Synthesis, characterization, antioxidant potential, and cytotoxicity screening of new Cu(II) complexes with 4-(arylchalcogenyl)-1H-pyrazoles ligands.

Two new Cu(II) complexes based on 4-(arylchalcogenyl)-1H-pyrazoles monodentate bis(ligand) containing selenium or sulfur groups (2a and 2b) have been synthesized and characterized by IR spectroscopy, high-resolution mass spectrometry (HRMS), and by X-ray crystallography. In the effort to propose new applications for the biomedical area, we evaluated the antioxidant activity and cytotoxicity of the newly synthesized complexes. The antioxidant activity of the Cu(II) complexes (2a - 2b) were assessed through their ability to inhibit the formation of reactive species (RS) induced by sodium azide and to scavenge the synthetic radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS+). Both copper complexes containing selenium (2a) and sulfur (2b) presented in vitro antioxidant activity. The (1a - 1b and 2a - 2b) compounds did not show cytotoxicity in V79 cells at low concentrations. Furthermore, the antiproliferative activity of free ligands (1a - 1b) and their complexes (2a - 2b) were tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and HepG2 (hepatocarcinoma). Also, 2a was tested against U2OS (osteosarcoma). Our results demonstrated that 1a and 1b show little or no growth inhibition activities on human cell lines.The 2a compound exhibited good cytotoxic activity toward human tumor cell lines. However, 2a showed no selectivity, with a selectivity index of 1.12-1.40. Complex 2b was selective for the MCF-7 human tumor cell lines with IC50 of 59 ± 2 µM. This study demonstrates that the Cu(II) complexes 2a and 2b represent promising antitumoral compounds, and further studies are necessary to understand the molecular mechanisms of these effects.

Mobile Phone Text Messaging for Tobacco Risk Communication Among Young Adult Community College Students: Protocol and Baseline Overview for a Randomized Controlled Trial.

BACKGROUND: Community-college students are at high risk for tobacco use. Because the use of mobile phone text messaging is nearly ubiquitous today, short message service (SMS) may be an effective strategy for tobacco risk communication in this population. Little is known, however, concerning the message structure significantly influencing perceived tobacco risk. OBJECTIVE: We aim to outline the rationale and design of Project Debunk, a randomized trial comparing the effects of different SMS text message structures. METHODS: We conducted a 6-month randomized trial comparing 8 arms, based on the combination of the 3 message structures delivered to young adults in a 2×2×2 study design: framing (gain-framed or loss-framed), depth (simple or complex), and appeal (emotional or rational). Participants were invited to participate from 3 community colleges in Houston from September 2016 to July 2017. Participants were randomized to 1 arm and received text messages in 2 separate campaigns. Each campaign consisted of 2 text messages per day for 30 days. Perceived tobacco risk was assessed at baseline, 2 months after the first campaign, and 2 months after the second campaign. We assessed the perceived risk of using conventional products (eg, combustible cigarettes) and new and emerging products (eg, electronic cigarettes). The validity of message structures was assessed weekly for each campaign. A 1-week follow-up assessment was also conducted to understand immediate reactions from participants. RESULTS: We completed data collection for the baseline survey on a rolling basis during this time and assessed the validity of the message structure after 1 week of SMS text messages. For the entire sample (N=636), the average age was 20.92 years (SD 2.52), about two-thirds were male (430/636, 67.6%), and most were black or African American (259/636, 40.7%) or white (236/636, 37.1%). After 1 week of receiving text messages, the following was noted: (a) loss-framed messages were more likely to be perceived as presenting a loss than gain-framed messages (F7,522=13.13, P<.001), (b) complex messages were perceived to be more complex than simple messages (F7,520=2.04, P=.05), and (c) emotional messages were perceived to be more emotionally involving than rational messages (F7,520=6.46, P<.001). CONCLUSIONS: This study confirms that the recruitment, randomization, and message composition have been successfully implemented. Further analyses will identify specific types of messages that are more effective than others in increasing the perceived risk of tobacco use. If our results suggest that any of the 8 specific message structures are more effective for helping young adults understand tobacco risk, this would provide evidence to include such messages as part of a larger technology-based campaign such as mobile phone apps, entertainment-based campaigns, and social media. TRIAL REGISTRATION: ClinicalTrials.gov NCT03457480; https://clinicaltrials.gov/ct2/show/NCT03457480 (Archived by WebCite at http://www.webcitation.org/6ykd4IIap). REGISTERED REPORT IDENTIFIER: RR1-10.2196/10977.

Validation of mobile phone text messages for nicotine and tobacco risk communication among college students: A content analysis.

INTRODUCTION: In the United States, young adults have the highest prevalence of tobacco use. The dissemination of mobile phone text messages is a growing strategy for tobacco risk communication among young adults. However, little has been done concerning the design and validation of such text messages. The Texas Tobacco Center of Regulatory Science (Texas-TCORS) has developed a library of messages based on framing (gain- or loss-framed), depth (simple or complex) and appeal (emotional or rational). This study validated the library based on depth and appeal, identified text messages that may need improvement, and explored new themes. METHODS: The library formed the study sample (N=976 messages). The Linguistic Inquiry and Word Count (LIWC) software of 2015 was used to code for word count, word length and frequency of emotional and cognitive words. Analyses of variance, logistic regression and scatter plots were conducted for validation. RESULTS: In all, 874 messages agreed with LIWC-coding. Several messages did not agree with LIWC. Ten messages designed to be complex indicated simplicity, while 51 messages designed to be rational exhibited no cognitive words. New relevant themes were identified, such as health (e.g. 'diagnosis', 'cancer'), death (e.g. 'dead', 'lethal') and social connotations (e.g. 'parents', 'friends'). CONCLUSIONS: Nicotine and tobacco researchers can safely use, for young adults, messages from the Texas-TCORS library to convey information in the intended style. Future work may expand upon the new themes. Findings will be utilized to develop new campaigns, so that risks of nicotine and tobacco products can be widely disseminated.

The role of gallery forests in maintaining Phlebotominae populations: potential Leishmania spp. vectors in the Brazilian savanna

BACKGROUND Knowledge on synanthropic phlebotomines and their natural infection by Leishmania is necessary for the identification of potential areas for leishmaniasis occurrence. OBJECTIVE To analyse the occurrence of Phlebotominae in gallery forests and household units (HUs) in the city of Palmas and to determine the rate of natural infection by trypanosomatids. METHODS Gallery forests and adjacent household areas were sampled on July (dry season) and November (rainy season) in 2014. The total sampling effort was 960 HP light traps and eight Shannon traps. Trypanosomatids were detected in Phlebotominae females through the amplification of the SSU rDNA region, and the positive samples were used in ITS1-PCR. Trypanosomatid species were identified using sequencing. FINDINGS A total of 1,527 sand flies representing 30 species were captured in which 949 (28 spp.) and 578 (22 spp.) were registered in July and November, respectively. In July, more specimens were captured in the gallery forests than in the HUs, and Nyssomyia whitmani was particularly frequent. In November, most of the specimens were found in the HUs, and again, Ny. whitmani was the predominant species. Lutzomyia longipalpis was commonly found in domestic areas, while Bichromomyia flaviscutellata was most frequent in gallery forests. Molecular analysis of 154 pools of females (752 specimens) identified Leishmania amazonensis, L. infantum, and Crithidia fasciculata in Ny. whitmani, as well as L. amazonensis in Lu. longipalpis, Trypanosoma sp. and L. amazonensis in Pintomyia christenseni, and L. amazonensis in both Psathyromyia hermanlenti and Evandromyia walkeri. MAIN CONCLUSIONS These results show the importance of gallery forests in maintaining Phlebotominae populations in the dry month, as well as their frequent occurrence in household units in the rainy month. This is the first study to identify Leishmania, Trypanosoma, and Crithidia species in Phlebotominae collected in Palmas, Tocantins, Brazil.

The role of gallery forests in maintaining Phlebotominae populations: potential Leishmania spp. vectors in the Brazilian savanna.

BACKGROUND: Knowledge on synanthropic phlebotomines and their natural infection by Leishmania is necessary for the identification of potential areas for leishmaniasis occurrence. OBJECTIVE: To analyse the occurrence of Phlebotominae in gallery forests and household units (HUs) in the city of Palmas and to determine the rate of natural infection by trypanosomatids. METHODS: Gallery forests and adjacent household areas were sampled on July (dry season) and November (rainy season) in 2014. The total sampling effort was 960 HP light traps and eight Shannon traps. Trypanosomatids were detected in Phlebotominae females through the amplification of the SSU rDNA region, and the positive samples were used in ITS1-PCR. Trypanosomatid species were identified using sequencing. FINDINGS: A total of 1,527 sand flies representing 30 species were captured in which 949 (28 spp.) and 578 (22 spp.) were registered in July and November, respectively. In July, more specimens were captured in the gallery forests than in the HUs, and Nyssomyia whitmani was particularly frequent. In November, most of the specimens were found in the HUs, and again, Ny. whitmani was the predominant species. Lutzomyia longipalpis was commonly found in domestic areas, while Bichromomyia flaviscutellata was most frequent in gallery forests. Molecular analysis of 154 pools of females (752 specimens) identified Leishmania amazonensis, L. infantum, and Crithidia fasciculata in Ny. whitmani, as well as L. amazonensis in Lu. longipalpis, Trypanosoma sp. and L. amazonensis in Pintomyia christenseni, and L. amazonensis in both Psathyromyia hermanlenti and Evandromyia walkeri. MAIN CONCLUSIONS: These results show the importance of gallery forests in maintaining Phlebotominae populations in the dry month, as well as their frequent occurrence in household units in the rainy month. This is the first study to identify Leishmania, Trypanosoma, and Crithidia species in Phlebotominae collected in Palmas, Tocantins, Brazil.

Developing mobile phone text messages for tobacco risk communication among college students: a mixed methods study.

BACKGROUND: Engaging young adults for the purpose of communicating health risks associated with nicotine and tobacco use can be challenging since they comprise a population heavily targeted with appealing marketing by the evolving tobacco industry. The Food and Drug Administration seeks novel ways to effectively communicate risks to warn about using these products. This paper describes the first step in developing a text messaging program delivered by smartphones that manipulate three messaging characteristics (i.e., depth, framing, and appeal). METHODS: Perceptions of community college students were described after previewing text messages designed to inform about risks of using conventional and new tobacco products. Thirty-one tobacco users and nonusers, aged 18-25 participated in five focus discussions held on two community college campuses. Attendees reviewed prototype messages and contributed feedback about text message structure and content. Qualitative data were coded and analyzed using NVivo Version 10. RESULTS: Most participants were female and two-thirds were ethnic minorities. A variety of conventional and new tobacco products in the past month were used by a third of participants. Three identified domains were derived from the qualitative data. These included perceived risks of using tobacco products, receptivity to message content, and logistical feedback regarding the future message campaign. CONCLUSION: Overall, participants found the messages to be interesting and appropriate. A gap in awareness of the risks of using new tobacco products was revealed. Feedback on the prototype messages was incorporated into message revisions. These findings provided preliminary confirmation that the forthcoming messaging program will be appealing to young adults.

Meningoencephalitis Caused by Reactivation of Chagas Disease in Patient Without Known Immunosuppression.

Central nervous system (CNS) involvement in Chagas disease (CD) is an uncommon complication that can result from direct involvement of the parasite or from thromboembolic phenomena. Direct involvement of CNS can occur in both acute and chronic forms of CD, and can also be secondary to reactivation. Reactivation of CD generally occurs in immunosuppressed patients such as those with human immunodeficiency infection or malignancies being rarely described in patients without apparent immunosuppression. We report a case of a patient living for many years in a nonendemic area for CD that presented to the emergency department with sudden onset of neurological symptoms as a result of reactivation of the disease. The microorganism was isolated from cerebrospinal fluid, and despite appropriate use of benznidazole, the patient died of sepsis after 22 days of treatment. Further investigation did not show any apparent cause of immunosuppression. This case report shows the importance of considering the diagnostic possibility of neurological complications from CD reactivation in patients that have ever lived in CD-endemic areas even without apparent underlying immunosuppression.

Species diversity of sandflies (Diptera: Psychodidae) during different seasons and in different environments in the district of Taquaruçú, state of Tocantins, Brazil.

Phlebotomine sandflies are the vectors for the protozoan parasites that cause leishmaniasis. The present study investigated the species composition of sandfly fauna in the rural district of Taquaruçú, municipality of Palmas, state of Tocantins, Brazil and compared the diversity of species among intradomicile, peridomicile and forest environments during the dry and rainy seasons. Sandflies were collected using CDC light traps over the course of three months during the dry and rainy seasons. A total of 767 specimens were captured, belonging to different 32 species. The most abundant species were Micropygomyia goiana (Martins, Falcão & Silva), Sciopemyia sordellii (Shannon & Del Ponte), Evandromyia carmelinoi (Ryan Fraiha, Lainson & Shaw), Evandromyia termitophila (Martins, Falcão & Silva), Nyssomyia whitmani (Antunes & Coutinho) and Lutzomyia longipalpis (Lutz & Neiva). The highest species diversity (30) and the greatest percentage of specimens (78.3%) were obtained during the rainy season. During the dry season, the species richness and abundance were greater in domestic environments. However, during the rainy season, the forest displayed the highest species richness and the domestic environment exhibited the greatest species abundance. Several important vector species are reported in this study.

Species diversity of sandflies (Diptera: Psychodidae) during different seasons and in different environments in the district of Taquaruçú, state of Tocantins, Brazil

Phlebotomine sandflies are the vectors for the protozoan parasites that cause leishmaniasis. The present study investigated the species composition of sandfly fauna in the rural district of Taquaruçú, municipality of Palmas, state of Tocantins, Brazil and compared the diversity of species among intradomicile, peridomicile and forest environments during the dry and rainy seasons. Sandflies were collected using CDC light traps over the course of three months during the dry and rainy seasons. A total of 767 specimens were captured, belonging to different 32 species. The most abundant species were Micropygomyia goiana (Martins, Falcão & Silva), Sciopemyia sordellii (Shannon & Del Ponte), Evandromyia carmelinoi (Ryan Fraiha, Lainson & Shaw), Evandromyia termitophila (Martins, Falcão & Silva), Nyssomyia whitmani (Antunes & Coutinho) and Lutzomyia longipalpis (Lutz & Neiva). The highest species diversity (30) and the greatest percentage of specimens (78.3%) were obtained during the rainy season. During the dry season, the species richness and abundance were greater in domestic environments. However, during the rainy season, the forest displayed the highest species richness and the domestic environment exhibited the greatest species abundance. Several important vector species are reported in this study.

ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis.

The ADAM23 gene is frequently silenced in different types of tumors, and, in breast tumors, silencing is correlated with tumor progression, suggesting that it might be associated with the acquisition of a metastatic phenotype. ADAM23 exerts its function mainly through the disintegrin domain, because its metalloprotease domain is inactive. Analysis of ADAM23 binding to integrins has revealed a specific interaction with alpha(v)beta(3) integrin mediated by the disintegrin domain. Altered expression of alpha(v)beta(3) integrin has been observed in different types of tumors, and expression of this integrin in the activated form has been shown to promote metastasis formation. Here, we investigated the possibility that interaction between ADAM23 and alpha(v)beta(3) integrin might negatively modulate alpha(v)beta(3) activation during metastatic progression. ADAM23 expression was knocked down using short hairpin RNA in the MDA-MB-435 cell line, which has been extensively used as a model for alpha(v)beta(3) integrin activation. Ablation of ADAM23 enhanced alpha(v)beta(3) integrin activation by at least 2- to 4-fold and ADAM23 knockdown cells showed enhanced migration and adhesion to classic alpha(v)beta(3) integrin ligands. Ablation of ADAM23 expression also enhanced pulmonary tumor cell arrest in immunodeficient mice. To complement our findings with clinical evidence, we showed that silencing of ADAM23 gene by DNA promoter hypermethylation in a collection of 94 primary breast tumors was significantly associated with lower distant metastases-free and disease-specific survivals and was an independent prognostic factor for poor disease outcome. Our results strongly support a functional role of ADAM23 during metastatic progression by negatively modulating alpha(v)beta(3) integrin activation.

Estudo da morfologia macular após a remoção da membrana epirretiniana idiopática utilizando a tomografia de coerência óptica (OCT): um estudo piloto / Study on macular morphology after removal of the idiopathic epiretinal membrane using the optical coherence tomography (OCT): a pilot study

OBJETIVO: Descrever a relação entre os resultados visuais e a morfologia macular através da tomografia de coerência óptica (OCT) em pacientes submetidos à remoção da membrana epirretiniana idiopática. MÉTODOS: Dez olhos de 10 pacientes com diagnóstico de membrana epirretiniana idiopática foram incluídos neste estudo. Todos os olhos foram submetidos à vitrectomia posterior via pars plana pelo mesmo cirurgião, durante o período de fevereiro de 2002 a março de 2004. A acuidade visual corrigida usando a tabela de Snellen, bem como a retinografia, a angiofluoresceinografia, a biomicroscopia de fundo e a tomografia de coerência óptica pré e pós-operatórios foram obtidos de todos os pacientes em todas as visitas. No estudo da tomografia de coerência óptica foram avaliadas três características em cada imagem: presença de depressão foveal, presença de edema macular cistóide e média da espessura central macular. RESULTADOS: A idade média dos pacientes foi de 63,3 anos (57 a 78). Cinco pacientes eram do sexo masculino e 5, do sexo feminino. A acuidade visual pré-operatória variou de 20/80 a conta dedos a 1 metro. A acuidade visual melhorou pelo menos duas linhas de visão em 8 olhos (80 por cento) e a metamorfopsia melhorou também na mesma proporção (80 por cento). Quatro pacientes não apresentavam metamorfopsia com a tabela de Amsler, e os demais apresentavam melhora parcial. À tomografia de coerência óptica todos os olhos mantiveram o aumento da espessura central, variando de 232 a 605 µ (média= 351,9 µ). Três olhos mantiveram o edema macular cistóide. Quatro olhos apresentaram acuidade visual final melhor ou igual a 20/30. Neste grupo a média de espessura central foi de 277 µ (265 a 285 µ). A recuperação do contorno foveal foi observada em dois destes olhos. Nos quatro pacientes não havia edema macular cistóide residual. CONCLUSÃO: A tomografia de coerência óptica é uma ferramenta capaz de avaliar as alterações estruturais antes e depois da cirurgia...

PURPOSE: To describe the relation between visual results and macular morphology through optical coherence tomography (OCT) in patients submitted to removal of the idiopathic epiretinal membranes. METHODS: Ten eyes of ten patients with diagnosis of idiopathic epiretinal membranes underwent standard 20-G pars plana vitrectomy. Posterior hyaloid attachments were identified and dealt with. Idiopathic epiretinal membranes were removed in all cases. Corrected visual acuity, retinography, fluorescein angiography, fundus biomicroscopy and the optical coherence tomography in the pre- and postoperative periods were performed in all patients. In OCT, three characteristics were considered in each image: presence of foveal depression, presence of cystoid macular edema and mean central macular thickness. RESULTS: Pre-operative visual acuity varied from 20/80 to counting fingers. The mean age was 63 years, ranging from 57 to 78 years. Five patients were male and five female. Preoperative visual acuity (VA) varied from 20/80 to CD to 1 meter. An improvement in VA of at least two lines was noted in all cases and metamorphopsia in eight eyes (80 percent). Four patients did not present metamorphopsia according to Amsler grid test, and the remaining presented partial improvement. On optical coherence tomography all eyes maintained increased central thickness, ranging from 232 to 605 µ (mean of 351.9 µ). Three eyes maintained cystoid macular edema. Four eyes presented final VA better or equal to 20/30. In this group the mean central thickness was of 277 µ. Foveal contour was recovered in two of these eyes. Four patients had no residual cystoid macular edema. CONCLUSIONS: Optical coherence tomography is a tool that evaluates the structural changes before and after surgery to remove idiopathic epiretinal membranes. Although the foveal area architecture stays irregular six months after surgery, the visual outcomes are very promising. Other prognostics factors...

Cloning and characterization of an alternative splicing transcript of the gene coding for human cytidine deaminase.

Human cytidine deaminase (HCD) catalyzes the deamination of cytidine or deoxycytidine to uridine or deoxyuridine, respectively. The genomic sequence of HCD is formed by 31 kb with 4 exons and several alternative splicing signals, but an alternative form of HCD has yet to be reported. Here we describe the cloning and characterization of a small form of HCD, HSCD, and it is likely to be a product of alternative splicing of HCD. The alignment of DNA sequences shows that the HSCD matches HCD in 2 parts, except for a deletion of 170 bp. Based on the HCD genome organization, exons 1 and 4 should be joined and all sequences of introns and exons 2 and 3 should be deleted by splicing. This alternative splicing shifted the translation of the reading frame from the point of splicing. The estimated molecular mass is 9.8 kDa, and this value was confirmed by Western blot and mass spectroscopy after expressing the gene fused with glutathionine-S-transferase in the pGEX vector. The deletion and shift of the reading frame caused a loss of HCD activity, which was confirmed by enzyme assay and also with NIH3T3 cells modified to express HSCD and challenged against cytosine arabinoside. In this work we describe the identification and characterization of HSCD, which is the product of alternative splicing of the HCD gene.

[Study on macular morphology after removal of the idiopathic epiretinal membrane using the optical coherence tomography (OCT): a pilot study]. / Estudo da morfologia macular após a remoção da membrana epirretiniana idiopática utilizando a tomografia de coerência óptica (OCT): um estudo piloto.

PURPOSE: To describe the relation between visual results and macular morphology through optical coherence tomography (OCT) in patients submitted to removal of the idiopathic epiretinal membranes. METHODS: Ten eyes of ten patients with diagnosis of idiopathic epiretinal membranes underwent standard 20-G pars plana vitrectomy. Posterior hyaloid attachments were identified and dealt with. Idiopathic epiretinal membranes were removed in all cases. Corrected visual acuity, retinography, fluorescein angiography, fundus biomicroscopy and the optical coherence tomography in the pre- and postoperative periods were performed in all patients. In OCT, three characteristics were considered in each image: presence of foveal depression, presence of cystoid macular edema and mean central macular thickness. RESULTS: Pre-operative visual acuity varied from 20/80 to counting fingers. The mean age was 63 years, ranging from 57 to 78 years. Five patients were male and five female. Preoperative visual acuity (VA) varied from 20/80 to CD to 1 meter. An improvement in VA of at least two lines was noted in all cases and metamorphopsia in eight eyes (80%). Four patients did not present metamorphopsia according to Amsler grid test, and the remaining presented partial improvement. On optical coherence tomography all eyes maintained increased central thickness, ranging from 232 to 605 micro (mean of 351.9 micro). Three eyes maintained cystoid macular edema. Four eyes presented final VA better or equal to 20/30. In this group the mean central thickness was of 277 micro. Foveal contour was recovered in two of these eyes. Four patients had no residual cystoid macular edema. CONCLUSIONS: Optical coherence tomography is a tool that evaluates the structural changes before and after surgery to remove idiopathic epiretinal membranes. Although the foveal area architecture stays irregular six months after surgery, the visual outcomes are very promising. Other prognostics factors may be involved in the final visual results of this pathology.

Over expression of the selectable marker blasticidin S deaminase gene is toxic to human keratinocytes and murine BALB/MK cells.

BACKGROUND: The blasticidin S resistance gene (bsr) is a selectable marker used for gene transfer experiments. The bsr gene encodes for blasticidin S (BS) deaminase, which has a specific activity upon BS. Therefore, its expression is supposed to be harmless in cells. The work reported on herein consisted of experiments to verify a possible toxicity of bsr on mammalian cells, which include several cell lines and primary cultures. RESULTS: Murine keratinocyte BALB/MK and human primary keratinocyte cells transduced with the retroviral vector LBmSN, which has an improved expression system of bsr, namely bsrm, died in five days after the transduction. Meanwhile the control vector LBSN, which expresses bsr, did not provoke cell death. The lethal activity of bsrm was observed only in human keratinocytes and BALB/MK cells among the cell types tested here. Death appears to be mediated by a factor, which is secreted by the BALB/MK transduced cells. CONCLUSION: By our study we demonstrated that the expression of bsrm gene is toxic to human keratinocytes and BALB/MK cells. It is likely over expression of BS deaminase gene is responsible for the death.