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Skin melanoma is one of the most common cancer types in the United States and worldwide, and its incidence continues to grow. Primary skin melanoma can be removed surgically when feasible and if detected at an early stage. Anti-cancer drugs can be applied topically to treat skin cancer lesions and used as an adjunct to surgery to prevent the recurrence of tumor growth. We developed a topical formulation composed of Navitoclax (NAVI), a BCL-2 inhibitor that results in apoptosis, and an ionic liquid of choline octanoate (COA) to treat early-stage melanoma. NAVI is a small hydrophobic molecule that solubilizes at 20% (w/v) when dissolved in 50% COA. Although NAVI is a highly effective chemotherapeutic, it is equally thrombocytopenic. We found that COA-mediated topical delivery of NAVI enhanced its penetration into the skin and held the drug in the deeper skin layers for an extended period. Topical delivery of NAVI produced a higher cancer-cell killing efficacy than orally administrated NAVI. In vivo experiments in a mouse model of human melanoma-induced skin cancer confirmed the formulation's effectiveness via an apoptotic mechanism without any significant skin irritation or systemic absorption of NAVI. Overall, this topical approach may provide a safe and effective option for better managing skin cancer in the clinic.

Cancer remains the second most common cause of death in the US. Due to a recurrent problem with anticancer drug resistance, there is a current need for anticancer drugs with distinct modes of action for combination drug therapy We have tested two novel piperidone compounds, named 2608 (1-dichloroacetyl - 3,5-bis(3,4-difluorobenzylidene)-4-piperidone) and 2610 (1-dichloroacetyl-3,5-bis(3,4-dichlorobenzylidene)-4-piperidone), for their potential cytotoxicity on numerous human cancer cell lines. We found that both compounds were cytotoxic for breast, pancreatic, leukemia, lymphoma, colon, and fibroblast cell lines, with a cytotoxic concentration 50% (CCsub50/sub) in the low micromolar to nanomolar concentration range. Further assays focused primarily on an acute lymphoblastic lymphoma and colon cancer cell lines since they were the most sensitive and resistant to the experimental piperidones. The cell death mechanism was evaluated through assays commonly used to detect the induction of apoptosis. These assays revealed that both 2608 and 2610 induced reactive oxygen species (ROS) accumulation, mitochondrial depolarization, and activated caspase-3/7. Our findings suggest that the piperidones induced cell death via the intrinsic apoptotic pathway. Additional assays revealed that both piperidones cause cell cycle alteration in lymphoma and colon cell lines. Both piperidones elicited DNA fragmentation, as evidenced by an increment in the sub-G0/G1 subpopulation in both cell lines. Similar to other related compounds, both piperidones were found to act as proteasome inhibitors by increasing the levels of poly-ubiquitinated proteins in both lymphoma and colon cell lines. Hence, the two piperidones exhibited attractive cytotoxic properties and suitable mechanisms of action, which makes them good candidates as anticancer drugs.

Objective The purpose of this study was to evaluate the in vitro antibacterial effects of a p‐Cymene‐based bis(pyrazolyl)methane derivative (SC‐19) to advance in developing alternative therapeutic compounds to fight against bacterial isolates from patients with otitis externa (OE). Methods Eighteen swab specimens were collected from patients aged over 18 years diagnosed with OE within at least 7 days of symptom onset, contaminated by only one bacterium type: Pseudomonas aeruginosa (n = 5); Staphylococcus aureus (n = 8); Klebsiella aerogenes (n = 2); Serratia marcescens (n = 1); Morganella morganii (n = 2). To appraise antibacterial activity, minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC) assays were run at different SC‐19 concentrations. Results When using SC‐19, S. aureus strains showed less bacterial growth, but no bactericidal effect was observed. The MIC and MBC of SC‐19 were 62.5 and 2000 μg/ml against S. aureus and were >2000 μg/ml against the other isolates obtained from OE, respectively. In addition, the MBICs and MBECs of SC‐19 against S. aureus were 125 and >2000 μg/ml, respectively. Conclusion Nowadays the acquired antibiotic resistance phenomenon has stimulated research into novel and more efficient therapeutic agents. Hence, we report that, helped by the structural diversity fostered herein by a range of bis(pyrazolyl)methane derivatives, SC‐19 can be a promising alternative therapeutic option for treating OE caused by S. aureus given the observed effects on both planktonic state and biofilm. Level of Evidence IV

Osteomyelitis is an inflammatory process of bone and bone marrow that may even lead to patient death. Even though this disease is mainly caused by Gram-positive organisms, the proportion of bone infections caused by Gram-negative bacteria, such as Escherichia coli, has significantly increased in recent years. In this work, mesoporous silica nanoparticles have been employed as platform to engineer a nanomedicine able to eradicate E. coli- related bone infections. For that purpose, the nanoparticles have been loaded with moxifloxacin and further functionalized with Arabic gum and colistin (AG+CO-coated MX-loaded MSNs). The nanosystem demonstrated high affinity toward E. coli biofilm matrix, thanks to AG coating, and marked antibacterial effect because of the bactericidal effect of moxifloxacin and the disaggregating effect of colistin. AG+CO-coated MX-loaded MSNs were able to eradicate the infection developed on a trabecular bone in vitro and showed pronounced antibacterial efficacy in vivo against an osteomyelitis provoked by E. coli. Furthermore, AG+CO-coated MX-loaded MSNs were shown to be essentially non-cytotoxic with only slight effect on cell proliferation and mild hepatotoxicity, which might be attributed to the nature of both antibiotics. In view of these results, these nanoparticles may be considered as a promising treatment for bone infections caused by enterobacteria, such as E. coli, and introduce a general strategy against bone infections based on the implementation of antibiotics with different but complementary activity into a single nanocarrier. Statement of significance: In this work, we propose a methodology to address E.coli bone infections by using moxifloxacin-loaded mesoporous silica nanoparticles coated with Arabic gum containing colistin (AG+CO-coated MX-loaded MSNs). The in vitro evaluation of this nanosystem demonstrated high affinity toward E. coli biofilm matrix thanks to the Arabic gum coating, a disaggregating and antibacterial effect of colistin, and a remarkable antibiofilm action because of the bactericidal ability of moxifloxacin and colistin. This anti-E. coli capacity of AG+CO-coated MX-loaded MSNs was brought out in an in vivo rabbit model of osteomyelitis where the nanosystem was able to eradicate more than 90% of the bacterial load within the infected bone, Financial support from the Eu-ropean Research Council through ERC-2015-AdG-694160 (VERDI) grant. AM is funded by grants from Instituto de Salud Carlos III through the “Miguel Servet” program (CP15/00053)

Introducción: desde el inicio de la pandemia de COVID-19 en la Argentina se estableció la identificación y seguimiento de casos y contactos estrechos como una estrategia clave para cortar la cadena de transmisión del virus. Desde el Hospital Italiano de Buenos Aires se desarrolló un circuito de llamados telefónicos a casos y contactos estrechos para brindar pautas de alarma, medidas de aislamiento domiciliario y detectar situaciones que requieran acciones de gestión. Materiales y métodos: ante el aumento de casos en el mes de junio de 2020, el “Voluntariado para el Abordaje Epidemiológico de casos COVID-19 y detección de contactos estrechos” surge como propuesta para incorporar estudiantes de grado al circuito de llamados. Durante el período julio-octubre se desarrollaron tres cohortes consecutivas y participaron 51 estudiantes de distintas carreras de salud del Instituto Universitario del Hospital Italiano de Buenos Aires. Este trabajo se enmarca en una sistematización de experiencias como propuesta metodológica para la cual se conformó un equipo integrado por coordinadores/as y estudiantes. Objetivos: analizar el voluntariado implementado desde el marco de la sistematización de experiencias. Además, este trabajo se propone describir el desarrollo y las estrategias de capacitación, organización y comunicación e indagar en los sentidos que tuvo el voluntariado para los/as estudiantes. Resultados: se contactó al 20% (n = 1226) del total de los 6068 casos positivos del Hospital Italiano de Buenos Aires en dicho período y se derivaron 195 acciones de gestión. Desde la perspectiva de los/as voluntarios/as se destacó la posibilidad de tener contacto con pacientes, desarrollar habilidades comunicacionales y sentir que aportaron un “granito de arena” en el contexto de pandemia. Conclusiones: el voluntariado excedió los objetivos iniciales del circuito de llamados, para transformarse en un espacio de aprendizaje, intercambio y formación. Este trabajo invita a reflexionar sobre los perfiles profesionales del campo de la salud y a dialogar con propuestas formativas basadas en el aprendizaje complejo y el encuentro con escenarios reales.

The E. E. Just Award commemorates the great African-American cell biologist Dr. Ernest Everett Just, who was a successful pioneer in an era of systemic exclusion of minorities in science and academia. Receiving this award is not only an honor but a recognition of my long-standing commitment to helping Persons Excluded due to Ethnicity or Race (PEERS) to achieve success in biomedical careers. As a proud member of this group, I have devoted most of my career to training underrepresented undergraduate and graduate students to pursue scientific careers. My early work as a molecular immunologist focused on the search for enzymes involved in antigen–receptor gene recombination, as well as the characterization of nuclear factors involved in recombination and the transcriptional regulation of the murine recombination-activating genes. Over the past two decades, my research has focused on discovering and evaluating novel anticancer agents that can be used to treat various cancer types.

Background Identifying patients with cardiac sarcoidosis (CS) who are at increased risk of sudden cardiac death (SCD) is imperative. Current guideline recommendations for implantable cardioverter-defibrillator (ICD) implantation in patients with CS are based on small observational studies and have not been validated in contemporary cohorts using multimodality cardiac imaging. Purpose The aim of this study was to characterize a cohort of patients with tissue-proven cardiac sarcoidosis who underwent multimodality cardiac imaging and identify predictors of appropriate ICD shock and mortality. Methods We retrospectively identified subjects with a diagnosis of CS established by clinical/imaging criteria, and tissue biopsy (N=273) seen at our tertiary care center between 2001 and 2021. Clinical characteristics and outcomes were collected from electronic medical records. The primary endpoint of interest was a composite of appropriate ICD shock and all-cause mortality. Secondary endpoints were individual rates of appropriate ICD shock and all-cause mortality. Cox proportional hazard regression analysis was used to identify independent predictors of the outcomes. Results Mean age was 59±11 years and 40% were female. Isolated CS was found in 49 subjects (17.9%). The prevalence of traditional cardiovascular risk factors was low. Atrial fibrillation prevalence was high (41%). After a median follow-up of 7.9 years, the rate of appropriate ICD shock and all-cause mortality was 29% (N=79). The 5-year overall survival rate of 97.5%. Age, left ventricular ejection fraction (LVEF), and delayed gadolinium enhancement (DGE) in cardiac magnetic resonance (CMR) were independent predictors of the primary composite endpoint; LVEF and DGE in CMR were independent predictors of appropriate ICD-shock; and LVEF and baseline serum NT proBNP were independent predictors of overall mortality. An LVEF of 47% was identified as the optimal cutoff in predicting the primary composite endpoint. Presence of scar, inflammation or mismatch pattern in positron emission tomography were not significant predictors of the outcomes. Conclusion In this large cohort of subjects with CS, we found that the presence of DGE in CMR was the strongest independent predictor of the composite endpoint of appropriate ICD-shock and mortality and of appropriate ICD-shock individually; LVEF by echocardiogram was an independent predictor of the primary and secondary endpoints with an optimal LVEF cutoff for predicting the composite endpoint of 47%. Funding Acknowledgement Type of funding sources: None.

Background: Tumor-associated antigens (TAAs) have been investigated for many years as potential early diagnosis tools, especially for hepatocellular carcinoma (HCC). Nonetheless, very few studies have focused on the Hispanic HCC group that may be associated with distinct etiological risk factors. In the present study, we investigated novel anti-TAA autoantibodies as diagnostic biomarkers for Hispanic HCC patients. Methods: Novel TAA targets were identified by the serological proteome analysis (SERPA) and from differentially expressed HCC driver genes via bioinformatics. The autoantibody levels were validated by enzyme-linked immunosorbent assay (ELISA). Results: Among 19 potential TAA targets, 4 anti-TAA autoantibodies were investigated as potential diagnostic biomarkers with significantly high levels in Hispanic HCC sera, including DNA methyltransferase 3A (DNMT3A), p16, Hear shock protein 60 (Hsp60), and Heat shock protein A5 (HSPA5). The area under the ROC curve (AUC) value of the single autoantibodies varies from 0.7505 to 0.8885. After combining all 4 autoantibodies, the sensitivity of the autoantibody panel increased to 75% compared to the single one with the highest value of 45.8%. In a separate analysis of the Asian cohort, autoantibodies against HSPA5 and p16 showed significantly elevated levels in HCC compared to normal healthy controls, but not for DNMT3A or HSP60. Conclusion: Anti-DNMT3A, p16, HSPA5, and HSP60 autoantibodies have the potential to be diagnostic biomarkers for Hispanic HCC patients, of which DNMT3A and HSP60 might be exclusive for Hispanic HCC diagnosis.

Background Cancer is an ongoing worldwide health problem. Although chemotherapy remains the mainstay therapy for cancer, it is not always effective and has detrimental side effects. Here, we present piperidone compounds P3, P4, and P5 that selectively target cancer cells via protein- and stress-mediated mechanisms. Methods We assessed typical apoptotic markers including phosphatidylserine externalization, caspase-3 activation, and DNA fragmentation through flow cytometry. Then, specific markers of the intrinsic pathway of apoptosis including the depolarization of the mitochondria and the generation of reactive oxygen species (ROS) were investigated. Finally, we utilized western blot techniques, RT-qPCR, and observed the cell cycle profile after compound treatment to evaluate the possible behavior of these compounds as proteasome inhibitors. For statistical analyses, we employed the one-way ANOVA followed by Bonferroni post hoc test. Results P3, P4, and P5 induce cytotoxic effects towards tumorigenic cells, as opposed to non-cancerous cells, at the low micromolar range. Compound treatment leads to the activation of the intrinsic pathway of apoptosis. The accumulation of poly-ubiquitinated proteins and the pro-apoptotic protein Noxa, both typically observed after proteasome inhibition, occurs after P3, P4, and P5 treatment. The stress-related genes PMAIP1, ATF3, CHAC1, MYC, and HMOX-1 were differentially regulated to contribute to the cytotoxic activity of P3–P5. Finally, compound P5 causes cell cycle arrest at the G2/M phase. Conclusion Taken together, compounds P3, P4, and P5 exhibit strong potential as anticancer drug candidates as shown by strong cytotoxic potential, activation of the intrinsic pathway of apoptosis, and show typical proteasome inhibitor characteristics.

This study was designed to propose alternative therapeutic compounds to fight against bacterial pathogens. Thus, a library of nitrogen-based compounds bis(triazolyl)methane (1T–7T) and bis(pyrazolyl)methane (1P–11P) was synthesised following previously reported methodologies and their antibacterial activity was tested using the collection strains of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Moreover, the novel compound 2P was fully characterized by IR, UV–Vis and NMR spectroscopy. To evaluate antibacterial activity, minimal inhibitory concentrations (MICs), minimal bactericidal concentrations (MBCs), minimum biofilm inhibitory concentrations (MBICs), and minimum biofilm eradication concentrations (MBECs) assays were carried out at different concentrations (2–2000 µg/mL). The MTT assay and Resazurin viability assays were performed in both human liver carcinoma HepG2 and human colorectal adenocarcinoma Caco-2 cell lines at 48 h. Of all the synthesised compounds, 2P had an inhibitory effect on Gram-positive strains, especially against S. aureus. The MIC and MBC of 2P were 62.5 and 2000 µg/mL against S. aureus, and 250 and 2000 µg/mL against E. faecalis, respectively. However, these values were > 2000 µg/mL against E. coli and P. aeruginosa. In addition, the MBICs and MBECs of 2P against S. aureus were 125 and > 2000 µg/mL, respectively, whereas these values were > 2000 µg/mL against E. faecalis, E. coli, and P. aeruginosa. On the other hand, concentrations up to 250 µg/mL of 2P were non-toxic doses for eukaryotic cell cultures. Thus, according to the obtained results, the 2P nitrogen-based compound showed a promising anti-Gram-positive effect (especially against S. aureus) both on planktonic state and biofilm, at non-toxic concentrations.

In recent years, the thienopyrazole moiety has emerged as a pharmacologically active scaffold with antitumoral and kinase inhibitory activity. In this study, high-throughput screening of 2000 small molecules obtained from the ChemBridge DIVERset library revealed a unique thieno[2,3-c]pyrazole derivative (Tpz-1) with potent and selective cytotoxic effects on cancer cells. Compound Tpz-1 consistently induced cell death at low micromolar concentrations (0.19 μM to 2.99 μM) against a panel of 17 human cancer cell lines after 24 h, 48 h, or 72 h of exposure. Furthermore, an in vitro investigation of Tpz-1’s mechanism of action revealed that Tpz-1 interfered with cell cycle progression, reduced phosphorylation of p38, CREB, Akt, and STAT3 kinases, induced hyperphosphorylation of Fgr, Hck, and ERK 1/2 kinases, and disrupted microtubules and mitotic spindle formation. These findings support the continued exploration of Tpz-1 and other thieno[2,3-c]pyrazole-based compounds as potential small-molecule anticancer agents.

Infection is one of the most common causes that leads to joint prosthesis failure. In the present work, biodegradable sol-gel coatings were investigated as a promising controlled release of antibiotics for the local prevention of infection in joint prostheses. Accordingly, a sol-gel formulation was designed to be tested as a carrier for 8 different individually loaded antimicrobials. Sols were prepared from a mixture of MAPTMS and TMOS silanes, tris(tri-methylsilyl)phosphite, and the corresponding antimicrobial. In order to study the cross-linking and surface of the coatings, a battery of examinations (Fourier-transform infrared spectroscopy, solid-state 29Si-NMR spectroscopy, thermogravimetric analysis, SEM, EDS, AFM, and water contact angle, thickness, and roughness measurements) were conducted on the formulations loaded with Cefoxitin and Linezolid. A formulation loaded with both antibiotics was also explored. Results showed that the coatings had a microscale roughness attributed to the accumulation of antibiotics and organophosphites in the surface protrusions and that the existence of chemical bonds between antibiotics and the siloxane network was not evidenced. This research was funded by the Regional Government of Madrid through the program ADITIMAT (ref. P2018/NMT-4411) and CIBERINFEC-CIBER of Infectious Diseases (CB21/13/00043). B.T. would like to thank the Spanish Ministry of Education, Culture, and Sports for the support through FPU grant (FPU17/05977).

Triple-negative breast cancer (TNBC) represents approximately 15-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women and has more aggressive course. The biology of TNBC in HL women has been poorly characterized, but some data suggest that molecular drivers of breast cancer might be different. Chemotherapy remains the only option for those patients. There is no clinical tool to help medical oncologist with the decision about appropriate individual chemotherapy, as well as no way to predict long-term outcomes. The aim of the study was to characterize individual patient gene expression profiles and to identify the relationship with clinical outcomes.Patients and Methods: From 2012-2019, we collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. All specimens were carefully examined by pathologists for adequacy and for a hormonal status. We analyzed gene mutation profiles of collected tumors and associated results with individual patient’s clinical history and outcomes.Results: Of 25 patients with TNBC, 24 (96%) identified as HL, one patient as NHL. Twenty-one (84%) had stage III/IV disease, and four (16%) had stage II at the diagnosis. Most commonly mutated genes were: TP53, Notch, AKT, MEP3K, PIK3CA and EGFR. Compared to other international cancer databases mostly included NHW, AA and Asian women, our study demonstrated statistically significant higher frequencies of those among HL women. With TNBC. Also a worse clinical course was among those patients whose tumor had mutations in Notch and PIK3CA. Conclusion: In conclusion, this study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could be different in HL women. Therefore, a deeper understanding of the biological mechanisms behind Notch, PIK3CA mutation, might lead to a new treatment approach. Citation Format: Alexander Philipovskiy, Alok Dwivedi, Roberto Gamez, Richard McCallum, Zeina Nahleh, Renato Aguilera, Sumit Gaur. Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-45.

STUDY QUESTION Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their ‘traffic light’ system for infertility treatment ‘add-ons’. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER Core Outcome Measures in Effectiveness Trials Initiative: 1023.

AIM The purpose of this study was to determine the level of adherence to adjuvant aromatase inhibitor (AI) therapy and factors associated with non-adherence among Hispanic/Latino women with hormonal receptor-positive breast cancer (BC) treated at an academic center at the American-Mexican border city of El Paso, TX. PATIENTS AND METHODS Institutional Review Board approval was obtained in this cross-sectional study using the validated Morisky Medication Adherence Scale to assess patient adherence to AI therapy. Patients diagnosed with stage I-III hormonal receptor-positive, human epidermal growth factor receptor 2-negative BC who were on adjuvant AIs therapy were recruited from the Texas Tech University Health Sciences Center El Paso breast clinic. RESULTS Between September 2017 and August 2018, 122 consecutive patients were enrolled; 119 were analyzed, three were lost to follow up. The mean age was 61.6±9.4 years, and 109 (91.6%) self-identified as Hispanic/Latino. A total of 58% reported an annual income of $15,000 or less. Overall, 40.3% had completed eighth grade or less education, 31.9% high school, and 12% had obtained a technical degree. The majority of patients (56%) had either a medium (45%) or a low level of adherence (11%). High adherence was noted in 44% of participants. Seven (5.6%) patients scored 2 or below on a 4-point scale for intentional adherence, and 18 (13.5%) scored 2 or below on a 4-point scale for unintentional adherence. CONCLUSION These data suggest that the majority of Hispanic/Latino women with breast cancer have medium or low levels of adherence to therapy with AIs. Factors associated with medium and low adherence were unintentional (forgetfulness), but also included intentional factors, such as avoidance of adverse effects and delays with obtaining refills (cost-related nonadherence).

Background: Breast cancer is the most frequently diagnosed cancer in women worldwide. Pyronaridine (PND), an antimalarial drug, was shown to exert anticancer activity on seventeen different human cancer cells, seven from female breast tissue. Additionally, PND induced apoptosis via mitochondrial depolarization, alteration of cell cycle progression, and DNA intercalation. However, the molecular target of PND in cells was not elucidated. Objective: Here, we have further investigated PND's mode of action by using transcriptome analysis. Preclinical studies were also performed to determine whether PND could affect tumor progression in a human breast cancer xenograft in mice. Moreover, we assessed the combined efficacy of PND with well-known anticancer drugs. Methods: Transcriptome analyses of PND-treated cancer cells were performed. Topoisomerase II activity was evaluated by an in vitro assay. In addition, daily oral administration of PND was given to mice with human breast cancer xenografts. The differential nuclear staining assay measured in- -vitro cell toxicity. Results: The transcriptome signatures suggested that PND might act as a topoisomerase II inhibitor. Thus, topoisomerase inhibition assays were performed, providing evidence that PND is a bona fide topoisomerase II inhibitor. Also, in-vivo studies suggest that PND hinders tumor progression. Besides, combination studies of PND with anticancer drugs cisplatin and gemcitabine revealed higher cytotoxicity against cancer cells than individual drug administration. Conclusion: The findings provide evidence that PND is a topoisomerase II inhibitor and can hinder cancer progression in an animal model, further demonstrating PND's favorable characteristics as a repurposed anticancer drug.

Funded by the National Institutes of Health (NIH), the Research Centers in Minority Institutions (RCMI) Program fosters the development and implementation of innovative research aimed at improving minority health and reducing or eliminating health disparities. Currently, there are 21 RCMI Specialized (U54) Centers that share the same framework, comprising four required core components, namely the Administrative, Research Infrastructure, Investigator Development, and Community Engagement Cores. The Research Infrastructure Core (RIC) is fundamentally important for biomedical and health disparities research as a critical function domain. This paper aims to assess the research resources and services provided and evaluate the best practices in research resources management and networking across the RCMI Consortium. We conducted a REDCap-based survey and collected responses from 57 RIC Directors and Co-Directors from 98 core leaders. Our findings indicated that the RIC facilities across the 21 RCMI Centers provide access to major research equipment and are managed by experienced faculty and staff who provide expert consultative and technical services. However, several impediments to RIC facilities operation and management have been identified, and these are currently being addressed through implementation of cost-effective strategies and best practices of laboratory management and operation.

A novel series of 1-[3-{3,5-bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone oximes 3a–h and related quaternary ammonium salts 4a–h were prepared as candidate antineoplastic agents. Evaluation against neoplastic Ca9-22, HSC-2 and HSC-4 cells revealed the compounds in series 3 and 4 to be potent cytotoxins with submicromolar CC50 values in virtually all cases. In contrast, the compounds were less cytocidal towards HGF, HPLF and HPC non-malignant cells revealing their tumour-selective toxicity. Quantitative structure–activity relationships revealed that, in general, both cytotoxic potency and selectivity index figures increased as the magnitude of the Hammett sigma values rose. In addition, 3a–h are cytotoxic towards a number of leukemic and colon cancer cells. 4b,c lowered the mitochondrial membrane potential in CEM cells, and 4d induced transient G2/M accumulation in Ca9-22 cells. Five compounds, namely 3c,d and 4c–e, were identified as lead molecules that have drug-like properties.

The purpose of this study was to evaluate the in vitro antibacterial effects of aEighteen swab specimens were collected from patients aged over 18 years diagnosed with OE within at least 7 days of symptom onset, contaminated by only one bacterium type:When using SC-19,Nowadays the acquired antibiotic resistance phenomenon has stimulated research into novel and more efficient therapeutic agents. Hence, we report that, helped by the structural diversity fostered herein by a range of bis(pyrazolyl)methane derivatives, SC-19 can be a promising alternative therapeutic option for treating OE caused byIV.

Particle-type solutions are observed in out-of-equilibrium systems. These states can be motionless, oscillatory, or propagative depending on the injection and dissipation of energy. We investigate a family of localized standing waves based on a liquid-crystal light valve with spatiotemporal modulated optical feedback. These states are nonlinear waves in which energy concentrates in a localized and oscillatory manner. The organization of the family of solutions is characterized as a function of the applied voltage. Close to the reorientation transition, an amplitude equation allows us to elucidate the origin of these localized states and establish their bifurcation diagram. Theoretical findings are in qualitative agreement with experimental observations. Our results open the possibility of manipulating localized states induced by light, which can be used to expand and improve the storage and manipulation of information.

A series of 3,5-bis(benzylidene)-4-piperidones 2a–u were prepared as candidate cytotoxic agents. In general, the compounds are highly toxic to human gingival carcinoma (Ca9-22), human squamous carcinoma-2 (HSC-2) and human squamous carcinoma-4 (HSC-4) neoplasms, but less so towards non-malignant human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF) and human pulp cells (HPC), thereby demonstrating tumour-selective toxicity. A further study revealed that most of the compounds in series 2 were more toxic to the human Colo-205 adenocarcinoma cell line (Colo-205), human HT29 colorectal adenocarcinoma cells (HT-29) and human CEM lymphoid cells (CEM) neoplasms than towards non-malignant human foreskin Hs27 fibroblast line (Hs27) cells. The potency of the cytotoxins towards the six malignant cell lines increased as the sigma and sigma star values of the aryl substituents rose. Attempts to condense various aryl aldehydes with 2,2,6,6-tetramethyl-4-piperidone led to the isolation of some 1,5-diaryl-1,4-pentadien-3-ones. The highest specificity for oral cancer cells was displayed by 2e and 2r. In the case of 2r, its selective toxicity exceeded that of doxorubicin and melphalan. The enones 2k, m, o have the highest SI values towards colon cancer and leukemic cells. Both 2e,r inhibited mitosis and increased the subG1 population (with a transient increase in G2/M phase cells). Slight activation of caspase-3, based on the cleavage of poly(ADP-ribose)polymerase (PARP) and procaspase 3, was detected.