School Connectedness and Suicide Among High School Youth: A Systematic Review.

BACKGROUND: Suicide is a leading cause of death for adolescents, and school connectedness is a potential, modifiable protective factor for suicide. We sought to examine if school connectedness protected against suicide among high school students and if potential moderators affected the relationship between school connectedness and suicide. METHODS: We searched online databases (PubMed, EMBASE, CINAHL, and PsycINFO) on December 12, 2021, for studies that examined the effects of school connectedness on suicide among high school students. RESULTS: This systematic review identified 34 studies that examined the effects of school connectedness on adolescent suicidality. Results indicated mixed findings of school connectedness on suicidality. Among studies that assessed a suicide ideation outcome, 73.3% found that school connectedness protected against suicide. Among studies that assessed a suicide attempts outcome, 50% found that school connectedness protected against suicide. Most included studies did not control for notable variables in their final models, such as sleep, impulsivity, substance use, or depression. No studies examined moderators of school connectedness and suicide. CONCLUSIONS: School connectedness is somewhat protective of suicidality, and more protective of suicidal ideation than suicide attempts. Researchers should examine the construct of school connectedness among modern youth to better understand school connectedness and suicide.

El abrazo, de las bases a su expresión en la vida y el arte / The embrace of the people to their expression in life and art

Resumen: El confinamiento y aislamiento social durante la pandemia por COVID-19 limitaron el contacto físico estrecho, en especial los de cercanía, del que destacan los abrazos. El impacto social del vacío y aislamiento afectivo aún perdura. El abrazo es una respuesta innata afectiva del ser humano que se expresa en diferentes circunstancias. Tiene su origen en diferentes regiones cerebrales, que van de las límbicas a las corticales, en las que se entrelaza una compleja interacción entre aferencias, sistemas de señalización y neurotransmisores que condicionan una respuesta neurohormonal con impacto multisistémico. El abrazo va más allá de este complejo sustrato, representa la sublimación de lo meramente anatómico y fisiológico, a la manifestación afectiva del espíritu humano. El objetivo de este breve ensayo es poner a su consideración las bases neurocientíficas del abrazo y su expresión en la complejidad de la vida y el arte.

Abstract: Confinement and social isolation during the COVID-19 pandemic limited close physical contact, especially close ones, of which hugs stand out. The social impact of emptiness and affective isolation still endures. The hug is an innate affective response of the human being that is expressed in different circumstances. It originates from different brain regions, ranging from limbic to cortical, in which a complex interaction between afferents, signaling systems, and neurotransmitters is intertwined, conditioning a neurohormonal response with multisystem impact. The hug goes beyond this complex substrate, it represents the sublimation of the merely anatomical and physiological, to the affective manifestation of the human spirit. The objective of this brief essay is to put to your consideration the neuroscientific bases of the hug and its expression in the complexity of life and art.

Monoacylglycerol Lipase Inhibition Prevents Short-Term Mitochondrial Dysfunction and Oxidative Damage in Rat Brain Synaptosomal/Mitochondrial Fractions and Cortical Slices: Role of Cannabinoid Receptors.

Inhibition of enzymes responsible for endocannabinoid hydrolysis represents an invaluable emerging tool for the potential treatment of neurodegenerative disorders. Monoacylglycerol lipase (MAGL) is the enzyme responsible for degrading 2-arachydonoylglycerol (2-AG), the most abundant endocannabinoid in the central nervous system (CNS). Here, we tested the effects of the selective MAGL inhibitor JZL184 on the 3-nitropropinic acid (3-NP)-induced short-term loss of mitochondrial reductive capacity/viability and oxidative damage in rat brain synaptosomal/mitochondrial fractions and cortical slices. In synaptosomes, while 3-NP decreased mitochondrial function and increased lipid peroxidation, JZL184 attenuated both markers. The protective effects evoked by JZL184 on the 3-NP-induced mitochondrial dysfunction were primarily mediated by activation of cannabinoid receptor 2 (CB2R), as evidenced by their inhibition by the selective CB2R inverse agonist JTE907. The cannabinoid receptor 1 (CB1R) also participated in this effect in a lesser extent, as evidenced by the CB1R antagonist/inverse agonist AM281. In contrast, activation of CB1R, but not CB2R, was responsible for the protective effects of JZL184 on the 3-NP-iduced lipid peroxidation. Protective effects of JZL184 were confirmed in other toxic models involving excitotoxicity and oxidative damage as internal controls. In cortical slices, JZL184 ameliorated the 3-NP-induced loss of mitochondrial function, the increase in lipid peroxidation, and the inhibition of succinate dehydrogenase (mitochondrial complex II) activity, and these effects were independent on CB1R and CB2R, as evidenced by the lack of effects of AM281 and JTE907, respectively. Our novel results provide experimental evidence that the differential protective effects exerted by JZL184 on the early toxic effects induced by 3-NP in brain synaptosomes and cortical slices involve MAGL inhibition, and possibly the subsequent accumulation of 2-AG. These effects involve pro-energetic and redox modulatory mechanisms that may be either dependent or independent of cannabinoid receptors' activation.

Factors Associated with Depressive Symptoms among Mexican-Origin Adults in a Community Sample at the US Mexico Border Region.

Using baseline data from three partnering federally qualified health centers, we examined factors associated with depressive symptoms among Mexican-origin adults at risk of chronic disease living in three counties in Southern Arizona (i.e., Pima, Yuma, and Santa Cruz). Multivariable linear regression models identified correlates of depressive symptoms for this population controlling for sociodemographic characteristics. Among 206 participants, 85.9% were female and 49% were between 45 and 64 years of age. The proportion of depressive symptoms was 26.8%. Low levels of physical pain and high levels of hope and social support were also reported. Physical pain was positively and significantly related to depressive symptoms (ß = 0.22; 95% CI = 0.13, 0.30). Conversely, hope was negatively and significantly associated with depressive symptoms (ß = -0.53; 95% CI = -0.78, -0.29). A better understanding of factors related to depressive symptoms among Mexican-origin adults is necessary to fulfill their mental health needs, as well as to achieve health equity and to eliminate health disparities in the US-Mexico border region.

Risk Factors Associated with Diabetes among Mexican-Origin Adults in Southern Arizona.

Diabetes is the seventh leading cause of death in the United States, and it is particularly problematic among the Latine population. This study employed multivariable logistic regression models to examine how hypertension, depression, and sociodemographics were associated with diabetes in a cross-sectional sample of Mexican-origin adults living in three counties of Southern Arizona. The overall prevalence of diabetes from this primary care sample was 39.4%. Holding covariates at fixed values, individuals having hypertension were 2.36 (95% CI: 1.15, 4.83) times more likely to have diabetes, when compared to individuals not having hypertension. The odds of having diabetes for individuals with ≥12 years of educational attainment were 0.29 (95% CI: 0.14, 0.61) times the corresponding odds of individuals with <12 years of educational attainment. For individuals with depression, the odds of having diabetes for those who were born in Mexico and had <30 years living in the US were 0.04 (95% CI: 0, 0.42) times the corresponding odds of individuals without depression and who were born in the US. Findings suggest clinical and public health systems should be aware of the potential increased risk of diabetes among Mexican-origin adults with hypertension and lower educational attainment.

Vaccine hesitancy and the willingness to recommend the COVID-19 vaccine to children in a rural country on the United States-Mexico border.

Introduction: As of October 26, 2022, only 9% of children in the United States aged 6 months to 4 years have received at least one dose of COVID-19 vaccine despite FDA approval since June 17, 2022. Rates are better yet still low for children aged 5 to 11 years as nearly 30% were fully vaccinated as of August 23, 2022. Vaccine hesitancy among adults is one of the major factors affecting low vaccine uptake rates in children against COVID-19, yet most studies examining vaccine hesitancy have targeted school-age and adolescent children. Methods: With the aim of assessing the willingness to recommend the COVID-19 vaccination to children under 5 years compared to children 5 to 12 years of age, a county-wide survey was conducted between January 11 and March 7, 2022, among adults on the United States-Mexico border. Results: Among the 765 responses, 72.5% were female and 42.3% were Latinx. The most significant factor associated with likelihood to recommend the COVID-19 vaccine to children less than 5 years and 5-12 years of age was adult vaccination status. Ordinal logistic regression also indicated that ethnicity, primary language, being a parent, previous COVID-19 infection, and concern about getting COVID-19 in the future were significantly associated with likelihood of COVID-19 vaccine recommendation to children < 5 years and 5-12 years old. Discussion: This study found high consistency among respondents in their willingness to vaccinate children aged < 5 years compared with children aged 5-12 years. Our findings support public health strategies that target adult vaccinations as an avenue to improve childhood vaccinations for young children.

Kynureninase Promotes Immunosuppression and Predicts Survival in Glioma Patients: In Silico Data Analyses of the Chinese Glioma Genome Atlas (CGGA) and of the Cancer Genome Atlas (TCGA).

Kynureninase (KYNU) is a kynurenine pathway (KP) enzyme that produces metabolites with immunomodulatory properties. In recent years, overactivation of KP has been associated with poor prognosis of several types of cancer, in particular by promoting the invasion, metastasis, and chemoresistance of cancer cells. However, the role of KYNU in gliomas remains to be explored. In this study, we used the available data from TCGA, CGGA and GTEx projects to analyze KYNU expression in gliomas and healthy tissue, as well as the potential contribution of KYNU in the tumor immune infiltrate. In addition, immune-related genes were screened with KYNU expression. KYNU expression correlated with the increased malignancy of astrocytic tumors. Survival analysis in primary astrocytomas showed that KYNU expression correlated with poor prognosis. Additionally, KYNU expression correlated positively with several genes related to an immunosuppressive microenvironment and with the characteristic immune tumor infiltrate. These findings indicate that KYNU could be a potential therapeutic target for modulating the tumor microenvironment and enhancing an effective antitumor immune response.

Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial.

PURPOSE: Hypoxia has been associated with chemoradioresistance secondary to vascular endothelial growth factor receptor induced by hypoxia-induced factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in tissues, and this may have antiangiogenic, proapoptotic, and antiefflux effects. Particularly, epidermal growth factor-mutated (EGFRm) tumor cell lines have been shown to overexpress both vascular endothelial growth factor and HIF. In this phase 2 study, we evaluated the effect of transdermal NTG plus whole brain radiation therapy (WBRT) in patients with non-small cell lung cancer (NSCLC) with brain metastases (BM). METHODS: This was an open-label, phase 2 clinical trial with 96 patients with NSCLC and BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. The primary endpoint was intracranial objective response rate (iORR) evaluated 3 months posttreatment. NTG was administered using a transdermal 36-mg patch from Monday through Friday throughout WBRT administration (10 days). The protocol was retrospectively registered at ClinicalTrials.gov (NCT04338867). RESULTS: Fifty patients were allocated to the control group, and 46 were allocated to the experimental group (NTG); among these, 26 (52%) had EGFRm in the control group and 21 (45.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response compared with controls (56.5% [n = 26/46 evaluable patients] vs 32.7% [n = 16/49 evaluable patients]; relative risk, 1.73; 95% confidence interval [CI], 1.08-2.78; P = .024). Additionally, patients who received NTG + WBRT had an independently prolonged intracranial progression-free survival (ICPFS) compared with those who received WBRT alone (27.7 vs 9.6; hazard ratio [HR], 0.5; 95% CI, 0.2-0.9; P = .020); this positively affected overall progression-free survival among patients who received systemic therapy (n = 88; HR, 0.5; 95% CI, 0.2-0.9; P = .043). The benefit of ICPFS (HR, 0.4; 95% CI, 0.2-0.9; P = .030) was significant in the EGFRm patient subgroup. No differences were observed in overall survival. A significantly higher rate of vomiting presented in the NTG arm of the study (P = .016). CONCLUSIONS: The concurrent administration of NTG and radiation therapy improves iORR and ICPFS among patients with NSCLC with BM. The benefit in ICPFS is significant in the EGFRm patient subgroup.

Conciencia de la consciencia durante la anestesia / Awareness of consciousness during anesthesia

Resumen: La definición de consciencia en sí encierra una gran dificultad por su esencia y la inmensa complejidad de los numerosos componentes y procesos que la conforman. La consciencia como característica inherente al ser humano ha sido objeto de numerosos estudios y tratados, no sólo científicos, sino además filosóficos, religiosos, éticos, etcétera. Esto también incluye la diferencia entre consciencia y conciencia. La dificultad para poder establecer el principio que da origen a la consciencia, representa, por lo tanto, un gran reto para poder dilucidar con certeza lo que sucede con ésta durante el evento anestésico. Gracias al entendimiento que se va logrando a través de las investigaciones concernientes a las funciones de diferentes y complejas estructuras, tales como la substancia activadora reticular ascendente, el tálamo, partes del cuerpo estriado y la corteza cerebral, entre otras, que se relacionan gracias a la existencia de redes neuronales, integradas a su vez por nodos con funciones específicas y a la vez variadas, capaces de intercomunicar estas estructuras encefálicas, aun estando distantes, se tiene ahora nociones sólidas de dónde, cómo y cuánto se puede ver afectada la integración de la consciencia como consecuencia del efecto de los diferentes anestésicos.

Abstract: To define consciousness per se, involves a great difficulty because of its essence and the huge complexity regarding the great number of its components and the processes within. Consciousness, as a human characteristic, has been matter of large researching not only through a scientific approach, but also from the perspective of philosophic, religious, ethics investigations among others, including the distinction between consciousness and awareness. The trouble to define the foundation of consciousness implies a great challenge to get to know, what is happening during the anesthesia period. Through the understanding that has been accomplished by way of investigations concerning the different and complex functions of diverse neural structures such as the brain stem reticular formation, the thalamus, some parts of the striatum and the cerebral cortex among others, how they become connected by the neuronal nets who are compounded by nodes that have not only specific but a wide array of functions, capable of interconnect all these encephalic structures, even though they are far away, we know now with a good amount of certainty, where, how and how much the integrity of consciousness can be affected as a consequence of the different anesthetics effect.

Modifying factors of PD-L1 expression on tumor cells in advanced non-small-cell lung cancer.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression predicts immunotherapy utility in nononcogenic addictive lung adenocarcinoma (ADC). However, its reproducibility and reliability may be compromised outside clinical trials. This study aimed to evaluate factors associated with PD-L1 expression in lung ADC. METHODS: This observational study assessed 547 tumor samples with advanced lung ADC from January 2016 to December 2020 in a single cancer institution. Tumor samples were stained by at least one approved PD-L1 clone, SP263 (Ventana) or 22C3 (Dako), and stratified in tumor proportion score (TPS) <1%, 1-49%, or ≥50%. RESULTS: Of all the tumor samples, positive PD-L1 staining was higher in poorly differentiated tumors (67.3% vs. 32.7%, p < 0.001). Analytical factors associated with a PD-L1 high expression (TPS ≥ 50%) were the SP263 clone (19.6% vs. 8.2%, p < 0.001), time of archival tumor tissue <12 months (15.3% vs. 3.8%, p = 0.024), whenever the analysis was performed in the most recent years (2019-2020) (19.0% vs. 8.3%, p < 0.001), and whenever the analysis was performed by pathologists in the academic setting (Instituto Nacional de Cancerologia, INCan) (19.9% vs. 11.9%, p = 0.001). In the molecular analysis, EGFR wild-type tumors had an increased proportion of PD-L1 positive and PD-L1 high cases (60.2% vs. 47.9%, p = 0.006 and 17.4% vs.8.5%, p = 0.004). A moderate correlation (r = 0.69) in the PD-L1 TPS% was observed between the two different settings (INCan vs. external laboratories). CONCLUSION: Clinicopathological factors were associated with an increased PD-L1 positivity rate. These differences were significant in the PD-L1 high group and associated with the academic setting, the SPS263 clone, time of archival tumor tissue <12 months, and a more recent period in the PD-L1 analysis.

Multi-trait genomic prediction improves selection accuracy for enhancing seed mineral concentrations in pea.

Multi-trait genomic selection (MT-GS) has the potential to improve predictive ability by maximizing the use of information across related genotypes and genetically correlated traits. In this study, we extended the use of sparse phenotyping method into the MT-GS framework by split testing of entries to maximize borrowing of information across genotypes and predict missing phenotypes for targeted traits without additional phenotyping expenditure. Using 300 advanced breeding lines from North Dakota State University (NDSU) pulse breeding program and ∼200 USDA accessions that were evaluated for 10 nutritional traits, our results show that the proposed sparse phenotyping aided MT-GS can further improve predictive ability by >12% across traits compared with univariate (UNI) genomic selection. The proposed strategy departed from the previous reports that weak genetic correlation is a limitation to the advantage of MT-GS over UNI genomic selection, which was evident in the partially balanced phenotyping-enabled MT-GS. Our results point to heritability and genetic correlation between traits as possible metrics to optimize and further improve the estimation of model parameters, and ultimately, prediction performance. Overall, our study offers a new approach to optimize the prediction performance using the MT-GS and further highlight strategy to maximize the efficiency of GS in a plant breeding program. The sparse-testing-aided MT-GS proposed in this study can be further extended to multi-environment, multi-trait GS to improve prediction performance and further reduce the cost of phenotyping and time-consuming data collection process.

We extended the use of sparse phenotyping into the multi-trait genomic selection (MT-GS) framework by split testing of entries. The sparse-phenotyping-aided MT-GS can increase predictive ability by >12% across traits. Heritability and genetic correlation are possible metrics to optimize and further improve prediction performance of MT-GS. The sparse-testing-aided MT-GS can be further extended to multi-environment, multi-trait GS framework.

The Arizona Prevention Research Center partnerships in Arizona to promote COVID-19 vaccine health equity.

Background: Vaccine hesitancy in the face of the COVID-19 pandemic is a complex issue that undermines our national ability to reduce the burden of the disease and control the pandemic. The COVID-19 pandemic revealed widening health disparities and disproportionate adverse health outcomes in terms of transmission, hospitalizations, morbidity and mortality among Arizona's Latinx rural, underserved, farmworker, disabled and elderly populations. In March 2021, ~8.1% of those vaccinated were Latinx, though Latinxs make up 32% of Arizona's population. The Arizona Vaccine Confidence Network (AzVCN) proposed to leverage the expertise of the Arizona Prevention Research Center (AzPRC) and the resources of the Mel and Enid Zuckerman College of Public Health (MEZCOPH) Mobile Health Unit (MHU) to identify, implement and evaluate a MHU intervention to increase uptake of COVID-19 vaccines. Methods: The AzVCN focused efforts on Latinx, rural, un/underinsured and farmworker communities in the four Arizona border counties that are at greater risk of COVID-19 morbidity and mortality and may have limited access to vaccination and other essential health services. The AzVCN used listening sessions to create a feedback loop with key stakeholders and critical health care workers to validate barriers/enablers and identify solutions to increase vaccination uptake emerging from the network. The AzVCN also implemented a community-based intervention using community health workers (CHWs) based in a MHU to increase knowledge of the COVID-19 vaccines, reduce vaccination hesitancy and increase vaccination uptake among Latinx rural, un/underinsured and farmworker populations in Southern Arizona. Results: AzVCN outcomes include: identification of enablers and barriers of COVID-19 vaccination in the priority populations; identification of strategies and solutions to address vaccine hesitancy and increase vaccine uptake among priority population; and evidence that the proposed solutions being tested through the AzVCN contribute to increased vaccine uptake among the priority populations. Conclusion: Through these efforts the AzPRC contributed to the CDC's Vaccinate with Confidence Strategy by collaborating with CHWs and other key stakeholders to engage directly with communities in identifying and addressing structural and misinformation barriers to vaccine uptake.

Will We Unlock the Benefit of Metformin for Patients with Lung Cancer? Lessons from Current Evidence and New Hypotheses.

Metformin has been under basic and clinical study as an oncological repurposing pharmacological agent for several years, stemming from observational studies which consistently evidenced that subjects who were treated with metformin had a reduced risk for development of cancer throughout their lives, as well as improved survival outcomes when diagnosed with neoplastic diseases. As a result, several basic science studies have attempted to dissect the relationship between metformin's metabolic mechanism of action and antineoplastic cellular signaling pathways. Evidence in this regard was compelling enough that a myriad of randomized clinical trials was planned and conducted in order to establish the effect of metformin treatment for patients with diverse neoplasms, including lung cancer. As with most novel antineoplastic agents, early results from these studies have been mostly discouraging, though a recent analysis that incorporated body mass index may provide significant information regarding which patient subgroups might derive the most benefit from the addition of metformin to their anticancer treatment. Much in line with the current pipeline for anticancer agents, it appears that the benefit of metformin may be circumscribed to a specific patient subgroup. If so, addition of metformin to antineoplastic agents could prove one of the most cost-effective interventions proposed in the context of precision oncology. Currently published reviews mostly rely on a widely questioned mechanism of action by metformin, which fails to consider the differential effects of the drug in lean vs. obese subjects. In this review, we analyze the pre-clinical and clinical information available to date regarding the use of metformin in various subtypes of lung cancer and, further, we present evidence as to the differential metabolic effects of metformin in lean and obese subjects where, paradoxically, the obese subjects have reported more benefit with the addition of metformin treatment. The novel mechanisms of action described for this biguanide may explain the different results observed in clinical trials published in the last decade. Lastly, we present novel hypothesis regarding potential biomarkers to identify who might reap benefit from this intervention, including the role of prolyl hydroxylase domain 3 (PHD3) expression to modify metabolic phenotypes in malignant diseases.

Metformin Enhances TKI-Afatinib Cytotoxic Effect, Causing Downregulation of Glycolysis, Epithelial-Mesenchymal Transition, and EGFR-Signaling Pathway Activation in Lung Cancer Cells.

The combination of metformin and TKIs for non-small cell lung cancer has been proposed as a strategy to overcome resistance of neoplastic cells induced by several molecular mechanisms. This study sought to investigate the effects of a second generation TKI afatinib, metformin, or their combination on three adenocarcinoma lung cancer cell lines with different EGFRmutation status. A549, H1975, and HCC827 cell lines were treated with afatinib, metformin, and their combination for 72 h. Afterwards, several parameters were assessed including cytotoxicity, interactions, apoptosis, and EGFR protein levels at the cell membrane and several glycolytic, oxidative phosphorylation (OXPHOS), and EMT expression markers. All cell lines showed additive to synergic interactions for the induction of cytotoxicity caused by the tested combination, as well as an improved pro-apoptotic effect. This effect was accompanied by downregulation of glycolytic, EMT markers, a significant decrease in glucose uptake, extracellular lactate, and a tendency towards increased OXPHOS subunits expression. Interestingly, we observed a better response to the combined therapy in lung cancer cell lines A549 and H1975, which normally have low affinity for TKI treatment. Findings from this study suggest a sensitization to afatinib therapy by metformin in TKI-resistant lung cancer cells, as well as a reduction in cellular glycolytic phenotype.

Clinical and pathological characteristics associated with the presence of the IS6110 Mycobacterim tuberculosis transposon in neoplastic cells from non-small cell lung cancer patients.

Lung cancer (LC) and pulmonary tuberculosis (TB) are the deadliest neoplastic and bacterial infectious diseases worldwide, respectively. Clinicians and pathologists have long discussed the co-existence of LC and TB, and several epidemiologic studies have presented evidence indicating that TB could be associated with the development of LC, particularly adenocarcinoma. Nonetheless, this data remains controversial, and the mechanism which could underlie the association remains largely unexplored. Some bioinformatic studies have shown that human cancer biopsies have a very high frequency of bacterial DNA integration; since Mycobacterium Tuberculosis (MTb) is an intracellular pathogen, it could play an active role in the cellular transformation. Our group performed an exploratory study in a cohort of 88 LC patients treated at the Instituto Nacional de Cancelorogía (INCan) of Mexico City to evaluate the presence of MTb DNA in LC tissue specimens. For the first time, our results show the presence of the MTb IS6110 transposon in 40.9% (n = 36/88) of patients with lung adenocarcinomas. Additionally, through in-situ PCR we identified the presence of IS6110 in the nuclei of tumor cells. Furthermore, shotgun sequencing from two samples identified traces of MTb genomes present in tumor tissue, suggesting that similar Mtb strains could be infecting both patients.

LKB1 Loss Assessed by Immunohistochemistry as a Prognostic Marker to First-Line Therapy in Advanced Non-Small-Cell Lung Cancer.

(1) Background: Liver kinase B1 (LKB1) is a tumor suppressor gene involved in cell growth and metabolism. However, its alterations are not routinely assessed for guiding therapy in clinical practice. We assessed LKB1 expression by immunohistochemistry as a potential biomarker. (2) Methods: This bicentric retrospective cohort study analyzed data from patients with advanced NSCLC who initiated platinum-based chemotherapy or epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI) between January 2016 and December 2020. Kaplan-Meier and Cox regression models were used for survival curves and multivariate analysis. (3) Results: 110 patients were evaluated, and the clinical stage IV predominated the lung adenocarcinoma histology. LKB1 loss was observed in 66.3% of cases. LKB1 loss was associated with non-smokers, the absence of wood smoke exposure and an EGFR wild-type status. The median progression-free survival (PFS) and overall survival (OS) in the population were 11.1 and 26.8 months, respectively, in the loss group, compared with cases exhibiting a positive expression. After an adjustment by age, smoking status, Eastern Cooperative Oncology Group Performance Score (ECOG-PS), EGFR status and type of administered therapy, LKB1 loss was significantly associated with worse PFS and OS. (4) Conclusion: Patients with an LKB1 loss had worse clinical outcomes. This study warrants prospective assessments to confirm the prognostic role of the LKB1 expression in advanced NSCLC.

Abordaje de la vía aérea en el paciente neuroquirúrgico / Airway approach in the neurosurgical patient

Resumen: El abordaje de la vía aérea en el paciente neuroquirúrgico presenta grandes retos debido al escenario tan complejo al cual nos enfrentamos; debemos considerar las características propias del paciente, las comorbilidades presentes y la patología neurológica por la que va a ser intervenido. Conocer la patología neurológica y las implicaciones o repercusiones que ésta puede llegar a tener en el manejo de la vía aérea ayudarán a la toma de decisiones y conocer los retos y escenarios que se pudieran presentar durante el evento anestésico-quirúrgico.

Abstract: The approach to the airway in the neurosurgical patient presents great challenges due to the complex scenario we face; we must consider the patient's own characteristics, the co-morbidities present and the neurological pathology for which it is going to be intervened. Knowing the neurological pathology and the implications or repercussions that this may have over the management of the airway will help decision making and manage the challenges and scenarios that could arise during the anesthetic surgical event.

On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence.

The endocannabinoid system (ECS) is composed of endogenous cannabinoids; components involved in their synthesis, transport, and degradation; and an expansive variety of cannabinoid receptors. Hypofunction or deregulation of the ECS is related to pathological conditions. Consequently, endogenous enhancement of endocannabinoid levels and/or regulation of their metabolism represent promising therapeutic approaches. Several major strategies have been suggested for the modulation of the ECS: (1) blocking endocannabinoids degradation, (2) inhibition of endocannabinoid cellular uptake, and (3) pharmacological modulation of cannabinoid receptors as potential therapeutic targets. Here, we focused in this review on degradation/reuptake inhibitors over cannabinoid receptor modulators in order to provide an updated synopsis of contemporary evidence advancing mechanisms of endocannabinoids as pharmacological tools with therapeutic properties for the treatment of several disorders. For this purpose, we revisited the available literature and reported the latest advances regarding the biomedical properties of fatty acid amide hydrolase and monoacylglycerol lipase inhibitors in pre-clinical and clinical studies. We also highlighted anandamide and 2-arachidonoylglycerol reuptake inhibitors with promising results in pre-clinical studies using in vitro and animal models as an outlook for future research in clinical trials.