Characterization of the oral microbiota and the relationship of the oral microbiota with the dental and periodontal status in children and adolescents with nonsyndromic cleft lip and palate. Systematic literature review and meta-analysis.

OBJECTIVE: To identify the characteristics of the oral microbiota and the relationship of the dental caries and periodontal status in patients aged 0 to 18 years with non-syndromic cleft lip and palate (CLP). MATERIALS AND METHODS: A systematic review of the literature was carried out. Five databases were consulted, including publications in English, Spanish and Portuguese. The evaluations of the quality of the observational studies and the experimental studies were carried out with the Newcastle-Ottawa scale and CONSORT guidelines, respectively. The risk of bias of the studies was determined using Rev Manager 5.4, and 5 publications were meta-analyzed. RESULTS: The cariogenic microbiota of children and adolescents with cleft lip and palate was similar to that of children without clefts, although with higher counts of Streptococcus mutans and Lactobacillus spp. The periodontopathogenic microbiota was related to the presence of Campylobacter spp, Fusobacterium spp, Fusobacterium nucleatum, Prevotella intermedia/nigrescens, Parvimonas micra and Porphyromonas gingivalis, considered microorganisms with high pathogenic capacity. Heterogeneity was shown in relation to the microbiota and the type of fissure, presenting numerous microorganisms associated with the pre- and post-surgical condition (cheilorrhaphy and palatorrhaphy) such as Staphylococcus aureus, Streptococcus beta hemolyticus, Klebsiella pneumoniae and Klebsiella oxytoca, Moraxella catarrhalis, Candida spp, Candida albicans, Candida krusei and Candida tropicalis. The meta-analysis revealed that patients with cleft lip and palate were 2.03 times more likely to have caries than the control group (p<0.005). CONCLUSION: In the microbiota, there was a great diversity of microorganisms that can vary according to the type of fissure and surgical interventions predisposing patients to a greater probability of dental caries, it is important to take into account the technique used to describe the oral microbiota in order to be able to compare the different studies. CLINICAL RELEVANCE: Studying the microbiota and the relationship of dental caries and periodontal status in children and adolescents with cleft lip and palate can facilitate the comprehensive care of patients with these conditions.

Mamografía con contraste: nuestra experiencia / Contrast-enhanced digital mammography: our experience

Resumen La mamografía contrastada (CEDM, contrast-enhanced digital mammography) es una herramienta nueva que ha ido implementándose de forma creciente. Aparece como alternativa a la resonancia magnética (RM), y al igual que esta, tiene como principio el uso de contraste endovenoso para explorar la angiogénesis tumoral. Combina la imagen de mamografía convencional (Mx) con la técnica de sustracción con energía dual poscontraste, lo que resulta en un incremento en la detección de cáncer de mama, en un tiempo corto de estudio y a un bajo costo. Es un método prometedor en casos seleccionados y de fácil lectura, siendo útil principalmente en pacientes con diagnóstico de cáncer de mama para detectar lesiones adicionales y determinar el tamaño tumoral, ayudando en la planificación quirúrgica, así como también en la evaluación de la respuesta a la neoadyuvancia. También en el seguimiento de pacientes operadas, para caracterizar lesiones dudosas en Mx y ecografía, o como alternativa ante contraindicación de la RM. El objetivo de este trabajo es valorar la utilidad de la mamografía contrastada en la práctica diaria y determinar sus principales indicaciones. Repasamos con casos propios las utilidades y características del método.

Abstract Contrast-enhanced digital mammography (CEDM) is an emerging tool that has been increasingly implemented. It appears as an alternative to magnetic resonance imaging (MRI), using intravenous contrast to explore tumor angiogenesis. It combines conventional mammography (Mx) with post-contrast dual energy subtraction technique, resulting in increased detection of breast cancer, in a short study time and at a low cost. It is a promising method in selected cases and easy to read, being useful mainly in patients with breast cancer to detect additional lesions and determine the tumor size, that helps surgical planning, as well as in the evaluation of post-neoadjuvant chemotherapy response in the follow-up of patients treated with surgery, to address inconclusive findings in screening mammogram, or as an alternative when MRI is contraindicated. The purpose of this article is to assess the usefulness of contrasted mammography in daily practice and to determine its main indications. We review with our own cases the applications and characteristics of this method.

Research priorities in multiple sclerosis in Latin America: A multi-stakeholder call to action to improve patients care: Research priorities in MS in LATAM.

As human and economic resources are limited, especially in Latin America (LATAM), it is important to identify research priorities to improve multiple sclerosis (MS) patients care in the region. The objective was to generate a multidisciplinary consensus on research priorities in MS for patients care in LATAM by involving healthcare professionals and MS patient associations. METHODS: consensus was reached through a four-step modified Delphi method designed to identify and rate research priorities in MS in LATAM. The process consisted of two qualitative assessments, a general ranking phase and a consensus meeting followed by a more detailed ranking phase RESULTS: a total of 62 participants (35 neurologists, 4 nurses, 12 kinesiologists, 7 neuropsychologists and 4 patient association members) developed the process. At the final ranking stage following the consensus meeting, each participant provided their final rankings, and the top priority research questions were outlined. 11 research priorities were identified focusing on healthcare access, costs of the disease, physical and cognitive evaluation and rehabilitation, quality of life, symptoms management, prognostic factors, the need of MS care units and patient's management in emergencies like COVID-19. CONCLUSION: this work establishes MS research priorities in LATAM from multiple perspectives. To pursue the actions suggested could launch the drive to obtain information that will help us to better understand the disease in our region and, especially, to better care for affected patients.

Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats.

The effect of perinatal asphyxia (PA) on oligodendrocyte (OL), neuroinflammation, and cell viability was evaluated in telencephalon of rats at postnatal day (P)1, 7, and 14, a period characterized by a spur of neuronal networking, evaluating the effect of mesenchymal stem cell (MSCs)-treatment. The issue was investigated with a rat model of global PA, mimicking a clinical risk occurring under labor. PA was induced by immersing fetus-containing uterine horns into a water bath for 21 min (AS), using sibling-caesarean-delivered fetuses (CS) as controls. Two hours after delivery, AS and CS neonates were injected with either 5 µL of vehicle (10% plasma) or 5 × 104 MSCs into the lateral ventricle. Samples were assayed for myelin-basic protein (MBP) levels; Olig-1/Olig-2 transcriptional factors; Gglial phenotype; neuroinflammation, and delayed cell death. The main effects were observed at P7, including: (i) A decrease of MBP-immunoreactivity in external capsule, corpus callosum, cingulum, but not in fimbriae of hippocampus; (ii) an increase of Olig-1-mRNA levels; (iii) an increase of IL-6-mRNA, but not in protein levels; (iv) an increase in cell death, including OLs; and (v) MSCs treatment prevented the effect of PA on myelination, OLs number, and cell death. The present findings show that PA induces regional- and developmental-dependent changes on myelination and OLs maturation. Neonatal MSCs treatment improves survival of mature OLs and myelination in telencephalic white matter.

Sustained Energy Deficit Following Perinatal Asphyxia: A Shift towards the Fructose-2,6-bisphosphatase (TIGAR)-Dependent Pentose Phosphate Pathway and Postnatal Development.

Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia (PA). PA causes an energy failure, leading to cell dysfunction and death if re-oxygenation is not promptly restored. PA is associated with long-term effects, challenging the ability of the brain to cope with stressors occurring along with life. We review here relevant targets responsible for metabolic cascades linked to neurodevelopmental impairments, that we have identified with a model of global PA in rats. Severe PA induces a sustained effect on redox homeostasis, increasing oxidative stress, decreasing metabolic and tissue antioxidant capacity in vulnerable brain regions, which remains weeks after the insult. Catalase activity is decreased in mesencephalon and hippocampus from PA-exposed (AS), compared to control neonates (CS), in parallel with increased cleaved caspase-3 levels, associated with decreased glutathione reductase and glutathione peroxidase activity, a shift towards the TIGAR-dependent pentose phosphate pathway, and delayed calpain-dependent cell death. The brain damage continues long after the re-oxygenation period, extending for weeks after PA, affecting neurons and glial cells, including myelination in grey and white matter. The resulting vulnerability was investigated with organotypic cultures built from AS and CS rat newborns, showing that substantia nigra TH-dopamine-positive cells from AS were more vulnerable to 1 mM of H2O2 than those from CS animals. Several therapeutic strategies are discussed, including hypothermia; N-acetylcysteine; memantine; nicotinamide, and intranasally administered mesenchymal stem cell secretomes, promising clinical translation.

Intranasal Administration of Mesenchymal Stem Cell Secretome Reduces Hippocampal Oxidative Stress, Neuroinflammation and Cell Death, Improving the Behavioral Outcome Following Perinatal Asphyxia.

Perinatal Asphyxia (PA) is a leading cause of motor and neuropsychiatric disability associated with sustained oxidative stress, neuroinflammation, and cell death, affecting brain development. Based on a rat model of global PA, we investigated the neuroprotective effect of intranasally administered secretome, derived from human adipose mesenchymal stem cells (MSC-S), preconditioned with either deferoxamine (an hypoxia-mimetic) or TNF-α+IFN-γ (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 °C for 21 min. Thereafter, 16 µL of MSC-S (containing 6 µg of protein derived from 2 × 105 preconditioned-MSC), or vehicle, were intranasally administered 2 h after birth to asphyxia-exposed and control rats, evaluated at postnatal day (P) 7. Alternatively, pups received a dose of either preconditioned MSC-S or vehicle, both at 2 h and P7, and were evaluated at P14, P30, and P60. The preconditioned MSC-S treatment (i) reversed asphyxia-induced oxidative stress in the hippocampus (oxidized/reduced glutathione); (ii) increased antioxidative Nuclear Erythroid 2-Related Factor 2 (NRF2) translocation; (iii) increased NQO1 antioxidant protein; (iv) reduced neuroinflammation (decreasing nuclearNF-κB/p65 levels and microglial reactivity); (v) decreased cleaved-caspase-3 cell-death; (vi) improved righting reflex, negative geotaxis, cliff aversion, locomotor activity, anxiety, motor coordination, and recognition memory. Overall, the study demonstrates that intranasal administration of preconditioned MSC-S is a novel therapeutic strategy that prevents the long-term effects of perinatal asphyxia.

Gold nanorods/siRNA complex administration for knockdown of PARP-1: a potential treatment for perinatal asphyxia.

BACKGROUND: Perinatal asphyxia interferes with neonatal development, resulting in long-term deficits associated with systemic and neurological diseases. Despite the important role of poly (ADP-ribose) polymerase 1 (PARP-1) in the regulation of gene expression and DNA repair, overactivation of PARP-1 in asphyxia-exposed animals worsens the ATP-dependent energetic crisis. Inhibition of PARP-1 offers a therapeutic strategy for diminishing the effects of perinatal asphyxia. METHODS: We designed a nanosystem that incorporates a specific siRNA for PARP-1 knockdown. The siRNA was complexed with gold nanorods (AuNR) conjugated to the peptide CLPFFD for brain targeting. RESULTS: The siRNA was efficiently delivered into PC12 cells, resulting in gene silencing. The complex was administered intraperitoneally in vivo to asphyxia-exposed rat pups, and the ability of the AuNR-CLPFFD/siRNA complex to reach the brain was demonstrated. CONCLUSION: The combination of a nanosystem for delivery and a specific siRNA for gene silencing resulted in effective inhibition of PARP-1 in vivo.

Regionally Impaired Redox Homeostasis in the Brain of Rats Subjected to Global Perinatal Asphyxia: Sustained Effect up to 14 Postnatal Days.

The present report evaluates the effect of global perinatal asphyxia on several parameters of oxidative stress and cell viability in rat brain tissue sampled at an extended neonatal period up to 14 days, a period characterised by intensive neuritogenesis, synaptogenesis, synaptic consolidation, pruning and delayed cell death. Perinatal asphyxia was induced by immersing foetus-containing uterine horns removed by a caesarean section from on term rat dams into a water bath at 37 °C for 21 min. Asphyxia-exposed and sibling caesarean-delivered foetuses were manually resucitated and nurtured by surrogate dams for 1 to 14 postnatal (P) days. Brain samples (mesencephalon, telencephalon and hippocampus) were assayed for glutathione (reduced and oxidated levels; spectrophotometry), tissue reducing capacity (potassium ferricyanide reducing assay, FRAP), catalase (the key enzyme protecting against oxidative stress and reactive oxygen species, Western blots and ELISA) and cleaved caspase-3 (the key executioner of apoptosis, Western blots) levels. It was found that global PA produced a regionally specific and sustained increase in GSSG/GSH ratio, a regionally specific decrease in tissue reducing capacity and a regionally and time specific decrease of catalase activity and increase of cleaved caspase-3 levels. The present study provides evidence for regionally impaired redox homeostasis in the brain of rats subjected to global PA, an effect observed up to P14, mainly affecting mesencephalon and hippocampus, suggesting a sustained oxidative stress after the posthypoxia period. The oxidative stress observed postnatally can in part be associated to a respiratory apneic-like deficit, since there was a statistically significant decrease in respiration frequency in AS compared to CS neonates, also up to P14, together with the signs of a decreased peripheral blood perfusion (pink-blue skin colour in AS, compared to the pink colour observed in all CS neonates). It is proposed that PA implies a long-term metabolic insult, triggered by the length of hypoxia, the resuscitation/reoxigenation manoevres, but also by the developmental stage of the affected brain regions, and the integrity of cardiovascular and respiratory physiological functions, which are fundamental for warrantying a proper development.

Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: a Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?

Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult.PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1α (HIF-1α) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD+ exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-κB subunit p65, overexpression of the pro-inflammatory cytokines IL-1ß and TNF-α, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss evidence showing that (i) inhibition of PARP-1 overactivation by nicotinamide and (ii) inhibition of extrasynaptic NMDA receptor overactivation by memantine can prevent the short- and long-term consequences of PA. These hypotheses have been evaluated in a rat preclinical model of PA, aiming to identify the metabolic cascades responsible for the long-term consequences induced by the insult, also assessing postnatal vulnerability to recurrent oxidative insults. Thus, we present and discuss evidence demonstrating that PA induces long-term changes in metabolic pathways related to energy and oxidative stress, priming vulnerability of cells with both the neuronal and the glial phenotype. The effects induced by PA are region dependent, the substantia nigra being particularly prone to cell death. The issue of short- and long-term consequences of PA provides a framework for addressing a fundamental issue referred to plasticity of the CNS, since the perinatal insult triggers a domino-like sequence of events making the developing individual vulnerable to recurrent adverse conditions, decreasing his/her coping repertoire because of a relevant insult occurring at birth.

Manual para la aplicación de las guías alimentarias para la población argentina / Procedures for the application of dietary guidelines for the Argentine population

Las "Guías Alimentarias para la Población Argentina" (GAPA) fueron actualizadas y publicadas por el Ministerio de Salud de la Nación en el año 2016. El propósito de la actualización de las GAPA se enmarcaron en la promoción de la salud y prevención de enfermedades crónicas no trasmisibles en aumento, tales como: como Diabetes enfermedades cardiovasculares, distintos tipos de canceres, enfermedad renal, respiratoria. También, se constituye una herramienta para trabajar diversas formas de malnutrición: aquellas asociadas a carencias nutricionales (Anemia, desnutrición) fundamentalmente, prevenir aquellas relacionadas con excesos, como el sobrepeso y la obesidad, actualmente con un crecimiento exponencial. El Objetivo de las GAPA es adaptar los avances del conocimiento científico nutricional, a mensajes prácticos que otorguen herramientas a la población para facilitar y promover la adopción de hábitos saludables. El presente manual constituye una herramienta para la aplicación de las GAPA, brindando elementos pedagógicos para diferentes actores (equipos de salud, equipos docentes, entre otros) a fin de colaborar en la formación de personas informadas acerca de Alimentación Saludable. Así entonces, el espíritu de las GAPA se enmarca en la implementación de acciones integrales para enfrentar y revertir la avanzada de las enfermedades no transmisibles, garantizando el ejercicio pleno del derecho a una alimentación saludable para toda la población argentina.

Caracterización fenotípica de la cepa N2 de Caenorhabditis elegans como un modelo en enfermedades neurodegenerativas / Phenotypic characterization of the N2 strain of Caenorhabditis elegans as a model in neurodegenerative diseases

Resumen El nematodo C. elegans se estableció desde I960, gracias al biólogo sudafricano Sydney Brenner, como un organismo modelo en investigación. Sus cualidades biológicas permiten mejorar la visión y comprensión de patologías en los seres humanos y otros seres pluricelulares; además, sus fenotipos claros y observables lo convierten en un organismo adecuado para el estudio básico de enfermedades neurodegenerativas, inmunológicas y procesos cancerígenos. Objetivo. Analizar las características fenotípicas de la cepa silvestre N2 de C. elegans para su posterior uso como modelo de tamizaje en el laboratorio de Biotecnología y Genética (Universidad Colegio Mayor de Cundinamarca). Materiales y Métodos. El nematodo fue cultivado y crecido en el medio NGM con la cepa E. coli OP50. La cepa N2 fue sincronizada para obtener huevos y posteriormente larvas L1. Se estandarizaron los ensayos de longevidad, reproducción, longitud y estrés térmico. Resultados. La caracterización fenotípica de la cepa N2 de C. elegans presentó: una longevidad de 16 a 22 días, una reproducción promedio de 225 crías, la longitud del nematodo fue de 1100±50 μm y la supervivencia bajo estrés térmico evaluada en las dos etapas de desarrollo del nematodo es muy reducida a 37°C en comparación de 35°C; además, los nematodos fueron más resistentes al primer día de adulto joven en comparación con el sexto día de adulto. Conclusiones. Los resultados aportados por este estudio permiten sugerir que las características fenotípicas del nematodo analizadas se encuentran dentro de lo reportado en la literatura, por lo cual es viable usarlo como como modelo biológico en diferentes ensayos tal como lo reportan otros estudios.

Abstract The nematode C. elegans was established since I960, thanks to the South African biologist Sydney Brenner, as a model organism in research. Their biological qualities allow to improve the vision and understanding of pathologies in human and other multicellular beings; In addition, its clear and observable phenotypes make it a suitable organism for the basic study of neurodegenerative, immunological diseases and carcinogenic processes. Objective. To analyze the phenotypic characteristics of the C. elegans N2 wild strain for later use as a screening model in the Biotechnology and Genetics Laboratory (Colegio Mayor de Cundinamarca University). Materials and Methods. The nematode was grown and grown in the NGM medium with the strain E. coli OP50. The N2 strain was synchronized to obtain eggs and later L1 larvae. The tests of longevity, reproduction, length and thermal stress were standardized. Results. The phenotypic characterization of the N2 strain of C. elegans presented a longevity of 16 to 22 days, an average reproduction of 225 offspring, the length of the nematode was 1100 ± 50 μm and the survival under thermal stress evaluated in the two Development stages of the nematode is greatly reduced at 37 ° C compared to 35 ° C; In addition, nematodes were more resistant to the first day of young adult compared to the sixth day of adulthood. Conclusions. The results of this study suggest that the phenotypic characteristics of the nematode analyzed are within the literature, so it is feasible to use it as a biological model in different trials as reported in other studies.

Sarcoma de Kaposi asociado a trasplante renal / Kaposi's sarcoma associated with renal transplant

Se describe un paciente trasplantado renal, bajo tratamiento inmunosupresor, que desarrolló un sarcoma de Kaposi de infrecuente localización, corto período de latencia y excelente respuesta al tratamiento instaurado

Enfermedad de Paget extramamaria / Extramammary Paget's disease

La enfermedad de Paget extramamaria (EPEM) es una entidad rara que presenta similitud clínica e histológica con múltiples patologías. Se asocia frecuentemente con carcinoma subyacente. Presentamos un caso de enfermedad de Paget extramamaria de localización perianal que fue tratada con radioterapia con excelente respuesta

Sarcoma de Kaposi asociado a trasplante renal / Kaposis sarcoma associated with renal transplant

Se describe un paciente trasplantado renal, bajo tratamiento inmunosupresor, que desarrolló un sarcoma de Kaposi de infrecuente localización, corto período de latencia y excelente respuesta al tratamiento instaurado (AU)

Enfermedad de Paget extramamaria / Extramammary Pagets disease

La enfermedad de Paget extramamaria (EPEM) es una entidad rara que presenta similitud clínica e histológica con múltiples patologías. Se asocia frecuentemente con carcinoma subyacente. Presentamos un caso de enfermedad de Paget extramamaria de localización perianal que fue tratada con radioterapia con excelente respuesta (AU)