Aerodynamically Levitated Droplets as Small-scale Reactors and Liquid Microprinters.

A thin liquid film spread over the inner surface of a rapidly rotating vial creates an aerodynamic cushion on which one or multiple droplets of various liquids can levitate stably for days or even weeks. These levitating droplets can serve as wall-less ("airware") chemical reactors that can be merged without touching - by remote impulses - to initiate reactions or sequences of reactions at scales down to hundreds of nanomoles. Moreover, under external electric fields, the droplets can act as the world's smallest chemical printers, shedding regular trains of pL or even fL microdrops. In one modality, the levitating droplets operate as completely wirelesss aliquoting/titrating systems delivering pg quantities of reagents into the liquid in the rotating vial; in another modality, they print microdroplet arrays onto target surfaces. The "airware", levitated reactors are inexpensive to set up, remarkably stable to external disturbances and, for printing applications, require operating voltages much lower than in electrospray, electrowetting, or ink jet systems.

Proving Cooperativity of a Catalytic Reaction by Means of Nanoscale Geometry: The Case of Click Reaction.

Establishing whether a reaction is catalyzed by a single-metal catalytic center or cooperatively by a fleeting complex encompassing two such centers may be an arduous pursuit requiring detailed kinetic, isotopic, and other types of studies─as illustrated, for instance, by over a decade-long work on single-copper versus di-copper mechanisms of the popular "click" reaction. This paper describes a method to interrogate such cooperative mechanisms by a nanoparticle-based platform in which the probabilities of catalytic units being proximal can be varied systematically and, more importantly, independently of their volume concentration. The method relies on geometrical considerations rather than a detailed knowledge of kinetic equations, yet the scaling trends it yield can distinguish between cooperative and non-cooperative mechanisms.

On-Nanoparticle Gating Units Render an Ordinary Catalyst Substrate- and Site-Selective.

When an organometallic catalyst is tethered onto a nanoparticle and is embedded in a monolayer of longer ligands terminated in "gating" end-groups, these groups can control the access and orientation of the incoming substrates. In this way, a nonspecific catalyst can become enzyme-like: it can select only certain substrates from substrate mixtures and, quite remarkably, can also preorganize these substrates such that only some of their otherwise equivalent sites react. For a simple, copper-based click reaction catalyst and for gating ligands terminated in charged groups, both substrate- and site-selectivities are on the order of 100, which is all the more notable given the relative simplicity of the on-particle monolayers compared to the intricacy of enzymes' active sites. The strategy of self-assembling macromolecular, on-nanoparticle environments to enhance selectivities of "ordinary" catalysts presented here is extendable to other types of catalysts and gating based on electrostatics, hydrophobicity, and chirality, or the combinations of these effects. Rational design of such systems should be guided by theoretical models we also describe.

Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer's disease mice.

The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9). These epi-editors altered critical histone marks and subsequently Dlg4/PSD95 expression, which, importantly, impacted several hippocampal neuron plasticity processes. Intriguingly, transduction of the artificial transcription factor PSD95-VP64 rescued memory deficits in aged and Alzheimer's disease mice. Conclusively, this work validates PSD95 as a key player in memory and establishes epigenetic editing as a potential therapy to treat human neurological disorders.

n-3 Polyunsaturated fatty acid supplementation restored impaired memory and GABAergic synaptic efficacy in the hippocampus of stressed rats.

While chronic stress induces dendritic atrophy in the hippocampus and impairs learning and memory, supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) is known to improve learning and memory of control rats. Whether n-3 PUFA supplementation improves dendritic morphology, synaptic transmission, and memory of chronically stressed rats remains unknown. In this work, we randomly assigned male Sprague-Dawley rats in four experimental groups: two unsupplemented groups, control and stress, and two supplemented groups with n-3 PUFA (DHA and EPA mix), control + n-3 PUFA and stress + n-3 PUFA. Dendritic morphology and synaptic transmission in the hippocampus were evaluated by Golgi stain and patch-clamp tools, respectively. The Y-maze and Morris water maze were used to analyze the effects of chronic stress on memory. Supplementation with n-3 PUFA improved dendritic architecture and restored the frequency of inhibitory post-synaptic currents of hippocampal pyramidal neurons of rats from stress group. In addition, n-3 PUFA supplementation improved spatial memory. Our results demonstrate that n-3 PUFA supplementation had three beneficial effects on stressed rats: prevented or compensated dendritic atrophy in CA3; restored the probability of GABA release in CA1; and improved spatial memory. We argue that n-3 PUFA supplementation can be used in treating stress-related psychiatric disorders such as depression and anxiety.

Long-term depression of inhibitory synaptic transmission induced by spike-timing dependent plasticity requires coactivation of endocannabinoid and muscarinic receptors.

The precise timing of pre-postsynaptic activity is vital for the induction of long-term potentiation (LTP) or depression (LTD) at many central synapses. We show in synapses of rat CA1 pyramidal neurons in vitro that spike timing dependent plasticity (STDP) protocols that induce LTP at glutamatergic synapses can evoke LTD of inhibitory postsynaptic currents or STDP-iLTD. The STDP-iLTD requires a postsynaptic Ca(2+) increase, a release of endocannabinoids (eCBs), the activation of type-1 endocananabinoid receptors and presynaptic muscarinic receptors that mediate a decreased probability of GABA release. In contrast, the STDP-iLTD is independent of the activation of nicotinic receptors, GABAB Rs and G protein-coupled postsynaptic receptors at pyramidal neurons. We determine that the downregulation of presynaptic Cyclic adenosine monophosphate/protein Kinase A pathways is essential for the induction of STDP-iLTD. These results suggest a novel mechanism by which the activation of cholinergic neurons and retrograde signaling by eCBs can modulate the efficacy of GABAergic synaptic transmission in ways that may contribute to information processing and storage in the hippocampus.

[A study of the predictive value of the primary review and complementary examinations in assessing the need for surgery in patients with stab wounds in the torso]. / Estudio del valor predictivo de la revisión primaria y de las exploraciones complementarias para anticipar la necesidad de intervención quirúrgica en pacientes con heridas de arma blanca en el torso.

INTRODUCTION: Observation is the gold standard for stable patients with stab wounds. The aim of the study was to analyse the value of the primary review and complementary examinations to predict the need for surgery in stab wound patients in order to decrease observation times. METHODS: A retrospective study of stab wound patients recorded in a database. Clinical and diagnostic workup parameters were analysed. The main variable was the need for surgery. RESULTS: A total of 198 patients were included between 2006 and 2009, with a mean injury severity score (ISS) of 7.8±7, and 0.5% mortality. More than half (52%) of the patients suffered multiple wounds. Wound distribution was 23% neck, 46% thorax and 31% abdomen. Surgery was required in 73 (37%) patients (59% immediate, 27% delayed and 14% delayed). The need for surgery was associated with a lower revised trauma score (RTS), evisceration, active bleeding, and fascial penetration. Initial and control haemoglobin levels were significantly lower in patients who required surgery. A positive computerised tomography (CT) scan was associated with surgery. There were complications in 18% of patients, and they were more frequent in those who underwent surgery. There was no difference in complication rates between immediate and delayed (P=.72). Surgery was finally required in 10% of the patients with no abnormalities in the primary review and diagnostic workup, and 6% of those developed complications. CONCLUSION: None of the parameters studied could individually assess the need for surgery. Primary and secondary reviews were the most important diagnostic tool, but CT scan should be used more often. An observation period of 24 hours is recommended in torso penetrating wounds.

On-nanoparticle monolayers as a solute-specific, solvent-like phase.

In addition to modifying surface properties, self-assembled monolayers, SAMs, on nanoparticles can selectively incorporate small molecules from the surrounding solution. This selectivity has been used in the design of substrate-specific catalytic systems but its degree has not been quantified. This work uses catalytic centers embedded in on-nanoparticle hydrophobic SAMs to monitor and quantify the partitioning of molecules between the bulk solvent and these monolayers. A combination of experiments and theory allows us to relate the logarithm of the incorporation-into-SAM constant to the "bulk" log P values, characterizing the incoming substrates. These results are in line with classic, semi-empirical linear free energy relationships between partitioning solvent systems; in this way, they substantiate the view of nanoscopic on-particle SAMs acting akin to a bulk solvent phase.

Scientific evidence of the duration of antibiotic treatment in intra-abdominal infections with surgical focus control.

A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections (IIA) with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 20171, as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72 h. And in those who present risk factors, it should be individualized with active monitoring every 24 h of fever, paralytic ileus and leukocytosis (FIL), before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice.

Mixed-Charge Nanocarriers Allow for Selective Targeting of Mitochondria by Otherwise Nonselective Dyes.

Targeted delivery of molecular cargos to specific organelles is of paramount importance for developing precise and effective therapeutics and imaging probes. This work describes a disulfide-based delivery method in which mixed-charged nanoparticles traveling through the endolysosomal tract deliver noncovalently bound dye molecules selectively into mitochondria. This system comprises three elements: (1) The nanoparticles deliver their payloads by a kiss-and-go mechanism - that is, they drop off their dye cargos proximate to mitochondria but do not localize therein; (2) the dye molecules are by themselves nonspecific to any cellular structures but become so with the help of mixed-charge nanocarriers; and (3) the dye is engineered in such a way as to remain in mitochondria for a long time, up to days, allowing for observing dynamic remodeling of mitochondrial networks and long-term tracking of mitochondria even in dividing cells. The selectivity of delivery and long-lasting staining derive from the ability to engineer charge-imbalanced, mixed [+/-] on-particle monolayers and from the structural features of the cargo. Regarding the former, the balance of [+] and [-] ligands can be adjusted to limit cytotoxicity and control the number of dye molecules adsorbed onto the particles' surfaces. Regarding the latter, comparative studies with multiple dye derivatives we synthesized rationalize the importance of polar groups, long alkyl chains, and disulfide moieties in the assembly of fluorescent nanoconstructs and long-lasting staining of mitochondria. Overall, this strategy could be useful for delivering hydrophilic and/or anionic small-molecule drugs difficult to target to mitochondria by classical approaches.

Priming of GABAergic Long-term Potentiation by Muscarinic Receptors.

Growing evidence indicates that GABAergic interneurons play a pivotal role to generate brain oscillation patterns, which are fundamental for the mnemonic processing of the hippocampus. While acetylcholine (ACh) is a powerful modulator of synaptic plasticity and brain function, few studies have been focused on the role of cholinergic signaling in the regulation of GABAergic inhibitory synaptic plasticity. We have previously shown that co-activation of endocannabinoids (CB1R) and muscarinic receptor (mAChR) in hippocampal interneurons can induce activity-dependent GABAergic long-term depression in CA1 pyramidal neurons. Here, using electrophysiological and pharmacological approaches in acute rat hippocampal slices, we show that activation of cholinergic receptors followed by either high-frequency stimulation of Schaeffer collaterals or exogenous activation of metabotropic glutamate receptor (mGluR) induces a robust long-term potentiation at GABAergic synapses (iLTP). These forms of iLTP are blocked by the M1 type of mAChR (MR1) or by the group I of mGluR (mGluR1/5) antagonists. These results suggest the existence of spatiotemporal cooperativity between cholinergic and glutamatergic pathways where activation of mAChR serves as a metaplastic switch making glutamatergic synapses capable to induce long-term potentiation at inhibitory synapses, that may contribute to the modulation of brain mechanisms of learning and memory.

Ion-Ion Repulsions and Charge-Shielding Effects Dominate the Permeation Mechanism through the OmpF Porin Channel.

OmpF is a wide channel bacterial porin frequently employed to study selective ionic translocation. The cationic preference of this porin is mainly determined by electrostatic forces between the translocated ion and the protein and the formation of ion pairs (e.g., K+···Cl-) being previously pointed as the main cause to favor the cationic transport through the constriction zone. Hybrid quantum mechanics/molecular mechanics-molecular dynamics simulations, which have provided polarization-containing potentials of mean force profiles for different permeation scenarios, reveal significant new insights related with the ion translocation mechanism. Results show that the permeation is dominated by electrostatic interactions, which in turn affect ion-protein interactions at the constriction zone. However, it is observed that ion flow is favored by ion-ion repulsions and, in a lesser extent, by charge-shielding effects, instead of the previously pointed ionic pair formation.

WASP-1, a canonical Wnt signaling potentiator, rescues hippocampal synaptic impairments induced by Aß oligomers.

Amyloid-ß (Aß) oligomers are a key factor in Alzheimer's disease (AD)-associated synaptic dysfunction. Aß oligomers block the induction of hippocampal long-term potentiation (LTP) in rodents. The activation of Wnt signaling prevents Aß oligomer-induced neurotoxic effects. The compound WASP-1 (Wnt-activating small molecule potentiator-1), has been described as a synergist of the ligand Wnt-3a, enhancing the activation of Wnt/ß-catenin signaling. Herein, we report that WASP-1 administration successfully rescued Aß-induced synaptic impairments both in vitro and in vivo. The activation of canonical Wnt/ß-catenin signaling by WASP-1 increased synaptic transmission and rescued hippocampal LTP impairments induced by Aß oligomers. Additionally, intra-hippocampal administration of WASP-1 to the double transgenic APPswe/PS1dE9 mouse model of AD prevented synaptic protein loss and reduced tau phosphorylation levels. Moreover, we found that WASP-1 blocked Aß aggregation in vitro and reduced pathological tau phosphorylation in vivo. These results indicate that targeting canonical Wnt signaling with WASP-1 could have value for treating AD.

Factores de riesgo de parto pretérmino en Bogotá D. C., Colombia / Risk factors for preterm birth in Bogota D. C., Colombia

Resumen Introducción. El parto pretérmino es aquel que ocurre antes de la semana 37 de gestación. Este tipo de parto se asocia a múltiples factores de riesgo, algunos de los cuales pueden ser prevenidos. En Colombia son escasos los estudios sobre los factores de riesgo asociados al parto pretérmino, de ahí la importancia de su análisis. Objetivo. Identificar los factores de riesgo para parto pretérmino en un grupo de gestantes de Bogotá D.C., Colombia. Materiales y métodos. Estudio de cohorte retrospectivo. La muestra estuvo compuesta por 452 pacientes que habían participado en un estudio primario y que ya habían dado a luz. Resultados. La incidencia de parto pretérmino fue de 10.40% (IC95%: 7.60-13.20) y los factores de riesgo asociados fueron los siguientes: ser diagnosticada con preeclampsia severa, con un riesgo relativo (RR) de 7.47 (IC95%: 4.59-11.95); tener preeclampsia (severa y no severa), con un RR=5.05 (IC95%: 3.0-8.51), y ocurrencia de restricción del crecimiento intrauterino (RCIU), con un RR=4.40 (IC95%: 2.44-7.98). Conclusiones. De acuerdo con los hallazgos reportados en el presente estudio, es necesario planear e implementar estrategias y políticas públicas en Bogotá D.C. que promuevan mejores prácticas de atención prenatal que, a su vez, permitan la detección temprana de condiciones como la preeclampsia y la RCIU, lo que hará posible reducir la incidencia de partos pretérmino en la ciudad y utilizar la experiencia y resultados obtenidos en el resto del país.

Abstract Introduction: A preterm birth occurs before the 37th week of pregnancy. It is associated with multiple risk factors, some of which can be prevented. In Colombia, few studies have addressed the risks factors associated with preterm birth, hence the importance of analyzing them. Objective: To identify risk factors for preterm birth in a population of pregnant women in Bogotá D.C., Colombia. Materials and methods: Retrospective cohort study. The sample was composed of 452 patients who had participated in a primary study and had already given birth. Results: The incidence of preterm birth was 10.40% (95%CI: 7.60-13.20). The following risk factors associated with preterm delivery were found: being diagnosed with severe preeclampsia, with a relative risk (RR)=7.47 (95%CI: 4.59-11.95); having preeclampsia (severe and non-severe), with a RR=5.05 (95%CI: 3.0-8.51); and occurrence of intrauterine growth restriction (IUGR), with a RR=4.40 (95%CI: 2.44-7.98). Conclusions: According to the findings reported in this study, it is necessary to plan and implement strategies and public policies in Bogotá D.C. that promote better prenatal care practices that, in turn, allow the early detection of conditions such as preeclampsia and IUGR. This will reduce the incidence of preterm birth in the city and will allow using the experience and results obtained here in the rest of the country.

Repeated restraint stress impairs auditory attention and GABAergic synaptic efficacy in the rat auditory cortex.

Chronic stress induces dendritic atrophy in the rat primary auditory cortex (A1), a key brain area for auditory attention. The aim of this study was to determine whether repeated restraint stress affects auditory attention and synaptic transmission in A1. Male Sprague-Dawley rats were trained in a two-alternative choice task (2-ACT), a behavioral paradigm to study auditory attention in rats. Trained animals that reached a performance over 80% of correct trials in the 2-ACT were randomly assigned to control and restraint stress experimental groups. To analyze the effects of restraint stress on the auditory attention, trained rats of both groups were subjected to 50 2-ACT trials one day before and one day after of the stress period. A difference score was determined by subtracting the number of correct trials after from those before the stress protocol. Another set of rats was used to study the synaptic transmission in A1. Restraint stress decreased the number of correct trials by 28% compared to the performance of control animals (p < 0.001). Furthermore, stress reduced the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) and miniature IPSC in A1, whereas glutamatergic efficacy was not affected. Our results demonstrate that restraint stress decreased auditory attention and GABAergic synaptic efficacy in A1.

Coloplastia vaginal, una opción en el tratamiento de la fístula rectovaginal grande / Vaginal coloplasty, an option in the treatment of large rectovaginal fistula

Objetivo: Presentar un tratamiento alternativo para una fistula recto vaginal grande producida por la radiación en una mujer joven tratada por cáncer de cuello uterino, basado en las sigmoideoplastias vaginales en pacientes con agenesia de vagina. Paciente y método: Paciente de sexo Femenino de 36 años que el año 2010 concurre al consultorio de proctología por presentar proctorragia asociada a la defecación de dos semanas de evolución. Antecedentes de conización en el año 2008 por carcinoma epidermoide de cuello uterino y en 2009 irradiada con braquiterapia y radioterapia por presentar recidiva en vagina de cáncer de cuello uterino. Se decide la internación y al día siguiente es llevada a quirófano donde se observa a nivel de recto inferior y medio, fístula con tercio medio e inferior de vagina de unos 4 a 5 cm de diámetro. Dada las características de la misma, el grado de incontinencia de la paciente, su retracción inmediata de sus actividades laborales y sociales, se le plantea la posibilidad de desfuncionalizarla resecado el recto medio e inferior, completar la cirugía oncológica de su cáncer y en un segundo acto reconstruir tanto el tránsito intestinal como su vagina con un segmento vascularizado de colon. Discusión: Existen varias formas de clasificar una fistula rectovaginal, en base a su ubicación, según su diámetro, por último se pueden clasificar según su complejidad en simples y complejas. Dentro de los tratamientos hallamos los perineales, rectales o vaginales, indicados en las fistulas bajas o medias y los abdominales en las fistulas altas. Existen algunas que no responde a los tratamientos habituales o que desde un principio no se pueden tratar por las técnicas habituales, llevando en contadas ocasiones a tratamientos más agresivos como la desfuncionalización, colgajos miocutáneos o la técnica de Simonsen.

Purpose: to present an alternative treatment for rectovaginal fistula secondary to radiation in a young female patient treated for cervical cancer, based on a vaginal sigmoideoplasty. Patient and Method: 36 years old female patient with a 2-week history of rectal bleeding. Personal history of conization in 2008 for cervical squamous carcinoma and postoperative treatment in 2009 with brachytherapy and radiaton therapy for local cancer recurrence. On surgical perineal exploration a recto-vaginal defect of 4-5 cm was identified in the middle-lower vagina. Proctectomy was performed based in surgical principles. During reconstructive surgery the vagina was replaced with a colonic segment. Results: there are several ways to classify a rectovaginal fistula, based on location, diameter and according to their complexity into simple and complex. Rectal, perineal and vaginal approaches have been described. In some cases, more aggressive techniques could be performed such as myocutaneous flaps and Simonsen technique.

Abdomen agudo neoplásico: nuestra visión actual / Approach to the patient with neoplasic acute abdomen

El dolor abdominal agudo es una consulta cada vez mas frecuente, siendo una de sus causas, también frecuente, la enfermedad neoplásica abdominal. Se realizó un estudio retrospectivo entre enero de 2004 y diciembre 2007 sob re 123 pacientes ingresados de urgencia al servicio de Cirugía General quienes fueron intervenidos quirúrgicamente por presentar cuadro de abdomen agudo quirúrgico de origen neoplásico.

Parálisis bilateral de las cuerdas vocales postiroidectomía / Bilateral vocal cord paralysis following thyroidectomy

La parálisis bilateral de las cuerdas vocales postiroidectomía es un evento muy grave y poco frecuente. El objetivo del trabajo es llamar la atención sobre este tipo de injuria que tiene implicancias medico legales trayendo graves consecuencias en el paciente, involucrando su esfera económica, social y psicológica.

Neumotórax iatrogénico: Nuestra experiencia / Iatrogenic Pneumothorax: authors' experience

Similar a lo observado por otros autores, notamos un incremento del neumotórax iatrogénico en nuestro hospital. El objetivo de este trabajo es conocer la incidencia y factores asociados a la morbimortalidad del NTXI y analizar la experiencia del operador como factor determinante.