Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents

The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years

A Mixed Method Evaluation of a Culturally Adapted, Brief, Bullying Bystander Intervention for Middle School Students

The purpose of this mixed method study was to examine the appropriateness of a brief, bullying bystander intervention (STAC) adapted for a middle school in a low-income, rural community with a predominantly White and Hispanic student body. We were also interested in understanding the experiences of the students who participated in the intervention. Quantitative analysis suggested that students gained knowledge about bullying, increased their confidence to intervene in bullying situations, and used the STAC strategies to intervene in bullying behavior. Analyzing the qualitative data using Consensual Qualitative Research methodology ([CQR] Hill et al.) revealed four domains in which students (a) reported using the STAC strategies across multiple contexts and settings, (b) spoke about fears related to intervening in bullying, yet intervened despite those fears, (c) described emotional benefits experienced after participating in the intervention and while using the STAC strategies, and (d) reported stronger interpersonal relationship after participating in the STAC intervention. This study extends the literature by providing preliminary support for a brief, bystander intervention adapted to address the need for culturally relevant bullying interventions for low-income, rural, ethnically-blended schools

Evaluation of a Youth Suicide Prevention Course: Increasing Counseling Students’ Knowledge, Skills, and Self-Efficacy

Adolescent suicide rates continue to rise within the United States. This study evaluated a Youth Suicide Prevention course in a Master’s in Counseling Program. Participants reported increases in knowledge and perceived ability to help suicidal clients post-training and in suicide prevention skills and suicide assessment and intervention self-efficacy at the 3-month follow-up. Implications for counselor education programs, such as using both experiential and didactic teaching methods, as well as timing suicide training before practicum, are discussed

Evaluation of a Youth Suicide Prevention Course: Increasing Counseling Students’ Knowledge, Skills, and Self-Efficacy

Adolescent suicide rates continue to rise within the United States. This study evaluated a Youth Suicide Prevention course in a Master’s in Counseling Program. Participants reported increases in knowledge and perceived ability to help suicidal clients post-training and in suicide prevention skills and suicide assessment and intervention self-efficacy at the 3-month follow-up. Implications for counselor education programs, such as using both experiential and didactic teaching methods, as well as timing suicide training before practicum, are discussed

Ingesta dietética e índices antropométricos en estudiantes de medicina mexicanos, estratificados por historia familiar de Diabetes Tipo 2

Introduction: Our aim was to evaluate the dietary intake and anthropometric indices in medical students with positive family history of type 2 diabetes (FH-T2D)(+) and without FH-T2D(-).Material and methods: 144 students were analyzed in this cross-sectional, observational study, conducted during the 2017-2018 school year using interviews and 7-day food diary. The participants were characterized anthropometrically. Waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), corrected mid-arm muscle area (MAMA), fat arm index (FAI), and tricipital skinfold (TSF) were calculated. Results: we found that 79.2% (95%CI: 72.5- 85.8) had FH-T2D. BMI was significantly higher in the participants with FH-T2D than without (23.7±3.8 v 25.0±3.7, respectively, p<0.05). No significant differences were determined in the indices based on central fat distribution (WHtR and WHR), peripheral distribution (FAI and TSF), or muscle mass (MAMA), when stratified by FH-T2D. Regarding dietary intake, when comparing participants with and without FH-T2D, respectively, we observed low/none legume consumption [30% (95%CI: 21.4-38.2) vs 23% (95%CI: 8.2-38.5)], diets high in proteins [38.6% (95%CI: 29.7-47.5) vs 46.7% (95%CI: 28.8-64.5)], low in carbohydrates [84.2% (95%CI: 77.5-90.9) vs 83.3% (95%CI: 70.0-96.7)], and insufficient energy intake [64% (95%CI: 55.2-72.8) vs 56.7% (95%CI: 38.9-74.4)], where the alterations in the dietary pattern were more detrimental for the FH-T2D(+) group. Lastly, the participants with FH-T2D consumed mainly late in the day [60% (95%CI: 50.6-68.6) vs 54% (95%CI: 35.5-71.2)].Conclusions: Even though there were minimal significant differences with the consumption by food categories, those students with FH-T2D presented with a poor, little varied and unbalanced dietary pattern with energy consumption mainly at night. These factors, if prolonged, could increase the risk of developing type 2 diabetes.Introducción: Nuestro objetivo fue evaluar la ingesta dietética y los índices antropométricos en estudiantes de medicina con historia familiar positiva de diabetes tipo 2 (FH-T2D)(+) y sin antecedentes familiares FH-T2D(-).Material y métodos: 144 estudiantes fueron analizados en este estudio transversal y observacional realizado durante el año escolar 2017-2018 mediante entrevistas y un diario de alimentos de 7 días. Los participantes se caracterizaron antropométricamente. Se calculó el ínidce cintura-cadera (WHR) y el índice cintura-altura (WHtR), el área muscular corregida de la mitad del brazo (MAMA), el índice de grasa del brazo (FAI) así como el pliegue cutáneo tricipital (TSF).Resultados:El 79,2% (95%CI: 72,5- 85,8) tenían FH-T2D. El IMC fue significativamente mayor en los participantes con FH-T2D que en aquellos sin FH-T2D (23,7 ± 3,8 v 25,0 ± 3,7, respectivamente, p <0,05). No se determinaron diferencias significativas en los índices basados en la distribución de grasa central (WHtR y WHR), la distribución periférica (FAI y TSF) o la masa muscular (MAMA), cuando se estratificó por FH-T2D. Al comparar la ingesta dietética de participantes con y sin FH-T2D, respectivamente, observamos un consumo bajo / ninguno de leguminosas [30% (95%CI: 21,4-38,2) frente a 23% (95%CI: 8,2-38,5)], dietas altas en proteínas [38,6% (95%CI: 29,7-47,5) frente a 46,7% (95%CI: 28,8-64,5)], bajas en carbohidratos [84,2% (95%CI: 77,5-90,9) frente a 83,3% (95%CI: 70,0-96,7)], y la ingesta de energía insuficiente [64% (95%CI: 55,2-72,8) frente a 56,7% (95%CI: 38,9-74,4)], donde las alteraciones en el patrón de la dieta fueron más perjudiciales para el grupo FH-T2D(+). Los participantes con FH-T2D consumieron al final del día [60% (95%CI: 50,6-68,6) frente a 54% (95%CI: 35,5-71,2)].Conclusiones: Aunque hubo diferencias mínimas significativas con el consumo por categorías de alimentos, aquellos estudiantes con FH-T2D presentaron un patrón dietético deficiente, poco variado y desequilibrado con un consumo de energía principalmente por la noche. Estos factores, si se prolongan, podrían aumentar el riesgo de desarrollar diabetes tipo 2

Implementation-effectiveness trial of an ecological intervention for physical activity in ethnically diverse low income senior centers.

BackgroundAs the US population ages, there is an increasing need for evidence based, peer-led physical activity programs, particularly in ethnically diverse, low income senior centers where access is limited.Methods/designThe Peer Empowerment Program 4 Physical Activity' (PEP4PA) is a hybrid Type II implementation-effectiveness trial that is a peer-led physical activity (PA) intervention based on the ecological model of behavior change. The initial phase is a cluster randomized control trial randomized to either a peer-led PA intervention or usual center programming. After 18 months, the intervention sites are further randomized to continued support or no support for another 6 months. This study will be conducted at twelve senior centers in San Diego County in low income, diverse communities. In the intervention sites, 24 peer health coaches and 408 adults, aged 50 years and older, are invited to participate. Peer health coaches receive training and support and utilize a tablet computer for delivery and tracking. There are several levels of intervention. Individual components include pedometers, step goals, counseling, and feedback charts. Interpersonal components include group walks, group sharing and health tips, and monthly celebrations. Community components include review of PA resources, walkability audit, sustainability plan, and streetscape improvements. The primary outcome of interest is intensity and location of PA minutes per day, measured every 6 months by wrist and hip accelerometers and GPS devices. Secondary outcomes include blood pressure, physical, cognitive, and emotional functioning. Implementation measures include appropriateness & acceptability (perceived and actual fit), adoption & penetration (reach), fidelity (quantity & quality of intervention delivered), acceptability (satisfaction), costs, and sustainability.DiscussionUsing a peer led implementation strategy to deliver a multi-level community based PA program can enhance program adoption, implementation, and sustainment.Trial registrationClinicalTrials.gov, USA ( NCT02405325 ). Date of registration, March 20, 2015. This website also contains all items from the World Health Organization Trial Registration Data Set

Evidence of noncovalent complexes in some natural extracts: Ceylon tea and mate extracts

AbstractConsidering the high complexity of natural extracts, because of the presence of organic molecules of different chemical nature, the possibility of formation of noncovalent complexes should be taken into account. In a previous investigation, the formation of bimolecular complexes between caffeine and catechins in green tea extracts (GTE) has been experimentally proven by means of mass spectrometric and 1H nuclear magnetic resonance experiments. The same approaches have been employed in the present study to evaluate the presence of bimolecular complexes in Ceylon tea and mate extracts. The obtained results show that in the case of Ceylon tea extracts, protonated theaflavin is detectable, together with theaflavin/caffein complexes, while caffeine/catechin complexes, already detected in green tea, are still present but at lower concentration. This aspect is evidenced by the comparison of precursor ion scans performed on protonated caffeine for the two extracts. The spectra obtained in these conditions for GTE and Ceylon tea show that the complexes of caffeine with epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG), highy abundant in the case of GTE (signal‐to‐chemical noise ratio in the range 50‐100), are negligible (signal‐to‐chemical noise ratio in the range 2‐3) in the case of Ceylon tea. Mate extracts show the formation of bimolecular complexes involving caffeine but not catechins, and chlorogenic acid becomes responsible for other complex formation. Under positive ion and negative ion conditions, accurate mass measurements allow the identification of malealdehyde, chlorogenic acid, caffeine, two isomers of dicaffeoylquinic acid, rutin, and kaempferol‐3‐O‐rutinoside. These data indicate that the formation of complexes in natural extracts is a common behavior, and their presence must be considered in the description of natural extracts and, consequently, in their biological activity

Targeting BRAF in thyroid cancer

Activating mutations in the gene encoding BRAF are the most commonly identified oncogenic abnormalities in papillary thyroid cancer. In vitro and in vivo models have demonstrated that overexpression of activated BRAF induces malignant transformation and aggressive tumour behaviour. BRAF and other RAF kinases are frequently activated by other thyroid oncogenes and are important mediators of their biological effects including dedifferentiation and proliferation. Because current therapeutic options for patients with thyroid cancers that are aggressive and/or do not respond to standard therapies are limited, BRAF and its downstream effectors represent attractive therapeutic targets. In this review, data supporting a role for BRAF activation in thyroid cancer development and establishing the potential therapeutic efficacy of BRAF-targeted agents in patients with thyroid cancer will be reviewed

The Combined Use of Melatonin and an Indoleamine 2,3-Dioxygenase-1 Inhibitor Enhances Vaccine-Induced Protective Cellular Immunity to HPV16-Associated Tumors

Immunotherapy has become an important ally in the fight against distinct types of cancer. However, the metabolic plasticity of the tumor environment frequently influences the efficacy of therapeutic procedures, including those based on immunological tools. In this scenario, immunometabolic adjuvants arise as an alternative toward the development of more efficient cancer therapies. Here we demonstrated that the combination of melatonin, a neuroimmunomodulator molecule, and an indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-DL-tryptophan, DL-1MT) improves the efficacy of an immunotherapy (gDE7) targeting human papillomavirus (HPV)-associated tumors. Melatonin or IDO inhibitors (D-1MT and DL-1MT) directly reduced proliferation, migration, adhesion and viability of a tumor cell line (TC-1), capable to express the HPV-16 E6 and E7 oncoproteins, but could not confer in vivo antitumor protection effects. Nonetheless, combination of gDE7 with melatonin or D-1MT or DL-1MT enhanced the antitumor protective immunity of gDE7-based vaccine in mice. Notably, expression of IDO1 in stromal cells and/or immune cells, but not in tumor cells, inhibited the antitumor effects of the gDE7, as demonstrated in IDO1-deficient mice. Finally, co-administration of gDE7, melatonin and DL-1MT further improved the protective antitumor effects and the numbers of circulating E7-specific CD8+ T cells in mice previously transplanted with TC-1 cells. The unprecedented combination of melatonin and IDO inhibitors, as immunometabolic adjuvants, thus, represents a new and promising alternative for improving the efficacy of immunotherapeutic treatments of HPV-associated tumors