Fermented Goat's Milk Contributes to the Recovery of Iron Deficiency Anemia via Modulation of the Gut Microbiome.

Iron deficiency anemia (IDA) is a global public health concern affecting 1.6 billion people worldwide. The administration of iron supplements during the treatment of IDA adversely affects the intestinal barrier function and the composition and functionality of the intestinal microbiome, both of which are already altered during IDA. For this reason, it is of great interest to develop nutritional strategies aimed at alleviating these gut alterations associated with IDA and its treatment. In this sense, fermented goat's milk (FGM) was studied due to its nutritional quality. Our findings showed that in anemic animals the consumption of a FGM-based diet, compared to a standard diet, had positive modulatory effects on the intestinal microbiome. FGM-based diet restored intestinal dysbiosis, the intestinal barrier functionality, and bacterial translocation, contributing to a more efficient recovery of IDA. Therefore, FGM is a useful nutritional tool to ease intestinal alterations occurring during IDA and during its treatment.

Single-Bud Expression Analysis of Bud Dormancy Factors in Peach.

Transcriptomic and gene expression analysis have greatly facilitated the identification and characterization of transcriptional regulatory factors and effectors involved in dormancy progression and other physiological processes orchestrated during bud development in peach and other temperate fruit species. Gene expression measurements are most usually based on average values from several or many individual buds. We have performed single-bud gene analysis in flower buds of peach across dormancy release using amplicons from the master regulatory DORMANCY-ASSOCIATED MADS-BOX (DAM) factors, several jasmonic acid biosynthetic genes, other genes related to flowering development, cell growth resumption, and abiotic stress tolerance. This analysis provides a close view on gene-specific, single-bud variability throughout the developmental shift from dormant to dormancy-released stages, contributing to the characterization of putative co-expression modules and other regulatory aspects in this particular tissue.

Gallic Acid: A Natural Phenolic Compound Exerting Antitumoral Activities in Colorectal Cancer via Interaction with G-Quadruplexes.

Natural phenolic compounds have gained momentum for the prevention and treatment of cancer, but their antitumoral mechanism of action is not yet well understood. In the present study, we screened the antitumoral potential of several phenolic compounds in a cellular model of colorectal cancer (CRC). We selected gallic acid (GA) as a candidate in terms of potency and selectivity and extensively evaluated its biological activity. We report on the role of GA as a ligand of DNA G-quadruplexes (G4s), explaining several of its antitumoral effects, including the transcriptional inhibition of ribosomal and CMYC genes. In addition, GA shared with other established G4 ligands some effects such as cell cycle arrest, nucleolar stress, and induction of DNA damage. We further confirmed the antitumoral and G4-stabilizing properties of GA using a xenograft model of CRC. Finally, we succinctly demonstrate that GA could be explored as a therapeutic agent in a patient cohort with CRC. Our work reveals that GA, a natural bioactive compound present in the diet, affects gene expression by interaction with G4s both in vitro and in vivo and paves the way towards G4s targeting with phenolic compounds.

Curvicollide D Isolated from the Fungus Amesia sp. Kills African Trypanosomes by Inhibiting Transcription.

Sleeping sickness or African trypanosomiasis is a serious health concern with an added socio-economic impact in sub-Saharan Africa due to direct infection in both humans and their domestic livestock. There is no vaccine available against African trypanosomes and its treatment relies only on chemotherapy. Although the current drugs are effective, most of them are far from the modern concept of a drug in terms of toxicity, specificity and therapeutic regime. In a search for new molecules with trypanocidal activity, a high throughput screening of 2000 microbial extracts was performed. Fractionation of one of these extracts, belonging to a culture of the fungus Amesia sp., yielded a new member of the curvicollide family that has been designated as curvicollide D. The new compound showed an inhibitory concentration 50 (IC50) 16-fold lower in Trypanosoma brucei than in human cells. Moreover, it induced cell cycle arrest and disruption of the nucleolar structure. Finally, we showed that curvicollide D binds to DNA and inhibits transcription in African trypanosomes, resulting in cell death. These results constitute the first report on the activity and mode of action of a member of the curvicollide family in T. brucei.

Gut microbiome-short-chain fatty acids interplay in the context of iron deficiency anaemia.

PURPOSE: Anaemia is a global health concern, with iron deficiency anaemia (IDA) causing approximately 50% of cases. Affecting mostly the elderly, pregnant and adult women and children, physiopathology of IDA in relation to the gut microbiome is poorly understood. Therefore, the objective of this study is to analyse, in an animal model, the effect of IDA on the gut microbiome along the gastrointestinal tract, as well as to relate intestinal dysbiosis to changes in microbial metabolites such as short chain fatty acids (SCFA). METHODS: IDA was experimentally induced through an iron deficient diet for a period of 40 days, with twenty weaned male Wistar rats being randomly divided into control or anaemic groups. Blood samples were collected to control haematological parameters, and so were faecal and intestinal content samples to study gut microbial communities and SCFA, using 16S rRNA sequencing and HPLC-UV respectively. RESULTS: An intestinal dysbiosis was observed as a consequence of IDA, especially towards the distal segments of the gastrointestinal tract and the colon. An increase in SCFA was also noticed during IDA, with the major difference appearing in the colon and correlating with changes in the composition of the gut microbiome. Clostridium_sensu_stricto_1 and Clostridium_sensu_stricto_4 showed the greatest correlation with variations in butyric and propionic concentrations in the colon of anaemic animals. CONCLUSIONS: Composition of intestinal microbial communities was affected by the generation of IDA. An enrichment in certain SCFA-producing genera and SCFA concentrations was found in the colon of anaemic animals, suggesting a trade-off mechanism against disease.

Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment.

Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory genomic regions. G4 targeting has emerged as a therapeutic approach in cancer. We have screened naphthalene-diimides (NDIs), a class of G4 ligands, in a cellular model of colorectal cancer (CRC). Here, we identify the leading compound T5 with a potent and selective inhibition of cell growth by high-affinity binding to G4s in ribosomal DNA, impairing RNA polymerase I (Pol I) elongation. Consequently, T5 induces a rapid inhibition of Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and autophagy. Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells to its preferential uptake through the overexpressed glucose transporter 1. Finally, we succinctly demonstrate that T5 could be explored as a therapeutic agent in a patient cohort with CRC. Therefore, we report a mode of action for these NDIs involving ribosomal G4 targeting.

Influence of 16S rRNA target region on the outcome of microbiome studies in soil and saliva samples.

Next generation sequencing methods are widely used in evaluating the structure and functioning of microbial communities, especially those centered on 16S rRNA subunit. Since Illumina Miseq, the most used sequencing platform, does not allow the full sequencing of 16S rRNA gene, this study aims to evaluate whether the choice of different target regions might affect the outcome of microbiome studies regarding soil and saliva samples. V1V3, V3V4, V4V5 and V6V8 domains were studied, finding that while some regions showed differences in the detection of certain bacterial taxa and in the calculation of alpha diversity, especially in soil samples, the overall effect did not compromise the differentiation of any sample type in terms of taxonomic analysis at the genus level. 16S rRNA target regions did affect the detection of specific bacteria related to soil quality and development, and microbial genera used as health biomarkers in saliva. V1V3 region showed the closest similarity to internal sequencing control mock community B, suggesting it might be the most preferable choice regarding data reliability.

Mamíferos medianos y grandes asociados al bosque tropical seco del centro de México / Medium and large mammals associated with the tropical dry forest of central Mexico

Resumen El bosque tropical seco es uno de los ecosistemas más amenazados alrededor del mundo, principalmente a causa de la deforestación. En México más de la mitad de su superficie ha desaparecido, lo que ha provocado pérdida de biodiversidad. El objetivo de este estudio fue comparar la riqueza, diversidad y abundancia relativa de la comunidad de mamíferos medianos y grandes en dos sitios con diferente manejo y estatus de conservación, y donde está presente el bosque tropical seco. También se buscó conocer las variables del hábitat y de influencia humana que se relacionan con la presencia de las especies más comunes. Los sitios de estudio fueron Pastorías, Actopan, Veracruz y San Juan Bautista Cuicatlán, Oaxaca, México. El primer sitio está muy transformado por las actividades antrópicas mientras que el segundo se encuentra dentro de la Reserva de la Biosfera de Tehuacán-Cuicatlán (RBTC). En Pastorías se establecieron 11 cámaras-trampa de septiembre 2015 a septiembre 2016; mientras que en Cuicatlán 10 cámaras-trampa de octubre 2013 a julio 2014. El esfuerzo de muestreo fue de 3 526 días/trampa y 443 registros independientes, y 2 690 días/trampa y 378 registros independientes para cada sitio respectivamente. En cada localidad se registraron 13 especies. Tres de estas especies están en peligro de extinción y dos bajo amenaza. Se encontraron diferencias estadísticamente significativas entre la diversidad verdadera de mamíferos medianos y grandes entre localidades. De acuerdo con el índice de abundancia relativa (IAR), las especies más abundantes fueron: Odocoileus virginianus, Urocyon cinereoargenteus y Canis latrans. Los análisis de regresión sugieren que las variables de temporada, la cobertura de vegetación secundaria arbórea y la distancia a la localidad más cercana se relacionan con el registro de estas especies. Los remanentes de bosque tropical seco en Pastorías mantienen una alta riqueza de especies, la cual es muy parecida a la de un sitio conservado como Cuicatlán. Sin embargo, el bajo número de registros fotográficos puede indicar que la calidad del hábitat no es adecuada. La información recabada en este estudio puede ser útil para el desarrollo de programas para conservar el bosque tropical seco del centro de Veracruz y contribuye con la ampliación del conocimiento que se tiene sobre la comunidad de mamíferos que habitan en la RBTC.

Abstract The tropical dry forest is one of the most endangered ecosystems in the world, mainly due to deforestation and fragmentation. In Mexico more than half of its surface has disappeared, affecting biodiversity. The objective of this study was to compare the richness, diversity, and relative abundance of medium and large mammals in two sites with different management and conservation status, and where tropical dry forest is present. We also sought to find out which variables of habitat and human influence are related to the presence of the most common species. The study sites were in Pastorias, Actopan, Veracruz and San Juan Bautista Cuicatlan, Oaxaca, Mexico. The first site is highly transformed by anthropogenic activities, while the second is within the protected natural area of the Tehuacan-Cuicatlan Biosphere Reserve (TCBR). In Pastorias 11 camera-traps were set up from september 2015 to september 2016; while in Cuicatlan 10 camera traps were set up from october 2013 to july 2014. The sampling effort was 3 526 days/trap, which yielded 443 independent records for the first site, and 2 690 days/trap that yielded 378 independent records for the second site. In each locality, 13 species of mammals were recorded. In particular, three of these species are endangered (Tamandua mexicana, Leopardus wiedii, and Lynx rufus) and two are under threat (Herpailurus yagouaroundi and Galictis vittata). The true diversity of medium and large mammals between communities was different. According to the relative abundance, index (RAI) the most abundant species are Odocoileus virginianus, Urocyon cinereoargenteus and Canis latrans. Regression analyses suggest that the variables of season, the cover of secondary vegetation and distance to the nearest human locality were related to the record of these species. Despite the anthropogenic pressure in Pastorias, tropical dry forest remnants still maintain high species richness, which is very similar to that of a site as preserved as Cuicatlan. However, the low RAIs value of several mammals may indicate that habitat quality could not maintain large population numbers. Therefore, it is necessary to develop programs to conserve this ecosystem. Rev. Biol. Trop. 66(3): 1232-1243. Epub 2018 September 01.

Identification of Trypanosomatids by detecting Single Nucleotide Fingerprints using DNA analysis by dynamic chemistry with MALDI-ToF.

Protozoan parasites of the Trypanosomatidae family can cause devastating diseases in humans and animals, such as Human African Trypanosomiasis or Sleeping Sickness, Chagas disease and Leishmaniasis. Currently, there are molecular assays for detecting parasitic infections and their post-treatment monitoring based on nucleic acid amplification, but there are still certain limitations which limit the development of assays that can detect and discriminate between parasite infections with a single test. Here, we present the development of a novel molecular assay for the rapid identification of Trypanosomatids, integrating DNA analysis by dynamic chemistry in conjunction with Matrix-Assisted Laser Desorption Ionization - Time-of-Flight Mass Spectrometry (MALDI-ToF). Differentiation of Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp. is now possible using a single reaction tube, and enables rapid identification of Trypanosomatids. The test is based on a singleplex PCR, using a specific primer pair that amplifies a 155 base pair segment of the 28S ribosomal RNA gene, within a conserved homology region of Trypanosomatidae species. Amplified fragments are analysed by dynamic chemistry using two abasic PNA probes and the four reactive nucleobases - containing an aldehyde functional group - with MALDI-ToF to identify unique molecular patterns created by each specie due to their single base differences (Single Nucleotide Fingerprint 'SNF') in this highly homologous region. This novel assay offers the possibility to expand routine diagnostic testing for Trypanosomatids, and monitoring of therapeutic responses to these infectious diseases.

Procalcitonin for selecting the antibiotic regimen in outpatients with low-risk community-acquired pneumonia using a rapid point-of-care testing: A single-arm clinical trial.

OBJECTIVE: We aimed to assess the role of procalcitonin (PCT) to guide the initial selection of the antibiotic regimen for low-risk community-acquired pneumonia (CAP). METHODS: A single-arm clinical trial was conducted including outpatients with CAP and Pneumonia Severity Index risk classes I-II. Antimicrobial selection was based on the results of PCT measured with a rapid point-of-care testing. According to serum PCT levels, patients were assigned to two treatment strategies: oral azithromycin if PCT was <0.5 ng/ml, or levofloxacin if levels were ≥0.5 ng/ml. Primary outcome was clinical cure rate. Short-term and long-term outcomes were assessed. Results were compared with those of a historical standard-of-care control-group treated in our centre. RESULTS: Of 253 subjects included, 216 (85.4%) were assigned to azithromycin. Pneumococcal infection was diagnosed in 26 (12%) and 21 (56.8%) patients allocated to azithromycin and levofloxacin groups, respectively. No patients in the azithromycin group developed bacteraemia. Atypical organisms were more common in patients given azithromycin (18.5% vs 8.1%, respectively). The majority (93%) of patients with atypical pneumonia had low PCT levels. Clinical cure rates were 95.8% in the azithromycin group, 94.6% in the levofloxacin group, and 94.4% in the historical control group. No 30-day mortality or recurrences were observed, and the 3-year rates of recurrence and mortality were very low in both groups. Adverse events occurrence was also infrequent. CONCLUSION: A PCT-guided strategy with a rapid point-of-care testing safely allowed selecting empirical narrow-spectrum antibiotics in outpatients with CAP. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov, number NCT02600806.

Specific Cell Targeting Therapy Bypasses Drug Resistance Mechanisms in African Trypanosomiasis.

African trypanosomiasis is a deadly neglected disease caused by the extracellular parasite Trypanosoma brucei. Current therapies are characterized by high drug toxicity and increasing drug resistance mainly associated with loss-of-function mutations in the transporters involved in drug import. The introduction of new antiparasitic drugs into therapeutic use is a slow and expensive process. In contrast, specific targeting of existing drugs could represent a more rapid and cost-effective approach for neglected disease treatment, impacting through reduced systemic toxicity and circumventing resistance acquired through impaired compound uptake. We have generated nanoparticles of chitosan loaded with the trypanocidal drug pentamidine and coated by a single domain nanobody that specifically targets the surface of African trypanosomes. Once loaded into this nanocarrier, pentamidine enters trypanosomes through endocytosis instead of via classical cell surface transporters. The curative dose of pentamidine-loaded nanobody-chitosan nanoparticles was 100-fold lower than pentamidine alone in a murine model of acute African trypanosomiasis. Crucially, this new formulation displayed undiminished in vitro and in vivo activity against a trypanosome cell line resistant to pentamidine as a result of mutations in the surface transporter aquaglyceroporin 2. We conclude that this new drug delivery system increases drug efficacy and has the ability to overcome resistance to some anti-protozoal drugs.

Terapia por presión negativa en el manejo de heridas complejas en traumatología. Innovación e indicación / Negative Pressure Therapy for treatment of complex wounds in Orthopaedic Surgery. Innovation and Indication

La terapia por presión negativa (TPN) es una modalidad terapéutica complementaria ampliamente difundida en la actualidad para el manejo de heridas complejas en el ámbito de la Traumatología y Ortopedia. Los dispositivos más modernos permiten adicionar a esta terapia la instilación intermitente de soluciones (Terapia por Presión Negativa con Instilación Intermitente, TPNII) para una mayor efi cacia del tratamiento. En el presente trabajo se revisarán los fundamentos de la terapia, así como sus principales indicaciones, recomendaciones de uso y nuestra experiencia clínica con el mismo

Negative Pressure Therapy (NPT) is an adjuvant method of treatment broadly widespread for management of complex wounds in the fi eld of Orthopaedic Surgery. Modern devices also allow intermitent instillation of different types of lavage solutions (Negative Pressure Therapy with Intermitent Instillation, NPTII), increasing the effi cacy of treatment. The present article reviews the basis of the described therapy as well as its main indications, recommendations of use and our personal clinical experience with the device

Hipertensión Arterial en el Embarazo: algunos aspectos epidemiológicos: 2do Semestre del 2004 / Arterial hypertension in pregnancy: some epidemiological aspects: second semester 2004

Se realizó un estudio longitudinal prospectivo en el Hospital General Docente “Guillermo Domínguez López” del municipio Puerto Padre, provincia Las Tunas, para determinar algunos aspectos epidemiológicos de la hipertensión en el embarazo, en el período comprendido desde el 1ro de Julio hasta el 31 de Diciembre del 2004. Se tomó una muestra de 50 pacientes atendidas en el servicio de Obstetricia con diagnóstico de hipertensión en el embarazo escogidas al azar, se concluyó que el grupo de edad que predominó fue el de 25 29 años, conjuntamente al de las pacientes con edad gestacional entre 28 36,6 semanas. La multiparidad, desnutrición y antecedentes familiares de hipertensión constituyeron los factores de riesgo de mayor incidencia y la preeclampsia leve fue el diagnóstico que predominó, así como el parto eutócico. Se recomendó la capacitación del personal médico(AU)

A longitudinal and prospective study was done in the General Teaching Hospital “Guillermo Domínguez López” of Puerto Padre municipality in Las Tunas province in order to determine some epidemiological aspects of hypertension in pregnancy from July 1 st to December 31 st 2004 . The sample was constituted by 50 patients selected at random in the obstetrical service with diagnose of hypertension in pregnancy. It was concluded that the group of 25 29 years old prevailed among the others together with the group of patients with gestational time between 28 36.6 weeks. Multiparity, malnutrition and family antecedents of hypertension constituted the greater incident risk factors and light preeclampsia was the prevailing diagnose as well as eutocia. Qualification of medical staff was recommended(AU)

Accidentes de tránsito en niños : aspectos médicos y epidemiológicos / Road accidents in children : medical and epidemiological aspects

Se presentan los resultados de un estudio retrospectivo de 105 casos de accidentes de tránsito en niños, tratados en el Hospital Nacional de Niños en un período de 2 meses. En él, se trata de establecer el tipo, sitio y frecuencia de las lesiones traumáticas y algunos aspectos socioeconómicos y ambientales que rodearon a los eventos y, con base en estos, ayudar a promover políticas institucionales para prevenirlos. Predominó el sexo masculino (2:1); los accidentes se presentaron con más frecuencia en los fines de semana (58%) horas de la tarde (44%); el 77%ocurrió en la calle. Los vehículos que más frecuentemente causaron lesiones fueron el automóvil y la bicicleta, sin embargo, el 67%de los niños eran peatones. Un 15%recibió alguna atención inmediata después del accidente, pero la primaria se hizo en el Hospital de Niños, quedando 18%internados y 26%en observación. El cráneo y la cara fueron los sitios más afectados, seguidos de los miembros, abdomen y tórax. Las heridas contusas y cortantes, con laceración en el 29%de los casos, fueron las lesiones más frecuentes. El entorno familiar y socioeconómico indicó que un 75%de los niños internados provienen de hogares de clase baja y pobre, con nivel de estudios de los padres hasta primaria en el 40%. Se concluye que, para prevenir los accidentes, es prioritaria la educación a nivel del hogar, escuelas y colegios y aumentar la calidad de las sanciones al conductor o peatón que transgreda las leyes.