A Rapid Unraveling of the Activity and Antibiotic Susceptibility of Mycobacteria.

The development of antibiotic-resistant bacteria is a worldwide health-related emergency that calls for new tools to study the bacterial metabolism and to obtain fast diagnoses. Indeed, the conventional analysis time scale is too long and affects our ability to fight infections. Slowly growing bacteria represent a bigger challenge, since their analysis may require up to months. Among these bacteria, Mycobacterium tuberculosis, the causative agent of tuberculosis, has caused more than 10 million new cases and 1.7 million deaths in 2016 only. We employed a particularly powerful nanomechanical oscillator, the nanomotion sensor, to characterize rapidly and in real time tuberculous and nontuberculous bacterial species, Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium abscessus, respectively, exposed to different antibiotics. Here, we show how high-speed and high-sensitivity detectors, the nanomotion sensors, can provide a rapid and reliable analysis of different mycobacterial species, obtaining qualitative and quantitative information on their responses to different drugs. This is the first application of the technique to tackle the urgent medical issue of mycobacterial infections, evaluating the dynamic response of bacteria to different antimicrobial families and the role of the replication rate in the resulting nanomotion pattern. In addition to a fast analysis, which could massively benefit patients and the overall health care system, we investigated the real-time responses of the bacteria to extract unique information on the bacterial mechanisms triggered in response to antibacterial pressure, with consequences both at the clinical level and at the microbiological level.

The ASACUSA antihydrogen and hydrogen program: results and prospects.

The goal of the ASACUSA-CUSP collaboration at the Antiproton Decelerator of CERN is to measure the ground-state hyperfine splitting of antihydrogen using an atomic spectroscopy beamline. A milestone was achieved in 2012 through the detection of 80 antihydrogen atoms 2.7 m away from their production region. This was the first observation of 'cold' antihydrogen in a magnetic field free region. In parallel to the progress on the antihydrogen production, the spectroscopy beamline was tested with a source of hydrogen. This led to a measurement at a relative precision of 2.7×10-9 which constitutes the most precise measurement of the hydrogen hyperfine splitting in a beam. Further measurements with an upgraded hydrogen apparatus are motivated by CPT and Lorentz violation tests in the framework of the Standard Model Extension. Unlike for hydrogen, the antihydrogen experiment is complicated by the difficulty of synthesizing enough cold antiatoms in the ground state. The first antihydrogen quantum states scan at the entrance of the spectroscopy apparatus was realized in 2016 and is presented here. The prospects for a ppm measurement are also discussed.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

Investigation into local cell mechanics by atomic force microscopy mapping and optical tweezer vertical indentation.

Investigating the mechanical properties of cells could reveal a potential source of label-free markers of cancer progression, based on measurable viscoelastic parameters. The Young's modulus has proved to be the most thoroughly studied so far, however, even for the same cell type, the elastic modulus reported in different studies spans a wide range of values, mainly due to the application of different experimental conditions. This complicates the reliable use of elasticity for the mechanical phenotyping of cells. Here we combine two complementary techniques, atomic force microscopy (AFM) and optical tweezer microscopy (OTM), providing a comprehensive mechanical comparison of three human breast cell lines: normal myoepithelial (HBL-100), luminal breast cancer (MCF-7) and basal breast cancer (MDA-MB-231) cells. The elastic modulus was measured locally by AFM and OTM on single cells, using similar indentation approaches but different measurement parameters. Peak force tapping AFM was employed at nanonewton forces and high loading rates to draw a viscoelastic map of each cell and the results indicated that the region on top of the nucleus provided the most meaningful results. OTM was employed at those locations at piconewton forces and low loading rates, to measure the elastic modulus in a real elastic regime and rule out the contribution of viscous forces typical of AFM. When measured by either AFM or OTM, the cell lines' elasticity trend was similar for the aggressive MDA-MB-231 cells, which were found to be significantly softer than the other two cell types in both measurements. However, when comparing HBL-100 and MCF-7 cells, we found significant differences only when using OTM.

Effect of antibiotics on mechanical properties of Bordetella pertussis examined by atomic force microscopy.

In recent years, the coevolution of microorganisms with current antibiotics has increased the mechanisms of bacterial resistance, generating a major health problem worldwide. Bordetella pertussis is a bacterium that causes whooping cough and is capable of adopting different states of virulence, i.e. virulent or avirulent states. In this study, we explored the nanomechanical properties of both virulent and avirulent B. pertussis as exposed to various antibiotics. The nanomechanical studies highlighted that only virulent B. pertussis cells undergo a decrease in their cell elastic modulus and height upon antimicrobial exposure, whereas their avirulent counterparts remain unaffected. This study also permitted to highlight different mechanical properties of individual cells as compared to those growing in close contact with other individuals. In addition, we analyzed the presence on the bacterial cell wall of Filamentous hemagglutinin adhesin (FHA), the major attachment factor produced by virulent Bordetella spp., under different virulence conditions by Force Spectroscopy.

Synthesis of cold antihydrogen in a cusp trap.

We report here the first successful synthesis of cold antihydrogen atoms employing a cusp trap, which consists of a superconducting anti-Helmholtz coil and a stack of multiple ring electrodes. This success opens a new path to make a stringent test of the CPT symmetry via high precision microwave spectroscopy of ground-state hyperfine transitions of antihydrogen atoms.

Nanomotion detection based on atomic force microscopy cantilevers.

Atomic force microscopes (AFM) or low-noise in-house dedicated devices can highlight nanomotion oscillations. The method consists of attaching the organism of interest onto a silicon-based sensor and following its nano-scale motion as a function of time. The nanometric scale oscillations exerted by biological specimens last as long the organism is viable and reflect the status of the microorganism metabolism upon exposure to different chemical or physical stimuli. During the last couple of years, the nanomotion pattern of several types of bacteria, yeasts and mammalian cells has been determined. This article reviews this technique in details, presents results obtained with dozens of different microorganisms and discusses the potential applications of nanomotion in fundamental research, medical microbiology and space exploration.

[Description of a case of Aicardi's syndrome]. / Descrizione di un caso di sindrome di Aicardi.

It is described a case of a Aicardi's syndrome: it is a question of a child observed for the first time when she was 3 months old in these was gived: alterations of the callosum corpus, and of the cerebellar vermis, ocular desed, epileptics convulsions and electroencephalographics alterations of ipsaritmic type.

A source of antihydrogen for in-flight hyperfine spectroscopy.

Antihydrogen, a positron bound to an antiproton, is the simplest antiatom. Its counterpart-hydrogen--is one of the most precisely investigated and best understood systems in physics research. High-resolution comparisons of both systems provide sensitive tests of CPT symmetry, which is the most fundamental symmetry in the Standard Model of elementary particle physics. Any measured difference would point to CPT violation and thus to new physics. Here we report the development of an antihydrogen source using a cusp trap for in-flight spectroscopy. A total of 80 antihydrogen atoms are unambiguously detected 2.7 m downstream of the production region, where perturbing residual magnetic fields are small. This is a major step towards precision spectroscopy of the ground-state hyperfine splitting of antihydrogen using Rabi-like beam spectroscopy.

Thorotrast: analysis of the time evolution of its α activity concentration, in the 70 years following the chemical purification of Thorium.

We simulate the α-activity of the Thorium series elements present in the contrast medium named Thorotrast, used until 1960 and cause of certified deaths until today. Assuming, as active components at t=0, (232)Th and (228)Th in the same relative concentration they have in nature, α-activity oscillates for some decades before reaching a stationary value that in absence of biological depletion would be AST =24000Bq/g. Our Montecarlo code generates the nuclear decays of the Thorium series with and without in-vivo biological depletion, arriving to three kinds of results for the activity: 1) Theoretical activity concentration (no biological depletion). Our result is fitted by: A(t)=A(ST).{[1-exp(-t/10)]+[exp(-t/tB)(1-0.8exp(-t/tA))]}, with t in years, tA=1.07.10(-2) years, and tB=2.38 years. 2) Weak biological depletion (228Ra/232 Th equilibrium activity ratio 0.6, 224Ra/228Ra e.a.r 0.9, 10% excretion for 220Rn). The ratio of the activity concentration to the theoretical activity concentration is fitted by: A weak (t)/A(t)=0.61+0.29 exp[-(t/15)2] (t in years). 3) Strong biological depletion (228Ra/232Th e.a.r 0.4, 224Ra/228Ra e.a.r. 0.8, 10% excretion for 220Rn). The ratio of the activity concentration to the theoretical activity concentration is fitted by A(strong)(t)/A(t)=0.44+0.4 exp[-(t/13)2](t in years). We also report fluctuation calculation for two cases where standard statistical behavior is not expected.

Temporally controlled modulation of antihydrogen production and the temperature scaling of antiproton-positron recombination.

We demonstrate temporally controlled modulation of cold antihydrogen production by periodic RF heating of a positron plasma during antiproton-positron mixing in a Penning trap. Our observations have established a pulsed source of atomic antimatter, with a rise time of about 1 s, and a pulse length ranging from 3 to 100 s. Time-sensitive antihydrogen detection and positron plasma diagnostics, both capabilities of the ATHENA apparatus, allowed detailed studies of the pulsing behavior, which in turn gave information on the dependence of the antihydrogen production process on the positron temperature T. Our data are consistent with power law scaling T (-1.1+/-0.5) for the production rate in the high temperature regime from approximately 100 meV up to 1.5 eV. This is not in accord with the behavior accepted for conventional three-body recombination.

Factores pronósticos en el cáncer vesicular subseroso / Prognostic factors in subserous gallbladder cancer

Introducción: Es importante identificar los factores pronósticos del cáncer vesicular subseroso para poder plantear distintas terapias dentro de este grupo tumoral. Objetivo: Evaluar qué factores pronósticos afectan la sobrevida en pacientes con cáncer vesicular subseroso. Material y métodos: Cohorte retrospectiva. Se analizan los pacientes con diagnóstico histopatológico de cáncer vesicular subseroso (T2), a partir de la biopsia de la pieza quirúrgica, operados en el Hospital Regional Valdivia (HRV) entre los años 2001-2005. Para caracterizar a la población se realizó estadística descriptiva. La sobrevida global se describió mediante curvas de Kaplan Meier. Para medir los factores pronósticos (reoperación, terapia adyuvante (quimioradioterapia), grado de diferenciación y el compromiso linfonodal), se realizó análisis bivariado mediante la prueba de Long Rank y análisis multivariado por medio de una regresión de Cox. Resultados: La cohorte incluyó 18 pacientes. Edad promedio 65 (39-86) años. Predominó el sexo femenino, 12 (66,66 por ciento). El diagnóstico preoperatorio "probable cáncer vesicular", se encontró en 5 pacientes (27,77 por ciento), colecistitis aguda en 8 (44,44 por ciento), colelitiasis sintomática en 3 (16,66 por ciento). Once pacientes (61,11 por ciento) fueron catalogados como N1 y 7 (38,88 por ciento) como N0. Cinco tumores (27,77 por ciento) se clasificaron como mal diferenciados, 9 (50,00 por ciento como moderadamente y 3 (16,66 por ciento) como bien diferenciados. Cuatro pacientes se reoperaron (22,22 por ciento). La sobrevida a 5 años fue 81,71 por ciento y 18,18 por ciento para los N0 y N1 respectivamente. Tanto el análisis bivariado (p=0.0049) como el multivariado (HR:18,34; IC 95 por ciento; 1,18-283, p=0.037) arrojó que el compromiso linfonodal es un factor de mal pronóstico. Conclusión: El compromiso linfonodal sería un factor pronóstico en el cáncer vesicular subseroso.

Introduction: It is important to identify the prognostic factors of the gallbladder cancer dye to be able to raise different therapies within this group tumor. Objective: To evaluate prognostic factors that affect the survival of patients with subserous gallbladder cancer. Material and methods: retrospective cohort study. We analyze the patients with histopathological diagnosis of subserous gallbladder cancer (T2) from the biopsy of the surgical specimen, operated in the Regional Hospital Valdivia (HRV) between the years 2001-2005. To characterize the population descriptive statistical analysis was carried out. Overall survival was described by Kaplan Meier curves. To measure the prognostic factors ( reoperation, adjuvant therapy (chemo), degree of differentiation and commitment linfonodal), bivariate analysis was performed using the Long rank test and multivariate analysis by means of a Cox's regression. Results: The cohort included 18 patients. Average age 65 (39-86) years. A predominance of females, 12 (66.66 percent. The preoperative diagnosis "vesicular likely cancer", was found in 5 patients (27.77 percent), acute cholecystitis in 8 (44.44 percent), symptomatic cholelithiasis in 3 (16.66 percent). Eleven patients (61.11 percent) were classified as N1 and 7 (38.88 percent) as N0. Five tumors (27.77 percent) were classified as poorly differentiated, 9 (50.00 percent) as moderately and 3 (16.66 percent) as well differentiated. Four patients surgery (22.22 percent). The survival at 5 years was 81.71 percent and 18.18 percent for the N0 and N1 respectively. Both the bivariate analysis (p=0.0049) as the multivariate (HR:18.34; 95 percent CI 1.18 -283, p=0,037) showed that the linfonodal involvement is a poor prognostic factor. Conclusion: The linfonodal involvement would be a prognostic factor in cancer subserous vesicular.

Evidence for the production of slow antiprotonic hydrogen in vacuum.

We present evidence showing how antiprotonic hydrogen, the quasistable antiproton (p)-proton bound system, has been synthesized following the interaction of antiprotons with the molecular ion H2+ in a nested Penning trap environment. From a careful analysis of the spatial distributions of antiproton annihilation events, evidence is presented for antiprotonic hydrogen production with sub-eV kinetic energies in states around n=70, and with low angular momenta. The slow antiprotonic hydrogen may be studied using laser spectroscopic techniques.

Search for laser-induced formation of antihydrogen atoms.

Antihydrogen can be synthesized by mixing antiprotons and positrons in a Penning trap environment. Here an experiment to stimulate the formation of antihydrogen in the n = 11 quantum state by the introduction of light from a CO2 continuous wave laser is described. An overall upper limit of 0.8% with 90% C.L. on the laser-induced enhancement of the recombination has been found. This result strongly suggests that radiative recombination contributes negligibly to the antihydrogen formed in the experimental conditions used by the ATHENA Collaboration.

Evaluación del compromiso linfonodal en el cáncer gástrico mediante Dímero D / No association between serum D Dimer levels and lymph node involvement among patients with gastric cancer

Background: D Dimer levels can be predictors of lymph node involvement in gastric cancer. Aim: To evaluate the association between D Dimer levels and lymph node involvement among patients with gastric cancer. Material and Methods: In 32 patients with gastric cancer, aged 38 to 86 years (24 males), subjected to a curative surgery, D Dimer was measured in the preoperative period. Its levels were associated with the number of regional lymph nodes involved and the tumor stage, according to the pathological report of the surgical piece. Results: There was no significant correlation between D Dimer levels and the number of involved lymph nodes (r = 0.18, p = NS). Conclusions: In this series of patients with gastric cancer, there was no association between serum D Dimer levels and the number of involved regional lymph nodes.

Introducción: En el cáncer gástrico resecado el principal factor pronóstico es el compromiso linfonodal. Estudios han demostrado que en el adenocarcinoma esofágico los niveles plasmáticos de Dímero D, se correlacionan con el compromiso linfonodal. Recientemente, Kwon HC demostró lo mismo en el adenocarcinoma gástrico. Objetivo: Establecer si el valor plasmático de Dímero D en el preoperatorio se correlaciona con el compromiso linfonodal en pacientes con adenocarcinoma gástrico resecado. Métodos: Estudio correlacional Durante un año, a los pacientes con diagnóstico de adenocarcinoma gástrico operados en el Hospital Base Valdivia, se les solicitó niveles plasmáticos de Dímero D, dentro del estudio preoperatorio. Causas de exclusión fueron: rechazo de ingreso al estudio, presencia de coagulopatía, los puncionados 48 horas antes del ingreso, los irresecables o con linfadenectomía insuficiente. El resultado del examen se correlacionó con el número de linfonodos comprometidos y el estadio tumoral (TNM) que informaba la biopsia definitiva de la pieza quirúrgica. Software utilizado: XLstat. Resultados: Para el análisis se incluyeron 32 casos. La mediana de edad: 66 años, la ubicación más frecuente fue tercio superior (52,94 por ciento) y el 28,13 por ciento de los pacientes se encontraban en estadio IIIA. El coeficiente de correlación entre nivel plasmático de Dímero D y el número de linfonodos comprometidos fue de 0,18 (p = 0,3411). Conclusión: De acuerdo a los resultados obtenidos en este estudio, existe correlación positiva débil entre los niveles plasmáticos de Dímero D y el número de linfonodos comprometidos en el adenocarcinoma gástrico, no concordando con lo actualmente publicado.

Gastrectomía subtotal en el cáncer gástrico antral mal diferenciado e indiferenciado / Subtotal gastrectomy for poorly differentiated and undifferentiated antral gastric cancer

Background: Total gastrectomy is recommended by some groups for poorly differentiated gastric cancer due to the multicentric nature of this tumor. Aim: To assess if subtotal gastrectomy achieves a good disease control in patients with undifferentiated or poorly differentiated gastric cancer. Material and Methods: Retrospective review of medical records of patients with undifferentiated or poorly differentiated gastric cancer, subjected to a subtotal gastrectomy between 1988 and 2006. Five years survival was calculated. Results: Fifty two patients aged 23 to 80 years were identified (30 males). Three had undifferentiated and 49 poorly differentiated tumors. One patient had a positive proximal margin. After a median follow up of 52 months, five years survival was 47 percent. Thirteen percent were lost from follow up. Conclusions: Five years survival of patients with undifferentiated or poorly differentiated gastric cancer and subjected to subtotal gastrectomy, was 47 percent.

Existen grupos quirúrgicos que preconizan la gastrectomía total para los cánceres gástricos mal diferenciados, por el riesgo de la multicentricidad y la infiltración oral no sospechada. Objetivo: Evaluar si la gastrectomía subtotal (GST) presenta un buen control de la enfermedad en el cáncer gástrico antral indiferenciado y mal diferenciado. Describir sus resultados anatomopatológicos y la sobrevida a 5 años. Material y Método: Estudio descriptivo. Se revisó el registro de pacientes con cáncer gástrico del servicio de cirugía del Hospital Base de Valdivia, entre los años 1988 y 2006. La población de estudio incluye pacientes con adenocarcinoma gástrico antral mal diferenciado e indiferenciado que fueron sometidos a una GST y aquellos pacientes con 2 cánceres en el estómago. Se recopilaron entre otras variables: edad, grado de diferenciación, tipo histológico, márgenes oral y caudal y se calculó la sobrevida global a 5 años. Además se describió el rendimiento de la endoscopia digestiva alta (EDA) en el diagnóstico de las lesiones multicéntricas. El Software utilizado fue el STATA 10.0. Resultados: Se incluyeron 52 pacientes. La mediana de edad fue 61 a±os. Tres (5,77 por ciento) tumores fueron indiferenciados y 49 (94,23 por ciento) mal diferenciados. Un (1,92 por ciento) paciente resultó con el margen oral positivo. La sobrevida global a 5 a±os fue 47 por ciento. La EDA detectó todos los tumores multicéntricos. Conclusión: La GST en el cáncer gástrico antral indiferenciado y mal diferenciado logra un buen control de la enfermedad con buena sobrevida a 5 años.

Spatial distribution of cold antihydrogen formation.

Antihydrogen is formed when antiprotons are mixed with cold positrons in a nested Penning trap. We present experimental evidence, obtained using our antihydrogen annihilation detector, that the spatial distribution of the emerging antihydrogen atoms is independent of the positron temperature and axially enhanced. This indicates that antihydrogen is formed before the antiprotons are in thermal equilibrium with the positron plasma. This result has important implications for the trapping and spectroscopy of antihydrogen.

New source of dense, cryogenic positron plasmas.

We have developed a new method, based on the ballistic transfer of preaccumulated plasmas, to obtain large and dense positron plasmas in a cryogenic environment. The method involves transferring plasmas emanating from a region with a low magnetic field (0.14 T) and relatively high pressure (10(-9) mbar) into a 15 K Penning-Malmberg trap immersed in a 3 T magnetic field with a base pressure better than 10(-13) mbar. The achieved positron accumulation rate in the high field cryogenic trap is more than one and a half orders of magnitude higher than the previous most efficient UHV compatible scheme. Subsequent stacking resulted in a plasma containing more than 1.2 x 10(9) positrons, which is a factor 4 higher than previously reported. Using a rotating wall electric field, plasmas containing about 20 x 10(6) positrons were compressed to a density of 2.6 x 10(10) cm(-3). This is a factor of 6 improvement over earlier measurements.

Colecistectomía preventiva del cáncer vesicular en adultos de 35 a 49 años sintomáticos: análisis de resultados obtenidos en el Hospital Clínico Regional de Valdivia entre los años 2007 y 2008 / Preventive cholecystectomy of gallbladder cancer in adults

Introducción: El cáncer vesicular es un problema de salud pública en Chile y corresponde a la primera causa de muerte por cáncer en la mujer chilena. Disminuir esta tasa es una prioridad en salud y es por esto que la colecistectomía preventiva en pacientes con colelitiasis se ha convertido en una de las principales armas para conseguirlo. Material y método: Estudio descriptivo y retrospectivo sobre la incidencia de cáncer vesicular y sus respectivos estadíos en pacientes sometidos a colecistectomías en el Hospital Clínico Regional de Valdivia entre el período GES 2007-2008. Resultados: Se realizaron 1857 colecistectomías, lo que supone un aumento de un 25 por ciento años en relación a años anteriormente analizados. De estas 915 (49,2 por ciento) se realizaron en pacientes con criterio GES. La incidencia de cáncer dentro del total de colecistectomías fue de 2,2 por ciento, muy por debajo del 3,09 y 4,57 por ciento encontrados en publicaciones previas en nuestro centro. Sólo un 27,2 por ciento de todos los diagnósticos de cáncer vesicular fueron en pacientes GES. Cabe destacar que no hubo cáncer en menores de 35 años. Lamentablemente la gran mayoría, 73,8 por ciento se encuentra avanzado al momento del diagnóstico. Discusión: Si bien los esfuerzo parecen ser correctos aún falta un período de tiempo para evaluar los verdaderos resultados, cuando el grupo que actualmente se está colecistectomizando gracias al GES alcance la edad de mayor incidencia de esta patología, que son los mayores de 55 años.