in municipalities of Mexico. Comparison between 2019 and 2020

Resumen Antecedentes: La esperanza de vida es un indicador relacionado con condiciones médicas, demográficas, sociales y geográficas. Objetivos: Analizar el efecto de la pandemia de COVID-19 en la esperanza de vida y de su distribución según variables sociodemográficas en municipios de México. Material y métodos: Se recabó información sobre mortalidad de la Secretaría de Salud, así como información demográfica del Censo de Población y Vivienda de 2020. La esperanza de vida se calculó conforme el método actuarial estándar. Se realizó análisis de riesgo entre la pérdida de la esperanza de vida en años y el tamaño de la población, población económicamente activa, años de escolaridad y población de habla indígena. Resultados: En 2020 se registró una caída promedio de 4.7 años en la esperanza de vida a nivel nacional, pero su distribución fue heterogénea en los municipios, con valores extremos de −2.8 años y 12.6 años. El análisis de riesgo mostró una relación inversa entre las variables sociodemográficas y la pérdida de años de esperanza de vida, con excepción de la población de habla indígena. Conclusiones: El impacto de la pandemia de COVID-19 en la esperanza de vida en México fue significativo, matizado por las variables sociodemográficas analizadas, particularmente por el tamaño de la población de los municipios.

Abstract Background: Life expectancy (LE) is an indicator related to medical, demographic, social and geographic conditions. Objectives: To analyze the effect of the COVID-19 pandemic on LE and of its distribution according to sociodemographic variables in municipalities of Mexico. Methods: Information on mortality was collected from data published by the Ministry of Health, and demographic information from the 2020 Population and Housing Census. LE was calculated according to the standard actuarial method. A risk analysis was carried out between expected years of life lost and the size of the population, economically active population, years of education and indigenous-speaking population. Results: In 2020, there was a nation-wide average drop of 4.7 years in LE, but its distribution was heterogeneous at the municipal level, with extreme values of -2.8 years and 12.6 years. The risk analysis showed an inverse relationship between sociodemographic variables and expected years of life lost, except for the indigenous-speaking population. Conclusions: The impact of the COVID-19 pandemic on LE in Mexico was significant, and was influenced by the analyzed sociodemographic variables, particularly by the municipalities' population size.

A Double-Headed Physiologic Monster: A Case Report and Literature Review.

Adrenal incidentaloma (AI) is rare and found in approximately 2-4% of abdominal computed tomography scans. Up to 10% of patients with AI have autonomous secretion of adrenal hormones. If not quickly diagnosed and adequately treated, the outcome may be devastating to the patient. On very rare occasions, a pheochromocytoma may, in addition to the production of catecholamine, produce adrenocorticotropic hormone causing Cushing disease. We present a case of a patient with pheochromocytoma and Cushing syndrome.

Recovery of plastic waste through its thermochemical degradation: a review.

The demand to produce plastic has increased yearly; only in 2020, there was a production of approximately 368 million tons worldwide. According to Plastics Europe, from 2016 to 2018, a total of 29.1 Mt of plastic waste was generated, and 24% of this ended up in a landfill, generating problems due to accumulation. The increase in the demand for plastics has begun to contribute to the shortage of oil sources, a non-renewable resource. On the other hand, various researchers have reported effects on human health such as neurological damage, cancer in the nasal cavities, prostate, and ovarian cancer, and in animal species, destruction of the digestive and respiratory tracts due to the consumption of microplastics in food. Due to these reasons, various solutions have been proposed for recovering and recycling plastic waste. One of the most promising technologies is thermal and catalytic degradation, known as pyrolysis. This technology allows the recovery of chemical compounds of high energy value. In this work, the various environmental and social impacts caused by plastic are discussed. Worldwide consumption data is provided by sector and type of plastic, and the different routes of thermal degradation for each type of thermoplastic are shown.

Low-intensity daily smoking and mortality risk among Mexican women.

OBJECTIVE: To examine the association between low-intensity smoking (10 or less cigarettes per day) and all-cause and cause-specific mortality risk among women who smoke and by age at cessation among women who previously smoked. METHODS: In this study, 104 717 female participants of the Mexican Teachers' Cohort Study were categorised according to self-reported smoking status at baseline (2006/2008) and were followed for mortality through 2019. We estimated HRs and 95% CIs for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models with age as the underlying time metric. RESULTS: Smoking as few as one to two cigarettes per day was associated with higher mortality risk for all causes (HR: 1.36; 95% CI 1.10 to 1.67) and all cancers (HR: 1.46; 95% CI 1.05 to 2.02), compared with never smoking. Similarly, slightly higher HRs were observed among participants smoking ≥3 cigarettes per day (all causes HR: 1.43; 95% CI 1.19 to 1.70; all cancers HR: 1.48; 95% CI 1.10 to 1.97; cardiovascular disease HR: 1.58; 95% CI 1.09 to 2.28). CONCLUSIONS: In this large study of Mexican women, low-intensity smoking was associated with higher mortality risk for all causes and all cancers. Interventions are needed to promote cessation among women who smoke at low-intensity in Mexico, regardless of how few cigarettes they smoke per day.

Breast cancer survival in Mexico between 2007 and 2016 in women without social security: a retrospective cohort study.

Background: Essential indicators of health system performance for breast cancer are lacking in Mexico. We estimated survival and clinical stage distribution for women without social insurance who were treated under a health financing scheme that covered 60% of the Mexican population. Methods: We conducted a retrospective cohort study cross-linking reimbursement claims for 56,847 women treated for breast cancer between 2007 and 2016 to a mortality registry. We estimated overall- and clinical stage-specific survival and breast cancer survival according to patient age, state of residence, marginalization, type of treatment facility, and patient volume of the treatment facility. We also explored the distribution of clinical stage according to age, year of treatment initiation, and state where the woman was treated. We used log-rank tests and estimated 95% CIs to compare differences between patient groups. Findings: Median age was 52 years (interquartile range [IQR] 45, 61) (Sixty five percent patients (36,731/56,847) had advanced disease at treatment initiation. Five-year overall survival was 72.2% (95% CI 71.7, 72.6). For early disease (excluding stage 0), 5-year overall survival was 89.0% (95% CI 88.4, 89.5), for locally advanced disease 69.9% (95% CI 69.0, 70.2) and for metastatic 36.9% (95% CI 35.4, 38.4). Clinical stage at treatment initiation and breast cancer survival remained unchanged in the period analyzed. Clinical stage and survival differed across age groups, state of residence, and type of facility where women received treatment. Interpretation: In the absence of population-based cancer registries, medical claims data may be efficiently leveraged to estimate essential cancer-related performance indicators. Funding: The authors received no financial support for this research.