RESUMEN

OBJECTIVE: To assess the difference in outcomes between single dilation (SingD) and sequential dilation (SeqD) in primary penile implantation, hypothesizing that patients who undergo SeqD had higher rates of noninfectious complications. METHODS: We performed a multicenter, retrospective study of men undergoing primary inflatable penile prosthesis placement. Intraoperative complications and postoperative noninfectious outcomes were assessed between the two groups. Multivariable analysis was performed to identify predictors of complications. RESULTS: A total of 3293 patients met inclusion criteria. After matching, there were 379 patients who underwent SingD and 379 patients who underwent SeqD. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length (20 cm with interquartile range [IQR] 18-21 cm vs 20 cm with IQR 18-20 cm respectively, P = .4). On multivariable analysis, SeqD (OR 5.23 with IQR 2.74-10, P < .001) and older age (OR 1.04 with IQR 1.01-1.06, P = .007) were predictive of postoperative noninfectious complications. There was no significant difference in intraoperative complications between patients who underwent SingD vs SeqD, nor was there any difference in cylinder length. SeqD and older age were predictive of postoperative noninfectious complications. CONCLUSION: During inflatable penile prosthesis placement in the uncomplicated patient without fibrosis, SingD is a safe technique to utilize during implantation that will minimize postoperative adverse events, and promote device longevity without loss of cylinder length.

Asunto(s)

Disfunción Eréctil , Implantación de Pene , Prótesis de Pene , Masculino , Humanos , Prótesis de Pene/efectos adversos , Estudios Retrospectivos , Dilatación , Implantación de Pene/efectos adversos , Implantación de Pene/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Complicaciones Intraoperatorias/etiología , Disfunción Eréctil/etiología

RESUMEN

Due to the pronounced effect of the confined environment on the photochemical properties of 4-hydroxybenzylidene imidazolinone (HBI), a GFP-related chromophore, imidazolidinone and imidazothiazolone analogues have been studied as fluorescent probes. Their photoisomerization and their thermal reversion were studied under 365-nm-irradiation, resulting in observation of an enthalpy-entropy compensation effect. Theoretical studies were carried out to shed light on the thermal reversion mechanism. Moreover, photophysical studies of benzylidene imidazothiazolone in the presence of dsDNA revealed fluorescence enhancement. The prepared compounds could be considered as a valuable tool for the detailed investigation of physicochemical, biochemical, or biological systems.

Asunto(s)

Colorantes Fluorescentes , Proteínas Fluorescentes Verdes/química , Fluorescencia , Termodinámica , Entropía

RESUMEN

Background: The ongoing coronavirus diseases 2019 (COVID-19) pandemic with its numerous variants of concern has shown the need to have a robust and complete global infectious diseases genomic surveillance network worldwide. Various clinical and research institutions have stepped up to perform SARS-CoV-2 sequencing thus enhancing the understanding of this virus' global evolution. However, given that genomic sequencing capacities and capabilities are not available in every region or country, significant gaps exist, which lead to geographic blind spots. One such region is the Caribbean. This paper measures the Caribbean region's SARS-CoV-2 genomic sequencing capacity and highlights the need to improve further regional genomics surveillance capacities and capabilities, which are essential for efficient health interventions for infectious diseases. Methods: A map showing SARS-CoV-2 sequences available for each Caribbean Island was constructed using SARS-CoV-2 genomic, epidemiological and populational data obtained from GISAID, the World Health Organization, the United Nations, and the World Bank. The number of reported SARS-CoV-2 cases and the proportion of cases sequenced in each Caribbean Island was then analysed by the Gross Domestic Product per capita and political status. Findings: As of August 6, 2022, the number of SARS-CoV-2 sequences from the Caribbean are underrepresented with only 40,190 (1.07%) of the over 3.76 million documented cases sequenced, which is further exacerbated by a disparity based not only on the country's income but also on its political status (sovereign country versus dependent or integrated) and accessibility to sequencing technologies. There are a limited number of sequencing centres based in the Caribbean islands with the majority located on the American and European continents. Using mobile sequencing technologies while concomitantly investing in data analysis training could lead to greater and more sustainable coverage. Interpretation: Considering the Caribbean region's dispersed heterogeneous populations, varying political regimes, and resource-constrained healthcare systems, further development of local next-generation sequencing capacity and capabilities in the Caribbean region is needed to achieve global public health goals. Funding: No funding source was required for this study.

RESUMEN

Leukemia cells accumulate DNA damage, but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/1-carbon cycle metabolism contributed to the accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases (OTKs: FLT3(internal tandem duplication [ITD]), JAK2(V617F), BCR-ABL1). To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLθ) via ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLθ and its proteasomal degradation. Overexpression of POLθ in OTK-positive cells resulted in the efficient repair of DPC-containing DNA double-strand breaks by POLθ-mediated end-joining. The transforming activities of OTKs and other leukemia-inducing oncogenes, especially of those causing the inhibition of BRCA1/2-mediated homologous recombination with and without concomitant inhibition of DNA-PK-dependent nonhomologous end-joining, was abrogated in Polq-/- murine bone marrow cells. Genetic and pharmacological targeting of POLθ polymerase and helicase activities revealed that both activities are promising targets in leukemia cells. Moreover, OTK inhibitors or DPC-inducing drug etoposide enhanced the antileukemia effect of POLθ inhibitor in vitro and in vivo. In conclusion, we demonstrated that POLθ plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions triggered by formaldehyde, and it can be targeted to achieve a therapeutic effect.

Asunto(s)

Proteína BRCA1 , Daño del ADN , Leucemia , Animales , Ratones , Proteína BRCA2 , ADN/metabolismo , Leucemia/enzimología , Leucemia/genética , ADN Polimerasa theta

RESUMEN

Although a growing body of evidence demonstrates that altered mtDNA content (mtDNAc) has clinical implications in several types of solid tumours, its prognostic relevance in acute promyelocytic leukaemia (APL) patients remains largely unknown. Here, we show that patients with higher-than-normal mtDNAc had better outcomes regardless of tumour burden. These results were more evident in patients with low-risk of relapse. The multivariate Cox proportional hazard model demonstrated that high mtDNAc was independently associated with a decreased cumulative incidence of relapse. Altogether, our data highlights the possible role of mitochondrial metabolism in APL patients treated with ATRA.

Asunto(s)

Leucemia Promielocítica Aguda , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/genética , Tretinoina/uso terapéutico , ADN Mitocondrial/genética , Relevancia Clínica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento

RESUMEN

Chagas Disease (CD), a chronic infection caused by the Trypanosoma cruzi parasite, is a Neglected Tropical Disease endemic to Latin America. With a re-emergence in Venezuela during the past two decades, the spread of CD has proved susceptible to, and inhibitable by a digital, real-time surveillance system effectuated by Citizen Scientists in communities throughout the country. The #TraeTuChipo (#BringYourKissingBug) campaign implemented in January 2020, has served as such a strategy counting on community engagement to define the current ecological distribution of CD vectors despite the absence of a functional national surveillance program. This pilot campaign collected data through online surveys, social media platforms, and/or telephone text messages. A total of 79 triatomine bugs were reported from eighteen Venezuelan states; 67 bugs were identified as Panstrongylus geniculatus, 1 as Rhodnius pictipes, 1 as Triatoma dimidiata, and 10 as Triatoma maculata. We analyzed 8 triatomine feces samples spotted from 4 Panstrongylus geniculatus which were confirmed positive by qPCR for T. cruzi . Further molecular characterization of discrete typing units (DTUs), revealed that all samples contained TcI, the most highly diverse and broadly distributed strain of T. cruzi. Moreover, analysis of the mitochondrial 12S gene revealed Myotis keaysi, Homo sapiens, and Gallus gallus as the main triatomine feeding sources. This study highlights a novel Citizen Science approach which may help improve the surveillance systems for CD in endemic countries.

RESUMEN

Trypanosoma cruzi the causative agent of Chagas disease shows a marked genetic diversity and divided into at least six Discrete Typing Units (DTUs). High intra genetic variability has been observed in the TcI DTU, the most widely distributed DTU, where patterns of genomic diversity can provide information on ecological and evolutionary processes driving parasite population structure and genome organization. Chromosomal aneuploidies and rearrangements across multigene families represent an evidence of T. cruzi genome plasticity. We explored genomic diversity among 18 Colombian T. cruzi I clones and 15 T. cruzi I South American strains. Our results confirm high genomic variability, heterozygosity and presence of a clade compatible with the TcIdom genotype, described for strains from humans in Colombia and Venezuela. TcI showed high structural plasticity across the geographical region studied. Differential events of whole and segmental aneuploidy (SA) along chromosomes even between clones from the same strain were found and corroborated by the depth and allelic frequency. We detected loss of heterozygosity (LOH) events in different chromosomes, however, the size and location of segments under LOH varied between clones. Genes adjacent to breakpoints were evaluated, and retrotransposon hot spot genes flanked the beginning of segmental aneuploidies. Our results suggest that T. cruzi genomes, like those of Leishmania, may have a highly unstable structure and there is now an urgent need to design experiments to explore any potential adaptive role for the plasticity observed.

Asunto(s)

Enfermedad de Chagas , Trypanosoma cruzi , Aneuploidia , Enfermedad de Chagas/parasitología , Variación Genética , Humanos , Pérdida de Heterocigocidad , Trypanosoma cruzi/genética

RESUMEN

Accurate prediction of vectors dispersal, as well as identification of adaptations that allow blood-feeding vectors to thrive in built environments, are a basis for effective disease control. Here we adopted a landscape genomics approach to assay gene flow, possible local adaptation, and drivers of population structure in Rhodnius ecuadoriensis, an important vector of Chagas disease. We used a reduced-representation sequencing technique (2b-RADseq) to obtain 2,552 SNP markers across 272 R. ecuadoriensis samples from 25 collection sites in southern Ecuador. Evidence of high and directional gene flow between seven wild and domestic population pairs across our study site indicates insecticide-based control will be hindered by repeated re-infestation of houses from the forest. Preliminary genome scans across multiple population pairs revealed shared outlier loci potentially consistent with local adaptation to the domestic setting, which we mapped to genes involved with embryogenesis and saliva production. Landscape genomic models showed elevation is a key barrier to R. ecuadoriensis dispersal. Together our results shed early light on the genomic adaptation in triatomine vectors and facilitate vector control by predicting that spatially-targeted, proactive interventions would be more efficacious than current, reactive approaches.

Asunto(s)

Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/genética , Rhodnius/genética , Adaptación Biológica/genética , Animales , Vectores de Enfermedades , Ecosistema , Ecuador/epidemiología , Expresión Génica/genética , Perfilación de la Expresión Génica/métodos , Flujo Génico , Insectos Vectores/genética , Metagenómica/métodos , Polimorfismo de Nucleótido Simple/genética , Densidad de Población , Rhodnius/patogenicidad , Transcriptoma/genética , Trypanosoma cruzi/genética

RESUMEN

Infections with parasitic helminths cause severe debilitating and sometimes lethal diseases in humans and domestic animals on a global scale. Unable to synthesize de novo their own fatty acids and sterols, helminth parasites (nematodes, trematodes, cestodes) rely on their hosts for their supply. These organisms produce and secrete a wide range of lipid binding proteins that are, in most cases, structurally different from the ones found in their hosts, placing them as possible novel therapeutic targets. In this sense, a lot of effort has been made towards the structure determination of these proteins, but their precise function is still unknown. In this review, we aim to present the current knowledge on the functions of LBPs present in parasitic helminths as well as novel members of this highly heterogeneous group of proteins.

Asunto(s)

Helmintos , Nematodos , Parásitos , Trematodos , Animales , Lípidos

RESUMEN

Underutilized marine food products such as cephalopods' ink could be sources of bioactive compounds providing health benefits. This study aimed to assess the anti-proliferative and anti-inflammatory effects from Octopus vulgaris ink extracts (hexane-, ethyl acetate-, dichloromethane- (DM), and water extracts) using human colorectal (HT-29/HCT116) and breast (MDA-MB-231) cancer cells, and LPS-challenged murine RAW 264.7 cells. Except by ethyl-acetate, all of the extracts exhibited anti-proliferative effects without being cytotoxic to ARPE-19 and RAW 264.7 cells. Among DM fractions (F1/F2/F3), DM-F2 showed the highest anti-proliferative effect (LC50 = 52.64 µg/mL), inducing pro-apoptotic morphological disruptions in HCT116 cells. On RAW 264.7 cells, DM-F2 displayed the lowest nitrites reduction and up-regulation of key-cytokines from the JAK-STAT, PI3K-Akt, and IL-17 pathways. Compared to control, DM-F2 increased IL-4 and decreased NF-κB fluorometric expression in peripheral blood mononuclear cells (PBMCs). Metabolomic analysis of DM-F2 highlighted hexadecanoic acid and 1-(15-methyl-1-oxohexadecyl)-pyrrolidine as the most important metabolites. These compounds also exhibited high in silico binding affinity (-4.6 to -5.8 kcal/mol) to IL-1α, IL-1ß, and IL-2. Results suggested the joint immuno-modulatory and anti-proliferative effect derived from selected compounds of underutilized marine food products such as ink. This is the first report of such biological activities in extracts from O. vulgaris ink.

Asunto(s)

Antiinflamatorios/farmacología , Proliferación Celular/efectos de los fármacos , Octopodiformes/química , Animales , Citocinas/metabolismo , Células HCT116 , Humanos , Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metabolómica , Cloruro de Metileno/química , Ratones , Nitritos/metabolismo , Células RAW 264.7 , Transducción de Señal

RESUMEN

Searching for new alternatives to antibiotic treatments is crucial to surmount the multidrug-resistant bacteria. In this work, the antimicrobial activity of synthetic imidazolidines was evaluated as well as their modulating effect on the resistance to fluoroquinolones in a S. aureus strain (SA-1199B), which overexpresses the norA gene that encodes the NorA efflux pump. Results showed weak antimicrobial activity (512 µg mL-1) for two fluorobenzylidene derivatives against this bacterial strain, while the other benzylidene derivatives were inactive. Despite this fact, both fluorinated compounds were able to enhance the activity of norfloxacin and ciprofloxacin against SA-1199B up to 6.4- and 3.2-fold, respectively. In addition, both derivatives potentiated the action of ethidium bromide against this strain, suggesting that the modulating effect probably involves the inhibition of the NorA efflux pump, which is in concordance with the fluorimetic assays and molecular docking analyses performed in this work.

Asunto(s)

Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Imidazolidinas/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Proteínas Bacterianas/metabolismo , Relación Dosis-Respuesta a Droga , Imidazolidinas/síntesis química , Imidazolidinas/química , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Staphylococcus aureus/metabolismo , Estereoisomerismo , Relación Estructura-Actividad

RESUMEN

INTRODUCTION: Venezuela and Colombia both adopted measures of containment early in response to the COVID-19 pandemic. However, Venezuela's ongoing humanitarian crisis has decimated its health care system, and forced millions of Venezuelans to flee through its porous border with Colombia. The extensive shared border, and illegal cross-border transit through improvised trails between the two countries are major challenges for public health authorities. We report the first SARS-CoV-2 genomes from Venezuela, and present a snapshot of the SARS-CoV-2 epidemiologic landscape in the Colombian-Venezuelan border region. METHODS: We sequenced and assembled viral genomes from total RNA extracted from nasopharyngeal (NP) clinical specimens using a custom reference-based analysis pipeline. Three assemblies obtained were subjected to typing using the Phylogenetic Assignment of Named Global Outbreak LINeages 'Pangolin' tool. A total of 376 publicly available SARS-CoV-2 genomes from South America were obtained from the GISAID database to perform comparative genomic analyses. Additionally, the Wuhan-1 strain was used as reference. RESULTS: We found that two of the SARS-CoV-2 genomes from Venezuela belonged to the B1 lineage, and the third to the B.1.13 lineage. We observed a point mutation in the Spike protein gene (D614G substitution), previously reported to be associated with increased infectivity, in all three Venezuelan genomes. Additionally, three mutations (R203K/G204R substitution) were present in the nucleocapsid (N) gene of one Venezuelan genome. CONCLUSIONS: Genomic sequencing demonstrates similarity between SARS-CoV-2 lineages from Venezuela and viruses collected from patients in bordering areas in Colombia and from Brazil, consistent with cross-border transit despite administrative measures including lockdowns. The presence of mutations associated with increased infectivity in the 3 Venezuelan genomes we report and Colombian SARS-CoV-2 genomes from neighboring borders areas may pose additional challenges for control of SARS-CoV-2 spread in the complex epidemiological landscape in Latin American countries. Public health authorities should carefully follow the progress of the pandemic and its impact on displaced populations within the region.

Asunto(s)

COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/transmisión , COVID-19/virología , Colombia , Genoma Viral/genética , Humanos , Mutación/genética , Polimorfismo de Nucleótido Simple/genética , SARS-CoV-2/clasificación , SARS-CoV-2/genética , Venezuela

RESUMEN

The SLIT-ROBO axis plays an important role in normal stem-cell biology, with possible repercussions on cancer stem cell emergence. Although the Promyelocytic Leukemia (PML) protein can regulate SLIT2 expression in the central nervous system, little is known about SLIT2 in acute promyelocytic leukemia. Hence, we aimed to investigate the levels of SLIT2 in acute promyelocytic leukemia (APL) and assess its biological activity in vitro and in vivo. Our analysis indicated that blasts with SLIT2high transcript levels were associated with cell cycle arrest, while SLIT2low APL blasts displayed a more stem-cell like phenotype. In a retrospective analysis using a cohort of patients treated with all-trans retinoic acid (ATRA) and anthracyclines, high SLIT2 expression was correlated with reduced leukocyte count (p = 0.024), and independently associated with improved overall survival (hazard ratio: 0.94; 95% confidence interval: 0.92-0.97; p < 0.001). Functionally, SLIT2-knockdown in primary APL blasts and cell lines led to increased cell proliferation and resistance to arsenic trioxide induced apoptosis. Finally, in vivo transplant of Slit2-silenced primary APL blasts promoted increased leukocyte count (p = 0.001) and decreased overall survival (p = 0.002) compared with the control. In summary, our data highlight the tumor suppressive function of SLIT2 in APL and its deteriorating effects on disease progression when downregulated.

RESUMEN

OBJECTIVES: To assess outcomes of a variant of traditional modeling ("optimal modeling," OM) in patients with residual curvature following prosthesis implantation. METHODS: We performed a retrospective review of all patients who underwent penile implant insertion. Patients with >30° of residual curvature after cylinder placement and inflation underwent OM and were compared 1:1 to a demographically-matched cohort who received implantation without ancillary straightening. Optimal modeling was performed by forcibly bending the erect penis in the direction opposite the point of maximal curvature while maintaining glanular pressure to prevent urethral injury. This was performed for 90-second intervals for as many cycles as necessary to achieve <15° curvature. RESULTS: Eighty patients were included in the final analysis; 40 (50.0%) underwent optimal modeling while 40 (50.0%) did not need additional straightening following surgery. The mean premodeling curvature was 47.8° (range 30°-90°) while post-modeling curvature improved to a mean of 10.6° (range 0°-30°, P < .001); 87.5% of patients had <15° of residual curvature. Patients in the OM cohort experienced longer operative times (82.7 vs 75.8 min, P = .15). No patient in either group experienced an intraoperative or postoperative complication at a mean follow-up of 29.9 months. CONCLUSION: Although many prosthetic urologists forego manual modeling in cases of moderate-severe penile curvature, our contemporary series shows it to be both safe and effective. OM may preclude the need for more time-consuming and complex surgical procedures.

Asunto(s)

Disfunción Eréctil/cirugía , Implantación de Pene/efectos adversos , Induración Peniana/cirugía , Prótesis de Pene/efectos adversos , Complicaciones Posoperatorias/terapia , Anciano , Disfunción Eréctil/etiología , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Implantación de Pene/instrumentación , Induración Peniana/complicaciones , Pene/anatomía & histología , Pene/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/psicología , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

A solid-phase microextraction (SPME) coupled to gas chromatography-mass spectrometry method was validated for the simultaneous determination of penconazole, cyproconazole, epoxiconazole, deltamethrin, azoxystrobin and kresoxim-methyl in paddy rice irrigation water. Different SPME fiber coatings and pH values were tested. Polydimethylsiloxane (PDMS) and pH 7 were chosen to optimize extraction. All pesticides presented a recovery percentage between 90.5 and 104.2%; and detection and quantification limits were 0.03 and 0.05 µg/kg for azoxystrobin and cyproconazole, 0.02 and 0.05 µg/kg for deltametrhin and epoxiconazole, 0.02 and 0.03 µg/kg for kresoxim-methyl, and 0.01 and 0.02 µg/kg for penconazole. The expanded uncertainty was estimated for all pesticides showing results lower than 20%. A total of 100 paddy rice irrigation water samples, collected in different rice fields from Argentina, were evaluated. The study showed that 86 of them presented residues. The concentrations exceeded the values that were set by European legislation and the frequencies were higher than 86% so the agricultural practices should be revised.

Asunto(s)

Riego Agrícola , Oryza , Plaguicidas/análisis , Contaminantes Químicos del Agua/análisis , Riego Agrícola/métodos , Argentina , Productos Agrícolas , Cromatografía de Gases y Espectrometría de Masas/métodos , Concentración de Iones de Hidrógeno , Límite de Detección , Microextracción en Fase Sólida/métodos , Encuestas y Cuestionarios , Incertidumbre

RESUMEN

Non-T cell activation linker (NTAL) is a lipid raft-membrane protein expressed by normal and leukemic cells and involved in cell signaling. In acute promyelocytic leukemia (APL), NTAL depletion from lipid rafts decreases cell viability through regulation of the Akt/PI3K pathway. The role of NTAL in APL cell processes, and its association with clinical outcome, has not, however, been established. Here, we show that reduced levels of NTAL were associated with increased all-trans retinoic acid (ATRA)-induced differentiation, generation of reactive oxygen species, and mitochondrial dysfunction. Additionally, NTAL-knockdown (NTAL-KD) in APL cell lines led to activation of Ras, inhibition of Akt/mTOR pathways, and increased expression of autophagy markers, leading to an increased apoptosis rate following arsenic trioxide treatment. Furthermore, NTAL-KD in NB4 cells decreased the tumor burden in (NOD scid gamma) NSG mice, suggesting its implication in tumor growth. A retrospective analysis of NTAL expression in a cohort of patients treated with ATRA and anthracyclines, revealed that NTAL overexpression was associated with a high leukocyte count (P = 0.007) and was independently associated with shorter overall survival (Hazard Ratio: 3.6; 95% Confidence Interval: 1.17-11.28; P = 0.026). Taken together, our data highlights the importance of NTAL in APL cell survival and response to treatment.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Leucemia Promielocítica Aguda/patología , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Anciano , Animales , Antraciclinas/farmacología , Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia sin Enfermedad , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Leucemia Promielocítica Aguda/sangre , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/mortalidad , Recuento de Leucocitos , Masculino , Microdominios de Membrana/metabolismo , Ratones , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Tretinoina/farmacología , Tretinoina/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto , Adulto Joven

RESUMEN

BACKGROUND: Trypanosoma cruzi, the causative agent of Chagas disease, and T. rangeli are kinetoplastid parasites endemic to Latin America. Although closely related to T. cruzi and capable of infecting humans, T. rangeli is non-pathogenic. Both parasite species are transmitted by triatomine bugs, and the presence of T. rangeli constitutes a confounding factor in the study of Chagas disease prevalence and transmission dynamics. Trypanosoma cruzi possesses high molecular heterogeneity: seven discrete typing units (DTUs) are currently recognized. In Ecuador, T. cruzi TcI and T. rangeli KP1(-) predominate, while other genetic lineages are seldom reported. METHODS: Infection by T. cruzi and/or T. rangeli in different developmental stages of triatomine bugs from two communities of southern Ecuador was evaluated via polymerase chain reaction product size polymorphism of kinetoplast minicircle sequences and the non-transcribed spacer region of the mini-exon gene (n = 48). Forty-three mini-exon amplicons were also deep sequenced to analyze single-nucleotide polymorphisms within single and mixed infections. Mini-exon products from ten monoclonal reference strains were included as controls. RESULTS: Trypanosoma cruzi genetic richness and diversity was not significantly greater in adult vectors than in nymphal stages III and V. In contrast, instar V individuals showed significantly higher T. rangeli richness when compared with other developmental stages. Among infected triatomines, deep sequencing revealed one T. rangeli infection (3%), 8 T. cruzi infections (23.5%) and 25 T. cruzi + T. rangeli co-infections (73.5%), suggesting that T. rangeli prevalence has been largely underestimated in the region. Furthermore, deep sequencing detected TcIV sequences in nine samples; this DTU had not previously been reported in Loja Province. CONCLUSIONS: Our data indicate that deep sequencing allows for better parasite identification/typing than amplicon size analysis alone for mixed infections containing both T. cruzi and T. rangeli, or when multiple T. cruzi DTUs are present. Additionally, our analysis showed extensive overlap among the parasite populations present in the two studied localities (c.28 km apart), suggesting active parasite dispersal over the study area. Our results highlight the value of amplicon sequencing methodologies to clarify the population dynamics of kinetoplastid parasites in endemic regions and inform control campaigns in southern Ecuador.

Asunto(s)

ADN Protozoario/genética , Exones/genética , Variación Genética , Trypanosoma cruzi/genética , Trypanosoma rangeli/genética , Animales , Ecuador/epidemiología , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Insectos Vectores/parasitología , Masculino , Filogenia , Triatominae/parasitología

RESUMEN

Imidazoline derivatives with different exocyclic substituents were simply prepared from common starting materials. The procedures were carried out in an eco-friendly manner. The antioxidant activity of these derivatives was explored by different experimental assays, such as ABTS.+ and DPPH. scavenging assay, as well as reducing power assay. The structural differences are discussed in terms of the results. Sulfur analogs showed higher antioxidant activity than their oxygenated counterparts. The same tendency was observed in microbiological studies, in which the same imidazoline compounds were assayed for light-mediated activity against of Staphylococcus aureus and Escherichia coli strains. A light-enhanced activity was observed for almost all the sulfated imidazolines after exposure to UV-A (400-320 nm) light.

Asunto(s)

Antibacterianos/farmacología , Antioxidantes/farmacología , Escherichia coli/efectos de los fármacos , Imidazolinas/farmacología , Luz , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Antibacterianos/química , Antioxidantes/síntesis química , Antioxidantes/química , Benzotiazoles/antagonistas & inhibidores , Compuestos de Bifenilo/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Imidazolinas/síntesis química , Imidazolinas/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Picratos/antagonistas & inhibidores , Relación Estructura-Actividad , Ácidos Sulfónicos/antagonistas & inhibidores

RESUMEN

Objetivo . El propósito de este estudio fue comparar los cambios mediante tomografía computarizada de haz cónico en el posicionamiento condilar de pacientes Clase III antes y después de una osteotomía sagital bilateral de rama mandibular indicada para la retro- posición mandibular. Métodos . Se analizaron 30 pacientes, 16 mujeres y 14 hombres con rango de edad de 15 a 40 años y deformidad dentofacial Clase III no tratada que asistieron a consulta de diagnóstico en el periodo del año 2013 al 2016 en el Hospital Regional "General Ignacio Zaragoza" (CDMX, México), realizándoseles mediciones de la posición condilar en tres tiempos: prequirúrgico, intermedio (4 días posquirúrgico) y final (9 meses posquirúrgico), en dos planos: corte sagital y corte coronal. Resultados . No se observó diferencia significativa en los espacios anterior, central y posterior antes (2,56 ± 0,55 mm; 1,78 ± 0,48 mm; 1,92 ± 0,36 mm) y después (2,68 ± 0,51 mm; 1,87 ± 0,43 mm; 2,01 ± 0,37 mm), diferencia de medias -0,120; -0,085; -0,090 p =0,921; 0,948 y 0,778, respectivamente. Del mismo modo, en el corte coronal no se observan cambios significativos en los ángulos condilares derecho antes (68,25 ± 1,56°) y después (68,77 ± 1,63°) p =0,217; e izquierdo antes (68,92 ± 1,63°) y después (69,30 ± 2°) p =0,215. Conclusiones . La osteotomía sagital bilateral de rama mandibular en pacientes Clase III es una técnica quirúrgica que ofrece mínimas alteraciones condilares, pues mantiene una estabilidad condilar en el posoperatorio a 9 meses.

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Objective. The purpose of this study was to compare the changes by conical beam com- puted tomography in the condylar positioning of Class III patients before and after a sagittal osteotomy of the bilateral mandibular ramus in Class III indicated for mandibu- lar retroposition. Methods. Thirty patients were analyzed, 16 women and 14 men with an age range of 15 to 40 years and untreated Class III dentofacial deformity who were attended by diagnostic consultation during the period from 2013 to 2016 at the "Gen eral Ignacio Zaragoza" Regional Hospital (CDMX, Mexico), performing measurements of the condylar position in three stages: presurgical, intermediate (4 days after surgery) and final (9 months after surgery), in two planes: sagittal section and coronal section. Re - sults. No significant difference was observed in the anterior, central and posterior spaces before (2.56 ± 0.55 mm; 1.78 ± 0.48 mm; 1.92 ± 0.36 mm) and after (2.68 ± 0.51 mm; 1.87 ± 0.43 mm; 2.01 ± 0.37 mm), mean difference -0.120; -0,085; -0.090 p =0.921; 0.948 and 0.778, respectively. Similarly, in the coronal section there are no significant changes in the right condylar angles before (68.25 ± 1.56 °) and after (68.77 ± 1.63°) p =0.217; and left before (68.92 ± 1.63°) and then (69.30 ± 2°) p =0.215. Conclusions. Sagittal osteotomy of the bilateral mandibular ramus in Class III patients is a surgical technique that offers minimal condylar alterations, since it maintains a condylar stability in the postoperative period at 9 months.