Nivel de dependencia funcional de los adultos mayores de la comunidad de Tula de Allende / Level of functional dependence of older adults in the community of Tula de Allende

Introducción: El estado funcional se mide mediante la autonomía que tienen las personas para desarrollar las actividades de la vida diaria, cuando no se pueden realizar de manera autónoma es necesario un cuidador. Esta medida se sustenta en el modelo de adaptación de Sor Callista Roy, ya que se identifica el proceso de envejecimiento como el estímulo focal que produce una respuesta inmediata en el adulto mayor de acuerdo con el modo de interdependencia. Objetivo: Conocer el nivel de dependencia funcional de los adultos mayores de la comunidad de Tula de Allende, Hidalgo. Material y métodos: Estudio de aplicabilidad básica, cuantitativo, descriptivo y trasversal. Participaron 366 adultos mayores de Tula de Allende, y se les dio a conocer los términos de confidencialidad conforme a lo establecido en la Ley General de Salud y Declaración de Helsinki mediante el consentimiento informado. Se aplicó el cuestionario de Índice de Barthel (IB), para medir la dependencia funcional en las actividades instrumentales de la vida diaria. Resultados: Predomina el género femenino con el 52.7% representado por 193 participantes, la mayoría son casadas y amas de casa. De acuerdo con el IB la mayoría de los participantes tiene una dependencia leve, con una frecuencia de 206 y un porcentaje de 56.3%, y el cruce de variables arroja como resultado una relación significativa. Conclusión: Los adultos mayores de la comunidad de Tula de Allende presentan un nivel de dependencia funcional leve.

Introduction: Functional status assesses people's ability to carry out daily activities; when these cannot be performed autonomously, a caregiver is necessary. This measure is based on the Roy Adaptation Model, which identifies the aging process as the focal stimulus that generates an effect according to the interdependence mode. Objective: To evaluate the level of functional dependence of the elderly in the community of Tula de Allende, Hidalgo. Material and methods: Quantitative, descriptive, and cross-sectional study of basic applicability. 366 older adults from Tula de Allende participated and were informed about confidentiality terms in accordance with the General Health Law and the Declaration of Helsinki through informed consent. The Barthel Index (BI) questionnaire was applied to measure functional dependence on daily instrumental activities. Results: The female gender predominates with 52.7% represented by 193 participants, the majority are married housewives. According to the BI, most of the participants have a slight dependency, with a frequency of 206 and a percentage of 56.3%; the correlation of variables showed statistical significance. Conclusion: Older adults in the community of Tula de Allende present a mild functional dependence level.

bZIP transcription factors PcYap1 and PcRsmA link oxidative stress response to secondary metabolism and development in Penicillium chrysogenum.

BACKGROUND: Reactive oxygen species (ROS) trigger different morphogenic processes in filamentous fungi and have been shown to play a role in the regulation of the biosynthesis of some secondary metabolites. Some bZIP transcription factors, such as Yap1, AtfA and AtfB, mediate resistance to oxidative stress and have a role in secondary metabolism regulation. In this work we aimed to get insight into the molecular basis of this regulation in the industrially important fungus Penicillium chrysogenum through the characterization of the role played by two effectors that mediate the oxidative stress response in development and secondary metabolism. RESULTS: In P. chrysogenum, penicillin biosynthesis and conidiation are stimulated by the addition of H2O2 to the culture medium, and this effect is mediated by the bZIP transcription factors PcYap1 and PcRsmA. Silencing of expression of both proteins by RNAi resulted in similar phenotypes, characterized by increased levels of ROS in the cell, reduced conidiation, higher sensitivity of conidia to H2O2 and a decrease in penicillin production. Both PcYap1 and PcRsmA are able to sense H2O2-generated ROS in vitro and change its conformation in response to this stimulus. PcYap1 and PcRsmA positively regulate the expression of brlA, the first gene of the conidiation central regulatory pathway. PcYap1 binds in vitro to a previously identified regulatory sequence in the promoter of the penicillin gene pcbAB: TTAGTAA, and to a TTACTAA sequence in the promoter of the brlA gene, whereas PcRsmA binds to the sequences TGAGACA and TTACGTAA (CRE motif) in the promoters of the pcbAB and penDE genes, respectively. CONCLUSIONS: bZIP transcription factors PcYap1 and PcRsmA respond to the presence of H2O2-generated ROS and regulate oxidative stress response in the cell. Both proteins mediate ROS regulation of penicillin biosynthesis and conidiation by binding to specific regulatory elements in the promoters of key genes. PcYap1 is identified as the previously proposed transcription factor PTA1 (Penicillin Transcriptional Activator 1), which binds to the regulatory sequence TTAGTAA in the pcbAB gene promoter. This is the first report of a Yap1 protein directly regulating transcription of a secondary metabolism gene. A model describing the regulatory network mediated by PcYap1 and PcRsmA is proposed.

Combined 1-Deoxynojirimycin and Ibuprofen Treatment Decreases Microglial Activation, Phagocytosis and Dopaminergic Degeneration in MPTP-Treated Mice.

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson's disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

[Diagnosis of atherogenic dyslipidaemia by primary care physicians in Spain]. / Diagnóstico de la dislipidemia aterogénica por los médicos de atención primaria en España.

OBJECTIVE: To describe the diagnostic management of patients with atherogenic dyslipidaemia (AD) by primary care physicians (PC). METHODOLOGY: An observational, descriptive, cross-sectional study was conducted based on a structured questionnaire. The content of the questionnaire was based on a review of the literature, and was validated by 3 AD experts. It included 23 questions, and was addressed to primary care physicians (PC). This sub-study will analyse questions related to the detection and diagnosis of AD. RESULTS: A total of 1,029 PC participated in the study. Almost all (96.99%) said that DA is a determining factor for cardiovascular risk (CVR), even with LDL-C targets. Residual CVR was evaluated by 88.43% in their clinical practice, but only 27.89% in secondary prevention. Most of the PCs used LDL-c-non-HDL-c (55.49% vs 20.02%) in AD as a control objective, and 15.35% used TG, and 9.14% HDL-C. For the diagnosis of AD, 82.22% used TC, TG, HDL-C, and non-HDL-C. PC physicians used the TC / HDL-C atherogenic ratio (53.06%) and LDL-C / HDL-C ratio (49.56%), considering them useful / very useful (86.30% and 85.04%, respectively), with only 28.08% using the TG / HDL-C index, with 69.29% considering it useful / very useful. CONCLUSIONS: The PCs have a high level of knowledge of the guidelines. Underdiagnosis continues, with heterogeneity in determining objectives, and low use of the TG / HDL-C index to evaluate these patients. Greater awareness is needed for the detection and diagnosis of AD.

In vitro Notch-mediated adjuvant immunogenic potency is induced by combining QS-21 and MPL in a co-culture model of PBMC and HUVEC cells.

Few vaccine adjuvants have been approved for human use although several are currently being studied in preclinical and clinical trial. MPL is a toll-like receptor agonist able to trigger a high and persistent antibody response via-TLR-4 while QS-21 activates the NLRP3 inflammasome. Data suggest that there is a cross-talk between Notch and TLR signaling pathways modulating the polarization of the immune response in a MyD88-dependent manner. However, the role of Notch on the mechanism action of immunogenic adjuvants has not been addressed yet. This study aims to evaluate the in vitro toxicity and inflammatory response triggered by MPL and QS-21 using an in vitro human cell co-culture model and to determine whether NFκB or Notch signaling pathways are involved in their mechanism of immunotoxicity. In order to do this, we evaluated the effect of QS- 21/MPL alone or in combination using a co-culture of PBMC and HUVEC using cytotoxicity, surface expression of ECAMs, cell adhesion and cytokine release, NF-κB activation and NOTCH1 expression as observation endpoints. We found that both MPL and QS-21 were cytotoxic at concentrations over 5 µg/mL. Both adjuvants were able to trigger the expression of ECAMs and induce firm adhesion of PBMC to the endothelium. QS-21 and MPL combination demonstrated a synergistic effect on cellular recruitment and cytokine release generating a switch from Th2 to Th1 cytokine profile. Both MPL and QS-21 by themselves were able to generate significant NF-κB activation. However, this effect was not observed when both adjuvants were combined. On the contrary, the adjuvants alone and combined induced an overexpression of NOTCH-1. This is an important finding, as it provides new evidence that these adjuvants could modulate reactogenicity of vaccines through Notch signaling.

Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

Aporphinoid alkaloids inhibit biofilm formation of Yersinia enterocolitica isolated from sausages.

AIMS OF THE STUDY: The ability of Yersinia enterocolitica strains to form biofilms and the capacity of different alkaloids to inhibit biofilm formation were investigated. METHODS AND RESULTS: The capacity to form biofilm on polystyrene of 31 Y. enterocolitica strains was evaluated. Biofilm and quorum sensing (QS) inhibition of 17 alkaloids were assayed; furthermore, minimum biofilm inhibitory concentration (MBIC) was determined. The capacity to form biofilms among the examined strains seemed to be a strain-related feature. The best biofilm inhibitors at 100 µmol l-1 were oliverine (1), guatterine (3), liriodenine (4), oliveridine (5) and pachypodanthine (6), which showed biofilm inhibition higher than 87%. Pachypodanthine (6) was the most effective compound with MBIC value of 12·5 µmol l-1 at subinhibitory concentration and also was able to inhibit QS system and reduce yenR expression at this concentration. CONCLUSION: This is the first study to demonstrate that oliverine, liriodenine, and pachypodanthine are able to inhibit biofilm formation of Y. enterocolitica without critically disturbing its growing capacity. At MBIC, pachypodanthine inhibited biofilm formation and QS. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of aporphinoid alkaloids as biofilms inhibitory agents might potentially be useful to treat biofilm-associated infections in the future.

Aporphinoid alkaloids as antimicrobial agents against Yersinia enterocolitica.

Foodborne diseases have become a health issue worldwide, mainly due to the consumption of contaminated foods that are either raw, improperly heat treated or cross-contaminated after adequate heat treatment foods. A group of alkaloids extracted from plants were tested to evaluate their antimicrobial effect against different strains of Yersinia enterocolitica and other foodborne bacteria. The results obtained reveal that oliveridine and pachypodanthine inhibited Y. enterocolitica growth, with MIC values of 25 µmol l-1 and 100 µmol l-1 respectively. The results indicated that both alkaloids are good growth inhibitors, but oliveridine showed greater inhibitory effect with lower MIC values. Inhibitory alkaloids can be developed as potential antimicrobials in food system to prevent or treat foodborne diseases, thus contributing to solve the global issue of contaminated food consumption. SIGNIFICANCE AND IMPACT OF THE STUDY: Alkaloids are abundant secondary metabolites in plants and represent one of the most widespread class of compounds endowed with multiple and varied pharmacological properties. In this work, we propose two aporphinoid alkaloids extracted from plants as new antimicrobial agents. Oliveridine and pachypodanthine inhibited Yersinia enterocolitica growth for up to 96 h of culture. This is the first reported study of the activity of these alkaloids as antimicrobial compounds.

Parkinson's disease: a short story of 200 years.

After Alzheimer's disease, Parkinson's disease (PD) is the second most prevalent and incidental neurodegenerative disorder, affecting more than 2% of the population older than 65 years old. Since it was first described 200 years ago by Dr James Parkinson, great steps have been made in the understanding of the pathology. However, the cause(s) that initiates and perpetuates the neurodegenerative process is (are) still not clear. Thus, early diagnosis is not available, nor are there efficient therapies that can stop neurodegeneration. PD clinical features are defined by motor (like bradykinesia, resting tremor, gait impairment) and non-motor symptoms (like constipation, apathy, fathigue, olfactory dysfunction, depression and cognitive decline) that get more severe as the disease advances. Neuropathological hallmarks comprise selective loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and Lewy bodies (LB) in different nuclei of the nervous system. Numerous studies have shown that these pathological features are aggravated by the confluence of other contributing factors, such as a genetic component, exposure to environmental toxins, mitochondrial dysfunction, increase of oxidative stress, calcium imbalance and chronic neuroinflammation, among others. Here, we provide a summary of the actual state of PD's pathology, the most studied molecular mechanisms, classic and novel therapeutic strategies and diagnosis methods, especially highlighting recent advances in these 200 years.

Animal production, animal health and food safety: Gaps and challenges in the chilean industry.

This paper summarizes the gaps and challenges related to animal production, health, and food safety as discussed by a panel at the 1st International Symposium of Food Safety (ISFS) in Santiago, Chile, in December 2016. Participating representatives of academia, industry, and government and statements from the audience confirmed that food safety is essential for increasing food security. First, panelists identified the need for a science-based regulatory framework to implement effective regulations. Second, they highlighted the importance of a risk analysis framework to quantify the risk of the potential for antimicrobial resistance associated with the use of antimicrobials, and the need of studies to evaluate foodborne prevention/control strategies. Third, the challenges of filling the gaps between industry and academia were addressed, including examples of successful collaboration, opportunities, and weakness identified by industry. Finally, challenges in animal food production included issues related to changing consumer preferences, animal welfare, the use of antimicrobials, and sustainable animal production. The symposium provided a regional platform to share experiences from the implementation of methods and approaches for food safety. The roundtable successfully explored the future science and technology challenges that are of strategic importance for Chile and the region in animal health and food safety.

Electrical stimulation or MK-801 in the inferior colliculus improve motor deficits in MPTP-treated mice.

The inferior colliculus (IC) is an important midbrain relay station for the integration of descending and ascending auditory information. Additionally, the IC has been implicated in processing sensorimotor responses. Glutamatergic and GABAergic manipulations in the IC can improve motor deficits as demonstrated by the animal model of haloperidol-induced catalepsy. However, how the IC influences motor function remains unclear. We investigated the effects of either intracollicular deep brain stimulation (DBS) or microinjection of the glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After DBS or microinjections, the mice were submitted to rotarod and open field tests, respectively. DBS in the IC was effective to increase the time spent on the rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not NMDA, MPTP-treated mice increased the distance travelled in the open field (p < 0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve motor performance in parkinsonian mice suggesting the IC as a new and non-conventional therapeutic target in motor impairment.

Determinación de mediadores de la respuesta inmune e inflamación en lágrimas: cambios en ojo seco y glaucoma frente a población sana / Determination of inmune response and inflammation mediators in tears: Changes in dry eye and glaucoma as compared to healthy controls

OBJETIVO: Determinar el perfil de expresión de las moléculas mediadoras de inflamación y respuesta inmune (IRI) en lágrimas de pacientes con ojo seco (OS) y pacientes en tratamiento médico por sospecha o diagnóstico de glaucoma primario de ángulo abierto (GPAA) para compararlos con sujetos sanos. MÉTODO: Estudio prospectivo observacional de cohortes de 107 participantes subdivididos en: pacientes con OS (GOS; n=30), pacientes con sospecha o diagnóstico de GPAA con tratamiento hipotensor ocular (GGPAA; n=41) y controles sanos (GC; n=36). Se obtuvieron muestras de lágrimas mediante capilaridad para analizarlas mediante sistema de multiinmunoanálisis basado en citometría de flujo (Luminex R-200®), determinando diversas interleucinas (IL): 1β, 2, 4, 5, 6 y 10, y también los factores de necrosis tumoral alfa (TNF-α), de crecimiento endotelial vascular (VEGF) y de crecimiento de colonias de granulocitos y macrófagos (GM-CSF). Los datos se procesaron mediante el programa SPSS 20.0. RESULTADOS: Las moléculas que aumentaron significativamente en lágrimas de pacientes en el GOS versus GGPAA fueron: IL-1β (p = 0.01), IL-6 (p = 0,004), IL-10 (p = 0,04), mientras que el VEGF disminuyó significativamente en el GOS. El GGPAA mostró aumento significativo de IL-6 (p < 0,0001) frente al GC. Comparando GOS y GGPAA, observamos diferencias significativas para IL-4 (p = 0,004), IL-6 (p = 0,002), TNF-α (p = 0,03), GM-CSF (p = 0,03) y VEGF (p = 0,002). CONCLUSIONES: El aumento de expresión de los mediadores de IRI en lágrimas de pacientes con OS o GPAA demuestra la importancia de estos procesos en ambas enfermedades, aunque las distintas moléculas implicadas indican diferentes vías de señalización para ambas, que requieren más investigaciones

OBJECTIVE: To determine the expression profile of immune response and inflammation (IRI) mediator molecules in tears from patients with dry eye (DE), and those suspected of having or have primary open-angle glaucoma (POAG) under treatment and compare them with healthy controls. METHODS: A prospective observational cohort study including 107 participants sub-divided into: healthy controls (CG; n=30), patients with DE (DEG; n=41) and patients suspected of having or have POAG and on hypotensive treatment (POAG-G; n=36). Tear samples were collected by capillary to be processed using a multi-immunoassay system based on flow cytometry (Luminex R-200 ®), in order to determine the interleukins (IL): 1β, 2, 4, 5, 6, and 10, and the growth factors: Tumour necrosis alpha (TNF-α), vascular endothelial (VEGF), and granulocyte-macrophage colony stimulating- (GM-CSF). Data were processed using the SPSS 20.0 program. RESULTS: Molecules that significantly increased in tears from DEG vs. POAG-G patients were: IL-1 (P=.01), IL-6 (P=.004), IL-10 (P=.04), whereas VEGF significantly decreased in the DEG. The POAG-G showed significantly higher IL-6 values (P<.0001) as compared to the CG. When comparing both the DEG and POAG-G, significant differences were observed in tear expression of IL-4 (P=.004), IL-6 (P=.002), TNF-α (P=.03), GM-CSF (P=.03), and VEGF (P=.002). CONCLUSIONS: The increased expression of IRI mediators in tears from patients with DE or POAG strongly demonstrated the importance of immune response in both pathologies. However, the different molecules involved also suggest distinct signalling pathways for these processes that still require further research

Determination of inmune response and inflammation mediators in tears: Changes in dry eye and glaucoma as compared to healthy controls. / Determinación de mediadores de la respuesta inmune e inflamación en lágrimas: cambios en ojo seco y glaucoma frente a población sana.

OBJECTIVE: To determine the expression profile of immune response and inflammation (IRI) mediator molecules in tears from patients with dry eye (DE), and those suspected of having or have primary open-angle glaucoma (POAG) under treatment and compare them with healthy controls. METHODS: A prospective observational cohort study including 107 participants sub-divided into: healthy controls (CG; n=30), patients with DE (DEG; n=41) and patients suspected of having or have POAG and on hypotensive treatment (POAG-G; n=36). Tear samples were collected by capillary to be processed using a multi-immunoassay system based on flow cytometry (Luminex R-200 ®), in order to determine the interleukins (IL): 1ß, 2, 4, 5, 6, and 10, and the growth factors: Tumour necrosis alpha (TNF-α), vascular endothelial (VEGF), and granulocyte-macrophage colony stimulating- (GM-CSF). Data were processed using the SPSS 20.0 program. RESULTS: Molecules that significantly increased in tears from DEG vs. POAG-G patients were: IL-1 (P=.01), IL-6 (P=.004), IL-10 (P=.04), whereas VEGF significantly decreased in the DEG. The POAG-G showed significantly higher IL-6 values (P<.0001) as compared to the CG. When comparing both the DEG and POAG-G, significant differences were observed in tear expression of IL-4 (P=.004), IL-6 (P=.002), TNF-α (P=.03), GM-CSF (P=.03), and VEGF (P=.002). CONCLUSIONS: The increased expression of IRI mediators in tears from patients with DE or POAG strongly demonstrated the importance of immune response in both pathologies. However, the different molecules involved also suggest distinct signalling pathways for these processes that still require further research.

Robotic-assisted laparoscopic bladder augmentation in the pediatric patient.

INTRODUCTION: Bladder augmentation is a common surgical intervention for neuropathic bladder dysfunction, and has conventionally been an open procedure. We present a robotic ileocystoplasty to demonstrate the feasibility of an entirely intracorporeal approach in a pediatric patient. METHODS: The patient was a 6 year old (18.5 kg) boy with a neurogenic bladder secondary to lumbar myelomeningocele. Urodynamics revealed a small capacity and poorly compliant bladder and he was incontinent between frequent catheterizations. A robotic augmentation cystoplasty was performed. RESULTS: At one-month postoperatively, a cystogram revealed no urine leak, and the suprapubic tube was removed. The patient resumed CIC every 3 h during the day and once overnight until postoperative urodynamic studies confirmed safe dynamics, after which the CIC interval was lengthened. CONCLUSION: Robotic bladder augmentation is safe and feasible in a select pediatric population. The entire procedure including preparation of the bowel segment can be completed intracorporeally, even in smaller children.

Sistemas genéticos para un nuevo abordaje del riesgo de progresión de la retinopatía diabética / Genetic systems for a new approach to risk of progression of diabetic retinopathy

OBJETIVO: Evaluar el riesgo de progresión de la retinopatía diabética (RD) utilizando nuevas estrategias para obtener información genética en diabéticos tipo 2 (DT2) basadas en interferencia por ácido ribonucleico (ARN). MATERIAL Y MÉTODOS: Estudio multicéntrico, prospectivo de casos-controles en 132 participantes divididos en: grupo DT2 (GDT2) con RD (+RD) y sin RD (-RD) (n = 77) y grupo control (GC) (n = 55). Tras entrevista personal y examen oftalmológico, se extrajeron lágrimas para análisis molecular (expresión de micro-ARN [miARN] [miRCURY™ ARN Isolation Kit, Qiagen]). En 18 muestras (GDT2+RD = 6; GDT2-RD = 6; GC = 6) obtuvimos librerías de 137 vs. 140 pares de bases (GeneMapper, Applied Biosystems) y realizamos secuenciación de próxima generación (NGS). El programa SPSS 15.0 vehiculizó el análisis estadístico. RESULTADOS: Edad media: 67 ± 12 años en GDT2 vs. 55 ± 21 años en GC. Distribución hombres/mujeres: 51/28 en GDT2 vs. 25/30 en GC. Los antecedentes familiares de DM, cumplir dieta, fumar, beber y realizar ejercicio mostraron diferencias significativas entre grupos (p < 0,001). Con 20-25 μL de lágrimas extrajimos 9,42 ± 3,30 ng/mL de ARN purificado, con diferencias significativas entre GDT2/GC (p = 0,002) y GDT2+RD/GC (p = 0,004). La expresión lagrimal de miARN en GDT2 correlacionó directamente con: edad/obesidad/duración de DM (p < 0,05), e indirectamente con: agudeza visual (p < 0,05). Hemos identificado 14 miARN relacionados con la presencia, mecanismos patogénicos y factores de riesgo para la progresión de la RD. CONCLUSIONES: Proponemos utilizar lágrimas como fuente de información genética para la DM. Los miARN específicos implicados en desarrollo o progresión de la RD pueden utilizarse como biomarcadores moleculares y, a partir de ellos, desarrollar futuras bioterapias

OBJECTIVE: To evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). MATERIAL AND METHODS: A prospective multicentre case-control study of 132 participants was distributed into: T2D with (+DR) or without (-DR) (T2DG; n = 77), and a control group (CG; n = 55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY(TM) ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140 bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR = 6; T2DG-DR = 6; CG = 6) by performing next-generation sequencing (NGS). SPSS 15.0 statistical program was used to perform data analysis. RESULTS: The mean age was 67 ± 12 years in the T2DG vs. 55 ± 21 years in the CG. Distribution men/women: 25/30 in T2DG vs. 51/28 in CG. A family history of DM, diet compliance, smoking, drinking and exercise, showed significant differences between groups (P<.001). A 20-25 microlitre sample of tears contained a mean of 9.42 ± 3.30 ng/mL of purified ARN, with significant differences between T2DG/CG (P=.002) and T2DG+RD/CG (P=.004). Tear expression of miARNs in T2DG directly correlated with age/obesity/T2D duration (P<.05), and indirectly with visual acuity (P<.05). A total of 14 miRNAs related to the presence, pathogenic mechanisms and risk factors for the progression of diabetic retinopathy, were identified. CONCLUSIONS: We propose to use tears as a source of genetic information for DM. Specific miRNAs involved in DR development and/or progression can be used as molecular biomarkers, and based on these, for developing future biotherapies

Metabolómica de la lágrima / Human tear metabolome

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Genetic systems for a new approach to risk of progression of diabetic retinopathy. / Sistemas genéticos para un nuevo abordaje del riesgo de progresión de la retinopatía diabética.

OBJECTIVE: To evaluate the risk of progression of diabetic retinopathy (DR) using new strategies to obtain genetic information in type 2 diabetes (T2D) based on interfering ribonucleic acid (RNA). MATERIAL AND METHODS: A prospective multicentre case-control study of 132 participants was distributed into: T2D with (+DR) or without (-DR) (T2DG; n=77), and a control group (CG; n=55). After an eye examination and personal interview, tears were collected for molecular analysis (expression of microRNAs [miRNAs] (miRCURY ™ ARN Isolation Kit, Qiagen)]. Libraries, 137 vs. 140bp (GeneMapper, Applied Biosystems), were obtained in 18 samples (T2DG+DR=6; T2DG-DR=6; CG=6) by performing next-generation sequencing (NGS). SPSS 15.0 statistical program was used to perform data analysis. RESULTS: The mean age was 67±12 years in the T2DG vs. 55±21 years in the CG. Distribution men/women: 25/30 in T2DG vs. 51/28 in CG. A family history of DM, diet compliance, smoking, drinking and exercise, showed significant differences between groups (P<.001). A 20-25 microlitre sample of tears contained a mean of 9.42±3.30 ng/mL of purified ARN, with significant differences between T2DG/CG (P=.002) and T2DG+RD/CG (P=.004). Tear expression of miARNs in T2DG directly correlated with age/obesity/T2D duration (P<.05), and indirectly with visual acuity (P<.05). A total of 14 miRNAs related to the presence, pathogenic mechanisms and risk factors for the progression of diabetic retinopathy, were identified. CONCLUSIONS: We propose to use tears as a source of genetic information for DM. Specific miRNAs involved in DR development and/or progression can be used as molecular biomarkers, and based on these, for developing future biotherapies.

Los miRNAs como potenciales biomarcadores de las enfermedades oculares / MicroRNAs as potential biomarkers of eye diseases

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