Risk factors associated with loneliness among mexican-origin adults in southern Arizona.

This study examines factors associated with symptoms of loneliness among a sample (n = 213) of mostly Mexican-origin adults at risk of chronic diseases in Southern Arizona's Pima, Yuma, and Santa Cruz counties. It uses baseline data from a community-based participatory research partnership and multinominal logistic regression models. Controlling for chronic diseases and sociodemographic characteristics, perceived social support and hope exhibit negative main effects on loneliness when comparing individuals who experienced loneliness for 5-7 days in the preceding week with those who did not encounter such feelings during the same period (adjusted odds ratio, AOR = 0.49 and 0.47; 95% confidence interval, CI = 0.34-0.73 and 0.29-0.75, respectively). However, when considered together, perceived social support and hope display a positive and statistically significant combined effect on loneliness (AOR = 1.03; 95% CI = 1.01-1.06). Holding all covariates constant, individuals reporting loneliness for 5-7 days exhibit a relative risk ratio of 1.24 (95% CI = 1.06-1.46) for a one-unit increase in physical problem severity compared to those who do not experience loneliness. Moreover, being 65 years old or older (AOR = 0.16, 95% CI = 0.03-0.84), and having been born in Mexico and lived in the US for less than 30 years (AOR = 0.12, 95% CI = 0.02-0.74) are associated with negative main effects on loneliness when comparing individuals who experienced loneliness 1-2, and 5-7 days in the preceding week with those who did not feel loneliness during the same timeframe, respectively. Recognizing the crucial role of loneliness in shaping health outcomes for Mexican-origin adults, our findings underscore the significance of fostering supportive environments that not only enhance well-being but also cultivate robust community bonds within the US-Mexico border region.

S-allylcysteine induces cytotoxic effects in two human lung cancer cell lines via induction of oxidative damage, downregulation of Nrf2 and NF-κB, and apoptosis.

In this study, we investigated the putative cytotoxic effect elicited by the garlic-derived compound S-allylcysteine (SAC) in two human cancer cell lines (HCC827 and NCI-H1975) in order to develop an experimental approach to the therapeutic potential of this molecule for lung cancer. Cells were incubated for 24, 48 and 72 h in the presence of SAC (10 or 20 mM), which resulted in a concentration- and time-dependent decrease in cell viability and culture confluence in both cell lines. These effects were contrasted with - and validated through - those observed in an immortalized but nontumorigenic epithelial cell line from human bronchial epithelium (BEAS-2B, negative control) and an adenocarcinoma human alveolar basal epithelial cell line (A549, positive control). SAC (20 mM at 72 h) also increased the oxidative damage to lipids, augmented apoptosis, and decreased the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappa B (NF-κB) proteins in HCC827 and NCI-H1975 cells. Our results establish the efficacy of SAC in reducing malignant growth and proliferation of lung tumor cells. This effect is mediated by the induction of oxidative damage associated with the downregulation of Nrf2 and NF-κB and their corresponding signaling pathways.

Municipal police support for harm reduction services in officer-led referrals of people who inject drugs in Tijuana, Mexico.

BACKGROUND: Police constitute a structural determinant of health and HIV risk of people who inject drugs (PWID), and negative encounters with law enforcement present significant barriers to PWID access to harm reduction services. Conversely, police may facilitate access via officer-led referrals, potentiating prevention of HIV, overdose, and drug-related harms. We aimed to identify police characteristics associated with support for officer-led referrals to addiction treatment services and syringe service programs (SSP). We hypothesized that officers who believe harm reduction services are contradictory to policing priorities in terms of safety and crime reduction will be less likely to support police referrals. METHODS: Between January and June 2018, police officers (n = 305) in Tijuana, Mexico, completed self-administered surveys about referrals to harm reduction services during the 24-month follow-up visit as part of the SHIELD police training and longitudinal cohort study. Log-binomial regression was used to estimate adjusted prevalence ratios and model policing characteristics and attitudes related to officers' support for including addiction treatment and SSP in referrals. RESULTS: Respondents were primarily male (89%), patrol officers (86%) with a median age of 38 years (IQR 33-43). Overall, 89% endorsed referral to addiction services, whereas 53% endorsed SSP as acceptable targets of referrals. Officers endorsing addiction services were less likely to be assigned to high drug use districts (adjusted prevalence ratio [APR] = 0.50, 95% CI 0.24, 1.08) and more likely to agree that methadone programs reduce crime (APR = 4.66, 95% CI 2.05, 9.18) than officers who did not support addiction services. Officers endorsing SSPs were younger (adjusted prevalence ratio [APR] = 0.96 95% CI 0.93, 0.98), less likely to be assigned to high drug use districts (APR = 0.50, 95% CI 0.29, 0.87), more likely to believe that methadone programs reduce crime (APR = 2.43, 95% CI 1.30, 4.55), and less likely to believe that SSPs increase risk of needlestick injury for police (APR = 0.44, 0.27, 0.71). CONCLUSIONS: Beliefs related to the occupational impact of harm reduction services in terms of officer safety and crime reduction are associated with support for referral to related harm reduction services. Efforts to deflect PWID from carceral systems toward harm reduction by frontline police should include measures to improve officer knowledge and attitudes about harm reduction services as they relate to occupational safety and law enforcement priorities. TRIAL REGISTRATION: NCT02444403.

Interactive Versus Video-Based Training of Police to Communicate Syringe Legality to People Who Inject Drugs: The SHIELD Study, Mexico, 2015-2016.

Objectives. To assess how instructional techniques affect officers' intent to communicate syringe legality during searches in Tijuana, Mexico, where pervasive syringe confiscation potentiates risk of HIV and HCV among people who inject drugs (PWID) and of occupational needle-stick injury among police. Methods. Using the SHIELD (Safety and Health Integration in the Enforcement of Laws on Drugs) model, Tijuana police underwent training to encourage communication of syringe possession legality to PWID. Trainees received either passive video or interactive role-play exercise on safer search techniques. We used logistic regression to assess the training's impact on self-reported intent to communicate syringe legality by training type and gender. Results. Officers (n = 1749) were mostly men (86%) assigned to patrol (84%). After the training, intent to communicate the law improved markedly: from 20% to 39% (video group) and 20% to 58% (interactive group). Gender and training type significantly predicted intent to communicate syringe legality. Male and female officers' adjusted odds ratios in the interactive group were 5.37 (95% confidence interval [CI] = 4.56, 6.33) and 9.16 (95% CI = 5.88, 14.28), respectively, after the training. Conclusions. To more effectively persuade police to endorse harm reduction and occupational safety practices, police trainings should include interactive elements.

Levels of peripheral blood polymorphonuclear myeloid-derived suppressor cells and selected cytokines are potentially prognostic of disease progression for patients with non-small cell lung cancer.

Polymorphonuclear-MDSC (PMN-MDSC) have emerged as an independent prognostic factor for survival in NSCLC. Similarly, cytokine profiles have been used to identify subgroups of NSCLC patients with different clinical outcomes. This prospective study investigated whether the percentage of circulating PMN-MDSC, in conjunction with the levels of plasma cytokines, was more informative of disease progression than the analysis of either factor alone. We analyzed the phenotypic and functional profile of peripheral blood T-cell subsets (CD3+, CD3+CD4+ and CD3+CD8+), neutrophils (CD66b+) and polymorphonuclear-MDSC (PMN-MDSC; CD66b+CD11b+CD15+CD14-) as well as the concentration of 14 plasma cytokines (IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12 p70, IL-17A, IL-27, IL-29, IL-31, and IL-33, TNF-α, IFN-γ) in 90 treatment-naïve NSCLC patients and 25 healthy donors (HD). In contrast to HD, NSCLC patients had a higher percentage of PMN-MDSC and neutrophils (P < 0.0001) but a lower percentage of CD3+, CD3+CD4+ and CD3+CD8+ cells. PMN-MDSC% negatively correlated with the levels of IL1-ß, IL-2, IL-27 and IL-29. Two groups of patients were identified according to the percentage of circulating PMN-MDSC. Patients with low PMN-MDSC (≤ 8%) had a better OS (22.1 months [95% CI 4.3-739.7]) than patients with high PMN-MDSC (9.3 months [95% CI 0-18.8]). OS was significantly different among groups of patients stratified by both PMN-MDSC% and cytokine levels. In sum, our findings provide evidence suggesting that PMN-MDSC% in conjunction with the levels IL-1ß, IL-27, and IL-29 could be a useful strategy to identify groups of patients with potentially unfavorable prognoses.

Improving police conceptual knowledge of Mexico's law on cannabis possession: Findings from an assessment of a police education program.

BACKGROUND AND OBJECTIVES: Policing practices do not reflect recent decriminalization of drug possession in Mexico. We assessed knowledge of cannabis law as part of a police education program (PEP) post-drug law reform in Tijuana. METHODS: Officers took pre-/post-PEP surveys; random subsample (n = 759) received follow-up assessments. Longitudinal logistic regression (pre-, post-, 3-months post-PEP) measured knowledge of cannabis law. RESULTS: PEP increased conceptual knowledge of cannabis law from baseline to post-training (AOR = 56.1, CI: 41.0-76.8) and 3 months post-PEP (AOR = 11.3, CI: 9.0-14.2). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: PEPs improve police knowledge of cannabis law. Reforms should be bundled with PEPs to improve policy implementation. (Am J Addict 2018;XX:XX-XX).

Factors associated with extrajudicial arrest for syringe possession: results of a department-wide survey of municipal police in Tijuana, Mexico.

BACKGROUND: Mexican law permits syringe purchase and possession without prescription. Nonetheless, people who inject drugs (PWID) frequently report arrest for syringe possession. Extrajudicial arrests not only violate human rights, but also significantly increase the risk of blood-borne infection transmission and other health harms among PWID and police personnel. To better understand how police practices contribute to the PWID risk environment, prior research has primarily examined drug user perspectives and experiences. This study focuses on municipal police officers (MPOs) in Tijuana, Mexico to identify factors associated with self-reported arrests for syringe possession. METHODS: Participants were active police officers aged ≥18 years, who completed a self-administered questionnaire on knowledge, attitudes and behaviors related to occupational safety, drug laws, and harm reduction strategies. Univariable and multivariable logistic regression was used to identify correlates of recent syringe possession arrest. RESULTS: Among 1044 MPOs, nearly half (47.9%) reported always/sometimes making arrests for syringe possession (previous 6mo). Factors independently associated with more frequent arrest included being male (Adjusted Odds Ratio [AOR] = 1.62; 95% Confidence Interval [95% CI] =1.04-2.52; working in a district along Tijuana River Canal (where PWID congregate) (AOR = 2.85; 95%CI = 2.16-3.77); having recently experienced a physical altercation with PWID (AOR = 2.83; 95% CI = 2.15-3.74); and having recently referred PWID to social and health services (AOR = 1.97; 95% CI = 1.48-2.61). Conversely, odds were significantly lower among officers reporting knowing that syringe possession is legal (AOR = 0.61; 95% CI = 0.46-0.82). CONCLUSIONS: Police and related criminal justice stakeholders (e.g., municipal judges, prosecutors) play a key role in shaping PWID risk environment. Findings highlight the urgent need for structural interventions to reduce extra-judicial syringe possession arrests. Police training, increasing gender and other forms of diversity, and policy reforms at various governmental and institutional levels are necessary to reduce police occupational risks, improve knowledge of drug laws, and facilitate harm reduction strategies that promote human rights and community health.

Interplay between Cellular and Molecular Inflammatory Mediators in Lung Cancer.

Inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Chronic inflammation plays a critical role in tumorigenesis. Tumor infiltrating inflammatory cells mediate processes associated with progression, immune suppression, promotion of neoangiogenesis and lymphangiogenesis, remodeling of extracellular matrix, invasion and metastasis, and, lastly, the inhibition of vaccine-induced antitumor T cell response. Accumulating evidence indicates a critical role of myeloid cells in the pathophysiology of human cancers. In contrast to the well-characterized tumor-associated macrophages (TAMs), the significance of granulocytes in cancer has only recently begun to emerge with the characterization of tumor-associated neutrophils (TANs). Recent studies show the importance of CD47 in the interaction with macrophages inhibiting phagocytosis and promoting the migration of neutrophils, increasing inflammation which can lead to recurrence and progression in lung cancer. Currently, therapies are targeted towards blocking CD47 and enhancing macrophage-mediated phagocytosis. However, antibody-based therapies may have adverse effects that limit its use.

RB mutation and RAS overexpression induce resistance to NK cell-mediated cytotoxicity in glioma cells.

Several theories aim to explain the malignant transformation of cells, including the mutation of tumor suppressors and proto-oncogenes. Deletion of Rb (a tumor suppressor), overexpression of mutated Ras (a proto-oncogene), or both, are sufficient for in vitro gliomagenesis, and these genetic traits are associated with their proliferative capacity. An emerging hallmark of cancer is the ability of tumor cells to evade the immune system. Whether specific mutations are related with this, remains to be analyzed. To address this issue, three transformed glioma cell lines were obtained (Rb(-/-), Ras(V12), and Rb(-/-)/Ras(V12)) by in vitro retroviral transformation of astrocytes, as previously reported. In addition, Ras(V12) and Rb(-/-)/Ras(V12) transformed cells were injected into SCID mice and after tumor growth two stable glioma cell lines were derived. All these cells were characterized in terms of Rb and Ras gene expression, morphology, proliferative capacity, expression of MHC I, Rae1δ, and Rae1αßγδε, mult1, H60a, H60b, H60c, as ligands for NK cell receptors, and their susceptibility to NK cell-mediated cytotoxicity. Our results show that transformation of astrocytes (Rb loss, Ras overexpression, or both) induced phenotypical and functional changes associated with resistance to NK cell-mediated cytotoxicity. Moreover, the transfer of cell lines of transformed astrocytes into SCID mice increased resistance to NK cell-mediated cytotoxicity, thus suggesting that specific changes in a tumor suppressor (Rb) and a proto-oncogene (Ras) are enough to confer resistance to NK cell-mediated cytotoxicity in glioma cells and therefore provide some insight into the ability of tumor cells to evade immune responses.

Varias teorías pretenden explicar la transformación maligna de las células, como es la mutación de genes supresores de tumor y proto-oncogenes. La deleción de Rb (un supresor de tumor), la sobreexpresión de Ras mutado (un proto-oncogén), o ambos, son suficientes para desarrollar gliomagénesis in vitro, y estas características genéticas se asocian con su alta tasa de proliferación. Un rasgo distintivo del cáncer es la capacidad de las células tumorales para evadir el sistema inmune. Por lo que en este estudio analizamos si las mutaciones específicas están relacionadas con la evasión de la respuesta inmune. Para abordar esta cuestión, tres líneas celulares de glioma transformadas se obtuvieron (Rb−/−, RasV12, y Rb−/−/RasV12) mediante transformación retroviral de astrocitos in vitro, reportado anteriormente. Además, las células transformadas RasV12 y Rb−/−/RasV12 fueron inyectadas en ratones SCID y después del crecimiento del tumor se obtuvieron dos líneas celulares de glioma estables. En todas las células se determinaron la expresión génica Rb y Ras, morfología, capacidad de proliferación, expresión de MHC I, Rae1δ, and Rae1αßγδε, mult1, H60a, H60b, H60c, como ligandos para receptores de células NK, y su susceptibilidad a la citotoxicidad mediada por células NK. Nuestros resultados muestran que la transformación de los astrocitos (pérdida de Rb, la sobreexpresión de Ras, o ambos) indujo cambios fenotípicos y funcionales asociados con la resistencia a la citotoxicidad mediada por células NK. Además, la transferencia de astrocitos transformados dentro de ratones SCID aumento la resistencia a la citotoxicidad mediada por células NK, lo que se sugiere que los cambios específicos en un supresor de tumores (Rb) y un proto-oncogén (Ras) son suficientes para conferir resistencia a la citotoxicidad mediada por células NK en células de glioma y, por tanto, proporcionar una idea de la capacidad de las células tumorales para evadir la respuesta inmune.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.