Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment.

Transition metal-based compounds have shown promising uses as therapeutic agents. Among their unique characteristics, these compounds are suitable for interaction with specific biological targets, making them important potential drugs to treat various diseases. Copper compounds, of which Casiopeinas® are an excellent example, have shown promising results as alternatives to current cancer therapies, in part because of their intercalative properties with DNA. Vanadium compounds have been extensively studied for their pharmacological properties and application, mostly in diabetes, although recently, there is a growing interest in testing their activity as anti-cancer agents. In the present work, two compounds, [Cu(Metf)(bipy)Cl]Cl·2H2O and [Cu(Impy)(Gly)(H2O)]VO3, were obtained and characterized by visible and FTIR spectroscopies, single-crystal X-ray diffraction, and theoretical methods. The structural and electronic properties of the compounds were calculated through the density functional theory (DFT) using the Austin-Frisch-Petersson functional with dispersion APFD, and the 6-311 + G(2d,p) basis set. Non-covalent interactions were analyzed using Hirshfeld surface analysis (HSA) and atom in molecules analysis (AIM). Additionally, docking analysis to test DNA/RNA interactions with the Casiopeina-like complexes were carried out. The compounds provide metals that can interact with critical biological targets. In addition, they show interesting non-covalent interactions that are responsible for their supramolecular arrangements.

Tris(2-Pyridylmethylamine)V(O)2 Complexes as Counter Ions of Diprotonated Decavanadate Anion: Potential Antineoplastic Activity.

The synthesis and theoretical-experimental characterization of a novel diprotanated decavanadate is presented here due to our search for novel anticancer metallodrugs. Tris(2-pyridylmethyl)amine (TPMA), which is also known to have anticancer activity in osteosarcoma cell lines, was introduced as a possible cationic species that could act as a counterpart for the decavanadate anion. However, the isolated compound contains the previously reported vanadium (V) dioxido-tpma moieties, and the decavanadate anion appears to be diprotonated. The structural characterization of the compound was performed by infrared spectroscopy and single-crystal X-ray diffraction. In addition, DFT calculations were used to analyze the reactive sites involved in the donor-acceptor interactions from the molecular electrostatic potential maps. The level of theory mPW1PW91/6-31G(d)-LANL2DZ and ECP = LANL2DZ for the V atom was used. These insights about the compounds' main interactions were supported by analyzing the noncovalent interactions utilizing the AIM and Hirshfeld surfaces approach. Molecular docking studies with small RNA fragments were used to assess the hypothesis that decavanadate's anticancer activity could be attributed to its interaction with lncRNA molecules. Thus, a combination of three potentially beneficial components could be evaluated in various cancer cell lines.

Racial and Language Microaggressions in the School Ecology.

The growth trajectory of ethnically and linguistically diverse individuals in the United States, particularly for youth, compels the education system to have urgent awareness of how diverse aspects of culture (e.g., Spanish-speaking, Black Latina student) are implicated in outcomes in American school systems. Students spend a significant amount of time in the school ecology, and this experience plays an important role in their well-being. Diverse ethnic, racial, and linguistic students face significant challenges and are placed at considerable risk by long-observed structural inequities evidenced in society and schools. Teachers must develop the capacity to be culturally sensitive, provide culturally responsive pedagogy, and regularly self-assess for biases implicated in positive academic outcomes for students in kindergarten through Grade 12. Research and practice have suggested that racism and discrimination in the form of racial microaggressions are observed daily in schools and classrooms. This article provides an overview of racial microaggressions in the school context and their damaging effects on students. We provide specific examples of microaggressions that may be observed in the U.S. classroom environment and how schools can serve as a positive intervention point to ameliorate racism, discrimination, and racial and language microaggressions. This comprehensive approach blends theory with practice to support the continued development of cultural humility, culturally sustaining pedagogy, and an equity-responsive climate.

Cyclo-tetravanadate bridged copper complexes as potential double bullet pro-metallodrugs for cancer treatment.

Over the last decade, copper and vanadium complexes have shown promising properties for the treatment of several types of cancer. In particular, Casiopeinas®, a group of copper-based complexes, has received specific attention, and their mechanism of action has been extensively studied since their structure is simple and their synthesis may be affordable. Similarly, vanadium-containing compounds in the form of complexes and simple polyoxovanadates have also been studied as antitumor agents. Here, potential prodrugs that would release the two metals, V and Cu, in usable form to act in conjunction against cancer cells are reported. The new series of Casiopeinas-like compounds are bridged by a cyclotetravanadate ion with the generic formula [Cu(N,N')(AA)]2•(V4O12), where (N,N') represent 1,10-phenanthroline and 2,2'-bipyridine, and (AA) are aminoacidate ions (Lysine and Ornithine). The compounds were characterized by elemental analysis, single-crystal X-ray diffraction and Visible, FTIR, and Raman spectroscopies, as well as 51V NMR, EPR, and Thermogravimetric Analysis. Additionally, theoretical calculations based on the Density Functional Theory (DFT) were carried out to model the compounds. Optimized structures, theoretical IR, and Raman spectra were also obtained, as well as docking analysis to test DNA interactions with the casiopeina-like complexes. The compounds may act as prodrugs by providing acting molecules that have showed potential pharmacological properties for the treatment of several types of cancer.

Hirschsprung disease in the U.S. associated Pacific Islands: more common than expected.

INTRODUCTION: Tripler Army Medical Center (TAMC) in Honolulu, Hawaii, is uniquely situated to serve patients from the United States Associated Pacific Islands (USAPIs) through the congressionally funded Pacific Island Health Care Project (PIHCP). Because of time differences and distance, a web-based store-and-forward consultation and referral network was established using the internet to more efficiently and economically facilitate patient care. Using both electronic and hard copy records, we sought to establish the incidence of Hirschsprung Disease (HD) in children from the USAPI and contrast it to that of the developed world. METHODS: PIHCP website records as well as all the inpatient and outpatient medical records of patients referred to TAMC fortreatment of HD from 1994 to 2002 were reviewed. A diagnosis of HD was confirmed in all cases with full thickness biopsy. Incidence figures for HD are based on this review and on the birth rates for these islands from the International Data Base of the U.S. Bureau of the Census. RESULTS: There were 14 cases of short-segment HD referred over a nine year study period. Nine patients came from the Federated States of Micronesia (FSM) with an average annual incidence of 1:3190, which is 1.5 to 2 times the reported incidence in Western nations. Remarkably, seven of these nine were from Pohnpei State, capital of the FSM (annual incidence of 1:1370 or3-5 times that in the West). Three patients came from the Republic of the Marshall Islands (RMI), and two came from American Samoa (AS). There were no reported consanguineous marriages, associated syndromes, or complications of surgery. CONCLUSION: HD was found to be up to 2-3 times more common among people from the FSM than has been reported in the developed world. Given the limitations of providing care and obtaining data from all the USAPls with a population that is spread over a massive expanse of ocean larger than the continental United States, this incidence is likely an underestimation of HD among Pacific Islanders. A secure web-based referral network developed in 1998 has been invaluable in collecting epidemiologic data from these islands as well as in providing health care workers in the USAPI with an efficient and inexpensive means to seek consultation from specialists and sub-specialists at a major tertiary care medical facility.

Efecto de la competición larval sobre poblaciones del vector del dengue colectadas en Medellín, Colombia / Effect of larval competition on populations of the dengue vector collected in Medellín, Colombia

Introducción: Aedes aegypti es el vector responsable de transmitir el virus dengue, la densidad de la población en los estadios larvales puede afectar las características de vida del adulto, con implicaciones en la capacidad de transmisión viral. Objetivo: determinar el efecto de la competición larval causada por la alta densidad en colonias de Aedes aegypti procedentes de zonas de alta y baja incidencia de dengue en la ciudad de Medellín, Colombia, así como en una colonia de referencia en el laboratorio. Métodos: en las 3 colonias se evaluó el tiempo de desarrollo y supervivencia larval, así como el tamaño y el tiempo de supervivencia de los adultos. Resultados: se encontró que la competición larval en condiciones de alta densidad redujo de manera significativa el tiempo de desarrollo y la supervivencia de los últimos estadios larvales. Por otro lado, la alta densidad experimentada durante la etapa larval, también generó cambios en los adultos de las 3 colonias, representados en una disminución significativa del tamaño y una disminución en el tiempo de supervivencia (esta última solo en las colonias de campo). Conclusión: a pesar de que no se obtuvieron diferencias frente al efecto competitivo entre las colonias de campo provenientes de zonas con desigualdades en la incidencia de dengue en Medellín, la diferencia en respuesta obtenida en la colonia de laboratorio en comparación con las colonias de campo, hace pensar que es importante la evaluación de parámetros ecológicos sobre poblaciones de Aedes aegypti silvestres, porque estas evaluaciones acercarían más al comportamiento del vector. Estudios en curso en el laboratorio permitirán conocer si las diferencias encontradas entre las colonias afectan la competencia de Aedes aegypti frente a la infección por virus dengue(AU)

Introduction: Aedes aegypti is the vector transmitting the dengue virus. Larval density may affect adult life, with an impact on viral transmission capacity. Objective: determine the effect of larval competition caused by high density in Aedes aegypti colonies from areas of high and low dengue incidence in the city of Medellín, Colombia, and in a reference colony in the laboratory. Methods: the three colonies were evaluated for larval development and survival time, as well as size and survival time in adults. Results: it was found that in high density conditions larval competition significantly shortened development and survival time in the last larval stages. High density during the larval stage also brought about changes in adults from the three colonies, represented by a significantly reduced size and a decrease in survival time (the latter only in the field colonies). Conclusion: no differences in competitive effect were found between the field colonies from areas with unequal dengue incidence in Medellín. However, the difference in the response obtained from the laboratory colony in contrast to the field colony, points to the need to evaluate the ecological parameters of wild Aedes aegypti populations to obtain a more accurate view of the behavior of the vector. Laboratory studies in progress will make it possible to know whether the differences found between the colonies affect the competence of Aedes aegypti for dengue virus infection(AU)

NIVELES DE MERCURIO EN HUEVOS, EMBRIONES Y NEONATOS DE Trachemys callirostris (TESTUDINES, EMYDIDAE) / Mercury Levels in Eggs, Embryos, and Neonates of Trachemys callirostris (Testudines, Emydidae)

Cuantificamos la concentración total de mercurio en cáscaras, yemas y embriones de 16 nidos de hicotea (Trachemys callirostris). Los nidos fueron colectados en diferentes estadios de desarrollo embrionario. No hubo una correlación entre el tiempo estimado desde el desove y los niveles de mercurio en los huevos, sugiriendo que el metal no fue absorbido del substrato, sino que probablemente éste fue transferido a los huevos durante el proceso de foliculogénesis en las hembras reproductivas, las cuales bioacumularon el mercurio de fuentes ambientales. La concentración promedio de mercurio fue mayor en los embriones que en las cáscaras o yemas, indicando que los embriones también bioacumulan el metal presente en otros tejidos del huevo. La variación de la concentración de mercurio dentro de una misma nidada fue relativamente alta. Las concentraciones de mercurio en las yemas no estuvieron asociadas con ninguna de las medidas de fitness que fueron evaluadas (éxito de eclosión, tamaño inicial de los neonatos y tasas de crecimiento de los juveniles en el primer mes). Después de cinco meses de mantenimiento en cautiverio, en un ambiente libre de mercurio, 86 % de los juveniles había eliminado completamente este metal de sus tejidos.

We quantified total mercury concentrations in eggshells, egg yolks, and embryos from 16 nests of the Colombian Slider (Trachemys callirostris). Nests were collected in different stages of development, but estimated time of incubation in natural substrates was not correlated with mercury levels in the eggs, suggesting that mercury was not absorbed from the substrate, but more likely passed on to the embryos during folliculogenesis by the reproductive females who had bioaccumulated the mercury from environmental sources. Mean mercury concentrations were higher in embryos than in eggshells or egg yolks, indicating that embryos also bioaccumulate mercury present in other egg tissues. Intra-clutch variation in egg yolk mercury concentrations was relatively high. Egg yolk mercury concentrations were not associated with any of the fitness proxies we quantified for the nests (hatching success rates, initial neonate sizes and first-month juvenile growth rates). After five months of captive rearing in a mercury-free laboratory environment, 86 % of the juveniles had eliminated the mercury from their tissues.

Análisis de ligamento genético de la diabetes mellitus tipo 1, a marcadores de los cromosomas 2 y 11 en familias antioqueñas / Genetic linkage analysis of type 1 diabetes mellitus to markers on chromosomes 2 and 11 in families from Antioquia, Colombia

La Diabetes Mellitus (DM) comprende un grupo heterogéneo de desordenes hiperglucémicos clasificados en subgrupos de acuerdo a su fisiopatología y etiología, entre los cuales se destacan la Diabetes Mellitus tipo1 (DM1) y la diabetes mellitus tipo 2 (DM2). La DM1 es de aparición temprana y una absoluta escasez de insulina hace que los pacientes sean insulino dependientes desde el inicio de los síntomas y la (DM2) que se manifiesta en la edad adulta y no todos los pacientes que la sufren son insulino dependientes

Diabetes mellitus (DM) comprises e heterogeneous group of hypoglycemic disorders, that are grouped according to their physiopathology and etiology; the most notorious ones are type 1 DM (DM1) and type 2 DM (DM2); DM1 is characterized by early onset and absolute lack of insulin; therefore, patients suffering from it depend on insulin since the beginning of their symptoms; in contrast, DM2 manifests during adult life and not all patients depend on insulin